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mslr2022

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[ "24080932", "28222947", "26733760", "22809314", "3174047", "1882649", "16873325", "4621948", "3562212", "4266206", "1455324", "14582587", "25768709", "24382182", "24971923", "10371003", "21032979", "22207667", "22672361", "26174571", "20865217", "28593734", "9497660", "27410169", "7488989", "1437030", "21728748", "25183909", "22916669", "20739691" ]

[ "A pilot study of a chiropractic intervention for management of chronic myofascial temporomandibular disorder.", "Comparison of the effectiveness of three different treatment methods for temporomandibular joint disc displacement without reduction.", "Effects of Massage Therapy and Occlusal Splint Usage on Quality of Life and Pain in Individuals with Sleep Bruxism: A Randomized Controlled Trial.", "Efficacy of stabilisation splint treatment on temporomandibular disorders.", "Disk-repositioning onlays in the treatment of temporomandibular joint disk displacement: comparison with a flat occlusal splint and with no treatment.", "Acupuncture in treatment of facial muscular pain.", "The efficacy of traditional, low-cost and nonsplint therapies for temporomandibular disorder: a randomized controlled trial.", "Management of painful temporomandibular joint clicking with different intraoral devices and counseling: a controlled study", "Evaluation of the effectiveness of a semi-finished occlusal appliance – a randomized, controlled clinical trial", "Effects of massage therapy and occlusal splint therapy on electromyographic activity and the intensity of signs and symptoms in individuals with temporomandibular disorder and sleep bruxism: a randomized clinical trial", "Acupuncture and occlusal splint therapy in the treatment of craniomandibular disorders. Part I. A comparative study.", "Treatment of temporomandibular disorders among adolescents: a comparison between occlusal appliance, relaxation training, and brief information", "Additional effect of occlusal splints on the improvement of psychological aspects in temporomandibular disorder subjects: A randomized controlled trial.", "A new aid in temporomandibular joint disorders' therapy: the universal neuromuscular immediate relaxing appliance.", "CGRP plasma level changes in patients with temporomandibular disorders treated with occlusal splints - a randomised clinical trial.", "Therapeutic jaw exercises and interocclusal appliance therapy. A comparison between two common treatments of temporomandibular disorders.", "Effects of Orofacial Myofunctional Therapy on Temporomandibular Disorders", "Evaluation of the short-term effectiveness of education versus an occlusal splint for the treatment of myofascial pain of the jaw muscles.", "Behavioural changes and occlusal splints are effective in the management of masticatory myofascial pain: a short-term evaluation.", "Efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for treating RDC/TMD axis I patients: a randomised controlled trial.", "Partial time use of anterior repositioning splints in the management of TMJ pain and dysfunction: a one-year controlled study.", "Can an NTI‐tss device be effective as a first‐line therapy in patients with TMD myofascial pain?", "Evaluation of acupuncture and occlusal splint therapy in the treatment of temporomandibular joint disorders.", "Comparison of three different options for immediate treatment of painful temporomandibular disorders: a randomized, controlled pilot trial", "A randomized clinical trial of intraoral soft splints and palliative treatment for masticatory muscle pain.", "Temporomandibular joint disk displacement without reduction. Treatment with flat occlusal splint versus no treatment.", "Correlation of splint therapy outcome with the electromyography of masticatory muscles in temporomandibular disorder with myofascial pain", "Efficacy of Appliance Therapy on Temporomandibular Disorder Related Facial Pain and Mandibular Mobility: A Randomized Controlled Study", "Approaching Temporomandibular Disorders From a New Direction: A Randomized Controlled Clinical Trial of the TMDesTM Ear System", "Randomized Clinical Trial of Treatment for TMJ Disc Displacement" ]

[ "BACKGROUND Temporom and ibular pain has multiple etiologies and a range of therapeutic options . In this pilot study , the authors assessed the feasibility of conducting a larger trial to evaluate chiropractic treatment of temporom and ibular disorders ( TMDs ) . METHODS The authors assigned 80 participants r and omly into one of the following four groups , all of which included a comprehensive self-care program : reversible interocclusal splint therapy ( RIST ) , Activator Method Chiropractic Technique ( AMCT ) ( Activator Methods International , Phoenix ) , sham AMCT and self-care only . They made assessment s at baseline and at month 2 and month 6 , including use of the Research Diagnostic Criteria for Temporom and ibular Disorders . RESULTS The authors screened 721 potential participants and enrolled 80 people ; 52 participants completed the six-month assessment . The adjusted mean change in current pain over six months , as assessed on the 11-point numerical rating scale , was 2.0 ( 95 percent confidence interval , 1.1 - 3.0 ) for RIST , 1.7 ( 0.9 - 2.5 ) for self-care only , 1.5 ( 0.7 - 2.4 ) for AMCT and 1.6 ( 0.7 - 2.5 ) for sham AMCT . The authors also assessed bothersomeness and functionality . CONCLUSIONS The authors found the study design and methodology to be manageable . They gained substantial knowledge to aid in conducting a larger study . AMCT , RIST and self-care should be evaluated in a future comparative effectiveness study . PRACTICAL IMPLICATION S This pilot study was a necessary step to prepare for a larger study that will provide clinicians with information that should be helpful when discussing treatment options for patients with TMD", "The aim of this study was to compare the effectiveness of three treatment methods for unilateral temporom and ibular joint ( TMJ ) disc displacement without reduction ( DDwoR ) . One hundred and twenty patients with unilateral TMJ DDwoR were assigned r and omly to one of three treatment groups ( 40 patients in each ) : group 1 received arthrocentesis , group 2 received stabilization splint therapy following arthrocentesis , and group 3 received splint therapy only . The groups were compared in terms of pain ( visual analogue scale ) , joint function ( maximum mouth opening and laterotrusive movements ) , disability and psychological status ( vali date d question naire ) , and success rates . These were recorded before treatment and during follow-up after treatment ( 1 , 3 , and 6 months ) . The between-group and within-group differences in the data were analyzed statistically . The baseline characteristics were similar in all groups ( P>0.05 ) . Significant improvements were noted in all parameters compared to baseline values in all groups ( all P<0.01 ) . Groups 1 and 2 showed comparable outcomes that were superior to those of group 3 . Arthrocentesis reduces pain and functional impairment more rapidly and effectively than splint therapy . Simultaneous splint application has no additional effect on the effectiveness of arthrocentesis for the treatment of unilateral", "PURPOSE The aim of the present study was to investigate the effects of massage therapy on the masticatory muscles and occlusal splint usage on quality of life and pain in individuals with sleep bruxism . METHOD A r and omized , controlled , blinded , clinical trial was conducted involving 78 volunteers aged 18 to 40 years with sleep bruxism . Quality of life and pain assessment s were performed . RESULTS Significant differences ( p < 0.05 ) were found on the physical functioning , general health state , vitality , role emotional and mental health subscales . A large effect size was found for all treatment protocol s with regard to pain . The largest effect was found in the combined treatment group . CONCLUSIONS The findings of the present study reveal that the occlusal splint usage alone led to improvements in components of quality of life among individuals with sleep bruxism . Moreover , both treatments ( occlusal splint usage and massage therapy on the masticatory muscles ) led to a reduction in pain", "The evidence supporting the use of stabilisation splints in the treatment of temporom and ibular disorders ( TMD ) is scarce and a need for well-controlled studies exists . The aim of this r and omised , controlled trial study was to assess the efficacy of stabilisation splint treatment on TMD . The sample consisted of 80 consecutive referred patients who were r and omly assigned to the splint group ( n = 39 ) and the control group ( n = 41 ) . Subjects in the splint group were treated with a stabilisation splint , whereas subjects in the control group did not receive any treatment except counselling and instructions for masticatory muscle exercises which were given also to the subjects in the splint group . Outcomes were visual analogue scale ( VAS ) on facial pain intensity and clinical findings for TMD which were measured at baseline and after 1-month follow-up . The differences in change between the groups were analysed using regression models . Facial pain decreased and most of the clinical TMD findings resolved in both of the groups . The differences in changes in VAS or clinical TMD findings between the groups were not statistically significant . The findings of this study did not show that stabilisation splint treatment in combination with counselling and masticatory muscle exercises has additional benefit in relieving facial pain and increasing the mobility of the m and ible than counselling and masticatory muscle exercises alone in a short time-interval", "Sixty-three patients with an arthrographic diagnosis of disk displacement with reduction were r and omly assigned to three treatment groups : ( I ) onlays to maintain disk repositioning , ( II ) flat occlusal splint , or ( III ) untreated controls . Guidance for construction of the disk-repositioning onlays was established during arthrography to obtain a recaptured disk position relative to the condyle . The onlays were cemented to the teeth and maintained the new intercuspal position anteriorly and inferiorly . The flat occlusal splint was used at night only and was adjusted to maintain a maximal occlusal contact in centric relation and centric occlusion . Clinical examinations were performed before and after 6 months of treatment . The disk-repositioning onlays improved joint function and reduced joint and muscle pain when compared with the flat occlusal splint and with nontreatment . The signs and symptoms in the flat occlusal splint group were no different from those in the control group . It is concluded that disk-repositioning onlays are effective in reducing pain and dysfunction associated with disk displacement with reduction in patients in whom the disk can be maintained in a normal relationship to the condyle with the aid of such onlays . The symptoms , however , returned when the onlays were removed after 6 months ; this raises the question of whether a permanent change in the intercuspal position is necessary for long-term success", "Forty-five individuals with long-st and ing facial pain or headache of muscular origin were r and omly allocated into three groups . The first group was treated with acupuncture , the second group received an occlusal splint , and the third group served as controls . Both acupuncture and occlusal splint therapy significantly reduced subjective symptoms and clinical signs from the stomatognathic system . No differences between these two groups were found with regard to treatment effects . It is concluded that acupuncture is an alternative method to conventional stomatognathic treatment for individuals with craniom and ibular disorders of muscular origin", "BACKGROUND Treatment recommendations for patients with painful temporom and ibular disorders ( TMDs ) range from conservative treatments such as physiotherapy to aggressive and irreversible treatments such as restorative reconstruction and joint surgery . METHODS The authors r and omized 200 subjects diagnosed with TMD into three groups : usual conservative , dentist-prescribed self-care treatment without any intraoral splint appliance ( UT ) ; UT plus a conventional flat-plane hard acrylic splint ( HS ) ; and UT plus a soft vinyl ( a low-cost athletic mouth guard ) splint ( SS ) . Subjects completed question naires and clinical examinations at three , six and 12 months . RESULTS The authors observed no significant differences among the groups in TMD-related pain levels or other common signs and symptoms of TMD at baseline ( BL ) or at any follow-up . The changes from BL were comparable for all three groups . The authors did not note any significant differences at any follow-up for compliance with study protocol s or for occurrences of adverse effects from either splint type . For HS versus SS , there were significant differences in rates of splint use , but these differences were not accompanied by differences in either self-reported symptoms or in clinical findings . CONCLUSIONS All patients improved over time , and traditional splint therapy offered no benefit over the SS splint therapy . Neither splint therapy provided a greater benefit than did self-care treatment without splint therapy . CLINICAL IMPLICATION S These findings suggest that clinicians who treat patients with TMD should consider prescribing low-cost nonsplint self-care therapy for most patients", "Objective The benefit of the use of some intraoral devices in arthrogenous temporom and ibular disorders ( TMD ) patients is still unknown . This study assessed the effectiveness of the partial use of intraoral devices and counseling in the management of patients with disc displacement with reduction ( DDWR ) and arthralgia . Material s and Methods A total of 60 DDWR and arthralgia patients were r and omly divided into three groups : group I ( n=20 ) wore anterior repositioning occlusal splints ( ARS ) ; group II ( n=20 ) wore the Nociceptive Trigeminal Inhibition Clenching Suppression System devices ( NTI-tss ) ; and group III ( n=20 ) only received counseling for behavioral changes and self-care ( the control group ) . The first two groups also received counseling . Follow-ups were performed after 2 weeks , 6 weeks and 3 months . In these sessions , patients were evaluated by means of a visual analogue scale , pressure pain threshold ( PPT ) of the temporom and ibular joint ( TMJ ) , maximum range of motion and TMJ sounds . Possible adverse effects were also recorded , such as discomfort while using the device and occlusal changes . The results were analyzed with ANOVA , Tukey ’s and Fisher Exact Test , with a significance level of 5 % . Results Groups I and II showed improvement in pain intensity at the first follow-up . This progress was recorded only after 3 months in Group III . Group II showed an increased in joint sounds frequency . The PPT values , m and ibular range of motion and the number of occlusal contacts did not change significantly . Conclusion The simultaneous use of intraoral devices ( partial time ) plus behavioral modifications seems to produce a more rapid pain improvement in patients with painful DDWR . The use of NTI-tss could increase TMJ sounds . Although intraoral devices with additional counseling should be considered for the management of painful DDWR , dentists should be aware of the possible side effects of the intraoral device ’s design", "Introduction Painful temporom and ibular disorders ( TMDs ) are usually treated with physiotherapy , self-exercises , medication-based therapy and splint therapy . For splint therapy different types of splints are available . Therefore this r and omized controlled study compared the effectiveness of a semi-finished occlusal appliance ( SB ) with a laboratory-made occlusal appliance ( SS ) in myofascial pain patients . Method The trial subjects allocated to the experimental groups with the ( SB ) occlusal appliance and those provided with a laboratory-made occlusal appliance ( SS ) did , in addition , receive conservative treatment ( self-exercises , drug-based and manual therapy ) . The control group was given conservative therapy ( CO ) only . Overall , a total of 63 patients participated in the study with each group consisting of 21 subjects . Results When the first follow-up examination took place ( 14 days after splint insertion ) mouth opening within the SB group was significantly enlarged . When the second examination was conducted ( 2.5 months after splint insertion ) mouth opening was significantly enlarged in both splint groups when compared with the initial value . In the control group , no significant enlargement of mouth opening was detected . At no point there was a significant reduction in the number of pressure-sensitive areas of the TMJ . On palpation of the masticatory muscles however , a significant reduction in the number of pressure-sensitive areas could be observed within the CO group and the SS group after 2.5 months . When comparing pain reduction ( muscle/joint pain ) and mouth opening , no significant differences could be detected between the treatments . Conclusion The results suggest that TMD should be treated conservatively . In cases of restricted mouth opening , the additional use of occlusal appliances can eliminate the patient ’s discomfort more quickly . In this context , the tested , semi-finished occlusal appliance appears to offer an immediately available , temporary alternative to laboratory-made splints", "Introduction Temporom and ibular disorder ( TDM ) is the most common source of orofacial pain of a non-dental origin . Sleep bruxism is characterized by clenching and /or grinding the teeth during sleep and is involved in the perpetuation of TMD . The aim of the present study was to investigate the effects of massage therapy , conventional occlusal splint therapy and silicone occlusal splint therapy on electromyographic activity in the masseter and anterior temporal muscles and the intensity of signs and symptoms in individuals with severe TMD and sleep bruxism . Methods Sixty individuals with severe TMD and sleep bruxism were r and omly distributed into four treatment groups : 1 ) massage group , 2 ) conventional occlusal splint group , 3 ) massage + conventional occlusal splint group and 4 ) silicone occlusal splint group . Block r and omization was employed and sealed opaque envelopes were used to conceal the allocation . Groups 2 , 3 and 4 wore an occlusal splint for four weeks . Groups 1 and 3 received three weekly massage sessions for four weeks . All groups were evaluated before and after treatment through electromyographic analysis of the masseter and anterior temporal muscles and the Fonseca Patient History Index . The Wilcoxon test was used to compare the effects of the different treatments and repeated- measures ANOVA was used to determine the intensity of TMD . Results The inter-group analysis of variance revealed no statistically significant differences in median frequency among the groups prior to treatment . In the intra-group analysis , no statistically significant differences were found between pre-treatment and post-treatment evaluations in any of the groups . Group 3 demonstrated a greater improvement in the intensity of TMD in comparison to the other groups . Conclusion Massage therapy and the use of an occlusal splint had no significant influence on electromyographic activity of the masseter or anterior temporal muscles . However , the combination of therapies led to a reduction in the intensity of signs and symptoms among individuals with severe TMD and sleep bruxism . Trial registration This study is registered in August , 2014 in the Clinical Trials.gov ( NCT01874041 )", "One hundred and ten patients , 23 males and 87 females , participated in a comparative study of the effect of acupuncture and occlusal splint therapy . All the patients exhibited signs and symptoms of craniom and ibular disorders ( CMD ) and had had pain for more than six months . The participants were r and omly assigned to three groups ; acupuncture treatment , occlusal splint therapy or control . The patients were evaluated before and immediately after treatment/control time . Ten different subjective and /or clinical assessment variables were used in the evaluation of the treatment effects . Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged . In this short-term study , acupuncture gave better subjective results ( p < 0.001 ) than the occlusal splint therapy", "In a r and omized trial the effects of occlusal appliance and relaxation therapy , each combined with brief information , were compared with brief information only , in adolescents with temporom and ibular disorder ( TMD ) pain . One-hundred- and -twenty-two adolescents ( 93 F and 29 M aged 12 - 18 years ) were r and omly assigned to one of the following 3 groups : brief information + occlusal appliance ( BI + OA ) , brief information + relaxation therapy ( BI + RT ) , or brief information ( BI ) . Included were subjects reporting pain once a week or more often , in addition to receiving a diagnosis of TMD according to the Research Diagnostic Criteria ( RDC/TMD ) . They were evaluated before and after treatment and at a 6-month follow-up by means of self-reports and clinical assessment . The result revealed a significantly higher reduction in frequency of pain , in pain intensity ( visual analog scale [ VAS ] ) , and in a composite pain index ( intensity x frequency ) for patients treated with BI + OA compared with those treated with BI alone . In the BI + OA group , 60 % of the patients attained a clinical ly significant improvement ( at least 50 % or more ) on the pain index , a significantly higher proportion compared to that obtained in the other 2 treatment groups . Analgesic consumption was also significantly more reduced in the BI + OA group compared to the BI group . However , no significant differences were found between the treatment groups in jaw opening or in muscle and TMJ tenderness scores . Occlusal appliance was found to be superior to both relaxation therapy and brief information regarding pain reduction and can therefore be recommended when treating adolescents with TMD pain", "OBJECTIVE To measure the effect of occlusal splints as an additional treatment on psychological aspects in temporom and ibular disorder patients . DESIGN A r and omized controlled trial was performed comprising 60 adults diagnosed with masticatory myofascial pain according the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) . The participants were divided equally into 2 treatment groups , which received only counselling ( Group 1 ) or occlusal splints in addition to counselling ( Group 2 ) . The assessment s occurred at baseline and at 2 and 5 months after treatment . The outcomes were symptoms of anxiety and depression , as well as pain catastrophizing . Two-way ANOVA , Friedman and Mann-Whitney tests were used to perform the statistical analysis , considering a significance level of 5 % . RESULTS In relation to the baseline assessment , 60 % of the subjects had at least mild anxiety and 25 % had at least mild depression , and the mean and st and ard deviation ( SD ) of pain catastrophizing was 2.41 ( 1.33 ) for Group 1 and 2.06 ( 1.04 ) for Group 2 . Comparisons between baseline and the fifth-month evaluation showed an improvement in anxiety and depression symptoms only in Group 2 ( p<0.05 ) . Otherwise , there was a significant reduction in pain catastrophizing in both groups ( p<0.05 ) , with a mean ( SD ) of 1.14 ( 1.28 ) for Group 1 and 0.76 ( 0.82 ) for Group 2 . CONCLUSION Minimally invasive strategies could provide an improvement in the psychological aspects of temporom and ibular disorder patients , and the use of an occlusal splint seems to hasten the manifestation of these effects", "Among the various treatment options currently indicated to deal with temporom and ibular joint disorders ( TMD ) an important role is played by occlusal devices , which can be used in an individualized or universal manner . A new universal occlusal appliance device was design ed and patented at the Clinical Gnathology Service of the Sapienza University of Rome . To assess its validity and efficacy a preliminary study on a sample of 50 patients was carried out . Patients were selected from a cohort of 158 according to the RDC-TMD ( SPEC ) criteria and r and omly assigned to two groups , the patient group ( PG ) , treated with the device , and a control group ( CG ) without any treatment . The two groups were evaluated by comparing four VAS pain scores : muscular , migraine , cervical and temporom and ibular joint ( TMJ ) . On the whole , all VAS pain scores in the PG showed a marked and statistically significant improvement after treatment , decreasing to about 50 - 80 percent , while the control group remained stable . The best improvement was achieved in muscular pain . Age did not affect neither the initial scores , nor the pain response to the treatment . The pain scores tended to slightly increase with time of application ( one , two or three months ) , but this trend was significant only for cervical pain . Overall the results are favourable to the application of this new occlusion device . However , the data should be considered preliminary and require further verification in time and on a higher sample of patients of both sexes", "INTRODUCTION Occlusal splint therapy is a well-known method for the treatment of TMD . Muscle stretching and pain relief are effects of occlusal appliance . The aim of this study was to evaluate the plasma level of CGRP in patients with myofascial pain ( RDC/TMD Ia ) and myofascial pain with limited opening ( RDC/TMD Ib ) before and after muscle stretching with occlusal splint therapy . MATERIAL AND METHODS A r and omised trial was performed including 35 subjects ( males = 10 , females = 25 ) in the experimental group and 30 subjects ( males = 9 , females = 21 ) in the control group . Blood sample s were taken from the external jugular vein before and after 30 days of occlusal splint therapy . Plasma levels of CGRP were measured with a Radio Immunoassay Kit ( Phoenix Pharmaceuticals Inc. ) and Cobra Series Auto-Gamma Counting System . RESULTS The results of the study demonstrated that CGRP concentrations were significantly higher after occlusal splint than before splint therapy : CGRP2 = 17.02 pg/mL ( SD = 5.85 ) , CGRP1 = 13.78 pg/mL ( SD = 5.12 ) , in the experimental group ( p < 0.05 ) . In the control group , there were no statistically significant changes in CGRP levels : CGRP1 = 14.5 pg/mL ( SD = 4.87 ) to CGRP2 = 13.5 pg/mL ( SD = 4.63 ) . In the experimental group , there was a statistically significant reduction in pain intensity , VAS1 = 5 ( SD = 2.5 ) to VAS2 = 1 ( SD = 1.04 ) after splint therapy ( p < 0.05 ) . In the control group , there were no statistically significant changes in pain intensity : VAS1 = 5 ( SD = 2.3 ) to VAS2 = 4 ( SD = 2.6 ) , ( p < 0.05 ) . CONCLUSIONS CGRP plays an important role in muscle blood flow , which is altered by changes in muscle length . Further investigation is needed to clarify the mechanism of muscle blood flow and the muscle healing process in patients with TMD", "From a total of 1344 consecutive patients referred to a TMD clinic , twenty-six patients fulfilled the strict inclusion criteria s of TMD of mainly muscular origin . Half of the patients were assigned to receive treatment with an interocclusal appliance , the treatment being performed by a dentist . The other half was instructed to perform individualized therapeutic jaw exercises , and this treatment was managed by a dental assistant . The treatment result was evaluated after six months . The two treatments had a positive and equal effect upon both signs and symptoms of TMD . A further follow-up by question naire one to four years after the final clinical examination showed a lasting treatment result in most patients . Many patients , however , continued to perform jaw exercises and /or to wear their appliances . This indicates that these two treatments are mostly symptomatic and not causal . The conclusion of the present investigation is that therapeutic jaw exercises , managed by a dentist or a dental assistant , is a cost effective treatment with a prognosis comparable to a treatment with an interocclusal appliance and can thus be recommended as the first therapy of choice in patients with TMD of mainly muscular origin", "Abstract The objectives of the current study were to analyze the effects of orofacial myofunctional therapy ( OMT ) on the treatment of subjects with associated articular and muscular temporom and ibular disorders ( TMD ) . Thirty subjects with associated articular and muscular TMD , according to the Research Diagnostic Criteria ( RDC/TMD ) , were r and omly divided into groups : 10 were treated with OMT ( T group ) , 10 with an occlusal splint ( OS group ) , and 10 untreated control group with TMD ( SC ) . Ten subjects without TMD represented the asymptomatic group ( AC ) . All subjects had a clinical examination and were interviewed to determine Helkimo ’s Indexes ( Di and Ai ) , the frequency and severity of signs and symptoms , and orofacial myofunctional evaluation . During the diagnostic phase , there were significant differences between groups T and AC . There were no significant differences between group T and OC and SC groups . During the final phase , groups T and OS presented significant improvement , however , the group T presented better results and differed significantly from group OS regarding the number of subjects classified as AiII ; the severity of muscular pain and TMJ pain ; the frequency of headache and the muscles and stomatognathic functions . The group T differed significantly from the SC group but no longer differed significantly from the AC group . OMT favored a significant reduction of pain sensitivity to palpation of all muscles studied but not for the TMJs ; an increased measure of m and ibular range of motion ; reduced Helkimo ’s Di and Ai scores ; reduced frequency and severity of signs and symptoms ; and increased scores for orofacial myofunctional conditions", "BACKGROUND The authors conducted a clinical trial to compare the effectiveness of an education program with that of an occlusal splint in treating myofascial pain of the jaw muscles across a short period . METHOD The authors assigned 44 patients r and omly to two treatment groups ; 41 patients completed the study . The first group ( four male , 19 female ; mean [ st and ard deviation { SD } ] age , 31.4 [ 14.0 ] years ) received information regarding the nature of temporom and ibular disorder ( TMD ) and self-care measures , whereas the second group ( five male , 13 female ; mean [ SD ] age , 31.1 [ 8.8 ] years ) received an occlusal splint . One of the authors evaluated each patient every three weeks during a three-month treatment period . Treatment outcomes included pain-free maximal mouth opening , spontaneous muscle pain , pain during chewing and headache . RESULTS After three months , changes in spontaneous muscle pain differed significantly between the education and occlusal splint groups ( P = .034 ; effect size = 0.33 ) . Changes in pain-free maximal mouth opening did not differ significantly between groups ( P = .528 ; effect size = 0.20 ) . Changes of headache and pain on chewing did not differ significantly between groups ( P ≥ .550 , effect size ≤ 0.10 ) . CONCLUSIONS During a short period , education was slightly more effective than an occlusal splint delivered without education in reducing spontaneous muscle pain in patients with TMD . Pain-free mouth opening , headache and pain during chewing were not significantly different between the two treatments", "The aim of this research was to test the hypothesis that treatment with intra-oral appliances with different occlusal design s was beneficial in the management of pain of masticatory muscles compared with a control group . A total of 51 patients were analysed according to the research diagnostic criteria for temporom and ibular disorders ( RDC/TMD ) to obtain the diagnosis of masticatory myofascial pain ( MMP ) . The sample was then r and omly divided into three groups : group I ( n = 21 ) wore a full coverage acrylic stabilisation occlusal splint ; group II ( n = 16 ) wore an anterior device nociceptive trigeminal inhibitory ( NTI ) system ; and group III ( n = 14 ) only received counselling for behavioural changes and self-care ( the control group ) . The first two groups also received counselling . Follow-ups were performed after 2 and 6 weeks and 3 months . In these sessions , patients were evaluated by means of a visual analogue scale ( VAS ) and pressure pain threshold ( PPT ) of the masticatory muscles . Possible adverse effects were also recorded , such as discomfort while using the appliance and occlusal changes . The results were analysed with Kruskal-Wallis , anova , Tukey 's and Friedman tests , with a significance level of 5 % . Group I showed improvement in the reported pain at the first follow-up ( 2 weeks ) , whereas for groups II and III , this progress was detected only after 6 weeks and 3 months , respectively . The PPT values did not change significantly . It was concluded that behavioural changes are effective in the management of pain in MMP patients . However , the simultaneous use of occlusal devices appears to produce an earlier improvement", "Stabilisation splint therapy has long been thought to be effective for the management of temporom and ibular disorders ( TMD ) . However , the superiority of stabilisation splint therapy compared to other TMD treatments remains controversial . The aim of this study was to determine the efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for TMD . A total of 181 TMD participants were r and omly allocated to a non-splint multimodal therapy ( NS ) group ( n = 85 ) or a non-splint multimodal therapy plus stabilisation splint ( NS+S ) group ( n = 96 ) . Non-splint multimodal therapy included self-exercise of the jaw , cognitive-behavioural therapy , self-management education and additional jaw manipulation . Three outcome measurements were used to assess treatment efficacy : mouth-opening limitation , oro-facial pain and temporom and ibular joint sounds . A two-factor repeated- measures analysis of variance ( anova ) was used to evaluate the efficacy of the two treatment modalities ( NS vs. NS+S ) , and Scheffe 's multiple comparison test was used to compare the treatment periods . Subgroup analyses were performed to disclose the splint effects for each TMD diagnostic group . All three parameters significantly decreased over time in both groups . However , there were no significant differences between the two treatment groups in the total comparison or subgroup analyses ; an exception was the group with degenerative joint disease . No significant difference between the NS and NS+S treatment approaches was revealed in this study . Therefore , we conclude that the additional effects of stabilisation splint are not supported for patients with TMD during the application of multimodal therapy", "This study aim ed at evaluating the effectiveness of partial use of anterior repositioning appliances in the management of TMJ pain and dysfunction when compared to stabilization splints and a control group in a one-year follow-up . Sample was initially constituted by 60 patients , r and omly divided into three groups : I- stabilization splints , II- repositioning splints and III- no treatment . The whole sample was evaluated by means of TMJ and muscle palpation , m and ibular AROM , analysis of occlusal contacts , joint sounds inspection and Visual Analogue Scale ( VAS ) for one year ; 52 patients composed the final sample . A significant ( after 15 days ) improvement in pain report ( VAS ) and palpation index was found for group II ( p < or = 0.01 ) . The occurrence of occlusal alterations as posterior open bite or gross interferences after the splint therapy and increased muscle tenderness were not problems in this study . Similar results in joint noises reduction were observed for the entire sample . It was concluded that controlled partial use of repositioning splints is a beneficial tool in the management of intra-articular pain and dysfunction , with no risks of irreversible occlusal changes", "This study was conducted to evaluate whether integrating a nociceptive trigeminal inhibition-tension suppression system ( NTI-tss ) device with first-line therapy of myofascial pain , which includes guidance , assurance , counselling and behavioural changes , would be more effective in alleviating symptoms . This r and omised controlled clinical trial included 40 patients who were clinical ly diagnosed with myofascial pain according to Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) . Patients were r and omly divided into two groups : the first group comprised patients who received guidance , assurance , counselling and behavioural changes ; an NTI-tss device was integrated to this protocol in the second group . Both groups exhibited reduction in pain levels and improvement of jaw function compared with baseline values , but the difference was not significant . Both groups demonstrated improvements in 6 weeks ; however , the integration of NTI-tss device into the therapy protocol did not provide any additional benefit in relieving symptoms of myofascial pain", "One hundred patients showed signs and symptoms of temporom and ibular joint disorder , were participated in a one year follow up study . The patients were r and omly divided into four groups : Acuhealth treatment ( group A ) , occlusal splint therapy ( group B ) , Acuhealth and occlusal splint therapy ( group C ) , and control ( group D ) . Each group comprised 25 patients . The patients were examined before and 3 , 6 , and 12 months after treatment . At the three month evaluation , the patients who were not satisfied with the treatment outcome were offered additional treatment . The result showed that 87 % of the patients treated by Acuhealth unit , 77.3 % of the patients treated with occlusal splint therapy , and 91.3 % of the patients received Acuhealth and occlusal splint therapy were improved subjectively and clinical ly after 3 months follow-up . The patients who responded well to treatment initially also responded well in the long run . The study showed that the Acuhealth unit proved to be an ideal early therapy for TMD , and complemented later with occlusal splint", "Abstract Objective : The purpose of this study was to compare the short-term effectiveness of three different types of immediate , non-pharmacological intervention for alleviation of the painful symptoms of temporom and ibular disorders ( TMD ) . Material and methods : Thirty-six patients ( mean age 41.6 ± 16.7 years , 25 females ) diagnosed with non-dysfunctional painful TMD received counselling and subsequently were r and omly allocated to three treatment groups : patients in Group A received prefabricated oral splints with water-filled elastic pads ( Aqualizer ® ) , those in Group B were provided with vacuum-formed co-polyester oral splints and those in Group C were given appointments to receive Michigan-type hard splints . Clinical examination was conducted , at baseline and after 2 weeks , by use of the RDC/TMD . Current pain intensity was determined by evaluation of grade d chronic pain status ( GCPS ) on a numerical rating scale ( NRS ) . Active maximum mouth opening without pain ( AMMOP ) was also measured . Paired sample t-tests and one-way analysis of variance with a significance level of p ≤ 0.05 were conducted . Results : After 2 weeks , overall mean current pain was reduced by 41.95 % ( p < 0.001 ) . Current pain reduction was significant for Group B ( 66.6 % , p < 0.001 ) but not for Groups A ( 37.88 % , p = 0.56 ) and C ( 22.29 % , p = 0.26 ) . After 2 weeks , current pain level for Group B was significantly lower than that for Group C ( p = 0.041 ) . Overall , there was a statistically significant increase of AMMOP ( p = 0.01 ) . Conclusion : All therapeutic options were pain-reducing . The results from this study suggest that cost-effective and time-effective intervention of counselling combined with use of a vacuum-formed splint is a favourable option for initial , short-term treatment of painful TMD", "Thirty subjects seeking treatment for masticatory muscle pain at a university-based TMJ clinic were r and omly assigned to soft-splint , palliative-treatment , and no-treatment groups . After 4 to 11 weeks of treatment , subjects were evaluated for changes from their baseline levels of symptoms , maximum pain-free opening , pain thresholds measured by a pressure algometer , and occlusal contacts . With the use of the multivariate analysis of variance and analysis of covariance , the results suggest that the soft-splint group had statistically significant improvement ( P < .01 ) , the palliative-treatment group had improvement that was not statistically significant , and the no-treatment group had a slight aggravation of symptoms . The soft-splint group had fewer occlusal contact changes assessed with shimstock compared to the palliative-treatment and no-treatment groups . The findings of this study suggest that the soft splint is an effective short-term treatment for reducing the signs and symptoms of masticatory muscle pain in patients , and the soft splint does not cause occlusal changes", "A flat occlusal splint has been extensively used in the treatment of patients with temporom and ibular joint disk displacement without reduction , but no studies with untreated controls have assessed its effect . We r and omly assigned 51 patients with temporom and ibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial . Pain symptoms disappeared in about one third of the patients in each group . Another third of the patients in the control group improved . Sixteen percent of the patients in the control group and 40 % of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study . Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group . A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction . The use of a flat occlusal splint in this patient group should therefore be reconsidered", "Abstract Objectives . The aim of this study was to assess the effect of occlusal splint therapy on the electromyographic amplitude records ( μV ) of masticatory muscles in temporom and ibular disorder ( TMD ) with myofascial pain and to detect a possible existence of a relationship between this effect and the treatment outcome . Material s and methods . Forty patients ( 23 females and 17 males ) having TMD with myofascial pain were included in this study . They were r and omly divided into two equal groups ( 20 of each ) . The first group ( A ) was treated by occlusal splints for 6 months while the second group ( B ) acted as a control . A clinical assessment and surface electromyography ( EMG ) for the masticatory muscles were performed at the beginning of the study , then 6 months later . The collected data were statistically analyzed using paired t-test . The differences were considered significant at p < 0.05 . Results . The results showed that 85 % of group A either completely recovered ( 35 % ) or clinical ly improved ( 50 % ) while only 20 % of group B had a spontaneous improvement . In group A , the means of the electromyographic amplitude records ( μV ) of the monitored muscles have decreased after 6 months . However , the decrease was statistically insignificant ( p > 0.05 ) in the patients ( 15 % ) who had no clinical changes . In group B , the means of the muscles ' records ( μV ) in the left side slightly increased while those of the right side slightly decreased . These changes were statistically insignificant ( p > 0.05 ) . Conclusions . Occlusal splint could eliminate or improve the signs and symptoms of TMD patients with myofascial pain . It reduces the electromyographic amplitude records ( μV ) of the masticatory muscles . The splint therapy outcome has a correlation with the electromyographic amplitude changes of the masticatory muscles", "There is limited evidence supporting the role of occlusal splints in Temporom and ibular disorder ( TMD ) therapy . The aim of this r and omized controlled clinical trial was to assess the efficacy of stabilization splint therapy on TMD related facial pain and m and ibular mobility . The sample of study consisted of eighty consecutive patients diagnosed with TMD . Patients were r and omly assigned into two groups : a splint group ( n = 40 ) comprising of patients treated with stabilization splint , councelling and masticatory muscle exercises , and a control group ( n = 40 ) , comprising of patients treated with councelling and masticatory muscle exercises alone . Data from both the groups were collected at the beginning of the study and after a 6-month follow up . The outcome variables were visual analogue scale on facial pain intensity and clinical findings for TMD ( anterior maximal opening , m and ibular right laterotrusion , m and ibular left laterotrusion , m and ibular protrusion , and number of painful muscle sites ) . Changes within the splint and control groups ( before treatment and 6 months after treatment ) were analyzed using paired sample s t test . Differences in change between the splint and control groups were analyzed using independent sample s t-test . The level of significance was set at p < 0.05 . Facial pain and number of painful muscle sites decreased , and the m and ibular mobility increased significantly in both groups after treatment ; however the differences in changes in VAS or clinical TMD findings between the two groups were not statistically significant . The findings of this study show that stabilization splint treatment in combination with counselling and masticatory muscle exercises has no additional benefit in relieving facial pain and increasing the mobility of the m and ible than counselling and masticatory muscle exercises alone over a 6-months ’ time interval", "Abstract TMDes ( Registered Trademark of Ascentia Health , Inc. , Rockford , Illinois ) , custom-fit ear inserts to aid in reducing temporom and ibular disorder ( TMD ) pain , were evaluated in a prospect i ve , three-month , open-label , three-arm , r and omized , unblinded clinical trial , which included patients with TMD diagnoses ( RDC/TMD ) of myofascial pain , arthralgia , and /or disc displacement with reduction ; and a screening VAS pain score of > 4 . The three treatment groups included : TMDes ( n=60 ) , stabilization splint ( n=64 ) , and jaw exercise regimen ( n=28 ) . The mean change in Craniom and ibular Index ( CMI ) scores ( reductions reflecting improvement ) from baseline to one month were -27 % ( TMDes ) , -20 % ( stabilization splint ) , -12 % ( jaw exercise regimen ) , and from baseline to three months were -45 % , -41 % , -36 % , reflecting statistically significant noninferiority ( p=0.0096 ) of the TMDes to the stabilization splint ( primary efficacy endpoint ) . The TMDes produced significant ( p<0.0001 ) mean changes in VAS pain scores from baseline of -46 % at one month and -58 % at three months and demonstrated comparable efficacy and safety to the stabilization splint . ( Registered at Clinical Trials.gov : NCT00815776 )", "Of the various conservative treatment modalities available for temporom and ibular disorders , we believe that therapeutic exercise has a good prognosis , especially for anterior disc displacement without reduction . Since its effectiveness has not been extensively evaluated , we conducted a comparative study to verify the hypothesis that treatment efficacy would not differ for exercise and occlusal splints . Fifty-two individuals with anterior disc displacement without reduction were r and omly assigned to a splint or a joint mobilization self-exercise treatment group . Four outcome variables were evaluated : ( i ) maximum mouth-opening range without and ( ii ) with pain , ( iii ) current maximum daily pain intensity , and ( iv ) limitation of daily functions . All outcome variables significantly improved after 8 weeks of treatment in both groups . In particular , the mouth opening range increased more in the exercise group than in the splint group . This result demonstrates that therapeutic exercise brings earlier recovery of jaw function compared with splints" ]

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[ "Effectiveness of Taiwanese traditional herbal diet for pain management in terminal cancer patients.", "The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring.", "Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey.", "[Observation on the effect of zhiling capsule in treating patients with lung cancer of middle/advanced stage].", "[Effects of Guben Yiliu II combined with arterial perfusion with chemotherapeutic agent in treating advanced pancreatic cancer].", "Treatment of middle/late stage primary hepatic carcinoma by Chinese medicine comprehensive therapy: A prospective randomized controlled study", "Alleviation of cancerous pain by external compress with Xiaozheng Zhitong Paste (消癥止痛方)", "[Clinical study on integrative medicine for preventing and treating post-transcatheter arterial chemoembolization].", "Clinical study on treatment of primary hepatocellular carcinoma by Shenqi mixture combined with microwave coagulation.", "[Clinical study on aitongping capsule in treating cancerous pain].", "Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists.", "[Study on effect of moxibustion and guben yiliu III combined with chemotherapy in treating middle-late stage malignant tumor].", "Reviewer bias: a blinded experimental study.", "A randomized controlled pilot trial of \"Feiji Recipe\" on quality of life of non-small cell lung cancer patients.", "[Effect of qi replenishing and blood circulation activating drugs in treatment of middle-advanced pancreatic cancer with radio- and chemotherapy]." ]

[ "In addition to modern medicinal therapy , many cancer patients in Taiwan are treated regularly with herbal medicines or prescribed a traditional herbal diet . In this paper , the effect of a Taiwanese traditional herbal diet ( TTHD ) on pain in terminal cancer patients was investigated . A total of 2,466 patients diagnosed with a variety of cancers were included . The most common patient-reported symptoms included troublesome pain ( 79.2 % ) , weakness ( 69.0 % ) , anorexia ( 46.4 % ) , fever ( 36.5 % ) , dyspnea ( 31.1 % ) , and leg edema ( 30.9 % ) . The 2,466 terminal cancer patients included in the study were r and omly divided into three groups . The TTHD group ( n=1044 ; 42.3 % ) were given the TTHD consisting of analgesic herbs ( paeony root : licorice root=1:1 ) and a Taiwanese tonic vegetable soup ( Lilii bulbus , Nelumbo seed , and Jujube fruit ) . The remaining patients were divided into a reference group , given the regular hospital diet , ( n=909 , 36.9 % ) and a control group , given the Taiwanese tonic vegetable soup without analgesic herbs , ( n=513 , 20.8 % ) . All patients maintained their assigned diets for one week . A verbal numerical scale was used to assess pain . Results revealed that the patients given TTHD reported enhanced pain relief ( p<0.05 ) compared to the reference and control groups . We found that TTHD could alleviate the pain among terminal cancer patients thereby supporting the supposition that Eastern and Western medicines can be effectively co-administered to enhance terminal patient 's quality of life . Further research is warranted", "BACKGROUND This study aim ed to evaluate traditional Chinese medicine ( TCM ) in improving quality of life ( QOL ) , reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy . PATIENTS AND METHODS Patients with ovarian cancer were r and omized to receive either TCM or placebo in addition to st and ard chemotherapy . The primary outcome was global health status ( GHS ) score , assessed by European Organization for Research and Treatment of Cancer question naire , while the secondary outcomes were other QOL items , chemotoxicity according to World Health Organization criteria and alterations in immune function as measured by immune cells count and the numbers of cytokines-secreting cells . RESULTS There was no significant difference in the GHS between the two groups . With adjustment for stage , chemotherapy type , disease status , age and baseline value , emotional function , cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy . The TCM group had less neutropenia after three cycles ( 0 % grade 4 neutropenia versus 28.6 % ) . There were no other significant differences in terms of chemotoxicity . Lymphocyte counts and cytokine activities decreased less in the TCM group . CONCLUSIONS TCM did not improve QOL but did have some effects in terms of maintaining immune function", "CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient", "OBJECTIVE To observe the effect and safety of Zhiling Capsule ( ZC ) in treating lung cancer of middle/advanced stage . METHODS With the multi-center , r and omized , double-blinded and parallel controlled method , the patients were divided into 4 groups , the 104 patients in the group A were treated with the whole recipe of ZC , the 52 in the group B with the disassembled recipe 1 ( Western medicines ) of ZC , the 46 in the group C with the disassembled recipe 2 ( Chinese medicines ) of ZC , and the 48 in the control group with Pingxiao Capsule , all the drugs were administered orally for 2 weeks . The changes of syndrome of qi-yin deficiency , symptoms , quality of life ( QOL ) , body weight and adverse reactions occurred in patients were observed . RESULTS The effective rate in alleviating syndrome in the groups A-D was 91.3 % , 80.8 % , 37.0 % and 14.6 % respectively ; in remitting stuffiness and chest pain 86.9 % , 60.5 % , 20.0 % and 10.0 % ; in improving appetite was 80.4 % , 47.9 % , 23.7 % and 10.3 % . QOL in the groups A-C was significantly elevated after treatment ( P < 0.05 or P < 0.01 ) , the improvement of group A was superior to that of other treatments ( P < 0.01 ) . Body weight in the group A was significantly increased and superior to that of others ( P < 0.05 ) . The whole recipe of ZC showed the therapeutic effect superior to that of the other treatments ( P < 0.05 ) . No obvious adverse reaction was found in all the 4 groups . CONCLUSION ZC can improve the symptoms and QOL in patients with lung cancer of middle/advanced stage", "OBJECTIVE To observe the effects ot Guben Yiliu II ( GY II ) combined with arterial perfusion with chemotherapeutic agent on advanced pancreatic cancer ( APC ) . METHODS Sixty-five APC patients were r and omly assigned to the treated group ( 35 cases ) given GY II and arterial perfusion with chemotherapeutic agent and the control group ( 30 cases ) with chemotherapeutic agent alone . RESULTS The clinical beneficial rate was 54.2 % in the treated group and 40.0 % in the control group , with significant difference between them ( P < 0.05 ) , the overall effective rate being 17.1 % and 13.3 % , and the effective rate in relieving pain being 64.5 % and 59.2 % in the treated and the control group respectively , all showed insignificant difference between groups ( P > 0.05 ) . Furthermore , in the treated group after treatment , the blood hypercoagulation state ameliorated , cellular immunity elevated , the toxic and side- effects of chemical medicine relieved , and the quality of life improved . CONCLUSION GY II is effective in enhancing clinical effects and relieving toxic and side-effects of chemotherapy , and so , better efficacy could be obtained by therapy of GY II and arterial perfusion with chemotherapeutic agent for treatment of APC", "Objective To observe the efficacy of Chinese medicine comprehensive therapeutic project in treating the middle/late stage primary hepatic carcinoma ( PHC ) . Methods With prospect i ve r and omized controlled design , 97 patients with PHC were assigned to the test group ( 49 cases ) treated with Chinese medicine comprehensive therapy using Oleum fructus bruceas intervention combining oral intake of Ganji Decoction ( 肝积方 ) and external application of Ailitong ( 癌理通 ) , and the control group ( 48 cases ) treated with chemotherapeutic agents combining iodized oil chemo-embolization and analgesics . The immediate and long-term efficacy , adverse reaction , pain-relieving initial time ( PRIT ) and pain-relieving sustained time ( PRST ) of the treatment , as well as the change in relieving patients ’ quality of life ( QOL ) were observed . Results The difference between the two groups in illness control rate was statistically insignificant ( P>0.05 ) , but the adverse reaction occurence rate in the test group was lesser than that in the control group ( P<0.05 ) . PRIT was insignificantly different in the two groups ( P>0.05 ) , but the PRST was significantly superior in the test group than that in the control group ( 10.37±2.18 h vs 7.78±1.95 h , P<0.01 ) . After treatment , the increased Karnofsky scores in the test group indicated that the patients ’ somatic activity , symptoms and QOL were improved significantly , which were significantly superior to those in the control group ( P<0.05 ) . The survival rate in the two groups was similar at the 3rd month after treatment , but the test group did show superiority in terms of half- and 1-year survival rate ( 65.9 % vs 42.5 % and 38.6 % vs 18.1 % , respectively , P<0.05 ) . The median survival time in the test group was 8.9 months and that in the control group was 5.3 months . Conclusion Chinese medicine comprehensive therapy is an effective treatment for the middle/late stage patients of PHC , and it could extend the PRST , improve the patients ’ QOL and long-term survival with less adverse reaction", "Objective To observe the clinical effectiveness of a topical application of Xiaozheng Zhitong : Paste ( 消癥止痛方 , XZP ) in alleviating the cancerous pain of patients with middle/late stage cancer Methods By : adopting a r and om number table , 124 patients enrolled were r and omized into the treatment group ( 64 patients ) and the control group ( 60 patients ) . In addition to the basic therapy [ including the three-ladder ( 3L ) analgesia ] used in both groups , topical application of XZP was given to patients in the treatment group for pain alleviation . The analgesic efficacy was recorded in terms of pain intensity , analgesia initiating time and sustaining time , and the optimal analgesic effect revealing time . Meanwhile , the quality of life ( QOL ) and adverse reactions that occurred in patients were recorded as well . Results The total effective rate in the treatment group was : 84.38 % ( 54/64 ) , and in the control group it was 88.33 % ( 53/60 ) , showing no significant difference between them ( P>0.05 ) , but the analgesia initiating time and the optimal analgesia effect revealing time in the treatment group were significantly shorter ( both P<0.01 ) . Moreover , XZP was better in improving patients ’ QOL , showing more significant improvements in the treatment group than those in the control group in aspects of mental condition , walking capacity , working capacity , social acceptability , sleep and joy of living ( P<0.05 or P<0.01 ) . Lower incidence of adverse reactions , such as nausea , vomiting , mouth dryness , dizziness , etc . , especially constipation , was noted in the treatment group ( P<0.05 or P<0.01 ) . Conclusion Applying an external compress : of XZP showed a synergistic action with 3L analgesia for shortening the initiating time and the optimal effect revealing time , and could evidently enhance patients ’ QOL with fewer adverse reactions", "OBJECTIVE To observe the effects of ginsenosides ( GS ) and low dose glucocorticoid for preventing and treating the post-transcatheter arterial chemoembolization ( TACE ) syndrome . METHODS Adopting r and omized , double blinded , controlled method , 80 patients with primary liver cancer were divided into 4 groups , placebo group , dexamethasone ( Dex ) group , Ginsenosides ( GS ) group , and Dex combined with GS group to observe the clinical effect of the patients after TACE . RESULTS Dex combined with GS could markedly lower the occurrence of nausea , vomiting , fever and pain , and the median time of symptoms persistence , also alleviate the bone marrow inhibition of chemotherapy . CONCLUSION Dex combined with GS could effectively prevent and treat TACE syndrome", "OBJECTIVE To observe the short-term efficacy and safety of Shenqi mixture ( SQM ) combined with microwave coagulation in treating primary hepatocellular carcinoma ( HCC ) . METHODS Seventy-two patients with primary HCC of stage II-III , Karnofsky scoring > or = 50 scores and predicted survival period > or = 3 months were selected and r and omly assigned into two groups , the treated group and the control group , 36 in each . Microwave therapy was applied to both groups by double leads , 60 W , 800 sec once a week for two weeks . To the treated group , SQM was given additionally through oral intake of 20 ml , three times a day for 1 month . The changes in tumor size , main symptoms , serum level of alpha-fetoprotein ( AFP ) , immune function and adverse reaction were observed after treatment and the immune parameters of the patients were compared with 30 healthy persons in the normal control group . RESULTS ( 1 ) In the SQM treated group , after treatment 3 patients got completely remitted ( CR ) , 24 partial remitted ( PR ) , 4 unchanged ( NC ) and 5 progressively deteriorated ( PD ) , the effective rate being 75.00 % ; while in the control group , 1 got CR , 19 PR , 9 NC and 7 PD , the effective rate being 55.56 % . Comparison of the effective rate between the two groups showed significant difference ( P < 0.05 ) . ( 2 ) AFP level decreased after treatment in both groups , but the decrement in the treated group was significantly higher than that in the control group ( P < 0.01 ) . ( 3 ) After treatment , in the treated group , CD3(+ ) , CD4(+ ) , CD4(+)/CD8(+ ) and NK activity were improved , Karnofsky scores increased and liver function bettered , with these improvements significantly superior to those in the control group ( P < 0.01 ) . ( 4 ) The improvement in symptoms such as hepatic region pain , fever , weakness , poor appetite and jaundice in the treated group after treatment was also superior to that in the control group ( P < 0.01 ) . ( 5 ) The 12-month , 18-month and 24-month survival rates were higher and the recurrence rate was lower in the treated group than those in the control group , showing significant difference ( P < 0.05 ) . CONCLUSION Combined therapy with SQM and microwave coagulation could not only kill the tumor and residue tumor cells to prevent recurrence , but also enhance the cellular immunity of organism . It is one of the effective therapies for patients with middle-advanced hepatocarcinoma , who have lost the chance of surgical operation . It could improve clinical symptoms , elevate the quality of life , prolong the survival period of patients , but shows no evident adverse reaction", "OBJECTIVE To explore the therapeutic effect and mechanism of Aitongping capsule ( ATP ) in treating cancerous pain . METHODS Sixty cancer patients were r and omly divided into two groups , 30 patients in the treated group took ATP and 30 patients in the control group took diclofenac , 1 week of treatment was applied . The relevant clinical conditions of cancerous pain , the content of plasma beta-endorphin ( beta-EP ) and c-AMP , hemorheological index , improuement of life quality of patients , occurrence rate of adverse reaction were observed before and after treatment . RESULTS The total effective rate in the treated group and in the control group was 90.0 % and 83.3 % , respectively , difference between them showed no significance . However , there were significant difference between the two groups in such aspects as the degree of pain relieving , the decrease of pain episodes , the shortening persistent time of pain and the initiation time of analgesic action and prolonged analgesic duration , the decrease of tenderness and percussion pain , the increase of plasma beta-EP content and the decrease of cAMP ( P < 0.05 or P < 0.01 ) . The evidence s also showed that it was better in improving quality of life , ameliorating hemorheologic indexes and reducing incidence of adverse reaction in the treated group than in the control group ( P < 0.05 or P < 0.01 ) . CONCLUSION ATP has affirmative effect on cancerous pain , its analgesic effect may be associated with the increasing of plasma beta-EP content , decreasing of cAMP level and ameliorating of hemorheologic indexes", "Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor", "OBJECTIVE To observe the complementary function of moxibustion and Guben Yiliu III ( GBYL ) , a Chinese herbal composite preparation , in combination with chemotherapy . METHODS Eighty-one patients of middle-late stage malignant tumor were r and omly divided into three groups , 16 in the control group treated with chemotherapy alone , 35 in the TCM group treated with chemotherapy combined GBYL and 30 in the TCM combined moxibustion group . The therapeutic effect of treatment was evaluated according to the immediate effect , living quality scoring , etc . RESULTS The comprehensive living quality score and Karnofsky score dropped significantly in the control group after treatment with significant increase of pain score and decrease of tongue figure score ( P < 0.05 or P < 0.01 ) . In the TCM group , the former two criteria lowered less than those in the control group , but no significant difference in the latter two criteria was shown . For those in the TCM combined moxibustion group , all the four criteria were improved better than those in the control group ( P < 0.01 or P < 0.05 ) . CONCLUSION GBYL combined or not combined with moxibustion could improve the living quality of patients received chemotherapy", "Peer review is the ordinary method for judging the acceptability of scientific papers for publication . Yet there are few prospect i ve data defining the accuracy or reproducibility of this method . This study was aim ed at evaluating interrater consistency in review ing a single manuscript and at determining whether a referee 's likely predisposition ( inferred from his or her own published papers in the field ) influences his or her attitude toward this manuscript . A computerized search identified 33 first authors of research papers about transcutaneous electrical nerve stimulation . They were asked to review part of a fictitious scientific paper on the topic ; they were not made aware of being tested . Review ers ' ratings were recorded by multiple-choice answers in a structured question naire . The answers revealed poor interrater reliability . Furthermore , referees were clearly influenced by their own preconceptions and judged according to their own published experience in that particular medical subject . That is , referees who would be expected to agree with the paper 's findings tended to judge is less harshly than did referees who would be expected to disagree . These results suggest significant impact of review er bias on referee 's judgment and imply that the peer review system in its present form has room for improvements in fairness and consistency", "In order to pilot a study observing the feasibility of applying the Core Quality of Life Question naire ( QLQ-C30 ) version 2.0 to assess the quality of life ( QOL ) of patients with NSCLC treated with Feiji Recipe , a r and omized , parallel controlled clinical trial was conducted in the university-affiliated hospital . Seventy in patients who met the inclusion criteria were r and omized into the study , and 60 cases were available as subjects for QOL data analysis . The subjects were r and omly assigned to one of three groups : the Feiji Recipe group ( A ) ; the Feiji Recipe combined with chemotherapy group ( B ) ; and the chemotherapy group ( C ) in which the patients were treated with vinorelbine plus cisplatin ( NP ) or gemcitabine plus cisplatin ( GP ) . QOL was assessed with the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 . Sixty cases that finished the question naires were analyzed , and we found that patients who received chemotherapy had low QOL , in terms of their global health , role , emotional , social , economic status and symptom burden including fatigue , nausea and vomiting , dyspnea , loss of appetite and abnormal bowel movements . Simultaneous treatment with Feiji Recipe and chemotherapy was able to prevent the worsening of function in terms of role , social , fatigue and global health . The Core Quality of Life Question naire ( QLQ-C30 ) version 2.0 can be used to evaluate the QOL of patients with NSCLC treated by Chinese herbal medicine . Feiji Recipe might partially improve the QOL of NSCLC patients when administered alone or in combination with chemotherapy . No unexpected side effects were observed . However , further double-blinded placebo controlled studies are strongly recommended", "OBJECTIVE To study the effect of Qi replenishing and blood circulation activating drugs ( QRBCAD ) in treatment of middle-advanced pancreatic cancer with radio- and chemotherapy . METHODS Patients were divided r and omly into two groups , 28 patients treated with radiotherapy and intervention treatment as Group A and 30 patients treated with the same therapy but with additional QRBCAD medication as the Group B , and the effects in the two groups were compared . RESULTS The short-term effective rate in Group A and B was 53.6 % and 67.6 % respectively ( P < 0.05 ) . The remission rates of jaundice and abdominal pain in Group A were 57.1 % and 50.0 % respectively , while in Group B , 83.3 % and 76.7 % respectively , there was significant difference between the two groups , P < 0.05 . The gastroenteric reaction occurred in Group B was significantly lesser than that in Group A , P < 0.05 . The 1- and 2-year survival rate in Group A were 50 % and 21.4 % , and in Group B , 80.0 % and 46.6 % respectively , significant difference ( P < 0.05 ) showed in comparison of the two groups . CONCLUSION QRBCAD could alleviate the gastroenteric reaction caused by radio- and chemotherapy , raise the clinical symptomatic effective rate of treatment , and prolong the 1- and 2-year survival rate of patients" ]

[ "15895715", "15126989", "15930196", "18502162", "16647419" ]

[ "Pharmacokinetic profile of recombinant human N‐acetylgalactosamine 4‐sulphatase enzyme replacement therapy in patients with mucopolysaccharidosis VI (Maroteaux–Lamy syndrome): a phase I/II study", "Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).", "Direct Comparison of Measures of Endurance, Mobility, and Joint Function During Enzyme-Replacement Therapy of Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome): Results After 48 Weeks in a Phase 2 Open-Label Clinical Study of Recombinant Human N-Acetylgalactosamine 4-Sulfatase", "Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase.", "Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study." ]

[ "Aim : Mucopolysaccharidosis VI ( Maroteaux – Lamy syndrome ) is a lysosomal storage disease caused by a deficiency of the enzyme N‐acetylgalactosamine 4‐sulphatase ( ASB ) . Enzyme replacement therapy with recombinant human ASB ( rhASB ) has been studied in a r and omized , double‐blind , two‐dose ( 0.2 and 1.0 mg/kg/week ) phase I/II study ( n=7 ) followed by an open‐label single dose ( 1.0 mg/kg/week ) extension study . We report the pharmacokinetic profile of rhASB and the impact of antibody development . Methods : Pharmacokinetic analysis was performed at weeks 1 , 2 , 12 , 24 , 83 , 84 and 96 . Infusions were administered over 4 hours using a ramp‐up protocol . Plasma ASB and rhASB antibody concentrations and urine glycosaminoglycan ( GAG ) concentrations were determined . Results : The area under the plasma concentration – time curve ( AUC0−t ) for the high‐dose group increased from week 1 to week 2 , but remained unchanged at weeks 12 and 24 . A large difference in mean AUC0−t was observed between the low‐ and high‐dose groups . Pharmacokinetic results at weeks 83 , 84 and 96 were similar to those at week 24 . Six patients developed antibodies to rhASB . One patient developed high antibody levels in combination with a high ASB concentration , while a second patient also developed high antibody levels with undetectable ASB concentrations . Antibodies from the second patient blocked detection of ASB . By week 72 , antibody levels had decreased in all patients . The high‐dose rhASB produced a more rapid and greater percentage reduction in urinary GAG concentrations than the lower dose ( 70 % versus 55 % at 24 weeks ) . Antibody levels did not appear to influence urinary GAG concentrations", "OBJECTIVES To evaluate the safety and efficacy of weekly treatment with human recombinant N-acetylgalactosamine 4-sulfatase ( rhASB ) in humans with mucopolysaccharidosis type VI ( MPS VI ) . STUDY DESIGN An ongoing Phase I/II , r and omized , two-dose , double-blind study . Patients were r and omized to weekly infusions of either high ( 1.0 mg/kg ) or low ( 0.2 mg/kg ) doses of rhASB . Six patients ( 3 male , 3 female ; age 7 - 16 years ) completed at least 24 weeks of treatment , five of this group have completed at least 48 weeks . RESULTS No drug-related serious adverse events , significant laboratory abnormalities , or allergic reactions were observed in the study . The high-dose group experienced a more rapid and larger relative reduction in urinary glycosaminoglycan that was sustained through week 48 . Improvements in the 6-minute walk test were observed in all patients with dramatic gains in those walking < 100 meters at baseline . Shoulder range of motion improved in all patients at week 48 and joint pain improved in patients with significant pain at baseline . CONCLUSIONS rhASB treatment was well-tolerated and reduced lysosomal storage as evidence d by a dose-dependent reduction in urinary glycosaminoglycan . Clinical responses were present in all patients , but the largest gains occurred in patients with advanced disease receiving high-dose rhASB", "Objective . Mucopolysaccharidosis VI ( MPS VI ; Maroteaux-Lamy syndrome ) is a lysosomal storage disease caused by a deficiency of the enzyme N-acetylgalactosamine 4-sulfatase ( ASB ) . This enzyme deficiency leads to a progressive disorder with multiple tissue and organ involvement . The disease is rare and is heterogeneous in its clinical presentation and progression . A potential treatment for this disease exists in the form of enzyme-replacement therapy ( ERT ) with recombinant human ASB ( rhASB ) , and a phase 1/2 r and omized , double-blind , 2-dose ( 0.2 and 1 mg/kg ) study in 6 patients showed the treatment at 48 weeks to be well tolerated . Greater biochemical efficacy based on a urine glycosaminoglycan occurred in the high-dose ( 1 mg/kg ) group , and functional improvement seemed greater in patients in the high-dose group with rapidly advancing disease . On the basis of the phase 1/2 results , a phase 2 , open-label study in patients with rapidly advancing disease was initiated primarily to evaluate efficacy variables that measure endurance , mobility , and joint function in a larger group of patients . Methods . This was an open-label , multinational study of 10 MPS VI patients who received 48 weekly intravenous treatments with 1.0 mg/kg rhASB and had assessment s of biochemical and clinical responses at regular intervals . Results . After 24 weeks of treatment , each patient on average experienced a 155-m ( 98 % ) improvement in the 12-minute walk , a 64-m ( 62 % ) improvement at the 6-minute time point of the 12-minute walk , and a 48-stair ( 110 % ) gain in the 3-minute stair climb versus the baseline mean values . Additional improvements after 48 weeks of treatment were observed , including mean values of 211 m ( 138 % ) in the 12-minute walk , 75 m ( 80 % ) at the 6-minute time point of the 12-minute walk , and 61-stair ( 147 % ) gain in the 3-minute stair climb versus the baseline mean values . Joint Pain and Stiffness Question naire scores improved by at least 50 % by week 24 and were maintained at week 48 , whereas there were only small improvements in active shoulder range of motion ( < 10 ° ) and in the time taken to st and , walk , and turn starting from a seated position ( Exp and ed Timed Get-Up and Go test ) . Improvement in pulmonary function based on forced vital capacity and forced expiratory volume at 1 minute in the absence of growth was observed in 3 of 6 patients , and the observed gains occurred in the 24- to 48-week treatment interval . A mean decrease of 76 % in urinary excretion of glycosaminoglycans indicated that a satisfactory biochemical response was achieved and the ERT was well tolerated . Conclusions . The results suggest that a 12-minute walk extends the dynamic range of the conventional 6-minute walk and , along with the 3-minute stair climb , provide a robust approach to documenting the improvement in endurance in MPS VI patients who undergo ERT with rhASB", "UNLABELLED The objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B ( rhASB ) treatment of mucopolysaccharidosis type VI ( MPS VI : Maroteaux-Lamy syndrome ) , a lysosomal storage disease . Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97 - 260 Weeks . All patients received weekly infusions of rhASB at 1 mg/kg . Efficacy was evaluated by ( 1 ) distance walked in a 12-minute walk test ( 12MWT ) or 6-minute walk test ( 6MWT ) , ( 2 ) stairs climbed in the 3-minute stair climb ( 3MSC ) , and ( 3 ) reduction in urinary glycosaminoglycans ( GAG ) . Safety was evaluated by compliance , adverse event ( AE ) reporting and adherence to treatment . RESULTS A significant reduction in urinary GAG ( 71 - 79 % ) was sustained . For the 12MWT , subjects in Phase 2 showed improvement of 255+/-191 m ( mean+/-SD ) at Week 144 ; those in Phase 3 Extension demonstrated improvement from study baseline of 183+/-26 m ( mean+/- SE ) in the rhASB/rhASB group at Week 96 and from treatment baseline ( Week 24 ) of 117+/-25 m in the placebo/rhASB group . The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements . Compliance was 98 % overall . Only 560 of 4121 reported AEs ( 14 % ) were related to treatment with only 10 of 560 ( 2 % ) described as severe . CONCLUSION rhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile", "OBJECTIVE The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B ( rhASB ) treatment of mucopolysaccharidosis type VI ( MPS VI ; Maroteaux-Lamy syndrome ) , a rare , fatal lysosomal storage disease with no effective treatment . STUDY DESIGN Thirty-nine patients with MPS VI were evaluated in a r and omized , double-blind , placebo-controlled , multicenter , multinational study for 24 weeks . The primary efficacy variable was the distance walked in a 12-minute walk test ( 12MWT ) , whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb ( 3MSC ) and the level of urinary glycosaminoglycan ( GAG ) excretion . All patients received drug in an open-label extension period for an additional 24 weeks . RESULTS After 24 weeks , patients receiving rhASB walked on average 92 meters ( m ) more in the 12MWT ( p=.025 ) and 5.7 stairs per minute more 3MSC ( p=.053 ) than patients receiving placebo . Continued improvement was observed during the extension study . Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo ( p<.001 ) . Infusions were generally safe and well tolerated . Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein . CONCLUSION rhASB significantly improves endurance , reduces GAG , and has an acceptable safety profile" ]

[ "21631856", "19228240" ]

[ "Heart failure self-management education: a systematic review of the evidence.", "Doctors' assistants' views of case management to improve chronic heart failure care in general practice: a qualitative study." ]

[ "OBJECTIVE The objective of this systematic review is to identify educational content and techniques that lead to successful patient self-management and improved outcomes in congestive heart failure education programs . METHODS MEDLINE , CINAHL and the Cochrane Central Register of Controlled Trials , as well as reference lists of included studies and relevant review s , were search ed . Eligible studies were r and omised controlled trials evaluating congestive heart failure self-management education programs with outcome measures . Two of the investigators independently abstract ed descriptive information , education content topics and outcomes data . RESULTS A total of 7413 patients participated in the 35 eligible congestive heart failure self-management education studies . The congestive heart failure self-management programs incorporated 20 education topics in four categories : ( i ) knowledge and self-management ( diagnosis and prognosis , pathophysiology of how congestive heart failure affects the body , aims of treatment , management and symptoms , medication review and discussion of side-effects , knowing when to access/call the general practitioner , communication with the physician , follow up for assessment or reinforcement ) ; ( ii ) social interaction and support ( social interaction and support , stress , depression ) ; ( iii ) fluids management ( sodium restriction , fluid balance , daily measurement of weight , ankle circumference , self-monitoring and compliance relative to fluids ) ; and ( iv ) diet and activity ( dietary assessment and instructions , physical activity and exercise , alcohol intake , smoking cessation ) . A total of 113 unique outcomes in nine categories ( satisfaction , learning , behaviour , medications , clinical status , social functioning , mortality , medical re source utilisation and cost ) were measured in the studies . Sixty ( 53 % ) of the outcomes showed significant improvement in at least one study . CONCLUSION Educational interventions should be based on scientifically sound research evidence . The education topic list developed in this review can be used by patients and clinicians to prioritise and personalise education", "AIM This paper is a report of a study to explore the views , concerns and experiences of doctors ' assistants of case management for patients with chronic heart failure , while experiencing the new role of being a case manager within the Heidelberg Integrated Case Management trial . BACKGROUND Case management is being investigated as part of a r and omised controlled trial aim ing to improve care for patients with chronic systolic heart failure . In a complex , multifaceted intervention , trained doctors ' assistants ( equivalent to a nursing role ) adopted new tasks using st and ardised case management involving telephone monitoring , home visits and diagnostic screening . METHOD In April 2007 , 3 months after implementation of the intervention programme , 27 doctors ' assistants participated in four focus group interviews discussing their views on , and experiences of , case management . Thematic analysis of the data was undertaken . FINDINGS Participants believed that the most positive factors in case management were about interaction with patients , including opportunities for identifying disease and psychosocial problems . However , barriers included lack of time allocated to perform case management in addition to their normal role and poor cooperation within the practice team . According to the doctors ' assistants , the routine implementation of case management was acceptable , feasible and effective in improving the management of patients with chronic systolic heart failure . CONCLUSION Case management enhanced the role of doctors ' assistants , leading to increased awareness of the perspective of patients with chronic disease . In the wider international primary care practice nursing context , the orchestrated delegation of tasks using specific case management may be a promising strategy for improving the quality of care of chronically ill patients and enabling patient self-management" ]

[ "27862066", "19572180", "19662486", "28815643", "20108089", "24373006", "25367640", "16393594", "26580869", "12439013", "12534515", "21272120", "25559589" ]

[ "Fractional CO2 laser treatment of caesarean section scars—A randomized controlled split‐scar trial with long term follow‐up assessment", "Comparison of the effectiveness of the pulsed dye laser 585 nm versus 595 nm in the treatment of new surgical scars", "Comparison of the effects of short- and long-pulse durations when using a 585-nm pulsed dye laser in the treatment of new surgical scars", "Early intervention with non‐ablative fractional laser to improve cutaneous scarring—A randomized controlled trial on the impact of intervention time and fluence levels", "Scar Prevention Using Laser-Assisted Skin Healing (LASH) in Plastic Surgery", "Treatment of Surgical Scars Using a 595‐nm Pulsed Dye Laser Using Purpuric and Nonpurpuric Parameters: A Comparative Study", "Comparison of non-ablative and ablative fractional laser treatments in a postoperative scar study.", "Clinical Effect of a Single Pulsed Dye Laser Treatment of Fresh Surgical Scars: Randomized Controlled Trial", "Pulsed Dye Laser for Early Treatment of Scars After Dermatological Surgery.", "Prophylactic Treatment of Deep Dermal Burn Scar to Prevent Hypertrophic Scarring Using the Pulsed Dye Laser: A Preliminary Study", "585‐nm Pulsed Dye Laser in the Treatment of Surgical Scars Starting on the Suture Removal Day", "Early Postoperative Treatment of Thyroidectomy Scars Using a Fractional Carbon Dioxide Laser", "Early postoperative single treatment ablative fractional lasing of Mohs micrographic surgery facial scars: a split-scar, evaluator-blinded study." ]

[ "BACKGROUND AND OBJECTIVES Caesarean section ( c-section ) scars can be pose functional and cosmetic challenges and ablative fractional laser ( AFXL ) treatment may offer benefit to patients . We evaluated textural and color changes over time in AFXL-treated versus untreated control scars . MATERIAL S AND METHODS A r and omized , controlled , intra-individual split-scar trial with three sessions of AFXL-treatments for mature c-section scars . Setting s of AFXL were adjusted to each individual scar . End-points were blinded on-site clinical evaluations at 1 , 3 , and 6 months follow-up ( Patient and Observer Scar Assessment Scale [ POSAS ] and Vancouver Scar Scale [ VSS ] ) , blinded photo-evaluations , reflectance measurements , tissue histology , and patients satisfaction . RESULTS Eleven of 12 patients completed the study . At 1 month follow-up , AFXL-treated scars were significantly improved in pliability ( POSAS P = 0.01 VSS P = 0.02 ) and smoother in surface relief ( POSAS P = 0.03 ) compared to control scars . At 1 - 3 months , overall scar appearance was dominated by transient erythema and hyperpigmentation , confirmed by reflectance measurements ( erythema% and pigmentation% peaked at 1 and 3 month follow-up , respectively ) . At 6 months follow-up , AFXL-treated scars improved on POSAS-total score though not significantly ( P = 0.06 ) . Correspondingly , blinded photo-evaluation found AFXL-treated scars significantly improved compared to controls ( VAS P = 0.02 ) . Histology indicated new dermal collagen and elastic fibers on AFXL-treated scars . At 6 months follow-up , a majority of patients ( 64 % ) favored subsequent AFXL-treatment of their untreated control scar tissue . CONCLUSIONS Scar remodeling is initiated 1 month after AFXL treatment , but overall scar improvement is concealed until laser-induced color changes resolve . At 6 months follow-up , the benefit of AFXL treatment on c-section scars emerges . Lasers Surg . Med . 49:189 - 197 , 2017 . © 2016 Wiley Periodicals ,", "The aim of this study was to compare the effects of the pulsed-dye laser ( PDL ) at a wavelength of 585 nm with those at 595 nm in the treatment of post-surgical scars , starting on the day of suture removal . The study was a prospect i ve , non-r and omized , double-blind , controlled , clinical trial , set in an outpatient clinic . Fifteen out patients with 21 post-operative scars at least 3 cm long were recruited , and 14 patients with 19 scars completed the study . Scars were divided into three equal portions . Each outer portion was r and omly allocated to PDL at 585 nm or at 595 nm ( 3.5 J/cm2 , 450 μs , 10 mm spot size ) , and the center was an untreated control ; treatment was composed of three laser sessions at 4-week intervals . A blinded examiner evaluated the three scar sections using the Vancouver scar scale for pigmentation , vascularity , pliability , and height . Cosmetic appearance was evaluated with a visual analog scale . Punch biopsies of three r and omly selected scars were evaluated . Pigmentation : more scars after laser treatments were of normal color than in the control , but the difference was not statistically significant . Vascularity : after treatment , more scars had normal vascularity in all three groups than at baseline ( P < 0.05 ) ; the largest increase was with a wavelength of 585 nm ( 10.5–94.7 % ) , then 595 nm ( 15.8–78.9 % ) , then control ( 5.2–36.6 % ) . Pliability : there was more normal pliability in all three groups than at baseline ( P < 0.05 ) , with greater improvements in the laser-treated groups . Height : significantly more flat scars after 585 nm PDL ( 63.2 % ) than at baseline ( 21.1 % ) ( P < 0.05 ) . We observed a slight but non-significant decrease in the scar heights with 595 nm PDL in comparison with the control . Histology : after laser irradiation , the treated sections were more similar to a non-scarring process than the control . Cosmetic outcome : visual analog scales increased in all groups ( P < 0.05 ) , but the greatest increases were observed in the 585 nm and 595 nm laser-treated groups ( 50 % and 60 % , respectively ) compared with controls ( 30 % ) . There were significantly higher scores with the lasers than for the control ( P < 0.001 ) at each visit after baseline . Both the 585 nm and 595 nm PDL treatments were effective in improving the appearance and normalizing the vascularity and pliability of post-operative scars . Both wavelengths improved the scars ’ visual appearance more than controls . We found that 585 nm appears to be the preferred wavelength , as it substantially normalized the height in addition to the vascularity and pliability in a significant number of scars", "More than 70 million surgical procedures are performed annually in the USA with the majority involving a skin lesion and almost all individuals in their lifetime will have one or more surgical procedures result ing in scars . Patients and physicians alike are thereby motivated to improve the cosmetic outcome of scars . Prior studies have shown that the pulsed dye laser ( PDL ) is effective in improving the quality and appearance of the scar when using the 585-nm PDL immediately after the removal of sutures . Most published studies used a pulse duration of 450 µs , which along with the other study parameters , has led to an overall improvement of the scars . However , a pulse duration of 1.5 ms is also available when using the pulsed dye laser and it should theoretically cause fewer side-effects . To our knowledge , there are no other studies comparing the effectiveness of different pulse duration s in the treatment of surgical scars starting on the day of suture removal . The purpose of this study is to compare the effect of different pulse duration s ( 450 µs vs. 1.5 ms ) in the treatments of postsurgical linear scars immediately after suture removal when using the 585-nm pulsed dye laser ( PDL ) . Twenty non-hospitalized male and female patients ( older than 18 years of age ) with skin types I – IV and with postoperative linear scars measuring at least 2.1 cm were enrolled in this prospect i ve study . Scars were r and omly divided into three equal sections . The different fields were r and omly chosen to receive treatment ( two out of three fields ) or remain as control ( one field ) . The two fields chosen to be treated received treatment with the 585-nm PDL using a 7-mm spot size at 4.0 J. One of the treated sections was r and omly selected to receive a pulse duration of 450 µs , and the other section to receive a 1.5-ms pulse . The remaining scar section was design ated as control ( no treatment ) . The three sections were mapped and recorded . The patient received treatment immediately after the sutures were removed from the wound and then monthly for 3 months . Evaluations were performed before each treatment and 1 month after the last treatment . The short-pulse and long-pulse 585-nm PDL-treated sections demonstrated a statistically significant overall average improvement of the VSS of 92 and 89 % , respectively , compared to 67 % for the control site ( Fig. 1 ) . Further , for individual parameters of the Vancouver scar scale ( VSS ) , there were significant ( p < 0.05 ) differences between control and treatment groups for all parameters , but there were no differences between the short- and long-pulse treatment groups for any parameter . Both short-pulse and long-pulse PDL are safe and effective in improving the quality and cosmetic appearance of surgical scars in skin type ’s I – IV starting on the day of suture removal with no significant difference between the two pulse duration", "BACKGROUND AND OBJECTIVES Laser treatment in the early phases of wound healing may reduce scar formation . However , little is known on when in the early wound healing phases laser exposure most optimally should be provided and at which fluence levels . This study investigates the clinical effect of non-ablative-fractional-laser ( NAFL ) performed at three early time points at a range of fluence levels versus untreated control scars . MATERIAL S AND METHODS A r and omized , controlled , intra-individual trial with erbium-glass 1,540 nm NAFL versus no laser treatment on sixteen subjects receiving 10 st and ardized full-thickness punch-biopsy wounds . A single NAFL-exposure was applied to test-wounds 1 day before , immediately after , or 2 weeks after wounding . Three fluence levels provided deep and superficial energy depositions ( range 30 - 70 mJ/microbeam ) . Primary outcome comprised the total-score of the observer part of Patient-Observer-Scar- Assessment -Scale ( POSAS ) , performed by blinded on-site assessment at 3 months follow-up . Secondary outcomes were clinical evaluation on visual-analogue-scale ( VAS ) , reflectance measurements , and histology . RESULTS NAFL-treatment applied 1 day before , immediately after or 2 weeks after wounding had the potential to offer subtle but detectable improvement in clinical scar appearance compared to untreated controls . Thus , NAFL-exposure 1 day before wounding ( POSAS-total : median of 15 vs. control-median of 16 , P = 0.03 , VAS : median 4.1 vs. control-median 5.5 , P = 0.03 , medium-fluence ) , as well as immediately- , and 2 weeks after wounding ( POSAS-total : P ≤ 0.05 , low-fluence ) induced improvement compared to untreated controls . No significant differences in dyschromia were detected between NAFL-treated and control scars . Histology showed subtle changes towards more mature interwoven bundles of collagen in NAFL-treated scars as compared to controls . CONCLUSIONS This study indicates that a single NAFL-treatment at low to medium fluence performed 1 day prior , or in the early phases of wound healing , may have the potential to optimize scar formation in full thickness wounds . Lasers Surg . Med . 50:28 - 36 , 2018 . © 2017 Wiley Periodicals ,", "Background The use of lasers has been proposed for scar revision . A recent pilot clinical study demonstrated that lasers could also be used immediately after surgery to reduce the appearance of scars . The LASH ( Laser-Assisted Skin Healing ) technique induces a temperature elevation in the skin which modifies the wound-healing process . We report a prospect i ve comparative clinical trial aim ed at evaluating an 810-nm diode-laser system to accelerate and improve the healing process in surgical scars immediately after skin closure . Methods Twenty-nine women and 1 man ( mean age = 41.4 years ; Fitzpatrick skin types I-IV ) were included to evaluate the safety and performance of the laser system . The laser dose ( or fluence in J/cm² ) was selected as a function of phototype and skin thickness . Each surgical incision ( e.g. , abdominoplasty ) was divided into two parts . An 8-cm segment was treated with the laser immediately after skin closure . A separate 8-cm segment was left untreated as a control . Clinical evaluations ( overall appearance ratings , comparative scar scale ) of all scars were conducted at 10 days , 3 months , and 12 months by both surgeon and patients . Profilometry analysis from silicone replicas of the skin was done at 12 months . Wilcoxon signed-rank test analyses were performed . Results Twenty-two patients were treated using a high dose ( 80–130 J/cm² ) and 8 patients with a low dose ( < 80 J/cm² ) . At 12 months in the high-dose group , both surgeon and patients reported an improvement rate of the laser-treated segment over the control area of 72.73 and 59.10 % , respectively . For these patients , profilometry results showed a decrease in scar height of 38.1 % ( p = 0.027 ) at 12 months for the laser-treated segment versus control . Three patients treated with higher doses ( > 115 J/cm² ) experienced superficial burns on the laser-treated segment , which resolved in about 5–7 days . For the eight patients treated at low dosage ( < 80 J/cm² ) , there was no significant difference in the treated segment versus the control segment . No side effects were observed . Conclusion This prospect i ve comparative trial demonstrates that an 810-nm diode laser treatment , performed immediately after surgery , can improve the appearance of a surgical scar . The dose plays a great role in scar improvement and must be well controlled . There is interest in LASH for hypertrophic scar revision . LASH can be used to prevent and reduce scars in plastic surgery", "BACKGROUND Many studies have examined laser treatment of scars , but cosmetic results have been variable . Although no studies have examined the effect of purpura on scar improvement using the pulsed dye laser ( PDL ) , many clinicians believe inducing purpura results in better and quicker improvement . OBJECTIVE To determine whether PDL treatment of fresh surgical scars with purpura‐inducing setting s improves clinical appearance more than non‐purpura‐inducing setting s or no treatment . METHODS Twenty‐six subjects with surgical scars enrolled in this prospect i ve study . Scars were divided into three equal segments ; treatment was r and omized : 595‐nm PDL with purpuric ( 1.5 ms ) or nonpurpuric ( 10 ms ) setting s or no treatment . Fluences were adjusted to Fitzpatrick skin type . Scars were treated three times , 1 month apart , beginning at suture removal . Outcome measures included Vancouver Scar Scale ( VSS ) and blind clinical ratings . RESULTS The nonpurpuric condition showed significant improvement on the VSS total score , vascularity , and pliability ratings . The purpuric condition demonstrated a trend for improvement on the VSS total . According to blind observer ratings , all conditions improved , without differences between groups . CONCLUSION Nonpurpuric setting s on the PDL result ed in significant improvements in the appearance of fresh surgical scars for vascularity , pliability , and VSS total scores , although all scar segments improved over time", "BACKGROUND AND OBJECTIVE Postoperative scarring after thyroidectomy is a problem for both patients and clinicians . Recently , both non-ablative and ablative fractional laser ( NFL and AFL ) systems have attracted attention as potential therapies for the revision of thyroidectomy scars . The present split-scar study was design ed to directly compare the efficacy of these two methods for the treatment of post-thyroidectomy scars . STUDY DESIGN / MATERIAL S AND METHODS Twenty females ( mean age 42.1 years , range 22 - 55 ) with scarring 2 - 3 months post-thyroidectomy were enrolled in the study . One half of the scar ( chosen at r and om ) was treated with NFL and the other half was treated with AFL . In each case , two treatments were given at 2-month intervals . Clinical photographs were taken at baseline , before each treatment , and at the final 3-month evaluation . Independent clinician grading of improvement and patient satisfaction were measured on a quartile scale . Color ( erythema and melanin indices ) and scar hardness were measured at baseline and at three months post-treatment with a dermaspectrometer and durometer , respectively . RESULTS The mean clinical improvement grade s for AFL and NFL were highly similar , 2.45 ± 0.99 and 2.35 ± 0.85 , respectively , without statistical significance ( P = 0.752 ) . However , NFL treatment result ed in statistically significant changes in erythema and pigmentation ( P = 0.035 and P = 0.003 , respectively ) , and skin hardness was significantly reduced after AFL treatment ( P = 0.026 ) . CONCLUSIONS Clinical improvement was not significantly different between the two systems ; however , AFL was better at reducing scar hardness whereas NFL was superior for lightening color . These data suggest that a study assessing the feasibility of a combined approach for the revision of post-thyroidectomy scarring might be warranted", "BACKGROUND Pulsed dye laser has been used to decrease erythema and telangiectasia associated with scars , including surgical scars . There is limited evidence indicating improved surgical scar appearance if pulsed dye laser treatments are commenced immediately at the time of suture removal . OBJECTIVE To determine whether a single one-pass pulsed dye laser treatment at the time of suture removal can improve the appearance of surgical scars . METHODS R and omized controlled trial enrolling 20 patients ( complete data for 17 patients ) at two geographic sites , with blinded ratings of pre- and post-treatment photographs obtained at various time points . Included patients underwent elliptical excision for atypical nevi of the trunk and /or extremities , with at least one result ing scar of at least 5 cm in length or two scars of at least 2.5 cm in length . For each patient , each scar or half-scar ( if a larger scar was used ) was r and omized to treatment or control groups . Treatment scars received a single one-pass treatment with a 595 nm pulsed dye laser ( Vbeam , C and ela Corporation , Wayl and , MA , USA ) at the time of suture removal ( ie , 2 weeks after excision ) at the following parameters : 7 J/cm2 fluence , 7 mm spot size , 1.5-millisecond pulse duration , and 30-millisecond spray , 20-millisecond delay of dynamic cooling . The treatment area included 1 cm on either side of the scar , and the round laser spots were overlapped 10 % . Control scars were not treated with laser . RESULTS Immediate purpura was induced from the laser treatment . Six weeks after laser treatment , no significant difference was found in the clinical appearance of surgical scars treated with a single pulsed dye laser treatment on suture removal day versus those surgical scars not treated with laser . Parameters on which no significant difference was found included visibility of incision , erythema , hyperpigmentation , hypopigmentation , in duration , and atrophy . Both sets of scars improved over time . CONCLUSIONS A single pulsed dye laser treatment at the time of suture removal does not appear to have a beneficial effect on clinical scar appearance . The point of minimal benefit for such laser treatments may lie somewhere between one and three treatments", "BACKGROUND Wound healing is a complex process ; during the process angiogenesis takes place , that presents clinical ly as erythema , telangiectasia and edema . Pulsed dye laser ( PDL ) has a wavelength of 585 - 595 nm , which targets the chromophore hemoglobin . OBJECTIVE Determine the level of improvement of post-dermatological surgery scars . METHODS Thirty patients attending for excision lesion were recruited . They were r and omized to 1 of 2 groups . Group 1 scar was r and omly divided into 2 parts , one half received PDL 595 nm on 3 occasions ; the first after suture removal , 15 and 45 days . Group 2 in one half laser application was simulated while the other was left untreated . The Vancouver scar scale ( VSS ) was used by an external evaluator to assess the scars . Two skin biopsies were also obtained one before and one after laser treatment . RESULTS The VSS at 45 days decreased in a significant way in the treatment group from 4 to 1 ( P = .005 ) . In the control group decreased from 2 to 1.3 ( P = .056 ) . No significant difference was found between the presence of inflammatory infiltrate of patients in the placebo group . CONCLUSION This study confirmed the usefulness of pulsed dye laser for improving the appearance of scars", "The pulsed dye laser , by selectively targeting blood vessels , has been used to treat established hypertrophic scars with good effect . This prospect i ve clinical study aims to assess the feasibility of treating deep dermal burn wounds prophylactically before the formation of hypertrophic scars . Patients with burn wounds that took longer than 2 weeks to heal were primarily recruited . Each patient 's burn area was divided into a treated area and a negative control . The area was laser treated with the pulsed dye laser ( Chromos 585 ; SLS , Wales ) twice at 6 weekly intervals . The appearance of the wound at both sites was inspected visually and scored at 6 weeks , and at 3 , 6 , and 9 months . Five patients with six burn sites ( forearm , arm , and back ) were treated . Treated areas achieved better scarring at 6 weeks ( p = 0.04 , paired t-test ) and at 3 months ( p = 0.003 , paired t-test ) . The difference , however , became insignificant at 6 and 9 months . No notable side effects were seen in all patients . Prophylactic treatment of burn wounds with the pulsed dye laser is effective in hastening the resolution of scarring . In the authors ’ opinion , this treatment may revolutionize the traditional method of hypertrophic burn scar prevention , and should be considered early , especially for patients who are prone to hypertrophic scarring , and in areas where hypertrophic scarring are common", "Background The optimal time frame to improve the quality and cosmetic appearance of scars by laser therapy has not been clearly eluci date d by prior controlled clinical trials . Objective To determine the efficacy of the 585-nm pulsed dye laser ( PDL ) in the treatment of surgical scars starting on the day of suture removal . Methods Eleven patients ( skin types I – IV ) with 12 postoperative linear scars that were greater than 2 cm were treated three times on monthly intervals with the 585-nm PDL ( 450 μs , 10-mm spot size , 3.5 J/cm2 with 10 % overlap ) on one scar half , whereas the other half received no treatment . Scars were later evaluated by a blinded examiner using the Vancouver Scar Scale ( VSS ) for pigmentation , vascularity , pliability , and height . Scars were then blindly examined for cosmetic appearance using a visual analog scale . Results One month after the last treatment , final scar analysis by the blinded examiner revealed a significant difference between treated and untreated sites , with the treated halves scoring better in all scar parameters in the VSS and in cosmetic appearance . The treated halves demonstrated an overall average improvement in the VSS between the first treatment score and the final score of 54 % versus 10 % in the controls ( P = 0.0002 ) . The cosmetic appearance score ( 0 = worst ; 10 = best ) at final assessment was significantly better for the treated scars , scoring 7.3 versus the averaged control score of 5.2 ( P = 0.016 ) . Conclusion The 585-nm PDL is effective and safe in improving the quality and cosmetic appearance of surgical scars in skin types I – IV starting on the day of suture removal", "BACKGROUND Ablative carbon dioxide fractional laser systems ( CO2 FS ) have been effectively used to improve the appearance of scarring after surgical procedures , but an optimal treatment time has not been established . OBJECTIVE To evaluate the efficacy and safety of CO2 FS in early postoperative thyroidectomy scars . METHODS Twenty‐three Korean women with thyroidectomy scars were enrolled in this study . All patients underwent a single session of two passes of a CO2 FS with a pulse energy setting of 50 mJ and a density of 100 spots/cm2 2 to 3 weeks after surgery . RESULTS Mean Vancouver Scar Scale ( VSS ) scores were statistically significantly lower after laser treatment . Three months after CO2 FS treatment of thyroidectomy scarring , 12 of 23 participants showed clinical improvement of more than 51 % from 2 to 3 weeks after surgery . The mean grade of clinical improvement based on independent clinical assessment was 2.6 ± 0.9 . CONCLUSION Early postoperative CO2 FS treatment of thyroidectomy scars is effective and safe . The authors have indicated no significant interest with commercial supporters", "BACKGROUND / OBJECTIVES Despite precise surgical technique , some postoperative facial scars will depress and widen over time , likely due to weakened or inadequately replaced collagen fibers in the underlying dermis . The purpose of this study is to evaluate whether a 10,600 nm ablative carbon dioxide ( CO2 ) fractional laser used early in the post-surgical setting results in improved postoperative facial scars after a single treatment session . STUDY DESIGN A prospect i ve r and omized , comparative split-scar study was conducted on 20 subjects between the ages of 20 - 90 . Subjects underwent Mohs surgery for nonmelanoma skin cancer of the face . Subsequent to tumor removal , subjects with a linear scar of 4 cm or greater were enrolled . On the day of suture removal , all subjects had one-half of their scar r and omly selected and treated with a 10,600 nm CO2 fractional laser ( energy = 10 mJ ; density = 10 % ; spot size = 7 mm ; pulse = 1 ) . The untreated scar half served as a control . Scars were re-evaluated 12 weeks later . An independent blinded observer grade d the scar halves with the Vancouver scar scale ( VSS ) immediately prior to treatment and 12 weeks after treatment . Subjects completed a visual analog scale ( VAS ) at the same time points . RESULTS Three months after laser treatment , a significant decrease in VSS and 3 of the 4 of its individual parameters were detected in both control and treated halves of the scar . When comparing the laser group versus the control group , a statistically significant difference was not noted in VSS ( P = 0.31 ) but a statistically significant difference in patient VAS was detected ( P = 0.002 ) . No side effects of the laser treatment were noted . CONCLUSION Facial wounds sutured in a layered manner heal well . Patients prefer early fractional CO2 lasing of surgical scars , though use of the VSS failed to detect an objective difference between laser and control halves of scars . Conservative laser setting s , a single session treatment , and VSS insensitivity for surgical scars may influence these findings" ]

[ "21316442", "24976566" ]

[ "Effects of resistance and aerobic exercise on physical function, bone mineral density, OPG and RANKL in older women", "Effects of a three-month therapeutic lifestyle modification program to improve bone health in postmenopausal Korean women in a rural community: a randomized controlled trial." ]

[ "This study compared the effects of a resistance training protocol and a moderate-impact aerobic training protocol on bone mineral density ( BMD ) , physical ability , serum osteoprotegerin ( OPG ) , and receptor activator of nuclear factor kappa B lig and ( RANKL ) levels . Seventy-one older women were r and omly assigned to resistance exercise ( RE ) , aerobic exercise ( AE ) or a control group ( CON ) . Both interventions were conducted 3 times per week for 8 months . Outcome measures included proximal femur BMD , muscle strength , balance , body composition , serum OPG , and RANKL levels . Potential confounding variables included dietary intake , accelerometer-based physical activity ( PA ) , and molecularly defined lactase nonpersistence . After 8 months , only RE group exhibited increases in BMD at the trochanter ( 2.9 % ) and total hip ( 1.5 % ) , and improved body composition . Both RE and AE groups improved balance . No significant changes were observed in OPG and RANKL levels , and OPG/RANKL ratio . Lactase nonpersistence was not associated with BMD changes . No group differences were observed in baseline values or change in dietary intakes and daily PA . Data suggest that 8 months of RE may be more effective than AE for inducing favourable changes in BMD and muscle strength , whilst both interventions demonstrate to protect against the functional balance control that is strongly related to fall risk", "In this r and omized controlled trial , we examined the effects of a 3-month therapeutic lifestyle modification ( TLM ) intervention on knowledge , self-efficacy , and health behaviors related to bone health in postmenopausal women in rural Korea . Forty-one women ages 45 or older were r and omly assigned to either the intervention ( n = 21 ) or control ( n = 20 ) group . The intervention group completed a 12-week , 24-session TLM program of individualized health monitoring , group health education , exercise , and calcium-vitamin D supplementation . Compared with the control group , the intervention group showed significant increases in knowledge and self-efficacy and improvement in diet and exercise after 12 weeks , providing evidence that a comprehensive TLM program can be effective in improving health behaviors to maintain bone health in women at high risk of osteoporosis" ]

[ "16210721", "15113712", "17613849", "12098721", "10422992", "12915499", "11735794", "16935586", "17320962", "17210852", "16556618", "11815895", "16877067", "17337063", "8439434", "14711717", "8363468" ]

[ "Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women.", "Dietary fat consumption and primary open-angle glaucoma.", "Prospective Study of Alcohol Consumption and the Risk of Primary Open-Angle Glaucoma", "Vitamin E supplementation and macular degeneration: randomised controlled trial", "Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus.", "Antioxidant intake and primary open-angle glaucoma: a prospective study.", "The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER.", "Risk factors for five-year incident age-related macular degeneration: the Reykjavik Eye Study.", "Cost-effectiveness of vitamin therapy for age-related macular degeneration.", "A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors.", "The Antioxidants in Prevention of Cataracts Study: effects of antioxidant supplements on cataract progression in South India", "The Roche European American Cataract Trial (REACT): A randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract", "Centrum use and progression of age-related cataract in the Age-Related Eye Disease Study: a propensity score approach. AREDS report No. 21.", "Cigarette smoking and age-related macular degeneration in the EUREYE Study.", "Cigarette smoking and lens opacities: the Beaver Dam Eye Study.", "Vitamin E supplementation and cataract: randomized controlled trial.", "The Linxian cataract studies. Two nutrition intervention trials." ]

[ "BACKGROUND Dry eye syndrome ( DES ) is a prevalent condition , but information on risk or protective factors is lacking . OBJECTIVE We aim ed to determine the association between the dietary intake and ratio of n-3 and n-6 fatty acids ( FAs ) and DES occurrence . DESIGN Of the 39876 female health professionals in the Women 's Health Study ( WHS ) , 32470 women aged 45 - 84 y who provided information on diet and DES were cross-sectionally studied . We assessed FA intakes by using a vali date d food-frequency question naire and assessed DES by using self-reports of clinical ly diagnosed cases . Of the sample , 1546 ( 4.7 % ) subjects reported DES . We used logistic regression models to estimate the odds ratios ( ORs ) and 95 % CIs to describe the relation of FA intake with DES . RESULTS After adjustment for demographic factors , hormone therapy , and total fat intake , the OR for the highest versus the lowest quintile of n-3 FAs was 0.83 ( 95 % CI : 0.70 , 0.98 ; P for trend = 0.05 ) . A higher ratio of n-6 to n-3 FA consumption was associated with a significantly increased risk of DES ( OR : 2.51 ; 95 % CI : 1.13 , 5.58 ) for > 15:1 versus < 4:1 ( P for trend = 0.01 ) . In addition , tuna consumption [ 1 serving was 113 g ( 4 oz ) ] was inversely associated with DES ( OR : 0.81 ; 95 % CI : 0.66 , 0.99 for 2 - 4 servings/wk ; OR : 0.32 ; 95 % CI : 0.13 , 0.79 for 5 - 6 servings/wk versus < or = 1 serving/wk ; P for trend = 0.005 ) . CONCLUSIONS These results suggest that a higher dietary intake of n-3 FAs is associated with a decreased incidence of DES in women . These findings are consistent with anecdotal clinical observations and postulated biological mechanisms", "BACKGROUND Prostagl and in F(2alpha ) analogues are effective intraocular-pressure-lowering drugs . Dietary fatty acids affect endogenous prostagl and in F(2alpha ) concentrations and may thus influence intraocular pressure . OBJECTIVE We prospect ively examined dietary fat consumption in relation to primary open-angle glaucoma ( POAG ) . DESIGN Women ( n = 76 199 in the Nurses ' Health Study ) and men ( n = 40 306 in the Health Professionals Follow-Up Study ) free of POAG in 1980 and 1986 , respectively , were followed until 1996 if they were > or = 40 y old and reported receiving eye exams during follow-up . Potential confounders were assessed on biennial question naires , and energy-adjusted cumulative averaged fat intakes were measured by using vali date d food-frequency question naires . We analyzed 474 self-reported POAG cases confirmed by medical chart review . Cohort-specific multivariate rate ratios ( RRs ) were obtained by using proportional hazards models and were then pooled . RESULTS Major fats and fat subtypes were not independently associated with POAG risk . Pooled multivariate RRs ( 95 % CI ) for POAG comparing the highest with the lowest quintile of fat intake were as follows : 0.90 ( 0.67 , 1.21 ) for total fat , 1.03 ( 0.77 , 1.38 ) for saturated fat , 0.76 ( 0.56 , 1.03 ) for monounsaturated fat , and 0.87 ( 0.66 , 1.16 ) for polyunsaturated fat , none of which were statistically significant . We found a suggestive positive association between a higher ratio of n-3 to n-6 polyunsaturated fat and risk of POAG [ RR = 1.49 ( 1.11 , 2.01 ) ; P for trend = 0.10 ] , which was stronger for high-tension POAG [ RR = 1.68 ( 1.18 , 2.39 ) ; P for trend = 0.009 ] . CONCLUSION A high ratio of n-3 to n-6 polyunsaturated fat appears to increase the risk of POAG , particularly high-tension POAG . Further studies are needed", "Purpose : Alcohol intake reduces intraocular pressure , a risk factor for primary open-angle glaucoma ( POAG ) . We investigated whether alcohol consumption is associated with a reduced risk of POAG . Methods : We followed female nurses from 1980 and male health professionals from 1986 to 2002 . Eligible participants were 40 + years old , did not have POAG , and reported receiving eye examinations during follow-up . Information on alcohol consumption , potential confounders and POAG diagnoses were up date d by using biennial question naires . We identified 856 self-reported POAG cases that were confirmed with medical record review . Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariable rate ratios ( RR ) of POAG . Results : Alcohol consumption < 30 g/day did not influence POAG risk : compared with non-drinkers , the pooled RRs were 0.99 ( 95 % Confidence Interval [ CI ] : 0.83–1.19 ) for drinking < 10 g/day , 0.96 ( 95 % CI : 0.76–1.22 ) for 10–19 g/day , and 0.95 ( 95 % CI : 0.68–1.33 ) for 20–29 g/day . Although there were suggestive inverse associations with drinking > 30 g/day ( RR = 0.71 ) , this was not significant ( 95 % CI : 0.49–1.04 ) , and no significant linear associations were detected . Risks of POAG did not differ by type of alcoholic beverage consumed . To evaluate the potential for detection bias , we controlled for additional factors , such as frequency of eye exams , but results were similar . Conclusion : In this large prospect i ve study of men and women , alcohol consumption did not influence the risk of POAG", "Objective : To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy ( AMD ) . Design : Prospect i ve r and omised placebo controlled clinical trial . Setting : An urban study centre in a residential area supervised by university research staff . Participants : 1193 healthy volunteers aged between 55 and 80 years ; 73 % completed the trial on full protocol . Interventions : Vitamin E 500 IU or placebo daily for four years . Main outcome measures : Primary outcome : development of early age related macular degeneration in retinal photographs . Other measures included alternative definitions of age related macular degeneration , progression , changes in component features , visual acuity , and visual function Results : The incidence of early age related macular degeneration ( early AMD 3 ) was 8.6 % in those receiving vitamin E versus 8.1 % in those on placebo ( relative risk 1.05 , 95 % confidence interval 0.69 to 1.61 ) . For late disease the incidence was 0.8 % versus 0.6 % ( 1.36 , 0.67 to 2.77 ) . Further analysis showed no consistent differences in secondary outcomes . Conclusion : Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration", "CONTEXT Despite nutrition information and guidelines that advise against depriving diabetic patients of the potential benefit of moderate alcohol intake against cardiovascular events , the association between alcohol consumption and risk of cardiovascular outcomes in diabetic individuals has not been determined . OBJECTIVE To examine the relationship between alcohol intake and coronary heart disease ( CHD ) mortality in persons with older-onset diabetes . DESIGN Population -based , prospect i ve cohort study conducted from 1984 through 1996 , with a follow-up of up to 12.3 years . SETTING AND PARTICIPANTS A total of 983 older-onset diabetic individuals ( mean [ SD ] age , 68.6 [ 11.0 ] years ; 45.2 % male ; 98.5 % white ) were interviewed about their past-year intake of alcoholic beverages during the 1984 - 1986 follow-up examination of a population -based study of diabetic persons in southern Wisconsin . MAIN OUTCOME MEASURE Time to mortality from CHD by category alcohol intake . RESULTS Alcohol use was inversely associated with risk of CHD mortality in older-onset diabetic subjects . The CHD mortality rates for never and former drinkers were 43.9 and 38.5 per 1000 person-years , respectively , while the rates for those with alcohol intakes of less than 2 , 2 to 13 , and 14 or more g/d were 25.3 , 20.8 , and 10.0 per 1000 person-years , respectively . Compared with never drinkers and controlling for age , sex , cigarette smoking , glycosylated hemoglobin level , insulin use , plasma C-peptide level , history of angina or myocardial infa rct ion , digoxin use , and the presence and severity of diabetic retinopathy , former drinkers had a relative risk ( RR ) of 0.69 ( 95 % confidence interval [ CI ] , 0.43 - 1.12 ) ; for those who drank less than 2 g/d ( less frequent than 1 drink a week ) , the RR was 0.54 ( 95 % CI , 0.33 - 0.90 ) ; for 2 to 13 g/d , it was 0.44 ( 95 % CI , 0.23 - 0.84 ) ; and for 14 or more g/d ( about 1 drink or more a day ) , it was 0.21 ( 95 % CI , 0.09 - 0.48 ) . Further adjustments for blood pressure , body mass index , education , physical activity , diabetes duration , hypertension history , overt nephropathy , peripheral neuropathy , lipid measures , or intake of medications such as aspirin and antihypertensive agents did not change the associations observed . CONCLUSION Our results suggest an overall beneficial effect of alcohol consumption in decreasing the risk of death due to CHD in people with older-onset diabetes", "The relation between dietary antioxidant intake and primary open-angle glaucoma risk was examined in participants aged over 40 years in the Nurses ' Health Study ( n = 76,200 ) and the Health Professionals Follow-up Study ( n = 40,284 ) . They were followed biennially from 1980 and 1986 , respectively , to 1996 , during periods when they received an eye examination . Dietary intakes were measured repeatedly from 1980 in the Nurses ' Health Study and from 1986 in the Health Professionals Follow-up Study using vali date d food frequency question naires . The authors analyzed 474 self-reported glaucoma cases confirmed by medical chart review to have primary open-angle glaucoma with visual field loss . The authors used Cox proportional hazards models for cohort-specific multivariate analyses , and results were pooled using r and om effects models . The pooled multivariate rate ratios for primary open-angle glaucoma comparing the highest versus lowest quintile of cumulative up date d intake were 1.17 ( 95 % confidence interval ( CI ) : 0.87 , 1.58 ) for alpha-carotene , 1.10 ( 95 % CI : 0.82 , 1.48 ) for beta-carotene , 0.95 ( 95 % CI : 0.70 , 1.29 ) for beta-cryptoxanthin , 0.82 ( 95 % CI : 0.60 , 1.12 ) for lycopene , 0.92 ( 95 % CI : 0.69 , 1.24 ) for lutein/zeaxanthin , 1.05 ( 95 % CI : 0.59 , 1.89 ) for vitamin C , 0.97 ( 95 % CI : 0.62 , 1.52 ) for vitamin E , and 1.11 ( 95 % CI : 0.82 , 1.51 ) for vitamin A. In conclusion , the authors did not observe any strong associations between antioxidant consumption and the risk of primary open-angle glaucoma", "OBJECTIVE To determine the prevalence of glaucoma in a population -based sample of Hispanic adults older than 40 years . METHODS Using 1990 census data for Arizona , groups of persons living in sections of the city in Nogales and Tucson were r and omly selected with a probability proportional to the Hispanic population older than 40 years . We tried to recruit all eligible adults in homes with 1 self-described Hispanic adult . Detailed ocular examinations at a local clinic included visual acuity testing , applanation tonometry , gonioscopy , an optic disc evaluation , and a threshold visual field test . Open-angle glaucoma ( OAG ) was defined using a proposed international system for prevalence surveys , including threshold visual field defect and optic disc damage . Angle-closure glaucoma was defined as bilateral appositional angle closure , combined with optic nerve damage ( judged by field and disc as for OAG ) . RESULTS Examinations were conducted in 72 % ( 4774/6658 ) of eligible persons , with a 1.97 % prevalence ( 95 % confidence interval , 1.58%-2.36 % ) of OAG ( 94 persons ) . The age-specific OAG prevalence increased nonlinearly from 0.50 % in those aged 41 to 49 years to 12.63 % in those 80 years and older . Angle-closure glaucoma was detected in 5 persons ( 0.10 % ) . Sex , blood pressure , and cigarette smoking were not significant OAG risk factors . Only 36 ( 38 % ) of the 94 persons with OAG were aware of their OAG before the study . Screening results with an intraocular pressure higher than 22 mm Hg ( in the eye with a higher pressure ) would miss 80 % of the OAG cases . CONCLUSIONS The prevalence of OAG in Hispanic persons was intermediate between reported values for white and black persons . The prevalence increased more quickly with increasing age than in other ethnic groups . Glaucoma was the leading cause of bilateral blindness", "PURPOSE To establish risk factors for five-year incidence of age-related macular degeneration ( AMD ) . DESIGN Population -based , prospect i ve cohort study , and risk analysis . METHODS A r and om sample from the Reykjavik Population Census for individuals 50 years and older was selected . We took fundus stereo color photographs and used st and ard grading system to study the five-year incidence of drusen , pigmentary abnormalities , and AMD and to examine possible risk factors . A question naire including information on disease , medication , diet , and lifestyle from the Reykjavik Eye Study data base provided additional information . RESULTS Current alcohol consumption decreased the risk for drusen . Being married rather than divorced or widowed decreased the risk for soft drusen ; being single decreased the risk of hypopigmentation as compared with being divorced or married . Both consuming dietary fiber-rich vegetables and meat and meat products once a week or less frequently was a risk factor for developing soft drusen and decreased the risk of pigmentary abnormalities . Those who had smoked 20 pack-years or more as compared with nonsmokers had decreased survival rate over the five years ( odds ratio ( OR ) 0.46 , 95 % confidence interval ( CI ) 0.27 to 0.80 ; P = .006 ) . CONCLUSIONS Risk factors for drusen appear to differ from risk factors for pigmentary abnormalities . The effect of smoking on developing AMD is partly masked by selective mortality", "OBJECTIVE To determine the cost-effectiveness of vitamin therapy ( antioxidants plus zinc ) for all indicated patients diagnosed with age-related macular degeneration ( AMD ) . DESIGN We compared the impacts of vitamin therapy with those of no vitamin therapy using a computerized , stochastic , agent-based model . The model simulated the natural history of AMD and patterns of ophthalmic service use in the United States in a cohort from age 50 years until 100 or death . PARTICIPANTS AND /OR CONTROLS The model created 20 million simulated individuals . These individuals each received both the intervention ( vitamin therapy after diagnosis ) and the control ( no vitamin therapy ) . Expected outcomes generated when vitamins were taken after diagnosis were compared with the expected outcomes generated when they were not . METHODS The model created individuals representative of patients in the U.S. Incidence of early AMD was based on published studies , as was vision loss and response to choroidal neovascularization therapies . Post-incident disease progression was governed by previously unpublished data drawn from the Age-Related Eye Disease Study . MAIN OUTCOME MEASURES Extent of disease progression , years and severity of visual impairment , cost of ophthalmic care and nursing home services , and quality -adjusted life years ( QALYs ) . Costs and benefits were considered from the health care perspective and discounted using a 3 % rate . The analysis was run for 50 years starting in 2003 . RESULTS Compared with no therapy , vitamin therapy yielded a cost-effectiveness ratio of $ 21,387 per QALY gained and lowered the percentage of patients with AMD who ever developed visual impairment in the better-seeing eye from 7.0 % to 5.6 % . CONCLUSIONS Our model demonstrates that vitamin therapy for AMD improves quality of life at a reasonable cost", "OBJECTIVES To delineate the magnitude of susceptibility to age-related macular degeneration ( AMD ) due to common variants in the gene for complement factor H ( CFH ) and the predicted gene LOC387715 and to determine whether these variants interact with modifiable risk factors . METHODS We compared cases who developed AMD ( n = 457 ) with 1071 age- and sex-matched control subjects in a prospect i ve nested case-control study within the Nurses ' Health Study and the Health Professionals Follow-up Study . We determined the incidence rate ratios and 95 % confidence intervals ( CIs ) for AMD for each genotype and examined the interactions with modifiable risk factors . RESULTS Participants with 1 or 2 copies of the Y402H variant of CFH were , respectively , 1.98 ( 95 % CI , 1.64 - 2.40 ) and 3.92 ( 95 % CI , 2.69 - 5.76 ) times more likely to develop AMD , whereas the incident rate ratios ( 95 % CIs ) for 1 and 2 copies of LOC387715 A69S were 2.38 ( 1.92 - 2.96 ) and 5.66 ( 3.69 - 8.76 ) , respectively . The fraction of AMD cases attributable to these 2 variants was 63 % ( 95 % CI , 58%-68 % ) . Subjects homozygous for both risk alleles had a 50-fold increased risk of AMD ( 95 % CI , 10.8 - 237 ) , and cigarette smoking and obesity multiplied the risks associated with these variants . CONCLUSION Age-related macular degeneration has emerged as a paradigmatic example of a common disease caused by the interplay of genetic predisposition and exposure to modifiable risk factors", "Aim : To determine if antioxidant supplements ( β carotene and vitamins C and E ) can decrease the progression of cataract in rural South India . Methods : The Antioxidants in Prevention of Cataracts ( APC ) Study was a 5 year , r and omised , triple masked , placebo controlled , field based clinical trial to assess the ability of interventional antioxidant supplements to slow cataract progression . The primary outcome variable was change in nuclear opalescence over time . Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear colour changes ; best corrected visual acuity change ; myopic shift ; and failure of treatment . Annual examinations were performed for each subject by three examiners , in a masked fashion . Multivariate modelling using a general estimating equation was used for analysis of results , correcting for multiple measurements over time . Results : Initial enrolment was 798 subjects . Treatment groups were comparable at baseline . There was high compliance with follow up and study medications . There was progression in cataracts . There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables . Conclusion : Antioxidant supplementation with β carotene , vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants", "context Funding surgery worldwide for age-related cataract ( ARC ) , a leading cause of blindness , is a huge economic burden . Non-surgical means of slowing ARC progression could benefit patients and reduce this burden . objective To determine if a mixture of oral antioxidant micronutrients [ mg/day ] ( ß-carotene [ 18 ] , vitamin C [ 750 ] , and vitamin E [ 600 ] ) would modify progression of ARC . design REACT was a multi-centered , prospect i ve , double-masked , r and omized , placebo-controlled , 3-year trial . setting Consecutive adult American and English out patients with early ARC were recruited . patients Four-hundred- and -forty-five patients were eligible ; 297 were r and omized ; 231 ( 78 % ) were followed for two years ; 158 ( 53 % ) were followed for three years ; 36 ( 12 % ) were followed for four years . Twelve patients died during the trial ( 9 on vitamins ; 3 on placebo ( p = 0.07 ) ) . There were no serious safety issues . intervention After a three-month placebo run-in , patients were r and omized by clinical center to the vitamin or placebo groups and followed every four months . main outcome measure Cataract severity was documented with serial digital retroillumination imagery of the lens ; progression was quantified by image analysis assessing increased area of opacity . This measure of area , ‘ increase % pixels opaque ’ ( IPO ) , was the main outcome measure . results There were no statistically significant differences between the treatment groups at baseline . The characteristics of dropouts and the mean follow-up times by treatment group were the same . After two years of treatment , there was a small positive treatment effect in U.S. patients ( p = 0.0001 ) ; after three years a positive effect was apparent ( p = 0.048 ) in both the U.S. and the U.K. groups . The positive effect in the U.S. group was even greater after three years : ( IPO = 0.389 ( vitamin ) vs. IPO = 2.517 ( placebo ) ; p = 0.0001 ) . There was no statistically significant benefit of treatment in the U.K. group . In spite of nearly perfect r and omization into treatment groups , the U.S. and U.K. cohorts differed significantly . conclusion Daily use of the afore-mentioned micronutrients for three years produced a small deceleration in progression of ARC", "PURPOSE To evaluate the effect of the multivitamin Centrum on the development and progression of age-related lens opacities . DESIGN Clinic-based prospect i ve cohort study . PARTICIPANTS Four thous and five hundred ninety individuals with at least one natural lens and photographic follow-up ( median , 6.3 years ) were assessed for development or progression of lens opacities . MAIN OUTCOME MEASURES Progression of \" any \" lens opacity or type-specific opacity was ascertained from lens photographs taken at baseline and at annual visits beginning at year 2 . METHODS The Age-Related Eye Disease Study ( AREDS ) showed no statistically significant effect of a high-dose antioxidant formulation on progression of lens opacities . Centrum also was provided to approximately two thirds of the study participants . Because Centrum use was elective , a logistic regression model of baseline characteristics was used to generate a propensity score for Centrum use . Repeated- measures logistic regression , adjusted for propensity score and other covariates , was used to evaluate associations of Centrum use and lens opacity . RESULTS Centrum use , adjusted for propensity score and other covariates , was associated with a reduction in \" any \" lens opacity progression ( odds ratio [ OR ] = 0.84 , 95 % confidence interval [ CI ] = 0.72 - 0.98 , P = 0.025 ) . Results for individual lens opacity types suggested that Centrum use was protective for nuclear opacity events ( OR = 0.75 , 95 % CI = 0.61 - 0.91 , P = 0.004 ) . CONCLUSION Observational data from the AREDS and other studies suggest that use of a multivitamin may delay the progression of lens opacities . A National Eye Institute-sponsored clinical trial scheduled for completion in 2007 will provide additional data on Centrum use and cataract development", "OBJECTIVE To examine the association between cigarette smoking and age-related maculopathy ( ARM ) including age-related macular degeneration ( AMD ) in the European population . DESIGN Cross-sectional study . PARTICIPANTS Four thous and seven hundred fifty r and omly sample d > or = 65-year-olds from 7 study centers across Europe ( Norway , Estonia , United Kingdom , France , Italy , Greece , and Spain ) . METHODS Participants underwent an eye examination and digital retinal photography . The images were grade d at a single center . Smoking history was ascertained by a structured question naire administered by trained fieldworkers . Multinomial and binary logistic regressions were used to examine the association between smoking history and ARM grade and type of AMD , taking account of potential confounders and the multicenter study design . MAIN OUTCOME MEASURES Photographic images were grade d according to the International Classification System for ARM and stratified using the Rotterdam staging system into 5 exclusive stages ( ARM 0 - 3 and ARM 4 , also known as AMD ) . Age-related macular degeneration also was classified as neovascular AMD or geographic atrophy ( GA ) . RESULTS One hundred fifty-eight cases were categorized as AMD ( 109 neovascular AMD and 49 GA ) ; 2260 had no signs of ARM ( ARM 0 ) . Current smokers had increased odds of neovascular AMD ( odds ratio [ OR ] , 2.6 ; 95 % confidence interval [ CI ] , 1.4 - 4.8 ) or GA ( OR , 4.8 ; 95 % CI , 2.1 - 11.1 ) , whereas for ex-smokers the odds were around 1.7 . Compared with people with unilateral AMD , those with bilateral AMD were more likely to have a history of heavy smoking in the previous 25 years ( OR , 5.1 ; 95 % CI , 1.3 - 20.0 ) . The attributable fraction for AMD due to smoking was 27 % ( 95 % CI , 19%-33 % ) . There was no consistent association with ARM grade s 1 to 3 and smoking . CONCLUSIONS These findings highlight the need for increasing public awareness of the risks associated with smoking and the benefit of quitting smoking . Patients with unilateral disease who are current smokers should be advised of the risk of second-eye disease", "We evaluated the relationship between cigarette smoking behavior and lens opacities in cross-sectional data on 4,926 adults in Beaver Dam , Wisconsin . The frequencies of more severe levels of nuclear sclerosis increased with packyears of cigarette smoking in women and men . For women , the odds ratio ( OR ) associated with 10 packyears was 1.09 ( confidence interval [ CI ] = 1.04 , 1.16 ) and for men it was 1.09 ( CI = 1.05 , 1.14 ) after controlling for age . The frequencies of posterior subcapsular opacities also increased in both sexes with increased packyears . The OR associated with 10 packyears of cigarette smoking was 1.06 ( CI = 0.98 , 1.14 ) for women and 1.05 ( CI = 1.00 , 1.11 ) for men after controlling for age . There was no significant effect on cortical opacities . Smoking was associated with past cataract surgery . The significant relationships of smoking with lens opacities suggest an etiologic effect . If confirmed prospect ively , our results would indicate another benefit of smoking cessation", "OBJECTIVE To determine whether treatment with vitamin E ( 500 IU daily ) reduces either the incidence or rate of progression of age-related cataracts . DESIGN A prospect i ve , r and omized , double-masked , placebo-controlled clinical trial entitled the Vitamin E , Cataract and Age-Related Maculopathy Trial . PARTICIPANTS Of 1906 screened volunteers , 1193 eligible subjects with early or no cataract , aged 55 to 80 years , were enrolled and followed up for 4 years . INTERVENTION Subjects were assigned r and omly to receive either 500 IU of natural vitamin E in soybean oil encapsulated in gelatin or a placebo with an identical appearance . MAIN OUTCOME MEASURES The incidence and progression rates of age-related cataract were assessed annually with both clinical lens opacity gradings and computerized analysis of Scheimpflug and retroillumination digital lens images obtained with a Nidek EAS-1000 lens camera . The analysis was undertaken using data from the eye with the more advanced opacity for each type of cataract separately and for any cataract changes in each individual . RESULTS Overall , 87 % of the study population completed the 4 years of follow-up , with 74 % of the vitamin E group and 76 % of the placebo group continuing on their r and omized treatment allocation throughout this time . For cortical cataract , the 4-year cumulative incidence rate was 4.5 % among those r and omized to vitamin E and 4.8 % among those r and omized to placebo ( P = 0.87 ) . For nuclear cataract , the corresponding rates were 12.9 % and 12.1 % ( P = 0.77 ) . For posterior subcapsular cataract , the rates were 1.7 % and 3.5 % ( P = 0.08 ) , whereas for any of these forms of cataract , they were 17.1 % and 16.7 % , respectively . Progression of cortical cataract was seen in 16.7 % of the vitamin E group and 18.4 % of the placebo group ( P = 0.76 ) . Corresponding rates for nuclear cataract were 11.4 % and 11.9 % ( P = 0.84 ) , whereas those of any cataract were 16.5 % and 16.7 % , respectively . There was no difference in the rate of cataract extraction between the 2 groups ( P = 0.87 ) . Lens characteristics of the participants withdrawn from the r and omized medications were not different from those who continued . CONCLUSIONS Vitamin E given for 4 years at a dose of 500 IU daily did not reduce the incidence of or progression of nuclear , cortical , or posterior subcapsular cataracts . These findings do not support the use of vitamin E to prevent the development or to slow the progression of age-related cataracts", "OBJECTIVE To determine whether the vitamin/mineral supplements used in two cancer intervention trials affected the risk of developing age-related cataracts . DESIGN Two r and omized , double-masked trials with a duration of 5 to 6 years and end-of-trial eye examinations . SETTING Rural communes in Linxian , China . PARTICIPANTS In trial 1 , 2141 participants aged 45 to 74 years , and , in trial 2 , 3249 participants aged 45 to 74 years . INTERVENTIONS Multivitamin/mineral supplement or matching placebo in trial 1 ; factorial design to test the effect of four different vitamin/mineral combinations in trial 2 ( retinol/zinc , riboflavin/niacin , ascorbic acid/molybdenum , and selenium/alpha-tocopherol/beta carotene ) . MAIN OUTCOME MEASURES Prevalence of nuclear , cortical , and posterior subcapsular cataracts in treatment groups at end of trials . RESULTS In the first trial , there was a statistically significant 36 % reduction in the prevalence of nuclear cataract for persons aged 65 to 74 years who received the supplements . In the second trial , the prevalence of nuclear cataract was significantly lower in persons receiving riboflavin/niacin compared with persons not receiving these vitamins . Again , persons in the oldest group , 65 to 74 years , benefited the most ( 44 % reduction in prevalence ) . No treatment effect was noted for cortical cataract in either trial . Although the number of posterior subcapsular cataracts was very small , there was a statistically significant deleterious effect of treatment with riboflavin/niacin . CONCLUSIONS Findings from the two trials suggest that vitamin/mineral supplements may decrease the risk of nuclear cataract . Additional research is needed in less nutritionally deprived population s before these findings can be translated into general nutritional recommendations" ]

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[ "Comparing two methods of follow up in a multicentre randomised trial", "Prevention of intraventricular haemorrhage by fresh frozen plasma.", "Randomised controlled trial of colloid infusions in hypotensive preterm infants.", "Concurrent administration of albumin with total parenteral nutrition in sick newborn infants.", "Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial.", "Central–peripheral temperature difference, blood pressure, and arginine vasopressin in preterm neonates undergoing volume expansion", "Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow.", "A comparison of 4.5% human albumin solution and Haemaccel in neonates undergoing major surgery.", "The role of exchange transfusions in the management of low-birth-weight infants with and without severe respiratory distress syndrome. II. Further observations and studies of mechanisms of action.", "Plasma volume expansion by medium molecular weight hydroxyethyl starch in neonates: A pilot study*", "Randomised trial of fluid restriction in ventilated very low birthweight infants", "Very-Low-Birth-Weight Infant Outcomes in 11 South American NICUs", "Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial.", "A comparison of two methods of follow-up in a trial of prophylactic volume expansion in preterm babies.", "Transfusion Volume in Infants With Very Low Birth Weight: A Randomized Trial of 10 Versus 20 mL/kg", "Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants", "Randomised controlled trial: comparison of colloid or crystalloid for partial exchange transfusion for treatment of neonatal polycythaemia", "Extracellular volume in preterm infants: influence of gestational age and colloids.", "A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants.", "Colloid infusion in the perinatal period and abnormal neurodevelopmental outcome in very low birth weight infants", "Effects of volume expansion on cardiac output in the preterm infant", "Randomized Trial of Normal Saline versus 5% Albumin for the Treatment of Neonatal Hypotension", "Empiric red cell transfusion in asymptomatic preterm infants", "Response to dobutamine and dopamine in the hypotensive very preterm infant.", "Water, Sodium and Acid‐Base Balance in Premature Infants: Therapeutical Aspects", "Single-dose dexamethasone treatment of hypotension in preterm infants.", "Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants.", "Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants.", "Randomized, blind trial of dopamine versus dobutamine for treatment of hypotension in preterm infants with respiratory distress syndrome.", "Intravenous immune globulin therapy for early-onset sepsis in premature neonates.", "The role of RBC transfusion in the premature infant.", "The haemodynamic effects of dopamine and volume expansion in sick preterm infants.", "Variance in albumin loading in exchange transfusions.", "Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants", "Haemodynamic effects of differing blood transfusion rates in infants less than 1500 g.", "The effects of large volume intravenous fluid infusion on neonatal renal function.", "Echocardiographic effects of high and low volumes of maintenance fluid administration in low-birth-weight infants.", "Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants.", "Beneficial effect of human albumin on neonatal cerebral edema.", "Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapy.", "Impact on blood pressure and intestinal perfusion of dobutamine or dopamine in hypotensive preterm infants.", "Renal function in preterm infants during the first five days of life: influence of maturation and early colloid treatment." ]

[ "AIMS To evaluate a parental question naire as a means of providing outcome measures for a multicentre r and omised controlled trial of treatment for post-haemorrhagic ventricular dilatation . METHODS The parents of 88 survivors were sent a question naire before a paediatric assessment at the age of 30 months . The parents ’ responses to individual questions taken mainly from the Griffiths ’ mental development scales and their perception of the child ’s ability to see and hear were compared with the paediatric findings . A model , based on the parents ’ responses to particular questions , allowed the categorisation of the children as normal , impaired , moderately or severely disabled ; this was compared with similar categorisation based on the full paediatric assessment . RESULTS Agreement on items concerning gross motor function ranged between 81 and 99 % , concerning dressing between 77 and 80 % , concerning feeding between 91 and 99 % , and concerning language between 85 and 93 % . Similar proportions of children were identified as disabled by the parents ( 60 % ) and by the paediatrician ( 66 % ) . Of 29 children who had developmental quotients less than 70 , parents identified 28 as disabled , 18 of them as severely disabled . They were not so good at identifying children with impairments without functional loss . CONCLUSIONS Further work is required but there is sufficient encouragement from the results to pursue this methodology further for use in comparing groups in r and omised trials", "Seventy three preterm infants weighing less than 1500 g or less than 32 weeks ' gestation , or both , were allocated r and omly to treatment ( fresh frozen plasma 10 ml/kg on admission and at 24 hours of age ) or control groups . Fifteen ( 41 % ) out of 37 control patients sustained intraventricular haemorrhage compared with five ( 14 % ) of 36 patients receiving treatment ( X2 = 5.24 , P = 0.022 ) . No difference was found in coagulation factors measured at birth or at 48 hours of age in both groups . Fresh frozen plasma appears to have a beneficial effect in the prevention of intraventricular haemorrhage", "Colloid infusions are often given to treat hypotension in preterm infants . The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure . Sixty preterm infants were r and omised ( 20 in each group ) to receive 5 ml/kg 20 % albumin , 15 ml/kg fresh frozen plasma , or 15 ml/kg 4.5 % albumin . All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids . The infants were r and omised when hypotensive ( systolic blood pressure less than 40 mm Hg for two hours ) . There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion . The mean increase in blood pressure one hour after completing the infusion , however , was significantly lower in infants receiving 20 % albumin : 9 % compared with 17 % in the group receiving 4.5 % albumin , and 19 % in the group receiving fresh frozen plasma . It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure", "The effects of concurrent administration of albumin with total parenteral nutrition were studied in 12 premature newborns ( birth weight 1.26 + /- 0.1 kg [ mean + /- SEM ] and gestational age 30 + /- 0.8 weeks [ mean + /- SEM ] ) compared with a control group of 12 premature newborns ( birth weight 1.17 + /- 0.2 kg and gestational age 29 + /- 0.1 weeks ) who received total parenteral nutrition . All newborns had a plasma albumin level below 3 g/dL and were in cardiorespiratory distress requiring assisted ventilation . Albumin supplementation of total parenteral nutrition result ed in a sustained increase in serum albumin concentration as well as increased mean arterial blood pressures in the study group . Slow albumin infusion had no observed effect on the severity of respiratory distress . Study group infants regained birth weight earlier than control group infants . These data suggest that the concurrent administration of albumin may be clinical ly beneficial in critically ill newborn infants", "To test the hypothesis that restriction of sodium intake during the first 3 to 5 days of life will prevent the occurrence of hypernatremia and the need for administration of large fluid volumes , we prospect ively and r and omly assigned 17 babies ( mean + /- SD : 850 + /- 120 gm ; 27 + /- 1 weeks of gestation ) to receive in blind fashion either daily maintenance sodium or salt restriction with physician-prescribed parenteral fluid intake . Maintenance-group infants received 3 to 4 mEq of sodium per kilogram per day ; restricted infants received no sodium supplement other than with such treatments as transfusion . Sodium balance studies conducted for 5 days demonstrated that maintenance salt intake result ed in a daily sodium balance near zero , whereas sodium-restricted infants continued to excrete urinary sodium at a high rate , which promoted a more negative balance ( average daily sodium balance -0.30 + /- 1.78 SD in maintenance group vs -3.71 + /- 1.47 mEq/kg per day in restriction group ; p less than 0.001 ) . Care givers tended to prescribe daily increases in parenteral fluids for the salt-supplemented infants , perhaps because serum sodium concentrations were elevated in these infants after the first day of the study ( p less than 0.001 ) . Hypernatremia developed in two sodium-supplemented infants ( greater than 150 mEq/L ) , and hyponatremia developed in two sodium-restricted infants ( less than 130 mEq/L ) ; however , the restricted infants were more likely to have normal serum osmolality ( p less than 0.05 ) . Both groups of infants produced urine that was neither concentrated nor dilute , with a high fractional excretion of sodium ; renal failure was not observed . The mortality rate was not affected , but the incidence of bronchopulmonary dysplasia was significantly less in the sodium-restricted babies ( p less than 0.02 ) . We conclude that in tiny premature infants , a fluid regimen that restricts sodium may simplify parenteral fluid therapy targeted to prevent hypernatremia and excessive administration of parenteral fluids", "AIM To examine the effect of intravascular volume expansion for the treatment of hypovolaemia in sick preterm neonates . METHODS An intravenous infusion of 20 ml per kg of 4.5 % albumin was given to 14 preterm neonates . The effects on systolic blood pressure , central peripheral temperature difference ( c-pT ) , and plasma arginine vasopressin concentration ( pAVP ) were measured . RESULTS Thirteen babies showed a rise in systolic blood pressure . The six babies with the highest initial values of pAVP and c-pT showed a fall in both of these after infusion . The babies with lower initial pAVP ( below 4 pmol/l ) showed either a rise ( two ) or no change ( six ) after albumin infusion . There was a significant correlation between c-pT and log pAVP before ( r2=0.61 ; p<0.05 ) and after infusion ( r2=0.45 ; p<0.05 ) . CONCLUSIONS Plasma AVP concentration is related to c-pT in unwell preterm newborns . This study suggests that clinical assessment of hypovolaemia in preterm newborns is poor and could be improved by using", "OBJECTIVE Our purpose was to determine if dobutamine or dopamine results in greater improvements in systemic blood flow in very preterm infants with low flow during the first 24 hours of life . STUDY DESIGN A 2-center , r and omized , double-blind study . Infants ( n = 42 ) with low superior vena cava ( SVC ) flow ( < 41 mL/kg/min ) in the first 12 hours were r and omly assigned to receive 10 mL/kg normal saline solution , followed by 10 microg/kg/minute of dobutamine or dopamine . If low flow persisted or recurred , the inotrope was increased to 20 microg/kg/minute , with crossover to the other inotrope if treatment failed to maintain flow . RESULTS Volume produced a more significant increase in SVC flow than dopamine ( + 43 % ) . At the highest dose , dobutamine result ed in a significantly greater increase in SVC flow than dopamine ( mean , + 9.9 vs -3.2 mL/kg/min , P = .02 ) . Dopamine result ed in a significantly greater increase in blood pressure . Infants receiving dobutamine only at 24 hours had a greater right ventricular output than infants receiving dopamine ( mean , 295 vs 167 mL/kg/min , P < .001 ) . Forty percent failed to increase or maintain SVC flow in response to either inotrope . No significant differences in mortality or morbidity were found . CONCLUSIONS Dobutamine produced a greater increase in blood flow than dopamine", "In a r and omized blinded study we compared two colloid solutions in 30 neonates undergoing major surgery . Fifteen neonates received 4.5 % Human albumin solution ( HAS ) ( mean volume 25.6 ml.kg-1 , SD 9.5 ) and the others received Haemaccel ( Hoechst ) ( 24.9 ml.kg-1 , SD 10 ) . Pre and postoperative plasma albumin and haemoglobin concentrations and plasma colloid osmotic pressure ( COP ) were compared . In the group given Haemaccel there was an appreciable and statistically significant decrease in the mean plasma albumin concentration from 34.27 to 28.27 g.1(-1 ) ( mean difference 6 , CI 3.38 to 8.62 ) and the mean COP decreased significantly from 22.2 to 19.9 mmHg ( mean difference 2.3 , CI 0.3 to 4.5 ) . In the HAS group there was no significant change in either the plasma albumin concentration or COP . There was a small but significant decrease in the mean haemoglobin concentration from 15.92 to 14.35 g.dl-1 ( mean difference 1.56 , CI 0.57 to 2.55 ) after HAS . We conclude that HAS is the superior colloid for volume replacement in neonates undergoing surgery", "Exchange transfusion , as a form of therapy , was contrasted with the use of fresh frozen plasma or conventional supportive care alone in the management of 19 infants with birth weights of less than 1,000 gm , without severe respiratory distress , and in the management of 82 infants , birth weights less than 2,000 gm , with severe respiratory distress whose disease manifested itself within the first 24 hours of life . Survival for more than five days was similar , regardless of therapy , in infants weighing less than 1,000 gm without severe RDS . In contrast , the use of exchange transfusion significantly decreased the case fatality rate of infants with severe RDS . In the groups receiving exchange transfusion , the mortality rate was 41 % , whereas the groups receiving either plasma or supportive care alone the mortality was 80 % . Study of coagulation factors and red cell concentrations of fetal hemoglobin and of 2,3-DPG failed to demonstrate any relationship between either improvement in coagulation or oxygen unloading and the improved survival of infants receiving exchange transfusion . Following exchange transfusion there was a significant decrease in the ratio of FIO2 to PaO2 , suggesting that pulmonary perfusion and /or ventilation was improved by the procedure", "Objective To study the renal effects ( measured by creatininemia ) of plasma volume expansion with a medium molecular weight hydroxyethyl starch in the newborn . Design A prospect i ve , r and omized , double-blinded , pilot study . Patients The study included 26 neonates weighing 690–4030 g ( gestational age , 26–40 wks ) , without cardiac or renal failure or major hemostasis abnormalities and requiring a peripherally inserted central catheter for parenteral nutrition . Setting Pediatric and neonatal intensive care unit of a university-affiliated hospital . Interventions Plasma volume expansion was performed to facilitate insertion of the central catheter . After parental consent , neonates were r and omly allocated to receive intravenous infusions at 10 mL·kg−1 of 5 % albumin or 6 % hydroxyethyl starch 200/0.5 . Sample size was calculated to detect an increase in mean creatininemia of > 20 & mgr;mol·L−1 ( with & agr ; = 0.05 , & bgr ; = 0.80 ) . Measurements and Main Results No clinical ly or statistically significant differences were found between the two groups 6 hrs , 24 hrs , 48 hrs , and 7 days after plasma volume expansion . The study could detect an increase in creatininemia ≥20 & mgr;mol·L−1 with a power of 80 % . Conclusions In 13 healthy neonates , plasma volume expansion with 10 mL·kg−1 of 6 % hydroxyethyl starch 200/0.5 does not increase creatininemia", "BACKGROUND Fluid restriction has been reported to improve survival of infants without chronic lung disease ( CLD ) , but it remains unknown whether it reduces CLD in a population at high risk of CLD routinely exposed to antenatal steroids and postnatal surfactant without increasing other adverse outcomes . AIM To investigate the impact of fluid restriction on the outcome of ventilated , very low birthweight infants . STUDY DESIGN A r and omised trial of two fluid input levels in the perinatal period was performed . A total of 168 ventilated infants ( median gestational age 27 weeks ( range 23–33 ) ) were r and omly assigned to receive st and ard volumes of fluid ( 60 ml/kg on day 1 progressing to 150 ml/kg on day 7 ) or be restricted to about 80 % of st and ard input . RESULTS Similar proportions of infants on the two regimens had CLD beyond 28 days ( 56%v 51 % ) and 36 weeks post conceptional age ( 26 % v 25 % ) , survived without oxygen dependency at 28 days ( 31 % v 27 % ) and 36 weeks post conceptional age ( 58 % v 52 % ) , and developed acute renal failure . There were no statistically significant differences between other outcomes , except that fewer of the restricted group ( 19 % v 43 % ) required postnatal steroids ( p < 0.01 ) . In the trial population overall , duration of oxygen dependency related significantly to the colloid ( p < 0.01 ) , but not crystalloid , input level ; after adjustment for specified covariates , the hazard ratio was 1.07 ( 95 % confidence interval 1.02 to 1.13 ) . CONCLUSIONS In ventilated , very low birthweight infants , fluid restriction in the perinatal period neither reduces CLD nor increases other adverse outcomes . Colloid infusion , however , is associated with increased duration of oxygen dependency . Key messages High fluid volumes increase the likelihood of a PDA , a risk factor for CLD development One of four previous r and omised trials showed that fluid restriction improved outcome —that is , a lower mortality in a relatively mature population We now show in ventilated VLBW infants that fluid restriction in the perinatal period does not reduce CLD ; colloid infusion , however , increases duration of oxygen", "OBJECTIVE : To describe and analyze outcomes in very-low-birth-weight ( VLBW ) infants treated in 11 Neonatal Intensive Care Units ( NICUs ) from four South American countries . This study is the first of a multination collaboration and can serve as a baseline for future quality and re source utilization efforts . STUDY DESIGN : Biodemographic data and multiple outcome measures were prospect ively collected from October 1997 until August 1998 . A logistic regression model was used to define risk factors in primary outcome measures , death , and bronchopulmonary dysplasia ( BPD ) . Center differences were compared using χ-squared analysis . RESULTS : In 385 VLBW infants enrolled , mortality rate was 27 % , with a range from 11 % to 51 % among NICUs . A lower BW , lower gestational age ( GA ) , lack of antenatal steroids ( AS ) , and air leaks ( AL ) were associated with increased risk of death . A lower BW , lower GA , AL , need for surfactant , necrotizing enterocolitis , and need for intubation were associated with increased risk of BPD . CONCLUSION : This study provides actual information about VLBW infants ' prognosis in a SA region . Mortality rate variability among NICUs may be explained by differences in population and re sources , but also by lack of implementation of proven beneficial therapies such as AS administration", "We conducted a controlled , prospect i ve trial to evaluate the effectiveness of rapidly infusing sodium bicarbonate ( NaHCO3 ) and salt-poor albumin into high-risk , premature infants in the first 2 hours of life . Fifty-three infants , r and omized into one of four treatment groups , received 8 ml . per kilogram of a solution containing either ( A ) glucose in water , ( B ) salt-poor albumin , ( C ) NaHCO3 , or ( D ) a combination of albumin and NaHCO3 . After the initial infusion , the babies received no colloid or alkali solutions until 4 hours of age . We managed them supportively with warmth , appropriate oxygen administration , isotonic fluid infusion , and close monitoring . Among the infants who received alkali , 14 of 26 acquired the respiratory distress syndrome ( RDS ) , 11 died , and four had intracranial hemorrhage . Among babies who received no alkali , RDS occurred in 11 of 27 , 5 died , and none had intracranial hemorrhage . These results do not support the common practice of rapidly infusing NaHCO3 into high-risk , premature infants , and they suggest that the early management of such infants needs renewed critical evaluation", "The outcome at age 2 years of preterm babies recruited into a three-arm r and omised controlled trial of prophylactic volume expansion was ascertained in two ways : from a neurodevelopmental assessment performed by a paediatrician and from responses on a brief question naire completed by the child 's personal health visitor . Of 776 babies recruited into the trial , 604 survived to the age of 2 years and the findings of a paediatric assessment were available for all survivors . Question naires were sent to the health visitors of 601 of the survivors ; 513 ( 85.4 % ) were returned . There was sufficient information on the returned question naires to categorise 449 of the children as normal , impaired , moderately disabled or severely disabled . We were unable to detect a response bias by severity of disability . Agreement on individual questions ranged between 86.3 % and 98.4 % . There was some mismatch in the reporting of vision ( weighted kappa = 0.71 ) and hearing ( weighted kappa = 0.73 ) , with differences in perception of level of severity of sensory loss . Health visitors tended to underestimate the child 's functional level compared with the paediatrician . However , of 56 children classified as severely disabled by the paediatrician , 48 were classified similarly and eight as moderately disabled on the basis of the question naire . The end point of the trial was death or severe disability at 2 years of age . There was close similarity in the trial results whether based on the paediatric assessment or on the question naire . Further refinement of the question naire is needed , but this methodology may be useful in ascertaining the frequency of severe disability in large cohorts of babies", "Background Although preterm infants often require transfusions of red blood cells for anemia of prematurity , the optimal volume of blood to be transfused has not been established . Observations Infants with birth weights between 500 and 1,500 g were r and omly assigned to receive 10 or 20 mL/kg red blood cells . Infants with transfusions of 20 mL/kg had a greater hemoglobin ( 14.2 ± 1.9 vs. 12.0 ± 1.9 g/dL , P = 0 . 003 ) and hematocrit ( 41.2 ± 5.9 vs. 32.3 ± 7.1 % , P = 0.001 ) levels after transfusion compared with those who received transfusions of 10 mL/kg . There were no measured differences in pulmonary function in either group after transfusion . Conclusions Transfusion with 20 mL/kg red blood cells produces a significantly greater increase in hemoglobin and hematocrit levels than does a transfusion with 10 mL/kg , without any detrimental effects on pulmonary function", "AIM To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive , very low birthweight ( VLBW ) infants . METHODS Forty infants were r and omly allocated to receive either hydrocortisone ( n=21 ) or dopamine ( n=19 ) . RESULTS All 19 infants r and omised to dopamine responded ; 17 of 21 ( 81 % ) did so in the hydrocortisone group . Three of the four non-responders in the hydrocortisone group had clinical ly significant left to right ductal shunting . The incidence of bronchopulmonary dysplasia , retinopathy of prematurity , intraventricular haemorrhage , necrotising enterocolitis , symptomatic patent ductus arteriosus , hyperglycaemia , sepsis ( bacterial or fungal ) or survival did not differ between groups . The adrenocorticotrophic hormone ( ACTH ) stimulated plasma cortisol activity , either before or after treatment , did not differ between the two groups of infants . Although a significant difference in efficacy between dopamine and hydrocortisone was not noted ( P = 0.108 ) , there were four treatment failures in the hydrocortisone group , compared with none in the dopamine group . CONCLUSION Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants", "AIM To compare the efficacy of using isotonic saline ( crystalloid ) or 5 % albumin ( colloid ) as replacement fluid in partial exchange transfusion ( PET ) for the treatment of neonatal polycythaemia . METHODS One hundred and two polycythaemic full term infants were r and omly allocated to receive PET with either isotonic saline or 5 % albumin . The criteria for PET were : ( a ) venous haematocrit ⩾ 0.7 ; or ( b ) venous haematocrit 0.65 - 0.69 with symptoms or signs attributable to polycythaemia . RESULTS PET with either saline ( n=53 ) or 5 % albumin ( n=50 ) result ed in a significant and sustained decline in haematocrit up to 24 hours after PET . Although the immediate haemodilution effect of isotonic saline was statistically smaller than that of 5 % albumin ( decline in haematocrit 19.3 % vs22.8 % of pre-PET value ) , the difference was too small to be of any clinical significance , and the haematocrit at 4 or 24 hours after PET did not differ significantly between the two groups . PET with either replacement fluid was not associated with any complication . The serum sodium and potassium concentrations were not significantly affected by the PET in either group . CONCLUSIONS Both isotonic saline and 5 % albumin are effective when used as replacement fluid in PET for the treatment of neonatal polycythaemia . Isotonic saline , which is cheaper and free of infection , should be the replacement fluid of choice", "We assessed the effect of fresh frozen plasma ( FFP ) on extracellular volume ( ECV ) during the first few days of life in two groups of preterm infants , group 1 ( gestational age less than 30 weeks ) and group 2 ( gestational age 30 - 34 weeks ) . The infants were r and omly assigned to one of two treatment groups , one receiving FFP , the other not ; group 1 infants receiving no treatment ( n = 8) and group 1 infants receiving FFP ( n = 11 ) , and group 2 infants receiving no treatment ( n = 9 ) and group 2 receiving FFP ( n = 10 ) . FFP was given at a dose of 10 ml/kg daily during a two-hour period for the first three days of life . ECV was measured on day 1 before FFP was given and on day 4 by the distribution of bromide . There was a significant correlation between birth weight and initial ECV ( r = 0.85 , P less than 0.001 ) . In group 1 ECV was significantly higher than in group 2 ( P less than 0.02 ) . In group 1 receiving no treatment mean weight loss and mean decrease in ECV were equal ( 84 g/kg and 78 ml/kg , respectively ) , but no correlation between the two parameters could be found ( r = 0.68 , P = 0.06 ) . In the other study groups , mean weight loss was higher than mean decrease in ECV , with no correlation between weight loss and change in ECV . ( ABSTRACT TRUNCATED AT 250 WORDS", "A multicenter prospect i ve , r and omized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia . The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes . Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were r and omly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates ( 10 ml/kg ) . The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions . In 22 ( 28 % ) of the 78 treated infants and 19 ( 26 % ) of the 74 control infants , either a new intracranial hemorrhage developed or an already-present one became more extensive ( p = 0.73 ) . Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography . Similar numbers of infants received fresh frozen plasma and packed red blood cells , but treated infants received less of both . The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened ( mean difference , 79.0 ; 95 % confidence interval , 73.1 to 84.9 ) . Sub analysis of the control group showed that infants with platelet counts < 60 x 10(9)/L ( n = 21 ) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L. ( ABSTRACT TRUNCATED AT 250 WORDS", "Abstract . In very low birth weight ( VLBW ) infants , colloid infusion is associated with impaired perinatal lung function and increased oxygen dependency duration . The aim of this study was to determine whether perinatal colloid infusion was associated with abnormal neurodevelopmental outcome . All perinatal fluid input ( crystalloid and colloid ) given to VLBW infants entered into a r and omised trial was recorded . At 1 and /or 2 years , the neurodevelopmental status of VLBW infants was routinely assessed . Of 131 survivors , median gestational age 27 weeks ( range 23–33 weeks ) , 95 were seen at follow-up . Nineteen had abnormal neurodevelopmental outcome and differed significantly from the rest of the cohort with regard to their birth weight , magnitude of colloid infusion received and the proportions who had received postnatal steroids , suffered prolonged oxygen dependency or having had intracerebral haemorrhage/periventricular leucomalacia development . Regression analysis demonstrated that only colloid infusion related significantly to abnormal neurodevelopmental outcome independent of other variables . Conclusion : These data suggest that colloid infusion should be used with caution in the perinatal period", "Clinical and echocardiography haemodynamic evaluations of response to volume expansion are described in 12 preterm neonates aged < 7days presenting without cardiac dysfunction and with a low cardiac output . They received 10 % albumin solution ( 20 ml kg‐1 ) for 3h . Measurements were made before infusion , at volumes 5 , 12 . 5 and 20 ml kg‐1 and 1 h later . All infants increased significantly their cardiac output ( CO ) ( from a median of 177 to 283 ml kg‐1 min‐1 ) . The rise of CO decreased with the volume infused . The index of systemic vascular resistance ( SVR = ratio of mean arterial pressure to the CO ) decreased for the six patients without PDA ( from 272 to 193 mmHg 1‐1 kg‐1 min‐1 , p < 0 . 05 ) showing that the hypovolemic preterm infant is able to shut down peripherally in response to hypovolemia . The four hypotensive infants responded by increasing mean arterial blood pressure ( from 29 to 44 mmHg ) . Cutaneous refilling time decreased during infusion ( from 6 . 7 to 3 . 8 s , p < 0 . 01 ) . One infant had an haemodynamically significant ductus arteriosus revealed by volume expansion , another one developed myocardial dysfunction", "OBJECTIVES : This study was design ed to assess the comparative efficacy of normal saline ( NS ) and 5 % albumin ( ALB ) for treatment of hypotension in the acutely ill newborn . STUDY DESIGN : Newborn infants who were < 24 hours old and were admitted to the Holden Neonatal Intensive Care Unit at the University of Michigan were r and omized to receive one of the two solutions for volume expansion . Hypotension was defined as a sustained ( ≥30 minutes ) mean arterial pressure ( MAP ) of < 30 mmHg for infants weighing ≤2500 g , or a MAP of < 40 mmHg for those weighing > 2500 g. The short-term outcome measure was the resolution of hypotension defined as a MAP over the minimum limits set for birthweight sustained for ≥30 minutes . RESULTS : In total 41 infants met criteria and were entered . Of these , 21 infants received ALB and 20 received NS . Successful treatment was seen in 17/21 ( 81 % ) of infants in the ALB group and 17/20 ( 85 % ) of infants in the NS group . There was no statistically significant difference in response to treatment ( p=0.30 ) . In addition , there was no statistically significant difference in the magnitude of change in MAP between the two ( p=0.41 ) . CONCLUSIONS : NS was shown to be as effective as ALB for the correction of acute hypotension in the newborn infant . Given comparable efficacy of NS , along with its relatively low cost and availability , it should be considered the initial treatment of choice in this setting", "In a prospect i ve r and omized trial , asymptomatic very low‐birth‐weight infants in a neonatal intensive care unit were either electively transfused with red cells to maintain capillary haematocrit greater than 0.35 l/l ( group 1 ; n= 9 ) , or were not transfused ( group2 ; n= 10 ) . Individuals from both groups were excluded if they subsequently received non‐elective transfusions , necessitated by their clinical condition . Electively transfused infants gained weight more rapidly than their non‐transfused counterparts , but the duration of hospitalization was not shortened . Criteria of morbidity , such as patent ductus murmurs , apnoea and failure to thrive , were similar in both groups . We conclude that in the absence of clinical indications , transfusion to achieve a haematocrit greater than 0.35 l/l as an empiric procedure , improves weight gain but the risks of transfusion are likely to outweigh the benefits", "A r and omised double blind study was design ed to evaluate haemodynamic response to dobutamine and dopamine in 20 hypotensive preterm infants of less than 32 weeks ' gestation . Neonates initially received dopamine or dobutamine 5 micrograms/kg/min . If mean arterial pressure ( MAP ) remained below 31 mm Hg , the infusion rate was increased in increments of 5 micrograms/kg/min . If 20 micrograms/kg/min of the initial drug failed to achieve a MAP above 30 mm Hg , it was discontinued and the other drug was administered at the same infusion rate . Left ventricular output ( LVO ) was measured by pulsed Doppler echocardiography . Mean ( SE ) MAP increased significantly from 24.4 ( 1.0 ) to 32.0 ( 1.4 ) mm Hg at a median dobutamine dosage of 20 micrograms/kg/min and from 25.6 ( 1.2 ) to 37.7 ( 1.5 ) mm Hg at a median dopamine dosage of 12.5 micrograms/kg/min . The percentage LVO increase was + 21 (7)% with dobutamine compared with -14 (8)% with dopamine . Dobutamine failed to increase MAP above 30 mm Hg in six infants out of 10 , whereas dopamine succeeded in all 10 infants . Six switches from dobutamine to dopamine were thus performed , providing a rise in MAP ( 29.2 ( 0.5 ) to 41.2 ( 2.0 ) mm Hg ) and drop in LVO ( 356 ( 40 ) to 263 ( 36 ) ml/kg/min ) . These data indicate that dopamine is more effective than dobutamine in raising and maintaining MAP above 30 mm Hg ; however dopamine does not increase LVO", "ABSTRACT . One of the main targets of fluid therapy in premature infants is to avoid variations in osmolality , which mainly means providing a stable sodium , glucose , and acid‐base balance . Water , sodium , and acid‐base balance were measured in 20 infants appropriate‐for‐gestational age with a gestational age 34 weeks . The infants were r and omly assigned to one of two treatment groups . Fluid intake was restricted and air humidity in the incubator was high in order to minimize insensible water loss . Sodium intake in Group 1 was 2 mmol/kg/day and consisted of sodium chloride . Sodium intake in Group 2 was 4 mmol/kg/day and consisted of both sodium chloride and acetate . Weight loss was appropriate in both groups . In the high sodium intake group there was a tendency towards a more stable plasma sodium concentration than in the low sodium intake group . The use of sodium acetate was efficient and practical as normal acid‐base balance was maintained . The protocol with restricted fluid intake ( 1st day 50 ml/kg , 2nd day 70 ml/kg , 3rd day 90 ml/kg , and 4th day 110 ml/kg ) , high air humidity , a sodium supply of 3 to 4 mmol/kg/day , and a slow correction of metabolic acidosis with sodium acetate , yields suitable guidelines in planning fluid and electrolyte therapy in premature infants 34 weeks ' gestation", "OBJECTIVE To test the efficacy of single-dose dexamethasone ( DXM ) in the management of severe arterial hypotension of newborn infants . Our hypothesis was that epinephrine infusions could be discontinued in 70 % of patients within 12 hours after DXM administration compared with 10 % in the placebo group . STUDY DESIGN Twenty preterm infants ( median birth weight 690 g , gestational age 28 weeks , age at intervention 2 days ) who did not respond to a st and ardized treatment protocol ( blood/colloid followed by dopamine infusion stepwise increased to 15 micrograms/kg and minute ) were started on an epinephrine infusion and were r and omly allocated to receive either DXM ( 0.25 mg/kg ) or placebo intravenously . The primary outcome criterion was the need for an epinephrine infusion 12 hours after treatment . RESULTS Three infants were excluded . Epinephrine infusion was discontinued in 5 of 8 infants with DXM but in only 1 of 9 infants in the control group . The duration of epinephrine infusion was significantly shorter in the DXM group ( exact log-rank test , P = . 023 ) . CONCLUSIONS DXM was effective for the management of severe arterial hypotension in preterm infants not responding to st and ardized treatment", "OBJECTIVES To determine hemodynamic and antecedent risk factors for early and late periventricular/intraventricular hemorrhage ( P/IVH ) in premature infants . METHODS Two prospect i ve cohort studies of 126 ( 1995 - 1996 ) and 128 ( 1998 - 1999 ) infants born < 30 weeks ' gestation . Head ultrasounds were performed at < 6 hours of age , and at 7 and 28 days of age . P/IVH was classified as early ( present on initial scan ) and late ( developed subsequently ) . Echocardiographic measurement of the superior vena cava ( SVC ) flow was performed at < 6 , 10 , and 24 hours of age . RESULTS Infants with early P/IVH were significantly more likely to be born by vaginal delivery in both cohorts ( 1995 - 1996 adjusted odds ratios [ OR ] : 13.29 ; 1998 - 1999 adjusted OR : 18.15 ) . An association with a 1-minute Apgar < or = 4 was only significant in the 1998 - 1999 cohort ( adjusted OR : 9.14 ) . Low SVC flow was the only independent risk factor for late P/IVH in both cohorts ( 1995 - 1996 adjusted OR : 20.39 ; 1998 - 1999 adjusted OR : 5.16 ) . Adjusted for perinatal risk factors , low SVC flow was associated with lower gestation and higher average mean airway pressure in both cohorts , and with a large diameter ductus diameter only in the 1995 - 1996 cohort . CONCLUSIONS Early and late P/IVH have distinct and different risk factors . Early P/IVH is associated with vaginal delivery and possibly low Apgar scores . Late P/IVH is associated with antecedent low SVC flow in the first day", "We conducted a case-control study of antecedents of bronchopulmonary dysplasia ( BPD ) in 223 infants enrolled in a prospect i ve , r and omized clinical trial of phenobarbital prophylaxis for intracranial hemorrhage . The trial took place at three Boston neonatal intensive care units between June 1981 and April 1984 . The 76 babies with BPD had radiographic evidence of the condition and required oxygen therapy for 28 days or more . All 147 control babies survived until day 28 of life without meeting either of these criteria for BPD . Compared with control infants , those with BPD received greater quantities of total , crystalloid , and colloid fluids per kilogram per day in the first 4 days of life . In addition , infants with BPD generally had a net weight gain in the first 4 days of life in contrast to the normal pattern of weight loss seen in control infants . Finally , the infants with BPD were more likely to be given a clinical diagnosis of patent ductus arteriosus and to have received furosemide on days 3 and 4 of life . From these observations we infer that early postnatal phenomena such as excessive fluid therapy may be important in the pathogenesis of BPD", "To compare the efficacy of dopamine and dobutamine for the treatment of hypotension ( mean arterial blood pressure , < or = 30 mm Hg ) in preterm ( < or = 34 weeks of gestation ) infants with respiratory distress syndrome in the first 24 hours of life , we enrolled 63 hypotensive preterm infants in a r and omized , blind trial . Inclusion criteria required an arterial catheter for measurement of mean arterial blood pressure , treatment with exogenous surfactant , and persistent hypotension after volume expansion with 20 ml/kg ( packed erythrocytes if hematocrit < 0.40 , 5 % albumin if > or = 0.40 ) . Intravenous study drug infusions were initiated at 5 micrograms/kg per minute and then increased in increments of 5 micrograms/kg per minute at 20-minute intervals until a mean arterial blood pressure > 30 mm Hg was attained and sustained for > or = 30 minutes ( success ) or a maximum rate of 20 micrograms/kg per minute was reached without resolution of hypotension ( failure ) . The study groups at entry were comparable for birth weight , gestational age , postnatal age , gender , birth depression , hematocrit < 0.40 , heart rate , oxygenation index , delivery route , maternal chorioamnionitis , and maternal magnesium or ritodrine therapy . No infants in the dopamine group had a treatment failure ( 0/31 ; 0 % ) ; ( 16 % ) of 32 infants failed to respond to dobutamine ( p = 0.028 ) . Success was attained at < or = 10 micrograms/kg per minute in 30 ( 97 % ) of 31 infants given dopamine and in 22 ( 69 % ) of 32 infants given dobutamine ( p < 0.01 ) . Among those treated successfully , the increase in mean arterial blood pressure was significantly higher in those given dopamine ( mean , 11.3 vs 6.8 mm Hg ; p = 0.003 ) . We conclude that dopamine is more effective than dobutamine for the early treatment of hypotension in preterm infants with respiratory distress syndrome", "Newborn infants may have IgG deficiencies that increase their susceptibility to bacterial infection . To determine whether intravenous immune globulin ( IVIG ) therapy improves survival rates in early-onset sepsis , we prospect ively entered 753 neonates ( birth weight 500 to 2000 gm , gestation less than or equal to 34 weeks , age less than or equal to 12 hours ) into a multicenter , double-blind , controlled trial . Blood culture specimens were obtained and infants r and omly assigned to receive 10 ml ( per kilogram ) intravenously of a selected IVIG ( 500 mg/kg ) or albumin ( 5 mg/kg ) preparation . Maternal and neonatal risk factors were not different between groups . Thirty-one babies ( 4.2 % ) had early-onset sepsis ; the causative organisms were group B streptococcus ( 12 babies ) , Escherichia coli ( 6 ) , and others ( 13 ) . Of these 31 neonates , 7 ( 23 % ) died . Total serum IgG was higher for 7 days after IVIG therapy than after albumin treatment ( p less than 0.05 ) . During these 7 days , 5 ( 30 % ) of 17 albumin-treated and none of 14 IVIG-treated patients died ( p less than 0.05 ) . The survival rate at 56 days of age , however , was not significantly improved . Group B streptococcus type-specific IgG antibody was significantly increased after IVIG treatment and appeared to be related to the amount of IVIG specific antibody . Infusion-related adverse reactions were less frequent in patients receiving IVIG therapy ( 0.5 % ) than in those receiving albumin . The IVIG therapy in neonates with early-onset sepsis , while reducing the early mortality rate , did not significantly affect the overall survival rate . Further studies are necessary to confirm these findings and to determine more effective therapeutic regimens", "Fifty-six premature infants with a mean gestational age at birth of 30 weeks were r and omly assigned to a transfusion group , for whom the hemoglobin level was kept above 10.0 g/dL , and a nontransfusion group , who were transfused only for specific clinical indications . The groups were followed up longitudinally with weekly determinations of reticulocyte count , the partial pressure of oxygen at which 50 % of hemoglobin is saturated , and hemoglobin F percentage , as well as weight gain , length of stay , hospital cost , and frequency and severity of apnea . At birth , there was no significant difference in birth weight , gestational age , and hemoglobin level between the two groups . At discharge , laboratory differences were noted between the two groups , but there was no clinical difference . We found no clinical advantage to the use of \" booster \" RBC transfusions in growing premature infants", "AIM To determine the haemodynamic effects of dopamine and volume expansion in preterm neonates . Effect parameters were mean arterial blood pressure ( MABP ) , left ventricular output ( LVO ) and global cerebral blood flow ( CBF ) . METHODS In a r and omised , clinical control trial 36 preterm neonates were r and omised to receive either dopamine 5 microg/kg per min , volume expansion with albumin 20 % 15 ml/kg or no treatment . Parameters were measured before and 2 h after initiation of treatment . RESULTS Dopamine was effective in increasing MABP ; both treatments increased LVO , whereas no significant difference between the treatment groups and the control group could be demonstrated with regard to CBF . CONCLUSION No effect on global cerebral blood flow could be demonstrated in this study , despite significant effects on systemic circulatory parameters . However , the variance on the measurement of cerebral blood flow indicates that a small but clinical ly significant effect may have been overlooked", "To assess the rationale of albumin priming prior to exchange transfusions , 42 hyperbilirubinemic infants who required exchange transfusions were r and omly assigned to one of two groups . Group I consisted of 15 infants who were given intravenously 1 gm/kg of salt-poor human serum albumin one hour before the exchanges . Group II , which consisted of 27 infants , received simple exchanges . No statistical differences were found in variations in reserve albumin-binding capacity , bilirubin , albumin , or red cell bilirubin at pre and one-hour post albumin infusion in the primed infants . The amount of bilirubin removed per kilogram is directly correlated to plasma bilirubin concentration ( r=0.87 ) . No significant difference in efficiency on bilirubin removal was seen between the two groups . Beneficial effects of albumin therapy was apparent only in those infants with low RABC as determined by the sephadex gel filtration technique", "AIM To compare the efficacy of a colloid ( 5 % albumin ) and a crystalloid ( isotonic saline ) solution for treating hypotension in mechanically ventilated preterm infants . METHODS Sixty three preterm infants weighing 540 to 1950 g at birth and with gestational ages of 23 to 34 weeks , who developed hypotension ( mean arterial pressure < 25 , 30 , and 35 mm Hg for infants with birthweight < 1 , 1 - 1.49 , and 1.5 - 1.99 kg , respectively ) within the first 2 hours of life , were r and omly allocated to receive intravenous infusions at 10 ml/kg of either 5 % albumin ( group 1 , n=32 ) or isotonic ( 0.9 % ) saline ( group 2 , n=31 ) . Inotropic support with dopamine infusion was given if the infants remained hypotensive after a total of three infusions ( 30 ml/kg ) . Subsequent extra doses of volume exp and er in the form of 5 % albumin was given , depending on the infant ’s blood pressure . RESULTS There was no difference in the volume of the test solutions required between the two groups . Outcome , as assessed by the number of infants requiring inotropic support and death or chronic lung disease , did not differ between the groups . After inotropic support , however , group 1 required significantly more volume exp and er to maintain normal blood pressure ( median : 27.5 ml/kgvs 10 ml/kg ; P=0.0187 ) and had a higher mean ( SEM ) percentage weight gain within the first 48 hours of life ( at 24 hours : 6.3(1.3)% vs 3.3(0.8)% ; P=0.049 ; at 48 hours : 5.9(1.9)%vs 0.9(1.7)% ; P=0.045 ) . The difference in weight gain was significant at 48 hours even when only those infants not requiring inotropic support or extra 5 % albumin were compared ( group 1 : 1.5(1.5)% , group 2 : -4.2(1.1)% ; P = 0.027 ) . CONCLUSIONS Isotonic saline is as effective as 5 % albumin for treating hypotension in preterm infants , and it has the additional advantage of causing less fluid retention in the first 48 hours", "OBJECTIVE To investigate whether the haemodynamic effects of the st and ard 2 - 3 h blood transfusion increases the risk for intraventricular haemorrhage ( IVH ) and patent ductus arteriosus ( PDA ) in very low birthweight infants . METHODOLOGY In a r and omized controlled study , haemodynamic changes using slow and rapid transfusion were compared . Twenty-seven very low birthweight infants were divided between 12h ( n = 14 ) and 3h ( n = 13 ) transfusion groups . Blood pressure , ejection fraction ( EF ) , anterior cerebral artery pulsatility index ( PI ) , blood gases , serum electrolytes and haematocrit were measured pre- and post-transfusion . Infectious status was also monitored . RESULTS Blood pressure ( 48.1/25.5 vs 55.7/30.2 mmHg ) and EF ( 0.68 vs 0.73 ) increased significantly during rapid transfusion ( P<0.01 ) but remained stable with slow transfusion . Serum potassium , base excess and incidence of infection did not increase in either group . CONCLUSIONS Slow transfusion causes less haemodynamic disturbance than rapid transfusion , thereby preventing the potential risk for IVH and PDA", "Twenty healthy infants weighing less than 2,000 gm were studied at low ( 3.6 ml/kg/hr ) or high ( 10.3 ml/kg/hr ) rates of intravenous infusion . Inulin clearance determined by the constant infusion method was greater at the high rate of infusion ( p = less than 0.05 ) . Inulin clearance in two groups of infants over 2,000 gm studies at the same low or high rates of infusion did not increase at the higher rate of infusion . Since the GFR in infants less than 2,000 gm depends partially on the rate of intravenous infusion , small , healthy preterm infants may benefit from a rate of fluid administration greater than the low rate . When studies at low and high rates of infusion were compared in the 20 infants less than 2,000 gm , the fractional urinary sodium excretion increased with the increased fluid load . Delivery of fluid from the proximal tubule ( CH2O = Na per dl GFR ) increased ( p less than 0.005 ) . Free-water clearance and the absolute volume of urine increased at the high rate of infusion . These data indicate that the healthy preterm infant less than 2,000 gm , like the adult , compensates by increasing free-water clearance and urine volume when challenged with a large fluid load . Although fluid changes of short duration are appropriately h and led , the effect of continuous rapid infusion on water and sodium balance in infants of this size remains to be determined", "Serial M-mode echocardiograms were performed during days 3 - 20 of life in 73 low-birth-weight infants r and omized on day 3 of life to ' high ' ( n = 40 ) and ' low ' ( n = 33 ) fluid regimens design ed to give significantly different maintenance fluid intakes ( 172 + /- 25 and 121 + /- 13 ml/kg/day , mean + /- SD , respectively , p less than 0.001 ) . The groups were comparable with respect to birth weight , gestational age , incidence of respiratory distress syndrome and mean number of serial echocardiograms performed per infant ( 9 and 9 ) , respectively . Calorie and electrolyte intake were not controlled in the study design . Cumulative echocardiographic data were compared by unpaired t test . Left ventricular end diastolic diameter , right ventricular end diastolic diameter , septal excursion , left ventricular posterior wall excursion and left atrial to aortic root ratio were slightly but statistically significantly larger in the ' high ' fluid group . Comparison of regression coefficients showed that left ventricular end-diastolic diameter tended to rise with postnatal age in the ' high ' group and fall with postnatal age in the ' low ' group . Left atrial to aortic root ratio tended to fall with postnatal age in the ' low ' group relative to the ' high ' group . These differences in echocardiographic measurements may reflect adaptation of the circulation to a degree of chronic volume overload in low-birth-weight infants", "We studied 170 premature infants with birth weights between 751 and 2000 g in a r and omized sequential trial comparing \" high \" and \" low \" volumes of fluid intake . Beginning on the third day of life , the low-volume group received only enough water to meet average estimated requirements , and the high-volume group received an excess of at least 20 ml per kilogram of body weight per day ( mean excess , 47 ml per kilogram per day ) . Sequential analysis showed that the risk of patent ductus arteriosus with congestive heart failure was greater in infants receiving the high-volume regimen . Thirty-five of 85 infants in the high-volume group acquired murmurs consistent with patent ductus arteriosus , and 11 of these 35 had congestive heart failure . Only nine of 85 infants in the low-volume group had murmurs consistent with patent ductus arteriosus , and two of these nine had congestive heart failure . More cases of necrotizing enterocolitis also occurred in the high-volume group . We conclude that limitation of fluid intake to amounts estimated to meet requirements for excretion , insensible loss , and growth can reduce the risks of patent ductus arteriosus and congestive heart failure in premature infants", "Despite advances in biophysical and biochemical monitoring of the fetus in labor and delivery , neonatal asphyxia , hypoxic ischemic encephalopathy ( HIE ) , and related brain edema ( BE ) still contribute heavily to neonatal mortality and morbidity rates . The therapeutic dilemma that confronts physicians in the management of HIE and associated BE in the newborn infant is not entirely bleak . In animal models , brain damage is diminished by early intervention ( free radical scavengers , brain cooling , etc . ) , but only few regimens have been applied to the care of asphyxiated infants . On the purely physiologic basis that maintenance of adequate plasma volume is preserved and controlled by plasma protein levels , therapy with human albumin solutions theoretically would increase plasma oncotic pressure and prevent loss of intravascular volume . Certainly , then , it should facilitate increased transcapillary fluid absorption from the interstitial spaces and removal of the excess fluid already present . In experimental studies , human serum albumin was found to significantly reduce BE . Treatment with albumin infusion in posttraumatic BE has been reported to reduce both mortality and morbidity rates . Albumin is a physiologic agent and has no antigenic properties , there is no risk of hepatitis virus contamination , and it may improve binding of bilirubin with a half-life of 19 days . Use of mannitol and other diuretics in neonatal BE may cause deterioration of the hemodynamic state . On the basis of this concept , 18 newborn infants ( mean ± SD gestational age : 38.8 ± 1.9 ; mean ± SD birth weight : 3010 ± 480 gr ; male-to-female ratio : 13/5 ) diagnosed with neonatal asphyxia and BE were enrolled in a clinical trial conducted in the neonatology unit of Dicle University Hospital , Turkey . All patients had restricted fluid administration and adequate delivery of oxygen in addition to supportive management . On the second day of treatment , nine of the neonates were assigned r and omly to receive 20 % human albumin solution ( 0.5 gr/kg ) , and the others were administered the routine fluid . Caretakers of the patients were blinded to albumin administration , and informed consent was obtained from parents . Clinical symptom scores modified from the Apgar scoring system were serially recorded ( Table 1 ) . Wilcoxon Matched-pairs , Mann – Whitney U , and Fisher Exact tests were used for statistical analysis . There were no significant differences between the two groups in birth weight , gestational age , gender , and baseline clinical and laboratory variables . Compared with the control group , the group receiving human Department of Pediatrics , Dicle University Medical School Hospital , Diyarbakir , Turkey . * Address for correspondence : Department of Pediatrics , Dicle University Medical School Hospital , Diyarbakir , Turkey ; e-mail :", "BACKGROUND The purpose of the present study was to evaluate the effect of intravenous albumin administration on the serum total and unbound bilirubin values in term non-hemolytic hyperbilirubinemic neonates during intensive phototherapy . METHODS Fifty-eight infants ( gestational age 39.4 + /- 1.4 weeks ; birth weight 3,245 + /- 435 g ) were given phototherapy with similar light energy . Twenty infants ( control group ) received only phototherapy , while 38 others ( albumin-treated group ) were also given human albumin at 1 g/kg bodyweight , i.v . , during the first 2 h of phototherapy . RESULTS When comparing changes in total and unbound bilirubin values 0 , 2 , 6 and 24 h after entering the study between the albumin-treated group and the control group , there was a significant reduction in the serum unbound bilirubin values at the end of albumin treatment and at 6 and 24 h. However , there was no significant reduction in total serum bilirubin values during the study period . In the albumin-treated group , the mean serum unbound bilirubin reduction from the baseline level at the end of albumin treatment and at 6 and 24 h was 0.40 + /- 0.19 , 0.41 + /- 0.20 and 0.43 + /- 0.20 microg/dL , respectively . CONCLUSIONS The results suggest that albumin priming may be effective for an immediate reduction in serum unbound bilirubin values , the fraction that is potentially neurotoxic", "In a prospect i ve study hemodynamic effects of dobutamine or dopamine ( 10 micrograms/kg/min ) were investigated in 20 preterm infants who had protracted arterial hypotension refractory to volume therapy . Doppler ultrasonography of the superior mesenteric artery ( SMA ) was applied to verify intestinal perfusion and blood pressure was recorded in parallel . Mean arterial pressure ( MAP ) raised significantly in both groups ( from 31.0 + /- 6.8 to 37.7 + /- 9.8 mm Hg during dobutamine and from 27.7 + /- 3.6 to 36.0 + /- 9.3 mm Hg during dopamine ) . Mean blood flow velocity increased from 25.8 + /- 13.5 to 31.5 + /- 16 cm/s with dobutamine and from 16.3 + /- 5.0 to 19.0 + /- 6.0 cm/s with dopamine ( significant for dobutamine ) . Vascular resistance of SMA ( indicated by resistance index ; RI ) decreased from 0.81 + /- 0.07 to 0.74 + /- 0.11 for dobutamine and from 0.89 + /- 0.06 to 0.79 + /- 0.07 for dopamine ( significant for both groups ) . These data indicate that in the dose tested here both catecholamines are equally effective in raising MAP and lead to a significant increase of intestinal perfusion . Thus , a negative impact on mesenteric blood supply , predisposing to necrotizing enterocolitis , is not probable", "We measured the influence of maturation and early freshly frozen plasma infusion ( FFP ) on renal function ( day 2 and day 5 ) in preterm infants in intensive care ; they were divided into two groups , those with gestational ages less than 30 weeks ( G less than 30 ) and those with gestational ages of 30 - 34 weeks ( G 30 - 34 ) . A total of 35 infants was studied . The infants were r and omly assigned to one of two treatment groups , one receiving FFP , the other not , yielding four study groups ; G less than 30 and no FFP ( 8 infants ) , G less than 30 and FFP ( 8 infants ) , G 30 - 34 and no FFP ( 9 infants ) and G 30 - 34 and FFP ( 10 infants ) . The infants in the two FFP groups received FFP 10 ml/kg on days 1 - 3 . FFP did not significantly influence creatinine clearance ( CCr ) or the urinary sodium excretion rate either in G less than 30 or G 30 - 34 . CCr was significantly lower ( p less than 0.001 ) and fractional urinary sodium excretion significantly higher ( p less than 0.002 ) in infants of G less than 30 than in infants of G 30 - 34 . Infants of G less than 30 had significantly higher plasma potassium concentrations ( p less than 0.01 ) than infants of G 30 - 34 . Despite the low CCr and the high urinary sodium excretion rate , infants of G less than 30 had stable fluid and electrolyte balance" ]

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[ "Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials", "The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study.", "Differences in Weight Loss Between Persons on Standard Balanced vs Nutrigenetic Diets in a Randomized Controlled Trial.", "Evaluation of weight loss and adipocytokines levels after two hypocaloric diets with different macronutrient distribution in obese subjects with rs9939609 gene variant.", "FTO predicts weight regain in the Look AHEAD Clinical Trial", "Impact of Positive Family History and Genetic Risk Variants on the Incidence of Diabetes", "Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study.", "Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study.", "Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries", "A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes", "Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans", "Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963 Variant with Body Weight Loss", "The FTO genotype as a useful predictor of body weight maintenance: initial data from a 5-year follow-up study.", "Fat mass- and obesity-associated genotype, dietary intakes and anthropometric measures in European adults: the Food4Me study." ]

[ "Clinical ly relevant weight loss is achievable through lifestyle modification , but unintentional weight regain is common . We investigated whether recently discovered genetic variants affect weight loss and /or weight regain during behavioral intervention . Participants at high-risk of type 2 diabetes ( Diabetes Prevention Program [ DPP ] ; N = 917/907 intervention/comparison ) or with type 2 diabetes ( Look AHEAD [ Action for Health in Diabetes ] ; N = 2,014/1,892 intervention/comparison ) were from two parallel arm ( lifestyle vs. comparison ) r and omized controlled trials . The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2–4 after a minimum of 3 % weight loss were tested . Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD . No such effect was observed across comparison arms , leading to a nominally significant single nucleotide polymorphism × treatment interaction ( P = 4.3 × 10−3 ) . However , this effect was not significant at a study -wise significance level ( Bonferroni threshold P < 5.8 × 10−4 ) . Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials , directly or via interactions with lifestyle", "The common single-nucleotide polymorphism in the FTO ( fat mass and obesity associated ) gene is consistently associated with an increased risk of obesity . However , the knowledge of a potential modifying effect of the FTO gene on changes in body weight achieved by lifestyle intervention is limited . We examined whether the FTO gene variant ( rs9939609 , T/A ) is associated with body weight and BMI and long-term weight changes in the Finnish Diabetes Prevention Study ( DPS ) . Altogether , 522 ( aged 40 - 65 years ; BMI > or=25 kg/m(2 ) ) subjects with impaired glucose tolerance ( IGT ) were r and omized to control and lifestyle intervention groups . SNP rs9939609 was genotyped from 502 subjects . At baseline , those with the AA genotype had higher BMI than subjects with other genotypes ( P = 0.006 ) . The association was observed in women ( P = 0.016 ) but not in men . During the 4-year follow-up , the subjects with the AA genotype had consistently the highest BMI ( P = 0.009 ) in the entire study population . The magnitude of weight reduction was greater in the intervention group , but the risk allele did not modify weight change in either of the groups . Our results confirm the association between the common FTO variant and BMI in a cross-sectional setting and during the long-term lifestyle intervention . We did not observe association between FTO variant and the magnitude of weight reduction achieved by long-term lifestyle intervention . Based on the results from the DPS , it is unlikely that the common variant of the FTO gene affects the success of lifestyle modification on weight loss", "BACKGROUND & AIMS Many companies provide genetic tests for obesity-related polymorphisms ( nutrigenetics ) and make dietary recommendations for weight loss that are based on the results . We performed a r and omized controlled trial to determine whether more participants who followed a nutrigenetic-guided diet lost ≥5 % of their body weight than participants on a st and ard balanced diet for 8 and 24 weeks . METHODS We performed a prospect i ve study of 51 obese or overweight U.S. veterans on an established weight management program at the Veterans Administration San Diego Healthcare System ( the MOVE ! program ) . Participants were r and omly assigned to groups placed on a nutrigenetic-guided diet ( balanced , low-carbohydrate , low-fat , or Mediterranean ; n = 30 ) or a st and ard balanced diet ( n = 21 ) . Nutrigenetic diets were selected on the basis of results from the Pathway FIT test . RESULTS There was no significant difference in the percentage of participants on the balanced diet vs the nutrigenetic-guided diet who lost 5 % of their body weight at 8 weeks ( 35.0 % ± 20.9 % vs 26.9 % ± 17.1 % , respectively ; P = .28 ) or at 24 weeks . Both groups had difficulty adhering to the diets . However , adherence to the nutrigenetic-guided diet correlated with weight loss ( r = 0.74 ; P = 4.0 × 10(-5 ) ) , but not adherence to st and ard therapy ( r = 0.34 ; P = .23 ) . Participants who had low-risk polymorphisms for obesity lost more weight than all other participants at 8 weeks ( 5.0 % vs 2.9 % , respectively ; P = .02 ) and had significantly greater reductions in body mass index ( 6.4 % vs 3.6 % , respectively ; P = .03 ) and waist circumference ( 6.5 % vs 2.6 % , respectively ; P = .02 ) at 24 weeks . CONCLUSIONS In a prospect i ve study , a nutrigenetic-based diet did not increase weight loss compared with a st and ard balanced diet . However , genetic features can identify individuals most likely to benefit from a balanced diet weight loss strategy ; these findings require further investigation . Clinical Trials.gov number : NCT01859403", "BACKGROUND Common polymorphisms of the fat mass and obesity associated gene ( FTO ) have been linked to obesity in some population s. One of these genetic variants ( rs9939609 ) has been related to an increased risk of obesity . OBJECTIVE Our aim was to evaluate weight loss and adipocytokine levels after two hypocaloric diets with different macronutrient distribution in obese subjects with RS9939609 gene variant . DESIGN 305 obese patients were enrolled in a prospect i ve way . In the basal visit , patients were r and omly allocated during 3 months to low carbohydrates and low fat . RESULTS After treatment with both diets and in both genotypes , weight , fat mass , waist circumference and systolic blood pressures decreased . With the diet type I and in TT genotype , insulin ( -6.6 ± 9.8 IU/L ) and homeostasis model assessment ( -2.9 ± 6.1 units ) decreased . With the diet type II and in both genotypes ( wild and mutant type ) , insulin ( -5.2 ± 6.1 vs. -3.8 ± 6.1 IU/L ; p < 0.05 ) and homeostasis model assessment ( -2.4 ± 4.8 vs. -1.1 ± 3.8 kg ; p < 0.05 ) decreased . In the A allele group , a significant decrease was detected in total cholesterol levels ( -11.5 ± 20.1 mg/dL ) , low density lipoprotein cholesterol levels ( -13.2 ± 20.9 mg/dL ) and c-reactive protein levels ( -1.3 ± 3.8 mg/dL ) secondary to weight loss after treatment with diet II . The decrease of leptin levels was higher in mutant type group than wild type group with low fat diet ( -10.3 ± 36.1 vs. -28.6 ± 53.7 ng/mL ; p < 0.05 ) . CONCLUSION Metabolic improvement secondary to weight loss was better in A carriers with a low fat hypocaloric diet", "Background : Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity . We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss . Methods : Established obesity risk alleles available on the Illumina CARe iSelect ( IBC ) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD ( Action for Health in Diabetes ) , a r and omized trial to determine the effects of intensive lifestyle intervention ( ILI ) and diabetes support and education ( DSE ) on cardiovascular morbidity and mortality . Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and r and omized treatment arm in predicting weight change at year 1 , and weight regain at year 4 among individuals who lost 3 % or more of their baseline weight by year 1 . Results : No single-nucleotide polymorphisms ( SNPs ) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1 . However , fat mass and obesity associated gene ( FTO ) rs3751812 predicted weight regain within DSE ( 1.56 kg per risk allele , P=0.005 ) , but not ILI ( P=0.761 ) , result ing in SNP × treatment arm interaction ( P=0.009 ) . In a partial replication of prior research , the obesity risk ( G ) allele at BDNF rs6265 was associated with greater weight regain across treatment arms ( 0.773 kg per risk allele ) , although results were of borderline statistical significance ( P=0.051 ) . Conclusions : Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss", "OBJECTIVE We aim ed to investigate the influence of positive family history ( FH+ ) of diabetes and 19 known genetic risk loci on the effectiveness of lifestyle changes and their predictive value on the incidence of type 2 diabetes in the Finnish Diabetes Prevention Study ( DPS ) . RESEARCH DESIGN AND METHODS A total of 522 subjects with impaired glucose tolerance ( IGT ) were r and omized into the control ( n = 257 ) and intervention ( n = 265 ) groups . The mean follow-up was 6.2 years ( median 7 years ) , and the lifestyle intervention , aim ed at weight reduction , healthy diet , and increased physical activity , lasted for 4 years ( range 1–6 years ) . An oral glucose tolerance test ( OGTT ) and assessment of basic clinical variables were performed annually . RESULTS The effect of intervention on the incidence of diabetes was almost similar in subjects with FH+ compared with subjects with a negative family history ( FH− ) of diabetes during the entire follow-up . In the Cox model , including FH , genetic risk SNPs , and r and omization group , and adjusted for the effects of age , sex , BMI , and study center , only lifestyle intervention had a significant effect ( hazard ratio 0.55 , 95 % CI 0.41–0.75 , P < 0.001 ) on the incidence of diabetes . Further analyses showed that in addition to the baseline glucose and insulin values , 1-year changes in 2-h glucose and 2-h insulin achieved by lifestyle intervention had a significant effect on the incidence of diabetes . CONCLUSIONS These results emphasize the effectiveness of lifestyle intervention in reducing the risk of diabetes in high-risk individuals independently of genetic or familial risk of type 2 diabetes", "BACKGROUND Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes . OBJECTIVE This study examined single nucleotide polymorphisms ( SNPs ) in presumed nutrient-sensitive c and i date genes for obesity and obesity-related diseases for main and dietary interaction effects on weight , waist circumference , and fat mass regain over 6 mo . DESIGN In total , 742 participants who had lost ≥ 8 % of their initial body weight were r and omly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein . The SNP main and SNP-diet interaction effects were analyzed by using linear regression models , corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile ( Q-Q ) plots . RESULTS After correction for multiple testing , none of the SNPs were significantly associated with weight , waist circumference , or fat mass regain . Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo ( -3.1 cm/allele ; 95 % CI : -4.6 , -1.6 ; P/Bonferroni-corrected P = 0.000039/0.076 ) , independently of diet . Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP , TNF , and KCNJ11 for main effects ; in LPL and TUB for glycemic index interaction effects on waist circumference regain ; in GHRL , CCK , MLXIPL , and LEPR on weight ; in PPARC1A , PCK2 , ALOX5AP , PYY , and ADRB3 on waist circumference ; and in PPARD , FABP1 , PLAUR , and LPIN1 on fat mass regain for dietary protein interaction . CONCLUSION The observed effects of SNP-diet interactions on weight , waist , and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet . This trial was registered at clinical trials.gov as NCT00390637", "OBJECTIVE To examine whether the effect of FTO loci on obesity-related traits could be modified by physical activity ( PA ) levels in European adults . METHODS Of 1,607 Food4Me participants r and omized , 1,280 were genotyped for FTO ( rs9939609 ) and had available PA data . PA was measured objective ly using accelerometers ( TracmorD , Philips ) , whereas anthropometric measures [ BMI and waist circumference ( WC ) ] were self-reported via the Internet . RESULTS FTO genotype was associated with a higher body weight [ β : 1.09 kg per risk allele , ( 95 % CI : 0.14 - 2.04 ) , P = 0.024 ] , BMI [ β : 0.54 kg m(-2 ) , ( 0.23 - 0.83 ) , P < 0.0001 ] , and WC [ β : 1.07 cm , ( 0.24 - 1.90 ) , P = 0.011 ] . Moderate-equivalent PA attenuated the effect of FTO on BMI ( P[interaction ] = 0.020 ) . Among inactive individuals , FTO increased BMI by 1.06 kg m(-2 ) per allele ( P = 0.024 ) , whereas the increase in BMI was substantially attenuated among active individuals ( 0.16 kg m(-2 ) , P = 0.388 ) . We observed similar effects for WC ( P[interaction ] = 0.005 ) : the FTO risk allele increased WC by 2.72 cm per allele among inactive individuals but by only 0.49 cm in active individuals . CONCLUSIONS PA attenuates the effect of FTO genotype on BMI and WC . This may have important public health implication s because genetic susceptibility to obesity in the presence of FTO variants may be reduced by adopting a physically active lifestyle", "Abstract Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases , promoting better health across the life-course and increasing well-being . However , realising this potential will require the development , testing and implementation of much more effective behaviour change interventions than are used conventionally . Therefore , the aim of this study was to conduct a multi-centre , web-based , proof-of-principle study of personalised nutrition ( PN ) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population -based advice . A total of 5,562 volunteers were screened across seven European countries ; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial . Participants were r and omly assigned to one of the following intervention groups for a 6-month period : Level 0—control group — receiving conventional , non-PN advice ; Level 1—receiving PN advice based on dietary intake data alone ; Level 2—receiving PN advice based on dietary intake and phenotypic data ; and Level 3—receiving PN advice based on dietary intake , phenotypic and genotypic data . A total of 1,607 participants had a mean age of 39.8 years ( ranging from 18 to 79 years ) . Of these participants , 60.9 % were women and 96.7 % were from white-European background . The mean BMI for all r and omised participants was 25.5 kg m−2 , and 44.8 % of the participants had a BMI ≥ 25.0 kg m−2 . Food4Me is the first large multi-centre RCT of web-based PN . The main outcomes from the Food4Me study will be su bmi tted for publication during 2015", "Introduction : The aim of this study was to analyze the effects of the rs9939609 ( T/A ) gene variant in fat mass and obesity-associated gene ( FTO ) on body weight changes after 3 years and its modification by a r and omized nutritional intervention with a Mediterranean-style diet in a population of subjects at high cardiovascular risk . Design : A sub study of PREDIMED , which is a r and omized trial aim ed at assessing the effect of the Mediterranean diet ( MD ) for primary cardiovascular disease prevention . There were three nutritional intervention groups : two of them with a Mediterranean-style diet and the third was a control group advised to follow a conventional low-fat diet . Subjects : A total of 776 high cardiovascular risk subjects aged 55–80 years . Measurements : Anthropometric measurements were recorded at baseline and at 3 years . The participants were genotyped by RT-PCR , followed by allelic discrimination . Results : Homozygous subjects had the highest baseline body weight . The dominant model showed that subjects carrying the A allele had the lowest body weight gain ( B=−0.685 ; P=0.022 ) after 3 years of nutritional intervention compared with nonmutated subjects ( TT genotype ) regardless of the nutritional intervention . Moreover , this effect was statistically significant in carriers of the A allele only among those allocated to the MD groups ( B=−0.830 ; P=0.018 ) , but it was not significant among those allocated to the control group ( P for interaction=0.649 ) . Conclusion : This study confirmed the association between body weight and the FTO rs9939609 polymorphism . Interestingly , our results showed that , although at baseline the A allele was associated with higher body weight , after 3 years of nutritional intervention with a Mediterranean-style-diet , A-allele carriers had lower body weight gain than wild type subjects . No interaction between nutritional intervention and the polymorphism was found", "Background : The A risk allele of rs9939609 of the fat mass- and obesity-associated gene ( FTO ) increases body fat mass . Objective : To examine whether FTO rs9939609 affects obese individuals ' response to a high-fat , low-carbohydrate ( CHO ) ( HF ) or low-fat , high-CHO ( LF ) , hypo-energetic diet and whether the effect of the FTO variant depends on dietary fat and CHO content . Design : In a 10-week , European , multi-centre dietary intervention study 771 obese women and men were r and omized to either LF ( 20–25 % of energy ( % E ) from fat , 60–65%E from CHO ) or HF ( 40–45%E from fat , 40–45%E from CHO ) , hypo-energetic diet ( measured resting metabolic rate multiplied by 1.3–600 kcal day−1 ) . Body weight , fat mass ( FM ) , fat-free mass ( FFM ) , waist circumference ( WC ) , resting energy expenditure ( REE ) , fasting fat oxidation as % of REE ( FatOx ) , insulin release ( HOMA-β ) and a surrogate measure of insulin resistance ( HOMA-IR ) were measured at baseline and after the intervention . In all , 764 individuals were genotyped for FTO rs9939609 . Results : For A-allele carriers the drop-out rate was higher on HF than LF diet ( in AT , P=0.002 ; in AT/AA combined , P=0.003 ) . Among those individuals completing the intervention , we found no effect of FTO rs9939609 genotype on Δweight , ΔFM , ΔFFM , ΔWC or ΔFatOx . However , participants with TT had a smaller reduction in REE on LF than on HF diet ( 75 kcal/24 h ; interaction : P=0.0055 ) . These individuals also showed the greatest reduction in HOMA-β and HOMA-IR ( interaction : P=0.0083 and P=0.047 ) . Conclusion : The FTO rs9939609 may interact with the macronutrient composition in weight loss diets in various ways ; carriers of the A allele on LF diet appear to have a lower risk for drop out , and TT individuals have a smaller decrease in REE and greater decrease in HOMA-β and HOMA-IR on LF than on HF diet", "Background / Aims : Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions . The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions . Methods : 167 subjects enrolled in a personalized nutritional intervention for weight loss ( 3 - 6 weeks ) were examined for anthropometric measurements , dietary habits and physical activity at baseline and at the first follow-up visit . Three polymorphisms , which have previously been associated with body weight regulation , rs10830963 ( MTNR1B ) , rs9939609 ( FTO ) and rs17782313 ( MC4R ) , were analyzed using the Luminex ® 100/200 ™ System . Results : After adjusting for covariates , females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype . In the total population , carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome . Moreover , among women , higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant . Conclusions : Our data evidence d that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet . This association was influenced by FTO and MC4R loci and modified by baseline protein intake", "OBJECTIVE We examined associations between the fat-mass and obesity-associated ( FTO ) gene ( rs9939609 ) and any weight change over a 5-year period following a 14-week lifestyle intervention among middle-aged Japanese women . MATERIAL S/ METHODS One hundred twenty-eight Japanese women ( BMI > 25 kg/m² ) participated in a 14-week weight loss intervention between 2004 and 2006 . Of the participants , 62 consented to the 5-year follow-up measurement session . Of these women , 47 women who achieved a weight loss of at least 10 % from their baseline values during the 14-week intervention were included in the analysis . Body weight , body fat , abdominal fat assessed by CT scans , and metabolic risk factors ( i.e. , blood pressure , lipids , and glucose ) were measured at baseline , post-intervention , and at the 5-year follow-up . RESULTS During the 5-year non-intervention period , increases in body weight , fat mass , total abdominal fat , and subcutaneous abdominal fat were significantly greater in subjects with the homozygous minor allele ( AA genotype , n=4 ; 8.5 % ) than in those with the homozygous major allele ( TT genotype , n=31 ; 66.0 % ) or heterozygous allele ( TA genotype , n=12 ; 25.5 % ) . In multiple regression analyses , the variation in rs9939609 was a significant and independent predictor ( P<0.001 ) for regaining weight during the 5-year follow-up . CONCLUSIONS Our data suggest that Japanese women with the risk allele ( AA ) of rs9939609 may have more difficulty preventing fat gain from reoccurring after weight loss intervention than women with the other genotypes", "The interplay between the fat mass- and obesity-associated ( FTO ) gene variants and diet has been implicated in the development of obesity . The aim of the present analysis was to investigate associations between FTO genotype , dietary intakes and anthropometrics among European adults . Participants in the Food4Me r and omised controlled trial were genotyped for FTO genotype ( rs9939609 ) and their dietary intakes , and diet quality scores ( Healthy Eating Index and PREDIMED-based Mediterranean diet score ) were estimated from FFQ . Relationships between FTO genotype , diet and anthropometrics ( weight , waist circumference ( WC ) and BMI ) were evaluated at baseline . European adults with the FTO risk genotype had greater WC ( AA v. TT : + 1·4 cm ; P=0·003 ) and BMI ( + 0·9 kg/m2 ; P=0·001 ) than individuals with no risk alleles . Subjects with the lowest fried food consumption and two copies of the FTO risk variant had on average 1·4 kg/m2 greater BMI ( Ptrend=0·028 ) and 3·1 cm greater WC ( Ptrend=0·045 ) compared with individuals with no copies of the risk allele and with the lowest fried food consumption . However , there was no evidence of interactions between FTO genotype and dietary intakes on BMI and WC , and thus further research is required to confirm or refute these findings" ]

[ "3407717", "11418543", "21198803", "16684985", "21356537", "10445898", "17101889", "2396286", "10445896", "1327666", "4194475", "4194605", "14722336", "19347683", "15121650", "17116916", "20945236", "19606455", "11885210" ]

[ "Comparing Dutch Case management care models for people with dementia and their caregivers: The design of the COMPAS study", "Research Paper: Controlled Trial of Direct Physician Order Entry: Effects on Physicians' Time Utilization in Ambulatory Primary Care Internal Medicine Practices", "Randomized controlled trial of a dementia care programme for families of home-resided older people with dementia.", "Effectiveness of collaborative care for older adults with Alzheimer disease in primary care: a randomized controlled trial.", "Effectiveness of case management among older adults with early symptoms of dementia and their primary informal caregivers: a randomized clinical trial.", "Effects of the Medicare Alzheimer's Disease Demonstration on nursing home entry.", "Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease", "The Effectiveness of a Home Care Program for Supporting Caregivers of Persons with Dementia in Developing Countries: A Randomised Controlled Trial from Goa, India", "Effects of the Medicare Alzheimer's Disease Demonstration on the use of community-based services.", "(Cost)-effectiveness of case-management by district nurses among primary informal caregivers of older adults with dementia symptoms and the older adults who receive informal care: design of a randomized controlled trial [ISCRTN83135728]", "Caregiver Supports: Outcomes From the Medicare Alzheimer's Disease Demonstration", "Effects of the Medicare Alzheimer's Disease Demonstration on Medicare Expenditures", "Effects of a caregiver intervention on negative caregiver appraisals of behavior problems in patients with Alzheimer's disease: results of a randomized trial.", "Dementia care consultation for family caregivers: Collaborative model linking an Alzheimer's association chapter with primary care physicians", "Sustained benefit of supportive intervention for depressive symptoms in caregivers of patients with Alzheimer's disease.", "The Effect of a Disease Management Intervention on Quality and Outcomes of Dementia Care", "Implementing dementia care models in primary care settings: The Aging Brain Care Medical Home", "A randomized controlled trial to examine the effectiveness of case management model for community dwelling older persons with mild dementia in Hong Kong.", "Continuum of care for Alzheimer's disease: a nurse education and counseling program." ]

[ "Background Dementia care in the Netherl and s is shifting from fragmented , ad hoc care to more coordinated and personalised care . Case management contributes to this shift . The linkage model and a combination of intensive case management and joint agency care models were selected based on their emerging prominence in the Netherl and s. It is unclear if these different forms of case management are more effective than usual care in improving or preserving the functioning and well-being at the patient and caregiver level and at the societal cost . The objective of this article is to describe the design of a study comparing these two case management care models against usual care . Clinical and cost outcomes are investigated while care processes and the facilitators and barriers for implementation of these models are considered . Design Mixed methods include a prospect i ve , observational , controlled , cohort study among persons with dementia and their primary informal caregiver in regions of the Netherl and s with and without case management including a qualitative process evaluation . Inclusion criteria for the cohort study are : community-dwelling individuals with a dementia diagnosis who are not terminally-ill or anticipate admission to a nursing home within 6 months and with an informal caregiver who speaks fluent Dutch . Person with dementia-informal caregiver dyads are followed for two years . The primary outcome measure is the Neuropsychiatric Inventory for the people with dementia and the General Health Question naire for their caregivers . Secondary outcomes include : quality of life and needs assessment in both persons with dementia and caregivers , activity of daily living , competence of care , and number of crises . Costs are measured from a societal perspective using cost diaries . Process indicators measure the quality of care from the participant ’s perspective . The qualitative study uses purposive sampling methods to ensure a wide variation of respondents . Semi-structured interviews with stakeholders based on the theoretical model of adaptive implementation are planned . Discussion This study provides relevant insights into care processes , description of two case management models along with clinical and economic data from persons with dementia and caregivers to clarify important differences in two case management care models compared to usual care", "OBJECTIVE Direct physician order entry ( POE ) offers many potential benefits , but evidence suggests that POE requires substantially more time than traditional paper-based ordering methods . The Medical Gopher is a well-accepted system for direct POE that has been in use for more than 15 years . The authors hypothesized that physicians using the Gopher would not spend any more time writing orders than physicians using paper-based methods . DESIGN A r and omized controlled trial of POE using the Medical Gopher system in 11 primary care internal medicine practice s. MEASUREMENTS The authors collected detailed time use data using time motion studies of the physicians and surveyed their opinions about the POE system . RESULTS The authors found that physicians using the Gopher spent 2.2 min more per patient overall , but when duplicative and administrative tasks were taken into account , physicians were found to have spent only 0.43 min more per patient . With experience , the order entry time fell by 3.73 min per patient . The survey revealed that the physicians believed that the system improved their patient care and wanted the Gopher to continue to be available in their practice s. CONCLUSIONS Little extra time , if any , was required for physicians to use the POE system . With experience in its use , physicians may even save time while enjoying the many benefits of POE", "AIM This paper reports a study to examine the effectiveness of a 6-month dementia care programme for Chinese families living with and caring for a relative with dementia , compared with routine family support services in Hong Kong . BACKGROUND Recognizing the adverse psychosocial health effects inherent in dementia care , different psychosocial interventions provided preliminary evidence of their effectiveness in improving family members ' knowledge and skills in caregiving and delaying dementia sufferers ' illness deterioration and institutionalization . Little is known about the effects of such interventions for family caregivers ' psychosocial health conditions , particularly in non-Western population s. METHODS A r and omized controlled trial was conducted with 92 Chinese families of a relative with dementia in two dementia care centres in Hong Kong . They were r and omly selected from a dementia client list and then r and omly assigned to receive either the dementia family care programme ( n=46 ) , or routine care only ( n=46 ) . Clients ' symptoms and institutionalization , and caregivers ' quality of life , burden and social support at recruitment , 1 week , and 12 and 18 months following intervention were measured and compared between the study groups using repeated measures MANOVAS followed by Helmert 's contrast tests . Data was collected over a period of 24 months , between September 2007 and August 2009 . RESULTS Results of the MANOVAS and contrast tests indicated that at 18-month follow-up , participants in the family programme reported significantly greater improvements in clients ' symptoms and institutionalization rates , and caregivers ' quality of life and burden , when compared with their counterparts in the routine care group . CONCLUSION These findings provide evidence that the dementia care family programme can improve the psychosocial functioning of both clients with dementia and their family caregivers in a Chinese population . Further research is recommended to investigate whether this intervention can also apply to families with different socio-economic background s and across cultures", "CONTEXT Most older adults with dementia will be cared for by primary care physicians , but the primary care practice environment presents important challenges to providing quality care . OBJECTIVE To test the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS Controlled clinical trial of 153 older adults with Alzheimer disease and their caregivers who were r and omized by physician to receive collaborative care management ( n = 84 ) or augmented usual care ( n = 69 ) at primary care practice s within 2 US university-affiliated health care systems from January 2002 through August 2004 . Eligible patients ( identified via screening or medical record ) met diagnostic criteria for Alzheimer disease and had a self-identified caregiver . INTERVENTION Intervention patients received 1 year of care management by an interdisciplinary team led by an advanced practice nurse working with the patient 's family caregiver and integrated within primary care . The team used st and ard protocol s to initiate treatment and identify , monitor , and treat behavioral and psychological symptoms of dementia , stressing nonpharmacological management . MAIN OUTCOME MEASURES Neuropsychiatric Inventory ( NPI ) administered at baseline and at 6 , 12 , and 18 months . Secondary outcomes included the Cornell Scale for Depression in Dementia ( CSDD ) , cognition , activities of daily living , re source use , and caregiver 's depression severity . RESULTS Initiated by caregivers ' reports , 89 % of intervention patients triggered at least 1 protocol for behavioral and psychological symptoms of dementia with a mean of 4 per patient from a total of 8 possible protocol s. Intervention patients were more likely to receive cholinesterase inhibitors ( 79.8 % vs 55.1 % ; P = .002 ) and antidepressants ( 45.2 % vs 27.5 % ; P = .03 ) . Intervention patients had significantly fewer behavioral and psychological symptoms of dementia as measured by the total NPI score at 12 months ( mean difference , -5.6 ; P = .01 ) and at 18 months ( mean difference , -5.4 ; P = .01 ) . Intervention caregivers also reported significant improvements in distress as measured by the caregiver NPI at 12 months ; at 18 months , caregivers showed improvement in depression as measured by the Patient Health Question naire-9 . No group differences were found on the CSDD , cognition , activities of daily living , or on rates of hospitalization , nursing home placement , or death . CONCLUSIONS Collaborative care for the treatment of Alzheimer disease result ed in significant improvement in the quality of care and in behavioral and psychological symptoms of dementia among primary care patients and their caregivers . These improvements were achieved without significantly increasing the use of antipsychotics or sedative-hypnotics . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00246896", "BACKGROUND It is believed that timely recognition and diagnosis of dementia is a pre-condition for improving care for both older adults with dementia and their informal caregivers . However , diagnosing dementia often occurs late in the disease . This means that a significant number of patients with early symptoms of dementia and their informal caregivers may lack appropriate care . OBJECTIVES To compare the effects of case management and usual care among community-dwelling older adults with early symptoms of dementia and their primary informal caregivers . DESIGN R and omized controlled trial with measurements at baseline and after 6 and 12 months . SETTING Primary care in West-Friesl and , the Netherl and s. PARTICIPANTS 99 pairs of community-dwelling older adults with dementia symptoms ( defined as abnormal screening for symptoms of dementia ) and their primary informal caregivers . INTERVENTION 12 months of case management by district nurses for both older adults and informal caregivers versus usual care . MEASUREMENTS PRIMARY OUTCOME informal caregiver 's sense of competence . SECONDARY OUTCOMES caregiver 's quality of life , depressive symptoms , and burden , and patient 's quality of life . Process measurements : intervention fidelity and caregiver 's satisfaction with the quality of case management . RESULTS Linear mixed model analyses showed no statistically significant and clinical ly relevant differences over time between the two groups . The process evaluation revealed that intervention fidelity could have been better . Meanwhile , informal caregivers were satisfied with the quality of case management . CONCLUSION This study shows no benefits of case management for older adults with dementia symptoms and their primary informal caregivers . One possible explanation is that case management , which has been recommended among diagnosed dementia patients , may not be beneficial if offered too early . However , on the other h and , it is possible that : ( 1 ) case management will be effective in this group if more fully implemented and adapted or aim ed at informal caregivers who experience more severe distress and problems ; ( 2 ) case management is beneficial but that it is not seen in the timeframe studied ; ( 3 ) case management might have undetected small benefits . This has to be established . Trial registration ISCRTN83135728", "STUDY QUESTION Did the Medicare Alzheimer 's Disease Demonstration , with its goal of improving caregiver outcomes through case management and subsidized community services , affect the nursing home entry rate of treatments with dementia compared to controls ? DATA SOURCES Interviews conducted at baseline and six months thereafter . Measures include date of nursing home entry , client and caregiver health , and income . STUDY DESIGN The demonstration r and omly assigned voluntary applicants into treatment and control groups . Treatment group cases were eligible for case management and for an 80 percent discount on community care benefits , up to about $ 600 per month . DATA COLLECTION All cases received baseline and semi-annual assessment interviews for up to three years after enrollment . Analyses are among cases that remained in the demonstration for more than 30 days after enrollment ( n = 8,095 ) . PRINCIPAL FINDINGS The intervention of case management and subsidized community service had no effect on nursing home entry rates for treatments overall , compared to those of controls , and few effects on treatment subgroups , with the exception of one site where it may have increased nursing home entry rates . CONCLUSIONS Providing case management and subsidized community services with the goal of improving caregiver outcomes may have little effect on nursing home entry rates for people with dementia", "Objective : To determine the effectiveness of a counseling and support intervention for spouse caregivers in delaying time to nursing home placement of patients with Alzheimer disease ( AD ) , and identify the mechanisms through which the intervention accomplished this goal . Methods : We conducted a r and omized controlled trial of an enhanced counseling and support intervention compared to usual care . Participants were a referred volunteer sample of 406 spouse caregivers of community-dwelling patients who had enrolled in the study over a 9.5-year period . The intervention consisted of six sessions of individual and family counseling , support group participation , and continuous availability of ad hoc telephone counseling . Structured question naires were administered at baseline and at regular follow-up intervals , every 4 months for the first year and every 6 months thereafter . Cox proportional hazard models were used to test the effects of the intervention on the time to nursing home placement for the patients after controlling for multiple time-invariant and time-dependent predictors of placement . Results : Patients whose spouses received the intervention experienced a 28.3 % reduction in the rate of nursing home placement compared with usual care controls ( hazard ratio = 0.717 after covariate adjustment , p = 0.025 ) . The difference in model-predicted median time to placement was 557 days . Improvements in caregivers ’ satisfaction with social support , response to patient behavior problems , and symptoms of depression collectively accounted for 61.2 % of the intervention ’s beneficial impact on placement . Conclusion : Greater access to effective programs of counseling and support could yield considerable benefits for caregivers , patients with Alzheimer disease , and society", "Objectives To develop and evaluate the effectiveness of a home based intervention in reducing caregiver burden , promoting caregiver mental health and reducing behavioural problems in elderly persons with dementia . Methodology and Principal Findings This was a r and omised controlled trial in which the person with dementia-caregiver dyad was r and omly allocated either to receive the intervention immediately or to a waiting list group which received the intervention after 6 months . It was carried out in communities based in two talukas ( administrative blocks ) in Goa , India . Mild to moderate cases with dementia ( diagnosed using the DSM IV criteria and grade d using the Clinical Dementia Rating scale ) and their caregivers were included in the trial . Community based intervention provided by a team consisting of Home Care Advisors who were supervised by a counselor and a psychiatrist , focusing on supporting the caregiver through information on dementia , guidance on behaviour management , a single psychiatric assessment and psychotropic medication if needed . We measured caregiver mental health ( General Health Question naire ) , caregiver burden ( Zarit Burden Score ) , distress due to behavioural disturbances ( NPI-D ) , behavioural problems in the subject ( NPI-S ) and activities of daily living in the elder with dementia ( EASI ) . Outcome evaluations were masked to the allocation status . We analysed each outcome with a mixed effects model . 81 families enrolled in the trial ; 41 were r and omly allocated to the intervention . 59 completed the trial and 18 died during the trial . The intervention led to a significant reduction of GHQ ( −1.12 , 95 % CI −2.07 to −0.17 ) and NPI-D scores ( −1.96 , 95%CI −3.51 to −0.41 ) and non-significant reductions in the ZBS , EASI and NPI-S scores . We also observed a non-significant reduction in the total number of deaths in people with dementia in the intervention arm ( OR 0.34 , 95 % CI 0.01 to 1.03 ) . Conclusion Home based support for caregivers of persons with dementia , which emphasizes the use of locally available , low-cost human re sources , is feasible , acceptable and leads to significant improvements in caregiver mental health and burden of caring . Clinical Trials.gov", "STUDY QUESTION Did the Medicare Alzheimer 's Disease Demonstration with its case management and community service waivers affect the use of community-based long-term care services among people with dementia and their primary caregivers ? DATA SOURCES Baseline and periodic caregiver interviews . Measures include client and caregiver attributes and self-reported service use . STUDY DESIGN The demonstration r and omly assigned voluntary applicants into treatment and control groups . Treatment group cases were eligible for case management and for up to $ 699 per month in community care benefits . The actual monthly entitlement varied among the eight demonstration communities due to regional cost and inflation adjustments over time . Analyses are for the year after enrollment . DATA COLLECTION Analyses are of cases surviving six months or more in the community after enrollment ( n = 5,209 ) . Cases received baseline and semi-annual assessment s. PRINCIPAL FINDINGS The intervention of case management and community service reimbursement had a strong , consistent , and positive effect on the likelihood of using home care ( including homemaker/chore services , personal care services , companion services ) and adult day care . Treatment group clients were at least twice as likely as control group clients to be using any of the four community-based services . A similar , but less pervasive effect was achieved with caregiver training and support group participation . Reimbursement provided by the demonstration 's Medicare waiver was generally not sufficient to exceed the level of control group service acquired through private payment . CONCLUSIONS Reimbursement levels within the demonstration may have enabled more individuals to purchase some services , but they were not sufficient to increase the average level of use over those in the control group . No consistent differences between demonstration models were found in service use likelihood or average use among users", "Background Dementia is an incurable disease with devastating consequences for both patients and their relatives . The objective of this study is to describe the study protocol of a r and omized controlled trial with assignment to either usual care or case-management by district nurses , among informal caregivers of older adults with dementia symptoms who live at home and the older adults who receive informal care . Methods / design In this r and omized controlled trial , effectiveness as well as cost-effectiveness of case-management is evaluated . It concerns case-management in early-detected patients with dementia symptoms and their primary informal caregivers . Participants are followed up to twelve months after baseline assessment . The main outcome measure of the effect evaluation is the caregiver 's sense of competence to care for the older person with dementia symptoms . The economic evaluation is performed from a societal perspective . Discussion This is one of the first trials on case-management that includes an economic evaluation . In addition , it concerns a tailor-made intervention in early-detected patients with dementia symptoms and their caregivers . The results of this r and omized controlled trial will provide valuable information for health professionals and policy makers on effectiveness and cost-effectiveness of early tailor-made case-management for patients and their informal caregivers . Moreover , positive effects will challenge current health care systems to move to more pro-active approaches for this group", "A r and omized 3-year study assessed the effect of exp and ed community-based services and case management on 5,254 caregivers of dementia clients . A tested policy concern was whether the financing of formal care would result in a reduction of informal assistance . Unmet needs task assistance for the demonstration 's treatment group caregivers decreased by 30 percent within 6 months and by about 20 percent over 36 months relative to controls . While treatment group members used slightly more formal care over time , there were no differences between treatment and control groups in primary caregiver hours after 36 months , or in the number of tasks in which primary or secondary caregivers provided assistance", "Applicants were r and omized either into a group with a limited Medicare community care service benefit and case management or into a control group receiving their regular medical care . Analyses assess whether or not community care management affected health care use . A tendency toward reduced expenditures was observed for the treatment group , combining all demonstration sites , and when observing each separately . These differences were or approached statistical significance in two sites for Medicare Part A and Parts A and B expenditures averaged over 3 years . Expenditure reductions approached budget neutrality with program costs in two sites", "Behavioral problems are among the most challenging aspects of caring for a person with Alzheimer 's disease . A sample of 406 spouses-caregivers of patients with Alzheimer 's disease was r and omized to an active multicomponent counseling and support intervention condition or to a usual care condition . Caregivers reported on the frequency of troublesome patient behaviors and their reactions to them at baseline and at regular follow-up interviews . R and om-effects regression models over the first 4 years after r and omization revealed that , although the intervention did not affect the frequency of patient behavioral problems , it did significantly reduce caregivers ' reaction ratings . Because caregiver appraisal s have been found to mediate the impact of caregiving stress on depression and to predict nursing home placement rates , they deserve greater attention as an important target of intervention services", "Objective : The primary objective is to report on the efficacy of an individualized dementia care consultation intervention for family caregivers of patients with diagnosed dementia living in the community . The secondary objective is to present evidence on the intervention process to inform the feasibility and sustainability of the model featuring collaboration between primary care physicians and a voluntary sector organization . Method : R and omization was based on primary care physician practice site . In the intervention group , dementia care consultants located at an Alzheimer 's association chapter provided individualized counseling and support over a 12-month period , and sent copies of care plans developed with family caregivers to referring primary care physicians . In the control group , family caregivers received educational and community re source information but no care consultation . Nursing home admission of patients during the 12-month study period was the primary outcome ; secondary outcomes included measures of caregiver self-efficacy for managing dementia , caregiver depressive symptoms , and caregiver burden . Results : A total of 84 family caregivers participated . After adjusting for baseline characteristics , patients whose family caregivers were in the intervention group were less likely than their control group counterparts to be admitted to a nursing home ( Adjusted odds ratio = 0.40 ; 95 % C.I. = 0.14–1.18 ; p = 0.10 ) . No other outcomes were significantly different between treatment groups ; however , intervention group caregivers reporting greater satisfaction with the intervention showed improved self-efficacy for managing dementia compared to their less satisfied counterparts . Medical record review s found that care plans were found in most patient records , but that only 27 % of intervention group caregivers reported discussing these care plans with physicians . Three different individuals occupied the dementia care consultant position during the study period , and this turnover led to family caregiver dissatisfaction . Conclusion : The dementia care consultation intervention showed favorable effects on nursing home admission and on caregiver outcomes among intervention group caregivers more satisfied with the intervention , but there are important barriers to sustaining this collaboration between primary care physicians and a voluntary sector organization such as an Alzheimer 's association chapter", "OBJECTIVE The long-term effect of counseling and support on symptoms of depression was examined in spouse-caregivers of patients with Alzheimer 's disease . METHOD The participants were 406 spouse-caregivers of Alzheimer 's disease patients who lived at home at baseline . The caregivers were r and omly assigned to either a group receiving enhanced counseling and support treatment or a group receiving usual care ( control group ) . Caregivers in the enhanced treatment group were provided with six sessions of individual and family counseling , agreed to join support groups 4 months after enrollment , and received ongoing ad hoc counseling . The Geriatric Depression Scale was administered at baseline and at regular follow-up intervals for as long as the caregiver participated in the study . RESULTS After baseline differences were controlled for , caregivers in the enhanced treatment group had significantly fewer depressive symptoms after the intervention than did the control subjects . These effects were sustained for 3.1 years after baseline , similar across gender and patient severity level , and sustained after nursing home placement or death of the patient . CONCLUSIONS Counseling and support lead to sustained benefits in reducing depressive symptoms in spouse-caregivers of Alzheimer 's disease patients and should be widely available to provide effective , evidence -based intervention for family caregivers", "Context Dementia is an incurable chronic disease , but assistance to caregivers can reduce the severity of patients ' symptoms and delay institutionalization . Because this assistance requires provision of multiple health care and social services , patients and caregivers might benefit from a coordinated system of care . Contribution The investigators r and omly assigned patients with dementia and their caregivers to usual care or to a coordinated system of care . In the coordinated system , care managers regularly assessed patient and caregiver pairs and coordinated guideline -recommended provision of services by health care providers and community agencies using computerized information systems . The study found that pairs cared for in the coordinated system received higher- quality health care and more needed assistance than those who received usual care . Caution s The study focused on a relatively homogeneous population of white , well-educated , otherwise healthy , noninstitutionalized patients with health insurance . The findings might not apply to other population s. Implication s The quality of care for patients with dementia and their caregivers can be improved with a model of care in which services provided by the health system and community agencies are coordinated by a care manager . The Editors Dementia has enormous health and financial consequences for affected individuals , their family caregivers , and society ( 15 ) . Although most dementia is currently neither preventable nor reversible , existing practice guidelines reflect evidence from r and omized , controlled trials that caregiver assistance and support can delay institutionalization ( 68 ) , and nonpharmacologic management of problem behaviors and depression can reduce symptom severity and improve patient health ( 9 , 10 ) . Yet , adherence to published dementia care guidelines ( 1114 ) is poor ( 15 ) , including inappropriate use of psychoactive medications for initial management of agitation ( 16 ) ; low referral rates to community agencies ( 17 , 18 ) ; and underdetection of elder abuse , for which cognitive impairment is a risk factor ( 19 ) , and of depression ( 20 ) , a common comorbid condition ( 21 ) . There are few controlled trials of improvement interventions for dementia care . An opinion leader intervention improved neurologists ' reported adherence to dementia care guidelines ( 18 ) , and a recent trial using advanced practice nurses within primary care improved care quality ( 22 ) ; other trials reported limited impacts ( 23 , 24 ) . All studies were conducted primarily within or outside of health care delivery systems ; to date , trials of comprehensive , guideline -based dementia care interventions that incorporate all chronic care model components , including substantive collaboration between health systems and community agencies ( 25 , 26 ) , have not been reported . Yet , this would seem to be a well-suited approach because of the multifaceted nature of dementia care management and the need for coordinated efforts across health care delivery systems and community agencies to provide recommended medical , behavioral , and social services and support . To address gaps in care quality for persons with dementia , we design ed and tested a guideline -based , comprehensive dementia care management intervention in a clinic-level , cluster r and omized , controlled trial ( 27 ) . Intervention components were based on the chronic care model and emphasized linkages with community re sources and multiagency coordination ( 25 , 26 , 28 ) . Key components included dementia care managers , formal procedures for communication within and between organizations and agencies , Internet-based care management , collaborative care planning with caregivers , caregiver self-management support , ongoing follow-up , and provider education . We hypothesized that patient and caregiver dyads in intervention clinics would receive care in higher accordance with guidelines ; receive more community re sources and services ; have fewer unmet caregiving assistance needs ; and have better patient and caregiver health and caregiving quality , social support , and perceived care quality than dyads receiving usual care . Methods The institutional review boards of the University of California , Los Angeles , and all participating health care organizations approved the study procedures . All enrolled patient and caregiver dyads provided written informed consent . Three health care organizations ( Kaiser Permanente San Diego , Scripps Clinic , University of California , San Diego , Healthcare ) and 3 community agencies ( Alzheimer 's AssociationSan Diego Chapter , Southern Caregiver Re source Center , Meals on WheelsGreater San Diego ) providing services for persons with dementia and their informal caregivers in the San Diego metropolitan area participated . Private group practice , academic group practice , and health maintenance organization practice types were represented by the 3 health care organizations . Study Participants The study included 18 clinics from the participating health care organizations ( 4 to 8 per organization ) ( Table 1 ) . The inclusion criterion was that these be primary care clinics . Table 1 . Characteristics of Participating Health Care Organizations * Patients with dementia who were age 65 years or older and receiving Medicare were identified by querying health care organization administrative data bases for occurrence during the previous year of a dementia diagnosis code ( 29 ) at an outpatient visit or hospitalization or a cholinesterase inhibitor prescription . Patient lists were grouped by primary provider and were circulated to those providers for confirmation of dementia diagnosis and identification of additional potential participants from his or her practice ( generating < 5 % of the sample ) . Patients had to have an informal caregiver ( age 18 years ) . Patients were recruited by mail with English- and Spanish- language letters from their physician and an opt-out postcard , followed by up to 3 mailings of a patient consent or assent form ( depending on the physician 's design ation of the patient 's ability to provide consent ) , a caregiver consent form ( containing a proxy consent for the patient if he or she was judged unable to provide consent ) , and a baseline caregiver survey . R and omization was conducted at the clinic level , based on the clinic-focused design of the care management intervention . Within each health care organization , we paired clinics by patient volume ; within each pair , we r and omly assigned 1 clinic to the intervention and the other clinic to usual care using a computerized r and om-number generator operated by a study statistician . Participants were unaware of clinic r and omization status at enrollment and at completion of the baseline survey and were not reminded of r and omization status at follow-up . Intervention A steering committee that included a physician from each health care organization , a leader from each community agency , a community caregiver , and investigators used a formal method ( 30 ) to identify 23 existing dementia guideline recommendations as care goals ( 11 , 12 , 14 ) . They also design ed a structured assessment , algorithms linking specific care management actions to assessment results , and interorganization care coordination and referral protocol s. A key intervention element was health care organization and community agencybased dementia care managers ( primarily social workers ) who received formal training and used an Internet-based care management software system for care planning and coordination ( 25 , 26 , 28 ) . Every enrolled patient and caregiver dyad in the intervention group was assigned 1 health care organization care manager , who contacted them to schedule a structured home assessment . Assessment responses were entered into the software system , generating a preliminary problem list and guides to care-plan actions . The care manager collaborated with the caregiver to prioritize problem areas ; teach problem-solving skills ; initiate care plan actions ; and send an assessment summary , a problem list , and selected recommendations to the patient 's primary care physician and other design ated providers . A menu of potential care plan actions ( for example , referral for respite care services ) was documented in a comprehensive care management manual . The care management protocol included ongoing follow-up , usually by telephone , with frequency based on need and a formal in-home re assessment every 6 months to assess the need for major care-plan revisions . The software system had a feature to enable efficient tracking of multiple cases and tasks . Referrals to a particular community agency were guided by flagged problem areas . With patient and caregiver consent , referrals were communicated through the software system to that agency , whose design ated care manager subsequently received system access to the assessment , problem list , and care plan . Each dyad could have 1 or more community agency care managers . Care managers from the health care organizations and community agencies received the same formal education and training program , which was conducted jointly , and met monthly to refine care coordination procedures . Care management began within a month after enrollment of the first dyads and was active throughout the study follow-up unless a case was closed , for example , because a patient moved out of the study area and no longer was enrolled in the health care organization . At each intervention clinic , more than 90 minutes of st and ardized , interactive seminars ( in up to 5 sessions ) on relevant care issues , including evaluation of acute behavioral changes , depression management , and determination of decision-making capacity ( 31 ) , were offered to primary care providers . Selected intervention tools and documents with more detailed descriptions can be accessed at www.adc.ucla.edu/access/access.swf . Patients , caregivers , and providers in the usual care group were not offered study interventions . Outcome Measures Primary Outcome The study 's primary outcome was", "Objectives : The purpose of this article is to describe our experience in implementing a primary care-based dementia and depression care program focused on providing collaborative care for dementia and late-life depression . Methods : Capitalizing on the substantial interest in the US on the patient-centered medical home concept , the Aging Brain Care Medical Home targets older adults with dementia and /or late-life depression in the primary care setting . We describe a structured set of activities that laid the foundation for a new partnership with the primary care practice and the lessons learned in implementing this new care model . We also provide a description of the core components of this innovative memory care program . Results : Findings from three recent r and omized clinical trials provided the rationale and basic components for implementing the new memory care program . We used the reflective adaptive process as a relationship building framework that recognizes primary care practice s as complex adaptive systems . This framework allows for local adaptation of the protocol s and procedures developed in the clinical trials . Tailored care for individual patients is facilitated through a care manager working in collaboration with a primary care physician and supported by specialists in a memory care clinic as well as by information technology re sources . Conclusions : We have successfully overcome many system-level barriers in implementing a collaborative care program for dementia and depression in primary care . Spontaneous adoption of new models of care is unlikely without specific attention to the complexities and re source constraints of health care systems", "OBJECTIVE To evaluate a case management ( CM ) model for people with mild dementia , whereby re sources within the family and in the community were mobilized and optimally used . METHOD Community dwelling psychiatric and geriatrics out patients with mild dementia were r and omized to receive CM by a trained occupational therapist for 4 months ( CM group , N = 59 ) or usual care only ( control group , N = 43 ) . Primary outcome indicators included the Zarit Burden Scale ( ZBI ) , General Health Question naire ( GHQ ) , and Personal Well-Being Index for Adult ( PWI-A ) of the family caregivers . Secondary outcome indicators included the Mini-Mental State Examination ( MMSE ) , Neuropsychiatric Inventory ( NPI ) , Cornell Scale for Depression in Dementia ( CSDD ) , and Personal Well-Being Index for Intellectually Disabled ( PWI-ID ) of the demented subjects as measured at fourth and twelfth months . RESULT CSDDis reduced in the CM group at fourth month , but not at twelfth month . The changes in outcome variables of persons with dementia did not differ between the groups ( Mann-Whitney U-test , p > 0.05 ) . At follow-up , CM group used more day care and domestic helpers than control group ( chi ( 2 ) , p > 0.05 ) . CONCLUSION Case management for Chinese persons with mild dementia out patients did not show significant effects in reducing caregiver burden , but encouraged family caregivers to seek external support", "This study evaluated a one year long course education and counseling program with 93 family caregivers of elders afflicted with Alzheimer 's disease . The elders had received treatment for agitation in an inpatient setting and were subsequently discharged to the caregivers ' home . Caregivers were r and omly assigned to an experimental group ( n = 68 ) and a control group ( n = 25 ) . Baseline assessment s ( Time 0 ) were conducted while the elder was an inpatient . Postdischarge interventions and assessment s were conducted at 2 weeks , 6 weeks , 12 weeks , and 6 and 12 months ( Times 1 - 5 respectively ) . There were no significant treatment effects for care recipient agitation , caregiver stress , depression , and physical health , and no significant differences between groups in rates of institutionalization for afflicted elders . Longitudinal data , however , revealed several important trends . Afflicted elders ' agitation rose steadily for control group subjects at Times 3 through 5 but declined for experimental group subjects . Caregiver depression increased for control group subjects at Time 5 , but declined for experimental group subjects . Caregiver physical health declined for control group subjects at Times 4 and 5 but was maintained for experimental group subjects . A significantly higher number of afflicted elders were still at home among experimental group subjects at the end of the one year study . The difficulties in demonstrating efficacy of interventions with family caregivers of Alzheimer 's disease are discussed . Finally , the issue of data collection being perceived as support by control group subjects is evaluated" ]

[ "11207351", "10433305", "11835701", "9023090", "16604824", "8258839", "11147897", "11153633", "15676086", "1613808", "12765810" ]

[ "Lack of effect of induction of hypothermia after acute brain injury.", "Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure.", "Changes of evoked potentials and evaluation of mild hypothermia for treatment of severe brain injury.", "Treatment of traumatic brain injury with moderate hypothermia.", "Effects of Selective Brain Cooling in Patients with Severe Traumatic Brain Injury: A Preliminary Study", "A phase II study of moderate hypothermia in severe brain injury.", "A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan.", "Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans", "Therapeutic effect of mild hypothermia on severe traumatic head injury.", "Systemic hypothermia in treatment of brain injury.", "Study on therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury." ]

[ "BACKGROUND Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies , but the results were not definitive . To study this issue , we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury . METHODS The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were r and omly assigned to be treated with hypothermia ( body temperature , 33 degrees C ) , which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling , or normothermia . All patients otherwise received st and ard treatment . The primary outcome measure was functional status six months after the injury . RESULTS The mean age of the patients and the type and severity of injury in the two treatment groups were similar . The mean ( + /-SD ) time from injury to r and omization was 4.3+/-1.1 hours in the hypothermia group and 4.1+/-1.2 hours in the normothermia group , and the mean time from injury to the achievement of the target temperature of 33 degrees C in the hypothermia group was 8.4+/-3.0 hours . The outcome was poor ( defined as severe disability , a vegetative state , or death ) in 57 percent of the patients in both groups . Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group ( P=0.79 ) . The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group . Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group . CONCLUSIONS Treatment with hypothermia , with the body temperature reaching 33 degrees C within eight hours after injury , is not effective in improving outcomes in patients with severe brain injury", "OBJECT This study was performed to determine whether mild hypothermia therapy is essential for the treatment of severely head injured patients in whom intracranial pressure ( ICP ) can be maintained below 20 mm Hg by using conventional therapies . METHODS Sixteen consecutive severely head injured patients fulfilled the following criteria : the patient 's ICP was maintained below 20 mm Hg by using fluid restriction , hyperventilation , and high-dose barbiturate therapy ; and the patient had a Glasgow Coma Scale score of 8 or less on admission . After conventional therapies had been applied , the patients were divided r and omly into two groups : the mild hypothermia group ( HT group ; eight patients ) and the normothermia group ( NT group ; eight patients ) . The HT group received mild hypothermia ( intracranial temperature 34 degrees C ) therapy for 48 hours followed by rewarming at 1 degree C per day for 3 days , whereas the NT group received normothermia ( intracranial temperature 37 degrees C ) therapy for 5 days . Specimens of cerebrospinal fluid ( CSF ) taken from an intraventricular catheter every 24 hours were analyzed for the presence of excitatory amino acids ( [ EAAs ] glutamate , aspartate , and glycine ) and cytokines ( tumor necrosis factor-alpha , interleukin [IL]-1beta , IL-6 , IL-8 , and IL-10 ) . The two groups did not differ significantly in patient age , neurological status , or level of ICP . There were no significant differences in daily changes in CSF concentrations of EAAs and cytokines between the two groups . The incidence of pneumonia was slightly higher in the HT group compared with the NT group ( p = 0.059 ) . The incidence of diabetes insipidus associated with hypernatremia was significantly higher in the HT group compared with that in the NT group ( p < 0.01 ) . The two groups did not differ with respect to their clinical outcomes . CONCLUSIONS The authors recommend normothermia therapy for the treatment of severely head injured patients in whom ICP can be maintained at lower than 20 mm Hg by using conventional therapies , because mild hypothermia therapy does not convey any advantage over normothermia therapy in such patients", "OBJECTIVE To observe the changes of evoked potentials after severe brain injury and the effect of mild hypothermia on acute severe brain injury . METHODS A total of 44 patients with severe closed head injury ( GCS 3 - 8 , admitted within 10 hours from injury ) admitted from May 1998 to March 1999 were selected for this study . All patients were admitted into the intensive care unit and divided into 2 groups , Group A ( GCS 3 - 5 ) and Group B ( GCS 6 - 8 ) . Patients were also r and omly assigned to either normothermia or hypothermia subgroups . Patients in the hypothermia group were cooled to 32 - 34 degrees C. Median nerve short-latency somatosensory evoked potentials ( SLSEP ) and brain stem auditory evoked potentials ( BAEP ) were recorded before cooling and 4 , 24 , 48 , 72 , 96 and 120 hours , respectively after cooling and temperature resuming . SLSEP and BAEP were measured at the same time in the normothermia group ( control group ) . The changes of evoked potentials ( EP ) were analyzed by statistical methods . RESULTS In the Group B , N(20 ) amplitudes in SLSEP and I/V amplitudes in BAEP after mild hypothermia treatment in the hypothermia group differed significantly from those in the control group ( P<0.05 ) . However , in the Group A , no significant difference in all parameters was found . CONCLUSIONS These results demonstrate that mild hypothermia treatment ( 32 - 34 degrees C ) in the Group B has a significant neuroelectrophysiological effect on severe brain injury . Nevertheless , the effect of mild hypothermia in the Group A is not apparent and needs further study ing", "BACKGROUND Traumatic brain injury initiates several metabolic processes that can exacerbate the injury . There is evidence that hypothermia may limit some of these deleterious metabolic responses . METHODS In a r and omized , controlled trial , we compared the effects of moderate hypothermia and normothermia in 82 patients with severe closed head injuries ( a score of 3 to 7 on the Glasgow Coma Scale ) . The patients assigned to hypothermia were cooled to 33 degrees C a mean of 10 hours after injury , kept at 32 degrees to 33 degrees C for 24 hours , and then rewarmed . A specialist in physical medicine and rehabilitation who was unaware of the treatment assignments evaluated the patients 3 , 6 , and 12 months later with the use of the Glasgow Outcome Scale . RESULTS The demographic characteristics and causes and severity of injury were similar in the hypothermia and normothermia groups . At 12 months , 62 percent of the patients in the hypothermia group and 38 percent of those in the normothermia group had good outcomes ( moderate , mild , or no disabilities ) . The adjusted risk ratio for a bad outcome in the hypothermia group was 0.5 ( 95 percent confidence interval , 0.2 to 1.2 ) . Hypothermia did not improve the outcomes in the patients with coma scores of 3 or 4 on admission . Among the patients with scores of 5 to 7 , hypothermia was associated with significantly improved outcomes at 3 and 6 months ( adjusted risk ratio for a bad outcome , 0.2 ; 95 percent confidence interval , 0.1 to 0.9 at both intervals ) , although not at 12 months ( risk ratio , 0.3 ; 95 percent confidence interval , 0.1 to 1.0 ) . CONCLUSIONS Treatment with moderate hypothermia for 24 hours in patients with severe traumatic brain injury and coma scores of 5 to 7 on admission hastened neurologic recovery and may have improved the outcome", "We prospect ively investigated noninvasive selective brain cooling ( SBC ) in patients with severe traumatic brain injury . Sixty-six in- patients were r and omized into three groups . In one group , brain temperature was maintained at 33 - 35 ° C by cooling the head and neck (SBC);in a second group , mild systemic hypothermia ( MSH ; rectal temperature 33 - 35 ° C ) was produced with a cooling blanket ; and a control group was not exposed to hypothermia . Natural re-warming began after 3 days . Mean intracranial pressure 24 , 48 or 72 h after injury was significantly lower in the SBC group than in the control group . Mean serum superoxide dismutase levels on Days 3 and 7 after injury in the SBC and MSH groups were significantly higher than in the control group . The percentage of patients with a good neurological outcome 2 years after injury was 72.7 % , 57.1 % and 34.8 % in the SBC , MSH and control groups , respectively . Complications were managed without severe sequelae . Non-invasive SBC was safe and effective", "Forty-six patients with severe nonpenetrating brain injury [ Glasgow Coma Scale ( GCS ) 4 - 7 ] were r and omized to st and ard management at 37 degrees C ( n = 22 ) and to st and ard management with systemic hypothermia to 32 to 33 degrees C ( n = 24 ) . The two groups were balanced in terms of age ( Wilcoxon 's rank sum test , p > 0.95 ) , r and omizing GCS ( chi-square test , p = 0.54 ) , and primary diagnosis . Cooling was begun within 6 h of injury by use of cooling blankets . Metocurine and morphine were given hourly during induction and maintenance of hypothermia . Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications . Seizure incidence was lower in the hypothermia group ( Fisher 's exact text , p = 0.019 ) . Sepsis was seen more commonly in the hypothermia group , but difference was not statistically significant ( chi-square test ) . Mean Glasgow Outcome Scale ( GOS ) score at 3 months after injury showed an absolute increase of 16 % ( i.e. , 36.4 - 52.2 % ) in the number of patients in the Good Recovery/Moderate Disability ( GR/MD ) category as compared with Severe Disability/Vegetative/Dead ( SD/V/D ) ( chi-square test , p > 0.287 ) . Based on evidence of improved neurologic outcome with minimal toxicity , we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted", "OBJECT The criteria for the use of mild hypothermia ( 34 degrees C ) in severely head injured patients have not been st and ardized . A prospect i ve r and omized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure ( ICP ) . METHODS At 11 medical centers , 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided r and omly into two groups : the mild hypothermia group ( HT group , 45 patients ) and the normothermia group ( NT group , 46 patients ) . Patients in the HT group were exposed to mild hypothermia ( 34 degrees C ) for 48 hours , followed by rewarming at 1 degrees C per day for 3 days , whereas patients in the NT group were exposed to normothermia ( 37 degrees C ) for 5 days . The two groups were similar with respect to prognostic factors , and there was no difference in clinical outcome at 3 months postinjury . During treatment , there was a significantly greater use of neuromuscular blocking agents in the HT group ( p = 0.011 ) . During the initial 2 weeks postinjury , the incidences of pneumonia , meningitis , leukocytopenia , thrombocytopenia , hypernatremia , hypokalemia , and hyperamylasemia were significantly higher in the HT than in the NT group ( p < 0.05 ) . CONCLUSIONS Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients", "Objective To examine the levels of thromboxane B2 ( TXB2 ) and 6-keto prostagl and in F1&agr ; ( 6-keto PGF1&agr ; ) production in arterial and internal jugular bulb sera in patients with traumatic brain injury ( TBI ) . TBI is associated with arachidonate release and may be associated with an imbalance of vasoconstricting and vasodilating cyclooxygenase metabolites . Design A prospect i ve , r and omized study . Setting The intensive care unit of a medical university hospital . Interventions Twenty-six ventilated TBI patents ( Glasgow Coma Scale score on admission , ≤8 points ) were divided r and omly into two groups : a hypothermic group ( n = 15 ) , in which the patients were cooled to 32 to 33 ° C after being giving vecuronium , midazolam , and buprenorphine ; and a normothermic group ( n = 11 ) , in which the patients ’ body temperature was controlled at 36 to 37 ° C by surface cooling using the same treatment as the hypothermic group . Body temperature control including normothermia was started 3 to 4 hrs after injury . The duration of hypothermia usually lasted for 3 to 4 days , after which the patients were rewarmed at a rate of approximately 1 ° C per day . Measurements and Main Results Blood sampling for TXB2 and 6-keto PGF1&agr ; was started shortly after admission in both groups . Arterial TXB2 levels on admission in both groups were elevated remarkably , but not 6-keto PGF1&agr ; , thereby causing an imbalance of the prostanoids after injury . In the normothermic group , TXB2 decreased transiently , but this prostanoid increased again 3 days after the injury . In the hypothermic group , such prostanoid differences disappeared shortly after therapy , and the condition was sustained for 10 days . Hypothermia attenuated differences in TXB2 levels between arterial and internal jugular bulb sera , which may reflect reduced cerebral prostanoid production . The Glasgow Outcome Scale score 6 months after the insult in the hypothermic group was significantly higher than that in the normothermic group ( p = .04 ) . Conclusion The current results from a limited number of patients suggest that moderate hypothermia may reduce prostanoid production after TBI , thereby attenuating an imbalance of thromboxane A2 and prostagl and in I2 . However , it must be clarified whether the changes in the prostanoid after moderate hypothermia are a secondary effect of other mediator changes or whether they simply represent an epiphenomenon that is mechanistically unrelated to damage in TBI", "OBJECTIVE To investigate the therapeutic effect of mild hypothermia on severe traumatic brain injury . METHODS Eighty-six in- patients with severe traumatic brain injury treated ordinarily were consecutively r and omized into two groups : a hypothermia group ( n=43 ) and a normothermia group ( the control group , n=43 ) . In the hypothermia group , the core temperature ( i.e. , nasopharyngeal or brain temperature ) of the patient was reduced to and maintained at 33 - 35 degrees C with a systemic cooling blanket . Natural rewarming began after 3 - 5 days ( mean : 4.3 days ) of hypothermia treatment . In the control group , the patient received no hypothermia treatment . The vital sign , extradural pressure and serum superoxide dismutase were observed and measured during treatment , and the complications as well as the Glasgow outcome scale were evaluated at 2 years after injury . RESULTS The mean extradural pressure in the hypothermia group ( 27.38 mm Hg + /- 4.88 mm Hg at 24 hours , 29.40 mm Hg + /- 4.50 mm Hg at 48 hours and 26.40 mm Hg + /- 4.13 mm Hg at 72 hours after injury ) was much lower than that in the control group ( 32.63 mm Hg + /- 3.00 mm Hg , 34.80 mm Hg + /- 6.00 mm Hg and 31.81 mm Hg + /- 4.50 mm Hg respectively at 24 , 48 and 72 hours , P<0.05 ) . The mean serum superoxide dismutase levels in the hypothermia group on days 3 and 7 ( 583.7 microg/L + /- 99.6 microg/L and 699.4 microg/L + /- 217.3 microg/L , respectively ) were much higher than those in the control group at the same time period ( 446.6 microg/L + /- 79.5 microg/L and 497.1 microg/L + /- 101.2 microg/L , respectively , P<0.01 ) . The recovery rates at 2 years after injury were 65.1 % in the hypothermia group and 37.2 % in the control group ( P<0.05 ) . The mortality rates were 25.6 % in the hypothermia group and 51.2 % in the control group ( P<0.05 ) . The complications , including pulmonary infections , thrombocytopenia ( platelet count < 100 x 10(9)/L ) , hemorrhage in the digestive tract , electrolyte disorders and renal malfunction , were managed without severe sequelae . CONCLUSIONS Mild hypothermia is a safe and effective therapeutic method , which can lower the extradural pressure , increase the serum superoxide dismutase and improve the neurological outcomes without severe complications in the patients with severe traumatic brain injury", "An extensive literature suggests that there are minimal complications of systemic hypothermia in humans at and above 30 degrees C for periods of several days . Intracranial hemorrhage has been found to complicate profound hypothermia ( 10 - 15 degrees C ) , and ventricular arrhythmias occur at temperatures below 30 degrees C. Our initial clinical studies were with 21 patients undergoing elective craniotomy cooled to 30 - 32 degrees C for 1 - 8 h ( mean 4 h ) . Hypothermia was induced by surface cooling with water blankets . No complications were found . Among 11 patients with severe brain injury , cooling to levels below 32 degrees C was associated with ventricular arrhythmias in 1 patient and atrioventricular block in 1 patient . Asymptomatic hypokalemia was found routinely and treated with potassium replacement . No intracranial hemorrhage or other complications were found . With surface cooling , intravascular temperature dropped at 1.6 degrees C/h . Based on the safety of surface cooling to a core temperature of 32 degrees C for 48 h , we are conducting a r and omized study of this level of hypothermia in patients with severe brain injury , cooled within 6 h of injury", "BACKGROUND The therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury were studied . METHODS All 396 patients with severe head injury [ Glasgow Coma Scale score ( GCS ) equal to or less than 8 on admission ] were r and omly divided into the hypothermic group ( 198 cases ) and the control group ( 198 cases ) . Hypothermia was induced within 24 hours of injury . Rewarming began 1 to 7 days ( average 62.4 + /- 27.6 h ) after the rectal temperature ( RT ) reached 32.0 to 35.0 degrees C. Meanwhile , the vital signs , intracranial pressure ( ICP ) , blood gas values , blood electrolytes , brain tissue oxygen pressure ( P(bt)O2 ) , brain tissue temperature ( BT ) , cerebral blood flow ( CBF ) , and jugular venous oxygen saturation ( S(jv)O2 ) were measured . The rectal temperature of control patients was induced to 36.5 to 37.0 degrees C. According to GOS , the prognosis of the patients was evaluated . RESULTS In comparison with control group , during mild hypothermia the high level of ICP , hyperglycemia and blood lactic acid significantly decreased ( p < 0.05 ) and cerebral flow improved dominantly . The vital signs , blood gas values , and blood electrolytes did not change significantly . Decreased mortality and good recovery were also found in hypothermia group . CONCLUSIONS Mild hypothermia is safe and effective for preventing brain damage on patients with severe head injury , as well as reducing mortality and improving the prognosis . It is important to monitor P(bt)O2 , BT , CBF , and S(jv)O2 in hypothermic therapy" ]

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[ "Effects of 3 month therapy with danazol after laparoscopic surgery for stage III/IV endometriosis: a randomized study.", "Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriomas: a prospective, randomized trial.", "Deep infiltrating endometriosis: relation between severity of dysmenorrhoea and extent of disease.", "A gonadotrophin‐releasing hormone agonist compared with expectant management after conservative surgery for symptomatic endometriosis", "Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis after conservative surgery.", "Incidence of symptom recurrence after hysterectomy for endometriosis.", "The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year follow-up.", "Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi.", "Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis.", "A levonorgestrel-releasing intrauterine system for the treatment of dysmenorrhea associated with endometriosis: a pilot study.", "Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis.", "Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis.", "Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation.", "Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial.", "Prolonged GnRH Agonist and Add‐Back Therapy for Symptomatic Endometriosis: Long‐term Follow‐up", "Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy) who received hormone replacement therapy.", "Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain.", "Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial.", "Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration.", "Laparoscopic presacral neurolysis for endometriosis-related pelvic pain.", "Correlation between endometriosis and pelvic pain.", "Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain.", "Prostaglandins and endometriosis.", "The impact of preoperative gonadotropin-releasing hormone agonist treatment on laparoscopic excision of ovarian endometriotic cysts.", "Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis.", "Laparoscopic endometriosis treatment: is it better?", "Low-dose danazol after combined surgical and medical therapy reduces the incidence of pelvic pain in women with moderate and severe endometriosis.", "Prostaglandin biosynthesis inhibitors and endometriosis.", "Naproxen Sodium in Dysmenorrhea Secondary to Endometriosis", "Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis." ]

[ "The effect of treatment with danazol was evaluated with respect to expectant management after laparoscopic conservative surgery . All patients conservatively operated at laparoscopy for stage III-IV endometriosis from July 1994 to October 1996 were requested to enter the study . Patients who underwent surgery for recurrent endometriosis were excluded from the study , as well as patients who had taken hormonal therapies before laparoscopy . Informed consent was obtained from 77 women who were r and omized after surgery to treatment with danazol 600 mg daily for 3 months ( n = 36 ) or to expectant management ( n = 41 ) . All patients were regularly followed up every 6 months for evaluation of fertility , recurrence of pain symptoms and disease . During the follow-up , six ( 55 % ) of the 11 infertile women allocated to danazol and eight ( 50 % ) of the 16 given no treatment became pregnant ( not significant ) . Moderate/severe pelvic pain recurred during follow-up in seven ( 23 % ) of the 31 women with pelvic pain allocated to the danazol group and nine ( 31 % ) of the 29 allocated to no treatment ; the respective cumulative pain recurrence rates at 12 months were 26 and 34 % ( log rank test , not significant ) . Three women ( 8.3 % ) treated with danazol and six ( 15 % ) who received no treatment had disease recurrence as demonstrated by gynaecological examination and /or pelvic ultrasonography ( not significant ) . Our results do not demonstrate a significant advantage of 3 month danazol therapy after laparoscopic surgery for stage III-IV endometriosis with respect to postoperative expectant management", "OBJECTIVE We sought to evaluate the efficacy of postoperative administration of monophasic , combined , low-dose oral contraceptives on endometrioma recurrence and on persistence-recurrence of associated pain symptoms after laparoscopic treatment of moderate-to-severe endometriosis . STUDY DESIGN In a prospect i ve , r and omized trial 70 patients who were not attempting to conceive , aged 20 to 35 years , underwent laparoscopic excision of ovarian endometriomas , followed by either postoperative administration of low-dose cyclic oral contraceptives for 6 months or no treatment on the basis of a computer-generated sequence . At 3 and 6 months after surgery and then at 6-month intervals , both groups underwent ultrasonographic examination for possible evidence of endometrioma recurrence and for evaluation of the absence , persistence , or recurrence of pain symptoms . RESULTS Two patients in the oral contraceptive group did not complete the study . After a mean follow-up of 22 months ( range , 12 - 48 months ) , there were 2 ( 6.1 % ) endometrioma recurrences in the 33 patients who received postoperative oral contraceptives versus 1 ( 2.9 % ) recurrence in the 35 patients in the control group ( not significant ) . The moderate-to-severe pain recurrence rate was 9.1 % in the oral contraceptive group versus 17.1 % in the control group ( not significant ) . The mean time to recurrence of either symptoms or endometriomas was 18.2 months in the oral contraceptive group versus 12.7 months in the control group . The 12-month cumulative recurrence rate at life-table analysis was significantly lower for patients receiving oral contraceptives versus control subjects , whereas no significant difference was evident at 24 and 36 months . CONCLUSION Postoperative administration of low-dose cyclic oral contraceptives does not significantly affect the long-term recurrence rate of endometriosis after surgical treatment . A delay in recurrence is evident at life-table analysis", "BACKGROUND Little is known about the precise nature of the relationship between dysmenorrhoea ( DM ) and endometriosis . Our aim was to evaluate the relationship between the severity of DM in women with posterior deep infiltrating endometriosis ( DIE ) and indicators of the extent of their disease . METHODS Various indicators of the extent of DIE were recorded during surgery in 209 women . The severity of their DM was assessed with a pain scale . The scale was retrospective for 155 women and prospect i ve for 54 . Correlations were sought with an ordinal logistic regression model with cumulative odds . RESULTS On univariate analysis the following variables were related to the severity of DM : number of previous surgical procedures for endometriosis ; revised American Fertility society classification ; extensiveness of adnexal adhesion ; Douglas obliteration ; size of the posterior DIE implant ; extent of the sub-peritoneal infiltration by the posterior DIE ( rectal , vaginal or both versus sub-peritoneal only ) . Current infertility was associated with less severe DM . After multiple regression analysis , presence of a rectal or vaginal infiltration by the posterior DIE and extensiveness of adnexal adhesion were the only factors that remained related to DM severity . CONCLUSIONS The concept of ' very deep infiltrating endometriosis ' , defined as implants invading the wall of the pelvic organ , should be tested in future classification systems specifically addressed to the prediction of endometriosis-related pain", "Objective To ascertain whether the frequency of pelvic pain recurrence is reduced and time to symptoms recurrence is prolonged in women with symptomatic endometriosis undergoing conservative surgery and post‐operative hormonal therapy compared with women treated with surgery only . Pregnancy rates and time to conception in women wanting children were also evaluated", "To evaluate the clinical value of postoperative hormone therapy in endometriosis , 60 patients with advanced disease were r and omized to receive in a double-blind study danazol ( 200 mg , 3 times daily ) , medroxyprogesterone acetate ( MPA ) ( 100 mg daily ) or placebo post-operatively for 6 months . Treatment efficacy was evaluated clinical ly and at laparoscopy 6 months after medication . In relation to placebo , danazol and high-dose MPA treatments , which did not differ from each other in efficacy , significantly alleviated pelvic pain . In addition , the peritoneal endometriosis lesions found at 6-months laparoscopy were significantly smaller in the MPA and danazol groups than in the placebo group . Breakthrough bleeding , weight gain and acne complicated danazol treatment but only breakthrough bleeding complicated MPA treatment . These data suggest that postoperative treatment of advanced endometriosis with high-dose MPA or danazol is clinical ly beneficial", "OBJECTIVES To determine the relative risk of symptom recurrence and /or reoperation after hysterectomy with ovarian preservation for the treatment of endometriosis . DESIGN Historical prospect i ve study of patients with endometriosis who underwent hysterectomy with or without ovarian preservation . PATIENTS One hundred thirty-eight women who underwent hysterectomy with the diagnosis of endometriosis . METHODS A computer search identified 138 women who underwent hysterectomy with the diagnosis of endometriosis at Johns Hopkins Hospital from 1979 to 1991 . Follow-up information was obtained from medical records , outpatient charts , and telephone surveys . RESULTS Twenty-nine women had hysterectomy with some ovarian tissue preserved ; 109 had all ovarian tissue removed . Of those with ovarian preservation , 18 of 29 ( 62 % ) had recurrent pain and 9 of 29 ( 31 % ) required reoperation . Of those who had no ovarian preservation , 11 of 109 ( 10 % ) had recurrent symptoms and 4 of 109 ( 3.7 % ) required reoperation . Ovarian conservation was associated with a relative risk for pain recurrence of 6.1 ( 95 % confidence interval [ CI ] 2.5 to 14.6 ) compared with patients with oophorectomy in a Cox proportional hazards model . The relative risk for reoperation in patients with ovarian conservation was 8.1 ( 95 % CI 2.1 to 31.3 ) . CONCLUSION Compared with women who had oophorectomy for endometriosis , patients who underwent hysterectomy with ovarian conservation had 6.1 times greater risk of developing recurrent pain and 8.1 times greater risk of reoperation", "BACKGROUND This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis . METHODS In this prospect i ve observational cohort study , 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis . Of these , 216 women underwent surgical assessment and 176 were confirmed to have endometriosis . Question naires and visual analogue scale ( VAS ) scores for dysmenorrhoea , non-menstrual pelvic pain , dyspareunia and dyschesia as well as quality of life instruments ; the EQ-5Dindex and EQ-5Dvas , Short-Form 12 ( SF-12 ) and sexual activity question naires were completed pre-operatively . Intra-operative details of revised American Fertility Society ( rAFS ) stage , site of disease , associated tests , duration of surgery and complications were noted . Follow-up was performed by postal question naire and chart review . For women who had further surgery , rAFS stage , site of disease , other procedures and histology were all recorded . RESULTS Pain scores were all significantly reduced at 2 - 5 years for dysmenorrhoea ( median VAS baseline versus follow-up 2 - 5 years ) ; 9 versus 3.3 ( P < 0.0001 ) , non-menstrual pelvic pain 8 versus 3 ( P < 0.0001 ) , dyspareunia 7 versus 0 ( P < 0.0001 ) and dyschesia 7 versus 2 ( P < 0.0001 ) . Quality of life was improved for the EQ-5Dindex ( P = 0.008 and the EQ-5Qvas ( P = 0.03 ) and for sexual function with pleasure ( P = 0.001 ) and habit ( P = 0.012 ) being improved and discomfort being decreased ( P = 0.001 ) . The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36 % . A rAFS score of > 70 was predictive of requiring further surgery ( P = 0.03 ) . Of women who had further surgery , endometriosis was found histologically in 68 % . CONCLUSIONS Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years . The probability of requiring further surgery is 36 % . Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence", "In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility , we conducted a r and omized clinical trial . Eligible patients were women aged < /=36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis ( stage I or II of the revised American Fertility Society classification ) and otherwise unexplained infertility for > /=2 years . Eligible women were r and omly assigned to resection or ablation of visible endometriosis ( 54 patients ) or diagnostic laparoscopy only ( 47 patients ) . After laparoscopy women tried to conceive spontaneously for 1 year ( follow-up period ) . A total of five women withdrew from the study : three for personal reasons , and two were lost to follow-up . Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period , 12 ( 24 % ) in the resection/ablation group and 13 ( 29 % ) in the no treatment group conceived ; the difference was not significant . Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one . Thus the 1 year birth rate was 10 out of 51 women ( 19.6 % ) in the resection/ablation group and 10 out of 45 women ( 22.2 % ) in the no-treatment group . In conclusion , the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates", "OBJECTIVE To examine whether ultralong GnRH analog ( GnRH-a ) therapy after surgical treatment of endometriosis and before ART influences the pregnancy rate . DESIGN Prospect i ve , r and omized , controlled study . SETTING University clinic for reproductive medicine and gynecologic endocrinology . PATIENT(S ) One hundred ten patients with stage II to IV endometriosis according to ASRM criteria . INTERVENTION(S ) Fifty-five patients received GnRH-a for 6 months after surgery and subsequently underwent up to 3 cycles of ART , and 55 patients received 3 cycles of ART alone immediately after surgery . MAIN OUTCOME MEASURE(S ) Clinical pregnancy rates . RESULTS The pregnancy rate per patient was higher among patients who received follow-up treatment with GnRH-a . The same results were found in patients with stage III or IV endometriosis who were undergoing IUI or IVF/ICSI . CONCLUSION ( S ) Ultralong GnRH-a therapy increases the pregnancy rate of ART in patients with severe endometriosis", "OBJECTIVE To evaluate the efficacy and safety of an intrauterine system releasing 20 microg of levonorgestrel per 24 hours in the long-term treatment of recurrent dysmenorrhea in women already operated on conservatively for endometriosis . DESIGN A prospect i ve noncomparative pilot study . SETTING A tertiary care and referral academic center for patients with endometriosis . PATIENT(S ) Twenty parous women with recurrent moderate or severe dysmenorrhea after conservative surgery for endometriosis who did not want further children . INTERVENTION(S ) A levonorgestrel-releasing intrauterine system was inserted in each woman within 7 days of the start of a menstrual cycle . MAIN OUTCOME MEASURE(S ) Variations in severity of dysmenorrhea during treatment according to a 100-mm visual analogue scale and a 0 - 3-point verbal rating scale , modification of a pictorial blood-loss assessment chart devised to evaluate the amount of menstrual flow , and degree of satisfaction after 12 months of therapy . RESULT ( S ) One woman was lost to follow-up after achieving amenorrhea and expressing satisfaction , and 1 requested system removal because of weight gain and abdominal bloating . In another subject , the levonorgestrel intrauterine system was expelled 3 months after insertion . The menstrual patterns in the remaining 17 women were characterized by amenorrhea in 4 cases , hypomenorrhea or spotting in 8 , and normal flow in 5 . Baseline and 12-month follow-up mean + /- SD blood loss scores were 111+/-36 and 27+/-26 , respectively . At the same time , mean + /- SD visual analogue and verbal rating scale scores dropped , respectively , from 76+/-12 to 34+/-23 points and from 2.5+/-0.5 to 1.2+/-0.5 points . Four women were very satisfied with treatment , 11 were satisfied , 2 were uncertain , and 3 were dissatisfied at 12-month follow-up . CONCLUSION ( S ) Because of the amenorrhea or hypomenorrhea induced in most women , a levonorgestrel intrauterine system greatly reduced menstrual pain associated with endometriosis and achieved a high degree of patient satisfaction", "BACKGROUND Minimal or mild endometriosis is frequently diagnosed in infertile women . It is often treated by resection or ablation of the lesions , but whether this improves fertility has not been established . We carried out a r and omized , controlled trial to determine whether laparoscopic surgery enhanced fecundity in infertile women with minimal or mild endometriosis . METHODS We studied 341 infertile women 20 to 39 years of age with minimal or mild endometriosis . During diagnostic laparoscopy the women were r and omly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy only . They were followed for 36 weeks after the laparoscopy or , for those who became pregnant during that interval , for up to 20 weeks of pregnancy . RESULTS Among the 172 women who had resection or ablation of endometriosis , 50 became pregnant and had pregnancies that continued for 20 weeks or longer , as compared with 29 of the 169 women in the diagnostic-laparoscopy group ( cumulative probabilities , 30.7 percent and 17.7 percent , respectively ; P=0.006 by the log-rank test ) . The corresponding rates of fecundity were 4.7 and 2.4 per 100 person-months ( rate ratio , 1.9 ; 95 percent confidence interval , 1.2 to 3.1 ) . Fetal losses occurred in 20.6 percent of all the recognized pregnancies in the laparoscopic-surgery group and in 21.6 percent of all those in the diagnostic-laparoscopy group ( P=0.91 ) . Four minor operative complications ( intestinal contusion , slight tear of the tubal serosa , difficult pneumoperitoneum , and vascular trauma ) were reported ( three in the surgery group and one in the control group ) . CONCLUSIONS Laparoscopic resection or ablation of minimal and mild endometriosis enhances fecundity in infertile women", "OBJECTIVE To evaluate the efficacy of the GnRH agonist ( GnRH-a ) nafarelin compared with placebo administered for 6 months after reductive laparoscopic surgery for symptomatic endometriosis . DESIGN R and omized , prospect i ve , placebo-controlled , multicenter clinical trial . SETTING Thirteen clinics including private practice and university centers . PATIENT(S ) One hundred nine women aged 18 - 47 with laparoscopically proven endometriosis and pelvic pain who had undergone reductive laparoscopic surgery for endometriosis . INTERVENTION(S ) Patients were r and omized to receive either the GnRH-a nafarelin ( 200 micrograms twice daily ) or placebo for 6 months . MAIN OUTCOME MEASURE(S ) Time to initiation of alternative treatment ( the length of time from beginning study medication to receiving alternative therapy or to deeming that the study drug was ineffective ) and patient-reported and physician-assessed pelvic pain scores . RESULT ( S ) The median time to initiation of alternative treatment was > 24 months in the nafarelin group versus 11.7 months in the placebo group . Fifteen ( 31 % ) of 49 nafarelin-treated patients required alternative therapy , compared with 25 ( 57 % ) of 44 placebo-treated patients . The patients ' pelvic pain scores dropped significantly in the nafarelin and placebo groups after 6 months of treatment . Physician summary ratings showed significant improvement in the nafarelin group and no significant changes in the placebo group after 6 months of treatment . CONCLUSION ( S ) Compared with placebo , nafarelin administered after reductive laparoscopic surgery for endometriosis significantly delays the return of endometriosis symptoms requiring further treatment", "OBJECTIVE To assess the efficacy of two laparoscopic methods for the management of endometriomas with regard to pain relief , pregnancy rate , and disease recurrence . DESIGN Prospect i ve , r and omized clinical trial . SETTING Tertiary care hospital . PATIENT(S ) Sixty-four patients with advanced stages of endometriosis . INTERVENTION(S ) Patients were r and omly allocated at the time of laparoscopy to undergo either cystectomy of the endometrioma ( group 1 ) or drainage of the endometrioma and bipolar coagulation of the inner lining ( group 2 ) . MAIN OUTCOME MEASURE(S ) Pain relief and pregnancy rate . RESULT ( S ) Thirty-two patients were enrolled in each group . The 24-month cumulative recurrence rates of dysmenorrhea , deep dyspareunia , and nonmenstrual pelvic pain were lower in group 1 than in group 2 ( dysmenorrhea : 15.8 % versus 52.9 % ; deep dyspareunia : 20 % versus 75 % ; nonmenstrual pelvic pain : 10 % versus 52.9 % ) . The median interval between the operation and the recurrence of moderate to severe pelvic pain was longer in group 1 than in group 2 ( 19 months [ range , 13.5 - 24 months ] versus 9.5 months [ range , 3 - 20 months ] ) . The 24-month cumulative pregnancy rate was higher in group 1 than in group 2 ( 66.7 % versus 23.5 % ) . CONCLUSION ( S ) For the treatment of ovarian endometriomas , a better outcome with a similar rate of complications is achieved with laparoscopic cystectomy than with drainage and coagulation", "OBJECTIVE To evaluate the efficacy of laparoscopic resection of the uterosacral ligaments in women with endometriosis and predominantly midline dysmenorrhea . DESIGN R and omized controlled trial . SETTING Two academic departments . One hundred eighty patients undergoing operative laparoscopy as first-line therapy for stage I to IV symptomatic endometriosis . INTERVENTION(S ) Operative laparoscopy including uterosacral ligament resection or conservative surgery alone . MAIN OUTCOME MEASURE(S ) Proportion of women with recurrence of moderate or severe dysmenorrhea 1 year after surgery . RESULT ( S ) No complications occurred . Among the patients who were evaluable 1 year after operative laparoscopy , 23 of 78 ( 29 % ) women who had uterosacral ligament resection and 21 of 78 ( 27 % ) women who had conservative surgery only reported recurrent dysmenorrhea . The corresponding numbers of patients at 3 years were 21 of 59 ( 36 % ) women and 18 of 57 ( 32 % ) women , respectively . Time to recurrence was similar in the two groups . Pain was substantially reduced , and patients in both groups experienced similar and significant improvements in health-related quality of life , psychiatric profile , and sexual satisfaction . Overall , 68 of 90 ( 75 % ) patients in the uterosacral ligament resection group and 67 of 90 ( 74 % ) patients in the conservative surgery group were satisfied at 1 year . CONCLUSION ( S ) Addition of uterosacral ligament resection to conservative laparoscopic surgery for endometriosis did not reduce the medium- or long-term frequency and severity of recurrence of dysmenorrhea", "OBJECTIVE To assess post‐treatment effects in endometriosis patients of a 12‐month course of GnRH agonist alone or with one of three “ add‐back ” regimens . METHODS This is a post‐treatment follow‐up analysis of a r and omized , double‐masked , placebo‐controlled 52‐week trial . All patients had received monthly leuprolide acetate and were r and omized to one of four groups : A — daily placebo ; B — daily norethindrone acetate 5 mg ; C — daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg ; and D — daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg . Of 201 patients enrolled in the initial trial , 123 completed at least 280 days of therapy and entered the follow‐up period . Physical findings and symptoms were quantified , and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post‐therapy . RESULTS Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups ( P < .05 ) . Findings were not affected by endometriosis scores noted on screening laparoscopy . Mean bone mineral density values remained at or above baseline in all add‐back groups . The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow‐up visit ( P < .001 ) . CONCLUSION GnRH agonist and norethindrone acetate alone or combined with low‐dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy", "OBJECTIVE To estimate the risk of recurrence after administration of hormone replacement therapy ( HRT ) among women who have had endometriosis and who underwent bilateral salpingo-oophorectomy ( BSO ) . DESIGN Prospect i ve r and omized trial ( 115 women receiving HRT and 57 not receiving HRT ) . SETTING ; Public university hospital . PATIENT(S ) Women with a histologic diagnosis of endometriosis in whom BSO was performed ; 91.8 % had a total hysterectomy . INTERVENTION(S ) Periodical clinical examination , vaginal ultrasound , and CA-125 levels ; surgical evaluation and histologic study . MAIN OUTCOME MEASURE(S ) Recurrence rate , prognostic factors , and a mean follow-up time of 45 months . RESULT ( S ) There was no recurrence among women who did not receive HRT , versus a 3.5 % rate ( 4 out of 115 ) , or 0.9 % per year , in women who received HRT . Two recurrences required abdominal surgery . There was one additional patient who required surgery , but the relationship to the endometriosis recurrence was controversial . Among women receiving HRT , the following risk factors were detected : peritoneal involvement > 3 cm ( 2.4 % recurrence per year vs. 0.3 % ) and incomplete surgery ( 22.2 % per patient vs. 1.9 % ) . CONCLUSION ( S ) Patients with a history of endometriosis in whom total hysterectomy and bilateral salpingo-oophorectomy have been performed have a low risk of recurrence when HRT is administered . In those patients , HRT is a reasonable option . However , in cases with peritoneal involvement > 3 cm , the recurrence rate makes HRT a controversial option ; if HRT is indicated , it should be monitored closely", "OBJECTIVES To determine the effectiveness of a 3-month course of nafarelin and , furthermore , to determine the long-term efficacy in patients treated for 3 and 6 months with nafarelin for symptoms associated with endometriosis . DESIGN Double-blind , prospect i ve , multicenter , clinical trial . SETTING Fifteen reproductive endocrine clinics throughout the United States . PATIENTS One hundred seventy-nine women with pelvic pain and endometriosis . INTERVENTIONS Patients were assigned r and omly to 3 months nafarelin followed by 3 months of placebo ( n = 91 ) or to 6 months nafarelin ( n = 88 ) in a prospect i ve , r and omized , double-blind multicenter trial . Patients were followed for 12 months after cessation of therapy . MAIN OUTCOME MEASURES Patient-reported pain scores and physician-reported physical exam findings . RESULTS Pain scores dropped significantly by the end of treatment in both groups . Symptoms recurred in both groups , and pain scores gradually increased during the follow-up period but always remained below baseline in both groups . No significant difference in efficacy was noted between the groups . A total of 26 % of patients in each group underwent retreatment for recurrent symptoms . CONCLUSIONS A 3-month course of nafarelin provided effective symptom relief for endometriosis . One year follow-up demonstrated continued pain relief but with gradual return of symptoms", "OBJECTIVE Our purpose was to investigate the efficacy of postsurgical treatment with nafarelin in women with advanced endometriosis . STUDY DESIGN Eligible for trial were women < or = 38 years old with unexplained infertility with or without chronic pelvic pain and stage III or IV endometriosis according to the American Fertility Society , revised , classification who underwent laparotomy as first surgical treatment for debulking or radical surgery of endometriotic lesions . Patients were assigned according to a r and omization list to nasal nafarelin , 400 micrograms/day ( 36 subjects ) or placebo nasal spray ( 39 subjects ) for 3 months . Pelvic pain was assessed before first surgery and at the 12-month follow-up visit in women with pelvic pain by means of a multidimensional score system and a 10-point linear pain scale . RESULTS No marked differences in pain scores emerged among women allocated to different treatments . The mean reduction of the multidimensional score was 3.6 and 4.0 , respectively , in women allocated to nafarelin and placebo and of the 10-point linear scale scores was 7.0 and 6.9 . These differences were not statistically significant . Within 1 year from r and omization , of the 36 women allocated to nafarelin and the 39 allocated to placebo , seven ( 19 % ) and seven ( 18 % ) , respectively , became pregnant . CONCLUSION This study suggests that medical treatment with nafarelin does not markedly improve pelvic pain and short-term reproductive prognosis in women with stages III and IV endometriosis", "OBJECTIVES To evaluate a clinical examination during menstruation and plasma CA-125 concentrations to diagnose deep endometriosis . DESIGN Prospect i ve study in 61 women scheduled for a laparoscopy , a retrospective study in 140 women with deep endometriosis , and a clinical validation study in 16 women with painful pelvic nodularities during menstruation . SETTING University Hospital Gasthuisberg , a tertiary referral center . RESULTS In the retrospective study , deep endometriosis was detected by routine clinical examination in only 36 % of women . Lesions infiltrating deeper than 15 mm were detected in 50 % . In the prospect i ve study pelvic nodularities were detected by routine clinical examination in 4 women but were detected in 22 by clinical examination during menstruation . The latter was highly reliable to diagnose deep endometriosis , cystic ovarian endometriosis , and cul-de-sac obliteration . CA-125 concentrations were higher during menstruation and correlated with deep endometriosis and with deep and cystic ovarian endometriosis . Nodularities at clinical examination or follicular phase CA-125 concentrations > 35 U/mL are useful to decide that a bowel preparation should be given , achieving a sensitivity of 87 % and a specificity of 83 % . In the clinical validation study , deep endometriosis was found in 14 of 16 women . CONCLUSION Clinical examination during menstruation can diagnose reliably deep endometriosis , cystic ovarian endometriosis , or cul-de-sac adhesions . This test , preferentially combined with a follicular phase CA-125 assay , should be used to decide whether a preparation for bowel surgery should be given", "BACKGROUND Some patients with endometriosis are c and i date s for sympathectomy of the superior hypogastric plexus . The objective of this paper is to describe our technique of laparoscopic presacral neurolysis for sympathectomy and to report 1 year results of the first 15 cases . METHODS To achieve this objective in a prospect i ve observational study of 1 year follow-up ; we performed laparoscopic presacral chemical neurolysis with phenol in 15 patients with pelvic pain and minimal-moderate endometriosis . The main outcome measures were : the impact of treatment on pelvic symptom resolution , non-opioid analgesic consumption during menses , sexual performance and observed complications and side effects during 1 year follow-up . RESULTS We noted a significant reduction in total pelvic symptom score as compared with baseline mean ( SD ) of 9.04 ( 1.2 ) . The mean difference [ 95 % confidence interval ( CI ) ] of reduction was 5.7 ( 4.9 - 6.5 ) , 5.8 ( 5.0 - 6.6 ) and 5.8 ( 4.9 - 6.6 ) from the baseline at the 3rd , 6th and 12th postoperative month ( P < 0.001 ) . We observed a significant improvement in Sabbatberg Sexual Rating Scale as compared with baseline mean ( SD ) of 30.9 ( 4.3 ) . The mean difference ( 95 % CI ) of increase was 33.4 ( 30.3 - 36.4 ) , 33.2 ( 30.1 - 36.2 ) and 33.2 ( 30.1 - 36.3 ) from the baseline at the 3rd , 6th and 12th postoperative month . We observed a significant reduction in analgesic consumption during menses in terms of total naproxen sodium tablets as compared with baseline mean ( SD ) of 8.9 ( 1.1 ) . The mean difference ( 95 % CI ) of reduction in the total number of naproxen sodium 250 mg tablets was 6.5 ( 5.5 - 7.5 ) , 6.7 ( 5.7 - 7.7 ) and 6.6 ( 5.6 - 7.6 ) from the baseline at the 3rd , 6th and 12th postoperative month . The most common side effect was constipation . CONCLUSION Laparoscopic presacral neurolysis is feasible and simple . More data is needed to support its efficacy and safety", "STUDY OBJECTIVE To evaluate the relationship between prevalence and severity of chronic pelvic pain ( CPP ) and stage , site , and type of endometriosis . DESIGN Prospect i ve , observational study ( Canadian Task Force classification II-2 ) . SETTING University Hospital . PATIENTS Of 90 consecutive women with biopsy-proved endometriosis , laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis . INTERVENTION Preoperatively , using a 10-point visual analog scale , the severity of dysmenorrhea , CPP , and deep dyspareunia was assessed . During laparoscopy all visible endometriotic lesions were recorded and treated . MEASUREMENTS AND MAIN RESULTS Ten women ( 11.1 % ) had no pain ; 72 had dysmenorrhea ( mild in 13 , moderate in 37 , severe in 22 ) ; 55 had CPP ( mild in 11 , moderate in 25 , severe in 19 ) ; and 39 deep dyspareunia ( mild in 5 , moderate in 31 , severe in 3 ) . The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions ( p = 0.004 ) ; the severity of CPP correlated with deep endometriosis on the uterosacral ligaments ( p = 0.0001 ) and extent of pelvic adhesions ( p = 0.02 ) ; and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments ( p = 0.04 ) . Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments ( p = 0.0001 ) , peritoneal adhesions ( p = 0.01 ) , and extent of adnexal adhesions ( p = 0.01 ) . No significant correlation was found among revised American Fertility Society stage of endometriosis ; presence and size of ovarian endometriomas ; extent , type , and site of peritoneal lesions ; and pain scores . By logistic regression analysis , the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis ( p = 0.0001 ) and presence and extent of adnexal adhesions without cystic endometriosis ( p = 0.01 ) , and by the presence of ovarian endometrioma with periovarian adhesions ( p = 0.03 ) . Chronic pelvic pain was predicted by both deep endometriosis ( p = 0.0001 ) and ovarian endometriomas with adnexal adhesions ( p = 0.03 ) . Deep dyspareunia was predicted simultaneously by deep endometriosis ( p = 0.01 ) and an ovarian endometrioma with periovarian adhesions ( p = 0 . 008 ) . Conclusion . Deep endometriosis , pelvic adhesions , and ovarian cystic endometriosis were independent predictors of pelvic pain . These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain", "In a 3-year prospect i ve study of 643 consecutive laparoscopies for infertility , pelvic pain , or infertility and pain , the pelvic area , the depth of infiltration , and the volume of endometriotic lesions were evaluated . The incidence , area , and volume of subtle lesions decreased with age , whereas for typical lesions these parameters and the depth of infiltration increased with age . Deeply infiltrating endometriosis was strongly associated with pelvic pain , women with pain having larger and deeper lesions . Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class , considerations for a simplifying revision with inclusion of deep lesions are suggested . In conclusion , suggestive evidence is presented to support the concept that endometriosis is a progressive disorder , and it is demonstrated that deep endometriosis is strongly associated with pelvic pain", "To study the production of prostacyclin ( PGI2 ) and thromboxane A2 ( TxA2 ) in endometriosis in vitro , sample s of endometriotic tissue taken during operation from 6 women were superfused for 4.5 hours in 95 % O2/5 % CO2 at 37 degrees C , and the stable metabolites of PGI2 ( = 6-keto-PGF1 alpha ) , and TxA2 ( = TxB2 ) were measured by radioimmunoassays from the superfusates . All sample s studied produced 6-keto-PGF1 alpha in the range from 0.2 to 10.5 nanograms/gram of dry tissue/minute with a mean of 3.6 ng/g/min during the whole experiment . TxB2 was also released by each sample at rates between 0.2 and 11.9 ng/g/min ( mean 2.6 ng/g/min ) . The production of these prostanoids tended to be greater in the serosal ( n = 2 ) than in the ovarian ( n = 4 ) endometriosis . The addition of indomethacin of 10(-5 ) - 10(-3 ) moles/l to the superfusion medium inhibited concentration-dependently the synthesis of these prostanoids . Apart from these in vitro data implying the production of PGs in endometriosis , 18 patients with pelvic endometriosis sustained no relief for their endometriotic symptoms from the treatments with three anti-prostagl and ins ( acetylsalicylic acid , indomethacin , tolfenamic acid ) in a double-blind , placebo-controlled trial", "OBJECTIVE To compare surgical performance and recurrence rates in patients su bmi tted to laparoscopy for endometrioma excision following GnRH agonist ( GnRH-a ) treatment versus no preoperative medical treatment . DESIGN Controlled clinical study . SETTING A tertiary care university hospital . PATIENTS Twenty patients with unilateral endometriomas underwent operative laparoscopy after 3-month GnRH-a treatment , whereas 21 patients underwent laparoscopic excision of endometriomas without preoperative medical treatment . INTERVENTIONS Operative laparoscopy was performed with the stripping technique using a four-puncture approach . MAIN OUTCOME MEASURE A blinded videotape review was undertaken to evaluate the duration and complexity of the different phases of surgery . Recurrence rates were evaluated at 1-year follow-up ultrasonography . RESULTS No significant difference was found between the two groups in total operative time , cyst excision time , time needed for cyst capsule stripping and coagulation of ovarian parenchyma , and the complexity of the latter phases ; recurrence rates also were comparable . CONCLUSION Preoperative GnRH-a treatment for endometriomas does not seem to offer any advantage in terms of subsequent surgical performance", "OBJECTIVE To evaluate the effect of a 3-month course of GnRH agonist administered immediately before IVF-ET in infertile patients with endometriosis . DESIGN Prospect i ve , r and omized trial . SETTING Three tertiary care assisted reproductive technology programs . PATIENT(S ) IVF-ET c and i date s with surgically confirmed endometriosis . INTERVENTION(S ) Twenty-five patients received three courses of a long-acting GnRH agonist , 3.75 mg i.m . every 28 days , followed by st and ard controlled ovarian hyperstimulation . Twenty-six patients received st and ard controlled ovarian hyperstimulation with mid-luteal phase GnRH agonist down-regulation or microdose flare regimens . MAIN OUTCOME MEASURE(S ) Response to controlled ovarian hyperstimulation , ongoing pregnancy rates per cycle , group implantation rates , and implantation rate per embryo transfer procedure . RESULT ( S ) The extent of surgically confirmed endometriosis was greater in patients who received the long-acting GnRH regimen for 3 months before IVF-ET . The groups did not differ significantly in terms of dose or duration of gonadotropin stimulation , number of oocytes retrieved , fertilization rate , or number of embryos transferred . Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates ( 80 % vs. 53.85 % ) and a trend toward higher implantation rates ( 42.68 % vs. 30.38 % ) . CONCLUSION ( S ) Prolonged use of GnRH agonist before IVF-ET in patients with endometriosis result ed in significantly higher ongoing pregnancy rates than did st and ard controlled ovarian hyperstimulation regimens . No deleterious effect on ovarian response was observed", "OBJECTIVE To assess the hypothesis that pregnancy rates ( PRs ) after operative laparoscopy ( Laparoscopy Group ) for endometriosis treatment would be equal to or greater than diagnostic laparoscopy only ( No Treatment Group ) , diagnostic laparoscopy with medical treatment ( Medical Treatment Group ) , and laparotomy ( Laparotomy Group ) . DESIGN Prospect ively recorded data were analyzed to identify significant variables affecting PRs . These variables were statistically controlled for using survival analysis with multiple fixed covariates to compare operative laparoscopy PRs versus other treatment PRs . SETTING Treatment was performed by the senior author in a referral reproductive endocrinology and surgery private practice . PATIENTS Five hundred seventy-nine infertile women were diagnosed with endometriosis . A subset ( n = 258 ) considered to have endometriosis only was evaluated separately ( Endometriosis-Only Subset ) . INTERVENTIONS Treatment groups included : No Treatment Group , Medical Treatment Group , Laparoscopy Group , and Laparotomy Group . MAIN OUTCOME MEASURE(S ) Pregnancy was used as the indicator of treatment success . RESULTS Laparoscopy Group PRs were at least equal to all other treatment groups and were significantly higher than some other treatment groups in some comparisons . CONCLUSIONS Operative laparoscopy is the treatment of choice for infertile women with endometriosis unless they have severe tubal and /or fimbrial disease", "The most effective therapy for endometriosis is a matter for debate . The aim of the present r and omized study was to evaluate the efficacy of low doses of danazol on recurrence of pelvic pain in patients with moderate or severe endometriosis , who had undergone laparoscopic surgery and 6 months of gonadotrophin-releasing hormone analogue ( GnRHa ) therapy . After surgery , 28 patients with moderate or severe endometriosis underwent therapy for 6 months with GnRHa i. m. every 4 weeks . They were then r and omized into two groups : group A ( 14 subjects ) was treated with 100 mg/day danazol for 6 months ; group B ( 14 subjects , control ) did not receive any type of therapy . After 12 months of treatment , group A had a significantly ( P < 0.01 ) lower pain score than group B. There was no significant difference between the groups in oestrogen concentrations , bone mineral density or side-effects . The results suggest that low-dose danazol therapy reduces recurrence of pelvic pain in patients with moderate or severe endometriosis , treated surgically , and has few or no metabolic side-effects", "Prostagl and ins ( PGs ) may be involved in the development of the symptoms of endometriosis . Therefore 18 patients with pelvic endometriosis were treated in placebo controlled double-blind trial with different prostagl and in bio synthesis inhibitors . These drugs were : acetylsalicylic acid ( 0.5 g x 3 ) exerting a weak PG-synthetase inhibition , indomethacin ( 25 mg x 3 ) inhibiting PG-synthetase , and as a representative of fenamates , tolfenamic acid ( 200 mg x 3 ) , which both inhibits PG-synthetase and antagonizes PGs at the target level . The therapeutic effect was evaluated using a specific endometriosis score separately during menstruation and in premenstrum . Prostagl and in bio synthesis inhibitors did not alleviate premenstrual complaints better than placebo . During menstruation tolfenamic acid relieved endometriotic symptoms more effectively than placebo while indomethacin and acetylsalicylic acid did not differ from placebo . A drug which inhibit both the synthesis and action of PGs can thus be used in the alleviation of secondary dysmenorrhea due to endometriosis", "Twenty patients with moderate to very severe painful menstrual periods secondary to endometriosis were treated in a double-blind , four-period , crossover clinical trial with naproxen sodium and placebo . Complete or substantial pain relief was obtained in 83 % of the cases of painful menstruation with naproxen sodium and in 41 % with placebo ( P=.008 ) . Only 5 % of the naproxen sodium-treated women needed supplemental analgesics compared with 36 % of the placebo-treated women ( P=.002 ) . There was a trend towards diminished interference of dysmenorrhea with normal patient activities during naproxen sodium treatment compared with placebo ( P=.069 ) . No significant side effects occurred with either treatment . These results indicated that naproxen sodium is efficacious and safe for the treatment of menstrual distress in patients with endometriosis . ( Obstet Gynecol 65:379 , 1985", "OBJECTIVE To evaluate the efficacy of superovulation and IUI versus no treatment for infertility associated with minimal or mild endometriosis . DESIGN R and omized trial . SETTING ( S ) London Health Sciences Centre , University Campus , The University of Western Ontario , London , Ontario ; and Royal Victoria Hospital , McGill University , Montreal , Quebec , Canada . PATIENT(S ) Three hundred eleven cycles in 103 couples in whom minimal or mild endometriosis was the sole identified subfertility factor . INTERVENTION(S ) Superovulation with FSH and IUI . MAIN OUTCOME MEASURE(S ) Live birth . RESULT ( S ) Live birth followed 14 of 127 ( 11 % ) superovulation and IUI cycles and 4 of 184 ( 2 % ) no-treatment cycles . The odds ratio was 5.6 ( 95 % confidence interval 1.8 to 17.4 ) in favor of superovulation and IUI . CONCLUSION ( S ) Treatment with superovulation and IUI was associated with superior outcome both by crude live-birth rates and proportional hazard analysis" ]

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[ "Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin's lymphoma: dose finding and identification of predictors of response.", "Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin Beta, in hematologic malignancies.", "Effective treatment of disease‐related anaemia in B‐chronic lymphocytic leukaemia patients with recombinant human erythropoietin", "Darbepoetin alpha for the treatment of anemia in patients with active cancer not receiving chemotherapy or radiotherapy: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study.", "Once-weekly epoetin-beta improves hemoglobin levels in cancer patients with chemotherapy-induced anemia: A randomized, double-blind, dose-finding study.", "The longitudinal relationship of hemoglobin, fatigue and quality of life in anemic cancer patients: results from five randomized clinical trials.", "The effectiveness and tolerability of epoetin alfa in patients with multiple myeloma refractory to chemotherapy", "Impact of epoetin‐β on survival of patients with lymphoproliferative malignancies: long‐term follow up of a large randomized study *", "Randomized phase II comparison of standard CHOP with weekly CHOP in elderly patients with non-Hodgkin's lymphoma.", "Once‐weekly epoetin beta is highly effective in treating anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin production", "Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial", "Randomized, dose‐finding study of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies", "Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing multiple myeloma", "Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma.", "Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebo-controlled trials.", "Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial.", "Approaches to the analysis of quality of life data: experiences gained from a Medical Research Council Lung Cancer Working Party palliative chemotherapy trial", "Quality‐of‐life and health benefits of early treatment of mild anemia", "Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia.", "Epoetin alfa for the treatment of the anemia of multiple myeloma. A prospective, randomized, placebo-controlled, double-blind trial.", "Efficacy of epoetin alfa in the treatment of anaemia of multiple myeloma" ]

[ "Previous phase I-II clinical trials have shown that recombinant human erythropoietin ( rHuEpo ) can ameliorate anemia in a portion of patients with multiple myeloma ( MM ) and non-Hodgkin 's lymphoma ( NHL ) . Therefore , we performed a r and omized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo . A total of 146 patients who had hemoglobin ( Hb ) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial . Patients were r and omized to receive 1,000 U ( n = 31 ) , 2,000 U ( n = 29 ) , 5,000 U ( n = 31 ) , or 10,000 U ( n = 26 ) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy ( n = 29 ) . Of the patients , 84 suffered from MM and 62 from low- to intermediate- grade NHL , including chronic lymphocytic leukemia ; 116 of 146 ( 79 % ) received chemotherapy during the study . The mean baseline Hb level was 9.4 + /- 1.0 g/dL. The median serum Epo level was 32 mU/mL , and endogenous Epo production was found to be defective in 77 % of the patients , as judged by a value for the ratio of observed-to-predicted serum Epo levels ( O/P ratio ) of < or = 0.9 . An intention-to-treat analysis was performed to evaluate treatment efficacy . The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 ( P = .57 ) , 0.22 ( P = .05 ) , 0.43 ( P = .01 ) , and 0.58 ( P = .0001 ) g/dL in the 1,000 U , 2,000 U , 5,000 U , and 10,000 U groups , respectively ( P values versus control ) . The probability of response ( delta Hb > or = 2 g/dL ) increased steadily and , after 8 weeks , reached 31 % ( 2,000 U ) , 61 % ( 5,000 U ) , and 62 % ( 10,000 U ) , respectively . Regression analysis using Cox 's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo , whereas only one quarter of those with adequate Epo levels did so . Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50 % of these patients are expected to respond to rHuEpo . Thus , rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production . From a practical point of view , we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels , whereas the choice of the initial dosage should be based on residual marrow function", "PURPOSE To investigate the effect of recombinant human erythropoietin ( epoetin beta ) on anemia , transfusion need , and quality of life ( QOL ) in severely anemic patients with low- grade non-Hodgkin 's lymphoma ( NHL ) , chronic lymphocytic leukemia ( CLL ) , or multiple myeloma ( MM ) . PATIENTS AND METHODS Transfusion-dependent patients with NHL ( n = 106 ) , CLL ( n = 126 ) , or MM ( n = 117 ) and a low serum erythropoietin concentration were r and omized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks . Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival ( hemoglobin [ Hb ] > 8.5 g/dL ) between weeks 5 to 16 . Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need . QOL was assessed by the Functional Assessment of Cancer Therapy scale . RESULTS Transfusion-free ( P = .0012 ) survival and transfusion- and severe anemia-free survival ( P = .0001 ) were significantly greater in the epoetin beta group versus placebo ( Wald chi(2 ) test ) , giving a relative risk reduction of 43 % and 51 % , respectively . The response rate was 67 % and 27 % in the epoetin beta versus the placebo group , respectively ( P < .0001 ) . After 12 and 16 weeks of treatment , QOL significantly improved in the epoetin beta group compared with placebo ( P < .05 ) ; this improvement correlated with an increase in Hb concentration ( > or = 2 g/dL ) . A target Hb that could be generally recommended could not be identified . CONCLUSION Many severely anemic and transfusion-dependent patients with advanced MM , NHL , and CLL and a low performance status benefited from epoetin therapy , with elimination of severe anemia and transfusion need , and improvement in QOL", "Nine B‐chronic lymphocytic leukaemia ( B‐CLL ) patients suffering from anaemia , due to no obvious cause except their disease , were treated with recombinant human erythropoietin ( r‐HuEPO ) . The treatment protocol provided a closed label phase of 3 months duration , during which the patients received r‐HuEPO or placebo in a ratio of 2:1 , followed by an open label phase , also of 3 months duration , during which r‐HuEPO was administered to all patients three times a week s.c . r‐HuEPO was given at a dose of 150 U/kg of body weight with an escalation of 50 U/kg up to a maximum of 300 U/kg three times a week . Complete response was achieved in 5/9 ( 55 % ) patients and partial response in 3/9 ( 33 % ) . The response obtained was independent of the pretreatment serum EPO levels , the duration of anaemia , the concomitant administration of chemotherapy , the presence of splenomegaly , or the degree of bone marrow infiltration by lymphocytes . It appears that r‐HuEPO is very effective in reversing the disease‐related anaemia of B‐CLL patients", "PURPOSE The efficacy and safety of darbepoetin alpha ( DA ) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated . PATIENTS AND METHODS Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III , multicenter , r and omized , placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks ( Q4W ) for up to 16 weeks with a 2-year follow-up for survival . Patients who completed 16 weeks of treatment could receive the same treatment as r and omized Q4W for an additional 16 weeks . The primary end point was all occurrences of transfusions from weeks 5 through 17 ; safety end points included incidence of adverse events and survival . RESULTS The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo . DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period . Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo ( P = .022 ) . This effect varied by baseline covariates including , sex , tumor type , and geographic region ; statistical significance diminished ( P = .12 ) when the analysis was adjusted for baseline imbalances or known prognostic factors . CONCLUSION DA was not associated with a statistically significant reduction in transfusions . Shorter survival was observed in the DA arm ; thus , this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer", "OBJECTIVE To determine a recommended dose of once-weekly epoetin-beta administration for anemic cancer patients receiving myelosuppressive chemotherapy , we conducted a multicenter , r and omized , double-blind trial . METHODS A total of 86 patients with malignant lymphoma or lung cancer who received chemotherapy containing platinum , taxanes or anthracyclines were enrolled in the study . Patients were r and omly assigned into groups that received three dose levels of epoetin-beta ( 9000 , 18,000 or 36,000 IU ) administered subcutaneously once a week for 12 weeks . The primary endpoint was change in hemoglobin , while the secondary endpoints were quality of life ( QOL ) assessed by Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) question naire and transfusion requirements . RESULTS Among the 69 patients ( per protocol set population ) assessable for efficacy , hemoglobin level change in the 36,000 IU group was significantly greater than that in the 9000 IU group ( 1.75 + /- 2.15 versus 0.04 + /- 1.98 g/dl ; P = 0.009 ) , and a significant dose-response relationship was observed for the change in hemoglobin level ( P = 0.003 ) . Although changes in FACT-An Total Fatigue subscale ( Fatigue subscale ) scores were similar for the three dosage groups , there was a statistically significant correlation ( r = 0.435 , P < 0.001 ) between the change in hemoglobin levels and the change in Fatigue subscale scores . The proportion of transfused patients was significantly smaller in the 36 000 IU group compared with that in the 9000 IU group ( P = 0.022 , not adjusted for pre- study transfusions ) . The incidence of adverse events was similar in the three dosage groups . CONCLUSIONS Once-weekly epoetin-beta 36,000 IU for 12 weeks was well tolerated and significantly increased hemoglobin levels in anemic cancer patients receiving chemotherapy", "BACKGROUND Anemia is common in cancer and has been associated with fatigue and reduced health-related quality of life ( HRQOL ) . We report the association between hemoglobin and fatigue and the impact of reducing fatigue on several domains of HRQOL . PATIENTS AND METHODS These analyses were based on five r and omized trials . Patients completed the Functional Assessment of Cancer Therapy ( FACT ) Anemia scales and numeric rating scales of Energy , Activity and Overall Health at baseline and after the 12-week treatment period . t-tests and linear regression models were used to evaluate associations . Analyses were stratified into three groups : solid tumor chemotherapy patients , lymphoproliferative malignancy chemotherapy patients and non-chemotherapy patients . RESULTS Adjusted mean differences ( 95 % CI ) in FACT Fatigue change scores between hemoglobin responders ( > or = 2 g/dl increase ) and non-responders were 3.0 ( 1.2 , 4.7 ) , 2.8 ( 0.6 , 5.0 ) and 5.8 ( 2.2 , 9.5 ) among the solid tumor , lymphoproliferative malignancy and non-chemotherapy groups , respectively . Significantly greater improvements ( P < 0.01 ) were observed in the FACT well-being scales for patients with meaningful improvement in fatigue ( FACT Fatigue change score > or =3 points ) . After controlling for other factors , patients whose fatigue improved reported substantially greater improvements in energy , ability to perform usual activities and overall health ( P < 0.0001 ) . CONCLUSIONS Across five trials of cancer patients on and off chemotherapy , hemoglobin response was associated with meaningful improvements in fatigue , which , in turn , was associated with improved physical , functional , emotional and overall well-being", "Anemia is a frequent complication of multiple myeloma , becoming chronic in patients who are resistant to chemotherapy . This r and omized , parallel , controlled multicenter study ( 71 patients receiving concomitant chemotherapy ) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy . Forty patients were treated with subcutaneous epoetin alfa ( 150 IU/kg per dose , increasing to 300 IU/kg per dose , every 3 weeks ) for 6 months , and 31 entered a control group . The epoetin alfa group had a significantly ( P≤0.001 ) greater percentage of patients ( 75 % vs. 21 % ) with increases in hemoglobin levels and /or reduced transfusion requirements . In 44 non pre-transfused patients ( 20 controls , 24 in the epoetin alfa group ) , the mean increase in hemoglobin was significantly ( P≤0.0001 ) greater in the epoetin alfa group ( + 2.1 vs. −0.2 g/dl ) . Increases in hematocrit and red blood cells were also significantly ( P≤0.0001 ) greater in epoetin alfa-treated patients , with corresponding reductions in transfusion requirement . In the 27 pre-transfused patients ( 11 controls , 16 in the epoetin alfa group ) , there was a trend towards reduced transfusional need in epoetin alfa-treated patients . Thus , in patients with multiple myeloma refractory to chemotherapy epoetin alfa is a well-tolerated treatment which improves anemia in non pre-transfused patients and appears to reduce transfusion need in those previously transfused", "Recent studies have suggested that epoetin treatment of anaemia may influence the survival of patients with cancer . We conducted an analysis of long‐term survival in patients with lymphoproliferative malignancies treated with epoetin‐β or placebo in a large‐scale study . This was a r and omized , double‐blind trial in which patients with transfusion‐dependent anaemia and lymphoproliferative malignancy received epoetin‐β 150 IU/kg or placebo three times weekly for 16 weeks . Long‐term survival data were analysed by st and ard Kaplan – Meier methods and differences between groups were assessed using a log‐rank test . The intention‐to‐treat population consisted of 343 patients ( epoetin‐β , n = 170 ; placebo , n = 173 ) . There were no major differences between the two treatment groups in demographic or clinical characteristics/prognostic factors . A total of 110 ( 65 % ) patients died in the epoetin‐β group ( censored , n = 60 ) and 109 ( 63 % ) died in the placebo group ( censored , n = 64 ) up to the end of long‐term follow up . Kaplan – Meier curves for survival were similar in both groups . Median survival was 17 months with epoetin‐β and 18 months with placebo . A log‐rank test indicated no significant difference in survival ( P = 0·76 ) . This long‐term follow up indicated that epoetin‐β has no significant effect on survival compared to placebo in anaemic patients with lymphoproliferative malignancies", "PURPOSE To determine whether modifying the st and ard regimen of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) from full doses given every 3 weeks to one-third doses given weekly ( chop ) increases the received chemotherapy dose-intensity in elderly patients with advanced-stage intermediate- grade lymphoma . PATIENTS AND METHODS Consenting patients , age > or = 65 years who had acceptable cardiac , renal , and liver function and an Eastern Cooperative Oncology Group ( ECOG ) performance status less than 4 , were stratified by bone marrow and performance status and r and omized to receive st and ard CHOP or weekly chop . Drug doses were attenuated or escalated according to a defined dose-modification schedule . The primary outcome was average relative received dose-intensity . Secondary outcomes included response , progression-free and overall survival , toxicity , and performance status . RESULTS Nineteen patients were allocated to each group . No difference in received dose-intensity was seen . When dose-intensity was calculated for the first six cycles of therapy , average relative received dose-intensity was .92 with CHOP versus .89 with weekly chop ( P = .5 ) ; when calculated for the first 18 weeks of therapy , values were .88 with CHOP versus .89 with weekly chop ( P = .8 ) . The complete response rate was 68 % with CHOP versus 74 % with weekly chop ( P = .9 ) . At 2 years , the progression-free survival rate was 57 % with CHOP versus 46 % with weekly chop ( P = .16 ) and the survival rate was 74 % with CHOP versus 51 % with weekly chop ( p = .05 ) . More myelotoxicity was seen with CHOP . CONCLUSION We conclude that CHOP can be given in sufficient doses to elderly patients and that weekly chop does not increase received dose-intensity . Progression-free and overall survival are unlikely to be superior with weekly chop , and may be worse . CHOP should remain the st and ard against which new therapies for elderly patients with intermediate- grade lymphoma are compared", "Summary . Epoetin beta , three‐times weekly ( t.i.w . ) , is effective in reversing anaemia in lymphoproliferative disorders . The current study investigated whether an epoetin beta dose of 30 000 IU given subcutaneously once weekly ( q.w . ) was at least as effective as 10 000 t.i.w . administration in anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin ( Epo ) production . Overall , 241 anaemic patients with multiple myeloma , low‐ grade non‐Hodgkin 's lymphoma or chronic lymphocytic leukaemia , all with serum Epo values ≤ 100 mU/ml , were r and omized to receive the q.w . ( n = 119 ) or t.i.w . ( n = 122 ) regimen for 16 weeks . The primary efficacy criterion , i.e. the time‐adjusted area under the haemoglobin – time curve from weeks 5–16 , was comparable between the q.w . and t.i.w . groups [ difference = − 0·20 g/dl ( 90 % confidence interval − 0·52–0·11 ) ] . Moreover , response rates were high and similar in both arms ( 72%vs 75 % , q.w . and t.i.w . groups respectively ) . Baseline serum Epo was predictive of response : the lower serum Epo , the higher the likelihood of response ( P = 0·002 ) . Thus , epoetin beta administered q.w . is an effective and convenient treatment for anaemia in patients with lymphoproliferative disorders . Tailoring this treatment modality to subjects with defective endogenous Epo production represents a rational use of epoetin from both a medical and a community perspective", "BACKGROUND Anaemia is associated with poor cancer control , particularly in patients undergoing radiotherapy . We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer . METHODS We did a multicentre , double-blind , r and omised , placebo-controlled trial in 351 patients ( haemoglobin < 120 g/L in women or < 130 g/L in men ) with carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx . Patients received curative radiotherapy at 60 Gy for completely ( R0 ) and histologically incomplete ( R1 ) resected disease , or 70 Gy for macroscopically incompletely resected ( R2 ) advanced disease ( T3 , T4 , or nodal involvement ) or for primary definitive treatment . All patients were assigned to subcutaneous placebo ( n=171 ) or epoetin beta 300 IU/kg ( n=180 ) three times weekly , from 10 - 14 days before and continuing throughout radiotherapy . The primary endpoint was locoregional progression-free survival . We assessed also time to locoregional progression and survival . Analysis was by intention to treat . FINDINGS 148 ( 82 % ) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L ( women ) or 150 g/L ( men ) compared with 26 ( 15 % ) given placebo . However , locoregional progression-free survival was poorer with epoetin beta than with placebo ( adjusted relative risk 1.62 [ 95 % CI 1.22 - 2.14 ] ; p=0.0008 ) . For locoregional progression the relative risk was 1.69 ( 1.16 - 2.47 , p=0.007 ) and for survival was 1.39 ( 1.05 - 1.84 , p=0.02 ) . INTERPRETATION Epoetin beta corrects anaemia but does not improve cancer control or survival . Disease control might even be impaired . Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials", "Summary . Darbepoetin alfa is a novel erythropoiesis‐stimulating protein with a prolonged serum half‐life . This r and omized , double‐blind , placebo‐controlled , dose‐finding study investigated the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies who were receiving chemotherapy . Patients were r and omized in a 1:2:2:1 ratio to receive darbepoetin alfa 1·0 μg/kg ( n = 11 ) , 2·25 μg/kg ( n = 22 ) , 4·5 μg/kg ( n = 22 ) or placebo ( n = 11 ) , administered subcutaneously once weekly for 12 weeks . No dose increases were allowed during the study . A higher proportion of patients achieved a haemoglobin response ( defined as a ≥ 2·0 g/dl increase from baseline ) in the darbepoetin alfa 1·0 μg/kg ( 45 % ) , 2·25 μg/kg ( 55 % ) and 4·5 μg/kg ( 62 % ) groups than in the placebo group ( 10 % ; P < 0·01 ) . The mean change in haemoglobin from baseline to week 13 was 1·56 g/dl in the 1·0 μg/kg group , 1·64 g/dl in the 2·25 μg/kg group and 2·46 g/dl in the 4·5 μg/kg group , compared with a mean change of 1·00 g/dl in the placebo group . The overall safety profile of darbepoetin alfa in this study was similar to that of placebo . These results show that darbepoetin alfa effectively and safely increased haemoglobin concentrations in patients with lymphoproliferative malignancies . Confirmative studies at doses of 2·25 and /or 4·5 μg/kg/week in this population are warranted", "Recombinant human erythropoietin ( rHu-EPO ) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions , including bone marrow tumors such as multiple myeloma ( MM ) . We studied a group of 54 patients with MM undergoing second-induction chemotherapy . Thirty of them were r and omly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week , increased to 300 units/kg from the sixth week to the end of the 24-week study . Hemoglobin ( Hb ) levels increased in 77.7 % of these patients by the eighth week . In addition , five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month , whereas seven control patients required frequent supplements . Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts , whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy . The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocol s combined with α-interferon ( α-IFN ) included an increase of serum IgM after the third month . This effect was not demonstrable in any other group , including three rHu-EPO-untreated patients undergoing α-IFN + VMCP combined therapy , as well as rHu-EPO-treated patients not receiving a-IFN . Our data suggest that α-IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function . These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro", "BACKGROUND In 1984 , the Eastern Cooperative Oncology Group began a r and omized controlled clinical trial of patients with advanced ( stage III or IV ) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates , survival , and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) , as compared with a regimen containing bleomycin , doxorubicin , cyclophosphamide , vincristine , dexamethasone , methotrexate , and leucovorin ( m-BACOD ) . METHODS From July 1984 through January 1988 , 392 patients were enrolled , 325 of whom ( 83 percent ) were eligible for the analysis and capable of being evaluated . The extent of disease was defined according to st and ard staging techniques , including bilateral bone-core biopsies in 88 percent of patients . R and omization was stratified according to age ( < 60 or > or = 60 years ) , performance status ( 0 , 1 , or other ) , stage ( III or IV ) , and histologic presentation ( diffuse mixed or diffuse large-cell lymphoma ) . RESULTS After a median follow-up of four years , there were no significant differences in rates of complete remission , time to treatment failure , disease-free survival , or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD . However , there was more severe and life-threatening pulmonary , infectious , and hematologic toxicity associated with the m-BACOD regimen . In an attempt to measure the importance of dose intensity in the 325 patients who could be analyzed , we retrospectively calculated dose intensity ( measured in milligrams per square meter of body-surface area per week ) and normalized dose intensity ( defined as a percentage of the prescribed dose ) for all drugs . The median normalized dose intensity for both cyclophosphamide and doxorubicin was found to be greater in the patients treated with CHOP than in those treated with m-BACOD . CONCLUSIONS For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma , CHOP is superior to m-BACOD , but the role of dose intensity is not yet clear", "PURPOSE To determine the effect of darbepoetin alfa ( DA ) on progression-free survival ( PFS ) and overall survival ( OS ) in patients with chemotherapy-induced anemia ( CIA ) . PATIENTS AND METHODS Two 16-week r and omized , double-blind , placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer ( n = 314 ) or lymphoproliferative malignancies ( LPMs ; n = 344 ) undergoing chemotherapy were analyzed with prospect ively defined long-term PFS and OS end points . Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding , double-blind , placebo-controlled studies in anemic patients with multiple tumor types ( n = 405 ) and LPMs ( n = 66 ) . RESULTS Median follow-up is 15.8 months ( lung cancer ) and 32.6 months ( LPM ) . Median duration of PFS was comparable between DA and placebo : 5.1 months ( 95 % CI , 4.1 to 6.9 months ) versus 4.4 months ( 95 % CI , 3.7 to 5.3 months ) for lung cancer and 14.2 months ( 95 % CI , 12.2 to 17.5 months ) versus 15.9 months ( 95 % CI , 13.1 to 19.0 months ) for LPMs . The estimated hazard ratio ( HR ) of death related to DA use for lung cancer was 0.77 ( 95 % CI , 0.59 to 1.01 ) and 1.26 ( 95 % CI , 0.92 to 1.71 ) for LPMs . In the pooled analyses of all four studies ( n = 1,129 ) , no differences in PFS or OS were observed between DA and placebo ( HR = 0.92 ; 95 % CI , 0.78 to 1.07 ; and HR = 0.95 ; 95 % CI , 0.78 to 1.16 , respectively ) . CONCLUSION Treatment with DA does not seem to influence PFS or OS in patients with CIA . Prospect i ve , r and omized clinical trials will provide additional insights into the effects of DA on PFS and OS in specific tumor types", "PURPOSE This r and omized , double-blind , placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements , hematopoietic parameters , quality of life ( QOL ) , and safety in anemic cancer patients receiving nonplatinum chemotherapy . The study also explored a possible relationship between increased hemoglobin and survival . PATIENTS AND METHODS Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL , or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy , were r and omized 2:1 to epoetin alfa 150 to 300 IU/kg ( n = 251 ) or placebo ( n = 124 ) three times per week subcutaneously for 12 to 24 weeks . The primary end point was proportion of patients transfused ; secondary end points were change in hemoglobin and QOL . The protocol was amended before unblinding to prospect ively collect and assess survival data 12 months after the last patient completed the study . RESULTS Epoetin alfa , compared with placebo , significantly decreased transfusion requirements ( P = .0057 ) and increased hemoglobin ( P < .001 ) . Improvement of all primary cancer- and anemia-specific QOL domains , including energy level , ability to do daily activities , and fatigue , was significantly ( P < .01 ) greater for epoetin alfa versus placebo patients . Although the study was not powered for survival as an end point , Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa ( P = .13 , log-rank test ) , and Cox regression analysis showed an estimated hazards ratio of 1.309 ( P = .052 ) favoring epoetin alfa . Adverse events were comparable between groups . CONCLUSION Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy . Encouraging results regarding increased survival warrant another trial design ed to confirm these findings", "St and ardization in the choice of quality of life ( QOL ) instruments and their application in r and omised clinical trials have been advocated and generally accepted . However , there is now an urgent need to address the problems relating to the analysis and presentation of the data thus generated . There are intrinsic difficulties associated with QOL data , namely its multidimensional nature , attrition and missing data , and there is no consensus as to how these problems should be dealt with . This paper therefore considers there problems using interim data from a large Medical Research Council r and omised trial in patients with small cell lung cancer and a poor prognosis , in which attrition and compliance are major concerns . Three possible approaches to the analysis of these data , which use different subsets of patients , are examined in detail . The strengths and weaknesses of these three methods are discussed , and examples of their use in the literature are given and compared with other reported approaches . The need for a st and ard definition of compliance is also emphasised , and a method of presentation suggested . The best current advice is that QOL data should be analysed in a number of different ways , and conclusions reached only when consistency is seen", "Chemotherapy‐related anemia is prevalent among patients with hematologic malignancies . A r and omized , open‐label , multicenter trial of early versus late epoetin alfa in this population was conducted , focusing on quality of life ( QOL )", "PURPOSE Previous trials have suggested a quality -of-life ( QOL ) improvement for anemic cancer patients treated with erythropoietin , but few used QOL as the primary outcome . We design ed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung ( NSCLC ) . PATIENTS AND METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was conducted . The proposed sample size was 300 patients . Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin ( Hgb ) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo , targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks . RESULTS Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been r and omly assigned ( 33 to the active arm and 37 to the placebo arm ) . This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial ( 63 v 129 days ; hazard ratio , 1.84 ; P = .04 ) . The Steering Committee closed the trial . Patient numbers compromised the interpretation of the QOL analysis , but a positive Hgb response was noted with epoetin alfa treatment . CONCLUSION An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa . Although infrequent , other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely", "BACKGROUND To determine the efficacy of epoetin alfa for the treatment of the anemia of multiple myeloma , a prospect i ve , r and omized , placebo-controlled , double-blind clinical trial enrolled 25 patients with the anemia of multiple myeloma and a hematocrit less than 0.30 . METHODS Epoetin alfa , 150 U/kg , or a matching volume of placebo was administered subcutaneously three times per week for 6 weeks . If the criterion for a response was not met , the dose was doubled . After 12 weeks , nonresponders in the placebo arm were switched to an open-label study of epoetin alfa at a dose of 150 U/kg for 6 weeks . After 6 weeks , the dose was doubled if no response was obtained . A partial response was defined as an increase of 6 percentage points or greater in the hematocrit without transfusion . A complete response required a final hematocrit of 0.38 or greater without transfusion . Complete responders had reduction of epoetin alfa to the lowest dose capable of maintaining the complete response . RESULTS Twenty patients were evaluable for response to therapy . During the double-blind phase , six patients who were receiving epoetin alfa had a complete response , one had a partial response , and three were non-responders . No responses occurred in the placebo arm . In the open-label phase , of the 10 patients who were originally receiving placebo , three had a complete response , one had a partial response , and six were nonresponders . Chemotherapy , pretreatment serum erythropoietin levels , disease duration , and reticulocyte count did not predict the response to epoetin alfa . The median final dose for the responding group was 120 U/kg three times per week to maintain a hematocrit greater than 0.38 . There was no effect on the course of the myeloma , and no hypertension was seen . CONCLUSION Treatment with epoetin alfa is effective and safe in patients with the anemia of multiple myeloma", "Effects of epoetin alfa on transfusions , haemoglobin ( Hb ) and quality of life ( QOL ) were evaluated in a placebo‐controlled study of 145 patients with multiple myeloma and anaemia ( Hb < 11 g/dl ) . During the 12‐week , double‐blind phase , patients received 150 IU/kg epoetin alfa or a matching volume of placebo subcutaneously three times weekly ; the dose ( or volume ) was doubled at week 4 if Hb response was inadequate . Patients completing this phase could enter the subsequent optional 12‐week phase of open‐label epoetin alfa treatment . During double‐blind treatment , epoetin alfa significantly decreased the incidence of transfusion compared with placebo ( 28 % vs. 47 % , P = 0·017 ) , regardless of patients ' transfusion history , and increased mean Hb ( 1·8 g/dl vs. 0·0 g/dl , P < 0·001 ) . Univariate analysis showed significant ( P ≤ 0·05 ) improvement in more QOL measures with epoetin alfa than with placebo ; multivariate analysis discerned no between‐treatment differences . Significantly ( P = 0·038 ) more epoetin alfa vs. placebo patients had improved performance scores . At the end of the open‐label treatment phase , patients who had continued epoetin alfa maintained Hb status , and placebo patients who were switched to epoetin alfa had mean Hb increases of 2·4 g/dl . Adverse events were similar between treatment groups . Epoetin alfa proved effective and well tolerated for treating anaemia in patients with multiple myeloma" ]

[ "23932541", "3196245", "25908245", "16053884", "3608968", "11025851", "18629552", "18571023", "24036775", "18355589", "24388635", "18848110", "24147994" ]

[ "Randomized clinical study comparing piezosurgery and conventional rotatory surgery in mandibular cyst enucleation.", "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", "Reduced somatosensory impairment by piezosurgery during orthognathic surgery of the mandible", "Ultrasonic surgery--an alternative way in orthognathic surgery of the mandible. A pilot study.", "Evaluation of surgically assisted rapid maxillary expansion with piezosurgery versus oscillating saw and chisel osteotomy - a randomized prospective trial", "Intra-operative blood loss and operating time in orthognathic surgery using induced hypotensive general anaesthesia: prospective study.", "Piezoosteotomy in orthognathic surgery versus conventional saw and chisel osteotomy", "Factors for intraoperative blood loss in bimaxillary osteotomies.", "Piezosurgery Versus Conventional Osteotomy in Orthognathic Surgery: A Paradigm Shift in Treatment", "Critical evaluation of piezoelectric osteotomy in orthognathic surgery: operative technique, blood loss, time requirement, nerve and vessel integrity.", "Effectiveness of piezoelectric surgery in reducing surgical complications after bilateral sagittal split osteotomy.", "Recovery after orthognathic surgery: short-term health-related quality of life outcomes.", "Piezoelectric vs. conventional drilling in implant site preparation: pilot controlled randomized clinical trial with crossover design." ]

[ "PURPOSE The aim of the present study is to compare piezoelectric surgery to the conventional rotatory surgery in m and ibular cyst enucleation , and to determine the 2 method 's suitability and the postoperative outcomes . MATERIAL AND METHODS Eighty patients were included in the study . 35 male and 45 female , which showed cystic m and ibular lesions , compared with the inferior alveolar nerve or the mental nerve . The patients were r and omly divided into two groups . In the test group , cystectomy was performed using conventional rotatory instrumentation ( rotatory-group ) , and in the other one piezoelectric surgery ( piezo-group ) . The swelling was documented 24/48/72 h and 1 week post-surgery and the patients recorded their subjective postoperative pain daily for 7 days using a Visual Analog Scale ( VAS ) . RESULTS Patients treated with piezoelectric technique have presented a lower VAS , minor swelling and less recovery time compared to the rotatory-group . No lesions of the m and ible nerve were detected with piezosurgery whereas surgery with rotary instruments result ed in 8 % hypesthesia at least up to one week . CONCLUSION The results of this study suggest that piezosurgery may be considered effective in cyst enucleation compared to traditional procedures with burs , since it grants the patients significantly less post-surgical pain and swelling", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Purpose This clinical trial aim ed to test the hypothesis that piezosurgery causes reduced nerval irritations and , thus , reduced somatosensory impairment when used in orthognathic surgery of the m and ible . Methods To this end , 37 consecutive patients with Angle Class II and III malocclusion were treated using bilateral sagittal split osteotomies ( BSSO ) of the m and ible . In a split mouth design , r and omized one side of the m and ible was operated using a conventional saw , while a piezosurgery device was used on the contralateral side . In order to test the individual qualities of somatosensory function , quantitative sensory testings ( QSTs ) were performed 1 month , 6 months and 1 year after surgery . Results A comparison of the data using a two-way analysis of variance ( ANOVA ) revealed a significant reduction in postoperative impairment in warm detection threshold ( WDT ) ( P = 0.046 ) , a decreased dynamic mechanical allodynia ( ALL ) ( P = 0.002 ) and a decreased vibration detection threshold ( VDT ) ( P = 0.030 ) on the piezosurgery side of the m and ible as opposed to the conventionally operated control side . In the remaining QSTs , minor deviations from the preoperative baseline conditions and a more rapid regression could be observed . Conclusions Piezosurgery caused reduced somatosensory impairment and a faster recovery of somatosensory functions in the present investigation", "The aim of this report is to present preliminary results and experiences using an ultrasonic bone-cutting device in bilateral sagittal split osteotomies of the m and ible ( BSSRO ) with particular attention to possible damages to the inferior alveolar nerve ( IAN ) . Seven patients with class II or class III malocclusion were treated by BSSRO with a conventional combined orthognathic and surgical approach . The osteotomy was carried out using an ultrasonic bone-cutting device . Subjective neurosensory deficits of the inferior alveolar nerve were assessed on 14 sides . Compared to the conventional techniques using saws , chisels and burs , the use of the ultrasonic device was more time-consuming , but the osteotomies were carried out at a high level of precision . In addition , this procedure offered the advantage of a blood-free surgical field and thus provided good control of the surgical procedure . Subjective neurosensory disturbances of the IAN showed a continuous decrease from 57.1 % ( eight sides ) 2 months after the surgical procedure to 14.3 % ( 2 sides ) after 5 months and to 7.1 % 7 months after BSSRO . Within the seven patients of this pilot study associated neurosensory disturbances were low . A possible advantage in terms of nerve protection is subject to a prospect i ve study", "Background Ultrasonic bone-cutting surgery has been introduced as a feasible alternative to the conventional sharp instruments used in craniomaxillofacial surgery because of its precision and safety . The piezosurgery medical device allows the efficient cutting of mineralized tissues with minimal trauma to soft tissues . Piezoelectric osteotome has found its role in surgically assisted rapid maxillary expansion ( SARME ) , a procedure well established to correct transverse maxillary discrepancies . The advantages include minimal risk to critical anatomic structures . The purpose of this clinical comparative study ( CIS 2007 - 237-M ) was to present the advantages of the piezoelectric cut as a minimally invasive device in surgically assisted , rapid maxillary expansion by protecting the maxillary sinus mucosal lining . Methods Thirty patients ( 18 females and 12 males ) at the age of 18 to 54 underwent a surgically assisted palatal expansion of the maxilla with a combined orthodontic and surgical approach . The patients were r and omly divided into two separate treatment groups . While Group 1 received conventional surgery using an oscillating saw , Group 2 was treated with piezosurgery . The following parameters were examined : blood pressure , blood values , required medication , bleeding level in the maxillary sinus , duration of inpatient stay , duration of surgery and height of body temperature . Results The results displayed no statistically significant differences between the two groups regarding laboratory blood values and inpatient stay . The duration of surgery revealed a significant discrepancy . Deploying piezosurgery took the surgeon an average of 10 minutes longer than working with a conventional-saw technique . However , the observation of the bleeding level in the paranasal sinus presented a major and statistically significant advantage of piezosurgery : on average the bleeding level was one category above the one of the remaining patients . Conclusion This method of piezoelectric surgery with all its advantages is going to replace many conventional operating procedures in oral and maxillofacial surgery . Trial registration CIS 2007 -", "We investigated the average operating time and extent of intra-operative blood loss in orthognathic surgeries performed using induced hypotensive general anaesthesia , with the intention of devising a practical guideline for blood unit preparation for these procedures . We prospect ively studied 32 Chinese patients undergoing surgery to correct dentofacial deformities at a public hospital in Hong Kong from 1 December 1997 to 1 December 1998 . Most patients ( 72 . 4 % ) needed double-jaw surgery . The mean estimated blood loss was approximately 617.6 mL. The blood loss during simple Le Fort I osteotomies was about half that of multiple segmentalised osteotomies . For m and ibular ramus osteotomies , the mean blood loss and operating time for were approximately 280 mL and 2 hours , respectively ; for anterior m and ibular osteotomies , the corresponding values were 171.3 mL and 1 hour 13 minutes . The average drop in the haematocrit value was 15.4 % , and the crossmatch to transfusion ratio was 29 . A bivariate correlation test between the blood loss and operating time gave a strong correlation ( P<0.01 ) , as did blood loss with a drop in haematocrit value ( P<0.01 ) . Orthognathic surgeries are thus safe and predictable in terms of intra-operative blood loss and operating time , and a ' type , screen , and save ' policy for blood unit preparation is more appropriate than a ' crossmatch ' policy", "Introduction Piezoosteotomy was assessed as alternative osteotomy method in orthognathic surgery regarding h and ling , time requirement , nerve and vessel impairment . Material s and methods In this comparative clinical experience , 90 patient ’s orthognathic surgery procedures were performed in typical distribution prospect ively by piezoosteotomy : 34 ( 38 % ) monosegment , 47 ( 52 % ) segmented LeFortI osteotomies , 94 ( 52 % ) sagittal split osteotomies , 11 ( 12 % ) symphyseal , and 4 ( 2 % ) m and ibular body osteotomies . As controls served 90 retrospective patients with conventional saw and chisel osteotomy : 58 ( 64 % ) monosegment , 27 ( 30 % ) segmented LeFortI osteotomies , 130 ( 72 % ) sagittal split , and 4 ( 4 % ) symphyseal osteotomies . Results and discussion Piezoosteotomies were individually design ed to interdigitate the jaw segments after repositioning . The pterygomaxillary suture weakened angulated tools ; auxiliary chisels were required in 100 % of cases for the nasal septum and lateral nasal walls , in 33 % for pterygoid processes . The dorsal maxilla as the pterygoid process were easily reduced ; 15 % m and ibular osteotomies required sawing , while the lingual dorsal osteotomy was performed by manual feedback due to limited visibility . Bloodloss decreased from average 537 ± 208 ml vs. 772 ± 338 ml ( p = 0.0001 ) . Operation time remained unchanged : 223 ± 70 min vs. 238 ± 60 min ( p = 0.2 ) for a conventional bimaxillary procedure . Clinical courses and reossification were unobtrusive . Alveolar inferior nerve sensitivity was retained in 98 % of the piezoosteotomy collective versus 84 % of controls ( p = 0.0001 ) at 3 months postoperative testing . Conclusion Piezoelectric osteotomy did not prolong the operation and reduced blood loss as alveolar nerve impairment . A few patients required additional sawing or chisel . Piezoelectric screw insertion as complex osteotomies may be initiated to simplify the procedure and increase segment interdigitation after repositioning as to minimize the osteofixation time and dimensions", "PURPOSE Autologous blood donation is not routinely recommended for all cases of orthognathic surgery . The aim of this study was to evaluate the factors for blood loss during bimaxillary osteotomies that might indicate preoperative blood donation . PATIENTS AND METHODS In a prospect i ve study , 127 consecutive patients undergoing bimaxillary surgery within a 14-month period were examined for hemoglobin and hematocrit reduction . Possible factors for intraoperative blood loss such as operating time , application of hydroxyethyl starch in segmental osteotomies , experience of the surgeon , and additional procedures ( genioplasty , malar osteotomy , iliac crest graft ) were statistically analyzed . RESULTS The experience of the surgeon had no influence on the blood loss . Operating time and Quick value correlated significantly with hemoglobin and hematocrit drop after surgery . There was no difference between 1-piece maxilla cases with or without additional procedures and segmental maxilla cases without additional procedures . Only for the group of patients with segmental osteotomies and additional procedures was a significant higher blood loss found . Two patients ( 1.6 % ) received 1 unit of blood . CONCLUSION For patients undergoing bimaxillary osteotomies with segmentation of the maxilla and additional procedures , a preoperative donation of autologous blood should be considered", "Abstract The aim of the study was to compare in a r and omized controlled clinical trial the use of the piezoelectric osteotomy as an alternative to the conventional approach in terms of surgery time , intraoperative blood loss , cut quality , nerve injury , and costs . One hundred ten patients who had orthognathic surgery procedures with bimaxillary osteotomy were divided into 2 groups : group A was treated with a piezosurgery device , and group B , with a reciprocating saw and bur . The piezosurgical bone osteotomy permitted individualized cut design s. The surgical time in group A was reduced , with a mean for the m and ibular osteotomy ( 1 side ) between 3 minutes 31 seconds and 5 minutes 2 seconds , whereas in group B , the surgical time was between 7 minutes 23 seconds and 10 minutes 22 seconds . The surgical time in group A for the Le Fort I osteotomy was between 5 minutes 17 seconds and 7 minutes 55 seconds in group A and between 8 minutes 38 seconds and 15 minutes 11 seconds in group B. All patients in group A had a low blood loss ( < 300 mL ) versus patients of group B who had a medium to high blood loss ( medium loss : 400 mL , high loss : > 500 mL ) . Inferior alveolar nerve sensation was retained in 98.2 % of group A versus 92.7 % in group B at 6 months postoperative testing . Piezoelectric osteotomy reduced surgical time , blood loss , and inferior alveolar nerve injury in bimaxillary osteotomy . Absence of macrovibrations makes the instrument more manageable and easy to use and allows greater intraoperative control with higher safety in cutting in difficult anatomical regions", "PURPOSE Piezo-osteotomy feasibility as a substitute for the conventional saw in orthognathic surgery was evaluated regarding operative technique , blood loss , time requirement , and nerve and vessel integrity . PATIENTS AND METHODS Fifty patients had orthognathic surgery procedures in typical distribution using piezosurgical osteotomy : 22 ( 44 % ) monosegment , 26 ( 52 % ) segmented Le Fort I osteotomies ; 48 ( 48 % ) sagittal split osteotomies , 6 ( 12 % ) symphyseal , and 4 ( 4 % ) m and ibular body osteotomies . Controls were 86 patients with conventional saw and chisel osteotomies : 57 ( 66 % ) monosegment , 25 ( 29 % ) segmented Le Fort I osteotomies , 126 ( 73 % ) sagittal split , and 4 ( 5 % ) symphyseal osteotomies . RESULTS Piezosurgical bone osteotomy permitted individualized cut design s , enabling segment interdigitation after repositioning . Angulated tools weakened the pterygomaxillary suture ; auxiliary chisels were required in 100 % of cases for the nasal septum , and lateral nasal walls as 46 % pterygoid processes . After downfracture , the dorsal maxillary sinus wall and pterygoid processes were easily reduced . Hemorrhage was successfully avoided with average blood loss of 541 + /- 150 mL versus 773 + /- 344 mL ( P = .001 ) for a conventional bimaxillary procedure . Sagittal m and ibular osteotomy required considerable time ( auxiliary saw in 13 % ) ; the lingual dorsal osteotomy was mostly performed tactile . Time investment remained unchanged : 227 + /- 73 minutes per bimaxillary st and ard osteotomy versus 238 + /- 61 minutes ( P = .5 ) ; clinical courses and reossification were unobtrusive . Alveolar inferior nerve sensitivity was retained in 95 % of the study collective versus 85 % in the controls ( P = .0003 ) at 3 months postoperative testing . CONCLUSIONS Piezoelectric osteotomy reduced blood loss and inferior alveolar nerve injury at no extra time investment . Single cases require auxiliary chiseling or sawing . Piezoelectric drilling for screw insertion and complex osteotomy design s may be developed to maintain bone contact or interdigitation after repositioning and minimize need for osteofixation", "Our aim was to investigate the effectiveness of piezoelectric surgery , where the osteotomy is made using ultrasonic vibration , in reducing surgical complications after bilateral sagittal split osteotomy ( BSSO ) . Fifty-nine patients with skeletal m and ibular prognathism who had m and ibular setback with BSSO between January 2009 and April 2011 were included in the study . Piezosurgery was used in 29 cases , and the bone was split using a separator . In the remaining 30 cases , a Lindeman bur was used for the osteotomy and a chisel was used to split the bone . The amount of intraoperative bleeding and the Semmes Weinstein test scores were used as objective variables to evaluate the degree of neurosensory disturbance , and sex , age , use of piezosurgery , degree of setback , operating time , and method of fixation were used as explanatory variables . We used analysis of covariance ( ANCOVA ) to assess the significance of differences . Intraoperative bleeding was significantly less with age ( p=0.003 ) , and longer when operating time was prolonged ( p=0.017 ) , and was not influenced by the use of piezosurgery . The Semmes Weinstein test score significantly increased with age ( p=0.01 ) , and was significantly greater when piezoelectric surgery was used ( p=0.008 ) , and at 3 months , there were signs of more neurosensory disturbance in older patients and those who had had piezoelectric surgery . In this retrospective non-r and om study piezoelectric surgery reduced neither blood loss nor the incidence of neurosensory disturbance in BSSO", "PURPOSE The purpose of this study was to assess the patient-reported time to recovery for quality of life outcomes : postsurgery sequelae , discomfort/pain , oral function , and daily activities after orthognathic surgery . PATIENTS AND METHODS A total of 170 patients ( age = 14 - 53 ) were enrolled in a prospect i ve study before orthognathic surgery . Each patient was given a 20-item health-related quality of life instrument ( OSPostop ) to be completed each postsurgery day ( PSD ) for 90 days . The instrument was design ed to assess patients ' perception of recovery for 4 domains : postsurgery sequelae , discomfort/pain , oral function , and daily activities . Discomfort/pain was recorded with a 7-point Likert-type scale ; all other items were measured on a 5-point Likert-type scale . RESULTS Postsurgery sequelae , except swelling , resolved within the first week after surgery for over 75 % of the subjects . Discomfort/pain and medication usage persisted for 2 to 3 weeks after surgery for most subjects . Return to usual activities , except for recreational activities , which took substantially longer , mirrored the resolution of discomfort/pain . Problems with oral function took the longest to resolve , approximately 6 to 8 weeks for the majority of subjects . CONCLUSION Comprehensive daily postoperative patient quality of life data provides the orthognathic surgeon with estimated recovery times in distinct domains . This information is vital in the provision of informed consent as well as preoperative education of patients regarding perioperative and postoperative expectations . Ultimately this data can be combined with individual risk factors to provide personalized consent and expectations as well as tailor perioperative and postoperative management regimens", "OBJECTIVE To compare implant stability throughout osseointegration , peri-implant marginal bone loss , and success rates of implants placed with conventional and mixed drilling/piezoelectric osteotomy . MATERIAL S AND METHODS A pilot r and omized-controlled trial was performed on 15 patients . Each patient received two implants in the m and ibular molar region . All sites were prepared with conventionally up to the 2.8 mm wide drill . Osteotomies were r and omly finalized with a 3 mm diameter drill ( control group ) or with two consecutive ultrasonic tips ( 2.8 mm and 3 mm wide , respectively ) ( test group ) . Resonance frequency analysis measurements were taken at implant placement and after 1 , 3 , 8 , and 12 weeks . Peri-implant marginal bone loss 12 months after loading was calculated using periapical radiographs . Wilcoxon test for related sample s was used to study differences in implant stability and in peri-implant marginal bone loss between the two groups . RESULTS Twenty-nine of 30 implants osseointegrated successfully ( one failure in the control group ) . Stability was significantly higher in the test group at the 8th week assessment ; differences were non-significant at all other time-points . Longitudinally , differences were observed between the patterns of implant stability changes : in the test group stability increased more progressively , while in the control group an abrupt change occurred between the 8th and 12th weeks assessment s. No difference was found in peri-implant marginal bone loss between the groups . All 29 implants were functionally successful at the 15-month visit . CONCLUSIONS Within the limit of this pilot study ( small sample size , short follow-up ) , data suggested that implant stability might develop slightly faster when implant site osteotomy is performed with a mixed drilling/ultrasonic technique" ]

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[ "Group treatments for sensitive health care problems: a randomised controlled trial of group versus individual physiotherapy sessions for female urinary incontinence", "Mobile App for Treatment of Stress Urinary Incontinence: A Cost-Effectiveness Analysis", "A cost-effectiveness analysis of retropubic midurethral sling versus transobturator midurethral sling for female stress urinary incontinence.", "Cost‐analyzes based on a prospective, randomized study comparing laparoscopic colposuspension with a tension‐free vaginal tape procedure", "Cost-effectiveness of involving nurse specialists for adult patients with urinary incontinence in primary care compared to care-as-usual: an economic evaluation alongside a pragmatic randomized controlled trial.", "Cost-effectiveness of duloxetine: the Stress Urinary Incontinence Treatment (SUIT) study.", "Urinary incontinence management costs are reduced following Burch or sling surgery for stress incontinence.", "Efficacy, safety and hospital costs of tension-free vaginal tape and pubovaginal sling in the surgical treatment of stress incontinence.", "The cost of preoperative urodynamics: A secondary analysis of the ValUE trial.", "A cost–utility analysis of tension‐free vaginal tape versus colposuspension for primary urodynamic stress incontinence", "Randomised controlled trial of nurse continence advisor therapy compared with standard urogynaecology regimen for conservative incontinence treatment: efficacy, costs and two year follow up", "Cost effectiveness of tension-free vaginal tape for the surgical management of female stress incontinence.", "Resource costing for multinational neurologic clinical trials: methods and results.", "Pubovaginal sling versus transurethral Macroplastique for stress urinary incontinence and intrinsic sphincter deficiency: a prospective randomised controlled trial", "Comparison of health care costs for open Burch colposuspension, laparoscopic colposuspension and tension-free vaginal tape in the treatment of female urinary incontinence.", "A prospective, randomized controlled trial of inpatient versus outpatient continence programs in the treatment of urinary incontinence in the female", "Treatment of Stress Urinary Incontinence with Non-Animal Stabilised Hyaluronic Acid/Dextranomer (NASHA/Dx) Gel", "Markov chain decision model for urinary incontinence procedures." ]

[ "Background The aim was to compare effectiveness of group versus individual sessions of physiotherapy in terms of symptoms , quality of life , and costs , and to investigate the effect of patient preference on uptake and outcome of treatment . Methods A pragmatic , multi-centre r and omised controlled trial in five British National Health Service physiotherapy departments . 174 women with stress and /or urge incontinence were r and omised to receive treatment from a physiotherapist delivered in a group or individual setting over three weekly sessions . Outcome were measured as Symptom Severity Index ; Incontinence-related Quality of Life question naire ; National Health Service costs , and out of pocket expenses . Results The majority of women expressed no preference ( 55 % ) or preference for individual treatment ( 36 % ) . Treatment attendance was good , with similar attendance with both service delivery models . Overall , there were no statistically significant differences in symptom severity or quality of life outcomes between the models . Over 85 % of women reported a subjective benefit of treatment , with a slightly higher rating in the individual compared with the group setting . When all health care costs were considered , average cost per patient was lower for group sessions ( Mean cost difference £ 52.91 95 % , confidence interval ( £ 25.82 - £ 80.00 ) ) . Conclusion Indications are that whilst some women may have an initial preference for individual treatment , there are no substantial differences in the symptom , quality of life outcomes or non-attendance . Because of the significant difference in mean cost , group treatment is recommended . Trial Registration Trial Registration number : IS RCT N", "Background Mobile apps can increase access to care , facilitate self-management , and improve adherence to treatment . Stress urinary incontinence ( SUI ) affects 10 - 35 % of women and , currently , an app with instructions for pelvic floor muscle training ( PFMT ) is available as first-line treatment . A previous r and omized controlled study demonstrated that the app benefitted symptom severity and quality of life ( QoL ) ; in this study we investigate the cost-effectiveness of the app . Objective The objective of this study was to evaluate the health economy of the app for treating SUI . Methods This deterministic cost-utility analysis , with a 1-year societal perspective , compared the app treatment with no treatment . Health economic data were collected alongside a r and omized controlled trial performed in Sweden from March 2013 to October 2014 . This study included 123 community-dwelling women participants of 18 years and above , with stress urinary incontinence ≥1 time per week . Participants were self-assessed with vali date d question naires and 2-day leakage diaries , and then r and omized to 3 months of treatment ( app group , n=62 ) or no treatment ( controls , n=61 ) . The app focused on pelvic floor muscle training , prescribed 3 times daily . We continuously registered treatment delivery costs . Data were collected on each participant ’s training time , incontinence aids , and laundry at baseline and at a 3-month follow-up . We measured quality of life with the International Consultation on Incontinence Modular Question naire on Lower Urinary Tract Symptoms and Quality of Life , and calculated the quality -adjusted life years ( QALYs ) gained . Data from the 3-month follow-up were extrapolated to 1 year for the calculations . Our main outcome was the incremental cost-effectiveness ratios compared between app and control groups . One-way and multiway sensitivity analyses were performed . Results The mean age of participants was 44.7 years ( SD 9.4 ) . Annual costs were € 547.0 for the app group and € 482.4 for the control group . Annual gains in quality -adjusted life years for app and control groups were 0.0101 and 0.0016 , respectively . Compared with controls , the extra cost per quality -adjusted life year for the app group ranged from −€2425.7 to € 14,870.6 , which indicated greater gains in quality -adjusted life years at similar or slightly higher cost . Conclusions The app for treating stress urinary incontinence is a new , cost-effective , first-line treatment with potential for increasing access to care in a sustainable way for this patient group", "AIMS To compare the cost-effectiveness ( CE ) of retropubic midurethral sling ( RMS ) versus transobturator midurethral sling ( TMS ) for the treatment of female stress urinary incontinence ( SUI ) . METHODS A Markov chain decision model was created to simulate treatment of SUI with RMS versus TMS . Costing data were obtained from the Medicare RBRVS . Data regarding the efficacy and complications associated with RMS versus TMS was compiled from a literature review of 21 r and omized RCTs with a minimum of 12 months follow-up , as were corresponding utilities for different continence states . Deterministic and probabilistic estimates of cost-effectiveness ( CE ) for each procedure were calculated and compared , and sensitivity analyses were performed . RESULTS In the base-case deterministic analysis , the efficacy of RMS was 6.275 versus 6.272 QALYs for TMS . QALYs represent a measure of disease burden accounting for both quantity and quality of life lived and are used to assess the monetary value of a medical intervention . The average cost for treatment with RMS however was higher at $ 9,579 versus $ 9,017 with TMS . TMS was therefore overall more cost-effective than RMS ( CE = $ 1,438/QALY vs. $ 1,527/QALY ) . Sensitivity analysis demonstrated that physician and sling characteristics such as device cost , surgeon fee , efficacy of treatment , operative time , and duration of hospitalization could all affect the relative CE of the therapies . CONCLUSIONS Our study demonstrated that TMS was more cost-effective than RMS as a treatment for female SUI . The efficacy of the two treatments could be affected by physician and sling characteristic factors", "Background . The aim of this study was to compare laparoscopic colposuspension with tension‐free vaginal tape ( TVT ) in terms of costs to the county", "AIMS To determine the 12-month , societal cost-effectiveness of involving urinary incontinence ( UI ) nurse specialists in primary care compared to care-as-usual by general practitioners ( GPs ) . METHODS From 2005 until 2008 an economic evaluation was performed alongside a pragmatic multicenter r and omized controlled trial comparing UI patients receiving care by nurse specialists with patients receiving care-as-usual by GPs in the Netherl and s. One hundred eighty-six adult patients with stress , urgency , or mixed UI were r and omly allocated to the intervention and 198 to care-as-usual ; they were followed for 1 year . Main outcome measures were Quality Adjusted Life Year ( QALY(societal ) ) based on societal preferences for health outcomes ( EuroQol-5D ) , QALY(patient ) based on patient preferences for health outcomes ( EuroQol VAS ) , and Incontinence Severity weighted Life Year ( ISLY ) based on patient-reported severity and impact of UI ( ICIQ-UI SF ) . Health care re source use , patient and family costs , and productivity costs were assessed . Data were collected by three monthly question naires . Incremental cost-effectiveness ratios were calculated . Uncertainty was assessed using bootstrap simulation , and the expected value of perfect information was calculated ( EVPI ) . RESULTS Compared to care-as-usual , nurse specialist involvement costs € 16,742/QALY(societal ) gained . Both QALY(patient ) and ISLY yield slightly more favorable cost-effectiveness results . At a threshold of € 40,000/QALY(societal , ) the probability that the intervention is cost-effective is 58 % . The EVPI amounts to € 78 million . CONCLUSIONS Based on these results , we recommend adopting the nurse specialist intervention in primary care , while conducting more research through careful monitoring of the effectiveness and costs of the intervention in routine practice", "OBJECTIVE To assess the cost-effectiveness of duloxetine compared with conservative therapy in women with stress urinary incontinence ( SUI ) . METHODS Cost and outcome data were taken from the Stress Urinary Incontinence Treatment ( SUIT ) study , a 12-month , prospect i ve , observational , naturalistic , multicenter , multicountry study . Costs were assessed in UK pound and outcomes in quality adjusted life years using responses to the EuroQol ( EQ-5D ) ; numbers of urine leaks were also estimated . Potential selection bias was countered using multivariate regression and propensity score analysis . RESULTS Duloxetine alone , duloxetine in combination with conservative treatment , and conservative treatment alone were associated with roughly two fewer leaks per week compared with no treatment . Duloxetine alone and with conservative treatment for SUI were associated with incremental quality -adjusted life-years ( QALYs ) of about 0.03 over a year compared with no treatment or with conservative treatment alone . Conservative treatment alone did not show an effect on QALYs . None of the interventions appeared to have marked impacts on costs over a year . Depending on the form of matching , duloxetine either dominated or had an incremental cost-effectiveness ratio ( ICER ) below pound900 per QALY gained compared with no treatment and with conservative treatment alone . Duloxetine plus conservative therapy had an ICER below pound5500 compared with no treatment or conservative treatment alone . Duloxetine compared with duloxetine plus conservative therapy showed similar outcomes but an additional cost for the combined intervention . CONCLUSIONS Although the limitations of the use of SUIT 's observational data for this purpose need to be acknowledged , the study suggests that initiating duloxetine therapy in SUI is a cost-effective treatment alternative", "OBJECTIVE The objective of the study was to estimate the effect of Burch and fascial sling surgery on out-of-pocket urinary incontinence ( UI ) management costs at 24 months postoperatively and identify predictors of change in cost among women enrolled in a r and omized trial comparing these procedures . STUDY DESIGN Re sources used for UI management ( supplies , laundry , dry cleaning ) were self-reported by 491 women at baseline and 24 months after surgery , and total out-of-pocket costs for UI management ( in 2012 US dollars ) were estimated . Data from the 2 surgical groups were combined to examine the change in cost for UI management over 24 months . Univariate and bivariate changes in cost were analyzed using the Wilcoxon signed rank test . Predictors of change in cost were examined using multivariate mixed models . RESULTS At baseline mean ( ±SD ) age of participants was 53 ± 10 years , and the frequency of weekly UI episodes was 23 ± 21 . Weekly UI episodes decreased by 86 % at 24 months ( P < .001 ) . The mean weekly cost was $ 16.60 ± $ 27.00 ( median $ 9.39 ) at baseline and $ 4.57 ± $ 15.00 ( median $ 0.10 ) at 24 months ( P < .001 ) , a decrease of 72 % . In multivariate analyses , cost decreased by $ 3.38 ± $ 0.77 per week for each decrease of 1 UI episode per day ( P < .001 ) and was strongly associated with greater improvement in Urogenital Distress Inventory and Incontinence Impact Question naire scores ( P < .001 ) and decreased 24-hour pad weight ( P < .02 ) . CONCLUSION Following Burch or fascial sling surgery , the UI management cost at 24 months decreased by 72 % ( $ 625 per woman per year ) and was strongly associated with decreasing UI frequency . Reduced out-of-pocket expenses may be a benefit of these established urinary incontinence procedures", "AIM The efficacy , safety and hospital costs of the tension-free vaginal tape procedure were compared with the pubovaginal sling operation . METHODS A total of 60 women urodynamically diagnosed as having stress or mixed urinary incontinence were operated on using either the tension-free vaginal tape or pubovaginal sling operation in a prospect i ve manner . Preoperative characteristics of the women were not significantly different for the groups . The women were followed for up to 24 months . RESULTS In the tension-free vaginal tape group , the operation time was shorter , numbers of analgesics postoperatively required were less and hospital charges were less expensive compared to those in the pubovaginal sling operation ( P < 0.01 ) . Kaplan-Meier survival analysis showed a marginal significant difference ( P = 0.059 ) in the objective cumulative cure rates at 24 months between the groups receiving the former ( 70.3 % ) and latter ( 48.3 % ) procedures . Subjective cure rates were not significantly different ( P = 0.101 ) . In both groups , an improvement in quality of life was significant and surgical complications were identical . De novo urge incontinence developed in 6 % and 10 % in the former and latter , respectively . CONCLUSIONS The tension-free tape was significantly superior to the pubovaginal sling in terms of operation time , postoperative pain , and hospital charges , but not in cure rates . A longer follow up with a larger sample size is necessary to draw definite conclusions", "AIMS Urodynamic studies ( UDS ) are generally recommended prior to surgical treatment for stress urinary incontinence ( SUI ) , despite insufficient evidence that it impacts treatment plans or outcomes in patients with uncomplicated SUI . This analysis aim ed to calculate the cost incurred when UDS was performed as a supplement to a basic office evaluation and to extrapolate the potential savings of not doing UDS in this patient population on a national basis . METHODS This is a secondary analysis from the Value of Urodynamic Evaluation ( ValUE ) trial , a multicenter non-inferiority r and omized trial to determine whether a basic office evaluation ( OE ) is non-inferior in terms of SUI surgery outcomes to office evaluation with addition of urodynamic studies ( UDS ) . All participants underwent an OE ; those patients who r and omized to supplementary UDS underwent non-instrumented uroflowmetry , filling cystometry , and a pressure flow study . Costs associated with UDS were calculated using 2014 U.S. Medicare allowable fees . Models using various patient population s and payor mixes were created to obtain a range of potential costs of performing UDS in patients undergoing SUI surgery annually in the United States . RESULTS Six hundred thirty women were r and omized to OE or OE plus UDS . There was no difference in surgical outcomes between the two groups . The per patient cost of UDS varied from site to site , and included complex cystometrogram $ 314-$343 ( CPT codes 51728 - 51729 ) plus complex uroflowmetry $ 16 ( CPT code 51741 ) . Extrapolating these costs for US women similar to our study population , 13 - 33 million US dollars could be saved annually by not performing preoperative urodynamics . CONCLUSION For women with uncomplicated SUI and a confirmatory preoperative basic office evaluation , tens of millions of dollars US could be saved annually by not performing urodynamic testing . In the management of such women , eliminating this preoperative test has a major economic benefit", "Objective To assess the cost effectiveness of tension‐free vaginal tape compared with open Burch colposuspension as a primary treatment for urodynamic stress incontinence", "Objective To compare the efficacy and labour costs of nurse continence advisors and urogynaecologists in conservative management of urinary incontinence", "OBJECTIVES Stress urinary incontinence affects between 10 percent and 50 percent of women . Surgery is commonly recommended for troublesome incontinence that does not respond to nonsurgical management . Tension-free vaginal tape ( TVT ) is a newer , minimal access surgical sling procedure , which is being increasingly adopted worldwide . The cost-effectiveness of TVT in comparison with other surgical procedures , particularly open colposuspension , is assessed . METHODS Effectiveness estimates came from a systematic review of TVT compared with other surgical procedures ( open and laparoscopic colposuspension , traditional slings , and injectables ) . Deterministic and probabilistic analyses were used to assess the likelihood of TVT being cost-effective . Sensitivity analyses assessed the impact of changing assumptions about cure rates and costs for TVT , cure rates for retreatment open colposuspension , and proportions of women who choose retreatment . RESULTS Reliable estimates of relative effectiveness were difficult to derive because the few r and omized controlled comparisons had not been optimally analyzed or fully reported . Results of the economic model suggested that TVT dominates open colposuspension ( lower cost and same quality of life years [ QALYs ] ) within 5 years after surgery . Stochastic analysis indicated that the likelihood of TVT being cost-effective was 100 percent if decision-makers are unwilling to pay for additional QALYs . TVT 's dominance depended on the assumption fact that retreatment open colposuspension has lower cure rates than a first colposuspension . CONCLUSIONS Analysis based on current short-term data indicates dominance of TVT over open colposuspension from approximately 5 years . There is a need for longer-term follow-up data from method ologically rigorous r and omized trials to provide a sounder basis for estimating the relative benefits and cost implication", "We present the results of a multinational re source costing study for a prospect i ve economic evaluation of a new medical technology for treatment of subarachnoid hemorrhage within a clinical trial . The study describes a framework for the collection and analysis of international re source cost data that can contribute to a consistent and accurate intercountry estimation of cost . Of the 15 countries that participated in the clinical trial , we collected cost information in the following seven : Australia , France , Germany , the UK , Italy , Spain , and Sweden . The collection of cost data in these countries was structured through the use of worksheets to provide accurate and efficient cost reporting . We converted total average costs to average variable costs and then aggregated the data to develop study unit costs . When unit costs were unavailable , we developed an index table , based on a market-basket approach , to estimate unit costs . To estimate the cost of a given procedure , the market-basket estimation process required that cost information be available for at least one country . When cost information was unavailable in all countries for a given procedure , we estimated costs using a method based on physician-work and practice -expense re source -based relative value units . Finally , we converted study unit costs to a common currency using purchasing power parity measures . Through this costing exercise we developed a set of unit costs for patient services and per diem hospital services . We conclude by discussing the implication s of our costing exercise and suggest guidelines to facilitate more effective multinational costing exercises", "Objective To compare the pubovaginal sling and transurethral Macroplastique in the treatment of female stress urinary incontinence ( SUI ) and intrinsic sphincter deficiency ( ISD )", "AIMS To compare direct health care costs of treatment for stress urinary incontinence in Sweden with four different procedures : ( i ) open Burch colposuspension ( OBC ) ; ( ii ) laparoscopic colposuspension with sutures ( LCS ) ; ( iii ) laparoscopic colposuspension with mesh and staples ( LCM ) , and ( iv ) Tension-free Vaginal Tape ( TVT ) . MATERIAL AND METHODS A model was constructed representing a hospital with st and ardized surgical equipment , staff and average unit costs in 2003 Euros . The time used for anesthesia and surgery was calculated . Clinical data was collected from three different sources , a multicenter , r and omized , prospect i ve study comparing OBC with LCM with 1 year follow-up , a three-armed , prospect i ve study where women were r and omized to either OBC , LCM , or LCS with 1 year follow-up and a descriptive study reporting results of TVT with 5 year follow-up . Data collected from the studies and hospital cost data were put into the model to create the different cost elements . RESULTS The total cost per individual , showed a lower cost for TVT compared to the other alternatives . The direct costs for a TVT , euro1,366 were only 56 % of the costs for an OBC , euro2,431 ( P < 0.001 ) and 59 % of the costs for a LCS , euro2,310 ( P < 0.001 ) . CONCLUSIONS When using a model and comparing health care costs for surgical treatment of female stress urinary incontinence in Sweden , the TVT procedure generated a lower direct cost than both open and laparoscopic colposuspension", "Seventy-four patients presenting with a mixed pattern of urinary symptoms were r and omly allocated to undergo either inpatient or outpatient continence programs as initial treatment , without prior urodynamic investigation . Both programs consisted of physiotherapy , bladder retraining , fluid normalization , dietary advice and general support and advice . Nine out of 39 in the outpatient group and 8 out of the 35 of the impatient group failed to complete the study . There was a significant decrease in frequency , nocturia , number of incontinent episodes and visual analog scores for both groups . In addition the out patients had a significant reduction in loss on pad testing , and a significantly greater improvement in their visual analog score . In each group 63 % were cured or improved to the extent that they did not require further treatment . Staff costs per outpatient were half those for an inpatient . We conclude that outpatient conservative treatment as detailed above is a successful first-line treatment of urinary incontinence in women . It is as successful and possibly better than inpatient treatment , and is significantly cheaper", "Abstract Background : The Zidex ® system is a treatment for stress urinary incontinence comprising four prefilled syringes of non-animal stabilised hyaluronic acid/ dextranomer ( NASHA/Dx ) gel and the Implacer ™ device . This study aim ed to investigate utility ( patients ’ preferences for given health states ) with NASHA/Dx gel therapy and to compare re source utilisation of NASHA/Dx gel treatment with tension-free vaginal tape ( TVT ) . Methods : Utility was measured using EuroQol ( EQ-5D ) , a generic utility instrument . For the cost of NASHA/Dx gel treatment , data were collected prospect ively from participants in a 12-month efficacy study ( n = 82 ) . Retrospective analysis of a comparable group of patients ( n = 77 ; 3–6 months ’ follow-up ) was used to obtain equivalent costs for TVT . Costs were analysed for both Sweden and France . Results : NASHA/Dx gel produced a utility gain of 0.048 at 3 months and 0.014 at 12 months . The estimated mean total 3-month cost per patient with NASHA/Dx gel was € 2412 in Sweden and € 2005 in France . The corresponding values for 12 months , including 14 % of patients undergoing TVT , were € 3370-€3417 and € 2935-€2976 for Sweden and France , respectively . In comparison , the total costsof treatment with TVT over 3–6 months were € 3169-€3504 and € 5181-€5471 for Sweden and France , respectively . Conclusions : NASHA/Dx gel provides utility benefits that are similar to those previously reported for TVT and , depending on the country in which the treatment is performed , are associated with similar or lower overall costs in the short to medium term . From an economic perspective , NASHA/Dx gel could be considered at least as favourable as TVT , pending the availability of long-term effectiveness data", "Purpose Urinary incontinence ( UI ) is a common chronic health condition , a problem specifically among elderly women that impacts quality of life negatively . However , UI is usually viewed as likely result of old age , and as such is generally not evaluated or even managed appropriately . Many treatments are available to manage incontinence , such as bladder training and numerous surgical procedures such as Burch colposuspension and Sling for UI which have high success rates . The purpose of this paper is to analyze which of these popular surgical procedures for UI is effective . Design / methodology /approach This research employs r and omized , prospect i ve studies to obtain robust cost and utility data used in the Markov chain decision model for examining which of these surgical interventions is more effective in treating women with stress UI based on two measures : number of quality adjusted life years ( QALY ) and cost per QALY . Treeage Pro Healthcare software was employed in Markov decision analysis . Findings Results showed the Sling procedure is a more effective surgical intervention than the Burch . However , if a utility greater than certain utility value , for which both procedures are equally effective , is assigned to persistent incontinence , the Burch procedure is more effective than the Sling procedure . Originality/value This paper demonstrates the efficacy of a Markov chain decision modeling approach to study the comparative effectiveness analysis of available treatments for patients with UI , an important public health issue , widely prevalent among elderly women in developed and developing countries . This research also improves upon other analyses using a Markov chain decision modeling process to analyze various strategies for treating UI" ]

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[ "Glycemic load, glycemic index, and pancreatic cancer risk in the Netherlands Cohort Study.", "Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women.", "Fasting serum glucose level and cancer risk in Korean men and women.", "Dietary glycemic index, glycemic load, and cancer risk: results from the EPIC-Italy study", "Glycemic index, glycemic load and invasive breast cancer incidence in postmenopausal women: The PREDIMED study", "Glycemic index of foods: a physiological basis for carbohydrate exchange.", "Dietary carbohydrate intake, glycaemic load, glycaemic index and ovarian cancer risk in African-American women.", "Dietary glycemic index and glycemic load and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).", "Dietary Glycemic Load, Glycemic Index, and Carbohydrate Intake on the Risk of Lung Cancer among Men and Women in Shanghai", "Diversity of dietary patterns observed in the European Prospective Investigation into Cancer and Nutrition (EPIC) project.", "Dietary fiber, whole grains, carbohydrate, glycemic index, and glycemic load in relation to risk of prostate cancer", "Dietary glycemic load and risk of colorectal cancer in the Women's Health Study.", "Dietary carbohydrate, fibre, glycaemic index, glycaemic load and the risk of postmenopausal breast cancer", "Glycemic index and glycemic load and risk of colorectal cancer: a population-based cohort study (JPHC Study)", "Dietary carbohydrates, fiber, and breast cancer risk.", "Glycemic load, carbohydrate intake, and risk of colorectal cancer in women: a prospective cohort study.", "Dietary Glycemic Load and Breast Cancer Risk in the Women’s Health Study", "Dietary carbohydrates, glycemic index, glycemic load, and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition cohort.", "Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study.", "Glycaemic index, glycaemic load and risk of endometrial cancer: a prospective cohort study.", "Dietary carbohydrate, glycemic index, and glycemic load in relation to risk of colorectal cancer in women.", "Dietary carbohydrate, glycemic index, glycemic load, and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort", "Dietary carbohydrates and breast cancer risk: a prospective study of the roles of overall glycemic index and glycemic load.", "Carbohydrate nutrition and risk of adiposity-related cancers: results from the Framingham Offspring cohort (1991-2013).", "Dietary glycemic index and glycemic load and risk of colorectal cancer: results from the EPIC-Italy study.", "Glycemic index, glycemic load, and pancreatic cancer risk (Canada)", "Dietary carbohydrates, fiber, and breast cancer risk in Chinese women.", "Dietary glycaemic index and glycaemic load in relation to all-cause and cause-specific mortality in a Japanese community: the Takayama study.", "Dietary carbohydrate, glycemic index, and glycemic load and the risk of colorectal cancer in the BCDDP cohort", "Glycemic Load, Glycemic Index, and the Risk of Breast Cancer Among Mexican Women", "Available carbohydrates, glycemic load, and pancreatic cancer: is there a link?", "Prospective Study of Glycemic Load, Glycemic Index, and Carbohydrate Intake in Relation to Risk of Biliary Tract Cancer", "Glycemic load, glycemic index and carbohydrate intake in relation to risk of stomach cancer: a prospective study.", "Food sources of carbohydrates in a European cohort of adults.", "Dietary glycemic load and risk of colorectal cancer in Chinese women.", "Dietary fiber, glycemic index, glycemic load and renal cell carcinoma risk.", "Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans." ]

[ "BACKGROUND Recent studies of pancreatic cancer suggest a role for hyperinsulinemia in carcinogenesis . Because insulin is secreted in response to elevated blood glucose concentrations , dietary factors that increase these concentrations may be important in pancreatic carcinogenesis . OBJECTIVE The objective was to examine prospect ively the relation between pancreatic cancer risk and dietary glycemic load ( GL ) , overall glycemic index ( GI ) , and intake of total carbohydrates and mono- and disaccharides . DESIGN The Netherl and s Cohort Study consisted of 120,852 men and women who completed a baseline question naire in 1986 . After 13.3 y of follow-up , 408 pancreatic cancer cases were detected , 66 % of which were microscopically confirmed . A vali date d 150-item food-frequency question naire , completed at baseline , was used to calculate carbohydrate and mono- and disaccharide intakes and the GL and GI of the diet . RESULTS Dietary GL , GI , or intake of carbohydrates and mono- and disaccharides were not associated with pancreatic cancer risk in this cohort . Also , the associations were not modified by sex . Our results did not change after the analysis was restricted to microscopically confirmed pancreatic cancer cases or after individuals who reported a history of diabetes at baseline were excluded from the analyses . CONCLUSIONS Overall , our findings do not support the hypothesis that GL , GI , or intake of carbohydrates and mono- and disaccharides are positively associated with pancreatic cancer risk . This is in agreement with previous prospect i ve studies that investigated the relation between GL and GI and pancreatic cancer risk", "Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive . Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels . The effect of consuming a high glycemic diet on colorectal risk , however , remains uncertain . Two prospect i ve cohort studies , the Nurses ' Health Study and the Health Professionals Follow-up Study , contributed up to 20 years of follow-up . After exclusions , 1,809 incident colorectal cancers were available for analyses . Dietary glycemic load ( GL ) was calculated as a function of glycemic index ( postpr and ial blood glucose response as compared with a reference food ) , carbohydrate content , and frequency of intake of individual foods reported on food frequency question naires . Multivariable Cox proportional hazards models were used to adjust for potential confounders . Intakes of dietary carbohydrate , GL , overall glycemic index , sucrose , and fructose were not associated with colorectal cancer risk in women . A small increase in risk was observed in men with high dietary GL ( multivariate relative risk , 1.32 ; 95 % confidence interval , 0.98 - 1.79 ; highest versus lowest quintile ) , sucrose or fructose ( multivariate relative risk , 1.37 ; 95 % confidence interval , 1.05 - 1.78 ; highest versus lowest quintile of fructose , P = 0.008 ) . Associations were slightly stronger among men with elevated body mass index ( > or = 25 kg/m(2 ) ) . Results among women were similar after stratifying by body mass index or physical activity . High intakes of GL , fructose , and sucrose were related to an elevated colorectal cancer risk among men . For women , however , these factors did not seem to increase the risk of colorectal cancer", "CONTEXT Diabetes is a serious and costly disease that is becoming increasingly common in many countries . The role of diabetes as a cancer risk factor remains unclear . OBJECTIVE To examine the relationship between fasting serum glucose and diabetes and risk of all cancers and specific cancers in men and women in Korea . DESIGN , SETTING , AND PARTICIPANTS Ten-year prospect i ve cohort study of 1,298,385 Koreans ( 829,770 men and 468,615 women ) aged 30 to 95 years who received health insurance from the National Health Insurance Corp and had a biennial medical evaluation in 1992 - 1995 ( with follow-up for up to 10 years ) . MAIN OUTCOME MEASURES Death from cancer and registry-documented incident cancer or hospital admission for cancer . RESULTS During the 10 years of follow-up , there were 20,566 cancer deaths in men and 5907 cancer deaths in women . Using Cox proportional hazards models and controlling for smoking and alcohol use , the stratum with the highest fasting serum glucose ( > or = 140 mg/dL [ > or = 7.8 mmol/L ] ) had higher death rates from all cancers combined ( hazard ratio [ HR ] , 1.29 ; 95 % confidence interval [ CI ] , 1.22 - 1.37 in men and HR , 1.23 ; 95 % CI , 1.09 - 1.39 in women ) compared with the stratum with the lowest level ( < 90 mg/dL [ < 5.0 mmol/L ] ) . By cancer site , the association was strongest for pancreatic cancer , comparing the highest and lowest strata in men ( HR , 1.91 ; 95 % CI , 1.52 - 2.41 ) and in women ( HR , 2.05 ; 95 % CI , 1.43 - 2.93 ) . Significant associations were also found for cancers of the esophagus , liver , and colon/rectum in men and of the liver and cervix in women , and there were significant trends with glucose level for cancers of the esophagus , colon/rectum , liver , pancreas , and bile duct in men and of the liver and pancreas in women . Of the 26,473 total cancer deaths in men and women , 848 were estimated as attributable to having a fasting serum glucose level of less than 90 mg/dL. For cancer incidence , the general patterns reflected those found for mortality . For persons with a diagnosis of diabetes or a fasting serum glucose level greater than 125 mg/dL ( 6.9 mmol/L ) , risks for cancer incidence and mortality were generally elevated compared with those without diabetes . CONCLUSION In Korea , elevated fasting serum glucose levels and a diagnosis of diabetes are independent risk factors for several major cancers , and the risk tends to increase with an increased level of fasting serum glucose", "Factors linked to glucose metabolism are involved in the etiology of several cancers . High glycemic index ( GI ) or high glycemic load ( GL ) diets , which chronically raise postpr and ial blood glucose , may increase cancer risk by affecting insulin-like growth factor . We prospect ively investigated cancer risk and dietary GI/GL in the EPIC-Italy cohort . After a median 14.9 years , 5112 incident cancers and 2460 deaths were identified among 45,148 recruited adults . High GI was associated with increased risk of colon and bladder cancer . High GL was associated with : increased risk of colon cancer ; increased risk of diabetes-related cancers ; and decreased risk of rectal cancer . High intake of carbohydrate from high GI foods was significantly associated with increased risk of colon and diabetes-related cancers , but decreased risk of stomach cancer ; whereas high intake of carbohydrates from low GI foods was associated with reduced colon cancer risk . In a Mediterranean population with high and varied carbohydrate intake , carbohydrates that strongly raise postpr and ial blood glucose may increase colon and bladder cancer risk , while the quantity of carbohydrate consumed may be involved in diabetes-related cancers . Further studies are needed to confirm the opposing effects of high dietary GL on risks of colon and rectal cancers", "The objective of this study was to evaluate the prospect i ve associations between dietary glycemic index ( GI ) and glycemic load ( GL ) and the risk for invasive breast cancer incidence in postmenopausal women at high cardiovascular disease ( CVD ) risk . This study was conducted within the framework of the PREvención con DIeta MEDiterránea ( PREDIMED ) study , a nutritional intervention trial for primary cardiovascular prevention . We included 4010 women aged between 60 and 80 years who were initially free from breast cancer but at high risk for CVD disease . Dietary information was collected using a vali date d 137-item food frequency question naire . We assigned GI values using the International Tables of GI and GL values . Cases were ascertained through yearly consultation of medical records and through consultation of the National Death Index . Only cases confirmed by results from cytology tests or histological evaluation were included . We estimated multivariable-adjusted hazard ratios for invasive breast cancer risk across tertiles of energy-adjusted dietary GI/GL using Cox regression models . We repeated our analyses using yearly repeated measures of GI/GL intakes . No associations were found between baseline dietary GI/GL and invasive breast cancer incidence . The multivariable hazard ratio and 95 % confidence interval ( CI ) for the top tertile of dietary GI was 1.02 ( 95 % CI : 0.42–2.46 ) and for dietary GL was 1.00 ( 95 % CI : 0.44–2.30 ) when compared with the bottom tertile . Repeated- measures analyses yielded similar results . In sensitivity analyses , no significant associations were observed for women with obesity or diabetes . Dietary GI and GL did not appear to be associated with an increased risk for invasive breast cancer in postmenopausal women at high CVD risk", "The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content", "Epidemiological evidence regarding the association between carbohydrate intake , glycaemic load ( GL ) and glycaemic index ( GI ) and risk of ovarian cancer has been mixed . Little is known about their impact on ovarian cancer risk in African-American women . Associations between carbohydrate quantity and quality and ovarian cancer risk were investigated among 406 cases and 609 controls using data from the African American Cancer Epidemiology Study ( AACES ) . AACES is an ongoing population -based case-control study of ovarian cancer in African-Americans in the USA . Cases were identified through rapid case ascertainment and age- and site-matched controls were identified by r and om-digit dialling . Dietary information over the year preceding diagnosis or the reference date was obtained using a FFQ . Multivariable logistic regression models were used to estimate odds ratios and 95 % CI adjusted for covariates . The OR comparing the highest quartile of total carbohydrate intake and total sugar intake v. the lowest quartile were 1·57 ( 95 % CI 1·08 , 2·28 ; P trend=0·03 ) and 1·61 ( 95 % CI 1·12 , 2·30 ; P trend<0·01 ) , respectively . A suggestion of an inverse association was found for fibre intake . Higher GL was positively associated with the risk of ovarian cancer ( OR 1·18 for each 10 units/4184 kJ ( 1000 kcal ) ; 95 % CI 1·04 , 1·33 ) . No associations were observed for starch or GI . Our findings suggest that high intake of total sugars and GL are associated with greater risk of ovarian cancer in African-American women", "BACKGROUND The glycemic potential of a diet is associated with chronically elevated insulin concentrations , which may augment breast cancer ( BC ) risk by stimulating insulin receptor or by affecting insulin-like growth factor I (IGF-I)-mediated mitogenesis . It is unclear whether this effect differs by BC phenotype . OBJECTIVE The objective was to investigate the relation between glycemic index ( GI ) , glycemic load ( GL ) , and total carbohydrate intake with BC by using data from the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . DESIGN We identified 11,576 women with invasive BC among 334,849 EPIC women aged 34 - 66 y ( 5th to 95th percentiles ) at baseline over a median follow-up of 11.5 y. Dietary GI and GL were calculated from country-specific dietary question naires . We used multivariable Cox proportional hazards models to quantify the association between GI , GL , and carbohydrate intake and BC risk . BC tumors were classified by receptor status . RESULTS Overall GI , GL , and carbohydrates were not related to BC . Among postmenopausal women , GL and carbohy date intake were significantly associated with an increased risk of estrogen receptor-negative ( ER(- ) ) BC when extreme quintiles ( Q ) were compared [ multivariable HR(Q5-Q1 ) ( 95 % CI ) = 1.36 ( 1.02 , 1.82 ; P-trend = 0.010 ) and HR(Q5-Q1 ) = 1.41 ( 1.05 , 1.89 ; P-trend = 0.009 ) , respectively ] . Further stratification by progesterone receptor ( PR ) status showed slightly stronger associations with ER(-)/PR(- ) BC [ HR(Q5-Q1 ) ( 95 % CI ) = 1.48 ( 1.07 , 2.05 ; P-trend = 0.010 ) for GL and HR(Q5-Q1 ) = 1.62 ( 1.15 , 2.30 ; P-trend = 0.005 ) for carbohydrates ] . No significant association with ER-positive BC was observed . CONCLUSION Our results indicate that a diet with a high GL and carbohydrate intake is positively associated with an increased risk of developing ER(- ) and ER(-)/PR(- ) BC among postmenopausal women", "ABSTRACT To investigate the potential influence of dietary glycemic index , glycemic load , or carbohydrate intake and lung cancer risk in Shanghai . We prospect ively investigated the associations among 130,858 participants in the Shanghai Women 's and Men 's Health Studies . Diet was assessed using vali date d food-frequency question naires . Lung cancer cases were ascertained through annual record linkage and every 2–3 years in-home visits . Cox proportional hazard regression model was used to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . After excluding the first 2 years of observation , 1312 participants ( including 649 women and 663 men ) developed lung cancer during an average follow-up of 14.8 ( SD : 2.0 ) years for SWHS and 9.3 ( SD : 1.6 ) years for SMHS . In multivariable analysis , no statistically significant associations were observed between glycemic index , glycemic load , and carbohydrate intake and lung cancer risk for either men or women . Similar results were observed among never smokers , and participants without history of lung disease , diabetes , or hypertension . Stratification by body mass index or menopause status also did not alter the findings . Our studies , conducted in population s who habitually have high-carbohydrate diets , provide no evidence that dietary glycemic index , glycemic load , or carbohydrate intake is associated with lung cancer risk", "OBJECTIVE To describe the diversity in dietary patterns existing across centres/regions participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . DESIGN AND SETTING Single 24-hour dietary recall measurements were obtained by means of st and ardised face-to-face interviews using the EPIC-SOFT software . These have been used to present a graphic multi-dimensional comparison of the adjusted mean consumption of 22 food groups . SUBJECTS In total , 35 955 men and women , aged 35 - 74 years , participating in the EPIC nested calibration study . RESULTS Although wide differences were observed across centres , the countries participating in EPIC are characterised by specific dietary patterns . Overall , Italy and Greece have a dietary pattern characterised by plant foods ( except potatoes ) and a lower consumption of animal and processed foods , compared with the other EPIC countries . France and particularly Spain have more heterogeneous dietary patterns , with a relatively high consumption of both plant foods and animal products . Apart from characteristics specific to vegetarian groups , the UK ' health-conscious ' group shares with the UK general population a relatively high consumption of tea , sauces , cakes , soft drinks ( women ) , margarine and butter . In contrast , the diet in the Nordic countries , The Netherl and s , Germany and the UK general population is relatively high in potatoes and animal , processed and sweetened/refined foods , with proportions varying across countries/centres . In these countries , consumption of vegetables and fruit is similar to , or below , the overall EPIC means , and is low for legumes and vegetable oils . Overall , dietary patterns were similar for men and women , although there were large gender differences for certain food groups . CONCLUSIONS There are considerable differences in food group consumption and dietary patterns among the EPIC study population s. This large heterogeneity should be an advantage when investigating the relationship between diet and cancer and formulating new aetiological hypotheses related to dietary patterns and disease", "Background The relationships between dietary fiber , whole grains , carbohydrate , glycemic index ( GI ) , glycemic load ( GL ) , and prostate cancer risk are unclear . We conducted a systematic review and meta- analysis to investigate these associations . Methods Relevant studies were identified by a search of PubMed data base and EMBASE data base up to April 2015 . A r and om effects model was used to calculate the summary relative risks ( RRs ) and their corresponding 95 % confidence intervals ( CIs ) . Results Twenty-seven epidemiological studies ( 18 case – control studies and nine cohort studies ) were included in the final analysis . The pooled RRs of prostate cancer were 0.94 ( 95 % CI 0.85–1.05 , P=0.285 ) , 1.13 ( 95 % CI 0.98–1.30 , P=0.095 ) , 0.96 ( 95 % CI 0.81–1.14 , P=0.672 ) , 1.06 ( 95 % CI 0.96–1.18 , P=0.254 ) , and 1.04 ( 95 % CI 0.91–1.18 , P=0.590 ) for dietary fiber , whole grains , carbohydrate , GI , and GL , respectively . There was no evidence of significant publication bias based on the Begg ’s test and Egger ’s test . Conclusion The findings of this meta- analysis indicate that , based on available information , dietary fiber , whole grains , carbohydrate , GI , and GL are not associated with the risk of prostate cancer", "Although diet is believed to influence colorectal cancer risk , the long-term effects of a diet with a high glycemic load are unclear . The growing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggests that a diet inducing high blood glucose levels and an elevated insulin response may contribute to a metabolic environment conducive to tumor growth . We prospect ively followed a cohort of 38 451 women for an average of 7.9 years and identified 174 with incident colorectal cancer . We used baseline dietary intake measurements , assessed with a semiquantitative food-frequency question naire , to examine the associations of dietary glycemic load , overall dietary glycemic index , carbohydrate , fiber , nonfiber carbohydrate , sucrose , and fructose with the subsequent development of colorectal cancer . Cox proportional hazards models were used to estimate relative risks ( RRs ) . Dietary glycemic load was statistically significantly associated with an increased risk of colorectal cancer ( adjusted RR = 2.85 , 95 % confidence interval [ CI ] = 1.40 to 5.80 , comparing extreme quintiles of dietary glycemic load ; P(trend ) = .004 ) and was associated , although not statistically significantly , with overall glycemic index ( corresponding RR = 1.71 , 95 % CI = 0.98 to 2.98 ; P(trend ) = .04 ) . Total carbohydrate ( adjusted RR = 2.41 , 95 % CI = 1.10 to 5.27 , comparing extreme quintiles of carbohydrate ; P(trend ) = .02 ) , nonfiber carbohydrate ( corresponding RR = 2.60 , 95 % CI = 1.22 to 5.54 ; P(trend ) = .02 ) , and fructose ( corresponding RR = 2.09 , 95 % CI = 1.13 to 3.87 ; P(trend ) = .08 ) were also statistically significantly associated with increased risk . Thus , our data indicate that a diet with a high dietary glycemic load may increase the risk of colorectal cancer in women", "Evidence that the insulin pathway may be involved in breast carcinogenesis has increased the interest in dietary factors that influence insulin secretion and resistance . We investigated dietary carbohydrate , fibre , glycaemic index ( GI ) and glycaemic load ( GL ) in a prospect i ve study of 324 breast cancers diagnosed in 12,273 post‐menopausal women . Although an increase of 1 st and ard deviation in carbohydrate was marginally associated with risk of breast cancer , relative risk ( RR ) 1.31 ( 95 % CI , 0.98 , 1.75 ) , there were no significant associations with fibre , 1.08 ( 0.92 , 1.26 ) , GI , 0.98 ( 0.88 , 1.10 ) or GL , 1.19 ( 0.93 , 1.52 ) or with carbohydrate foods ( bread , rice , pasta ) . The RR for carbohydrate and localized disease was elevated , 1.40 ( 1.02 , 1.92 ) , but like those for fibre , GI and GL did not differ significantly between localized and non‐localized disease . RRs for grade I , but not grade II or III , tumours were elevated for fibre , 1.38 ( 1.08 , 1.75 ) , carbohydrate , 1.56 ( 1.08 , 2.25 ) and GL , 1.41 ( 1.01 , 1.98 ) but not for GI , 0.84 ( 0.65 , 1.09 ) . The RRs for fibre and oestrogen receptor ( ER ) positive ( + ) and progesterone receptor ( PR ) positive ( + ) tumours , 1.36 ( 1.10 , 1.67 ) , differed significantly from those for ER positive ( + ) and PR negative ( − ) tumours , 1.01 ( 0.61 , 1.69 ) and ER−/PR− tumours , 0.65 ( 0.43 , 0.99 ) , p = 0.005 . Our data do not support a strong role for GI and GL in breast carcinogenesis but suggest that increased intake of fibre and carbohydrate may be associated with the diagnosis of cancers of more favourable prognosis . © 2005 Wiley‐Liss ,", "Purpose The aim of this study was for the first time to assess the association between glycemic index ( GI ) , glycemic load ( GL ) , and colorectal cancer using a prospect i ve Japanese population -based cohort . Methods In our study participants aged 40–69 at baseline of the Japan Public Health Center-based prospect i ve Study ( JPHC Study ) in 10 prefectural public health centers ( PHC ) were included . Subjects responding to the five-year follow-up survey ( 1995–1999 ) without previous history of cancer and missing data were included in the current analysis n = 73,501 ( men n = 34,560 and women n = 38,941 ) . We reported results as hazard ratios ( HR ) and 95 % confidence intervals ( CI ) by Cox proportional hazards modeling . Results The average follow-up time was 12.5 years ( 919,276 person-years ) . A total of 1,468 colorectal cancer cases were detected . Overall , no significant results were observed ; however , GL was inversely nonsignificantly associated with colon cancer in men HR = 0.74 ( 95 % CI 0.51–1.09 ) and rectal cancer in women 0.52 ( 95 % CI 0.24–1.14 ) . The GL tended to be inversely associated with proximal colon cancer among men 0.62 ( 95 % CI 0.36–1.08 ) , while a positive association with the GI was observed among women 1.37 ( 95 % CI 0.88–2.14 ) . Sensitivity analyses excluding the first three years of observation showed similar results . Results stratified by diabetes status , BMI , smoking and red meat were nonsignificant . Conclusions In conclusion , the prospect i ve JPHC Study suggests that the GI and GL do not have a substantial impact on the risk of colorectal cancer in Japanese adults", "Dietary fiber , fiber fractions , carbohydrate , glycemic index , and glycemic load were prospect ively assessed five times over 18 years with a vali date d food frequency question naire in relation to breast cancer risk among 88,678 women ( aged 34 - 59 years at baseline ) in the Nurses ' Health Study . Incident breast cancer occurred in 4,092 of these women between 1980 and 1998 . The authors observed no material association between carbohydrate intake , glycemic index and glycemic load , total dietary fiber intake , and breast cancer risk . The relative risks for the highest versus the lowest quintile of intake were 0.97 ( 95 % confidence interval ( CI ) : 0.87 , 1.08 ) for carbohydrates , 1.08 ( 95 % CI : 0.97 , 1.19 ) for glycemic index , 0.99 ( 95 % CI : 0.89 , 1.10 ) for glycemic load , and 0.98 ( 95 % CI : 0.87 , 1.11 ) for fiber . The relative risk comparing those in the highest 0.7 % of fiber intake ( > 30 g/day ) with those in the lowest 10 % of fiber intake ( < or = 10 g/day ) was 0.68 ( 95 % CI : 0.43 , 1.06 ) . Analyses stratified by menopausal status and body mass index also showed no clear risk pattern . In this cohort of middle-aged women , no overall association was found for dietary carbohydrates , glycemic index and glycemic load , and breast cancer risk . This study also confirmed the lack of an overall association between intake of fiber and fiber types and breast cancer risk observed in other prospect i ve studies", "Mounting evidence suggests that high circulating levels of insulin might be associated with increased colorectal cancer risk . The glycemic effects of diets high in refined starch may increase colorectal cancer risk by affecting insulin and /or insulin-like growth factor-I levels . We examined the association between dietary intake and colorectal cancer risk in a cohort of 49 124 women participating in a r and omized , controlled trial of screening for breast cancer in Canada . Linkages to Canadian mortality and cancer data bases yielded data on mortality and cancer incidence up to December 31 , 2000 . During an average 16.5 years of follow-up , we observed 616 incident cases of colorectal cancer ( 436 colon cancers , 180 rectal cancers ) . Rate ratios for colorectal cancer for the highest versus the lowest quintile level were 1.05 ( 95 % confidence interval [ CI ] = 0.73 to 1.53 ; P(trend ) = .94 ) for glycemic load , 1.01 ( 95 % CI = 0.68 to 1.51 ; P(trend ) = .66 ) for total carbohydrates , and 1.03 ( 95 % CI = 0.73 to 1.44 ; P(trend ) = .71 ) for total sugar . Our data do not support the hypothesis that diets high in glycemic load , carbohydrates , or sugar increase colorectal cancer risk", "A diet with a high glycemic load ( GL ) may contribute to a metabolic environment that enhances tumorigenesis . Little is known , however , about whether high glycemic diets increase breast cancer risk in women . We examined the associations between baseline measurements of dietary GL and overall glycemic index ( GI ) and subsequent breast cancer in a cohort of 39,876 women , ages 45 years or older , participating in the Women ’s Health Study . During a mean of 6.8 years of follow-up there were 946 confirmed cases of breast cancer . We found no association between dietary GL [ multivariable-adjusted relative risk ( RR ) , 1.01 ; confidence interval ( CI ) , 0.76–1.35 , comparing extreme quintiles ; P for trend = 0.96 ] or overall GI ( corresponding RR , 1.03 ; CI , 0.84–1.28 ; P for trend = 0.66 ) and breast cancer risk in the cohort as a whole . Exploratory analyses stratified by baseline measurements of menopausal status , physical activity , smoking history , alcohol use , and history of diabetes mellitus , hypertension , or hypercholesterolemia showed no significant associations , except in the subgroup of women who were premenopausal and reported low levels of physical activity ( GL multivariable-adjusted RR , 2.35 ; CI , 1.03–5.37 ; P for trend = 0.07 ; GI multivariable-adjusted RR , 1.56 ; CI , 0.88–2.78 ; P for trend = 0.02 , comparing extreme quintiles ) . Although we did not find evidence that a high glycemic diet increases overall breast cancer risk , the increase in risk in premenopausal women with low levels of physical activity suggests the possibility that the effects of a high glycemic diet may be modified by lifestyle and hormonal factors . Prospect i ve studies of a larger sample size and longer duration are warranted to confirm our findings", "The associations of dietary total carbohydrates , overall glycemic index , total dietary glycemic load , total sugars , total starch , and total fiber with endometrial cancer risk were analyzed among 288,428 women in the European Prospect i ve Investigation into Cancer and Nutrition cohort ( 1992 - 2004 ) , including 710 incident cases diagnosed during a mean 6.4 years of follow-up . Cox proportional hazards models were used to estimate relative risks and 95 % confidence intervals . There were no statistically significant associations with endometrial cancer risk for increasing quartile intakes of any of the exposure variables . However , in continuous models calibrated by using 24-hour recall values , the multivariable relative risks were 1.61 ( 95 % confidence interval : 1.06 , 2.45 ) per 100 g/day of total carbohydrates , 1.40 ( 95 % confidence interval : 0.99 , 1.99 ) per 50 units/day of total dietary glycemic load , and 1.36 ( 95 % confidence interval : 1.05 , 1.76 ) per 50 g/day of total sugars . These associations were stronger among women who had never used postmenopausal hormone therapy compared with ever users ( total carbohydrates p(heterogeneity ) = 0.04 ) . Data suggest no association of overall glycemic index , total starch , and total fiber with risk , and a possible modest positive association of total carbohydrates , total dietary glycemic load , and total sugars with risk , particularly among never users of hormone replacement therapy", "Incidence rates of differentiated thyroid carcinoma ( TC ) have increased in many countries . Adiposity and dietary risk factors may play a role , but little is known on the influence of energy intake and macronutrient composition . The aim of this study was to investigate the associations between TC and the intake of energy , macronutrients , glycemic index ( GI ) and glycemic load in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort . The study included 477,274 middle-age participants ( 70.2 % women ) from ten European countries . Dietary data were collected using country-specific vali date d dietary question naires . Total carbohydrates , proteins , fats , saturated , monounsaturated and polyunsaturated fats ( PUFA ) , starch , sugar , and fiber were computed as g/1,000 kcal . Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios ( HR ) and 95 % confidence interval ( CI ) by intake quartile ( Q ) . After a mean follow-up time of 11 years , differentiated TC was diagnosed in 556 participants ( 90 % women ) . Overall , we found significant associations only with total energy ( HRQ4 vs .Q1 , 1.29 ; 95 % CI , 1.00 - 1.68 ) and PUFA intakes ( HRQ4 vs .Q1 , 0.74 ; 95 % CI , 0.57 - 0.95 ) . However , the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index ( BMI ) groups , i.e. , positive associations with starch and GI were found in participants with a BMI ≥ 25 and with sugar intake in those with BMI < 25 . Moreover , inverse associations with starch and GI were observed in subjects with BMI < 25 . In conclusion , our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC . Positive associations with starch intake and GI in participants with BMI ≥ 25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people", "OBJECTIVE High-glycaemic-load diets may increase endometrial cancer risk by increasing circulating insulin levels and , as a consequence , circulating oestrogen levels . Given the paucity of epidemiological data regarding the relationship between dietary glycaemic index and glycaemic load and endometrial cancer risk , we sought to examine these associations using data from a prospect i ve cohort study . DESIGN , SETTING AND SUBJECTS We examined the association between dietary glycaemic load and endometrial cancer risk in a cohort of 49,613 Canadian women aged between 40 and 59 years at baseline who completed self-administered food-frequency question naires between 1982 and 1985 . Linkages to national mortality and cancer data bases yielded data on deaths and cancer incidence , with follow-up ending between 1998 and 2000 . RESULTS During a mean of 16.4 years of follow-up , we observed 426 incident cases of endometrial cancer . Hazard ratios for the highest versus the lowest quartile level of overall glycaemic index and glycaemic load were 1.47 ( 95 % confidence interval ( CI ) = 0.90 - 2.41 ; P for trend = 0.14 ) and 1.36 ( 95 % CI = 1.01 - 1.84 ; P for trend = 0.21 ) , respectively . No association was observed between total carbohydrate or total sugar consumption and endometrial cancer risk . Among obese women ( body mass index > 30 kg m(-2 ) ) the hazard ratio for the highest versus the lowest quartile level of glycaemic load was 1.88 ( 95 % CI = 1.08 - 3.29 ; P for trend = 0.54 ) and there was a 55 % increased risk for the highest versus the lowest quartile level of glycaemic load among premenopausal women . There was also evidence to support a positive association between glycaemic load and endometrial cancer risk among postmenopausal women who had used hormone replacement therapy . CONCLUSIONS Our data suggest that diets with high glycaemic index or high glycaemic load may be associated with endometrial cancer risk overall , and particularly among obese women , premenopausal women and postmenopausal women who use hormone replacement therapy", "Diets with a high glycemic index and glycemic load have been hypothesized to be implicated in the etiology of colorectal cancer owing to their potential to increase postpr and ial glucose and insulin levels . Prospect i ve data on glycemic index and glycemic load in relation to colorectal cancer risk are limited and inconsistent . Therefore , the authors prospect ively investigated the associations of dietary carbohydrate , glycemic index , and glycemic load with the incidence of colorectal cancer among 61,433 Swedish women who were free of cancer in 1987 - 1990 and completed a 67-item food frequency question naire . During follow-up through June 2005 , 870 incident cases of colorectal adenocarcinoma were diagnosed . Carbohydrate intake , glycemic index , and glycemic load were not associated with risk of colorectal cancer , colon cancer , or rectal cancer . The multivariate hazard ratios for colorectal cancer comparing the highest with the lowest quintile were 1.10 ( 95 % confidence interval : 0.85 , 1.44 ) for carbohydrate intake , 1.00 ( 95 % confidence interval : 0.75 , 1.33 ) for glycemic index , and 1.06 ( 95 % confidence interval : 0.81 , 1.39 ) for glycemic load . Results did not vary by body mass index . The findings from this prospect i ve study do not support the hypothesis that a high carbohydrate intake , a high glycemic index , and a high glycemic load increase the risk of colorectal cancer", "Objective To evaluate the associations between dietary carbohydrate , glycemic index ( GI ) , glycemic load ( GL ) , and incident prostate cancer in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial ( PLCO ) cohort . Methods Between September 1993 and September 2000 , 38,343 men were r and omized to the screening arm of the trial at one of 10 PLCO centers . A food frequency question naire administered at baseline assessed usual dietary intake over the preceding 12 months . Prostate cancer was ascertained by medical follow-up of suspicious screening results and annual mailed question naires and confirmed with medical records . Cox proportional hazards regression was used to model the associations of carbohydrate , GI , and GL with prostate cancer risk . Results During follow-up ( median = 9.2 years ) , 2,436 incident prostate cancers were identified among 30,482 eligible participants . Overall , there were no associations of baseline carbohydrate , GI , or GL with incident prostate cancer in minimally or fully adjusted models . There were no associations when the 228 advanced and 2,208 non-advanced cancers were analyzed separately . Conclusions Dietary carbohydrate , GI , and GL were not associated with incident prostate cancer in PLCO . The narrow range of GI in this cohort may have limited our ability to detect associations , an issue that future studies should address", "We examined breast cancer risk in association with overall glycemic index ( GI ) , glycemic load ( GL ) , and dietary carbohydrate and sugar intake in a prospect i ve cohort of 49,613 Canadian women enrolled in the National Breast Screening Study who completed a self-administered food frequency question naire between 1980 and 1985 . Linkages to national mortality and cancer data bases yielded data on deaths and cancer incidence , with follow-up ending between 1998 and 2000 . During a mean follow-up of 16.6 years , we observed 1,461 incident breast cancer cases . GI , GL , total carbohydrate and total sugar intake were not associated with breast cancer risk in the total cohort . However , there was evidence of effect modification of the association between GI and breast cancer risk by menopausal status ( p = 0.01 ) , the hazard ratio for the highest versus the lowest quintile level of GI being 0.78 ( 95 % CI = 0.52 - 1.16 ; ptrend = 0.12 ) in premenopausal women and 1.87 ( 95 % CI = 1.18 - 2.97 ; ptrend = 0.01 ) in postmenopausal women . The associations between GI and GL were not modified by body mass index ( BMI ) or by vigorous physical activity among pre- or postmenopausal women . Similarly , the associations between GI/GL and risk in postmenopausal women were not modified by BMI , vigorous physical activity , or ever use of hormone replacement therapy ( HRT ) , although the associations were slightly stronger among those who reported no vigorous physical activity ( ptrend = 0.02 ) , among those who reported ever using HRT ( ptrend = 0.02 ) and among normal-weight women ( BMI < 25 kg/m2 ; ptrend = 0.03 ) . Our data suggest that consumption of diets with high GI values may be associated with increased risk of breast cancer among postmenopausal women , possibly more so among subgroups defined by participation in vigorous physical activity , ever use of HRT and those who are not overweight", "Higher carbohydrate intake , glycaemic index ( GI ) , and glycaemic load ( GL ) are hypothesised to increase cancer risk through metabolic dysregulation of the glucose-insulin axis and adiposity-related mechanisms , but epidemiological evidence is inconsistent . This prospect i ve cohort study investigates carbohydrate quantity and quality in relation to risk of adiposity-related cancers , which represent the most commonly diagnosed preventable cancers in the USA . In exploratory analyses , associations with three site-specific cancers : breast , prostate and colorectal cancers were also examined . The study sample consisted of 3184 adults from the Framingham Offspring cohort . Dietary data were collected in 1991 - 1995 using a FFQ along with lifestyle and medical information . From 1991 to 2013 , 565 incident adiposity-related cancers , including 124 breast , 157 prostate and sixty-eight colorectal cancers , were identified . Cox proportional hazards models were used to evaluate the role of carbohydrate nutrition in cancer risk . GI and GL were not associated with risk of adiposity-related cancers or any of the site-specific cancers . Total carbohydrate intake was not associated with risk of adiposity-related cancers combined or prostate and colorectal cancers . However , carbohydrate consumption in the highest v. lowest quintile was associated with 41 % lower breast cancer risk ( hazard ratio ( HR ) 0·59 ; 95 % CI 0·36 , 0·97 ) . High- , medium- and low-GI foods were not associated with risk of adiposity-related cancers or prostate and colorectal cancers . In exploratory analyses , low-GI foods , were associated with 49 % lower breast cancer risk ( HR 0·51 ; 95 % CI 0·32 , 0·83 ) . In this cohort of Caucasian American adults , associations between carbohydrate nutrition and cancer varied by cancer site . Healthier low-GI carbohydrate foods may prevent adiposity-related cancers among women , but these findings require confirmation in a larger sample", "A carbohydrate-rich diet , result ing in high blood glucose and insulin , has been hypothesized as involved in colorectal cancer etiology . We investigated dietary glycemic index ( GI ) and glycemic load ( GL ) , in relation to colorectal cancer , in the prospect ively recruited EPIC-Italy cohort . After a median 11.7 years , 421 colorectal cancers were diagnosed among 47,749 recruited adults . GI and GL were estimated from vali date d food frequency question naires . Multivariable Cox modeling estimated hazard ratios ( HRs ) for associations between colorectal cancer and intakes of total , high GI and low GI carbohydrate and GI and GL . The adjusted HR of colorectal cancer for highest versus lowest GI quartile was 1.35 ; 95 % confidence interval ( CI ) 1.03 - 1.78 ; p trend 0.031 . Increasing high GI carbohydrate intake was also significantly associated with increasing colorectal cancer risk ( HR 1.45 ; 95 % CI 1.04 - 2.03 ; p trend 0.034 ) , whereas increasing low GI carbohydrate was associated with reducing risk ( HR 0.73 ; 95 % CI 0.54 - 0.98 ; p trend 0.033 ) . High dietary GI and high GI carbohydrate were associated with increased risks of cancer at all colon sites ( HR 1.37 ; 95 % CI 1.00 - 1.88 , HR 1.80 ; 95 % CI 1.22 - 2.65 , respectively ) , whereas high GI carbohydrate and high GL were associated with increased risk of proximal colon cancer ( HR 1.94 ; 95 % CI 1.18 - 3.16 , HR 2.01 ; 95 % CI 1.08 - 3.74 , respectively ) . After stratification for waist-to-hip ratio ( WHR ) , cancer was significantly associated with GI , and high GI carbohydrate , in those with high WHR . These findings suggest that high dietary GI and high carbohydrate intake from high GI foods are associated with increased risk of colorectal cancer", "There is some evidence that plasma insulin and postload plasma glucose may be associated with risk of pancreatic cancer . Glycemic index and glycemic load are measures , which allow the carbohydrate content of individual foods to be classified according to their postpr and ial glycemic effects and hence their effects on circulating insulin levels . Therefore , we examined pancreatic cancer risk in association with glycemic index ( GI ) , glycemic load ( GL ) , and intake of dietary carbohydrate and sugar in a prospect i ve cohort of 49,613 Canadian women enrolled in the National Breast Screening Study ( NBSS ) who completed a self-administered food frequency question naire between 1980 and 1985 . Linkages to national cancer and mortality data bases yielded data on cancer incidence and deaths , with follow-up ending between 1998 and 2000 . During a mean 16.5 years of follow-up , we observed 112 incident pancreatic cancer cases . There was no association between overall glycemic index , glycemic load , total carbohydrate and total sugar intake and pancreatic cancer risk . In multivariate adjusted models , the hazard ratio ( HR ) for the highest versus lowest quartile levels of overall GI and GL were 1.43 ( 95 % confidence interval [CI]=0.56–3.65 , Ptrend=0.58 ) and 0.80 ( 95 % CI=0.45–1.41 , Ptrend=0.41 ) , respectively . Our data suggest that overall glycemic index and glycemic load , as well as total sugar and total carbohydrate intake , are not associated with pancreatic cancer risk . However , given the limited literature regarding the role of diet in the etiology of pancreatic cancer , particularly with respect to glycemic index/load , further investigation is warranted", "BACKGROUND Few studies have investigated the association of dietary carbohydrate and fiber intake with breast cancer risk in women in China , where carbohydrate intake is traditionally high . OBJECTIVE The objective was to prospect ively evaluate the association of dietary carbohydrates , glycemic index , glycemic load , and dietary fiber with breast cancer risk and to determine whether the effect of these dietary intakes is modified by age and selected insulin- or estrogen-related risk factors . DESIGN A total of 74,942 women aged 40 - 70 y were recruited into the Shanghai Women 's Health Study , a population -based cohort study . Dietary intake was assessed by in-person interviews . A Cox proportional hazards regression model was used to evaluate associations . RESULTS During an average of 7.35 y of follow-up , 616 incident breast cancer cases were documented . A higher carbohydrate intake was associated with a higher risk of premenopausal breast cancer ( P for trend = 0.002 ) . Compared with the lowest quintile , the hazard ratios ( and 95 % CIs ) were 1.47 ( 1.00 , 2.32 ) and 2.01 ( 1.26 , 3.19 ) for the fourth and fifth quintiles , respectively . A similar pattern was found for glycemic load . The association between carbohydrate intake and breast cancer was significantly modified by age ; the increased breast cancer risk associated with carbohydrate intake was restricted to women who were younger than 50 y. No significant association of breast cancer risk with glycemic index or dietary fiber intake was found . CONCLUSION Our data suggest that a high carbohydrate intake and a diet with a high glycemic load may be associated with breast cancer risk in premenopausal women or women < 50", "Diets with a high glycaemic index ( GI ) or glycaemic load ( GL ) have been hypothesised to increase the risk of diabetes , CVD and some cancers . In the present study , the associations of dietary GI and GL with the risk of all-cause and cause-specific mortality were prospect ively examined in a general population in Japan , where white rice is the main contributor of dietary GI and GL . A total of 28,356 residents of Takayama City , Japan , who responded to a self-administered question naire in 1992 were included in the present analyses . Dietary intake was assessed using a vali date d FFQ . Mortality was ascertained over 16 years . In men , dietary GI was found to be significantly inversely associated with the risk of all-cause and non-cancer , non-cardiovascular mortality ; the hazard ratios ( HR ) for the highest v. lowest quartile were 0.80 ( 95 % CI 0.68 , 0.95 ) and 0·64 ( 95 % CI 0.49 , 0.84 ) , respectively . Dietary GL was found to be significantly inversely associated with the risk of all-cause , cancer , and non-cancer , non-cardiovascular mortality ; the HR for the highest v. lowest quartile were 0.71 ( 95 % CI 0.59 , 0.86 ) , 0.71 ( 95 % CI 0.52 , 0.99 ) nd 0.64 ( 95 % CI 0.48 , 0.87 ) , respectively . The results obtained for the GL derived from white rice , but not from other foods , closely mirrored those obtained for overall GL . In women , dietary GI was found to be significantly positively associated with the risk of cardiovascular mortality ; the HR for the highest v. lowest quartile was 1.56 ( 95 % CI 1.15 , 2.13 ) . The results of the present study suggest potential favourable effects of dietary GI and GL on mortality in men , but an association between high GI and an increased risk of cardiovascular mortality in women", "Background There is considerable support for associations between insulin and IGF-I levels and colorectal cancer . Diet may relate to colorectal cancer through this mechanism , for example , diets high in glycemic index , glycemic load and /or carbohydrate are hypothesized to increase insulin load and the risk of insulin resistance , hyperinsulinemia . Case – control studies support this hypothesis , but prospect i ve cohorts have had mixed results . Methods In the Breast Cancer Detection Demonstration Project ( BCDDP ) follow-up cohort of 45,561 women , we used Cox proportional hazards regression to assess the distribution of 490 incident cases of colorectal cancer ascertained during 8.5 years of follow-up across quintiles of carbohydrate intake , glycemic index , and glycemic load . We also stratified by combined BMI and physical activity levels . Results We found reductions in colorectal cancer risk for diets high in carbohydrate ( RR for Q5 vs. Q1 = 0.70 , 95 % CI : 0.50–0.97 ) and glycemic index ( 0.75 , 95 % CI : 0.56–1.00 ) , and no significant association for glycemic load ( 0.91 , 95 % CI : 0.70–1.20 ) . Inverse associations were weakest in normal weight active persons . The inverse association for glycemic index was strongest for the portion from dairy food . Conclusions These results do not support an association between diets high in carbohydrate , glycemic index or glycemic load and colorectal cancer", "Objective : The amount and composition of dietary carbohydrates is a major determinant of postpr and ial blood glucose and insulin , and risk of breast cancer has been positively associated with plasma levels of insulin and insulin-like growth factor 1 . We sought to evaluate dietary glycemic load ( GL ) and overall glycemic index ( GI ) in relation to breast cancer risk in Mexican women . Methods : We examined dietary GL and overall GI and breast cancer risk among 475 women with histologically-confirmed breast cancer and a r and om sample of 1391 women from Mexico City households . Diet was assessed using a food frequency question naire adapted to the Mexican population . Results : The multivariate adjusted or for all women comparing the highest quartile of dietary GL with the lowest quartile was 1.62 ( 95 % CI 1.13–2.32 ; p-test for trend = 0.02 ) with a significant trend . In postmenopausal women , the multivariate adjusted or comparing the extreme quartiles was 2.18 ( 95 % CI 1.34–3.55 ; p-test for trend=0.005 ) . Overall GI was not significantly associated with risk of breast cancer . Conclusion : High intake of rapidly absorbed carbohydrate appears to play an important role in the risk of breast cancer in Mexican women", "High-carbohydrate diets have been linked to pancreatic cancer risk in case-control studies , but prospect i ve studies have shown mostly null results . The authors investigated the associations of glycemic load , glycemic index , and carbohydrate intake with pancreatic cancer risk in the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . Dietary intake was assessed by using a self-administered question naire . Between 1998 and 2006 ( median follow-up = 6.5 years ) , 266 incident , confirmed pancreatic cancers were identified among 109,175 participants . Hazards ratios and 95 % confidence intervals were adjusted for sex , smoking , body mass index , and total energy . Overall , elevated risks for pancreatic cancer were observed in the 90th versus 10th percentile of glycemic load ( hazards ratio ( HR ) = 1.45 , 95 % confidence interval ( CI ) : 1.05 , 2.00 ) , available carbohydrate ( HR = 1.47 , 95 % CI : 1.05 , 2.06 ) , and sucrose ( HR = 1.37 , 95 % CI : 0.99 , 1.89 ) intake . The positive association for available carbohydrate intake was observed during the first 4 years of follow-up ( HR(<2 years ) = 2.60 , 95 % CI : 1.34 , 5.06 ; HR(2-<4 years ) = 1.94 , 95 % CI : 1.06 , 3.55 ) but not subsequently ( HR = 0.86 , 95 % CI : 0.52 , 1.44 ) ; the opposite pattern was observed for total fat and saturated fat intake . Rather than being causal , the short-term increase in pancreatic cancer risk associated with high available carbohydrate and low fat intake may be capturing dietary changes associated with sub clinical disease", "OBJECTIVES : Diets that induce a high glycemic response might increase the risk of biliary tract cancer ( BTC ) . We evaluated the hypothesis that diets with high glycemic load ( GL ) and high glycemic index ( GI ) , which are measures of the glycemic effect of foods , are associated with an increased incidence of BTC . METHODS : We used data from a population -based prospect i ve study of 76,014 Swedish adults ( age 45−83 years ; 57 % men ) who were free of cancer and had completed a food-frequency question naire in the autumn of 1997 . Incident cancer cases were ascertained by linkage with the Swedish Cancer Registry . Data were analyzed using Cox proportional hazards regression models . RESULTS : During a mean follow-up of 13.3 years ( 1,010,777 person-years ) , we identified 140 extrahepatic BTC cases ( including 77 gallbladder cancers ) and 23 intrahepatic BTC cases . A high dietary GL was associated with an increased risk of BTC . The multivariable relative risks for the highest versus lowest quartile of dietary GL were 1.63 ( 95 % confidence interval ( 95 % CI ) , 1.01–2.63 ) for extrahepatic BTC , 2.14 ( 95 % CI , 1.06–4.33 ) for gallbladder cancer , and 3.46 ( 95 % CI , 1.22–9.84 ) for intrahepatic BTC . Dietary GI was statistically significantly positively associated with risk of extrahepatic BTC and gallbladder cancer . We observed no statistically significant association between carbohydrate intake and BTC risk , although all associations were positive . CONCLUSION : Although these data do not prove a causal relationship , they are consistent with the hypothesis that high-GL and high-GI diets are associated with an increased risk of BTC", "The glycemic effects of diets high in refined grains and starchy foods might increase stomach cancer risk by affecting circulating glucose , insulin and insulin-like growth factor-I levels . No prospect i ve data on the role of high glycemic load and glycemic index diets on stomach cancer risk have been reported . We therefore prospect ively investigated dietary glycemic load , overall glycemic index and carbohydrate intake in relation to the incidence of stomach cancer among 61,433 women in the population -based Swedish Mammography Cohort . Diet was assessed at baseline ( 1987 - 1990 ) and again in 1997 . During 903,586 person-years of follow-up , a total of 156 incident cases of stomach cancer were ascertained . We observed no material associations of dietary glycemic load , overall glycemic index and total carbohydrate intake with the risk of stomach cancer . The multivariate hazard ratios for the highest versus the lowest quintile were 0.76 ( 95 % CI = 0.46 - 1.25 ) for glycemic load , 0.77 ( 95 % CI = 0.46 - 1.30 ) for overall glycemic index and 0.85 ( 95 % CI = 0.50 - 1.43 ) for carbohydrate intake . The associations did not vary according to body mass index . Lack of information on Helicobacter pylori infection status did not allow stratification by this potential effect modifier . Findings from this population -based prospect i ve cohort of middle-aged and elderly women did not provide evidence of a positive association between glycemic load , glycemic index and carbohydrate intake with risk of stomach cancer", "OBJECTIVE To describe the average consumption of carbohydrate-providing food groups among study centres of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) . METHODS Of the 27 redefined EPIC study centres , 19 contributed subjects of both genders and eight centres female participants only ( men , women , after exclusion of subjects under 35 and over 74 years of age from the original 36 900 total ) . Dietary data were obtained using the 24-hour recall methodology using the EPIC-SOFT software . The major sources of dietary carbohydrate were identified , and 16 food groups were examined . RESULTS The 10 food groups contributing most carbohydrate were bread ; fruit ; milk and milk products ; sweet buns , cakes and pies ; potato ; sugar and jam ; pasta and rice ; vegetables and legumes ; crispbread ; and fruit and vegetable juices . Consumption of fruits as well as vegetables and legumes was higher in southern compared with northern centres , while soft drinks consumption was higher in the north . Italian centres had high pasta and rice consumption , but breakfast cereal , potato , and sweet buns , cakes and pies were higher in northern centres . In Sweden , lower bread consumption was balanced with a higher consumption of crispbread , and with sweet buns , cakes and pies . Overall , men consumed higher amounts of vegetables and legumes , bread , soft drinks , potatoes , pasta and rice , breakfast cereal and sugar and jam than women , but fruit consumption appeared more frequent in women . CONCLUSION The study supports the established idea that carbohydrate-rich foods chosen in northern Europe are different from those in the Mediterranean region . When comparing and interpreting diet-disease relationships across population s , research ers need to consider all types of foods", "BACKGROUND Mixed results have been reported in recent epidemiologic studies in Western population s that have investigated the hypothesis that high glycemic load may increase the risk of colorectal cancer . This association has not been prospect ively evaluated in other population s. OBJECTIVE We examined the association of overall glycemic index and glycemic load with colorectal cancer risk in a prospect i ve cohort of Chinese women . DESIGN A total of 73,061 women aged 40 - 70 y and free of cancer at enrollment were included in this analysis . Usual dietary intake was assessed at baseline ( 1997 - 2000 ) and reassessed during the first follow-up ( 2000 - 2002 ) through in-person interviews by using a vali date d food-frequency question naire . RESULTS During an average follow-up of 9.1 y , 475 incident colorectal cancer cases were identified . Glycemic load was not associated with colorectal cancer risk ( P for trend = 0.84 ) . The multivariable hazard ratio for the highest compared with the lowest quintile of glycemic load was 0.94 ( 95 % CI : 0.71 , 1.24 ) . Similar results were also observed for associations with dietary glycemic index and total carbohydrate intake , and results did not vary by excluding individuals with a history of diabetes from the analysis . CONCLUSION This prospect i ve study , conducted in a population with a high intake of carbohydrates , provides no evidence that a high-glycemic index diet or high glycemic load is associated with an increased risk of colorectal cancer", "Several epidemiological studies have investigated the potential association between dietary fiber , glycemic index ( GI ) or glycemic load ( GL ) , and renal cell carcinoma ( RCC ) risk with inconsistent results . The aim of this study was to systematic ally evaluate this issue with a meta- analysis approach . A comprehensive literature search up to March 2018 was performed in PubMed and Web of Science data bases . Summary relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were estimated with a r and om-effects model . Twelve studies were finally included in this study ( eight for fiber analysis , five for GI and five for GL ) . A significant positive association was observed between GI and the risk of RCC ( summary RR 1.16 , 95 % CI 1.02 - 1.32 ) , and no significant heterogeneity was detected among studies ( I2 = 22.8 % , P = 0.262 ) . A significant inverse association was found between fiber intake and the risk of RCC ( summary RR 0.82 , 95 % CI 0.72 - 0.92 ) , and no significant heterogeneity was observed across studies ( I2 = 27.6 % , P = 0.218 ) . GL was not significantly associated with RCC risk ( summary RR 1.14 , 95 % CI 0.81 - 1.60 ) , and significant heterogeneity was found across studies ( I2 = 78.6 % , P < 0.001 ) . In conclusion , this systematic review and meta- analysis suggests that dietary GI and fiber may be associated with the risk of RCC . Further large prospect i ve cohort studies are still warranted to confirm our preliminary findings", "BACKGROUND The type and quantity of dietary carbohydrate as quantified by glycemic index ( GI ) and glycemic load ( GL ) , and dietary fiber may influence the risk of liver and biliary tract cancers , but convincing evidence is lacking . PATIENTS AND METHODS The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma ( HCC ; N = 191 ) , intrahepatic bile duct ( IBD ; N = 66 ) , and biliary tract ( N = 236 ) cancer risk was investigated in 477 206 participants of the European Prospect i ve Investigation into Cancer and Nutrition cohort . Dietary intake was assessed by country-specific , vali date d dietary question naires . Hazard ratios and 95 % confidence intervals were estimated from proportional hazard models . HBV/HCV status was measured in a nested case-control subset . RESULTS Higher dietary GI , GL , or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk . For HCC , divergent risk estimates were observed for total sugar = 1.43 ( 1.17 - 1.74 ) per 50 g/day , total starch = 0.70 ( 0.55 - 0.90 ) per 50 g/day , and total dietary fiber = 0.70 ( 0.52 - 0.93 ) per 10 g/day . The findings for dietary fiber were confirmed among HBV/HCV-free participants [ 0.48 ( 0.23 - 1.01 ) ] . Similar associations were observed for IBD [ dietary fiber = 0.59 ( 0.37 - 0.99 ) per 10 g/day ] , but not biliary tract cancer . CONCLUSIONS Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk . In addition , high dietary fiber intake could be associated with lower IBD cancer risk" ]

[ "19553641", "12460789" ]

[ "Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.", "Moderate progress for ovarian cancer in the last 20 years: prolongation of survival, but no improvement in the cure rate." ]

[ "BACKGROUND The inhibition of poly(adenosine diphosphate [ADP]-ribose ) polymerase ( PARP ) is a potential synthetic lethal therapeutic strategy for the treatment of cancers with specific DNA-repair defects , including those arising in carriers of a BRCA1 or BRCA2 mutation . We conducted a clinical evaluation in humans of olaparib ( AZD2281 ) , a novel , potent , orally active PARP inhibitor . METHODS This was a phase 1 trial that included the analysis of pharmacokinetic and pharmacodynamic characteristics of olaparib . Selection was aim ed at having a study population enriched in carriers of a BRCA1 or BRCA2 mutation . RESULTS We enrolled and treated 60 patients ; 22 were carriers of a BRCA1 or BRCA2 mutation and 1 had a strong family history of BRCA-associated cancer but declined to undergo mutational testing . The olaparib dose and schedule were increased from 10 mg daily for 2 of every 3 weeks to 600 mg twice daily continuously . Reversible dose-limiting toxicity was seen in one of eight patients receiving 400 mg twice daily ( grade 3 mood alteration and fatigue ) and two of five patients receiving 600 mg twice daily ( grade 4 thrombocytopenia and grade 3 somnolence ) . This led us to enroll another cohort , consisting only of carriers of a BRCA1 or BRCA2 mutation , to receive olaparib at a dose of 200 mg twice daily . Other adverse effects included mild gastrointestinal symptoms . There was no obvious increase in adverse effects seen in the mutation carriers . Pharmacokinetic data indicated rapid absorption and elimination ; pharmacodynamic studies confirmed PARP inhibition in surrogate sample s ( of peripheral-blood mononuclear cells and plucked eyebrow-hair follicles ) and tumor tissue . Objective antitumor activity was reported only in mutation carriers , all of whom had ovarian , breast , or prostate cancer and had received multiple treatment regimens . CONCLUSIONS Olaparib has few of the adverse effects of conventional chemotherapy , inhibits PARP , and has antitumor activity in cancer associated with the BRCA1 or BRCA2 mutation . ( Clinical Trials.gov number , NCT00516373 .", "Although ovarian cancer treatment has advanced in the last 20 years , long-term survival remains stable . The purpose of this study was to determine whether survival has improved in line with treatment advances in a population -based prospect i ve cohort of ovarian cancer patients ( 1978 - 1997 , with a follow-up through to 2000 ) . The 10-year overall survival rate for cancer patients was similar before and after 1988 : 32.2 % ( n=1661 ) and 34.4 % ( n=2089 ) . For patients after 1988 , a 12-month prolongation of median survival was observed . In terms of stage according to the International Federation of Gynecology and Obstetrics ( FIGO ) , only FIGO I and FIGO II patients showed , in addition to a prolongation in survival , an absolute improvement of 12.9 and 12.6 % after 5 years and of 13.2 and 8.6 % after 10 years . This hardly affected the survival of the total sample . For the most frequent stage FIGO III patients and for FIGO IV patients , a prolongation in survival time , but no improvement in survival rate , was seen after five or 10 years . The progress in FIGO I and II patients may be due to more accurate staging . More effective chemotherapy may also explain some of the improvement . The prolongation in FIGO-stages III-IV may be due to more radical surgery . Patient selection criteria , not only the treatment modalities , may be responsible for the superior results reported in clinical trials . Cancer registries are important for evaluating the quality of healthcare delivery" ]

[ "18983318", "3196245", "18807574", "17956569", "12814319", "19719736", "11759868", "16731387", "19405825", "17618925", "15732861", "19302238", "21197501", "19865633", "20681808", "16713809", "21365053", "20862420" ]

[ "Two-year prospective clinical comparison of immediate replacement vs. immediate restoration of single tooth in the esthetic zone.", "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", "Immediate versus delayed loading of dental implants placed in fresh extraction sockets in the maxillary esthetic zone: a clinical comparative study.", "Esthetic outcomes of immediate implant placements.", "Clinical and radiologic evaluation of 2-stage IMZ implants placed in a single-stage procedure: 2-year results of a prospective comparative study.", "Clinical outcome of submerged vs. non-submerged implants placed in fresh extraction sockets.", "Immediate implantation in fresh extraction sockets. A controlled clinical and histological study in man.", "Immediate placement of implants in periapical infected sites: a prospective randomized study in 50 patients.", "A prospective multicenter 5-year radiographic evaluation of crestal bone levels over time in 596 dental implants placed in 192 patients.", "Periimplant tissue response following immediate provisional restoration of scalloped implants in the esthetic zone: a one-year pilot prospective multicenter study.", "Bucco-lingual crestal bone changes after immediate and delayed implant placement.", "Instant provisionalization of immediate single-tooth implants is essential to optimize esthetic treatment outcome.", "Comparison of radiographic and clinical outcomes following immediate provisionalization of single-tooth dental implants placed in healed alveolar ridges and extraction sockets.", "Radiographic evaluation of marginal bone levels around platform-switched and non-platform-switched implants used in an immediate loading protocol.", "Bone regeneration around implants in periodontally compromised patients: a randomized clinical trial of the effect of immediate implant with immediate loading.", "Immediate loading versus immediate provisionalization of maxillary single-tooth replacements: a prospective randomized study with BioComp implants.", "Influence of implant-abutment interface design on bone and soft tissue levels around immediately placed and restored single-tooth implants: a randomized controlled clinical trial.", "A comparison of clinical outcomes for implants placed in fresh extraction sockets versus healed sites in periodontally compromised patients: a 1-year follow-up report." ]

[ "AIM To compare the immediate restoration of single implants in the esthetic zones performed on implants placed immediately after tooth extraction or 8 weeks later ( immediate replacement vs. immediate restoration ) . METHODS Sixteen patients ( 10 women and 6 men ) with a mean age of 35 years ( ranging from 21 to 49 years old ) were treated from 2004 to 2005 for single-tooth replacement in the upper arch . The patients were r and omly divided into two groups : in the test group patients received implants placed and restored ( non-occlusal loading ) at the time of tooth extraction ; in the control group implants were placed 8 weeks after tooth extraction and immediately restored . All the patients received tapered effect ( TE ) implants from the Straumann Dental Implant System . The following parameters were evaluated at the moment of provisional restoration ( within 48 h after implant placement ) and at the 2 years follow-up visit : marginal bone resorption , papilla index , position of the mucosal margin . The implant stability quotient was measured at the moment of implant placement and at the moment of the delivery of the definitive restoration . RESULTS No statistically significant differences were found in any of the studied parameters between the test and the control groups ( P>0.05 ) . The implant stability quotient values between the test and control groups were significant ( P<0.05 ) at the moment of implant placement but were no more significant at the loading of the definitive restoration ( P>0.05 ) . CONCLUSION The results of the present study suggest that immediate replacement without functional loading may be considered a valuable therapeutic option for selected cases of single-tooth replacement in the esthetic area when TE implants are used . Implant stability at the moment of implant placement is slightly inferior in the immediate replacement group , but it does not affect the treatment result", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "PURPOSE The aim of this study was to report a clinical comparative assessment of crestal bone level change around single implants in fresh extraction sockets in the esthetic zone of the maxilla either immediately loaded or loaded after a delay . MATERIAL S AND METHODS Forty patients were included in a prospect i ve , r and omized study . All patients required 1 tooth extraction ( ie , 1 tooth with a hopeless prognosis ) and were r and omized into either the test group or the control group . Implants were positioned immediately after tooth extraction and were loaded immediately in the test group ( 20 implants ) and after 3 months in the control group ( 20 implants ) . The implant site was prepared , with at least 4 mm of sound apical bone below the implant apex , and the coronal margin of the implant was placed at the buccal level of the bone crest . All implants were 13 mm long ; 30 implants had a diameter of 5 mm , and 10 had a diameter of 3.75 mm . Radiographic examinations were made at baseline , at 6 months , and at 24 months . To compare the mean values between test and control group , a paired t test was performed ( considered statistically significant at P < .05 ) . RESULTS After a 24-month follow-up period , a cumulative survival rate of 100 % was reported for all implants . The control group result ed in a mean mesial bone loss of 1.16 + /- 0.32 mm and a mean distal bone loss of 1.17 + /- 0.41 ( mean bone loss , 1.16 + /- 0.51 mm ) . The test group result ed in a mesial bone loss of 0.93 + /- 0.51 mm and a distal bone loss of 1.1 + /- 0.27 mm ( mean bone loss , 1.02 + /- 0.53 mm ) . No statistically significant difference between control and test groups ( P > .05 ) was found . CONCLUSION The success rate and radiographic results of immediate restorations of dental implants placed in fresh extraction sockets were comparable to those obtained in delayed loading group", "BACKGROUND Single-rooted teeth deemed not restorable via conventional means may be c and i date s for implant placement at the time of tooth extraction . Immediate implant placements are believed to preserve soft and hard tissue form and contours , reduce the need for augmentation procedures , minimize surgical exposure of the patient , reduce treatment time and improve esthetic outcomes . METHOD This retrospective review analyzed the esthetic outcomes of 42 non-adjacent single-unit implant restorations completed using an immediate implant surgical placement protocol . RESULTS The mean time in function was 18.9 months ( range 6 - 50 months ) and the majority of implants placed had a restorative platform diameter of 4.1 and 4.8 mm . A highly significant change in crown height due to marginal tissue recession of 0.9 + /- 0.78 mm ( P=0.000 ) was recorded for all sites , with no difference seen between implant systems ( P=0.837 ) . Thin tissue biotype showed slightly greater recession than thick tissue biotype ( 1 + /- 0.9 vs. 0.7 + /- 0.57 mm , respectively ) ; however , this difference was not statistically significant ( P=0.187 ) . Implants with a buccal shoulder position showed three times more recession than implants with a lingual shoulder position ( 1.8 + /- 0.83 vs. 0.6 + /- 0.55 mm , respectively ) with the difference being highly statistically significant ( P=0.000 ) . CONCLUSIONS Immediate implant placement requires very careful case selection and high surgical skill levels if esthetic outcomes are to be achieved . Long-term prospect i ve studies on tissue stability and esthetic outcomes are needed", "PURPOSE The aim of this study was to evaluate the feasibility of using a 2-stage implant system in a single-stage procedure and to study the impact of the microgap between the implant and the abutment . MATERIAL S AND METHODS Sixty edentulous patients ( Cawood class V or VI ) participated in this study . After r and omization , 20 patients received 2 IMZ implants placed in a single-stage procedure , 20 patients received 2 IMZ implants placed in the traditional 2-stage procedure , and 20 patients were treated with 2 ITI implants ( single-stage procedure ) . The implants were placed in the canine area of the m and ible . After 3 months , m and ibular overdentures were fabricated , supported by a bar- and -clip attachment . A st and ardized clinical and radiographic evaluation was performed immediately after prosthesis placement and after 12 and 24 months . RESULTS One IMZ implant of the 1-stage group and 1 IMZ implant of the 2-stage group were lost after 6 and 12 months , respectively . Apart from several significant but clinical ly irrelevant differences , the 3 groups did not appear to differ markedly with regard to clinical parameters during the evaluation period . The mean bone loss within the first 2 years of functioning ( 1.1 mm IMZ 1-stage , 0.8 mm IMZ 2-stage , 1.2 mm ITI ) was comparable for the 3 groups . DISCUSSION AND CONCLUSIONS The results of this study suggest that dental implants design ed for a submerged implantation procedure can also be used in a single-stage procedure and may be as predictable as when the same implants used in a 2-stage procedure or as 1-stage implants . Placement of the microgap at the crestal level in 2-stage implants did not appear to have an adverse effect on the amount of peri-implant bone loss at 2 years in this study population", "AIM The aim of this study was to compare the clinical outcome of submerged vs. non-submerged tapered implants placed into fresh extraction sockets . MATERIAL S AND METHODS A prospect i ve , controlled , multicenter , r and omized , clinical trial has been performed in two centers in Rome and Torino ( Italy ) . Thirty healthy patients were recruited according to the following inclusion criteria : need for an immediate post extraction implant , ages between 18 and 70 , horizontal defect depth < 2 mm , smokers < 10 cigarettes/day and absence of any circumstance or condition that could represent contraindications to implant surgery . The patients were r and omly allocated to submerged or non-submerged treatment groups immediately after flap elevation and tooth extraction . Submerged implants were exposed 8 weeks after the first surgery ; all implants were loaded with provisional restorations 12 weeks after the first surgery and with definitive restoration 12 weeks thereafter . Clinical and radiographic parameters were evaluated at baseline , at implant loading and at the 1-year follow-up visit . RESULTS The results showed statistically significant differences between the two groups in the mean value of keratinized tissue ( KT ) height after surgery that was significantly reduced for submerged implants when compared with transmucosal implants ( mean reduction of KT at year follow-up : T group 0.2 mm , S group 1.3 mm ; P=0.007 ) . CONCLUSION Similar outcomes were found for submerged and non-submerged implants placed in fresh extraction sockets with a horizontal peri-implant defect smaller than 2 mm , except for a reduction of KT in the submerged group . Either with a submerged or a non-submerged procedure , 1 mm of mean soft tissue recession is seen after 1 year when compared with the pre- extraction situation", "BACKGROUND Early implantation may preserve the alveolar anatomy , and the placement of a fixture in a fresh extraction socket helps to maintain the bony crest . Although a number of clinical studies exist , no histological reports show the outcome of implantation in fresh extraction sockets without the use of membranes in humans compared to implants placed in mature bone . METHODS Forty-eight healthy patients , receiving at least 4 fixtures in each of 2 symmetrical quadrants , underwent placement of 1 experimental fixture placed in a fresh extraction socket ( TI ) and 1 contralateral fixture in mature bone ( CI ) . TI were placed after atraumatical tooth extraction , with a surgical site at the apex of the socket and a tight contact between the fixture and the socket 's walls , but without the use of filling material s or membranes . The flap was coronally repositioned to obtain primary wound closure . Immediately after surgical intervention , a st and ardized periapical radiograph was taken . Second-stage surgery was done after 6 months . Six months after the second surgery , a second st and ardized periapical radiograph was taken and clinical parameters ( bleeding and plaque index ) recorded . Marginal bone loss ( MBL ) from the time of implant placement to the time of fixture removal was calculated by comparing periapical radiographs . TI and CI were then removed by a hollow drill to obtain histological specimens . Non-demineralized sections were stained by acid fuchsin and toluidine blue , and by von Kossa to evaluate the degree of bone mineralization . The percentage of direct implant-bone contact ( DBC ) was calculated by a computerized microscopic digitizer . RESULTS No significant differences in the clinical and radiographic parameters were observed between the 2 experimental categories . There was no statistically significant difference between TI and CI for DBC either in the maxilla or in the m and ible . No connective or fibrous tissues were present around TI or CI . Bone resorption was not present in any of the histological sections . CONCLUSIONS The present study shows that when a screw-type dental implant is placed without the use of barrier membranes or other regenerative material s into a fresh extraction socket with a bone-to-implant gap of 2 mm or less , the clinical outcome and degree of osteointegration does not differ from implants placed in healed , mature bone", "OBJECTIVE To determine clinical success when implants are placed in chronic periapical infected sites . STUDY DESIGN Fifty patients ( 25 females , 25 males , mean age 39.7 + /- 14.5 years ) were included in this prospect i ve controlled study . After r and omization , 25 Frialit-2 Synchro implants were immediately placed ( IP ) after extraction , and 25 Frialit-2 Synchro implants were placed after a 3-month healing period ( DP ) . Thirty-two implants were placed in the anterior maxilla and 18 implants were placed in the premolar region . Implant survival , mean Implant Stability Quotient ( ISQ ) values , gingival aesthetics , radiographic bone loss , and microbiologic characteristics of periapical lesions were evaluated for both groups . RESULTS Overall , 2 implants belonging to the IP group were lost , result ing in a survival rate of 92 % for IP implants versus 100 % for DP implants . Mean ISQ , gingival aesthetics and radiographic bone resorption , and periapical cultures were not significantly different with the IP and DP implants . CONCLUSIONS Immediate implant placement in chronic periapical lesions may be indicated", "BACKGROUND Dental implants have been used to replace missing teeth to provide function and esthetics . One goal of such restorations is to maintain host tissue around the implants . The purpose of this prospect i ve multicenter human clinical trial was to evaluate radiographic marginal bone levels around non-submerged hollow cylindrical and solid-screw implants for 5 years after loading . METHODS Patients older than 18 years of age with sufficient native bone to surround a dental implant without imposing on a vital structure were recruited at five sites . Solid-screw or hollow-cylinder implants with a titanium plasma-sprayed implant surface were placed in the anterior maxilla or anterior m and ible and restored with fixed restorations . Baseline radiographs were taken at the time of implant placement . Subsequent radiographs were taken at the time of final prosthesis placement , at 6 months after prosthesis placement , and annually from prosthesis placement for 5 years . RESULTS The results of 596 implants in 192 patients at five international sites revealed that clinical ly significant remodeling of the marginal bone occurred during the first 6 months after implant placement , with a mean ( + /- SD ) marginal bone loss of 2.44 + /- 1.20 mm . After that , clinical ly insignificant mean changes in the bone were observed . Overall , 0.22 + /- 0.42 mm of bone loss occurred between the time of prosthesis placement and 1-year postloading . Between 1-year postloading and the last 5-year recall , 0.18 + /- 0.88 mm bone loss occurred . Because 2.84 + /- 1.63 mm of bone loss occurred between implant placement and the 5-year postloading follow-up , 86 % of the total mean bone loss over the course of 5 years was accounted for at the time of prosthesis placement . These same trends occurred if the data were analyzed with regard to implant design ( solid screw and hollow cylinder ) , type of restoration ( single and multiple ) , and length of implant ( 8 to 10 , 12 , and 14 to 16 mm ) . CONCLUSIONS These data demonstrate that , in general , clinical ly significant marginal bone remodeling occurred between the time of implant placement and final prosthesis placement around one-stage non-submerged titanium implants with a titanium plasma-sprayed surface . Subsequent to that , bone loss observed around implants up to 5 years postloading was minimal . These results suggest that the factors that influence early healing around implants are significantly different from those that affect later marginal bone remodeling", "STATEMENT OF PROBLEM Flat platform implants may present a limitation when irregular or scalloped bone topography is encountered , result ing in compromised periimplant bone and soft tissue contours . PURPOSE This 1-year pilot prospect i ve multicenter study assessed the success rates and periimplant tissue response of scalloped implants undergoing immediate provisional restoration in the maxillary esthetic zone . MATERIAL AND METHODS Twenty-nine patients , 15 men and 14 women , mean age of 45.1 ( range : 18 - 70 ) years , were included in this study . Thirty-eight scalloped implants with a 1.5-mm machined surface collar and a titanium oxide surface ( TiUnite ) were placed both in healed sites ( 15 ) and extracted sites ( 23 ) , and provisional restorations were placed immediately . The definitive restorations were placed an average of 12.6 months later . The patients were evaluated clinical ly with respect to gingival papilla appearance , presence or absence of plaque and gingivitis , and radiographically for bone level measurements at 0 , 3 , 6 , and 12 months after implant placement . Descriptive statistics were used to analyze the data . RESULTS At 12 months , all implants remained in function . The mean ( SD ) marginal bone change from the time of implant placement to 12 months was 0.1 ( 3.3 ) mm . For implants placed in extracted sites the mean ( SD ) marginal bone change was 1.0 ( 3.6 ) mm , compared to those in healed sites , which was -1.6 ( 1.9 ) mm . The marginal bone level in 9 of the initial 22 sites ( 41 % ) was retained in the scalloped area of the implants at 12 months . In the follow-up , after 3 months of function , no significant changes with respect to mean papilla index score were observed . The patients maintained acceptable hygiene throughout the follow-up period . CONCLUSIONS Although favorable implant success rates and periimplant tissue response can be achieved with immediate provisional restoration of scalloped implants in the esthetic zone , bone was not regularly maintained at the original levels around the scalloped area of the implants", "BACKGROUND Implants placed immediately after tooth extraction offer several advantages , but many authors have reported problems in filling the residual gap between the implant and the socket walls . Barrier and grafting techniques have been tested and yield varying results , so it has been suggested that the timing of implant placement may be important for success . The aim of this study was to analyze bone healing and coronal bone remodeling around 35 implants , 20 placed immediately after tooth removal and 15 placed 6 to 8 weeks after extraction . METHODS All the implants were submerged and placed within the alveoli confines , leaving circumferential defects because the implants did not contact the bone at their coronal aspects ; stabilization was achieved in the bone apically . After implant placement the mean distance from buccal bone to lingual bone was 10 mm ( SD 1.522 ) for immediate implants and 8.86 mm ( SD 2.356 ) for delayed implants . No membrane or filling material s were used . Primary flap closure was accomplished in all cases . RESULTS At second-stage surgery all peri-implant defects were filled , and the mean distance from buccal bone to lingual bone was 8.1 mm ( SD 1.334 ) for immediate implants and 5.8 mm ( SD 1.265 ) for delayed implants . This pattern of coronal bone remodeling , showing a narrowing of the bucco-lingual width , was clinical ly similar for the two groups , although it should be noted that the delayed implants exhibited smaller bucco-lingual bone width already at the first measurement : it can be speculated that early remodeling may start immediately after tooth extraction and continue , non-uniformly , even after delayed implant placement . CONCLUSIONS This study suggests that circumferential defects could heal clinical ly without any guided bone regeneration ( GBR ) in both experimental groups , and that the procedure was virtually free from complications in the postoperative period , probably because of the absence of barrier membranes and /or grafting material s. Histologically , peri-implant defects of over 1.5 mm heal by connective tissue apposition , rather than by direct bone-to-implant contact , but clinical ly this healing may be very successful . No histological analysis was carried out in the present study , but even the largest residual gaps were filled with hard tissue that could not be probed . Thus , such outcomes can be considered clinical ly successful . The different rate of bone remodeling around immediate or delayed implants could have implication s for the preferred timing of implant placement in sites of high esthetic concern", "OBJECTIVE The immediate single-tooth implant has become a viable treatment option . However , the impact of the restorative procedure on esthetics is currently unclear . The goal of this study was to compare the soft tissue outline at immediate implants following two restorative protocol s : immediate connection of a temporary crown or submerged healing during which a removable partial denture is used . MATERIAL AND METHODS A 1-year single-blind r and omized clinical study was performed in 49 patients . Twenty-four patients were assigned to the immediate restoration group and 25 to the delayed restoration group . Clinical and radiographic evaluations of soft and hard tissues were carried out after 3 , 6 and 12 months . RESULTS Implant survival , bone remodeling , probing depth and bleeding tendency were not influenced by the restorative protocol . Delayed restoration result ed in initial papilla loss taking up to 1 year to attain comparable height as for immediate restoration . Midfacial recession was systematic ally 2.5 - 3 times higher following delayed restoration pointing to a 0.75 mm additional loss in comparison with immediate restoration after 1 year . CONCLUSIONS If the primary implant stability permits it , immediate single-tooth implants should be instantly provisionalized in the interest of optimal midfacial esthetics", "PURPOSE The primary goal of this study was to compare implant survival 12 months after immediate loading of single implants placed in healed ridges versus extraction sockets . Secondary outcomes were to compare marginal bone adaptation and soft tissue changes over time . MATERIAL S AND METHODS A prospect i ve multicenter clinical investigation was initiated to assess clinical performance of immediately loaded implants in the maxilla . Implant survival was ascertained at the time of impression making ( 8 to 10 weeks ) and after 1 year by clinical stability . Radiographic marginal bone levels , soft tissue levels , and plaque and bleeding scores were compared with baseline values ( implant placement and provisionalization ) . RESULTS One hundred thirty-nine patients received 157 implants in the maxilla . Single implants with provisional crowns were placed in extraction sockets of 55 patients ( 58 implants ) and in healed ridges of 60 patients ( 65 implants ) . In addition , 19 patients ( 23 implants ) required bone grafting prior to implant placement , and 11 implants in 10 patients among all groups were not immediately loaded because of insufficient initial stability after surgery . Three implants ( 5.2 % ) failed in extraction sites and one implant ( 1.5 % ) failed in a healed ridge . The mean change in marginal bone level 1 year after implant placement was 1.30 mm ( SD 2.52 ) ( gain ) in extraction sockets and -0.40 mm ( SD 1.43 ) ( loss ) in healed ridges . The mucosal zenith was stable or moved incisally following definitive crown placement in 83.7 % of immediate implants and 87.0 % of implants placed in healed ridges . Plaque and inflammation scores were low and did not differ between groups . CONCLUSIONS The responses of local bone and soft tissues at immediately loaded implants placed in extraction sockets or healed ridges were similar . Furthermore , these 1-year results suggest that clinical management of esthetically critical soft tissue may be predictably achieved in both indications", "PURPOSE The aim of this clinical study was to assess the marginal bone around two different types of implant-abutment junctions-a so-called platform-switched assembly and a conventional external-hexagon connection-after 24 months . MATERIAL S AND METHODS Forty-five patients were included in this prospect i ve study . All selected patients required the extraction of one or two hopeless teeth in maxillary and m and ibular region monoradicular and second premolar teeth , and were r and omly assigned to one of two groups . The first group received 34 implants with an external-hexagon junction with the abutment and the second group received 30 implants with platform-switched abutments . Implants were positioned immediately after tooth extraction and were loaded immediately . RESULTS After 24 months , a cumulative survival rate of 100 % was reported for all implants . The platform-switching group showed a mean bone loss of 0.78 + /- 0.49 mm and the external-hexagon group showed a mean bone loss of 0.73 + /- 0.52 mm ( no statistically significant difference between groups ) . CONCLUSION The results of this study indicate that implants placed immediately in fresh extraction sockets and loaded immediately represent a predictable procedure , with no differences in bone level changes between \" platform-switched \" and conventional external-hexagon implants after 24 months", "BACKGROUND This 2-year r and omized clinical trial compared bone regeneration and esthetic outcome between immediate and conventional loading of dental implants placed immediately after extraction in patients with a history of periodontal disease . METHODS Patients were r and omly assigned to receive immediate implants with either immediate loading or conventional loading after 3 months . Both groups received a periodontal flap , tooth extraction , implant placement , allograft bone , and membrane placement . The immediate loading group received a temporary crown . In the conventional loading group primary closure was achieved . All patients were followed up at 3 , 6 , 12 , and 24 months . Evaluation included radiographic bone changes , papillary esthetic outcome , and implant survival rate . RESULTS Seventy-two patients were recruited into the study . However , 60 patients received immediate implant placement after extraction : 30 with conventional loading and 30 with immediate loading . In the immediate loading group the implant survival rate at 2 years was 96.7 % , and the mean bone gain was 1.19 mm . The corresponding figures in the conventional loading group were 93.3 % and 1 mm . The gain in bone level occurred mainly from baseline to 1 year postoperatively in both groups ( P < 0.001 ) . The papilla index decreased from baseline to 1 year in both groups ( P < 0.001 ) and changed only slightly thereafter . There were no significant differences between the two groups in the amount of bone gain or papilla index change during 2 years . CONCLUSIONS Immediate loading of a single implant placed in a fresh extraction site in periodontally compromised patients result ed in similar bone gain and soft tissue esthetic outcomes compared to delayed loading . Primary closure and delayed loading to ensure bone regeneration around implants were not critical in this study", "PURPOSE The aim of this prospect i ve r and omized study was to evaluate the clinical outcome of immediately loaded solid plasma sprayed ( TPS ) BioComp ( BioComp Industries BV , Vught , The Netherl and s ) implants versus immediate provisionalized but non-loaded BioComp implants in the anterior and premolar region of the maxilla . MATERIAL S AND METHODS Forty-eight patients ( 31 females and 17 males ) with a mean age of 42.3+/-13.1 years ( range 19 to 78 years ) were included in the study . Fifty threaded TPS implants were placed and provisionalized within 24 hours after surgery . The patients were r and omly assigned to 2 groups . In the immediate loaded ( IL ) group ( n=24 ) the occlusion of the provisional was design ed with normal contacts in centric relation and at lateral excursions , while in the non-immediate loaded ( IP ) group ( n=24 ) the provisional restoration was adjusted to clear all occlusal contacts or contacts at lateral excursions . Patients were instructed to eat a soft diet and to avoid placing food in the area of the provisional crown during the first 6 weeks . Regular clinical and radiographic controls were performed and the survival rate and implant stability quotient ( ISQ ) values were evaluated at delivery of the definitive restoration at 6 months . At 1 year , radiographic coronal bone defects and gingival esthetics between the 2 groups were assessed . RESULTS Of the IL group , 2 fixtures were lost , while 3 implants were lost in the IP group . The failing implants showed increasing mobility at 2 to 3 weeks after insertion , and were removed . The remaining 45 implants were stable at every subsequent follow-up examination , and 6 months after implant placement , ISQ values were measured . The mean ISQ value in the IL group was 63.7+/-5.8 versus 63.2+/-4.3 for the IP group ( P=.78 ) . The mean mesial marginal bone loss after 12 months in the IL group was 0.27+/-0.2 mm versus 0.28+/-0.22 mm in the IP group ( P=.9 ) . The mean distal marginal bone loss after 12 months in the IL group was 0.19+/-0.15 mm versus 0.2+/-0.11 mm in the IP group ( P=.87 ) . All implants of the IL group had an ideal gingival buccal margin , versus 91 % of the IP group . Full regeneration of the mesial interdental papilla was observed in 70 % of the IL group versus 91 % of the IP group , while full regeneration of the distal papilla was observed in 91 % of both the IL and IP implants . CONCLUSION No significant differences in ISQ mean values in radiographic bone loss and gingival esthetics were found between immediate non-loaded provisionalization and immediately loaded BioComp implants in the maxilla", "PURPOSE The purpose of the present study was to compare the clinical and radiographic outcomes of single implants immediately placed and restored with two different implant-abutment connections . MATERIAL S AND METHODS Forty subjects requiring single maxillary premolar replacement were consecutively included in this study and prospect ively followed for 12 months . One implant was placed at the time of tooth extraction and immediately restored in each patient . Subjects were r and omly selected to receive either prosthetic abutments with a Morse taper connection and a platform switch ( test group ) or conventional abutments with an internal connection and a matching diameter ( control group ) . A provisional screw-retained crown was positioned and adjusted for nonfunctional loading within 24 hours . Four months later , the definitive crowns were delivered . Periodontal parameters and clinical and radiographic measurements of soft and hard tissue levels were recorded at the moment of prosthesis placement and at 4 and 12 months afterward . Means of the two groups were compared using paired and independent- sample t tests ( P = .05 ) . RESULTS Of the 40 patients recruited , 38 ( 24 women and 14 men ) completed the study . No implants were lost in the control group , whereas one implant failed in the test group . At the 12-month examination , no statistically significant differences were seen between the two groups for periodontal parameters , marginal soft tissue level change , or papilla height ( P > .05 ) , but greater marginal bone loss was observed at the control sites ( 0.51 ± 0.24 mm ) compared to the test sites ( 0.2 ± 0.17 mm ) ( P = .0004 ) . CONCLUSION Although the control group demonstrated a slight increase in marginal bone loss compared to the test group , the peri-implant soft tissues were very stable with both types of implant-abutment connection after 12 months of loading", "PURPOSE The aim of this 1-year prospect i ve study was to evaluate , in patients with severe periodontitis , the clinical performance of implants placed immediately after extraction of remaining teeth or in healed sockets and immediately loaded for prosthetic oral rehabilitation , and to compare the clinical outcomes for implants placed in fresh extraction sockets versus healed sites . MATERIAL S AND METHODS All patients in this study had received periodontal treatment ; however , the teeth were eventually deemed hopeless . The remaining teeth were extracted , the periodontally compromised sites were debrided , implants were inserted guided by a surgical template , and a provisional restoration was delivered immediately . The opposing arch was restored with a complete denture . Definitive prostheses were inserted after 6 months . Initial implant and prosthesis stability and the inflammatory response were evaluated . Clinical and radiographic analyses were performed . RESULTS A total of 84 rough-surfaced implants were placed ( 50 in the maxilla and 34 in the m and ible ) . Of these , 32 were placed in fresh extraction sockets . Four implants in three patients failed within the first 6 months , result ing in an implant survival rate of 95.2 % . All of the failed implants had been placed in fresh maxillary extraction sockets . The survival rates were 92 % ( 46/50 ) in the maxilla and 100 % ( 34/34 ) in the m and ible . Prosthetic success was 100 % . The mean bone level change ( ± SE ) between baseline and 12 months was -1.12 ± 0.18 mm . There were no statistically significant differences in insertion torque and alveolar bone loss between post extraction sites and healed sites . CONCLUSIONS The implant failure rate was higher in maxillary post extraction sites . This indicates a heightened risk of failure for immediate implants placed in periodontally compromised maxillae . Nevertheless , a satisfactory prosthetic success was achieved after 1 year" ]

[ "23952466", "26676457", "8931972", "3196245", "9671862", "9255293", "12559281", "21420124", "11489700", "15592062", "14499682", "28499730", "9563145", "24332123" ]

[ "Evaluation of patient outcome after discontinuation of alfuzosin treatment for benign prostatic hyperplasia: a multicentre, prospective study.", "Effect of Discontinuation of Tamsulosin in Korean Men with Benign Prostatic Hyperplasia Taking Tamsulosin and Dutasteride: An Open-Label, Prospective, Randomized Pilot Study.", "The international terazosin trial: a multicentre study of the long-term efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia. The ITT Group.", "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", "Intermittent alpha-blocker therapy in the treatment of men with lower urinary tract symptoms.", "Doxazosin in men with lower urinary tract symptoms: urodynamic evaluation at 15 months.", "Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.", "Update on AUA guideline on the management of benign prostatic hyperplasia.", "Discontinuation of alpha-blockade after initial treatment with finasteride and doxazosin in men with lower urinary tract symptoms and clinical evidence of benign prostatic hyperplasia.", "Intermittent tamsulosin therapy in men with lower urinary tract symptoms.", "Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride.", "Effects of Withdrawing &agr;1‐Blocker from Combination Therapy with &agr;1‐Blocker and 5&agr;‐Reductase Inhibitor in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: A Prospective and Comparative Trial Using Urodynamics", "Comparative Study of Therapeutic Effect of Dibenyline, Finasteride, and Combination Drugs for Symptomatic Benign Prostatic Hyperplasia", "Progression of lower urinary tract symptoms after discontinuation of 1 medication from 2-year combined alpha-blocker and 5-alpha-reductase inhibitor therapy for benign prostatic hyperplasia in men--a randomized multicenter study." ]

[ "AIMS The aim of this study was to assess patient outcome after discontinuation of alfuzosin treatment in patients with benign prostatic hyperplasia ( BPH ) . METHODS This study included 200 BPH patients . Alpha-blockers were discontinued after 12 weeks of treatment when the International Prostatic Symptom Score ( IPSS ) was reduced to < 8 points , peak urine flow rate ( Q(max ) ) was increased to ≥ 15 ml/s , the postvoiding residual ( PVR ) urine volume was ≤ 100 ml and the patient agreed to discontinue treatment . Urinary symptoms of the patients were assessed at 4 , 8 , 12 and 24 weeks after discontinuation of medication , and surveys were performed asking whether patients wanted to restart administration of medication . RESULTS Of 200 enrolled patients , 142 ( 71.00 % ) received 12 weeks of treatment with 10 mg of alfuzosin . The medication was discontinued in 58 of 142 patients ( 40.85 % ) because urinary symptoms had improved . Among these patients , follow-up observations were performed for 49 patients up to 24 weeks after treatment discontinued . Of these 49 patients , 28 ( 57.14 % ) showed correct urination without a need to restart treatment up to 24 weeks after the medication was discontinued . The discontinuation group demonstrated improved voiding symptoms , including Q(max ) and PVR , relative to the re-administration group at baseline . Furthermore , the discontinuation group showed a smaller prostate volume than the re-administration group ( p = 0.045 ) . CONCLUSION When patients with BPH displayed symptomatic improvement upon treatment with alpha-blockers , the improvements were maintained in a select sub population of patients without the need to re-administer the alpha-blockers", "OBJECTIVE This study was conducted to examine the effect of discontinuing tamsulosin in patients with benign prostatic hyperplasia who had been receiving combination therapy with tamsulosin and dutasteride . METHODS The study sample consisted of 108 men with benign prostatic hyperplasia and lower urinary tract symptoms who visited our urology clinics between April 2008 and December 2010 . All were assessed using the International Prostate Symptom Score ( IPSS ) . The patients had IPSS of 8 - 19 and prostate volumes ≥25 mL by transrectal ultrasonography . They were put on tamsulosin and dutasteride , and the efficacy of this regimen was assessed every 12 weeks . After 48 weeks , patients were divided at r and om into a group continuing to take the same drug combination ( group 1 ) and a group taking only dutasteride 0.5 mg ( group 2 ) . RESULTS Sixty-nine of the original 108 patients completed the study , 36 ( 52 % ) in group 1 and 33 ( 48 % ) in group 2 . The mean age of all patients was 67.96 ± 7.88 years and mean prostatic volume was 40.45 ± 12.81 mL. Mean prostate-specific antigen was 3.31 ( 0.4 - 9.9 ) ng/mL at the outset . The IPSS scores of the two groups at first visit , 48 and 72 weeks were , respectively , 14.69 versus 15.85 ( P = 0.322 ) , 12.08 versus 12.85 ( P = 0.582 ) and 10.89 versus 11.06 ( P = 0.897 . ) There was a statistically significant difference between the baseline and 72-week IPSS scores in both groups ( group 1 : P < 0.001 , group 2 : P < 0.001 ) . CONCLUSION In patients with moderate IPSS , discontinuing tamsulosin after 48 weeks of combined tamsulosin and dutasteride therapy has no significant effect on outcome", "OBJECTIVE To evaluate the long-term efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia ( BPH ) . METHODS Thirty-three sites in 13 countries enrolled men with BPH who had an International Prostate Symptom Score ( IPSS ) > or = 12 [ corrected ] . After a 2-week , no-treatment lead-in period and a 26-week , single-blind treatment period , patients responding to terazosin were r and omly assigned to receive either terazosin or placebo for a 24-week , double-blind withdrawal period . RESULTS Of the initial 427 patients enrolled , 378 were evaluable , 273 of whom completed the single-blind period , of which 186 patients were r and omized . During the single-blind treatment period , IPSS , quality -of-life score ( QOL ) , peak flow rate ( PFR ) , and nocturia score ( NOC ) improved significantly ( p < or = 0.05 ) . During the double-blind withdrawal period , IPSS , QOL , PFR , and NOC deteriorated significantly in the placebo group compared with the terazosin group . The most common adverse event result ing in premature termination from the study was dizziness . There were no clinical ly important mean reductions in diastolic blood pressure ( DBP ) for patients normotensive at baseline . Terazosin significantly reduced mean DBP in hypertensive patients during the single-blind period and maintained the reduction during the double-blind period . CONCLUSION Treatment with terazosin has a beneficial effect on BPH , continuing for at least 12 months , and can be safely considered for medium- to long-term use in those who benefit", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "OBJECTIVES To determine the safety and efficacy of intermittent alpha-blocker therapy in men with lower urinary tract symptoms ( LUTS ) in a prospect i ve study . Alpha-blockers have been demonstrated to be safe and effective in the treatment of men with LUTS . To date , the role of varying dosing regimens in responding patients has not been well studied . METHODS Men with LUTS were entered into this prospect i ve open label , parallel , r and omized trial . In phase 1 , patients were treated with alfuzosin , 2.5 mg three times daily for 3 months . In phase 2 , those patients who had a significant therapeutic response were r and omized into one of the following three groups : ( 1 ) maintenance of alfuzosin ; ( 2 ) alfuzosin every other day ; and ( 3 ) discontinuation of alfuzosin ( ie , no treatment ) . Patients were followed up for a total of 6 months . Parameters of evaluation included the International Prostate Symptom Score ( IPSS ) , global satisfaction , peak urinary flow rate ( Qmax ) , and adverse events . RESULTS At 3 months , there were 79 patients who were categorized as having obtained a therapeutic response : IPSS decreased to 7.6 + /- 3.2 and Qmax increased to 11.3 + /- 2.9 mL/s . After r and omization , IPSS was 7.1 + /- 2.9 and 6.5 + /- 2.5 for group 1 ; 6.5 + /- 3.2 and 6.7 + /- 2.1 for group 2 ; and 11.4 + /- 4.8 and 12.3 + /- 4.9 for group 3 at 3 and 6 months , respectively . Qmax was 12.7 + /- 4.8 and 11.7 + /- 5.2 mL/s for group 1 ; 12.2 + /- 3.9 and 11.9 + /- 3.7 mL/s for group 2 ; and 9.7 + /- 2.5 and 9.3 + /- 2.1 mL/s for group 3 at 3 and 6 months , respectively . Global satisfaction at 6 months was the same for groups 1 and 2 . There were no differences in adverse events among the three groups . CONCLUSIONS In men with LUTS who responded to alfuzosin , changing the dosing regimen from daily to once every other day result ed in similar efficacy and safety at 3 and 6 months . By contrast , complete cessation of alfuzosin result ed in recurrence of both symptoms and impaired urinary flow . These data provide evidence that in responding patients , intermittent alpha-blocker therapy may be a reasonable therapeutic regimen . The role of intermittent alpha-blocker therapy using other agents , as well as in a large cohort of men with LUTS , remains to be determined", "OBJECTIVES To assess the results of doxazosin treatment in men with lower urinary tract symptoms ( LUTS ) treated for 15 months and to correlate symptomatic changes with alterations in urodynamic measures . METHODS After an initial 3-month treatment period with doxazosin 4 mg/day , 50 men with LUTS were given the choice of continued treatment with this agent or other therapeutic options . All patients were evaluated by International Prostate Symptom Score ( IPSS ) question naires and urodynamic evaluation initially and after 3 months of treatment . Patients were followed for an additional 12 months and those who continued doxazosin treatment underwent repeat urodynamic testing . RESULTS Among the original 50 patients , 24 men ( 48 % ) continued doxazosin treatment for 15 months , 18 men ( 36 % ) discontinued therapy , and 8 men ( 16 % ) were either dead or lost to follow-up or had been diagnosed and treated for prostate cancer . Comparison of values at 3 and 15 months of follow-up ( 9.4 versus 13.4 , P = 0.03 ) showed significant worsening of voiding symptoms , as assessed by the IPSS , in the 24 men still receiving doxazosin . This deterioration of subjective results with doxazosin occurred despite continued improvements in peak urinary flow rate ( Qmax ) , detrusor pressure at peak flow ( PdetQmax ) , and objective measures of obstruction ( Abrams-Griffiths number ) from 3 to 15 months of follow-up . CONCLUSIONS Relief of voiding symptoms in men with LUTS treated with doxazosin over prolonged intervals of 15 months does not correlate well with changes in urodynamic measures", "OBJECTIVES To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride , alone and in combination , for the symptomatic treatment of benign prostatic hyperplasia . METHODS In a prospect i ve , double-blind , placebo-controlled trial , 1095 men aged 50 to 80 years were r and omized to treatment for 52 weeks with doxazosin , finasteride , the combination of doxazosin and finasteride , or placebo . The dose of finasteride ( or its matched placebo ) was 5 mg/day . Doxazosin ( or its matched placebo ) was initiated at 1 mg/day , and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate ( Qmax ) and International Prostate Symptom Score ( IPSS ) . The IPSS and Qmax were assessed at baseline and at weeks 10 , 14 , 26 , 39 , and 52 or at the endpoint . RESULTS An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone ( P < 0.05 ) . Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax . All treatments were generally well tolerated . CONCLUSIONS Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia , and was more effective than finasteride alone or placebo . The addition of finasteride did not provide further benefit to that achieved with doxazosin alone", "PURPOSE To revise the 2003 version of the American Urological Association 's ( AUA ) Guideline on the management of benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS From MEDLINE ® search es of English language publications ( January 1999 through February 2008 ) using relevant MeSH terms , articles concerning the management of the index patient , a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms ( LUTS ) were identified . Qualitative analysis of the evidence was performed . Selected studies were stratified by design , comparator , follow-up interval , and intensity of intervention , and meta-analyses ( quantitative synthesis ) of outcomes of r and omized controlled trials were planned . Guideline statements were drafted by an appointed expert Panel based on the evidence . RESULTS The studies varied as to patient selection ; r and omization ; blinding mechanism ; run-in periods ; patient demographics , comorbidities , prostate characteristics and symptoms ; drug doses ; other intervention characteristics ; comparators ; rigor and intervals of follow-up ; trial duration and timing ; suspected lack of applicability to current US practice ; and techniques of outcomes measurement . These variations affected the quality of the evidence review ed making formal meta- analysis impractical or futile . Instead , the Panel and extractors review ed the data in a systematic fashion and without statistical rigor . Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases . Guideline statements concerning pharmacotherapies , watchful waiting , surgical options and minimally invasive procedures were either up date d or newly drafted , peer review ed and approved by AUA Board of Directors . CONCLUSIONS New pharmacotherapies and technologies have emerged which have impacted treatment algorithms . The management of LUTS/BPH continues to evolve", "OBJECTIVES To determine the effect of discontinuation of alpha-blockade and continuation of finasteride in men with lower urinary tract symptoms and enlarged prostates receiving combination treatment and to determine whether the alpha-blocker dose influences the ability to discontinue it . METHODS We treated 272 consecutive men with a prostate size greater than 40 g and American Urological Association symptom score greater than 20 with 5 mg finasteride and 2 mg doxazosin daily . Two hundred forty men reported a favorable response to therapy , defined as any reduction in symptom score and toleration of the medications . The dose was maintained at 2 mg doxazosin in 100 men and was titrated to 4 mg doxazosin in 80 patients and to 8 mg doxazosin in an additional 60 patients . We discontinued doxazosin at 3 , 6 , 9 , or 12 months , while continuing finasteride , and then re-evaluated the patients 1 month later to determine whether any worsening of symptoms had result ed . RESULTS In patients discontinuing doxazosin at 3 months , success ( defined as no increase in symptom score and no desire to resume doxazosin ) was reported by 20 % , 15 % , and 13 % of those taking 2 , 4 , and 8 mg , respectively . In patients discontinuing doxazosin at 6 months , success was reported by 48 % , 45 % , and 40 % of those taking 2 , 4 , and 8 mg , respectively . In patients discontinuing doxazosin at 9 months , success was reported by 84 % , 80 % , and 73 % of those taking 2 , 4 , and 8 mg , respectively . In patients discontinuing doxazosin at 12 months , success was reported by 84 % , 85 % , and 87 % of those taking 2 , 4 , and 8 mg , respectively . CONCLUSIONS Patients with lower urinary tract symptoms and moderately enlarged prostates initially receiving combination therapy using finasteride and an alpha-blocker are likely to experience no significant symptom deterioration after discontinuing the alpha-blocker after 9 to 12 months of combination therapy regardless of the dose of alpha-blocker chosen", "PURPOSE We investigated in what is to our knowledge the first prospect i ve study the safety and efficacy of intermittent tamsulosin therapy in patients with lower urinary tract symptoms . MATERIAL S AND METHODS This study was performed between January 2001 and February 2003 in 140 patients . In phase 1 of this study patients received 1 , 0.4 mg tamsulosin capsule daily for 3 months and were reevaluated after 3 months . At this assessment uroflowmetry , International Prostate Symptom Score and ultrasonographic estimation of residual urine were determined . In phase 2 responders to tamsulosin therapy were then r and omized into 1 of 3 groups , namely group 1 - -continued 4 mg tamsulosin once daily every day , group 2 - -0.4 mg tamsulosin once daily every other day and group 3 - -discontinued tamsulosin . Efficacy assessment s were done again at 4 , 12 and 24 weeks . RESULTS There were no statistically differences among the patients in groups 1 and 2 at 6 months for International Prostate Symptom Score , maximum or average urine flow , or residual urine . Differences between patients in groups 1 and 3 were statistically significant at 6 months . Differences between patients in groups 2 and 3 were also statistically significant at 6 months for these parameters . CONCLUSIONS Tamsulosin at a dose of 0.4 mg once daily and 0.4 mg once daily every other day for lower urinary tract symptoms provide comparable improvements in urinary flow and symptoms . Each treatment was well tolerated", "OBJECTIVES The Symptom Management After Reducing Therapy ( SMART-1 ) study examined the combination of the dual action 5alpha-reductase inhibitor ( 5ARI ) dutasteride , and alpha(1)-blocker tamsulosin , followed by withdrawal of tamsulosin in men with symptomatic BPH . METHODS 327 BPH patients were r and omised to 0.5 mg dutasteride and 0.4 mg tamsulosin for 36 weeks ( DT36 ) or 0.5 mg dutasteride and 0.4 mg tamsulosin for 24 weeks followed by dutasteride and tamsulosin matched placebo for the remaining 12 weeks ( DT24+D12 ) . Patients ' assessment of their symptoms , IPSS at weeks 24 , 30 , and drug safety were evaluated . RESULTS 77 % of DT24+D12 patients felt the same/better at week 30 compared with week 24 ( changes in IPSS were consistent with this finding ) . Of those subjects with an IPSS < 20 who changed to dutasteride monotherapy at week 24 , 84 % switched without a noticeable deterioration in their symptoms . In the 27 % of men with severe baseline symptoms ( IPSS > or=20 ) who had withdrawal of tamsulosin therapy at week 24 , 42.5 % reported a worsening of their symptoms compared with 14 % in the DT36 group . The regimens were well tolerated . CONCLUSIONS Dutasteride can be used in a 24-week combination with tamsulosin , to achieve rapid onset of symptom relief in patients at risk of underlying disease progression . This symptom relief is maintained in the majority of patients after the alpha(1)-blocker is removed from the combination . Patients with severe symptoms may benefit from longer-term combination therapy", "Purpose : We compared the effects on lower urinary tract symptoms and bladder outlet obstruction of combination therapy with & agr;1‐blocker and 5&agr;‐reductase inhibitor or a switch to 5&agr;‐reductase inhibitor monotherapy . We determined the factors influencing changes in lower urinary tract symptoms after & agr;1‐blocker withdrawal . Material s and Methods : A total of 140 out patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia received combination therapy with silodosin 8 mg per day and dutasteride 0.5 mg per day for 12 months . Of the patients 132 were r and omized to continue combination therapy or switched to dutasteride monotherapy through silodosin withdrawal as the monotherapy group . Parameter changes from before r and omization to 12 months after r and omization were assessed based on subjective symptoms and urodynamic findings of voiding and storage function . Results : Efficacy analysis included 57 patients on combination therapy and 60 on monotherapy . The change in I‐PSS ( International Prostate Symptom Score ) after r and omization was −0.7 and −0.6 in the combination therapy and monotherapy groups , respectively . The bladder outlet obstruction index changed from 46.1 to 41.8 in the combination therapy group and from 42.9 to 39.9 in the monotherapy group . No significant differences in subjective symptoms and bladder outlet obstruction were observed between the 2 groups . However , storage function decreased in the monotherapy group and lower urinary tract symptoms deteriorated significantly after the switch to dutasteride monotherapy in patients with a higher body mass index . Conclusions : We found that & agr;1‐blocker withdrawal from combination therapy was reasonable and tolerable with regard to the effect on lower urinary tract symptoms and bladder outlet obstruction . However , withdrawal must be performed carefully in patients with a high body mass index", "Objectives : A prospect i ve study was conducted in a community hospital in order to evaluate the therapeutic effect of dibenyline , finasteride , and a combination of the two drugs for symptomatic benign prostatic hyperplasia ( BPH ) . Methods : 190 men suffering from severe prostatism entered this study . They were assessed by IPSS symptom score , digital rectal examination , transrectal sonography of the prostate , uroflowmetry and residual urine . The patients were r and omly selected for medical treatment with dibenyline 10 mg b.i.d . ( n = 71 ) , finasteride 5 mg q.d . ( n = 54 ) , and a combination ( n = 65 ) . Clinical assessment s were carried out before treatment and 3 and 6 months after starting treatment . Patients who could not complete the treatment and those with prostatic cancer were excluded from the final statistics . The quality of life after 6 months of treatment and side effects were also assessed . Results : A total of 172 patients completed the treatment course and 153 patients completed the periodic clinical assessment s. Improvement in IPSS was noted in all 3 groups of patients both at 3 and 6 months . The prostatic volume was found to decrease in the finasteride group and the combination group at 6 months by 24.3 and 10.5 % , respectively . Maximal flow rate ( Qmax ) was significantly improved in the dibenyline and combination groups but not in the finasteride group at 3 months . At 6 months a significant increase in Qmax was noted in all groups with a mean increase of 1.4–1.8 ml/s . The quality of life after treatment was satisfactory in 71.9 % of the dibenyline group , 70.4 % of the finasteride group and 83.1 % of the combination group . Side effects were higher in the dibenyline than the finasteride or combination group . The dropout rate was higher in the dibenyline group ( 15.5 % ) than in the finasteride ( 7.5 % ) and combination ( 4.6 % ) groups . After 6 months of treatment , some of the patients discontinued medication and symptom relapse was noted in 92.6 % of the dibenyline group , 57.6 % of the finasteride group , and 71 % of the combination group . Conclusions : Medical treatment is effective in treating symptomatic BPH . Combination dibenyline and finasteride provides a weak synergistic clinical effect without additive side effects", "OBJECTIVE To investigate the treatment outcome of discontinuing 1 medication from 2-year combination therapy for male benign prostatic hyperplasia/lower urinary tract symptoms . MATERIAL S AND METHODS Patients with International Prostate Symptom Score ≥ 8 , total prostatic volume ( TPV ) > 30 mL , and maximum flow rate ( Qmax ) < 15 mL/s were r and omly assigned to the 5α-reductase inhibitor ( 5ARI ) discontinue ( DC-5ARI ) or α-blocker discontinue ( DC-α-blocker ) group . All patients received combination therapy with dutasteride ( 0.5 mg QD ) and doxazosin ( 4 mg QD ) for 2 years and then discontinued either one drug for 12 months . The primary endpoint was the occurrence of resuming medication . The secondary endpoints were the net parameters changed or the need of transurethral resection of the prostate ( TURP ) . RESULTS A total of 117 patients in DC-5ARI and 113 in DC-α-blocker group completed the study . The baseline TPV and Qmax were similar between groups before combination therapy . Resumption of combination therapy was significantly more in DC-5ARI than DC-α-blocker group ( 51.3 % vs 31.0 % ; P = .005 ) . The mean duration from discontinuing to resuming medication was 5.0 ± 4.4 months in DC-α-blocker and 7.8 ± 3.8 months in DC-5ARI group ( P < .05 ) . The TPV progression ( 29.1 % vs 8.0 % ; P < .001 ) and the need for TURP ( 14.5 % vs 7.1 % ; P = .043 ) were significantly higher in DC-5ARI than DC-α-blocker group . Patients with larger TPV ( 45.8 ± 18.1 mL ) had significantly greater need for resuming 5ARI than smaller TPV ( 36.3 ± 16.9 mL ; P = .007 ) , and a lower Qmax might predict resuming α-blocker . CONCLUSION After a 2-year combination therapy , discontinuation of either one drug induced benign prostatic hyperplasia progression in either group . Greater risk of resuming medication and needing TURP were noted in patients who discontinued 5ARI" ]

[ "17459521", "12377151", "9503245", "12356443", "15996878", "16084858", "21205361", "20630712", "18628661", "11490171" ]

[ "Food intake affects state body image: Impact of restrained eating patterns and concerns about eating, weight and shape", "Neural Substrates of Human Facial Expression of Pleasant Emotion Induced by Comic Films: A PET Study", "Attentional biases in eating disorders: a visual probe detection procedure.", "PET studies of somatosensory processing of light touch", "Anterior cingulate activity during error and autonomic response", "Functional Neuroanatomy of Body Shape Perception in Healthy and Eating-Disordered Women", "Changes in neuronal correlates of body image processing by means of cognitive-behavioural body image therapy for eating disorders: a randomized controlled fMRI study.", "Effects of body image therapy on the activation of the extrastriate body area in anorexia nervosa: An fMRI study", "Differential brain activation in anorexia nervosa to Fat and Thin words during a Stroop task", "Selective Handling of Information in Patients Suffering from Restrictive Anorexia in an Emotional Stroop Test and a Word Recognition Test" ]

[ "Body image disturbances play a significant role in the development of eating disorders . Since body image can vary in diverse context s , the aim of the present experiment was to investigate whether it is affected by recent food intake . Fifty-seven females without clinical ly relevant eating disorders were r and omly assigned to an experimental group ( EG , n=28 ) that consumed a milkshake while watching a neutral film and a control group ( CG , n=29 ) that only viewed the movie . Before and after the tasks , participants filled in the \" Body Image States Scale \" and the \" Mood Question naire \" and indicated their own \" actual \" , \" felt \" and \" ideal \" body dimensions with a digital distortion technique based on a photograph of themselves . It was shown that after milkshake consumption , state body dissatisfaction as well as the discrepancy between \" actual-ideal \" and \" felt-ideal \" body size estimations was higher in the EG than in the CG . Judgements of the \" actual \" , \" felt \" and \" ideal \" body dimensions and of mood were not affected . Further analyses revealed that the effect of milkshake consumption on body image and mood was higher the more the participants displayed restrained eating or eating , weight and shape concerns in general . Clinical implication s are discussed", "Laughter or smile is one of the emotional expressions of pleasantness with characteristic contraction of the facial muscles , of which the neural substrate remains to be explored . This currently described study is the first to investigate the generation of human facial expression of pleasant emotion using positron emission tomography and H(2)(15)O. Regional cerebral blood flow ( rCBF ) during laughter/smile induced by visual comics and the magnitude of laughter/smile indicated significant correlation in the bilateral supplementary motor area ( SMA ) and left putamen ( P < 0.05 , corrected ) , but no correlation in the primary motor area ( M1 ) . In the voluntary facial movement , significant correlation between rCBF and the magnitude of EMG was found in the face area of bilateral M1 and the SMA ( P < 0.001 , uncorrected ) . Laughter/smile , as opposed to voluntary movement , activated the visual association areas , left anterior temporal cortex , left uncus , and orbitofrontal and medial prefrontal cortices ( P < 0.05 , corrected ) , whereas voluntary facial movement generated by mimicking a laughing/smiling face activated the face area of the left M1 and bilateral SMA , compared with laughter/smile ( P < 0.05 , corrected ) . We demonstrated distinct neural substrates of emotional and volitional facial expression and defined cognitive and experiential processes of a pleasant emotion , laughter/smile", "OBJECTIVE To investigate attentional biases for body shape and weight-related stimulus words among subjects with anorexia nervosa , bulimia nervosa , and control subjects classified using a measure of dietary restraint . METHODS A visual probe detection task was used to assess attention toward stimulus words reflecting either a thin or a large physique and positively or negatively valenced emotion words . RESULTS In comparison to controls , subjects with eating disorders detected target probes more slowly when they appeared in the same location as had stimulus words connoting a thin physique . In addition , there was a trend toward faster detection or target probes that appeared in the same location as had stimulus words connoting a large physique . Neither of these effects were observed among restrained eaters . DISCUSSION Our results extend prior work suggesting information-processing biases for body shape and weight-related stimuli among persons with eating disorders", "The studies discussed in this report investigate the neural mechanisms involved in processing a light tactile stimulus as measured by positron emission tomography ( PET ) . This light tactile stimulus ( a 2-Hz tap with a von Frey hair ) produced a significant increase in regional cerebral blood flow ( rCBF ) in contralateral primary somatosensory cortex ( SI ) and bilateral secondary somatosensory cortex ( SII ) , with a larger response in the side contralateral to the stimulus . Light tactile stimulation also produced activity in multiple discrete areas in the human inferior parietal lobule ( IPL ) , which we believe to comprise a region homologous to the monkey area 7b or feline tertiary somatosensory cortex ( SIII ) . Directing attention to the tactile stimulus increased blood flow to SIII and activated a right-lateralized cortical network , regardless of the side of body stimulated . Directed attention to the stimulus decreased blood flow to visual cortex , but minimally modulated SI rCBF", "The contribution of anterior cingulate cortex ( ACC ) to human cognition remains unclear . The rostral ( rACC ) and dorsal ( dACC ) ACC cortex are implicated in tasks that require increased response control due to emotional and cognitive interference , respectively . However , both rACC and dACC are activated by conditions that induce changes in visceral arousal , suggesting that ACC supports a generation of integrated bodily responses . To clarify the relationship between purely cognitive and psychophysiological accounts of ACC function , we scanned 15 subjects using functional magnetic resonance imaging while they performed numerical versions of the Stroop task . To index autonomic arousal , we simultaneously measured pupil diameter . Performance errors accounted for most of the variance in a pupil-derived measure of evoked autonomic arousal . In analysis of the functional imaging data , activity within a region spanning rACC and dACC predicted trial-by-trial variation in autonomic response magnitude and was enhanced during error trials , shown using conjunction analyses . Activity within other loci within rACC predicted evoked autonomic arousal and showed sensitivity to errors but did not meet criteria for both . These data highlight the role of ACC in psychophysiological aspects of error processing and suggest that an interface exists within ACC between cognitive and biobehavioral systems in the service of response adaptation", "BACKGROUND Abnormalities in perception and evaluation of body shape are a hallmark of eating disorders . METHODS Brain responses to line drawings of underweight , normal weight , and overweight female bodies were measured with functional magnetic resonance imaging in 9 women with bulimia nervosa , 13 with anorexia nervosa , and 18 healthy women . Participants rated the stimuli for fear and disgust . RESULTS In the three groups , the lateral fusiform gyrus , inferior parietal cortex , and lateral prefrontal cortex were activated in response to body shapes compared with the control condition ( drawings of houses ) . The responses in the lateral fusiform gyrus and in the parietal cortex were less strong in patients with eating disorders compared with healthy control subjects . Patients with eating disorders rated the body shapes in all weight categories as more aversive than did healthy women . In the group with eating disorders , the aversion ratings correlated positively with activity in the right medial apical prefrontal cortex . CONCLUSIONS Processing of female body shapes engages a distributed neural network , parts of which are underactive in women with eating disorders . The considerable variability in subjective emotional reaction to body shapes in patients with eating disorders is associated with differential activity in the prefrontal cortex", "BACKGROUND Previous neuroimaging studies have demonstrated abnormalities in visual body image processing in anorexia and bulimia nervosa , possibly underlying body image disturbance in these disorders . Although cognitive behavioural interventions have been shown to be successful in improving body image disturbance in eating disorders , no r and omized controlled study has yet analysed treatment-induced changes in neuronal correlates of visual body image processing . METHOD Altogether , 32 females with eating disorders were r and omly assigned either to a manualized cognitive behavioural body image therapy consisting of 10 group sessions , or to a waiting list control condition . Using functional magnetic resonance imaging , brain responses to viewing photographs of one 's own and another female 's body taken from 16 st and ardized perspectives while participants were wearing a uniform bikini were acquired before and after the intervention and the waiting time , respectively . RESULTS Data indicate a general blood oxygen level dependent signal enhancement in response to looking at photographs of one 's own body from pre- to post-treatment , whereas exclusively in the control group activation decreases from pre- to post-waiting time were observed . Focused activation increases from pre- to post-treatment were found in the left middle temporal gyrus covering the coordinates of the extrastriate body area and in bilateral frontal structures including the middle frontal gyrus . CONCLUSIONS Results point to a more intense neuronal processing of one 's own body after the cognitive behavioural body image therapy in cortical regions that are responsible for the visual processing of the human body and for self-awareness", "To test effects of body image therapy in anorexia nervosa , functional magnetic resonance imaging was used to assess neuronal responses to viewing photographs of one 's own body before and after treatment . Activation decreases emerged in a distributed network and increases were observed in the extrastriate body area , possibly reflecting more intense body image processing", "We measured brain activation in six anorexia nervosa patients and six healthy controls performing a novel emotional Stroop task using Fat , Thin , and Neutral words , and words made of XXXXs . Reaction times increased in the patient group in Thin and Fat conditions . In the Thin – XXXX contrast , patients showed greater activation than controls at the junction of left insula , frontal and temporal lobes and in left middle and medial frontal gyri . In the Fat – XXXX contrast , controls showed greater activation in left dorsolateral prefrontal cortex and right parietal areas . Mechanisms underlying attentional bias in anorexia nervosa likely differ under conditions of positive and negative valence . This paradigm is a promising tool to examine neural mediation of emotional response in anorexia nervosa", "Several studies have been carried out using the Stroop test in eating disorders . Some of these studies have brought to light the existence of cognitive and attention deficits linked principally to weight and to food in anorexic and bulimic patients . The aim of the current study is to replicate and to clarify the existence of cognitive and attention deficits in anorexic patients using the Stroop test and a word recognition test . The recognition test is made up of 160 words ; 80 words from the previous Stroop experiment mixed at r and om and matched from a semantic point of view to 80 distractions . The recognition word test is carried out 2 or 3 days after the Stroop test . Thirty-two subjects took part in the study : 16 female patients hospitalised for anorexia nervosa and 16 normal females as controls . Our results do not enable us to confirm the existence of specific cognitive deficits in anorexic patients" ]

[ "3345384", "12711662", "20537811", "16389236", "11373259", "11691667", "17497548", "19919594", "16047525", "16034289", "10723834", "18436573" ]

[ "An evaluation of three treatment programmes for alcoholism: an experimental study with 6- and 8-month follow-ups.", "Motivational intervention: an individual counselling vs a group treatment approach for alcohol-dependent in-patients.", "The role of alcohol misuse in PTSD outcomes for women in community treatment: a secondary analysis of NIDA's Women and Trauma Study.", "Shelter-based managed alcohol administration to chronicallyhomeless people addicted to alcohol", "Brief intervention for male heavy drinkers in routine general practice: a three-year randomized controlled study.", "The epidemiology of the homeless population and its impact on an urban emergency department.", "Contingency Management to Reduce Substance Use in Individuals Who are Homeless with Co-Occurring Psychiatric Disorders", "Randomized controlled trial of cognitive-behavioural therapy for coexisting depression and alcohol problems: short-term outcome.", "Alcohol screening and brief intervention in primary care settings: implementation models and predictors.", "Can Shelter-Based Interventions Improve Treatment Engagement in Homeless Individuals With Psychiatric and/or Substance Misuse Disorders?: A Randomized Controlled Trial", "The process of relapse in severely dependent male problem drinkers.", "Pilot study of assertive community treatment methods to engage alcohol-dependent individuals." ]

[ "Summary The comparative effects of alcoholism treatment programmes were examined by r and omly assigning 113 male and female detoxified alcoholics to either : a 6-week inpatient programme , a 6-week outpatient programme or a single confrontational interview . On a variety of outcome measures , that included both levels of drinking and general functioning taken 6 and 18 months after intake , no treatment appeared to be consistently more effective than another . Furthermore , those who stayed in treatment did not show significantly more long-term improvement than those who refused or dropped out of treatment . Abstinent subjects felt more often than drinkers that they had achieved the goals they had set themselves and by the final follow-up there were many positive differences in apparent lifestyle . Although individual drinking patterns were unstable , on average , almost half the subjects located had either abstained or were drinking moderately . Patient and treatment variables combined explained up to 57 % of the variance in amount drunk after treatment , with patient variables providing the strongest associations", "AIMS The present study aim ed to evaluate whether individual counselling for alcohol-dependent patients in three sessions is as effective as a 2-week group treatment programme as part of an in-patient stay in a psychiatric hospital which was to foster motivation to seek further help and to strengthen the motivation to stay sober . Of particular importance was the external validity of the results , i.e. a ' normal ' intake load of in- patients in detoxification and a wide variety of motivation to stop drinking were to be investigated . METHODS Subjects eligible for the study were all patients with alcohol problems admitted to a psychiatric hospital , but without psychosis , as the main diagnosis , and with a maximum of 10 detoxification treatments in the past . A r and omized-controlled trial was conducted with 161 alcohol-dependent in- patients who received three individual counselling sessions on their ward in addition to detoxification treatment and 161 in- patients who received 2 weeks of in-patient treatment and four out-patient group sessions in addition to detoxification . Both interventions followed the principles and strategies of motivational interviewing . RESULTS Six months after intervention , group-treatment patients showed a higher rate of participation in self-help groups ; however , this difference had disappeared 12 months after treatment . The abstinence rate among the former patients did not differ between the two intervention groups . CONCLUSION Group treatment may lead to a higher rate of participation in self-help groups , but does not increase the abstinence rate 6 months after treatment", "BACKGROUND Individuals with comorbid substance use and posttraumatic stress disorder may differentially benefit from integrated trauma-focused interventions based on specific presenting characteristics such as substance use type and PTSD severity . The current study is a secondary analysis of a NIDA Clinical Trials Network study exploring the effectiveness of two interventions for women with comorbid PTSD and substance use disorders . METHOD Generalized estimating equations were used to examine the association of baseline alcohol misuse with PTSD outcome measures over time for all r and omized participants . RESULTS Women entering treatment with baseline alcohol misuse had higher Post Traumatic Stress Disorder Symptom Scale ( PSS-SR ) total scores ( t=2.43 , p<.05 ) , cluster C ( avoidance/numbing ) scores ( t=2.63 , p<.01 ) , and cluster D ( hyper-arousal ) scores ( t=2.31 , p<.05 ) . For women with alcohol misuse , after treatment week 1 , PSS-SR scores were significantly lower in the Seeking Safety intervention during treatment ( chi(2)(1)=4.00 , p<.05 ) and follow-up ( chi(2)(1)=4.87 , p<.05 ) compared to those in the health education intervention . Alcohol misusers in the Seeking Safety group who had higher baseline hyper-arousal severity improved more quickly than those with lower baseline hyper-arousal severity during treatment ( chi(2)(1)=4.06 , p<.05 ) . CONCLUSIONS These findings suggest that the type of substance abuse at treatment entry may inform treatment selection , predict treatment response among those with co-occurring PTSD and substance use disorders , and indicate a more severe clinical picture", "Background : People who are homeless and chronically alcoholic have increased health problems , use of emergency services and police contact , with a low likelihood of rehabilitation . Harm reduction is a policy to decrease the adverse consequences of substance use without requiring abstinence . The shelter-based Managed Alcohol Project ( MAP ) was created to deliver health care to homeless adults with alcoholism and to minimize harm ; its effect upon consumption of alcohol and use of crisis services is described as proof of principle . Methods : Subjects enrolled in MAP were dispensed alcohol on an hourly basis . Hospital charts were review ed for all emergency department ( ED ) visits and admissions during the 3 years before and up to 2 years after program enrolment , and the police data base was accessed for all encounters during the same periods . The results of blood tests were analyzed for trends . A question naire was administered to MAP participants and staff about alcohol use , health and activities of daily living before and during the program . Direct program costs were also recorded . Results : Seventeen adults with an average age of 51 years and a mean duration of alcoholism of 35 years were enrolled in MAP for an average of 16 months . Their monthly mean group total of ED visits decreased from 13.5 to 8 ( p = 0.004 ) ; police encounters , from 18.1 to 8.8 ( p = 0.018 ) . Changes in blood test findings were nonsignificant . All program participants reported less alcohol consumption during MAP , and subjects and staff alike reported improved hygiene , compliance with medical care and health . Interpretation : A managed alcohol program for homeless people with chronic alcoholism can stabilize alcohol intake and significantly decrease ED visits and police encounters", "The aim of this research was to evaluate the effectiveness of long-term brief intervention in routine general practice . In five primary care out-patient clinics in a Finnish town , 296 male early-phase heavy drinkers consulting a general practitioner ( GP ) for various reasons were identified . Control group C ( n = 88 ) was informed of the risks of drinking after the screening and were advised at the subsequent feedback about 2 weeks later to reduce their drinking . Groups A ( n = 109 ) and B ( n = 99 ) were offered in addition seven and three brief intervention sessions , respectively . All GPs took part , whether or not they indicated a special interest . The main outcome measures were differences between beginning and end-point at 3 years in self-reported alcohol consumption , mean corpuscular volume ( MCV ) , and serum carbohydrate-deficient transferrin , aspartate aminotransferase , alanine aminotransferase and gamma-glutamyltransferase . There were no statistically significant differences between study groups A , B and C in mean changes in outcome measures . Within all the groups , MCV decreased . Depending on the outcome measure used and the study group analysed , clinical ly significant reduction of drinking was found in 25 - 53 % of the subjects . In routine general practice , giving additional sessions of brief intervention may not be as effective as in special research conditions . Factors reducing the effectiveness of brief intervention programmes should be investigated , so that primary health care staff can be better supported in their efforts", "OBJECTIVES To characterize the homeless adult population of an urban emergency department ( ED ) and study the medical , psychiatric , and social factors that contribute to homelessness . METHODS A prospect i ve , case-control survey of all homeless adult patients presenting to an urban , tertiary care ED and a r and om set of non-homeless controls over an eight-week period during summer 1999 . Research assistants administered a 50-item question naire and were trained in assessing dentition and triceps skin-fold thickness . INCLUSION CRITERIA all homeless adults who consented to participate . Homelessness was defined as being present for any person not residing at a private address , group home , or drug treatment program . R and omly selected controls were concurrently enrolled with a 3:1 homeless : control rate . EXCLUSION CRITERIA critically ill , injured , or incapacitated patients , or patients < 21 years of age . Univariate analysis with appropriate statistical tests was used . The Mantel-Haenszel test was used to adjust for population differences . RESULTS Two hundred fifty-two homeless subjects and 88 controls were enrolled . Data are presented for homeless vs control patients , and all p-values were < 0.01 . Odds ratios ( ORs ) with 95 % confidence intervals ( 95 % CIs ) are given where appropriate : mean age ( + /-SD ) = 42 + /- 10 vs 48 + /- 13 ; male gender 95 % vs 54 % ( OR = 17 ; 95 % CI = 8 to 37 ) ; history of ( hx ) tuberculosis 49 % vs 15 % ( OR = 2.5 ; 95 % CI = 1.2 to 3 ) ; hx HIV infection 35 % vs 13 % ( OR = 3.8 ; 95 % CI = 1.8 to 8) ; hx penetrating trauma 62 % vs 16 % ( OR = 8.62 ; 95 % CI = 4.4 to 17.1 ) ; hx depression 70 % vs 15 % ( OR = 13.4 ; 95 % CI = 6.7 to 27 ) ; hx schizophrenia 27 % vs 7 % ( OR = 5.1 ; 95 % CI = 2.0 to 14 ) ; hx alcoholism 81 % vs 15 % ( OR = 24 ; 95 % CI = 12 to 49 ) ; significant tooth loss ( > 3 ) 43 % vs 18 % ( OR = 3.3 ; 95 % CI = 1.8 to 6.4 ) ; percentage of body fat 16.5 % vs 19.7 % ; hx social isolation ( no weekly social contacts ) 81 % vs 11 % ( OR = 33.3 ; 95 % CI = 14 to 100 ) ; mean number of ED visits/year 6.0 vs 1.6 . CONCLUSIONS In the study population homelessness was associated with a history of significantly higher rates of infectious disease , ethanol and substance use , psychiatric illness , social isolation , and rates of ED utilization", "Homeless shelters provide a unique opportunity to intervene with occupants who have substance abuse problems , as not addressing these issues may lead to continuation of problems playing a contributing role in homelessness . Attempts to implement Contingency Management ( CM ) with this population have often been complex , costly , and not straightforward to replicate in community setting s. We conducted a r and omized trial evaluating a simple , low-cost 4-week CM program for 30 individuals seeking shelter in a community-based homeless shelter who had both current substance and psychiatric disorders . Behavioral assessment s were performed at baseline , weekly , and termination of the study . Overall retention in the trial was high ; participants assigned to CM reduced their cocaine and alcohol use more than those in assessment -only . This pilot trial suggests that application of low-cost CM procedures is feasible within this novel setting and may decrease substance use", "AIMS Alcohol use disorders and depression co-occur frequently and are associated with poorer outcomes than when either condition occurs alone . The present study ( Depression and Alcohol Integrated and Single-focused Interventions ; DAISI ) aim ed to compare the effectiveness of brief intervention , single-focused and integrated psychological interventions for treatment of coexisting depression and alcohol use problems . METHODS Participants ( n = 284 ) with current depressive symptoms and hazardous alcohol use were assessed and r and omly allocated to one of four individually delivered interventions : ( i ) a brief intervention only ( single 90-minute session ) with an integrated focus on depression and alcohol , or followed by a further nine 1-hour sessions with ( ii ) an alcohol focus ; ( iii ) a depression focus ; or ( iv ) an integrated focus . Follow-up assessment s occurred 18 weeks after baseline . RESULTS Compared with the brief intervention , 10 sessions were associated with greater reductions in average drinks per week , average drinking days per week and maximum consumption on 1 day . No difference in duration of treatment was found for depression outcomes . Compared with single-focused interventions , integrated treatment was associated with a greater reduction in drinking days and level of depression . For men , the alcohol-focused rather than depression-focused intervention was associated with a greater reduction in average drinks per day and drinks per week and an increased level of general functioning . Women showed greater improvements on each of these variables when they received depression-focused rather than alcohol-focused treatment . CONCLUSIONS Integrated treatment may be superior to single-focused treatment for coexisting depression and alcohol problems , at least in the short term . Gender differences between single-focused depression and alcohol treatments warrant further study", "OBJECTIVE This study compared two different implementation strategies for Cutting Back , a primary care alcohol screening and brief intervention ( SBI ) program for hazardous and harmful drinkers . It also identified organizational factors contributing to the success or failure of SBI implementation . METHOD Cutting Back was implemented in 10 primary care practice s associated with managed care organizations ( MCOs ) in five states , through a system of planning , training , technical assistance and clinic feedback . Clinics were r and omly assigned to one of two brief intervention systems : In the P Model , medical providers were responsible for delivering interventions , whereas in the S Model mid-level professionals ( usually nurses ) acted as the clinic specialists to provide that service . Data were collected to measure the performance of screening and delivery of interventions in each clinic . RESULTS The S Model screened a higher percentage of patients than did the P Model during the best month of program operation ( 50 % vs 44 % ) and over all months of operation ( 24 % vs 19 % ) . Of those patients who screened positive , more patients in the S condition received an intervention than in the P condition ( 73.1 % vs 57.1 % ) , but there was a considerable range of performance among the five sites within each condition . Results at the clinic level were mixed , with some MCOs performing alcohol SBI significantly better with the S model and others doing better with the P model . The ability of clinics to conduct SBI was significantly correlated with both provider characteristics and organizational factors ( e.g. , prior SBI experience , MCO stability , number of clinicians trained and the quality of the MCO coordinator 's work ) . Lack of provider time , staff turnover and competing priorities correlated negatively with SBI performance . CONCLUSIONS The extent to which a given delivery model is likely to work best within an MCO depends on complex provider and organizational characteristics", "Background : High proportions of homeless individuals have mental illness and substance use disorders . Few of these individuals engage in consistent treatment , although they are likely to benefit from it . Shelter-based interventions to help this population engage in treatment have not been studied in a rigorous manner . Objectives : We sought to evaluate the effectiveness of a shelter-based intervention , including intensive outreach by a psychiatric social worker and availability of weekly psychiatrist visits with continuity of care to engage homeless individuals with psychiatric and substance use problems . Research Design : This was a r and omized controlled trial . Subjects : A total of 102 individuals were referred to a shelter-based psychiatric clinic . Measures : The primary outcome measure was first appointment attendance at a community mental health center ( CMHC ) . Secondary outcome measures were attendance at second and third CMHC appointments , participation in a substance abuse program , and employment and housing status at shelter exit . Results : Individuals receiving the intervention were more likely to attend ≥1 CMHC appointment ( 64.7 % versus 37.3 % , P = 0.006 ) and to participate in a substance abuse program ( 51.4 % versus 12.5 % , P = 0.0006 ) than those in the control group . There was a trend towards being more likely to attend 2 CMHC visits ( 33.3 % versus 17.7 % , P = 0.083 ) , but no significant differences in attending 3 visits , being employed , or having housing . Conclusions : Shelter-based interventions hold promise for improving treatment engagement in homeless population s with psychiatric and substance use problems . Further study should address how to foster care beyond an initial CMHC appointment and clarify key program components using a wider range of outcome measures", "AIMS The aim of the study was to investigate factors hypothesized to influence the relapse process , with a focus on the role of self-efficacy , alcohol dependence and cognitive functioning . DESIGN The study was conducted in the context of a controlled trial of a relapse prevention programme . Subjects were assessed prior to treatment , at immediate conclusion of treatment and at 6- and 12-month follow-up . SETTING The study was conducted in an Alcohol Treatment Unit ( ATU ) in Scotl and . PARTICIPANTS Subjects were 60 male problem drinkers who were patients at the ATU . They were heavy drinkers , with corresponding high levels of alcohol dependence and alcohol-related harm . MEASUREMENTS The independent variables were post-treatment self-efficacy , alcohol dependence , cognitive functioning , level of depression and alcohol consumption prior to admission to treatment . The dependent variables were post-treatment drinking behaviour and functioning and time to lapse and relapse . FINDINGS Although the methodology does not allow identification of causality , support was found for the hypothesis that post-treatment self-efficacy was an intervening variable between treatment and outcome . Higher post-treatment self-efficacy predicted better outcome at 6-month follow-up and was associated with a reduced risk of lapse and relapse over the 12-month follow-up . Poorer cognitive functioning was significantly associated with being categorized as a problem drinker at 6-month follow-up and with higher risk of a lapse over the 12-month follow-up . Level of alcohol dependence did not predict outcome . CONCLUSIONS It was concluded that post-treatment self-efficacy rating is a predictor of treatment outcome and time to lapse and relapse and that cognitive functioning is a predictor of treatment outcome and time to lapse", "AIMS Assertive approaches to treatment , which are becoming established for individuals with severe and enduring mental illness , may also be beneficial for engaging alcohol-dependent individuals without severe psychiatric co-morbidity , but so far there has been little research on this . This pilot study looked at the feasibility and potential benefits of introducing assertive community methods into the treatment of alcohol-dependent individuals with a history of poor engagement . METHODS Non-r and omized parallel cohort study comparing a Flexible Access Clinic employing assertive community treatment methods with the Usual Care Clinic . Participants were individuals re-referred to our service after they had previously disengaged from treatment . RESULTS Patients receiving assertive treatment attended assessment a mean of 14 days earlier than those receiving treatment as usual . Treatment at the Flexible Access Clinic was associated with significantly higher rates of completing assisted alcohol withdrawal ( 35 % versus 26 % ) and entering an aftercare placement ( 23 % versus 14 % ) . Aftercare was entered significantly earlier in the Flexible Access Clinic group ( 93 days versus 125 days ) . CONCLUSIONS These promising results point to the feasibility and potential efficacy of assertive community treatment methods for alcohol dependence , and the need for a r and omized controlled trial of effectiveness and cost effectiveness" ]

[ "20610635", "17473774", "23095336", "8858403", "12547747", "9516205", "9497183", "24476776", "11194101", "14967866", "12137176", "23254544", "24458265", "16270704", "9390958", "11507680", "12432178", "24195864", "8937796", "20798660", "14748941", "9189727", "10776891", "20544486", "9682624", "9764259", "15302082", "16118573", "21540144", "10950828", "23860287", "12672711", "11834107", "10647539", "1505536", "20029506", "24326929", "19092696", "15714291", "12439089", "12792212", "11842271", "21088972", "7890460", "19085695", "2407768", "14704800", "20589591", "18580398", "17611906", "20709302", "23222083" ]

[ "Physiologic and behavioral indicators of energy deficiency in female adolescent runners with elevated bone turnover.", "Postexercise whole-body protein turnover response to three levels of protein intake.", "Plasma leptin and energy expenditure during prolonged, moderate intensity, treadmill exercise", "Comparison of exercise and normal variability on HDL cholesterol concentrations and lipolytic activity.", "Physiological factors associated with low bone mineral density in female endurance runners", "Effects of short-term inactivity on glucose tolerance, energy expenditure, and blood flow in trained subjects.", "Substrate oxidation and energy expenditure in athletes and nonathletes consuming isoenergetic high- and low-fat diets.", "Physiological and Psychological Responses to Outdoor vs. Laboratory Cycling", "Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur.", "Substrate utilization during exercise performed with and without glucose ingestion in female and male endurance trained athletes.", "Bone mineral density in triathletes over a competitive season", "The Effect of Squat Depth on Multiarticular Muscle Activation in Collegiate Cross-Country Runners", "Importance of Standardized DXA Protocol for Assessing Physique Changes in Athletes.", "Heat Production and Storage Are Positively Correlated With Measures of Body Size/Composition and Heart Rate Drift During Vigorous Running", "Postexercise protein-carbohydrate and carbohydrate supplements increase muscle glycogen in men and women.", "Relation between lean body mass and thyroid volume in competition rowers before and during intensive physical training.", "Oral bovine colostrum supplementation enhances buffer capacity but not rowing performance in elite female rowers.", "Iron supplementation improves energetic efficiency in iron-depleted female rowers.", "Haematological status in elite long-distance runners: influence of body composition.", "Effect of increased dietary protein on tolerance to intensified training.", "Antioxidant supplementation preserves antioxidant response in physical training and low antioxidant intake.", "Effects of 3 days of carbohydrate supplementation on muscle glycogen content and utilisation during a 1-h cycling performance", "Growth, dietary intake, and trace element status in pubescent athletes and schoolchildren.", "Energy turnover during 24 hours and 6 days of adventure racing", "Prospective evaluation of risk factors for exercise-induced hypogonadism in male runners.", "The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.", "Effects of creatine supplementation on the performance and body composition of competitive swimmers.", "Muscle cytokine mRNA changes after 2.5 h of cycling: influence of carbohydrate.", "Submaximal exercise intensities do not provoke variations in plasma magnesium concentration in well-trained euhydrated endurance athletes with no magnesium deficiency.", "Increased thermogenic response to food and fat oxidation in female athletes: relationship with VO(2 max).", "Mixed Maximal and Explosive Strength Training in Recreational Endurance Runners", "Antioxidant Supplementation and Tapering Exercise Improve Exercise-Induced Antioxidant Response", "The Acute 1‐Week Effects of the Zone Diet on Body Composition, Blood Lipid Levels, and Performance in Recreational Endurance Athletes", "Intravenous versus oral rehydration during a brief period: responses to subsequent exercise in the heat.", "The effect of a high carbohydrate diet on running performance during a 30-km treadmill time trial", "Quercetin's effect on cycling efficiency and substrate utilization.", "Bone Loss Over 1 Year of Training and Competition in Female Cyclists", "Plasma visfatin and ghrelin response to prolonged sculling in competitive male rowers.", "Nutrient intake and performance during a mountain marathon: an observational study", "Energy intake and energy expenditure in elite lightweight female rowers.", "Change in Serum Sodium Concentration During a Cold Weather Ultradistance Race", "Effects of creatine monohydrate supplementation during combined strength and high intensity rowing training on performance.", "No effect of menstrual cycle phase on fuel oxidation during exercise in rowers", "The effects of two different periods of weight-reduction on selected performance parameters in elite lightweight oarswomen.", "Nutritional composition in different training stages in young female athletes (swimming) and association with leptin, IGF-1 and estradiol.", "Dietary intakes and biochemical markers of selected minerals: comparison of highly trained runners and untrained women.", "Leptin response to acute prolonged exercise after training in rowers", "Effects of intermittent hypoxia on running economy.", "Effect of oral contraceptives on weight and body composition in young female runners.", "Effect of prolonged training period on plasma adiponectin in elite male rowers.", "Nutritional factors that influence change in bone density and stress fracture risk among young female cross-country runners.", "Circulating Adiponectin Concentration and Body Composition Are Altered in Response to High-Intensity Interval Training" ]

[ "BACKGROUND Female adolescent runners have an elevated prevalence of low bone mass for agemdashan outcome that may be partially due to inadequate energy intake . OBJECTIVE The objective was to evaluate diet , menstrual history , serum hormone concentrations , and bone mass in female adolescent runners with normal or abnormal bone turnover . DESIGN Thirty-nine cross-country runners ( age : 15.7 plusmn 0.2 y ) participated in the study , which included a 7-d dietary assessment with the use of a food record and daily 24-h dietary recalls ; serum measures of insulin-like growth factor I , estradiol , leptin , parathyroid hormone , progesterone , triiodothyronine , 25-hydroxycholecalciferol , bone-specific alkaline phosphatase ( BAP ) , and cross-linked C-telopeptides of type I collagen ( CTX ) ; an evaluation of height , weight , bone mass , and body composition with the use of dual-energy X-ray absorptiometry ; and a question naire to assess menses and sports participation . Age- and sex-specific BAP and CTX concentrations of at least the 97th percentile and no greater than the third percentile , respectively , were considered abnormal . RESULTS All abnormal BAP and CTX concentrations fell within the elevated ( ge 97 % ) range . Runners with an elevated bone turnover ( EBT ) ( n = 13 ) had a lower body mass , fewer menstrual cycles in the past year , lower estradiol and 25-hydroxycholecalciferol concentrations , and a higher prevalence of body mass index lt 10 % for age , vitamin D insufficiency , amenorrhea , and low bone mass . Girls with EBT consumed less than the recommended amounts of energy and had a higher prevalence of consuming lt 1300 mg Ca than did those with normal bone turnover . CONCLUSIONS Runners with EBT had a profile consistent with energy deficiency . Nutritional support to increase energy , calcium intake , and 25-hydroxycholecalciferol concentrations may improve bone mineral accrual in young runners with EBT . This trial was registered at clinical trials.gov as NCT01059968", "PURPOSE This investigation examined the effect of variations in protein intake on whole-body protein turnover ( WBPTO ) after exercise in endurance-trained males . METHODS Five male runners ( 21.3 + /- 0.3 yr , 179 + /- 2 cm , 70.6 + /- 0.1 kg , 8.7 + /- 0.4 % body fat , 70.6 + /- 0.1 VO2peak ) participated in a r and omized , crossover- design diet intervention , where they consumed either a low- ( 0.8 g.kg(-1 ) ; LP ) , moderate- ( 1.8 g.kg(-1 ) ; MP ) , or high-protein ( 3.6 g.kg(-1 ) ; HP ) diet for 4 wk . WBPTO ( Ra , leucine rate of appearance ; NOLD , nonoxidative leucine disposal ; and Ox , leucine oxidation ) were assessed after a 75-min run at 70 % VO2peak after each diet-intervention period . RESULTS Leucine Ra ( indicator of protein breakdown ) and leucine Ox were greater on the HP diet than on the LP diet ( Ra , 123.4 + /- 6.9 vs 97.9 + /- 6.0 micromol.kg(-1).h(-1 ) ; Ox , 23.9 + /- 0.5 vs 17.0 + /- 0.8 micromol.kg(-1).h(-1 ) , P < 0.05 ) . No differences were noted in NOLD ( an indicator of protein synthesis ) across diets . Plasma branched chain amino acids ( BCAA ) at rest were greater for MP and HP than for LP , and nonessential amino acids ( NEAA ) were greater for LP than MP at rest and greater than MP and HP after exercise . CONCLUSION Findings from this study show that variations in protein intake can alter plasma amino acid levels and modulate rates of WBPTO after exercise . Additionally , a lower protein intake was associated with decreased rates of WBPTO after exercise", "Background : Current literature shows conflicting results regarding the possible direct role of exercise on leptin concentrations , mainly because of a non-homogeneous level of energy expenditure ( EE ) and the lack of st and ardization of energy balance . Aim : The aim of the study was to evaluate the effect of exercise duration and its corresponding EE on leptin levels , during prolonged treadmill exercise , in a well-controlled laboratory setting . Material s and methods : Seven young trained males underwent a 4-h treadmill exercise . The starting intensity was set at 65 % of maximal oxygen consumption . At the start of the test and throughout the exercise , venous blood sample s were drawn for the assays of leptin , glucose , free fatty acids ( FFA ) , cortisol , epinephrine ( E ) and norepinephrine ( NE ) . Hourly and total EE was monitored with gas analysis . Results : Plasma leptin levels decreased from 1.10±0.15 to 0.85±0.26 µg/l ( p<0.01 ) at the end of the exercise , reaching a significant reduction already after the second hour . FFA and cortisol showed a progressive significant increase , while glucose did not significantly change throughout the test . Plasma E and NE significantly increased at all sampling times compared to basal values ( 48.1±30.3 to 352.3±187.7 pg/ml , p<0.001 and 238.1±118.9 to 1798.7±413.5 pg/ml , p<0.001 ) . The r and om-effects model for panel data analysis showed negative correlation between leptin , NE and the values of progressive EE ( r2=0.745 , p<0.05 ) . Conclusions : Our data demonstrate that , during a prolonged moderate intensity exercise , leptin decrease is significantly related to the total EE . Further , NE concentrations seem to play an important role in the inhibition of leptin secretion", "In order to compare the influence of a single bout of exercise on HDL-C metabolism with normal variability , 12 male runners ( mean age : 24.9 + /- 4 yr ) who ran 15 - 30 miles per week underwent exercise ( E ) and control ( C ) experimental conditions . During the E trial subjects ran on a motor driven treadmill at 75 % ( 42.5 + /- 4.7 ml.kg-1.min-1 ) VO2max until 800 Kcals were expended . The C trial consisted of no exercise . Subjects were instructed to follow the same diet and keep a four d food diary during each experimental condition . Fasted blood sample s were obtained at the same time of day in each condition at time points corresponding to 24 h pre-exercise ( 24 PRE ) , 6 h post- ( 6 h ) and 24 h post-exercise ( 24 h ) . Plasma was analyzed for HDL-C , HDL2-C and HDL3-C ( mg.dl-1 ) . In addition post-heparin plasma sample s were analyzed for lipoprotein lipase ( LPL ) and hepatic lipase ( HL ) activity ( mumol . FFA-1.ml-1 ) . All values were adjusted for changes in plasma volume and compared to Baseline . HDL-C levels were unaltered following the C trial . However , following the E trial , HDL-C increased ( p < 0.01 ) above baseline values at 24 h. The increase in HDL-C was reflected in the HDL3-C subfraction ( p < 0.05 ) . Analysis of lipolytic activity revealed an overall greater LPL activity ( p < 0.05 ) in the E trial vs the C trial . In addition , a decrease in HL was observed at 24 h ( p < 0.05 ) but was not different between experimental conditions . These data suggest that exercise and not normal variability are responsible for alterations in lipolytic activity and corresponding increases in HDL-C levels", "Objective : To explore potential factors that could be associated with low bone mineral density ( BMD ) in female endurance runners . Methods : Fifty two female endurance runners ( 1500 m to marathon ) , aged 18–44 years , took part . Body fat percentage , lumbar spine BMD , and femoral neck BMD were measured using the Hologic QDR 4500w bone densitometer . Data on training , menstrual cycle status , osteoporosis , and health related factors were obtained by question naire . Dietary variables were assessed from a prospect i ve seven day dietary record of macronutrients and micronutrients . Results : The mean ( SD ) lumbar spine and femoral neck BMD were 1.11 ( 0.11 ) and 0.89 ( 0.12 ) g/cm2 respectively . A backward elimination regression analysis showed that age , body mass , body fat , distance run , magnesium , and zinc intake were the variables significantly associated with BMD . Lumbar spine BMD ( g/cm2 ) = −1.90 + ( 0.0486 × age ( years ) ) + ( 0.342 × log mass ( kg ) ) − ( 0.000861 × age2 ( years ) ) − ( 0.00128 × distance ( km/week ) ) , with an R2 = 30.1 % ( SEE = 0.089 ( 95 % confidence interval ( CI ) 0.05 to 0.23 ) ; p<0.001 ) . Femoral neck BMD ( g/cm2 ) = −2.51 − ( 0.00989 × age ( years ) ) + ( 0.720 × log mass ( kg ) ) + ( 0.000951 × magnesium ( mg/day ) ) −(0.0289 × zinc ( mg/day ) ) − ( 0.00821 × body fat ( % ) ) − ( 0.00226 × distance ( km/week ) ) , with an R2 = 50.2 % ( SEE = 0.100 ( 95 % CI 0.06 to 0.22 ) ; p<0.001 ) . The negative association between skeletal BMD and distance run suggested that participants who ran longer distances had a lower BMD of the lumbar spine and femoral neck . Further , the results indicated a positive association between body mass and BMD , and a negative association between body fat and BMD . Conclusions : The results suggest a negative association between endurance running distance and lumbar spine and femoral neck BMD , with a positive association between body mass and femoral neck and lumbar spine BMD . However , longitudinal studies are required to assess directly the effect of endurance running and body mass on BMD , and to see if the addition of alternative exercise that would increase lean body mass would have a positive effect on BMD and therefore help to prevent osteoporosis", "The purpose of this investigation was to examine the effects of 7 - 10 days of inactivity ( IA ) on glucose tolerance ( GT ) , resting metabolic rate ( RMR ) , thermic effect of a meal ( TEM ) , and limb blood flow in endurance-trained men . Eight highly trained ( peak O2 consumption 64 + /- 2 ml . kg-1 . min-1 ) endurance athletes participated in this study involving two identical test days , one approximately 24 h after a normal training bout ( Tr ) and the second after 7 - 10 days of IA . The following tests were conducted at each visit : 75-g oral glucose tolerance test ( OGTT ) , RMR , and TEM and measurements of calf and forearm blood flow ( BF ) by using venous occlusive plethysmography . Body weight remained unchanged during this short period of IA ( Tr , 78.5 + /- 1 kg ; IA , 78.7 + /- 1 kg ) . The area under the glucose and insulin curves increased 65 % ( Tr , 3,375 + /- 877 vs. IA , 5,559.4 + /- 621 mg . dl-1 . 180 min-1 ) and 73 % ( Tr , 2,182.5 + /- 270 vs. IA , 3,793.1 + /- 739 microU . ml-1 . 180 min-1 ) after IA , respectively ( P < 0.01 ) . RMR decreased significantly ( 4 % ; 1.5 + /- 0 . 02 vs. 1.44 + /- 0.02 kcal/min ; P < 0.05 ) and respiratory exchange ratio during the OGTT increased ( 4 % , 0.812 + /- 0.011 vs. 0.842 + /- 0 . 009 ; P < 0.05 ) after IA , whereas TEM increased similarly in the Tr and IA states . In the Tr state , mean calf BF increased by 22 % ( 3.17 + /- 0.22 vs. 3.87 + /- 0.38 ml . 100 ml-1 . min-1 ; P < 0.05 ) during the OGTT but remained unchanged after IA , whereas no differences at rest or during OGTTs existed between the two conditions for forearm BF . Incremental insulin area above fasting during the OGTT was correlated with mean calf BF in the Tr ( r = 0.76 , P < 0.05 ) and IA ( r = 0.72 , P < 0.05 ) states . In conclusion , 7 - 10 days of IA results in a deterioration in GT and a reduction in RMR . After glucose ingestion , calf BF was elevated compared with resting levels in the Tr state but was unchanged in the IA state ; however , limb BF was not related to GT or RMR . Thus our findings raise questions regarding the relative contribution of BF in modulating glucose tolerance and energy expenditure in endurance athletes in their habitual Tr or IA state", "Changes in substrate oxidation with isoenergetic high-carbohydrate ( HC ) and high-fat ( HF ) diets in male nonathletic subjects , aerobically trained athletes , and weight-trained athletes were examined in a crossover study . A whole-room respiration chamber was used to measure 24-h energy expenditure ( EE ) and substrate oxidation with control , HC , or HF diets for 7 d. The nonathletic group had higher 24-h EE ( P < 0.05 ) , exercise EE ( P < 0.03 ) , and resting metabolic rate ( P < 0.04 ) than did the aerobically trained athletes when these measurements were corrected for lean body mass . Fat oxidation was significantly correlated with lean body mass and diet . However , athletic status had no effect on substrate oxidation . Carbohydrate oxidation across groups increased acutely by 23 % after 24 h of the HC diet ( P < 0.0001 ) . Carbohydrate balance increased significantly over time with the HC diet ( P < 0.002 ) and decreased acutely after return to the control diet ( P < 0.0001 ) . With the HF diet , carbohydrate balance increased and was significantly different from balance with the control diet by day 7 ( P < 0.03 ) . Fat balance decreased significantly with both the HF ( P < 0.04 ) and HC ( P = 0.0075 ) diets by day 7 . Carbohydrate oxidation correlated with carbohydrate intake with both the control ( r = 0.61 , P < 0.01 ) and HC diets ( r = 0.59 , P < 0.02 ) , but not the HF diet . Fat oxidation was not correlated with fat intake . In conclusion , substrate oxidation in a respiration chamber is significantly affected by diet , but not by prior athletic training", "Abstract Mieras , ME , Heesch , MWS , and Slivka , DR . Physiological and psychological responses to outdoor vs. laboratory cycling . J Strength Cond Res 28(8 ) : 2324–2329 , 2014—The purpose of this study was to determine the physiological and psychological responses to laboratory vs. outdoor cycling . Twelve recreationally trained male cyclists participated in an initial descriptive testing session and 2 experimental trials consisting of 1 laboratory and 1 outdoor session , in a r and omized order . Participants were given a st and ardized statement instructing them to give the same perceived effort for both the laboratory and outdoor 40-km trials . Variables measured include power output , heart rate ( HR ) , core temperature , skin temperature , body weight , urine specific gravity ( USG ) , Rating of Perceived Exertion ( RPE ) , attentional focus , and environmental conditions . Wind speed was higher in the outdoor trial than in the laboratory trial ( 2.5 ± 0.6 vs. 0.0 ± 0.0 m·s−1 , p = 0.02 ) whereas all other environmental conditions were similar . Power output ( 208.1 ± 10.2 vs. 163.4 ± 11.8 W , respectively , p < 0.001 ) and HR ( 152 ± 4 and 143 ± 6 b·min−1 , respectively , p = 0.04 ) were higher in the outdoor trial than in the laboratory trial . Core temperature was similar , whereas skin temperature was cooler during the outdoor trial than during the laboratory trial ( 31.4 ± 0.3 vs. 33.0 ± 0.2 ° C , respectively , p < 0.001 ) , thus creating a larger thermal gradient between the core and skin outdoors . No significant differences in body weight , USG , RPE , or attentional focus were observed between trials . These data indicate that outdoor cycling allows cyclists to exercise at a higher intensity than in laboratory cycling , despite similar environmental conditions and perceived exertion . In light of this , cyclists may want to ride at a higher perceived exertion in indoor setting s to acquire the same benefit as they would from an outdoor ride", "PURPOSE Strenuous training can be associated with amenorrhea leading to amenorrhea-related accelerated bone loss . Insufficient calorie energy , calcium , and /or protein intakes can also be frequently encountered in women with intense training , possibly contributing to bone loss . Long-distance runners with or without regular menses ( age range 19 - 37 yr ) were prospect ively studied . METHODS Changes in areal bone mineral density ( BMD ) were measured at 1-yr interval . RESULTS Among 10 eumenorrheic , 11 oligo-amenorrheic , and 9 oral contraceptive users , there was no difference in energy , calcium , or protein intakes . Baseline BMD values were significantly lower in the oligo-amenorrheic group than in the two others at the level of lumbar spine ( anteroposterior view : 0.941+/-0.039 in oligo-amenorrheic vs 1.077+/-0.029 or 1.051 + /-0.017 g x cm(-2 ) , P < 0.005 , in the eumenorrheic and contraceptive user groups , respectively ) but not in weight-bearing bone such as proximal and midshaft femur . Over a 1-yr interval , during which the three groups did not differ in terms of running distances and dietary intakes , oligo-amenorrheic women displayed a significant decrease in lumbar spine BMD in lateral view ( -0.049+/-0.012 in oligo-amenorrheic vs -0.001+/-0.013 and 0.014+/-0.012 g x cm(-2 ) , p < 0.005 , in the eumenorrheic and contraceptive user groups , respectively ) . We did not detect any significant change in femoral neck , trochanter , or midshaft BMD . CONCLUSIONS Oligo-amenorrhea in long-distance runners , with adequate dietary intakes , was associated with a decrease in BMD affecting more the lumbar spine than the proximal and midshaft femur during a 1-yr follow-up", "Compared to males , females oxidize proportionately more fat and less carbohydrate during endurance exercise performed in the fasted state . This study was design ed to test the hypothesis that there may also be gender differences in exogenous carbohydrate ( CHOexo ) oxidation during exercise . Healthy , young males ( n = 7 ) and females ( n = 7 ) each completed 2 exercise trials ( 90 min cycle ergometry at 60 % VO2peak ) , 1 week apart . Females were eumenorrheic and were tested in the midfollicular phase of their menstrual cycle . Subjects drank intermittently either 8 % CHOexo ( 1 g glucose x kg x h(-1 ) ) enriched with U-13C glucose or an artificially sweetened placebo during the trial . Whole-body substrate oxidation was determined from RER , urinary urea excretion , and the ratio of 13C:12C in expired gas during the final 60 min of exercise . During the placebo trial , fat oxidation was higher in females then in males ( 0.42 + /- 0.07 vs 0.32 + /- 0.09 g.min(-1).kg LBM(-1 ) x 10(2 ) ) at 30 min of exercise ( p < .05 ) . When averaged over the final 60 min of exercise , the relative proportions of fat , total carbohydrate , and protein were all similar between groups . During CHOexo ingestion , both the ratio of 13C:12C in expired gas ( p < .05 ) and the proportion of energy derived from CHOexo relative to LBM ( p < .05 ) were higher in females compared to males at 75- and 90-min exercise . When averaged over the final 60 min of exercise , the percentage of CHOexo to the total energy contribution tended to be higher in females ( 14.3 + /- 1.2 % ) than in males ( 11.2 + /- 1.2 % ; p = .05 ) . Compared to males , females may oxidize a greater relative proportion of CHOexo during endurance exercise which , in turn , may spare more endogenous fuel . Based on these observations , ingested carbohydrate may be a particularly beneficial source of fuel during endurance exercise for females", "There is evidence from previous cross-sectional studies that high volumes of certain sports , including running , swimming and cycling , may have a negative impact on bone mineral density . The aim of the present study was to evaluate prospect ively the effects of high athletic training in individuals who engage in high volumes of all three of these activities ( triathletes ) . Bone mineral density for the total body , arms and legs was determined by dual-energy X-ray absorptiometry in 21 competitive triathletes ( 9 men , 12 women ) at the beginning of the training season and 24 weeks later . Age , body mass index , calcium intake and training volume were also recorded to examine potential mediators of bone mineral density change . Men had greater bone mineral density at all sites than women . No significant changes were observed over the 24 weeks for either total body or leg bone mineral density . Bone mineral density in both arms increased by approximately 2 % in men ( P ≪ 0.03 ) , but no change was observed for women . Change in bone mineral density at all sites was unrelated to age , body mass index , calcium intake and training volume . The results suggest that adverse changes in bone mineral density do not occur over the course of 6 months of training in competitive triathletes", "Abstract Gorsuch , J , Long , J , Miller K , Primeau , K , Rutledge , S , Sossong , A , and Durocher , JJ . The effect of squat depth on multiarticular muscle activation in collegiate cross-country runners . J Strength Cond Res 27(9 ) : 2619–2625 , 2013—The squat is a closed-chain lower body exercise commonly performed by many athletes . Muscle activity has been examined during partial and parallel squats in male weightlifters , but not in male and female runners . Therefore , this study measured muscle activity with surface electromyography ( EMG ) during partial and parallel squats in 20 Division I collegiate cross-country runners ( 10 males and 10 females ) in a r and omized crossover design . We hypothesized the parallel squat would increase extensor muscle activitation ( i.e. hamstrings and erector spinae ) . Furthermore , we sought to determine if changes in muscle activity were different between males and females . Participants performed 6 repetitions using their 10 repetition maximum loads for each condition during EMG testing . EMG was performed on the right rectus femoris , biceps femoris , lumbar erector spinae , and lateral head of the gastrocnemius . Rectus femoris activity ( 0.18 ± 0.01 vs. 0.14 ± 0.01 mV ) and erector spinae activity ( 0.16 ± 0.01 vs. 0.13 ± 0.01 mV ) were significantly higher ( p < 0.05 ) during the parallel squat than during the partial squat condition . This increase in muscle activity may be attributed to greater ranges of motion at the hip and knee joints . Biceps femoris and gastrocnemius activity were similar between conditions . No significant differences existed between males and females ( squat condition × gender ; p > 0.05 ) . During preliminary isokinetic testing , both male and female runners demonstrated deficient hamstrings-to-quadriceps ratios , which would not likely improve by performing parallel squats based on our EMG findings . Despite the reduced load of the parallel squat , rectus femoris and erector spinae activity were elevated . Thus , parallel squats may help runners to train muscles vital for uphill running and correct posture , while preventing injury by using lighter weights through a larger range of motion", "PURPOSE The implication s of undertaking DXA scans using best practice protocol s ( subjects fasted and rested ) or a less precise but more practical protocol in assessing chronic changes in body composition following training and a specialized recovery technique were investigated . METHODS Twenty-one male cyclists completed an overload training program , in which they were r and omized to four sessions per week of either cold water immersion therapy or control groups . Whole-body DXA scans were undertaken with best practice protocol ( Best ) or r and om activity protocol ( R and om ) at baseline , after 3 weeks of overload training , and after a 2-week taper . Magnitudes of changes in total , lean and fat mass from baseline-overload , overload-taper and baseline-taper were assessed by st and ardization ( Δmean/SD ) . RESULTS The st and ard deviations of change scores for total and fat-free soft tissue mass ( FFST ) from R and om scans ( 2 - 3 % ) were approximately double those observed in the Best ( 1 - 2 % ) , owing to extra r and om errors associated with R and om scans at baseline . There was little difference in change scores for fat mass . The effect of cold water immersion therapy on baseline-taper changes in FFST was possibly harmful ( -0.7 % ; 90 % confidence limits ±1.2 % ) with Best scans but unclear with R and om scans ( 0.9 % ; ±2.0 % ) . Both protocol s gave similar possibly harmful effects of cold water immersion therapy on changes in fat mass ( 6.9 % ; ±13.5 % and 5.5 % ; ±14.3 % , respectively ) . CONCLUSIONS An interesting effect of cold water immersion therapy on training-induced changes in body composition might have been missed with a less precise scanning protocol . DXA scans should be undertaken with Best", "Abstract The purpose s of this study were to determine the relationships between : ( a ) measures of body size/composition and heat production/storage , and ( b ) heat production/storage and heart rate ( HR ) drift during running at 95 % of the velocity that elicited lactate threshold , which was determined for 20 healthy recreational male runners . Subsequently , changes in skin and tympanic temperatures associated with a vigorous 20-min run , HR , and VO2 data were recorded . It was found that heat production was significantly correlated with body mass ( r = .687 ) , lean mass ( r = .749 ) , and body surface area ( BSA , r = .699 ) . Heat storage was significantly correlated with body mass ( r = .519 ) , fat mass ( r = .464 ) , and BSA ( r = .498 ) . The percentage of produced heat stored was significantly correlated with body mass ( r = .427 ) , fat mass ( r = .455 ) , and BSA ( r = .414 ) . Regression analysis showed that the sum of body mass , percentage of body fat , BSA , lean mass , and fat mass accounted for 30 % of the variability in heat storage . It was also found that HR drift was significantly correlated with heat storage ( r = .383 ) , percentage of produced heat stored ( r = .433 ) , and core temperature change ( r = .450 ) . It was concluded that heavier runners experienced greater heat production , heat storage , and core temperature increases than lighter runners during vigorous running", "We have previously demonstrated that women did not increase intramuscular glycogen in response to an increased percent of dietary carbohydrate ( CHO ) ( from 60 to 75 % of energy intake ) ( M. A. Tarnopolsky , S. A. Atkinson , S. M. Phillips , and J. D. MacDougall . J. Appl . Physiol . 78 : 1360 - 1368 , 1995 ) . CHO and CHO-protein ( Pro ) supplementation postexercise can potentiate glycogen re synthesis compared with placebo ( K. M. Zawadzki , B. B. Yaspelkis , and J. L. Ivy . J. Appl . Physiol . 72 : 1854 - 1859 , 1992 ) . We studied the effect of isoenergetic CHO and CHO-Pro-Fat supplements on muscle glycogen re synthesis in the first 4 h after endurance exercise ( 90 min at 65 % peak O2 consumption ) in trained endurance athletes ( men , n = 8 ; women , tested in midfollicular phase , n = 8) . Each subject completed three sequential trials separated by 3 wk ; a supplement was provided immediately and 1-h postexercise : 1 ) CHO ( 0.75 g/kg ) + Pro ( 0.1 g/kg ) + Fat ( 0.02 g/kg ) , 2 ) CHO ( 1 g/kg ) , and 3 ) placebo ( Pl ; artificial sweetener ) . Subjects were given prepackaged , isoenergetic , isonitrogenous diets , individualized to their habitual diet , for the day before and during the exercise trial . During exercise , women oxidized more lipid than did men ( P < 0.05 ) . Both of the supplement trials result ed in greater postexercise glucose and insulin compared with Pl ( P < 0.01 ) , with no gender differences . Similarly , both of these trials result ed in increased glycogen re synthesis ( 37.2 vs. 24 . 6 mmol . kg dry muscle-1 . h-1 , CHO vs. CHO-Pro-Fat , respectively ) compared with Pl ( 7.5 mmol . kg dry muscle-1 . h-1 ; P < 0.001 ) with no gender differences . We conclude that postexercise CHO and CHO-Pro-Fat nutritional supplements can increase glycogen re synthesis to a greater extent than Pl for both men and women", "OBJECTIVE Lean body mass is a better determinant of thyroid size than body weight as demonstrated in a previous crosssectional study . We now evaluated if intra-individual changes in body composition and especially changes in lean body mass , due to physical training , could give rise to changes in thyroid volume . SUBJECTS AND METHODS We investigated 17 freshmen ( group 1 ) before and after six months of competition rowing ; controls ( group II ) were 19 senior rowers , already participating in a training program for more than 2 years . RESULTS In group I body weight ( BW ; p < 0.01 ) , lean body mass ( LBM ; p < 0.05 ) , fat weight ( FW ; p < 0.05 ) , body mass index ( BMI ; p < 0.01 ) and thyroid volume ( TV ; p = 0.08 ) all decreased ; in group II body composition and thyroid volume did not change at all during the 6 months observation period . Whereas serum TSH and T3 did not change , free thyroxine ( FT4 ) concentrations increased slightly in both groups ( p < 0.01 ) , presumably caused by the combination of exercise and insufficient energy intake . Taking together all subjects , baseline TV was directly related to BW ( r = 0.35 , p<0.05 ) , to LBM ( r=0.40 , p<0.05 ) and to BMI ( r=0.43 , p < 0.01 ) but not to FW ( r = - 0.06 , NS ) . The decrease in thyroid volume was related to the decrease in LBM ( r = 0.32 , p = 0.05 ) , in BW ( r = 0.49 , p < 0.005 ) , in FW ( r = 0.42 , p = 0.01 ) and in BMI ( r = 0.53 , p = 0.001 ) . CONCLUSIONS After a six-month period of intensive physical training , changes in thyroid volume correlate directly with changes in body composition", "A r and omized , double-blind , placebo controlled design was used in which 13 elite female rowers , all of whom had competed at World Championships , were supplemented with 60 g day-1 of either bovine colostrum ( BC ; n = 6 ) or concentrated whey protein powder ( WP ; n = 7 ) during 9 weeks of pre-competition training . All subjects undertook the study as a group and completed the same training program . Prior to , and after 9 weeks of supplementation and training , subjects completed an incremental rowing test ( ROW1 ) on a rowing ergometer consisting of 3 3 4-min submaximal workloads and a 4-min maximal effort ( 4 max ) , each separated by a 1-min recovery period . The rowing test was repeated after a 15-min period of passive recovery ( ROW2 ) . The 4 max for ROW1 provided a measure of performance , and the difference between the 4 max efforts of ROW1 and ROW2 provided an index of recovery . Blood lactate concentrations and pH measured prior to exercise and at the end of each workload were used to estimate blood buffer capacity ( beta ) . Food intake was recorded daily for dietary analysis . There were no differences in macronutrient intakes ( p > .56 ) or training volumes ( p > .99 ) between BC and WP during the study period . Rowing performance ( distance rowed and work done ) during 4 max of ROW2 was less than ROW1 at baseline ( p < .05 ) but not different between groups ( p > .05 ) . Performance increased in both rows by Week 9 ( p < .001 ) , with no difference between groups ( p > .75 ) . However , the increase was greatest in ROW2 ( p < .05 ) , such that by Week 9 there was no longer a difference in performance between the two rows in either group ( p > .05 ) . b was not different between groups for ROW1 at baseline ( BC 38.3 5.0 , WP 38.2 7.2 slykes ; p > .05 ) but was higher in BC by Week 9 ( BC 40.8 5.9 , WP 33.4 5.3 slykes ; p < .05 ) . b for ROW2 followed the same pattern of change as for ROW1 . We conclude that supplementation with BC improves b , but not performance , in elite female rowers . It was not possible to determine whether b had any effect on recovery", "PURPOSE Studies in both animals and humans show a relationship between iron depletion without anemia ( IDNA ) and physical performance . Compared with their sedentary counterparts , female endurance athletes are at greater risk of IDNA , and consequences relevant to endurance athletes include reduced work capacity and energetic efficiency ( EF ) . We conducted a r and omized placebo-controlled trial to investigate the effects of iron ( Fe ) supplementation on Fe status and performance in nonanemic female rowers during training . METHODS At the beginning of a training season , 40 rowers were r and omized to receive either 100 mg·d FeSO4 ( n = 21 ) or placebo ( n = 19 ) using a double-blind design . Thirty-one ( n = 15 Fe , 16 placebo ) completed the 6-wk trial . Fe status ( hemoglobin , serum ferritin , soluble transferrin receptor ) , body composition , and laboratory tests of physical performance ( 4-km time trial , V˙O2peak , energetic EF , and blood lactate ) were assessed at baseline and after training . RESULTS Rowers in both groups increased their fat-free mass ( P < 0.001 ) and V˙O2peak ( P < 0.001 ) after training . Multiple regression analyses revealed improvements in Fe stores ( serum ferritin ) in the Fe treatment group after controlling for baseline Fe stores ( P = 0.07 ) . Rowers in the Fe group had slower lactate response during the first half of the time trial and after 5 min of recovery ( P = 0.05 ) and showed greater improvements in energy expenditure ( P = 0.01 for group-by time ) and energetic EF compared with placebo ( P = 0.03 for group-by time ) . CONCLUSIONS Female rowers with depleted Fe stores who consumed supplemental Fe during training improved their Fe status and energetic EF during endurance exercise . These results are important for endurance athletes whose dietary patterns and physical training increase their risk of IDNA and suggest that Fe supplementation may maximize the benefits of endurance training", "In 10 female and eight male Danish elite middle- and long-distance runners , haematological status , including blood volume , was examined . Haemoglobin , haematocrit and serum (s)-ferritin concentrations were all within the normal range . In both men and women , blood volume , plasma volume and erythrocyte volume were increased in relation to various reference values . However , the runners had a low body weight due to a reduced fat level , 9.5 % ( 7.3 - 15.1 % ) fat for the women , 5.9 % ( 5.0 - 8.8 % ) fat ( median and ranges ) for the men , measured by dual-energy X-ray absorptiometry ( DEXA ) scanning . When the runners ' body weights were ' normalized ' to a reference population ( 25 % fat for women , 15 % fat for men ) , only plasma volume remained increased in relation to body weight for the women , whereas all the volumes remained increased for the men . This confirms that endurance training induces a true increased plasma volume . The lower erythrocyte volume in the women compared with the men could be a consequence of the generally poorer iron status in the women , indicating that a combination of haemolysis , menstruation and low caloric ( iron ) intake makes it difficult for trained women to obtain optimal effects on erythrocyte volume equal to those obtained by trained men . Furthermore , the study emphasizes the importance of taking body composition into consideration when comparing well-trained athletes with a reference population", "PURPOSE The purpose of the present study was to examine the effect of increased protein intake on short-term decrements in endurance performance during a block of high-intensity training . METHODS Trained male cyclists ( VO(2max ) = 64.2 ± 6.5 mL·kg(-1)·min(-1 ) ) completed two 3-wk trials both divided equally into normal ( NOR ) , intensified ( INT ) , and recovery ( REC ) training . In a counterbalanced crossover experimental design , cyclists received either a high-protein ( PRO ; 3 g protein·kg(-1 ) body mass (BM)·d(-1 ) ) or a normal diet ( CON ; 1.5 g protein·kg(-1 ) BM·d(-1 ) ) during INT and REC . Dietary carbohydrate content remained constant at 6 g·kg(-1 ) BM·d(-1 ) . Energy balance was maintained during each training week . Endurance performance was assessed with a VO(2max ) test and a preloaded time trial . Alterations in blood metabolite responses to exercise were measured at rest , during , and after exercise . Cyclists completed the Daily Analysis of Life Dem and s for Athletes ( DALDA ) question naire each day . RESULTS Increased dietary protein intake led to a possible attenuation ( 4.3 % ; 90 % confidence limits ×/÷5.4 % ) in the decrement in time trial performance after a block of high-intensity training compared with NOR ( PRO = 2639 ± 350 s ; CON = 2555 ± 313 s ) . Restoration of endurance performance during recovery training possibly benefited ( 2.0 % ; ×/÷4.9 % ) from additional protein intake . Frequency of symptoms of stress described as \" worse than normal \" reported after a block of high-intensity training was very likely ( 97 % ) attenuated ( 17 ; ±11 AUC of \" a \" scores part B , DALDA for INT + REC ) by increasing the protein content of the diet . No discernable changes in blood metabolite concentrations were observed in PRO . CONCLUSIONS Additional protein intake reduced symptoms of psychological stress and may result in a worthwhile amelioration of the performance decline experienced during a block of high-intensity training", "The present controlled-training double-blind study ( supplemented ( S ) group , n 7 ; placebo ( P ) group , n 10 ) was design ed to investigate whether an antioxidant mixture ( Se 150 microg , retinyl acetate mg , ascorbic acid 120 mg , alpha-tocopheryl succinate 20 mg ) would allow overloaded triathletes to avoid adaptation failure in the antioxidant system [ corrected ] . Dietary intakes were recorded . The supplement of Se , and vitamins A and E provided 100 % of the French RDA . Four weeks of overloaded training ( OT ) followed 4 weeks of normal training ( NT ) . After NT and OT , biological studies were conducted at rest and after a duathlon test ( run 5 km , cycle 20 km , run 5 km ) . During the 4-week period of NT , blood levels of GSH levels increased in response to supplementation ( P<0.05 ) and remained elevated during OT . Plasma glutathione peroxidase activity was significantly higher in the S group in all situations after NT and OT ( P<0.01 ) . The S group had increased erythrocyte Cu , Zn-superoxide dismutase activity in response to OT ( P<0.05 ) . Supplementation significantly reduced ( P<0.05 ) the magnitude in duathlon-induced creatine kinase isoenzyme MB mass increase , which tended to be higher with OT ( P=0.09 ) . We conclude that the antioxidant mixture helped to preserve the antioxidant system during an OT-induced stress in subjects with initially low antioxidant intakes . Effects of supplementation during NT and /or OT are shown mostly by the alleviated muscle damage . The effects of the antioxidant mixture were observed for doses that can be provided by a diversified and well-balanced diet . The maintenance of normal nutritional status with regard to the antioxidant intake ( Se , vitamins C and E ) plays a key role in antioxidant adaptive effects during NT and OT", "Abstract This study compared the effects of supplementing the normal diets of six trained cyclists [ maximal oxygen uptake $ ( \\dot {V}$O2max ) 4.5 (0.36)l · min−1 ; values are mean ( SD ) ] with additional carbohydrate ( CHO ) on muscle glycogen utilisation during a 1-h cycle time-trial ( TT ) . Using a r and omised crossover design , subjects consumed either their normal diet ( NORM ) for 3 days , which consisted of 426 ( 137 ) g · day−1 CHO [ 5.9 ( 1.4 ) g · kg−1 body mass ( BM ) ] , or additional CHO ( SUPP ) to increase their intake to 661 ( 76 ) g · day−1 [ 9.3 ( 0.7 ) g · kg−1 BM ] . The SUPP diet elevated muscle glycogen content from 459 ( 83 ) to 565 ( 62 ) mmol · kg−1 dry weight ( d.w . ) ( P < 0.05 ) . However , despite the increased pre-exercise muscle glycogen stores , there was no difference in the distance cycled during the TT [ 40.41 ( 1.44 ) vs 40.18 ( 1.76 ) km for NORM and SUPP , respectively ] . With NORM , muscle glycogen declined from 459 ( 83 ) to 175 ( 64 ) mmol · kg−1 d.w . , whereas with SUPP the corresponding values were 565 ( 62 ) and 292 ( 113 ) mmol · kg−1 d.w . Accordingly , both muscle glycogen utilisation [ 277 ( 64 ) vs 273 ( 114 ) mmol · kg−1 d.w . ] and total CHO oxidation [ 169 ( 20 ) vs 165 ( 30 ) g · h−1 for NORM and SUPP , respectively ] were similar . Neither were there any differences in plasma glucose or lactate concentrations during the two experimental trials . Plasma glucose concentration averaged 5.5 ( 0.5 ) and 5.6 ( 0.6 ) mmol · l−1 , while plasma lactate concentration averaged 4.4 ( 1.9 ) and 4.4 ( 2.3 ) mmol · l−1 for NORM and SUPP , respectively . The results of this study show that when well-trained subjects increase the CHO content of their diet for 3 days from 6 to 9 g · kg−1 BM there is only a modest increase in muscle glycogen content . Since supplementary CHO did not improve TT performance , we conclude that additional CHO provides no benefit to performance for athletes who compete in intense , continuous events lasting 1 h. Furthermore , the substantial muscle CHO reserves observed at the termination of exercise indicate that whole-muscle glycogen depletion does not determine fatigue at this exercise intensity and duration", "PURPOSE To examine interactions between club-level sports training , dietary intake , and nutritional status during puberty . METHODS A 2-yr prospect i ve study was undertaken with 64 boys ( 40 ice hockey players , 24 controls ) and 71 girls ( 28 gymnasts , figure skaters , and runners , 43 controls ) . The boys ' age in the beginning of the study was 12 - 13 yr , whereas the girls were 11 - 12 yr . The following variables were measured in the beginning , and after 1 and 2 yr : physical activity level ( record ) , dietary intake ( record ) , blood hemoglobin concentration , serum ferritin , zinc and copper concentration , anthropometric indices ( height , weight , skinfolds , upper arm muscle girth ) , and biological maturation ( self-report ) . RESULTS AND CONCLUSIONS The changes in the anthropometric variables throughout the study period were not different between the athletes and controls ( P = 0.09 ) . The athlete boys had higher mean energy , iron and zinc intakes , and higher mean serum zinc concentration than the controls ( P < or = 0.003 ) . The athlete and control girls ' dietary intakes and biochemical indices of trace element status were not different from each other ( P < or = 0.13 ) . Moreover , sports participation was not associated with the longitudinal changes in trace element status ( P > or = 0.08 ) . These data suggest that club-level sports training does not affect growth , maturation or nutritional status during puberty", "Abstract Energy turnover was assessed in two conditions of mixed ultra-endurance exercise . In Study 1 , energy expenditure and intake were measured in nine males in a laboratory over 24 h. In Study 2 , energy expenditure was assessed in six males during an 800-km Adventure race ( mean race time 152.5 h ) . Individual correlations between heart rate and oxygen uptake ( [Vdot]O2 ) were established during pre-tests when kayaking , cycling , and running . During exercise , energy expenditure was estimated from continuous heart rate recordings . Heart rate and [Vdot]O2 were measured regularly during fixed cycling work rates to correct energy expenditure for drift in oxygen pulse . Mean energy expenditure was 18,050 ± 2,390 kcal ( 750 ± 100 kcal · h−1 ) and 80,000 ± 18,000 kcal ( 500 ± 100 kcal · h−1 ) in Study 1 and Study 2 respectively , which is higher than previously reported . Energy intake in Study 1 was 8,450 ± 1,160 kcal , result ing in an energy deficit of 9,590 ± 770 kcal . Body mass decreased in Study 1 ( −2.3 ± 0.8 kg ) but was unchanged in Study 2 . Fat mass decreased in Study 2 ( −2.3 ± 1.5 kg ) . In Study 1 , muscle glycogen content decreased by only 60 % . Adventure racing requires a high energy expenditure , with large inter-individual variation . A large energy deficit is caused by inadequate energy intake , possibly due to suppressed appetite and gastrointestinal problems . The oxygen pulse , comparing start to 12 h of exercise and beyond , increased by 10 % and 5 % in Study 1 and Study 2 respectively . Hence , estimations of energy expenditure from heart rate recordings should be corrected according to this drift", "Exercise-induced hypogonadotropic hypogonadism is well recognized among female endurance athletes but is less commonly observed in male endurance athletes . We have reported a well-characterized case of severe acquired hypogonadotropic hypogonadism in a male distance runner with osteopenia , stress fracture , and sexual dysfunction . Using this case as an index , we hypothesized that the presence of 1 or more specific risk factors would prospect ively identify male endurance athletes with exercise-induced hypogonadotropic hypogonadism . These include a history of stress fracture , sexual dysfunction , or the initiation of endurance exercise before age 18 years . We studied 28 male endurance runners younger than 50 years who ran more than 40 miles per week . Of these runners , 15 had 1 or more of the above risk factors ( group 1 ) , and the remaining 13 had none of the putative risk factors ( group 2 ) . A group of 10 sedentary control subjects was also studied ( group 3 ) . There was no difference between groups 1 and 2 in weekly training mileage . Group 1 was younger than group 2 ( 32 + /- 10 years versus 39 + /- 6 years , P < .05 ) and had a lower body mass index ( 22.4 + /- 1.9 kg per m2 versus 23.9 + /- 2.2 kg per m2 , P < .05 ) . By bioelectric impedance , preliminary data showed that group 1 had a reduced body fat content ( group 1 , 14.5 % + /- 2.8 % ; group 2 , 16.9 % + /- 2.0 % ; and group 3 , 17.5 % + /- 4.1 % ; P < .05 ) . Fasting morning concentrations of free testosterone ( group 1 , 45.3 + /- 26.4 pmol/l ; group 2 , 88.8 + /- 24.3 pmol/l ; and group 3 , 69.1 + /- 21.5 pmol/l ) and luteinizing hormone ( group 1 , 1.7 + /- 0.7 IU per liter ; group 2 , 2.0 + /- 1.1 IU per liter ; and group 3 , 1.9 + /- 0.6 IU per liter ) did not differ among the groups ( P > .05 ) . One subject with primary hypogonadism was identified in group 1 . The presence of the aforementioned risk factors does not predict the occurrence of exercise-induced hypogonadotropic hypogonadism among male endurance runners in this pilot study . A larger sample size or more discriminating risk factors ( or both ) may be necessary to identify this uncommon but potentially debilitating condition", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "The objective of this study was to determine the effect of creatine supplementation on performance and body composition of swimmers . Eighteen swimmers were evaluated in terms of post-performance lactate accumulation , body composition , creatine and creatinine excretion , and serum creatinine concentrations before and after creatine or placebo supplementation . No significant differences were observed in the marks obtained in swimming tests after supplementation , although lactate concentrations were higher in placebo group during this period . In the creatine-supplemented group , urinary creatine , creatinine , and body mass , lean mass and body water were significantly increased , but no significant difference in muscle or bone mass was observed . These results suggest that creatine supplementation can not be considered to be an ergogenic supplement ensuring improved performance and muscle mass gain in swimmers", "PURPOSE To study the effect of carbohydrate compared to placebo ingestion on plasma cytokines and muscle cytokine mRNA following 2.5 h of intensive cycling in 15 trained cyclists . METHODS Fifteen trained cyclists cycled for 2.5 h at 60 % Wmax on two occasions while receiving 4 mL.kg.15 min carbohydrate ( 6 % ) ( CHO ) or placebo ( PLA ) beverages in a r and omized , counterbalanced design . Blood and vastus lateralis muscle biopsy sample s were collected before and after exercise and 12 h postexercise and compared to sample s taken from five cyclists who rested in the lab during the exercise sessions . Blood cell counts were determined , and plasma was analyzed for interleukin (IL)-6 , IL-10 , IL-1 receptor antagonist ( ra ) , IL-8 , cortisol , epinephrine , glucose , and insulin . Muscle was analyzed for glycogen content and relative gene expression of four cytokines , IL-6 , IL-8 , tumor necrosis factor ( TNF ) alpha , and IL-1beta , using real-time quantitative reverse transcriptase polymerase chain reaction . RESULTS Plasma glucose and insulin were higher , and epinephrine , cortisol , IL-6 , IL-10 , and IL-1ra , but not IL-8 , were significantly lower postexercise in CHO versus PLA . Muscle glycogen content decreased 68 % immediately postexercise and the pattern of change did not differ between CHO and PLA . Muscle IL-6 , IL-8 , TNF-alpha , but not IL-1beta mRNA increased immediately postexercise compared to controls , with no differences between CHO and PLA . CONCLUSION CHO compared to PLA beverage ingestion attenuated the increase in plasma cortisol , epinephrine , IL-6 , IL-10 , and IL-1ra , but not muscle IL-6 , IL-8 , and TNF-alpha mRNA in athletes cycling 2.5 h at 60 % Wmax", "The purpose of this study was to assess the effect of exercise intensity during an incremental exercise test on plasma Mg concentration in well-trained euhydrated athletes . Twenty-seven well-trained endurance athletes carried out a cycloergometer test : after a warm-up of 10 min at 2.0 W·kg(-1 ) , the workload increased by 0.5 W·kg(-1 ) every 10 min until exhaustion . Oxygen uptake ( VO(2 ) ) , blood lactate concentration ( [La(-)](b ) ) , catecholamines , and plasma Mg were measured at rest , at the end of each stage and at 3 , 5 and 7 minutes post-exercise . Urine specific gravity ( U(SG ) ) was analyzed before and after the test , and subjects drank water ad libitum . Fat oxidation rate ( FAT(oxr ) ) , carbohydrate oxidation rate ( CHO(oxr ) ) , energy expenditure from fat ( EE(FAT ) ) , energy expenditure from carbohydrate ( EE(CHO ) ) , and total EE ( EE(TOTAL ) ) were estimated using stoichiometric equations . Plasma Mg concentration at each relative exercise intensity ( W·kg(-1 ) ) were compared by means of repeated- measures ANOVA . Pearson 's correlations were performed to assess the relationship between variables . The significance level was set at p<0.05 . No significant differences were found in U(SG ) between before and after the test ( 1.014±0.004 vs 1.014±0.004 g·cm(-3 ) ) . Nor were significant differences found in plasma Mg as a function of the different exercise intensities . Further , no significant correlations were detected between Mg and metabolic variables . In conclusion , acute exercise at a range of submaximal intensities in euhydrated well-trained endurance athletes does not affect plasma Mg concentration , suggesting that the plasma volume plays an important role in Mg homeostasis during exercise", "The thermogenic response to food ( TRF ) and substrate oxidation were studied in 12 endurance-trained and 13 untrained female subjects . Energy expenditure and substrate oxidation were calculated by indirect calorimetry before and for 6 h after an oral test meal and after the same meal given intragastrically on a separate occasion . The TRF was calculated after the oral meal , the obligatory component after the intragastric meal ( OTRF ) , and the facultative component from the difference between the two . VO(2 max ) was measured on a treadmill and body composition by underwater weighing . The TRF and OTRF were significantly higher in trained than in untrained subjects : 223 + /- 63 vs. 185 + /- 50 kJ/6 h ( P < 0.03 ) and 174 + /- 38 vs. 131 + /- 37 kJ/6 h ( P < 0.01 ) for the TRF and OTRF in trained vs. untrained subjects , respectively . Multiple regression analysis showed that maximum O(2 ) consumption ( VO(2 max ) ) , but not percentage of body fat , was significantly related to OTRF ( r = 0.68 , P < 0.01 ) . Trained subjects had higher fatty acid oxidation than untrained subjects before ( 0.6 vs. 0.4 mg . kg(-1 ) . min(-1 ) , P < 0.05 ) and after the oral meal ( 13 + /- 6 vs. 8 + /- 4 g/6 h P < 0.05 ) . These results demonstrate that 1 ) TRF is higher in trained than in untrained women ; 2 ) this is due to a higher cost of nutrient digestion , absorption and storage ; 3 ) the difference is related to higher VO(2 max ) ; and 4 ) fatty acid oxidation is greater in trained women in both the postabsorptive and postpr and ial states . These observations suggest that endurance training induces metabolic changes that favor leanness", "Abstract Taipale , RS , Mikkola , J , Salo , T , Hokka , L , Vesterinen , V , Kraemer , WJ , Nummela , A , and Häkkinen , K. Mixed maximal and explosive strength training in recreational endurance runners . J Strength Cond Res 28(3 ) : 689–699 , 2014—Supervised periodized mixed maximal and explosive strength training added to endurance training in recreational endurance runners was examined during an 8-week intervention preceded by an 8-week preparatory strength training period . Thirty-four subjects ( 21–45 years ) were divided into experimental groups : men ( M , n = 9 ) , women ( W , n = 9 ) , and control groups : men ( MC , n = 7 ) , women ( WC , n = 9 ) . The experimental groups performed mixed maximal and explosive exercises , whereas control subjects performed circuit training with body weight . Endurance training included running at an intensity below lactate threshold . Strength , power , endurance performance characteristics , and hormones were monitored throughout the study . Significance was set at p ⩽ 0.05 . Increases were observed in both experimental groups that were more systematic than in the control groups in explosive strength ( 12 and 13 % in men and women , respectively ) , muscle activation , maximal strength ( 6 and 13 % ) , and peak running speed ( 14.9 ± 1.2 to 15.6 ± 1.2 and 12.9 ± 0.9 to 13.5 ± 0.8 km Ł h−1 ) . The control groups showed significant improvements in maximal and explosive strength , but Speak increased only in MC . Submaximal running characteristics ( blood lactate and heart rate ) improved in all groups . Serum hormones fluctuated significantly in men ( testosterone ) and in women ( thyroid stimulating hormone ) but returned to baseline by the end of the study . Mixed strength training combined with endurance training may be more effective than circuit training in recreational endurance runners to benefit overall fitness that may be important for other adaptive processes and larger training loads associated with , e.g. , marathon training", "Objective and Methods : The present controlled-training , double-blind study ( supplemented , n = 7 ; placebo , n = 9 ) investigated whether taper training ( TT ) and antioxidant supplementation , i.e. , 150 μg of selenium , 2000 IU of retinol , 120 mg of ascorbic acid and 30 IU of α-tocopherol , modulates antioxidant potential , redox status and oxidative damage occurrence both at rest and in response to exercise . Two weeks of TT followed four weeks of overloaded training . Dietary intakes were recorded . Before and after TT , triathletes did a duathlon consisting of 5-km run , 20-km bike and 5-km run . Biological studies were conducted at rest and after exercise . Results : Whatever the nutritional status , TT induced a decrease in resting blood reduced glutathione ( GSH ) concentration ( p < 0.001 ) , erythrocyte superoxide dismutase ( SOD ) activity ( p < 0.0001 ) and plasma total antioxidant status ( TAS ) ( p < 0.05 ) . Only in the supplemented group ( Su ) with TT , did plasma glutathione peroxidase ( GSH-Px ) activity decrease ( p < 0.05 ) and CD4 + cell concentration increase ( p < 0.05 ) . However , antioxidant supplementation increased plasma TAS increase in response to exercise and TT ( p < 0.05 ) . After exercise , TT also induced a lower decrease in blood reduced and oxidized ( GSSG ) glutathione ( p < 0.01 ) in both groups , but TT had no effect on lipoperoxidation as estimated by plasma thiobarbituric reactive substances or on muscular damage occurrence estimated by plasma creatine kinase isoenzyme MB mass . Conclusion : During TT , antioxidant supplementation at nutritional doses reinforces antioxidant status response to exercise , with an effect on exercise-induced oxidative stress , and no effect on oxidative damage", "The aim of this study was to examine the effects of a 7-day Zone diet compared with a normal diet on maximal oxygen uptake ( Vo2max ) , running time to exhaustion during endurance performance , and body composition . Eight men , with the following physical characteristics ( mean ± SE ) , participated in this study : age , 26.1 ± 1.9 years ; height , 178 ± 1.7 cm ; mass , 70.7 ± 2.1 kg ; and Vo2max , 54.6 ± 3.1 ml.kg-1.min-1 . All subjects undertook pretesting for Vo2max , time to exhaustion ( 80 % Vo2max ) , and body composition ( Biostat 1500 ) before following either the normal diet or the Zone diet for 7 days . These performance trials were performed before and after the dietary period . There was a significant ( p < 0.05 ) decrease in total energy consumption from a mean of 2,314 ± 334 kcal on a pretest diet to 1,994 ± 438 kcal on the Zone diet . Subjects showed a significant reduction ( p < 0.02 ) in body mass from 70.7 ± 2.1 kg to 69.8 ± 2.1 kg . In the 80 % Vo2max time to exhaustion trial , there was a significant reduction ( p < 0.05 ) in time to exhaustion from 37.68 ± 8.6 minutes for the pretest diet to 34.11 ± 7.01 minutes for the Zone diet . In conclusion , the cl aim of the authors of the Zone diet that performance time and Vo2max can be improved was not shown in this 1-week research trial . We would suggest that this is not a nutritional strategy that athletes should use until further work has been conducted", "PURPOSE The purpose of this study was to assess whether a brief period ( 20 min ) of intravenous ( i.v . ) fluid rehydration versus oral rehydration differentially affects cardiovascular , thermoregulatory , and performance factors during exhaustive exercise in the heat . METHODS Following dehydration ( -4 % of body weight ) , eight nonacclimated highly trained cyclists ( age = 23.5 + /- 1.2 yr ; VO2peak = 61.4 + /- 0.8 mL x kg x min(-1 ) ; body fat = 13.5 + /- 0.6 % ) rehydrated and then cycled at 70 % VO2peak to exhaustion in 37 degrees C. Rehydration ( r and omized , cross-over design ) included : 1 ) CONTROL ( no fluid ) , 2 ) DRINK ( oral rehydration , 0.45 % NaCl ) equal to 50 % of prior dehydration , and 3 ) IV ( intravenous rehydration , 0.45 % NaCl ) , equal to 50 % of prior dehydration . Thus , in the DRINK and IV treatments subjects began exercise ( EX ) at -2 % of body weight . RESULTS Exercise time to exhaustion was not different ( P = 0.07 ) between DRINK ( 34.9 + /- 4 min ) and IV ( 29.5 + /- 3.5 min ) , but both were significantly ( P < 0.05 ) longer than CONTROL ( 18.9 + /- 2.7 min ) . Plasma volume was better ( P < 0.05 ) restored during IV than CONTROL and DRINK at pre-exercise and 5 min EX , but different ( P < 0.05 ) from only CONTROL at 15 min EX . Plasma lactate during DRINK was lower ( P < 0.05 ) than IV at 15 min EX and postexercise . Heart rate during CONTROL was greater ( P < 0.05 ) than DRINK and IV from 0 - 8 min EX , and greater ( P < 0.05 ) than DRINK from 10 - 14 min EX . Rectal temperature during DRINK was less ( P < 0.05 ) than IV from 0 - 24 min EX . Mean weighted skin temperature during DRINK was less ( P < 0.05 ) than IV from 4 - 12 min EX . CONCLUSIONS Thus , despite no statistically significant performance differences between DRINK and IV , it appears that certain physiological parameters were better maintained in the DRINK trial , and the trend toward performance differences may be important to elite athletes", "Summary The purpose of the present study was to examine the influence of a high carbohydrate diet on running performances during a 30-km treadmill time trial . Eighteen runners ( 12 men and 6 women ) took part in this study and completed a 30-km time trial on a level treadmill without modifying their food intake ( trial 1 ) . The runners were then r and omly assigned to a control or a carbohydrate ( CHO ) group . The CHO group supplemented their normal diets with additional carbohydrate in the form of confectionery products during the 7 days before trial 2 ; the control group matched the increased energy intake of the CHO group by consuming additional fat and protein . The mean ( SEM ) carbohydrate intake of both groups was 334 ( 22 ) g before trial 1 , after which the CHO group consumed 566 ( 29 ) g · day−1 for the first 3 days and 452 ( 26 ) g · day−1 for the remaining 4 days of recovery . Although there was no overall difference between the performance times for the two groups during trial 2 , the CHO group ran faster during the last 5 km of trial 2 than during trial−1 [ 3.64 ( 0.24 ) m · s−1 vs 3.44 ( 0.26 ) m · s−1P < 0.05 ] . Furthermore , the 6 men in the CHO group ran the 30 km faster after carbohydrate loading [ 131.0 ( 5.4 ) min vs 127.4 ( 4.9 ) min;P < 0.05 ] , whereas there was no such improvement in times of the men in the control group . Blood glucose concentrations of both groups decreased below pre-exercise values during trial−1 ( P < 0.001 ) , but only the control group had a decrease in blood glucose concentrations during trial 2 ( P < 0.001 ) . There were no differences between the concentrations of plasma catecholamines of the control group during the two trials . However , the adrenaline concentrations of the CHO group were lower ( P < 0.05 ) during trial 2 than during trial 1 , even though they ran faster during trial 2 . These results confirm that dietary carbohydrate loading improves endurance performance during prolonged running and that confectionery can be used as an effective means of supplementing the normal carbohydrate intake in preparation for endurance races", "Previous evidence suggests that quercetin supplementation increases performance in humans . We examined the effects of 3 weeks of quercetin supplementation on fuel utilization , gross efficiency ( GE ) , and perceived effort during 3 h of cycling over 3 successive days . Forty cyclists were r and omized into quercetin and placebo groups and tested for maximal oxygen consumption ( 53.2 + /- 1.2 and 54.7 + /- 1.1 mL.kg(-1).min(-1 ) ) . For 3 weeks following maximal oxygen consumption testing , subjects supplemented either 1000 mg.day(-1 ) quercetin or placebo during normal training . Following supplementation , subjects cycled at 57 % maximum power for 3 h , on 3 successive days , using their own bicycles fitted to CompuTrainer Pro Model trainers ( RacerMate , Seattle , Wash. ) . Metabolic measurements were taken every 30 min for each 3-h ride . Muscle biopsies obtained from the vastus lateralis immediately pre-exercise and postexercise on days 1 and 3 were analyzed for muscle glycogen content . Power output remained constant for all 3 exercise trials , but significant decreases over time were measured for GE , cadence , respiratory exchange ratio , blood glucose , and muscle glycogen . Significant increases were measured for heart rate and volume of oxygen consumption over time . No quercetin treatment effect was observed for any of the outcome measures in this study . These data indicate that GE is reduced during an exhausting 3-h bout of exercise . However , quercetin did not significantly affect any outcomes in these already well-trained subjects", "Objective : To observe changes in hip , spine , and tibia bone characteristics in female cyclists over the course of 1 year of training . Design : Prospect i ve observational study . Setting : Laboratory . Participants : Female cyclists ( n = 14 ) aged 26 - 41 years with at least 1 year of competition history and intent to compete in 10 or more races in the coming year . Assessment of Risk Factors : Women who train and compete in road cycling as their primary sport . Main Outcome Measures : Total body fat-free and fat mass and lumbar spine and proximal femur areal bone mineral density ( aBMD ) and bone mineral content ( BMC ) assessment s by dual-energy x-ray absorptiometry . Volumetric BMD and BMC of the tibia were measured by peripheral quantitative computed tomography at sites corresponding to 4 % , 38 % , 66 % , and 96 % of tibia length . Time points were baseline and after 12 months of training and competition . Results : Weight and body composition did not change significantly over 12 months . Total hip aBMD and BMC decreased by −1.4 % ± 1.9 % and −2.1 % ± 2.3 % ( P < 0.02 ) and subtrochanter aBMD and BMC decreased by −2.1 % ± 2.0 % and −3.3 % ± 3.7 % ( P < 0.01 ) . There was a significant decrease in lumbar spine BMC ( −1.1 % ± 1.9 % ; P = 0.03 ) . There were no significant bone changes in the tibia ( P > 0.11 ) . Conclusions : Bone loss in female cyclists was site specific and similar in magnitude to losses previously reported in male cyclists . Research is needed to underst and the mechanisms for bone loss in cyclists", "PURPOSE The aim of this investigation was to measure plasma visfatin and ghrelin responses to a single endurance rowing training session in male competitive single scull rowers . METHODS Nine national level male rowers ( 20.1 + /- 1.5 yr ; 183.9 + /- 4.3 cm ; 81.0 + /- 5.0 kg ; 10.8 + /- 3.3 % body fat ) completed two trials ( exercise or control ) on separate days . The exercise consisted of a prolonged rowing training session lasting approximately 2 h ( distance = 20.7 + /- 1.4 km ; HR = 133 + /- 4 bpm ; intensity = 80.2 + /- 1.6 % of the HR turn point ) followed by a 30-min rest . Venous blood sample s were collected before and after on-water rowing . The control trial consisted of rest and blood collection similar to exercise trial . RESULTS No differences were found at baseline values for plasma visfatin , ghrelin , and leptin for both trials . The estimated energy expenditure of the exercise trial was 1200 - 1500 kcal . Plasma visfatin ( -10.0 % ; P < 0.05 ) and leptin ( -20.0 % ; P < 0.05 ) were reduced , and ghrelin concentration was increased ( + 12.2 % ; P < 0.05 ) after a 30-min postexercise . No differences in plasma visfatin , ghrelin , or leptin over time were observed during control trial . There was no relationship between basal visfatin and body composition , energy balance , aerobic power , or blood biochemical data . Plasma visfatin ( r = -0.76 ) and ghrelin ( r = 0.75 ) measured immediately after the training session were related ( P < 0.05 ) to the distance covered , and no relation was observed for postexercise leptin ( r = -0.16 ; P > 0.05 ) . CONCLUSION Acute negative energy balance induced by a single endurance rowing training session elicited an inverse metabolic response in visfatin and ghrelin in competitive male rowers . Our results suggest that peripheral markers of negative energy balance , such as visfatin and ghrelin , may be regarded as signals for metabolic reaction to the energy cost of acute exercise . The results of our study also suggest that an energy-deficit threshold must be met for the response to occur", "In order to study nutrient intake of amateur runners during a mountain marathon , compliance with recommendations , and association with performance , an intake of 42 participants in a Swiss mountain marathon was assessed by direct observation . Data on demographics , dietary preparation and race experience were obtained by question naires . Anthropometrical measures were performed before and after the race . Mean hourly intakes ( SD ) of fluid , carbohydrate , energy and sodium were 545 ( 158 ) ml , 31 ( 14 ) g , 141 ( 63 ) kcal [ or 590 ( 264 ) kJ ] , and 150 ( 203 ) mg respectively . A third of the runners drank 600 ml h−1 or more , 52 % consumed less than 30 g h−1 carbohydrates , 95 % consumed less than 500 mg h−1 sodium . Mean weight loss was 4 ( 1.5 ) kg ; 30 runners ( 71 % ) lost over 3 % body mass . Mean running time was 7 h 3 min ( 1 h 17 min ) . Most participants failed to meet nutritional recommendations . None were at risk of overhydration . Body composition and race experience were correlated with performance , but not nutrient intake . Because experienced runners are well trained , fitter , and know better their personal needs during such a race , it is difficult to disentangle these associations . As causal relationship can not be proven with this cross-sectional design , non-compliance with intake recommendations requires additional experimental research on the impact of nutrient intake on field performance", "PURPOSE The training program undertaken by many athletes will affect directly the total , habitual energy requirements of that individual . Unless that energy requirement is met via the diet and or supplementation , chronic negative energy balance will ensue , which will have both short-term and long-term effects not only on performance but also on general health . The aim of this research was therefore to determine the energy expenditure ( EE ) and hence energy requirements of lightweight female rowers and , further , to compare this with their self-reported energy intake ( EI ) . METHODS The EI of seven lightweight female rowers was measured using a self-reported 4-d weighed dietary record . EE was determined using the doubly labeled water ( DLW ) technique over a 14-d period . RESULTS The mean ( + /-SD ) age , height , and weight of the subjects was 20 ( + /-1.1 ) yr , 168.8 ( + /-4.7 ) cm , and 60.9 ( + /-2.3 ) kg , respectively . The rowers self-reported EI was 2,214 ( + /-313 ) kcal x d(-1 ) and their total EE was 3,957 ( + /-1,219 ) kcal x d(-1 ) . After adjusting total EE for changes in body weight ( mean ( + /-SD ) -1.2 ( + /-1.2 ) kg ) , the comparison between adjusted EI and reported showed a bias to underreporting of 1,133 ( + /-1,539 ) kcal x d(-1 ) or 34 % . The bias was not consistent across adjusted EI , and two of the seven subjects overreported their intake . CONCLUSIONS Due to the underreporting of EI , diet recording may not be an appropriate way of assessing energy requirements in lightweight female rowers . A benefit of accurately determining energy requirements , as with DLW , is that female lightweight rowers will be able to successfully manipulate their EI and achieve the set weight cut-off for participation without compromising their health or performance", "Objective To investigate change in serum sodium concentration and its potential causes during a cold weather ultradistance race . Design Descriptive research . Setting A 100-mile ( 161-km ) race over a snow-packed course in the Alaskan wilderness . Athletes competed in 1 of 3 divisions : foot , bike , or ski . Participants Twenty athletes ( 11 runners , 6 cyclists , 3 skiers ) volunteered for the study . Interventions None . Main Outcome Measures Subjects were weighed and had blood drawn for hematocrit , serum sodium , serum aldosterone , and plasma arginine vasopressin concentrations pre- and postrace . Fluid and sodium intake were determined by race dietary analysis . Results Serum sodium concentration decreased significantly prerace ( 140.8 ± 1.2 mmol/L ) to postrace ( 138.4 ± 2.2 mmol/L ) , although no athletes were classified as hyponatremic . Mean weight loss was significant during the race ( −1.2 kg ) , although 1 athlete maintained his weight , and 3 athletes gained small amounts of weight ( 0.2 kg , 0.2 kg , and 0.5 kg , respectively ) . Hematocrit decreased significantly prerace ( 42.2 ± 3.5 ) to postrace ( 40.3 ± 4.1 ) . Plasma arginine vasopressin and serum aldosterone increased significantly during the race ( 2.6 ± 0.7 to 6.0 ± 4.6 pg/mL and 5.1 ± 2.6 to 40.8 ± 25.1 ng/dL , respectively ) . Fluid consumption was 300 ± 100 mL/h , and sodium intake was 310 ± 187 mg/h . Conclusions Decreased serum sodium concentration after a cold weather ultradistance race was due to fluid overload caused by excessive fluid consumption . Current recommendations that ultradistance athletes consume 500 to 1000 mL/h may be too high for athletes competing in the extreme cold", "This study investigated the effect of creatine monohydrate ( Cr ) supplementation on performance and training volume in rowers . Twenty-two rowers trained with continuous and interval rowing and resistance training 4 and 2 days/week , respectively , for 6 weeks . Cr supplementation consisted of a 5-day load ( 0.3 g/kg(-1 ) x day(-1 ) ) followed by a 5-week maintenance dose ( 0.03 g/kg(-1 ) x day(-1 ) ) while training . Five days of Cr loading did not change body composition , repeated interval rowing performance , 2,000-m rowing times , or strength performance . Five additional weeks of training with a maintenance dose of Cr or placebo significantly improved body composition , VO2max , 2,000-m rowing times , repeated power interval performance , and strength to a similar extent in both groups . Subjects training with Cr did not perform more repetitions per set of strength exercise nor produce or maintain higher power outputs during repeated rowing sessions . Cr supplementation did not increase performance or training volume over a placebo condition in rowers that performed a combined high intensity rowing and strength program", "The aim of this investigation was to examine the effects of menstrual cycle phase on substrate oxidation and lactate concentration during exercise . Eleven eumenorrheic female rowers ( 18.4 ± 1.9 years ; 172.0 ± 4.0 cm ; 67.2 ± 8.4 kg ; 27.7 ± 4.8 % body fat ) completed 1 h rowing ergometer exercise at 70 % of maximal oxygen consumption ( VO2max ) during two different phases of the menstrual cycle : the follicular phase ( FP ) and the luteal phase ( LP ) . Resting and exercise measurements of the whole body energy expenditure , oxygen consumption ( VO2 ) , respiratory exchange ratio ( RER ) , substrate oxidation and lactate blood levels were made . Energy expenditure , VO2 and heart rate during the 1-h exercise were not significantly different ( P > 0.05 ) among menstrual cycle phases . Resting RER and RER during the entire 1 h exercise period were not significantly different among menstrual cycle phases . There was an increase ( P < 0.05 ) in RER in the transition between rest and exercise and a further increase in RER occurred after the first 30 min of exercise at both menstrual cycle phases . Blood lactate concentrations significantly increased in the transition between rest and exercise and remained relatively constant during the whole 1 h of exercise in both menstrual cycle phases . No menstrual cycle phase effect ( P > 0.05 ) was observed for blood lactate concentrations . In conclusion , our results demonstrated no effect of menstrual cycle phase on substrate oxidation and blood lactate concentration during rowing exercise at 70 % of VO2max in athletes . Normally menstruating female rowers should not be concerned about their menstrual cycle phase with regard to substrate oxidation in everyday training", "Six successful members of the British Women 's Lightweight Rowing Team were assessed before and after two-month ( 1990 ) and four-month ( 1991 ) periods of weight-reduction controlled by reduced caloric intake , while engaged in their normal physical training . Fat free mass ( FFM ) was calculated from body weight ( BW ) by utilising total body potassium measurements . Maximal oxygen intake ( VO2max ) , respiratory anaerobic threshold ( Tvent ) , upper body anaerobic peak power ( PP ) and mean power ( MP ) outputs , and knee flexor ( KF ) and extensor ( KE ) isokinetic peak torques were among the physiological parameters assessed . No statistical differences were noted between the data obtained prior to the two weight-reduction periods , and both periods result ed in lower BW ( p < 0.001 ) and FFM ( p < 0.05 ) ; approximately 50 % of the lost BW was FFM . At the end of the two-month weight-reduction period Tvent ( p < 0.02 ) and KF ( p < 0.02 ) decreased . In contrast , a similar BW loss during the four-month period was associated with higher VO2max ( p < 0.01 ) and PP ( p < 0.05 ) compared with values prior to weight reduction . Comparisons between the percentage changes pre to post BW loss showed that the longer weight-reduction period was associated with significantly improved VO2max ( p < 0.01 ) , Tvent ( p < 0.005 ) , PP ( p < 0.05 ) and KF ( p < 0.05 ) . We conclude : a ) the proportion ( 50 % ) of weight lost as FFM in the present elite rowers is higher than the suggested optimal figure of 22 % , and b ) compared to four months , 6 - 7 % of BW loss over two months may adversely influence fitness-related parameters in international lightweight oarswomen", "OBJECTIVES To investigate the interaction of serum leptin , IGF-1 , estradiol and cortisol in salvia as well as IL-6 with nutritional composition in female athletes ( swimming ) according to the training protocol ( competition ( C ) , sprint ( S ) , recreation ( R ) , endurance ( E ) ) . DESIGN / METHODS In 23 young ( 10 - 19 years old ) female athletes ( Bavarian swimming competition ) in different training stages nutritional protocol s were evaluated using st and ardized question naires . Body composition was measured by using analysis of bioimpedance . Estradiol , IGF-1 , leptin and IL-6 in serum were measured by ELISA . To obtain circadian profiles of cortisol salvia probes were sample d at 4 h intervals and cortisol in saliva was measured . RESULTS Daily intake of kilocalories varied significantly and was highest during R with the highest percentage of nutritional fat intake ( 37.3 % ) when compared to C ( 28.1 % , p=0.001 ) . BMI was associated with leptin in all training stages and IL-6 in R , C and E. Leptin , IGF-1 and cortisol in salvia were dependent on training stages while serum levels of estradiol were not . Nutritional fat intake ( p=0.07 in R ) as well as serum levels of IGF-1 ( p=0.014 in E ) were significantly associated with estradiol but not with serum leptin levels or salivary cortisol . CONCLUSIONS In female athletes nutritional composition has an impact on serum hormones ( leptin , IGF-1 as well as estradiol ) and may be also on cytokines ( IL-6 ) . Leptin , IGF-1 and salivary cortisol levels represent the intensity of physical training and possibly overtraining . In our female athletes no findings indicative of female athlete triad could be demonstrated", "Mineral status of highly trained ( HT ) women runners ( n = 14 ) and untrained ( UT ) women ( n = 11 ) , as determined from 3-day dietary records , blood , and urine sample s , was compared . HT women had significantly higher energy ( HT : 2331 + /- 121 vs UT : 1973 + /- 107 kcal/day ; p less than 0.05 ) , magnesium ( Mg ) ( HT : 369 + /- 29 vs UT : 262 + /- 18 mg/day , p less than 0.05 ) , and potassium ( K ) ( HT : 3874 + /- 384 vs UT : 2646 + /- 244 mg/day ; p less than 0.05 ) intakes than UT women . However , mean daily intakes of calcium ( Ca ) , iron ( Fe ) , copper ( Cu ) , and sodium ( Na ) were not different for the two groups . Plasma concentrations and urinary excretion of Ca , Mg , and Cu of HT and UT women did not differ . Plasma Fe concentrations of the two groups were also similar ( HT : 21 + /- 2 vs UT : 22 + /- 1 mumol/L ) , and , although serum ferritin concentrations of HT women were lower than UT women ( HT : 18 + /- 4 vs UT : 30 + /- 6 micrograms/L ) , the difference was not significant . Urinary Na excretion of the two groups did not differ . HT women had a higher K intake than UT women but urinary K excretion of the two groups did not differ . Whether present mineral intakes by HT women are adequate during periods of intensive training remains to be determined", "The aim of this study was to determine if there is a training effect on leptin levels at rest or after prolonged exercise during an 8-month training season of rowers . Eleven trained rowers were evaluated at three sessions ( control , early and late ) during the season . At the early and late sessions , leptin and insulin concentrations were measured before and after 90 min of rowing exercise ( 70 - 75 % maximal oxygen consumption , VO(2)max ) , 120 min and 24 h afterwards . Anthropometrics data were collected at each session . Energy balance was determined on the days of exercise sessions . Resting leptin levels were not modified over the season and were in correlation with weight and body fat ( P<0.05 ) . At exercise sessions , a delayed reducing effect of acute exercise on leptin levels appeared ( P<0.01 compared to pre-exercise ) . After 24 h of recovery , leptin levels remained lower at early ( P<0.001 ) but not at late sessions , and a training effect appeared between early and late sessions ( P<0.001 ) . Leptin levels were correlated with energy balance at early and late sessions ( P<0.05 ) . At the two training sessions , insulin levels were decreased immediately post-exercise and at 120 min of recovery compared to pre-exercise ( P<0.01 and P<0.001 respectively for the two sessions ) . A training effect on insulin levels appeared at 24 h of recovery ( P<0.05 between early and late sessions ) . We concluded that rowing training over a season did not alter resting leptin levels but it attenuated the exercise-induced reduction in leptin . This could be attributed to an alteration in energy balance , although an influence of training on insulin may also be involved in the leptin response to acute exercise", "We investigated the effects of two 5-wk periods of intermittent hypoxia on running economy ( RE ) . 11 male and female middle-distance runners were r and omly assigned to the intermittent hypoxia group ( IHG ) or to the control group ( CG ) . All athletes trained for a 13-wk period starting at pre-season until the competition season . The IHG spent additionally 2 h at rest on 3 days/wk for the first and the last 5 weeks in normobaric hypoxia ( 15 - 11 % FiO2 ) . RE , haematological parameters and body composition were determined at low altitude ( 600 m ) at baseline , after the 5 ( th ) , the 8 ( th ) and the 13 ( th ) week of training . RE , determined by the relative oxygen consumption during submaximal running , ( -2.3+/-1.2 vs. -0.3+/-0.7 ml/min/kg , P<0.05 ) and total running time ( + 1.0+/-0.9 vs. + 0.4+/-0.5 min , P<0.05 ) changed significantly between the IHG and CG only during the first 5-wk period . Haematological and cardiorespiratory changes indicate that the improved RE was associated with decreased cardiorespiratory costs and greater reliance on carbohydrate . Intermittent hypoxia did not affect RE during the second 5-wk period . These findings suggest that the effects of intermittent hypoxia on RE strongly depend on the training phase", "PURPOSE To examine the effect of oral contraceptives ( OC ) on body weight , fat mass , percent body fat , and lean mass in young female distance runners . METHODS The study population consisted of 150 female competitive distance runners aged 18 - 26 yr who had participated in a 2-yr r and omized trial of the effect of the OC Lo/Ovral ( 30 microg of ethinyl estradiol and 0.3 mg of norgestrel ) on bone health . Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry , respectively . RESULTS Women r and omized to the OC group tended to gain slightly less weight ( adjusted mean difference ( AMD ) = -0.54 + /- 0.31 kg.yr , P = 0.09 ) and less fat ( AMD = -0.35 + /- 0.25 kg.yr , P = 0.16 ) than those r and omized to the control group . OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women ( those who had 10 or more menstrual cycles in the year before baseline ; AMD = 0.77 + /- 0.17 kg.yr , P < 0.0001 ) but not among women with fewer than 10 menstrual cycles in that year ( AMD = 0.02 + /- 0.35 kg.yr , P = 0.96 ) . Treatment-received analyses yielded similar results . CONCLUSION This r and omized trial confirms previous findings that OC use does not cause weight or fat mass gain , at least among young female runners . Our finding that this OC is associated with lean mass gain in eumenorrheic runners , but not in those with irregular menses , warrants examination in other studies", "Adiponectin is secreted by adipocytes and has been implicated in the regulation of energy homeostasis . Vigorous training program represents a physical stress condition in which heavy changes in energy expenditure might increase adiponectin concentration in athletes . Therefore , the aim of the present study was to investigate if there are changes in fasting adiponectin concentration during preparatory period in elite male rowers . Twelve rowers ( mean and SD ; age : 20.8+/-3.0 years ; height : 192.9+/-4.7 cm ; body mass : 91.9+/-5.3 kg ; body fat percentage : 11.9+/-1.4 % ) were tested seven times over a 24-week training season . In addition to adiponectin , leptin , insulin , growth hormone , and glucose values were evaluated . Maximal oxygen consumption ( VO ( 2 max ) ) and aerobic power ( Pa ( max ) ) were determined before and after the training period . Training was mainly organized as low-intensity prolonged training . Significant increases in VO ( 2 max ) ( by 3.2+/-1.8 % ; from 6.2+/-0.5 to 6.4+/-0.4 l/min ) , VO ( 2 max/kg ) ( by 2.2+/-2.0 % ; from 67.9+/-3.0 to 69.4+/-3.0 ml/min/kg ) and Pa ( max ) ( by 4.6+/-6.3 % ; from 444.6+/-39.1 to 465.8+/-25.0 W ) were observed after the 24-week period . All measured body compositional values were similar to pretraining values after the training period . Fasting adiponectin did not change during the preparatory period . Likewise , leptin , insulin , growth hormone , and glucose values were not significantly changed after the training period . Adiponectin concentration was significantly correlated ( all p<0.05 ) with body mass ( r=-0.40 ) , body fat mass ( r=-0.33 ) , body fat free mass ( r=0.38 ) , and leptin ( r=-0.31 ) values . In conclusion , fasting adiponectin does not change throughout the prolonged training period in elite male rowers despite substantial changes in training volume . Further studies are needed to clarify possible mechanisms by which adiponectin might influence energy homeostasis during heavy training in elite athletes", "OBJECTIVE To identify nutrients , foods , and dietary patterns associated with stress fracture risk and changes in bone density among young female distance runners . DESIGN AND SETTING Two-year , prospect i ve cohort study . Observational data were collected in the course of a multicenter r and omized trial of the effect of oral contraceptives on bone health . PARTICIPANTS One hundred and twenty-five female competitive distance runners ages 18 - 26 years . ASSESSMENT OF RISK FACTORS Dietary variables were assessed with a food frequency question naire . MAIN OUTCOME MEASUREMENTS Bone mineral density and content ( BMD/ BMC ) of the spine , hip , and total body were measured annually by dual x-ray absorptiometry ( DEXA ) . Stress fractures were recorded on monthly calendars , and had to be confirmed by radiograph , bone scan , or magnetic resonance imaging . RESULTS Seventeen participants had at least one stress fracture during follow-up . Higher intakes of calcium , skim milk , and dairy products were associated with lower rates of stress fracture . Each additional cup of skim milk consumed per day was associated with a 62 % reduction in stress fracture incidence ( P < .05 ) ; and a dietary pattern of high dairy and low fat intake was associated with a 68 % reduction ( P < .05 ) . Higher intakes of skim milk , dairy foods , calcium , animal protein , and potassium were associated with significant ( P < .05 ) gains in whole-body BMD and BMC . Higher intakes of calcium , vitamin D , skim milk , dairy foods , potassium , and a dietary pattern of high dairy and low fat were associated with significant gains in hip BMD . CONCLUSIONS In young female runners , low-fat dairy products and the major nutrients in milk ( calcium , vitamin D , and protein ) were associated with greater bone gains and a lower stress fracture rate . Potassium intake was also associated with greater gains in hip and whole-body BMD", "Abstract Shing , CM , Webb , JJ , Driller , MW , Williams , AD , and Fell , JW . Circulating adiponectin concentration and body composition are altered in response to high-intensity interval training . J Strength Cond Res 27(8 ) : 2213–2218 , 2013—Adiponectin influences metabolic adaptations that would prove beneficial to endurance athletes , and yet to date there is little known about the response of adiponectin concentrations to exercise , and , in particular , the response of this hormone to training in an athlete population . This study aim ed to determine the response of plasma adiponectin concentrations to acute exercise after 2 different training programs and to determine the influence of the training on body composition . Seven state-level representative rowers ( age : 19 ± 1.2 years [ mean ± SD ] , height : 1.77 ± 0.10 m , body mass : 74.0 ± 10.7 kg , V[Combining Dot Above]O2peak 62.1 ± 7.0 ml·kg−1·min−1 ) participated in the double-blind , r and omized crossover investigation . Rowers performed an incremental grade d exercise test before and after completing 4 weeks of high-intensity interval ergometer training and 4 weeks of traditional ergometer rowing training . Rowers ' body composition was assessed at baseline and after each training program . Significant increases in plasma adiponectin concentration occurred in response to maximal exercise after completion of the high-intensity interval training ( p = 0.016 ) but not after traditional ergometer rowing training ( p = 0.69 ) . The high-intensity interval training also result ed in significant increases in mean 4-minute power output ( p = 0.002 ) and V[Combining Dot Above]O2peak ( p = 0.05 ) , and a decrease in body fat percentage ( p = 0.022 ) . Mean 4-minute power output , V[Combining Dot Above]O2peak , and body fat percentage were not significantly different after 4 weeks of traditional ergometer rowing training ( p > 0.05 ) . Four weeks of high-intensity interval training is associated with an increase in adiponectin concentration in response to maximal exercise and a reduction in body fat percentage . The potential for changes in adiponectin concentration to reflect positive training adaptations and athlete performance level should be further explored" ]

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[ "Perceived self-efficacy and pain control: opioid and nonopioid mechanisms.", "A comparison of psychological and pharmacological treatment of pediatric migraine.", "Relaxation and imagery and cognitive-behavioral training reduce pain during cancer treatment: a controlled clinical trial", "Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey.", "The importance of enhancing self-efficacy in rheumatoid arthritis.", "Hypnosis: practical applications and theoretical considerations in normal labour.", "A prospective investigation of dispositional optimism as a predictor of health-related quality of life in head and neck cancer patients", "Hypnosis or cognitive behavioral training for the reduction of pain and nausea during cancer treatment: a controlled clinical trial", "EMG Biofeedback Training, Relaxation Training, and Placebo for the Relief of Chronic Back Pain", "Hypnosis compared to relaxation in the outpatient management of chronic low back pain.", "Pain self-efficacy beliefs and pain behaviour. A prospective study" ]

[ "In this experiment , we tested for opioid and nonopioid mechanisms of pain control through cognitive means and the relation of opioid involvement to perceived coping efficacy . Subjects were taught cognitive methods of pain control , were administered a placebo , or received no intervention . Their pain tolerance was then measured at periodic intervals after they were administered either a saline solution or naloxone , an opiate antagonist that blocks the effects of endogenous opiates . Training in cognitive control strengthened perceived self-efficacy both to withst and and to reduce pain ; placebo medication enhanced perceived efficacy to withst and pain but not reductive efficacy ; and neither form of perceived self-efficacy changed without any intervention . Regardless of condition , the stronger the perceived self-efficacy to withst and pain , the longer subjects endured mounting pain stimulation . The findings provide evidence that attenuation of the impact of pain stimulation through cognitive control is mediated by both opioid and nonopioid mechanisms . Cognitive copers administered naloxone were less able to tolerate pain stimulation than were their saline counterparts . The stronger the perceived self-efficacy to reduce pain , the greater was the opioid activation . Cognitive copers were also able to achieve some increase in pain tolerance even when opioid mechanisms were blocked by naloxone , which is in keeping with a nonopioid component in cognitive pain control . We found suggestive evidence that placebo medication may also activate some opioid involvement . Because placebos do not impart pain reduction skills , it was perceived self-efficacy to endure pain that predicted degree of opioid activation", "A comparison was carried out of the efficacy of psychological and drug treatments for children with migraine . Forty-three children aged between 8 and 16 years ( mean age : 11.3 years ) who suffered from migraine received either progressive relaxation or cephalic vasomotor feedback , both with stress management training , or metoprolol , a beta-blocker . Psychological treatment was administered in ten sessions lasting six weeks and the drug treatment lasted ten weeks . Relaxation and stress management training reduced the headache index ( frequency x intensity of headache episodes ) , more effectively than metoprolol with cephalic vasomotor feedback and stress management training in between . An overall improvement over time was found with regard to frequency and intensity of headache episodes and analgesics intake . When comparing pre- to post-treatment data , children treated with relaxation training improved significantly in headache frequency and intensity , whereas those treated with cephalic vasomotor feedback improved significantly in headache frequency and duration as well as mood . The clinical improvement was stable at an 8-months follow-up", "& NA ; Few controlled clinical trials of psychological interventions for cancer pain relief exist in spite of frequent support for their importance as adjuncts to medical treatment . This study compared oral mucositis pain levels in 4 groups of cancer patients receiving bone marrow transplants ( BMT ) : ( 1 ) treatment as usual control , ( 2 ) therapist support , ( 3 ) relaxation and imagery training , and ( 4 ) training in a package of cognitive‐behavioral coping skills which included relaxation and imagery . A total of 94 patients completed the study which involved two training sessions prior to treatment and twice a week ‘ booster ’ sessions during the first 5 weeks of treatment . Results confirmed our hypothesis that patients who received either relaxation and imagery alone or patients who received the package of cognitive‐behavioral coping skills would report less pain than patients in the other 2 groups . The hypothesis that the cognitive‐behavioral skills package would have an additive effect beyond relaxation and imagery alone was not confirmed . Average visual analogue scale ( VAS ) report of pain within the therapist support group was not significantly lower than the control group ( P = 0.103 ) nor significantly higher than the training groups . Patient reports of relative helpfulness of the interventions for managing pain and nausea matched the results of VAS reports . From these results , we conclude that relaxation and imagery training reduces cancer treatment‐related pain ; adding cognitive‐behavioral skills to the relaxation with imagery does not , on average , further improve pain relief", "CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient", "OBJECTIVE To examine relationships among changes in self-efficacy and changes in other clinical ly relevant outcome measures . METHOD Subjects ( n = 44 ) were participants in a prospect i ve , r and omized stress-management study followed over 15 months . Outcome measures included self-efficacy , depression , pain , health status , and disease activity . RESULTS Correlational analyses revealed significant associations between changes in self-efficacy ( particularly total self-efficacy ) and changes in selected measures of depression , pain , health status , and disease activity . The observed associations were not due to changes in medication regimen or to nonadherence to the stress-management program . CONCLUSIONS Evidence is provided that induced changes in self-efficacy following a stress-management program were significantly related to other clinical ly important outcome measures", "OBJECTIVE To assess the effects of hypnotherapy on the first and second stages of labour in a large group of pregnant women . DESIGN A semi- prospect i ve case control study in which women attending antenatal clinics were invited to undergo hypnotherapy . SUBJECTS One hundred twenty-six primigravid women with 300 age matched controls , and 136 parous women having their second baby with 300 age matched controls . Only women who had spontaneous deliveries were included . SETTING Aberdare District Maternity Unit , Mid Glamorgan , Wales . INTERVENTION Six sessions of hypnotherapy given by a trained medical hypnotherapist during pregnancy . OUTCOME MEASURES Analgesic requirements , duration of first and second stages of labour . RESULTS The mean lengths of the first stage of labour in the primigravid women was 6.4 h after hypnosis and 9.3 h in the control group ( P < 0.0001 ) ; the mean lengths of the second stage were 37 min and 50 min , respectively ( P < 0.001 ) . In the parous women the corresponding values were 5.3 h and 6.2 h ( P < 0.01 ) ; and 24 and 22 min ( ns ) . The use of analgesic agents was significantly reduced ( P < 0.001 ) in both hypnotised groups compared with their controls . CONCLUSION In addition to demonstrating the benefits of hypnotherapy , the study gives some insight into the relative proportions of mechanical and psychological components involved in the longer duration of labour in primigravid women", "The aim of this study was to investigate the role of dispositional optimism ( DO ) as a predictor of health-related quality of life ( HRQL ) in a sample of upper aerodigestive tract cancer ( UADT ) patients . A prospect i ve observational study design was used with a cohort of patients from one centre . DO was evaluated using a French version of the Life Orientation Test ( the FLOT ) translated and vali date d for this study . HRQL was evaluated using the EORTC QLQ-C30 prior to and 3 months following treatment . The association between FLOT ratings and HRQL was evaluated using linear multiple regression analysis and a two-way ANOVA with repeated measures . Baseline data were gathered on 101 subjects and follow-up data on 88 of these . The sample was dichotomized around the median FLOT score creating ‘ optimist ’ and ‘ pessimist ’ groups . Before treatment , optimists reported better role , cognitive and emotional function , less pain and fatigue and a better global rating of HRQL than did pessimists . Following treatment , optimists reported better role and cognitive functioning , less pain and better global HRQL than did pessimists . Pessimists reported a greater deterioration in the role domain following treatment than did optimists . At no point did pessimists rate HRQL better than optimists . The results suggest that optimism is associated with better HRQL in French UADT cancer patients", "& NA ; Few controlled clinical trials have tested the efficacy of psychological techniques for reducing cancer pain or post‐chemotherapy nausea and emesis . In this study , 67 bone marrow transplant patients with hematological malignancies were r and omly assigned to one of four groups prior to beginning transplantation conditioning : hypnosis training (HYP);cognitive behavioral coping skills training (CB);therapist contact control ( TC ) ; ortreatment as usual ( TAU ; no treatment control ) . Patients completed measures of physical functioning ( Sickness Impact Profile ; SIP ) and psychological functioning ( Brief Symptom Inventory ; BSI ) , which were used as covariates in the analyses . Biodemographic variables included gender , age and a risk variable based on diagnosis and number of remissions or relapses . Patients in the HYP , CB and TC groups met with a clinical psychologist for two pre‐transplant training sessions and ten in‐hospital “ booster ” sessions during the course of transplantation . Forty‐five patients completed the study and provided all covariate data , and 80 % of the time series outcome data . Analyses of the principal study variables indicated that hypnosis was effective in reducing reported oral pain for patients undergoing marrow transplantation . Risk , SIP , and BSI pre‐transplant were found to be effective predictors of inpatient physical symptoms . Nausea , emesis and opioid use did not differ significantly between the treatment groups . The cognitive behavioral intervention , as applied in this study , was not effective in reducing the symptoms measured", "24 patients with chronic low back pain were r and omly assigned to three treatment conditions : ( a ) EMG biofeedback , ( b ) relaxation training , and ( c ) a placebo condition . Patients were seen for eight sessions and were evaluated before Session 1 and after Session 8 . Eight analyses of covariance which were adjusted for age and pretest scores were computed on the final scores to find which variables could detect significant difference between treatments . Age was included as a covariate because the differences in age between conditions were significant . Four variables with significant and nearly significant differences were chosen for analysis . The second set of analyses identified the nature of the differences among the three conditions . These included a priori planned comparisons among conditions , and paired t tests . Relaxation-trained subjects were significantly superior to subjects in the placebo condition , in decreasing pain during the function test , increasing relaxation , and decreasing Upper Trapezius EMG . They were superior to EMG Biofeedback training in increasing reported activity . Both Relaxation and EMG trained subjects were able to reduce Upper Trapezius EMG by Session 8 Relaxation-trained subjects showed significant change on eight of the 14 possible comparisons for each treatment condition . EMG biofeedback training showed significant favorable results in only one condition ; the placebo condition showed no significant results . Relaxation training gave better results in reducing EMG and pain , and in increasing relaxation and activity than either EMG biofeedback alone or a placebo condition", "Chronic low back pain ( CLBP ) presents a problem of massive dimensions . While inpatient approaches have been evaluated , outpatient treatment programs have received relatively little examination . Hypnosis and relaxation are two powerful techniques amenable to outpatient use . Seventeen outpatient subjects suffering from CLBP were assigned to either Self-Hypnosis ( n = 9 ) or Relaxation ( n = 8) treatments . Following pretreatment assessment , all subjects attended a single placebo session in which they received minimal EMG feedback . One week later the subjects began eight individual weekly treatment sessions . Subjects were assessed on a number of dependent variables at pretreatment , following the placebo phase , one week after the completion of treatment , and three months after treatment ended . Subjects in both groups showed significant decrements in such measures as average pain rating , pain as measured by derivations from the McGill Pain Question naire , level of depression , and length of pain analog line . Self-Hypnosis subjects reported less time to sleep onset , and physicians rated their use of medication as less problematic after treatment . While both treatments were effective , neither proved superior to the other . The placebo treatment produced nonsignificant improvement", "& NA ; This study examined the relationship between pain self‐efficacy beliefs and a range of pain behaviours , as measured by the pain behaviour question naire ( PBQ ) , using a prospect i ve design . A heterogeneous sample of 145 chronic pain patients completed sets of question naires on four occasions over a nine‐month period . Multiple hierarchical regression analyses revealed that the subjects ' confidence in their ability to perform a range of tasks despite pain ( assessed at baseline ) , was predictive of total pain behaviour and avoidance behaviour over the nine‐month study period . This finding was particularly significant because the analyses controlled for the possible effects of pain severity ( at each measurement occasion ) , pain chronicity , age , gender , physical disability , depression , neuroticism and catastrophising . These findings suggest that pain self‐efficacy beliefs are an important determinant of pain behaviours and disability associated with pain , over and above the effects of pain , distress and personality variables . In particular , higher pain self‐efficacy beliefs are predictive of reduced avoidance behaviours over an extended period" ]

[ "12949224", "3675670", "23719048", "24992897", "18281890", "12244081", "24486425", "24027289", "2967471", "22031888", "23756431", "25010032", "22445135", "24176927", "24968188", "10990547", "21665534", "21440562" ]

[ "Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.", "Long-Term Enhancement of Brain Function and Cognition Using Cognitive Training and Brain Stimulation", "Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants.", "Use of transcranial direct current stimulation (tDCS) to enhance cognitive training: effect of timing of stimulation", "Time-dependent effect of transcranial direct current stimulation on the enhancement of working memory", "Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.", "Concurrent Cognitive Control Training Augments the Antidepressant Efficacy of tDCS: A Pilot Study", "Transfer of Cognitive Training across Magnitude Dimensions Achieved with Concurrent Brain Stimulation of the Parietal Lobe", "Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG", "Random Noise Stimulation Improves Neuroplasticity in Perceptual Learning", "Effects of Repeated Anodal tDCS Coupled With Cognitive Training for Patients With Severe Traumatic Brain Injury: A Pilot Randomized Controlled Trial", "Comparison of the Effects of Transcranial Random Noise Stimulation and Transcranial Direct Current Stimulation on Motor Cortical Excitability", "Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities", "Long-term effects of transcranial direct current stimulation combined with computer-assisted cognitive training in healthy older adults", "Increase in PAS-induced neuroplasticity after a treatment course of transcranial direct current stimulation for depression.", "Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation.", "Improving working memory: Exploring the effect of transcranial random noise stimulation and transcranial direct current stimulation on the dorsolateral prefrontal cortex", "The enhancement of cortical excitability over the DLPFC before and during training impairs categorization in the prototype distortion task" ]

[ "Transcranial direct current stimulation ( tDCS ) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation . Anodal tDCS enhances and cathodal stimulation reduces excitability . Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation , while cathodal tDCS hyperpolarises cortical neurones . However , not much is known about the ion channels and receptors involved in these effects . Thus , the impact of the sodium channel blocker carbamazepine , the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested . tDCS- protocol s inducing excitability alterations ( 1 ) only during tDCS and ( 2 ) eliciting long-lasting after-effects were applied after drug administration . Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS . Flunarizine result ed in similar changes . Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation , which elicits no after-effects , but prevented the induction of long-lasting after-effects independent of their direction . These results suggest that , like in other animals , cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation , thus modulating the conductance of sodium and calcium channels . Moreover , they suggest that the after-effects may be NMDA receptor dependent . Since NMDA receptors are involved in neuroplastic changes , the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting . The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS , which may have important future clinical applications", "Summary Noninvasive brain stimulation has shown considerable promise for enhancing cognitive functions by the long-term manipulation of neuroplasticity [ 1–3 ] . However , the observation of such improvements has been focused at the behavioral level , and enhancements largely restricted to the performance of basic tasks . Here , we investigate whether transcranial r and om noise stimulation ( TRNS ) can improve learning and subsequent performance on complex arithmetic tasks . TRNS of the bilateral dorsolateral prefrontal cortex ( DLPFC ) , a key area in arithmetic [ 4 , 5 ] , was uniquely coupled with near-infrared spectroscopy ( NIRS ) to measure online hemodynamic responses within the prefrontal cortex . Five consecutive days of TRNS-accompanied cognitive training enhanced the speed of both calculation- and memory-recall-based arithmetic learning . These behavioral improvements were associated with defined hemodynamic responses consistent with more efficient neurovascular coupling within the left DLPFC . Testing 6 months after training revealed long-lasting behavioral and physiological modifications in the stimulated group relative to sham controls for trained and nontrained calculation material . These results demonstrate that , depending on the learning regime , TRNS can induce long-term enhancement of cognitive and brain functions . Such findings have significant implication s for basic and translational neuroscience , highlighting TRNS as a viable approach to enhancing learning and high-level cognition by the long-term modulation of neuroplasticity", "Computer-administered cognitive training ( CT ) tasks are a common component of cognitive remediation treatments . There is growing evidence that transcranial direct current stimulation ( tDCS ) , when given during cognitive tasks , improves performance . This r and omized , controlled trial explored the potential synergistic effects of CT combined with tDCS in healthy participants . Altogether , 60 healthy participants were r and omized to receive either active or sham tDCS administered during training on an adaptive CT task ( dual n-back task ) , or tDCS alone , over 10 daily sessions . Cognitive testing ( working memory , processing speed , executive function , reaction time ) was conducted at baseline , end of the 10 sessions , and at 4-wk follow-up to examine potential transfer effects to non-trained tasks . Altogether , 54 participants completed the study . Over the 10 ' online ' sessions , participants in the active tDCS+CT condition performed more accurately on the CT task than participants who received sham tDCS+CT . The performance enhancing effect , however , was present only during tDCS and did not result in greater learning ( i.e. improvement over sessions ) on the CT task . These results confirm prior reports of enhancement of cognitive function during tDCS stimulation . At follow-up , the active tDCS+CT group , but not the sham tDCS+CT group , showed greater gains on a non-trained test of attention and working memory than the tDCS-only group ( p < 0.01 ) . Although this gain can mainly be attributable to training , this result suggests that active tDCS may have a role in further enhancing outcomes", "The capacity for transcranial direct current stimulation ( tDCS ) to increase learning and cognition shows promise for the development of enhanced therapeutic interventions . One potential application is the combination of tDCS with cognitive training ( CT ) , a psychological intervention which aims to improve targeted cognitive abilities . We have previously shown that tDCS enhanced performance accuracy , but not skill acquisition , on a dual n-back working memory ( WM ) CT task over repeated sessions . In the current study , we investigated the optimal timing for combining tDCS with the same CT task to enhance within and between session performance outcomes across two daily CT sessions . Twenty healthy participants received in a r and omised order 30 min of anodal tDCS to the left dorsolateral prefrontal cortex immediately before ( ‘ offline ’ tDCS ) and during performance ( ‘ online ’ tDCS ) on a dual n-back WM CT task , in an intra-individual crossover design . Analyses examined within and between session consolidation effects of tDCS on CT performance outcomes . Results showed that ‘ online ’ tDCS was associated with better within session skill acquisition on the CT task , with a significant difference found between conditions the following day . These results suggest that ‘ online ’ tDCS is superior to ‘ offline ’ tDCS for enhancing skill acquisition when combining anodal tDCS with CT . This finding may assist with the development of enhanced protocol s involving the combination of tDCS with CT and other rehabilitation protocol", "The time-dependent effect of transcranial direct current stimulation ( tDCS ) on working memory was investigated by applying anodal stimulation over the left prefrontal cortex . This single-blind , sham-controlled crossover study recruited 15 healthy participants . A three-back verbal working-memory task was performed before , during , and 30 min after 1 mA anodal or sham tDCS . Anodal tDCS , compared with sham stimulation , significantly improved working-memory performance . Accuracy of response was significantly increased after 20 min of tDCS application , and was further enhanced after 30 min of stimulation . This effect was maintained for 30 min after the completion of stimulation . These results suggest that tDCS at 1 mA enhances working memory in a time-dependent manner for at least 30 min in healthy participants", "Weak transcranial direct current stimulation ( tDCS ) induces persisting excitability changes in the human motor cortex . These plastic excitability changes are selectively controlled by the polarity , duration and current strength of stimulation . To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity , we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine ( CBZ ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan ( DMO ) . Monitored by transcranial magnetic stimulation ( TMS ) , motor cortical excitability changes of up to 40 % were achieved in the drug-free condition . Increase of cortical excitability could be selected by anodal stimulation , and decrease by cathodal stimulation . Both types of excitability change lasted several minutes after cessation of current stimulation . DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation , strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity . In contrast , CBZ selectively eliminated anodal effects . Since CBZ stabilizes the membrane potential voltage-dependently , the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials . Similar to the induction of established types of short- or long-term neuroplasticity , a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS . On the basis of these results , we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects , leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation", "BACKGROUND Major depressive disorder ( MDD ) is frequently associated with underactivity of the dorsolateral prefrontal cortex ( DLPFC ) which has led to this brain region being identified as an important target for the development of neurobiological treatments . Transcranial direct current stimulation ( tDCS ) administered to the DLPFC has antidepressant efficacy , however the magnitude of antidepressant outcomes are limited . Concurrent cognitive activity has been shown to enhance tDCS induced stimulation effects . Cognitive control training ( CCT ) is a new cognitive therapy for MDD that aims to enhance DLPFC activity via behavioral methods . HYPOTHESIS We tested the hypothesis that co-administration of DLPFC tDCS and CCT would result in a greater reduction in depressive symptomology than administration of tDCS or CCT alone . METHODS 27 adult participants with MDD were r and omized into a three-arm sham-controlled between-groups pilot study comparing the efficacy of 2 mA tDCS + CCT , sham tDCS + CCT and sham CCT + 2 mA tDCS ( 5 sessions administered on consecutive working days ) . Blinded assessment s of depression severity and cognitive control were conducted at baseline , end of treatment and a three week follow up review . RESULTS All three treatment conditions were associated with a reduction in depression severity at the end of five treatment sessions . However , only administration of tDCS + CCT result ed in sustained antidepressant response at follow up , the magnitude of which was greater than that observed immediately following conclusion of the treatment course . CONCLUSIONS The results provide preliminary evidence that concurrent CCT enhances antidepressant outcomes from tDCS . In the current sample , participants receiving concurrent tDCS and CCT continued to improve following cessation of treatment . The clinical superiority of a combined therapeutic approach was apparent even in a small sample and following a relatively short treatment course", "Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation . Here we ask whether training-induced changes can be maintained long term and , crucially , whether they can extend to other related but untrained skills . We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity – or the number of items in a set – which is thought to rely on an “ approximate number sense ” ( ANS ) associated with parietal lobes . We coupled training with parietal stimulation in the form of transcranial r and om noise stimulation ( tRNS ) , a noninvasive technique that modulates neural activity . This yielded significantly better and longer lasting improvement ( up to 16 weeks post-training ) of the precision of the ANS compared with cognitive training in absence of stimulation , stimulation in absence of cognitive training , and cognitive training coupled to stimulation to a control site ( motor areas ) . Critically , only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment , i.e. , time and space discrimination , but not to quantity-unrelated tasks measuring attention , executive functions , and visual pattern recognition . These results indicate that coupling intensive cognitive training with tRNS to critical brain regions result ed not only in the greatest and longer lasting improvement of numerosity discrimination , but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components", "Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation ( tDCS ) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants . Recently , transcranial alternating current stimulation ( tACS ) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp . Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation . No direct electrophysiological evidence of tACS has been reported . We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation . The tACS but not the sham stimulation elevated the endogenous alpha power in parieto- central electrodes of the electroencephalogram . Additionally , in a network of spiking neurons , we simulated how tACS can be affected even after the end of stimulation . The results show that spike-timing-dependent plasticity ( STDP ) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to . Thus , tACS influences STDP which in turn results in aftereffects upon neural activity . The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex . The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application", "Perceptual learning is considered a manifestation of neural plasticity in the human brain . We investigated brain plasticity mechanisms in a learning task using noninvasive transcranial electrical stimulation ( tES ) . We hypothesized that different types of tES would have varying actions on the nervous system , which would result in different efficacies of neural plasticity modulation . Thus , the principal goal of the present study was to verify the possibility of inducing differential plasticity effects using two tES approaches [ i.e. , direct current stimulation ( tDCS ) and r and om noise stimulation ( tRNS ) ] during the execution of a visual perceptual learning task", "Objective : To determine whether cumulative anodal transcranial direct current stimulation ( A-tDCS ) of the left dorsolateral prefrontal cortex ( DLPFC ) could enhance rehabilitation of memory and attention in patients with traumatic brain injury ( TBI ) . Setting : Inpatient and outpatient neurorehabilitation unit . Participants : Twenty-three adult patients , 4- to 92- months post severe TBI . Design : Participants were r and omly allocated to 2 groups . The experimental group received A-tDCS ( 10 minutes ; 1 mA ; in the DLPFC ) , followed by rehabilitative cognitive training , daily for 15 days . Controls received A-tDCS for 25 seconds ( sham condition ) with the same rehabilitation . Main Measures : Battery of memory and attention tests , which included visual and auditory modalities . Participants were tested twice before beginning rehabilitation ( to control for spontaneous recovery ) , after rehabilitation completion , and 4 months later . Results : Tests scores in both groups were similar at 3 weeks before and immediately before treatment . After treatment , the experimental group exhibited larger effect sizes in 6 of 8 cognitive outcome measures , but they were not significantly different from controls . At follow-up , differences remained insignificant . Conclusion : In contrast to previous studies , our study did not provide sufficient evidence to support the efficacy of repeated A-tDCS for enhancing rehabilitation of memory and attention in patients after severe TBI", "Objective The objective of this study was to examine the effect of transcranial r and om noise stimulation ( tRNS ) with and without a direct current ( DC ) offset on motor cortical excitability and compare results to transcranial DC stimulation ( tDCS ) . Methods Fifteen healthy participants were tested in a within-subjects design . Motor-evoked potentials were measured before and up to 90 minutes after stimulation using transcranial magnetic stimulation . Five stimulation conditions were examined : sham , 1-mA tDCS , 2-mA tDCS , 2-mA tRNS ( with no DC offset ) , and 2-mA tRNS + 1-mA DC offset . Results There were no significant differences between the stimulation conditions . An analysis of individual stimulation conditions found that there was a significant increase in motor-evoked potential amplitudes after 1-mA tDCS , 2-mA tDCS , and 2-mA tRNS + DC offset when compared with baseline . Sham and 2-mA tRNS did not result in changes in cortical excitability . Conclusions Although differences between the stimulation conditions did not reach a statistical significance , the findings suggest that stimulation involving a DC ( tDCS and tRNS + DC offset ) but not solely tRNS is more likely to lead to increases in cortical excitability", "BACKGROUND Recently we have shown that transcranial r and om noise ( tRNS ) and 140 Hz transcranial alternating current stimulations ( tACS ) , applied over the primary motor cortex ( M1 ) and using 10 min stimulation duration and 1 mA intensity , significantly increases cortical excitability as measured by motor evoked potentials at rest before and after stimulation . OBJECTIVE /HYPOTHESIS Here , by decreasing the stimulation intensity in 0.2 mA steps from 1.0 mA , we investigate to what extent intensity depends on the induced after-effects . METHODS All twenty-five subjects participated in two different experimental sessions each . They received tACS using 140 Hz frequency and full spectrum tRNS at five different intensities on separate days . Sham stimulation was used as a control . RESULTS Instead of receiving a simple threshold , unexpectedly , in these two independent data sets at threshold intensities of 0.4 mA we found a switch of the already known excitation achieved with an intensity of 1 mA to inhibition . The intermediate intensity ranges of 0.6 and 0.8 mA had no effect at all . Interestingly , the inhibition produced by 140 Hz tACS was stronger than that induced by tRNS . CONCLUSIONS In summary , we have shown here the possibility of selectively controlling the enhancement or reduction of M1 excitability by applying different intensities of high frequency transcranial electrical stimulation", "The aim of the present study was to analyze the long-term effects of transcranial direct current stimulation ( tDCS ) of the bilateral prefrontal cortex combined with computer-assisted cognitive training on working memory and cognitive function in healthy older adults aged at least 65 years . Forty healthy older adults were enrolled and r and omly assigned to two groups : anodal and sham tDCS . All participants completed 10 sessions of computer-assisted cognitive training , combined with tDCS of the bilateral prefrontal cortex . The accuracy of the verbal working memory task and performance of the digit span forward test were significantly improved after computer-assisted cognitive training combined with bifrontal anodal tDCS as compared with that after computer-assisted cognitive training combined with sham tDCS . Moreover , the effect lasts for 4 weeks in the verbal working memory task . We suggest that the tDCS-induced changes in the bilateral prefrontal excitability during computer-assisted cognitive training may have beneficial effects on age-related cognitive decrement in healthy older adults", "BACKGROUND Several lines of evidence suggest that neuroplasticity is impaired in depression and improves with effective treatment . However until now , this evidence has largely involved measures such as learning and memory which can be influenced by subject effort and motivation . This pilot study aim ed to objective ly measure neuroplasticity in the motor cortex using paired associative stimulation ( PAS ) , which induces short term neuroplastic changes . It is hypothesized that neuroplasticity would improve after effective treatment for depression . METHODS Neuroplasticity was measured in 18 depressed subjects before and after a course of anodal transcranial direct current stimulation ( tDCS ) , given as treatment for depression . The relationships between PAS results , mood state and brain-derived neurotrophic factor ( BDNF ) serum levels were examined . RESULTS Neuroplasticity ( PAS-induced change ) was increased after a course of tDCS ( t(17)=-2.651 , p=0.017 ) . Treatment with tDCS also led to significant mood improvement , but this did not correlate with improved neuroplasticity . Serum BDNF levels did not change after tDCS , or correlate with change in neuroplasticity after tDCS treatment . LIMITATIONS While this study showed evidence of improved neuroplasticity in the motor cortex after effective treatment , we are unable to present evidence that this change is generalized in the depressed brain . Also , the presence of antidepressant medications and the small sample of patients ( n=18 ) meant the study could not definitively resolve the relationship between neuroplasticity , mood and BDNF . CONCLUSION This novel preliminary study provides evidence that a treatment course of tDCS can improve neuroplasticity in depressed patients", "In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp . Excitability changes of up to 40 % , revealed by transcranial magnetic stimulation , were accomplished and lasted for several minutes after the end of current stimulation . Excitation could be achieved selectively by anodal stimulation , and inhibition by cathodal stimulation . By varying the current intensity and duration , the strength and duration of the after-effects could be controlled . The effects were probably induced by modification of membrane polarisation . Functional alterations related to post-tetanic potentiation , short-term potentiation and processes similar to postexcitatory central inhibition are the likely c and i date s for the excitability changes after the end of stimulation . Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive , painless , reversible , selective and focal way", "OBJECTIVE The aim of this study was to determine if working memory ( WM ) performance is significantly improved after the delivery of transcranial r and om noise stimulation ( tRNS ) to the left dorsolateral prefrontal cortex ( DLPFC ) , compared to an active comparator or sham . METHODS Ten participants undertook three experimental sessions in which they received 10 min of anodal tDCS ( active comparator ) , tRNS or sham tDCS whilst performing the Sternberg WM task . Intra-stimulation engagement in a WM task was undertaken as this has been previously shown to enhance the effects of tDCS . Experimental sessions were separated by a minimum of 1 week . Immediately prior to and after each stimulation session the participants were measured on speed and accuracy of performance on an n-back task . RESULTS There was significant improvement in speed of performance following anodal tDCS on the 2-back WM task ; this was the only significant finding . CONCLUSIONS The results do not provide support for the hypothesis that tRNS improves WM . However , the study does provide confirmation of previous findings that anodal tDCS enhances some aspects of DLPFC functioning . Method ological limitations that may have contributed to the lack of significant findings following tRNS are discussed . SIGNIFICANCE Anodal tDCS may have significant implication s for WM remediation in psychiatric conditions , particularly schizophrenia", "The present study investigated the effects of transcranial weak electrical stimulation techniques applied to the right and left dorsolateral prefrontal cortex ( DLPFC ) on categorization learning measured using a variant of the prototype distortion task . During the training phase of this task subjects saw low- and high distortions of a prototype dot-pattern . 60 participants received 10min of either anodal or cathodal transcranial direct current ( tDCS ) , transcranial r and om noise ( tRNS ) or sham stimulation before and during the training . We have assessed the effects of the intervention during a test phase , where the subjects had to decide whether the consecutive high- and low-distortion versions of the prototype or r and om patterns that were presented belonged to the category established in the training phase . Our results show that the categorization of prototypes is significantly impaired by the application of anodal tDCS and tRNS to the DLPFC . The prototype-effect , observable in the case of the sham stimulation group , was severed in all active stimulation conditions" ]

[ "22892463", "20671206", "3549940", "23392087", "3198550", "19641152", "22736448", "3538059", "4730599", "22369560", "22251037", "27208876", "16040729", "22621162", "26037274", "21118796", "23441792" ]

[ "Randomized clinical trial on effectiveness of silver diamine fluoride and glass ionomer in arresting dentine caries in preschool children.", "A Randomized Trial on Root Caries Prevention in Elders", "Caries preventive efficacy of silver diammine fluoride (SDF) and ART sealants in a school-based daily fluoride toothbrushing program in the Philippines", "Silver Diamine Fluoride and Education to Prevent and Arrest Root Caries among Community-Dwelling Elders", "Remineralizing efficacy of silver diamine fluoride and glass ionomer type VII for their proposed use as indirect pulp capping materials – Part II (A clinical study)", "Efficacy of Silver Diamine Fluoride for Arresting Caries Treatment", "Randomized Trial on Fluorides and Sealants for Fissure Caries Prevention", "Short term serum pharmacokinetics of diammine silver fluoride after oral application", "Implementing PRISMA-P: recommendations for prospective authors", "Effect of silver and fluoride ions on enamel demineralization: a quantitative study using micro-computed tomography.", "Paradigm shift in the effective treatment of caries in schoolchildren at risk.", "Randomized clinical trial on arresting dental root caries through silver diammine fluoride applications in community-dwelling elders.", "Efficacy of Silver Diamine Fluoride for Caries Reduction in Primary Teeth and First Permanent Molars of Schoolchildren: 36-month Clinical Trial", "Effect of silver diamine fluoride on microtensile bond strength to dentin.", "A randomized clinical trial on arresting dentine caries in preschool children by topical fluorides--18 month results.", "The Short-term Effects of Diammine Silver Fluoride on Tooth Sensitivity", "An in vitro study of silver and fluoride ions on remineralization of demineralized enamel and dentine." ]

[ "OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p<0.001 ) , and those in buccal/lingual smooth surfaces ( OR=15.6 , p=0.004 ) . CONCLUSION Annual application of either SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome", "Root caries is common in institutionalized elders , and effective prevention methods are needed . This clinical trial compared the effectiveness of four methods in preventing new root caries . From 21 residential homes , 306 generally healthy elders having at least 5 teeth with exposed sound root surfaces were r and omly allocated into one of four groups : ( 1 ) individualized oral hygiene instruction ( OHI ) ; ( 2 ) OHI and applications of 1 % chlorhexidine varnish every 3 months ; ( 3 ) OHI and applications of 5 % sodium fluoride varnish every 3 months ; and ( 4 ) OHI and annual applications of 38 % silver diamine fluoride ( SDF ) solution . Two-thirds ( 203/306 ) of the elders were followed for 3 years . Mean numbers of new root caries surfaces in the four groups were 2.5 , 1.1 , 0.9 , and 0.7 , respectively ( ANOVA , p < 0.001 ) . SDF solution , sodium fluoride varnish , and chlorhexidine varnish were more effective in preventing new root caries than giving OHI alone", "Background Occlusal surfaces of erupting and newly erupted permanent molars are particularly susceptible to caries . The objective of the study was to assess and compare the effect of a single application of 38 % SDF with ART sealants and no treatment in preventing dentinal ( D3 ) caries lesions on occlusal surfaces of permanent first molars of school children who participated in a daily school-based toothbrushing program with fluoride toothpaste . Methods The prospect i ve community clinical trial in the Philippines was conducted over a period of 18 months and included 704 six- to eight-year-old school children in eight public elementary schools with a daily school-based fluoride toothpaste brushing program . Children were r and omly assigned for SDF application or ART sealant treatment . Children from two of the eight schools did not receive SDF or ART sealant treatment and served as controls . SDF or ART sealant treatment was applied on sound occlusal surfaces of permanent first molars . Surfaces that were originally defined as sound at baseline but which changed to dentinal ( D3 ) caries lesions were defined as surfaces with new caries ( caries increment ) . Non-compliance to the daily toothbrushing program in three schools offered the opportunity to analyze the caries preventive effect of SDF and sealants separately in fluoride toothpaste brushing and in non-toothbrushing children . Results In the brushing group , caries increment in the SDF treatment group was comparable with the non-treatment group but caries increment in the sealant group was lower than in the non-treatment group with a statistically significant lower hazard ratio of 0.12 ( 0.02 - 0.61 ) . In the non-brushing group , caries increment in the SDF treatment group and the sealant group was lower than the non-treatment group but the hazard ratio was only statistically significant for the sealant group ( HR 0.33 ; 0.20 - 0.54 ) . Caries increment was lower in toothbrushing children than in non-toothbrushing children . Hazard ratios reached statistical significance for the non-treated children ( HR 0.43 ; 0.21 - 0.87 ) and the sealant-treated children ( HR 0.15 ; 0.03 - 0.072 ) . Conclusions A one-time application of 38 % SDF on the occlusal surfaces of permanent first molars of six- to eight-year-old children is not an effective method to prevent dentinal ( D3 ) caries lesions . ART sealants significantly reduced the onset of caries over a period of 18 months . Trial registration numberGerman Clinical Trial Register", "Background / Aims : Root caries among elderly communities is of growing public health concern globally . This controlled clinical trial investigated the effectiveness of silver diamine fluoride and oral health education in preventing and arresting root caries . Methods : Two hundred sixty-six elderly subjects who had at least 5 teeth with exposed root surfaces and did not have serious life-threatening medical diseases were allocated to 3 groups according to a computer-generated r and om list : group 1 ( the control group ) received oral hygiene instructions ( OHI ) annually ; group 2 received OHI and silver diamine fluoride ( SDF ) application annually , and group 3 was given OHI and SDF application annually , plus an oral health education ( OHE ) programme every 6 months . Results : Two hundred twenty-seven elderly subjects were followed for 24 months . The mean numbers of new root caries surfaces in groups 1 , 2 and 3 were 1.33 , 1.00 and 0.70 , respectively ( ANOVA , p < 0.05 ) . Group 3 had fewer root surfaces with new caries than group 1 ( Scheffé multiple-comparison test , p < 0.05 ) . The mean numbers of arrested root caries surfaces in groups 1 , 2 and 3 were 0.04 , 0.28 and 0.33 , respectively ( ANOVA , p < 0.01 ) . Group 3 and group 2 had a greater number of active root caries surfaces which became arrested than group 1 ( Scheffé multiple-comparison test , p < 0.05 ) . Conclusion : Annual application of SDF together with biannual OHE was effective in preventing new root caries and arresting root caries among community-dwelling elderly subjects", "Aim : To evaluate in vivo the remineralizing efficacy of silver diamine fluoride ( SDF ) , glass ionomer Type VII ( GC VII ) and calcium hydroxide ( Dycal ) . Material s and Methods : 60 subjects in the age group of 18 - 35 years , matching the inclusion criteria and having deep carious lesions in the permanent first and second molars were selected . The teeth were aseptically opened under rubber dam and after gross caries removal , approximately 0.4 mg of soft discolored dentin was removed with a sharp spoon excavator from the mesial or distal aspect of the cavity . The test material was r and omly selected and applied in a thickness of 1.5 - 2 mm and the cavity sealed with cavit . The patients were followed up at regular intervals with radiographic evaluation at 12 weeks . At 3 months the temporary restoration was removed and dentin sample s were collected from the other half of the cavity which was left in the first appointment . Atomic absorption spectrophotometry , Colorimetric test using UV-vis spectrometer and potentiometric titration were used for determining calcium , phosphorous and fluoride respectively . Results : Almost equivalent rise in the percentage of calcium level was seen in GC VII and Ca(OH)2 groups , followed by SDF group . Highest percentage rise in phosphate ions was seen in GC VII group followed by SDF group and Ca(OH)2 group . Highest percentage of fluoride rise was seen in GC VII group followed by SDF group and Ca(OH)2 group . Conclusions : The results indicated that both GC VII and SDF can be potential indirect pulp capping material", "Arresting Caries Treatment ( ACT ) has been proposed to manage untreated dental caries in children . This prospect i ve r and omized clinical trial investigated the caries-arresting effectiveness of a single spot application of : ( 1 ) 38 % silver diamine fluoride ( SDF ) with tannic acid as a reducing agent ; ( 2 ) 38 % SDF alone ; ( 3 ) 12 % SDF alone ; and ( 4 ) no SDF application in primary teeth of 976 Nepalese schoolchildren . The a priori null hypothesis was that the different treatments have no effect in arresting active cavitated caries . Only the single application of 38 % SDF with or without tannic acid was effective in arresting caries after 6 months ( 4.5 and 4.2 mean number of arrested surfaces ; p < 0.001 ) , after 1 year ( 4.1 and 3.4 ; p < 0.001 ) , and after 2 years ( 2.2 and 2.1 ; p < 0.01 ) . Tannic acid conferred no additional benefit . ACT with 38 % SDF provides an alternative when restorative treatment for primary teeth is not an option", "To investigate the effectiveness of topical fluorides in preventing fissure caries , we conducted a r and omized controlled trial with parallel groups . In total , 501 children ( 1,539 molars , 3,078 sites ) , mean age 9.1 years , who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited . They were r and omly allocated among four groups : ( 1 ) resin sealant , single placement ; ( 2 ) 5 % NaF varnish , semi-annual application ; ( 3 ) 38 % silver diamine fluoride ( SDF ) solution , annual application ; and ( 4 ) placebo control . Follow-up examinations were conducted every 6 months by a masked examiner . After 24 months , 485 children ( 97 % ) were examined . Proportions of pit/fissure sites with dentin caries in the sealant , NaF , SDF , and control groups were 1.6 % , 2.4 % , 2.2 % , and 4.6 % , respectively . A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls ( p < 0.05 ) . We concluded that placement of resin sealant , semi-annual application of NaF varnish , and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars ( Clinical Trials.gov number CT01446107 )", "Background There is growing interest in the use of diammine silver fluoride ( DSF ) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world . While DSF has been available in various formulations for many years , most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized . Methods This preliminary study determined the applied doses ( 3 teeth treated ) , maximum serum concentrations , and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode , and silver was determined using inductively coupled plasma-mass spectrometry . The mean amount of DSF solution applied to the 3 teeth was 7.57 mg ( 6.04 μL ) . Results Over the 4 hour observation period , the mean maximum serum concentrations were 1.86 μmol/L for fluoride and 206 nmol/L for silver . These maximums were reached 3.0 h and 2.5 h for fluoride and silver , respectively . Conclusions Fluoride exposure was below the U.S. Environmental Protection Agency ( EPA ) oral reference dose . Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime , but for occasional use was well below concentrations associated with toxicity . This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults . Clinical trials registration NCT01664871", "Systematic review s have become very popular . A recent estimate suggests that 22 new systematic review s are published daily [ 1 ] . One reason for this interest is that they serve many purpose s. For example , the influential Institute of Medicine has indicated that a systematic review is an essential component when developing clinical practice guidelines within the USA [ 2 ] . Some granting agencies are now advocating for the use of systematic review s as an evidence -based rationale for the conduct of a proposed r and omized trial [ 3 ] . And journals are now dem and ing the use of systematic review s to provide readers with context of the results of a clinical trial [ 4 ] . For systematic review s to be useful , they need to be reported in the highest possible quality thus facilitating their accurate use across a wide spectrum of stakeholders , including patients . Unfortunately , surveys of the published literature indicate that the quality of reporting is not optimal . For example , there is evidence indicating that reporting biases , particularly selective outcome reporting , is prevalent . An early example of differences between outcomes reported in protocol s and the paired completed review was an examination of 47 Cochrane review s in which 43 ( 91 % ) contained a major change , such as the addition or deletion of outcomes , between the protocol and the full publication [ 5 ] . More recently , in an examination of 485 Cochrane protocol - review pairs , 38 % ( 95 % CI 23 to 54 % ) were found to have discrepant outcomes ( i.e. , added , omitted , or changed the priority ) between the protocol and completed review [ 6 ] . The vast majority of these discrepancies were without attribution with more significant outcomes being up grade d or added . Whether or not , and to what extent , these examples reflect reporting biases is not clear . However , they represent inconsistencies that should be avoided by authors . The gold st and ard for identifying reporting biases is a comparison of the completed review with its paired protocol . Such an examination is difficult with systematic review s as too few of them report working from a protocol , although a growing number of funders are now requiring them . Perhaps , systematic review ers do not report or use protocol s because there has been little guidance on how to report them until recently . To help facilitate the use of reporting systematic review protocol s , the three of us and several colleagues developed Preferred Reporting Items for Systematic Review and Meta- Analysis Protocol s ( PRISMA -P ) [ 7 ] . This is a reporting guideline consisting of a 17-item checklist , to help prospect i ve authors in the preparation and reporting of a scientifically rigorous systematic review protocol . We also prepared a pedagogical explanation and elaboration document to facilitate its use [ 8 ] . Readers appear interested in the guidance . Since its publication a little more than a year ago , it has been downloaded about 45,000 times and cited ( Google scholar ) nearly 100 times . This journal and others have endorsed PRISMA -P. Here , we describe how the journal intends to implement it . All protocol su bmi ssions to the journal should use continuous line numbering in their manuscript . Authors should also include a completed PRISMA -P checklist indicating whether or not the requested item information is reported ( by completing the check mark ) . If the item is checked , authors should then specify the line number ( or range of line numbers ) where this information is described . Manuscripts accepted for publication will have the completed PRIMSA-P checklist ( on su bmi ssion ) included as an Appendix to their publication , which must be referenced within the main text ( Additional file 1 ) . Prospect i ve authors can download a Word version of the PRISMA -P checklist , which includes the two added columns , from the journal ’s website ( URL to be added)or the PRISMA website ( ttp://www . prisma -statement.org/Extensions/ Protocol s.aspx ) . If PRISMA -P was used to help report the protocol , it should be cited or the PRISMA -P URL ( http://www . prisma -statement.org/Extensions/ Protocol s.aspx ) on the PRISMA website should be reported . About half of what the journal publishes are protocol s of systematic review s. We want to ensure they are published to the highest possible quality . Endorsement and implementation of reporting guidelines appears to improve the completeness of reporting . For example , a systematic review examining the completeness of reporting in more than 16,000 r and omized trials in journals that endorsed the CONSORT statement , compared to journals that did not , found more complete reporting [ 9 ] . Similarly , examining 300 systematic review s published in February 2014 found that mention of PRISMA was associated with better reporting [ 1 ] . There is always a tension between an optimal implementation strategy and ensuring minimal barriers to su bmi ssion for prospect i ve authors . We believe the journal has achieved a good balance with this strategy . Protocol s su bmi tted for publication consideration from now on that do not include a completed checklist , including the two aforementioned columns , will be returned to the authors with instructions about the journal ’s systematic review protocol implementation strategy and invited to resu bmi t their continuously line numbered manuscript and appropriately completed checklist", "BACKGROUND This study aim ed to investigate the effect of silver and fluoride ions on demineralization of enamel . METHODS The coronal parts of 40 extracted sound premolars were prepared into tooth blocks . An unvarnished occlusal surface window ( OW ) and a flat buccal/lingual surface window ( FW ) were created for each tooth by covering all other surfaces with an acid-resistant varnish . These blocks were r and omly allocated into four groups of 10 blocks each and immersed in respective solutions for 5 minutes : Group 1 - -2.36 M silver fluoride ; Group 2 - -2.36 M potassium fluoride ; Group 3 - -2.36 M silver nitrate ; and Group 4 - -deionized water . After 7-day immersion in a buffered demineralization solution at pH 4.4 , micro-CT scans were taken . RESULTS Mean lesion depth in the FW area for tooth blocks in AgF , KF , AgNO(3 ) and control groups were 0 μm , 3.3 ± 10.3 μm , 156.3 ± 30.8 μm , and 173.6 ± 48.6 μm , respectively ( p < 0.001 ) . The difference in mean lesion depth between the AgNO(3 ) and control groups was not statistically significant ( p > 0.05 ) . Similar OW and FW lesions were observed in tooth blocks in the AgNO(3 ) and control groups . CONCLUSIONS Topical application of a 2.36 M fluoride solution can inhibit demineralization of enamel while topical application of silver ions has little effect", "BACKGROUND Silver diamine fluoride ( SDF ) is an effective agent for the arrest of caries in children , is easy to apply and can be used outside the clinical environment . Interim restorative treatment ( IRT ) using glass ionomer cement has also been cl aim ed to be a simple and effective method to arrest caries in deciduous teeth . OBJECTIVE To examine whether , for underprivileged schoolchildren with cavities , treatment with 30 % SDF gives better results than IRT for carries arrest . METHOD This r and omised controlled study compares the effect of IRT ( FUJI IX ) with 30 % SDF in 91 children aged 5 - 6 years . RESULTS After 1 year , treatment with SDF was more effective [ relative risk ( RR ) = 66.9 % ] than IRT ( RR = 38.6 % ) for the arrest of caries ; this was statistically significant ( P < 0.05 ) . CONCLUSION The SDF technique showed better results than IRT for the arrest of cavities in deciduous teeth , indicating that its use for underprivileged communities may justify a paradigm shift in paediatric dentistry", "OBJECTIVES To investigate the effectiveness of silver diammine fluoride ( SDF ) solution application in arresting dental root caries and to assess the color of arrested caries lesions . METHODS This study was conducted in elderly centers in Hong Kong . A total of 83 elders with 157 root surfaces with active caries lesion were r and omly allocated into 3 groups : Gp1 ( placebo control)-annual application of soda water ; Gp2-annual application of SDF solution ; Gp3-annual application of SDF solution immediately followed by potassium iodide ( KI ) solution . Color of the arrested root caries lesion was assessed with reference to PANTONE color plates and classified into one of the followings : yellow ( 7401U ) ; light brown ( 1245U ) ; dark brown ( 4635U ) ; and black ( Black U ) . Status of root surfaces was assessed every 6 months by the same independent examiner . RESULTS After 30 months , 100 ( 64 % ) of the included root caries lesions were review ed . The arrest rates of root caries were 45 % , 90 % , and 93 % in Gp1 ( control ) , Gp2 ( SDF ) and Gp3 ( SDF/KI ) , respectively ( χ(2 ) test , p<0.001 ) . Pairwise comparisons showed elders in the control group had a lower proportion of the active root caries changed to arrested ( p<0.001 ) and the proportions of root caries being arrested in the SDF and SDF/KI groups were not significantly different ( p>0.05 ) . The distributions of arrested caries lesions by color were not significantly different between the SDF and SDF/KI groups ( χ(2 ) test , p>0.05 ) . CONCLUSIONS Application of SDF solution , with or without application of KI afterwards , is effective in arresting root caries among elders in a water fluori date d area . In the long term , blackening of arrested root caries is not reduced by immediate application of KI after the application of SDF . CLINICAL SIGNIFICANCE In a water fluori date d area , annual application of SDF solution or SDF/KI solution can arrest dental root caries in elders . In the long term , application of KI does not reduce the blackening of arrested caries lesions caused by SDF", "We hypothesized that the six-monthly application of silver diamine fluoride ( SDF ) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars . A prospect i ve controlled clinical trial was conducted on the efficacy of a 38 % SDF solution for caries reduction . Four hundred and twenty-five six-year-old children were divided into two groups : One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos . The second group served as controls . The 36-month follow-up was completed by 373 children . The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls . The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls . The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren", "The aim of this in vitro study was to investigate the effect of the cariostatic and preventive agent silver diamine fluoride ( SDF ) on the microtensile bond strength of resin composite to dentin . Forty-two caries-free , extracted molars were flattened occlusally and apically using a diamond saw , and the exposed occlusal dentin was polished with a series of silicon carbide papers , all under water irrigation . The teeth were then r and omly divided into six groups of seven teeth each that were treated as follows : 1 ) Peak SE self-etch bonding agent ; 2 ) 12 % SDF + Peak SE ; 3 ) 38 % SDF + Peak SE ; 4 ) Peak LC etch- and -rinse bonding agent ; 5 ) 12 % SDF + Peak LC ; and 6 ) 38 % SDF + Peak LC . Four-millimeter buildups of Amelogen Plus were incrementally placed on all teeth ; after a 24-hour storage period in distilled water , the specimens were sectioned perpendicular to the adhesive interface to produce beams of cross-sectional surface area measuring approximately 1 mm(2 ) . The beams were placed on a microtensile testing machine , which utilized a single-speed pump motor and force gauge at 20 kgf × 0.01 second to record maximum tensile force before failure occurred . Two-way analysis of variance and post hoc Tukey tests were performed to compare the effects of the SDF on microtensile bond strength , with statistical significance set at α = 0.05 . None of the experimental groups treated with different concentrations of SDF showed a significant difference in bond strength compared to the control groups , and there was no significant difference in bond strength between self-etch and etch- and -rinse groups . However , the effect of SDF on self-etch bonded teeth compared to etch- and -rinse bonded teeth was statistically significant ( p=0.0363 ) , specifically at the 12 % concentration . SDF does not adversely affect the bond strength of resin composite to noncarious dentin", "OBJECTIVES This study aim ed to compare the effectiveness of three topical fluoride application protocol s in arresting dentine caries in primary teeth of preschool children in a fluori date d area . METHODS Children aged 3 - 4 years who had at least one active dentine caries lesion were r and omly allocated into three intervention groups : Group 1-application of 30 % silver diammine fluoride ( SDF ) solution every 12 months ; Group 2-three applications of 30 % SDF solution at weekly interval at baseline ; and Group 3-three applications of 5 % sodium fluoride ( NaF ) varnish at weekly interval at baseline . A masked examiner carried out follow-up examinations every 6 months to assess whether the treated lesions had become arrested . RESULTS A total of 304 children with 1670 tooth surfaces with dentine caries received treatment at baseline . After 18 months , 275 children ( 91 % ) remained in the study . The caries arrest rates at tooth surface level were 40 % , 35 % and 27 % for Groups 1 , 2 and 3 , respectively ( p<0.001 ) . Result of the multi-level survival analysis showed that the two SDF application protocol s could shorten the time to arrest of dentine caries compared with the NaF application protocol . Presence of plaque on lesion surface , tooth type and tooth surface all had significant effects on caries arrest rates . CONCLUSIONS Annual or three consecutive weekly applications of SDF solution is more effective in arresting dentine caries in primary teeth than three consecutive weekly applications of NaF varnish . CLINICAL SIGNIFICANCE In a water fluori date d area , application of SDF solution , either three weekly applications at baseline or annually , can arrest active dentine caries lesions in primary teeth faster than three weekly applications of NaF varnish at baseline", "Tooth sensitivity is a common clinical problem . This multi-center r and omized clinical trial assessed the effectiveness and safety of topical diammine silver fluoride . From two sites ( Lima and Cusco , Peru ) , 126 adults with at least one tooth sensitive to compressed air were r and omly assigned to either the experimental treatment or sterile water , and pain was assessed by means of a 100-mm visual analogue scale at 24 hours and 7 days . The diammine silver fluoride reduced pain at 7 days at both sites . At the Lima site , the average change in pain scores between baseline and day 7 for the silver fluoride group was -35.8 ( SD = 27.7 ) mm vs. 0.4 ( SD = 16.2 ) mm for the control group ( P < 0.001 ) . In Cusco , the average change in pain scores for the silver fluoride group was −23.4 ( SD = 21.0 ) mm and -5.5 ( 18.1 ) mm for the control group ( P = 0.002 ) . No tissue ulceration , white changes , or argyria was observed . A small number of participants in the silver fluoride group experienced a mild but transient increase in erythema in the gingiva near the tooth . No changes were observed in the Gingival Index . We concluded that diammine silver fluoride is a clinical ly effective and safe tooth desensitizer", "BACKGROUND The purpose of this study was to compare the effect of silver fluoride , silver nitrate and potassium fluoride on remineralization of demineralized enamel and dentine in vitro . METHODS Forty premolars were cut into cuboidal blocks . Acid-resistant varnish was painted onto each block to cover all surfaces , except two windows , one in enamel and one in dentine . The tooth blocks were placed in demineralizing solution for 96 hours . They were then r and omly divided into four groups of 10 blocks each and immersed in solutions of AgF , AgNO(3 ) , KF or water for 3 minutes . Afterwards , they were immersed in a remineralizing solution for 108 hours . Micro CT scanning was conducted before and after remineralization . RESULTS The increase in linear attentuation coefficient ( LAC ) for the enamel lesions after remineralization was 1.08/cm , 0.95/cm , 0.86/cm and 0.60/cm in the AgF , AgNO(3 ) , KF and control groups , respectively ( ANOVA , p < 0.001 ; AgF , AgNO(3 ) , KF > control ; AgF > KF ) . The increase in LAC for the dentine lesions was 1.01/cm , 0.92/cm , 0.88/cm and 0.53/cm , respectively ( ANOVA , p < 0.001 ; AgF , AgNO(3 ) , KF > control ) . CONCLUSIONS Topical application of silver or fluoride ions can increase the mineral density of demineralized enamel and dentine lesions during remineralization . The synergistic effect of silver and fluoride ions is relatively small" ]

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[ "Efficacy of low-dose continuous infusion of alpha-human atrial natriuretic peptide (hANP) during cardiac surgery: possibility of postoperative left ventricular remodeling effect.", "Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery.", "Atrial natriuretic factor does not improve the outcome of cadaveric renal transplantation.", "Effects of atrial natriuretic peptide versus mannitol on renal blood flow during radiocontrast infusion in chronic renal failure.", "Significance of prophylactic urodilatin (INN: ularitide) infusion for the prevention of acute renal failure in patients after heart transplantation.", "Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients", "Prophylactic use of low-dose urodilatin for prevention of renal impairment following liver transplantation: a randomized placebo-controlled study.", "Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans", "[Urodilatin (INN: ularitide). A new peptide in the treatment of acute kidney failure following liver transplantation].", "Concomitant treatment with urodilatin (ularitide) does not improve renal function in patients with acute renal failure after major abdominal surgery--a randomized controlled trial.", "Anaritide in acute tubular necrosis. Auriculin Anaritide Acute Renal Failure Study Group.", "Therapeutic use of the natriuretic peptide ularitide in acute renal failure.", "Atrial natriuretic peptide as a preload depressor in acute renal failure secondary to congestive heart failure.", "Effects of atrial natriuretic peptide in clinical acute renal failure.", "Effects of intraoperative administration of atrial natriuretic peptide.", "Prevention of Renal Impairment by Continuous Infusion of Human Atrial Natriuretic Peptide after Liver Transplantation", "Long‐term infusion of atrial natriuretic peptide (ANP) improves renal blood flow and glomerular filtration rate in clinical acute renal failure", "Effect of 1-28 alpha-h atrial natriuretic peptide on acute renal failure in cadaveric renal transplantation.", "Synthetic human alpha-atrial natriuretic peptide improves the management of postoperative hypertension and renal dysfunction after the repair of abdominal aortic aneurysm.", "Recombinant human atrial natriuretic peptide in ischemic acute renal failure: A randomized placebo-controlled trial*", "Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy.", "Efficacy of Continuous Low-Dose Human Atrial Natriuretic Peptide Given from the Beginning of Cardiopulmonary Bypass for Thoracic Aortic Surgery", "URODILATIN (INN: ULARITIDE) AS A NEW DRUG FOR THE THERAPY OF ACUTE RENAL FAILURE FOLLOWING CARDIAC SURGERY", "Atrial natriuretic factor improves renal function and lowers systolic blood pressure in renal allograft recipients treated with cyclosporin A." ]

[ "BACKGROUND The aim of the present study was to evaluate the efficacy of alpha-human atrial natriuretic peptide ( hANP ) in cardiac surgery under cardiopulmonary bypass ( CPB ) . METHODS AND RESULTS A prospect i ve r and omized study was conducted with 150 patients who underwent scheduled coronary artery bypass grafting to compare a group of patients receiving 0.02 microg x kg(-1 ) x min(-1 ) of hANP from the initiation of CPB with a group not receiving hANP . Hemodynamics , levels of atrial and brain natriuretic peptides ( BNP ) , angiotensin-II and aldosterone , renin activity , and left ventricular ( LV ) function were examined . The hANP group showed significantly lower renin activity and lower levels of angiotensin-II and aldosterone during the early postoperative period , compared with the non-hANP group . The incidence of postoperative ventricular arrhythmia and the postoperative peak level of creatine kinase-MB were significantly lower in the hANP group . BNP at 1 month after surgery and measures of LV function were also significantly lower in the hANP group . CONCLUSIONS Low-dose continuous infusion of hANP during cardiac surgery not only had a compensatory effect for the imperfections of CPB during the early postoperative period but also an inhibitory effect on postoperative LV remodeling and a reduction in ischemia/reperfusion injury . hANP should be part of the postoperative care for cardiac surgery", "BACKGROUND We evaluated the effects of human atrial natriuretic peptide ( hANP ) during cardiopulmonary bypass ( CPB ) . METHODS Forty patients undergoing coronary artery bypass grafting were investigated . A group of patients given hANP for 24 hours from the start of CPB ( hANP group ) was compared with a non-hANP group . Parameters examined were hemodynamics , urine volume , dosage of furosemide , respiratory index , pleural effusion , ANP , cyclic guanosine monophosphate , renin activity ( renin ) , angiotensin-II , aldosterone , and glomerular filtration rate . RESULTS Central venous pressure , systemic vascular resistance index , and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group . The hANP group showed significantly higher levels of ANP , cyclic guanosine monophosphate , glomerular filtration rate , and respiratory index , and significantly lower levels of renin , angiotensin-II , aldosterone , and pleural effusion , as compared with the non-hANP group . The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group . CONCLUSIONS hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance , suppressing the renin-angiotensin-aldosterone system , and exerting a strong diuretic effect", "Atrial natriuretic factor ( ANF ) ameliorates renal damage in animal models of acute ischemic renal failure . Consequently , ANF could blunt acute tubular necrosis related to ischemia that occurs frequently in cadaveric renal transplants . Ten pairs of cadaveric kidneys were transplanted into 20 recipients . Paired recipients received either alpha-human ANF ( hANF ) or vehicle alone in a prospect i ve , double-blind protocol . Upon revascularization of the allograft , either hANF or vehicle was administered intravenously as a 50-micrograms bolus , followed by a 4-h infusion ( 0.1 microgram/kg/min ) . Glomerular filtration rate ( [125I]iothalamate clearance ) was measured between 4 and 7 days posttransplant and again between 14 and 21 days posttransplant . Serum creatinine was measured daily when patients were in the hospital , then twice weekly as patients were examined in the outpatient clinic . Between the groups , there was no significant difference in age of the recipients or donors , cold ischemia time , or histocompatibility leukocyte antigen match . Infusion of hANF had no adverse effects . When subjects receiving hANF were compared with those treated with vehicle alone , there were no significant differences in serum creatinine or glomerular filtration rate . Three hANF and four vehicle recipients required dialysis postoperatively . At 1 month posttransplant , 19 of 20 patients had functioning allografts ; an allograft from one hANF recipient never functioned . It was concluded that hANF , when given by the protocol of this study , had no beneficial effect on the outcome of cadaveric renal transplantation in humans", "This study was performed to investigate the effects of atrial natriuretic peptide ( ANP ) and mannitol on renal blood flow ( RBF ) and radiocontrast-induced nephropathy ( RCIN ) in human subjects with chronic renal failure . ANP preserves glomerular filtration rate or RBF ( or both ) in severe animal models of acute renal failure . Radiocontrast is known to substantially decrease RBF and can induce acute renal failure . Twenty consecutive patients with chronic renal failure ( 60 % with diabetes ) were r and omized in a prospect i ve , double-blind fashion to receive either ANP ( 50 micrograms bolus , then 1 microgram/min infusion ) or mannitol ( 15 % at 100 ml/hr ) for 2 hours before and during cardiac catheterization with diatrizoate . Baseline serum creatinine level ( ANP 2.4 + /- 0.7 mg/dl , mannitol 2.5 + /- 0.8 mg/dl ) , medications , and quantity of radiocontrast were similar in both groups . Direct measurements of RBF were made with thermodilution catheters placed in the left renal vein . RBF rose significantly ( p less than 0.05 ) , to 198 % of baseline at 15 minutes and 166 % of baseline at 65 minutes in the group receiving ANP and remained stable in the group receiving mannitol . ANP levels rose significantly from baseline at 5 , 15 , 65 and 120 minutes in both groups ( p less than 0.05 ) . Acute renal failure defined as a 0.5 mg/dl rise of creatinine within 24 hours of cardiac catheterization , developed only in patients with diabetes mellitus and was similar in both experimental groups ( ANP , 50 % ; mannitol , 30 % ) . Only patients with diabetes mellitus responded with an increase in RBF after a 5-minute infusion of either ANP or mannitol ( diabetes , 165 % + /- 28 % baseline ; no diabetes , 96 % + /- 8 % baseline ) ( p less than 0.05 ) . In conclusion , RBF was maintained or increased despite administration of radiocontrast , a documented renal vasoconstrictor . Patients with diabetes mellitus had a renal vasodilatory response to drug infusion . Acute renal failure occurred to a similar extent in both groups . Plasma ANP levels rose significantly in both groups . Mannitol may induce ANP release , thus contributing to mannitol 's renal effects", "Acute renal failure is a serious problem following heart transplantation . In first uncontrolled clinical trials , Urodilatin revealed beneficial effects in the prophylaxis and therapy of acute renal failure following heart and liver transplantation . Here , we present the first r and omized , placebo-controlled , double-blind study on 24 patients following heart transplantation to investigate whether prophylactic i.v . Urodilatin infusion can prevent acute renal failure requiring renal replacement therapy . Postoperative drug management was characterized by intravenous application of high furosemide , cyclosporine , and vancomycin doses . Urodilatin infusion was started postoperatively with a dose of 40 ng / kg bw / min for 6 days . 6 of the 12 patients in the Urodilatin group and 6 of the 12 patients in the placebo group had a stable diuresis ( 3 - 4 l / day ) during the study period of 6 days . In contrast , the remaining 6 patients of each group developed oliguria / anuria and required subsequent hemofiltration / hemodialysis . Cumulative duration of hemofiltration ( 88 + /- 7.39 hours in the placebo treated patients versus 44 + /- 5.35 hours in the Urodilatin treated patients , p < 0 . 05 ) as well as frequency of hemodialysis ( 3.0 + /- 0.49 times in the placebo group vs 1.2 + /- 0.29 times in the Urodilatin group , p < 0 . 05 ) were significantly reduced using Urodilatin . Mean arterial blood pressure was stable during the Urodilatin infusion period and was not different to that observed in placebo patients . We conclude that Urodilatin does not reduce the incidence of acute renal failure and the subsequent requirement for hemofiltration / hemodialysis in our patient population , but seems to reduce the duration of hemofiltration and frequency of hemodialysis compared to the placebo group", "Summary Renal failure after heart transplantation ( HTx ) still remains a serious problem , especially when cyclosporin A is used for immunosuppression in the early postoperative therapy . To preserve good renal function without reducing immunosuppressive cyclosporin A treatment , we administered urodilatin ( CDD/ANP-95 - 126 ) in a long-term , low-dose infusion in addition to the usual medication after heart transplantation . From November 1990 to June 1991 , 51 patients ( 46 male and 5 female ; mean age 48 years ) were treated with a 620 ng/kg bw·min infusion for 96 h after HTx . The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients ( 33 male and 7 female ; mean age 49 years ) who had undergone HTx previously from May to November , 1990 , as controls . In this phase IIa study , both groups did not differ significantly with respect to age , sex , indication for HTx , and preoperative renal function . In comparison with controls patients treated with urodilatin had a significantly better renal function : a reduction in the peak plasma creatinine ( PC values day 4 : 1.5 ± 0.11 vs. 2.19 ± 0.19 mg/dl ; P = 0.002 ) , a lower peak serum urea ( SU values day 4 : 109 ± 8 vs. 154.7 ± 8.94 mg/dl ; P = 0.0036 ) , and a lower incidence of hemodialysis ( 6 % vs. 10 % ) were observed . Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60 % ( P = 0.005 ) on each day of urodilatin infusion in comparison with controls . The mean central venous pressure was significantly lower by about 50 % ( P = 0.02 ) during the administration of urodilatin in spite of reduced vasodilator medication with nitroglycerin . From this phase IIa study , we may conclude that urodilatin could be an important drug in intensive care treatment . For patients undergoing HTx , this peptide seems to be indicated for the improvement of renal function and cardiovascular status , especially in postoperative therapy using high-dose cyclosporin A treatment", "Many therapeutic measures have been employed to prevent or at least ameliorate postoperative renal impairment following liver transplantation . Recent clinical phase II studies have demonstrated that the new natriuretic peptide urodilatin has beneficial effects on renal function following heart and liver transplantation . The present study reports the first prospect i ve r and omized placebo-controlled trial of prophylactic urodilatin administration following liver transplantation . Seventy consecutive recipients of primary liver transplants were included in the study following r and omization , and 33 patients continuously received urodilatin at a dose of 20 ng/kg/min for 7 d. The remaining 37 patients received a placebo infusion for the same time period . The course of serum creatinine and urea did not differ between the two groups nor did the daily urine production . However , the urodilatin group showed a higher preoperative median serum creatinine and a significant reduction on days 1 and 2 , whereas this observation was not made in the placebo group . Furthermore , less furosemide was administered to the patients in the urodilatin group during the first 2 d. The incidence of postoperative hemodialysis and the number of treatments did not differ between the groups either ( urodilatin group 4 , vs. placebo group 6 and 22 for both groups , respectively ) . Side effects of the urodilatin therapy were not detected . The prophylactic low-dose urodilatin administration result ed in a trend towards amelioration of the renal function , but did not result in significant differences between the two experimental groups . Further studies , using higher doses , will be required to define the value of urodilatin for prevention of renal impairment after liver transplantation", "Objective Imbalance in the renal medullary oxygen supply/dem and relationship can cause hypoxic medullary damage and ischemic acute renal failure . Human atrial natriuretic peptide ( h-ANP ) increases glomerular filtration rate in clinical acute renal failure . This would increase renal oxygen consumption due to increased tubular load of sodium . Loop diuretics are commonly used in acute renal failure . Data on the effects of loop diuretics on glomerular filtration rate and renal oxygen consumption in humans are , however , controversial . We evaluated the effects of h-ANP and furosemide on renal oxygen consumption , glomerular filtration rate , and renal hemodynamics in humans . Design and setting Prospect i ve two-agent interventional study in a university hospital cardiothoracic ICU Patients Nineteen uncomplicated , mechanically ventilated postcardiac surgery patients with normal renal function . Interventions h-ANP ( 25 and 50 ng/kg per minute , n=10 ) or furosemide ( 0.5 mg/kg per hour , n=9 ) Measurements and results Renal plasma flow and glomerular filtration rate were measured using the infusion clearance technique for 51Cr-labeled EDTA and paraaminohippurate , corrected for by renal extraction of PAH . h-ANP increased glomerular filtration rate , renal filtration fraction , fractional excretion of sodium , and urine flow . This was accompanied by an increase in tubular sodium reabsorption ( 9 % ) and renal oxygen consumption ( 26 % ) . Furosemide infusion caused a 10- and 15-fold increase in urine flow and fractional excretion of sodium , respectively , accompanied by a decrease in tubular sodium reabsorption ( –28 % ) , renal oxygen consumption ( –23 % ) , glomerular filtration rate and filtration fraction ( –12 % and −7 % , respectively ) . Conclusions The filtered load of sodium is an important determinant of renal oxygen consumption . h-ANP improves glomerular filtration rate but does not have energy-conserving tubular effects . In contrast , furosemide decreases tubular sodium reabsorption and renal oxygen consumption and thus has the potential to improve the oxygen supply/dem and relationship in clinical ischemic acute renal failure", "UNLABELLED Acute renal failure ( ARF ) is a serious complication following liver transplantation . Many therapeutic regimens have been used so far but with limited success . Urodilatin ( URO ) is a new member of the atrial natriuretic peptide ( ANP ) family . When administered intravenously , URO induces strong diuresis and natriuresis with tolerable hemodynamic side effects . Preliminary non-controlled clinical studies demonstrate beneficial effects using URO as a therapeutic agent in patients suffering from ARF following heart and liver transplantation ( HTx , LTx ) . These results prompted us to initiate this first controlled clinical trial to investigate whether URO infusion can improve renal function in patients with emerging ARF following LTx . METHOD We initiated a r and omized , double-blind , placebo-controlled study comparing five patients receiving i.v . URO infusion ( 20 ng/kg bw/min ) with four placebo patients after informed consent was obtained . Optional inclusion criteria were oliguria/anuria ( < 0.5 ml/kg/h ) , refractory to conventional treatment including administration of furosemide and dopamine , increase of serum creatinine to a least 200 % of preoperative values , and BUN levels > or = 25 mmol/l . The primary parameters for efficacy was the frequency of hemodialysis/hemofiltration . RESULTS The frequency of hemodialysis/hemofiltration during URO or placebo infusion was significantly reduced ( P = 0.03 ) in the URO-treated patients in comparison with placebo . BUN levels did not differ between two groups , but serum creatinine levels were consistently lower in the URO group . Diuresis tended to be stronger in the URO group , maintaining high levels despite a significant reduction in the administration of furosemide in comparison with placebo . CONCLUSION We conclude that URO seems to be a new approach for the treatment of therapy-resistant postoperative ARF following LTx", "Acute renal failure after major abdominal surgery is a severe complication in critically ill patients in intensive care units ( ICU ) . The aim of the study was to investigate the effect of urodilatin on the peak value and course of serum creatinine in patients with acute renal insufficiency after major abdominal surgery and the necessity of apparatus-based renal replacement treatment . Furthermore , the incidence and nature of adverse events under urodilatin was documented . In a prospect i ve r and omized double-blind placebo-controlled study , 12 critically ill patients after major abdominal surgery with acute renal failure in an intensive care unit ( ICU ) received 20 ng/kg b.w./min urodilatin ( ularitide , INN ) or placebo in addition to the st and ard diuretic therapy or low-dose dopamine ( 2.5 micrograms/kg b.w./min ) and furosemide ( 1000 mg/24 hr ) for a minimum of 96 hours . All patients received mechanical ventilation . Both groups had similar serum creatinine values on the day before the onset of urodilatin/placebo infusion ( 2.80 + /- 0.24 mg/dl , 2.93 + /- 0.48 mg/dl ) . Peak serum creatinine was lower in the urodilatin group ( 4.65 + /- 0.57 mg/dl ) compared to vehicle treatment ( 5.78 + /- 1.58 mg/dl ) , although the difference did not reach statistical significance ( P = 0.148 ) . The total number of hemodialyses due to oligo-/anuria and /or hyperkalemia was the same in both groups during the study . In 4 patients of the placebo group , diuresis was reduced to anuria , whereas only 1 of the patients treated with urodilatin became anuric . No hemodynamic side effects or adverse events due to urodilatin were observed . This clinical study under double blind conditions revealed that the addition of urodilatin to the st and ard diuretic therapy of low-dose dopamine and furosemide failed to improve renal function in patients with established acute renal failure and that urodilatin did not eliminate the need for apparatus-based renal replacement treatment", "BACKGROUND Atrial natriuretic peptide , a hormone synthesized by the cardiac atria , increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles . It has been shown to improve glomerular filtration , urinary output , and renal histopathology in laboratory animals with acute renal dysfunction . Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled clinical trial of anaritide in 504 critically ill patients with acute tubular necrosis . The patients received a 24-hour intravenous infusion of either anaritide ( 0.2 microgram per kilogram of body weight per minute ) or placebo . The primary end point was dialysis-free survival for 21 days after treatment . Other end points included the need for dialysis , changes in the serum creatinine concentration , and mortality . RESULTS The rate of dialysis-free survival was 47 percent in the placebo group and 43 percent in the anaritide group ( P = 0.35 ) . In the prospect ively defined subgroup of 120 patients with oliguria ( urinary output , < 400 ml per day ) , dialysis-free survival was 8 percent in the placebo group ( 5 of 60 patients ) and 27 percent in the anaritide group ( 16 of 60 patients , P = 0.008 ) . Anaritide-treated patients with oliguria who no longer had oliguria after treatment benefited the most . Conversely , among the 378 patients without oliguria , dialysis-free survival was 59 percent in the placebo group ( 116 of 195 patients ) and 48 percent in the anaritide group ( 88 of 183 patients , P = 0.03 ) . CONCLUSIONS The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis . However , anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis", "BACKGROUND Ularitide is a member of the natriuretic peptide family . This hormone exhibits an N-terminal extension by four amino acids compared with atrial natriuretic peptide . Ularitide was shown to exert strong diuretic and natriuretic effects when infused intravenously . Its main action sites are the glomerulum , inducing preglomerular vasodilation and postglomerular vasoconstriction and thereby elevating the glomerular filtration rate , and the tubular system inhibiting Na(+)-reabsorption . In initial uncontrolled clinical trials , this peptide was shown to have beneficial effects in patients suffering from oliguric acute renal failure . METHODS We conducted a double-blind , placebo-controlled , multicenter , dose-finding trial recruiting 176 patients r and omized into 4 different Ularitide doses groups ( U5 , U20 , U40 , and U80 ng/kg/min ) and a placebo group ( U0 ) . Ularitide/placebo infusion was performed for 5 days with half the originally infused dose on day 5 . The primary objective of the study was to test various doses of Ularitide in patients suffering from oliguric acute renal failure to avoid mechanical renal replacement therapy during the first 12 hours . FINDINGS The results indicate that Ularitide does not reduce the incidence of mechanical renal replacement therapy compared with placebo-treated patients during the first 12 h of treatment ( U0 : 36 ( 20 ) , U5 : 35 ( 11 ) , U20 : 36 ( 9 ) , U40 : 28 ( 8) , U80 : 41 ( 12 ) , ( % ( n ) ( p = 0.87 ) ) . Diuresis increased in the Ularitide-treated groups and the placebo group after onset of infusion and did not show any significant difference in the first 12 h collection period ( U0 : 576 , U5 : 514 , U20 : 500 , U40 : 360 , U80 : 158 ML/12h ( Median ) , ( p = 0.16 ) ) . INTERPRETATION In summary , the incidence of mechanical renal replacement therapy in critically ill patients suffering from oliguric acute renal failure could not be altered positively by Ularitide administration according to our protocol . Further prospect i ve clinical trials are needed to answer the question whether a different patient collective or a prophylactic administration of Ularitide are more promising approaches in the clinical setting of oliguric acute renal failure", "The present study was undertaken to verify the hypothesis that infusion of atrial natriuretic peptide ( ANP ) might lower preload and be beneficial in the treatment of pulmonary congestion even without a diuresis in patients with acute renal failure ( ARF ) secondary to severe congestive heart failure ( CHF ) . We studied 22 patients with ARF secondary to CHF . The mean age of the patients ( 14 men and 8 women ) was 72 years ( range 36 to 85 years ) . Seven of the patients had dilated cardiomyopathy , ten had ischemic heart disease , and five had valvular heart disease . ANP was infused intravenously and the following data before and 1 hour after the start of ANP infusion were recorded ; urinary output , systemic blood pressure ( SBP ) , pulmonary blood pressure ( PBP ) , right atrial pressure ( RAP ) , cardiac index ( CI ) , heart rate ( HR ) , and arterial blood oxygen partial pressure . Diastolic PBP were employed as pulmonary capillary wedge pressure . Urinary output did not change . Mean SBP decreased from 92 to 85 mmHg ( p < 0.05 ) , and mean PBP decreased from 34 to 28 mmHg ( p < 0.01 ) . Mean RAP decreased from 11 to 9 mmHg ( p < 0.01 ) and diastolic PBP decreased from 25 to 19 mmHg ( p < 0.01 ) . HR did not change significantly and CI increased 2.4 to 2.5 mi/min/m2 ( p < 0.05 ) . Arterial blood oxygen partial pressure increased significantly from 71 to 82 mmHg ( p < 0.05 ) . In conclusion , ANP decreased preload and improved arterial blood oxygen partial pressure , though diuretic response to ANP is attenuated in ARF secondary to CHE . Infusion of ANP will be very beneficial in cases in which dyspnea and pulmonary edema due to elevation of preload are the principal clinical problems", "Fifty-three consenting patients meeting clinical and urine composition criteria for established intrinsic ARF were assigned to two treatment groups . Group I patients were treated with human atrial natriuretic peptide ( ANP ) with or without diuretics . Groups II patients were treated with or without diuretics and with no ANP . Age , sex , etiology of ARF , entry serum creatinines ( SCr ) ( Group I , 5.3 + /- 1.8 ; Group II , 5.1 + /- 2.1 mg/dl ) and creatinine clearances ( CCr ) ( Group I , 9.9 + /- 2.1 ; Group II , 9.2 + /- 2.1 ml/min ) were similar . Thirty patients received ANP [ 0.20 micrograms/kg/min i.v . x 24 hr ( N = 20 ) or 0.08 micrograms/kg/min i.a . x 8 hr ( N = 10 ) ] and furosemide , 0.5 mg/kg/hr x 24 hr or mannitol , 12.5 g every six hours x 4 , or no diuretic ; 23 Group II patients received diuretics as above or no diuretic in a similar distribution to Group I. CCr ( verified with simultaneous inulin clearances x 12 , r = 0.93 , P < 0.001 ) increased significantly by eight hours of ANP treatment to 17.1 + /- 3.2 ml/min and by 24 hours after discontinuing ANP to 21.0 + /- 4.4 ml/min ( both P < 0.05 ) . There was no corresponding increase in CCr in Group II . Dialysis was required in 23 % of Group I and in 52 % of Group II patients ( different at P < 0.05 ) . Mortality rates of 17 % for Group I and 35 % for Group II were not significantly different ( P = 0.11 ) . It is concluded that parenteral ANP increases CCr and reduces need for dialysis in patients with established intrinsic ARF", "BACKGROUND Biological activity of endogenous atrial natriuretic peptide ( ANP ) may decrease during cardiopulmonary bypass . To evaluate the effects of intraoperative administration of exogenous ANP in patients undergoing cardiopulmonary bypass , we conducted a prospect i ve r and omized study . METHODS Eighteen patients undergoing mitral valve surgery were r and omized to receive either ANP treatment ( ANP group ; n = 9 ) or no ANP treatment ( control group ; n = 9 ) . Atrial natriuretic peptide was given immediately after initiation of cardiopulmonary bypass for 6 hours ( 0.05 microg x kg(-1 ) x min(-1 ) ) . Plasma ANP , brain natriuretic peptide and cyclic guanosine monophosphate ( cGMP ) levels , hemodynamic variables and renal function were assessed perioperatively . RESULTS Administration of ANP increased plasma cyclic guanosine monophosphate levels , urine output and fractional sodium excretion , and decreased preload , afterload and plasma brain natriuretic peptide levels significantly ( p < 0.05 ) . Plasma cyclic guanosine monophosphate levels correlated with plasma ANP levels ( r = 0.95 , p = 0.0001 ) , correlated with fractional sodium excretion ( r = 0.53 , p = 0.02 ) , and correlated inversely with systemic vascular resistance ( r = -0.54 , p = 0.02 ) . CONCLUSIONS Intraoperative administration of ANP had potent effects on natriuresis and systemic vasodilation by elevating cyclic guanosine monophosphate levels . The results suggest that the technique is useful for the management of hemodynamics and water-sodium retention after cardiopulmonary bypass", "Background . Acute renal failure occurring immediately after liver transplantation and requiring hemodialysis is a major problem result ing in a poor prognosis . We investigated the efficacy of human atrial natriuretic peptide , which has potent natriuretic effects and unique protective effects for glomeruli in preventing acute renal failure after liver transplantation . Methods . Thirty-seven patients who underwent live donor liver transplantation with model for end-stage liver disease scores greater than 15 were the subjects of the study . Subjects were prospect ively r and omized into two groups : patients that received synthetic human atrial natriuretic peptide infusion ( Group H : n=19 ) and those that received conventional diuretics , furosemide and potassium canrenoate ( Group C : n=18 ) . The peri- and postoperative changes in hemodynamic status and renal function were compared between the two groups . Results . There were no statistical differences in the changes in hemodynamic status between groups . Hemodialysis was required after liver transplantation in nine patients , two in Group H and seven in Group C ( P=0.04 ) . Postoperative creatinine clearance was higher in Group H ( P=0.03 ) . Aldosterone level was suppressed in group H ( P=0.006 ) . Conclusions . Continuous infusion of synthetic human atrial natriuretic peptide might be effective for preventing acute renal failure requiring hemodialysis after liver transplantation", "Background : Short‐term infusion of atrial natriuretic peptide ( ANP ) increases renal blood flow ( RBF ) and glomerular filtration rate ( GFR ) in patients with acute renal dysfunction . In the present study we evaluated the effects of long‐term infusion ( > 48 h ) of ANP on ( RBF ) and ( GFR ) in 11 postcardiac surgical patients requiring pharmacological circulatory support and with acute renal impairment", "The efficacy and safety of ( 1 - 28 ) alpha-human ANP in preventing acute tubular necrosis ( ATN ) in cadaveric renal transplantation was tested by comparing ANP infusion with a maximal hydration ( MH ) regimen which we previously reported as effective in lowering the incidence of ATN ( 1 , 2 ) . Since the production of endogenous ANP increases with volume overloading ( 3 ) , we hypothesized that increased endogenous ANP production may contribute to the beneficial effects of MH in renal transplant recipients . We thus conducted an open r and omized study comparing the effect on early renal allograft function of MH ( control group ) versus moderate hydration plus ANP infusion ( ANP group ) . Forty patients were blindly paired in two groups of 20 according to the duration of cold ischemia time ( mean + /- 2 h ) . The demographic characteristics of donors and recipients were similar . Using a Swan-Ganz catheter , hemodynamic parameters were monitored for 4 h after transplantation . The group receiving ANP and moderate hydration was perfused to a mean pulmonary arterial pressure ( PAP ) of < or = 20 mmHg . The PAP in patients receiving MH was driven to > or = 25 mmHg . In the ANP group , a bolus of 100 micrograms of ANP was infused into the graft 's renal artery at the time of unclamping , followed by 24 h of continuous intravenous infusion at 0.03 microgram/kg/min . Thereafter , the patients received ANP at a rate of 0.01 microgram/kg/min until the serum creatinine reached < 2 mg/dl . As a consequence of the hydration regimen , the PAP at unclamping was lower in the ANP group than in the control group ; 20 + /- 3 and 26 + /- 4 mmHg , respectively ( p < 0.05 ) . The ANP plasma levels were significantly higher during the first 3 d in the ANP group ( p < 0.001 ) . The median recovery rate of renal function was similar in both groups . No patients in the ANP group experienced ATN while 4 patients ( 20 % ) in the control group did ( p = 0.125 ) . The need for hemodialysis was markedly reduced in the ANP group compared to the control group ( 1 ANP-treated patient required dialysis once whereas 5 patients from the control group underwent dialysis a total of 26 times ; p = 0.068 ) . ANP administration was well-tolerated and no hypotensive episodes were reported . This preliminary study suggests that ANP infusion is at least as effective as maximal hydration in preventing ATN and represents an efficient alternative for transplantation centers which do not use maximal hydration as a st and ard regimen in managing kidney allograft recipients", "OBJECTIVE Delayed hypertension ( HT ) and renal dysfunction ( RD ) are observed after aortic operations accompanied by infra-renal aortic cross-clamping ( AXC ) . Atrial natriuretic peptide ( ANP ) has effects on vasodilation and renal protection , and we examined the hypothesis that synthetic human alpha-ANP ( hANP ) improves the postoperative management for abdominal aortic aneurysm ( AAA ) . METHODS Fifty patients undergoing elective aneurysmectomy for infrarenal-AAA between 1998 and 2001 ( M : F = 43:7 , mean age 70.5 + /- 7.7 years ) were r and omly allocated to one of 2 groups ; Group H ( n = 24 ) received hANP immediately after operation ( initial dose : 0.025 microg/kg/min ) , and Group C ( n = 26 ) served as a control group . RESULTS All patients in Group C required nicardipine hydrochloride ( 4.41 + /- 1.68 mg/h ) for prevention of postoperative HT , whereas only 6 patients in Group H required the increase in hANP dose due to HT ( P < 0.0001 ) . Maximum hANP dose was 0.035 + /- 0.019 microg/kg/min . Group H showed significantly smaller furosemide dosage in the initial 3 days ( H vs. C ; 9.2 + /- 11.0 vs. 58.8 + /- 41.5 mg , P < 0.0001 ) , significantly lower peak-Crn ( H vs. C ; 1.16 + /- 0.53 vs. 2.58 + /- 1.42 mg/dL , P < 0.0001 ) , and significantly lower plasma renin-activity ( 7.09 + /- 2.38 vs. 11.52 + /- 4.89 ng/mL/h , P = 0.0002 ) and aldosterone ( 51.6 + /- 12.7 vs. 81.2 + /- 34.2 pg/mL , P = 0.0002 ) on the first postoperative day than Group C did . CONCLUSIONS These results imply that renin-angiotensin system may play a role in the incidence of postoperative HT and RD , and suggest that hANP infusion is a simple , reliable , and effective method for management during the immediate period after AAA operations", "Objective : Acute renal failure is associated with significant morbidity and mortality rates . Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery . Human atrial natriuretic peptide ( h-ANP ) is a potent endogenous natriuretic and diuretic substance . Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure . We have studied the effects of h-ANP on renal outcome in ischemic acute renal failure . Design : A prospect i ve , double-blind , r and omized , placebo-controlled study . Setting : Cardiothoracic intensive care units of two tertiary care centers . Patients : Sixty-one patients with normal preoperative renal function suffering from postcardiac surgical heart failure requiring significant inotropic and vasoactive support . Interventions : The patients were r and omized to receive a continuous infusion of either recombinant h-ANP ( 50 ng·kg−1·min−1 ) or placebo when serum creatinine increased by > 50 % from baseline . The treatment with h-ANP/placebo continued until serum creatinine decreased below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis . Measurements and Main Results : The primary outcome variable was dialysis on or before day 21 after the start of treatment . Secondary renal outcome variables were dialysis-free survival at day 21 and creatinine clearance . Twenty-nine patients were assigned h-ANP and 30 placebo . Six ( 21 % ) patients in the h-ANP group compared with 14 ( 47 % ) in the placebo group needed dialysis before or at day 21 ( hazard ratio , 0.28 ; 95 % confidence interval , 0.10–0.73 ; p = .009 ) . Eight ( 28 % ) patients in the h-ANP group compared with 17 ( 57 % ) in the placebo group suffered from the combined end point dialysis or death before or at day 21 ( hazard ratio , 0.35 ; 95 % confidence interval , 0.14–0.82 ; p = .017 ) . h-ANP improved creatinine clearance in contrast to placebo ( p = .040 ) . Conclusions : Infusion of h-ANP at a rate of 50 ng·kg−1·min−1 enhances renal excretory function , decreases the probability of dialysis , and improves dialysis-free survival in early , ischemic acute renal dysfunction after complicated cardiac surgery", "Radiocontrast-induced nephropathy ( RCIN ) is a common cause of hospital-acquired acute renal failure and is associated with a high mortality rate . RCIN is potentially preventable , because administration of the radiocontrast agent is predictable , and a high-risk population has been identified . This multicenter , prospect i ve , r and omized , double-blind , placebo-controlled trial was performed to evaluate the efficacy of intravenous atrial natriuretic peptide ( anaritide , ANP 4 - 28 ) to prevent RCIN . Patients with stable chronic renal failure ( serum creatinine greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with estimated creatinine clearance of < or = 65 mL/min ) were assigned to receive either placebo or one of three doses of anaritide ( 0.01 microg/kg/min , 0.05 microg/kg/min , or 0.1 microg/kg/min ) for 30 minutes before and continuing for 30 minutes after radiocontrast administration . All patients were given intravenous 0.45 % saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast . Both ionic and nonionic radiocontrast agents were administered . RCIN was defined as either an absolute increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25 % over baseline . Of the 247 patients who completed the study , 50 % had diabetes mellitus . There were no statistical differences in baseline serum creatinine , change in serum creatinine , or the incidence of RCIN . The incidence of RCIN was placebo , 19 % ; anaritide ( 0.01 ) , 23 % ; anaritide ( 0.05 ) , 23 % ; anaritide ( 0.1 ) , 25 % . Patients with diabetes mellitus had a significantly greater incidence of RCIN : placebo , 26 % versus 9 % ; anaritide ( 0.01 ) , 33 % versus 13 % ; anaritide ( 0.05 ) , 26 % versus 21 % ; anaritide ( 0.1 ) , 39 % versus 8 % ( diabetic v nondiabetic , P < 0.002 ) . There was no effect in the diabetic or nondiabetic groups by anaritide on the incidence of RCIN . Comparison of the highest-risk group of patients , defined as patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL , with the lowest-risk group , defined as patients without diabetes mellitus and a baseline serum creatinine of 1.8 mg/dL or less , did not show a beneficial effect of anaritide administration . In conclusion , administration of intravenous anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting chronic renal failure , with or without diabetes mellitus", "Purpose Cardiac surgery performed under cardiopulmonary bypass ( CPB ) causes abnormalities of the renin-angiotensin-aldosterone system , result ing in decreased urine output and an accumulation of water in the third space . We studied the efficacy of continuous low-dose human atrial natriuretic peptide ( hANP ) in patients undergoing thoracic aortic surgery . Methods We divided 40 patients undergoing thoracic aortic surgery into two groups : the hANP group , which received 0.02 μg/kg per minute of hANP and the non-hANP group , which did not . The hemodynamics , urine output , intensive care unit ( ICU ) and hospital stay , bleeding volume , homologous blood transfusion volume , furosemide dose , corrected KCl volume , and postoperative respiratory , hepatic , and renal function were compared in the two groups . Results The urine output during CPB and from CPB weaning to return to ICU was significantly better in the hANP group . The bleeding volume , homologous blood transfusion volume , furosemide dose , and corrected KCl volume were all significantly less in the hANP group . Conclusions These findings support the consensus that hANP exerts its diuretic effects to their full potential when administered continuously at low doses during thoracic aortic surgery . We found it to be effective for postoperative hemostasis and for preventing ischemic reperfusion injury", "1 . Acute renal failure is a severe complication following major cardiac surgery", "OBJECTIVE Atrial natriuretic factor ( ANF ) has several properties which suggest that it may ameliorate cyclosporin A nephrotoxicity . We therefore investigated the response to a pharmacological dose of ANF in renal transplant recipients treated with cyclosporin A. DESIGN A single-blind r and omized crossover design comparing the renal and haemodynamic effects of D-glucose ( placebo ) with ANF . METHODS Seven patients with stable renal function following renal transplantation were studied under maximal water diuresis . Glomerular filtration rate and effective renal plasma flow were estimated from clearances of inulin and para-aminohippurate , respectively . RESULTS Plasma ANF levels increased significantly in association with increased diuresis and natriuresis . Glomerular filtration rate was unchanged after placebo but increased significantly after ANF fusion . Likewise , effective renal plasma flow increased significantly with ANF infusion . There was a significant fall in systolic blood pressure , with no apparent change in heart rate and diastolic blood pressure . CONCLUSIONS These results suggest that ANF may have beneficial effects in protecting against cyclosporin A-induced nephrotoxicity and hypertension" ]

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[ "Effect of periodic letters on evidence-based drug therapy on prescribing behaviour: a randomized trial", "The impact of evidence-based guideline dissemination for the assessment and treatment of major depression in a managed behavioral health care organization", "Impact of clinical trials on clinical practice: example of thrombolysis for acute myocardial infarction", "Early Physician Notification of Patient Disability Risk and Clinical Guidelines After Low Back Injury: A Randomized, Controlled Trial", "Drug treatment of stable angina pectoris and mass dissemination of therapeutic guidelines: a randomized controlled trial.", "Do tailored behavior change messages enhance the effectiveness of health risk appraisal? Results from a randomized trial.", "Economic and Policy Analysis of University-based Drug “Detailing", "The impact of reading on physicians' nonadherence to recommended standards of medical care.", "Effect of audit and feedback, and reminder messages on primary-care radiology referrals: a randomised trial", "Internists' Attitudes about Clinical Practice Guidelines", "Chest radiography guidelines for general practitioners: a practical approach.", "Promotion and prescribing of hormone therapy after report of harm by the Women's Health Initiative.", "Understanding the Effects of Printed Health Education Materials: Which Features Lead to Which Outcomes?", "Implementation of the Dutch Low Back Pain Guideline for General Practitioners: A Cluster Randomized Controlled Trial", "Promoting brief alcohol intervention by nurses in primary care: a cluster randomised controlled trial.", "Nutrition Practice Guidelines for Type 1 Diabetes Mellitus positively affect dietitian practices and patient outcomes. The Diabetes Care and Education Dietetic Practice Group.", "A randomized trial to increase smoking intervention by physicians. Doctors Helping Smokers, Round I.", "Impact of the ICD-10 Primary Health Care (PHC) diagnostic and management guidelines for mental disorders on detection and outcome in primary care. Cluster randomised controlled trial.", "Synergy between publication and promotion: comparing adoption of new evidence in Canada and the United States." ]

[ "Background : The effect of regular and expected printed educational material s on physician prescribing behaviour has not been studied . We sought to measure the impact of a series of evidence -based drug therapy letters mailed to physicians in British Columbia on prescribing to newly treated patients . Methods : A paired , cluster r and omized community design was used . The study population included 499 physicians from 24 local health areas in British Columbia . Local health areas were paired by number of physicians , and 1 of each pair was r and omly selected and its physicians assigned to an intervention group or a control group . The intervention was 12 issues of an evidence -based series called Therapeutics Letter . Physicians in the control group ( n = 241 ) received the letters 3–8 months after physicians in the intervention group ( n = 258 ) . The impact on prescribing to newly treated patients ( defined as patients who had not previously made a cl aim for any medication from the class of drugs profiled in the letter ) was analyzed using the drug cl aims data base of BC Pharmacare , a publicly funded drug benefits program that covered all seniors and people receiving social assistance . Results : The probability of prescribing a drug recommended in the Therapeutics Letter rather than another drug in the same class increased by 30 % in the 3 months after the mailing of the letter relative to the preceding 3 months , adjusted for any before – after changes in the control group ( relative risk 1.30 ; 95 % confidence interval 1.13–1.52 ) . No letter achieved statistical significance on its own . However , 11 of the 12 letters produced prescribing changes in the predicted direction such that the overall result was significant when their effect was combined . Interpretation : The combined effect of an ongoing series of printed letters distributed from a credible and trusted source can have a clinical ly significant effect on prescribing to newly treated patients", "This study tests whether a managed behavioral health care organization can influence adherence to practice guidelines for the treatment of major depression in a r and omized trial of guideline dissemination . Guidelines were disseminated to mental health clinicians ( N=443 ) under one of three conditions : ( 1 ) a general mailing of guidelines to clinicians , ( 2 ) a mailing in which guidelines were targeted to a patient starting treatment with the clinician , and ( 3 ) no mailing of guidelines . The results showed no effects of guideline dissemination as measured by self-report of patients and clinicians and through episode characteristics derived from cl aims data , despite sentinel effects . Results also showed high rates of clinician-reported guideline adherence that were not detected in the cl aims data , indicating significant undertreatment of depression . Results suggest that mental health systems must look to other dissemination strategies to improve adherence to st and ards of care and raise the performance of independent practicing", "Little is known about incorporation of new knowledge from r and omised clinical trials into clinical practice . Thrombolytic therapy was shown to reduce the mortality of acute myocardial infa rct ion in several large trials published during 1986 - 88 . To examine the effect of these data on clinical practice , we analysed the supply of thrombolytic drugs in a representative English region ( population 4.7 million ) in 1987 - 92 . During the study period there were over 10,000 hospital admissions per year in the region for acute myocardial infa rct ion . From a very low initial level , thrombolytic drug use rose slowly for several years after publication of the trial results and reached a plateau in 1991 - 92 . Rates of use per 1000 patients admitted with myocardial infa rct ion varied almost six-fold between districts in 1989 - 90 and over two-fold in 1991 - 92 . Level of use attained by districts in the latter period was strongly associated with the extent of their previous participation in multicentre trials of thrombolysis ( p = 0.003 ) ; we estimate that 35 - 50 % of patients admitted with acute myocardial infa rct ion were receiving thrombolytics . The full potential of thrombolytic treatment has still not been achieved in routine care and the limiting factors need to be defined", "Study Design . Back‐injured workers with high disability risk scores on a predictive question naire participated in a r and omized , controlled trial of physician notification , with outcomes follow‐up 3 months after injury . Objectives . To test whether physician intervention improves return to work and self‐ assessment outcomes for people at relatively high risk for disability . Summary of Background Data . Only a small number of back‐injured workers suffer significant disability . Ouick identification of these people would facilitate more efficient targeting and trials of interventions . Controlling variations in practice through practice guidelines has been recommended as a promising strategy for improving care and reducing disability . Methods . Workers filing back injury reports responded to a disability prediction question naire . Those with high risk scores were r and omly assigned to control or intervention groups . Patient‐ design ated physicians in the intervention group received two letters identifying the patient 's risk and making recommendations for care , including the Agency for Health Care Policy and Research 's algorithms for acute low back pain . Predictive accuracy of the question naire and efficacy of physician intervention were evaluated on the basis of work status and self‐ assessment s 3 months after injury . Results . Of the 268 workers completing the question naire portion of the study , 32 ( 12 % ) were out of work because of back pain 3 months after injury . The question naire 's predictive accuracy included maximum κ of 0.277 and a receiver operating curve area of 0.78 . Fifty‐three people completed the physician intervention trial . The intervention had no significant impact on return to work , self‐assessed pain , or satisfaction with health care . Conclusions . Stratification of back‐injured people according to disability risk can can increase intervention efficiency by identifying those who require treatment and sparing those who do not . The apparent failure of risk notification and practice guidelines to reduce disability in this study may be improved by different application methods in the future", "BACKGROUND Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines , but the effectiveness of mass dissemination of guidelines is unknown . AIM To study the effects of guideline dissemination on physicians ' prescribing practice s for the treatment of stable angina pectoris . DESIGN R and omized controlled trial . METHODS A sample of 3293 Quebec physicians were r and omly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina ( in February 1999 ) , to receive the summary and a reminder ( in February and March 1999 , respectively ) , or to receive no intervention ( controls ) . The prescribing profiles of participants , as well as sociodemographic characteristics of the physicians and their patients , were examined for June-December 1999 . RESULTS The intervention had no effect on prescription rates of beta-blockers , antiplatelet agents , or hypolipaemic drugs . Compared to 1997 data for the same physicians , there was an overall 10 % increase in appropriate prescription rates , irrespective of the intervention . DISCUSSION In-house production and dissemination of clinical practice guidelines may not improve physicians ' practice patterns if there is pre-existing substantial scientific consensus on the issue", "Health risk appraisal ( HRA ) remains one of the most widely used health promotion tools despite only equivocal evidence for its effectiveness . Theories of behavior change predict conventional HRA 's ineffectiveness because risk information alone is seldom sufficient to change complex behaviors . In this study , a r and omized trial compared the effects of feedback from an enhanced HRA with a typical HRA and a control group among adult patients from eight family medicine practice s. The enhanced HRA assessed behavior-specific psychosocial factors and provided patients with computer-generated , individually-tailored behavior change information in addition to typical HRA risk feedback . Changes in seven behaviors were assessed at a 6 month follow-up . Overall , patients receiving enhanced HRA feedback were 18 % more likely to change at least one risk behavior than were patients receiving typical HRA feedback or no feedback ( OR = 1.18 , 95 % CI = 1.00 , 1.39 ) . The enhanced HRA feedback appeared to promote changes in cholesterol screening , dietary fat consumption and physical activity , but not in smoking , seat belt use , mammography and Pap smears . We conclude that the addition of theory-based , individually-tailored behavior change information may improve the effectiveness of HRA", "The cost-effectiveness of quality assurance programs is often poorly documented , especially for innovative approaches . The authors analyzed the economic effects of an experimental educational outreach program design ed to reduce inappropriate drug prescribing , based on a four-state r and omized controlled trial ( N = 435 physicians ) . Primary care physicians r and omized into the face-to-face group were offered two individualized educational sessions with clinical pharmacists , lasting an average of 18 minutes each , concerning optimal use of three drug groups that are often used inappropriately . After the program , expenditures for target drugs prescribed by these physicians to Medicaid patients decreased by 13 % , compared with controls ( P = 0.002 ) ; this effect was stable over three quarters . Implementation of this program for 10,000 physicians would lead to projected drug savings ( to Medicaid only ) of $ 2,050,000 , compared with re source costs of $ 940,000 . Net savings remain high , even after adjustment for use of substitution medications . Although there was a ninefold difference in average preintervention prescribing levels between the highest and lowest thirds of the sample , all groups reduced target drug expenditures at the same rate . Targeting of higher-volume prescribers would thus further raise the observed benefit-to-cost ratio from approximately 1.8 to at least 3.0 . Net benefits would also increase further if non-Medicaid savings were added , or if the analysis included quality -of-care considerations . Although print material s alone may be marginally cost-effective , print plus face-to-face approaches offer greater net benefits . The authors conclude that a program of brief , face-to-face “ detailing ” visits conducted by academic rather than commercial sources can be a highly cost-effective method for improving drug therapy decisions . Such an approach makes possible the enhancement of physicians ' clinical expertise without relying on restriction of drug choices", "In order to increase physicians ' adherence to recommended st and ards of medical care and to examine factors presumed to contribute to such changes , we conducted a r and omized , controlled trial using reading material s targeted to specific practice recommendations . Seventy-nine internal medicine residents completed baseline question naires stating their intentions to follow 13 common preventive care actions . They were r and omly assigned to receive one of two different sets of readings covering these care actions . Thus , each physician was in the experimental group for one set of readings ( A or B ) while serving as a control for the other set . The impact of the reading was determined by : the physicians ' knowledge of the recommended care actions detailed in the combined readings , their post-reading intentions , and clinical behavior when faced with patients having indications for the recommended actions . The 73 residents ( 92 % ) who read the material judged 39 % of the information to be new and 72 % useful . Residents had significantly better performance on the knowledge questions based on their own readings than did their control group peers for both sets of readings . For the Group A physicians , reading significantly ( P less than 0.05 ) increased intentions to follow one of the seven clinical actions while Group B residents increased their intentions in three out of six . Step-wise multiple regression analyses were used to predict physicians ' post-reading adherence to the recommended actions . For the Group A actions , pre-reading actions accounted for most of the variance in their post-reading actions . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Radiological tests are often used by general practitioners ( GPs ) . These tests can be overused and contribute little to clinical management . We aim ed to assess two methods of reducing GP requests for radiological tests in accordance with the UK Royal College of Radiologists ' guidelines on lumbar spine and knee radiographs . METHODS We assessed audit and feedback , and educational reminder messages in six radiology departments and 244 general practice s that they served . The study was a before- and -after , pragmatic , cluster r and omised controlled trial with a 232 factorial design . A r and om subset of GP patients ' records were examined for concordance with the guidelines . The main outcome measure was number of radiograph requests per 1000 patients per year . Analysis was by intention to treat . FINDINGS The effect of educational reminder messages ( ie , the change in request rate after intervention ) was an absolute change of -1.53 ( 95 % CI -2.5 to -0.57 ) for lumbar spine and of -1.61 ( -2.6 to -0.62 ) for knee radiographs , both relative reductions of about 20 % . The effect of audit and feedback was an absolute change of -0.07 ( -1.3 to 0.9 ) for lumbar spine of 0.04 ( -0.95 to 1.03 ) for knee radiograph requests , both relative reductions of about 1 % . Concordance between groups did not differ significantly . INTERPRETATION 6-monthly feedback of audit data is ineffective but the routine attachment of educational reminder messages to radiographs is effective and does not affect quality of referrals . Any department of radiology that h and les referrals from primary care could deliver this intervention to good effect", "Documentation of unexplained geographic variations in medical practice s [ 1 ] and use of interventions inappropriately [ 2 ] or before their effectiveness has been established [ 3 ] has led to the rapid proliferation of clinical practice guidelines . These systematic ally developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances [ 4 ] are an attempt to discourage ineffective medical practice s , encourage effective practice s , and improve health outcomes [ 5 - 10 ] . Despite increasing enthusiasm for guidelines , evidence exists that guidelines often do not affect clinical practice s or health outcomes [ 11 - 17 ] . One possible obstacle to effective guideline implementation is physician concern about the intent and validity of these documents [ 18 - 22 ] . Many physicians first encounter guidelines in the context of peer review , utilization management , and quality control programs , experiences that they may not perceive positively . Such outsider scrutiny is considered by some to be a challenge to autonomous clinical decision making . Little systematic study of physicians ' attitudes toward guidelines , however , has been done [ 23 , 24 ] . We did a national survey of a r and om sample of American College of Physicians ( ACP ) members to assess ACP members ' familiarity with , confidence in , and attitudes about guidelines issued by ACP and other organizations and members ' perceptions of the effect of ACP and other guidelines on their practice s. Methods Question naire We design ed a practice guidelines question naire that sought information about 1 ) demographic and professional characteristics of responders , including their year of graduation from medical school , board certification , academic affiliations , hours per week devoted to patient care , practice type , practice setting , and the principal method of clinical reimbursement ; 2 ) responders ' ratings of their familiarity with and confidence in practice guidelines issued by ACP , various medical specialty societies , and other major health care organizations ; 3 ) responders ' attitudes regarding guidelines and their effects on medical care ; 4 ) any change in responders ' clinical practice during the last year as a result of guidelines ; and 5 ) responders ' ratings of the importance of practice guidelines and other sources of information for clinical decision making . The question naire was approved by the ACP Clinical Efficacy Assessment Subcommittee ( CEAS ) after it was pilot-tested with 80 primary care physicians affiliated with the Johns Hopkins Health Plan [ 25 ] and 95 volunteers at the 1991 ACP Annual Meeting . Familiarity with , confidence in , and attitudes about guidelines were assessed using 5-point ordinal scales , with anchors appropriate to the judgment requested ( for example , 5 = very familiar to 1 = not familiar ; 5 = great confidence to 1 = no confidence ) . Estimated effects of guidelines on various aspects of medical practice were scored as likely to decrease , to have no effect , and likely to increase Sample We drew a stratified r and om sample of 400 associates , 1000 general internists , and 1200 internist specialists from ACP membership records . Members with specialty certification were over sample d because their response rate to previous ACP surveys was lower than that of other members . ( Johnson White L. Personal communication . ) The total sample of 2600 physicians represented 3.5 % of the ACP membership and included internists from every state . The sample size for the survey was based on assumptions of a response rate of 65 % and a 2-point st and ard deviation on the 5-point ordinal scales that comprised most items in our survey . Under these assumptions , a sample size of 2600 gave us greater than 90 % power to detect a 1-point difference for comparisons involving the smallest subspecialty groups ( for which we expected about 100 responders ) . Survey Procedure The survey was mailed in December 1991 , accompanied by a letter from the executive vice-president of ACP encouraging participation in the survey . Follow-up mailings were sent to nonresponders 1 and 2 months later , and data collection was terminated 6 weeks after the third mailing . Each physician was assigned a number that was placed on the cover sheet of mailed question naires . The same number was used to access information in an ACP membership data base about physician year of graduation , specialty certification , practice location , and membership status . Cover sheets were removed from returned question naires after recording the identification number . In this way , we were able to identify nonresponders , compare demographic characteristics of responders and nonresponders , and preserve the anonymity of physicians during data abstract ion and analysis . Analysis Data from returned question naires were double-entered and audited . Self-reported year of graduation and subspecialty certification were compared with information obtained from ACP data bases , with statistics of 0.98 and 0.53 , respectively . The low for subspecialty certification result ed from responders reporting a qualification that was not in ACP files . Many physicians join ACP before completing their specialty training , and ACP has not previously up date d its files for specialty status more often than once every 3 years . Therefore , we used self-reported professional characteristics from our survey in our analysis . To compensate for oversampling of subspecialists and undersampling of Associate ACP members , the ratio of the proportion of Associates , generalists , and specialists in the final sample to their true proportion in the ACP membership was used to generate adjustment weights that were applied to all analyses . Questions answered by fewer than 90 % of responders were not considered in the analysis . Frequency distributions of responses to question naire items were examined before statistical tests were selected and applied . Physician characteristics were coded as dichotomous variables except for year of graduation , which was recoded into four categories . We then tested the statistical significance of associations between physician characteristics and dichotomous question responses ( for example , impact compared with no impact on clinical practice ) using the chi-square test . For items with 5-point response scales , we tested the statistical significance of differences between ratings for different physician subgroups using analysis of variance . Stepwise logistic and multiple linear regression models were used to explore relations between sets of physician characteristics and responses to individual questions . Given the multiple comparisons , differences in response distributions between physician subgroups were considered statistically significant at the P 0.005 level . We developed an overall measure of physician attitudes toward guidelines by summing ordinal scale ratings regarding four positive views of guidelines ( strength of agreement with statements that guidelines generally are good educational tools , unbiased syntheses of expert opinion , a convenient source of advice , and intended to improve quality of care ) and the inverse of ordinal ratings regarding four negative views of guidelines ( oversimplified or cookbook medicine , a challenge to physician autonomy , too rigid to apply to individual patients , and intended to cut costs ) . Possible scores ranged from 8 to 40 , with 40 representing the most positive attitudes about guidelines . The internal consistency coefficient ( Chronbach ) for this scale was 0.76 . Results Description of Responders and Nonresponders Of the 2600 physicians in our original sample , 35 % returned question naires after the first mailing , 18 % after the second mailing , and 8 % after the third mailing . Eighty-seven physicians from the original sample were determined to be ineligible because of death ( n = 5 ) , retirement ( n = 48 ) , survey damage ( n = 1 ) , or no forwarding address ( n = 33 ) . Thus , we received completed question naires from 1513 ( 60 % ) of 2513 eligible physicians . Characteristics of those who did and did not respond to the survey were compared using data available from the ACP membership file . Responders and nonresponders were similar in terms of their year of graduation from medical school , geographic location of practice , and prevalence of generalist and subspecialty certification in internal medicine ( Table 1 ) . In addition , the characteristics of responders were similar to those of the target population of College members , after adjustment for intentional oversampling in some strata ( Table 2 ) . Table 1 . Characteristics of Members of the American College of Physicians : Survey Responders and Nonresponders Table 2 . Professional Characteristics of Survey Responders * Familiarity with Guidelines The percentage of responders reporting that they were familiar ( 4 or 5 on a scale of 1 = not at all familiar to 5 = very familiar ) with the content of selected guidelines varied from 11 % for ACP exercise stress test guidelines to 59 % for National Cholesterol Education Program ( NCEP ) guidelines ( Table 3 ) . Ratings of familiarity with guidelines that have actually been published were significantly greater than ratings for a fictitious ACP guideline about computed tomography of the head ( mean score , 1.8 of 5 ; P < 0.001 for comparison with mean score for any of the other guidelines ) , which was included in the survey to provide a measure of the degree to which familiarity scores might be inflated because of a general desire to appear knowledgeable . The responders who reported familiarity with this nonexistent guideline ( 7 % of total ) provide a baseline for interpretation of the familiarity reported for the other guidelines . Table 3 . Responders ' Familiarity with Selected Clinical Practice Guidelines by Responder Specialty Subspecialists were more likely to report familiarity with guidelines pertaining to their own subspecialty than with those pertaining to other subspecialties or to general medical practice . For example ,", "An intensive programme of guideline development and dissemination is not always practical . We design ed general practitioner guidelines for chest radiography and disseminated them to a group of 33 practice s selected r and omly from the practice s that refer more than five patients for chest radiography annually . The subsequent 2500 requests were analysed and demographic data , the referring practice and the relevant history noted . We documented a reduction in the proportion of referrals that were contrary to the guidelines by 30.5 % ( from 8.2 % to 5.7 % , P = 0.016 ) , a reduction in referral rate with an inadequate history by 29.7 % ( from 15.5 % to 10.9 % , P = 0.0008 ) and an increase in the frequency that a presumptive diagnosis was stated by 14.5 % ( from 42.9 % to 49.1 % , P = 0.0025 ) . There was no overall reduction in referral rate in the study group and the reasons for this are discussed . We conclude that guidelines for chest radiography are effective in reducing inappropriate requests and can also improve the clinical information provided", "CONTEXT Little is known about how the pharmaceutical industry responds to evidence of harm associated with its products , such as the publication in July 2002 of the Women 's Health Initiative Estrogen Plus Progestin Trial ( WHI E+P ) report demonstrating that st and ard-dose Prempro produced significant harm and lacked net benefits . OBJECTIVE To examine pharmaceutical industry response to the WHI E+P results by analyzing promotional expenditures for hormone therapy before and after July 2002 . DESIGN AND SETTING Nationally representative and prospect ively collected longitudinal data ( January 2001 through December 2003 ) on prescribing and promotion of hormone therapies were obtained from IMS Health and Consumer Media Reports . MAIN OUTCOME MEASURES Trends in quarterly prescriptions for hormone therapy and expenditures on 5 modes of drug promotion : sample s , office-based detailing , hospital-based promotion , journal advertisements , and direct-to-consumer advertising . RESULTS Prior to the WHI E+P report , prescribing rates and promotional spending for hormone therapy were stable . In the quarter before the WHI E+P report ( April-June 2002 ) , 22.4 million prescriptions for hormone therapy were dispensed and 71 million dollars was spent on promotion ( in annual terms , 350 dollars per year per US physician ) . Within 9 months of the report 's publication ( quarter 1 of 2003 ) , there was a 32 % decrease in hormone therapy prescriptions , and a nadir had been reached for promotional spending ( 37 % decrease compared with pre-WHI E+P levels ) . Spending decreased for all promotional activities and most hormone therapies . Overall , the greatest declines were for sample s ( 36 % decrease as of quarter 1 of 2003 ) and direct-to-consumer advertising ( 100 % decrease ) . The greatest declines in promotion occurred for st and ard-dose Prempro ( 61 % decrease as of quarter 1 of 2003 ) , the agent implicated by the WHI E+P report . More recently , promotional efforts have increased , particularly for lower-dose Prempro , a resurgence associated with modestly increased prescriptions for this newer agent . CONCLUSIONS Concordant with its widespread use , hormone therapy was among the most heavily promoted medications prior to the WHI E+P report . Following reporting of the evidence of harm from this trial , there was a substantial decline in promotional spending for hormone therapy , particularly for the agents most directly implicated in the trial . Interrelated with the impact of the trial results themselves and the ensuing media coverage , reduced promotion may have contributed to a substantial decline in hormone therapy prescriptions", "Printed health education material s ( HEMs ) are widely used to increase awareness and knowledge , change attitudes and beliefs , and help individuals adopt and maintain healthy lifestyle behaviors . While much of the contemporary research and development of persuasive communication is based on McGuire 's input/output model , to date few studies have compared the impact of a large set of inputs across a comprehensive set of the 12 outputs . We examined the effects of printed HEMs on weight loss on the cognitive , affective , and behavioral responses of 198 overweight adults . Participants were recruited via a newspaper advertisement and were r and omly assigned to review one of three HEMs . Participants were interviewed and asked to complete a series of question naires both before and after viewing the HEMs . Regression analyses were conducted to identify the input characteristics associated with success at each of the output steps . The results revealed attractiveness , encouragement , level of information , and application to one 's life were significantly associated with early steps ( attention , liking , and underst and ing ) as well as some of the mediating steps ( recalling , keeping , and rereading HEMs ) . Later steps , such as intention to change behavior and show others , were associated with readiness to change , self-efficacy , and perceived application to one 's life . Behavior change was more likely for those who received tailored material s and those who had higher self-efficacy . These results provide useful direction for the use of computers in tailoring the content of HEMs and the development of effective communication of health information on weight loss", "Study Design . Cluster r and omized controlled trial for a multifaceted implementation strategy . Objectives . To assess the effectiveness of tailored interventions ( multifaceted implementation strategy ) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations . Summary of Background Data . Guidelines for the management of low back pain in primary care have been developed in various countries , but little is known about the optimal implementation strategy . A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners . Methods . General practitioners were r and omized to an intervention or a control group . The general practitioners in the intervention group ( n = 21 ) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners , a 2-hour educational and clinical practice workshop ; two scientific articles on low back pain management ; the guideline for occupational physicians ; a tool for patient education ; and a tool for reaching agreement on low back care with physical , exercise , and manual therapists . The control group ( n = 20 ) received no intervention . The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation . General practitioners completed registration forms of each individual consultation with regard to the main outcome measures : advice and information , referral to other health-care providers , and prescription of medication . Results . Forty-one of the 67 r and omized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain . The advice and explanation provided by the general practitioners , the prescription of paracetamol or nonsteroidal anti-inflammatory drugs , and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups . There were also no differences in overall referral rate . However , in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group . Conclusions . The multifaceted intervention strategy modestly improved implementation ( for parts of the recommendations in ) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management . The implementation strategy produced fewer referrals to therapists during follow-up consultations", "This trial evaluated the clinical impact and cost-effectiveness of strategies promoting screening and brief alcohol intervention ( SBI ) by nurses in primary care . R and omisation was at the level of the practice and the interventions were : written guidelines ( controls , n=76 ) ; outreach training ( n=68 ) ; and training plus telephone-based support ( n=68 ) . After 3 months , just 39 % of controls implemented the SBI programme compared to 74 % of nurses in trained practice s and 71 % in trained and supported practice s. Controls also screened fewer patients and delivered fewer brief interventions to risk drinkers than other colleagues . However , there was a trade-off between the extent and the appropriateness of brief intervention delivery with controls displaying the least errors in overall patient management . Thus cost-effectiveness ratios ( cost per patient appropriately treated ) were similar between the three strategies . Given the potential for anxiety due to misdirected advice about alcohol-related risk , the balance of evidence favoured the use of written guidelines to promote SBI by nurses in primary care", "OBJECTIVES Assess the acceptance and ease of use of Nutrition Practice Guidelines for Type 1 Diabetes Mellitus by dietitians in a variety of setting s ; determine if nutrition care activities of dietitians change when practice guidelines are available ; measure changes in patient control of blood glucose level , measured as glycated hemoglobin ( HbA1c ) ; compare patient satisfaction with care and perceptions about quality of life . DESIGN Using the approach of outcomes research , volunteer dietitians were recruited and assigned r and omly to a usual care group or a practice guidelines group . Patients with type 1 diabetes were enrolled by dietitians and followed up for a 3-month period . Outcome measures included dietitian care activities , changes in patient HbA1c levels , and patient satisfaction and perceptions about quality of life . SUBJECTS/ SETTING S Dietitians from across the United States who responded to a recruitment notice participated . Their work setting s included diabetes referral centers , endocrinology clinics , primary care and community health clinics , hospitals , and a worksite clinic . They recruited patients from their setting for the study . Outcome data were available from dietitians providing care to 24 patients using the new practice guidelines and dietitians providing care to 30 patients using more traditional methods . STATISTICAL ANALYSIS chi 2 Test , t test , and analysis of covariance . RESULTS Dietitians in the practice guidelines group spent 63 % more time with patients and were more likely to do an assessment and discuss results with patients than dietitians in the usual care group . Practice guidelines dietitians paid greater attention to glycemic control goals . Levels of HbA1c improved at 3 months in 21 ( 88 % ) of practice guidelines patients compared with 16 ( 53 % ) of usual care patients . Practice guidelines patients achieved greater reductions in HbA1c level than usual care patients ( -1.00 vs -0.33 ) . This difference was statistically significant and clinical ly meaningful . CONCLUSIONS /APPLICATIONS Dietitians responded positively to practice guidelines for type 1 diabetes . Use of guidelines result ed in changes in dietitian practice s and produced greater improvements in patient blood glucose outcomes at 3 months compared with usual care . Practice guidelines did not significantly influence patient satisfaction with care of perceived quality of life", "Sixty-six physicians were r and omized to three groups to conduct a 1-month campaign to help their patients stop smoking . The workshop group received free patient education material s and a 6-hour training workshop . The material s group received free patient education material s , and the no-assistance group received nothing . A telephone interview was completed with 89 % of the 6767 eligible adult patients seen during the month of the campaign . The brief training program and patient education material s marginally increased the smoking intervention activities of volunteer physicians in private practice . Both workshop and material s physicians asked 54 % of their smoking patients to stop ; no-assistance physicians asked 40 % . One year later , 36 % of patients who had not even been asked by their doctors if they smoked reported that they had tried to stop smoking . If the physician had asked the patient if he or she smoked , the probability of a quit attempt was 47 % . Patients who had been asked if they smoked were more likely to cl aim to have stopped ( 13 % ) than patients who had not been asked ( 9 % ) . However , the proportion of patients cl aim ing continued abstinence ( range , 12 % to 14 % ) was not related to the group of the physician", "BACKGROUND The World Health Organization ( WHO ) ICD-10 Primary Health Care ( PHC ) Guidelines for Diagnosis and Management of Mental Disorders ( 1996 ) have not been evaluated in a pragmatic r and omised controlled trial ( RCT ) . AIMS To evaluate the effect of local adaptation and dissemination of the guidelines . METHOD Pragmatic , pair-matched , cluster RCT involving 30 practice s. RESULTS Guideline practice s were less sensitive but more specific in identifying morbidity , but these differences were not significant . Guideline patients did not differ from usual-care patients on 12-item General Health Question naire scores at 3-month follow-up or in the proportion who were still cases . There were no significant differences in secondary outcomes . CONCLUSIONS Attempts to influence clinician behaviour through a process of adaptation and extension of guidelines are unlikely to change detection rates or outcomes", "PURPOSE Few studies have examined the effect of new evidence from clinical trials on physician practice . We took advantage of differences in promotional activity in Canada and the United States for the Heart Outcomes Prevention and Evaluation ( HOPE ) study and the R and omized Aldactone Evaluation Study ( RALES ) to determine if publication of new evidence changes practice , and the extent to which promotion influences adoption of new evidence . METHODS We used longitudinal dispensing data , collected from 1998 to 2001 , to examine changes in prescribing patterns for ramipril and other angiotensin-converting enzyme ( ACE ) inhibitors before and after the HOPE study . We also obtained estimates for promotional expenditures . We stratified analyses by country , to isolate the effect of promotion , and used interrupted time series methods to adjust for pre-existing prescribing trends . Similar analyses were conducted for spironolactone use before and after RALES . RESULTS Publication of the HOPE study results was associated with rapid increases in the use of ramipril . After adjusting for pre-existing prescribing trends , ramipril prescribing increased by 12 % per month ( P = 0.001 ) in Canada versus 5 % per month ( P = 0.001 ) in the United States after the study results were presented and published . One year later , ramipril accounted for 30 % of the ACE inhibitor market in Canada versus 6 % in the United States . The year before publication of these results , expenditures for detailing increased by 20 % in Canada ( to 18 US dollars per physician ) but decreased by 7 % in the United States ( to 13 US dollars per physician ) ; the year after publication , spending increased to 27 US dollars per physician in Canada versus 23 US dollars per physician in the United States . In the absence of promotional activity for RALES in either country , publication of results was associated with more modest but similar increases of 2 % per month ( P = 0.001 ) in spironolactone use in both countries . CONCLUSION Publication of new evidence is associated with modest changes in practice . Promotional activity appears to increase the adoption of evidence . Rather than relying on the publication of articles and creation of guidelines , those wishing to accelerate the adoption of new evidence may need to undertake more active promotion" ]

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[ "No evidence of large genetic effects on steroid response in asthma patients", "Pharmacogenetics of asthma controller treatment", "Oral Montelukast, Inhaled Beclomethasone, and Placebo for Chronic Asthma", "TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids", "Characterization of within-subject responses to fluticasone and montelukast in childhood asthma.", "Pharmacogenetic study of the effects of NK2R G231E G>A and TBX21 H33Q C>G polymorphisms on asthma control with inhaled corticosteroid treatment.", "FCER2: a pharmacogenetic basis for severe exacerbations in children with asthma.", "Predictors of poor response during asthma therapy differ with definition of outcome.", "The Ubiquitous Pharmacogenomics consortium: making effective treatment optimization accessible to every European citizen.", "Pharmacodynamic genome-wide association study identifies new responsive loci for glucocorticoid intervention in asthma" ]

[ "Background : Inhaled corticosteroids ( ICSs ) are considered the most effective anti‐inflammatory therapy for asthma control and management ; however , there is substantial treatment response variability . Objective : We sought to identify genetic markers of ICS response by conducting the largest pharmacogenetic investigation to date in 2672 ICS‐treated patients with asthma . Methods : Genotyping and imputation was performed in fluticasone furoate ( FF ) or fluticasone propionate – treated patients with asthma from 3 phase IIB and 4 phase IIIA r and omized , double‐blind , placebo‐controlled , parallel group , multicenter studies . The primary end point analyzed was change in trough FEV1 ( & Dgr;FEV1 ) from baseline to 8 to 12 weeks of treatment . Results : More than 9.8 million common genetic variants ( minor allele frequency ≥ 1 % ) were analyzed to test for association with & Dgr;FEV1 . No genetic variant met the prespecified threshold for statistical significance . Conclusions : This study provides no evidence to confirm previously reported associations between c and i date genetic variants and ICS response ( & Dgr;FEV1 ) in patients with asthma . In addition , no variant satisfied the criterion for genome‐wide significance in our study . Common genetic variants are therefore unlikely to prove useful as predictive biomarkers of ICS response in patients with asthma", "The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability . The goal of the present study was to identify novel variants that associate with response to common asthma controllers : fluticasone , combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms ( SNPs ) in β2-adrenergic receptor , corticosteroid and leukotriene pathway c and i date genes . Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study . A total of 169 SNPs in 26 c and i date genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone ( 100 μg bid ) , fluticasone propionate ( 100 μg ) + salmeterol ( 50 μg ) ( FP/Salm ) or montelukast ( 5 or 10 mg ) each night for 16 weeks . Primary outcomes were the slopes of plots of Asthma Control Question naire ( ACQ ) scores versus time following r and omization ; and the percent change in percent predicted FEV1 ( ΔFEV1%pred ) from enrollment to the end of the study . Associations between SNPs and outcomes were analyzed using general linear models . False discovery rate and Bonferroni corrections were used to correct for multiple comparisons . In all , 16 SNPs in seven genes were significantly associated with outcomes . For FP/Salm , three SNPs in CHRM2 associated with ACQ slope ( P=2.8 × 10−5 ) , and rs1461496 in HSPA8 associated with ΔFEV1%pred . For fluticasone , five SNPs in CRHR1 ( P=1.9 × 10−4 ) , and three SNPs in COL2A1 associated with ACQ slope and ΔFEV1%pred , respectively . For montelukast , four SNPs in CHRM2 associated with ΔFEV1%pred and predicted an opposite effect compared with fluticasone ( P=9 × 10−3 ) . The present study indentified several novel SNPs that associate with response to common asthma controllers , and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment", "For patients with persistent asthma , the National Asthma Education and Prevention Program recommends the regular use of controller medications to provide long-term control , together with as-needed use of rescue medications ( 1 ) . Inhaled corticosteroids are currently the most commonly used controller medications ( 1 ) . Although inhalation into the airway has advantages in terms of both safety and efficacy , problems with compliance with inhaled agents may limit their real-world effectiveness , especially in elderly and pediatric patients ( 2 , 3 ) . Cysteinyl leukotrienes are important pro-inflammatory mediators of asthma ( 4 ) . Recent clinical studies of leukotriene receptor antagonists ( 5 - 7 ) and a 5-lipoxygenase inhibitor ( 8) have shown these agents to have clinical benefit in patients with chronic asthma , and treatment guidelines now consider these agents alternative , first-line controller medications ( 1 ) . Recent studies showed that montelukast , a potent and specific leukotriene receptor antagonist ( 9 ) , had efficacy in adult ( over a 12-week period ) and pediatric ( over an 8-week period ) patient with chronic asthma and had a tolerability profile similar to that of placebo ( 10 - 12 ) . To date , no comparisons of leukotriene receptor antagonists and inhaled corticosteroids have been published . Our placebo-controlled , parallel-group study , which was primarily design ed to compare the effect of montelukast with that of placebo in a phase III clinical development trial , also compared montelukast and inhaled beclomethasone in patients with chronic asthma who require the daily use of a controller medication . Methods Patients Healthy , nonsmoking , male and female patients 15 years of age and older were eligible to participate if they had had asthma for at least 1 year before the initial study evaluation . Each patient also had to have 1 ) an FEV1 between 50 % and 85 % of predicted value , 2 ) an increase of at least 15 % in absolute FEV1 after the use of inhaled -agonist on at least two of three visits during period 1 [ see below ] , 3 ) a daytime asthma symptom score of at least 64 [ of a possible 336 ] , and 4 ) average daily use of at least one puff of as-needed , short-acting , inhaled -agonist ( salbutamol ) . Patients were excluded from the study if they had used inhaled and oral corticosteroids , cromolyn , or nedocromil within 4 weeks before the initial evaluation ; had used long-acting -agonists , antimuscarinics , and newly instituted theophylline within 2 weeks before the initial evaluation ; or had used long-acting antihistamines ( for example , they could not have used astemizole within 3 months of the initial evaluation , and they could not have used terfenadine or loratadine within 2 weeks of the initial evaluation ) . Intermittent use of short-acting antihistamines was allowed , and immunotherapy was permitted if it had been started at least 6 months before the initial study evaluation and if the monthly dose remained constant . Protocol Our r and omized , double-dummy , placebo-controlled , parallel-group trial had a 2-week , single-blind placebo run-in period ( period 1 ) ; a 12-week , double-blind treatment period ( period 2 ) ; and a 3-week , double-blind placebo washout period [ period 3 ] . Eligible patients were r and omly assigned to one of three treatment regimens : 1 ) montelukast , 10 mg once daily in the evening ; 2 ) inhaled beclomethasone , 200 g twice daily ; or 3 ) placebo . The ratio of montelukast recipients to beclomethasone recipients to placebo recipients was 3:2:2 , with a blocking factor of 7 , according to a single , computer-generated allocation schedule . Patients , investigators , and coordinating center staff were blinded to the treatment schedule until all corrections to the data base were completed . During period 3 , a subset of patients originally assigned to receive active treatment ( approximately 40 , as determined by the allocation schedule ) was switched to placebo in a blinded manner . The other patients originally assigned to receive active treatment continued to receive that treatment . This allowed us to assess withdrawal from therapy . The study was done at 36 clinical centers in 19 countries in Europe , Africa , Australia , Central America , and South America . The study protocol and informed consent were approved by local ethics review committees . All participants gave written informed consent before participation ; consent of parents or guardians was obtained for patients younger than 18 years of age . Patients were recruited from the patient pool of each clinical study center and through local newspaper advertisements . Medication The study medication consisted of 10-mg montelukast film-coated tablets , placebo tablets that were identical in appearance to the montelukast tablets , beclomethasone ( 100 g/puff ) in inhalers ( Allen & Hanburys , Stockley Park , United Kingdom ) , and placebo in inhalers identical to those used for beclomethasone . Patients were instructed to take one tablet at bedtime and to take two puffs from the inhaler ( using the AeroChamber spacer device [ Clement Clark , Columbus , Ohio ] ) at bedtime and in the morning . Short-acting , inhaled -agonist ( salbutamol , 100 g/puff ) ( Allen & Hanburys ) was to be used as needed . Patients with worsening episodes of asthma that required additional therapy were treated with oral corticosteroids according to a st and ard protocol . Patients who had more than two worsening episodes of asthma requiring corticosteroid therapy were dropped from the study . Measurements Central ized spirometry training was done according to st and ard American Thoracic Society criteria before the start of the study . Spirometry was done at each visit after inhaled -agonist therapy had been withheld for at least 6 hours , theophylline therapy had been withheld for at least 24 hours , and antihistamine therapy had been withheld for at least 48 hours . At least three spirometry maneuvers were done , and the largest FEV1 was reported . Spirometry data were transmitted electronically to a central data base and monitored continuously for quality , and feedback was given to the study centers ( 13 ) . If quality was not maintained , sites were visited by coordinating center personnel . Answers to four questions on daytime asthma symptoms and one question on nocturnal awakenings were collected on a daily diary card , as were morning and evening peak expiratory flow rate and daily use of as-needed salbutamol . With respect to daytime asthma symptoms , patients used a 7-point scale ( on which 0 means best and 6 means worst ) to rate the severity of symptoms , their frequency , the degree to which they were bothersome , and their impact on daily activities . These ratings were combined into a mean daily score . Nocturnal awakenings were evaluated by the patient 's response ( on a four-point scale ) to a single question ( 14 ) . The validation of these questions has been published elsewhere ( 14 ) . Peak expiratory flow was measured in the morning and in the evening immediately before study medication was taken . The best of three measurements was recorded . Prespecified end points other than peak expiratory flow included peripheral blood eosinophil counts , global evaluations by physicians and patients ( on a 7-point scale , on which 6 means very much worse and 0 means very much better ) ( 7 ) , and asthma-specific quality of life ( 15 ) . Asthma outcome end points , including asthma attacks ( defined as worsening asthma requiring oral corticosteroid treatment or an unscheduled visit to a physician , emergency department , or hospital ) , percentage of days with asthma exacerbations , and percentage of asthma-control days ( as defined elsewhere [ 11 , 16 ] ) , were also evaluated . The diary card , the Asthma Quality -of-Life Question naire ( 15 ) , and the global evaluation questions were translated from English into appropriate local language s and were vali date d for linguistic equivalence and cultural differences ( 17 ) . Patient compliance with study therapy was determined by weighing inhalers and counting tablets . The weight of a full canister was determined by averaging the weights of at least 50 canisters of beclomethasone and placebo . A st and ard puff weight was determined by repeatedly actuating and weighing 10 canisters . Laboratory safety tests , including hematologic tests , serum biochemistry analysis , and urinalysis , were done at prespecified visits , and the results were analyzed by a central laboratory . The central laboratory also determined eosinophil counts with an automated cell counter . Statistical Analysis Our primary objective was to compare montelukast with placebo with respect to two prespecified primary end points : FEV1 and daytime symptom score . Other objectives were to compare beclomethasone with placebo and to compare montelukast with beclomethasone in a stepwise manner in accordance with the Dunnet-Tamhane approach , with the comparison of montelukast and beclomethasone prespecified as an estimation of the difference using 95 % CIs ( 18 ) . No multiplicity adjustments were made for each of the secondary end points , which were prespecified as supportive . The analysis for each efficacy end point included all patients who had a measurement taken at baseline and at least one measurement taken after r and omization . Treatment responses were calculated as the average change or percentage change from baseline to period 2 ; the baseline value was the average value for period 1 . With SAS software ( SAS Institute , Inc. , Cary , North Carolina ) , we used an analysis of variance ( ANOVA ) model to estimate treatment group means and between-group differences and to construct 95 % CIs by using the least-square means and the differences in least-square means . The model contained factors for treatment , study center , and stratum ( theophylline use ) . The consistency of the treatment effect across study centers , strata , and subgroups ( which were formed according to sex , age , ethnicity , history of allergic rhinitis , and history of exercise-induced asthma ) was assessed by interaction testing done using the ANOVA model with an", "TBX21 encodes for the transcription factor T-bet ( T-box expressed in T cells ) , which influences naïve T lymphocyte development and has been implicated in asthma pathogenesis . Specifically , the T-bet knockout mouse spontaneously develops airway hyperresponsiveness and other changes consistent with asthma . Because airway responsiveness is moderated by the use of inhaled corticosteroids in asthma , it is conceivable that genetic variation in TBX21 may alter asthma phenotypes in a treatment-specific fashion . Here we demonstrate that the nonsynonymous variation in TBX21 coding for replacement of histidine 33 with glutamine is associated with significant improvement in the PC20 ( a measure of airway responsiveness ) of asthmatic children in a large clinical trial spanning 4 years . We note that this increase occurs only in the children r and omized to inhaled corticosteroids and that it dramatically enhances the overall improvement in PC20 associated with inhaled corticosteroid usage . The average PC20 at trial end for subjects on inhaled corticosteroids possessing a variant allele was in the normal range for nonasthmatics . In cellular models , we show that the TBX21 variant increases T helper 1 and decreases T helper 2 cytokine expression comparably with wild type . TBX21 may thus be an important determinant pharmacogenetic response to the therapy of asthma with inhaled corticosteroids", "BACKGROUND Responses to inhaled corticosteroids ( ICSs ) and leukotriene receptor antagonists ( LTRAs ) vary among asthmatic patients . OBJECTIVE We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other . METHODS Children 6 to 17 years of age with mild-to-moderate persistent asthma were r and omized to one of 2 crossover sequences , including 8 weeks of an ICS , fluticasone propionate ( 100 microg twice daily ) , and 8 weeks of an LTRA , montelukast ( 5 - 10 mg nightly depending on age ) , in a multicenter , double-masked , 18-week trial . Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers . RESULTS Defining response as improvement in FEV 1 of 7.5 % or greater , 17 % of 126 participants responded to both medications , 23 % responded to fluticasone alone , 5 % responded to montelukast alone , and 55 % responded to neither medication . Compared with those who responded to neither medication , favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide , total eosinophil counts , levels of serum IgE , and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20 ) and pulmonary function ; favorable response to montelukast alone was associated with younger age and shorter disease duration . Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use , bronchodilator response , exhaled nitric oxide levels , and eosinophil cationic protein levels and lower methacholine PC(20 ) and pulmonary function values . CONCLUSIONS Response to fluticasone and montelukast vary considerably . Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy . Other children could receive either ICSs or LTRAs", "BACKGROUND AND OBJECTIVE Inhaled corticosteroids ( ICS ) are widely used as maintenance regimens for asthma patients . However , response to ICS shows marked inter-individual variability . Genetic factors have been shown to be potential predictors of responsiveness to ICS . We aim ed to evaluate those pharmacogenetic effects on asthma control in further detail . METHODS Fifty-three mild-to-moderate asthmatics were genotyped for four genetic polymorphisms of four genes : beta2-adrenergic receptor ( ADRB2 ) , adenylate cyclase 9 ( ADCY9 ) , neurokinin receptor 2 ( NK2R ) and T-box 21 ( TBX21 ) . The principal clinical outcome was the achievement of asthma control , as assessed using the Global Initiative for Asthma ( GINA ) guidelines . During treatment with ICS , the forced expiratory volume in 1 second ( FEV(1 ) ) , maximal mid-expiratory flow ( MMEF ) and peak expiratory flow rate ( PEFR ) were monitored every 4 weeks and twice daily . RESULTS Forty-eight of the 53 patients with asthma were in a controlled or partly controlled state after 12 weeks of treatment with ICS , whereas five asthmatics were in an uncontrolled state even after active treatment . Of the four genetic polymorphisms examined , NK2R G231E G > A and TBX21 H33Q C > G were significantly associated with asthma control status ( P = 0.041 and P = 0.006 ) . The subjects with wild-type alleles at each polymorphism showed a significant association with the well-controlled or partly controlled state , as compared to those with mutant alleles . At 5 - 12 weeks after ICS treatment , the NK2R G231E G > A was associated with therapeutic response to ICS , as reflected by improvement in predicted FEV(1)% . CONCLUSION Our results suggest that NK2R G231E G > A and TBX21 H33Q C > G are genetic predictors of response to ICS , at least with respect to asthma control status and changes in FEV(1)% , in Korean patients with asthma . Further prospect i ve validation of those associations is necessary", "BACKGROUND Although inhaled corticosteroids ( ICSs ) generally protect against severe exacerbations in asthma , they may result in elevated IgE levels , which are associated with exacerbations . OBJECTIVE To determine whether variation in the low-affinity IgE receptor gene , FCER2 , is associated with severe exacerbations defined as emergency department visits and /or hospitalizations in patients with asthma on ICSs . METHODS We resequenced , then genotyped 10 FCER2 single nucleotide polymorphisms ( SNPs ) in 311 children r and omized to inhaled budesonide as part of the Childhood Asthma Management Program . We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial . We also evaluated differences in cellular expression of the novel FCER2 SNP , T2206C . RESULTS In white subjects , 3 FCER2 SNPs were significantly associated ( P < .05 ) with elevated 4-year IgE level ; each was also associated with increased severe exacerbations . Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children ( hazard ratio , 3.95 ; 95 % CI , 1.64 - 9.51 ; and hazard ratio , 3.08 ; 95 % CI , 1.00 - 9.47 ) , despite ICS use . Interaction models supported a true gene-environment effect in white subjects ( interaction P = .004 ) . T2206C was also associated with decreased FCER2 expression ( P = .02 ) . CONCLUSION FCER2 predicts the likelihood of treatment protocol success in asthma . The associations of T2206C with IgE level , severe exacerbations , and FCER2 expression may provide a mechanistic basis for the observed findings . CLINICAL IMPLICATION S Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma", "AIMS To evaluate phenotypic and genetic variables associated with a poor long-term response to inhaled corticosteroid therapy for asthma , based independently on lung function changes or asthma exacerbations . MATERIAL S & METHODS We tested 17 phenotypic variables and polymorphisms in FCER2 and CRHR1 in 311 children ( aged 5 - 12 years ) r and omized to a 4-year course of inhaled corticosteroid during the Childhood Asthma Management Program ( CAMP ) . RESULTS Predictors of recurrent asthma exacerbations are distinct from predictors of poor lung function response . A history of prior asthma exacerbations , younger age and a higher IgE level ( p < 0.05 ) are associated with recurrent exacerbations . By contrast , lower bronchodilator response to albuterol and the minor alleles of RS242941 in CRHR1 and T2206C in FCER2 ( p < 0.05 ) are associated with poor lung function response . Poor lung function response does not increase the risk of exacerbations and vice versa ( p = 0.72 ) . CONCLUSION Genetic and phenotypic predictors of a poor long-term response to inhaled corticosteroids differ markedly depending on definition of outcome ( based on exacerbations vs lung function ) . These findings are important in comparing outcomes of clinical trials and in design ing future pharmacogenetic studies", "Physicians and pharmacists increasingly recognize that pharmacogenomics (PGx)-informed prescribing and dispensing improves both the efficacy and safety of drug treatment [ 1,2 ] . An estimated 15 % of the medicines recently evaluated by the EMA contain PGx information in the label that directly impacts patient treatment and this percentage will increase in the near future [ 3 ] . Several r and omized controlled trials have shown the clinical utility of single drug – gene pre-emptive PGx testing . Examples include PGx testing to guide dosing of thiopurines , acenocoumarol and warfarin [ 4,5,6 ] , and PGx testing to guide drug selection for carbamazepine and abacavir [ 7,8 ] . Interestingly , this gold-st and ard evidence has focused on individual single gene – drug pair(s ) . Pre-emptive PGx testing for a panel of relevant pharmacogenes may be even more informative and clinical ly relevant than testing for individual gene – drug pairs . Reasons for this being threefold . First , PGx test results are static and can , therefore , be utilized lifelong . Second , over the course of their lifespan most patients will likely use multiple drugs of which multiple may benefit from PGx-informed prescribing [ 9 ] . Third , actionable PGx variants are highly common in the population and recent studies show that more than 95 % of the population carry at least one actionable PGx variant when tested for a panel of six to eight well-recognized pharmacogenes [ 10,11,12,13 ] . Indeed , the positive effects of pre-emptive PGx testing for a panel of genes have recently been demonstrated in several small studies [ 14,15,16 ] . Nevertheless , convincing evidence from well- design ed , sufficiently powered prospect i ve studies is needed . To fill this unmet need and to achieve implementation of PGxguided prescribing in Europe , the Ubiquitous Pharmacogenomics ( U-PGx ) consortium was founded", "Asthma is a chronic lung disease that has a high prevalence . The therapeutic intervention of this disease can be made more effective if genetic variability in patients ’ response to medications is implemented . However , a clear picture of the genetic architecture of asthma intervention response remains elusive . We conducted a genome-wide association study ( GWAS ) to identify drug response-associated genes for asthma , in which 909 622 SNPs were genotyped for 120 r and omized participants who inhaled multiple doses of glucocorticoids . By integrating pharmacodynamic properties of drug reactions , we implemented a mechanistic model to analyze the GWAS data , enhancing the scope of inference about the genetic architecture of asthma intervention . Our pharmacodynamic model observed associations of genome-wide significance between dose-dependent response to inhaled glucocorticoids ( measured as % FEV1 ) and five loci ( P=5.315 × 10−7 to 3.924 × 10−9 ) , many of which map to metabolic genes related to lung function and asthma risk . All significant SNPs detected indicate a recessive effect , at which the homozygotes for the mutant alleles drive variability in % FEV1 . Significant associations were well replicated in three additional independent GWAS studies . Pooled together over these three trials , two SNPs , chr6 rs6924808 and chr11 rs1353649 , display an increased significance level ( P=6.661 × 10−16 and 5.670 × 10−11 ) . Our study reveals a general picture of pharmacogenomic control for asthma intervention . The results obtained help to tailor an optimal dose for individual patients to treat asthma based on their genetic makeup" ]

[ "19184217", "16328673", "22783709", "24681179", "19399934", "26550332", "23742777", "19452582", "16938157", "6020598", "6020555", "30066738", "6079331", "30158029", "30236241" ]

[ "Effectiveness for pain after laparoscopic cholecystectomy of 0.5% bupivacaine-soaked Tabotamp® placed in the gallbladder bed: a prospective, randomized, clinical trial", "Postoperative pain relief after laparoscopic cholecystectomy: A placebo-controlled double-blind randomized trial of preincisional infiltration and intraperitoneal instillation of levobupivacaine 0.25%", "A randomized, double-blind, controlled trial on non-opioid analgesics and opioid consumption for postoperative pain relief after laparoscopic cholecystectomy.", "Preoperative intravenous parecoxib reduces length of stay on ambulatory laparoscopic cholecystectomy.", "Efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy: a prospective, randomized study.", "Comparison of bupivacaine and parecoxib for postoperative pain relief after laparoscopic cholecystectomy: a randomized controlled trial.", "Double-blind randomized sham controlled trial of intraperitoneal bupivacaine during emergency laparoscopic cholecystectomy.", "Local anesthesia with ropivacaine for patients undergoing laparoscopic cholecystectomy.", "Parecoxib vs. lornoxicam in the treatment of postoperative pain after laparoscopic cholecystectomy: a prospective randomized placebo‐controlled trial", "Intraperitoneal Instillation of Bupivacaine and Ropivacaine for Postoperative Analgesia in Laparoscopic Cholecystectomy", "Intraperitoneal Levobupivacaine Alone or with Dexmedetomidine for Postoperative Analgesia after Laparoscopic Cholecystectomy", "Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.", "Effects of Gabapentinoids Premedication on Shoulder Pain and Rehabilitation Quality after Laparoscopic Cholecystectomy: Pregabalin versus Gabapentin", "Effect of Bupivacaine on Postoperative Pain after Laparoscopic Cholecystectomy.", "Evidence‐based management of pain after laparoscopic cholecystectomy: a PROSPECT review update" ]

[ "Background Some scientific studies , with controversial results , have evaluated the efficacy in reducing pain of some different local anesthetic molecules , which were administered at different dosages and in different ways . The primary goal of this r and omized , controlled , prospect i ve study ( Clinical Trials.gov ID NCT00599144 ) was to assess the effectiveness of 0.5 % bupivacaine for pain control after video-laparoscopic cholecystectomy at its optimal dosage of 2 mg/kg infiltrated in the muscular fasciae of the trocars , or positioned in the gallbladder soaking a sheet of regenerated oxidized cellulose ( Tabotamp ® ) . Methods A total of 45 patients underwent elective video-laparoscopic cholecystectomy . They were r and omized in three groups each made of 15 patients : group A ( bupivacaine-soaked Tabotamp ® positioned in the gallbladder bed ) , group B ( bupivacaine infiltrated in the muscular fasciae of the trocars ’ seat ) , group C ( control group , not using local anesthetic ) . Six and twenty-four hours after the intervention , the nature of the pain and its intensity were recorded with the use of a Visual Analogue Scale ( VAS ) . Results Six hours after the intervention , VAS average was 29.6 ± 10.92 for group A , 25.86 ± 16.06 for group B , and 36.13 ± 16.62 for group C. At 24 h , we recorded 19.26 ± 15.81 , 18.53 ± 12.3 , and 20.46 ± 20.08 for groups A , B , and C , respectively ( p > 0.05 ) . Comparing groups A and B between them and with the control group at 6 and 24 h , we deduced how only the first group showed a statistically significant advantage ( p < 0.05 ) in reducing visceral and shoulder pain compared with the two other groups . Wound infiltration result ed in being statistically favorable in reducing parietal pain only when compared with Group A. For groups A and B , bupivacaine significantly reduced the use of postoperative pain killers . Conclusion Bupivacaine , either infiltrated in trocars ’ wounds or kept soaked in a regenerated oxidized cellulose sheet positioned in the gallbladder bed , although safe and not economically dem and ing , can increase postoperative comfort", "Background The aim of this study was to test the use of preincisional and intraperitoneal levobupivacaine ( L-B ) 0.25 % in laparoscopic cholecystectomies for postoperative analgesia . Methods A total of 108 patients under general anesthesia were r and omly assigned to receive preincisional local infiltration of 20 ml solution and intraperitoneal instillation of another 20 ml solution . Group A received for local infiltration and intraperitoneal instillation normal saline ( NS ) . Group B received for local infiltration L-B 0.25 % and for intraperitoneal instillation NS . Group C received for local infiltration NS and for intraperitoneal instillation L-B 0.25 % . Group D received both for local infiltration and intraperitoneal instillation L-B 0.25 % . Abdominal and right shoulder pain were recorded for 24 h postoperatively . Results The pain scores were lower in group D than in the other groups during rest , cough , and movement ( p < 0.05 ) . Rescue analgesic treatment was significantly lower in patients of group D ( 35 % ) as compared with that of group A ( 84 % ) ( p < 0.05 ) . The incidence of right shoulder pain was significantly lower in groups C ( 22 % ) and D ( 18 % ) than in any of the other groups ( p < 0.05 ) . Conclusions The combination of preincisional local infiltration and intraperitoneal instillation of L-B 0.25 % shows an advantage for postoperative analgesia after laparoscopic cholecystectomy", "BACKGROUND Following laparoscopic cholecystectomy , an effective post-operative pain control is necessary , at least during the first 24 hours . We present a r and omized , double-blind trial on the effect of the combined use of intravenous parecoxib , and metamizol or paracetamol on piritramide consumption using a patient-controlled analgesia ( PCA ) pump in patients recovering from laparoscopic cholecystectomy . METHODS 120 patients were r and omly allocated to four patient groups treated with normal saline or one of non-opioid analgesics ( parecoxib 40 mg twice daily , metamizol 1 g three times daily , paracetamol 1 g three times daily ) in addition to piritramide using the PCA pump . Beginning in the post-anesthesia care unit ( PACU ) , patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience at rest while piritramide consumption was recorded . RESULTS In all groups , piritramide consumption was high in PACU . Only metamizol significantly reduced piritramide consumption compared to the others upon discharge from PACU . Overall , cumulative piritramide consumption was slightly lower in the metamizol group and higher in the NaCl group ; however , these findings were statistically not significant . VAS scores were highest upon arrival in PACU and dropped almost continuously after surgery . A significantly lower postoperative pain intensity was only found in the parecoxib group at 24 h after surgery compared to the metamizol group . CONCLUSION The efficacy of tested additive medications on piritramide consumption and pain relief is weak and there is no clear-cut difference between the non-opioid drugs used", "BACKGROUND The complexity of pain after laparoscopic cholecystectomy ( LC ) needs multi-module analgesia . Opioids are widely used for perioperative pain but associated with numerous adverse effects . We investigated the effect of parecoxib administrated preoperatively and postoperatively for analgesia after ambulatory laparoscopic cholecystectomy . METHODS 120 patients scheduled for ambulatory LC with general anesthesia were r and omly assigned to three groups : group A received 40 mg parecoxib injection 30 - 45 min before anesthesia induction and 4 ml saline injection when gallbladder was removed ; group B received 4 ml saline injection 30 - 45 min before anesthesia induction and 40 mg parecoxib injection when gallbladder was removed ; group C received 4 ml saline injection 30 - 45 min before anesthesia induction and the time when gallbladder was removed . We recorded the time achieve to modified Aldrete 's score > 9 in the post-anesthesia care unit ( PACU ) and modified Post-Anesthetic Discharge Scoring System ( PADSS ) > 9 in ambulatory unit . The visual analog scale ( VAS ) was used to assess the degree of the postoperative pain in the first 24 h , and the numbers of patients who need additional analgesic and postoperative adverse effects were also recorded . RESULTS Patients of group A had a shorter length of stay ( LOS ) in PACU compared to these of group B and group C ( 32.4 ± 7.2 min vs. 39.1 ± 10.4 min and 42.2 ± 7.6 min , P < 0.05 ) . Patients of group A also had a shorter discharge time compared to these of group B and group C ( 148.4 ± 39.3 min vs. 187.9 ± 47.7 min and 223.4 ± 52.5 min , P < 0.05 ) . Moreover , patients of group A experienced reduced pain intensity , less postoperative side effect , and less additional analgesic requirement . CONCLUSION Preoperative administration of parecoxib for postoperative analgesia provided significant effect on reducing PACU length of stay ( LOS ) and discharge time , and improving patient outcome after ambulatory LC", "AIM To determine the efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy . METHODS A prospect i ve , double-blind , r and omized , placebo-controlled study was conducted on 70 patients who underwent elective laparoscopic cholecystectomy under general anesthesia at Siriraj Hospital , Bangkok , from January 2006 to December 2007 . Patients were r and omized to receive either 20 mg parecoxib infusion 30 min before induction of anesthesia and at 12 h after the first dose ( treatment group ) , or normal saline infusion , in the same schedule , as a placebo ( control group ) . The degree of the postoperative pain was assessed every 3 h in the first 24 h after surgery , and then every 12 h the following day , using a visual analog scale . The consumption of analgesics was also recorded . RESULTS There were 40 patients in the treatment group , and 30 patients in the control group . The pain scores at each time point , and analgesic consumption did not differ between the two groups . However , there were fewer patients in the treatment group than placebo group who required opioid infusion within the first 24 h ( 60 % vs 37 % , P = 0.053 ) . CONCLUSION Perioperative administration of parecoxib provided no significant effect on postoperative pain relief after laparoscopic cholecystectomy . However , preoperative infusion 20 mg parecoxib could significantly reduce the postoperative opioid consumption", "BACKGROUND Pain is the most common complaint of patients on the first day after laparoscopic cholecystectomy ( LC ) . The aim of this study was to compare the efficacy of local anesthesia with bupivacaine and intravenous parecoxib on postoperative abdominal pain relief up to 24 h after surgery . METHODS One hundred and eighty patients who underwent LC were r and omized to one of three groups with sixty patients each : Group A received 50 mg 0.5 % bupivacaine subcutaneously at trocar sites before incision closure ; Group B received intravenous parecoxib ( 40 mg ) after entering the recovery room ; Group C did not receive postoperative analgesia unless needed and was served as control . The postoperative pain at 1 , 2 , 4 , 8 , 12 , and 24 h after the operation was assessed using a visual analog scale ( VAS ) . Secondary outcomes , including intraoperative and postoperative complications , the incidence of shoulder pain , pethidine requirements , postoperative nausea and vomiting , and hospital stay were also recorded . RESULTS At 1 , 2 , and 4 hours after surgery , VAS pain scores were significantly lower in group A and B compared with group C ( P < 0.05 for all ) . There was no significant difference among the three groups at 8 , 12 , and 24 hours after the procedure ( P > 0.05 for all ) . A repeated- measures ANOVA analysis revealed that VAS pain scores over the first 24 hours after LC were significantly lower in group A and B compared with group C ( P = 0.014 and P = 0.029 for between-group comparison , respectively ) . Furthermore , the percentage of patients requiring postoperative rescue analgesics was significantly higher in group C as compared with group A and group B ( P = 0.018 ) . CONCLUSION Local anesthesia with bupivacaine and intravenous parecoxib are both effective at decreasing postoperative pain and pethidine requirements after LC", "BACKGROUND Intraperitoneal local anesthesia ( IPLA ) during elective laparoscopic cholecystectomy ( el-LC ) decreases post-operative pain . None of the studies have explored the efficacy of IPLA at emergency laparoscopic cholecystectomy ( em-LC ) . A longer operative duration , the greater frequency of washing , and the inflammation associated with cholecystitis or pancreatitis are a few reasons why it can not be assumed that a benefit in pain scores will be seen in em-LC with IPLA . This study was undertaken to assess the efficacy of IPLA in patients undergoing em-LC . METHODS Double-blind r and omized sham controlled trial was conducted of 41 consecutive subjects undergoing em-LC . IPLA was delivered by a combination of injection to the diaphragmatic and topical wash over the liver and gallbladder with bupivacaine or saline . The primary outcome was visual analogue scale pain scores until discharge . Secondary outcomes included pain scores in theatre recovery and analgesic consumption . RESULTS One patient had a procedure converted to open and was excluded . There was no significant difference in pain scores in the ward or theatre recovery . Analgesic use , respiratory rate , oxygen saturation , duration to ambulation , eating , satisfaction scores , and time to discharge were comparable between the two groups . CONCLUSIONS IPLA during em-LC does not influence postoperative pain . Other modalities of analgesia should be explored for decreasing the interval between diagnosis of acute admission and em-LC", "AIM To investigate the effect of pain relief after infusion of ropivacaine at port sites at the end of surgery . METHODS From October 2006 to September 2007 , 72 patients undergoing laparoscopic cholecystectomy ( LC ) were r and omized into two groups of 36 patients . One group received ropivacaine infusion at the port sites at the end of LC and the other received normal saline . A visual analog scale was used to assess postoperative pain when the patient awakened in the operating room , 6 and 24 h after surgery , and before discharge . The amount of analgesics use was also recorded . The demographics , laboratory data , hospital stay , and perioperative complications were compared between the two groups . RESULTS There was no difference between the two groups preoperatively in terms of demographic and laboratory data . After surgery , similar operation time , blood loss , and no postoperative morbidity and mortality were observed in the two groups . However , a significantly lower pain score was observed in the patients undergoing LC with local anesthesia infusion at 1 h after LC and at discharge . Regarding analgesic use , the amount of meperidine used 1 h after LC and the total used during admission were lower in patients undergoing LC with local anesthesia infusion . This group also had a shorter hospital stay . CONCLUSION Local anesthesia with ropivacaine at the port site in LC patients significantly decreased postoperative pain immediately . This explains the lower meperidine use and earlier discharge for these patients", "Background and objective : Non‐steroidal anti‐inflammatory drugs are considered as an effective treatment of postoperative pain after laparoscopic cholecystectomy . COX‐2 inhibitors are newer drugs having less adverse effects . Data supporting their efficacy postoperatively in comparison to older non‐steroidal anti‐inflammatory drugs are scarce . Our study is a prospect i ve , r and omized , double‐blinded , placebo‐controlled trial comparing the efficacy of lornoxicam vs. parecoxib for the management of pain after laparoscopic cholecystectomy . Material s and methods : We enrolled 76 patients , ASA I and II , scheduled for elective laparoscopic cholecystectomy . The patients were r and omized to receive before induction parecoxib 40 mg i.v . , lornoxicam 8 mg i.v . or placebo . Pain at rest and on movement was assessed using a visual analogue scale at 0 , 6 , 12 h postoperatively . Total meperidine consumption and adverse effects were also recorded . Results : At 12 h , visual analogue scale scores at rest and on movement were significantly lower with parecoxib and lornoxicam compared with control ( P = 0.047 ) . The percentage of patients needing meperidine and the average dose of meperidine administered was significantly lower with parecoxib and lornoxicam compared with control ( P < 0.001 and P = 0.018 ) . There was no difference between parecoxib and lornoxicam . One patient receiving lornoxicam vomited . Conclusions : Parecoxib 40 mg i.v . and lornoxicam 8 mg i.v . were equianalgesic and both were more efficacious than placebo for the management of pain after laparoscopic cholecystectomy", "Background : Intraperitoneal instillation of local anesthetics in laparoscopic cholecystectomy ( LC ) has been used to reduce postoperative pain and to decrease the need for postoperative analgesics . Aims : This study aim ed to compare intraperitoneal instillation of bupivacaine and ropivacaine for postoperative analgesia in patients undergoing LC . Setting s and Design : This was a prospect i ve , r and omized , double-blind study . Material s and Methods : After obtaining ethical committee 's clearance and informed consent , sixty patients , aged 18–65 years , of either gender , and American Society of Anesthesiologists physical status I to III scheduled for LC were included and categorized into two groups ( n = 30 ) . Group A patients received 20 mL of 0.5 % bupivacaine intraperitoneally after cholecystectomy and Group B patients received 20 mL of 0.5 % ropivacaine intraperitoneally after cholecystectomy . Statistical Analysis : The data were analyzed using paired t-test . The results were analyzed and compared to previous studies . SPSS software version 22 was used , released 2013 ( IBM Corp. , Armonk , NY , USA ) . Results : Pulse rate , systolic blood pressure , and diastolic blood pressure were comparatively lower in Group B than in Group A. The visual analog scale ( VAS ) score was significantly lower in Group B. Rescue analgesia was given when VAS was > 6 . Verbal rating scale score was significantly lower in Group B , showing longer duration of analgesia in this group . Rescue analgesic requirement was also less in Group B. Conclusion : The instillation of bupivacaine and ropivacaine intraperitoneally was an effective method of postoperative pain relief in LC . It provided good analgesia in immediate postoperative period with ropivacaine , providing longer duration of analgesia", "Background and Aims : Local anesthetic injection in the peritoneal cavity decreases intensity of postoperative pain after laparoscopic surgeries . We compared adding dexmedetomidine to intraperitoneal levobupivacaine in patients undergoing laparoscopic cholecystectomy . Methods : A total of 105 patients were included in this prospect i ve , double-blinded , r and omized study . Patients were r and omly divided into three equal sized ( n = 35 ) study groups . Group C patients received intraperitoneal 40 ml normal saline as controlled group . Group L was given 40 ml 0.25 % levobupivacaine . Group LD received 40 ml 0.25 % levobupivacaine + dexmedetomidine 1 μg/kg . The degree of postoperative pain was measured by visual analog scale ( VAS ) score . The time of first analgesic dem and was recorded and also total dose of painkiller in the first 24 h and postoperative complications were collected . SPSS version 16 was used for statistical analysis . P < 0.05 was considered statistically significant . Results : Postoperative VAS at different time intervals was significantly lower , time to the first dem and of painkiller ( min ) was longer ( 30.2 ± 14.4 , 45.9 ± 20.1 , and 56.5 ± 13.2 ) , and total painkiller consumption ( mg ) was lower ( 203.5 ± 42.9 , 117.8 ± 63.7 , and 46.3 ± 41.3 ) in Group LD than Group L than Group C. Conclusion : Adding dexmedetomidine to intraperitoneal levobupivacaine is superior to and gives better results than levobupivacaine alone in patients undergoing laparoscopic cholecystectomy", "Inappropriate therapy of postoperative pain in laparoscopic cholecystectomy may lead to late mobilization , patient dissatisfaction , delayed hospital discharge , and chronic pain development . Our objective was to identify the best therapeutic strategy available to the anesthesiologist for the acute postoperative pain of patients su bmi tted to elective laparoscopic cholecystectomy . This is a systematic review that included 36 complete articles indexed in the Medline , Scopus , Web of Science and LILACS data bases , with a five-year time cut ( 2012 to 2016 ) , result ing from controlled and r and omized studies that were su bmi tted to qualitative analysis . In a proposal for multimodal analgesia , it is important to consider the contraindications , adverse effects , dose and optimal timing of interventions . Non-opioid drugs , such as non-steroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase-2 ( COX-2 ) inhibitors , gabapentin/pregabalin , N-methyl-D-aspartate ( NMDA ) receptor antagonists , and others . Opioids may be used at low doses associated with multimodal therapy or are restricted to cases where non-opioid multimodal analgesia is insufficient . We conclude that there is no consensus as to the best analgesic strategy to be implemented in the acute postoperative pain of laparoscopic cholecystectomy , which requires its applicability in an individualized way , based on the scientific evidence found in the literature . As contribution to medical learning and practice , we point out the theoretical enrichment of the analgesic drug options available for the therapy of postoperative pain in patients su bmi tted to elective laparoscopic cholecystectomy , and alert the team to consider the adverse effects of the interventions implemented", "Introduction Gabapentinoids are increasingly used in preoperative premedication despite controversial results . The aim of our study was to evaluate the effects of preemptive use of gabapentin or pregabalin on postoperative shoulder pain and rehabilitation quality after laparoscopic cholecystectomy . Methods This is a clinical trial comparing the effects of a preoperative premedication with 600 mg of gabapentin or 150 mg of pregabalin versus placebo on postoperative pain and recovery quality after laparoscopic cholecystectomy . Premedication was taken 2 hours before the surgery beginning . Ninety patients were included and r and omized into 3 groups ( gabapentin , pregabalin , and placebo ) . The anesthetic protocol was the same for all patients . Primary endpoint was the shoulder pain intensity at the 48th postoperative hour . Secondary endpoints were postoperative nausea and vomiting ( PONV ) , sleep quality during the first night , and the onset time for the first st and ing position . Results During the first 48 postoperative hours , the gabapentin and pregabalin groups had significantly lower shoulder pain than the placebo group ( p < 0.05 ) . In gabapentinoids groups , the incidence of PONV was lower and the sleep quality during the first postoperative night was better with significant results . Mean Spiegel scores were 22.43 ± 1.45 , 22.30 ± 1.44 , and 17.17 ± 1.66 , respectively , in pregabalin , gabapentin , and placebo groups ( p < 0.05 ) . The delay for the first st and ing position was 14.9 ± 4.9 hours in the pregabalin group , 9.7 ± 3.6 hours in the gabapentin group , and 21.6 ± 2.1 hours in the placebo group . No superiority was found between gabapentin and pregabalin . Conclusion Preemptive premedication with gabapentinoids can enhance postoperative rehabilitation quality after laparoscopic cholecystectomy by reducing postoperative shoulder pain , decreasing PONV incidence , and improving sleep quality during the first postoperative night . This trial is registered with Clinical Trial.gov ( NCT03241875 )", "OBJECTIVE To determine whether intraoperative local injection of 0.5 % bupivacaine around port sites would decrease early postoperative pain after laparoscopic cholecystectomy , and the use of intravenous opioid analgesics postoperatively . STUDY DESIGN R and omised controlled trial . PLACE AND DURATION OF STUDY Department of Surgery , Khyber Teaching Hospital , Peshawar , from July 2016 to June 2017 . METHODOLOGY Patients who underwent laparoscopic cholecystectomy were divided into two groups . Group A had instillation of 20 ml of 0.5 % Inj . bupivacaine at the end of procedure into port sites and group B had no bupivacaine injection at trocar sites . Both groups had postoperative intravenous ketorolac 30 mg three times daily and intravenous opioid analgesics on dem and . Pain was assessed 2 hours after recovery from general anesthesia , and at 6 , 12 and 24 hours through visual analog scale 0 - 10 . RESULTS One hundred and twenty patients completed this study with 60 patients in each group . A significant difference in mean postoperative pain scores was observed at 2 and 6 hours after surgery between the groups . Pain scores at 2 and 6 hours after surgery were 3.97 + 1.327 and 3.02 ±1.08 in group A , while it was 4.65 + 1.448 and 4.72 ±1.277 in group B with p-values of 0.008 and 0.005 , respectively . There was no significant difference in mean postoperative pain scores at 12 and 24 hours between the groups , with pain scores of 3.72 ±0.78 and 3.75 ±0.95 ( p=0.488 and 0.744 , respectively ) . However , there was a significant difference in opioid analgesics use in first 24 hours with less analgesics use in bupivacaine injected group . CONCLUSION Injecting 0.5 % bupivacaine at trocar sites during laparoscopic cholecystectomy offers significant reduction in early postoperative pain", "Background : Significant pain can be experienced after laparoscopic cholecystectomy . This systematic review aims to formulate PROSPECT ( PROcedure SPECific Postoperative Pain ManagemenT ) recommendations to reduce postoperative pain after laparoscopic cholecystectomy . Methods : R and omised controlled trials published in the English language from January 2006 ( date of last PROSPECT review ) to December 2017 , assessing analgesic , anaesthetic , or operative interventions for laparoscopic cholecystectomy in adults , and reporting pain scores , were retrieved from MEDLINE and Cochrane data bases using PRISMA ( Preferred Reporting Items for Systematic Review s and Meta‐Analyses ) search protocol s. PROSPECT methodology was used , and recommendations were formulated after review and discussion by the PROSPECT group ( an international group of leading pain specialists and surgeons ) . Results : Of 1988 r and omised controlled trials identified , 258 met the inclusion criteria and were included in this review . The studies were of mixed method ological quality , and quantitative analysis was not performed because of heterogeneous study design and how outcomes were reported . Conclusions : We recommend basic analgesic techniques : paracetamol + NSAID or cyclooxygenase‐2 specific inhibitor + surgical site local anaesthetic infiltration . Paracetamol and NSAID should be started before or during operation with dexamethasone ( GRADE A ) . Opioid should be reserved for rescue analgesia only ( GRADE B ) . Gabapentanoids , intraperitoneal local anaesthetic , and transversus abdominis plane blocks are not recommended ( GRADE D ) unless basic analgesia is not possible . Surgically , we recommend low‐pressure pneumoperitoneum , postprocedure saline lavage , and aspiration of pneumoperitoneum ( GRADE A ) . Single‐port incision techniques are not recommended to reduce pain ( GRADE A )" ]

[ "2664810", "16998133", "15749950", "11300174" ]

[ "A randomised control trial of the effectiveness of personalised letters sent subsequent to school dental inspections in increasing registration in unregistered children", "The Effectiveness of School Dental Screening: a Cluster-randomized Control Trial", "Does school-based dental screening for children increase follow-up treatment at dental school clinics?", "Effectiveness of the school dental screening programme in stimulating dental attendance for children in need of treatment in Northern Ireland." ]

[ "Background Recent studies have cast doubt on the effectiveness and efficiency of school based dental screening programmes in improving dental attendance or improving dental health . In 2002 the National Dental Inspection Programme was introduced in Scotl and which categorises children by their dental health and informs parents of the findings via a personalised letter home and encourages dental registration . In addition , epidemiological data for local and national planning purpose s is collected . This replaced an earlier school screening system in Lothian where a generic letter urging registration was sent to children who were identified as not being registered with a dentist . The objective of this study is to compare dental registration s rates among unregistered children in these two school inspection systems with a system where letters were sent home but no dental inspection was carried out . Methods The study was design ed as a single blinded , cluster r and omised , controlled trial involving 12,765 12–13-year-old children attending all 65 state Secondary schools in Lothian and Fife during the academic year 2003/4.After stratifying for school size and range of social deprivation , schools were r and omly allocated to one of four groups:1 . ' Traditional ' inspection , letter to unregistered children only,2 . Letter sent home to unregistered children only , no inspection,3 . National Dental Inspection Programme , letter to all children,4 . Control group in which the children were neither inspected nor sent a letter . Dental Registration status was compared at baseline and 3 months post inspection . Results The registration levels in both the ' Traditional ' screening and the NDIP inspection groups rose 3 months post inspection ( 14 % and 15.8 % respectively ) but were not significantly different from one another or the control group which rose by 15.8 % ( p > 0.05 ) . The group who were sent a letter home but were not inspected also has a rise in registration levels of 18.1 % which was not significantly different from either of the groups who were inspected or the control group ( p > 0.05 ) . The only significant predictors of registration were previous registration ( p < 0.05 ) and within those who previously registered , the length of time since last registration ( P < 0.001 ) . Conclusion Neither of the two dental inspection methods nor a letter home to unregistered children result ed in a significant rise in registration rates in 12–13-year-olds compared to a control group of children who received no intervention", "Dental screening of children in schools is undertaken in many countries . There is no evidence that this activity is effective . The objective of our study was to determine if school dental screening of children reduces untreated disease or improves attendance at the population level . A four-arm cluster-r and omized controlled trial was undertaken in the northwest of Engl and . In total , 16,864 children aged 6–9 years in 168 schools were r and omly allocated to 3 test groups , which received screening according to different models , and a control , which received no intervention . There were no significant differences in caries increment in the primary and secondary dentitions or in the proportions of children attending a dentist after screening between the control group and the 3 intervention arms . School dental screening delivered according to 3 different models was not effective at reducing levels of active caries and increasing attendance in the population under study", "The purpose of this study was to evaluate the effectiveness of a screening program and referral system in stimulating dental attendance of children in need of treatment at Bapuji Dental College and Hospital of Davangere , India . A total of fourteen schools in the Davangere area were selected r and omly and divided into two groups : seven schools that had a dental screening program ( study group , n=2100 children ) , and seven schools that did not have one ( control group , n=2400 children ) . The attendance rate by members of the study group was determined during the three-month period from the date of initiating the school screening program . During this same period the students who visited the college from the control group underwent a dental examination . Chi-square tests were used to test the difference between different variables . The response rate for seeking treatment was 31 percent for the study group ( 34.2 percent for males ; 26.2 percent for females ) and 10 percent for the control group ( 9.6 percent for males ; 10.5 percent for females ) . In both the groups , the treatment need was highest for dental caries ( study group=36.3 percent , control group=11.1 percent ) and least for fluorosis ( study group=21.2 percent , control group=1.2 percent ) . The study demonstrated that screening and motivation significantly improved the percentage of school children who sought dental care", "UNLABELLED The school dental screening programme has been in existence from the beginning of the 20th century yet its value in encouraging attendance among children with a dental health need is not fully established . OBJECTIVE To evaluate the effectiveness of school dental screening in promoting dental attendance among children with a treatment need and to examine the relative importance of screening , social class and other factors in dental attendance . METHODS Sixty-four participating schools were assigned to study and control groups using a stratified , blocked r and omisation technique . The study group children received the st and ard school dental screening and the dental attendance of those with a positive screening result was assessed after 2 months by means of a question naire issued to the children 's parents . The control group children were not , at this stage , screened , yet their parents received the same question naire assessing dental attendance over the 2-month period . However , only question naires from control group children who had a positive result at a subsequent screening were retained for analysis . RESULTS A total of 2,321 children were screened , with 980 having a positive result . The mean dmft of those screening positive was 4.85 . In all , 664 completed question naires were returned , giving a response rate of 67.8 % . Dental attendance was reported among 45.5 % of the study group ( n=352 ) in the 2 months following screening . In the same period , 27.6 % of the control group ( n=312 ) cl aim ed attendance . The effect was found to be significant among the high employed group ( P<0.01 ) and the unemployed group ( P<0.05 ) . CONCLUSION School dental screening was capable of stimulating dental attendance . The strong effect among the lowest socio-economic group shows that school dental screening may be used to decrease dental health inequalities" ]

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[ "A comparison between chiropractic management and pain clinic management for chronic low-back pain in a national health service outpatient clinic.", "United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care", "A Randomized Trial of Combined Manipulation, Stabilizing Exercises, and Physician Consultation Compared to Physician Consultation Alone for Chronic Low Back Pain", "Single-blind randomised controlled trial of chemonucleolysis and manipulation in the treatment of symptomatic lumbar disc herniation", "Lymphocyte profiles in patients with chronic low back pain enrolled in a clinical trial.", "Predictive factors for 1-year outcome of low-back and neck pain in patients treated in primary care: comparison between the treatment strategies chiropractic and physiotherapy", "Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial", "A Randomized, Controlled Trial of Manual Therapy and Specific Adjuvant Exercise for Chronic Low Back Pain", "United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care", "Comparison of general exercise, motor control exercise and spinal manipulative therapy for chronic low back pain: A randomized trial", "Chronic Spinal Pain: A Randomized Clinical Trial Comparing Medication, Acupuncture, and Spinal Manipulation", "Long-term effectiveness of bone-setting, light exercise therapy, and physiotherapy for prolonged back pain: a randomized controlled trial.", "The short-term effect of a spinal manipulation on pain/pressure threshold in patients with chronic mechanical low back pain.", "Socioeconomic status predicts functional disability in patients participating in a back pain trial", "Supervised exercise, spinal manipulation, and home exercise for chronic low back pain: a randomized clinical trial.", "Effects of different treatment modalities on gait symmetry and clinical measures for sacroiliac joint patients.", "Randomised clinical trial of manipulative therapy and physiotherapy for persistent back and neck complaints: results of one year follow up.", "The Nordic back pain subpopulation program: predicting outcome among chiropractic patients in Finland", "Do baseline characteristics predict response to treatment for low back pain? Secondary analysis of the UK BEAM dataset [ISRCTN32683578].", "A Randomized Controlled Trial Investigating the Efficiency of Musculoskeletal Physiotherapy on Chronic Low Back Disorder", "Orthopaedic manual therapy, McKenzie method or advice only for low back pain in working adults: a randomized controlled trial with one year follow-up.", "Controlled trial of mobilisation and manipulation for low back pain: hospital patients.", "Does folk medicine work? A randomized clinical trial on patients with prolonged back pain.", "Stretching in the Rehabilitation of Low-Back Pain Patients", "Economic Evaluation of Four Treatments for Low-Back Pain: Results From a Randomized Controlled Trial", "A comparison of manual therapy and active rehabilitation in the treatment of non specific low back pain with particular reference to a patient's Linton & Hallden psychological screening score: a pilot study", "Naprapathic Manual Therapy or Evidence-based Care for Back and Neck Pain: A Randomized, Controlled Trial", "Long-term follow-up of a randomized clinical trial assessing the efficacy of medication, acupuncture, and spinal manipulation for chronic mechanical spinal pain syndromes.", "Amount of health care and self-care following a randomized clinical trial comparing flexion-distraction with exercise program for chronic low back pain", "Low back pain of mechanical origin: randomised comparison of chiropractic and hospital outpatient treatment.", "The impact of treatment confidence on pain and related disability among patients with low-back pain: results from the University of California, Los Angeles, low-back pain study.", "Satisfaction as a Predictor of Clinical Outcomes Among Chiropractic and Medical Patients Enrolled in the UCLA Low Back Pain Study", "Back pain and sciatica: controlled trials of manipulation, traction, sclerosant and epidural injections.", "The effect of spinal manipulation on pain and prostaglandin levels in women with primary dysmenorrhea.", "Dose-response for chiropractic care of chronic low back pain.", "RELATIVE THERAPEUTIC EFFICACY OF VERTEBRAL MANIPULATION AND CONVENTIONAL TREATMENT IN BACK PAIN MANAGEMENT1", "CONTROLLED COMPARISON OF SHORT-WAVE DIATHERMY TREATMENT WITH OSTEOPATHIC TREATMENT IN NON-SPECIFIC LOW BACK PAIN", "Spinal manipulation for low back pain.", "Rasch Analysis of the Roland Disability Questionnaire", "Clinical trial of common treatments for low back pain in family practice.", "A randomized clinical trial of manual versus mechanical force manipulation in the treatment of sacroiliac joint syndrome.", "Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial.", "Patient perceptions of physical therapy within a trial for back pain treatments (UK BEAM) [ISRCTN32683578].", "A randomized clinical trial and subgroup analysis to compare flexion–distraction with active exercise for chronic low back pain", "Manipulation in treatment of low back pain: a multicentre study.", "Identifying Subgroups of Patients With Acute/Subacute “Nonspecific” Low Back Pain: Results of a Randomized Clinical Trial", "Variance in manual treatment of nonspecific low back pain between orthomanual physicians, manual therapists, and chiropractors.", "Manipulative Therapy Versus Education Programs in Chronic Low Back Pain", "A randomized clinical trial of manual therapy and physiotherapy for persistent back and neck complaints: subgroup analysis and relationship between outcome measures.", "The Effectiveness of Manual Therapy, Physiotherapy, and Treatment by the General Practitioner for Nonspecific Back and Neck Complaints: A Randomized Clinical Trial", "Dynamic surface electromyographic responses in chronic low back pain treated by traditional bone setting and conventional physical therapy.", "One-year follow-up of a randomized clinical trial comparing flexion distraction with an exercise program for chronic low-back pain.", "A comparison of osteopathic spinal manipulation with standard care for patients with low back pain.", "A randomized controlled trial comparing 2 types of spinal manipulation and minimal conservative medical care for adults 55 years and older with subacute or chronic low back pain.", "The McKenzie Method Compared With Manipulation When Used Adjunctive to Information and Advice in Low Back Pain Patients Presenting With Centralization or Peripheralization: A Randomized Controlled Trial", "Chronic spinal pain syndromes: a clinical pilot trial comparing acupuncture, a nonsteroidal anti-inflammatory drug, and spinal manipulation.", "Controlled trial of mobilisation and manipulation for patients with low back pain in general practice.", "Efficacy of treating low back pain and dysfunction secondary to osteoarthritis: chiropractic care compared with moist heat alone.", "Osteopathic Manipulative Treatment for Chronic Low Back Pain: A Randomized Controlled Trial", "Recruitment and enrollment for the simultaneous conduct of 2 randomized controlled trials for patients with subacute and chronic low back pain at a CAM research center.", "Back pain: a randomized clinical trial of rotational manipulation of the trunk", "Spinal manipulation compared with back school and with individually delivered physiotherapy for the treatment of chronic low back pain: a randomized trial with one-year follow-up", "Spinal manipulation, epidural injections, and self-care for sciatica: a pilot study for a randomized clinical trial.", "One‐Year Follow‐up Comparison of the Cost and Effectiveness of Chiropractic and Physiotherapy as Primary Management for Back Pain: Subgroup Analysis, Recurrence, and Additional Health Care Utilization", "A Prospective Randomized Three‐Week Trial of Spinal Manipulation, Transcutaneous Muscle Stimulation, Massage and Corset in the Treatment of Subacute Low Back Pain", "An open controlled assessment of osteopathic manipulation in nonspecific low-back pain.", "Second Prize: The effectiveness of physical modalities among patients with low back pain randomized to chiropractic care: findings from the UCLA low back pain study.", "Effectiveness of traditional bone setting in treating chronic low back pain: a randomised pilot trial.", "A NEW APPROACH TO THE TREATMENT OF CHRONIC LOW BACK PAIN", "A Randomized Trial of Medical Care With and Without Physical Therapy and Chiropractic Care With and Without Physical Modalities for Patients With Low Back Pain: 6-Month Follow-Up Outcomes From the UCLA Low Back Pain Study", "A blinded randomized clinical trial of manual therapy and physiotherapy for chronic back and neck complaints: physical outcome measures.", "Comparing the satisfaction of low back pain patients randomized to receive medical or chiropractic care: results from the UCLA low-back pain study.", "Differential recruitment in a cluster randomized trial in primary care: the experience of the UK Back pain, Exercise, Active management and Manipulation (UK BEAM) feasibility study", "Self-Report Measures Best Explain Changes in Disability Compared With Physical Measures After Exercise Rehabilitation for Chronic Low Back Pain", "Manipulation does not add to the effect of extension exercises in chronic low-back pain (LBP). A randomized, controlled, double blind study.", "Effects of recreational physical activity and back exercises on low back pain and psychological distress: findings from the UCLA Low Back Pain Study.", "Good Prognosis for Low Back Pain When Left Untampered: A Randomized Clinical Trial", "Short-term responsiveness of manual thoracic end-play assessment to spinal manipulation: a randomized controlled trial of construct validity.", "A randomized-control study of active and passive treatments for chronic low back pain following L5 laminectomy.", "Cost-effectiveness of Combined Manipulation, Stabilizing Exercises, and Physician Consultation Compared to Physician Consultation Alone for Chronic Low Back Pain: A Prospective Randomized Trial With 2-Year Follow-up", "A Randomized Trial of Chiropractic and Medical Care for Patients With Low Back Pain: Eighteen-Month Follow-up Outcomes From the UCLA Low Back Pain Study", "A Randomized Clinical Trial Comparing Two Physiotherapy Interventions for Chronic Low Back Pain", "Randomised comparison of chiropractic and hospital outpatient management for low back pain: results from extended follow up", "Stabilizing training compared with manual treatment in sub-acute and chronic low-back pain.", "Effectiveness of Four Conservative Treatments for Subacute Low Back Pain: A Randomized Clinical Trial", "Treatment of pelvic joint dysfunction in primary care--a controlled study.", "Cost and Effectiveness Analysis of Chiropractic and Physiotherapy Treatment for Low Back and Neck Pain: Six‐Month Follow‐Up", "A randomized, controlled trial of osteopathic manipulative treatment for acute low back pain in active duty military personnel", "Manual Therapy and Exercise Therapy in Patients With Chronic Low Back Pain: A Randomized, Controlled Trial With 1-Year Follow-up", "A comparison of physical therapy, chiropractic manipulation, and provision of an educational booklet for the treatment of patients with low back pain.", "The acceptability to primary care staff of a multidisciplinary training package on acute back pain guidelines.", "Cross-sectional and longitudinal associations of low-back pain and related disability with psychological distress among patients enrolled in the UCLA Low-Back Pain Study." ]

[ "OBJECTIVES To compare outcomes in perception of pain and disability for a group of patients suffering with chronic low-back pain ( CLBP ) when managed in a hospital by either a regional pain clinic or a chiropractor . DESIGN The study was a pragmatic , r and omized , controlled trial . SETTING The trial was performed at a National Health Service ( NHS ) hospital outpatient clinic ( pain clinic ) in the United Kingdom . SUBJECTS AND INTERVENTIONS Patients with CLBP ( i.e. , symptom duration of > 12 weeks ) referred to a regional pain clinic ( outpatient hospital clinic ) were assessed and r and omized to either chiropractic or pain-clinic management for a period of 8 weeks . The study was pragmatic , allowing for normal treatment protocol s to be used . Treatment was administered in an NHS hospital setting . OUTCOME MEASURES The Rol and -Morris Disability Question naire ( RMDQ ) and Numerical Rating Scale were used to assess changes in perceived disability and pain . Mean values at weeks 0 , 2 , 4 , 6 , and 8 were calculated . The mean differences between week 0 and week 8 were compared across the two treatment groups using Student 's t-tests . Ninety-five percent ( 95 % ) confidence intervals ( CIs ) for the differences between groups were calculated . RESULTS R and omization placed 12 patients in the pain clinic and 18 in the chiropractic group , of which 11 and 16 , respectively , completed the trial . At 8 weeks , the mean improvement in RMDQ was 5.5 points greater for the chiropractic group ( decrease in disability by 5.9 ) than for the pain-clinic group ( 0.36 ) ( 95 % CI 2.0 points to 9.0 points ; p = 0.004 ) . Reduction in mean pain intensity at week 8 was 1.8 points greater for the chiropractic group than for the pain-clinic group ( p = 0.023 ) . CONCLUSIONS This study suggests that chiropractic management administered in an NHS setting may be effective for reducing levels of disability and perceived pain during the period of treatment for a sub population of patients with CLBP", "Abstract Objective To estimate the effect of adding exercise classes , spinal manipulation delivered in NHS or private premises , or manipulation followed by exercise to “ best care ” in general practice for patients consulting with back pain . Fig 1 Progress of the UK BEAM trial Design Pragmatic r and omised trial with factorial design . Setting 181 general practice s in Medical Research Council General Practice Research Framework ; 63 community setting s around 14 centres across the United Kingdom . Participants 1334 patients consulting their general practice s about low back pain . Main outcome measures Scores on the Rol and Morris disability question naire at three and 12 months , adjusted for centre and baseline scores . Results All groups improved over time . Exercise improved mean disability question naire scores at three months by 1.4 ( 95 % confidence interval 0.6 to 2.1 ) more than “ best care . ” For manipulation the additional improvement was 1.6 ( 0.8 to 2.3 ) at three months and 1.0 ( 0.2 to 1.8 ) at 12 months . For manipulation followed by exercise the additional improvement was 1.9 ( 1.2 to 2.6 ) at three months and 1.3 ( 0.5 to 2.1 ) at 12 months . No significant differences in outcome occurred between manipulation in NHS premises and in private premises . No serious adverse events occurred . Conclusions Relative to “ best care ” in general practice , manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months ; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months ; and exercise achieved a small benefit at three months but not 12 months", "Study Design . A prospect i ve r and omized controlled trial . Objectives . To examine the effectiveness of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain . Summary of Background Data . Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain . The evidence for long-term effect is lacking . Methods . Two hundred four chronic low back pain patients , whose Oswestry disability index was at least 16 % , were r and omly assigned to either a manipulative-treatment group or a consultation group . All were clinical ly examined , informed about their back pain , provided with an educational booklet , and were given specific instructions based on the clinical evaluation . The treatment included four sessions of manipulation and stabilizing exercises aim ing to correct the lumbopelvic rhythm . Question naires inquired about pain intensity , self-rated disability , mental depression , health-related quality of life , health care costs , and production costs . Results . At the baseline , the groups were comparable , except for the percentage of employees ( P = 0.01 ) . At the 5- and 12-month follow-ups , the manipulative-treatment group showed more significant reductions in pain intensity ( P < 0.001 ) and in self-rated disability ( P = 0.002 ) than the consultation group . However , we detected no significant difference between the groups in health-related quality of life or in costs . Conclusions . The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone . The present study showed that short , specific treatment programs with proper patient information may alter the course of chronic low back pain", "Abstract This single-blind r and omised clinical trial compared osteopathic manipulative treatment with chemonucleolysis ( used as a control of known efficacy ) for symptomatic lumbar disc herniation . Forty patients with sciatica due to this diagnosis ( confirmed by imaging ) were treated either by chemonucleolysis or manipulation . Outcomes ( leg pain , back pain and self-reported disability ) were measured at 2 weeks , 6 weeks and 12 months . The mean values for all outcomes improved in both groups . By 12 months , there was no statistically significant difference in outcome between the treatments , but manipulation produced a statistically significant greater improvement for back pain and disability in the first few weeks . A similar number from both groups required additional orthopaedic intervention ; there were no serious complications . Crude cost analysis suggested an overall financial advantage from manipulation . Because osteopathic manipulation produced a 12-month outcome that was equivalent to chemonucleolysis , it can be considered as an option for the treatment of symptomatic lumbar disc herniation , at least in the absence of clear indications for surgery . Further study into the value of manipulation at a more acute stage is warranted", "OBJECTIVE Our earlier findings suggest that patients with musculoskeletal complaints have lower numbers and percentages of natural killer ( NK ) cells than asymptomatic subjects . This study examines patient lymphocyte profiles , as a secondary outcome measure , in a trial of manipulative therapies to treat chronic low back pain ( LBP ) of mechanical origin . DESIGN The patients were compared in a r and omized controlled trial . Baseline measures were collected at the initial visit ; all patients were scheduled for 11 treatments in 14 days . Treatment consisted of either a high-force , high-velocity , low-amplitude manipulation procedure ; a low-force , high-velocity , low-amplitude procedure or a series of educational lectures on lower back pain . Posttreatment measures were collected at the final treatment session ; follow-up measures were obtained 2 wk later . SETTING The study was conducted at a chiropractic teaching clinic in the suburban Chicago area . PARTICIPANTS Individuals over 18 were eligible if they were new patients or repeat patients with a 6 month 's hiatus , if the chief complaint was LBP of greater than 50 days ' duration , if pain was elicited with palpation over one or more of the facet joints from the spinal levels between L1 and S1 and including the sacroiliac joints , and if there was absence of pain referral or if pain referral was only scleratogenous in nature . Criteria for excluding patients included hard neurologic signs , systemic disease potentially affecting the musculoskeletal system , contraindication to spinal manipulation such as osteoporosis , fracture or other bony pathology , or treatment with medication intended to relieve symptoms associated with their LBP . Eligibility was determined by a staff diagnostic team independent of the attending physician . Three hundred sixty-seven of 1,275 consecutive new patients met the eligibility criteria . Of these , 209 participated . These results are for 201 patients from whom flow cytometric data were obtained . OUTCOME MEASURES Both absolute numbers and percentages of B-lymphocytes , T-lymphocytes , T-Helper ( TH ) , T-Suppressor ( TS ) and NK lymphocytes were determined . Blood sample s were collected at the same time that the primary outcome measures were obtained . Cells were stained with two-color monoclonal antibodies directed against specific cell surface antigens , and each lymphocyte sub population was quantified directly from lysed whole blood with a Coulter Epics Profile II flow cytometer . RESULTS Thirty-five patients dropped out before the follow-up visit and technical problems result ed in the loss of data from 17 more and the exclusion of some sub population data . In all , 148 cases were analyzed for B cells , 146 for TH , TS and NK cells and 138 for cells that carried both the NK and TS marker . A one-way analysis of variance revealed no significant differences in the lymphocyte profiles at baseline among the three groups . All sub population baseline values were within reported reference ranges for normal adult population s. However , the percentage of NK cells ( 9.1 % ) was below the published minimum critical value . A repeated measures analysis of variance was used to determine whether treatment effects changed over time , that is , treatment-time interaction . The cell types for which the interaction tests were at or near statistical significance were : TH cells ( p = .0208 ) , total T cell percent ( p = .0928 ) and absolute total T cells ( p = .0908 ) . Interaction tests for differences in either percent or absolute counts of B cells , TS cells , or NK cells were not statistically significant . CONCLUSIONS This is the first report of lymphocyte profiles in patients with diagnosed chronic LBP . Our finding of a lower percentage of NK cells in these patients confirms our earlier finding that patients with musculoskeletal problems have a lower percentage of NK cells than do asymptomatic subjects . However , manipulative therapy was not shown to have a clinical ly significant effect on either the absolute", "Abstract The inability to predict outcome in patients with low back/neck pain leads to inappropriate or unnecessary treatment . The aims of the study were to identify prognostic factors for disability at 1‐year follow‐up in patients with back pain visiting primary care , and to compare the effect of these in two treatment strategies – chiropractic and physiotherapy . Data were taken from a r and omised trial on patients with back/neck pain visiting the general practitioner , in which patients were allocated to chiropractic and physiotherapy as primary management . Three hundred and twenty‐three patients , aged 18–60 years , who had no contraindications to manipulation and who had not been treated within the previous month were included in the study . Multiple regression analysis was used to identify prognostic factors . Dependent variables were mean Oswestry score and mean change in Oswestry score at 12‐month follow‐up . The multiple regression analysis revealed five significant ( P<0.001–0.01 ) prognostic factors ; duration of current episode , Oswestry score at entry , expectations of treatment , number of localisations , and well‐being . Besides , the regression coefficients for the significant factors were compared between the two treatment strategies . No significant difference in effect or regression coefficients for the prognostic factors were seen between the two treatment strategies . Twelve per cent of the patients had poor prognostic factors ( duration ≥1 month , more than one localisation , low expectations of treatment and low well‐being ) at entry . These patients had a mean Oswestry score above 20 % at 1‐year follow‐up . Clinical decision models for the management of patients with back pain visiting primary care that consider prognostic factors need to be implemented and prospect ively evaluated", "Background Reporting numbers needed to treat ( NNT ) improves interpretability of trial results . It is unusual that continuous outcomes are converted to numbers of individual responders to treatment ( i.e. , those who reach a particular threshold of change ) ; and deteriorations prevented are only rarely considered . We consider how numbers needed to treat can be derived from continuous outcomes ; illustrated with a worked example showing the methods and challenges . Methods We used data from the UK BEAM trial ( n = 1 , 334 ) of physical treatments for back pain ; originally reported as showing , at best , small to moderate benefits . Participants were r and omised to receive ' best care ' in general practice , the comparator treatment , or one of three manual and /or exercise treatments : ' best care ' plus manipulation , exercise , or manipulation followed by exercise . We used established consensus thresholds for improvement in Rol and -Morris disability question naire scores at three and twelve months to derive NNTs for improvements and for benefits ( improvements gained+deteriorations prevented ) . Results At three months , NNT estimates ranged from 5.1 ( 95 % CI 3.4 to 10.7 ) to 9.0 ( 5.0 to 45.5 ) for exercise , 5.0 ( 3.4 to 9.8 ) to 5.4 ( 3.8 to 9.9 ) for manipulation , and 3.3 ( 2.5 to 4.9 ) to 4.8 ( 3.5 to 7.8 ) for manipulation followed by exercise . Corresponding between-group mean differences in the Rol and -Morris disability question naire were 1.6 ( 0.8 to 2.3 ) , 1.4 ( 0.6 to 2.1 ) , and 1.9 ( 1.2 to 2.6 ) points . Conclusion In contrast to small mean differences originally reported , NNTs were small and could be attractive to clinicians , patients , and purchasers . NNTs can aid the interpretation of results of trials using continuous outcomes . Where possible , these should be reported alongside mean differences . Challenges remain in calculating NNTs for some continuous outcomes .Trial Registration UK BEAM trial registration : IS RCT N32683578", "Objective : This article examines the effectiveness of manual therapy with specific adjuvant exercise for treating chronic low back pain and disability . Methods : A single blind , r and omized , controlled trial was employed . Patients were prescribed an exercise program that was tailored to treat their musculoskeletal dysfunctions or given a nonspecific program of general stretching and aerobic conditioning . In addition , patients received manual therapy or sham manual therapy . Participants were seen for 6 weekly sessions and were asked to perform their exercise program twice daily . Results : Seventy-two out of 100 patients completed the study . Multivariate tests conducted for measures of pain and disability revealed a significant group by time interaction ( P = 0.04 and P = 0.05 , respectively ) , indicating differential change in these measures pretreatment to posttreatment as a function of the treatment received . When controlling for pretreatment scores , patients receiving manual therapy with specific adjuvant exercise reported significant reductions in pain . No change in perceived disability was observed , with the exception that patients receiving sham manual therapy with specific adjuvant exercise reported significantly greater disability at posttreatment . Discussion : Manual therapy with specific adjuvant exercise appears to be beneficial in treating chronic low back pain . Despite changes in pain , perceived function did not improve . It is possible that impacting chronic low back pain alone does not address psychosocial or other factors that may contribute to disability . Further studies are needed to examine the long-term effects of these interventions and to address what adjuncts are beneficial in improving function in this population", "Abstract Objective To assess the cost effectiveness of adding spinal manipulation , exercise classes , or manipulation followed by exercise ( “ combined treatment ” ) to “ best care ” in general practice for patients consulting with low back pain . Design Stochastic cost utility analysis alongside pragmatic r and omised trial with factorial design . Setting 181 general practice s and 63 community setting s for physical treatments around 14 centres across the United Kingdom . Participants 1287 ( 96 % ) of 1334 trial participants . Main outcome measures Healthcare costs , quality adjusted life years ( QALYs ) , and cost per QALY over 12 months . Results Over one year , mean treatment costs relative to “ best care ” were £ 195 ( $ 360 ; € 279 ; 95 % credibility interval £ 85 to £ 308 ) for manipulation , £ 140 ( £ 3 to £ 278 ) for exercise , and £ 125 ( £ 21 to £ 228 ) for combined treatment . All three active treatments increased participants ' average QALYs compared with best care alone . Each extra QALY that combined treatment yielded relative to best care cost £ 3800 ; in economic terms it had an “ incremental cost effectiveness ratio ” of £ 3800 . Manipulation alone had a ratio of £ 8700 relative to combined treatment . If the NHS was prepared to pay at least £ 10 000 for each extra QALY ( lower than previous recommendations in the United Kingdom ) , manipulation alone would probably be the best strategy . If manipulation was not available , exercise would have an incremental cost effectiveness ratio of £ 8300 relative to best care . Conclusions Spinal manipulation is a cost effective addition to “ best care ” for back pain in general practice . Manipulation alone probably gives better value for money than manipulation followed by exercise", "Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain", "Study Design . A r and omized controlled clinical trial was conducted . Objective . To compare medication , needle acupuncture , and spinal manipulation for managing chronic ( > 13 weeks duration ) spinal pain because the value of medicinal and popular forms of alternative care for chronic spinal pain syndromes is uncertain . Summary of Background Data . Between February 1999 and October 2001 , 115 patients without contraindication for the three treatment regimens were enrolled at the public hospital ’s multidisciplinary spinal pain unit . Methods . One of three separate intervention protocol s was used : medication , needle acupuncture , or chiropractic spinal manipulation . Patients were assessed before treatment by a sports medical physician for exclusion criteria and by a research assistant using the Oswestry Back Pain Disability Index ( Oswestry ) , the Neck Disability Index ( NDI ) , the Short-Form-36 Health Survey question naire ( SF-36 ) , visual analog scales ( VAS ) of pain intensity and ranges of movement . These instruments were administered again at 2 , 5 , and 9 weeks after the beginning of treatment . Results . R and omization proved to be successful . The highest proportion of early ( asymptomatic status ) recovery was found for manipulation ( 27.3 % ) , followed by acupuncture ( 9.4 % ) and medication ( 5 % ) . Manipulation achieved the best overall results , with improvements of 50 % ( P = 0.01 ) on the Oswestry scale , 38 % ( P = 0.08 ) on the NDI , 47 % ( P < 0.001 ) on the SF-36 , and 50 % ( P < 0.01 ) on the VAS for back pain , 38 % ( P < 0.001 ) for lumbar st and ing flexion , 20 % ( P < 0.001 ) for lumbar sitting flexion , 25 % ( P = 0.1 ) for cervical sitting flexion , and 18 % ( P = 0.02 ) for cervical sitting extension . However , on the VAS for neck pain , acupuncture showed a better result than manipulation ( 50%vs 42 % ) . Conclusions . The consistency of the results provides , despite some discussed shortcomings of this study , evidence that in patients with chronic spinal pain , manipulation , if not contraindicated , results in greater short-term improvement than acupuncture or medication . However , the data do not strongly support the use of only manipulation , only acupuncture , or only nonsteroidal antiinflammatory drugs for the treatment of chronic spinal pain . The results from this exploratory study need confirmation from future larger studies", "BACKGROUND Chiropractic manipulation and strenuous exercise therapy have been shown effective in the treatment of nonspecific back pain . Bone- setting , the predecessor of modern manual therapies , still survives in some parts of Finl and and was compared with a light exercise therapy and non-manipulative , pragmatic physiotherapy in a year-long r and omized controlled trial on patients with long-term back pain . METHODS One hundred fourteen ambulatory patients of working age with back pain for 7 weeks or more were r and omly assigned to the therapies , which were offered in up to 10 sessions during a 6-week treatment period . The outcome was measured by the Oswestry Disability Question naire . Sick-leaves and visits to health centers were recorded for 1 year before and after the therapy . RESULTS The Oswestry disability scores improved most in the bone- setting group ( P = .02 , Kruskall-Wallis test ) . Visits to health centers for back pain were reduced only in the physiotherapy group ( P = .01 , Wilcoxon test ) . Sick-leaves were not significantly different between groups . A secondary analysis based on the use of additional therapies after the intervention showed a possible subgroup with an enhanced effect from bone- setting . CONCLUSIONS Traditional bone- setting seemed more effective than exercise or physiotherapy on back pain and disability , even 1 year after therapy", "OBJECTIVE The purpose of this study was to evaluate the pain/pressure threshold of selected myofascial points in subjects with chronic mechanical back pain after a single manipulation or mobilization . DESIGN The study design was a r and omized control trial . SETTING Chiropractic College outpatient clinic . PARTICIPANTS Thirty subjects aged 18 - 50 yr ( mean age 31 yr , SD = 7 yr ) with chronic mechanical low back pain ( mean duration of pain 74 months , SD = 83 months ) were r and omized into two groups . One group received a manipulation and the other received a mobilization . OUTCOME MEASURE Pain/pressure threshold of selected myofascial points were measured before , immediately after , and 15 and 30 min postintervention . RESULTS Sixteen patients were allocated to the manipulation group and 14 to the mobilization group . Repeated measured analysis of variance for all locations failed to show clinical or statistical significance ( p > .287 ) . The overall effect between treatments and the interaction between treatment and time was not significant ( p > .268 ) . CONCLUSION The absence of significant changes may be attributed to the selection of myofascial points , the instrument sensitivity to small changes , the differences in baseline measures and the absence of effect from one intervention", "Purpose . To investigate whether socioeconomic status in patients with back pain participating in a r and omised controlled trial was predictive of functional disability ( Rol and Disability Question naire , RDQ ) . Method . Secondary analysis of data ( n = 949 ) from a national primary care trial of physical treatments for back pain ( UKBEAM trial ) using multilevel modelling . The three indicators were Townsend scores , educational levels and work status . Results . All indicators were significant predictors of outcome after adjusting for baseline variables . As Townsend scores increased ( indicating greater deprivation ) RDQ scores ( functional disability related to back pain ) increased . Lower levels of educational attainment were associated with higher RDQ scores . Those ‘ Not in Work ’ reported markedly higher levels of RDQ scores which increased over time . There was no evidence that one particular treatment was more suitable for participants of different socioeconomic status . Conclusions . The findings from this study add to the body of literature which suggests the importance of socioeconomic factors as an influence on health , including result ant disability related to chronic musculoskeletal conditions such as back pain . Work status was particularly dominant in our findings and may suggest that helping patients with back pain back to work where appropriate , is an especially important part of the management process", "BACKGROUND CONTEXT Several conservative therapies have been shown to be beneficial in the treatment of chronic low back pain ( CLBP ) , including different forms of exercise and spinal manipulative therapy ( SMT ) . The efficacy of less time-consuming and less costly self-care interventions , for example , home exercise , remains inconclusive in CLBP population s. PURPOSE The purpose of this study was to assess the relative efficacy of supervised exercise , spinal manipulation , and home exercise for the treatment of CLBP . STUDY DESIGN / SETTING An observer-blinded and mixed- method r and omized clinical trial conducted in a university research clinic in Bloomington , MN , USA . PATIENT SAMPLE Individuals , 18 to 65 years of age , who had a primary complaint of mechanical LBP of at least 6-week duration with or without radiating pain to the lower extremity were included in this trial . OUTCOME MEASURES Patient-rated outcomes were pain , disability , general health status , medication use , global improvement , and satisfaction . Trunk muscle endurance and strength were assessed by blinded examiners , and qualitative interviews were performed at the end of the 12-week treatment phase . METHODS This prospect i ve r and omized clinical trial examined the short- ( 12 weeks ) and long-term ( 52 weeks ) relative efficacy of high-dose , supervised low-tech trunk exercise , chiropractic SMT , and a short course of home exercise and self-care advice for the treatment of LBP of at least 6-week duration . The study was approved by local institutional review boards . RESULTS A total of 301 individuals were included in this trial . For all three treatment groups , outcomes improved during the 12 weeks of treatment . Those who received supervised trunk exercise were most satisfied with care and experienced the greatest gains in trunk muscle endurance and strength , but they did not significantly differ from those receiving chiropractic spinal manipulation or home exercise in terms of pain and other patient-rated individual outcomes , in both the short- and long-term . CONCLUSIONS For CLBP , supervised exercise was significantly better than chiropractic spinal manipulation and home exercise in terms of satisfaction with treatment and trunk muscle endurance and strength . Although the short- and long-term differences between groups in patient-rated pain , disability , improvement , general health status , and medication use consistently favored the supervised exercise group , the differences were relatively small and not statistically significant for these individual outcomes", "The purpose of this study was to assess the effects of two different treatment modalities on the rehabilitation process of chronic sacroiliac joint patients . The treatment modalities included spinal manipulative therapy given by a chiropractor and a program of back school therapy given by a physiotherapist . The rehabilitation process was assessed using clinical and biomechanical measures . It was found that back school therapy was a better treatment modality than the spinal manipulative therapy , according to the clinical measures of rehabilitation . Precisely the opposite result was found for the biomechanical measures", "OBJECTIVE --To compare the effectiveness of manipulative therapy , physiotherapy , treatment by the general practitioner , and placebo therapy in patients with persistent non-specific back and neck complaints . DESIGN --R and omised clinical trial . SETTING -- Primary health care in the Netherl and s. PATIENTS --256 patients with non-specific back and neck complaints of at least six weeks ' duration who had not received physiotherapy or manipulative therapy in the past two years . INTERVENTIONS --At the discretion of the manipulative therapists , physiotherapists , and general practitioners . Physiotherapy consisted of exercises , massage , and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manipulative therapy consisted of manipulation and mobilisation of the spine . Treatment by general practitioners consisted of drugs ( for example , analgesics ) , advice about posture , home exercises , and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 minutes ) and detuned ultrasound ( 10 minutes ) . MAIN OUTCOME MEASURES --Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients . RESULTS --Many patients in the general practitioner and placebo groups received other treatment during follow up . Improvement in the main complaint was larger with manipulative therapy ( 4.5 ) than with physiotherapy ( 3.8 ) after 12 months ' follow up ( difference 0.9 ; 95 % confidence interval 0.1 to 1.7 ) . Manipulative therapy also gave larger improvements in physical functioning ( difference 0.6 ; -0.1 to 1.3 ) . The global perceived effect after six and 12 months ' follow up was similar for both treatments . CONCLUSIONS --Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment . Furthermore , manipulative therapy is slightly better than physiotherapy after 12 months", "Background In a previous Swedish study it was shown that it is possible to predict which chiropractic patients with persistent LBP will not report definite improvement early in the course of treatment , namely those with LBP for altogether at least 30 days in the past year , who had leg pain , and who did not report definite general improvement by the second treatment . The objectives of this study were to investigate if the predictive value of this set of variables could be reproduced among chiropractic patients in Finl and , and if the model could be improved by adding some new potential predictor variables . Methods The study was a multi-centre prospect i ve outcome study with internal control groups , carried out in private chiropractic practice s in Finl and . Chiropractors collected data at the 1st , 2nd and 4th visits using st and ardized question naires on new patients with LBP and /or radiating leg pain . Status at base-line was identified in relation to pain and disability , at the 2nd visit in relation to disability , and \" definitely better \" at the 4th visit in relation to a global assessment . The Swedish question naire was used including three new questions on general health , pain in other parts of the spine , and body mass index . Results The Swedish model was reproduced in this study sample . An alternative model including leg pain ( yes/no ) , improvement at 2nd visit ( yes/no ) and BMI ( underweight/normal/overweight or obese ) was also identified with similar predictive values . Common throughout the testing of various models was that improvement at the 2nd visit had an odds ratio of approximately 5 . Additional analyses revealed a dose-response in that 84 % of those patients who fulfilled none of these ( bad ) criteria were classified as \" definitely better \" at the 4th visit , vs. 75 % , 60 % and 34 % of those who fulfilled 1 , 2 or all 3 of the criteria , respectively . Conclusion When treating patients with LBP , at the first visits , the treatment strategy should be different for overweight/obese patients with leg pain as it should be for all patients who fail to improve by the 2nd visit . The number of predictors is also important", "OBJECTIVES To identify characteristics of r and omized controlled trial participants which predict greater benefits from physical treatments for low back pain . If successful , this would allow more appropriate selection of patients for different treatments . METHODS We did a secondary analysis of the UK Back pain Exercise And Manipulation trial ( UK BEAM n = 1334 ) data set to identify baseline characteristics predicting response to manipulation , exercise and manipulation followed by exercise ( combined treatment ) . Rather than simply identifying factors associated with overall outcome , we tested for the statistical significance of the interaction between treatment allocation , baseline characteristics and outcome to identify factors that predicted response to treatment . We also did a post-hoc subgroup analysis to present separate results for trial participants with subacute and chronic low back pain to inform future evidence synthesis . RESULTS Age , work status , age of leaving school , ' pain and disability ' , ' quality of life ' and ' beliefs ' at baseline all predicted overall outcome . None of these predicted response to treatment . In those allocated to combined treatment , there was a suggestion that expecting treatment to be helpful might improve outcome at 1 yr . Episode length at study entry did not predict response to treatment . CONCLUSION Baseline participant characteristics did not predict response to the UK BEAM treatment packages . Using recognized prognostic variables to select patients for different treatment packages , without first demonstrating that these factors affect response to treatment , may be inappropriate . In particular , this analysis suggests that the distinction between subacute and chronic low back pain may not be useful when considering treatment choices", "Study Design . R and omized , single blind , controlled trial . Objective . To determine the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back disorder . Summary of Background Data . Musculoskeletal physiotherapy encompasses many treatment methods , however , manual therapy and exercises to rehabilitate spinal stabilization are the most frequently used . Despite their popularity , scant evidence supports their use on subjects with chronic low back disorder . Methods . A total of 346 subjects were r and omized to manual therapy , a 10-week spinal stabilization rehabilitation program , or a minimal intervention control group . Data were collected at baseline , and 3 , 6 , 12 , and 24 months after intervention . Outcome measures recorded intensity of low back pain , disability , h and icap , medication , and quality of life . There were 4 main variables combined in a primary component analysis to form a single outcome measure ( i.e. , a measure of dysfunction ) . Results . The results indicated statistically significant improvements in favor of the spinal stabilization group at the 6-month stage in pain ( 65.9 % reduction in symptoms ) and dysfunction ( combined mean reduction of 134 , st and ard error 23.84 ) , and at the 1-year stage in medication ( 34.3 % reduction in medication ) , dysfunction ( combined mean reduction of 134 , st and ard error 18.2 ) , and disability ( mean difference in change 15.71 Oswestry Disability Index , 95 % confidence interval 19.3–10.01 ) . Conclusions . As a component of musculoskeletal physiotherapy , the spinal stabilization program is more effective than manually applied therapy or an education booklet in treating chronic low back disorder over time . Both manual therapy and the spinal stabilization program are significantly effective in pain reduction in comparison to an active control . To our knowledge and up until now , this result has not been shown in patients with chronic low back disorder", "OBJECTIVE To examine the effects of 2 manual therapy methods compared with one counselling session with a physiotherapist with \" advice-only to stay active \" for treating low back pain/leg pain and disability . DESIGN A r and omized , controlled trial with a 1-year follow-up . SUBJECTS A total of 134 subjects with low back disorders . METHODS Participants with acute to chronic first or recurrent low back pain , excluding those with \" red flag \" criteria , were assigned r and omly to one of the 3 intervention groups : an orthopaedic manual therapy group ( n=45 ) , a McKenzie method group ( n=52 ) , and an \" advice only to be active \" group ( advice-only ) ( n=37 ) . Data on leg and low back pain intensity and disability ( Rol and -Morris Disability question naire ) were collected at baseline , and at 3- , 6- , and 12-month follow-up points . RESULTS At the 3-month follow-up point , significant improvements had occurred in all groups in leg and low back pain and in the disability index , but with no significant differences between the groups . At the 6-month follow-up , leg pain ( -15 mm ; 95 % confidence interval ( CI ) -30 to -1 ) , back pain ( effect : -15 mm ; -27 to -4 ) , and disability index ( -4 points ; -7 to -1 ) improved ( p < 0.05 ) more in the McKenzie method group than in the advice-only group . At the 1-year follow-up , the McKenzie method group had ( p=0.028 ) a better disability index ( -3 points ; -6 to 0 ) than did the advice-only group . In the orthopaedic manual therapy group at the 6-month and 1-year follow-up visits , improvements in the pain and disability index were somewhat better than in the advice-only group ( p=0.067 and 0.068 , respectively ) . No differences emerged between the orthopaedic manual therapy and McKenzie method groups in pain- and disability-score changes at any follow-up . CONCLUSION The orthopaedic manual therapy and McKenzie methods seemed to be only marginally more effective than was one session of assessment and advice-only", "Ninety-four patients with non-specific lumbar pain referred to hospital rheumatology and orthopaedic clinics participated in a double-blind controlled trial comparing mobilisation and manipulation with placebo physiotherapy . Results were assessed immediately after the tratment course , two months later , and at one year . Many patients showed improvement , but in contrast to a study on general-practitioner patients with nonspecific back pain no definite advantage could be associated with mobilisation and manipulation . The benefits of mobilisation and manipulation for low back pain are probably restricted to hastening recovery in patients likely rapidly to improve spontaneously . Hence patients whose severity and duration of symptoms warrant specialist referral are less likely to benefit from the technique", "OBJECTIVE To determine whether traditional bone- setting or continuous light exercise therapy could case back pain and improve function better than ordinary physiotherapy . DESIGN Observer-blinded , r and omized clinical trial with a 6-month follow-up . SETTING An outpatient institution for folk medicine research . PATIENTS Of 147 back pain patients recruited from local health centers and by newspaper announcements , 132 were found eligible ( non-retired-no contraindications to manipulation ) and entered . A final 114 ( one dropout ) with back pain for longer than 7 weeks were included in this intent to treat analysis . INTERVENTIONS Bone- setting , guidance for continuous light back movements or physiotherapy for up to ten 1-hour sessions during 6 weeks . MAIN OUTCOME MEASURES Spinal mobility and muscular performance . Back pain assessed by visual analog scales ( VAS ) . RESULTS The physical measures changed only modestly , from one tenth to half of st and ard deviation , while the VAS was halved . The thoracolumbar side-bending , the modified Schober , and the VAS were significantly better improved by bone- setting than by exercise but not better than by physiotherapy . CONCLUSION Neither bone- setting nor exercise differed significantly from physiotherapy , but bone- setting improved lateral and forward bending of the spine and back pain more than did exercise", "The major objective of this investigation was to study the effectiveness of the physical conditioning program used at the University of Miami Comprehensive Pain and Rehabilitation Center in restoring certain elements of the functional abilities of individuals suffering from chronic low-back pain and to evaluate the effectiveness of using a systematic ally applied , aggressive stretching maneuver as an add-on therapy in the treatment of chronic low-back pain patients . The effect(s ) of the proposed stretching maneuver was evaluated . Twenty-eight chronic low-back pain patients were r and omly assigned to one of two groups . The control group underwent a multimodal rehabilitation program , and the experimental group underwent the same rehabilitation program in addition to the systematic stretching maneuver under investigation . The results obtained showed that patients undergoing the multimodal rehabilitation program with and without the proposed systematic stretching maneuver showed a significant improvement in their functional abilities as seen from the significant increase in the static strength of the back extensors , with corresponding significant increase in back muscle myoelectric signals . Also , a significant decrease in their pain level was reported after 2 weeks of continuous treatment . The use of the systematic stretching maneuver enhanced the functional gains of chronic low-back pain patients compared to the control group", "Objective : We sought to compare total outpatient costs of 4 common treatments for low-back pain ( LBP ) at 18-months follow-up . Methods : Our work reports on findings from a r and omized controlled trial within a large medical group practice treating HMO patients . Patients ( n = 681 ) were assigned to 1 of 4 treatment groups , ie , medical care only ( MD ) , medical care with physical therapy ( MDPt ) , chiropractic care only ( DC ) , or chiropractic care with physical modalities ( DCPm ) . Total outpatient costs , excluding pharmaceuticals , were measured at 18 months . We did not perform a cost-effectiveness analysis because previously published findings showed no clinical ly meaningful difference in outcomes among the 4 treatment groups . Thirty-seven participants were lost to follow-up at 18 months , leaving a final sample size of n = 654 . Results : Adjusting for covariates , DC was 51.9 % more expensive than MD ( P < 0.001 ) , DCPm 3.2 % more expensive than DC ( P = 0.76 ) , and MDPt 105.8 % more expensive than MD ( P < 0.001 ) . The adjusted mean outpatient costs per treatment group were $ 369 for MD , $ 560 for DC , $ 579 for DCPm , and $ 760 for MDPt . Conclusions : This study is the first r and omized trial to show higher costs for chiropractic care without producing better clinical outcomes , but our findings are likely to understate the costs of medical care with or without physical therapy because of the absence of pharmaceutical data . Physical therapy provided in combination with medical care and physical modalities provided in combination with chiropractic care do not appear to be cost-effective strategies for treatment of LBP ; they produce higher costs without clinical ly significant improvements in outcome", "Background Clinical guidelines for the management of back pain frequently recommend ' manual therapy ' as a first line intervention , with psychosocial screening and ' active rehabilitation ' for those not improving at 6 weeks post onset . The potential for psychosocial factors to predict treatment response and therefore outcome has not been adequately explored . The purpose of this pilot study was to determine the feasibility of a study to compare manual therapy and active rehabilitation outcomes for subjects with sub-acute/chronic back pain , investigate whether any difference in outcome was related to psychosocial factors , and to inform the design of a main study . Methods A convenience sample of 39 patients with non-specific low back pain referred to the physiotherapy department of an acute NHS Trust hospital was recruited over a nine month period . Patients completed the Linton and Hallden psychological screening question naire ( LH ) and were allocated to a low LH ( 105 or below ) or high LH ( 106 or above ) scoring group . The low or high LH score was used to sequentially allocate patients to one of two treatment groups – Manual Therapy comprising physiotherapy based on manual means as chosen by the treating therapist or Active Rehabilitation comprising a progressive exercise and education programme – with the first low LH scoring patient being allocated to active rehabilitation and the next to manual therapy and so on . Treatment was administered for eight sessions over a four-week period and outcome measures were taken at baseline and at four weeks . Measures used were the Rol and Morris Question naire ( RMQ ) , two components of the Short Form McGill ( total pain rating index [ PRI ] and pain intensity via visual analogue scale [ VAS ] ) , and the LH . Results The manual therapy group demonstrated a greater treatment effect compared with active rehabilitation for RMQ ( mean difference 3.6 , 95 % CI 1.1 – 6.2 , p = 0.006 ) and PRI ( 7.1 , 95 % CI 2.0 – 12.2 , p = 0.007 ) and marginally significant results for VAS ( 15 , 95 % CI -1.1 to 31.2 , p = 0.067 ) . A linear model allowing for confounding effects and the interaction between high or low LH scores supported these results . The interaction effect was not significant for any outcome measure but this could be due to an insufficient number of subjects to detect this effect . Conclusion Comparative evaluation of manual therapy and active rehabilitation with reference to LH psychosocial scores is likely to be detectable by the methods used here . However several alterations to the study design are recommended for the main study . A pragmatic trial using a r and omisation process with stratification on the LH score and priori power analysis to determine sample size are suggested for the main study", "Objectives To compare naprapathic manual therapy with evidence -based care for back or neck pain regarding pain , disability , and perceived recovery . Naprapathy that is common in the Nordic countries and in some states in the United States is characterized by manual manipulations with a focus on soft and connective tissues , aim ing to decrease pain and disability in the musculoskeletal system . Methods Four hundred and nine patients with pain and disability in the back or neck lasting for at least 2 weeks , recruited at 2 large public companies in Sweden in 2005 , were included in this r and omized controlled trial . The 2 interventions were naprapathy , including spinal manipulation/mobilization , massage , and stretching ( Index Group ) and support and advice to stay active and how to cope with pain , according to the best scientific evidence available , provided by a physician ( Control Group ) . Pain , disability , and perceived recovery were measured by question naires at baseline and after 3 , 7 , and 12 weeks . Results At 7-week and 12-week follow-ups , statistically significant differences between the groups were found in all outcomes favoring the Index Group . At 12-week follow-up , a higher proportion in the naprapathy group had improved regarding pain [ risk difference (RD)=27 % , 95 % confidence interval ( CI ) : 17 - 37 ] , disability ( RD=18 % , 95 % CI : 7 - 28 ) , and perceived recovery ( RD=44 % , 95 % CI : 35 - 53 ) . Separate analysis of neck pain and back pain patients showed similar results . Discussion This trial suggests that combined manual therapy , like naprapathy , might be an alternative to consider for back and neck pain patients", "OBJECTIVE To assess the long-term benefits of medication , needle acupuncture , and spinal manipulation as exclusive and st and ardized treatment regimens in patients with chronic ( > 13 weeks ) spinal pain syndromes . STUDY DESIGN Extended follow-up ( > 1 year ) of a r and omized clinical trial was conducted at the multidisciplinary spinal pain unit of Townsville 's General Hospital between February 1999 and October 2001 . PATIENTS AND METHODS Of the 115 patients originally r and omized , 69 had exclusively been treated with the r and omly allocated treatment during the 9-week treatment period ( results at 9 weeks were reported earlier ) . These patients were followed up and assessed again 1 year after inception into the study reapplying the same instruments ( ie , Oswestry Back Pain Index , Neck Disability Index , Short-Form-36 , and Visual Analogue Scales ) . Question naires were obtained from 62 patients reflecting a retention proportion of 90 % . The main analysis was restricted to 40 patients who had received exclusively the r and omly allocated treatment for the whole observation period since r and omization . RESULTS Comparisons of initial and extended follow-up question naires to assess absolute efficacy showed that only the application of spinal manipulation revealed broad-based long-term benefit : 5 of the 7 main outcome measures showed significant improvements compared with only 1 item in each of the acupuncture and the medication groups . CONCLUSIONS In patients with chronic spinal pain syndromes , spinal manipulation , if not contraindicated , may be the only treatment modality of the assessed regimens that provides broad and significant long-term benefit", "Background Previous clinical trials have assessed the percentage of participants who utilized further health care after a period of conservative care for low back pain , however no chiropractic clinical trial has determined the total amount of care during this time and any differences based on assigned treatment group . The objective of this clinical trial follow-up was to assess if there was a difference in the total number of office visits for low back pain over one year after a four week clinical trial of either a form of physical therapy ( Exercise Program ) or a form of chiropractic care ( Flexion Distraction ) for chronic low back pain . Methods In this r and omized clinical trial follow up study , 195 participants were followed for one year after a four-week period of either a form of chiropractic care ( FD ) or a form of physical therapy ( EP ) . Weekly structured telephone interview questions regarded visitation of various health care practitioners and the practice of self-care for low back pain . Results Participants in the physical therapy group demonstrated on average significantly more visits to any health care provider and to a general practitioner during the year after trial care ( p < 0.05 ) . No group differences were noted in the number of visits to a chiropractor or physical therapist . Self-care was initiated by nearly every participant in both groups . Conclusion During a one-year follow-up , participants previously r and omized to physical therapy attended significantly more health care visits than those participants who received chiropractic care", "OBJECTIVE --To compare chiropractic and hospital outpatient treatment for managing low back pain of mechanical origin . DESIGN --R and omised controlled trial . Allocation to chiropractic or hospital management by minimisation to establish groups for analysis of results according to initial referral clinic , length of current episode , history , and severity of back pain . Patients were followed up for up two years . SETTING --Chiropractic and hospital outpatient clinics in 11 centres . PATIENTS --741 Patients aged 18 - 65 who had no contraindications to manipulation and who had not been treated within the past month . INTERVENTIONS --Treatment at the discretion of the chiropractors , who used chiropractic manipulation in most patients , or of the hospital staff , who most commonly used Maitl and mobilisation or manipulation , or both . MAIN OUTCOME MEASURES --Changes in the score on the Oswestry pain disability question naire and in the results of tests of straight leg raising and lumbar flexion . RESULTS --Chiropractic treatment was more effective than hospital outpatient management , mainly for patients with chronic or severe back pain . A benefit of about 7 % points on the Oswestry scale was seen at two years . The benefit of chiropractic treatment became more evident throughout the follow up period . Secondary outcome measures also showed that chiropractic was more beneficial . CONCLUSIONS --For patients with low back pain in whom manipulation is not contraindicated chiropractic almost certainly confers worthwhile , long term benefit in comparison with hospital outpatient management . The benefit is seen mainly in those with chronic or severe pain . Introducing chiropractic into NHS practice should be considered", "BACKGROUND CONTEXT Although many research ers and practitioners believe that patients ' positive expectations of their treatment favorably influence clinical outcomes , there is little scientific evidence to support this belief . PURPOSE To describe the level of patients ' initial confidence in the success of their assigned treatment , by treatment group and other factors ; and to estimate the effects of treatment confidence on subsequent changes in low-back pain and related disability . STUDY DESIGN AND PATIENT SAMPLE : R and omized clinical trial involving 681 patients treated for low-back pain in a managed-care facility in Southern California . OUTCOME MEASURES Treatment confidence ; and changes in three clinical measures of low-back pain : average pain , most severe pain and back-pain-related disability . METHODS Patients were r and omly assigned to one of four treatment groups : medical care with and without physical therapy , and chiropractic care with and without physical modalities . Information was collected by question naires at baseline , 2 weeks , 6 weeks and 6 months . Treatment confidence was measured just after r and omization on a scale of 0 to 10 . RESULTS Treatment confidence was lowest , on average , for patients assigned to medical care only and highest for patients assigned to medical care plus physical therapy . Other predictors of high treatment confidence were having acute pain and being older , female and nonwhite . Although treatment confidence was only weakly associated with subsequent changes in low-back pain or disability in the total sample , high treatment confidence was associated with greater improvement among patients assigned to medical care plus physical therapy . CONCLUSIONS Initial confidence in treatment for low-back pain varies by type of care and other factors . Higher confidence may have some beneficial effect on the course of low-back pain in certain patients , but this effect may depend on the type of interaction between client and provider", "Study Design . Observational study conducted within a r and omized clinical trial . Objectives . The objective of this study is to estimate the effects of patient satisfaction on subsequent changes in pain and disability among low back pain patients r and omized to chiropractic or medical care in a managed-care practice setting . Summary of Background Data . Recent studies of low back pain treatments have shown chiropractic patients to be more satisfied with their care than medical patients . However , little is known about the relation between patient satisfaction and clinical outcomes . Methods . A total of 681 low back pain patients presenting to three southern California healthcare clinics and screened for serious spinal pathology and contraindications were r and omized to medical care with and without physical therapy , and chiropractic care with and without physical modalities , and followed for 18 months . Satisfaction with back care was measured on a 40-point scale and observed at 4 weeks following r and omization . The primary outcome variables , observed between 6 weeks and 18 months of follow-up , are average and most severe low back pain intensity in the past week , assessed with 0 to 10 numerical rating scales , low back-related disability , assessed with the 24-item Rol and -Morris Disability Question naire , and remission from clinical ly meaningful pain and disability . Perceived change in low back symptoms was a secondary outcome . Results . Greater satisfaction increased the odds of remission from clinical ly meaningful pain and disability at 6 weeks ( adjusted odds ratio [ OR ] for 10-point increase in satisfaction = 1.61 , 95 % confidence interval [ CI ] = 0.99 , 2.68 ) , but not at 6 , 12 , or 18 months ( 6 months : adjusted OR = 1.05 , 95 % CI = 0.73 , 1.52 ; 12 months : adjusted OR = 0.94 , 95 % CI = 0.67 , 1.32 ; 18 months : adjusted OR = 1.07 ; 95 % CI = 0.76 , 1.50 ) . Perception of improvement was greater among highly satisfied than less satisfied patients throughout the 18-month follow-up period . The estimated effects of satisfaction on clinical outcomes were similar for medical and chiropractic patients . Conclusions . Patient satisfaction may confer small short-term clinical benefits for low back pain patients . Long-term perceived improvement may reflect , in part , perceived past improvement as measured by satisfaction", "Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated . The largest group studied had low back pain with limited straight-leg raising ( SLR ) and in them the beneficial effect of manipulation in hastening pain relief was highly significant . In similar patients without limitation of SLR , the effect was of borderline significance . In all the other groups , treated patients also recovered more quickly than their controls . Traction , for patients with low back pain and sciatica , and epidural injections when a root palsy was present also produced some significant pain relief . The effect of sclerosants for back pain was less clear", "OBJECTIVE The primary objectives of this study were to compare the effect of spinal manipulation vs. sham manipulation on a ) circulating plasma levels of the prostagl and in F2a metabolite , 15-keto-13,14-dihydroprostagl and in ( KDPGF2a ) , b ) perceived abdominal and back pain and c ) perceived menstrual distress in women with primary dysmenorrhea . DESIGN This r and omized clinical pilot study investigated the outcome measures before and after either a spinal manipulation treatment ( SMT ) or a sham manipulation . SETTING All subjects were treated at the National College Chiropractic clinic , a private chiropractic clinic in the suburban Chicago area . PARTICIPANTS Forty-five women with a history of primary dysmenorrhea were recruited from the local community . The volunteers ranged in age from 20 - 49 ( mean age = 30.3 yr ) , and were entered into the study between April 1990 and January 1991 . Twenty-four were r and omly assigned to the spinal manipulation group and 21 were assigned to the sham group . INTERVENTIONS Subjects treated with spinal manipulation were placed in a side-lying position with the bottom leg straight and the top leg flexed at the knee and hip . They received a high-velocity , short lever , low-amplitude thrust to all clinical ly relevant vertebral levels within T10 and L5-S1 and the sacroiliac joints . In the sham manipulation , subjects were placed in a side-lying position with both hips and knees flexed . Their manipulation consisted of a similar thrust administered to the midline base of the sacrum . OUTCOME MEASURES Perceived abdominal and back pain were measured with a visual analog scale , and menstrual distress was measured with the Menstrual Distress Question naire . Both were administered 15 min before and 60 min after treatment . Blood sample s were collected by venipuncture for the determination of plasma levels of KDPGF2a at the same times . The plasma was then assayed for KDPGF2a by radioimmunoassay . RESULTS Analysis of covariance and paired Student 's t tests were used for the statistical evaluation . Immediately after treatment , the perception of pain and the level of menstrual distress were significantly reduced by SMT . This reduction was associated with a significant reduction in plasma levels of KDGPF2a in the SMT group . A significant and similar reduction in plasma KDPGF2a also occurred in the sham group , indicating that a placebo effect was associated with a single sham intervention . CONCLUSIONS This r and omized pilot study suggests that SMT may be an effective and safe nonpharmacological alternative for relieving the pain and distress of primary dysmenorrhea . However , the large change in KDPGF2a observed in both treatment groups clearly indicates that further studies with more subjects , studied over a longer time frame , are needed to resolve the question of a placebo effect", "BACKGROUND CONTEXT There have been no trials of optimal chiropractic care in terms of number of office visits for spinal manipulation and other therapeutic modalities . PURPOSE To conduct a pilot study to make preliminary identification of the effects of number of chiropractic treatment visits for manipulation with and without physical modalities ( PM ) on chronic low back pain and disability . STUDY DESIGN / SETTING R and omized controlled trial with a balanced 4x2 factorial design . Conducted in the faculty practice of a chiropractic college outpatient clinic . PATIENT SAMPLE Seventy-two patients with chronic , nonspecific low back pain of mechanical origin . MAIN OUTCOME MEASURES Von Korff pain and disability ( 100-point ) scales . METHODS Patients were r and omly allocated to visits ( 1 , 2 , 3 or 4 visits/week for 3 weeks ) and to treatment regimen ( spinal manipulation only or spinal manipulation with PM ) . All patients received high-velocity low-amplitude spinal manipulation . Half received one or two of the following PM at each visit : soft tissue therapy , hot packs , electrotherapy or ultrasound . RESULTS Pain intensity : At 4 weeks , there was a substantial linear effect of visits favoring a larger number of visits : 5.7 points per 3 visits ( SE=2.3 , p=.014 ) . There was no effect of treatment regimen . At 12 weeks , the data suggested the potential for a similar effect of visits on patients receiving both manipulation and PM . Functional disability : At 4 weeks , a visits effect was noted ( p=.018 ) ; the slope for group means was approximately 5 points per 3 visits . There were no group differences at 12 weeks . CONCLUSIONS There was a positive , clinical ly important effect of the number of chiropractic treatments for chronic low back pain on pain intensity and disability at 4 weeks . Relief was substantial for patients receiving care 3 to 4 times per week for 3 weeks", "A study was conducted to compare the relative efficacy of conventional ( heat , pelvic tilt exercises , postural education and lifting instructions ) and manipulation therapy in back pain management . Twenty-five females were in the conventional therapy group ( CTG ) and 26 females in the manipulation therapy group ( MTG ) . Range of motion of total flexion and extension , total side-flexion and total rotation of the lumbar spine and the straight-leg-raising test were used as criteria to determine efficacy of treatment . The results showed that while the mean treatment time for CTG subjects was 160 minutes ( SD = 7.9 ) that for MTG patients was 121.2 ( SD = 10.2 ) with a significant difference p less than 0.001 . There were significant differences between the two groups with regards to post-treatment differences in total flexion and extension p less than 0.01 ; total side flexion p less than 0.05 ; and total rotation p less than 0.05 in favour of the MTG subjects . There was also significant difference in post-treatment straight-leg-raising values between the two groups p less than 0.05 in favour of the MTG group . It was concluded that manipulation therapy as shown by this study was superior to the conventional method in the treatment of the type of patient described", "The effectiveness of spinal manipulation carried out by a non-medical qualified osteopath was compared with that of short-wave diathermy ( SWD ) and a placebo ( detuned SWD ) in 109 patients with low back pain . More than half the subjects in each of the 3 treatment groups benefited immediately from therapy . Significant improvements were observed in the 3 groups at the end of 2 weeks ' treatment , and these were still apparent at 12 weeks . The outcome of treatment was unrelated to the initial severity or duration of pain or to the trend of pain towards deterioration or improvement . It is , therefore , unlikely that the results simply reflect the natural history of low back pain . Benefits obtained with osteopathy and SWD in this study may have been achieved through a placebo effect", "A r and omized clinical trial of rotational manipulation was conducted on 95 patients with low back pain selected for ( 1 ) the absence of any contraindications for vertebral manipulation , ( 2 ) the absence of any psychosocial problems that might affect the outcome of treatment , ( 3 ) the absence of any previous experience with manipulative therapy , and ( 4 ) the presence of palpatory cues indicating that manipulation might be successful . Patients were r and omly assigned to one of two groups : an experimental group receiving manipulation therapy and a control group receiving soft-tissue massage . Comparison of the two groups indicated that ( 1 ) patients who received manipulative treatment were much more likely to report immediate relief after the first treatment , and ( 2 ) at discharge , there was no significant difference between the two groups because both showed substantial improvement", "Study Design . A cross-sectional survey using patient question naires was conducted . Objective . To assess whether the Rol and Disability Question naire satisfies the Rasch model including unidimensionality and item separation . Summary of Background Data . The Rol and Disability Question naire , the most widely used patient-assessed measure of health outcome for back pain , has undergone several evaluations for its measurement properties including reliability , validity , and responsiveness . However , there is no published work relating to the underlying dimensionality of the instrument and the extent to which individual items contribute to the construct of physical disability result ing from low back pain . Methods . Patients entering a r and omized controlled trial of exercise , manipulation , and usual management for back pain completed a question naire that included the Rol and Disability Question naire . The Winsteps program was used to assess whether the Rol and Disability Question naire fits the Rasch model . Item fit was assessed using the Infit and Outfit statistics . Results . The Rol and Disability Question naire was completed by 1008 ( 90 % ) of the patients taking part in the trial . Most of the items in the Rol and Disability Question naire contribute to a single underlying construct . However , four items had poor Outfit statistics , suggesting that they do not contribute sufficiently to the scale hierarchy . Several items positioned around the middle of the hierarchy are not sufficiently distinct in terms of difficulty . There were very few items positioned at the extremes of the hierarchy . Conclusions . The Rol and Disability Question naire largely satisfies the Rasch model for unidimensionality . However , the instrument could be improved through the removal of poorly fitting items and the addition of items at the upper and lower points of the scale hierarchy . The distribution of Rol and Disability Question naire scores should be carefully considered before statistical testing is undertaken . Rasch transformed scores can be used to deal with deficiencies in the scale hierarchy", "The results of a multicentered r and omised clinical trial are reported of bed rest and of a physiotherapy and education programme for patients who presented in family practice with an acute episode of low back pain . No beneficial effect of either treatment was observed on several clinical outcome measures , including straight leg raising , lumbar flexion , activities of daily living , and pain . In fact the results favoured early mobilisation over bed rest and suggested that the physiotherapy and education programme was doing more harm than good . Moreover , additional analyses , which focused on clinical ly interesting patient subgroups , discovered no subset of patients who benefited from either of the treatments under study . Having failed to identify any clinical ly important benefits , or other explanations for these negative results , we can only conclude that family doctors have little reason to prescribe either bed rest or isometric exercises to patients who suffer from low back pain", "OBJECTIVE To investigate the effect of instrument-delivered compared with traditional manual-delivered thrust chiropractic adjustments in the treatment of sacroiliac joint syndrome . METHODS Prospect i ve , r and omized , comparative clinical trial . Sixty patients with sacroiliac syndrome were r and omized into two groups of 30 subjects . Each subject received 4 chiropractic adjustments over a 2-week period and was evaluated at 1-week follow-up . One group received side-posture , high-velocity , low-amplitude chiropractic adjustments ; the other group received mechanical-force , manually-assisted chiropractic adjustments using an Activator Adjusting Instrument ( Activator Methods International , Ltd , Phoenix , Ariz ) . RESULTS No significant differences between groups were noted at the initial consultation for any of the outcome variables . Statistically significant improvements were observed in both groups from the first to third , third to fifth , and first to fifth consultations for improvements ( P < .001 ) in mean numerical pain rating scale 101 ( group 1 , 49.1 - 23.4 ; group 2 , 48.9 - 22.5 ) , revised Oswestry Low Back Pain Disability Question naire ( group 1 , 37.4 - 18.5 ; group 2 , 36.6 - 15.1 ) , orthopedic rating score ( group 1 , 7.6 - 0.6 ; group 2 , 7.5 - 0.8 ) , and algometry measures ( group 1 , 4.8 - 6.5 ; group 2 , 5.0 - 6.8 ) for first to last visit for both groups . CONCLUSIONS The results indicate that a short regimen of either mechanical-force , manually-assisted or high-velocity , low-amplitude chiropractic adjustments were associated with a beneficial effect of a reduction in pain and disability in patients diagnosed with sacroiliac joint syndrome . Neither mechanical-force , manually-assisted nor high-velocity , low-amplitude adjustments were found to be more effective than the other in the treatment of this patient population", "OBJECTIVES To study the relative efficacy of three different treatment for chronic low back pain ( CLBP ) . Two preplanned comparisons were made : ( a ) Spinal manipulative therapy ( SMT ) combined with trunk strengthening exercises ( TSE ) vs. SMT combined with trunk stretching exercises , and ( b ) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug ( NSAID ) therapy combined with TSE . STUDY DESIGN Interdisciplinary , prospect i ve , observer-blinded , r and omized clinical trial with a 1-yr follow-up period . The trial evaluated therapies in combination only and was not design ed to test the individual treatment components . SETTING Primary contact , college out-patient clinic . PATIENTS In total , 174 patients aged 20 - 60 yr were admitted to the study . MAIN OUTCOME MEASURES Patient-rated low back pain , disability , and functional health status at 5 and 11 wk . INTERVENTIONS Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise , followed by and additional 6 wk of supervised exercise alone . RESULTS Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinical ly important or statistically significant differences . There seemed to be a sustained reduction in medication use at the 1-yr follow-up . in the SMT/TSE group . Continuance of exercise during the follow-up year , regardless of type , was associated with a better outcome . CONCLUSION Each of the three therapeutic regimens was associated with similar and clinical ly important improvement over time that was considered superior to the expected natural history of long-st and ing CLBP . For the management of CLBP , trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile . The magnitude of nonspecific therapeutic ( placebo ) effects , cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies", "OBJECTIVES To explore the views of participants in a r and omized controlled trial of physical treatments for low back pain about the treatment packages they received in the trial . METHODS Within a r and omized controlled trial that found small to moderate benefits from adding a manipulation package or an exercise programme to general practice care , we elicited participants ' views on the treatment using an open question in participant question naires . These data were analysed using an adapted framework approach . RESULTS We received a total of 1259 comments from 1334 participants . Participants r and omized to usual general practice care reported dissatisfaction with receiving only ' usual care ' , which consisted of providing analgesic medication without providing an explanation for their pain . Those r and omized to a manipulation package felt the intervention was appropriate to their needs and commonly reported striking benefits . Participants assigned to the exercise programme developed a sense of self-reliance in managing back pain , although some failed to be sufficiently motivated to continue their exercise regimen outside the classes . CONCLUSIONS This qualitative analysis has found much clearer differences between the groups than the main quantitative analysis . This suggests that some of the added value from being allocated to additional physical treatment for low back pain is not being captured by existing methods of measurement . Improved methods of assessment that consider a wider range of domains may be needed when interpreting the added value of such treatments to individual patients", "Many clinical trials on chiropractic management of low back pain have neglected to include specific forms of care . This study compared two well-defined treatment protocol s. The objective was to compare the outcome of flexion – distraction ( FD ) procedures performed by chiropractors with an active trunk exercise protocol ( ATEP ) performed by physical therapists . A r and omized clinical trial study design was used . Subjects , 18 years of age and older , with a primary complaint of low back pain ( > 3 months ) were recruited . A 100 mm visual analogue scale ( VAS ) for perceived pain , the Rol and Morris ( RM ) Question naire for low back function , and the SF-36 for overall health status served as primary outcome measures . Subjects were r and omly allocated to receive either FD or ATEP . The FD intervention consisted of the application of flexion and traction applied to specific regions in the low back , with the aid of a specially design ed manipulation table . The ATEP intervention included stabilizing and flexibility exercises , the use of modalities , and cardiovascular training . A total of 235 subjects met the inclusion /exclusion criteria and signed the informed consent . Of these , 123 were r and omly allocated to FD and 112 to the ATEP . Study patients perceived significantly less pain and better function after intervention , regardless of which group they were allocated to ( P<0.01 ) . Subjects r and omly allocated to the flexion – distraction group had significantly greater relief from pain than those allocated to the exercise program ( P=0.01 ) . Subgroup analysis indicated that subjects categorized as chronic , with moderate to severe symptoms , improved most with the flexion – distraction protocol . Subjects categorized with recurrent pain and moderate to severe symptoms improved most with the exercise program . Patients with radiculopathy did significantly better with FD . There were no significant differences between groups on the Rol and Morris and SF-36 outcome measures . Overall , flexion – distraction provided more pain relief than active exercise ; however , these results varied based on stratification of patients with and without radiculopathy and with and without recurrent symptoms . The subgroup analysis provides a possible explanation for contrasting results among r and omized clinical trials of chronic low back pain treatments and these results also provide guidance for future work in the treatment of chronic low back pain", "In a multicentre trial 456 selected patients with low back pain were r and omly allocated to one of four treatments-manipulation , definitive physiotherapy , corset , or analgesic tablets . Patients were reassessed clinical ly after three weeks ' treatment and again after a further three weeks . Question naires were used to find out the patients ' condition three months and one year after admission to the trial . There were never any important differences among the four groups of patients . A few patients responded well and quickly to manipulation , but there was no way of identifying such patients in advance . The response to a corset was slow , but the long-tern effects were at least as good as those of the other treatments . Patients treated only with analgesics fared marginally worse than those on the other three treatments . There is no strong reason , however , for recommending manipulation over physiotherapy or corset", "Study Design . R and omized clinical trial . Objective . Compare outcomes of patients with low back pain receiving treatments matched or unmatched to their subgrouping based on initial clinical presentation . Summary of Background Data . Patients with “ nonspecific ” low back pain are often viewed as a homogeneous group , equally likely to respond to any particular intervention . Others have proposed methods for subgrouping patients as a means for determining the treatment most likely to benefit patients with particular characteristics . Methods . Patients with low back pain of less than 90 days ’ duration referred to physical therapy were examined before treatment and classified into one of three subgroups based on the type of treatment believed most likely to benefit the patient ( manipulation , stabilization exercise , or specific exercise ) . Patients were r and omly assigned to receive manipulation , stabilization exercises , or specific exercise treatment during a 4-week treatment period . Disability was assessed in the short-term ( 4 weeks ) and long-term ( 1 year ) using the Oswestry . Comparisons were made between patients receiving treatment matched to their subgroup , versus those receiving unmatched treatment . Results . A total of 123 patients participated ( mean age , 37.7 ± 10.7 years ; 45 % female ) . Patients receiving matched treatments experienced greater short- and long-term reductions in disability than those receiving unmatched treatments . After 4 weeks , the difference favoring the matched treatment group was 6.6 Oswestry points ( 95 % CI , 0.70–12.5 ) , and at long-term follow-up the difference was 8.3 points ( 95 % CI , 2.5–14.1 ) . Compliers-only analysis of long-term outcomes yielded a similar result . Conclusions . Nonspecific low back pain should not be viewed as a homogenous condition . Outcomes can be improved when subgrouping is used to guide treatment decision-making", "OBJECTIVE The aim of the study was to identify differences in the diagnosis and treatment of nonspecific low back pain among 3 professional groups in the Netherl and s : orthomanual physicians , manual therapists , and chiropractors . METHODS Information was obtained from training material s from professional groups , literature search es , and observation of selected practitioners at work . RESULTS In The Netherl and s , there are differences in education between the 3 professional groups . The focus of orthomanual medicine is on abnormal positions of components of the skeleton and symmetry in the spine . Manual therapy focuses on functional disorders of the musculoskeletal system . Chiropractic focuses on the musculoskeletal and nervous systems in relation to patients ' health in general . Orthomanual medicine considers inspection and palpation the most important diagnostic tools . Manual therapists and chiropractors additionally perform tests to determine functional disorders and manual therapists evaluate psychosocial influences . Chiropractors take radiographs if necessary . Orthomanual physicians apply mobilization techniques using fixed protocol s. Manual therapists and chiropractors use various manipulation and mobilization techniques and their manipulation techniques differ in amplitude and velocity . CONCLUSIONS Diagnostic techniques and treatment methods of the 3 professional groups differ considerably . For more accurate reporting of the efficacy of manipulative and mobilizing therapies , the characteristics of treatments should be described in more detail when reported in studies such as r and omized clinical trials", "Study Design A r and omized trial was conducted on a representative sample of patients with untreated low back pain lasting 7 weeks or longer , or having more than 6 episodes in 12 months . Objectives To contrast the effectiveness of manipulation , a manipulation mimic , and a back education program . Method ologic criticisms of earlier studies were addressed . Summary of Background Data Published meta-anal-yses suggest clinical benefit from manipulation for acute patients . Data are inconclusive for patients having symptoms for longer than 1 month . Methods A total of 1267 consecutive patients were screened . Block r and omization was used to assign 209 qualifying patients to treatment groups . Self-reported pain and activity tolerance served as primary outcome measures . Patients were assessed at enrollment , after 2 weeks of treatment , and again after 2 weeks without treatment . Multiple teams conducted recruitment , r and omization , assessment , treatment , and data analysis independently without sharing information . Treatments were carefully described , monitored , and balanced for physician attention and physical contact effects . Results A total of 81.3 % of subjects completed the study . Confounding factors and missing data were identified in approximately 20 % of those completing the final follow-up . Analysis of the remaining data was carried out . A strong time effect under treatment was observed . Greater improvement was noted in pain and activity tolerance in the manipulation group . Immediate benefit from pain relief continued to accrue after manipulation , even for the last encounter at the end of the 2-week treatment interval . Conclusion Time is a strong ally of the low back pain patient . In human terms , however , there appears to be clinical value to treatment according to a defined plan using manipulation even in low back pain exceeding 7 weeks ' duration", "OBJECTIVE To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints . The second objective was to determine the correlation between three important outcome measures used in this trial . DESIGN R and omized clinical trial ( subgroup analysis ) . SETTING Primary health care in the Netherl and s. PATIENTS Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr . INTERVENTIONS At the discretion of the manual therapists , physiotherapists and general practitioners . Physiotherapy consisted of exercises , massage and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manual therapy consisted of manipulation and mobilization of the spine . Treatment by the general practitioner consisted of drugs ( e.g. , analgesics ) , advice about posture , home exercises and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 min ) and detuned ultrasound ( 10 min ) . MAIN OUTCOME MEASURES Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients . RESULTS Improvement in the main complaint was larger with manual therapy ( 4.3 ) than with physiotherapy ( 2.5 ) for patients with chronic conditions ( duration complaint of 1 yr or longer ) . Also , improvement in the main complaint was larger with manual therapy ( 5.5 ) than with physiotherapy ( 4.0 ) for patients younger than 40 yr ( both were measured after 12-mo follow-up ) . Labeling of patients by the treating manual therapists as \" suitable \" or \" not suitable \" for treatment with manual therapy did not predict differences in outcomes . Generally , there was a moderate to strong correlation between the three outcome measures , although a considerable number of patients gave a relatively low score for perceived benefit , while the research assistant gave a high improvement score for the main complaint and physical functioning . CONCLUSIONS The subgroup analysis suggests better results of manual therapy compared to physiotherapy in chronic patients ( duration of present complaints of 1 yr or longer ) and in patients younger than 40 yr old ) . Differences for other subgroups were less clear . The explorative findings of these subgroup analyses have to be investigated in future research", "In a r and omized trial , the effectiveness of manual therapy , physiotherapy , continued treatment by the general practitioner , and placebo therapy ( detuned ultrasound and detuned short-wave diathermy ) were compared for patients ( n = 256 ) with nonspecific back and neck complaints lasting for at least 6 weeks . The principle outcome measures were severity of the main complaint , global perceived effect , pain , and functional status . These are presented for 3 , 6 , and 12 weeks follow-up . Both physiotherapy and manual therapy decreased the severity of complaints more and had a higher global perceived effect compared to continued treatment by the general practitioner . Differences in effectiveness between physiotherapy and manual therapy could not be shown . A substantial part of the effect of manual therapy and physiotherapy appeared to be due to nonspecific ( placebo ) effects", "OBJECTIVE This study compared the dynamic surface electromyographic ( EMG ) activities of back muscles and pain before and after traditional bone setting and physical therapy . METHODS This study was a prospect i ve clinical trial that compared surface EMG dynamic activities after traditional bone setting and physical therapy . Sixty-one patients ( mean age , 41 years ) with nonspecific low back pain were r and omized into two subgroups by treatment . The patients underwent a dynamic EMG evaluation for which they were asked to st and and then bend forward as far as possible , stay fully flexed , and return to st and ing . A flexion-relaxation ratio was calculated by comparing maximal EMG activity while flexing with the average EMG activity in full flexion . Concentric ( maximal EMG activity during extension ) and eccentric ( maximal EMG activity during flexion ) ratios were also used in the analyses . RESULTS Disability , depression , and visual analog scale scores decreased significantly after both treatments . The concentric ratio increased statistically in both groups after the treatments . The study failed to show a significant association between experienced back pain and EMG parameters . CONCLUSIONS Both treatments seem to have a positive influence on back muscle function by improving muscle symmetry ; however , the treatments had no effect on the flexion-relaxation phenomenon after 1 month . Active back exercise at home together with rehabilitation treatments might be effective and improve function for patients with chronic low back pain", "OBJECTIVE Flexion distraction is a commonly used form of chiropractic care with chiropractor utilization rates of 58 % . However , no previous r and omized clinical trial has assessed the effectiveness of this form of care . The objective of this investigation was to compare the pain and disability during the year after active care based on treatment group allocation ( Flexion Distraction versus Exercise Program ) . STUDY DESIGN R and omized clinical trial , follow-up . SUBJECTS Two hundred and thirty-five ( 235 ) subjects who were previously r and omized to either chiropractic care ( flexion distraction ) or physical therapy ( exercise program ) within a clinical trial . OUTCOME MEASURES Subjects were followed for 1 year via mailed question naires to assess levels of pain ( Visual Analog Scale ) and dysfunction ( Rol and Morris ) . RESULTS Study subjects had a decrease in pain and disability after intervention regardless of which group they attended ( p < 0.002 ) , however , during the year after care , subjects who received chiropractic care ( flexion distraction therapy ) had significantly lower pain scores than subjects who received physical therapy ( exercise program ) ( p = 0.02 ) . CONCLUSIONS In this first trial on flexion distraction care , flexion distraction was found to be more effective in reducing pain for 1 year when compared to a form of physical therapy", "BACKGROUND The effect of osteopathic manual therapy ( i.e. , spinal manipulation ) in patients with chronic and subchronic back pain is largely unknown , and its use in such patients is controversial . Nevertheless , manual therapy is a frequently used method of treatment in this group of patients . METHODS We performed a r and omized , controlled trial that involved patients who had had back pain for at least three weeks but less than six months . We screened 1193 patients ; 178 were found to be eligible and were r and omly assigned to treatment groups ; 23 of these patients subsequently dropped out of the study . The patients were treated either with one or more st and ard medical therapies ( 72 patients ) or with osteopathic manual therapy ( 83 patients ) . We used a variety of outcome measures , including scores on the Rol and -Morris and Oswestry question naires , a visual-analogue pain scale , and measurements of range of motion and straight-leg raising , to assess the results of treatment over a 12-week period . RESULTS Patients in both groups improved during the 12 weeks . There was no statistically significant difference between the two groups in any of the primary outcome measures . The osteopathic-treatment group required significantly less medication ( analgesics , antiinflammatory agents , and muscle relaxants ) ( P < 0.001 ) and used less physical therapy ( 0.2 percent vs. 2.6 percent , P<0.05 ) . More than 90 percent of the patients in both groups were satisfied with their care . CONCLUSIONS Osteopathic manual care and st and ard medical care had similar clinical results in patients with subacute low back pain . However , the use of medication was greater with st and ard care", "OBJECTIVE Chiropractic care is used by many older patients for low back pain ( LBP ) , but there are no published results of r and omized trials examining spinal manipulation ( SM ) for older adults . The purpose of this study was to compare the effects of 2 biomechanically distinct forms of SM and minimal conservative medical care ( MCMC ) for participants at least 55 years old with subacute or chronic nonradicular LBP . METHODS R and omized controlled trial . The primary outcome variable was low back-related disability assessed with the 24-item Rol and Morris Disability question naire at 3 , 6 , 12 , and 24 weeks . Participants were r and omly allocated to 6 weeks of care including 12 visits of either high-velocity , low-amplitude (HVLA)-SM , low-velocity , variable-amplitude (LVVA)-SM , or 3 visits of MCMC . RESULTS Two hundred forty participants ( 105 women and 135 men ) ages 63.1 + /- 6.7 years without significant comorbidities . Adjusted mean Rol and Morris Disability change scores ( 95 % confidence intervals ) from baseline to the end of active care were 2.9 ( 2.2 , 3.6 ) and 2.7 ( 2.0 , 3.3 ) in the LVVA-SM and HVLA-SM groups , respectively , and 1.6 ( 0.5 , 2.8 ) in the MCMC group . There were no significant differences between LVVA-SM and HVLA-SM at any of the end points . The LVVA-SM group had significant improvements in mean functional status ranging from 1.3 to 2.2 points over the MCMC group . There were no serious adverse events associated with any of the interventions . CONCLUSIONS Biomechanically distinct forms of SM did not lead to different outcomes in older LBP patients and both SM procedures were associated with small yet clinical ly important changes in functional status by the end of treatment for this relatively healthy older population . Participants who received either form of SM had improvements on average in functional status ranging from 1 to 2.2 over those who received MCMC . From an evidence -based care perspective , patient preference and clinical experience should drive how clinicians and patients make the SM procedure decision for this patient population", "Study Design . R and omized controlled trial . Objective . To compare the effects of the McKenzie method performed by certified therapists with spinal manipulation performed by chiropractors when used adjunctive to information and advice . Summary of Background Data . Recent guidelines recommend a structured exercise program tailored to the individual patient as well as manual therapy for the treatment of persistent low back pain . There is presently insufficient evidence to recommend the use of specific decision methods tailoring specific therapies to clinical subgroups of patients in primary care . Methods . A total of 350 patients suffering from low back pain with a duration of more than 6 weeks who presented with central ization or peripheralization of symptoms with or without signs of nerve root involvement , were enrolled in the trial . Main outcome was number of patients with treatment success defined as a reduction of at least 5 points or an absolute score below 5 points on the Rol and Morris Question naire . Secondary outcomes were reduction in disability and pain , global perceived effect , general health , mental health , lost work time , and medical care utilization . Results . Both treatment groups showed clinical ly meaningful improvements in this study . At 2 months follow-up , the McKenzie treatment was superior to manipulation with respect to the number of patients who reported success after treatment ( 71 % and 59 % , respectively ) ( odds ratio 0.58 , 95 % confidence interval [ CI ] 0.36 to 0.91 , P = 0.018 ) . The number needed to treat with the McKenzie method was 7 ( 95 % CI 4 to 47 ) . The McKenzie group showed improvement in level of disability compared to the manipulation group reaching a statistical significance at 2 and 12 months follow-up ( mean difference 1.5 , 95 % CI 0.2 to 2.8 , P = 0.022 and 1.5 , 95 % CI 0.2 to 2.9 , P = 0.030 , respectively ) . There was also a significant difference of 13 % in number of patients reporting global perceived effect at end of treatment ( P = 0.016 ) . None of the other secondary outcomes showed statistically significant differences . Conclusion . In patients with low back pain for more than 6 weeks presenting with central ization or peripheralization of symptoms , we found the McKenzie method to be slightly more effective than manipulation when used adjunctive to information and advice", "OBJECTIVE To compare needle acupuncture , medication ( tenoxicam with ranitidine ) , and spinal manipulation for managing chronic ( > 13 weeks duration ) spinal pain syndromes . DESIGN Prospect i ve , r and omized , independently assessed preintervention and postintervention clinical pilot trial . SETTING Specialized spinal pain syndrome out-patient unit at Townsville General Hospital , Queensl and , Australia . SUBJECTS Seventy-seven patients ( without contraindication to manipulation or medication ) were recruited . INTERVENTIONS One of three separate , clearly defined intervention protocol s : needle acupuncture , nonsteroidal anti-inflammatory medication , or chiropractic spinal manipulation . MAIN OUTCOME MEASURES Main outcome measures were changes ( 4 weeks vs. initial visit ) in the scores of the ( 1 ) Oswestry Back Pain Disability Index , ( 2 ) Neck Disability Index , and ( 3 ) three visual analogue scales of local pain intensity . RESULTS R and omization was successful . After a median intervention period of 30 days , spinal manipulation was the only intervention that achieved statistically significant improvements ( all expressed as percentages of the original scores ) with ( 1 ) a reduction of 30.7 % on the Oswestry scale , ( 2 ) an improvement of 25 % on the neck disability index , and ( 3 ) reductions on the visual analogue scale of 50 % for low back pain , 46 % for upper back pain , and 33 % for neck pain ( all P<.001 ) . Neither of the other interventions showed any significant improvement on any of the outcome measures . CONCLUSIONS The consistency of the results provides , in spite of several discussed shortcomings of this pilot study , evidence that in patients with chronic spinal pain syndromes spinal manipulation , if not contraindicated , results in greater improvement than acupuncture and medicine", "Ninety-four patients with non-specific lumbar pain who were seen by their general practitioners took part in a double-blind controlled trial to compare mobilisation and manipulation with placebo physiotherapy . Immediately after treatment most patients showed improvements in the various features studied , but for several features improvement was more common in the treated group than the controls . At three months the condition of most patients was still improved but the differences between the two groups had largely disappeared . At one year the groups were identical . Prognostic presenting features were sought , but only a shorter history correlated with clinical improvement . This study indicates the high rate of spontaneous resolution of low back pain . A course of mobilisation and manipulation may hasten improvement but does not affect the long-term prognosis", "OBJECTIVE To evaluate the efficacy of chiropractic spinal manipulation , manual flexion/distraction , and hot pack application for the treatment of low back pain from osteoarthritis ( OA ) compared with moist heat alone . METHODS Two hundred fifty-two patients with low back pain secondary to OA were r and omly assigned to either the treatment group ( moist hot pack plus chiropractic care ) or the moist heat group subjects , which attended 20 treatment sessions over several weeks . At sessions 1 , 5 , 10 , 15 , and 20 , they rated pain using a visual analog pain scale , activities of daily living using the Oswestry Low Back Pain Question naire , and a range of motion ( ROM ) using the J-Tech Dual Digital Inclinometer ( JTECH Medical Model no. AA036 ) . RESULTS Session I ratings indicated that the two groups were equivalent on all pain and flexion scores . The treatment group reported greater and more rapid pain reduction and greater and more rapid ROM improvement than the moist heat group . The treatment group also had greater improvements than the moist heat group in daily living activities in 4 of the 9 areas measured . CONCLUSION Chiropractic care combined with heat is more effective than heat alone for treating OA-based lower back pain . Pain reduction occurs more rapidly and to a greater degree , and ROM increases more rapidly and to a greater degree", "Study Design . A r and omized controlled trial was conducted . Objective . To determine the efficacy of osteopathic manipulative treatment as a complementary treatment for chronic nonspecific low back pain . Summary of Background Data . Osteopathic manipulative treatment may be useful for acute or subacute low back pain . However , its role in chronic low back pain is unclear . Methods . This trial was conducted in a university-based clinic from 2000 through 2001 . Of the 199 subjects who responded to recruitment procedures , 91 met the eligibility criteria . They were r and omized , with 82 patients completing the 1-month follow-up evaluation , 71 completing the 3-month evaluation , and 66 completing the 6-month evaluation . The subjects were r and omized to osteopathic manipulative treatment , sham manipulation , or a no-intervention control group , and they were allowed to continue their usual care for low back pain . The main outcomes included the SF-36 Health Survey , a 10-cm visual analog scale for overall back pain , the Rol and –Morris Disability Question naire , lost work or school days because of back pain , and satisfaction with back care . Results . As compared with the no-intervention control subjects , the patients who received osteopathic manipulative treatment reported greater improvements in back pain , greater satisfaction with back care throughout the trial , better physical functioning and mental health at 1 month , and fewer cotreatments at 6 months . The subjects who received sham manipulation also reported greater improvements in back pain and physical functioning and greater satisfaction than the no-intervention control subjects . There were no significant benefits with osteopathic manipulative treatment , as compared with sham manipulation . Conclusions . Osteopathic manipulative treatment and sham manipulation both appear to provide some benefits when used in addition to usual care for the treatment of chronic nonspecific low back pain . It remains unclear whether the benefits of osteopathic manipulative treatment can be attributed to the manipulative techniques themselves or whether they are related to other aspects of osteopathic manipulative treatment , such as range of motion activities or time spent interacting with patients , which may represent placebo effects", "OBJECTIVE To describe recruitment and enrollment experiences of 2 low back pain ( LBP ) r and omized controlled trials ( RCTs ) . DESIGN Descriptive report . SETTING Chiropractic research center in the midwest United States that is not a fee-for-service clinic . PARTICIPANTS Both trials enrolled participants with subacute or chronic LBP without neurologic signs who had not received spinal manipulative care during the previous month . For study 1 we screened 1940 potential participants to enroll 192 participants ( 89 women and 103 men ) , mean age 40.0 + /- 9.4 years ( range , 21 - 54 years ) . For study 2 we screened 1849 potential participants to enroll 240 participants ( 105 women and 135 men ) at least 55 years old ( mean , 63.1 + /- 6.7 years ) . INTERVENTIONS Study 1 r and omly assigned participants to 2 weeks of 2 different chiropractic techniques or a wait list control group . Study 2 r and omly assigned participants to 6 weeks of 2 different chiropractic techniques or medical care consisting of 3 provider visits for medications . OUTCOME MEASURES Recruitment source costs and yield , and baseline characteristics of enrolled versus non participants were recorded . RESULTS We conducted 3789 telephone screens for both trials to enroll 432 ( 11 % ) participants , at a cost in excess of $ 156,000 for recruitment efforts . The cost per call for all callers averaged $ 41 , ranging from $ 4 to $ 300 based on recruitment method ; for enrolled participants , the cost per call was $ 361 , ranging from $ 33 to $ 750 . Direct mail efforts accounted for 62 % of all callers , 57 % for enrolled participants , and had the second lowest cost per call for recruitment efforts . CONCLUSIONS It is important that complementary and alternative medicine ( CAM ) research can be successfully conducted at CAM institutions . However , the costs associated with recruitment efforts for studies conducted at CAM institutions may be higher than expected and many self-identified participants are users of the CAM therapy . Therefore , strategies for efficient recruitment methods and targeting nonusers of CAM therapies should be developed early for CAM trials", "Glover , J. R. , Morris , Jean G. , and Khosla , T. (1974).British Journal of Industrial Medicine,31 , 59 - 64 . Back pain : a r and omized clinical trial of rotational manipulation of the trunk . A therapeutic trial was conducted in a medium-sized engineering works on patients suffering from back pain with its accompanying tenderness and hyperaesthesia . The patients were r and omly allocated to two treatment groups , ( a ) manipulation , and ( b ) de-tuned ( i.e. , simulated ) short-wave diathermy , the latter acting as a placebo . The manipulated group were given one lumbar rotational manipulation session of 15 minutes or less and this was followed by four daily detuned short-wave diathermy sessions of 15 minutes . The control group were given five 15-minute daily sessions of detuned short-wave diathermy only . The patients ' own subjective assessment of relief from pain was recorded in the range 0 % ( no relief ) to 100 % ( complete relief ) . The responses were measured at three stages , ( 1 ) within 15 minutes , ( 2 ) three days after treatment , and ( 3 ) seven days after treatment . Although each of the two treatment groups showed progressive and marked improvement in the percentage of relief from pain during the seven-day period , there was no demonstrable difference between the two , except that at the 15-minute stage the relief from pain in the manipulated group was always greater than in the controls", "Objective : To compare spinal manipulation , back school and individual physiotherapy in the treatment of chronic low back pain . Design : R and omized trial , 12-month follow-up . Setting : Outpatient rehabilitation department . Participants : 210 patients with chronic , non-specific low back pain , 140/210 women , age 59 ± 14 years . Interventions : Back school and individual physiotherapy scheduled 15 1-hour-sessions for 3 weeks . Back school included : group exercise , education/ ergonomics ; individual physiotherapy : exercise , passive mobilization and soft-tissue treatment . Spinal manipulation , given according to Manual Medicine , scheduled 4 to 6 20’-sessions once-a-week . Outcome : Rol and Morris Disability Question naire ( scoring 0 - 24 ) and Pain Rating Scale ( scoring 0 - 6 ) were assessed at baseline , discharge 3 , 6 , and 12 months . Results : 205 patients completed the study . At discharge , disability score decreased by 3.7 ± 4.1 for back school , 4.4 ± 3.7 for individual physiotherapy , 6.7 ± 3.9 for manipulation ; pain score reduction was 0.9 ± 1.1 , 1.1 ± 1.0 , 1.0 ± 1.1 , respectively . At 12 months , disability score reduction was 4.2 ± 4.8 for back school , 4.0 ± 5.1 for individual physiotherapy , 5.9 ± 4.6 for manipulation ; pain score reduction was 0.7 ± 1.2 , 0.4 ± 1.3 , and 1.5 ± 1.1 , respectively . Spinal manipulation was associated with higher functional improvement and long-term pain relief than back school or individual physiotherapy , but received more further treatment at follow-ups ( P<0.001 ) ; pain recurrences and drug intake were also reduced compared to back school ( P < 0.05 ) or individual physiotherapy ( P < 0.001 ) . Conclusions : Spinal manipulation provided better short and long-term functional improvement , and more pain relief in the follow-up than either back school or individual physiotherapy", "OBJECTIVE To assess the feasibility of recruiting sciatica patients and to evaluate their compliance in preparation for a full-scale r and omized clinical trial . We also aim ed to determine the responsiveness of key outcome measures . METHODS Thirty-two subjects were r and omly assigned to spinal manipulation ( n=11 ) , epidural steroid injections ( n=11 ) , or self-care education ( n=10 ) . No between-group comparisons were planned because of the small sample size . RESULTS At week 12 ( the end of the treatment phase ) , the outcome measures indicating the most improvement/change were the Oswestry disability score ( mean , 22.9 ; SD , 19.9 ; effect size [ ES ] , 1.8 ) , leg pain severity ( mean , 2.9 ; SD , 1.7 ; ES , 1.7 ) , and if the symptoms were bothersome ( mean , 25.2 ; SD , 16.0 ; ES , 1.6 ) . Twenty-four patients were either \" very satisfied \" or \" completely satisfied , \" and 22 of 32 patients reported 75 % or 100 % improvement . After 52 weeks , the outcome measure showing the most improvement/change was leg pain severity ( mean , 2.3 ; SD , 2.6 ; ES , 1.35 ) , followed by the Oswestry disability score ( mean , 15.6 ; SD , 20 ; ES , 1.2 ) and if symptoms were bothersome ( mean , 18.1 ; SD , 22.6 ; ES , 1.1 ) . Eighteen patients were either \" very satisfied \" or \" completely satisfied , \" and 15 of 32 patients reported 75 % or 100 % improvement . CONCLUSIONS The results of this pilot study suggest that it is feasible to recruit subacute and chronic sciatica patients and to obtain their compliance for a full-scale r and omized clinical", "Study Design . A r and omized trial was conducted in which patients with back and neck pain , visiting a general practitioner , were allocated to chiropractic or physiotherapy . Objectives . To compare outcome and costs of chiropractic and physiotherapy as primary treatment for patients with back and neck pain , with special reference to subgroups , recurrence rate , and additional health care use at follow‐up evaluation 12 months after treatment . Summary of Background Data . Earlier studies on the effect of spinal manipulation have shown inconsistent results . Mostly they include only short‐term follow‐up periods , and few cost‐effectiveness analyses have been made . Methods . A group of 323 patients aged 18‐60 years who had no contraindications to manipulation and who had not been treated within the previous month were included . Outcome measures were changes in Oswestry scores , pain intensity , and general health ; recurrence rate ; and direct and indirect costs . Results . No differences were detected in health improvement , costs , or recurrence rate between the two groups . According to Oswestry score , chiropractic was more favorable for patients with a current pain episode of less than 1 week ( 5 % ) and physiotherapy for patients with a current pain episode of greater than 1 month ( 6.8 % ) . Nearly 60 % of the patients reported two or more recurrences . More patients in the chiropractic group ( 59 % ) than in the physiotherapy group ( 41 % ) sought additional health care . Costs varied considerably among individuals and subgroups ; the direct costs were lower for physiotherapy in a few subgroups . Conclusions . Effectiveness and costs of chiropractic or physiotherapy as primary treatment were similar for the total population , but some differences were seen according to subgroups . Back problems often recurred , and additional health care was common . Implication s of the result are that treatment policy and clinical decision models must consider subgroups and that the problem often is recurrent . Models must be implemented and tested", "Study Design A r and omized prospect i ve trial of manipulation , massage , corset and transcutaneous muscle stimulation ( TMS ) was conducted in patients with subacute low back pain . Objectives The authors determined the relative efficacy of chiropractic treatment to massage , corset , and TMS . Summary of Background Data Although all of these treatments are used for subacute low back pain treatment , there have been few comparative trials using objective outcome criteria . Patients were enrolled for a period of 3 weeks . They were evaluated once a week by question naires , visual analog scale , range of motion , maximum voluntary extension effort , straight leg raising and Biering-Sorensen fatigue test . The dropout rate was highest in the muscle stimulation and corset groups and lowest in the manipulation group . Rates of full compliance did not differ significantly across treatments . A measure of patient confidence was greatest in the manipulation group . Results After 3 weeks , the manipulation group scored the greatest improvements in flexion and pain while the massage group had the best extension effort and fatigue time , and the muscle stimulation group the best extension . Conclusion None of the changes in physical outcome measures ( range of motion , fatigue , strength or pain ) were significantly different between any of the groups", "An open controlled pilot trial on nonspecific low-back pain sufferers demonstrated responsiveness to osteopathic manipulation of some patients presenting with pain duration s of 14 to 28 days . No response was demonstrated in those with shorter episodes at presentation . The advantage to manipulated patients was maximal between 1 and 2 weeks after commencing treatment , but was not discernable after 4 weeks . The demonstration of a similar responsive stratum by other investigators , with both teams totally unaware of each other 's work during data collection , suggests a high degree of reliability for this finding", "BACKGROUND Although chiropractors often use physical modalities with spinal manipulation , evidence that modalities yield additional benefits over spinal manipulation alone is lacking . OBJECTIVE The purpose of the study was to estimate the net effect of physical modalities on low back pain ( LBP ) outcomes among chiropractic patients in a managed-care setting . METHODS Fifty percent of the 681 patients participating in a clinical trial of LBP treatment strategies were r and omized to chiropractic care with physical modalities ( n = 172 ) or without physical modalities ( n = 169 ) . Subjects were followed for 6 months with assessment s at 2 , 4 , and 6 weeks and at 6 months . The primary outcome variables were average and most severe LBP intensity in the past week , assessed with numerical rating scales ( 0 - 10 ) , and low back-related disability , assessed with the 24-item Rol and -Morris Disability Question naire . RESULTS Almost 60 % of the subjects had baseline LBP episodes of more than 3 months ' duration . The 6-month follow-up was 96 % . The adjusted mean differences between groups in improvements in average and most severe pain and disability were clinical ly insignificant at all follow-up assessment s. Clinical ly relevant improvements in average pain and disability were more likely in the modalities group at 2 and 6 weeks , but this apparent advantage disappeared at 6 months . Perceived treatment effectiveness was greater in the modalities group . CONCLUSIONS Physical modalities used by chiropractors in this managed-care organization did not appear to be effective in the treatment of patients with LBP , although a small short-term benefit for some patients can not be ruled out", "OBJECTIVES The aim of this trial was to establish the effectiveness of traditional bone setting ( TBS ) compared with conventional physical and exercise therapy ( PhT ) in treating chronic low back pain ( cLBP ) . DESIGN R and omised clinical trial . SETTING Working-aged cLBP patients ( n=131 , age range 29 - 51 years ) were r and omised into two treatment groups : TBS and PhT. Follow-up assessment s took place 1 , 6 and 12 months after treatment . INTERVENTIONS TBS is a popular traditional manual mobilisation therapy for musculoskeletal disorders in Finl and . Conventional PhT was used as the reference treatment . MAIN OUTCOME MEASURES LBP intensity ( Visual Analog Scale 0 - 100 , VAS ) , the Oswestry Disability Index ( ODI ) , the global assessment score ( scale -1 to + 10 ) , a health-related quality of life ( HRQoL ) assessment and spine mobility measurements were used as measures . RESULTS 118 patients ( 95.9 % , 59 men and 59 women ) completed the treatment program . Both treatments reduced the VAS and ODI levels after 1 month . Changes in VAS did not differ between the two treatment groups ( mean -0.2 , CI -11.3 to 10.9 ) . The improvement in ODI ( mean 2.4 , CI -1.2 to 6.0 , p=0.069 , repeated measurements ANOVA ) and quality of life scores ( mean -0.03 , CI -0.06 to 0 , p=0.056 ) tended to be greater after TBS . Additionally , global assessment scores were better for TBS-treated patients ( Mann-Whitney test , p=0.001 ) . There were no differences between the spine mobility test results of the two groups . Changes in both VAS ( mean -2.4 , CI -15.5 to 10.6 ) and ODI ( mean 1.0 , CI -3.0 to 5.1 ) measures did not , however , differ between the groups at the 1-year follow-up stage . CONCLUSIONS Most cLBP patients found the treatments to be beneficial . Although the long-term dynamics of pain and disability did not differ between the groups , the subjective benefits appeared to be more significant after TBS", "81 patients with chronic low back pain ( average duration 10 years ) were r and omised to two treatment groups . 40 received an empirically devised regimen of forceful spinal manipulation and injections of a dextrose-glycerine-phenol ( \" proliferant \" ) solution into soft-tissue structures , as part of a programme to decrease pain and disability . The other 41 patients received parallel treatment in which the main differences were less extensive initial local anaesthesia and manipulation , and substitution of saline for proliferant . Neither patients nor assessors knew which treatment had been given . When assessed by disability scores the experimental group had greater improvement than the control group at one ( p less than 0.001 ) , three ( p less than 0.004 ) , and six ( p less than 0.001 ) months from the end of treatment ; at six months an improvement of more than 50 % was recorded in 35 of the experimental group versus 16 of the control group and the numbers free from disability were 15 and 4 , respectively ( p less than 0.003 ) . Visual analogue pain scores and pain diagrams likewise showed significant advantages for the experimental regimen", "Study Design . A r and omized clinical trial . Objectives . To compare the effectiveness of medical and chiropractic care for low back pain patients in managed care ; to assess the effectiveness of physical therapy among medical patients ; and to assess the effectiveness of physical modalities among chiropractic patients . Summary of Background Data . Despite the burden that low back pain places on patients , providers , and society , the relative effectiveness of common treatment strategies offered in managed care is unknown . Methods . Low back pain patients presenting to a large managed care facility from October 30 , 1995 , through November 9 , 1998 , were r and omly assigned in a balanced design to medical care with and without physical therapy and to chiropractic care with and without physical modalities . The primary outcome variables are average and most severe low back pain intensity in the past week , assessed with 0 to 10 numerical rating scales , and low back-related disability , assessed with the 24-item Rol and -Morris Disability Question naire . Results . Of 1,469 eligible patients , 681 were enrolled ; 95.7 % were followed through 6 months . The mean changes in low back pain intensity and disability of participants in the medical and chiropractic care-only groups were similar at each follow-up assessment ( adjusted mean differences at 6 months for most severe pain , 0.27 , 95 % confidence interval , -0.32–0.86 ; average pain , 0.22 , -0.25–0.69 ; and disability , 0.75 , -0.29–1.79 ) . Physical therapy yielded somewhat better 6-month disability outcomes than did medical care alone ( 1.26 , 0.20–2.32 ) . Conclusions . After 6 months of follow-up , chiropractic care and medical care for low back pain were comparable in their effectiveness . Physical therapy may be marginally more effective than medical care alone for reducing disability in some patients , but the possible benefit is small", "In a blinded r and omized clinical trial , we compared the effectiveness of manual therapy , physiotherapy , ( continued ) treatment by the general practitioner ( GP ) , and a placebo therapy ( detuned ultrasound and detuned short wave diathermy ) for patients ( n = 256 ) with chronic nonspecific back and neck complaints . The physical outcome measures ( spinal mobility and physical functioning ) are presented for 3 , 6 and 12 wk follow-up . Manual therapy showed a faster and larger improvement in physical functioning compared to the other three therapies . The changes in spinal mobility among the four study groups appear to be small and show no consistent pattern", "OBJECTIVES This study examined the difference in satisfaction between patients assigned to chiropractic vs medical care for treatment of low back pain in a managed care organization . METHODS Satisfaction scores ( on a 10 - 50 scale ) after 4 weeks of follow-up were compared among 672 patients r and omized to receive medical or chiropractic care . RESULTS The mean satisfaction score for chiropractic patients was greater than the score for medical patients ( crude difference = 5.5 ; 95 % confidence interval = 4.5 , 6.5 ) . Self-care advice and explanation of treatment predicted satisfaction and reduced the estimated difference between chiropractic and medical patients ' satisfaction . CONCLUSIONS Communication of advice and information to patients with low back pain increases their satisfaction with providers and accounts for much of the difference between chiropractic and medical patients ' satisfaction", "Background Cluster r and omized trials , which r and omize groups of patients rather than individuals , are commonly used to evaluate healthcare interventions such as training programmes targeted at health professionals . This article reports the dangers of r and omizing entire primary care practice s when participants can not be identified before r and omization , as shown by a UK national trial . Method The UK BEAM trial , a national cluster r and omized 322 factorial trial , was design ed to evaluate three treatments for back pain in primary care : “ active management ” ; r and omized by practice ; and spinal manipulation and exercise classes , both r and omized by individual . Results Two hundred and thirty-one participants were recruited in the feasibility study , 165 ( 141 % of expected recruitment ) from active ( management ) practice s but only 66 ( 54 % of expected recruitment ) from traditional ( management ) practice s. The participants in active practice s were significantly different from those in traditional practice s , notably in suffering from milder back pain . Conclusions The feasibility study highlighted the dangers of r and omizing clusters when individuals can not be identified beforeh and . Different numbers and types of participants were recruited in the two types of cluster . This differential recruitment led us to change the main trial design by ab and oning practice level r and omization . Instead all practice s were trained in active management to maximize recruitment . Ideally cluster r and omized trials should identify patients beforeh and , to minimize the chance of selection bias . If this is not possible , patient recruitment should be independent in both intervention and control clusters . Pilot studies are especially important for cluster r and omized trials , to identify unforeseen problems", "Study Design . Sixteen-week intervention for chronic patients with low back pain ( LBP ) with 9-month follow-up . Primary r and omization at 4 weeks into either supervised Swiss ball exercise or an exercise advice group . Objective . To evaluate changes in disability and pain in individuals with chronic LBP after combined treatment and exercise interventions , and to evaluate whether changes in self-report or physical measures would best explain improvements in disability Summary of Background Data . There is a need to underst and what the effectiveness of a clinical ly applicable treatment intervention is for an individual ’s perception of their back pain . There is insufficient evidence about the different combinations of manual treatment that commonly precede involvement in exercise programs . Methods . Sixty individuals with chronic nonspecific LBP ( at least 3-month duration ) were r and omly assigned ( after 4 weeks of manipulative or nonmanipulative treatment ) to either a supervised Swiss ball exercise group , or an advice group . The exercise intervention was for 12 weeks with a long-term follow-up of 9 months . Self-report measures and physical measures ( endurance times and myoelectric fatigue ) were collected throughout the study . Results . Self-rated disability improved more after the treatment period for individuals who received supervised exercise compared with advice alone . There was no difference found between individuals who received manipulative or nonmanipulative treatment . Multiple regression analysis found that self-report measures best explained improvements in disability throughout the study . Long-term findings showed no group differences . Conclusion . Supervised exercise is a more successful subsequent to manual treatment compared with exercise advice . The improvements associated with this type of program were primarily manifested in the psychologic self-report measures rather than physical measurements", "OBJECTIVES Both exercises and manipulation are recommended as basic therapy in back diseases , while a possible synergistic effect of these treatments have not been clarified . This study was conducted to test a possible further effect of manipulation as adjunct to extension exercises for unspecific LBP . METHODS 72 patients with chronic LBP ( mean 12 months ) were examined by a specialist in manual medicine , who detected localized binding between the lumbar segments . All patients were instructed in extension exercises , while r and omized to either pretreatment with specific manipulation or control . The patients were blinded to the manipulation , which was performed at the end of the manual examination , and repeated after two and four weeks . The manipulator only knew the group of the particular patient just before manipulation by the end of the examination . The primary end point was pain , measured by a visual analogue scale . RESULTS Pain in both back and leg decreased without differences between groups . Segmental binding of the low-back was associated with persisting clinical symptoms at four weeks . CONCLUSION No additional effect was demonstrated of manipulation , when extension exercises were used as basic therapy", "OBJECTIVES We sought to estimate the effects of recreational physical activity and back exercises on low back pain , related disability , and psychological distress among patients r and omized to chiropractic or medical care in a managed care setting . METHODS Low back pain patients ( n=681 ) were r and omized and followed for 18 months . Participation in recreational physical activities , use of back exercises , and low back pain , related disability , and psychological distress were measured at baseline , at 6 weeks , and at 6 , 12 , and 18 months . Multivariate logistic regression modeling was used to estimate adjusted associations of physical activity and back exercises with concurrent and subsequent pain , disability , and psychological distress . RESULTS Participation in recreational physical activities was inversely associated -- both cross-sectionally and longitudinally -- with low back pain , related disability , and psychological distress . By contrast , back exercise was positively associated -- both cross-sectionally and longitudinally -- with low back pain and related disability . CONCLUSIONS These results suggest that individuals with low back pain should refrain from specific back exercises and instead focus on nonspecific physical activities to reduce pain and improve psychological health", "Objective . This r and omized clinical trial was design ed to determine the effect of treating low back pain as a benign , self limiting condition by light normal activity . Methods . Patients on sickness leave from work for more than 8 weeks were r and omized into two groups : intervention ( n = 463 ) and control ( n = 512 ) . Those in the intervention group were examined , provided information , and given instruction . Outcome was measured by return or failure to return to work ( still on sickness leave ) . Results . Survival analysis showed a highly significant ( P = 0.000 ) reduction in sickness leave in the intervention group as compared with the control group . At 200 days 60 % were still on sickness leave in the control group vs. 30 % in the intervention group . A multivariate analysis with age , sex , and treatment as cofactors showed that sex had no effect on length of sickness leave and that treatment retained its effect when adjusting for differences in age composition . Conclusion . This study indicates that low back pain treated as a benign , self limiting condition recommended to light mobilization gives superior results as compared to treatment within a conventional medical system", "OBJECTIVE To evaluate the short-term responsiveness of rotatory thoracic end-play assessment to spinal manipulation and , thereby , motion palpation construct validity . DESIGN Prospect i ve , single-blind , r and omized , controlled trial ( r and omized blocks design ) . SETTING Laboratory , Center for Technique Research . PARTICIPANTS Sixty first-year chiropractic college student volunteers ; seventy-three possible c and i date s were screened . INTERVENTIONS The treatment group received manual high-velocity , low-amplitude rotatory manipulation . The control group received no intervention to minimize nonspecific effects of sham treatment . MAIN OUTCOME MEASURES End-play response , defined as the change from restricted to normal end play immediately after intervention . Responsiveness , defined as the percentage of the end-play response attributable to spinal manipulation : relative response attributable to the maneuver , RRAM = ( treatment group response -- control group response)/treatment group response . RESULTS Ten percent of the tests were positive for restriction of end play in left or right rotation from T3-T4 to T12-L1 ; the average rate was 2.1 restrictions per subject ( SD = 1.4 ) . End-play response was 60 % in the treatment group , in contrast to the 37 % response in the control group ( z = 1.86 , p = .04 ) . More than a third of the response in the treatment group was attributable to spinal manipulation ( RRAM = 39 % ) . For one examiner , RRAM = 51 % . Mild symptomatology did not affect responsiveness . CONCLUSIONS The data suggest a moderate short-term responsiveness of rotatory thoracic end-play restriction to spinal manipulation , hence it has utility as a posttreatment evaluative test . This study was the first to use an external st and ard ( manipulation ) to demonstrate that segmental end-play restriction changes , hence end-play restriction itself , are detectable in human subjects with manual palpation by chiropractors . Further research is required to determine the generalizability of the study findings", "The professional literature contains relatively few r and omized-control studies that have assessed the efficacy of physical therapy approaches to the management of patients with chronic low back pain ( CLBP ) . The purpose s of this study were : 1 ) to investigate the effects of physical agents , joint manipulation , low-tech exercise , and high-tech exercise on objective measures of CLBP ; 2 ) to track the length of CLBP relief ; and 3 ) to determine treatment cost-effectiveness . Two-hundred-fifty subjects ( 68 females , 182 males ; ages 34 - 51 years ) with CLBP following an L5 laminectomy were r and omly assigned into five separate groups for a treatment period of 8 weeks . Chronic low back pain status was measured by modified-modified Schober , Cybex Liftask , and Oswestry procedures . Results revealed that : 1 ) only low-tech and high-tech exercise produced significant improvements ( p < .05 ) in CLBP , 2 ) the mean period of CLBP relief ranged from 1.6 weeks ( control ) to 91.4 weeks ( low-tech exercise ) , and 3 ) low-tech exercise was most cost-effective . It was concluded that : 1 ) low-tech and high-tech exercise were the only effective treatments for CLBP , 2 ) low-tech exercise produced the longest period of CLBP relief , and 3 ) low-tech exercise was the most cost-effective form of treatment . Clinical ly , low-tech exercise may be the treatment method of choice for the effective management of chronic low back pain", "Study Design . A prospect i ve , r and omized controlled trial . Objective . To examine long-term effects and costs of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain ( cLBP ) . Summary of Background Data . An obvious gap exists in knowledge concerning long-term efficacy and cost-effectiveness of manipulative treatment methods . Methods . Of 204 patients with cLBP whose Oswestry Disability Index ( ODI ) was at least 16 % , 102 were r and omized into a combined manipulative treatment , exercise , and physician consultation group ( i.e. , a combination group ) , and 102 to a consultation alone group . All patients were clinical ly examined , informed about their back pain , and encouraged to stay active and exercise according to specific instructions based on clinical evaluation . Treatment included 4 sessions of manual therapy and stabilizing exercises aim ed at correcting the lumbopelvic rhythm . Question naires inquired about pain ( visual analog scale [ VAS ] ) , disability ( ODI ) , health-related quality of life ( 15D Quality of Life Instrument ) , satisfaction with care , and costs . Results . Significant improvement occurred in both groups on every self-rated outcome measurement . Within 2 years , the combination group showed only a slightly more significant reduction in VAS ( P = 0.01 , analysis of variance ) but clearly higher patient satisfaction ( P = 0.001 , Pearson & khgr;2 ) as compared to the consultation group . Incremental analysis showed that for combined group compared to consultation group , a one-point change in VAS scale cost $ 512 . Conclusions . Physician consultation alone was more cost-effective for both health care use and work absenteeism , and led to equal improvement in disability and health-related quality of life . It seems obvious that encouraging information and advice are major elements for the treatment of patients with cLBP", "Study Design . R and omized clinical trial . Objectives . To compare the long-term effectiveness of medical and chiropractic care for low back pain in managed care and to assess the effectiveness of physical therapy and modalities among patients receiving medical or chiropractic care . Summary of Background Data . Evidence comparing the long-term relative effectiveness of common treatment strategies offered to low back pain patients in managed care is lacking . Methods . A total of 681 low back pain patients presenting to a managed-care facility were r and omized to chiropractic with or without physical modalities , or medical care with or without physical therapy , and followed for 18 months . The primary outcome variables are low back pain intensity , disability , and complete remission . The secondary outcome is participants ' perception of improvement in low back symptoms . Results . Of the 681 patients , 610 ( 89.6 % ) were followed through 18 months . Among participants not assigned to receive physical therapy or modalities , the estimated improvements in pain and disability and 18-month risk of complete remission were a little greater in the chiropractic group than in the medical group ( adjusted RR of remission = 1.29 ; 95 % CI = 0.80–2.07 ) . Among participants assigned to medical care , mean changes in pain and disability and risk of remission were larger in patients assigned to receive physical therapy ( adjusted RR = 1.69 ; 95 % CI = 1.08–2.66 ) . Among those assigned to chiropractic care , however , assignment to methods was not associated with improvement or remission ( adjusted RR = 0.98 ; 95 % CI = 0.62–1.55 ) . Compared with medical care only patients , chiropractic and physical therapy patients were much more likely to perceive improvement in their low back symptoms . However , less than 20 % of all patients were pain-free at 18 months . Conclusions . Differences in outcomes between medical and chiropractic care without physical therapy or modalities are not clinical ly meaningful , although chiropractic may result in a greater likelihood of perceived improvement , perhaps reflecting satisfaction or lack of blinding . Physical therapy may be more effective than medical care alone for some patients , while physical modalities appear to have no benefit in chiropractic care", "Study Design . A r and omized clinical trial with blinded assessment . Objectives . To investigate the clinical efficacy of 2 active interventions for patients with chronic low back pain . Summary of Background Data . Manual therapy and exercise prescription are treatments frequently prescribed for patients with chronic low back pain . The evidence for the relative benefit of these treatments is limited , and questions concerning the most appropriate type of intervention remain unanswered . Methods . Eighty patients with chronic low back pain ( > 3 months ) were r and omized to one of the following treatments , involving 8 treatments over 8 weeks ; 1 ) one-to-one treatment involving 30 minutes of manual therapy ( mobilizations to the spine ) and spinal stabilization exercises , and 2 ) a 10 station exercise class involving aerobic exercises , spinal stabilization exercises , and manual therapy . Three physiotherapists led the hour long group with a maximum of 10 patients . Question naires were completed , and physical measurements were taken by a blinded observer before r and omization , at the completion of treatment , and at 6 months and 12 months after the completion of treatment . The intention-to-treat principle was used in data analysis . Results . Eleven patients dropped out of the individual treatment sessions and 7 dropped out of the exercise group . There was a significant reduction ( reduced disability ) in the question naire score in both groups , and there were significant increases in range for all the physical movements tested in both groups . The exercise group was 40 % more cost effective than the individual treatments . Conclusion . Both forms of intervention were associated with significant improvement . On-going clinical research is necessary to provide guidance as to the clinical efficacy of various forms of intervention", "Abstract Objective : To compare the effectiveness over three years of chiropractic and hospital outpatient management for low back pain . Design : R and omised allocation of patients to chiropractic or hospital outpatient management . Setting : Chiropractic clinics and hospital outpatient departments within reasonable travelling distance of each other in 11 centres . Subjects : 741 men and women aged 18 - 64 years with low back pain in whom manipulation was not contraindicated . Outcome measures : Change in total Oswestry question naire score and in score for pain and patient satisfaction with allocated treatment . Results : According to total Oswestry scores improvement in all patients at three years was about 29 % more in those treated by chiropractors than in those treated by the hospitals . The beneficial effect of chiropractic on pain was particularly clear . Those treated by chiropractors had more further treatments for back pain after the completion of trial treatment . Among both those initially referred from chiropractors and from hospitals more rated chiropractic helpful at three years than hospital management . Conclusions : At three years the results confirm the findings of an earlier report that when chiropractic or hospital therapists treat patients with low back pain as they would in day to day practice those treated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals", "The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain ( LBP ) . Forty-seven patients were r and omized to a stabilizing training group ( ST group ) or a manual treatment group ( MT group ) . The patients underwent a 6-week treatment programme on a weekly basis . Pain , health and functional disability level at the start of treatment , after treatment , and at 3- and 12-month follow-ups were assessed . In the ST group all assessed variables improved significantly ( P<0.05 ) after the treatment period and were maintained long term . After the treatment period there was a significant difference between the groups in assessed function ( P<0.05 ) . More individuals in the ST group had improved than in the MT group . At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain , general health and functional disability levels . In the long term , significantly more ( P<0.05 ) patients in the MT group reported recurrent treatment periods . The study did not indicate any clear short-term differences between the groups in the accessed outcome measures . In the long term , however , stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods", "Study Design . A r and omized , assessor-blinded clinical trial was conducted . Objective . To investigate the relative effectiveness of three manual treatments and back school for patients with subacute low back pain . Summary of Background Data . Literature comparing the relative effectiveness of specific therapies for low back pain is limited . Methods . Among the 5925 inquiries , 206 patients met the specific admission criteria , and 200 patients r and omly received one of four treatments for 3 weeks : back school , joint manipulation , myofascial therapy , and combined joint manipulation and myofascial therapy . These patients received assessment s at baseline , after 3 weeks of therapy , and 6 months after the completion of therapy . The primary outcomes were evaluated using visual analog pain scales and Rol and –Morris activity scales . Results . All four groups showed significant improvement in pain and activity scores after 3 weeks of care , but did not show further significant improvement at the 6-month follow-up assessment . No statistically significant between-group differences were found either at the 3-week or 6-month re assessment s. Conclusions . For subacute low back pain , combined joint manipulation and myofascial therapy was as effective as joint manipulation or myofascial therapy alone . Additionally , back school was as effective as three manual treatments", "The study evaluated the manual treatment of dysfunction of the pelvic joints . This is one of many condition causing low back pain . In 1987 - 1988 a general practitioner with special knowledge of physical examination and manual treatment of lumbar and pelvic dysfunctions made a survey of patients with acute or subacute low back pain as the main cause of the patient-to-doctor contact . Patients with defined criteria of pelvic joint dysfunction ( n = 46 ) were r and omized . After dropouts and exclusions , 18 patients with defined criteria of pelvic joint dysfunction received manual treatment , while 21 patients with similar dysfunction served as controls and received placebo treatment in a form of massage . Both groups were seen only once to evaluate whether a single treatment might be sufficient . After a period of three weeks , evaluation was made by an independent observer . Subjective pain measurement and a mobility test showed no significant difference . Sick-leave and consumption of analgesics ( both decided by patient ) were significantly less in the treatment group", "Study Design . A r and omized , clinical trial was conducted in which patients with back/neck problems , visiting a general practitioner , were allocated to chiropractic or physiotherapy as primary management . Objectives . To compare outcome and costs of chiropractic and physiotherapy in managing patients with low back or neck pain . Summary of Background Data . Earlier studies on the treatment of back pain by spinal manipulation have shown inconsistent results . When a \" new \" strategy ‐chiropractic‐in the treatment of back pain was introduced in public health care in Sweden , there was a need to compare the effects and costs of chiropractic with the established physiotherapy . Methods . Three hundred twenty‐three patients aged 18 to 60 years who had no contraindications to manipulation and who had not been treated within the previous month were included in the study . Treatment was carried out at the discretion of the therapist . Outcome measures were primarily changes in pain intensity and general health , both assessed with visual analog scale and Oswestry pain disability question naire . Direct and indirect costs were measured . Results . For patients with low back or neck pain visiting the general practitioner in primary care , both chiropractic and physiotherapy as primary treatment reduced the symptoms . No difference in outcome or direct or indirect costs between the two groups could be seen , nor in subgroups defined as duration , history , or severity . Conclusions . The effectiveness and total costs of chiropractic or physiotherapy as primary treatment were similar to reach the same result after treatment and after 6 months", "Abstract Objective Acute low back pain ( ALBP ) may limit mobility and impose functional limitations in active duty military personnel . Although some manual therapies have been reported effective for ALBP in military personnel , there have been no published r and omized controlled trials ( RCTs ) of osteopathic manipulative treatment ( OMT ) in the military . Furthermore , current military ALBP guidelines do not specifically include OMT . Methods This RCT examined the efficacy of OMT in relieving ALBP and improving functioning in military personnel at Fort Lewis , Washington . Sixty-three male and female soldiers ages 18 to 35 were r and omly assigned to a group receiving OMT plus usual care or a group receiving usual care only ( UCO ) . Results The primary outcome measures were pain on the quadruple visual analog scale , and functioning on the Rol and Morris Disability Question naire . Outcomes were measured immediately preceding each of four treatment sessions and at four weeks post-trial . Intention to treat analysis found significantly greater post-trial improvement in ‘ Pain Now ’ for OMT compared to UCO ( P = 0·026 ) . Furthermore , the OMT group reported less ‘ Pain Now ’ and ‘ Pain Typical ’ at all visits ( P = 0·025 and P = 0·020 respectively ) . Osteopathic manipulative treatment subjects also tended to achieve a clinical ly meaningful improvement from baseline on ‘ Pain at Best ’ sooner than the UCO subjects . With similar baseline expectations , OMT subjects reported significantly greater satisfaction with treatment and overall self-reported improvement ( P<0·01 ) . Conclusion This study supports the effectiveness of OMT in reducing ALBP pain in active duty military personnel", "Study Design . A multicenter , r and omized , controlled trial with 1-year follow-up . Objectives . To compare the effect of manual therapy to exercise therapy in sick-listed patients with chronic low back pain ( > 8 wks ) . Summary and Background Data . The effect of exercise therapy and manual therapy on chronic low back pain with respect to pain , function , and sick leave have been investigated in a number of studies . The results are , however , conflicting . Methods . Patients with chronic low back pain or radicular pain sick-listed for more than 8 weeks and less than 6 months were included . A total of 49 patients were r and omized to either manual therapy ( n = 27 ) or to exercise therapy ( n = 22 ) . Sixteen treatments were given over the course of 2 months . Pain intensity , functional disability ( Oswestry disability index ) , general health ( Dartmouth COOP function charts ) , and return to work were recorded before , immediately after , at 4 weeks , 6 months , and 12 months after the treatment period . Spinal range of motion ( Schober test ) was measured before and immediately after the treatment period only . Results . Although significant improvements were observed in both groups , the manual therapy group showed significantly larger improvements than the exercise therapy group on all outcome variables throughout the entire experimental period . Immediately after the 2-month treatment period , 67 % in the manual therapy and 27 % in the exercise therapy group had returned to work ( P < 0.01 ) , a relative difference that was maintained throughout the follow-up period . Conclusions . Improvements were found in both intervention groups , but manual therapy showed significantly greater improvement than exercise therapy in patients with chronic low back pain . The effects were reflected on all outcome measures , both on short and long-term follow-up", "BACKGROUND AND METHODS There are few data on the relative effectiveness and costs of treatments for low back pain . We r and omly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy , chiropractic manipulation , or a minimal intervention ( provision of an educational booklet ) . Patients with sciatica were excluded . Physical therapy or chiropractic manipulation was provided for one month ( the number of visits was determined by the practitioner but was limited to a maximum of nine ) ; patients were followed for a total of two years . The bothersomeness of symptoms was measured on an 11-point scale , and the level of dysfunction was measured on the 24-point Rol and Disability Scale . RESULTS After adjustment for base-line differences , the chiropractic group had less severe symptoms than the booklet group at four weeks ( P=0.02 ) , and there was a trend toward less severe symptoms in the physical therapy group ( P=0.06 ) . However , these differences were small and not significant after transformations of the data to adjust for their non-normal distribution . Differences in the extent of dysfunction among the groups were small and approached significance only at one year , with greater dysfunction in the booklet group than in the other two groups ( P=0.05 ) . For all outcomes , there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain . About 75 percent of the subjects in the therapy groups rated their care as very good or excellent , as compared with about 30 percent of the subjects in the booklet group ( P<0.001 ) . Over a two-year period , the mean costs of care were $ 437 for the physical-therapy group , $ 429 for the chiropractic group , and $ 153 for the booklet group . CONCLUSIONS For patients with low back pain , the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs , and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet . Whether the limited benefits of these treatments are worth the additional costs is open to question", "BACKGROUND Implementing clinical guidelines is more likely to be successful when the whole practice team is committed to the process . Practice s from the MRC General Practice Research Framework in two distinct geographical centres in the UK ( West Yorkshire and Greater Manchester ) participated in the feasibility study for the UK Back pain Exercise And Manipulation ( UK BEAM ) trial . Practice teams were r and omized to continue with their usual care for back pain patients , or to be trained in managing back pain in line with national guidelines . Those r and omized to the intervention arm of the trial were invited to attend training , delivered by either a generic trainer or a back pain expert . OBJECTIVES Our aims were to assess the general acceptability of the training package to staff , to assess the acceptability of the multidisciplinary approach and to determine if a generic primary care educator could deliver the training as effectively as a clinical back pain expert . METHODS All staff ( clinical and non- clinical ) from intervention practice s were invited to attend multidisciplinary training sessions on the active management of back pain . Practice staff in West Yorkshire were trained by a generic primary care educator and practice staff in Greater Manchester were trained by a clinical back pain expert . The content of sessions was st and ardized for both trainers and included didactic and interactive components and small group , case study discussion s. Detailed notes were taken of observations made of participants during sessions , and evaluation forms were completed by all those who attended . RESULTS The majority of participants found the training useful and said that the session had lived up to their expectations . Most found that the session was well planned and that they had sufficient opportunity to participate in learning . The training package was well received by clinical staff , but was less acceptable to non- clinical staff . GPs dominated the small group work discussion s. No differences were found between the preferences of participants for the two different trainers . CONCLUSION The training package was appropriate for clinical staff , but did not always meet the needs of non- clinical staff and may require modification for this group . A generic educator can successfully lead multidisciplinary educational sessions addressing clinical issues", "The objectives of the study are to test the hypotheses that psychological distress affects subsequent low-back pain , and pain affects subsequent distress . Six hundred eighty-one participants in a r and omized clinical trial of low-back pain treatments were followed for 18 months with assessment s for pain , disability , and psychological distress at 6 weeks and 6 , 12 , and 18 months . Multivariable logistic regression modeling with generalized estimating equations was used to estimate effects . Current pain and disability increased the odds of subsequent psychological distress [ pain : adjusted odds ratio (OR)=1.36 , 95 % confidence interval (CI)=1.07 , 1.72 ; disability : adjusted OR=1.23 , 95 % CI=0.98 , 1.55 ] , and current distress increased the odds of subsequent pain and disability ( pain : adjusted OR=1.51 , 95 % CI=1.24 , 1.86 ; disability : adjusted OR=1.49 ; 95 % CI=1.20 , 1.85 ) . Cross-sectional associations were much stronger than the longitudinal associations , suggesting bias in the former due to selection factors and /or temporal ambiguity . The longitudinal findings suggest that pain/disability and psychological distress may be causes and consequences of each other , although the associations are small" ]

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[ "Comparison of general exercise, motor control exercise and spinal manipulative therapy for chronic low back pain: A randomized trial", "Preliminary development of a clinical prediction rule for determining which patients with low back pain will respond to a stabilization exercise program.", "The PEDro scale is a valid measure of the methodological quality of clinical trials: a demographic study.", "Pilates Exercise or Stationary Cycling for Chronic Nonspecific Low Back Pain: Does it Matter? A Randomized Controlled Trial With 6-Month Follow-up", "Motor Control Exercises, Sling Exercises, and General Exercises for Patients With Chronic Low Back Pain: A Randomized Controlled Trial With 1-Year Follow-up", "Effects of Pilates and trunk strengthening exercises on health-related quality of life in women with chronic low back pain.", "Graded Exercise for Recurrent Low-Back Pain: A Randomized, Controlled Trial With 6-, 12-, and 36-Month Follow-ups", "The effect of motor control and tactile acuity training on patients with non-specific low back pain and movement control impairment.", "Stabilizing training compared with manual treatment in sub-acute and chronic low-back pain.", "Effectiveness and Cost-Effectiveness of Three Types of Physiotherapy Used to Reduce Chronic Low Back Pain Disability: A Pragmatic Randomized Trial With Economic Evaluation", "Effects of assisted sit-up exercise compared to core stabilization exercise on patients with non-specific low back pain: A randomized controlled trial.", "[Inpatient multimodal pain therapy : Additive value of neuromuscular core stability exercises for chronic back pain]." ]

[ "Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain", "OBJECTIVE To develop a clinical prediction rule to predict treatment response to a stabilization exercise program for patients with low back pain ( LBP ) . DESIGN A prospect i ve , cohort study of patients with nonradicular LBP referred to physical therapy ( PT ) . SETTING Outpatient PT clinics . PARTICIPANTS Fifty-four patients with nonradicular LBP . INTERVENTION A st and ardized stabilization exercise program . MAIN OUTCOME MEASURE Treatment response ( success or failure ) was categorized based on changes in the Oswestry Disability Question naire scores after 8 weeks . RESULTS Eighteen subjects were categorized as treatment successes , 15 as treatment failures , and 21 as somewhat improved . After using regression analyses to determine the association between st and ardized examination variables and treatment response status , preliminary clinical prediction rules were developed for predicting success ( positive likelihood ratio [ LR ] , 4.0 ) and failure ( negative LR , .18 ) . The most important variables were age , straight-leg raise , prone instability test , aberrant motions , lumbar hypermobility , and fear-avoidance beliefs . CONCLUSIONS It appears that the response to a stabilization exercise program in patients with LBP can be predicted from variables collected from the clinical examination . The prediction rules could be used to determine whether patients with LBP are likely to benefit from stabilization exercises", "QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis", "Study Design . R and omized controlled trial . Objective . This is the companion study to a previous publication that presented 8-week pain , disability , and trunk muscle motor control results . The objective of this study was to compare the effect of 8 weeks of specific trunk exercises and stationary cycling on outcomes measures of catastrophizing and fear-avoidance beliefs ( FAB ) in patients with chronic nonspecific low back pain , and provide 6-month outcome data for all self-report measures . Summary of Background Data . It is thought that any form of moderate-to-vigorous physical activity is sufficient to address catastrophizing and FAB , and concomitant levels of pain and disability . Methods . Sixty-four patients with low back pain were r and omly assigned to 8 weeks of specific trunk exercise group ( SEG ) , or stationary cycling group ( CEG ) . Self-rated pain , disability , catastrophizing and FAB scores were collected before , immediately after ( 8 wk ) , and 6 months after the training program . Clinical ly meaningful improvements were defined as greater than a 30 % reduction from baseline in pain and disability scores . “ Intention-to-treat ” principles were used for missing data . Per- protocol analysis was performed on participants who attended at least two-thirds of the exercise sessions . Results . At 8 weeks , disability was significantly lower in the SEG compared with the CEG ( d = 0.62 , P = 0.018 ) . Pain was reduced from baseline in both the groups after training ( P < 0.05 ) , but was lower for the SEG ( P < 0.05 ) . FAB scores were reduced in the SEG at 8 weeks , and in the CEG at 6 months . No between-group differences in FAB scores were observed . Similar reductions in catastrophizing in each group were observed at each time point . At 6 months , the overall data pattern suggested no long-term difference between groups . Per- protocol analysis of clinical ly meaningful improvements suggests no between-group differences for how many patients are likely to report improvement . Conclusion . Inferential statistics suggest greater improvements at 8 weeks , but not 6 months , for the SEG . Inspection of clinical ly meaningful changes based on a minimum level of adherence suggests no between-group differences . If a patient with low back pain adheres to either specific trunk exercises or stationary cycling , it is reasonable to think that similar improvements will be achieved . Level of Evidence :", "Background Exercise benefits patients with chronic nonspecific low back pain ; however , the most effective type of exercise remains unknown . Objective This study compared outcomes after motor control exercises , sling exercises , and general exercises for low back pain . Design This was a r and omized controlled trial with a 1-year follow-up . Setting The study was conducted in a primary care setting in Norway . Patients The participants were patients with chronic nonspecific low back pain ( n=109 ) . Interventions The interventions in this study were low-load motor control exercises , high-load sling exercises , or general exercises , all delivered by experienced physical therapists , once a week for 8 weeks . Measurements The primary outcome measure was pain reported on the Numeric Pain Rating Scale after treatment and at a 1-year follow-up . Secondary outcome measures were self-reported activity limitation ( assessed with the Oswestry Disability Index ) , clinical ly examined function ( assessed with the Fingertip-to-Floor Test ) , and fear-avoidance beliefs after intervention . Results The postintervention assessment showed no significant differences among groups with respect to pain ( overall group difference ) or any of the outcome measures . Mean ( 95 % confidence interval ) group differences for pain reduction after treatment and after 1 year were 0.3 ( −0.7 to 1.3 ) and 0.4 ( −0.7 to 1.4 ) for motor control exercises versus sling exercises , 0.7 ( −0.6 to 2.0 ) and 0.3 ( −0.8 to 1.4 ) for sling exercises versus general exercises , and 1.0 ( −0.1 to 2.0 ) and 0.7 ( −0.3 to 1.7 ) for motor control exercises versus general exercises . Limitations The nature of the interventions made blinding impossible . Conclusions This study gave no evidence that 8 treatments with individually instructed motor control exercises or sling exercises were superior to general exercises for chronic low back pain", "BACKGROUND Pilates programs are widely used as a form of regular exercise in a broad range of population s investigating their effectiveness for chronic low back pain ( CLBP ) treatment . OBJECTIVE The aim of this study was to compare the effects of a Pilates program and a trunk strengthening exercise program on functional disability and health-related quality of life ( HRQOL ) in women with nonspecific CLBP . METHODS A total of 101 volunteer women with CLBP provided data with a 3-month follow-up . They were r and omized to either a Pilates ( n= 37 ) , trunk strengthening exercise ( n= 36 ) or a control group ( n= 28 ) , exercising for a period of 8 weeks , three times a week . Data were collected on HRQOL using the Short-Form 36 Health Survey ( SF-36v2 ) , and functional disability using the Rol and Morris Disability Question naire prior to program initiation , mid-intervention , immediately after program termination , and three months post-intervention . RESULTS The Pilates participants reported greater improvements on self-reported functional disability and HRQOL compared with participants in the trunk strengthening exercise and control groups ( p < 0.05 ) . The effects were retained for a period of three months after program termination for the Pilates group and to a lesser extent for the trunk strengthening exercise group . CONCLUSIONS An 8-week Pilates program improved HRQOL and reduced functional disability more than either a trunk strengthening exercise program or controls among women with CLBP", "Study Design . The study was a r and omized controlled trial . Treatment was for 8 weeks , with follow-up posttreatment and at 6- , 12- , and 36- months . Objective . The purpose was to evaluate the effect of a grade d exercise intervention emphasizing stabilizing exercises in patients with nonspecific , recurrent low back pain ( LBP ) . Summary of Background Data . Exercise therapy is recommended and widely used as treatment for LBP . Although stabilizing exercises are reportedly effective in the management of certain subgroups of LBP , such intervention protocol s have not yet been evaluated in relation to a more general exercise regimen in patients with recurrent LBP , all at work . Methods . Seventy-one patients recruited consecutively ( 36 men , 35 women ) with recurrent nonspecific LBP seeking care at an outpatient physiotherapy clinic were r and omized into 2 treatment groups ; grade d exercise intervention or daily walks . The primary outcome was perceived disability and pain at 12-month follow-up . Secondary outcomes included physical health , fear-avoidance , and self-efficacy beliefs . Results . Of the participants , 83 % provided data at the 12-month follow-up and 79 % at 36 months . At 12 months , between-group comparison showed a reduction in perceived disability in favor of the exercise group , whereas such an effect for pain emerged only immediately postintervention . Ratings of physical health and self-efficacy beliefs also improved in the exercise group over the long term , though no changes were observed for fear-avoidance beliefs . Conclusion . A grade d exercise intervention , emphasizing stabilizing exercises , for patients with recurrent LBP still at work seems more effective in improving disability and health parameters than daily walks do . However , no such positive results emerged for improvement regarding pain over a longer term , or for fear-avoidance beliefs", "BACKGROUND Movement control impairment is a clinical subgroup of non-specific low back pain which can be assessed reliably . There is a strong correlation between tactile acuity and movement control suggesting these two treatments might have additive effects . The first research aim was to determine if patients with a motor control impairment demonstrated improvement in outcome with combined tactile acuity and motor control training . The second aim was to determine if tactile acuity training enhanced the effect of motor control training . METHOD The primary study was a single-arm cohort study conducted in three physiotherapy practice s in the German-speaking part of Switzerl and . 40 patients ( 23 males and 17 females ) suffering from non-specific low back pain ( NSLBP ) and movement control impairment were treated . Patients were assessed at baseline and immediately post treatment . Treatment included exercises to lumbopelvic control and graphesthesia training to improve tactile acuity . Treatment effects were evaluated using the Rol and Morris disability question naire ( RMQ ) and the patient-specific functional scale ( PSFS ) . The performance on a set of six movement control tests and lumbar two-point discrimination were also assessed . The results of this cohort study were compared with a historic control group which was comparable with the primary study but included only motor control exercises . RESULTS All the outcomes improved significantly with the combined training ( RMQ - 2.2 pts . , PSFS - 2.8 pts . ; MCTB - 2.02 pts . & TPD - 17.07 mm ; all p < 0.05 ) . In comparison to the outcomes of the historic control , there was no significant differences in movement control , patient-specific functional complaints or disability between the groups . CONCLUSIONS The results of this study , based on a before and after intervention comparison , showed that outcome improved significantly following combined tactile acuity and motor control training . However , compared to an earlier study , the tactile acuity training did not have an additional effect to the results . The use of historical controls does not control for allocation bias and the results obtained here require verification in a r and omized controlled trial", "The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain ( LBP ) . Forty-seven patients were r and omized to a stabilizing training group ( ST group ) or a manual treatment group ( MT group ) . The patients underwent a 6-week treatment programme on a weekly basis . Pain , health and functional disability level at the start of treatment , after treatment , and at 3- and 12-month follow-ups were assessed . In the ST group all assessed variables improved significantly ( P<0.05 ) after the treatment period and were maintained long term . After the treatment period there was a significant difference between the groups in assessed function ( P<0.05 ) . More individuals in the ST group had improved than in the MT group . At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain , general health and functional disability levels . In the long term , significantly more ( P<0.05 ) patients in the MT group reported recurrent treatment periods . The study did not indicate any clear short-term differences between the groups in the accessed outcome measures . In the long term , however , stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods", "Study Design . Pragmatic , r and omized , assessor blinded , clinical trial with economic analysis . Objective . To compare the effectiveness and cost-effectiveness of three kinds of physiotherapy commonly used to reduce disability in chronic low back pain . Summary of Background Data . Physiotherapy reduces disability in chronic back pain , but there are several forms of physiotherapy and it is unclear which is most effective or cost effective . Methods . A total of 212 patients referred to physiotherapy with chronic low back pain were r and omized to receive usual outpatient physiotherapy , spinal stabilization classes , or physiotherapist-led pain management classes . Primary outcome was Rol and Disability Question naire score 18 months from baseline ; secondary measures were pain , health-related quality of life , and time off work . Healthcare costs associated with low back pain and quality -adjusted life years ( QALYs ) were also measured . Results . A total of 71 participants were assigned to usual outpatient physiotherapy , 72 to spinal stabilization , and 69 to physiotherapist-led pain management . A total of 160 ( 75 % ) provided follow-up data at 18 months , showing similar improvements with all interventions : mean ( 95 % confidence intervals ) Rol and Disability Question naire score improved from 11.1 ( 9.6–12.6 ) to 6.9 ( 5.3–8.4 ) with usual outpatient physiotherapy , 12.8 ( 11.4−14.2 ) to 6.8 ( 4.9–8.6 ) with spinal stabilization , and 11.5 ( 9.8–13.1 ) to 6.5 ( 4.5–8.6 ) following pain management classes . Pain , quality of life , and time off work also improved within all groups with no between-group differences . Mean ( SD ) healthcare costs and QALY gain were £ 474 ( 840 ) and 0.99 ( 0.27 ) for individual physiotherapy , £ 379 ( 1040 ) and 0.90 ( 0.37 ) for spinal stabilization , and £ 165 ( 202 ) and 1.00 ( 0.28 ) for pain management . Conclusions . For chronic low back pain , all three physiotherapy regimens improved disability and other relevant health outcomes , regardless of their content . Physiotherapist-led pain management classes offer a cost-effective alternative to usual outpatient physiotherapy and are associated with less healthcare use . A more widespread adoption of physiotherapist-led pain management could result in considerable cost savings for healthcare providers", "BACKGROUND Traditional sit-up exercise is a simple method to strengthen core muscles . However , it can increase the potential of lumbar spine injury during the bending process . OBJECTIVE To evaluate the effect of assisted sit-up exercise ( SUE ) using a new training device , HubEX-LEX ® , on strengthening core muscles and improving non-specific low back pain ( NSLBP ) compared to conventional core stabilization exercise ( CSE ) . METHODS Subjects with chronic NSLBP were r and omly divided into two groups : SUE ( n= 18 ) or CSE ( n= 18 ) . They participated in 12 sessions of the exercise program . Before and after the training , thickness and activity of core muscles were measured using ultrasonogram and surface electromyography respectively . Pain and disability were assessed using two question naires . RESULTS Thickness ratios ( contracted/rest ) of rectus abdominis and external oblique in the SUE group and those of transversus abdominis in the CSE group showed statistically significant difference between before and after exercise ( p < 0.05 ) . The ratio of activation of internal oblique relative to rectus abdominis and all measurements for pain and disability showed statistically significant improvement in both groups ( p < 0.05 ) . CONCLUSIONS Assisted SUE using new training device can be an effective therapeutic exercise to strengthen dynamic abdominal muscles and improve core muscle activation pattern in NSLBP patients", "INTRODUCTION The medical and healthcare economic burden caused by chronic lumbar back pain ( CLBP ) requires the use of interdisciplinary treatment approaches . The present study aim ed to evaluate whether the effectiveness of inpatient multimodal pain therapy ( MPT , operations and procedures ( OPS ) coding 8 - 918.02 ) , can be increased by implementing additional neuromuscular core stability exercises ( NCSE ) . MATERIAL AND METHODS As part of a prospect i ve controlled study , subjects with CLBP ( n = 48 , 17 males , 58.2 ± 11.7 years ) were allocated to one of two groups . One group received st and ard care ( SC , n = 23 ) encompassing manual , pharmacological and psychological therapy in addition to passive physiotherapeutic applications . The intervention group ( IG , n = 25 ) additionally completed NCSE . On the day of admission and on discharge as well as 1 and 6 weeks after inpatient care , pain intensity ( numeric rating scale ) , pain-related routine daily functions ( Oswestry disability index ) , well-being ( SF-12 Health Survey ) and motor function parameters ( trunk strength , endurance and postural control ) were assessed . Data analysis was performed using statistical inference methods . In addition , effect sizes ( Cohen 's d ) of intergroup differences were calculated . RESULTS Both groups showed significant reductions in pain intensity ( p < 0.05 , d > 0.6 ) at all measurement points ( MP ) . Physical well-being and disability ( p < 0.05 , d > 0.6 ) were improved 1 week after discharge in the intervention group only . Overall , no systematic differences between groups were detected ( p > 0.05 ) . In relation to the motor outcomes , no significant changes over time nor between groups were verified ( p > 0.05 ) . DISCUSSION Despite the use of an additional NCSE , no significant added value in individuals with CLBP could be detected , although a systematic pre-post effect in daily functions and physical well-being ( one week after discharge ) was observed for the IG only . Therefore , on the basis of the study results , the implementation of additional NCSE into the inpatient MPT can not be clearly recommended . To further delineate the therapeutic relevance , studies with larger sample sizes are needed" ]

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[ "Frequency of Inappropriate Medication Prescription in Hospitalized Elderly Patients in Italy", "Potentially inappropriate medication related to weakness in older acute medical patients", "Adverse drug events in patients with advanced chronic conditions who have a prognosis of limited life expectancy at hospital admission", "Potentially inappropriate drug use among hospitalised older adults: results from the CRIME study.", "Inappropriate prescribing in hospitalised Australian elderly as determined by the STOPP criteria", "Development of an intervention to improve appropriate polypharmacy in older people in primary care using a theory-based method", "STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers' criteria.", "Excessive polypharmacy and survival in polypathological patients", "Inappropriate prescribing to the oldest old patients admitted to hospital: prevalence, most frequently used medicines, and associated factors", "Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients.", "Potentially inappropriate prescribing including under-use amongst older patients with cognitive or psychiatric co-morbidities.", "Potentially inappropriate medications and functional decline in elderly hospitalized patients.", "Potentially inappropriate medications and adverse drug effects in elders in the ED.", "Frequency of potentially inappropriate prescriptions in older people at discharge according to Beers and STOPP criteria", "Does dementia predict adverse hospitalization outcomes? A prospective study in aged inpatients.", "Epidemiology of potentially inappropriate medication use in elderly patients in Japanese acute care hospitals.", "Polypharmacy among inpatients aged 70 years or older in Australia.", "Potentially inappropriate medications in elderly Japanese patients: effects of pharmacists’ assessment and intervention based on Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions criteria ver.2", "Assessing Care of Vulnerable Elders: ACOVE Project Overview", "Inappropriate prescribing in elderly people with diabetes admitted to hospital.", "Potentially Inappropriate Use of Psychotropic Medications in Hospitalized Elderly Patients in France" ]

[ "Background Older people often need comprehensive treatment , including many medications , and polypharmacy is common . The aims of this cross-sectional investigation were to examine the potentially inappropriate medication during the hospitalization and to identify the factors that may influence such inappropriateness among elderly in Italy . Methods A sample of 605 individuals aged 65 years and older admitted in non-academic public acute care hospitals was r and omly selected . Prescription of inappropriate medications were evaluated during the period from the day of admission to a r and omly preselected day ( index day ) . Beers Criteria were used to evaluate appropriateness . Results At least one potentially inappropriate medication prescription from the day of hospital admission to the index day has been observed in 188 patients ( 31.1 % ) , and respectively 84.1 % and 15.9 % of them had received one or two inappropriate medications . A total of 15 medications was prescribed inappropriately to these 188 patients , for 215 times with a total of 1143 doses . The multivariate logistic regression analysis revealed that the significant predictors for having at least one potentially inappropriate medication prescription during the hospitalization were : patients having an elementary education level , a lower pre-admission performance-based measure of basic activities of daily living , having received an inappropriate drug before the hospitalization , a hospital stay in the general and in the specialties surgical wards , a longer length of hospital stay from the admission to the index day , and having received a higher number of drugs from the day of the hospital admission to the index day . The most prevalent inappropriate medications administered were ketorolac ( 27.4 % ) , amiodarone ( 19.1 % ) , and clonidine ( 11.2 % ) . Conclusions This study supports the need for clinical guidelines implementation to assist physicians in choosing the most appropriate drugs for the elderly and for effective education of all physicians", "Background The use of potentially inappropriate medications ( PIMs ) is common in the older population . Inappropriate medications as well as polypharmacy expose older people to a greater risk of adverse drug reactions and may result in hospitalizations . Objective To evaluate the prevalence of PIMs among acutely hospitalized patients aged ≥65 years in an acute medical unit , and to investigate the relationship between use of PIMs and weakness . Setting This longitudinal observational study was undertaken in the Acute Medical Unit , Hvidovre Hospital , University of Copenhagen , Denmark . Method Patients aged ≥65 years admitted to the acute medical unit during the period October to December 2011 were included . Patients were interviewed at admission and at a follow-up visit 30 days after discharge . Data included information about medications , social status , functional status , cognitive status , h and grip strength , health-related quality of life , visual acuity , days of hospitalization , and comorbidities , and was prospect ively collected . Polypharmacy was defined as regular use of 5 or more drugs . The Charlson Comorbidity Index was used to categorize comorbidities . Main outcome measure The prevalence of PIMs and the association with PIMs and functional status h and grip strength , HRQOL , comorbidities , social demographic data and vision . Results Seventy-one patients ( 55 % men ) with a median age of 78.7 years participated . The median number of medications was eight per person . Eighty percent were exposed to polypharmacy . PIMs were used by 85 % of patients , and PIMs were associated with low functional status ( p = 0.032 ) , low h and grip strength ( p = 0.006 ) , and reduced health-related quality of life ( p = 0.005 ) , but not comorbidities ( p = 0.63 ) , age ( p = 0.60 ) , sex ( p = 0.53 ) , education ( p = 0.94 ) , cognition ( p = 0.10 ) , pain ( p = 0.46 ) , or visual acuity ( p = 0.55 ) . Conclusions Use of PIMs was very common among older people admitted to an acute medical unit . The use of PIMs is associated with low functional status , low h and grip strength , and reduced health-related quality of life", "Purpose Adverse drug events ( ADEs ) lead to adverse clinical outcomes such as hospitalization . There is little information about the characteristics of ADEs in patients with advanced chronic conditions and have a prognosis of limited life expectancy . This study aim ed to evaluate ( i ) the prevalence of ADEs at the time of admission to hospital , ( ii ) the causality , severity , and preventability of the ADEs , and ( iii ) the clinical and pharmacological characteristics associated with the ADEs . Methods This is a prospect i ve cross-sectional study ( county of Osona , Catalonia , Spain ) . We included patients who required palliative care as identified by the NECPAL CCOMS-ICO tool who were hospitalized in an acute geriatric unit ( AGU ) . A system of alerts ( trigger tool ) was used together with a multidisciplinary review for the detection of the ADEs . Results Over the course of 10 months , 235 patients were recruited . Seventy-six ADEs affecting 24.68 % of the sample were identified , and of these , 23 ( 30.26 % of the ADEs ; 8.51 % of the sample ) were directly related to hospitalization . The multivariate logistic regression analysis identified the following risk factors : presence of extreme polypharmacy ( ≥10 medications ) ( OR = 3.02 ; 95 % CI = 1.48–6.19 ) , anticholinergic burden according to the Anticholinergic Drug Scale ( ADS ) ( OR = 2.32 ; 95 % CI = 1.13–4.78 ) , and treatment complexity according to the Medication Regimen Complexity Index ( MRCI ) scale ( OR = 2.90 ; 95 % CI = 1.44–5.83 ) . The vast majority ( 94.45 % ) of the ADEs were considered to be preventable . There were no differences in the survival of the patients . Conclusions ADEs are common , largely preventable , and implicated in the hospitalization of patients who require palliative care", "BACKGROUND Beers criteria and screening tool of older person 's prescriptions ( STOPP ) criteria are widely used to assess potentially inappropriate drug use ( PIDU ) . OBJECTIVE the aims of the present study are ( i ) to assess the prevalence of PIDU based on 2012 Beers criteria and STOPP criteria and ( ii ) to determine the impact of PIDU , as defined by these criteria , on health outcomes among older in-hospital patients . DESIGN prospect i ve observational study . SETTING AND SUBJECTS a total of 871 in-hospital patients participating to the CRIteria to Assess Appropriate Medication Use among Elderly Complex Patients project . METHODS outcome measures were ( i ) adverse drug reactions ( ADR ) ; ( ii ) decline in functional status ; ( iii ) combined outcome ( ADR or declined in functional status ) . RESULTS the prevalence of PIDU was 58.4 % applying Beers criteria , 50.4 % applying STOPP criteria and 75.0 % combining both sets of criteria . PIDU defined based on STOPP criteria was significantly associated with ADR [ odds ratio ( OR ) 2.36 ; 95 % confidence interval ( CI ) 1.10 - 5.06 ] , and decline in physical function ( OR : 2.00 ; 95 % CI : 1.10 - 3.64 ) , while , despite a positive trend , no significant association was observed for Beers criteria or the combination of both criteria . The combined outcome was significantly associated with PIDU defined based on Beers ( OR : 1.74 ; 95 % CI : 1.06 - 2.85 ) , STOPP criteria ( OR : 2.14 ; 95 % CI : 1.32 - 3.47 ) or both ( OR 2.02 ; 95 % CI : 1.06 - 3.84 ) . CONCLUSIONS PIDU is common in hospitalised older adults and the combination of Beers and STOPP criteria might lead to the identification of a larger number of cases of PIDU than the application of a single set of criteria . STOPP criteria significantly predict all in-hospital outcomes considered , while Beers criteria were significantly associated with the combined outcome only", "Background The elderly population is increasing worldwide . Due to age-related physiological changes that affect the pharmacokinetics and pharmacodynamics of drugs , the elderly are predisposed to adverse drug reactions . Prescribing of potentially inappropriate medications ( PIMs ) has been found to be prevalent among the elderly and PIM use has been associated with hospitalisations and mortality . Objectives This study aims to identify the prevalence and nature of pre-admission inappropriate prescribing by using the STOPP ( screening tool of older people ’s prescriptions ) criteria amongst a sample of hospitalised elderly in patients in South Australia . Setting Medical , surgical and rehabilitation wards of a public teaching hospital in Adelaide , South Australia . Main outcome measure Pre-admission prevalence of PIM . Method Medication management plans of 100 patients of ≥65 years old were prospect ively studied to determine the prevalence of pre-admission PIM use . Sixty-five criteria of STOPP were applied to identify PIMs . Results The total number of pre-admission medications screened during the study period was 949 ; the median number of medicines per patient was nine ( range 2–28 ) . Overall the STOPP criteria identified 138 PIMs in 60 % of patients . The most frequently encountered PIM was opiates prescribed in patients with recurrent falls ( 12.3 % ) , followed by benzodiazepines in fallers ( 10.1 % ) and proton pump inhibitors when prescribed for peptic ulcer disease for long-term at maximum doses ( 9.4 % ) . The number of medications were found to have a positive correlation with pre-admission PIM use ( rs = 0.49 , P < 0.01 ) . Conclusions Pre-admission PIM use is highly prevalent among the studied population . Strategies to reduce PIM use should be undertaken by physicians and pharmacists . The use of the STOPP criteria in clinical practice to reduce prescriptions of inappropriate medications requires further investigation", "Background It is advocated that interventions to improve clinical practice should be developed using a systematic approach and intervention development methods should be reported . However , previous interventions aim ed at ensuring that older people receive appropriate polypharmacy have lacked details on their development . This study formed part of a multiphase research project which aim ed to develop an intervention to improve appropriate polypharmacy in older people in primary care . Methods The target behaviours for the intervention were prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners ( GPs ) and community pharmacists . Intervention development followed a systematic approach , including previous mapping of behaviour change techniques ( BCTs ) to key domains from the Theoretical Domains Framework that were perceived by GPs and pharmacists to influence the target behaviours . Draft interventions were developed to operationalise selected BCTs through team discussion . Selection of an intervention for feasibility testing was guided by a subset of the APEASE ( Affordability , Practicability , Effectiveness/cost-effectiveness , Acceptability , Side-effects/safety , Equity ) criteria . Results Three draft interventions comprising selected BCTs were developed , targeting patients , pharmacists and GPs , respectively . Following assessment of each intervention using a subset of the APEASE criteria ( affordability , practicability , acceptability ) , the GP-targeted intervention was selected for feasibility testing . This intervention will involve a demonstration of the behaviour and will be delivered as an online video . The video demonstrating how GPs can prescribe appropriate polypharmacy during a typical consultation with an older patient will also demonstrate salience of consequences ( feedback emphasising the positive outcomes of performing the behaviour ) . Action plans and prompts/cues will be used as complementary intervention components . The intervention is design ed to facilitate the prescribing of appropriate polypharmacy in routine practice . Conclusion A GP-targeted intervention to improve appropriate polypharmacy in older people has been developed using a systematic approach . Intervention content has been specified using an established taxonomy of BCTs and selected to maximise feasibility . The results of a future feasibility study will help to determine if the theory-based intervention requires further refinement before progressing to a larger scale r and omised evaluation", "INTRODUCTION STOPP ( Screening Tool of Older Persons ' potentially inappropriate Prescriptions ) is a new , systems-defined medicine review tool . We compared the performance of STOPP to that of established Beers ' criteria in detecting potentially inappropriate medicines ( PIMs ) and related adverse drug events ( ADEs ) in older patients presenting for hospital admission . METHODS we prospect ively studied 715 consecutive acute admissions to a university teaching hospital . Diagnoses , reason for admission and concurrent medications were recorded . STOPP and Beers ' criteria were applied . PIMs with clear causal connection or contribution to the principal reason for admission were determined . RESULTS median patient age ( interquartile range ) was 77 ( 72 - 82 ) years . Median number of prescription medicines was 6 ( range 0 - 21 ) . STOPP identified 336 PIMs affecting 247 patients ( 35 % ) , of whom one-third ( n = 82 ) presented with an associated ADE . Beers ' criteria identified 226 PIMs affecting 177 patients ( 25 % ) , of whom 43 presented with an associated ADE . STOPP-related PIMs contributed to 11.5 % of all admissions . Beers ' criteria -related PIMs contributed to significantly fewer admissions ( 6 % ) . CONCLUSION STOPP criteria identified a significantly higher proportion of patients requiring hospitalisation as a result of PIM-related adverse events than Beers ' criteria . This finding has significant implication s for hospital geriatric practice", "Purpose The purpose of this study was to determine whether excessive polypharmacy is associated with a higher survival rate in polypathological patients . Patients and methods An observational , prospect i ve , and multicenter study was carried out on those polypathological patients admitted to the internal medicine and acute geriatrics departments between March 1 and June 30 , 2011 . For each patient , data concerning age , sex , comorbidity , Barthel and Lawton-Brody indexes , Pfeiffer ’s question naire , socio-familial Gijon scale , delirium , number of drugs , and number of admissions during the previous year were gathered , and the PROFUND index was calculated . Polypharmacy was defined as the use of ≥5 drugs and excessive polypharmacy as the use of ≥10 . A 1-year long follow-up was carried out . A logistic regression model was performed to analyze the association of variables with excessive polypharmacy and a Cox proportional hazard model to determine the association between polypharmacy and survival . Results We included 457 polypathological patients . Mean age was 81.0 ( 8.8 ) years and 54.5 % were women . The mean number of drugs used was 8.2 ( 3.4 ) . Excessive polypharmacy was directly associated with heart disease [ hazard ratio ( HR ) 2.33 95 % CI 1.40–3.87 ; p = 0.001 ] , respiratory disease [ HR 1.87 95 % CI 1.13–3.09 ; p = 0.01 ] , peripheral artery disease/diabetes with retinopathy and /or neuropathy [ HR 2.02 95 % CI 1.17–3.50 ; p = 0.01 ] , and the number of admissions during the previous year [ HR 1.21 96 % CI 1.01–1.44 ; p = 0.04 ] . It was inversely associated with delirium [ HR 0.48 95 % CI 0.25–0.91 ; p = 0.02 ] . There were no statistical differences regarding the probability of 1-year survival between patients with no polypharmacy , with simple polypharmacy , and with excessive polypharmacy ( 0.66 , 0.60 , and 0.57 , respectively , p = 0.12 ) . Conclusions A greater use of drugs may not be harmful but is also not associated with a higher probability of survival in polypathological patients", "Background Scientific evidence on treatments of chronic diseases in patients 85 years old or older is very limited , as is available information on inappropriate prescription ( IP ) and its associated factors . The study aim ed to describe medicine prescription , potentially inappropriate medicines ( PIM ) and potentially prescribing omissions ( PPO ) and their associated factors on this population . Methods In the context of an observational , prospect i ve and multicentric study carried out in elderly patients admitted to seven Spanish hospitals for a year , a sub- analysis of those aged 85 years and over was performed . To assess PIMs , the Beers and STOPP criteria were used , and to assess PPOs , the START and the ACOVE-3 criteria were used . To assess factors associated with IP , a multivariate logistic regression analysis was performed . Patients were selected r and omly every week on consecutive days from the hospitalization lists . Results A total of 336 patients were included in the sub- analysis with a median ( Q1-Q3 ) age of 88 ( 86–90 ) years . The median medicines taken during the month prior to admission was 10 ( 7–13 ) . Forty-seven point two per cent of patients had at least one Beers-listed PIM , 63.3 % at least one STOPP-listed PIM , 53.6 % at least one START-listed PPO , and 59.4 % at least one ACOVE-3-listed PPO . Use of benzodiazepines in patients who are prone to falls ( 18.3 % ) and omission of calcium and vitamin D supplements in patients with osteoporosis ( 13.3 % ) were the most common PIM and PPO , respectively . The main factor associated with the Beers-listed and the STOPP-listed PIM was consumption of 10 or more medicines ( OR = 5.7 , 95 % CI 1.8 - 17.9 and OR = 13.4 , 95 % CI 4.0 - 44.0 , respectively ) . The main factors associated with the START-listed PPO was a non-community dwelling origin ( OR 2.3 , 95 % CI 1.0 - 5.0 ) , and multimorbidity ( OR1.8 , 95 % CI 1.0 - 3.1 ) . Conclusions Prescribed medicines and PIM and PPO prevalence were high among patients 85 years and over . Benzodiazepine use in those who are prone to falls and omission of calcium and vitamin D in those with osteoporosis were the most frequent PIM and PPO , respectively . Factors associated with PIM and PPO differed with polypharmacy being the most important factor associated with PIM", "BACKGROUND Previous studies have not demonstrated a consistent association between potentially inappropriate medicines ( PIMs ) in older patients as defined by Beers criteria and avoidable adverse drug events ( ADEs ) . This study aim ed to assess whether PIMs defined by new STOPP ( Screening Tool of Older Persons ' potentially inappropriate Prescriptions ) criteria are significantly associated with ADEs in older people with acute illness . METHODS We prospect ively studied 600 consecutive patients 65 years or older who were admitted with acute illness to a university teaching hospital over a 4-month interval . Potentially inappropriate medicines were defined by both Beers and STOPP criteria . Adverse drug events were defined by World Health Organization-Uppsala Monitoring Centre criteria and verified by a local expert consensus panel , which also assessed whether ADEs were causal or contributory to current hospitalization . Hallas criteria defined ADE avoidability . We compared the proportions of patients taking Beers criteria PIMs and STOPP criteria PIMs with avoidable ADEs that were causal or contributory to admission . RESULTS A total of 329 ADEs were detected in 158 of 600 patients ( 26.3 % ) ; 219 of 329 ADEs ( 66.6 % ) were considered causal or contributory to admission . Of the 219 ADEs , 151 ( 68.9 % ) considered causal or contributory to admission were avoidable or potentially avoidable . After adjusting for age , sex , comorbidity , dementia , baseline activities of daily living function , and number of medications , the likelihood of a serious avoidable ADE increased significantly when STOPP PIMs were prescribed ( odds ratio , 1.847 ; 95 % confidence interval [ CI ] , 1.506 - 2.264 ; P < .001 ) ; prescription of Beers criteria PIMs did not significantly increase ADE risk ( odds ratio , 1.276 ; 95 % CI , 0.945 - 1.722 ; P = .11 ) . CONCLUSION STOPP criteria PIMs , unlike Beers criteria PIMs , are significantly associated with avoidable ADEs in older people that cause or contribute to urgent hospitalization", "OBJECTIVE the study aim ed to determine the prevalence of and risk factors for inappropriate prescribing ( IP ) and prescribing omission ( PO ) in elderly with mental co-morbidities . PARTICIPANTS One hundred fifty consecutive in patients with mental co-morbidities hospitalised for acute medical illness ( mean age 80 + /- 9 , 70 % of women ) were considered for the study . MEASUREMENTS IP and PO were prospect ively identified according to STOPP/START criteria at hospital admission . RESULTS over 95 % were taking > or=1 medication ( median = 7 ) which amounted to 1,137 prescriptions . The prevalence of IP was 77 % and PO was 65 % . The most frequent encountered IP concerned drugs adversely affecting fallers ( 25 % ) and antiaggregants therapy without atherosclerosis ( 14 % ) . PO concerned antidepressants with moderate/severe depression ( 20 % ) and calcium-vitamin D supplementation ( 18 % ) . Independent predictors for IP were increased number of concomitant drugs ( odds ratio [ OR ] 1.54 , 95 % confidence interval [ CI ] 1.13 - 1.89 ) , being cognitively impaired ( OR 1.83 , 95 % CI 1.55 - 2.24 ) , and having fallen in the preceding 3 months ( OR 2.03 , 95 % CI 1.52 - 2.61 ) or hospitalised in the preceding year ( OR 1.09 , 95 % CI 1.02 - 1.23 ) . Concerning PO , psychiatric disorder ( OR 1.64 , 95 % CI 1.42 - 2.01 ) and increase level of co-morbidities ( OR 1.79 , 95 % CI 1.48 - 1.99 ) were identified . Living in an institutional setting was a predictive maker for both IP ( OR 1.45 , 95 % CI 1.27 - 1.74 ) and PO ( OR 1.67 , 95 % CI 1.32 - 1.91 ) . CONCLUSION IP and PO were highly prevalent raising the need of a greater health literacy concerning geriatric conditions in non-geriatrician practitioners who care elderly as well as in the community , in hospital and institutional setting s for improving quality and safety in prescribing medication", "OBJECTIVES To verify whether the use of potentially inappropriate medications ( PIMs ) is associated with loss of independence in elderly in- patients by promoting adverse drug reactions ( ADRs ) . DESIGN Prospect i ve observational study . PARTICIPANTS Five hundred six patients aged 65 and older admitted to 11 acute care medical wards . MEASUREMENTS In-hospital loss of one or more activities of daily living ( ADLs ) and three or more ADLs . PIMs were identified according to diagnosis-independent Beers criteria and ascertained by study physicians based on daily review of medical and nurse records . The relationship between risk factors and outcomes was assessed using logistic regression . RESULTS Overall , 104 patients ( 20.6 % ) were taking at least one PIM at the time of admission ( baseline users ) , and 49 ( 9.7 % ) were newly prescribed at least one PIM during their hospital stay . The loss of one or more ADLs occurred in 9.6 % of baseline users , 16.3 % of new users , and 8.5 % of nonusers ( P=.21 ) and that of three or more ADLs in 7.7 % of baseline users , 12.2 % of new users , and 4.8 % of nonusers ( P=.10 ) . The lack of association was confirmed after correction for potential confounders , including ADRs . The occurrence of ADRs was strongly associated with both outcomes ( odds ratio (OR)=7.80 , 95 % confidence interval (CI)=3.53 - 17.3 for the loss of > or = 1 ADLs ; OR=3.98 , 95 % CI=1.50 - 10.5 for the loss of > or =3 ADLs ) , but PIMs caused only six of 106 ADRs . CONCLUSIONS ADRs to any drugs more than the use of PIMs might be associated with functional decline in elderly hospitalized patients , but because the power of this study was too limited to definitively exclude a direct relationship between PIMs and functional decline , this merits further investigation", "The objective of this study was to examine the prevalence of potentially inappropriate medications ( PIMs ) and potential adverse drug effects ( ADEs ) in older adults presenting to the emergency department ( ED ) . This was a prospect i ve observational study of a convenience sample of adults 65 years and older presenting to the ED at an urban , tertiary care hospital . Potentially inappropriate medications were defined according to 2003 Beers criteria . Potential ADEs were defined as either ( 1 ) a potential drug-drug interaction , ( 2 ) alternative medication likely to cause toxicity or drug interactions , or ( 3 ) toxic doses of vitamins or minerals . Of 174 eligible patients , 124 were enrolled . The mean number of medications used per patient was 8.6 ( range , 0 - 20 ) . Thirty six patients ( 29 % , 95 % confidence interval , 27%-37 % ) presented to the ED with at least one PIM . Eight PIMs were prescribed in the ED , representing 16 % of all prescriptions in the ED . Potential ADEs meeting the defined criteria were found in 26.6 % of patients . A sub analysis of a r and om sample of charts revealed significant discordance between medication lists obtained by the research assistants and that of the health care providers . Older ED patients are at high risk for use of potentially inappropriate medications and ADEs . This problem may be magnified by inaccurate medication lists obtained by ED providers . A larger multicenter study may help to better define the scope of this problem", "Background Potentially inappropriate prescriptions ( PIP ) are frequent , generate negative outcomes , and are to a great extent avoidable . Although there is general agreement about the definition of PIP , how to measure them is a matter of debate . Objective Our aim was to measure the frequency of PIP in older people at hospital discharge using two sets of criteria —Beers ( 2012 up date ) and STOPP . Setting A University Hospital in southern Spain . Method This cross sectional study involved a r and om sample of patients 65 years or more discharged from the University Hospital San Cecilio ( Granada , Spain ) , from July 1 , 2011 to June 30 , 2012 . Age , gender , length of hospital stay , type of hospital service , drugs prescribed and pathologies were obtained from discharge reports . Main outcome measure The main outcome measures were : ( 1 ) the prevalence of PIP according to each set of criteria ( Beers and STOPP ) and its 95 % confidence interval , globally and stratified for different categories of the study variables ; ( 2 ) the degree of agreement between the two criteria using Kappa statistics ; and ( 3 ) the drugs most commonly involved in PIP according to both criteria . Results There were 624 patients ( median age 78 ) included in our study . According to Beers criteria , 22.9 % ( 19.6–26.2 % ) of the patients had at least one PIP . This figure was 38.4 % ( 34.6–42.2 % ) for STOPP criteria . Just 13.6 % of the patients had prescriptions simultaneously inappropriate for both criteria . Higher PIP frequency was observed in patients discharged from internal medicine . PIP increased with the Charlson Index and with the number of drugs prescribed , but not with gender , age or length of hospital stay . Conclusion A very high frequency of PIP at discharge was observed . By intervening in five drug groups , about 80 % of PIP might be avoided according to either of the two criteria", "BACKGROUND Dementia is often considered a predictor of adverse hospitalization outcomes . However , the relative contributions of dementia and other risk factors remain unclear . OBJECTIVE To assess , in a prospect i ve study , the relative value of dementia for predicting hospitalization outcomes , taking into account comorbidity , functional and nutritional status in 435 in patients ( age 85.3 + /- 6.7 ; 207 cognitively normal , 48 with mild cognitive impairment and 180 demented ) from the acute and rehabilitation geriatric hospital of Geneva . Hospitalization outcomes ( death in hospital , length of stay , institutionalisation and formal home care needs ) were predicted using logistic regression models with sociodemographic characteristics , cognitive status , comorbid Charlson index-CCI , functional and nutritional status as independent variables . RESULTS Moderate and severe dementia and poor physical function strongly predicted longer hospital stay , institutionalization and greater home care needs in univariate analyses . CCI was the best single predictor , with a four-fold difference in mortality rates between the highest and lowest scores . In multivariate analysis , the best predictor of institutionalisation was dementia , whereas the best predictor of death in hospital or longer hospital stay was higher comorbidity score , regardless of cognitive status . Functional status was the best predictor of greater home care needs . CONCLUSIONS Dementia in very old medically ill in patients was predictive only of discharge to a nursing home . Higher levels of comorbidity and poor functional status were more predictive than dementia for the other three hospitalization outcomes . Thus , comorbid medical conditions , functional and nutritional status should be considered , together with cognitive assessment , when predicting hospitalization outcome", "PURPOSE The elderly receive many medications which may have adverse effects . Little evidence is available about the epidemiology of potentially inappropriate medications being prescribed to the elderly in Japan as defined by the Beers criteria , or whether or not these medications result in harm when used in this population . METHODS We conducted a prospect i ve cohort study of patients aged ≥65 years who were admitted to three acute care hospitals in Japan . Trained research nurses followed up patients from r and omly selected wards and collected data about their medications and all potential adverse drug events ( ADEs ) . Two independent review ers evaluated all the data . The use of potentially inappropriate medications and their effects on patients were identified using the up date d Beers criteria . RESULTS A total of 2155 elderly patients were eligible ; 56.1 % received at least one drug listed in the Beers criteria ( BL drug ) . The rates of BL drug prescriptions were 103.8 per 100 admissions and 53.6 [ DOSAGE ERROR CORRECTED ] per 1000 patient-days , and the incidence rate of ADEs related to BL drugs was 1.7 per 100 BL drug prescriptions . Among patients aged ≥65 years , relatively younger patients ( p = 0.0002 ) and those with less complications ( p = 0.04 ) were likely to be prescribed BL drugs . CONCLUSIONS Although BL drugs were frequently prescribed to elderly Japanese in patients , the incidence of related ADEs appeared infrequent . These data suggest that re-evaluation of the appropriateness of the Beers criteria is needed before they are used in Japan and other nations to assess quality or for decision support", "OBJECTIVES To investigate medication changes for older patients admitted to hospital and to explore associations between patient characteristics and polypharmacy . DESIGN Prospect i ve cohort study . PARTICIPANTS AND SETTING Patients aged 70 years or older admitted to general medical units of 11 acute care hospitals in two Australian states between July 2005 and May 2010 . All patients were assessed using the interRAI assessment system for acute care . MAIN OUTCOME MEASURES Measures of physical , cognitive and psychosocial functioning ; and number of regular prescribed medications categorised into three groups : non-polypharmacy ( 0 - 4 drugs ) , polypharmacy ( 5 - 9 drugs ) and hyperpolypharmacy ( ≥ 10 drugs ) . RESULTS Of 1220 patients who were recruited for the study , medication records at admission were available for 1216 . Mean age was 81.3 years ( SD , 6.8 years ) , and 659 patients ( 54.2 % ) were women . For the 1187 patients with complete medication records on admission and discharge , there was a small but statistically significant increase in mean number of regular medications per day between admission and discharge ( 7.1 v 7.6 ) , while the prevalence of medications such as statins ( 459 [ 38.7 % ] v 457 [ 38.5 % ] patients ) , opioid analgesics ( 155 [ 13.1 % ] v 166 [ 14.0 % ] patients ) , antipsychotics ( 59 [ 5.0 % ] v 65 [ 5.5 % ] patients ) and benzodiazepines ( 122 [ 10.3 % ] v 135 [ 11.4 % ] patients ) did not change significantly . Being in a higher polypharmacy category was significantly associated with increase in comorbidities ( odds ratio [ OR ] , 1.27 ; 95 % CI , 1.20 - 1.34 ) , presence of pain ( OR , 1.31 ; 1.05 - 1.64 ) , dyspnoea ( OR , 1.64 ; 1.30 - 2.07 ) and dependence in terms of instrumental activities of daily living ( OR , 1.70 ; 1.20 - 2.41 ) . Hyperpolypharmacy was observed in 290/1216 patients ( 23.8 % ) at admission and 336/1187 patients ( 28.3 % ) on discharge , and the proportion of preventive medication in the hyperpolypharmacy category at both points in time remained high ( 1209/3371 [ 35.9 % ] at admission v 1508/4117 [ 36.6 % ] at discharge ) . CONCLUSIONS Polypharmacy is common among older people admitted to general medical units of Australian hospitals , with no clinical ly meaningful change to the number or classification ( symptom control , prevention or both ) of drugs made by treating physicians", "WHAT IS KNOWN AND OBJECTIVES The Screening Tool of Older Persons ' Potentially Inappropriate Prescriptions ( stopp ) criteria were up date d in 2014 ( stopp criteria ver.2 ) , but few studies have evaluated the usefulness of stopp criteria in elderly patients . This prospect i ve observational study evaluated the prevalence of potentially inappropriate medications ( PIMs ) , and the efficacy of hospital pharmacists ' assessment and intervention based on stopp criteria ver.2 . METHODS The study was conducted at three medical units of Kobe University Hospital between April 2015 and March 2016 . Pharmacists assessed and detected PIMs based on stopp criteria ver.2 and considered the patient 's intention to change the prescription at the time of admission of each patient . If the pharmacists judged that benefits outweighed risks of prescription change and the patients consented to change the medications , they recommended the doctor to change the prescription . If there was a risk of exacerbation of disease by the change of medications and the pharmacists judged it to be difficult to adjust medications during hospitalization or the patients did not consent to change the medications , they did not recommend to change it . The pharmacists and the doctors discussed and finally decided whether to change the PIMs or not . The number of patients prescribed PIMs , the number and contents of PIMs , and the number of medications changed after pharmacists ' intervention were calculated . RESULTS Totally , 822 new in patients aged ≥65 years prescribed ≥1 daily medicine were included . Their median ( interquartile range ) age was 75·0 ( 71·0 - 80·0 ) years , and 54·9 % were male . According to the criteria , 346 patients ( 42·1 % ) were prescribed ≥1 PIMs . Patients prescribed PIMs took significantly more medications than others : 10·0 ( 7·0 - 13·0 ) vs. 6·0 ( 4·0 - 9·0 ) , P < 0·001 . The total number of PIMs was 651 % , 47·6 % of which ( n = 310 ) were recommended the doctors to change , and 292 of 651 PIMs ( 44·9 % ) were finally discontinued/changed after pharmacists ' assessment and intervention . PIMs related to benzodiazepines , including Z-drugs , were most frequent , with a detailed classifications as follows ( changed/total ) : ( i ) benzodiazepines for 4 or more weeks ( 75/205 ) , ( ii ) drugs that predictably increase the risk of falls in older people ( benzodiazepines ) ( 30/67 ) and ( iii ) drugs that predictably increase the risk of falls in older people ( hypnotic Z-drugs ) ( 15/31 ) . CONCLUSION Over 40 % elderly patients were prescribed PIMs , and pharmacists ' assessment s and interventions based on stopp criteria ver.2 were useful in detecting and correcting prescription of PIMs", "Civilization and modern medicine now allow an unprecedented number of people to survive to old age . Not only has the definition of old evolved , but the aims of medical care for the elderly have progressed far beyond survival to maximizing functional and cognitive status , improving quality of life , and preserving productivity . Although many health problems in older age can be prevented or postponed by medical interventions , the quality of medical care for older persons remains largely unexamined . Previous work on quality -of-care measurement has focused on specific diseases or aspects of care , and in some cases targeted only a slice of the older population ( 16 ) . Such targeted approaches may not present a fair picture of overall quality and may lead to unintended incentives ( gaming the system ) ( 7 ) . Although broad systems of quality -of-care evaluation are less susceptible to gaming , they seldom include quality indicators focused on aspects of care important to older sick persons ( 8 , 9 ) . Substantial variation in preferences may make quality of care for older adults particularly difficult to measure . For example , older adults do not consistently prefer care that prolongs life , particularly if this care occurs at the expense of comfort . Furthermore , many ill , older adults can not advocate for themselves and may have no family members or friends to do so on their behalf . Thus , objective measures of the care they receive are particularly important . The Assessing Care of Vulnerable Elders ( ACOVE ) project endeavored to develop a comprehensive set of quality - assessment tools for ill older persons . Because ill older persons constitute a heterogeneous cohort that is not easily delineated , we created a system to identify high-risk , community-dwelling individuals and targeted the most important clinical conditions affecting them . Specifically , our goals for this project were the following : 1 . Develop a definition of vulnerable elders that delineates a group of community-living persons 65 years of age and older who are at high risk for death or functional decline , and develop a system to identify them . 2 . Identify important medical conditions that affect vulnerable elders and for which effective methods of prevention or management exist . 3 . Develop a set of evidence -based , quality -of-care indicators that are relevant to vulnerable elders using systematic literature review s , expert opinion , and the guidance of expert groups and stakeholders . 4 . Design a chart abstract ion tool , interview instrument , and administrative data analytic methods to implement the quality -of-care indicator system . Project Structure : Advisory Boards To make the ACOVE tools as clinical ly useful as possible and to enhance their value to those who may use them , two advisory committees oversaw the project . The Clinical Committee directed the definition of the target population and identified the target conditions . It also review ed the full set of quality indicators assembled by the expert panels ( see the Methods paper ) . The Policy Advisory Committee directed the structure of the quality indicator system and the measurement approach . This committee review ed the sampling system , considered the value of a community surveybased sample versus a sample drawn from administrative data , advised the project on methods of data collection , and advocated the use of process measures rather than outcomes .Project Overview The Appendix lists the members and institutional affiliations of the Clinical Committee and the Policy Advisory Committee and ACOVE investigators and staff . Definition and Selection of the Patient Sample We termed our target sample vulnerable elders . With the assistance of the Clinical Committee , we defined vulnerable elders as persons 65 years of age and older who are at increased risk for death or functional decline . We considered several methods of identifying a community-based sample for measurement , including use of administrative data and survey sampling . The Policy Advisory Committee advised against using a sampling method based solely on administrative data because , by definition , using utilization data to define health status and disease burden disproportionately sample s persons with higher utilization of health services and may not identify persons who are undertreated or underdiagnosed . We selected a survey method that would identify vulnerable elders regardless of the amount of health care they used and that would be versatile for use across venues and health insurance systems . Using the Medicare Current Beneficiary Survey , we determined that functional status is a more important predictor of death and functional decline than are specific clinical conditions . A parsimonious set of factors that could be asked about in a brief interview , including age , self-rated health , and functional disabilities and limitations , predicted functional decline and death . Using these factors , we developed a scoring system that identified 32 % of a nationally representative sample as vulnerable : This group had more than four times the risk for death or functional decline over a 2-year period compared to the lower-scoring majority of the sample ( 10 ) . When we applied this definition to a r and om sample of persons 65 years of age and older enrolled in managed care plans , 21 % of elders were classified as vulnerable . Target Conditions for Assessing Quality of Care We selected the target conditions for quality -of-care assessment using literature review s and a formal group-judgment process . Target conditions were conceptualized as prevalent , important to health status and quality of life , having outcomes affected by medical care , feasible to measure , and geriatric . The Clinical Committee used these criteria to select 21 diseases , geriatric syndromes , physiologic impairments , and clinical situations ( see the Methods article for a list of these 21 conditions ) . The Policy Advisory Committee added a 22nd condition , continuity and coordination of care . According to national survey estimates , the prevalence of the selected conditions ranged from 10 % to 50 % among community-dwelling elders . These conditions accounted for at least 43 % of acute hospital admissions and 33 % of office visits for persons 65 years of age and older . The process of selecting the conditions is discussed in detail elsewhere ( 11 ) . Developing Quality -of-Care Indicators for Vulnerable Elders Clinical experts developed potential quality indicators for each target condition using existing guidelines and clinical opinion . Indicators covered the domains of prevention , diagnosis , treatment , and follow-up . Structured literature review s were then performed to assess the evidence supporting a link between the proposed processes of care and improved outcomes in older adults . We subsequently presented the proposed quality indicators and the literature syntheses to panels of experts in geriatric care and medical specialists . These expert panels considered the indicators ' validity and feasibility . On the basis of the panels ' ratings and a comprehensive review of the set by the Clinical Committee , we developed a set of 236 quality indicators covering the 22 conditions . The Methods article describes this process in detail . This set of indicators was review ed and modified by the American College of PhysiciansAmerican Society of Internal Medicine ( ACPASIM ) Task Force on Aging . The full set of quality indicators with the literature substantiation for 11 of the conditions constitute the remainder of this supplement . A review of the accepted quality indicators reveals their decidedly geriatric nature . Many of them focus on the transfer of information between the health care provider and the patient or patient 's proxy . In addition to disease management , the indicators pay attention to detecting classically underidentified conditions , such as depression , dementia , and functional impairment . Consideration of proportionate care , informed consent , and end-of-life issues permeates the set . Implementing the Quality Indicators We developed instruments to implement the quality indicators using information collected from three sources : the medical record , a patient ( or , if necessary , proxy ) interview , and administrative data . Medical records include all inpatient and outpatient care over a 1-year period . The interview is design ed to be conducted by telephone with the patient to identify aspects of care that are not well captured in the medical record . The quality indicators presented here are currently undergoing feasibility testing in two managed care plans . Scoring the quality indicators accounts for clinical circumstances , patient preferences , and patient prognosis . The scoring of each quality indicator accounts for these factors at the following five levels : 1 . Any chart documentation indicating that a care process does not apply to the patient excludes application of this indicator to the patient . 2 . Any care process that is contraindicated because of comorbidity , allergy , or intolerance ( such as contraindications to medication ) excludes application of the indicator to the patient . 3 . If an indicator states that a care process should be offered to a patient , this indicator is satisfied if the care process occurs , if the medical record ( or patient interview ) indicates that the patient rejected the care process , or if the medical record ( or patient interview ) documents that the care process was offered to the patient . 4 . If the medical record contains documentation or if during an interview a patient states that he or she would not want , under any circumstances , to be hospitalized , then the 11 indicators that would require hospitalization do not apply . Similarly , a preference not to accept surgery would exclude from application to that patient the 9 indicators that prescribe surgery or procedures that would lead to surgery . 5 . If a patient has advanced dementia or a chart-documented poor prognosis ( expected survival < 6 months ) , then", "AIMS To assess inappropriate prescribing in older people with diabetes mellitus during the month prior to a hospitalization , using tools on potentially inappropriate medicines ( PIMs ) and potential prescribing omissions ( PPOs ) and comparing inappropriate prescribing in patients with without diabetes . METHODS In an observational , prospect i ve multicentric study , we assessed inappropriate prescribing in 672 patients aged 75 years and older during hospital admission . The Beers , Screening Tool of Older Person 's Prescriptions ( STOPP ) and Screening Tool to Alert Doctors to Right Treatment ( START ) criteria and Assessing Care of Vulnerable Elders ( ACOVE-3 ) medicine quality indicators were used . We analysed demographic and clinical factors associated with inappropriate prescribing . RESULTS Of 672 patients , 249 ( mean age 82.4 years , 62.9 % female ) had a diagnosis of diabetes mellitus . The mean number of prescribing drugs per patient with diabetes was 12.6 ( 4.5 ) vs. 9.4 ( 4.3 ) in patients without diabetes ( P < 0.001 ) . Of those patients with diabetes , 74.2 % used 10 or more medications ; 54.5 % of patients with diabetes had at least one Beers-listed PIM , 68.1 % had at least one STOPP-listed PIM , 64.6 % had at least one START-listed PPO and 62.8 % had at least one ACOVE-3-listed PPO . Except for the Beers criteria , these prevalences were significantly higher in patients with diabetes than in those without . After excluding diabetes-related items from these tools , only STOPP-listed PIMs remained significantly higher among patients with diabetes ( P = 0.04 ) . CONCLUSIONS Polypharmacy is common among older patients with diabetes mellitus . Inappropriate prescribing is higher in older patients with diabetes , even when diabetes-related treatment is excluded from the inappropriate prescribing evaluation", "Abstract Background : In France , there is evidence to suggest that 50 % of elderly individuals are prescribed psychotropic medications . However , it is known that use of these agents increases the risk of falls , fractures and delirium in older people . Objective : To study the consumption of ‘ potentially inappropriate medication ’ ( PIM ) among patients aged ≥75 years , paying particular attention to psychotropic drugs and the factors influencing the use of ‘ potentially inappropriate psychotropics ’ ( PIPs ) . Method : This was a cross-sectional analysis of a prospect i ve multicentre cohort of 1306 hospitalized French patients aged ≥75 years ( the SAFEs [ Sujet Âgé Fragile : Évaluation et suivi ( Frail Elderly Subjects : Evaluation and follow-up ) ] cohort ) . The present analysis involved the 1176 patients for whom there was information on the usual treatments being taken in the 2 weeks before hospitalization . The drugs were coded according to the Anatomical Therapeutic Chemical classification ; the Beers list as up date d in 2003 defined which medications were considered PIPs . St and ardized geriatric assessment variables were recorded on inclusion in the study . Logistic regression analysis was performed to identify factors linked to use of psychotropics and PIPs . Results : The mean number of drugs taken was 5.7 ± 2.9 per patient . Twenty-eight percent of patients took at least one PIM . The number of patients who had taken at least one psychotropic drug in the 2 weeks before hospitalization ( mean 1.6 ± 0.9 psychotropics per patient ) was 589 ( 50.1 % ) . More than half of both the 510 patients with a depressive syndrome and the 543 patients affected by dementia were treated with psychotropics . Multivariate analysis showed that prescription of psychotropics was linked to the presence of a dementia syndrome ( odds ratio [ OR ] = 1.4 ; 95 % CI 1.1 , 1.9 ; p = 0.03 ) , the presence of a depressive syndrome ( OR = 1.7 ; 95 % CI 1.3 , 2.1 ; p < 0.001 ) , living in an institution ( OR = 2.2 ; 95 % CI 1.5 , 3.4 ; p < 0.001 ) , use of more than five drugs ( OR = 3.2 ; 95 % CI 2.5 , 4.2 ; p < 0.001 ) and Charlson ’s co-morbidity score > 1 ( OR = 0.6 ; 95 % CI 0.5 , 0.8 ; p = 0.001 ) . Nineteen percent of all psychotropics prescribed were PIPs . Of these PIPs , 66.5 % were anxiolytics , 28.4 % were antidepressants and 5.1 % were antipsychotics . Use of PIPs in the multivariate analysis was associated only with consumption of more than five drugs ( OR = 1.7 ; 95 % CI 1.1 , 2.5 ; p = 0.01 ) . Conclusion : PIM use is common among hospitalized older adults in France . The most important determinant of risk of receiving a psychotropic medication or a PIP was the number of drugs being taken . The elderly , who have multiple comorbidities , complex chronic conditions and are usually receiving polypharmacy , are at increased risk for adverse drug events . These adverse events are often linked to problems that could be preventable such as delirium , depression and falls . Regular review of prescriptions would help optimize prescription of psychotropics in the elderly . The Beers list is a good tool for evaluating PIMs but is too restrictive with respect to psychotropics ; in the latter respect , the list could usefully be widened" ]

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[ "Endoscopic radiofrequency ablation combined with endoscopic resection for early neoplasia in Barrett's esophagus longer than 10 cm.", "Predictors for Neoplastic Progression in Patients With Barrett's Esophagus: A Prospective Cohort Study", "Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial.", "Complete ablation of esophageal epithelium with a balloon-based bipolar electrode: a phased evaluation in the porcine and in the human esophagus.", "The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.", "Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follow-up of 100 patients.", "Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.", "Circumferential and Focal Ablation of Barrett's Esophagus Containing Dysplasia", "Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.", "Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia.", "Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial", "Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up.", "Efficacy of radiofrequency ablation combined with endoscopic resection for barrett's esophagus with early neoplasia." ]

[ "BACKGROUND Radiofrequency ablation ( RFA ) is safe and effective for eradicating Barrett 's esophagus ( BE ) and BE-associated early neoplasia . Most RFA studies have limited the baseline length of BE ( < 10 cm ) , and therefore little is known about RFA for longer BE . OBJECTIVE To assess the safety and efficacy of RFA with or without prior endoscopic resection ( ER ) for BE ≥ 10 cm containing neoplasia . DESIGN Prospect i ve trial . SETTING Two tertiary-care centers . PATIENTS This study involved consecutive patients with BE ≥ 10 cm with early neoplasia . INTERVENTION Focal ER for visible abnormalities , followed by a maximum of 2 circumferential and 3 focal RFA procedures every 2 to 3 months until complete remission . MAIN OUTCOME MEASUREMENTS Complete remission , defined as endoscopic resolution of BE and no intestinal metaplasia ( CR-IM ) or neoplasia ( CR-neoplasia ) in biopsy specimens . RESULTS Of the 26 patients included , 18 underwent ER for visible abnormalities before RFA . The ER specimens showed early cancer in 11 , high- grade intraepithelial neoplasia ( HGIN ) in 6 , and low- grade intraepithelial neoplasia ( LGIN ) in 1 . The worst residual histology , before RFA and after any ER , was HGIN in 16 patients and LGIN in 10 patients . CR-neoplasia and CR-IM were achieved in 83 % ( 95 % confidence interval [ CI ] , 63%-95 % ) and 79 % ( 95 % CI , 58%-93 % ) , respectively . None of the patients had fatal or severe complications and 15 % ( 95 % CI , 4%-35 % ) had moderate complications . During a mean ( ± st and ard deviation ) follow-up of 29 ( ± 9.1 ) months , no neoplasia recurred . LIMITATIONS Tertiary-care center , short follow-up . CONCLUSION ER for visible abnormalities , followed by RFA of residual BE is a safe and effective treatment for BE ≥ 10 cm containing neoplasia , with a low chance of recurrence of neoplasia or BE during follow-up", "OBJECTIVES : Patients with Barrett 's esophagus ( BE ) have an increased risk of developing esophageal adenocarcinoma ( EAC ) . As the absolute risk remains low , there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs . The aim of this study was to identify such predictors of progression to high- grade dysplasia ( HGD ) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors . METHODS : We included 713 patients with BE ( ≥2 cm ) with no dysplasia ( ND ) or low- grade dysplasia ( LGD ) in a multicenter , prospect i ve cohort study . Data on age , gender , body mass index ( BMI ) , reflux symptoms , tobacco and alcohol use , medication use , upper gastrointestinal ( GI ) endoscopy findings , and histology were prospect ively collected . As part of this study , patients with ND underwent surveillance every 2 years , whereas those with LGD were followed on a yearly basis . Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance . RESULTS : After 4 years of follow-up , 26/713 ( 3.4 % ) patients developed HGD or EAC , with the remaining 687 patients remaining stable with ND or LGD . Multivariable analysis showed that a known duration of BE of ≥10 years ( risk ratio ( RR ) 3.2 ; 95 % confidence interval ( CI ) 1.3–7.8 ) , length of BE ( RR 1.11 per cm increase in length ; 95 % CI 1.01–1.2 ) , esophagitis ( RR 3.5 ; 95 % CI 1.3–9.5 ) , and LGD ( RR 9.7 ; 95 % CI 4.4–21.5 ) were significant predictors of progression to HGD or EAC . In a prediction model , we found that the annual risk of developing HGD or EAC in BE varied between 0.3 % and up to 40 % . Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC ( < 1 % ) , whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression ( 18–40 % ) . CONCLUSIONS : In patients with BE , the risk of developing HGD or EAC is predominantly determined by the presence of LGD , a known duration of BE of ≥10 years , longer length of BE , and presence of esophagitis . One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE", "BACKGROUND Barrett 's esophagus ( BE ) may lead to high- grade dysplasia ( HGD ) and adenocarcinoma . The objective was to examine the impact of treating patients with BE and with HGD by using porfimer sodium ( POR ) and photodynamic therapy ( PDT ) for ablating HGD and reducing the incidence of esophageal adenocarcinoma . METHODS The design was a multicenter , partially blinded ( pathology ) , r and omized clinical trial conducted in patients with BE who have HGD . There were 30 contributing centers . A total of 485 patients were screened , with 208 in the intent-to-treat population and 202 in the safety population . Patients were r and omized on a 2:1 basis to compare PDT with POR plus omeprazole ( PORPDT ) with omeprazole only ( OM ) . The main outcome measurement was complete HGD ablation occurring at any time during the study period . RESULTS There was a significant difference ( p < 0.0001 ) in favor of PORPDT ( 106/138 [ 77 % ] ) compared with OM ( 27/70 [ 39 % ] ) in complete ablation of HGD at any time during the study period . The occurrence of adenocarcinoma in the PORPDT group ( 13 % ) ( n=18 ) was significantly lower ( p < 0.006 ) compared with the OM group ( 28 % ) [ corrected ] ( n=20 ) . The safety profile showed 94 % of patients in the PORPDT group and 13 % of patients in the OM group had treatment-related adverse effects . The limitations of the study were that PDT therapy may have had to be applied more than once and that patients spent more time in treatment . The patients and the physicians were not blinded to the treatment . CONCLUSIONS PORPDT in conjunction with omeprazole is an effective therapy for ablating HGD in patients with BE and in reducing the incidence of esophageal adenocarcinoma", "BACKGROUND The aim of this study was to evaluate the endoscopic and the histologic effects of a balloon-based bipolar radiofrequency electrode for ablation of porcine and human esophageal epithelium . METHODS All procedures were performed with a balloon-based , bipolar radiofrequency system that creates a circumferential , thin-layer epithelial ablation zone within the esophagus . In Phase I , multiple ablations were created in 10 farm swine , followed by acute euthanasia and histologic assessment for completeness of epithelial removal and ablation depth . In Phase II , multiple ablations were created in 19 farm swine , with varying power and energy density , followed by endoscopy at 2 and 4 weeks to assess stricture formation . In Phase III , 3 ablations were created in 12 farm swine , with varying energy density ( 5 , 8 , 10 , 12 , 15 , or 20 J/cm 2 ) at 350 W. Animals were euthanized at 48 hours . Histologic examination determined the percentage of epithelium removed and the ablation depth . In Phase IV , 3 patients underwent esophageal epithelial ablation before esophagectomy , creating separate lesions proximal to the tumor . Completeness of epithelial ablation and ablation depth was quantified histologically . RESULTS In Phase I , complete removal of esophageal epithelium was achieved at energy density setting s of 9.7 to 29.5 J/cm 2 . In Phase II , 9.7 and 10.6 J/cm 2 produced no stricture , whereas more than 20 J/cm 2 produced a stricture in every case . In Phase III , 8 - 20 J/cm 2 result ed in 100 % epithelial ablation . Five and 8 J/cm 2 spared the muscularis mucosae , whereas 10 J/cm 2 caused injury to the muscularis mucosae but preserved the submucosa . In Phase IV , histologic examination demonstrated full-thickness epithelial removal in areas of electrode contact . Ablation extended only to the muscularis mucosae , without injury to submucosa . CONCLUSIONS In the porcine and the human esophagus , circumferential , full-thickness ablation of epithelium without direct injury to the submucosa is possible and was well tolerated . In all cases , depth of ablation was linearly related to energy density of treatment", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "OBJECTIVE To assess the dose-response , safety , and efficacy of circumferential endoscopic ablation of Barrett 's esophagus ( BE ) by using an endoscopic balloon-based ablation device ( HALO360 System ) . DESIGN This study was conducted in 2 serial phases ( dosimetry phase and effectiveness phase ) to evaluate a balloon-based ablation device that delivers a pre-set amount of energy density ( J/cm2 ) to BE tissue . The dosimetry phase evaluated the dose-response and the safety of delivering 6 to 12 J/cm2 . The effectiveness phase used 10 J/cm2 ( delivered twice [ x2 ] ) for all patients , followed by EGD with biopsies at 1 , 3 , 6 , and 12 months . A second ablation procedure was performed if BE was present at 1 or 3 months . Patients received esomeprazole 40 mg twice a day for 1 month after ablation , and 40 mg every day thereafter . Postablation symptoms were quantified by using a 14-day symptom diary ( scale , 0 - 100 ) . A complete response ( CR ) was defined as all biopsy specimens negative for BE at 12 months . SETTING Eight U.S. centers , between September 2003 and September 2005 . PATIENTS Patients were 18 to 75 years of age , with a diagnosis of BE ( without dysplasia ) , with histopathology reconfirmation of the diagnosis within 6 months of enrollment . RESULTS In the dosimetry phase , 32 patients ( 29 men ; mean age , 56.8 years ) were enrolled . Median symptom scores returned to a score of 0 of 100 by day 3 . There were no dose-related serious adverse events , and the outcomes at 1 and 3 months permitted the selection of 10 J/cm2 ( x2 ) for the subsequent effectiveness phase of the study . In the effectiveness phase , 70 patients ( 52 men , 18 women ; mean age , 55.7 years ) were enrolled . Median symptom scores returned to a score of 0 of 100 by day 4 . At 12 months ( n = 69 ; mean , 1.5 sessions ) , a CR for BE was achieved in 70 % of patients . There were no strictures and no buried gl and ular mucosa in either study phase ( 4306 biopsy fragments evaluated ) . CONCLUSIONS Circumferential ablation of nondysplastic BE by using this balloon-based ablation device can be performed with no subsequent strictures or buried gl and s and with complete elimination of BE in 70 % of patients at 1-year follow-up", "BACKGROUND AND STUDY AIMS The AIM -II Trial included patients with nondysplastic Barrett 's esophagus ( NDBE ) treated with radiofrequency ablation ( RFA ) . Complete eradication of NDBE ( complete response-intestinal metaplasia [ CR-IM ] ) was achieved in 98.4 % of patients at 2.5 years . We report the proportion of patients demonstrating CR-IM at 5-year follow-up . PATIENTS AND METHODS Prospect i ve , multicenter US trial ( NCT00489268 ) . After endoscopic RFA of NDBE up to 6 cm , patients with CR-IM at 2.5 years were eligible for longer-term follow-up . At 5 years , we obtained four-quadrant biopsies from every 1 cm of the original extent of Barrett 's esophagus . All specimens were review ed by one expert gastrointestinal pathologist , followed by focal RFA and repeat biopsy if NDBE was identified . Primary outcomes were ( i ) proportion of patients demonstrating CR-IM at 5-year biopsy , and ( ii ) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA . RESULTS Of 60 eligible patients , 50 consented to participate . Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue ( per patient , mean 30 , st and ard deviation [ SD ] 13 ) . CR-IM was demonstrated in 92 % ( 46 / 50 ) of patients , while 8 % ( 4 / 50 ) had focal NDBE ; focal RFA converted all these to CR-IM . There were no buried gl and s , dysplasia , strictures , or serious adverse events . Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 ( 95 % confidence interval [ CI ] 0.77 - 0.97 ) and mean duration of CR-IM was 4.22 years ( st and ard error [ SE ] 0.12 ) . CONCLUSIONS In patients with NDBE treated with RFA , CR-IM was demonstrated in the majority of patients ( 92 % ) at 5-year follow-up , biopsy depth was adequate to detect recurrence , and all failures ( 4 / 4 , 100 % ) were converted to CR-IM with single-session focal RFA", "OBJECTIVES : Dysplasia in a Barrett 's esophagus ( BE ) is associated with an increased risk for developing esophageal adenocarcinoma . Ablation using the HALO system has shown promise for the treatment of BE with dysplasia . The objective of this study was to assess the safety and efficacy of a stepwise regimen of circumferential and focal ablation using the HALO system for the treatment of BE with dysplasia . METHODS : BE patients with low- grade dysplasia ( LGD ) or high- grade dysplasia ( HGD ) were enrolled . Primary circumferential ablation was followed every 3 months by further circumferential ablation or focal ablation until complete endoscopic eradication of BE was achieved . At 3- or 6-month intervals , depending on baseline grade , targeted and four quadrant r and om biopsies were obtained to assess the histological response to ablation . A complete response ( CR ) is defined as all biopsies negative for intestinal metaplasia ( IM ) ( CR-IM ) or dysplasia ( CR-D ) at last available follow-up . RESULTS : A total of 63 patients were treated ( 57 men ; median age 71 years ; median BE length 5 cm ) , with worst grade of dysplasia being LGD ( n=39 ) and HGD ( n=24 ) . Follow-up is available for 62 patients ( median 24 months ) . Overall , CR-IM is 79 % and CR-D is 89 % . For the LGD cohort , CR-IM is 87 % and CR-D is 95 % . For the HGD cohort , CR-IM is 67 % and CR-D is 79 % . CONCLUSIONS : Stepwise circumferential and focal ablation of BE containing dysplasia appears to be a safe and effective intervention , achieving a CR for dysplasia in 95 % and 79 % of LGD and HGD patients , respectively", "BACKGROUND & AIMS Radiofrequency ablation ( RFA ) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett 's esophagus ( BE ) , and reduce rates of esophageal adenocarcinoma . We assessed long-term rates of eradication , durability of neosquamous epithelium , disease progression , and safety of RFA in patients with dysplastic BE . METHODS We performed a r and omized trial of 127 subjects with dysplastic BE ; after cross-over subjects were included , 119 received RFA . Subjects were followed for a mean time of 3.05 years ; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years . Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years , durability of response , disease progression , and adverse events . RESULTS After 2 years , 101 of 106 patients had complete eradication of all dysplasia ( 95 % ) and 99 of 106 had eradication of intestinal metaplasia ( 93 % ) . After 2 years , among subjects with initial low- grade dysplasia , all dysplasia was eradicated in 51 of 52 ( 98 % ) and intestinal metaplasia was eradicated in 51 of 52 ( 98 % ) ; among subjects with initial high- grade dysplasia , all dysplasia was eradicated in 50 of 54 ( 93 % ) and intestinal metaplasia was eradicated in 48 of 54 ( 89 % ) . After 3 years , dysplasia was eradicated in 55 of 56 of subjects ( 98 % ) and intestinal metaplasia was eradicated in 51 of 56 ( 91 % ) . Kaplan-Meier analysis showed that dysplasia remained eradicated in > 85 % of patients and intestinal metaplasia in > 75 % , without maintenance RFA . Serious adverse events occurred in 4 of 119 subjects ( 3.4 % ) ; the rate of stricture was 7.6 % . The rate of esophageal adenocarcinoma was 1 per 181 patient-years ( 0.55%/patient-years ) ; there was no cancer-related morbidity or mortality . The annual rate of any neoplastic progression was 1 per 73 patient-years ( 1.37%/patient-years ) . CONCLUSIONS In subjects with dysplastic BE , RFA therapy has an acceptable safety profile , is durable , and is associated with a low rate of disease progression , for up to 3 years", "BACKGROUND Endoscopic ablation to treat Barrett 's esophagus ( BE ) with high- grade dysplasia ( HGD ) is associated with a decreased incidence of esophageal adenocarcinoma . Endoscopic spray cryotherapy ( CRYO ) demonstrates promising preliminary data . OBJECTIVE To assess the safety and efficacy of CRYO in BE with HGD . DESIGN Multicenter , retrospective cohort study . SETTING Nine academic and community centers ; treatment period , 2007 to 2009 . PATIENTS Subjects with HGD confirmed by 2 pathologists . Previous EMR was allowed if residual HGD remained . INTERVENTIONS CRYO with follow-up biopsies . MAIN OUTCOME MEASUREMENTS Complete eradication of HGD with persistent low- grade dysplasia , complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia , and complete eradication of all intestinal metaplasia . RESULTS Ninety-eight subjects ( mean age 65.4 years , 83 % male ) with BE and HGD ( mean length 5.3 cm ) underwent 333 treatments ( mean 3.4 treatments per subject ) . There were no esophageal perforations . Strictures developed in 3 subjects . Two subjects reported severe chest pain managed with oral narcotics . One subject was hospitalized for bright red blood per rectum . Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis . Fifty-eight subjects ( 97 % ) had complete eradication of HGD , 52 ( 87 % ) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia , and 34 ( 57 % ) had complete eradication of all intestinal metaplasia . Subsquamous BE was found in 2 subjects ( 3 % ) . LIMITATIONS Nonr and omized , retrospective study with no control group , short follow-up ( 10.5 months ) , lack of central ized pathology , and use of surrogate outcome for decreased cancer risk . CONCLUSIONS CRYO is a safe and well-tolerated therapy for BE and HGD . Short-term results suggest that CRYO is highly effective in eradicating HGD", "Objective After focal endoscopic resection ( ER ) of high- grade dysplasia ( HGD ) or early cancer ( EC ) in Barrett 's oesophagus ( BO ) , eradication of all remaining BO reduces the recurrence risk . The aim of this study was to compare the safety of stepwise radical ER ( SRER ) versus focal ER followed by radiofrequency ablation ( RFA ) for complete eradication of BO containing HGD/EC . Methods A multicentre r and omised clinical trial was carried out in three tertiary centres . Patients with BO ≤5 cm containing HGD/EC were r and omised to SRER or ER/RFA . Patients in the SRER group underwent piecemeal ER of 50 % of BO followed by serial ER . Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA . Follow-up endoscopy with biopsies ( four-quadrant/2 cm BO ) was performed at 6 and 12 months and then annually . The main outcome measures were : stenosis rate ; complications ; complete histological response for neoplasia ( CR-neoplasia ) ; and complete histological response for intestinal metaplasia ( CR-IM ) . Results CR-neoplasia was achieved in 25/25 ( 100 % ) SRER and in 21/22 ( 96 % ) ER/RFA patients . CR-IM was achieved in 23 ( 92 % ) SRER and 21 ( 96 % ) ER/RFA patients . The stenosis rate was significantly higher in SRER ( 88 % ) versus ER/RFA ( 14 % ; p<0.001 ) , result ing in more therapeutic sessions in SRER ( 6 vs 3 ; p<0.001 ) due to dilations . After median 24 months follow-up , one SRER patient had recurrence of EC , requiring ER . Conclusions In patients with BO ≤5 cm containing HGD/EC , SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia . However , SRER was associated with a higher number of complications and therapeutic sessions . For these patients , a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER . Clinical trial number NTR1337", "BACKGROUND For patients with Barrett 's esophagus ( BE ) , life-long surveillance endoscopy is recommended because of an elevated risk for developing dysplasia and esophageal adenocarcinoma . Various endoscopic therapies have been used to eradicate BE . Recently circumferential radiofrequency ablation has been used with encouraging short-term results . OBJECTIVE To provide longer follow-up and to assess the long-term safety and efficacy of step-wise circumferential ablation with the addition of focal ablation for BE . DESIGN Prospect i ve , multicenter clinical trial ( NCT00489268 ) . SETTING Eight U.S. centers , between May 2004 and February 2007 . PATIENTS Seventy subjects with 2 to 6 cm of BE and histologic evidence of intestinal metaplasia ( IM ) . INTERVENTIONS Circumferential ablation was performed at baseline and repeated at 4 months if there was residual IM . Follow-up biopsy specimens were obtained at 1 , 3 , 6 , 12 , and 30 months . Specimens were review ed by a central pathology board . Focal ablation was performed after the 12-month follow-up for histological evidence of IM at the 12-month biopsy ( absolute indication ) or endoscopic appearance suggestive of columnar-lined esophagus ( relative indication ) . Subjects received esomeprazole for control of esophageal reflux . MAIN OUTCOME MEASUREMENTS Complete absence of IM per patient from biopsy specimens obtained at 12 and 30 months , defined as complete remission-IM ( CR-IM ) . RESULTS At 12 months , CR-IM was achieved in 48 of 69 available patients ( 70 % per protocol [ PP ] , 69 % intention to treat [ ITT ] ) . At 30 months after additional focal ablative therapy , CR-IM was achieved in 60 of 61 available patients ( 98 % PP , 97 % ITT ) . There were no strictures or buried gl and ular mucosa detected by the st and ardized biopsy protocol at 12 or 30 months , and there were no serious adverse events . LIMITATIONS This was an uncontrolled clinical trial with 2.5-year follow-up . CONCLUSION Stepwise circumferential and focal ablation result ed in complete eradication of IM in 98 % of patients at 2.5-year follow-up", "BACKGROUND & AIMS Radiofrequency ablation ( RFA ) is safe and effective for eradicating intestinal metaplasia and neoplasia in patients with Barrett 's esophagus . We sought to assess the safety and efficacy of RFA in conjunction with baseline endoscopic resection for high- grade intraepithelial neoplasia ( HGIN ) and early cancer . METHODS This multicenter , prospect i ve cohort study included 24 patients ( mean age , 65 years ; median Barrett 's esophagus , 8 cm ) , with Barrett 's esophagus of < or = 12 cm containing HGIN or early cancer , from 3 European tertiary-care medical centers . Visible lesions were endoscopically resected , followed by serial RFA . Focal escape endoscopic resection was used if Barrett tissue persisted despite RFA . Complete response , defined as all biopsies negative for intestinal metaplasia and neoplasia , was assessed during endoscopy with 4-quadrant biopsies taken every 1 cm of the original Barrett 's segment 2 months after the patient was last treated . RESULTS Twenty-three patients underwent pre-RFA endoscopic resection for visible lesions ; 16 patients had early cancer and 7 patients had HGIN . The worst residual histology results , pre-RFA ( after any endoscopic resection ) were : HGIN ( 10 patients ) , low- grade intraepithelial neoplasia ( 11 patients ) , and intestinal metaplasia ( 3 patients ) . Neoplasia and intestinal metaplasia were eradicated in 95 % and 88 % of patients , respectively ; after escape endoscopic resection in 2 patients , rates improved to 100 % and 96 % , respectively . Complications after RFA included melena ( n = 1 ) and dysphagia ( n = 1 ) . After additional follow-up ( median , 22 months ; interquartile range , 17.2 - 23.8 months ) no neoplasia recurred . CONCLUSIONS This European multicenter study to show that early neoplasia in Barrett 's esophagus can be effectively and safely treated with RFA , in combination with prior endoscopic resection of visible lesions" ]

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[ "Prevalence of rheumatic diseases in Greece: a cross-sectional population based epidemiological study. The ESORDIG Study.", "Efficacy of different therapy regimes of low-power laser in painful osteoarthritis of the knee: a double-blind and randomized-controlled trial.", "Acupuncture in patients with osteoarthritis of the knee: a randomised trial", "TENS, electroacupuncture and ice massage: comparison of treatment for osteoarthritis of the knee.", "A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations", "Minimal perceptible clinical improvement with the Western Ontario and McMaster Universities osteoarthritis index questionnaire and global assessments in patients with osteoarthritis.", "Optimal stimulation duration of tens in the management of osteoarthritic knee pain.", "Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain thresholds in healthy human subjects", "Electroacupuncture versus Diclofenac in symptomatic treatment of Osteoarthritis of the knee: a randomized controlled trial", "Transcutaneous electrical nerve stimulation in osteoarthrosis: a therapeutic alternative?", "Pulsed magnetic field therapy for osteoarthritis of the knee--a double-blind sham-controlled trial.", "A placebo controlled double blind trial to evaluate the effectiveness of pulsed short wave therapy for osteoarthritic hip and knee pain", "Acupuncture for the treatment of pain of osteoarthritic knees.", "Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment", "The comparative analgesic efficacy of transcutaneous electrical nerve stimulation and a non-steroidal anti-inflammatory drug for painful osteoarthritis.", "Transcutaneous neural stimulation use in postoperative knee rehabilitation", "Optimal stimulation frequency of transcutaneous electrical nerve stimulation on people with knee osteoarthritis.", "Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee.", "Randomised controlled trial of magnetic bracelets for relieving pain in osteoarthritis of the hip and knee", "Randomized Trial of Codetron for pain Control in Osteoarthritis of the Hip/Knee", "Effects of intensity of electroacupuncture upon experimental pain in healthy human volunteers: A randomized, double-blind, placebo-controlled study", "Magnetic Pulse Treatment for Knee Osteoarthritis: A Randomised, Double-Blind, Placebo-Controlled Study", "Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimal clinically important improvement.", "Treatment of osteoarthritis of the knee with transcutaneous electrical nerve stimulation", "Minimal clinically important rehabilitation effects in patients with osteoarthritis of the lower extremities.", "Laser acupuncture in knee osteoarthritis: a double-blind, randomized controlled study.", "A comparison of lower extremity muscle strength, obesity, and depression scores in elderly subjects with knee pain with and without radiographic evidence of knee osteoarthritis." ]

[ "OBJECTIVE To assess the prevalence of rheumatic diseases in Greek urban , suburban , and rural adult general population s. METHODS This cross-sectional population based epidemiological study of rheumatic diseases in Greece ( the ESORDIG Study ) was conducted on the total adult population of 2 urban , one suburban , and 4 rural communities ( 8547 subjects ) , as well as on 2100 out of 5686 r and omly selected subjects in one suburban and one rural community . The study , based on a st and ardized question naire and clinical evaluation and laboratory investigation when necessary , was carried out by rheumatologists who visited the target population at their homes . Either established classification criteria or criteria set for the purpose s of the study were used for diagnosis . RESULTS A total of 8740 subjects participated in the study ( response rate 82.1 % ) . The overall age and sex adjusted prevalence ( prevalence(asa ) ) of rheumatic diseases in the total target adult population was 26.9 % ( 95 % CI 26.2 - 27.6 ) , being significantly higher among women ( 33.7 % ) than men ( 19.9 % ) ( p < 0.0005 ) . Disease prevalence(asa ) increased significantly with age ( p < 0.0005 ) . The most common disease group was low back pain , with a prevalence(asa ) of 11.0 % , followed by symptomatic peripheral osteoarthritis ( 7.9 % ) , neck pain ( 4.8 % ) , miscellaneous rheumatic disorders ( 4.4 % ) , soft tissue rheumatism disorders ( 4.3 % ) , and inflammatory rheumatic disease ( 2.1 % ) . Logistic regression analysis showed a significant positive association of female or male sex , age > or= 50 years , high body mass index , low level of education , moderate or heavy alcohol consumption , and high socioeconomic level with particular diseases or disease groups . CONCLUSION These findings indicate rheumatic diseases are very common in the general adult population of Greece ; 26.9 % of adults currently have active or chronic rheumatic disease in remission", "BACKGROUND AND OBJECTIVES A prospect i ve , double-blind , r and omized , and controlled trial was conducted in patients with knee osteoarthritis ( OA ) to evaluate the efficacy of infrared low-power Gallium-Arsenide ( Ga-As ) laser therapy ( LPLT ) and compared two different laser therapy regimes . STUDY DESIGN / MATERIAL S AND METHODS Ninety patients were r and omly assigned to three treatment groups by one of the nontreating authors by drawing 1 of 90 envelopes labeled ' A ' ( Group I : actual LPLT consisted of 5 minutes , 3 J total dose + exercise ; 30 patients ) , ' B ' ( Group II : actual LPLT consisted of 3 minutes , 2 J total dose + exercise ; 30 patients ) , and ' C ' ( Group III : placebo laser group + exercise ; 30 patients ) . All patients received a total of 10 treatments , and exercise therapy program was continued during study ( 14 weeks ) . Subjects , physician , and data analysts were unaware of the code for active or placebo laser until the data analysis was complete . All patients were evaluated with respect to pain , degree of active knee flexion , duration of morning stiffness , painless walking distance and duration , and the Western Ontario and Mc Master Universities Osteoarthritis Index ( WOMAC ) at week 0 , 6 , 10 , and 14 . RESULTS Statistically significant improvements were indicated in respect to all parameters such as pain , function , and quality of life ( QoL ) measures in the post-therapy period compared to pre-therapy in both active laser groups ( P < 0.01 ) . Improvements in all parameters of the Group I and in parameters , such as pain and WOMAC of the Group II , were more statistically significant when compared with placebo laser group ( P < 0.05 ) . CONCLUSIONS Our study demonstrated that applications of LPLT in different dose and duration have not affected results and both therapy regimes were a safe and effective method in treatment of knee OA", "BACKGROUND Acupuncture is widely used by patients with chronic pain although there is little evidence of its effectiveness . We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with osteoarthritis of the knee . METHODS Patients with chronic osteoarthritis of the knee ( Kellgren grade < or = 2 ) were r and omly assigned to acupuncture ( n=150 ) , minimal acupuncture ( superficial needling at non-acupuncture points ; n=76 ) , or a waiting list control ( n=74 ) . Specialised physicians , in 28 outpatient centres , administered acupuncture and minimal acupuncture in 12 sessions over 8 weeks . Patients completed st and ard question naires at baseline and after 8 weeks , 26 weeks , and 52 weeks . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index at the end of week 8 ( adjusted for baseline score ) . All main analyses were by intention to treat . RESULTS 294 patients were enrolled from March 6 , 2002 , to January 17 , 2003 ; eight patients were lost to follow-up after r and omisation , but were included in the final analysis . The mean baseline-adjusted WOMAC index at week 8 was 26.9 ( SE 1.4 ) in the acupuncture group , 35.8 ( 1.9 ) in the minimal acupuncture group , and 49.6 ( 2.0 ) in the waiting list group ( treatment difference acupuncture vs minimal acupuncture -8.8 , [ 95 % CI -13.5 to -4.2 ] , p=0.0002 ; acupuncture vs waiting list -22.7 [ -27.5 to -17.9 ] , p<0.0001 ) . After 52 weeks the difference between the acupuncture and minimal acupuncture groups was no longer significant ( p=0.08 ) . INTERPRETATION After 8 weeks of treatment , pain and joint function are improved more with acupuncture than with minimal acupuncture or no acupuncture in patients with osteoarthritis of the knee . However , this benefit decreases over time", "The purpose of this study was to compare the effectiveness of transcutaneous nerve stimulation ( TENS ) , electroacupuncture ( EA ) , and ice massage with placebo treatment for the treatment of pain . Subjects ( n = 100 ) diagnosed with osteoarthritis ( OA ) of the knee were treated with these modalities . The parameters for evaluating the effectiveness of treatment include pain at rest , stiffness , 50 foot walking time , quadriceps muscle strength , and knee flexion degree . The results showed ( a ) that all three methods could be effective in decreasing not only pain but also the objective parameters in a short period of time ; and ( b ) that the treatment results in TENS , EA and ice massage were superior to placebo", "Background : Low level laser therapy ( LLLT ) has gained increasing popularity in the management of tendinopathy and arthritis . Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action . Objective : To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon . Subjects : Seven patients with bilateral Achilles tendinitis ( 14 tendons ) who had aggravated symptoms produced by pain inducing activity immediately before the study . Method : Infrared ( 904 nm wavelength ) LLLT ( 5.4 J per point , power density 20 mW/cm2 ) and placebo LLLT ( 0 J ) were administered to both Achilles tendons in r and om blinded order . Results : Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 ( 95 % confidence interval 0.87 to 0.95 ) . Prostagl and in E2 concentrations were significantly reduced 75 , 90 , and 105 minutes after active LLLT compared with concentrations before treatment ( p = 0.026 ) and after placebo LLLT ( p = 0.009 ) . Pressure pain threshold had increased significantly ( p = 0.012 ) after active LLLT compared with placebo LLLT : the mean difference in the change between the groups was 0.40 kg/cm2 ( 95 % confidence interval 0.10 to 0.70 ) . Conclusion : LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis . LLLT may therefore have potential in the management of diseases with an inflammatory component", "OBJECTIVE To determine the minimal perceptible clinical improvement ( MPCI ) in patients with osteoarthritis ( OA ) with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) question naire , and patient and investigator global assessment of disease status in r and omized clinical trials for treatment of OA . METHODS Subjects with OA of the knee or hip were r and omized to receive either rofecoxib 12.5 or 25 mg once daily , ibuprofen 800 mg 3 times daily , or placebo for 6 weeks . The WOMAC and global assessment s were completed at baseline and Weeks 2 , 4 , and 6 . A patient global assessment of response to therapy ( 0 to 4 scale ) was used to \" anchor \" the WOMAC scores . MPCI was defined as the difference in mean change from baseline in WOMAC ( 100 mm normalized visual analog scale , VAS ) between patients with 0 = \" None \" global response to therapy and patients with 1 = \" Poor \" global response to therapy . RESULTS MPCI was determined to be 9.7 , 9.3 , and 10.0 mm for the WOMAC pain , physical function and stiffness subscales , respectively , and 11.1 mm for WOMAC question 1 : Pain walking on a flat surface . The MPCI for the investigator was 0.4 with investigator assessment of disease status reported on a 0 to 4 Likert scale . Of note , the estimated MPCI for the WOMAC and investigator globals were similar irrespective of treatment , sex , age , or geographic region . CONCLUSION In this analysis , mean changes of roughly 9 to 12 mm ( 100 mm normalized VAS ) on WOMAC scales were perceptible changes to patients with hip and knee OA . A mean decrease of 0.4 in global disease status ( 0 to 4 Likert scale ) as assessed by the investigator corresponded to the patients ' MPCI . Underst and ing the minimal perceptible differences may permit a better assessment of the clinical relevance of therapeutic interventions in OA", "OBJECTIVE This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation ( TENS ) for relieving osteoarthritic knee pain and the duration ( as measured by half-life ) of post-stimulation analgesia . SUBJECTS Thirty-eight patients received either : ( i ) 20 minutes ( TENS20 ) ; ( ii ) 40 minutes ( TENS40 ) ; ( iii ) 60 minutes ( TENS60 ) of TENS ; or ( iv ) 60 minutes of placebo TENS ( TENS(PL ) ) 5 days a week for 2 weeks . METHODS A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation . RESULTS By Day10 , a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 ( 83.40 % ) and TENS60 ( 68.37 % ) groups than in the TENS20 ( 54.59 % ) and TENS(PL ) ( 6.14 % ) groups ( p < 0.000 ) , such a group difference was maintained in the 2-week follow-up session ( p < 0.000 ) . In terms of the duration of post-stimulation analgesia period , the duration for the TENS40 ( 256 minutes ) and TENS60 ( 258 minutes ) groups was more prolonged than in the other 2 groups ( TENS20 = 168 minutes , TENS(PL ) = 35 minutes ) by Day10 ( p < 0.000 ) . However , the TENS40 group produced the longest pain relief period by the follow-up session . CONCLUSION 40 minutes is the optimal treatment duration of TENS , in terms of both the magnitude ( VAS scores ) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis", "& NA ; Transcutaneous electrical nerve stimulation ( TENS ) is a popular form of electrostimulation . Despite an extensive research base , there remains no consensus regarding the parameter selection required to achieve maximal hypoalgesic effects . The aim of this double blind , sham‐controlled study was to investigate the relative hypoalgesic effects of different TENS parameters ( frequency , intensity and stimulation site ) upon experimentally induced mechanical pain . Two hundred and forty participants were recruited in order to provide statistical analysis with 80 % power at & agr;=0.05 . Subjects were r and omised to one of the six TENS groups , a control , and a sham TENS group ( n=30 , 15 males , 15 females , per group ) . TENS groups differed in their combinations of stimulation ; frequency ( 4 or 110 Hz ) , intensity ( ‘ to tolerance ’ or ‘ strong but comfortable ’ ) and stimulation site ( segmental – over the distribution of the radial nerve or , extrasegmental – over acupuncture point ‘ gall bladder 34 ’ , or a combination of both segmental and extrasegmental ) . Pulse duration was fixed at 200 & mgr;s . Stimulation was delivered for 30 min and subjects were then monitored for a further 30 min . Mechanical pain threshold ( MPT ) was measured using a pressure algometer and taken from the first dorsal interosseous muscle of the dominant h and , ipsilateral to the stimulation site . MPT measures were taken , at baseline , and at 10‐min intervals for 60 min . Difference scores were analysed using repeated measures and one‐way ANOVA and relevant post hoc tests . Low frequency , high intensity , extrasegmental stimulation produced a rapid onset hypoalgesic effect , which increased during the stimulation period ( P<0.0005 control and sham ) and was sustained for 30 min post‐stimulation ( P<0.0005control , P=0.024sham ) . Whilst high frequency , ‘ strong but comfortable ’ intensity , segmental stimulation produced comparable hypoalgesic levels during stimulation , this effect was not sustained post‐stimulation . Stimulation at a combination of the two sites did not produce any greater hypoalgesic effects . These results may have implication s for the clinical use of sensory stimulation", "Background The purpose of this study was to compare the efficacy of electroacupuncture ( EA ) , diclofenac and their combination in symptomatic treatment of osteoarthritis ( OA ) of the knee . Methods This study was a r and omized , single-blind , placebo controlled trial . The 193 out- patients with OA of the knee were r and omized into four groups : placebo , diclofenac , EA and combined ( diclofenac plus EA ) . Paracetamol tablets were prescribed as a rescue analgesic during the study . The patients were evaluated after a run-in period of one week ( week 0 ) and again at the end of the study ( week 4 ) . The clinical assessment s included the amount of paracetamol taken/week , visual analog scale ( VAS ) , Western Ontario and McMaster Universities ( WOMAC ) OA Index , Lequesne 's functional index , 50 feet-walk time , and the orthopedist 's and patient 's opinion of change . Results One hundred and eighty six patients completed the study . The improvement of symptoms ( reduction in mean changes ) in most outcome parameters was greatest in the EA group . The proportions of responders and patients with an overall opinion of \" much better \" were also greatest in the EA group . The improvement in VAS was significantly different between the EA and placebo group as well as the EA and diclofenac group . The improvement in Lequesne 's functional index also differed significantly between the EA and placebo group . In addition , there was a significant improvement in WOMAC pain index between the combined and placebo group . Conclusion EA is significantly more effective than placebo and diclofenac in the symptomatic treatment of OA of the knee in some circumstances . However , the combination of EA and diclofenac treatment was no more effective than EA treatment alone", "Thirty patients with chronic pain due to osteoarthrosis ( OA ) of the knee were enrolled in a r and omised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation ( TENS ) and placebo TENS . Medication was st and ardised to paracetamol tablets only . As measured on visual analogue scales for pain relief 46 % of patients responded to active therapy and 43 % to placebo . The length of pain relief during active therapy was significantly longer than that during placebo . At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication . Although most of the parameters observed favoured active TENS , it was not possible to establish its clear superiority over placebo , because the response rate to placebo TENS was high and sustained for at least 3 weeks . This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis", "BACKGROUND AND METHODS Pulsed magnetic field therapy is frequently used to treat the symptoms of osteoarthritis , although its efficacy has not been proven . We conducted a r and omized , double-blind comparison of pulsed magnetic field and sham therapy in patients with symptomatic osteoarthritis of the knee . Patients were assigned to receive 84 sessions , each with a duration of 30 minutes , of either pulsed magnetic field or sham treatment . Patients administered the treatment on their own at home , twice a day for six weeks . RESULTS According to a sample size estimation , 36 consecutive patients were enrolled . 34 patients completed the study , two of whom had to be excluded from the statistical analysis , as they had not applied the PMF sufficiently . Thus , 15 verum and 17 sham-treated patients were enrolled in the statistical analysis . After six weeks of treatment the WOMAC Osteoarthritis Index was reduced in the pulsed magnetic field-group from 84.1 ( + /- 45.1 ) to 49.7 ( + /- 31.6 ) , and from 73.7 ( + /- 43.3 ) to 66.9 ( + /- 52.9 ) in the sham-treated group ( p = 0.03 ) . The following secondary parameters improved in the pulsed magnetic field group more than they did in the sham group : gait speed at fast walking [ + 6.0 meters per minute ( 1.6 to 10.4 ) vs. -3.2 ( -8.5 to 2.2 ) ] , stride length at fast walking [ + 6.9 cm ( 0.2 to 13.7 ) vs. -2.9 ( -8.8 to 2.9 ) ] , and acceleration time in the isokinetic dynamometry strength tests [ -7.0 % ( -15.2 to 1.3 ) vs. 10.1 % ( -0.3 to 20.6 ) ] . CONCLUSION In patients with symptomatic osteoarthritis of the knee , PMF treatment can reduce impairment in activities of daily life and improve knee function", "& NA ; The aim of this study was to investigate the effectiveness of pulsed short wave ( PSW ) in the relief of pain in osteoarthritis of the hip and knee . Ninety‐two patients , mean age 63 years , ( 34 men and 58 women ) were r and omly allocated to one of three groups : ( 1 ) Active PSW , using the dosage found in a pilot study to be non‐significantly most effective , ( 2 ) Placebo PSW , ( 3 ) No treatment control group . Nine sessions of treatment were provided over a 3‐week period , each application lasting for 15 min . The machine was modified by the manufacturers so that the therapist was able to administer the treatment and carry out assessment s without being aware of the treatment allocation . Outcome measures included sensory and affective pain diary reports averaged over days and weeks , self‐reported benefit and the General Health Question naire . Analysis of variance with repeated measures over time was used to find out if the active treatment had a specific effect , incremental to the placebo effect . There were no significant differences between the active and placebo groups over time . According to the pain diary reports , both active and placebo groups tended to improve slightly during treatment , but worsened after its withdrawal . Patients who were given the placebo application tended to report more benefit than those who had the active treatment , although this did not quite reach statistical significance ( P < 0.06 ) . Patients who were not on a waiting list for surgery did significantly better over time than those who were ( P < 0.03 ) . There were no significant differences between the groups over time for the other outcome variables . Any treatment effect on this patient population appears to have been largely placebo‐mediated . No evidence was found therefore for the specific effectiveness of PSW for treatment of osteoarthritic hip or knee pain", "OBJECTIVE The purpose of this study was to determine whether acupuncture was more effective than sham acupuncture in the reduction of pain in persons with osteoarthritis ( OA ) of the knee . METHODS Forty subjects ( 20 men , 20 women ) with radiographic evidence of OA of the knee were stratified by gender and r and omly assigned to either the experimental ( real acupuncture ) or control ( sham acupuncture ) groups . Subjects were treated three times per week for 3 weeks and evaluated at three test sessions . Outcome measures were : 1 ) the Pain Rating Index of the McGill Pain Question naire , 2 ) the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index , and 3 ) pain threshold at four sites at the knee . RESULTS The analyses of variance showed that both real and sham acupuncture significantly reduced pain , stiffness , and physical disability in the OA knee , but that there were no significant differences between groups . CONCLUSIONS Acupuncture is not more effective than sham acupuncture in the treatment of OA pain", "It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect , as suggested by the gate control theory . Electrical stimulation ( by way of Interferential Current ) applied at the pain area ( segmental ) was administered to 4 groups of patients with osteoarthritis ( OA ) knee pain . Two groups were administered with noxious stimulation ( 30 % above pain threshold ) and two with innocuous stimulation ( 30 % below pain threshold ) . In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived . Group 5 and 6 received sham stimulation and no treatment , respectively . The outcome measures were : chronic pain intensity , morning stiffness , range of motion ( ROM ) , pain threshold and % pain reduction . Both noxious and innocuous stimulation significantly decreased chronic pain ( P<0.001 ) and morning stiffness ( P<0.01 ) and significantly increased pain threshold ( P<0.001 ) and ROM ( P<0.001 ) compared with the control groups . Nevertheless , noxious stimulation decreased pain intensity ( P<0.05 ) and increased pain threshold ( P<0.001 ) significantly more than innocuous stimulation . No differences in treatment outcomes were found between adjusted and unadjusted stimulation . ( a ) Interferential current is very effective for chronic OA knee pain , ( b ) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation , ( c ) the fading of sensation during treatment , does not decrease the analgesic effect . Possible mechanisms explaining the findings are discussed", "Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation ( TENS ) and naproxen , an NSAID . All pre-experiment treatment was withdrawn . Each subject experienced in some order three 3-week treatment phases : NSAID plus placebo TENS ; TENS plus placebo drug ; and double placebo . A broad range of pain measures was used , including daily diary ratings , and four-times-per-day ratings entered into a small electronic data logger ( the PIPER ) worn by the subject . A substantial placebo response occurred across all conditions , which may have masked treatment differences . Broad comparisons across subjects , combining the four main measures of pain , found no significant differences among the three experimental treatments . Analysis of diary and PIPER data for individuals suggested that , in a small minority of subjects , the NSAID plus placebo TENS combination may be more effective than double placebo . The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures , suggesting the value of very frequent pain assessment s , such as those entered by a subject into the PIPER , in the study of chronic pain", "A prospect i ve study of 100 patients who were oper ated on in 1979 and 1980 was performed to determine the effect of transcutaneous neural stimulation ( TNS ) on the patients ' postoperative knee rehabilitation pro gram . The patients were then divided into four study groups . Fifty patients had a single incision arthrotomy with a meniscectomy . Of these surgical patients , Group A included 25 patients who were treated with a TNS unit postoperatively , and Group B includes 25 patients who did not use TNS . Fifty other patients had a total condylar-total knee replacement . Of these sur gical patients , Group C includes 25 patients who used TNS postoperatively and Group D includes 25 patients who did not use TNS . In the arthrotomy group the TNS patients ( Group A ) had a shorter average hospital stay ( 3.84 versus 5.40 days ) , initiated straight leg raises sooner ( 1.72 days versus 3.17 days ) and began am bulation sooner ( 1.4 days versus 2.44 days ) than the patients who did not use TNS ( Group B ) . As compared to Group B , Group A had a reduction in number of meperidine injections of 42.75 % and a reduction of meperidine dosage of 31.49 % . In the total knee pa tients , the group treated with TNS ( Group C ) also had a shorter hospital stay ( 14.92 days versus 17.88 days ) and performed straight leg raises sooner ( 4.92 days versus 7.54 days ) than patients who did not use TNS ( Group D ) . There was no difference in the ambulation times in Group C and Group D ( 4.96 days ) . There was a reduction of meperidine injections of 35.88 % and a reduction of meperidine dosage of 44.48 % in Group C. The use of TNS in postoperative knee patients improved their rehabilitation performance and shortened their hospital stay . No side effects were noted", "OBJECTIVE This is a double blind study that examined the optimal stimulation frequency of transcutaneous electrical nerve stimulation in reducing pain due to knee osteoarthritis . SUBJECTS Thirty-four subjects were r and omly allocated into 4 groups receiving transcutaneous electrical nerve stimulation at either : ( i ) 2 Hz ; ( ii ) 100 Hz ; ( iii ) an alternating frequency of 2 Hz and 100 Hz ( 2/100 Hz ) ; or ( iv ) a placebo transcutaneous electrical nerve stimulation . METHODS Treatment was administered 5 days a week for 2 weeks . The outcome measures included : ( i ) a visual analogue scale ; ( ii ) a timed up- and -go test ; and ( iii ) a range of knee motion . RESULTS The 3 active transcutaneous electrical nerve stimulation groups ( 2 Hz , 100 Hz , 2/100 Hz ) , but not the placebo group , significantly reduced osteoarthritic knee pain across treatment sessions . However , no significant between-group difference was found . Similarly , the 3 active transcutaneous electrical nerve stimulation groups , but not the placebo group , produced significant reductions in the amount of time required to perform the timed up- and -go test , and an increase in the maximum passive knee range of motion . CONCLUSION Our findings suggested that 2 weeks of repeated applications of transcutaneous electrical nerve stimulation at 2 Hz , 100 Hz or 2/100 Hz produced similar treatment effects for people suffering from osteoarthritic knee", "Within the context of a double blind r and omized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs , we vali date d WOMAC , a new multidimensional , self-administered health status instrument for patients with osteoarthritis of the hip or knee . The pain , stiffness and physical function subscales fulfil conventional criteria for face , content and construct validity , reliability , responsiveness and relative efficiency . WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials", "Abstract Objective To determine the effectiveness of commercially available magnetic bracelets for pain control in osteoarthritis of the hip and knee . Design R and omised , placebo controlled trial with three parallel groups . Setting Five rural general practice s. Participants 194 men and women aged 45 - 80 years with osteoarthritis of the hip or knee . Intervention Wearing a st and ard strength static bipolar magnetic bracelet , a weak magnetic bracelet , or a non-magnetic ( dummy ) bracelet for 12 weeks . Main outcome measures Change in the Western Ontario and McMaster Universities osteoarthritis lower limb pain scale ( WOMAC A ) after 12 weeks , with the primary comparison between the st and ard and dummy groups . Secondary outcomes included changes in WOMAC B and C scales and a visual analogue scale for pain . Results Mean pain scores were reduced more in the st and ard magnet group than in the dummy group ( mean difference 1.3 points , 95 % confidence interval 0.05 to 2.55 ) . Self reported blinding status did not affect the results . The scores for secondary outcome measures were consistent with the WOMAC A scores . Conclusion Pain from osteoarthritis of the hip and knee decreases when wearing magnetic bracelets . It is uncertain whether this response is due to specific or non-specific ( placebo ) effects", "Patients suffering from pain due to osteoarthritis of the hip and knee participated in a double-blind placebo controlled trial using daily Codetron home care units for 6 weeks over the tibial , saphenous , popliteal and sciatic nerves , and tender points . Seventy-four percent of patients in the real Codetron ( Group A ) and 28 % of the patients in sham Codetron ( Group B ) improved their pain level more than 25 % as measured by visual analogue scale . The difference in pain improvement in the two groups was statistically significant ( p < 0.02 using Fisher 's exact probability ratio ) Other functional parameters proved to be insensitive to change in this study . This is highly suggestive of beneficial effect of chronic pain conditions such as osteoarthritis", "Abstract Electroacupuncture is commonly used for pain relief . Despite an extensive evidence ‐base guiding the selection of stimulation parameters , little method ologically robust research exists regarding the level of intensity required to provide effective doses . This study investigated the hypoalgesic effects of two stimulation intensities compared to placebo on pressure pain thresholds ( PPTs ) in pain‐free humans . Forty‐eight acupuncture‐naïve volunteers ( mean age 23 ) , stratified by gender , were screened for relevant contraindications and r and omly allocated to four groups : control , placebo , high‐intensity ( “ to tolerance but sub‐noxious ” ) or low‐intensity ( “ strong but comfortable ” ) . True or placebo electroacupuncture , using the Streitberger placebo needle , was administered to acupoints on dominant forearm ( LI10 , TH5 ) and ipsilateral leg ( GB34 , ST38 ) . True needles ( 30 mm long , 0.3 mm diameter ) were inserted 20–25 mm and “ de‐qi ” was elicited from active groups , prior to administering 30 min of 4 Hz , 200 & mgr;s electroacupuncture . No electrical stimulation was performed on control and placebo groups , and placebo needles were used . After the intervention period , all needles were removed . Volunteers were monitored for 30 further minutes . Two PPT measurements were taken bilaterally from muscle bellies of first dorsal interosseous by an independent rater , at baseline and at six subsequent 10‐min intervals . Square‐root transformed data were analysed using repeated‐ measures ANOVA , with baseline data as covariate . The high‐intensity group was significantly different from the placebo group for both measurement sites ( p = .020 , p = .033 ) . The control group displayed stable PPT readings over time . No significant differences were observed between the placebo and control groups . These findings suggest that high‐intensity levels may be important in optimal dose selection", "Summary We assessed the efficacy and tolerability of low-frequency pulsed electromagnetic fields ( PEMF ) therapy in patients with clinical ly symptomatic knee osteoarthritis ( OA ) in a r and omised , placebo-controlled , double-blind study of six weeks ' duration . Patients with radiographic evidence and symptoms of OA ( incompletely relieved by conventional treatments ) , according to the criteria of the American College of Rheumatology , were recruited from a single L tertiary referral centre . 75 patients fulfilling the above criteria were r and omised to receive active PEMF treatment by unipolar magnetic devices ( Medicur ) manufactured by Snowden Healthcare ( Nottingham , UK ) or placebo . Six patients failed to attend after the screening and were excluded from analysis . The primary outcome measure was reduction in overall pain assessed on a four-point Likert scale ranging from nil to severe . Secondary outcome measures included the WOMAC Osteoarthritis Index ( Likert scale ) and the EuroQol ( Euro- Quality of Life , EQ-5D ) . Baseline assessment s showed that the treatment I groups were equally matched . Although there were no significant differences between active and sham treatment groups in respect of any outcome measure after treatment , paired analysis of the follow-up observations on each patient showed significant improvements in the actively treated group in the WOMAC global score ( p = 0.018 ) , WOMAC pain score ( p = 0.065 ) , WOMAC disability score ( p = 0.019 ) and EuroQol score ( p = 0.001 ) at study end compared to baseline . In contrast , there were no improvements in any variable in the placebo-treated group . There were no clinical ly relevant adverse effects attributable to active treatment . These results suggest that the Medicur unipolar magnetic devices are beneficial in reducing pain and disability in patients with knee OA resistant to conventional treatment in the absence of significant side-effects . Further studies using different types of magnetic devices , treatment protocol s and patient population s are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions", "BACKGROUND In clinical trials , at the group level , results are usually reported as mean and st and ard deviation of the change in score , which is not meaningful for most readers . OBJECTIVE To determine the minimal clinical ly important improvement ( MCII ) of pain , patient 's global assessment of disease activity , and functional impairment in patients with knee and hip osteoarthritis ( OA ) . METHODS A prospect i ve multicentre 4 week cohort study involving 1362 out patients with knee or hip OA was carried out . Data on assessment of pain and patient 's global assessment , measured on visual analogue scales , and functional impairment , measured on the Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) function subscale , were collected at baseline and final visits . Patients assessed their response to treatment on a five point Likert scale at the final visit . An anchoring method based on the patient 's opinion was used . The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA , 211 with hip OA ) . RESULTS For knee and hip OA , MCII for absolute ( and relative ) changes were , respectively , ( a ) -19.9 mm ( -40.8 % ) and -15.3 mm ( -32.0 % ) for pain ; ( b ) -18.3 mm ( -39.0 % ) and -15.2 mm ( -32.6 % ) for patient 's global assessment ; ( c ) -9.1 ( -26.0 % ) and -7.9 ( -21.1 % ) for WOMAC function subscale score . The MCII is affected by the initial degree of severity of the symptoms but not by age , disease duration , or sex . CONCLUSION Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients", "Abstract Ten patients with pain due to osteoarthritis of the knee were treated in a double‐blind cross‐over study with two weeks of transcutaneous electrical nerve stimulation ( TENS ) and placebo . There was statistically significant pain relief by TENS and half of the patients chose to continue using TENS for pain control after the test month . However , at one year 's follow‐up , only two patients had sufficient benefit to continue using the device", "OBJECTIVE To estimate minimal clinical ly important differences ( MCID ) of effects measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) in patients with osteoarthritis ( OA ) of the lower extremities undergoing a comprehensive inpatient rehabilitation intervention . METHODS A prospect i ve cohort study assessed patients ' health by the WOMAC at baseline ( entry into the clinic ) and at the 3 month followup , and by a transition question naire asking about the change of \" health in general related to the OA joint \" during that time period . The WOMAC section score differences between the \" equal \" group and the \" slightly better \" and \" slightly worse \" groups result ed in the MCID for improvement and for worsening . RESULTS In total 192 patients were followed up . The MCID for improvement ranged from 0.80 to 1.01 points on the continuous WOMAC numerical rating scale from 0 to 10 , reflecting changes of 17 to 22 % of baseline scores . The MCID for worsening conditions ranged from 0.29 ( 6 % ) to 1.03 points ( 22 % ) . In the transition reply subjectively unchanged patients reported a \" pessimistic bias \" of 0.35 to 0.51 points , except for the stiffness section . Both MCID and pessimistic bias showed regression to the mean and baseline dependency . CONCLUSION The assessment of MCID using the transition method is a heuristic and valid strategy to detect particular rehabilitation effects in patients with OA of the lower extremities with the use of the WOMAC , and it is worth implementing . The size of the MCID and of the systematic bias is comparable to that assessed by other methods and in other therapeutic setting", "OBJECTIVE The purpose of this study was to investigate the effects and minimum effective dose of laser acupuncture in knee osteoarthritis ( KOA ) , and to determine if it is superior to placebo treatment ( sham ) in the evaluation of clinical -functional outcome and quality of life . METHODS In this r and omized , placebo-controlled study , patients with grade 2 and 3 primary KOA were selected . Group I ( n = 27 ) received 904-nm low-level laser irradiation with 10 mW/cm(2 ) power density , 4 mW output power , 0.4 cm(2 ) spot size , 0.48 J dose per session , and 120-sec treatment time on the medial side of the knee to the acupuncture point Sp9 . Group II ( n = 25 ) received placebo-laser therapy at the same place on the same point . Patients in both of the groups had treatment 5 days per week ( total duration of therapy was 10 days ) and 20 min per day . The study was comprised of a 2-week ( 10-session ) intervention . Participants were evaluated before treatment ( baseline ) , after treatment ( 2nd week ) , and at the 12th week . In this double-blind study , a blind examiner carried out all outcome assessment s. The main outcome measures were as follows : pain on movement ( pVAS ) , 50-foot walking time ( 50 foot w ) , knee circumference ( KC ) , medial tenderness score ( MTS ) , Western Ontario and McMaster Universities osteoarthritis index ( WOMAC ) , and Nottingham Health Profile ( NHP ) . RESULTS Statistically significant improvement was observed in PVAS , 50 foot w , and KC in group 1 . In Group II , statistically significant improvement was observed in PVAS , 50 foot w , and WOMAC . When groups were compared with each other , the improvement observed in KC was superior in Group I at the 2(nd ) week ( p = 0.005 ) . CONCLUSION Laser acupuncture was found to be effective only in reducing periarticular swelling when compared with placebo laser", "OBJECTIVE To determine , in subjects with knee pain but no radiographic changes of tibiofemoral or patellofemoral compartment osteoarthritis ( OA ) , whether mean body weight , quadriceps and hamstring strength , lower extremity muscle mass , depression scores , and perceptions of their general health status differed from those of subjects with symptomatic knee OA . METHODS Subjects were 25 women and 10 men with knee pain and radiographic evidence of OA at the baseline examination , and 21 women and 16 men who had knee pain at the baseline examination but no radiographic evidence of knee OA at either baseline examination or followup evaluation performed , on average , 31 months later . These individuals were a subset of a cohort of 462 independently living elderly individuals recruited by telephone interview after r and om selection through r and om digit dialing of households in central Indiana . Data from an additional 134 subjects who had neither knee pain nor radiographic changes of OA at either the baseline or followup examination were analyzed for comparison . Lower extremity muscle strength was measured by isokinetic dynamometry , lean tissue ( i.e. , muscle ) mass in the lower extremities by dual x-ray absorptiometry , depression by Center for Epidemiology Depression ( CES-D ) scale . knee pain by Western Ontario McMaster University OA instrument , and perceived general health status by the Medical Outcome Survey Short Form-36 . RESULTS In contrast to those with symptomatic knee OA , those who had knee pain but no radiographic evidence of OA were less obese , had hamstring as well as quadriceps weakness , and had CES-D scores high enough to qualify for a diagnosis of clinical depression . CONCLUSION Among subjects with knee pain but no OA-- and among women in this subset , in particular -- knee pain may be a manifestation of depression . rather than of joint disease" ]

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[ "Predictors of opioid misuse in patients with chronic pain: a prospective cohort study", "Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio?", "Effects of opioids on driving ability.", "Oxytrex minimizes physical dependence while providing effective analgesia: a randomized controlled trial in low back pain.", "Long-term Use of Controlled-release Oxycodone for Noncancer Pain: Results of a 3-year Registry Study", "Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated patients with chronic low back pain: a randomized, placebo-controlled study*", "Urine Toxicology Screening Among Chronic Pain Patients on Opioid Therapy: Frequency and Predictability of Abnormal Findings", "The effects of transdermal fentanyl on driving, cognitive performance, and balance in patients with chronic nonmalignant pain conditions.", "Opioid rotation from high-dose morphine to transdermal buprenorphine (Transtec) in chronic pain patients.", "Use of opioid medications for chronic noncancer pain syndromes in primary care", "Long term effects of oral sustained release morphine on neuropsychological performance in patients with chronic non-cancer pain", "Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool.", "Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study.", "A randomized, double-blind, placebo-controlled, cross-over pilot study to assess the effects of long-term opioid drug consumption and subsequent abstinence in chronic noncancer pain patients receiving controlled-release morphine.", "Patients with chronic pain and abnormal pituitary function require investigation", "Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: a nine-month follow-up study", "Lost productive time and cost due to common pain conditions in the US workforce.", "Driving ability under long-term treatment with transdermal fentanyl.", "Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study.", "Opioid switching from morphine to methadone causes a minor but not clinically significant increase in QTc time: A prospective 9-month follow-up study.", "Association between mental health disorders, problem drug use, and regular prescription opioid use.", "Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction--a 21-day treatment-randomized clinical trial.", "Measurement of QTc in patients receiving chronic methadone therapy.", "A community-based evaluation of sudden death associated with therapeutic levels of methadone." ]

[ "Background Opioid misuse can complicate chronic pain management , and the non-medical use of opioids is a growing public health problem . The incidence and risk factors for opioid misuse in patients with chronic pain , however , have not been well characterized . We conducted a prospect i ve cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice . Methods One-hundred and ninety-six opioid-treated patients with chronic , non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals . Opioid misuse was defined as : 1 . Negative urine toxicological screen ( UTS ) for prescribed opioids ; 2 . UTS positive for opioids or controlled substances not prescribed by our practice ; 3 . Evidence of procurement of opioids from multiple providers ; 4 . Diversion of opioids ; 5 . Prescription forgery ; or 6 . Stimulants ( cocaine or amphetamines ) on UTS . Results The mean patient age was 52 years , 55 % were male , and 75 % were white . Sixty-two of 196 ( 32 % ) patients committed opioid misuse . Detection of cocaine or amphetamines on UTS was the most common form of misuse ( 40.3 % of misusers ) . In bivariate analysis , misusers were more likely than non-misusers to be younger ( 48 years vs 54 years , p < 0.001 ) , male ( 59.6 % vs. 38 % ; p = 0.023 ) , have past alcohol abuse ( 44 % vs 23 % ; p = 0.004 ) , past cocaine abuse ( 68 % vs 21 % ; p < 0.001 ) , or have a previous drug or DUI conviction ( 40 % vs 11 % ; p < 0.001 % ) . In multivariate analyses , age , past cocaine abuse ( OR , 4.3 ) , drug or DUI conviction ( OR , 2.6 ) , and a past alcohol abuse ( OR , 2.6 ) persisted as predictors of misuse . Race , income , education , depression score , disability score , pain score , and literacy were not associated with misuse . No relationship between pain scores and misuse emerged . Conclusion Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice . Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed . Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion", "PURPOSE To define the dose ratio between morphine and methadone in relation to the previous morphine dose and the number of days needed to achieve the same level of analgesia in a group of patients with advanced cancer with pain who switched from morphine to oral methadone . PATIENTS AND METHODS A cross-sectional prospect i ve study of 38 consecutive cancer patients who switched from morphine to oral methadone was performed . The intensity of pain before , during , and after the switching period was assessed through a four-point verbal Likert scale . The relationship between previous morphine dose and the final equianalgesic methadone dose , dose ratio between morphine and methadone , and the number of days required to achieve equianalgesia have been examined by means of Pearson 's correlation coefficient , scatter plots , and Cuzick 's test for trend respectively . RESULTS Before the switch , the median oral equivalent daily dose of morphine was 145 mg/d ; after the switch , the median equianalgesic oral methadone dose was 21 mg/d . A median time of 3 days ( range , 1 to 7 days ) was necessary to achieve the equianalgesia with oral methadone ; the lower the preswitching morphine dose , the fewer days necessary to achieve equianalgesia with oral methadone ( P < .001 ) . Dose ratios ranged from 2.5:1 to 14.3:1 ( median , 7.75:1 ) , which indicated that , in most cases , the dose ratio was much higher than that suggested by the published equianalgesic tables . A strong linear positive relationship between morphine and methadone equianalgesic doses was obtained ( Pearson 's correlation coefficient , 0.91 ) . The dose ratio increased with the increase of the previous morphine dose with a much higher increase at low morphine doses . CONCLUSION The results of our study confirm that methadone is a potent opioid , more potent than believed . Caution is recommended when switching from any opioid to methadone , especially in patients who are tolerant to high doses of opioids", "Driving has been regarded as an activity of daily living that is important in maintaining a person 's independence in the community , access to employment , and social activities . Many patients , however , using opioid medications on a regular basis ( Chronic Opioid Analgesic Therapy : COAT ) to ameliorate their intractable pain have been restricted from driving out of concern that skills would be impaired and driving safety compromised by these medications . Yet there are no driving studies which have explored the effects of using opioid analgesics for an extended period of time . This pilot study was design ed to determine the effects of medically prescribed , stable opioid use on the driving abilities of patients with persistent , nonmalignant pain . Sixteen patients with chronic nonmalignant pain on COAT , who met criteria for participation in the study , underwent a comprehensive off-road driving evaluation using measures which have been shown to be sensitive in predicting on-road driving performance . The evaluation consisted of a pre-driver evaluation ( PDE ) , a simulator evaluation ( SDE ) , and behavioral observation during simulator performance . Patients in the COAT group were compared to a historical control group of 327 cerebrally compromised patients ( CComp ) who had undergone the same evaluation and then passed an on-road , behind-the-wheel evaluation ( BTW Pass ; n = 162 ) or failed ( BTW Fail ; n = 165 ) . Results revealed that COAT patients generally outperformed the CComp patients as a group by equaling or exceeding PDE and SDE scores of the BTW Fail patients as well as the BTW Pass patients on all measures that differentiated the groups . Notably , COAT patients had a relatively poorer performance than CComp patients on specific neuropsychometric tests in the PDE ; however , the differences were not statistically significant and did not imply a systematic pattern of scores that reflected domain-specific deficits . Behaviorally , COAT patients were generally superior to CComp patients , also ; however , COAT patients had greater difficulty in following instructions and as well as a tendency toward impulsivity , like the BTW fail group . While there was general support for the notion that COAT did not significantly impair the perception , cognition , coordination , and behavior measured in off-road tests that have been regarded as requisite for on-road driving , method ological problems may limit the generalizability of results and recommendations are made for research beyond a pilot study", "UNLABELLED Physical dependence or withdrawal is an expected effect of prolonged opioid therapy . Oxytrex ( oxycodone + ultralow-dose naltrexone ) is an investigational drug shown here to minimize physical dependence while providing strong analgesia with twice-daily dosing . In this 719-patient , double-blind , placebo- and active-controlled Phase III clinical trial in chronic low back pain , patients were r and omized to receive placebo , oxycodone qid , or oxytrex qid or bid . Each oxytrex tablet contains 1 microg naltrexone ; oxytrex bid and qid treatments provide 2 and 4 microg naltrexone/day , respectively . Following a washout , patients with pain > or=5 on a 0 - 10 scale were dose-escalated weekly from 10 up to 80 mg/day until reaching adequate pain relief ( < or=2 ) or a tolerable level of side effects . Following titration , the dose was fixed for 12 weeks . Active treatment groups attained comparable analgesia despite significantly lower drug use ( P = .03 ) by oxytrex patients . Patients taking oxytrex bid reported 55 % less physical dependence than patients on oxycodone ( P = .01 ) by the Short Opiate Withdrawal Scale 24 h after treatment cessation . Oxytrex bid patients also reported decreased moderate-to-severe constipation ( by 44 % , P = .01 ) , somnolence ( by 33 % , P = .03 ) , and pruritus ( by 51 % , P < .001 ) . This is the first large well controlled study to show strong analgesia with minimal withdrawal symptoms and better safety compared with oxycodone . PERSPECTIVE Previous clinical data have shown ultralow-dose naltrexone enhances and prolongs oxycodone analgesia , and pre clinical data also show a suppression of opioid tolerance and dependence . A cellular mechanism of action has been demonstrated to be the prevention of aberrant G protein signaling by mu opioid receptors caused by chronic opioid administration", "Objective To evaluate the outcomes associated with the use of controlled-release ( CR ) oxycodone for up to 3 years in the treatment of noncancer pain . Methods Adult patients who previously participated in controlled trials of CR oxycodone for osteoarthritis pain , diabetic neuropathy pain , or low back pain , and who continued to require opioid analgesia for moderate or severe pain , were enrolled in an open-label , uncontrolled , registry study . Data collected over time included dose , pain severity on a numeric scale , treatment acceptability , adverse events , and descriptions of problematic drug-related behavior . Results Two hundred thirty-three patients were enrolled . When the study closed , 141 , 86 , and 39 patients had taken CR oxycodone for at least 1 , 2 , and 3 years , respectively ; mean duration of treatment was 541.5 days . Among the 219 intent-to-treat patients ( received at least 1 dose and provided at least 1 postdose study observation ) , the mean ( SD , range ) daily dose was 52.5 ( ±38.5 , 10.0 to 293.5 ) mg . Before the end of month 3 , 44 % required an increase in total daily dose ; this dropped to 23 % during months 4 to 6 , to 17 % during months 10 to 12 , and remained at approximately 10 % for each time interval thereafter ( range 8 % to 13 % ) . Among the large majority of patients with stable or lower dose requirements after the initial 3 months of treatment , the average pain intensity ratings were unchanged or improved for approximately 70 % to 80 % of patients at all subsequent time points through month 33 , and for 54 % ( 7/13 patients ) at month 36 . A decrease in pain was initially seen by the end of month 3 , and for the majority of patients , the Average Pain Intensity score remained the same , better , or minimally worse ( <3 points ) for the remainder of the 3-year study period . The most common adverse events were constipation and nausea , and the incidence of these events declined over time on treatment . Investigators reported 6 cases ( 2.6 % ) of possible drug misuse but no evidence of de novo addiction was observed . Discussion These registry data demonstrate that a subgroup of patients with noncancer pain experienced prolonged relief with tolerable side effects and modest need for dose escalation during long-term therapy with CR oxycodone", "ABSTRACT Background : Short-acting opioids are commonly used to treat breakthrough pain ( BTP ) and rapid-onset formulations are being developed to improve the effectiveness of this approach . Fentanyl buccal tablet ( FBT ) is a new formulation of fentanyl that enhances transbuccal drug delivery via an effervescent reaction and may provide relatively rapid-onset analgesia . FBT was evaluated for BTP in opioid-treated patients with chronic low back pain – the first such study in a population with chronic non-cancer pain . Design : R and omized , double-blind , placebo-controlled . Patients and setting : Patients with chronic low back pain receiving long-term opioid therapy at 16 pain treatment centers in the United States . Procedures : Following open-label titration to identify an effective FBT dose , patients were r and omly assigned to one of three double-blind dose sequences ( six doses of FBT , three placebo ) to treat nine BTP episodes . Pain intensity ( PI ) , measured on an 11-point scale ( 0 = no pain ; 10 = worst pain ) , and other outcomes were assessed for 2 h after dosing . Data analysis : The primary efficacy measure was the sum of pain intensity differences ( PIDs ) for the first 60 min ( SPID60 ) ; secondary efficacy measures included PIDs at other time points , pain relief ( PR ) , meaningful PR , time to meaningful PR , use of supplementary BTP medication , and self/investigator-reported adverse events . Results : Of the 124 patients screened , 105 patients were enrolled , 84 identified an effective FBT dose , and 77 entered the double-blind phase . SPID60 significantly favored FBT ( p < 0.0001 ) . All secondary measures also favored FBT , with PIDs and PR showing significant differences versus placebo as early as 10 and 15 min , respectively . An improvement in PI score of ≥ 33 % occurred in a significantly larger proportion of FBT-treated episodes versus placebo from 15 min ( 20 % vs. 11 % , p < 0.01 ) through 2 h ( 65 % vs. 28 % , p < 0.0001 ) . Patients were approximately four times more likely to require supplemental opioids for BTP episodes following administration of placebo compared with episodes treated with FBT . AEs were typical for opioids , and were mostly reported during dose titration . Limitations of this study may be related to its open-label dose-titration phase ( which has the potential to compromise blinding ) and the recruitment of patients from pain clinics , which could potentially yield a study population that is not representative of the general population with BTP . Conclusions : FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain", "Objective To examine the incidence of abnormal urine toxicology screening among chronic pain patients prescribed opioids for their pain and to relate these results to patient descriptors and type , number , and dose of prescribed opioids . Methods A retrospective analysis of data from 470 patients who had urine screening at a pain management program in an urban teaching hospital was performed . Urine sample s were analyzed using gas chromatography-mass spectrometry . Patients were categorized as having urine screens that were “ normal ” ( expected findings based on their prescribed drugs ) or abnormal . Abnormal findings were those of ( 1 ) absence of a prescribed opioid , ( 2 ) presence of an additional nonprescribed controlled substance , ( 3 ) detection of an illicit substance , and ( 4 ) an adulterated urine sample . Results Forty-five percent of the patients were found to have abnormal urine screens . Twenty percent were categorized as having an illicit substance in their urine . Illicit substances and additional drugs were found more frequently in younger patients than in older patients ( P<0.001 ) . No other variables were found to predict abnormal urine screen results . Discussion These results confirm past findings that r and om urine toxicology screens among patients prescribed opioids for pain reveal a high incidence of abnormal findings . Common patient descriptors , and number , type , and dose of prescribed opioids were found to be poor predictors of abnormal results", "OBJECTIVE To evaluate driving performance , cognition , and balance in patients with chronic nonmalignant pain before and after the addition of transdermal fentanyl to their treatments . DESIGN Prospect i ve , one-group pretest-posttest design . SETTING Outpatient pain center associated with a large , urban medical school . INTERVENTIONS Patients taking less than a 15-mg equivalent of oxycodone per day took baseline driving performance , cognitive , and balance tests . Transdermal fentanyl was initiated and titrated in 25-microg/hour increments , weighing benefits and side effects . At the end of a 1-month period , the achieved dose was maintained for another month . After they were stabilized for 1 month , patients repeated driving , cognitive , and balance tests . RESULTS Twenty three patients completed the study ; three discontinued secondary to side effects . The median dose at the end of the titration period was 50 microg/hour ( 48 % ) . No differences were found in driving simulation measures between the pretreatment and posttreatment periods . No decrements in cognitive performance were found . Improvements in visual motor tracking , visual memory , and attention were found during treatment with transdermal fentanyl . No differences in balance or body sway were found . Pain decreased over the course of treatment . CONCLUSIONS The addition of transdermal fentanyl to a treatment regimen containing no opiates or small amounts of opiates for patients with chronic nonmalignant pain did not negatively affect their driving performances , reaction times , cognition , or balance . Future studies in this area are needed to guide treatment decisions", "Opioid rotation is increasingly becoming an option to improve pain management especially in long-term treatment . Because of insufficient analgesia and intolerable side effects , a total of 42 patients ( 23 male , 19 female ; mean age 64.1 years ) suffering from severe musculoskeletal ( 64 % ) , cancer ( 21 % ) or neuropathic ( 19 % ) pain were converted from high-dose morphine ( 120 to > 240 mg/day ) to transdermal buprenorphine . The dose of buprenorphine necessary for conversion ( at least 52.5 microg/h ) was titrated individually by the treating physician . No conversion recommendations were given and the treating physician used his or her own judgment for dose adjustment . Pain relief , overall satisfaction and quality of sleep ( very good , good , satisfactory , poor , or very poor ) , and the incidence and severity of adverse drug reactions over a period of at least 10 weeks and up to 1 year was assessed . Following rotation , patients experiencing good/very good pain relief increased from 5 % to 76 % ( P < 0.001 ) . Only 5 % reported insufficient relief . Relief was achieved with buprenorphine alone in 77.4 % , while 17 % needed an additional opioid for breakthrough pain . Sleep quality ( good/very good ) increased from 14 % to 74 % ( P < 0.005 ) . Adverse effects were reported in 11.9 % , mostly because of local irritation , did not result in termination of therapy . Neither tolerance nor refractory effect following rotation from morphine to buprenorphine was noted . Conversion tables with a fixed conversion ratio are of limited value in patients treated with high-dose morphine", "Abstract OBJECTIVES : To define the spectrum of chronic noncancer pain treated with opioid medications in 2 primary care setting s , and the prevalence of psychiatric comorbidity in this patient population . We also sought to determine the proportion of patients who manifested prescription opioid abuse behaviors and the factors associated with these behaviors . DESIGN : A retrospective cohort study . SETTING : A VA primary care clinic and an urban hospital-based primary care center ( PCC ) located in the northeastern United States . PATIENTS : A r and om sample of VA patients ( n=50 ) and all PCC patients ( n=48 ) with chronic noncancer pain who received 6 or more months of opioid prescriptions during a 1-year period ( April 1 , 1997 through March 31 , 1998 ) and were not on methadone maintenance . MEASUREMENTS : Information regarding patients ’ type of chronic pain disorder , demographic , medical , and psychiatric status , and the presence of prescription opioid abuse behaviors was obtained by medical record review . MAIN RESULTS : Low back pain was the most common disorder accounting for 44 % and 25 % of all chronic pain diagnoses in the VA and PCC sample s , respectively , followed by injury-related ( 10 % and 13 % ) , diabetic neuropathy ( 8 % and 10 % ) , degenerative joint disease ( 16 % and 13 % ) , spinal stenosis ( 10 % and 4 % ) , headache ( 4 % and 13 % ) and other chronic pain disorders ( 8 % and 22 % ) . The median duration of pain was 10 years ( range 3 to 50 years ) in the VA and 13 years in the PCC sample ( range 1 to 49 years ) . Among VA and PCC patients , the lifetime prevalence rates of psychiatric comorbidities were : depressive disorder ( 44 % and 54 % ) , anxiety disorder ( 20 % and 21 % ) , alcohol abuse/dependence ( 46 % and 31 % ) , and narcotic abuse/dependence ( 18 % and 38 % ) . Prescription opioid abusive behaviors were recorded for 24 % of VA and 31 % of PCC patients . A lifetime history of a substance use disorder ( adjusted odds ratio [ OR ] , 3.8 ; 95 % confidence interval [ CI ] , 1.4 to 10.8 ) and age ( adjusted OR , 0.94 ; 95 % CI , 0.89 to 0.99 ) were independent predictors of prescription opioid abuse behavior . CONCLUSIONS : A broad spectrum of chronic noncancer pain disorders are treated with opioid medications in primary care setting s. The lifetime prevalence of psychiatric comorbidity was substantial in our study population . A significant minority of patients manifested prescription opioid abusive behaviors , and a lifetime history of a substance use disorder and decreasing age were associated with prescription opioid abuse behavior . Prospect i ve studies are needed to determine the potential benefits as well as risks associated with opioid use for chronic noncancer pain in primary care", "& NA ; Morphine is increasingly used in patients with chronic non‐cancer pain , but a major concern associated with chronic use relates to possible cognitive side‐effects . The aim of this long‐term prospect i ve study was to evaluate the cognitive impact of oral sustained release morphine in patients with non‐cancer pain . A battery of neuropsychological tests to explore attention , psychomotor speed and memory was administered . The effects of morphine on pain , quality of life , mood , subjective memory impairment and side‐effects were also investigated . Evaluations were performed at baseline in patients free from opioids and then after 3 , 6 and 12 months . Twenty‐eight patients were included : 18 received oral sustained morphine ( range 40–140 mg/day ) , ten patients stopped morphine prematurely because of side‐effects or insufficient pain relief and were followed as a control group . There was no impairment of any neuropsychological variable over time in the morphine treated patients in comparison with the control group . Two measures of information processing speed – the Stroop interference score and the digit symbol test were improved at 6 and 12 months and there were significant correlations with the pain relief and improvement of mood . Self‐reported memory impairment improved notably in responders to morphine . Morphine induced persisting effects on pain , and to a lesser extent on quality of life and mood . The visual analog scale score for side‐effects increased at 12 months and essentially consisted of gastrointestinal disorders . This study demonstrates that 12 months treatment with oral morphine does not disrupt cognitive functioning in patients with chronic non‐cancer pain and instead results in moderate improvement of some aspects of cognitive functioning , as a consequence of the pain relief and concomitant improvement of well‐being and mood", "OBJECTIVE To provide clinicians with a brief screening tool to predict accurately which individuals may develop aberrant behaviors when prescribed opioids for chronic pain . DESIGN One hundred and eighty-five consecutive new patients treated in one pain clinic took the self-administered Opioid Risk Tool ( ORT ) . The ORT measured the following risk factors associated in scientific literature with substance abuse : personal and family history of substance abuse ; age ; history of preadolescent sexual abuse ; and certain psychological diseases . Patients received scores of 0 - 3 ( low risk ) , 4 - 7 ( moderate risk ) , or > or= 8 ( high risk ) , indicating the probability of their displaying opioid-related aberrant behaviors . All patients were monitored for aberrant behaviors for 12 months after their initial visits . RESULTS For those patients with a risk category of low , 17 out of 18 ( 94.4 % ) did not display an aberrant behavior . For those patients with a risk category of high , 40 out of 44 ( 90.9 % ) did display an aberrant behavior . The authors used the c statistic to vali date the ORT , because it simultaneously assesses sensitivity and specificity . The ORT displayed excellent discrimination for both the male ( c = 0.82 ) and the female ( c = 0.85 ) prognostic models . CONCLUSION In a preliminary study , among patients prescribed opioids for chronic pain , the ORT exhibited a high degree of sensitivity and specificity for determining which individuals are at risk for opioid-related , aberrant behaviors . Further studies in a variety of pain and nonpain setting s are needed to determine the ORT 's universal applicability", "BACKGROUND Patients with chronic noncancer pain , including neuropathic pain , may have transitory exacerbations of pain ( median duration , 60 minutes ) , termed breakthrough pain ( BTP ) , that may reach peak intensity within minutes . Typical short-acting oral opioids may not provide sufficiently rapid relief ( 30- to 60-minute onset of analgesia ) . The fentanyl buccal tablet ( FBT ) provides a rapid onset of analgesia ( 10 - 15 minutes ) by enhancing fentanyl absorption across the buccal mucosa . OBJECTIVE This study evaluated the efficacy and tolerability of FBT in opioid-tolerant patients with BTP associated with chronic noncancer neuropathic pain . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled study in men and women aged 18 to 80 years who were opioid tolerant ; had a > /= 3-month history of chronic persistent neuropathic pain associated with diabetic peripheral neuropathy , postherpetic neuralgia , traumatic injury , or complex regional pain syndrome ; and reported having episodes of BTP . After an open-label titration period to identify an effective FBT dose ( the dose at which the patient reported receiving adequate pain relief within 30 minutes after administration of a single tablet of that dose during at least 2 of 3 BTP episodes ) , patients were r and omly assigned to treat 9 consecutive episodes of BTP over the next 21 days with 1 of 3 double-blind dose sequences of FBT and placebo tablets . Pain intensity ( PI ) ( rated on an 11-point pain scale , from 0 = no pain to 10 = worst pain ) and other outcomes were assessed before dosing and for 2 hours after dosing . The primary efficacy measure was the sum of PI differences ( PIDs ) for the first 60 minutes ( SPID(60 ) ) . Secondary efficacy measures included the proportion of BTP episodes with > /= 33 % and > /= 50 % improvement in PI from baseline ; PID at other time points ( 5 , 10 , 15 , 30 , 45 , 60 , 90 , and 120 minutes after dosing ) ; pain relief ( PR ) at the same time points ( rated on a 5-point Likert scale from 0 = none to 4 = complete ) ; proportion of BTP episodes with meaningful PR ; time to meaningful PR ; and proportion of BTP episodes in which supplemental medication was required after administration of study drug . Adverse events ( AEs ) spontaneously reported by the patient or elicited by the investigator were recorded throughout the study . RESULTS Of 102 patients in the open-label titration period , 80 identified an effective dose of FBT and 79 entered the double-blind phase . Of these 79 patients , 77 ( 97 % ) completed the study and 75 ( 95 % ) were evaluable for efficacy . Of the 79 patients who entered the double-blind phase , 63 % were women and 92 % were white ; their mean ( SD ) age was 48.3 ( 10.42 ) years , and their mean weight was 96.8 ( 33.42 ) kg . Baseline demographic and pain characteristics were similar between the overall population and the double-blind population . SPID(60 ) was significantly greater for BTP episodes treated with FBT compared with those in which placebo was administered ( mean [ SE ] , 9.63 [ 0.75 ] vs 5.73 [ 0.72 ] , respectively ; P < 0.001 ) . Significant differences between FBT and placebo were seen beginning at 10 minutes for PID ( mean , 0.740 [ 0.149 ] vs 0.427 [ 0.081 ] ; P < 0.047 ) and PR ( mean , 0.561 [ 0.087 ] vs 0.324 [ 0.056 ] ; P < 0.001 ) . A > /= 33 % improvement in PI from baseline was seen in a greater proportion of BTP episodes treated with FBT compared with placebo from 10 minutes ( 9 % vs 3 % ; P = 0.008 ) through 2 hours ( 66 % vs 37 % ; P < 0.001 ) . Patients were almost 4 times less likely to require supplemental opioids when BTP episodes were treated with FBT compared with placebo ( odds ratio = 0.28 ; 95 % Cl , 0.18 - 0.42 ) . AEs were reported by 64 ( 63 % ) of 102 patients . The most commonly reported AEs were those typical of opioids ( nausea [ 13 % ] , dizziness [ 13 % ] , somnolence [ 10 % ] , and vomiting [ 5 % ] ) and occurred more often during the dose-titration phase ( 55/102 [ 54 % ] ) than during the double-blind phase ( 22/79 [ 28 % ] ) . CONCLUSION In these opioid-tolerant patients with chronic neuropathic pain who identified an effective FBT dose , FBT had a rapid onset of action and was effective and well tolerated in the treatment of BTP", "OBJECTIVES The long-term use of strong opioid analgesics among chronic noncancer pain ( CNCP ) patients remains controversial because of concerns over problematic drug use . However , previous surveys suggest that this is not necessarily the case . Therefore , we design ed a controlled study to generate evidence in support of these findings . PATIENTS / SETTING Ten CNCP patients attending the pain clinic in a district general hospital had been taking an average daily dose of 40 mg controlled-release morphine sulphate ( mean 40 , range 10 - 90 , SD 21 mg ) , for an average of 2 years ( mean 2.175 , range 2 - 2.25 , SD 0.2 years ) . DESIGN R and omized , double-blind , placebo controlled cross-over study . The study was based on the premise that abrupt cessation of opioid drugs is most likely to highlight problematic use and the consequent inability to stop using opioids . Morphine was substituted with placebo for 60-hour periods to compare the effects of abstinence with those of continued use . Assessment of morphine cessation and abstinence effects was through direct observation , physiological measurements , question naire responses , and Brief Pain Inventory scores . RESULTS Following cessation and abstinence , there were no indications of psychological dependence or drug craving , but there was evidence of the detrimental effects of pain intensity on activity , mood , relationships , sleep , and enjoyment of life . Three patients ( 30 % ) reported opioid drug withdrawal symptoms . Pharmacokinetic data demonstrated compliance with abstinence by all patients . CONCLUSION The results suggest the existence of a group of CNCP patients whose long-term opioid consumption can be beneficial and remain moderate without them suffering from the consequences of problematic opioid drug use", "Misuse of opioids is associated with abnormalities of pituitary function . Patients with chronic pain frequently complain of fatigue and undergo endocrine testing . To test whether oral opioid treatment causes abnormal pituitary function we prospect ively assessed pituitary function in 37 patients with chronic pain who were receiving either oral opioid analgesia or non-opioid analgesia . Oral opioid treatment was not associated with abnormal pituitary function although a few patients had abnormal results mainly related to obesity . Our results suggest that patients with chronic pain who have abnormal endocrine results should have a complete assessment , since abnormal test results can not be attributed to their analgesia", "Twelve patients with poor pain control or unacceptable side effects during treatment with morphine were switched to methadone and followed for nine months in this open prospect i ve study . Primary outcomes were patient preference for opioid and pain control while physical , cognitive and role functioning were secondary outcomes . The morphine dose was decreased by 1/3 daily and was replaced with an equianalgesic dose of methadone over a three-day period . During switching and a one-week dose titration period , patients were given additional methadone if required . During dose titration one patient experienced sedation requiring naloxone . Four patients were switched back to morphine due to poor pain control , drowsiness or sweating . Seven patients preferred long-term ( > nine months ) treatment with methadone and reported reduced pain and improved functioning while cognition was not improved . This study brings novel information on the long-term consequences for pain control , health-related quality of life and cognitive functioning with a switch from morphine to methadone in the treatment of chronic non-malignant pain", "CONTEXT Common pain conditions appear to have an adverse effect on work , but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain . OBJECTIVE To measure lost productive time ( absence and reduced performance due to common pain conditions ) during a 2-week period . DESIGN AND SETTING Cross-sectional study using survey data from the American Productivity Audit ( a telephone survey that uses the Work and Health Interview ) of working adults between August 1 , 2001 , and July 30 , 2002 . PARTICIPANTS R and om sample of 28 902 working adults in the United States . MAIN OUTCOME MEASURES Lost productive time due to common pain conditions ( arthritis , back , headache , and other musculoskeletal ) expressed in hours per worker per week and calculated in US dollars . RESULTS Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition . Headache was the most common ( 5.4 % ) pain condition result ing in lost productive time . It was followed by back pain ( 3.2 % ) , arthritis pain ( 2.0 % ) , and other musculoskeletal pain ( 2.0 % ) . Workers who experienced lost productive time from a pain condition lost a mean ( SE ) of 4.6 ( 0.09 ) h/wk . Workers who had a headache had a mean ( SE ) loss in productive time of 3.5 ( 0.1 ) h/wk . Workers who reported arthritis or back pain had mean ( SE ) lost productive times of 5.2 ( 0.25 ) h/wk . Other common pain conditions result ed in a mean ( SE ) loss in productive time of 5.5 ( 0.22 ) h/wk . Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year . The majority ( 76.6 % ) of the lost productive time was explained by reduced performance while at work and not work absence . CONCLUSIONS Pain is an inordinately common and disabling condition in the US workforce . Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance", "Clinical experience shows that neuropsychological side effects due to opioid therapy usually decrease during the first weeks of therapy . However , the effect of long-term treatment with transdermal fentanyl on complex activities , such as driving , is not yet clear . In a prospect i ve trial , patients with continuous noncancer pain , who had received stable doses of transdermal fentanyl for at least 2 weeks , completed a series of computerized tests to measure attention , reaction , visual orientation , motor coordination and vigilance . Data from 90 healthy volunteers were matched to 30 patients ; 9 patients were excluded from the per- protocol analysis because they took additional drugs in violation of the protocol . None of the performance measures for the 21 remaining fentanyl patients was significantly inferior to the controls . We conclude that stable doses of transdermal fentanyl for the treatment of chronic non-cancer pain are not associated with significant impairments in psychomotor and cognitive performance . The threshold for fitness to drive as defined by German law did not differ significantly between the groups", "UNLABELLED There is accumulating evidence that opioid therapy might not only be associated with the development of tolerance but also with an increased sensitivity to pain , a condition referred to as opioid-induced hyperalgesia ( OIH ) . However , there are no prospect i ve studies documenting the development of opioid tolerance or OIH in patients with chronic pain . This preliminary study in 6 patients with chronic low back pain prospect ively evaluated the development of tolerance and OIH . Patients were assessed before and 1 month after initiating oral morphine therapy . The cold pressor test and experimental heat pain were used to measure pain sensitivity before and during a target-controlled infusion with the short-acting mu opioid agonist remifentanil . In the cold pressor test , all patients became hyperalgesic as well as tolerant after 1 month of oral morphine therapy . In a model of heat pain , patients exhibited no hyperalgesia , although tolerance could not be evaluated . These results provide the first prospect i ve evidence for the development of analgesic tolerance and OIH by using experimental pain in patients with chronic back pain . This study also vali date d methodology for prospect ively study ing these phenomena in larger population s of pain patients . PERSPECTIVE Experimental evidence suggests that opioid tolerance and opioid-induced hyperalgesia might limit the clinical utility of opioids in controlling chronic pain . This study vali date s a pharmacologic approach to study these phenomena prospect ively in chronic pain patients and suggests that both conditions do occur within 1 month of initiating opioid therapy", "Case reports and retrospective studies suggest that methadone causes an increase in QTc ( QT time corrected for heart rate ) time and risk of torsades de pointes arrhythmia . No prospect i ve studies in pain patients have been conducted , and data on whether a methadone-induced increase in QTc time persists during long-term treatment have not been reported . Eight chronic nonmalignant pain patients experiencing insufficient pain control or intolerable side effects during treatment with oral morphine switched to oral methadone and were included in this study . Electrocardiograms were obtained at baseline and at follow-up 2 weeks , and 3 and 9 months after the opioid switch . Start of methadone caused a minor but statistically significant increase in QTc time , while fluctuations in QTc during treatment with stable doses of methadone were neither clinical ly nor statistically significant . We observed no episodes of arrhythmias", "BACKGROUND Use of opioids for chronic noncancer pain is increasing , but st and ards of care for this practice are poorly defined . Psychiatric disorders are associated with increased physical symptoms such as pain and may be associated with opioid use , but no prospect i ve population -based studies have addressed this issue . METHODS Analysis of longitudinal data from 6439 participants in the 1998 and 2001 waves of Healthcare for Communities , a nationally representative telephone community survey . RESULTS Two hundred thirty-seven subjects ( 3.6 % ) reported regular prescription opioid use in 2001 . In unadjusted logistic regression models , respondents with a common mental health disorder in 1998 ( 1165 [ 12.6 % ] ; major depression , dysthymia , generalized anxiety disorder , or panic disorder ) were more likely to report opioid use in 2001 than those without any of these disorders ( odds ratio [ OR ] , 4.43 ; 95 % confidence interval [ CI ] , 3.64 - 5.38 ; P<.001 ) . Risk was increased for initiation ( OR , 3.26 ; 95 % CI , 2.44 - 4.34 ; P<.001 ) and continuation ( OR , 2.30 ; 95 % CI , 1.02 - 5.17 ; P = .04 ) of opioids . Respondents reporting problem drug use ( 136 [ 2.0 % ] ; OR , 3.57 ; 95 % CI , 2.32 - 5.50 ; P<.001 ) but not problem alcohol use ( 401 [ 6.5 % ] ; OR , 0.73 ; 95 % CI , 0.43 - 1.24 ; P = .25 ) reported higher rates of prescribed opioid use than those without problem use . In multivariate logistic regression models controlling for 1998 demographic and clinical variables , common mental health disorder ( OR , 1.96 ; 95 % CI , 1.47 - 2.62 ; P<.001 ) and problem drug use ( OR , 2.98 ; 95 % CI , 1.68 - 5.30 ; P<.001 ) remained significant predictors of opioid use in 2001 . CONCLUSIONS Common mental health disorders and problem drug use are associated with initiation and use of prescribed opioids in the general population . Attention to psychiatric disorders is important when considering opioid therapy", "Alvimopan has been shown to reverse the inhibitory effect of opioids on gastrointestinal transit without affecting analgesia . We evaluated oral alvimopan , 0.5 or 1 mg , versus placebo , once daily for 21 days , in 168 patients with opioid-induced bowel dysfunction ( OBD ) who were receiving chronic opioid therapy ( minimum , 1 month ) for nonmalignant pain ( n = 148 ) or opioid dependence ( n = 20 ) . The primary outcome was the proportion of patients having at least one bowel movement ( BM ) within 8 hours of study drug on each day during the 21-day treatment period . Averaged over the 21-day treatment period , 54 % , 43 % , and 29 % of patients had a BM within 8 hours after alvimopan 1 mg , 0.5 mg , or placebo , respectively ( P < .001 ) . Secondary outcomes of median times to first BM were 3 , 7 , and 21 hours after initial doses of 1 mg , 0.5 mg , and placebo , respectively ( P < .001 ; 1 mg vs placebo ) . Weekly BMs and overall patient satisfaction were increased after the 1-mg dose ( P < .001 at weeks 1 and 2 vs placebo , and P = .046 , respectively ) . Treatment-emergent adverse events were primarily bowel-related , occurred during the first week of treatment , and were of mild to moderate severity . Alvimopan was generally well tolerated and did not antagonize opioid analgesia . Patients treated with chronic opioid therapy often experience opioid-induced bowel dysfunction as a result of undesirable effects on peripheral opioid receptors located in the gastrointestinal tract . Alvimopan , a novel peripheral opioid mu-receptor antagonist , has demonstrated significant efficacy for the management of opioid-induced bowel dysfunction without compromise of central ly mediated opioid-induced analgesia", "Recent reports suggest that methadone may prolong the QTc interval and cause torsades de pointes . This study was conducted to evaluate the prevalence of QTc prolongation during oral methadone therapy and identify factors associated with prolongation . Patients receiving oral methadone as treatment for chronic pain or addiction were eligible for the study . One hundred four patients who were receiving > or = 20 mg methadone per day for > or = 2 weeks underwent electrocardiograms to measure QTc interval duration . Sixty-three ( 61 % ) patients were male and 63 ( 61 % ) were receiving methadone maintenance for opioid addiction . The mean ( + /- SD ) age was 45.3 + /- 9.4 years . The median ( range ) methadone dose was 110 mg/day ( 20 - 1200 mg/day ) ; median ( range ) number of months on methadone was 12.5 months ( 1 - 444 months ) . The median ( range ) QTc interval was 428 msec ( 396 - 494 msec ) . Thirty-three percent had QTc prolongation ( males 40 % , females 20 % ; P=0.03 ) . No patient had a QTc longer than 500 msec . Significant dose response was observed in males on methadone < 12 months ( rho=0.60 , P=0.02 ) . Our study suggests that methadone may prolong the QTc interval in specific sub population s but poses little risk of serious prolongation", "BACKGROUND Published case reports have associated the therapeutic use of methadone with the occasional occurrence of sudden cardiac death . Because of the established utility of this drug and with the eventual goal of enhancing safety of use , we performed a community-based study to evaluate this association . METHODS During a 4-year period , we prospect ively evaluated all patients who consecutively had sudden cardiac death and underwent investigation by the medical examiner in the metropolitan area of Portl and , Ore. Case subjects of interest were those with a therapeutic blood level of methadone ( < 1 mg/L ) , and case comparison subjects were those with no methadone identified . Patients with recreational drug use or any drug overdose were excluded from either group . Detailed autopsies were conducted , including the detection and quantification of all substances in the blood . RESULTS A total of 22 sudden cardiac death cases with therapeutic levels of methadone ( mean 0.48+/-0.22 mg/L ; range 0.1 - 0.9 mg/L ) were identified ( mean age 37.0+/-10 years , 68 % were male ) and compared with 106 consecutive sudden cardiac death cases without evidence of methadone ( mean age 42+/-13 years , 69 % were male ) . The most common indication for methadone use was pain control ( n=12 , 55 % ) . Among cases receiving methadone therapy , sudden death-associated cardiac abnormalities were identified in only 23 % ( n=5 ) , with no clear cause of sudden cardiac death in the remaining 77 % ( n=17 ) . Among cases with no methadone , sudden death-associated cardiac abnormalities were identified in 60 % ( n=64 , P=.002 ) . CONCLUSION The significantly lower prevalence of cardiac disease in the case group implicates methadone , even at therapeutic levels , as a likely cause of sudden death . These findings point toward an association between methadone and occurrence of sudden death in the community . Clinical safeguards and further prospect i ve studies specifically design ed to enhance safety of methadone use are warranted" ]

[ "23819827", "21077956", "15479748", "20335313", "3786124", "12176504", "23759395", "15608704", "23263559", "11678959", "16824155", "19295316", "9884266" ]

[ "Improving Outcomes of Renal Transplant Recipients With Behavioral Adherence Contracts: A Randomized Controlled Trial", "Taking immunosuppressive medications effectively (TIMELink): a pilot randomized controlled trial in adult kidney transplant recipients", "Modifiable risk factors for non-adherence to immunosuppressants in renal transplant recipients: a cross-sectional study.", "CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials", "Mobile Health Medication Adherence and Blood Pressure Control in Renal Transplant Recipients: A Proof-of-Concept Randomized Controlled Trial", "Noncompliance postrenal transplantation: measuring the extent of the problem using electronic surveillance and nurse practitioner interviews.", "Mobilizing Your Medications: An Automated Medication Reminder Application for Mobile Phones and Hypertension Medication Adherence in a High-Risk Urban Population", "The TREND Statement", "Improved Adherence to Tacrolimus Once-Daily Formulation in Renal Recipients: A Randomized Controlled Trial Using Electronic Monitoring", "Impact of clinical pharmacy services on renal transplant patients’ compliance with immunosuppressive medications", "Supporting medication adherence in renal transplantation (SMART): a pilot RCT to improve adherence to immunosuppressive regimens", "Quantitative Patterns of Azathioprine Adherence After Renal Transplantation", "Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study." ]

[ "The objective of this r and omized controlled trial was to assess the effects of a 1‐year behavioral contract intervention on immunosuppressant therapy ( IST ) adherence and healthcare utilizations and costs among adult renal transplant recipients ( RTRs ) . The sample included adult RTRs who were at least 1 year posttransplant , taking tacrolimus or cyclosporine and served by a specialty pharmacy . Pharmacy refill records were used to measure adherence and monthly question naires were used to measure healthcare utilizations . Direct medical costs were estimated using the 2009 Medicare Expenditure Panel Survey . Adherence was analyzed using the GLM procedure and the MIXED procedure of SAS . Rate ratios and 95 % confidence intervals were estimated to quantify the rate of utilizing healthcare services relative to treatment assignment . One hundred fifty RTRs were enrolled in the study . Intervention group RTRs ( n = 76 ) had higher adherence than control group RTRs ( n = 74 ) over the study period ( p < 0.01 ) . And 76.1 % of the intervention group compared with 42.7 % of the control group was not hospitalized during the 1‐year study period ( RR = 1.785 ; 95 % CI : 1.314 , 2.425 ) , result ing in cost savings . Thus , evidence supports using behavioral contracts as an effective adherence intervention that may improve healthcare outcomes and lower costs", "Russell C , Conn V , Ashbaugh C , Madsen R , Wakefield M , Webb A , Coffey D , Peace L. Taking immunosuppressive medications effectively ( TIMELink ) : a pilot r and omized controlled trial in adult kidney transplant recipients . Clin Transplant 2011 : 25 : 864–870 . © 2010 John Wiley & Sons", "BACKGROUND Non-adherence to immunosuppressants is a major cause of renal transplant failure . Interventions to improve adherence need to target modifiable risk factors . METHODS Adherence was measured using the ' gold st and ard ' measure of electronic monitoring in 58 adult renal transplant recipients from a UK transplant unit . Subjects were identified from a stratified r and om sample of 153 recipients recruited to a larger cross-sectional study comparing different measures of adherence . Inclusion criteria included age over 18 years and a functioning renal transplant , transplanted 6 - 63 months previously . Exclusion criteria included residence outside the region served by the unit and inability to give informed consent . Health beliefs , depression and functional status were measured using st and ardized question naires ( Beliefs about Medicines Question naire , Illness Perception Question naire , Revised Clinical Interview Schedule and SF-36 ) and semi-structured interview . Transplant and demographic details were collected from the notes . RESULTS Seven [ 12 % , 95 % confidence interval ( CI ) 4 - 20 % ] subjects missed at least 20 % of days medication and 15 ( 26 % , 15 - 37 % ) missed at least 10 % of days . Lower belief in the need for medication and having a transplant from a live donor were the major factors associated with non-adherence . Depression was common , although not strongly associated with non-adherence . CONCLUSIONS Beliefs about medication are a promising target for interventions design ed to improve adherence . The lower adherence in recipients of transplants from live donors needs confirming but may be clinical ly important in light of the drive to increase live donation", "The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience .", "Background Mobile phone based programs for kidney transplant recipients are promising tools for improving long-term graft outcomes and better managing comorbidities ( eg , hypertension , diabetes ) . These tools provide an easy to use self-management framework allowing optimal medication adherence that is guided by the patients ’ physiological data . This technology is also relatively inexpensive , has an intuitive interface , and provides the capability for real-time personalized feedback to help motivate patient self-efficacy . Automated summary reports of patients ’ adherence and blood pressure can easily be uploaded to providers ’ networks helping reduce clinical inertia by reducing regimen alteration time . Objective The aim of this study was to assess the feasibility , acceptability , and preliminary outcomes of a prototype mobile health ( mHealth ) medication and blood pressure ( BP ) self-management system for kidney transplant patients with uncontrolled hypertension . Methods A smartphone enabled medication adherence and BP self-management system was developed using a patient and provider centered design . The development framework utilized self-determination theory with iterative stages that were guided and refined based on patient/provider feedback . A 3-month proof-of-concept r and omized controlled trial was conducted in 20 hypertensive kidney transplant patients identified as non-adherent to their current medication regimen based on a month long screening using an electronic medication tray . Participants r and omized to the mHealth intervention had the reminder functions of their electronic medication tray enabled and received a bluetooth capable BP monitor and a smartphone that received and transmitted encrypted physiological data and delivered reminders to measure BP using text messaging . Controls received st and ard of care and their adherence continued to be monitored with the medication tray reminders turned off . Providers received weekly summary reports of patient medication adherence and BP readings . Results Participation and retention rates were 41/55 ( 75 % ) and 31/34 ( 91 % ) , respectively . The prototype system appears to be safe , highly acceptable , and useful to patients and providers . Compared to the st and ard care control group ( SC ) , the mHealth intervention group exhibited significant improvements in medication adherence and significant reductions in clinic-measured systolic blood pressures across the monthly evaluations . Physicians made more anti-hypertensive medication adjustments in the mHealth group versus the st and ard care group ( 7 adjustments in 5 patients versus 3 adjustments in 3 patients ) during the 3-month trial based on the information provided in the weekly reports . Conclusions These data support the acceptability and feasibility of the prototype mHealth system . Further trials with larger sample sizes and additional biomarkers ( eg , whole blood medication levels ) are needed to examine efficacy and effectiveness of the system for improving medication adherence and blood pressure control after kidney transplantation over longer time periods . Trial Registration Clinical trials.gov NCT01859273 ; http:// clinical trials.gov/ct2/show/NCT01859273 ( Archived by WebCite at http://www.webcitation.org/6IqfCa3A3 )", "ONCOMPLIANCE posttransplant is postulated to account for up to one third of graft failures due to chronic graft dysfunction . Due to its covert nature , determining the extent of the problem is not easy , and traditional methods tend to underestimate the true scale . More recently , methods of electronic monitoring have been introduced that tend to give a more accurate picture . One hundred stable renal transplant patients ( transplanted 1 year ) were approached and asked if they would use a “ smart top ” pill bottle ( Aardex , Switzerl and ) for their azathioprine/ prednisolone . The tops contain a microprocessor that records the date and time on each occasion the bottle is opened . This information can then be downloaded onto a computer via a modem at their regular clinic visits . The patients were r and omly assigned to groups ; 75 were given smart top bottles , and the other 25 were given plain tops . This latter group received regular interviews by a nurse practitioner and pill counts to assess their compliance . Of 92 patients whose data was available after 3 months ( 93 days ) , 11 ( 46 % ) of the plain top group and 31 ( 46 % ) of the smart top group missed at least one dose in the 3-month period . Twenty-two ( 33 % ) of the smart top group took extra doses in the 3-month period , none of the plain top group were found to have taken extra doses . Only 13 ( 54 % ) of the plain top group and 25 ( 37 % ) of the smart top group were 100 % compliant in the 3-month period ( not significant , chi-square test ) . Both electronic monitoring and nurse practitioner interviews with pill counting appear to be equally sensitive for detecting missed doses , but electronic monitoring measures timing of dosage and can also pick up when consecutive doses are missed . It also picks up when extra doses are taken . Missed doses and extra doses can cancel each other out when pill counts alone are used , which probably accounts for the higher 100 % compliance rate in the plain top group . METHOD One hundred stable renal transplant patients more than 1 year posttransplant were asked if they would use a smart top bottle for their regular once-daily azathioprine or prednisolone . Smart top bottles are medicine bottles with a microprocessor in the cap that records the date and time on each occasion the bottle is opened and closed . This information can then be downloaded onto a computer data base via a special modem at their regular outpatient visits . The patients were r and omly placed into one of two groups . Twenty-five of the patients were given a pill bottle with an ordinary lid on it . They were asked to bring their pill bottles with them to their regular outpatient clinic appointments , at approximately 3-month intervals , along with any remaining medication . They were then interviewed by a nurse practitioner about their compliance , and their remaining tablets were counted . The other 75 patients were given smart top bottles that they were asked to bring with them to their regular out patient appointments . The information was then downloaded from the lid onto the computer data base", "Background : Hypertension frequently accompanies diabetes mellitus , worsening prognosis and complicating medical care for patients . Low medication adherence with multiple medications is a major factor in the inadequate achievement of blood pressure treatment goals . Widespread access to mobile phones offers a new opportunity to communicate with patients and enhance disease self-management . Methods : We recruited 50 high-risk urban patients with hypertension , who are using at least two prescription medications for hypertension , into an open-label trial using medication reminder software on a mobile phone . Medication adherence was assessed by review of pharmacy refill rates before , during , and after availability of the medication reminder software ( pre-activation , activation , and post-activation phase , respectively ) . Results : Forty-eight patients completed the study . All subjects were insured by Medicaid , 96 % were African-American , and the majority had diabetes mellitus . The proportion of days covered for each study phase was as follows : Pre-activation phase = 0.54 , activation phase = 0.58 , and post-activation phase = 0.46 . A significant difference was found between the activation and post-activation phases ( p = .001 ) . The increase in measured adherence between the pre-activation and activation phases approached significance ( p = .057 ) . Forty-six patients completed the pre- and post-Morisky medication adherence survey . The median score rose from 2.0 at baseline to 3.0 at study completion ( p < .001 ) . Average blood pressure and level of control during study period improved significantly after initiation of the study and remained improved from baseline through the course of the study . The 48 subjects who completed the study reported a high level of satisfaction with the medication reminder application at the final study visit . Conclusions : A mobile-phone-based automated medication reminder system shows promise in improving medication adherence and blood pressure in high-cardiovascular-risk individuals", "Readers will be familiar with the CONSORT guidelines for the reporting of r and omised controlled trials . These guidelines were design ed to improve the reporting of RCTs and are of considerable use to research ers design ing and reporting studies as well as to editors and to systematic review ers . However , a major limitation of CONSORT is that they are limited to RCTs and there are far more research design s than RCTs . Some topics just can not be investigated using RCTs and yet it may often be desirable to try to identify whether or not there is a causal link between two factors . It is therefore very welcome to see the development of the TREND statement ( www.trend-statement.org/asp/trend.asp ) — the Transparent Reporting of Evaluations with NonR and omised design s. As the authors state these guidelines are developing — there is room for alteration and improvement but their prime focus is to encourage the transparency or clarity of reporting . In view of the evolutionary state of these guidelines , I would encourage research ers , editors and review ers to become familiar with them and to start using them . As they are used , areas , primarily of omission , will become apparent . The first area that needs exp and ing , in my opinion , is that more detail is required describing the characteristics of each population subgroup . I consider that more prominence of the potential for confounding factors needs to be acknowledged . As CONSORT has helped both investigators and review ers improve the quality of RCTs and systematic review s there is the possibility for TREND to do the", "Background With effective agents available to prevent posttransplantation acute organ rejection , medication adherence becomes a key factor for successful treatment outcomes after renal transplantation . A once-daily , modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence . Methods Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a r and omized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake . After enrolment , all patients continued the twice-daily regimen for 3 months and then were r and omized 2:1 between the two formulations and followed for 6 months . Adherence was decomposed into patients ’ persistence and implementation of each regimen . Results Two hundred nineteen patients ( 45 % male ; 3±2 years after transplantation ) were analyzed ( 145 once daily and 74 twice daily ) . At 6 months after r and omization , 81.5 % of the once-daily group and 71.9 % of the twice-daily group remained persistent with the treatment ( P=0.0824 ) . Among patients who remained engaged with the regimen , 88.2 % of the once-daily group and 78.8 % of the twice-daily group ( P=0.0009 ) took the prescribed number of daily doses . When the patients took the twice-daily regimen , the average percentage of missed doses was 11.7 % in the morning and 14.2 % in the evening ( P=0.0035 ) . Conclusions Regimen implementation of tacrolimus once daily is significantly superior to the twice-daily regimen . There was a residual prevalence of suboptimal adherence that will have to be countered by means other than reformulation and regimen simplification . Electronically compiled dosing histories provide detailed data on patient adherence that can be used for efficient medication management", "Background : Non‐compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post‐transplant care . This r and omized , controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients ’ compliance with immunosuppressive agents . Methods : Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were r and omized in the intervention or control group provided they met study criteria . In addition to routine clinic services at each clinic visit , patients in the intervention group received clinical pharmacy services , which included medication histories and review of patients ’ medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events . The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes . To promote medication compliance by using compliance enhancement strategies , the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications . Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction . Compliance rate ( CR ) was calculated and patient 's compliance status was determined from the CR . The CR , the fraction of patients remaining compliant for each month , and the mean time patients were compliant were compared between groups . Whether there was a difference in the frequency of patients achieving ‘ target ’ immunosuppressive levels in the control and study groups was evaluated . Results : The mean CR for patients who had clinical pharmacist intervention ( n=12 ) was statistically higher than the control group 's ( n=12 ) mean CR ( p<0.001 ) . During the 12‐month post‐transplant study period , patients in the intervention group had a longer duration of compliance than patients in the control group ( p<0.05 ) . Additionally , patients who had clinical pharmacy services had a greater achievement of ‘ target ’ levels than patients who did not receive these services ( p<0.05 ) . Conclusions : Patients who received clinical pharmacy services with traditional patient care services had better compliance with immunosuppressants than patients who only received traditional patient care services . Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post‐transplant patients is beneficial for enhancing medication compliance", "Abstract : Background : Although non‐adherence to an immunosuppressive regimen ( NAH ) is a major risk factor for poor outcome after renal transplantation ( RTx ) , very few studies have examined non‐adherence intervention in this context . This pilot r and omized controlled trial ( RCT ) tested the efficacy of an educational – behavioural intervention to increase adherence in non‐adherent RTx patients . We also assessed how NAH evolves over time", "Background . Renal transplant recipients regularly fail to take their prescribed immunosuppressive medications , frequently leading to adverse outcomes . Methods . Medication vials incorporating electronic monitor circuits in their caps compiled prospect i ve data files on the azathioprine dosing patterns of 180 adult renal transplant recipients monitored up to 4 years . These patients were followed for a mean of 8.7 years posttransplantation . Results . Patients were divided into three groups by the medication doses missed during the first 6 months posttransplant . These initial dosing patterns remained remarkably consistent up to 4 years . Patients ( n=47 ) missing the most doses ( ≥5 % ) experienced earlier and more frequent acute rejection episodes ( P=0.025 ) . This group also demonstrated significantly longer interdose intervals ( P=0.005 ) , with more frequent ( P<0.001 ) and longer ( P<0.001 ) “ drug holidays . ” A patient subgroup with early declining medication adherence ( n=23 ) experienced dramatically poorer outcomes , with significantly increased acute rejection ( P<0.001 ) , chronic rejection ( P=0.034 ) , graft loss before death ( P<0.001 ) , and death ( P=0.04 ) . In all tertiles there was a trend toward missing more medication over time . Conclusions . Excellent posttransplant medication adherence is critical to improved outcomes . Individual dosing patterns are established early after hospital discharge and remain remarkably consistent , despite gradual erosion in adherence over time . The later consequences of medication nonadherence , especially early declines in adherence , include increased frequencies of rejection , graft loss , and death", "BACKGROUND Noncompliance with medication is a major cause of renal allograft failure among adult renal transplant patients . We summarize previous studies of noncompliance and report results of a large , multicenter survey design ed to identify variables that ( 1 ) affect the likelihood of compliance with immunosuppressive medication regimens and ( 2 ) distinguish among noncompliant patients . METHODS Question naires were distributed to 2500 patients at 56 U.S. transplant centers . Compliance was determined by patient responses to questions concerning whether , within the previous 4 weeks , one or more doses of immunosuppressive medications had been missed . Independent variables included patient and transplant characteristics , memories of dialysis , posttransplant symptoms and beliefs , and beliefs concerning the efficacy and importance of immunosuppressants . RESULTS The incidence of noncompliance reported by the 1402 respondents was 22.4 % . A logistic regression model that included age , occupation , time since transplant , and three medication-related beliefs was most predictive of the likelihood of compliance . Donor type and histories of diabetes and of infection entered the multivariate model when belief-related variables were excluded . Cluster analyses identified three distinct profiles of noncompliers : accidental noncompliers , invulnerables , and decisive noncompliers . CONCLUSIONS Results of this study , which included nearly three times more patients than the largest previously reported study , can be used by clinicians to identify patients likely to become noncompliant , by research ers to develop r and omized , prospect i ve clinical trials of interventions design ed to increase compliance , and by educators to tailor patient education programs" ]

[ "23416804", "11148527", "9820429", "389344", "1804731" ]

[ "Efficacy of Peppermint oil in diarrhea predominant IBS - a double blind randomized placebo - controlled study.", "Enteric-coated, pH-dependent peppermint oil capsules for the treatment of irritable bowel syndrome in children.", "PEPPERMINT OIL AND IRRITABLE BOWEL SYNDROME", "Treating irritable bowel syndrome with peppermint oil.", "Stress management for irritable bowel syndrome: a controlled trial." ]

[ "Irritable bowel syndrome ( IBS ) is one of the most common functional gastrointestinal disorder which is associated with considerable sufferings of patient and Peppermint oil is volatile oil , its active principle is menthol-contain a cyclic monoterpine which has anti-spasmotic properties due to its ability to block calcium channel of intestinal smooth muscles . This study observed the efficacy of peppermint oil for relieving the symptoms and changes of quality of life ( QOL ) in diarrhea predominant IBS . This was a prospect i ve double blind r and omized placebo-controlled study conducted in the Bangab and hu Sheikh Mujib Medical University during July 2008 to September 2009 . Patients who fulfilled ROME II were initially selected but those had red flag signs or any organic disease was excluded from the study . Seventy four patients were enrolled in the study and r and omly allocated to receive either peppermint oil or placebo three times daily for six weeks . Changes of symptoms were assessed three week interval during treatment and two weeks after the end of treatment . Data were analyzed by paired and unpaired ' t ' test . Finally sixty five patients completed the trial . It was observed that , at six weeks of therapy abdominal pain is markedly improved ( mean±SD ) 4.94±1.30 in peppermint oil group compared with 6.15±1.24 in placebo group and the difference was statistically highly significant ( p>0.001 ) . But two weeks after end of trials pain score again increased ( 6.09±1.93 ) . Other symptoms and quality of life did not improve significantly . So the study result concludes that peppermint oil is effective in reliving only abdominal pain in diarrhea predominant IBS transiently", "In a r and omized , double-blind controlled trial , 42 children with irritable bowel syndrome ( IBS ) were given pH-dependent , enteric-coated peppermint oil capsules or placebo . After 2 weeks , 75 % of those receiving peppermint oil had reduced severity of pain associated with IBS . Peppermint oil may be used as a therapeutic agent during the symptomatic phase of IBS", "ABSTRACT To determine the efficacy and tolerability of an enteric-coated peppermint-oil formulation ( Colpermin ) , a prospect i ve , r and omized , double-blind , placebo-controlled clinical study was conducted in 110 out patients ( 66 men and 44 women ; 18–70 yr old ) with symptoms of irritable bowel syndrome . Patients took one capsule ( Colpermin or placebo ) 3–4 times daily , 15–30 min before meals , for 1 month . Fifty-two patients on Colpermin and 49 on placebo completed the study . Forty-one patients on Colpermin ( 79 % ) experienced an alleviation of the severity of abdominal pain ( 29 were pain free ) ; 43 ( 83 % ) had less abdominal distension , 43 ( 83 % ) had reduced stool frequency , 38 ( 73 % ) had fewer borborygmi , and 41 ( 79 % ) had less flatulence . Corresponding figures for the placebo group were : 21 patients ( 43 % ) with reduced pain ( four were pain free ) , 14 ( 29 % ) with reduced distension , 16 ( 32 % ) with reduced stool frequency , 15 ( 31 % ) with fewer borborygmi , and 11 ( 22 % ) with less flatulence . Symptom improvements after Colpermin were significantly better than after placebo ( p < 0.05 ; Mann-Whitney U-test ) . One patient on Colpermin experienced heartburn ( because of chewing the capsules ) and one developed a mild transient skin rash . There were no significant changes in liver function test results . The authors conclude that Colpermin was effective and well tolerated . ( Am J Gastroenterol 1998;93:2304–2305 . © 1998 by Am . Coll . of Gastroenterology", "The incidence of imported malaria in the UK has steadily increased during the past decade , ' with 1909 cases reported in 1978 . At St Thomas 's Hospital P falciparunz malaria is much commoner than P vivax and is mostly acquired in tropical Africa.2 Most of the malaria reported in Asian immigrants is P vivax,5 and , although the World Health Organisation has reported an increase in the incidence of falciparum malaria in Bangladesh , India , and Sri Lanka , ' we have not previously seen a falciparum infection in an Asian . Chloroquineresistant falciparum malaria has been reported in South-east Asia and South America for many years , but its occurrence in the Asian subcontinent and in East Africa is much more recent . Two cases of imported chloroquine-resistant falciparum infections have recently occurred in the UK ; both were from Kenya and one was fatal.4 Our patient would appear to have shown RI resistance to chloroquine in that parasites reappeared after 23 days , although the initial course of chloroquine had apparently eradicated the infection . We made no attempt to culture the malarial parasites to confirm in-vitro resistance . This patient probably acquired her malaria from blood transfusion in Bangladesh , and there have been no reports of chloroquine-resistant P falciparum being transmitted by this route , although transfusion malaria is known to be common and underreported in the developing countries , and many cases of falciparum are described.5 Malaria in our patient was initially diagnosed by chance when blood films were being examined . The patient at this time was relatively well and afebrile , and malaria was not suspected clinical ly . The resurgence of the falciparum was unexpected and delayed diagnosis in view of the many other possible causes of fever in a neutropenic postoperative patient with leukaemia . Malaria was not initially entertained as a likely diagnosis because of the apparently successful treatment with chloroquine . It is of interest that the clinical response to intravenous quinine was slow , particularly defervescence , and perhaps \" quinine fever \" may have been contributory . The disappearance of parasites was also slow ; indeed , the parasitaemia appeared unchanged after two infusions of quinine . Although we are unaware of the effect of severe neutropenia and immunosuppression on the clinical course of malaria , it seems likely that this patient was infected with a chloroquine-resistant strain of P falciparum", "Thirty-five patients with irritable bowel syndrome were r and omized to receive treatment in a stress management programme or conventional therapy which included the antispasmodic Colpermin . The stress management programme involved a median of six 40-min sessions with a physiotherapist during which patients were helped to underst and the nature of their symptoms , their relationship to stress and were taught relaxation exercises . Two thirds of those in the stress management programme found the programme effective in relieving symptoms and experienced fewer attacks of less severity . This benefit was maintained for at least 12 months . Few of those given conventional management had any benefit . A stress management programme would appear to be of value for patients with irritable bowel syndrome" ]

[ "2907823", "1968355", "7912633", "6142067", "11083272", "1368982", "11856080", "2567150", "12846051", "11856079", "12154206", "12102471", "15271770", "12839376", "1980911", "11669169", "2572047", "9588731", "2864741", "10599365", "2868964", "11469522", "35824", "2869625", "2861876", "12115219", "8610215", "14057", "4150435", "11192489", "6105118", "2903927" ]

[ "Influence of salazosulphapyridine and 5-aminosalicylic acid on seminal qualities and male sex hormones.", "Sulphasalazine in psoriatic arthritis: a double-blind placebo-controlled study.", "Methotrexate and sulphasalazine as combination therapy in rheumatoid arthritis.", "Desensitization to sulfasalazine after hypersensitivity reactions in patients with inflammatory bowel disease.", "Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine.", "A phase 1–2, prospective, double blind, randomized study of the safety and efficacy of Sulfasalazine for the treatment of progressing malignant gliomas: study protocol of [ISRCTN45828668]", "A double‐blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis", "A double blind comparative study of sulphasalazine and hydroxychloroquine in rheumatoid arthritis: evidence of an earlier effect of sulphasalazine.", "Treatment of early RA in clinical practice: a comparative study of two different DMARD/corticosteroid options.", "A double‐blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis", "Analysis of improvements, full responses, remission and toxicity in rheumatoid patients treated with step-up combination therapy (methotrexate, cyclosporin A, sulphasalazine) or monotherapy for three years.", "Treating rheumatoid arthritis early with disease modifying drugs reduces joint damage: a randomised double blind trial of sulphasalazine vs diclofenac sodium.", "When a DMARD fails, should patients switch to sulfasalazine or add sulfasalazine to continuing leflunomide?", "Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis.", "Therapeutic effectiveness and tolerance of 5-aminosalicylic acid in short term treatment of patients with ulcerative colitis at a low or medium phase of activity.", "A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis.", "Effects of mesalazine substitution on salicylazosulfapyridine-induced seminal abnormalities in men with ulcerative colitis.", "Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group.", "Does sulphasalazine cause folate deficiency in rheumatoid arthritis?", "Sulphasalazine. An alternative drug for second-line treatment of juvenile chronic arthritis.", "Azodisal sodium in the treatment of ulcerative colitis. A study of tolerance and relapse-prevention properties.", "Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine.", "The relapse-preventing effect of methyl-salazosulphapyridine compared to salazosulphapyridine during long-term treatment of ulcerative colitis. A double-blind controlled trial.", "Sulphasalazine in the treatment of rheumatoid arthritis.", "Sulphasalazine in the treatment of rheumatoid arthritis: relationship of dose and serum levels to efficacy.", "Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial.", "Comparison of intramuscular gold and sulphasalazine in the treatment of early rheumatoid arthritis. A one year prospective study.", "Sulphasalazine in asymptomatic Crohn's disease. A multicentre trial.", "A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphasalazine (Salazopyrin)", "Efficacy of sulphasalazine plus methotrexate in rheumatoid arthritis.", "Optimum dose of sulphasalazine for maintenance treatment in ulcerative colitis.", "Comparison of responses to and adverse effects of graded doses of sulfasalazine in the treatment of rheumatoid arthritis." ]

[ "Seminal abnormalities are a common side effect of salazosulphapyridine ( SASP ) treatment . We evaluated semen qualities and sex hormone concentrations in 11 patients with inflammatory bowel disease ( IBD ) during SASP treatment and 4 months after replacing SASP with an oral slow-release preparation of 5-aminosalicylic acid ( 5-ASA ) . Significant improvement in sperm count ( p less than 0.01 ) , morphology ( p less than 0.02 ) , and motility ( p less than 0.02 ) could be observed during 5-ASA therapy , in comparison with SASP treatment . Three pregnancies occurred during the study period . The serum concentrations of gonadotrophins , prolactin , and sex hormone-binding globulin were normal in all patients and not significantly different in the two treatment periods . The mean total testosterone concentration decreased significantly ( p less than 0.02 ) after 5-ASA substitution , together with serum albumin ( p less than 0.005 ) , although all values remained within normal limits . The apparent free testosterone concentration was not significantly different in the two treatment periods . It is concluded that a significant improvement in semen quality can be obtained in male patients with IBD after replacing SASP with 5-ASA", "Sulphasalazine ( SASP ) is now accepted as an effective slow-acting antirheumatic drug for treating active rheumatoid arthritis ( RA ) , but has not been previously evaluated in psoriatic arthritis . An earlier open study suggested that it was well tolerated and potentially beneficial . The present double-blind placebo-controlled trial of 30 patients has now confirmed its efficacy . Greater improvement occurred in those patients on active treatment than on placebo , with more benefit being detected in those patients with the symmetrical polyarticular but seronegative pattern of arthritis associated with a high acute-phase response . SASP was stopped in 26 % because of side-effects but these were mild . No exacerbation or remission of psoriasis was observed . Further studies are in progress to determine the degree of efficacy of SASP in different clinical subgroups of psoriatic arthritis", "Sulphasalazine ( SASP ) and methotrexate ( MTX ) are well-established treatments for RA but the use of these drugs in combination has been avoided as both have antifolate activity . In this paper we report our experience with 32 patients treated with the combination MTX/SASP and compare the toxicity and tolerability of the combination with 63 patients treated with MTX alone . The median duration of exposure to the combination was 23 months . Nineteen patients have continued this regime for over 18 months . Five patients on MTX/SASP combination discontinued MTX , in four cases due to toxicity and in one because MTX/SASP was ineffective . In 17 patients on MTX alone , the drug was withdrawn permanently . In seven cases the cause was toxicity including two patients with severe reactions . In patients known to tolerate SASP alone , the combination of MTX/SASP is also well tolerated . In our experience of 48 patient-years of such combination therapy , there is no increase in toxicity compared to therapy with MTX alone in RA", "Desensitization to sulfasalazine was successful in 40/47 ( 85 % ) patients with IBD who previously had hypersensitivity reactions . The desensitization with sulfasalazine was well-tolerated with no serious complications in short- or long-term follow-up . The course of IBD was subsequently favorable in 35/40 ( 87 % ) for extended periods including 17/17 ( 100 % ) with ulcerative colitis . Desensitization should be attempted in patients who have had typical hypersensitivity reactions to sulfasalazine", "OBJECTIVE Case reports have suggested that minocycline , sulfasalazine , and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis . This study evaluated ANCA seroconversion due to these agents in serum sample s prospect ively collected in r and omized , double-blind , controlled trials . METHODS The sources of study sera were 3 clinical trials : 1 ) a 48-week trial of minocycline for early rheumatoid arthritis , with 64 patients receiving minocycline compared with 68 receiving placebo ; 2 ) a 37-week trial of sulfasalazine for rheumatoid arthritis , with 51 receiving sulfasalazine compared with 38 receiving placebo ; and 3 ) a 104-week trial of penicillamine for early systemic sclerosis , with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine . ANCA were measured in the baseline and study -end serum sample s by indirect immunofluorescence ( IIF ) for perinuclear ANCA ( pANCA ) and cytoplasmic ANCA ( cANCA ) patterns , and by antigen-specific enzyme-linked immunosorbent assay ( ELISA ) for antibodies to myeloperoxidase ( anti-MPO ) and proteinase 3 ( anti-PR3 ) . Laboratory personnel were blinded to the group identity of the sample s. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing . RESULTS No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results . Twelve of the 248 patients ( 5 % ) were positive for anti-MPO with pANCA at baseline . No subject was positive for anti-PR3 with cANCA . There were no findings suggestive of vasculitis in any of these patients . CONCLUSION From our study results , there was no suggestion of ANCA seroconversion induced by minocycline , sulfasalazine , or penicillamine . However , these findings do not rule out the possibility of rare , sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs", "Background The prognosis of patients suffering from WHO grade 3 and 4 astrocytic glioma remains poor despite surgery , radiation therapy and the use of current chemotherapy regimen . Indeed , the median survival of glioblastoma multiforme ( WHO grade 4 ) patients is at best 14.6 month with only 26.5 percents of the patients still alive after 2 years and the median survival of anaplastic astrocytomas ( WHO grade 3 ) is 19.2 month . Recent evidence suggests that the transcription factor NF-kappaB is constitutively expressed in malignant gliomas and that its inhibition by drugs like Sulfasalazine may block the growth of astrocytic tumors in vitro and in experimental models of malignant gliomas . Design ULg_GBM_04/1 is a prospect i ve , r and omized , double blind single-center phase 1–2 study . A total of twenty patients with progressive malignant glioma despite surgery , radiation therapy and a first line of chemotherapy will be recruited and assigned to four dosage regimen of Sulfasalazine . This medication will be taken orally t.i.d . at a daily dose of 1.5–3–4 or 6 g , continuously until complete remission , evidence of progression or drug intolerance . Primary endpoints are drug safety in the setting of malignant gliomas and tumor response as measured according to MacDonald 's criteria . An interim analysis of drug safety will be conducted after the inclusion of ten patients . The complete evaluation of primary endpoints will be conducted two years after the enrolment of the last patient or after the death of the last patient should this occur prematurely . Discussion The aim of this study is to evaluate the safety and efficacy of Sulfasalazine as a treatment for recurring malignant gliomas . The safety and efficacy of this drug are analyzed as primary endpoints . Overall survival and progression-free survival are secondary endpoint", "Sulfasalazine is accepted therapy for active ulcerative colitis , but side‐effects and intolerance are common . Balsalazide is an azo‐bonded pro‐drug which also releases 5‐aminosalicylic acid into the colon , but uses an inert carrier molecule", "In a double blind , single observer , 48 week study the effects of sulphasalazine ( 2 g daily ) and hydroxychloroquine ( 400 mg daily months 0 - 6 , thereafter 200 mg daily ) were compared in 60 patients with definite or classical rheumatoid arthritis . They had not been treated previously with second line drugs . The onset of response with sulphasalazine was earlier than with hydroxychloroquine . After 48 weeks a comparison of the treatments showed no statistically significant differences in disease activity variables . Adverse reaction was the main reason for withdrawal in the sulphasalazine group and lack of efficacy in the hydroxychloroquine group . All adverse reactions , one being agranulocytosis after eight weeks of sulphasalazine treatment , appeared in the first three months of treatment and were completely reversible", "OBJECTIVES To study the outcome in clinical practice of first DMARD and /or corticosteroid ( CS ) treatment in patients with recent onset rheumatoid arthritis ( RA ) . PATIENTS 245 patients with active RA , not previously treated with DMARDs or CS , were r and omised to one of two treatment groups , T1 = 7.5 - 15 mg of prednisolone ( PRE ) daily for one to three months followed , if needed , by methotrexate ( MTX ) in a weekly dose of 5 - 15 mg in addition to the lowest possible dose of PRE or T2 = sulfasalazine ( SAL ) , supplemented with lowest possible CS dose if needed . METHODS The EULAR individual response criteria were applied and remission was defined as a final DAS28 < 2.6 . Function was assessed by the HAQ and radiographic progression by Larsen scores . A patient who managed to remain on the allocated treatment for two years was described as a \" completer \" . RESULTS After 2 years of treatment , 70 % of the patients in T1 and 63 % in T2 were responders ( 30 % and 33 % \" good responders \" , respectively ) . In T1 29 % and in T2 19 % were in remission . There was a significant functional improvement in both groups but radiographic progression occurred . The mean decrease in HAQ and increase in the Larsen score were similar in the two groups . One-third of the patients were non-completers , 19 % from T1 and 47 % from T2 . Non-completers had , compared with completers , a significantly lower rate of individual response and remission . Completers and non-completers had similar functional improvement and similar radiological progression . CONCLUSIONS Individual response and remission was reduced in patients who did not complete their first DMARD/CS treatment option . Treatment failures were significantly more frequent in the sulfasalazine plus optional CS than in the CS plus optional methotrexate treatment group", "Sulfasalazine is well established in the treatment of active ulcerative colitis . Intolerance to sulfasalazine , however , is a common problem . Balsalazide has been design ed to deliver 5‐aminosalicylic acid to the colon without the poor tolerability of sulfasalazine", "OBJECTIVE To evaluate two monotherapies followed by step-up combination therapy with two or three complementary drugs in active rheumatoid arthritis ( RA ) in comparison with sulphasalazine ( SSZ ) alone . METHODS One hundred and twenty-six consecutive patients with early active RA were enrolled in this open controlled clinical trial . The primary end-point was 50 % improvement according to the ACR criteria ( ACR50 ) at 6 , 12 or 18 months . The secondary end-points were a full response ( Magnusson criteria ) and /or remission ( ACR criteria ) at 3 yr . Methotrexate ( MTX ) ( group 1 ) , cyclosporin A ( CsA ) ( group 2 ) or SSZ ( group 3 ) was used first . After 6 months , a combination of two drugs ( CsA and MTX ) was employed in groups 1 and 2 . SSZ was added after 12 months if improvement was less than ACR50 with the combination . Group 3 continued with SSZ alone . RESULTS After 6 months , 57 % of patients in group 1 , 31 % of group 2 ( MTX vs CsA , P=0.002 ) and 33 % of group 3 ( MTX vs SSZ , P=0.01 ) had reached ACR50 improvement according to intention-to-treat analysis . At month 12 after starting a drug combination , 67 % of group 1 and 76 % of group 2 had reached ACR50 compared with 24 % of group 3 . At the 18-month follow-up , 90 % of group 1 and 88 % of group 2 but only 24 % of group 3 had reached ACR50 . After 18 months , 62 % of group 1 , 60 % of group 2 and 48 % of group 3 showed side-effects and three , five and eight patients in the three groups respectively had dropped out of the study . At the 3-yr follow-up , 9 % of the patients in groups 1 and 2 and 7 % of group 3 were in remission according to the ACR criteria ; according to the Magnusson criteria , 40 % showed a full response in groups 1 and 2 but only 21 % did so in group 3 . CONCLUSION MTX appears to be the fastest-acting agent . A step-up approach with MTX plus CsA plus SSZ led to a 50 % improvement according to the ACR criteria in most patients . After 3 yr , 40 % of patients receiving combination therapy and 21 % of patients receiving monotherapy showed a full response , while 9 and 7 % respectively attained remission", "BACKGROUND Current disease management in rheumatoid arthritis ( RA ) has moved towards \" inverting the therapeutic pyramid \" by introducing disease-modifying anti-rheumatic drugs ( DMARDs ) early . Despite the logic of early DMARD therapy , there is a dearth of supportive evidence for this approach . We report a r and omised controlled trial comparing sulphasalazine monotherapy with diclofenac monotherapy in early RA . The primary aim was to provide unequivocal evidence that early DMARDs prevent erosive damage . The secondary aim was to evaluate if sulphasalazine used alone has comparable symptomatic benefits to NSAIDs . METHODS 117 patients with RA for under 12 months of diagnosis ( mean 2 months ) were r and omised ( 62 sulphasalazine ; 55 diclofenac ) . Sulphasalazine patients comprised 76 % women , and 58 % were rheumatoidfactor positive . Diclofenac patients comprised 74 % women , and 54 % were seropositive . 36 % completed 12 months of therapy ( 16 sulphasalazine ; 26 diclofenac ) ; sulphasalazine was given for a mean period of 21 weeks and diclofenac for a mean period of 33 weeks . Results were analysed on an intention to treat basis . RESULTS After 12 months the mean number of new erosions in patients r and omised to receive sulphasalazine was 2.0 ( 95%CI 0.9 , 3.1 ) and in patients r and omised to receive diclofenac was 7.5 ( 95%CI 4.1 , 10.9 ; p = 0.002 by Student 's unpaired t-test ) . An analysis of valid compliant completers showed the mean number of new erosions in patients who received 12 months therapy with sulphasalazine was 2.3 ( 95%CI 0.6 , 4.0 ) and in patients who received 12 months diclofenac was 10.5 ( 95%CI 5.0 , 15.9 ; p = 0.018 by Student 's unpaired t-test ) . The Ritchie articular index , swollen joint counts and pain scores decreased with both sulphasalazine and diclofenac , with mean falls in both groups of 15 - 20 % at 2 weeks and 30 - 40 % at 4 and 8 weeks . There were no differences between treatments . Disease activity scores showed similar highly significant mean decreases within both treatment groups ( P < 0.001 in all cases ) of 0.5 at 2 weeks and 1.0 at 4 weeks ; at 12 and 26 weeks they were significantly lower with sulphasalazine ( p = 0.036 and 0.045 ) . 75 % of the patients given sulphasalazine and 65 % of those given diclofenac had one or more adverse events with no major differences between treatments . CONCLUSIONS These results show that an accelerated dosing schedule of sulphasalazine has identical effects to diclofenac in reducing symptoms , indicating it is a rapidly effective DMARD . They also provide unequivocal evidence , analysed on an intention to treat basis , that early treatment with sulphasalazine significantly reduces the extent of radiological progression in active RA", "OBJECTIVE To evaluate the efficacy and safety of adding sulfasalazine to leflunomide treatment compared with switching to sulfasalazine alone in patients with RA with an inadequate response to leflunomide monotherapy . METHODS Patients with active RA ( ( DAS28 ) > 3.2 ) who were enrolled in the first open label phase of the RELIEF study received leflunomide for 24 weeks . Inadequate responders then entered the double blind phase and received a further 24 weeks ' treatment with leflunomide ( 20 mg once daily ) plus sulfasalazine ( final dose 2 g once daily ) , or placebo plus sulfasalazine ( dose as above ) . The primary efficacy variable was the DAS28 response rate , and secondary efficacy outcomes were ACR 20 % , 50 % , and 70 % response rates . Adverse events , including st and ard laboratory tests , were recorded . RESULTS 106 inadequate responders entered the double blind phase ; 56 received leflunomide plus sulfasalazine , and 50 placebo plus sulfasalazine . In the intention to treat population , more patients receiving leflunomide plus sulfasalazine ( 25/56 ( 45 % ) ) achieved a DAS28 response than those receiving placebo plus sulfasalazine ( 17/50 ( 34 % ) ) ( p = 0.179 ) . In week 24 completers , more patients receiving leflunomide plus sulfasalazine ( 17/56 ( 30 % ) ) were DAS28 responders than those receiving placebo plus sulfasalazine ( 10/50 ( 20 % ) ) ( p = 0.081 ) . Comparable numbers in each group were ACR 20 % responders ; the ACR 50 % response rate was significantly higher in the leflunomide plus sulfasalazine group ( 8.9 % ) than in the placebo plus sulfasalazine group ( 0 % ) ( p = 0.038 ) . The safety profiles of both groups were comparable . CONCLUSION Patient numbers are small and firm conclusions can not be reached , but a non-significant benefit is indicated for combining leflunomide with sulfasalazine compared with switching to sulfasalazine alone in patients inadequately responding to leflunomide", "BACKGROUND Azathioprine is useful as a steroid-sparing drug in patients with ulcerative colitis . Its role as monotherapy in the maintenance of disease remission has not been evaluated . METHODS In this prospect i ve , r and omized , open-label study , 25 patients with severe ulcerative colitis received either azathioprine ( 2.5 mg/Kg/day ; Group A , n = 12 ) or sulfasalazine ( 6 g/day ; Group B , n = 13 ) . All patients received oral corticosteroids in a tapering dosage schedule initially . Treatment failure was defined as either disease relapse or drug withdrawal because of adverse effects . RESULTS Five of 12 patients in Group A and 8 of 13 patients in Group B had sustained remission during the stipulated study period of 18 months ( p = ns ) . Two patients in Group A had to stop azathioprine because of adverse effects ( bone marrow suppression and acute pancreatitis ) . In Group A , all patients who had treatment failure developed it in the first half of the study while in Group B treatment failure occurred in both halves . CONCLUSIONS The relapse rate of ulcerative colitis on maintenance therapy with azathioprine or sulfasalazine is comparable ; there was a trend towards earlier treatment failure with azathioprine", "The therapeutic effectiveness and tolerance of 5-aminosalicylic acid ( 5ASA ) , compared with Salazosulphapyridine ( SASP ) in treatment of ulcerative colitis have been evaluated in 86 patients with the disease at a low or medium phase of activity . After a treatment of six weeks , an improvement was noted in 63.6 % ( 5ASA ) and 61.3 % ( SASP ) of these patients . However in no case was a complete remission of the disease observed on the basis of endoscopic inspection . In patients with pancolitis the improvement was lower ( 37.5 % with 5ASA , 40 % with SASP ) . The only side-effect was gastric intolerance , which occurred in 18.1 % of the 5ASA and in 19 % of the SASP patients . In conclusion we can assume that 5ASA and SASP largely overlap each other as regards both therapeutic effectiveness and occurrence of side-effects", "OBJECTIVE To compare the efficacy and tolerability of cyclosporine ( CSA ) with that of symptomatic therapy ( ST ) alone and sulfasalazine ( SSZ ) in the treatment of psoriatic arthritis ( PsA ) . METHODS Twelve rheumatology centers recruited 99 patients with active PsA in a 24 week , prospect i ve , r and omized , open , controlled study . The patients were treated with CSA ( 3 mg/kg/day ) or SSZ ( 2,000 mg/day ) plus ST , or ST alone ( nonsteroidal antiinflammatory drugs , analgesics , and /or prednisone < or = 5 mg/day ) . The primary endpoint was the 6 month change in pain . Analyses were on the basis of the intention-to-treat principle . RESULTS In comparison with both SSZ and ST , there was a statistically significant difference in favor of CSA in terms of the mean changes in the pain score ( p < 0.05 ) , which was considered the primary response variable . A significant decrease in favor of CSA versus ST alone was also observed for swollen joint count ( p = 0.05 ) , tender joint count ( p = 0.01 ) , joint/pain tenderness score ( p = 0.002 ) , patient and physician global assessment by at least one point ( p = 0.04 and 0.01 , respectively ) , total Arthritis Impact Measurement Scale score ( p = 0.002 ) , and spondylitis functional index ( p = 0.002 ) . There was a statistically significant difference in the ACR 50 % and ACR 70 % response rates between the CSA and ST groups ( p = 0.02 , 0.05 ) . Comparing the SSZ and ST alone groups , only the spondylitis functional index decreased significantly in the SSZ treated patients ( p = 0.03 ) . The Psoriasis Area and Severity Index was significantly lower in the CSA than in the ST and SSZ groups ( p = 0.0001 and 0.01 , respectively ) . Decrease in erythrocyte sedimentation rate was significant only in the SSZ versus the ST group ( p = 0.02 ) , whereas reduction in C-reactive protein was significant in the CSA treated patients compared with the ST group ( p = 0.006 ) . The most common adverse event in the CSA group was mild , reversible kidney dysfunction . CONCLUSION The results of this open trial confirm that CSA is well tolerated by patients with PsA and suggest that it is more efficacious than ST or SSZ", "Some semen characteristics of eight male patients with clinical ly inactive ulcerative colitis were investigated . Semen analysis was carried out twice during salicylazosulfapyridine ( SASP ) treatment and repeated twice after at least 3 months ' treatment with mesalazine . The motility variables all showed significant improvement during mesalazine treatment : the grade d motility ( p less than 0.05 ) , motility in percentage ( p less than 0.01 ) , and the penetration in egg white ( p less than 0.05 ) . The semen plasma was analyzed for mesalazine and the metabolite Ac-mesalazine during both regimens . There was no difference in the semen plasma concentration of mesalazine during the two regimens , whereas Ac-mesalazine was significantly higher during mesalazine treatment than during SASP treatment , indicating that other SASP metabolites , most likely sulfapyridine , are the agent causing the abnormal sperm characteristics . We suggest that pure mesalazine preparations are a safer alternative in young men with chronic inflammatory bowel disease", "OBJECTIVE To assess the efficacy , tolerability , and safety of sulfasalazine ( SSZ ) in the treatment of juvenile chronic arthritis ( JCA ) . METHODS We conducted a 24-week r and omized , placebo-controlled , double-blind , multicenter study of patients with active JCA of both oligoarticular and polyarticular onset . Patients were treated with a dosage of 50 mg/kg/day of SSZ ( maximum 2,000 mg/day ) or placebo . The efficacy variables were joint scores , physician 's , parents ' , and patient 's overall assessment s , and laboratory parameters of inflammation . RESULTS Of the 69 patients enrolled , 52 ( 75 % ) completed the trial . Six patients ( 18 % ) withdrew from the placebo group , and 11 ( 31 % ) withdrew from the SSZ group ( P = 0.18 ) . In the intention-to-treat analysis of end point efficacy , between-group differences were significant for the overall articular severity score ( P = 0.02 ) , all global assessment s ( P = 0.01 ) , and the laboratory parameters ( P < 0.001 ) . Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal ( P < 0.001 ) , but in all instances , these events were transient or reversible upon cessation of treatment . CONCLUSION The results of this first placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA , although it was not well tolerated in one-third of the patients", "Sulphasalazine impairs folic acid absorption and metabolism but rarely leads to folate deficiency in inflammatory bowel disease ( IBD ) . In rheumatoid arthritis ( RA ) , however , serum and red cell folate concentrations are often low and sulphasalazine might stress folate metabolism . In a prospect i ve study , 2 g sulphasalazine was compared with 500 mg penicillamine daily in 30 patients over 24 weeks . Pre-treatment serum and red cell folate concentrations were low-normal . Improvements in disease activity and haemoglobin occurred in both treatment groups , but MCV increased only in patients taking sulphasalazine . Serum and red cell folate concentrations did not change in either group . Increased MCV with sulphasalazine might therefore reflect reticulocytosis secondary to drug-induced haemolysis . The mechanisms by which sulphasalazine antagonizes folate metabolism are dose-dependent and , consequently , higher doses might precipitate folate deficiency", "Sulphasalazine has been established to be an effective drug for second line treatment of early mild to moderate rheumatoid arthritis . Its application for juvenile chronic arthritis ( JCA ) is limited so far and controversial results for the efficacy of this therapy have been published . We studied the efficacy and tolerance of the sulphasalazine treatment in 32 patients with JCA ( 10 with polyarthritis , 21 with pauciarthritis and 1 with systemic form ) . Our results revealed significant response of the treatment at the end of the 6th month in 24/31 patients ( 77 % ) . In one patient the treatment was discontinued because of transitory neutropenia at the end of the 1st month . No significant difference was observed between the efficacy of the treatment in the polyarticular and pauciarticular disease , as well as newly-diagnosed cases and those with longst and ing disease . From the group of 17 children treated up to the end of the 1st year 88 % achieved complete remission . No serious toxic effects were observed , with the exception of two cases with transitory low- grade neutropenia . According to our results sulphasalazine is an effective and well tolerated drug for second line treatment of JCA- patients", "One hundred sixty patients intolerant of or allergic to sulfasalazine ( Salazopyrin , Azulfidine ) participated in an open tolerance study of azodisal sodium ( Dipentum ) . More than 4 of every 5 patients tolerated azodisal sodium well , but 12.5 % of patients stopped medication because of diarrhea . Even after 7 patients who had also experienced diarrhea when taking sulfasalazine were excluded , there still remained a group of patients ( 9.8 % ) who had to discontinue azodisal sodium because of diarrhea . Apart from this , only minor side effects occurred . No serious drug-related changes were seen in hematologic or biochemical parameters . Male fertility appeared to be unaffected . One hundred two patients , who were in clinical and sigmoidoscopic remission , took part in a double-blind , placebo-controlled maintenance trial . Of these , 23.1 % of the patients treated with azodisal sodium and 44.9 % of the patients treated with placebo had a clinical and sigmoidoscopic relapse during a 6-mo trial period ( p = 0.02 ) . Azodisal sodium appears to be an effective agent for the maintenance treatment of ulcerative colitis", "Radiographic disease progression with leflunomide and sulfasalazine treatment was assessed in rheumatoid arthritis patients in a double-blind trial that was placebo controlled for the first 6 months . Completers at 6 months opted to continue on 12- and 24-month double-blind extensions ; patients in the placebo group were switched to sulfasalazine . Changes in Larsen scores were assessed in evaluable patient cohorts at 6 ( n=228 ) , 12 ( n=136 ) , and 24 ( n=65 ) months . Changes in Larsen scores and erosive joint counts with leflunomide and sulfasalazine at 6 months showed significantly less radiographic progression than placebo . Sustained retardation of radiographic progression was seen in the 24-month intent-to-treat cohorts ( delta Larsen scores : leflunomide -0.07 , sulfasalazine -0.03 ) . Changes in erosive joint counts within the 24-month leflunomide cohort suggest halting of disease progression for patients who continued in the study for 2 years ( leflunomide -0.92 , sulfasalazine 0.80 ) . Leflunomide was well tolerated with no unexpected adverse events during the 2-year period . This study demonstrates that slowing of disease progression with leflunomide , observed as early as 6 months , is maintained long term in patients who complete 2 years of treatment", "In an attempt to improve the relapse-preventing effect of salazosulphapyridine ( SASP ) and to encircle the part of the molecule essential for therapeutic actin , methyl-SASP was compared to SASP in a controlled double-blind trial without cross-over . The patient group comprised 33 patients with ulcerative colitis who had been symptom-free for 1 - -6 months on continuous treatment with SASP ( on an average 2 g daily ) . The daily doses were SASP 1 g X 3 and methyl-SASP 125 mg x 3 . Thirty patients completed the trial , 14 on SASP and 16 on methyl-SASP . Applying clinical criteria , the relapse rate after 6 months was 0.14 in the SASP group and 0.69 in the methyl-SASP group . The difference is highly significant . The blood concentrations of SASP , methyl-SASP , sulphapyridine ( SP ) , and methyl-sulphapyridine ( methyl-SP ) were measured after 3 and 6 months . The methyl-SASP concentration was on an average twice as high as that of SASP , and the methyl-SP on an average 1/10 of SP ( the differences are significant ) . It is concluded that whereas SASP showed a relapse-preventing effect in ulcerative colitis in this study comparable to that previously reported , the effect of methyl-SASP was only comparable to that of placebo , and the active substance in SASP does not seem to be unsplit SASP", "Recent reports have found sulphasalazine to have a disease-modifying effect in patients with rheumatoid arthritis . We report on the results of an open study of this drug . Sulphasalazine was given to 20 patients with active rheumatoid arthritis ( definite or classical by ARA criteria ) during a period of 6 months . Response to the treatment was assessed by subjective symptoms and objective ly by changes in selected clinical and laboratory parameters . After 2 to 6 months ' therapy some of these measurements had improved significantly in 18 patients . Three patients went into remission by preliminary ARA criteria . The treatment was discontinued in two patients because of side effects ( toxic-allergic cutaneous reactions ) . From these results we conclude that sulphasalazine may be a useful second-line drug in the treatment of rheumatoid arthritis", "Previous studies of sulphasalazine in rheumatoid arthritis have chosen an empirical dose based upon its use in ulcerative colitis . In this study we compare the efficacy and toxicity of two doses ( 1.5 g/day and 3 g/day , 30 patients per group ) , and attempt to relate efficacy to serum levels of sulphasalazine and its metabolites . After six months 24 of the low-dose group and 20 of the high-dose group remained on treatment . Greater improvement was seen in the high-dose group . When dose was expressed as mg/kg , the dose efficacy ratio became more apparent and a dose of greater than 40 mg/kg/day appears to confer greater benefit . No relationship was demonstrated between serum levels of sulphasalazine or its measured metabolites , and efficacy . We conclude that response to sulphasalazine in rheumatoid arthritis is dose dependent but does not relate to serum levels of sulphasalazine , sulphapyridine , or acetyl sulphapyridine", "OBJECTIVE To compare the efficacy of combination therapy with methotrexate ( MTX ) and hydroxychloroquine ( HCQ ) , MTX and sulfasalazine ( SSZ ) , and MTX , HCQ , and SSZ in patients with rheumatoid arthritis ( RA ) . METHODS RA patients ( n = 171 ) who had not previously been treated with combinations of the study medications were r and omized to receive 1 of the 3 treatment combinations in this 2-year , double-blind , placebo-controlled protocol . HCQ was given at a dosage of 200 mg twice a day . The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission . Similarly , the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission . The primary end point of the study was the percentage of patients who had a 20 % response to therapy according to the American College of Rheumatology ( ACR ) criteria at 2 years . RESULTS Intent-to-treat analysis revealed that patients receiving the triple combination responded best , with 78 % achieving an ACR 20 % response at 2 years , compared with 60 % of those treated with MTX and HCQ ( P = 0.05 ) and 49 % of those treated with MTX and SSZ ( P = 0.002 ) . Similar trends were seen for the ACR 50 % response , with 55 % , 40 % , and 29 % of patients in the 3 treatment groups , respectively , achieving these results at 2 years ( P = 0.005 for the triple combination group versus the MTX and SSZ group ) . All combination treatments were well-tolerated . Fourteen patients ( evenly distributed among the 3 groups ) withdrew from the protocol because of symptoms that were potentially related to the study medication . CONCLUSION The triple combination of MTX , SSZ , and HCQ is well-tolerated , and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ", "We compared the effects of intramuscular gold and sulphasalazine on early , active rheumatoid arthritis in 128 consecutive patients . Intramuscular gold was started in the first 70 consecutive patients and sulphasalazine in the subsequent 58 patients . The patient groups were comparable with regard to clinical characteristics . In both groups clinical and laboratory parameters improved , but there was no significant difference between the two groups . The clinical improvement was most pronounced during the first three months . However , despite the clinical improvement a clear progression in radiological changes was observed in both groups , 40 % of the patients taking gold and 48 % of patients taking sulphasalazine discontinued the treatment because of adverse drug reactions or inefficacy during the one year follow-up . Adverse drug reactions were the main reason in both groups . These findings suggest that intramuscular gold and sulphasalazine seem to have an equal , positive effect on symptoms and clinical variables , but that radiological progression does occur in most patients none the less", "During a six year period 43 patients with Crohns disease were included in a double-blind controlled trial of sulphasalazine given for one year as a possible treatment for reducing the relapse rate after resection or in asymptomatic patients with established disease . No trend in favour of sulphasalazine over the control group was observed . The difficulties of such a trial due to the small number of patients entered from nine hospitals , the varied nature of the disease , and the high incidence of complications , such as intraperitoneal abscess formation , are discussed", "Sixty-four patients with proven ulcerative colitis who had been maintained on sulphasalazine as their sole form of treatment for a minimum period of one year were entered into a controlled trial of sulphasalazine versus dummy tablets for a period of six months . All the patients admitted were not only symptom-free but also showed no evidence of inflammation on sigmoidoscopy and rectal biopsy . A patient was judged to have relapsed when there was a recurrence of colitic symptoms accompanied by sigmoidoscopic and histological evidence of inflammation . The patients who received dummy tablets had more than four times the relapse rate of those receiving sulphasalazine . The results were similar in patients who had been on maintenance treatment with sulphasalazine for less than three years before entry into the trial and in those who had been on this treatment for more than three years . It is concluded that maintenance treatment of ulcerative colitis with sulphasalazine should be continued indefinitely unless contraindicated by side effects", "Early intervention with slow acting anti-rheumatic drugs ( SAARDs ) has led to improvement in substantial proportion of rheumatoid arthritis ( RA ) patients . The present open , controlled study was design ed to assess whether a combination of SAARDs offer any added benefit . Fifty-four adult RA patients were r and omly allocated to methotrexate ( MTX ) ( n = 27 ) and MTX plus sulphasalazine ( SSZ ) ( n = 27 ) groups . The subjects were followed-up fortnightly for four weeks then monthly for six months . The disease activity was assessed with the help of 10 clinical and four laboratory indices . The improvement was grade d as : minor , mild decreases in indices , non-steroidal anti-inflammatory drugs ( NSAIDs ) continued , physician 's global assessment ( PGA ) decreased by one ; marked , acceptable decreases in indices , NSAIDs being taken sparingly , PGA decreased by at least 2 , and complete , all indices normalised and patients discontinued NSAIDs completely . The improvement was considered clinical ly important when marked or complete improvement occurred . Adverse drug reactions result ed in withdrawal of 4 subjects from the MTX + SSZ group and 1 from the control groups . Four and three subjects in the combined and MTX groups respectively were lost to follow-up . Subjects in both groups showed significant decline in all indices except hemoglobin and neutrophil count . The differences between the two groups in the pre-treatment and post-treatment values were insignificant . Complete , marked , minor and no improvement occurred in 4 ( 21 % ) , 12 ( 63 % ) , 3 ( 16 % ) & 0 in the MTX and in 11 ( 48 % ) , 7 ( 30 % ) , 4 ( 17 % ) & 1 ( 4 % ) in MTX + SSZ groups respectively . The differences in the rates of complete and clinical ly important improvement between the two groups were insignificant ( P 0.1398 and 0.7092 ) . The incidence of side effects was insignificantly higher in the MTX + SSZ group . Most of them were mild and transient . The combination of SAARDs offered little added advantage in RA . However , the higher rate of complete improvement in the combination group justifies trials including larger sample", "Sulphasalazine is widely used in the maintenance treatment of ulcerative colitis but the optimum dose is not known . In the present study , 170 patients were allotted at r and om to three treatment groups , in which the daily dose was 1 , 2 and 4 g respectively , and the trial period of treatment lasted for six months . A daily dose of 2 g was found to be much more efficacious than 1 g. A daily dose of 4 g was more efficacious than 2 g but at the price of fairly frequent symptomatic side-effects . Haematological abnormalities were observed at all dosage levels , but they occurred chiefly among the patients on 4 g daily . Both symptomatic and the haematological side-effects were usually associated with high concentrations of serum sulphapyridine and these high levels occurred chiefly among the slow acetylators . It is concluded that , for general use , a daily dose of 2 g sulphasalazine is satisfactory for the maintenance treatment of ulcerative colitis . If a patient does not do well on 2 g daily , it is worth trying a larger dose but in this case the patient 's condition should be monitored by blood film , haemoglobin , MCV , and reticulocyte count", "Sulfasalazine ( 0 , 0.5 , 1 , or 2 g daily in divided doses ) was given to patients with definite or classical rheumatoid arthritis ( RA ) insufficiently controlled by a nonsteroidal antiinflammatory drug . Grip strength , Westergren sedimentation rate , and physician and patient global assessment improved in those patients given 2 g/day . Inadequate response was the primary reason for withdrawal in the groups given placebo or 0.5 g/day , while adverse reactions ( mainly gastrointestinal upset or rash ) accounted for most withdrawals from the groups that received 1 or 2 g/day . Although its use is limited by adverse reactions , sulfasalazine is effective in the treatment of patients with RA" ]

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[ "The Effects of Two Modes of Exercise on Aerobic Fitness and Fat Mass in an Overweight Population", "Effect of 2 weeks of sprint interval training on health-related outcomes in sedentary overweight/obese men.", "Both aerobic endurance and strength training programmes improve cardiovascular health in obese adults.", "The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes.", "Superior Cardiovascular Effect of Aerobic Interval Training Versus Moderate Continuous Training in Heart Failure Patients: A Randomized Study", "Aerobic interval training reduces blood pressure and improves myocardial function in hypertensive patients", "The Effect of a High-Intensity Interval Training Program on High-Density Lipoprotein Cholesterol in Young Men", "Sprint interval and traditional endurance training induce similar improvements in peripheral arterial stiffness and flow-mediated dilation in healthy humans.", "Aerobic interval training versus continuous moderate exercise after coronary artery bypass surgery: a randomized study of cardiovascular effects and quality of life.", "Muscle performance and enzymatic adaptations to sprint interval training.", "Run sprint interval training improves aerobic performance but not maximal cardiac output.", "Effect of intensity of aerobic training on VO2max.", "Continuous vs interval training on glycemic control and macro- and microvascular reactivity in type 2 diabetic patients.", "Effects of high-intensity interval training on pulmonary function", "The Effect of In‐Season, High‐Intensity Interval Training in Soccer Players", "Aerobic high-intensity intervals improve VO2max more than moderate training.", "Peak Oxygen Uptake after Cardiac Rehabilitation: A Randomized Controlled Trial of a 12-Month Maintenance Program versus Usual Care", "Effects of recovery mode (active vs. passive) on performance during a short high-intensity interval training program: a longitudinal study", "Continuous Exercise but Not High Intensity Interval Training Improves Fat Distribution in Overweight Adults", "Low- and High-Volume of Intensive Endurance Training Significantly Improves Maximal Oxygen Uptake after 10-Weeks of Training in Healthy Men", "The response of interleukin-6 and soluble interleukin-6 receptor isoforms following intermittent high intensity and continuous moderate intensity cycling", "High intensity interval exercise training in overweight young women.", "Effect of sprint interval training on circulatory function during exercise in sedentary, overweight/obese women", "Aerobic interval training increases peak oxygen uptake more than usual care exercise training in myocardial infarction patients: a randomized controlled study", "The effects of high-intensity intermittent exercise training on cardiovascular response to mental and physical challenge.", "The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.", "Adaptations to high-intensity training are independent of gender", "The effects of training intensity on muscle buffer capacity in females", "Feasibility and preliminary efficacy of high intensity interval training in type 2 diabetes.", "The effects of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women", "Effects of a low-volume aerobic-type interval exercise on VO2max and cardiac mass.", "Effect of high-intensity interval training on progression of cardiac allograft vasculopathy.", "Heart rate response to exercise and cardiorespiratory fitness of young women at high familial risk for hypertension: effects of interval vs continuous training", "Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to beta-adrenergic stimulation.", "High-intensity intermittent exercise and cardiovascular and autonomic function", "Determination of inflammatory and prominent proteomic changes in plasma and adipose tissue after high-intensity intermittent training in overweight and obese males", "Effects of Four Weeks of High-Intensity Interval Training and Creatine Supplementation on Critical Power and Anaerobic Working Capacity in College-Aged Men", "Six Weeks of High-Intensity Interval Training With and Without β-Alanine Supplementation for Improving Cardiovascular Fitness in Women", "High intensity aerobic interval exercise is superior to moderate intensity exercise for increasing aerobic capacity in patients with coronary artery disease", "One year of high-intensity interval training improves exercise capacity, but not left ventricular function in stable heart transplant recipients: A randomised controlled trial", "Effective training for patients with intermittent claudication", "Rating of Perceived Exertion after 12 Weeks of High-Intensity, Intermittent Sprinting", "Continuous glucose monitoring reveals delayed nocturnal hypoglycemia after intermittent high-intensity exercise in nontrained patients with type 1 diabetes.", "High-intensity interval training attenuates the exercise-induced increase in plasma IL-6 in response to acute exercise.", "Manipulating high-intensity interval training: effects on VO2max, the lactate threshold and 3000 m running performance in moderately trained males.", "Aerobic interval training and continuous training equally improve aerobic exercise capacity in patients with coronary artery disease: the SAINTEX-CAD study.", "Greater Improvement in Cardiorespiratory Fitness Using Higher-Intensity Interval Training in the Standard Cardiac Rehabilitation Setting", "Sprint interval and endurance training are equally effective in increasing muscle microvascular density and eNOS content in sedentary males.", "Cardiac autonomic function and high-intensity interval training in middle-age men.", "High-Intensity Intermittent Swimming Improves Cardiovascular Health Status for Women with Mild Hypertension" ]

[ "We examined the effects of an 8-week exercise intervention on aerobic fitness , and roid and gynoid fat mass , and blood lipids in overweight and obese participants . Twenty-four sedentary participants ( average BMI = 30 ± 2 kg/m2 ; 18 females , 6 males ) were r and omized into either interval training and diet education ( INT group ) , continuous aerobic exercise and diet education ( CON group ) , or diet education only ( DIET group ) . Duration s of exercise sessions were similar ( ∼30 minutes ) , with both exercise groups completing the same amount of work . The INT and CON groups demonstrated significant improvements over time for ( p < 0.01 and p < 0.05 , ES = 1.1 and 1.2 , respectively ) and time to exhaustion on a grade d exercise test ( p < 0.01 and ES = 0.8 for both groups ) . Further , a large effect size ( 0.7 ) was recorded for the loss in and roid fat mass over time in the INT group only", "The aim of this study was to investigate the effects of very high intensity sprint interval training ( SIT ) on metabolic and vascular risk factors in overweight/obese sedentary men . Ten men ( age , 32.1 ± 8.7 years ; body mass index , 31.0 ± 3.7 kg m(-2 ) ) participated . After baseline metabolic , anthropometric , and fitness measurements , participants completed a 2-week SIT intervention , comprising 6 sessions of 4 to 6 repeats of 30-second Wingate anaerobic sprints on an electromagnetically braked cycle ergometer , with 4.5-minute recovery between each repetition . Metabolic , anthropometric , and fitness assessment s were repeated post-intervention . Both maximal oxygen uptake ( 2.98 ± 0.15 vs 3.23 ± 0.14 L min(-1 ) , P = .013 ) and mean Wingate power ( 579 ± 24 vs 600 ± 19 W , P = .040 ) significantly increased after 2 weeks of SIT . Insulin sensitivity index ( 5.35 ± 0.72 vs 4.34 ± 0.72 , P = .027 ) and resting fat oxidation rate in the fasted state ( 0.13 ± 0.01 vs 0.11 ± 0.01 g min(-1 ) , P = .019 ) were significantly higher and systolic blood pressure ( 121 ± 3 vs 127 ± 3 mm Hg , P = .020 ) and resting carbohydrate oxidation in the fasted state ( 0.03 ± 0.01 vs 0.08 ± 0.02 g min(-1 ) , P = .037 ) were significantly lower 24 hours post-intervention compared with baseline , but these changes were no longer significant 72 hours post-intervention . Significant decreases in waist ( 98.9 ± 3.1 vs 101.3 ± 2.7 cm , P = .004 ) and hip ( 109.8 ± 2.2 vs 110.9 ± 2.2 cm , P = .017 ) circumferences compared with baseline were also observed after the intervention . Thus , 2 weeks of SIT substantially improved a number of metabolic and vascular risk factors in overweight/obese sedentary men , highlighting the potential for this to provide an alternative exercise model for the improvement of vascular and metabolic health in this population", "Regular exercise training is recognized as a powerful tool to improve work capacity , endothelial function and the cardiovascular risk profile in obesity , but it is unknown which of high-intensity aerobic exercise , moderate-intensity aerobic exercise or strength training is the optimal mode of exercise . In the present study , a total of 40 subjects were r and omized to high-intensity interval aerobic training , continuous moderate-intensity aerobic training or maximal strength training programmes for 12 weeks , three times/week . The high-intensity group performed aerobic interval walking/running at 85 - 95 % of maximal heart rate , whereas the moderate-intensity group exercised continuously at 60 - 70 % of maximal heart rate ; protocol s were isocaloric . The strength training group performed ' high-intensity ' leg press , abdominal and back strength training . Maximal oxygen uptake and endothelial function improved in all groups ; the greatest improvement was observed after high-intensity training , and an equal improvement was observed after moderate-intensity aerobic training and strength training . High-intensity aerobic training and strength training were associated with increased PGC-1alpha ( peroxisome-proliferator-activated receptor gamma co-activator 1alpha ) levels and improved Ca(2 + ) transport in the skeletal muscle , whereas only strength training improved antioxidant status . Both strength training and moderate-intensity aerobic training decreased oxidized LDL ( low-density lipoprotein ) levels . Only aerobic training decreased body weight and diastolic blood pressure . In conclusion , high-intensity aerobic interval training was better than moderate-intensity aerobic training in improving aerobic work capacity and endothelial function . An important contribution towards improved aerobic work capacity , endothelial function and cardiovascular health originates from strength training , which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform", "OBJECTIVE To compare the response of blood glucose levels to intermittent high-intensity exercise ( IHE ) and moderate-intensity exercise ( MOD ) in individuals with type 1 diabetes . RESEARCH DESIGN AND METHODS Seven healthy individuals with type 1 diabetes were tested on two separate occasions , during which either a 30-min MOD or IHE protocol was performed . MOD consisted of continuous exercise at 40 % Vo(2peak ) , while the IHE protocol involved a combination of continuous exercise at 40 % Vo(2peak ) interspersed with 4-s sprints performed every 2 min to simulate the activity patterns of team sports . RESULTS Both exercise protocol s result ed in a decline in blood glucose levels . However , the decline was greater with MOD ( -4.4 + /- 1.2 mmol/l ) compared with IHE ( -2.9 + /- 0.8 mmol/l ; P < 0.05 ) , despite the performance of a greater amount of total work with IHE ( P < 0.05 ) . During 60 min of recovery from exercise , glucose levels remained higher in IHE compared with MOD ( P < 0.05 ) . Furthermore , glucose levels remained stable during recovery from IHE , while they continued to decrease after MOD ( P < 0.05 ) . The stabilization of blood glucose levels with IHE was associated with elevated levels of lactate , catecholamines , and growth hormone during early recovery from exercise ( P < 0.05 ) . There were no differences in free insulin , glucagon , cortisol , or free fatty acids between MOD and IHE . CONCLUSIONS The decline in blood glucose levels is less with IHE compared with MOD during both exercise and recovery in individuals with type 1 diabetes", "Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies", "Aims : Exercise is recommended as prevention , management , and control of all stages of hypertension . There are still controversies about the optimal training dose , frequency , and intensity . We aim ed to study the effect of aerobic interval training on blood pressure and myocardial function in hypertensive patients . Methods and results : A total of 88 patients ( 52.0 ± 7.8 years , 39 women ) with essential hypertension were r and omized to aerobic interval training ( AIT ) ( > 90 % of maximal heart rate , correlates to 85–90 % of VO2max ) , isocaloric moderate intensity continuous training ( MIT ) ( ∼70 % of maximal heart rate , 60 % of VO2max ) , or a control group . Exercise was performed on a treadmill , three times per week for 12 weeks . Ambulatory 24-hour blood pressure ( ABP ) was the primary endpoint . Secondary endpoints included maximal oxygen uptake ( VO2max ) , mean heart rate/24 hour , flow mediated dilatation ( FMD ) , total peripheral resistance ( TPR ) , and myocardial systolic and diastolic function by echocardiography . Systolic ABP was reduced by 12 mmHg ( p < 0.001 ) in AIT and 4.5 mmHg ( p = 0.05 ) in MIT . Diastolic ABP was reduced by 8 mmHg ( p < 0.001 ) in AIT and 3.5 mmHg ( p = 0.02 ) in MIT . VO2max improved by 15 % ( p < 0.001 ) in AIT and 5 % ( p < 0.01 ) in MIT . Systolic myocardial function improved in both exercise groups , diastolic function in the AIT group only . TPR reduction and increased FMD were only observed in the AIT group . Conclusions : This study indicates that the blood pressure reducing effect of exercise in essential hypertension is intensity dependent . Aerobic interval training is an effective method to lower blood pressure and improve other cardiovascular risk factors", "Musa , DI , Adeniran , SA , Dikko , AU , and Sayers , SP . The effect of a high-intensity interval training program on high-density lipoprotein cholesterol in young men . J Strength Cond Res 23(2 ) : 587 - 592 , 2009-This study examined the impact of an 8-week program of high-intensity interval training on high-density lipoprotein cholesterol ( HDL-C ) , total cholesterol ( TC ) , and the atherogenic index ( TC/HDL-C ) in 36 untrained men ages 21 - 36 years . Participants were r and omly assigned to an interval training group ( n = 20 ) or a control group ( n = 16 ) . Participants in the experimental group performed 3.2 km of interval running ( 1:1 work : rest ratio ) 3 times a week for 8 weeks at an intensity of 90 % of maximal heart rate ( ∼423 kcal per session ) . Results indicated significant pre- to posttraining changes in HDL-C ( 1.1 vs. 1.3 mmol·L−1 , p < 0.0001 ) and TC/HDL-C ( 3.8 vs. 3.1 , p < 0.0001 ) but no significant changes in TC ( 3.9 vs. 3.8 mmol·L−1 , p > 0.05 ) with interval training . It was concluded that an 8-week program of high-intensity interval training is effective in eliciting favorable changes in HDL-C and TC/HDL-C but not TC in young adult men with normal TC levels . Our findings support the recommendations of high-intensity interval training as an alternative mode of exercise to improve blood lipid profiles for individuals with acceptable physical fitness levels", "Low-volume sprint interval training ( SIT ) , or repeated sessions of brief , intense intermittent exercise , elicits metabolic adaptations that resemble traditional high-volume endurance training ( ET ) . The effects of these different forms of exercise training on vascular structure and function remain largely unexplored . To test the hypothesis that SIT and ET would similarly improve peripheral artery distensibility and endothelial function and central artery distensibility , we recruited 20 healthy untrained subjects ( age : 23.3 + /- 2.8 yr ) and had them perform 6 wk of SIT or ET ( n = 5 men and 5 women per group ) . The SIT group completed four to six 30-s \" all-out \" Wingate tests separated by 4.5 min of recovery 3 days/wk . The ET group completed 40 - 60 min of cycling at 65 % of their peak oxygen uptake ( Vo2peak ) 5 days/wk . Popliteal endothelial function , both relative and normalized to shear stimulus , was improved after training in both groups ( main effect for time , P < 0.05 ) . Carotid artery distensibility was not statistically altered by training ( P = 0.29 ) in either group ; however , popliteal artery distensibility was improved in both groups to the same degree ( main effect , P < 0.05 ) . We conclude that SIT is a time-efficient strategy to elicit improvements in peripheral vascular structure and function that are comparable to ET . However , alterations in central artery distensibility may require a longer training stimuli and /or greater initial vascular stiffness than observed in this group of healthy subjects", "BACKGROUND Peak oxygen uptake ( Vo(2peak ) ) strongly predicts mortality in cardiac patients . We compared the effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on Vo(2peak ) and quality of life after coronary artery bypass grafting ( CABG ) . METHODS Fifty-nine CABG patients were r and omized to either AIT at 90 % of maximum heart rate or MCT at 70 % of maximum heart rate , 5 d/wk , for 4 weeks at a rehabilitation center . Primary outcome was Vo(2peak ) , at baseline , after rehabilitation ( 4 weeks ) , and after 6 months of home-based exercise ( 6 months ) . RESULTS Vo(2peak ) increased between baseline and 4 weeks in AIT ( 27.1 + /- 4.5 vs 30.4 + /- 5.5 mL.kg(-1).min(-1 ) , P < .001 ) and MCT ( 26.2 + /- 5.2 vs 28.5 + /- 5.6 mL.kg(-1).min(-1 ) , P < .001 ; group difference , not significant ) . Aerobic interval training increased Vo(2peak ) between 4 weeks and 6 months ( 30.4 + /- 5.5 vs 32.2 + /- 7.0 mL.kg(-1).min(-1 ) , P < .001 ) , with no significant change in MCT ( 28.5 + /- 5.6 vs 29.5 + /- 5.7 mL.kg(-1).min(-1 ) ) . Quality of life improved in both groups from baseline to 4 weeks , remaining improved at 6 months . There were no changes in echocardiographic systolic and diastolic left ventricular function . Adiponectin increased between 4 weeks and 6 months in both groups ( group differences , not significant ) . CONCLUSIONS Four weeks of intense training increased Vo(2peak ) significantly after both AIT and MCT . Six months later , the AIT group had a significantly higher Vo(2peak ) than MCT . The results indicate that AIT and MCT increase Vo(2peak ) similarly in the short term , but with better long-term effect of AIT after CABG", "Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance . Twelve healthy men ( 22 + /- 2 yr of age ) underwent intense interval training on a cycle ergometer for 7 wk . Training consisted of 30-s maximum sprint efforts ( Wingate protocol ) interspersed by 2 - 4 min of recovery , performed three times per week . The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7 . Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption ( VO2 max ) were measured before and after the training program . Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase , total glycogen phosphorylase , phosphofructokinase , lactate dehydrogenase , citrate synthase , succinate dehydrogenase , malate dehydrogenase , and 3-hydroxyacyl-CoA dehydrogenase . The training program result ed in significant increases in peak power output , total work over 30 s , and VO2 max . Maximal enzyme activity of hexokinase , phosphofructokinase , citrate synthase , succinate dehydrogenase , and malate dehydrogenase was also significantly ( P < 0.05 ) higher after training . It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity , maximum short-term power output , and VO2 max", "UNLABELLED Repeated maximal-intensity short- duration exercise ( sprint interval training , SIT ) can produce muscle adaptations similar to endurance training ( ET ) despite a much reduced training volume . However , most SIT data use cycling , and little is known about its effects on body composition or maximal cardiac output ( Qmax ) . PURPOSE The purpose of this study was to assess body composition , 2000-m run time trial , VO(2max ) , and Q(max ) effects of run SIT versus ET . METHODS Men and women ( n = 10 per group ; mean ± SD : age = 24 ± 3 yr ) trained three times per week for 6 wk with SIT , 30-s all-out run sprints ( manually driven treadmill ) , four to six bouts per session , 4-min recovery per bout , versus ET , 65 % VO(2max ) for 30 to 60 min·d(-1 ) . RESULTS Training improved ( P < 0.05 ) body composition , 2000-m run time trial performance , and VO(2max ) in both groups . Fat mass decreased 12.4 % with SIT ( mean ± SEM ; 13.7 ± 1.6 to 12.0 ± 1.6 kg ) and 5.8 % with ET ( 13.9 ± 1.7 to 13.1 ± 1.6 kg ) . Lean mass increased 1 % in both groups . Time trial performance improved 4.6 % with SIT ( -25.6 ± 8.1 s ) and 5.9 % with ET ( -31.9 ± 6.3 s ) . VO(2max ) increased 11.5 % with SIT ( 46.8 ± 1.6 to 52.2 ± 2.0 mL·kg·(-1)·min(-1 ) ) and 12.5 % with ET ( 44.0 ± 2.0 to 49.5 ± 2.6 mL·kg·(-1)·min(-1 ) ) . None of these improvements differed between groups . In contrast , Q(max ) increased by 9.5 % with ET only ( 22.2 ± 2.0 to 24.3 ± 1.6 L·min(-1 ) ) . CONCLUSIONS Despite a fraction of the time commitment , run SIT induces similar body composition , VO(2max ) , and performance adaptations as ET , but with no effect on Q(max ) . These data suggest that adaptations with ET are of central origin primarily , whereas those with SIT are more", "PURPOSE To determine whether various intensities of aerobic training differentially affect aerobic capacity as well as resting HR and resting blood pressure ( BP ) . METHODS Sixty-one health young adult subjects were matched for sex and VO2max and were r and omly assigned to a moderate- ( 50 % VO2 reserve ( VO2R ) , vigorous ( 75 % VO2R ) , near-maximal-intensity ( 95 % VO2R ) , or a nonexercising control group . Intensity during exercise was controlled by having the subjects maintain target HR based on HR reserve . Exercise volume ( and thus energy expenditure ) was controlled across the three training groups by varying duration and frequency . Fifty-five subjects completed a 6-wk training protocol on a stationary bicycle ergometer and pre- and posttesting . During the final 4 wk , the moderate-intensity group exercised for 60 min , 4 d.wk the vigorous-intensity group exercised for 40 min , 4 d.wk and the near-maximal-intensity group exercised 3 d.wk performing 5 min at 75 % VO2R followed by five intervals of 5 min at 95 % VO2R and 5 min at 50 % VO2R . RESULTS VO2max significantly increased in all exercising groups by 7.2 , 4.8 , and 3.4 mL.min.kg in the near-maximal- , the vigorous- , and the moderate-intensity groups , respectively . Percent increases in the near-maximal- ( 20.6 % ) , the vigorous- ( 14.3 % ) , and the moderate-intensity ( 10.0 % ) groups were all significantly different from each other ( P < 0.05 ) . There were no significant changes in resting HR and BP in any group . CONCLUSION When volume of exercise is controlled , higher intensities of exercise are more effective for improving VO2max than lower intensities of exercise in healthy , young adults", "To determine the effects of continuous aerobic exercise training ( CON ) vs interval aerobic exercise training ( INT ) on glycemic control and endothelium-dependent vasodilatation , 43 participants with type 2 diabetes were r and omly allocated to the sedentary , CON , and INT groups . The CON and INT exercise training programs were design ed to yield the same energy expenditure/exercise session and included walking on treadmill for 30 and 40 min/day , 3 times/week for 12 weeks . Body fatness and heart rate at rest decreased and leg muscle strength increased ( all P < 0.05 ) in both the CON and INT groups . Fasting blood glucose levels decreased ( P < 0.05 ) in both exercise groups but glycosylated hemoglobin levels decreased ( P < 0.05 ) only in the INT group . Maximal aerobic capacity , flow-mediated dilation , and cutaneous reactive hyperemia increased significantly in both exercise groups ; however , the magnitude of improvements was greater in the INT group . Only the INT group experienced reductions in erythrocyte malondialdehyde and serum von Willebr and factor and increases in plasma glutathione peroxidase and nitric oxide ( all P < 0.05 ) . We concluded that both continuous and interval training were effective in improving glycemic control , aerobic fitness , and endothelium-dependent vasodilation , but the interval training program appears to confer greater improvements than the continuous training program", "To determine whether high-intensity interval training ( HIT ) would increase respiratory muscle strength and expiratory flow rates more than endurance training ( ET ) , 15 physically active , healthy subjects ( untrained ) were r and omly assigned to an ET group ( n = 7 ) or a HIT group ( n = 8) . All subjects performed an incremental test to exhaustion ( VO2max ) on a cycle ergometer before and after training . St and ard pulmonary function tests , maximum inspiratory pressure ( PImax ) , maximum expiratory pressure ( PEmax ) , and maximal flow volume loops were performed pre training and after each week of training . HIT subjects performed a 4-week training program , 3 days a week , on a cycle ergometer at 90 % of their VO2max final workload , while the ET subjects performed exercise at 60–70 % VO2max . The HIT group performed five 1-min bouts with 3-min recovery periods and the ET group cycled for 45 min continuously . A five-mile time trial ( TT ) was performed prior to , after 2 weeks , and after completion of training . Both groups showed improvements ( P < 0.05 ) in VO2max ( ~8–10 % ) and TT ( HIT 6.5 ± 1.3 % , ET 4.4 ± 1.8 % ) following training with no difference ( P > 0.05 ) between groups . Both groups increased ( P < 0.05 ) PImax post training ( ET ~ 25 % , HIT ~ 43 % ) with values significantly higher for HIT than ET . There was no change ( P > 0.05 ) in expiratory flow rates with training in either group . These data suggest that both whole-body exercise training and HIT are effective in increasing inspiratory muscle strength with HIT offering a time-efficient alternative to ET in improving aerobic capacity and performance", "& NA ; Dupont , G. , K. Akakpo , and S. Berthoin . The effect of in‐season , high‐intensity interval training in soccer players . J. Strength Cond . Res . 18(3):584–589 . 2004.—The effects of inseason , high‐intensity interval training on professional male soccer players ’ running performances were investigated . Twentytwo subjects participated in 2 consecutive training periods of 10 weeks . The first period was considered a control period and was compared with a period where 2 high‐intensity interval training exercises were included in the usual training program . Intermittent runs consisted of 12–15 runs lasting 15 seconds at 120 % of maximal aerobic speed alternated with 15 seconds of rest . Sprint repetitions consisted of 12–15 all‐out 40‐m runs alternated with 30 seconds of rest . Results from the high‐intensity interval training have shown that maximal aerobic speed was improved ( + 8.1 ± 3.1 % ; p < 0.001 ) and that the time of the 40‐m sprint was decreased ( ‐3.5 ± 1.5 % ; p < 0.001 ) , whereas no change in either parameters were observed during the control period . This study shows that improvements in physical qualities can be made during the in‐season period", "PURPOSE The present study compared the effects of aerobic endurance training at different intensities and with different methods matched for total work and frequency . Responses in maximal oxygen uptake ( VO2max ) , stroke volume of the heart ( SV ) , blood volume , lactate threshold ( LT ) , and running economy ( CR ) were examined . METHODS Forty healthy , nonsmoking , moderately trained male subjects were r and omly assigned to one of four groups:1 ) long slow distance ( 70 % maximal heart rate ; HRmax ) ; 2)lactate threshold ( 85 % HRmax ) ; 3 ) 15/15 interval running ( 15 s of running at 90 - 95 % HRmax followed by 15 s of active resting at 70 % HRmax ) ; and 4 ) 4 x 4 min of interval running ( 4 min of running at 90 - 95 % HRmax followed by 3 min of active resting at 70%HRmax ) . All four training protocol s result ed in similar total oxygen consumption and were performed 3 d.wk for 8 wk . RESULTS High-intensity aerobic interval training result ed in significantly increased VO2max compared with long slow distance and lactate-threshold training intensities ( P<0.01 ) . The percentage increases for the 15/15 and 4 x 4 min groups were 5.5 and 7.2 % , respectively , reflecting increases in V O2max from 60.5 to 64.4 mL x kg(-1 ) x min(-1 ) and 55.5 to 60.4 mL x kg(-1 ) x min(-1 ) . SV increased significantly by approximately 10 % after interval training ( P<0.05 ) . CONCLUSIONS : High-aerobic intensity endurance interval training is significantly more effective than performing the same total work at either lactate threshold or at 70 % HRmax , in improving VO2max . The changes in VO2max correspond with changes in SV , indicating a close link between the two", "Background Exercise capacity is a strong predictor of survival in patients with coronary artery disease ( CAD ) . Exercise capacity improves after cardiac rehabilitation exercise training , but previous studies have demonstrated a decline in peak oxygen uptake after ending a formal rehabilitation program . There is a lack of knowledge on how long-term exercise adherence can be achieved in CAD patients . We therefore assessed if a 12-month maintenance program following cardiac rehabilitation would lead to increased adherence to exercise and increased exercise capacity compared to usual care . Material s and Methods Two-centre , open , parallel r and omized controlled trial with 12 months follow-up comparing usual care to a maintenance program . The maintenance program consisted of one monthly supervised high intensity interval training session , a written exercise program and exercise diary , and a maximum exercise test every third month during follow-up . Forty-nine patients ( 15 women ) on optimal medical treatment were included following discharge from cardiac rehabilitation . The primary endpoint was change in peak oxygen uptake at follow-up ; secondary endpoints were physical activity level , quality of life and blood markers of cardiovascular risk . Results There was no change in peak oxygen uptake from baseline to follow-up in either group ( intervention group 27.9 ( ±4.7 ) to 28.8 ( ±5.6 ) mL·kg ( -1 ) min ( −1 ) , control group 32.0 ( ±6.2 ) to 32.8 ( ±5.8 ) mL·kg ( −1 ) min ( −1 ) , with no between-group difference , p = 0.22 ) . Quality of life and blood biomarkers remained essentially unchanged , and both self-reported and measured physical activity levels were similar between groups after 12 months . Conclusions A maintenance exercise program for 12 months did not improve adherence to exercise or peak oxygen uptake in CAD patients after discharge from cardiac rehabilitation compared to usual care . This suggests that infrequent supervised high intensity interval training sessions are inadequate to improve peak oxygen uptake in this patient group . Trial Registration Clinical Trials.gov", "The aim of this longitudinal study was to compare two recovery modes ( active vs. passive ) during a seven-week high-intensity interval training program ( SWHITP ) aim ed to improve maximal oxygen uptake ( $ $ \\dot{V}{\\text{O } } _ { { 2 { \\text{max } } } } $ $ ) , maximal aerobic velocity ( MAV ) , time to exhaustion ( tlim ) and time spent at a high percentage of $ $ \\dot{V}{\\text{O } } _ { { 2 { \\text{max } } } } $ $ , i.e. , above 90 % ( t90 $ $ \\dot{V}{\\text{O } } _ { { 2 { \\text{max } } } } $ $ ) and 95 % ( t95 $ $ \\dot{V}{\\text{O } } _ { { 2 { \\text{max } } } } $ $ ) of $ $ \\dot{V}{\\text{O } } _ { { 2 { \\text{max } } } } $ $ . Twenty-four adults were r and omly assigned to a control group that did not train ( CG , n = 6 ) and two training groups : intermittent exercise ( 30 s exercise/30 s recovery ) with active ( IEA , n = 9 ) or passive recovery ( IEP , n = 9 ) . Before and after seven weeks with ( IEA and IEP ) or without ( CG ) high-intensity interval training ( HIT ) program , all subjects performed a maximal grade d test to determine their $ $ \\dot{V}{\\text{O } } _ { { 2 { \\text{max } } } } $ $ and MAV . Subsequently only the subjects of IEA and IEP groups carried out an intermittent exercise test consisting of repeating as long as possible 30 s intensive runs at 105 % of MAV alternating with 30 s active recovery at 50 % of MAV ( IEA ) or 30 s passive recovery ( IEP ) . Within IEA and IEP , mean tlim and MAV significantly increased between the onset and the end of the SWHITP and no significant difference was found in t90 VO2max and t95 VO2max . Furthermore , before and after the SWHITP , passive recovery allowed a longer tlim for a similar time spent at a high percentage of VO2max . Finally , within IEA , but not in IEP , mean VO2max increased significantly between the onset and the end of the SWHITP both in absolute ( p < 0.01 ) and relative values ( p < 0.05 ) . In conclusion , our results showed a significant increase in VO2max after a SWHITP with active recovery in spite of the fact that tlim was significantly longer ( more than twice longer ) with respect to passive recovery", "Objective . The purpose of this study was to assess the effect of high intensity interval training ( HIIT ) versus continuous aerobic exercise training ( CONT ) or placebo ( PLA ) on body composition by r and omized controlled design . Methods . Work capacity and body composition ( dual-energy X-ray absorptiometry ) were measured before and after 12 weeks of intervention in 38 previously inactive overweight adults . Results . There was a significant group × time interaction for change in work capacity ( P < 0.001 ) , which increased significantly in CONT ( 23.8 ± 3.0 % ) and HIIT ( 22.3 ± 3.5 % ) but not PLA ( 3.1 ± 5.0 % ) . There was a near-significant main effect for percentage trunk fat , with trunk fat reducing in CONT by 3.1 ± 1.6 % and in PLA by 1.1 ± 0.4 % , but not in HIIT ( increase of 0.7 ± 1.0 % ) ( P = 0.07 ) . There was a significant reduction in and roid fat percentage in CONT ( 2.7 ± 1.3 % ) and PLA ( 1.4 ± 0.8 % ) but not HIIT ( increase of 0.8 ± 0.7 % ) ( P = 0.04 ) . Conclusion . These data suggest that HIIT may be advocated as a time-efficient strategy for eliciting comparable fitness benefits to traditional continuous exercise in inactive , overweight adults . However , in this population HIIT does not confer the same benefit to body fat levels as continuous exercise training", "Regular exercise training improves maximal oxygen uptake ( VO2max ) , but the optimal intensity and volume necessary to obtain maximal benefit remains to be defined . A growing body of evidence suggests that exercise training with low-volume but high-intensity may be a time-efficient means to achieve health benefits . In the present study , we measured changes in VO2max and traditional cardiovascular risk factors after a 10 wk . training protocol that involved three weekly high-intensity interval sessions . One group followed a protocol which consisted of 4 × 4 min at 90 % of maximal heart rate ( HRmax ) interspersed with 3 min active recovery at 70 % HRmax ( 4-AIT ) , the other group performed a single bout protocol that consisted of 1 × 4 min at 90 % HRmax ( 1-AIT ) . Twenty-six inactive but otherwise healthy overweight men ( BMI : 25–30 , age : 35–45 y ) were r and omized to either 1-AIT ( n = 11 ) or 4-AIT ( n = 13 ) . After training , VO2max increased by 10 % ( ∼5.0 mL⋅kg−1⋅min−1 ) and 13 % ( ∼6.5 mL⋅kg−1⋅min−1 ) after 1-AIT and 4-AIT , respectively ( group difference , p = 0.08 ) . Oxygen cost during running at a sub-maximal workload was reduced by 14 % and 13 % after 1-AIT and 4-AIT , respectively . Systolic blood pressure decreased by 7.1 and 2.6 mmHg after 1-AIT and 4-AIT respectively , while diastolic pressure decreased by 7.7 and 6.1 mmHg ( group difference , p = 0.84 ) . Both groups had a similar ∼5 % decrease in fasting glucose . Body fat , total cholesterol , LDL-cholesterol , and ox-LDL cholesterol only were significantly reduced after 4-AIT . Our data suggest that a single bout of AIT performed three times per week may be a time-efficient strategy to improve VO2max and reduce blood pressure and fasting glucose in previously inactive but otherwise healthy middle-aged individuals . The 1-AIT type of exercise training may be readily implemented as part of activities of daily living and could easily be translated into programs design ed to improve public health . Trial Registration Clinical Trials.gov", "As interleukin-6 ( IL-6 ) , its soluble receptor ( sIL-6R ) , and the IL-6/sIL-6R complex is transiently elevated in response to prolonged moderate-intensity exercise , this study investigated how these levels would be modulated by an acute bout of high-intensity intermittent ( HIIT ) exercise in comparison to continuous moderate-intensity exercise ( MOD ) . This study also investigated the expression of the differentially spliced sIL-6R ( DS-sIL-6R ) in response to exercise . Eleven healthy males completed two exercise trials matched for external work done ( 582 ± 82 kJ ) . During MOD , participants cycled at 61.8 (2.6)% VO2peak for 58.7 ( 1.9 ) min , while HIIT consisted of ten 4-min intervals cycling at 87.5 (3.4)% $ $ \\dot{V}{{\\hbox{O}}_{2{\\rm{peak } } } } $ $ separated by 2-min rest . Blood sample s were collected pre-exercise , post-exercise , and 1.5 , 6 , and 23 h post-exercise . Plasma IL-6 , sIL-6R , IL-6/sIL-6R complex , and DS-sIL-6R levels were measured by enzyme-linked immunosorbent assay . HIIT caused a significantly greater increase in IL-6 than MOD ( P = 0.018 ) . Both MOD and HIIT result ed in an increase in sIL-6R and IL-6/sIL-6R complex ( P < 0.001 ) , however , this was not significantly different between trials . Soluble IL-6R peaked at 6 h post-exercise in both trials . DS-sIL-6R increased significantly with exercise ( P = 0.02 ) , representing 0.49 % of the total sIL-6R increase . This investigation has demonstrated that the IL-6 response is greater after intermittent high-intensity exercise than comparable moderate-intensity exercise ; however , increased IL-6/sIL-6R complex nor sIL-6R was different between HIIT and MOD . The current study has shown for the first time that elevated sIL-6R after HIIT exercise is derived from both proteolytic cleavage and differential splicing", "AIM The purpose of this study was intended to evaluate the effects of a high intensity interval training ( HIIT ) program on the body composition , cardiac function and aerobic capacity in overweight young women . METHODS Sixty female university students ( aged 19 - 20 , BMI ≥25kg/m2 and percentage body fat ≥ 30 % ) were chosen and then r and omly assigned to each of the HIIT group , the moderate intensity continuous training ( MICT ) group and the non-training control group . The subjects in both the HIIT and MICT groups underwent exercise training five times per week for 12 weeks . In each of the training sessions , the HIIT group performed interval exercises at the individualized heart rate ( HR ) of 85 % of VO2max and separated by brief periods of low intensity activity ( HR at 50 % of VO2max ) , while the MICT group did continuous walking and /or jogging at the individualized HR of 50 % of VO2max . RESULTS Both of these exercise training programs produced significant improvements in the subjects ' body composition , left ventricular ejection fraction , heart rate at rest , maximal oxygen uptake and ventilatory threshold . However , the HIIT group achieved better results than those in the MICT group , as it was evaluated by the amount of the effect size . The control group did not achieve any change in all of the measured variables . CONCLUSION The tangible results achieved by our relatively large groups of homogeneous subjects have demonstrated that the HIIT program is an effective measure for the treatment of young women who are overweight", "Very high-intensity , low-volume , sprint interval training ( SIT ) increases muscle oxidative capacity and may increase maximal oxygen uptake ( $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ ) , but whether circulatory function is improved , and whether SIT is feasible in overweight/obese women is unknown . To examine the effects of SIT on $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ and circulatory function in sedentary , overweight/obese women . Twenty-eight women with BMI > 25 were r and omly assigned to SIT or control ( CON ) groups . One week before pre-testing , subjects were familarized to $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ testing and the workload that elicited 50 % $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ was calculated . Pre- and post-intervention , circulatory function was measured at 50 % of the pre-intervention $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ , and a GXT was performed to determine $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ . During the intervention , SIT training was given for 3 days/week for 4 weeks . Training consisted of 4–7 , 30-s sprints on a stationary cycle ( 5 % body mass as resistance ) with 4 min active recovery between sprints . CON maintained baseline physical activity . Post-intervention , heart rate ( HR ) was significantly lower and stroke volume ( SV ) significantly higher in SIT ( −8.1 and 11.4 % , respectively ; P < 0.05 ) during cycling at 50 % $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ ; changes in CON were not significant ( 3 and −4 % , respectively ) . Changes in cardiac output ( $ $ { \\dot{\\text{Q } } } $ $ ) and arteriovenous oxygen content difference [ ( a − v)O2 diff ] were not significantly different for SIT or CON . The increase in $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ by SIT was significantly greater than by CON ( 12 vs. −1 % ) . Changes by SIT and CON in HRmax ( −1 vs. −1 % ) were not significantly different . Four weeks of SIT improve circulatory function during submaximal exercise and increases $ $ { \\dot{V}\\text{O } } _ { { 2 { \\text{max } } } } $ $ in sedentary , overweight/obese women", "Objective : Exercise capacity strongly predicts survival and aerobic interval training ( AIT ) increases peak oxygen uptake effectively in cardiac patients . Usual care in Norway provides exercise training at the hospitals following myocardial infa rct ion ( MI ) , but the effect and actual intensity of these rehabilitation programmes are unknown . Design : R and omized controlled trial . Setting : Hospital cardiac rehabilitation . Subjects : One hundred and seven patients , recruited two to 12 weeks after MI , were r and omized to usual care rehabilitation or treadmill AIT . Interventions : Usual care aerobic group exercise training or treadmill AIT as 4 × 4 minutes intervals at 85–95 % of peak heart rate . Twice weekly exercise training for 12 weeks . Main measures : The primary outcome measure was peak oxygen uptake . Secondary outcome measures were endothelial function , blood markers of cardiovascular disease , quality of life , resting heart rate , and heart rate recovery . Results : Eighty-nine patients ( 74 men , 15 women , 57.4 ± 9.5 years ) completed the programme . Peak oxygen uptake increased more ( P = 0.002 ) after AIT ( from 31.6 ± 5.8 to 36.2 ± 8.6 mL·kg−1·min−1 , P < 0.001 ) than after usual care rehabilitation ( from 32.2 ± 6.7 to 34.7 ± 7.9 mL·kg−1·min−1 , P < 0.001 ) . The AIT group exercised with significantly higher intensity in the intervals compared to the highest intensity in the usual care group ( 87.3 ± 3.9 % versus 78.7 ± 7.2 % of peak heart rate , respectively , P < 0.001 ) . Both programmes increased endothelial function , serum adiponectin , and quality of life , and reduced serum ferritin and resting heart rate . High-density lipoprotein cholesterol increased only after AIT . Conclusions : AIT increased peak oxygen uptake more than the usual care rehabilitation provided to MI patients by Norwegian hospitals", "The purpose was to examine the effect of a 12-week exercise intervention on the cardiovascular and autonomic response of males to mental and physical challenge . Thirty four young overweight males were r and omly assigned to either an exercise or control group . The exercise group completed a high-intensity intermittent exercise ( HIIE ) program three times per week for 12weeks . Cardiovascular response to the Stroop task was determined before and after the intervention by assessing heart rate ( HR ) , stroke volume ( SV ) , arterial stiffness , baroreflex sensitivity ( BRS ) , and skeletal muscle blood flow . The exercise group improved their aerobic fitness levels by 17 % and reduced their body weight by 1.6 kg . Exercisers compared to controls experienced a significant reduction in HR ( p<0.001 ) and a significant increase in SV ( p<0.001 ) at rest and during Stroop and exercise . For exercisers , arterial stiffness significantly decreased at rest and during Stroop ( p<0.01 ) , whereas BRS was increased at rest and during Stroop ( p<0.01 ) . Forearm blood flow was significantly increased during the first two minutes of Stroop ( p<0.05 ) . HIIE induced significant cardiovascular and autonomic changes at rest and during mental and physical challenge after 12weeks of training", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "The purpose of this study was to identify potential gender discrepancies in adaptation to low-volume high-intensity interval training ( HIT ) . Active , young men ( n = 11 , age = 25.3 ± 5.5 years ) and women ( n = 9 , age = 25.2 ± 3.1 years ) matched for age , physical activity , and VO2max completed six sessions of HIT separated by 48 h over a 2–3 week period . Subjects completed four Wingate tests on days 1 and 2 , five on days 3 and 4 , and six on days 5 and 6 . A control group of five men and four women ( age = 22.8 ± 2.8 years ) completed all testing , but did not perform HIT . Changes in VO2max , oxygen ( O2 ) pulse , peak/mean power output , fatiguability , substrate oxidation , and voluntary force production of the knee flexors and extensors were examined pre- and post-training with repeated measures ANOVA , with gender and group as between-subjects variables . Results showed significant ( p < 0.05 ) improvements in VCO2max and peak/mean power output in response to HIT , as well as reduced respiratory exchange ratio and heart rate during submaximal exercise . The magnitude of change in VO2max ( 5.9 vs. 6.8 % ) , power output ( 10.4–14.9 % vs. 9.1–10.9 % ) , and substrate oxidation was similar ( p > 0.05 ) between men and women . Data show that adaptations to 6 days of low-volume HIT are similar in men and women matched for VO2max and physical activity", "Abstract We examined changes in muscle buffer capacity ( βmin vitro ) , $ $ \\ifmmode\\exp and after\\dot\\else\\exp and after\\.\\fi{V}{\\text{O}}_{{{\\text{2peak } } } } $ $ and the lactate threshold ( LT ) after 5 weeks of high-intensity interval training ( INT ) above the LT or moderate-intensity continuous training ( CON ) just below the LT . Prior to and immediately after training , 16 female subjects performed a grade d exercise test to determine $ $ \\ifmmode\\exp and after\\dot\\else\\exp and after\\.\\fi{V}{\\text{O}}_{{{\\text{2peak } } } } $ $ and the LT , followed 2 days later by a resting muscle biopsy from the vastus lateralis muscle to determine βmin vitro . Following baseline testing , the subjects were r and omly placed into the INT ( n=8 ) or CON training group ( n=8 ) . Subjects then performed 5 weeks of cycle training ( 3 days per week ) , performing either high-intensity INT ( 6–10 × 2 min at 120–140 % LT with 1 min rest ) or moderate-intensity CON ( 80–95 % LT ) training . Total training volume was matched between the two groups . After the training period , both groups had significant improvements in $ $ \\ifmmode\\exp and after\\dot\\else\\exp and after\\.\\fi{V}{\\text{O}}_{{{\\text{2peak } } } } $ $ ( 12–14 % ; P<0.05 ) and the LT ( 7–10 % ; P<0.05 ) , with no significant differences between groups . The INT group , however , had significantly greater improvements in βmin vitro ( 25 % ; 123±5–153±7 μmol H+·g muscle dm−1·pH−1 ; P<0.05 ) than the CON group ( 2 % ; 130±12–133±7 μmol H+·g muscle dm−1·pH−1 , P>0.05 ) . Our results show that when matched for training volume , high-intensity interval training above the LT results in similar improvements in $ $ \\ifmmode\\exp and after\\dot\\else\\exp and after\\.\\fi{V}{\\text{O}}_{{{\\text{2peak } } } } $ $ and the LT , but greater improvements in βmin vitro than moderate-intensity continuous training below the LT . This suggests that training intensity is an important determinant of changes to βmin vitro", "AIMS To compare the feasibility of high intensity interval exercise ( HI-IE ) versus moderate intensity continuous exercise ( MI-CE ) in patients with type 2 diabetes ( T2D ) , and to investigate the preliminary efficacy of HI-IE and MI-CE for improving glycated hemoglobin A1c ( HbA1c ) and body composition . METHODS Individuals with T2D were recruited and r and omly assigned to HI-IE and MI-CE . Exercise training was performed 5 days per week for 12 weeks . Recruitment , retention , adherence , feeling states and self-efficacy were analyzed for feasibility . Changes in HbA1c and percent body fat from baseline were investigated at 12 weeks to determine the preliminary efficacy . RESULTS Of 126 participants showing interest to join the study , 15 individuals were r and omized and completed the program . No participants dropped out from the study after enrollment . Adherence rates were high and did not differ between HI-IE and MI-CE ( p>0.05 ; > 97.2 % of the eligible exercise sessions for both groups ) . Feeling states and self-efficacy did not differ between the groups . Percent trunk fat decreased in both HI-IE and MI-CE ( p=0.007 and 0.085 , respectively ) . Total percent body fat , percent leg fat , and subcutaneous fat width were significantly reduced in both groups ( p<0.05 ) , whereas HbA1c did not change from baseline ( p>0.05 ) . The degree of improvement was similar between the interventions ( p>0.05 ) . CONCLUSION In individuals with T2D , implementing a 12-week structured HI-IE training can be as feasible as MI-CE training . Both interventions are equally effective in lowering total body fat but have little impact on HbA1c in relatively well controlled participants with T2D", "Objective : To determine the effects of a 15-week high-intensity intermittent exercise ( HIIE ) program on subcutaneous and trunk fat and insulin resistance of young women . Design and procedures : Subjects were r and omly assigned to one of the three groups : HIIE ( n=15 ) , steady-state exercise ( SSE ; n=15 ) or control ( CONT ; n=15 ) . HIIE and SSE groups underwent a 15-week exercise intervention . Subjects : Forty-five women with a mean BMI of 23.2±2.0 kg m−2 and age of 20.2±2.0 years . Results : Both exercise groups demonstrated a significant improvement ( P<0.05 ) in cardiovascular fitness . However , only the HIIE group had a significant reduction in total body mass ( TBM ) , fat mass ( FM ) , trunk fat and fasting plasma insulin levels . There was significant fat loss ( P<0.05 ) in legs compared to arms in the HIIE group only . Lean compared to overweight women lost less fat after HIIE . Decreases in leptin concentrations were negatively correlated with increases in VO2peak ( r=−0.57 , P<0.05 ) and positively correlated with decreases in TBM ( r=0.47 ; P<0.0001 ) . There was no significant change in adiponectin levels after training . Conclusions : HIIE three times per week for 15 weeks compared to the same frequency of SSE exercise was associated with significant reductions in total body fat , subcutaneous leg and trunk fat , and insulin resistance in young women", "PURPOSE The aim of this study was to compare the effects of time-efficient , low-volume interval exercises on cardiorespiratory capacity and left ventricular ( LV ) mass with traditional continuous exercise in sedentary adults . METHODS Forty-two healthy but sedentary male subjects ( age 26.5 ± 6.2 yr ) participated in an 8-wk , five times per week , supervised exercise intervention . They were r and omly assigned to one of three exercise protocol s : sprint interval training ( SIT , 5 min , 100 kcal ) , high-intensity interval aerobic training ( HIAT , 13 min , 180 kcal ) , and continuous aerobic training ( CAT , 40 min , 360 kcal ) . Cardiorespiratory capacity ( V˙O2max ) and LV mass ( 3T-MRI ) were measured preintervention and postintervention . RESULTS We observed significant ( P < 0.01 ) increases in V˙O2max in all three groups , and the effect of the HIAT was the greatest of the three ( SIT , 16.7 % ± 11.6 % ; HIAT , 22.5 % ± 12.2 % ; CAT , 10.0 % ± 8.9 % ; P = 0.01 ) . There were significant changes in LV mass , stroke volume ( SV ) , and resting HR in both the SIT ( LV mass , 6.5 % ± 8.3 % ; SV , 5.3 % ± 8.3 % ; HR , -7.3 % ± 11.1 % ; all P < 0.05 ) and HIAT ( LV mass , 8.0 % ± 8.3 % ; SV , 12.1 % ± 9.8 % ; HR , -12.7 % ± 12.2 % ; all P < 0.01 ) but not in the CAT ( LV mass , 2.5 % ± 10.1 % ; SV , 3.6 % ± 6.6 % ; HR , -2.2 % ± 13.3 % ; all P > 0.05 ) . CONCLUSIONS Our study revealed that V˙O2max improvement with the HIAT was greater than with the CAT despite the HIAT being performed with a far lower volume and in far less time than the CAT . This suggests that the HIAT has potential as a time-efficient training mode to improve V˙O2max in sedentary adults", "BACKGROUND Cardiac allograft vasculopathy ( CAV ) is a progressive form of atherosclerosis occurring in heart transplant ( HTx ) recipients , leading to increased morbidity and mortality . Given the atheroprotective effect of exercise on traditional atherosclerosis , we hypothesized that high-intensity interval training ( HIIT ) would reduce the progression of CAV among HTx recipients . METHODS Forty-three cardiac allograft recipients ( mean ± SD age 51 ± 16 years ; 67 % men ; time post-HTx 4.0 ± 2.2 years ) , all clinical ly stable and > 18 years old , were r and omized to either a HIIT group or control group ( st and ard care ) for 1 year . The effect of training on CAV progression was assessed by intravascular ultrasound ( IVUS ) . RESULTS IVUS analysis revealed a significantly smaller mean increase [ 95 % CI ] in atheroma volume ( PAV ) of 0.9 % [ 95 % CI -;0.3 % to 1.9 % ] in the HIIT group as compared with the control group , 2.5 % [ 1.6 % to 3.5 % ] ( p = 0.021 ) . Similarly , the mean increase in total atheroma volume ( TAV ) was 0.3 [ 0.0 to 0.6 ] mm(3)/mm in the HIT group vs 1.1 [ 0.6 to 1.7 ] mm(3)/mm in the control group ( p = 0.020 ) , and mean increase in maximal intimal thickness ( MIT ) was 0.02 - 0.01 to 0.04 ] mm in the HIIT group vs 0.05 [ 0.03 to 0.08 ] mm in the control group ( p = 0.054 ) . Qualitative plaque progression ( virtual histology parameters ) and inflammatory activity ( biomarkers ) were similar between the 2 groups during the study period . CONCLUSIONS HIIT among maintenance HTx recipients result ed in a significantly impaired rate of CAV progression . Future larger studies should address whether exercise rehabilitation strategies should be included in CAV management protocol", "Exercise training is an effective intervention for treating and preventing hypertension , but its effects on heart rate ( HR ) response to exercise and cardiorespiratory fitness ( CRF ) of non-hypertensive offspring of hypertensive parents ( FH+ ) has not been studied . We compared the effects of three times per week equal-volume high-intensity aerobic interval ( AIT ) and continuous moderate-intensity exercise ( CME ) on HR response to exercise and CRF of FH+ . Forty-four young FH+ women ( 25.0 ± 4.4 years ) r and omized to control ( CON ; n = 12 ) , AIT ( 80–90 % of VO2MAX ; n = 16 ) , or CME ( 50–60 % of VO2MAX ; n = 16 ) performed a grade d exercise test ( GXT ) before and after 16 weeks of follow-up to evaluate HR response to exercise and several parameters of CRF . Resting , maximal , and reserve HR did not change after the follow-up in all groups . HR recovery ( difference between HRMAX and HR at 1 minute of GXT recovery phase ) improved only after AIT ( 11.8 ± 4.9 vs. 20.6 ± 5.8 bpm , p < 0.01 ) . Both exercise programmes were effective for improving CRF parameters , but AIT was more effective than CME for improving oxygen consumption at the respiratory compensation point ( VO2RCP ; 22.1 % vs. 8.8 % , p = 0.008 ) and maximal effort ( VO2MAX ; 15.8 % vs. 8.0 % , p = 0.036 ) , as well as tolerance time ( TT ) to reach anaerobic threshold ( TTAT ; 62.0 vs. 37.7 , p = 0.048 ) , TTRCP ( 49.3 vs. 32.9 , p = 0.032 ) , and TTMAX ( 38.9 vs. 29.2 , p = 0.042 ) . Exercise intensity was an important factor in improving HR recovery and CRF of FH+women . These findings may have important implication s for design ing exercise-training programmes for the prevention of an inherited hypertensive disorder", "Sprint interval training ( SIT ) and traditional endurance training elicit similar physiological adaptations . From the perspective of metabolic function , superior glucose regulation is a common characteristic of endurance-trained adults . Accordingly , we have investigated the hypothesis that short-term SIT will increase insulin sensitivity in sedentary/recreationally active humans . Thirty one healthy adults were r and omly assigned to one of three conditions : ( 1 ) SIT ( n = 12 ) : six sessions of repeated ( 4 - 7 ) 30 s bouts of very high-intensity cycle ergometer exercise over 14 days ; ( 2 ) sedentary control ( n = 10 ) ; ( 3 ) single-bout SIT ( n = 9 ) : one session of 4 x 30 s cycle ergometer sprints . Insulin sensitivity was determined ( hyperinsulinaemic euglycaemic clamp ) prior to and 72 h following each intervention . Compared with baseline , and sedentary and single-bout controls , SIT increased insulin sensitivity ( glucose infusion rate : 6.3 + /- 0.6 vs. 8.0 + /- 0.8 mg kg(1 ) min(1 ) ; mean + /- s.e.m . ; P = 0.04 ) . In a separate study , we investigated the effect of SIT on the thermogenic response to beta-adrenergic receptor ( beta-AR ) stimulation , an important determinant of energy balance . Compared with baseline , and sedentary and single-bout control groups , SIT did not affect resting energy expenditure ( EE : ventilated hood technique ; 6274 + /- 226 vs. 6079 + /- 297 kJ day(1 ) ; P = 0.51 ) or the thermogenic response to isoproterenol ( 6 , 12 and 24 ng ( kg fat-free mass)(1 ) min(1 ) : % EE 11 + /- 2 , 14 + /- 3 , 23 + /- 2 vs. 11 + /- 1 , 16 + /- 2 , 25 + /- 3 ; P = 0.79 ) . Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose , insulin , adiponectin , pigment epithelial-derived factor , non-esterified fatty acids or noradrenaline ( all P > 0.05 ) . Sixteen minutes of high-intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to beta-AR stimulation", "Objective The effect of 12 weeks of high-intensity intermittent exercise ( HIIE ) on cardiac , vascular , and autonomic function of young males was examined . Methods Thirty-eight young men with a BMI of 28.7 ± 3.1 kg m−2 and age 24.9 ± 4.3 years were r and omly assigned to either an HIIE or control group . The exercise group underwent HIIE three times per week , 20 min per session , for 12 weeks . Aerobic power and a range of cardiac , vascular , and autonomic measures were recorded before and after the exercise intervention . Results The exercise , compared to the control group , recorded a significant reduction in heart rate accompanied by an increase in stroke volume . For the exercise group forearm vasodilatory capacity was significantly enhanced , P < 0.05 . Arterial stiffness , determined by pulse wave velocity and augmentation index , was also significantly improved , after the 12-week intervention . For the exercise group , heart period variability ( low- and high-frequency power ) and baroreceptor sensitivity were significantly increased . Conclusion High-intensity intermittent exercise induced significant cardiac , vascular , and autonomic improvements after 12 weeks of training", "This study aim ed to determine whether 2 wk of high-intensity intermittent training ( HIIT ) altered inflammatory status in plasma and adipose tissue in overweight and obese males . Twelve participants [ mean ( SD ) : age 23.7 ( 5.2 ) yr , body mass 91.0 ( 8.0 ) kg , body mass index 29.1 ( 3.1 ) kg/m2 ] undertook six HIIT sessions over 2 wk . Resting blood and subcutaneous abdominal adipose tissue sample s were collected and insulin sensitivity determined , pre- and posttraining . Inflammatory proteins were quantified in plasma and adipose tissue . There was a significant decrease in soluble interleukin-6 receptor ( sIL-6R ; P = 0.050 ) , monocyte chemotactic protein-1 ( MCP-1 , P = 0.047 ) , and adiponectin ( P = 0.041 ) in plasma posttraining . Plasma IL-6 , intercellular adhesion molecule-1 ( ICAM-1 ) , tumor necrosis factor-α ( TNF-α ) , IL-10 , and insulin sensitivity did not change . In adipose tissue , IL-6 significantly decreased ( P = 0.036 ) and IL-6R increased ( P = 0.037 ) , while adiponectin tended to decrease ( P = 0.056 ) , with no change in ICAM-1 posttraining . TNF-α , MCP-1 , and IL-10 were not detectable in adipose tissue . Adipose tissue homogenates were then resolved using one-dimensional gel electrophoresis , and major changes in the adipose tissue proteome , as a consequence of HIIT , were evaluated . This proteomic approach identified significant reductions in annexin A2 ( P = 0.046 ) and fatty acid synthase ( P = 0.016 ) as a response to HIIT . The present investigation suggests 2 wk of HIIT is sufficient to induce beneficial alterations in the resting inflammatory profile and adipose tissue proteome of an overweight and obese male cohort", "Kendall , KL , Smith , AE , Graef , JL , Fukuda , DH , Moon , JR , Beck , TW , Cramer , JT , and Stout , JR . Effects of four weeks of high-intensity interval training and creatine supplementation on critical power and anaerobic working capacity in college-aged men . J Strength Cond Res 23(6 ) : 1663 - 1669 , 2009-The critical power test provides 2 measures , critical power ( CP ) and anaerobic working capacity ( AWC ) . In theory , the CP measurement represents the maximal power output that can be maintained without fatigue , and AWC is an estimate of work capacity associated with muscle energy reserves . High-intensity interval training ( HIIT ) has been shown to be an effective training method for improving endurance performance , including & OV0312;O2PEAK . In addition , creatine ( Cr ) supplementation has been reported to improve AWC without training ; however , it has shown no effect on CP . The purpose of this study was to examine the effects of 4 weeks of HIIT with Cr supplementation on CP and AWC . Forty-two recreationally active men volunteered to participate in this study . Participants were r and omly assigned to 1 of 3 groups : Cr ( n = 16 ) , 10 g Cr + 10 g dextrose ; placebo ( PL , n = 16 ) , 20 g dextrose ; control ( CON , n = 10 ) , no treatment . Before and after supplementation , each participant performed a maximal oxygen consumption test ( & OV0312;O2PEAK ) on a cycle ergometer to establish peak power output ( PPO ) . Participants then completed a CP test involving 3 exercise bouts with the workloads set as a percentage of their PPO to determine CP and AWC . After a 2-week familiarization period of training and supplementing , PPO , CP , and AWC were remeasured before an additional 4 weeks of HIIT and supplementation were completed . Training consisted of 5 sets of 2-minute exercise bouts with 1 minute rest in between performed on the cycle ergometer , with intensities based on PPO . A significant improvement in CP was observed in the Cr group ( 6.72 % ± 2.54 % ) , whereas PL showed no significant change ( 3.87 % ± 2.30 % ) , and CON significantly decreased ( 6.27 % ± 2.38 % ) . Furthermore , no changes in AWC were observed in any of the groups after treatment . The current findings suggest that Cr supplementation may enhance the effects of intense interval endurance training on endurance performance changes", "Walter , AA , Smith , AE , Kendall , KL , Stout , JR , and Cramer , JT . Six weeks of high-intensity interval training with and without β-alanine supplementation for improving cardiovascular fitness in women . J Strength Cond Res 24(5 ) : 1199 - 1207 , 2010-The purpose of the present study was to evaluate the effects of cycle ergometry high-intensity interval training ( HIIT ) with and without β-alanine supplementation on maximal oxygen consumption rate ( & OV0312;o2peak ) , cycle ergometer workload at the ventilatory threshold ( VTW ) , and body composition . Forty-four women ( mean ± SD age = 21.8 ± 3.7 years ; height = 166.5 ± 6.6 cm ; body mass ( BM ) = 65.9 ± 10.8 kg ; & OV0312;o2peak = 31.5 ± 6.2 ml·kg−1·min−1 ) were r and omly assigned to 1 of 3 groups : β-alanine ( BA , n = 14 ) 1.5 g + 15 g dextrose powder ; placebo ( PL , n = 19 ) 16.5 g dextrose powder ; or control ( CON , n = 11 ) . Testing was conducted at baseline ( week 0 ) , after 3 weeks ( week 4 ) , and after 6 weeks ( week 8) . & OV0312;o2peak ( ml·kg−1·min−1 ) and VTW were measured with a metabolic cart during grade d exercise tests on a corival cycle ergometer , and body composition ( percent fat = % fat and fat-free mass = FFM ) were determined by air displacement plethysmography . High-intensity interval training was performed on a corival cycle ergometer 3 times per week with 5 2-minute work intervals and 1-minute passive recovery with undulating intensities ( 90 - 110 % of the workload recorded at & OV0312;o2peak ) during each training session . & OV0312;o2peak increased ( p ≤ 0.05 ) in the BA and PL groups at weeks 4 and 8 , but did not change ( p > 0.05 ) for the CON group . VTW increased ( p ≤ 0.05 ) for all groups at weeks 4 and 8 . Body mass increased ( p ≤ 0.05 ) only for the BA group at weeks 4 and 8 , whereas % fat decreased ( p ≤ 0.05 ) and FFM increased ( p ≤ 0.05 ) at weeks 4 and 8 for all groups ( BA , PL , and CON ) . Although it is unclear why β-alanine supplementation increased BM , there was no additive effects for increasing & OV0312;o2peak beyond the PL . Overall , these results suggested that HIIT may be an effective and time-efficient method of training to improve maximal oxygen uptake", "Background Increased aerobic exercise capacity appears to reduce both all-cause mortality and cardiovascular disease mortality . Physical exercise to improve peak oxygen uptake ( VO2peak ) is thus strongly recommended , however evidence regarding the most efficient training intensity for patients with coronary artery disease ( CAD ) is still lacking . The purpose of this r and omized study was therefore to assess the effects of high intensity aerobic interval exercise compared to moderate intensity exercise , representing the same total training load , for increasing VO2peak in stable CAD- patients . Methods Twenty-one stable CAD- patients were r and omized to supervised treadmill walking at either high intensity ( 80–90 % of VO2peak ) or moderate intensity ( 50–60 % of VO2peak ) three times a week for 10 weeks . Results After training VO2peak increased by 17.9 % ( P = 0.012 ) in the high intensity group and 7.9 % ( P = 0.038 ) in the moderate intensity group . The training-induced adaptation was significantly higher in the high intensity group ( P = 0.011 ) . Conclusions High intensity aerobic interval exercise is superior to moderate exercise for increasing VO2peak in stable CAD- patients . As VO2peak seems to reflect a continuum between health and cardiovascular disease and death , the present data may be useful in design ing effective training programmes for improved health in the future", "Background Heart transplant recipients have lower exercise capacity and impaired cardiac function compared with the normal population . High-intensity interval training ( HIIT ) improves exercise capacity and cardiac function in patients with heart failure and hypertension , but the effect on cardiac function in stable heart transplant recipients is not known . Thus , we investigated whether HIIT improved cardiac function and exercise capacity in stable heart transplant recipients by use of comprehensive rest- and exercise-echocardiography and cardiopulmonary exercise testing . Design and methods Fifty-two clinical ly stable heart transplant recipients were r and omised either to HIIT ( 4 × 4 minutes at 85–95 % of peak heart rate three times per week for eight weeks ) or to control . Three such eight-week periods were distributed throughout one year . Echocardiography ( rest and submaximal exercise ) and cardiopulmonary exercise testing were performed at baseline and follow-up . Results One year of HIIT increased VO2peak from 27.7 ± 5.5 at baseline to 30.9 ± 5.0 ml/kg/min at follow-up , while the control group remained unchanged ( 28.5 ± 7.0 vs. 28.0 ± 6.7 ml/kg per min , p < 0.001 for difference between the groups ) . Systolic and diastolic left ventricular functions at rest and during exercise were generally unchanged by HIIT . Conclusions Whereas HIIT is feasible in heart transplant recipients and effectively improves exercise capacity , it does not alter cardiac systolic and diastolic function significantly . Thus , the observed augmentation in exercise capacity is best explained by extra-cardiac adaptive mechanisms", "Objective . Current guidelines for treatment of intermittent claudication ( IC ) do not include a specific recommendation for the intensity of exercise therapy . Thus , the purpose of this study was to determine the relative effectiveness of high versus low intensity exercise for patients with IC , and further to study the effect of such training on blood flow to the legs during exercise . Design . The effect of eight weeks of supervised endurance training was examined in 16 patients with IC . The patients were r and omly assigned to training at intensities corresponding to either 60 % or 80 % of their peak oxygen consumption ( VO2peak ) , respectively . Results . VO2peak and time to exhaustion increased significantly ( 9 % and 16 % , respectively ) more in the high intensity group ( p<0.05 ) . Blood flow to the legs did not change after training in any of the groups . Conclusion . High intensity training gave larger improvements in VO2peak and time to exhaustion than low intensity training . As blood flow did not change after the exercise program , it is likely that the observed different increase of VO2peak was due to changed mitochondrial oxidative capacity and /or skeletal muscle diffusive capacity", "The effect of a 12-week high-intensity intermittent exercise ( HIIE ) intervention on the rating of perceived exertion ( RPE ) response of young males was examined . Participants ( N = 38 ; M BMI = 28.7 kg · m2 , SD = 3.1 ; M age = 24.9 yr . , SD = 4.3 ) were r and omly assigned to either an exercise or control group . The exercise group received HIIE three times per week , 20 min . per session , for 12 weeks . RPE was assessed before and after HIIE training and during pre- and post-maximal oxygen uptake ( VO2 max ) testing . After HIIE training , RPE was significantly higher in Weeks 11–12 compared to Weeks 1–2 . In contrast , heart rate was similar throughout training . Comparing post- to pre-VO2 max test , RPE was significantly lower in the exercise group , whereas for controls , RPE was similar . Aerobic power improved 15 % for the exercise group , with no significant change for controls . HIIE result ed in significant increases in RPE , whereas RPE during the VO2 max test was significantly decreased", "OBJECTIVE Exercise is a cornerstone of diabetes therapy in type 1 diabetes mellitus ( DMT1 ) patients . The type of exercise is important in determining the propensity to hypoglycemia . We assessed , by continuous glucose monitoring ( CGM ) , the glucose profiles during and in the following 20h after a session of two different types of exercise . RESEARCH DESIGN AND METHODS Eight male volunteers with well-controlled DMT1 were studied . They underwent 30min of both intermittent high-intensity exercise ( IHE ) and moderate-intensity exercise ( MOD ) in r and om order . Expired air was recorded during exercise , while metabolic and hormonal determinations were performed before and for 120 min after exercises . The CGM system and activity monitor were applied for the subsequent 20h . RESULTS Blood glucose level declined during both type of exercise . At 150 min following the start of exercise , plasma glucose content was slightly higher after IHE . No changes were observed in plasma insulin concentration . A significant increase of norepinephrine concentration was noticed during IHE . Between midnight and 6:00 a.m. the glucose levels were significantly lower after IHE than those observed after MOD ( area under the curve , 23.3 ± 3 vs. 16 ± 3 mg/dL/420 min [ P = 0.04 ] ; mean glycemia at 3 a.m. , 225 ± 31 vs. 147 ± 17 mg/dL [ P<0.05 ] ) . The number of hypoglycemic episodes after IHE was higher than that observed after MOD ( seven vs. two [ P<0.05 ] ) . CONCLUSIONS We demonstrate that ( 1 ) CGM is a useful approach in DMT1 patients who undergo an exercise program and ( 2 ) IHE is associated with delayed nocturnal hypoglycemia", "This aims of this study were to investigate the effects of carbohydrate availability during endurance training on the plasma interleukin (IL)-6 , IL-8 , and tumor necrosis factor (TNF)-alpha response to a subsequent acute bout of high-intensity interval exercise . Three groups of recreationally active males performed 6 weeks of high-intensity interval running . Groups 1 ( LOW+GLU ) and 2 ( LOW+PLA ) trained twice per day , 2 days per week , and consumed a 6.4 % glucose or placebo solution , respectively , before every second training session and at regular intervals throughout exercise . Group 3 ( NORM ) trained once per day , 4 days per week , and consumed no beverage during training . Each group performed 50 min of high-intensity interval running at the same absolute workloads before and after training . Muscle glycogen utilization in the gastrocnemius muscle during acute exercise was reduced ( p < 0.05 ) in all groups following training , although this was not affected by training condition . Plasma IL-6 concentration increased ( p < 0.05 ) after acute exercise in all groups before and after training . Furthermore , the magnitude of increase was reduced ( p < 0.05 ) following training . This training-induced attenuation in plasma IL-6 increase was similar among groups . Plasma IL-8 concentration increased ( p < 0.05 ) after acute exercise in all groups , although the magnitude of increase was not affected ( p > 0.05 ) by training . Acute exercise did not increase ( p > 0.05 ) plasma TNF-alpha when undertaken before or after training . Data demonstrate that the exercise-induced increase in plasma IL-6 concentration in response to customary exercise is attenuated by previous exercise training , and that this attenuation appears to occur independent of carbohydrate availability during training", "The aim of this study was to compare the effects of two high-intensity interval training ( HIT ) programmes on maximal oxygen uptake ( .VO(2max ) ) , the lactate threshold ( LT ) and 3000 m running performance in moderately trained male runners . .VO(2max ) , the running speed associated with .VO(2max ) ( V.VO(2max ) ) , the time for which V.VO(2max ) can be maintained ( T(max ) ) , the running speed at LT ( v(LT ) ) and 3000 m running time ( 3000 mTT ) were determined before and following three different training programmes performed for 10 weeks . Following the pre-test , 17 moderately trained male runners ( V O(2max)=51.6+/-2.7ml kg(-1)min(-1 ) ) were divided into training groups based on their 3000 mTT ( Group 1 , G(1 ) , N=6 , 8 x 60 % of T(max ) at V.VO(2max ) , 1:1 work : recovery ratio ; Group 2 , G(2 ) , N=6 , 12 x 30s at 130 % V.VO(2max ) , 4.5 min recovery ; control group , G(CON ) , N=5 , 60 min at 75 % V.VO(2max ) ) . G(1 ) and G(2 ) performed two HIT sessions and two 60 min recovery run sessions ( 75 % V.VO(2max ) ) each week . Control subjects performed four 60 min recovery run sessions ( 75 % V.VO(2max ) ) each week . In G(1 ) , significant improvements ( p<0.05 ) following HIT were found in .VO(2max ) ( + 9.1 % ) , V.VO(2max ) ( + 6.4 % ) , T(max ) ( 5 % ) , v(LT ) ( + 11.7 % ) and 3000 mTT ( -7.3 % ) . In G(2 ) , significant improvements ( p<0.05 ) following HIT were found in .VO(2max ) ( + 6.2 % ) , V.VO(2max)(+7.8 % ) , T(max ) ( + 32 % ) and 3000 mTT ( -3.4 % ) , but not in v(LT ) ( + 4.7 % ; p=0.07 ) . No significant changes in these variables were found in G(CON ) . The present study has shown that 3000 m running performance , .VO(2max ) , V.VO(2max ) , T(max ) and v(LT ) can be significantly enhanced using different HIT programmes in moderately trained runners , but that changes in performance and physiological variables may be more profound using prolonged HIT at intensities of V.VO(2max ) with interval duration s of 60 % T(max )", "BACKGROUND Exercise-based cardiac rehabilitation increases peak oxygen uptake ( peak VO₂ ) , which is an important predictor of mortality in cardiac patients . However , it remains unclear which exercise characteristics are most effective for improving peak VO₂ in coronary artery disease ( CAD ) patients . Proof of concept papers comparing Aerobic Interval Training ( AIT ) and Moderate Continuous Training ( MCT ) were conducted in small sample sizes and findings were inconsistent and heterogeneous . Therefore , we aim ed to compare the effects of AIT and Aerobic Continuous Training ( ACT ) on peak VO₂ , peripheral endothelial function , cardiovascular risk factors , quality of life and safety , in a large multicentre study . METHODS Two-hundred CAD patients ( LVEF > 40 % , 90 % men , mean age 58.4 ± 9.1 years ) were r and omized to a supervised 12-week cardiac rehabilitation programme of three weekly sessions of either AIT ( 90 - 95 % of peak heart rate ( HR ) ) or ACT ( 70 - 75 % of peak HR ) on a bicycle . Primary outcome was peak VO₂ ; secondary outcomes were peripheral endothelial function , cardiovascular risk factors , quality of life and safety . RESULTS Peak VO₂ ( ml/kg/min ) increased significantly in both groups ( AIT 22.7 ± 17.6 % versus ACT 20.3 ± 15.3 % ; p-time<0.001 ) . In addition , flow-mediated dilation ( AIT+34.1 % ( range -69.8 to 646 % ) versus ACT+7.14 % ( range -66.7 to 503 % ) ; p-time<0.001 ) quality of life and some other cardiovascular risk factors including resting diastolic blood pressure and HDL-C improved significantly after training . Improvements were equal for both training interventions . CONCLUSIONS Contrary to earlier smaller trials , we observed similar improvements in exercise capacity and peripheral endothelial function following AIT and ACT in a large population of CAD patients", "PURPOSE : We tested the hypothesis that higher-intensity interval training ( HIIT ) could be deployed into a st and ard cardiac rehabilitation ( CR ) setting and would result in a greater increase in cardiorespiratory fitness ( ie , peak oxygen uptake , ) versus moderate-intensity continuous training ( MCT ) . METHODS : Thirty-nine patients participating in a st and ard phase 2 CR program were r and omized to HIIT or MCT ; 15 patients and 13 patients in the HIIT and MCT groups , respectively , completed CR and baseline and followup cardiopulmonary exercise testing . RESULTS : No patients in either study group experienced an event that required hospitalization during or within 3 hours after exercise . The changes in resting heart rate and blood pressure at followup testing were similar for both HIIT and MCT . at ventilatory-derived anaerobic threshold increased more ( P < .05 ) with HIIT ( 3.0 ± 2.8 mL·kg·−1min−1 ) versus MCT ( 0.7 ± 2.2 mL·kg·−1min−1 ) . During followup testing , submaximal heart rate at the end of stage 2 of the exercise test was significantly lower within both the HIIT and MCT groups , with no difference noted between groups . Peak V˙o2 improved more after CR in patients in HIIT versus MCT ( 3.6 ± 3.1 mL·kg.−1·min−1 vs 1.7 ± 1.7 mL·kg.−1·min−1 ; P < .05 ) . CONCLUSIONS : Among patients with stable coronary heart disease on evidence -based therapy , HIIT was successfully integrated into a st and ard CR setting and , when compared to MCT , result ed in greater improvement in peak exercise capacity and submaximal endurance", "Sprint interval training ( SIT ) has been proposed as a time efficient alternative to endurance training ( ET ) for increasing skeletal muscle oxidative capacity and improving certain cardiovascular functions . In this study we sought to make the first comparisons of the structural and endothelial enzymatic changes in skeletal muscle microvessels in response to ET and SIT . Sixteen young sedentary males ( age 21 ± SEM 0.7 years , BMI 23.8 ± SEM 0.7 kg m(-2 ) ) were r and omly assigned to 6 weeks of ET ( 40 - 60 min cycling at ∼65 % , 5 times per week ) or SIT ( 4 - 6 Wingate tests , 3 times per week ) . Muscle biopsies were taken from the m. vastus lateralis before and following 60 min cycling at 65 % to measure muscle microvascular endothelial eNOS content , eNOS serine(1177 ) phosphorylation , NOX2 content and capillarisation using quantitative immunofluorescence microscopy . Whole body insulin sensitivity , arterial stiffness and blood pressure were also assessed . ET and SIT increased skeletal muscle microvascular eNOS content ( ET 14 % ; P < 0.05 , SIT 36 % ; P < 0.05 ) , with a significantly greater increase observed following SIT ( P < 0.05 ) . Sixty minutes of moderate intensity exercise increased eNOS ser(1177 ) phosphorylation in all instances ( P < 0.05 ) , but basal and post-exercise eNOS ser(1177 ) phosphorylation was lower following both training modes . All microscopy measures of skeletal muscle capillarisation ( P < 0.05 ) were increased with SIT or ET , while neither endothelial nor sarcolemmal NOX2 was changed . Both training modes reduced aortic stiffness and increased whole body insulin sensitivity ( P < 0.05 ) . In conclusion , in sedentary males SIT and ET are effective in improving muscle microvascular density and eNOS protein content", "PURPOSE The effects of short-term high-intensity interval training ( HIT ) on cardiac autonomic function are unclear . The present study assessed cardiac autonomic adaptations to short-term HIT in comparison with aerobic endurance training ( AET ) . METHODS Twenty-six healthy middle-age sedentary men were r and omized into HIT ( n = 13 , 4 - 6 × 30 s of all-out cycling efforts with 4-min recovery ) and AET ( n = 13 , 40 - 60 min at 60 % of peak workload ) groups , performing six sessions within 2 wk . The participants underwent a 24-h ECG recording before and after the intervention and , additionally , recorded R-R interval data in supine position ( 5 min ) at home every morning during the intervention . Mean HR and low-frequency ( LF ) and high-frequency ( HF ) power of R-R interval oscillation were analyzed from these recordings . RESULTS Peak oxygen consumption ( V˙O2peak ) increased in both groups ( P < 0.001 ) . Compared with AET ( n = 11 ) , HIT ( n = 13 ) increased 24-h LF power ( P = 0.024 ) , tended to increase 24-h HF power ( P = 0.068 ) , and increased daytime HF power ( P = 0.038 ) . In home-based measurements , supine HF power decreased on the days after HIT ( P = 0.006 , n = 12 ) but not AET ( P = 0.80 , n = 9 ) session . The acute response of HF power to HIT session did not change during the intervention . CONCLUSIONS In conclusion , HIT was more effective short-term strategy to increase R-R interval variability than aerobic training , most probably by inducing larger increases in cardiac vagal activity . The acute autonomic responses to the single HIT session were not modified by short-term training", "To test the hypothesis that high-intensity swim training improves cardiovascular health status in sedentary premenopausal women with mild hypertension , sixty-two women were r and omized into high-intensity ( n = 21 ; HIT ) , moderate-intensity ( n = 21 ; MOD ) , and control groups ( n = 20 ; CON ) . HIT performed 6 - 10 × 30 s all-out swimming interspersed by 2 min recovery and MOD swam continuously for 1 h at moderate intensity for a 15-week period completing in total 44 ± 1 and 43 ± 1 sessions , respectively . In CON , all measured variables were similar before and after the intervention period . Systolic BP decreased ( P < 0.05 ) by 6 ± 1 and 4 ± 1 mmHg in HIT and MOD ; respectively . Resting heart rate declined ( P < 0.05 ) by 5 ± 1 bpm both in HIT and MOD , fat mass decreased ( P < 0.05 ) by 1.1 ± 0.2 and 2.2 ± 0.3 kg , respectively , while the blood lipid profile was unaltered . In HIT and MOD , performance improved ( P < 0.05 ) for a maximal 10 min swim ( 13 ± 3 % and 22 ± 3 % ) , interval swimming ( 23 ± 3 % and 8 ± 3 % ) , and Yo-Yo IE1 running performance ( 58 ± 5 % and 45 ± 4 % ) . In conclusion , high-intensity intermittent swimming is an effective training strategy to improve cardiovascular health and physical performance in sedentary women with mild hypertension . Adaptations are similar with high- and moderate-intensity training , despite markedly less total time spent and distance covered in the high-intensity group" ]

[ "10494936", "3899021", "11030854", "15054168", "9314792", "10224546", "10589320" ]

[ "Mechanical failure of the latex condom in a cohort of women at high STD risk.", "Changes in sexual attitudes and lifestyles in Britain through the life course and over time: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal)", "Economic evaluation of Safer Choices: a school-based human immunodeficiency virus, other sexually transmitted diseases, and pregnancy prevention program.", "A community level syphilis prevention programme: outcome data from a controlled trial", "Condom availability in New York City public high schools: relationships to condom use and sexual behavior.", "Evaluation of the efficacy of a polyurethane condom: results from a randomized, controlled clinical trial.", "Encouraging use of coupons to stimulate condom purchase." ]

[ "BACKGROUND AND OBJECTIVES Mechanical failure may reduce the efficacy of condoms . Little is known about frequency and determinants of condom failure in groups at high risk of sexually transmitted diseases ( STD ) . GOAL To measure condom breakage and slippage rates and evaluate potential determinants of failure among women attending a public STD clinic . STUDY DESIGN Women attending an STD clinic participated in a 6-month prospect i ve study of barrier contraception for the prevention of STD . They completed sexual diaries that were review ed at monthly follow-up visits . No data were collected from the male partners . Baseline characteristics of the participants and time-dependent behaviors were evaluated as potential determinants of condom failure . RESULTS Of 21,852 condoms used by 892 women , 500 broke during intercourse ( 2.3 % ) and 290 slipped ( 1.3 % ) . Breakage was more common among young , black , single nulliparae who engaged in high-risk behavior . Slippage was more common among married women with children . Failure rates decreased with condom use , with coital frequency , and with use of spermicides . CONCLUSION User characteristics and experience are determinants of breakage and slippage , which are often regarded only as the effect of product design flaws . Attention to modifiable determinants of failure may improve user counseling and product labeling", "Summary Background Sexual behaviour and relationships are key components of wellbeing and are affected by social norms , attitudes , and health . We present data on sexual behaviours and attitudes in Britain ( Engl and , Scotl and , and Wales ) from the three National Surveys of Sexual Attitudes and Lifestyles ( Natsal ) . Methods We used a multistage , clustered , and stratified probability sample design . Within each of the 1727 sample d postcode sectors for Natsal-3 , 30 or 36 addresses were r and omly selected and then assigned to interviewers . To over sample individuals aged 16–34 years , we r and omly allocated addresses to either the core sample ( in which individuals aged 16–74 years were eligible ) or the boost sample ( in which only individuals aged 16–34 years were eligible ) . Interviewers visited all sample d addresses between Sept 6 , 2010 , and Aug 31 , 2012 , and r and omly selected one eligible individual from each household to be invited to participate . Participants completed the survey in their own homes through computer-assisted face-to-face interviews and self-interview . We analysed data from this survey , weighted to account for unequal selection probabilities and non-response to correct for differences in sex , age group , and region according to 2011 Census figures . We then compared data from participants aged 16–44 years from Natsal-1 ( 1990–91 ) , Natsal-2 ( 1999–2001 ) , and Natsal-3 . Findings Interviews were completed with 15 162 participants ( 6293 men , 8869 women ) from 26 274 eligible addresses ( 57·7 % ) . 82·1 % ( 95 % CI 81·0–83·1 % ) of men and 77·7 % ( 76·7–78·7 % ) of women reported at least one sexual partner of the opposite sex in the past year . The proportion generally decreased with age , as did the range of sexual practice s with partners of the opposite sex , especially in women . The increased sexual activity and diversity reported in Natsal-2 in individuals aged 16–44 years when compared with Natsal-1 has generally been sustained in Natsal-3 , but in men has generally not risen further . However , in women , the number of male sexual partners over the lifetime ( age-adjusted odds ratio 1·18 , 95 % CI 1·08–1·28 ) , proportion reporting ever having had a sexual experience with genital contact with another woman ( 1·69 , 1·43–2·00 ) , and proportion reporting at least one female sexual partner in the past 5 years ( 2·00 , 1·59–2·51 ) increased in Natsal-3 compared with Natsal-2 . While reported number of occasions of heterosexual intercourse in the past 4 weeks had reduced since Natsal-2 , we recorded an expansion of heterosexual repertoires — particularly in oral and anal sex — over time . Acceptance of same-sex partnerships and intolerance of non-exclusivity in marriage increased in men and women in Natsal-3 . Interpretation Sexual lifestyles in Britain have changed substantially in the past 60 years , with changes in behaviour seeming greater in women than men . The continuation of sexual activity into later life — albeit reduced in range and frequency — emphasises that attention to sexual health and wellbeing is needed throughout the life course . Funding Grants from the UK Medical Research Council and the Wellcome Trust , with support from the Economic and Social Research Council and the Department of Health", "OBJECTIVE To evaluate the cost-effectiveness and cost benefit of Safer Choices , a school-based human immunodeficiency virus , other sexually transmitted diseases , and unintended pregnancy prevention intervention for high school students . METHODS The baseline cost-effectiveness and cost benefit were derived in 4 steps : ( 1 ) estimation of intervention costs ; ( 2 ) adaptation of the Bernoulli model to translate increases in condom use into cases of human immunodeficiency virus and other sexually transmitted diseases averted , and development of a model to translate increases in contraceptive use into cases of pregnancy averted ; ( 3 ) translation of cases averted into medical costs and social costs averted ; and ( 4 ) calculation of the net benefit of the program . Multivariable sensitivity analysis was performed to determine the robustness of the base-case results . RESULTS Under base-case assumptions , at an intervention cost of $ 105,243 , Safer Choices achieved a 15 % increase in condom use and an 11 % increase in contraceptive use within 1 year among 345 sexually active students . An estimated 0.12 cases of human immunodeficiency virus , 24.37 cases of chlamydia , 2.77 cases of gonorrhea , 5.86 cases of pelvic inflammatory disease , and 18.5 pregnancies were prevented . For every dollar invested in the program , $ 2.65 in total medical and social costs were saved . Results of most of the scenarios remained cost saving under a wide range of model variable estimates . CONCLUSIONS The Safer Choices program is cost-effective and cost saving in most scenarios considered . School-based prevention programs of this type warrant careful consideration by policy makers and program planners . Program cost data should be routinely collected in evaluations of adolescent prevention programs", "Objectives : This study investigated the impact of a small media campaign to reduce syphilis through testing , treatment , and condom use in two urban predominantly African-American communities with high syphilis rates . Methods : Data were collected from intervention and comparison zip codes using cross sectional street intercept interviews at baseline and 2 years later ( n = 1630 ) following a small media syphilis prevention campaign with role model story posters , billboards , and other merch and ise . Community businesses and a community based organisation served as partners , distributing condoms and small media . Results : Comparing intervention with comparison zip codes , there were significant increases in condom use in last sexual act , and some aspects of knowledge of syphilis . However , there was significant cross contamination of media impact , with respondents in the comparison zip code seeing an average of two media items compared with three in the intervention zip code . Media exposure was associated with significant increases in knowledge of syphilis , testing , and condom use . Conclusions : Targeted community based small media interventions using community partners for distribution are effective in increasing syphilis knowledge , testing , and condom use", "OBJECTIVES This study examines the impact of the condom availability program in New York City public high schools by comparing rates of sexual activity and condom use for New York students and similar students in Chicago . METHODS A total of 7119 students from 12 r and omly selected New York schools and 5738 students from 10 Chicago schools participated in a cross-sectional survey . RESULTS New York students , compared with Chicago students , reported equal rates of sexual activity but higher rates of condom use at last intercourse ( odds ratio [ OR ] = 1.36 ) . For higher-risk students ( those with three or more sexual partners in the past 6 months ) , condom use was greater in New York ( OR = 1.85 ) than in Chicago . CONCLUSIONS Condom availability has a modest but significant effect on condom use and does not increase rates of sexual activity . These findings suggest that school-based condom availability can lower the risk of HIV and other sexually transmitted diseases for urban teenagers in the United States", "CONTEXT Condoms made of latex are not comfortable or appropriate for all consumers . Polyurethane condoms may provide a needed alternative . METHODS In a double-masked study , 805 monogamous couples were r and omized to use either the polyurethane condom or the latex condom for six months . Couples recorded the frequency of intercourse , of condom use and of breakage and slippage throughout the trial in coital diaries and in detailed reports on the first five uses . Breakage and slippage rates were determined , and typical-use and consistent-use pregnancy rates were calculated using life-table analysis , adjusted for use of emergency contraception . RESULTS The six-month pregnancy rate during typical use ( adjusted for use of emergency contraception ) was 4.8 % for the polyurethane condom and 6.3 % for the latex condom . Similarly adjusted pregnancy rates during consistent use over six completed menstrual cycles--2.4 % for the polyurethane condom and 1.1 % for the latex condom -- did not differ significantly . Clinical failure rates ( including breakage and slippage occurring during either intercourse or withdrawal ) were 8.5 % for the polyurethane condom and 1.6 % for the latex condom . In general , male participants were more satisfied with the latex condom , and users of latex were significantly less likely to drop out of the study for condom-related reasons than were users of polyurethane . CONCLUSIONS Although polyurethane and latex condoms provide equivalent levels of contraceptive protection , the polyurethane condom 's higher frequency of breakage and slippage suggests that this condom may confer less protection from sexually transmitted infections than does the latex condom", "OBJECTIVES This study examined the feasibility of using high-value coupons to induce condom purchase and evaluated execution factors that can influence the effectiveness of this form of promotion . METHODS Two levels of coupon discount value ( 10 % off and 75 % off ) were used to promote condom purchase among young adults . Coupons were distributed according to a widespread strategy or a more focused in-store disbursement method . RESULTS Redemption of coupons distributed through the widespread disbursement strategy was negligible . In contrast , coupons from the in-store distribution method , particularly the higher value coupon , result ed in a high redemption rate . CONCLUSIONS This research provides strong evidence that discount coupons , particularly high-value ones distributed at the purchase location , can be used successfully as a condom promotional incentive" ]

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[ "Retarding progression of chronic renal disease: the neglected issue of residual proteinuria.", "Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?", "A Double-Blind, Randomized, Placebo-Controlled Clinical Trial on Benfotiamine Treatment in Patients With Diabetic Nephropathy", "Ethnicity and race influence the folate status response to controlled folate intakes in young women.", "Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.", "Effect of short-term folate and vitamin B supplementation on blood homocysteine level and carotid artery wall thickness in chronic hemodialysis patients.", "Effects of Pyridoxamine in Combined Phase 2 Studies of Patients with Type 1 and Type 2 Diabetes and Overt Nephropathy", "Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD.", "Reduction of microalbuminuria by using losartan in normotensive patients with type 2 diabetes mellitus: A randomized controlled trial.", "Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial.", "The effect of vitamin B12 on total plasma homocysteine concentration in folate-replete hemodialysis patients.", "Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.", "Urinary albumin excretion rate and glomerular filtration rate in the prediction of diabetic nephropathy; a long-term follow-up study of childhood onset type-1 diabetic patients.", "[Treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients with vitamin B].", "Homocysteine-Lowering Therapy and Stroke Risk, Severity, and Disability: Additional Findings From the HOPE 2 Trial", "Pyridorin in type 2 diabetic nephropathy.", "No effect of folic acid on markers of endothelial dysfunction or inflammation in patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia.", "Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study", "Smoking and progression of diabetic nephropathy in type 1 diabetes.", "Pharmacological Dose of Vitamin B12 Is as Effective as Low-Dose Folinic Acid in Correcting Hyperhomocysteinemia of Hemodialysis Patients", "Effect of high-dose thiamine and pyridoxine on advanced glycation end products and other oxidative stress markers in hemodialysis patients: a randomized placebo-controlled study.", "The influence of vitamin B6 supplementation on the bone marrow morphology in patients on regular haemodialysis treatment. A double-blind study.", "[Hyperhomocysteinemia and alternate vitamin supplementation].", "Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism", "High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study", "Homocysteine lowering with folic acid and B vitamins in vascular disease.", "Glomerular filtration rate, urinary albumin excretion rate, and blood pressure changes in normoalbuminuric normotensive type 1 diabetic patients: an 8-year follow-up study.", "Effects of folic acid and vitamin B complex on serum C-reactive protein and albumin levels in stable hemodialysis patients*", "Smoking Is Associated With Progression of Diabetic Nephropathy", "Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients.", "Comparative study of response to treatment with supraphysiologic doses of B-vitamins in hyperhomocysteinemic hemodialysis patients.", "The course of kidney function in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy", "Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin.", "Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study", "Effects of folic acid before and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotypes.", "The Effect of Oral Niacinamide on Plasma Phosphorus Levels in Peritoneal Dialysis Patients", "Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study", "The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.", "High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfotiamine", "Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease--results of the renal Hope-2 study.", "Vitamin B6 Therapy Does Not Improve Hematocrit in Hemodialysis Patients Supplemented with Iron and Erythropoietin", "Homocysteine-lowering therapy and carotid intima-media thickness in renal transplant recipients.", "Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients", "Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects.", "Hyperhomocysteinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins.", "Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia.", "Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64).", "Chicken and Fish Diet Reduces Glomerular Hyperfiltration in IDDM Patients", "A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients.", "Alteration of thiamine pharmacokinetics by end-stage renal disease (ESRD).", "High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis patients.", "Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients.", "Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia.", "Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.", "B Vitamins and the Risk of Total Mortality and Cardiovascular Disease in End-Stage Renal Disease: Results of a Randomized Controlled Trial" ]

[ "BACKGROUND Findings that early changes in proteinuria independently predict long-term glomular filtration rate ( GFR ) decline ( Delta GFR ) would highlight proteinuria as a major determinant of progression in chronic renal disease . METHODS We investigated whether percent changes ( 3 months vs. baseline ) in proteinuria ( adjusted for concomitant changes in GFR ) and residual proteinuria at 3 months , predicted Delta GFR [ over a median ( IQ range ) follow up of 31.3 ( 24.5 to 50.3 ) months ] in 273 patients with proteinuric chronic nephropathies enrolled in the Ramipril Efficacy In Nephropathy ( REIN ) study . RESULTS Short-term changes and residual proteinuria ( r = -0.23 , P = 0.0001 for both ) significantly correlated with Delta GFR and , at multivariate analyses , independently predicted Delta GFR ( beta = -0.23 , P = 0.0002 ; beta = -0.21 , P = 0.0004 , respectively ) . For comparable levels of residual proteinuria , patients with greater short-term reduction had slower Delta GFR ( -0.28 + /- 0.04 mL/min/1.73 m2/ vs. -0.53 + /- 0.07 mL/min/1.73 m2/month , P = 0.04 ) . On ramipril and conventional treatment , specular short-term changes in proteinuria ( -18.2 + /- 3.5 % vs. 24.2 + /- 6.7 % , P < 0.0001 , respectively ) were associated with significantly different Delta GFRs . However , similar changes in proteinuria result ed in a difference in Delta GFR ( ramipril , 0.39 + /- 0.07 mL/min/1.73 m2/month ; conventional therapy , 0.74 + /- 0.11 mL/min/1.73 m2/month ; P < 0.01 ) that was sevenfold higher ( 0.35 vs. 0.05 mL/min/1.73 m2/month ) in patients with basal proteinuria > or =3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours ( ramipril , 0.25 + /- 0.06 mL/min/1.73 m2/month ; conventional therapy , 0.30 + /- 0.07 mL/min/1.73 m2/month ; P = NS ) . CONCLUSION Regardless of blood pressure control and treatment r and omization , short-term changes in proteinuria and residual proteinuria reliably predict long-term disease progression . Reducing proteinuria is renoprotective , particularly in nephrotic patients . As for arterial hypertension , proteinuria should be a specific target for renoprotective treatment", "BACKGROUND Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction . Although folic acid reduces hyperhomocysteinemia , the effect on adverse vascular events is unknown . We hypothesized that in patients with chronic renal failure , a condition associated with both hyperhomocysteinemia and atherosclerosis , treatment with folic acid would improve endothelial function . METHODS AND RESULTS In a prospect i ve , double-blind protocol , 100 patients ( mean age 62 years , 67 men ) with predialysis chronic renal failure were r and omized to 5 mg folic acid or placebo daily for 12 weeks . Endothelial function was assessed by measuring ( 1 ) endothelium-dependent dilation of the brachial artery , ( 2 ) combined serum nitrite/nitrate concentrations , and ( 3 ) plasma von Willebr and factor concentration . Baseline characteristics of the 2 groups were similar . At the end of the study , both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [ mean ( 95 % CI ) 39.0 ( 29.8 to 51.0 ) versus 7.7 ( 6.6 to 8.9 ) microg/L and 739 ( 613 to 891 ) versus 220 ( 184 to 262 ) microg/L , respectively ; both P<0.001 ] . Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [ 15.1 ( 14.1 to 16.2 ) versus 20.1 ( 18.2 to 22.2 ) micromol/L ; P<0.001 ] , there were no significant differences in endothelium-dependent dilation , combined serum nitrite/nitrate concentrations , or plasma von Willebr and factor concentration between the 2 groups . CONCLUSIONS High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure . This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia", "OBJECTIVE To investigate the effect of benfotiamine on urinary albumin excretion ( UAE ) and the tubular damage marker kidney injury molecule-1 ( KIM-1 ) in patients with type 2 diabetes and nephropathy . RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and UAE equivalent to 15–300 mg/24 h , despite ACE inhibitors ( ACE-Is ) or angiotensin receptor blockers ( ARBs ) , were r and omly assigned to 12 weeks of benfotiamine ( 900 mg/day ) ( n = 39 ) or placebo ( n = 43 ) . RESULTS Compared with placebo , benfotiamine treatment result ed in significant improvement of thiamine status ( P < 0.001 ) . Benfotiamine treatment did not significantly decrease 24-h UAE or 24-h KIM-1 excretion . CONCLUSIONS In patients with type 2 diabetes and nephropathy , high-dose benfotiamine treatment for 12 weeks in addition to ACE-Is or ARBs did not reduce UAE or KIM-1 excretion , despite improvement of thiamine status", "Population -based studies report differences in folate status indicators among Mexican American ( MA ) , African American ( AA ) and Caucasian ( CA ) women . It is unclear , however , whether these differences are due to variations in dietary folate intake . The present study was design ed to investigate the influence of ethnicity/race on folate status parameters in MA , AA , and CA women ( 18 - 45 y ; n = 14 in each group ) under conditions of strictly controlled folate intake . In addition , the adequacy of the 1998 folate U.S. recommended dietary allowance ( RDA ) , 400 micro g/d as dietary folate equivalents ( DFE ) , for non-Caucasian women was assessed . Subjects ( n = 42 ) with the methylenetetrahydrofolate reductase 677 CC genotype consumed a low-folate diet ( 135 micro g DFE/d ) for 7 wk followed by repletion with 400 ( 7 MA , 7 AA , 7 CA ) or 800 micro g DFE/d ( 7 MA , 7 AA , 7 CA ) for 7 wk . AA women had lower ( P < /= 0.05 ) blood folate concentrations and excreted less ( P < /= 0.05 ) urinary folate throughout folate depletion and repletion with 400 and /or 800 micro g DFE/d compared with MA and /or CA women . MA women had lower ( P < /= 0.05 ) plasma total homocysteine ( tHcy ) throughout folate depletion and during repletion with 400 micro g DFE/d relative to the other ethnic/racial groups . Repletion with the 1998 folate U.S. RDA led to normal blood folate and plasma tHcy for all 3 ethnic/racial groups . Collectively , these data demonstrate that ethnicity/race is an important determinant of folate status under conditions of strictly controlled dietary folate intake and support the adequacy of the 1998 folate U.S. RDA for the 3 largest ethnic/racial groups in the United States", "BACKGROUND In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose , i.v . folinic acid combined with high-dose i.v . pyridoxine was highly effective in correcting plasma total homocysteine ( tHcy ) concentrations in haemodialysis patients . To confirm these findings , we conducted a r and omized , controlled trial aim ed at evaluating whether i.v . or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid . METHODS In a 6-month prospect i ve , r and omized , controlled trial , 60 chronic haemodialysis patients , matched for age , gender , dialysis duration , and average screening pre-treatment-fasting tHcy levels , were given either 50 mg/week of i.v . calcium folinate ( group 1 ) , 50 mg/week of oral calcium folinate ( group 2 ) , or 45 mg/week oral folic acid ( group 3 ) . All 60 patients also received 750 mg/week of i.v . vitamin B6 and 3 mg/week of oral vitamin B12 . RESULTS Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months ( 16.6+/-3.5 , 18.3+/-4 , and 19.1+/-3.1 , in groups 1 , 2 , and 3 , respectively , P = NS ) . Mean percentage reduction at 6 months was also similar in the three treatment groups ( 46 , 43 , and 42 % in groups 1 , 2 , and 3 , respectively , P = NS ) . CONCLUSIONS These findings show that the tHcy-lowering effects of high-dose i.v . folinic acid , oral folinic acid , or oral folic acid were comparable , suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism . Furthermore , they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients", "OBJECTIVE Hyperhomocysteinemia is an independent risk factor for atherosclerotic vascular disease in chronic hemodialysis patients . This stratified r and omized controlled trial was design ed to measure the effect of high dose oral vitamin B6 , vitamin B12 , and folic acid on homocysteine levels , and to evaluate the effect on atherosclerosis as measured by Intima-Media Thickness ( IMT ) of carotid arteries . MATERIAL AND METHOD Fifty-four chronic hemodialysis patients with hyperhomocysteinemia were r and omized to receive oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 daily ( treatment group ) or oral 5 mg folic acid alone ( control group ) for 6 months . Homocysteine level and IMT were measured in both groups . RESULTS At 6 months , homocysteine levels in the treatment group were significantly reduced from 27.94 + /- 8.54 to 22.71 + /- 3.68 mmol/l ( p = 0.009 ) and were not significantly increased from 26.81 + /- 7.10 to 30.82 + /- 8.76 mmol/l in control group ( p = 0.08 ) . Mean difference between both groups was statistically significant ( p = 0.002 ) . There was no significant difference of IMT of carotid arteries , however , a tendency that the treatment group would have less thickness was observed ( 0.69 + /- 0.29 mm and 0.62 + /- 0.16 mm , p = 0.99 ) . CONCLUSION Treatment of hyperhomocysteinemia in chronic hemodialysis patients with daily oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 for 6 months decreases homocysteine levels and tends to reduce IMT of carotid arteries . A long term study for the prevention of atherosclerosis is warranted", "Background / Aims : Treatments of diabetic nephropathy ( DN ) delay the onset of end-stage renal disease . We report the results of safety/tolerability studies in patients with overt nephropathy and type 1/type 2 diabetes treated with pyridoxamine , a broad inhibitor of advanced glycation . Methods : The two 24-week studies were multicenter Phase 2 trials in patients under st and ard-of-care . In PYR-206 , patients were r and omized 1:1 and had baseline serum creatinine ( bSCr ) ≤2.0 mg/dl . In PYR-205/207 , r and omization was 2:1 and bSCr was ≤2.0 for PYR-205 and ≧2.0 but ≤3.5 mg/dl for PYR-207 . Treated patients ( 122 active , 90 placebo ) received 50 mg pyridoxamine twice daily in PYR-206 ; PYR-205/207 patients were escalated to 250 mg twice daily . Results : Adverse events were balanced between the groups ( p = NS ) . Slight imbalances , mainly in the PYR-205/207 groups , were noted in deaths ( from diverse causes , p = NS ) and serious adverse events ( p = 0.05 ) that were attributed to pre-existing conditions . In a merged data set , pyridoxamine significantly reduced the change from baseline in serum creatinine ( p < 0.03 ) . In patients similar to the RENAAL/IDNT studies ( bSCr ≧1.3 mg/dl , type 2 diabetes ) , a treatment effect was observed on the rise in serum creatinine ( p = 0.007 ) . No differences in urinary albumin excretion were seen . Urinary TGF-β1 also tended to decrease with pyridoxamine ( p = 0.049 ) as did the CML and CEL AGEs . Conclusion : These data provide a foundation for further evaluation of this AGE inhibitor in DN", "BACKGROUND Hyperhomocysteinemia is seen in most hemodialysis ( HD ) patients and is an independent risk factor for cardiovascular disease . Homocysteine metabolism via remethylation requires activated folate and vitamin B12 and metabolism via transsulfuration requires serine and vitamin B6 . Prior studies have shown highly variable effects of supplemental B vitamin and folate therapy for hyperhomocysteinemia . We undertook a fully controlled trial with abnormally high doses of folic acid alone or with supplemental vitamin B6 and B12 compared with active folate alone or with serine . METHODS Two prospect i ve studies were undertaken in hemodialysis patients . In the first study ( protocol A ) , hyperhomocysteinemia was treated in 77 patients with 30 or 60 mg folic acid with or without vitamins B6 and B12 for eight weeks and compared with matching placebos . In the second study ( protocol B ) , hyperhomocysteinemia was treated in 37 patients with intravenous folinic acid given alone or with serine and compared with matching placebos . All patients received the st and ard of care treatment with a multivitamin tablet before and throughout the protocol to test the hypothesis that additional therapy is required over and above the routine therapy for maximum reduction in total homocysteine ( tHcy ) . RESULTS Normal volunteers ; The mean ( SD ) tHcy of 128 normal subjects was 6.5 ( 4 ) micromol/L. Protocol A ; Plasma folate increased significantly in the groups given folic acid at both four and eight weeks ( P = 0.0001 at both time points ) . Plasma vitamin B12 was significantly increased at four weeks ( P = 0.0018 ) but not at eight weeks ( P = 0.064 ) in those given Vitamin B12 . However , tHcy did not differ between treatment groups at baseline ( P = 0.63 ) , four weeks ( P = 0.79 ) or eight weeks ( P = 0.74 ) . Protocol B : Plasma folate increased significantly at four weeks in those receiving folinic acid ( P = 0.0001 ) but tHcy was not significantly different between groups ( P = 0.92 ) . In neither study was there any significant change in tHcy comparing before and during any treatment intervention . CONCLUSIONS In our studies high dose oral folic acid , intravenous folinic acid , vitamins B6 and B12 and oral serine were ineffective at lowering tHcy in patients on hemodialysis when given folic acid , folinic acid serine or B vitamins in addition to routine folic acid and B vitamin supplements", "Type 2 diabetes mellitus ( T2DM ) is a worldwide p and emic that may lead to diabetic kidney disease ( DKD ) , a complication which is the single most important and globally prevalent cause of chronic kidney disease . Microalbuminuria has been shown to be an early indicator of DKD and data suggest that angiotensin receptor blockers ( ARBs ) reduce urinary albumin excretion and retard the progression of renal disease in hypertensive T2DM patients . However , the effects of ARBs on preventing microalbuminuria and ensuing DKD in normotensive patients with T2DM is yet to be fully established . The objective of this study is to assess the anti-microalbuminuric effects of losar-tan therapy versus placebo in normotensive T2DM patients . This r and omized single blinded controlled trial was performed at the Diabetic Clinic , Jinnah Hospital , Lahore over a period of 10 months . A total of 361 normotensive patients with T2DM and microalbuminuria were selected ; of them , 171 patients were r and omly allocated to the test group and 190 enrolled into the control group . The patients in the test group were started on losartan 50 mg/day for a six month period while those in the control group were put on vitamin B-12 500 mcg/day . The patients as well as the primary attending phy-sicians/lab evaluators were blinded to the study . All study patients were followed up on a monthly basis . Quantitative microalbuminuria was tested at the beginning and at the end of the study . Out of the 171 patients in the test group , 149 ( 87.1 % ) had significant reduction of albuminuria by > 30 % of their baseline ( mean 101.9 + /- 21.7 baseline and , 47.5 + /- 12.9 post-therapy ) . The corresponding values for albuminuria in the 190 patients in the control group was mean 104.7 + /- 26.3 baseline and post 6-month mean 103.9 + /- 22.9 , with P < 0.0001 . The anti-albuminuric effect of losartan was reversible as seen on re-checking the urinary albumin two months after discontinuation of treatment . Our study shows that losartan was well tolerated and demonstrated significant anti-proteinuric effects in patients with T2DM with early nephropathy independent of hypertension", "CONTEXT Hyperhomocysteinemia is frequently observed in patients with diabetic nephropathy . B-vitamin therapy ( folic acid , vitamin B(6 ) , and vitamin B(12 ) ) has been shown to lower the plasma concentration of homocysteine . OBJECTIVE To determine whether B-vitamin therapy can slow progression of diabetic nephropathy and prevent vascular complications . DESIGN , SETTING , AND PARTICIPANTS A multicenter , r and omized , double-blind , placebo-controlled trial ( Diabetic Intervention with Vitamins to Improve Nephropathy [ DIVINe ] ) at 5 university medical centers in Canada conducted between May 2001 and July 2007 of 238 participants who had type 1 or 2 diabetes and a clinical diagnosis of diabetic nephropathy . INTERVENTION Single tablet of B vitamins containing folic acid ( 2.5 mg/d ) , vitamin B(6 ) ( 25 mg/d ) , and vitamin B(12 ) ( 1 mg/d ) , or matching placebo . MAIN OUTCOME MEASURES Change in radionuclide glomerular filtration rate ( GFR ) between baseline and 36 months . Secondary outcomes were dialysis and a composite of myocardial infa rct ion , stroke , revascularization , and all-cause mortality . Plasma total homocysteine was also measured . RESULTS The mean ( SD ) follow-up during the trial was 31.9 ( 14.4 ) months . At 36 months , radionuclide GFR decreased by a mean ( SE ) of 16.5 ( 1.7 ) mL/min/1.73 m(2 ) in the B-vitamin group compared with 10.7 ( 1.7 ) mL/min/1.73 m(2 ) in the placebo group ( mean difference , -5.8 ; 95 % confidence interval [ CI ] , -10.6 to -1.1 ; P = .02 ) . There was no difference in requirement of dialysis ( hazard ratio [ HR ] , 1.1 ; 95 % CI , 0.4 - 2.6 ; P = .88 ) . The composite outcome occurred more often in the B-vitamin group ( HR , 2.0 ; 95 % CI , 1.0 - 4.0 ; P = .04 ) . Plasma total homocysteine decreased by a mean ( SE ) of 2.2 ( 0.4 ) micromol/L at 36 months in the B-vitamin group compared with a mean ( SE ) increase of 2.6 ( 0.4 ) micromol/L in the placebo group ( mean difference , -4.8 ; 95 % CI , -6.1 to -3.7 ; P < .001 , in favor of B vitamins ) . CONCLUSION Among patients with diabetic nephropathy , high doses of B vitamins compared with placebo result ed in a greater decrease in GFR and an increase in vascular events . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N41332305", "AIM Results from several studies indicate that the total homocysteine ( tHcy ) concentration in plasma is an independent risk factor for cardiovascular disease in hemodialysis patients . Folic acid is the established mainstay of homocysteine-lowering treatment , but since such treatment does not normalize plasma tHcy concentration in hemodialysis patients , it is of importance to search for additional therapy . METHODS Twenty-eight folate-replete hemodialysis patients were r and omized to 2 equally sized groups , a treatment group and a control group . The treatment group received vitamin B12 tablets at a dose of 2 mg 3 times a week for 6 weeks ( after each dialysis session ) while the control group received no such treatment . Blood sample s were collected before and at the end of the treatment period for analysis of tHcy in plasma and vitamin B12 , methylmalonic acid as well as folate in serum . RESULTS At the end of the study period , serum vitamin B12 concentrations were significantly higher in the treatment group than in the control group . Plasma tHcy concentrations decreased significantly in both groups during the study period . However , there was no difference between the responses of the 2 groups . CONCLUSION The results of this open , r and omized controlled study did not support the hypothesis that treatment with oral vitamin B12 has considerable homocysteine-lowering effect in folate-replete hemodialysis patients", "OBJECTIVE Hyperhomocysteinemia occurs in nearly 100 % of patients with end-stage renal disease ( ESRD ) and is associated with increased morbidity and mortality . Means to reduce elevated homocysteine concentrations is supplementation with folic acid , vitamin B6 , and vitamin B12 . However , doses of vitamins required for optimized treatment are subject of debate . Therefore , the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared . DESIGN Patients received 3 times per week either 2 tablets of preparation A ( 800 microg folic acid , 6 microg vitamin B12 , 10 mg vitamin B6 ) , 2 tablets of preparation B ( 160 microg folic acid , no vitamin B12 , 10 mg vitamin B6 ) , or placebo for a period of 12 weeks with control of total homocysteine ( tHcy ) levels at baseline , and at 4 , 8 , and 12 weeks . SETTING The study was performed at the University Hospital of Magdeburg , Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis . RESULTS Preparation A reduced the tHcy concentration significantly by nearly 50 % , whereas preparation B did not change the tHcy concentration in comparison with placebo . However , tHcy was not normalized in the majority of patients receiving preparation A. CONCLUSION The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone . Nevertheless , hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation , in contrast with results obtained in healthy volunteers", "BACKGROUND Predictors of diabetic nephropathy are only partly known . The role of glomerular hyperfiltration is much discussed . We have studied the cumulative incidence of micro and macroalbuminuria and the predictive value of glomerular filtration rate ( GFR ) and screening value of albumin excretion rate ( AER ) in type-1 diabetes . METHODS A cohort of diabetic children was followed up at a mean duration of 29+/-3 years . All 75 children treated in one hospital with diabetes duration > or = 8 years were prospect ively followed for 8 years examining GFR , AER , blood pressure and HbA1c . After another 8 - 10 years , 60 of them were traced for endpoint follow-up . RESULTS Seven patients ( 12 % ) developed macroalbuminuria , i.e. persistent overnight AER>200 mg/min , 12 ( 20 % ) developed persistent microalbuminuria ( AER 15 - 200 mg/min ) and 17 ( 28 % ) transient microalbuminuria ( > 15 mg/min on two consecutive occasions , normalized at endpoint ) . One baseline screening value of 24-h AER>15 mg/min predicted 93 % of patients with persistent micro or macroalbuminuria . The negative predictive value was 78 % . Six of seven macroalbuminuric and 10 of 12 microalbuminuric patients had a baseline GFR above the normal limit of the method ( > or = 125 ml/min/1.73 m(2 ) ) . When adjusted for diabetes duration , increased GFR predicted macro or microalbuminuria ( odds ratios=5.44 , P=0.04 ) . The positive predictive value for having an increased baseline GFR was 53 % . The negative predictive value was 77 % . Stratification for HbA1c did not change the effect of an increased GFR . CONCLUSIONS At a mean diabetes duration of 29 years the cumulative incidence of macroalbuminuria was 12 % ; however , another 20 % had persistent microalbuminuria . A screening value of 24-h AER > 15 mg/min was a strong predictor , whereas increased GFR was a weaker but significant predictor for micro and macroalbuminuria", "OBJECTIVE To study the effect of vitamin B on treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients . METHODS Thirty-six stable hyperhomocysteinemic renal-transplant recipients were r and omly assigned to vitamin treatment ( group A , n = 18 , folic acid 5 mg/d , vitamin B(6 ) 50 mg/d , B(12 ) 1000 microg/d ) or controlled group ( group B , n = 18 ) for 6 months . All subjects underwent assessment of levels for creatinine , creatinine clearance , average pressure , total cholesterol , triglyceride and fasting homocysteine . Endothelial function was evaluated using high-resolution vascular ultrasound . RESULTS The levels of homocysteine markedly decreased in group A [ ( 13 + /- 4 ) micromol/L vs ( 20 + /- 5 ) micromol/L , t = 5.3 , P < 0.01 ] after treatment , whereas no significant changes were observed in group B. In group A , endothelium dependent [ ( 12 + /- 5)% vs ( 9 + /- 5)% , t = 2.9 , P < 0.01 ] and independent [ ( 18 + /- 4)% vs ( 12 + /- 5)% , t = 3.4 , P < 0.01 ] vasodilatation responses significantly increased after treatment , no significant changes were observed in group B. Endothelium dependent [ ( 9 + /- 6)% , t = 2.8 , P < 0.01 ] and independent [ ( 12 + /- 5)% , t = 3.5 , P < 0.01 ] vasodilatation responses of group A were significantly lower than that of group B after treatment . CONCLUSIONS Vitamin B supplementation can reduce the levels of homocysteine and improve the endothelial function in hyperhomocysteinemic renal-transplant recipients", "Background and Purpose — Elevated total homocysteine is associated with a higher risk of cerebrovascular disease . It is not known whether lowering homocysteine impacts on stroke risk , both in terms of severity and ischemic vs hemorrhagic stroke subtypes . Our aim was to determine whether vitamin therapy reduces the risk of ischemic and hemorrhagic stroke , as well as stroke-related disability . Methods — We analyzed stroke outcomes among participants of the Heart Outcomes Prevention Evaluation 2 ( HOPE 2 ) trial that r and omized 5522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid , 50 mg of vitamin B6 , and 1 mg of vitamin B12 , or matching placebo , for 5 years . Results — Among 5522 participants , stroke occurred in 258 ( 4.7 % ) individuals during a mean of 5 years of follow-up . The geometric mean homocysteine concentration decreased by 2.2 & mgr;mol/L in the vitamin therapy group and increased by 0.80 & mgr;mol/L in the placebo group . The incidence rate of stroke was 0.88 per 100 person-years in the vitamin therapy group and 1.15 per 100 person-years in the placebo group ( hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.59–0.97 ) . Vitamin therapy also reduced the risk of nonfatal stroke ( HR , 0.72 ; 95 % CI , 0.54–0.95 ) but did not impact on neurological deficit at 24 hours ( P=0.45 ) or functional dependence at discharge or at 7 days ( OR , 0.95 ; 95 % CI , 0.57–1.56 ) . In subgroup analysis , patients aged younger than 69 years , from regions without folic acid food fortification , with higher baseline cholesterol and homocysteine levels , and those not receiving antiplatelet or lipid-lowering drugs at enrollment had a larger treatment benefit . Conclusions — Lowering of homocysteine with folic acid and vitamins B6 and B12 did reduce the risk of overall stroke , but not stroke severity or disability", "Pyridoxamine dihydrochloride ( Pyridorin , NephroGenex ) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls , but whether these actions translate into renoprotective effects is unknown . In this double-blind , r and omized , placebo-controlled trial , we r and omly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo ; Pyridorin , 150 mg twice daily ; or Pyridorin , 300 mg twice daily , for 52 weeks . At baseline , the mean age ± SD was 63.9±9.5 years , and the mean duration of diabetes was 17.6±8.5 years ; the mean serum creatinine level was 2.2±0.6 mg/dl , and the mean protein-to-creatinine ratio was 2973±1932 mg/g . Regarding the primary end point , a statistically significant change in serum creatinine from baseline to 52 weeks was not evident in either Pyridorin group compared with placebo . However , analysis of covariance suggested that the magnitude of the treatment effect differed by baseline renal function . Among patients in the lowest tertile of baseline serum creatinine concentration , treatment with Pyridorin associated with a lower average change in serum creatinine concentration at 52 weeks ( 0.28 , 0.07 , and 0.14 mg/dl for placebo , Pyridorin 150 mg , and Pyridorin 300 mg , respectively ; P=0.05 for either Pyridorin dose versus placebo ) ; there was no evidence of a significant treatment effect in the middle or upper tertiles . In conclusion , this trial failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year , although it suggests that patients with less renal impairment might benefit", "BACKGROUND Mild hyperhomocysteinaemia is a cardiovascular risk factor in patients with type 2 diabetes mellitus . Homocysteine may exert its detrimental effects through induction of endothelial dysfunction and /or chronic inflammation . In this study , we examined the effects of homocysteine-lowering therapy with folic acid on biochemical markers of endothelial dysfunction and low- grade inflammation in patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia ( > or = 14 micromol/l ) . METHODS In a r and omised , double-blind , controlled trial , patients were treated with folic acid 5 mg or placebo for six months . At 0 and 6 months , albuminuria , von Willebr and factor , soluble cellular adhesion molecules , C-reactive protein , interleukin-6 and tumour necrosis factor-alpha were determined . RESULTS Forty-one patients completed the study ( folic acid 23 , placebo 18 ) . Baseline hyperhomocysteinaemia ( median 17 micromol/l , range 14 to 30 micromol/l ) was reduced by 29 % in the folic-acid-treated group , and remained unchanged in patients receiving placebo . On average , folic acid treatment did not significantly affect any of the endothelial ( e.g. von Willebr and factor : difference folic acid minus placebo + 1 % , confidence interval -3 to + 16 % ) or inflammation ( e.g. C-reactive protein : difference folic acid minus placebo + 13 % , confidence interval -42 to + 52 % ) markers studied . Multiple regression analyses without and with adjustment for baseline differences in cardiovascular disease and ethnicity confirmed these results . An apparent beneficial effect of folic acid on albuminuria in crude analysis was attenuated by multiple adjustment ( difference folic acid minus placebo -35 % , confidence interval -178 to + 32 % , p=0.08 , adjusted 0.26 ) . CONCLUSION The data indicate that , in this group of patients with type 2 diabetes mellitus and mild hyperhomocysteinaemia , lowering homocysteine with folic acid for six months does not improve biochemical markers of endothelial dysfunction or low- grade inflammation", "Abstract Objective : To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4801 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any complications or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , lower extremity amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photocoagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 10 mm Hg decrease in up date d mean systolic blood pressure adjusted for specific confounders Results : The incidence of clinical complications was significantly associated with systolic blood pressure , except for cataract extraction . Each 10 mm Hg decrease in up date d mean systolic blood pressure was associated with reductions in risk of 12 % for any complication related to diabetes ( 95 % confidence interval 10 % to 14 % , P<0.0001 ) , 15 % for deaths related to diabetes ( 12 % to 18 % , P<0.0001 ) , 11 % for myocardial infa rct ion ( 7 % to 14 % , P<0.0001 ) , and 13 % for microvascular complications ( 10 % to 16 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure . Any reduction in blood pressure is likely to reduce the risk of complications , with the lowest risk being in those with systolic blood pressure less than 120 mm Hg", "OBJECTIVE Cigarette smoking contributes to development of diabetic nephropathy . However , long-term studies on the effect of smoking on decline in kidney function in diabetic nephropathy are lacking . We assessed the impact of smoking on progression of diabetic nephropathy in type 1 diabetic patients enrolled in a prospect i ve observational cohort study started in 1983 . RESEARCH DESIGN AND METHODS We identified all albuminuric type 1 diabetic patients ( n = 301 ) followed for at least 3 years , median ( range ) 7 years ( 3 - 14 ) , who underwent at least yearly measurement of glomerular filtration rate ( GFR ) by the (51)Cr-EDTA plasma clearance technique ( n = 8 , range 3 - 24 ) . In total , 192 men and 109 women were included ( age [ mean + /- SD ] 36 + /- 11 years , duration of diabetes 22 + /- 8 years ) ; 271 patients were treated with antihypertensive drugs , predominantly ACE inhibitors in 179 patients . Patients were classified as smokers if they smoked more than one cigarette per day during a portion of or the entire observation period . Blood pressure , albuminuria , HbA(1c ) , and serum cholesterol were measured every 3 - 4 months during the study . RESULTS In all 301 patients , the mean ( SE ) rate of decline in GFR ( deltaGFR ) was 4.0 ( 0.2 ) mlx min(-1 ) x year(-1 ) during the investigation period . No difference in Delta GFR was demonstrated between nonsmokers ( n = 94 ) , deltaGFR 4.5 ( 0.4 ) , ex-smokers ( n = 31 ) , deltaGFR 3.1 ( 0.7 ) , and smokers ( n = 176 ) , deltaGFR 3.9 ( 0.3 ) ml x min(-1 ) x year(-1 ) , respectively ( NS ) . Adjustment for other risk factors for progression of diabetic nephropathy did not alter the results : smoking was not associated with deltaGFR , whereas blood pressure , albuminuria , HbA(1c ) , and serum cholesterol were demonstrated to be independent progression promoters . CONCLUSIONS In our study , smoking was not associated with decline in kidney function in type 1 diabetic patients with diabetic nephropathy", "Various regimens of folic acid-based and vitamin B12 ( Vit B12 ) supplementations have been tried for lowering plasma homocysteine ( Hcy ) levels in uremic patients . However , the therapeutic potency of low-dose folic acid and Vit B12 alone is not properly understood . In this study , seventy-five patients on chronic hemodialysis ( HD ) therapy were r and omized into three groups . The FNA group received intravenous ( IV ) supplementation with folinic acid 3 mg weekly ; the Vit B12 group received IV supplementation with vitamin B12 1 mg weekly ; and the combination group received IV supplementation with both agents weekly . Blood levels of Hcy , folic acid , and Vit B12 were measured monthly for three months . After three months of treatment , plasma levels of Hcy decreased significantly in all three groups when compared with their baselines ( all p < 0.05 ) . The final Hcy level was significantly lower in the combination group ( 11.5 ± 2.3 μmol/L ) when compared with that of the FNA group ( 15.9 ± 5.6 μmol/L , p < 0.05 ) but not with the Vit B12 group ( 15.9 ± 11.6 μmol/L ) , although their baseline levels were similar . The percentage decreases of tHcy at the end of the treatment in the FNA group , Vit B12 group , and combination group were 16.4 % , 29.3 % , and 38.9 % respectively . Our study showed that IV pharmacologic dose of Vit B12 alone is as effective as low-dose folic acid in correcting hyperhomocysteinemia in chronic HD patients , and combining both drugs in low doses may have added effects", "OBJECTIVE To study the effect of high doses of thiamine ( 250 mg/day ) and pyridoxine ( 200 mg/day ) supplementation on plasma levels of advanced glycation end products and other oxidative stress markers in hemodialysis patients . DESIGN An interventional survey . SETTING This study was conducted at an outpatient nephrology clinic . INTERVENTION AND PATIENTS : We performed a r and omized placebo-controlled study over 8 weeks in 50 patients ( 53 % men , age 52.9 + /- 3.4 years ) on regular hemodialysis . MAIN OUTCOME MEASURES The patients were divided into 2 groups of 25 patients in each arm . Before starting the study , the patients in both groups were matched by age , gender , inflammatory profile ( plasma interleukin [IL]-6 and high-sensitivity C-reactive protein [ hsCRP ] ) , and nutritional status ( subjective global assessment and protein nitrogen appearance ) . RESULTS In all , 40 of 50 patients completed the study ( 19 patients in the vitamin group and 21 in the placebo group ) . Serum albumin , plasma hsCRP , IL-6 , advanced oxidation protein products , pentosidine and 8-hydroxy-2'-deoxyguanosine were measured before and after treatment in each group . In both groups , over 8 weeks of follow-up , no significant differences could be observed in oxidative stress , inflammatory , or nutritional markers . CONCLUSIONS There was no evidence showing that high doses of thiamine and pyridoxine affects oxidative stress in hemodialysis patients", "Bone marrow smears from 20 patients with chronic renal failure and on regular haemodialysis treatment ( RDT ) were morphologically analysed . A double-blind study of treatment with high doses of vitamin B6 showed that the patients receiving pyridoxine got raising frequencies of lymphocytes and monocytes in the bone marrow and there were morphologic signs of a normalization within the granulopoiesis . It is suggested that this is a sign of an enhancement of the immune response . The vitamin supplementation had no significant effects on the pronounced anemia of the patients", "BACKGROUND Treatment with folic acid and vitamin B 12 appears to be effective in lowering total plasma Homocysteine ( tHcy ) concentration , but whether vitamin B 12 alone decreases tHcy in patients with normal vitamin B 12 status is still unknown . The aims of the present study were to explore the effect of alternate vitamin supplementation with folic acid or vitamin B 12 on tHcy concentrations in haemodialysis ( HD ) patients , and to compare changes in tHcy concentrations with MTHFR genotype . METHODS 74 patients , 44 men and 30 women , were recruited and r and omized blindly into two groups of 37 subjects each . The first group was initially treated with vitamin B 12 for two months , and with folic acid for the following two months ; the second group was supplemented in the reverse order . In both groups the treatment was followed by a 2-month washout period . tHcy levels were measured at the beginning of treatment ( T0 ) , after two months ( T1 ) , four months ( T2 ) , and at the end of the washout period ( T3 ) . Vitamin B 12 and folate were taken at T0 and T3 . RESULTS The genotype frequency was : C/C 37 % , C/T 34 % , T/T 29 % . tHcy decreased in both groups following the alternate vitamins therapy . This decrease was greater for the T/T genotype ( p<0.05 ) and was more significant when the treatment start-ed with folic acid ( p<0.01 ) . Moreover , after the washout period , tHcy increased remarkably without significant differences between diffusive and convective techniques . Folate levels at the end of study appeared to be reduced in haemodialysis patients . Vitamin B 12 concentration significantly increased in patients on diffusive haemodialysis , confirming the fundamental role of membrane performance . CONCLUSION The alternate vitamin treatment demonstrated the importance of folate therapy and the secondary contribution of vitamin B 12 in lowering tHcy in HD patients", "Context In observational studies , elevated plasma homocysteine levels were associated with venous thromboembolism . A multicenter trial of folic acid and B vitamins to reduce cardiovascular events investigated the effect of homocysteine lowering on venous thromboembolism . Contribution In this trial , 5522 adults were r and omly assigned to receive placebo , or folic acid and vitamins B6 and B12 daily for 5 years . Vitamin therapy decreased homocysteine levels , but the incidence of venous thromboembolism was the same in both groups , even in participants with the highest levels of homocysteine . Caution Venous thromboembolism events were not central ly adjudicated . Implication Decreasing homocysteine levels with supplements containing folic acid and vitamins B6 and B12 does not reduce the incidence of venous thromboembolism . The Editors Observational studies have found an association between elevated total plasma homocysteine levels and venous thromboembolism ( 14 ) . Homocysteine is thought to promote thrombosis through enhanced platelet activation , increased thrombin generation , and impaired fibrinolysis and by causing endothelial dysfunction ( 5 ) . Although homocysteine levels can be decreased by 25 % by using a supplement of folic acid and vitamins B6 and B12 ( 6 ) , whether the risk for venous thromboembolism is reduced as a result is not known . The Heart Outcomes Prevention Evaluation 2 ( HOPE-2 ) evaluated the effect of homocysteine-lowering therapy on the risk for major vascular arterial disease ( 7 ) . In conjunction with the trial , we collected data prospect ively to determine whether decreasing homocysteine levels would reduce the occurrence of symptomatic venous thromboembolism . Methods Design The design of HOPE-2 , a large r and omized , placebo-controlled clinical trial , is described elsewhere ( 7 , 8) . Soon after HOPE-2 began , a decision was made to include venous thromboembolism as a study outcome . A diagnosis of venous thromboembolism was based on prespecified , accepted criteria ( 7 ) . An independent data and safety monitoring board evaluated the safety of the participants and the overall quality and scientific integrity of HOPE-2 . The research ethics review board of each participating center approved the trial , and all participants provided written informed consent . Participants The HOPE-2 included 5522 participants 55 years of age or older who had a history of coronary , cerebrovascular , or peripheral vascular disease ; diabetes mellitus ; and at least 1 additional risk factor for cardiovascular disease , regardless of baseline homocysteine level ( 7 , 8) . Persons taking daily vitamin supplementation that contained more than 0.2 mg of folic acid were excluded . A history of venous thromboembolism or the presence or absence of risk factors for venous thromboembolism did not affect eligibility . A complete list of inclusion and exclusion criteria appears elsewhere ( 7 , 8) . Data on all persons who were enrolled in HOPE-2 are included in the current report . Centers Individuals were recruited from 145 centers in 13 countries , including Canada ( n= 3568 ) , the United States ( n= 414 ) , Brazil ( n= 265 ) , western European countries ( n= 426 ) , and Slovakia ( n= 849 ) . Intervention and R and omization Between January 2000 and December 2000 , participants were r and omly assigned to receive a once-daily supplement containing 2.5 mg of folic acid , 50 mg of vitamin B6 , and 1 mg of vitamin B12 , or matching placebo . R and omization was computer generated , with a block size of 4 ; was stratified by clinical center ; and was performed by having clinical centers call an automated central ized system . Information about block size and whether it was r and om or fixed was kept confidential for all study investigators . The r and omization sequence was concealed , and all study personnel and study participants were masked to treatment allocation . The vitamin and placebo pill formulations were indistinguishable by size , color , weight , taste , or dissolution in water . Changes in blood levels of folate , vitamins B6 and B12 , and homocysteine , which are affected by the study intervention , are not commonly measured in clinical practice , and the results of any such measurements that were performed as part of the study were kept confidential . No request was made to unmask treatment allocation for a participant . Baseline Measurements and Follow-up Baseline demographic data ; medical history ; and medication use , including current anticoagulant therapy , were recorded for all participants at study entry . History of venous thromboembolism was not documented . Baseline homocysteine levels were obtained in 3306 r and omly selected participants ( 60 % of total ) who had fasted overnight . Stratified r and om sampling was used to achieve proportional representation of a subset of participants in countries with folic acid food fortification ( Canada and the United States ) and countries without this st and ard ( all other countries with participating centers ) . Homocysteine was measured by using a fluorescence polarization immunoassay ( Abbott IMx , Abbott Laboratories , Abbott Park , Illinois ) . The distribution of homocysteine was statistically significantly skewed ; thus , these measures were log-transformed and inverse transformations were used to generate geometric mean values . The first evaluation for venous thromboembolism occurred 18 months after r and omization ; at this visit , all participants were assessed for any venous thromboembolism event arising between trial entry and the 18-month visit . Thereafter , venous thromboembolism was assessed routinely every 6 months , to an average follow-up of 5 years . The trial used simple case report forms , which were faxed toll-free to the study coordinating office and were entered into a data base by using optical character recognition ( Data Fax , Clinical Data Fax Systems , Hamilton , Ontario , Canada ) . The data base was fit for quality control assessment s and statistical analyses . At each 6-month interval , participants were assessed in the study clinics . These assessment s were directed primarily to ascertain study end points . Side effects were also evaluated , and adherence to treatment was assessed by interview and pill count . When in-person visits were not possible , participants were contacted by telephone . Outcomes The primary outcome in our study was symptomatic venous thromboembolism , which included deep venous thrombosis or pulmonary embolism ( or both ) . In the original HOPE-2 report ( 8) , venous thromboembolism was included under other outcomes . Diagnosis of deep venous thrombosis required confirmation with duplex leg ultrasonography or venography . Diagnosis of pulmonary embolism required confirmation with ventilationperfusion lung scanning , computed tomographic pulmonary angiography , or conventional pulmonary angiography . When diagnostic testing had indeterminate results or was not done , which rarely occurred , we required oral anticoagulant therapy to be initiated at the same time that new-onset venous thromboembolism was recorded on the case report form . A maximum of 1 episode of venous thromboembolism per participant was counted during follow-up . We subcategorized episodes as unprovoked venous thromboembolism if they occurred in participants who did not have cancer at baseline and occurred 90 days or more after a lower limb fracture or 30 days or more after a hospitalization . We ascertained all events with concealment to r and omization for study participants and assessors . Statistical Analysis Our primary analysis was a comparison of the incidence of venous thromboembolism in the 2 study groups . We prespecified secondary analyses and included comparisons between the groups of rates of venous thromboembolism ( including unprovoked events ) according to subgroups and strata ( Figure 1 ) . Figure 1 . Risk for venous thromboembolism ( VTE ) in prespecified subgroups . We used an intention-to-treat analysis to compare the effect of homocysteine-lowering therapy with that of placebo on the subsequent development of venous thromboembolism . We conducted the time-to-event analysis by using a Cox proportional hazards regression model and expressed unadjusted risk as hazard ratios and 95 % CIs . We examined the proportional hazards assumption by fitting the models with the interaction terms between time and treatment . We estimated a survival curve according to the KaplanMeier procedure and compared treatment groups by using a log-rank test . At each interval clinic visit , follow-up was greater than 99 % . In the rare circumstance that an individual could not be assessed at a clinic visit and could not be contacted by telephone , we considered the individual to be free of venous thromboembolism at that point . Individuals who were lost to follow-up were censored at the time of last contact . The original HOPE-2 was design ed to recruit 5000 participants , with a mean of 5 years of follow-up , to detect a relative risk reduction of 17 % to 20 % and a statistical power of 80 % and 90 % in the primary composite outcome of cardiovascular death , myocardial infa rct ion , and stroke , given an annual event rate of 4 % in the placebo group and a 2-sided P value of 0.05 . We did not estimate a formal sample size . A 2-sided P value less than 0.05 was considered significant for all analyses , which we performed by using SAS , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Sources The study was funded by the Canadian Institutes of Health Research and Jamieson Laboratories . The funding sources had no role in the design , conduct , or reporting of the study or in the decision to su bmi t the manuscript for publication . Results Study Participants and Homocysteine Levels Of the 5522 study participants , 2758 were r and omly assigned to receive homocysteine-lowering therapy and 2764 were assigned to receive placebo ( Table 1 ) . A total of 3982 participants ( 72 % ) were from Canada and the United States , where universal food fortification with folic acid was in place before the start of the trial . Adherence to", "Abstract Aims /hypothesisHigh-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes . The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes . Methods Type 2 diabetic patients ( 21 male , 19 female ) with microalbuminuria were recruited at the Diabetes Clinic , Sheikh Zayed Hospital , Lahore , Pakistan , and r and omised to placebo and treatment arms . R and omisation was by central office in sequentially numbered opaque , sealed envelopes . Participants , caregivers and those assessing the outcomes were blinded to group assignment . Patients were given 3 × 100 mg capsules of thiamine or placebo per day for 3 months with a 2 month follow-up washout period . The primary endpoint was change in urinary albumin excretion ( UAE ) . Other markers of renal and vascular dysfunction and plasma concentrations of thiamine were determined . Results UAE was decreased in patients receiving thiamine therapy for 3 months with respect to baseline ( median −17.7 mg/24 h ; p < 0.001 , n = 20 ) . There was no significant decrease in UAE in patients receiving placebo after 3 months of therapy ( n = 20 ) . UAE was significantly lower in patients who had received thiamine therapy compared with those who had received placebo ( 30.1 vs 35.5 mg/24 h , p < 0.01 ) but not at baseline . UAE continued to decrease in the 2 month washout period in both groups , but not significantly . There was no effect of thiamine treatment on glycaemic control , dyslipidaemia or BP . There were no adverse effects of therapy . Conclusions /interpretationIn this pilot study , high-dose thiamine therapy produced a regression of UAE in type 2 diabetic patients with microalbuminuria . Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy . Trial registration : CTRI ( India ) CTRI/2008/091/000112 Funding : Pakistan Higher Education", "BACKGROUND In observational studies , lower homocysteine levels are associated with lower rates of coronary heart disease and stroke . Folic acid and vitamins B6 and B12 lower homocysteine levels . We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease . METHODS We r and omly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid , 50 mg of vitamin B6 , and 1 mg of vitamin B12 or with placebo for an average of five years . The primary outcome was a composite of death from cardiovascular causes , myocardial infa rct ion , and stroke . RESULTS Mean plasma homocysteine levels decreased by 2.4 micromol per liter ( 0.3 mg per liter ) in the active-treatment group and increased by 0.8 micromol per liter ( 0.1 mg per liter ) in the placebo group . Primary outcome events occurred in 519 patients ( 18.8 percent ) assigned to active therapy and 547 ( 19.8 percent ) assigned to placebo ( relative risk , 0.95 ; 95 percent confidence interval , 0.84 to 1.07 ; P=0.41 ) . As compared with placebo , active treatment did not significantly decrease the risk of death from cardiovascular causes ( relative risk , 0.96 ; 95 percent confidence interval , 0.81 to 1.13 ) , myocardial infa rct ion ( relative risk , 0.98 ; 95 percent confidence interval , 0.85 to 1.14 ) , or any of the secondary outcomes . Fewer patients assigned to active treatment than to placebo had a stroke ( relative risk , 0.75 ; 95 percent confidence interval , 0.59 to 0.97 ) . More patients in the active-treatment group were hospitalized for unstable angina ( relative risk , 1.24 ; 95 percent confidence interval , 1.04 to 1.49 ) . CONCLUSIONS Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease . ( Clinical Trials.gov number , NCT00106886 ; Current Controlled Trials number , IS RCT N14017017 . )", "OBJECTIVE To analyze the changes in glomerular filtration rate ( GFR ) , urinary albumin excretion rate ( UAER ) , and blood pressure ( BP ) levels in a cohort of normoalbuminuric and normotensive type 1 diabetic patients . RESEARCH DESIGN AND METHODS This is an 8.4+/-2.1-year prospect i ve study of 33 normotensive normoalbuminuric ( 24-h UAER < 20 microg/min ) type 1 diabetic patients . UAER ( radioimmunoassay ) , GFR ( 51Cr-EDTA single-injection technique ) , and GHb ( ion-exchange chromatography ) were measured at baseline and at 1- to 2-year intervals . RESULTS The GFR decreased ( 137.6+/-16.5 to 116.4+/-21.3 ml x min(-1 ) x 1.73 m(-2 ) P < 0.05 ) during the follow-up period . GFR reduction ( -0.20+/-0.29 ml x min(-1 ) x month(-1 ) ; P < 0.05 ) was associated with baseline GFR and mean GHb ( R2 = 0.30 ; beta = 0.072 ; F = 6.54 ; P = 0.004 ) . UAER was higher at the end of the study ( 3.7 - 7.1 microg/min ; P = 0.017 ) . Microalbuminuria was observed in two patients , while macroalbuminuria was observed in one . No changes in UAER were observed when these three patients were excluded from the analysis . Mean blood pressure ( MBP ) increased during the study ( 85.8+/-9.7 to 99.6+/-11.6 mmHg ; P < 0.001 ) . MBP at the end of the study was associated with age and GFR at baseline ( R2 = 0.39 ; beta = 0.074 ; F = 9.64 ; P = 0.001 ) . CONCLUSIONS In this cohort of normoalbuminuric normotensive type 1 diabetic patients , GFR decreased and BP levels increased during the follow-up period . The predictors for the GFR change were baseline GFR level and metabolic control . For end-of- study MBP , the predictor was baseline GFR level", "ABSTRACT Objective : Folic acid and vitamin B complex administration in uremic patients has been reported to lower plasma total homocysteine ( tHcy ) levels , but whether or not this has a beneficial effect on the inflammatory state is not clear . Methods : We conducted a r and omized open labeled study to determine the effects of folic acid ( 5 mg daily ) and vitamin B complex administration on plasma tHcy levels as well as inflammatory ( serum high-sensitivity C reactive protein , hs‑CRP ) and nutritional ( serum albumin ) markers in patients on maintenance hemodialysis . Treatment was given for 3 consecutive months to 61 patients on maintenance hemodialysis . Another 60 patients , all age- , sex- , hemodialysis duration -matched served as control group . Main outcome measures : Plasma tHcy , serum hs‑CRP , albumin , creatinine ( Cr ) , post-dialysis body weight ( BW ) , and normalized protein catabolism rate ( nPCR ) . Results : After 3 months , levels of plasma tHcy and serum hs‑CRP , Cr , and nPCR were significantly decreased while levels of serum albumin , vitamin B12 , folate , and BW were significantly increased . The dialytic dose ( KT/V ) and dietary intake remained unchanged . However , correlations between the magnitude of reduction of tHcy & hs‑CRP , tHcy & Cr , and Cr & nPCR were statistically significant . Conclusions : Folic acid and vitamin B complex co-administration effectively lowers tHcy and hs‑CRP levels and increases albumin levels in stable hemodialysis subjects , underscoring their potential benefit to attenuate the state of inflammation and possibly improve the nutritional status in patients on hemodialysis", "OBJECTIVE To investigate the association between cigarette smoking and the progression of diabetic nephropathy . RESEARCH DESIGN AND METHODS A prospect i ve , follow-up study over one year was conducted in a sequential sample of 34 smokers , 35 nonsmokers , and 24 ex-smokers with type I diabetes , hypertension , and diabetic nephropathy . Progression of renal disease was defined according to the stage of nephropathy as an increase in proteinuria or serum creatinine or a decrease in the glomerular filtration rate . RESULTS Progression of nephropathy was less common in nonsmokers ( 11 % ) than in smokers ( 53 % ) and patients who had quit smoking ( 33 % ) , P > 0.001 . In a stepwise logistic regression analysis , cigarette pack years , 24-h sodium excretion , and GHb were independent predictive factors for the progression of diabetic nephropathy . Because blood pressure ( BP ) was well controlled in these patients and most values were within a normotensive range , neither st and ing , sitting , nor supine BP values were associated with progression of nephropathy . CONCLUSIONS Cigarette smoking represents an important factor associated with progression of nephropathy in treated hypertensive type I diabetic patients", "To evaluate the efficacy of supplementation with high dose folic acid with and without vitamin B 12 in lowering plasma total homocysteine ( tHcy ) concentrations in hemodialysis ( HD ) patients , we studied 36 HD patients r and omized into four groups according to the received therapeutic regimen : group I ( only folic acid ( FA ) , 5 mg/day ) , group II ( FA , 5 mg/day + vitamin B 12 , 1 mg/day ) group III ( only FA , 15 mg/day ) , group IV ( FA , 15 mg/day , vitamin B 12 , 1 mg/day ) for a period of 8 weeks . Plasma tHcy and serum FA and vitamin B 12 levels were measured at baseline and after the supplementation period . Dietary intakes were assessed during the study period . At baseline , 27.8 % of the patients had normal levels of tHcy and 72.2 % had hyperhomocysteinemia . After supplementation , plasma tHcy increased by 1.35 % in group I and decreased by 6.99 % , 14.54 % and 30.09 % in groups II , III and IV respectively , which was only significant in group IV ( P= 0.014 ) . The patients did not show any significant changes in serum folic acid , but a significant change in serum vitamin B 12 in group IV ( P= 0.006 ) . Percentage of patients reaching normal levels of plasma tHcy was 5.6 fold higher in group IV than in the reference group ( group I ) . No correlations were found between changes of plasma tHcy levels and dietary intakes . We conclude that oral supplementation with 15 mg/day folic acid together with 1 mg/day of vitamin B 12 is effective in reducing tHcy levels in HD patients . These supplements also have a desirable effect on serum folic acid and vitamin B12", "BACKGROUND Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients . OBJECTIVES To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment . METHODS In a r and omized prospect i ve study , we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia . Patients were divided into two groups : 26 patients ( group A ) who received 25 mg of vitamin B6 daily and one monthly injection of 200 microg vitamin B12 , and 24 patients ( group B ) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 microg vitamin B12 . In addition , both groups received 15 mg folic acid daily . Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile . Baseline Hcy levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given . MFTHR alleles were analyzed , as were activated protein C resistance , von Willebr and factor and lupus anticoagulant . RESULTS Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects ( 33.8 + /- 4.3 vs. 4.5 to 14.0 micromol/L ) . Following treatment , Hcy levels were significantly reduced to 21.2 + /- 1.6 in group A and 18.6 + /- 1.4 micromol/L in group B ( P < 0.01 ) . There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study . There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients . Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR ( n = 5 ) was associated with higher Hcy levels and better response to treatment ( Hcy levels decreased by 58 % , from 46.2 + /- 14.6 to 19.48 + 4.1 micromol/ L following treatment ) . In patients with heterozygous thermolabile MTHFR ( n = 25 ) , Hcy levels decreased by 34 % , from 31.2 + /- 3.7 to 18.1 + /- 1.1 micromol/L following treatment . The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable . CONCLUSIONS Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients , independently of the tested doses . In addition , mutations in MTHFR were associated with elevated plasma levels of Hcy . Neither vascular access nor the presence of diabetes was associated with higher pre- or post-treatment homocysteine level", "Summary We evaluated the impact of some putative progression promoters on kidney function in albuminuric Type 2 ( non-insulin-dependent ) diabetic patients with biopsyproven diabetic glomerulosclerosis . Twenty-six patients ( 1 female ) with a mean age of 52 ( st and ard error 2 ) years and a known mean duration of diabetes of 9 ( 1 ) years were followed-up prospect ively for a mean of 5.2 ( range 1.0–7.0 ) years . Twenty-one patients received antihypertensive treatment . During the observation period the glomerular filtration rate decreased from 83 ( 24–146 ) to 58 ( 2–145 ) ml·min−1·1.73 m−2 ( mean ( range ) ) ( p<0.001 ) . The mean rate of decline in glomerular filtration rate was 5.7 ( −3.5 to 22.0 ) ml/min per year . Albuminuria increased from 1.2 ( 0.3–7.2 ) to 2.3 ( 0.4–8.0 ) g/24 h ( geometric mean ( range ) ) ( p<0.001 ) . Arterial blood pressure remained unchanged : 162/93 ( SE 4/3 ) and 161/89 ( 4/2 ) mm Hg . Univariate analysis showed the rate of decline in glomerular filtration rate to correlate with systolic blood pressure ( r=0.71,p<0.001 ) , mean blood pressure ( r=0.56,p<0.005 ) , albuminuria ( r=0.58,p<0.005 ) and the initial glomerular filtration rate ( r=−0.49,p<0.02 ) . The rate of decline in glomerular filtration rate did not correlate significantly with dietary protein intake , total cholesterol , high-density lipoprotein cholesterol or HbA1c . Three patients died from uraemia and four patients died from cardiovascular disease . Two patients required renal replacement therapy at the end of the observation period . Our prospect i ve observational study revealed that one-fifth of the patients developed end-stage renal failure during the 5-year observation period . The decline in glomerular filtration rate varied considerably between patients . Increase in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy . Elevated systolic blood pressure accelerates the progression of diabetic nephropathy in Type 2 diabetic patients", "BACKGROUND High-flux haemodialysis ( HD ) has recently been vigorously promoted as a novel st and ard , and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and /or underdialysis . However , some symptoms remain problematical , particularly peripheral polyneuropathy ( PPN ) . One of the possible reasons for this is that the patients may have low concentrations of some nutrients , e.g. vitamin B(6 ) , necessary for normal peripheral neuron function . METHODS Predialysis serum pyridoxal-5'-phosphate ( P5P ) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin . Among them , 26 patients suffered from PPN . Prior to supplementation , these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score . Vitamin B(6 ) ( 60 mg/day ) was r and omly prescribed to 14 of them , and vitamin B(12 ) ( 500 microg/day ) was prescribed to the others . After 4 weeks , all the patients were re-examined . RESULTS We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN . Nonetheless , it was demonstrated that supplementation with vitamin B(6 ) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms . No improvement was observed in response to vitamin B(12 ) supplementation . CONCLUSION This result suggests that although vitamin B(6 ) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD , vitamin B(6 ) supplementation was effective in improving PPN symptoms of various aetiologies , possibly because of vitamin B(6 ) resistance to PPN in these patients", "Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % )", "BACKGROUND Treatment with folic acid and vitamin B12 appears to be effective in lowering total plasma homocysteine ( tHcy ) concentrations , but whether vitamin B12 alone lowers tHcy in patients with normal vitamin B12 status is unknown . The aims of the present study were to explore the effect of individual supplementation with folic acid or vitamin B12 on tHcy concentrations in hemodialysis ( HD ) patients and to compare changes in tHcy concentrations with MTHFR genotype . METHODS We recruited 200 HD patients ( 119 men ) from the \" Umberto I \" Hospital ( Frosinone , Italy ) and the Dialysis Unit of University Hospital \" Tor Vergata \" . These patients were r and omized blindly into 2 groups of 100 each . Unfortunately , during the study , 36 patients in the first group and 16 in the second group died . The first group was treated initially with vitamin B12 for 2 months and with folic acid for a following 2 months . The second group was treated initially with folic acid and then with vitamin B12 . Sample s were drawn before administration of either , after the first and second periods , and again 2 months after treatment . RESULTS The concentrations of tHcy decreased in both groups after the consecutive vitamin therapies , and the decrease was genotype-dependent . The decrease was greater for the T/T genotype ( P < 0.05 ) and was more significant when the treatment was started with folic acid ( P < 0.01 ) . CONCLUSION The alternating vitamin treatment demonstrated for the first time the importance of folate therapy and the secondary contribution of vitamin B12 in lowering tHcy in HD patients", "Background Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality . Current treatment options include dietary restriction , dialysis , and phosphate binders . Treatment using the latter is frequently limited by cost , tolerability , and calcium loading . One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients . Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis ( PD ) patients already receiving st and ard phosphorus-lowering therapies . Methods An 8 week , r and omized , double blind , placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients . Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were r and omized to niacinamide or placebo and prescribed 250 mg twice daily , with titration to 750 mg twice daily , as long as safety parameters were not violated . Phosphate binders , active vitamin D , and cinacalcet were kept constant during the study . The primary end point was change in plasma phosphorus . Secondary end points included changes in lipid parameters . Results 15 patients started on the study drug ( 8 niacinamide , 7 placebo ) and 7 in each arm had at least one on- study phosphorus measurement . The niacinamide treatment group experienced an average 0.7 ± 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 ± 0.8 mg/dL increase . The treatment effect difference ( 1.1 mg/dL ) was significant ( p = 0.037 ) . No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated . Two of the 8 patients r and omized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects . Adverse effects may limit the use of niacinamide in PD patients . Conclusion Niacinamide , when added to st and ard phosphorus-lowering therapies , result ed in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks . [ Clinical Trials.gov number NCT00508885 ( Clinical Trials.gov )", "Abstract Objective : To evaluate putative risk factors for the development of incipient diabetic nephropathy ( persistent microalbuminuria ) and overt diabetic nephropathy ( persistent macroalbuminuria ) in patients with non-insulin dependent diabetes . Design : Prospect i ve , observational study of a cohort of white , non-insulin dependent diabetic patients followed for a median period of 5.8 years . Setting : Outpatient clinic in tertiary referral centre . Subjects : 191 patients aged under 66 years with non-insulin dependent diabetes and normoalbuminuria ( urinary albumin excretion rate<30 mg/24 h ) who attended the clinic during 1987 . Main outcome measures : Incipient and overt diabetic nephropathy . Results : Fifteen patients were lost to follow up . Thirty six of the 176 remaining developed persistent microalbuminuria ( 30 - 299 mg/24 h in two out of three consecutive 24 hour urine collection s ) and five developed persistent macroalbuminuria ( ≥300 mg/24 h in two out of three consecutive collection s ) during follow up . The five year cumulative incidence of incipient diabetic nephropathy was 23 % ( 95 % confidence interval 17 % to 30 % ) . Cox 's multiple stepwise regression analysis revealed the following risk factors for the development of incipient or overt diabetic nephropathy : increased baseline log urinary albumin excretion rate ( relative risk 11.1 ( 3.4 to 35.9 ) ; P<0.0001 ) ; male sex ( 2.6 ( 1.2 to 5.4 ) ; P<0.02 ) ; presence of retinopathy ( 2.4 ( 1.3 to 4.7 ) ; P<0.01 ) ; increased serum cholesterol concentration ( 1.4 ( 1.1 to 1.7 ) ; P<0.01 ) ; haemoglobin A 1c concentration ( 1.2 ( 1.0 to 1.4 ) ; P<0.05 ) ; and age ( 1.07 ( 1.02 to 1.12 ) ; P<0.01 ) . Known duration of diabetes , body mass index , arterial blood pressure , serum creatinine concentration , pre-existing coronary heart disease , and history of smoking were not risk factors . Conclusion : Several potentially modifiable risk factors predict the development of incipient and overt diabetic nephropathy in normoalbuminuric patients with non-insulin dependent diabetes", "BACKGROUND Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus , it remains uncertain whether microalbuminuria and /or gross proteinuria are independent risk factors for cardiovascular mortality . Moreover , the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US population s. OBJECTIVE To estimate the relative risks ( RRs ) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus . METHODS We conducted a prospect i ve cohort study of 840 people with older-onset diabetes mellitus who provided urine sample s in the 1984 - 1986 examination of a population -based study of diabetic persons . The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip . The main outcome was time to mortality from cardiovascular disease , as determined from death certificates . RESULTS Of the 840 older-onset diabetic persons , 54.8 % had normoalbuminuria , while 24.8 % had microalbuminuria and 20.5 % had gross proteinuria . During the 12-year follow-up ( 6127 person-years ) , we identified 364 deaths from cardiovascular disease . Compared with persons with normoalbuminuria , those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality . The RR as controlled for age , sex , glycemic control , insulin use , alcohol intake , physical activity , cardiovascular disease history , antihypertensive use , and retinopathy severity , was 1.84 ( 95 % confidence interval [ CI ] , 1.42 - 2.40 ) for those with microalbuminuria and 2.61 ( 95 % CI , 1.99 - 3.43 ) for those with gross proteinuria . Further adjustment for other factors did not change the relations we found . When the end point used was mortality from coronary heart disease , stroke , or all causes , the increased risks were significant for both microalbuminuria ( adjusted RRs [ 95 % CIs ] , 1.96 [ 1.42 - 2.72 ] , 2.20 [ 1.29 - 3.75 ] , and 1.68 [ 1.35 - 2.09 ] , respectively ) and gross proteinuria ( adjusted RRs [ 95 % CIs ] , 2.73 [ 1.95 - 3.81 ] , 2.33 [ 1.28 - 4.24 ] , and 2.47 [ 1.97 - 3.10 ] , respectively ) . CONCLUSIONS Results from our population -based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular , cerebrovascular , and coronary heart diseases . These associations were independent of known cardiovascular risk factors and diabetes-related variables", "Abstract Objective : The influence of either orally administered S-benzoylthiamine-O-monophosphate ( benfotiamine ) or thiamine nitrate on the thiamine status was tested in a r and omised , two-group comparison study in 20 end-stage renal disease ( ESRD ) patients . Main outcome measures were the pharmacokinetics of thiamine diphosphate ( TDP ) in blood , the in vitro erythrocyte transketolase activity , its activation coefficient ( α-ETK ) and the TDP concentration in erythrocytes . Methods : After ingestion of a single dose of either 100 mg thiamine nitrate ( corresponding to 305 μmol thiamine ) or 100 mg benfotiamine ( corresponding to 214 μmol thiamine ) , the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period . The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood . Erythrocyte transketolase activity and α-ETK were measured before and 10 h after administration . The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from data base query . Results : Regarding the blood concentrations of TDP , the patients with ESRD had a 4.3 times higher area under the concentration – time curve after benfotiamine administration than after thiamine nitrate . After benfotiamine administration , the peak plasma concentration of TDP exceeded that in healthy subjects by 51 % . In the ESRD patients , after 24 h , the mean TDP concentration in erythrocytes increased from 158.7 ± 30.9 ng/ml initially to 325.8 ± 50.9 ng/ml after administration of benfotiamine and from 166.2 ± 51.9 ng/ml to 200.5 ± 50.0 ng/ml after thiamine nitrate administration . The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66 ± 0.6 in the benfotiamine group and 1.44 ± 0.2 in the group receiving thiamine nitrate ( P < 0.001 ) . After 24 h , it was 2.11 ± 0.4 and 1.23 ± 0.2 , respectively . The transketolase activity increased from 3.54 ± 0.7 μkat/l initially to 3.84 ± 0.6 μkat/l after benfotiamine intake ( P=0.02 ) and from 3.71 ± 0.8 μkat/l to 4.02 ± 0.7 μkat/l after thiamine nitrate intake ( P=0.08 ) . Likewise , α-ETK decreased from initially 1.10 ± 0.07 to 1.04 ± 0.04 ( P=0.04 ) and from 1.12 ± 0.05 to 1.08 ± 0.06 ( P=0.09 ) . After 24 h , the phosphorylation ratio in whole blood decreased from 12.9 ± 6.9 initially to 5.6 ± 3.2 after benfotiamine administration ( P=0.02 ) and from 13.5 ± 7.3 to 9.0 ± 4.8 ( P=0.03 ) after administration of thiamine nitrate . No correlation between erythrocyte TDP concentration and transketolase activity and /or α-ETK was observed in ESRD patients , either before or 10 h after administration . Conclusion : Compared with thiamine nitrate , the oral administration of benfotiamine leads to higher TDP concentrations in erythrocytes accompanied with a significant improvement of the erythrocyte transketolase activity in ESRD patients", "BACKGROUND Elevated plasma homocysteine levels are reported to be associated with higher rates of vascular diseases . Plasma homocysteine increases in chronic kidney disease ( CKD ) and could contribute to the increased cardiovascular risk in CKD . METHODS Participants aged 55 years or older with CKD , defined as estimated GFR<60 ml/min and at high cardiovascular risk , were r and omly assigned to the combination of folic acid , 2.5 mg , vitamin B6 , 50 mg and vitamin B12 , 1 mg ( n = 307 ) or placebo ( n = 312 ) daily for 5 years . The primary outcome was a composite of death from cardiovascular causes , myocardial infa rct ion and stroke . RESULTS Mean baseline plasma homocysteine was 15.9 + /- 7.3 micromol/l in the active treatment group and 15.7 + /- 5.7 micromol/l in placebo group and decreased to 11.9 + /- 3.3 micromol/l ( P < 0.001 ) on active treatment ( 15.5 + /- 4.5 on placebo ) . Primary outcome events occurred in 90 participants ( 29.3 % ) on active therapy and in 80 ( 25.6 % ) on placebo ( relative risk , 1.19 ; 95 % confidence interval , 0.88 - 1.61 ; P = 0.25 ) . There were no significant treatment benefits on death from cardiovascular causes ( 1.24 ; 0.84 - 1.83 ) , myocardial infa rct ion ( 1.10 ; 0.76 - 1.61 ) and stroke ( 1.00 ; 0.54 - 1.85 ) . More participants in the active treatment group were hospitalized for heart failure ( 1.98 ; 1.21 - 3.26 ; P = 0.007 ) and for unstable angina ( 1.70 ; 1.02 - 2.83 ; P = 0.04 ) . Incidence of primary outcome increased with decreasing GFR . CONCLUSIONS Active treatment with B vitamins lowered homocysteine levels in participants with CKD but did not reduce cardiovascular risk", "Background / Aim : Pyridoxine deficiency may be the cause of failure to respond appropriately to iron and erythropoietin ( EPO ) administration in hemodialysis patients . Method : We studied 36 patients on chronic hemodialysis amply supplemented with iron and EPO , who failed to raise hematocrit levels > 33 % . Patients were divided into three equal groups and evaluated for 6 months as follows : Group A – no additional therapy ; group B – supplemented with oral pyridoxine 50 mg/day , and group C received 100 mg/day pyridoxine orally . Results : In all our patients , erythrocyte pyridoxine levels were initially within reference range for a healthy population and did not vary significantly during the study period . Likewise , ferritin levels and iron saturation values remained normal and constant . Hemoglobin and /or hematocrit levels remained practically unchanged in all three groups . Conclusions : The results indicate that in hemodialysis patients with normal pyridoxine status who , despite appropriate supplementation of iron and EPO , fail to reach optimal hematocrit levels , additional pyridoxine treatment does not produce any hematocrit elevation", "The aim of this study was to document , in hyperhomocysteinemic renal transplant recipients , the effect of vitamin supplementation on carotid intima-media thickness ( cIMT ) . Fifty-six hyperhomocysteinemic stable renal transplant recipients were r and omly assigned to either vitamin supplementation ( group A ) or placebo treatment ( group B ) . All patients underwent high-resolution B mode ultrasound to measure IMT of common carotid arteries before and after 6 months of vitamin supplementation . In group A , cIMT significantly decreased after treatment , whereas no significant changes were observed in group B. In conclusion , our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on an early sign of atherosclerosis in a group of renal transplant recipients", "Background . We previously demonstrated among renal-transplant recipients ( RTRs ) a high prevalence of hyperhomocysteinemia , which might account for their elevated cardiovascular risk . The purpose of our study was to document , in hyperhomocysteinemic RTRs , the effect of vitamin supplementation on carotid intima-media thickness ( cIMT ) , which is an early sign of atherosclerosis . Methods . A total of 56 stable hyperhomocysteinemic RTRs were r and omly assigned to vitamin supplementation ( folic acid 5 mg/day ; vitamin B6 50 mg/day ; vitamin B12 400 & mgr;g ) ( group A ) or placebo treatment ( group B ) for 6 months . All subjects underwent cardiovascular risk-factor assessment , including fasting homocysteine ( Hcy ) levels assay , and high resolution B-mode ultrasound to measure the intima-media thickness of common carotid arteries , at time of enrollment and after 6 months . Results . Fasting Hcy levels markedly decreased in group A after treatment ( 21.8 [ 15.5–76.6 ] & mgr;mol/L vs. 9.3 [ 5.8–13 ] & mgr;mol/L;P < 0.0001 ) , whereas no significant changes were observed in group B ( 20.5 [ 17–37.6 ] & mgr;mol/L vs. 20.7 [ 15–34 ] & mgr;mol/L;P = not significant ) . In group A , cIMT significantly decreased after treatment ( 0.95±0.20 mm vs. 0.64±0.17 mm;P < 0.0001 ) . All except one patient showed a reduction of cIMT and the mean percentage of cIMT decrease was −32.2±12.9 % . Patients with methylenetetrahydrofolate reductase ( MTHFR ) C677 T + /+ genotype , with higher Hcy levels , had the major percentage of decrease of Hcy with respect to the other genotypes ( mean decrease : MTHFR + /+ 74.8±5.7 % ; MTHFR ± 58.1±10 % ; MTHFR −/− 56.3±8.6 % ) . In hyperhomocysteinemic patients without vitamin supplementation ( group B ) we documented a significant increase in cIMT after 6 months ( 0.71±0.16 mm vs. 0.87±0.19 mm;P < 0.05 ) . In 19 of 28 subjects we observed an increase in cIMT , and in 9 of 28 the cIMT was unmodified . The mean percentage of cIMT increase was + 23.3±21.1 % . Conclusions . Our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on cIMT in a group of RTRs", "BACKGROUND AND PURPOSE Increased urinary albumin and protein excretion is associated with cardiovascular disease mortality independent of other cardiovascular risk factors in subjects with non-insulin-dependent diabetes mellitus ( NIDDM ) . We assessed the relationship between the different degrees of proteinuria at baseline and the incidence of stroke , as well as other atherosclerotic vascular disease events , in a prospect i ve study of nondiabetic and NIDDM subjects . METHODS Our study was based on the 7-year follow-up of cohorts of nondiabetic ( n = 1375 ) and NIDDM ( n = 1056 ) subjects in Finl and . The urinary protein concentration at baseline was stratified into three categories : no proteinuria ( < 150 mg/L ) , borderline ( 150 to 300 mg/L ) , and clinical proteinuria ( > 300 mg/L ) . RESULTS The association between the different degrees of proteinuria and the atherosclerotic vascular events was similar in nondiabetic and NIDDM subjects . Cardiovascular disease mortality was higher both in nondiabetic and NIDDM subjects with clinical proteinuria than in those without proteinuria . The incidence of stroke was 1.6 % in nondiabetic subjects without proteinuria , 3.2 % in subjects with borderline proteinuria , and 8.5 % in subjects with clinical proteinuria ( P < .001 for trend ) . In NIDDM patients , the corresponding rates were 7.2 % , 11.1 % , and 23.0 % , respectively ( P < .001 for trend ) . The association between clinical proteinuria and the incidence of stroke remained significant both in nondiabetic and in NIDDM subjects after adjustment for other cardiovascular risk factors . Clinical proteinuria was also associated with the incidence of coronary heart disease events and that of lower-extremity amputation . NIDDM independently increased the risk of atherosclerotic vascular disease events regardless of the proteinuria status . CONCLUSIONS Clinical proteinuria significantly predicted stroke and other atherosclerotic vascular disease events independent of other cardiovascular risk factors . This finding is compatible with the view that increased urinary protein excretion rate may be associated with widespread vascular damage", "BACKGROUND High-efficiency hemodialysis may induce a deficiency in hydrosoluble vitamins . Supplementation with B-complex vitamins has been shown to lower serum homocysteine concentrations in several groups , but relatively few studies have concerned hemodialysis patients . Our objectives were to determine the status in B-complex vitamins in a large cohort of unsupplemented hemodialysis patients and to assess the effects of supplementation with hydrosoluble vitamins on serum homocysteine over one year . METHODS Serum total homocysteine ( tHcy ) , vitamin B12 , folate , pyridoxal-5'-phosphate ( P-5'-P ; the active moiety of vitamin B6 ) , as well as red blood cell folate concentrations , were measured in 168 chronic dialysis patients on three times weekly high-efficiency hemodialysis and not supplemented with hydrosoluble vitamins . Their methylenetetrahydrofolate reductase C677 T ( MTHFR ) genotypes were also determined ( homozygotes TT , heterozygotes CT , without mutation CC ) . All involved patients were then supplemented with hydrosoluble vitamins ( once daily by mouth , DiaVite ; R&D Laboratories , Minneapolis , MN , USA ) , and half of them were r and omized to receive in addition 10 mg intravenously of folic acid posthemodialysis ( 30 mg intravenously per week ) . Serum tHcy was monitored after 6 and 12 months of supplementation in the 140 and 128 patients available for follow-up . RESULTS At baseline , serum and red blood cell folate concentrations were within normal limits in all patients except for two with borderline serum folate ( mean values of 21 + /- 8 and 1195 + /- 454 nmol/L ) , whereas serum vitamin B12 and P-5'-P were below normal in 11 and 65 patients , respectively ( mean values of 327 + /- 215 pmol/L and 19 + /- 16 nmol/L for the 168 patients ) . Initial tHcy levels were increased in all patients ( mean 33.3 + /- 16.6 for a normal below 11.8 + /- 1.5 micromol/L ) ; tHcy significantly decreased to 23.5 + /- 7.6 micromol/L after six months ( P < 0.0001 vs. baseline ) and to 21.7 + /- 6.1 micromol/L after 12 months ( P < 0.0001 vs. baseline ) for the entire group , but was normalized in only four patients at 12 months . After six months , the mean reduction in tHcy was slightly but significantly greater for patients receiving intravenous folic acid ( 12.2 + /- 18.5 micromol/L ) compared with patients not receiving it ( 8.3 + /- 9.8 micromol/L , P < 0.05 ) . However , at 12 months , no difference between both subgroups persisted . When considering the different genotypes , tHcy at baseline tended to be higher for TT than CT and CC ( 39.8 + /- 30.9 vs. 31.4 + /- 10.5 vs. 31.6 + /- 11.8 micromol/L ) and decreased to respective values of 21.1 + /- 6.9 versus 21.4 + /- 6.1 versus 22.2 + /- 5.9 micromol/L at 12 months . The impact of the addition of folic acid to DiaVite appeared particularly significant in TT patients at six months . CONCLUSIONS ( 1 ) Hyperhomocysteinemia was present in 100 % of our hemodialysis patients . ( 2 ) Nearly 40 % of our unsupplemented hemodialysis patients were deficient in vitamin B6 . ( 3 ) Supplementation with DiaVite(R ) has result ed in significant tHcy reductions for all three genotypes . ( 4 ) The impact of the proposed supplementation protocol was found after six months and was maintained , but did not increase further after 12 months of the same regimen . ( 5 ) The addition of intravenous folic acid has been associated with a more pronounced decrease in tHcy in TT patients", "BACKGROUND The control of hyperglycemia is of major importance in the treatment of patients with type 1 diabetes mellitus . However , there is no consensus about the required degree of metabolic control in patients with type 2 diabetes mellitus and about the role of hyperglycemia in diabetic nephropathy and in the development of atherosclerosis in relation to other risk factors . PATIENTS AND METHODS A prospect i ve , long-term follow-up study was conducted on 574 patients , aged 40 to 60 years , with recent onset of type 2 diabetes mellitus . Patients were initially normotensive and had normal renal function and a normal urinary albumin excretion rate ( < 30 mg/24 h ) . The patients were followed up for 2 to 9 years ( mean + /- SD , 7.8 + /- 0.9 years ) . Levels of hemoglobin A1c and plasma lipids , mean blood pressure , and body mass index ( calculated as the weight in kilograms divided by the square of the height in meters ) were determined periodically . Cigarette smoking and socioeconomic status were recorded . Renal status was evaluated by the logarithm of the final urinary albumin excretion rate and by the decline in reciprocal creatinine values . Definite clinical events including death , nonfatal myocardial infa rct ion , angina pectoris , congestive heart failure , and peripheral vascular disease were recorded . RESULTS At the end of the study the urinary albumin excretion rate remained normal ( < 30 mg/24 h ) in 373 patients ( 65 % ) , 111 ( 19 % ) had microalbuminuria ( 30 - 300 mg/24 h ) , and 90 ( 16 % ) had overt albuminuria ( > 300 mg/24 h ) . Logistic regression models demonstrated that the correlation between hemoglobin A1c levels and the risk of albuminuria is exponential . Multiple logistic regression analysis indicated that levels of total cholesterol , mean blood pressure , and hemoglobin A1c were the main factors associated with the decrease in renal function and with the increase in albuminuria . The combination of values higher than the 50th percentile of all 3 factors defined a high-risk patient population . These high-risk patients had an odds ratio of 43 ( 95 % confidence interval , 25 - 106 ) for microalbuminuria and 15 ( 95 % confidence interval , 9 - 25 ) for clinical events related to arteriosclerosis compared with the rest of the group . Low levels of high-density lipoprotein , body mass index , cigarette smoking , low socioeconomic status , and male sex were all significantly associated with diabetic nephropathy , as well as with the manifestations of arteriosclerosis . CONCLUSIONS The combination of blood pressure values in the high-normal range with moderately elevated levels of total cholesterol and hemoglobin A1c defines a high-risk group for the progression to diabetic nephropathy and for clinical events related to arteriosclerotic cardiovascular disease", "BACKGROUND The progression of nephropathy from diagnosis of type 2 diabetes has not been well described from a single population . This study sought to describe the development and progression through the stages of microalbuminuria , macroalbuminuria , persistently elevated plasma creatinine or renal replacement therapy ( RRT ) , and death . METHODS Using observed and modeled data from 5097 subjects in the UK Prospect i ve Diabetes Study , we measured the annual probability of transition from stage to stage ( incidence ) , prevalence , cumulative incidence , ten-year survival , median duration per stage , and risk of death from all-causes or cardiovascular disease . RESULTS From diagnosis of diabetes , progression to microalbuminuria occurred at 2.0 % per year , from microalbuminuria to macroalbuminuria at 2.8 % per year , and from macroalbuminuria to elevated plasma creatinine ( > or=175 micromol/L ) or renal replacement therapy at 2.3 % per year . Ten years following diagnosis of diabetes , the prevalence of microalbuminuria was 24.9 % , of macroalbuminuria was 5.3 % , and of elevated plasma creatinine or RRT was 0.8 % . Patients with elevated plasma creatinine or RRT had an annual death rate of 19.2 % ( 95 % confidence interval , CI , 14.0 to 24.4 % ) . There was a trend for increasing risk of cardiovascular death with increasing nephropathy ( P < 0.0001 ) , with an annual rate of 0.7 % for subjects in the stage of no nephropathy , 2.0 % for those with microalbuminuria , 3.5 % for those with macroalbuminuria , and 12.1 % with elevated plasma creatinine or RRT . Individuals with macroalbuminuria were more likely to die in any year than to develop renal failure . CONCLUSIONS The proportion of patients with type 2 diabetes who develop microalbuminuria is substantial with one quarter affected by 10 years from diagnosis . Relatively fewer patients develop macroalbuminuria , but in those who do , the death rate exceeds the rate of progression to worse nephropathy", "OBJECTIVE To compare the effect of a normal protein diet ( test diet ) in which chicken and fish were substituted for red meat with a low-protein diet ( LPD ) on glomerular nitration rate ( GFR ) in normoalbuminuric insulin-dependent-diabetes mellitus ( IDDM ) patients . RESEARCH DESIGN AND METHODS A crossover r and omized clinical trial was performed in 15 normoalbuminuric IDDM patients , 9 normofiltering , and 6 hyperfiltering patients . They followed three diets for a 3-week period each : a usual diet ( UD ) , an LPD ( 0.5 g · kg–1 · day–1 of proteins , 7 % calories as protein , 33 % as fat , and 60 % as carbohydrates ) , and a normoproteic isocaloric test diet in which white meat ( chicken and fish ) was substituted for red meat of the UD . At the end of each diet , a clinical evaluation and measurements of GFR ( 51Cr-ethylenediaminetetraacetate ( EDTA ) single injection technique ) , urinary albumin excretion ( UAE ) , and plasma amino acids were performed . Dietary compliance was assessed by a 24-h urinary urea and weekly interviews with the dietitian . RESULTS In all diabetic patients , GFR after the LPD ( 114.9 ± 16.5ml · min–1 · 1.73 m∼2 ) and after the test diet ( 122.7 ± 16.7 ml · min–1 · 1.73 m∼2 ) was significantly lower than after the UD ( 132.0 ± 27.7 ml · min–1 · 1.73 m∼2 ) ( P = 0.001 ) . Similar results were found in the hyperfiltering group : after UD = 161.1 ± 15.4 ml · min–1 · 1.73 m–2 , after LPD = 129.8 ± 9.0 ml-min–1 · 1.73 m–2 , and after the test diet = 136.5 ± 3.1 ml · min–1 · 1.73 m–2 , ( P < 0.001 ) . In the normofiltering group , no significant changes in GFR were observed after the three diets . Metabolic control , nutritional indexes , blood pressure ( BP ) , and UAE did not change after the three diets in all patients . CONCLUSIONS A normoproteic diet with chicken and fish as the only meat protein source decreases the GFR in the hyperfiltering normoalbuminuric IDDM patients . The GFR reduction after this diet is similar to that observed after an LPD", "BACKGROUND AND OBJECTIVES Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies . A prospect i ve , r and omized , double-blind , placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Hemodialysis patients with phosphorus levels > or = 5.0 mg/dl were r and omly assigned to 8 wk of niacinamide or placebo , titrated from 500 to 1500 mg/d . After a 2-wk washout period , patients switched to 8 wk of the alternative therapy . Vitamin D analogs and calcimimetics were held constant ; phosphorus binders were not changed unless safety criteria were met . RESULTS Thirty-three patients successfully completed the trial . Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo ( 5.85 to 5.98 mg/dl ) . A concurrent fall in calcium-phosphorus product was seen with niacinamide , whereas serum calcium , intact parathyroid hormone , uric acid , platelet , triglyceride , LDL , and total cholesterol levels remained stable in both arms . Serum HDL levels rose with niacinamide ( 50 to 61 mg/dl but not with placebo . Adverse effects were similar between both groups . Among patients who were > or = 80 % compliant , results were similar , although the decrease in serum phosphorus with niacinamide was more pronounced ( 6.45 to 5.28 mg/dl ) and the increase in HDL approached significance ( 49 to 58 mg/dl ) . CONCLUSIONS In hemodialysis patients , niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol . Further study in larger r and omized trials and other chronic kidney disease population s is indicated", "OBJECTIVE In a comparative study with 20 end-stage renal disease ( ESRD ) patients the pharmacokinetics of two therapeutically used thiamine ( vitamin B1 ) preparations were assessed . SUBJECTS , MATERIAL AND METHODS After a single oral dose of either 100 mg benfotiamin ( S-benzoylthiamine-o-monophosphate , BTMP ) or 100 mg thiamine mononitrate ( TN ) , blood levels of thiamine phosphate esters were analyzed by HPLC after precolumn derivatization to thiochrome phosphate esters for a 24-hour period . RESULTS The pharmacokinetic parameters AUC0 - 24h , Cmax and tmax of the benfotiamin group in whole blood and plasma exceeded significantly those in the TN group . Only 1.0 vs. 0.6 % of the administered dose were excreted in urine in the BTMP group and TN group , respectively . A high cellular efficacy , as was concluded from the short-term stimulation of the thiamine-dependent transketolase activity in erythrocytes ( ETKA ) , was assessed for BTMP as well as TN . The activation coefficient ( ETK-AC ) decreased significantly from 1.10 to 1.04 vs. 1.12 to 1.07 in both the BTMP as well as TN groups , respectively . In addition , a high transfer rate to thiamine diphosphate ( TDP ) was observed in the patients after ingestion of BTMP . The TDP concentration in whole blood increased by 2.6 and 1.4 times from baseline levels to Cmax in the BTMP and TN groups , respectively . The AUC0 - 24h of TDP in whole blood after BTMP ingestion exceeded those after TN ingestion by 420 % . CONCLUSION These findings justify the therapeutic application of BTMP in ESRD , because a high intracellular concentration of TDP may protect against numerous adverse effects of uremia in the long run", "Hyperhomocysteinemia , an arteriosclerotic risk factor , persists in 75 % of dialysis patients despite routine low dose supplementation with the B-vitamin co-factors/substrates for homocysteine ( Hcy ) metabolism , and normal or supernormal plasma status of these vitamins ( Atherosclerosis 114:93 , 1995 ) . We conducted a placebo-controlled eight-week trial of the effect on plasma homocysteine of adding supraphysiologic dose folic acid ( 15 mg/day ) , B-6 ( 100 mg/day ) , and B-12 ( 1 mg/day ) to the usual daily dosing of 1 mg folic acid , 10 mg B-6 , and 12 micrograms B-12 , in 27 hyperhomocysteinemic dialysis patients . Total plasma homocysteine was measured at baseline , and after four and eight weeks . Blinded analyses revealed no evidence of toxicity in the group r and omized to supraphysiologic dose B-vitamin supplementation . Plasma homocysteine was significantly reduced after both four weeks ( -29.8 % vs. -2.0 % ; P = 0.0024 ) and eight weeks ( -25.8 % vs. + 0.6 % ; P = 0.0009 ) of active versus placebo treatment . Also , 5 of 15 treated versus 0 of 12 placebo group patients had their plasma Hcy reduced to within the normative range ( < 15 mumol/liter ) . Supraphysiologic doses of B-vitamins may be required to correct hyperhomocysteinemia in dialysis patients", "BACKGROUND Plasma homocysteine is elevated in patients with end-stage renal disease ( ESRD ) and is a risk factor for cardiovascular disease . Folic acid has been shown to partially reduce homocysteine levels in dialysis patients . It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient . AIM To determine whether 1 mg vitamin B12 lowers homocysteine in stable , chronic , haemodialysis patients independent of folic acid . METHODS Twenty-eight haemodialysis patients were r and omized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals . Fasting plasma total homocysteine , folic acid , red-cell folate , vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection . The study was powered to detect a 30 % reduction in homocysteine over the 3 months . RESULTS Both the two groups were well matched with respect to total homocysteine levels , folic acid , red-cell folate and vitamin B12 levels . Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo ( 217.7 pmol/L ; 95 % confidence interval ( CI ) 103.0 - 332.5 ; P < 0.001 ) at the end of the trial but homocysteine levels were not significantly different ( 3.08 micromol/L ; 95 % CI -4.44 - 10.61 ; P= 0.406 ) . CONCLUSIONS The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status , however reductions of < 30 % can not be excluded by the present study . High-dose folic acid remains the treatment of choice in reducing homocysteine , but whether this results in a reduction in cardiovascular events remains to be determined", "BACKGROUND Hyper-homocyst(e)inemia is an independent risk factor for atherosclerotic vascular disease in patients with end-stage renal disease ( ESRD ) , although optimal treatment remains unknown . This r and omized , double-blind , placebo-controlled study was design ed to measure the effect of high-dose oral vitamin B(12 ) and folic acid on predialysis total homocyst(e)ine levels in patients with ESRD . METHODS We studied 81 hemodialysis patients who had hyper-homocyst(e)inemia ( > 16 micromol/L ) on varied doses of a multivitamin containing 1 mg of folic acid/day . After screening blood work , all patients were switched to daily multivitamin therapy , including 1 mg of folic acid for four weeks . For all patients , vitamin B(12 ) , 1 mg/day , was added for an additional four weeks . Patients were then r and omized to receive four weeks of 0 , 5 , or 20 mg of folic acid in addition to the multivitamin and vitamin B(12 ) ( all given daily ) . RESULTS Screening homocyst(e)ine levels ( mean 27.7 micromol/L ) decreased by 19.2 % after four weeks of treatment with a daily multivitamin containing 1 mg of folic acid ( P < 0.001 ) . Homocyst(e)ine levels were reduced further from 22.3 to 18.6 micromol/L ( mean reduction 16.7 % , 95 % CI 11.8 to 21.6 % , P < 0.001 ) after four weeks of therapy with vitamin B(12 ) ( 1 mg/day ) . There was no significant difference in mean reduction of homocyst(e)ine levels after therapy with high-dose folic acid compared with placebo ( P = 0.35 ) . CONCLUSIONS The optimal oral treatment of hyper-homocyst(e)inemia in hemodialysis patients consists of 1 mg of folic acid and 1 mg of oral vitamin B(12 ) daily . Whether this treatment will lower the risk of future atherosclerotic vascular events remains to be investigated", "BACKGROUND In patients with type 2 diabetes , the effects of intensive glucose control on vascular outcomes remain uncertain . METHODS We r and omly assigned 11,140 patients with type 2 diabetes to undergo either st and ard glucose control or intensive glucose control , defined as the use of gliclazide ( modified release ) plus other drugs as required to achieve a glycated hemoglobin value of 6.5 % or less . Primary end points were composites of major macrovascular events ( death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke ) and major microvascular events ( new or worsening nephropathy or retinopathy ) , assessed both jointly and separately . RESULTS After a median of 5 years of follow-up , the mean glycated hemoglobin level was lower in the intensive-control group ( 6.5 % ) than in the st and ard-control group ( 7.3 % ) . Intensive control reduced the incidence of combined major macrovascular and microvascular events ( 18.1 % , vs. 20.0 % with st and ard control ; hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.82 to 0.98 ; P=0.01 ) , as well as that of major microvascular events ( 9.4 % vs. 10.9 % ; hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , primarily because of a reduction in the incidence of nephropathy ( 4.1 % vs. 5.2 % ; hazard ratio , 0.79 ; 95 % CI , 0.66 to 0.93 ; P=0.006 ) , with no significant effect on retinopathy ( P=0.50 ) . There were no significant effects of the type of glucose control on major macrovascular events ( hazard ratio with intensive control , 0.94 ; 95 % CI , 0.84 to 1.06 ; P=0.32 ) , death from cardiovascular causes ( hazard ratio with intensive control , 0.88 ; 95 % CI , 0.74 to 1.04 ; P=0.12 ) , or death from any cause ( hazard ratio with intensive control , 0.93 ; 95 % CI , 0.83 to 1.06 ; P=0.28 ) . Severe hypoglycemia , although uncommon , was more common in the intensive-control group ( 2.7 % , vs. 1.5 % in the st and ard-control group ; hazard ratio , 1.86 ; 95 % CI , 1.42 to 2.40 ; P<0.001 ) . CONCLUSIONS A strategy of intensive glucose control , involving gliclazide ( modified release ) and other drugs as required , that lowered the glycated hemoglobin value to 6.5 % yielded a 10 % relative reduction in the combined outcome of major macrovascular and microvascular events , primarily as a consequence of a 21 % relative reduction in nephropathy . ( Clinical Trials.gov number , NCT00145925 .", "Background — In observational studies , hyperhomocysteinemia has been found to be a risk factor for total mortality and cardiovascular events in patients with end-stage renal disease . These patients have grossly elevated homocysteine levels that can be lowered by supplementation with folic acid and vitamin B12 . We conducted a r and omized clinical trial with B vitamins to reduce homocysteine levels and therefore cardiovascular events and total mortality . Methods and Results — This r and omized , double-blind multicenter study was conducted in 33 dialysis centers in north and east Germany between July 2002 and July 2008 . We r and omly assigned 650 patients with end-stage renal disease who were undergoing hemodialysis to 2 postdialysis treatments : 5 mg folic acid , 50 & mgr;g vitamin B12 , and 20 mg vitamin B6 ( active treatment ) or 0.2 mg folic acid , 4 & mgr;g vitamin B12 , and 1.0 mg vitamin B6 ( placebo ) given 3 times per week for an average of 2 years . The primary outcome was total mortality ; the secondary outcome was fatal and nonfatal cardiovascular events . The primary outcome occurred in 102 patients ( 31 % ) receiving the active treatment and in 92 ( 28 % ) receiving placebo ( hazard ratio , 1.13 ; 95 % confidence interval , 0.85 to 1.50 ; P=0.51 ) . The secondary outcome occurred in 83 patients ( 25 % ) receiving the active treatment and in 98 ( 30 % ) receiving placebo ( hazard ratio , 0.80 ; 95 % confidence interval , 0.60 to 1.07 ; P=0.13 ) . Conclusions — Increased intake of folic acid , vitamin B12 , and vitamin B6 did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease . Clinical Trial Registration — URL : www.anzctr.org.au . Unique identifier : ACTRN12609000911291 . URL : www.cochrane-renal.org . Unique identifier : CRG010600027" ]

[ "5571451", "12411035", "7793195", "4895339", "7006441", "378022", "8291726", "19943458", "8317641", "17158129", "15777291", "4014617", "8694158", "5007074", "2378593", "7072998", "11213000", "15636826", "5926260", "6696214", "10401882", "8001404" ]

[ "Comparative Effect of Pethidine, Trichloroethylene, and Entonox on Fetal and Neonatal Acid-Base and Po2", "Clinical study on labor pain relief using the combined spinal-epidural analgesia and inhaling nitrous oxide.", "Desflurane analgesia for vaginal delivery", "Methoxyflurane and Nitrous Oxide as Obstetric Analgesics. II.—A Comparison by Self-administered Intermittent Inhalation", "Maternal opinion about analgesia for labour", "Self‐administered intermittent nitrous oxide analgesia for labour", "Nitrous Oxide in Early Labor Safety and Analgesic Efficacy Assessed by a Double‐blind, Placebo‐controlled Study", "Entonox for labor pain: a randomized placebo controlled trial.", "Isoflurane in labour", "Analgesia with sevoflurane during labour: ii. Sevoflurane compared with Entonox for labour analgesia.", "Comparison of remifentanil and nitrous oxide in labour analgesia", "Self‐administered isoflurane in labour", "Gas kinetics during nitrous oxide analgesia for labour", "Kidney Function after Methoxyflurane Analgesia during Labour", "Effectiveness of transcutaneous electric nerve stimulator for pain relief in labour.", "Neonatal Neurobehavioral Effects of Inhalation Analgesia for: Vaginal Delivery", "A randomised controlled trial of epidural compared with non‐epidural analgesia in labour", "Self-administered mixture of Entonox and isoflurane in labour.", "Methoxyflurane as an obstetric analgesic: a comparison with trichloroethylene.", "Enflurane as an analgesic in labour", "Hormone replacement therapy and colon cancer among members of a health maintenance organization.", "[Application of nitrous oxide in labor analgesia]." ]

[ "The second stage of labour is associated with relative fetal hypoxia and progressive metabolic acidosis . Maternal analgesia can increase the danger , especially for the high-risk fetus . In 152 patients the effect on the fetus of pethidine alone , pethidine + trichloroethylene , or pethidine + Entonox was assessed by fetal scalp blood sampling . Fetal pH , Pco2 , and Po2 were measured and base excess was calculated . Capillary sample s were also taken 45 to 60 minutes after birth in 88 of the babies to estimate the rate of neonatal recovery . Entonox proved safer than trichloroethylene , and babies treated with it maintained their Po2 before birth , had better Apgar scores at birth , and one hour later were significantly less acidotic and much better oxygenated", "OBJECTIVE To study the pain relief effectiveness of the combined spinal-epidural analgesia ( CSEA ) and the inhalation of nitrous oxide , and the influences on the mothers and infants . METHODS The 300 cases of pregnant women were r and omly divided into 3 groups : CSEA group , nitrous oxide group and control group . The nitrous oxide group was that pregnant women inhaled nitrous oxide premixed with oxygen ( 50%:50 % ) , the pregnant women of the CSEA group were injected fentanyl and bupivacaine in the subarachnoid and epidural space , analgesic was not used in the control group . The degree of labor pain , duration of the labor , way of delivery , bleeding volume , rate of anoxia of newborn , blood gas analysis to maternal radius artery and fetal umbilical blood among 3 groups were observed . RESULTS The effect for analgesia labor of the CSEA group was much better than that of the nitrous oxide group ( P < 0.01 ) . In the first stage of labor and total stage of labor , the CSEA group was shorter than the others ( P < 0.05 ) , but there was no difference between the nitrous oxide group and the control group ( P > 0.05 ) . In the second stage of labor , the 3 groups were alike to each other . The bleeding volume of caesarean section ( 373 + /- 77 ) ml in the nitrous oxide group was much more than the other 2 groups , there was no difference between the CSEA group ( 259 + /- 78 ) ml and the control group ( 239 + /- 89 ) ml . The rate of obstetric forceps of CSEA group was higher than the control group ( P < 0.01 ) , and the rate of caesarean section of the nitrous oxide group was much higher than the CSEA group . The blood gas analysis to maternal radius artery and fetal umbilical blood and the rate of anoxia of newborn of 3 groups revealed no significant difference . CONCLUSIONS The effectiveness of the combined spinal-epidural analgesia CSEA for analgesia labor is confirmed and has rarely side-effect , and it can be the first choice , and the inhalation of nitrous oxide can safely provide effective labor analgesia , too", "The use of subanaesthetic concentration of inhalational anaesthetic for vaginal delivery offers many advantages to the mother and newborn‐ Desflurane , with the characteristics of rapid onset and minimal metabolism , may provide better analgesia and safety for labour pain control", "Methoxyflurane ( 0·35 % ) in air and nitrous oxide/oxygen ( 50%/50 % ) self-administered intermittently in the usual way have been compared as analgesics for labour . There were 25 patients in each group . Objective assessment by an anaesthetist showed that methoxyflurane is the more effective analgesic , and this was supported by the opinion of the multiparae . Nausea and vomiting were significantly less with methoxyflurane . Fifty per cent . nitrous oxide in oxygen given intermittently does not appear to be the best analgesic concentration . Nevertheless , since a considerable variation in sensitivity exists , it would probably be unwise to consider the introduction of higher concentrations for use by unsupervised midwives . This trial confirms the predictions made by us using a method for screening inhalational analgesics , in which methoxyflurane and nitrous oxide were given continuously", "In a r and omised controlled trial epidural analgesia with bupivacaine 0·5 % ( mean dose 112·8 mg ) was compared with pethidine ( mean dose 200 mg ) and inhalational analgesia in primipara ( 28 and 30 mothers ) and multipara ( 17 and 18 mothers ) . Mothers who had an uneventful pregnancy and labour and agreed to have either treatment were studied during labour and followed‐up at interviews for 5 months after delivery . Epidural block was rated significantly superior in respect of pain relief and comfort , there were no differences between the groups in reports of perineal discomfort . Twice as many primipara required forceps delivery after epidural block . Very few mothers , in each group , reported something missing in their experience of childbirth . Two thirds of each group would use the same method again . Epidural block can therefore be recommended to uncommitted mothers as a satisfying and effective method of pain relief for labour", "Since Minnitt ’ introduced an apparatus for the self-administration of nitrous oxide in air during labour , many attempts have been made to improve its effectiveness . One investigatorZ suggested the substitution of air by oxygen , so that a higher concentration of nitrous oxide could be used . It was found3 that 70 % nitrous oxide with 30 % oxygen was the optimum analgesic mixture but this led to a small and unacceptable incidence of mothers who became unconscious4 and therefore 50 % nitrous oxide with 50 % oxygen is recommended for use by midwives . The arterial concentration of nitrous oxide , which is relatively insoluble , rapidly equilibrates with the inspired concentration but when used intermittently for short periods there is always a vital delay between starting self-administration and reaching an effective arterial concentration . On stopping self-administration between uterine contractions nitrous oxide is almost completely eliminated , so that the start of each inhalation is a re-induction . Timing is therefore crucial to successful pain relief with nitrous oxide analge ~ ia.~ When breathed continuously , the inspired concentration being adjusted by an anaesthetist , the optimum mean concentration of nitrous oxide for pain relief in labour was 41.2%.6 However , when 50 % nitrous oxide with 50 % oxygen is self-administered intermittently during labour , in the usual way , the mean peak arterial concentration is equivalent to 26.4 % nitrous oxide concentration . ’ In an attempt to reduce the vital need for accurate timing a low concentration of nitrous oxide has been administered continuously by the nasal route , and in volunteers,8 and mothers in labour.g This raised the end-tidal concentration at the beginning of each period of selfadministration . This study extends those investigations . During labour , the reduction in time to reach specified end-expired nitrous oxide concentrations has been measured during each period of inhalation and the effectiveness of a nasal supplement to intermittent inhalation of Entonox has been assessed", "Background Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor , but its efficacy has not been adequately established . Questions about its effect on maternal oxygenation between labor contractions also have been raised . Methods Twenty-six women were recrulted to participate in a r and omized , double-blind , cross-over , placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation ( SpO2 ) during the first stage of labor . Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air . Results Mean visual analog scale pain scores for five contractions were 5.1 , 5.2 , 5.7 , 5.2 , and 5.6 ( nitrous oxide ) and 4.9 , 5.2 , 6.1 , 5.6 , and 5.7 ( compressed air ) . There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered . Pain scores did not differ significantly over time as a function of inhaled substance ( F = 0.41 , P = 0.53 ) . The mean lowest SpO2 observed between these contractions after self-administration of nitrous oxide and air were 97 , 97 , 97 , 97 , and 97 % ( nitrous oxide ) and 97 , 96 , 96 , 96 , and 96 % ( compressed air ) . SpO2 was significantly higher after nitrous oxide administration ( F = 8.8 , P = 0.007 ) . Conclusions While intermittent self-administered 50 % nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation , its analgesic effect has yet to be clearly demonstrated", "This study aims to investigate the effectiveness of nitrous oxide on pain of labor contractions and on maternal SaO2 . The patients were r and omized to receive either a pre-prepared mixture of 50 % nitrous oxide and oxygen or 50 % oxygen by a coin . Study drugs started as early as the onset of pain with each contraction . The patient herself administered gases via a facemask connected to the uni-directional valve which enables the patients to breathe fresh gas in each inspiration . The gas administration was continued to the end of contraction pain at which the patient breathed the room air . Variables such as SaO2 , blood pressure , pain and side effects were recorded . 534 ASA I and II parturients , aged from 16 to 35 years , scheduled for elective labor from September 2004 to 2006 were evaluated . Four patients were lost from the study . The mean age of patients was 25.5+/-4.3 years . During the first three measurements , the SaO2 was significantly higher in control group . In addition , the mean arterial pressure was comparable between groups except two first measurements in which the control group was higher . All the Visual Analogue Scale ( VAS ) values were significantly lower in nitrous oxide group . There were no significant differences in 1st and 5th min apgar scores between groups . All of the side effects were significantly higher among patients in nitrous oxide . In conclusion , our data indicate that using nitrous oxide 50 % provides significant pain relief . Nonetheless , it is associated with few side effects , nitrous oxide can be quickly implemented during advanced painful labor", "A comparison of the analgesic efficacy of Entonox ( 50 % nitrous oxide in oxygen ) and Entonox with 0.2 % isofturane was made in 18 consenting mothers during the first stage of labour . The inhalational gases were self‐administered during contractions over a 3 h study period using a st and ard Entonox dem and valve and breathing system . Isoflurane 0.2 % was added from an Ohmeda Isotec drawover vaporizer and the inspired concentration ofisoflurane was analysed continuously using a Date x Ultima analyser . Linear analogue scores for pain were significantly lower ( p < 0.001 ) during the Entonox‐isoflurane administration compared with Entonox alone . Drowsiness was not a clinical problem and there was a high acceptance rate for Entonox‐isoflurane inhalational analgesia during labour", "BACKGROUND We determined the optimal inspired sevoflurane concentration for use during labour as 0.8 % in our previous study . This study compared sevoflurane at a concentration of 0.8 % and Entonox((R ) ) ( nitrous oxide 50 % : oxygen 50 % ) for analgesia during labour in 32 healthy parturients . METHODS Each mother underwent two open-label , three-part sequences in r and om order , Entonox-sevoflurane-Entonox or sevoflurane-Entonox-sevoflurane . In each part the agent was self-administered during 10 contractions . A 100 mm visual analogue scores for pain relief and sedation was completed immediately after each contraction . RESULTS Two patients withdrew during administration of sevoflurane ( because of its odour ) and five during Entonox ( requesting epidural analgesia ) . Of the remaining women , data were available for analysis from 29 participants : median ( IQR [ range ] ) pain relief scores were significantly higher for sevoflurane 67 ( 55 - 74 [ 33 - 100 ] ) mm than for Entonox 51 ( 40 - 69.5 [ 13 - 100 ] ) mm ( P<0.037 ) . Nausea and vomiting were more common in the Entonox group [ relative risk 2.7 ( 95 % CI 1.3 - 5.7 ) ; P=0.004 ] . No other adverse effects were observed in the mothers or babies . There was significantly more sedation with sevoflurane than with Entonox { 74 ( 66.5 - 81 [ 32.5 - 100 ] ) and 51 ( 41 - 69.5 [ 13 - 100 ] ) mm , respectively ; P<0.001}. Twenty-nine patients preferred sevoflurane to Entonox and found its sedative effects helpful . CONCLUSIONS We conclude that self-administered sevoflurane at subanaesthetic concentration ( 0.8 % ) can provide useful pain relief during the first stage of labour , and to a greater extent than Entonox . Although greater sedative effects were experienced with sevoflurane , it was preferred to Entonox", "Background : We compared the efficacy and side‐effects of remifentanil with those of nitrous oxide during the first stage of labour", "Entonox ( 50 % nitrous oxide in oxygen ) and isoflurane ( 0.75 % in oxygen ) were compared as analgesics in the first stage of labour in 32 consenting women . The drugs were self‐administered and given in r and om sequence , each during five consecutive uterine contractions . Each patient acted as her own control . Linear analogue pain scores were signijicantly lower ( p < 0.001 ) with isoflurane than with Entonox , but scores for drowsiness were higher for isoflurane . Further study is needed to assess the effects of more prolonged use of isoflurane in labour", "Hypoxaemia may occur after hyperventilation with nitrous oxide during labour . The purpose of this study was to assess whether diffusion hypoxia is a contributory factor . Twenty‐four parturients were r and omly allocated to receive 50 or 70 % nitrous oxide in oxygen . The median nitrous oxide inhalation time per contraction was 58 s and 33 s , respectively . The end‐tidal carbon dioxide and the minute ventilation remained unchanged . The end‐tidal oxygen concentration was lowest at 120s , reaching 15.4 % in both groups . The oxygen saturation did not differ between the groups with a lowest median value of 96 % before the start of nitrous oxide inhalation . Two parturients had episodes ofdesaturation . Both had low end‐tidal oxygen concentrations in association with the desaturation but , as the end‐tidal nitrous oxide concentrations were low , the desaturations could not be attributed to diffusion hypoxia", "In a study of the effects of methoxyflurane on renal function , the urinary and blood urea concentrations , the urinary and plasma osmolalities , and the packed cell volume were studied in each of 50 mothers before and after delivery . Methoxyflurane 0·35 % was used as an analgesic in 25 patients and the other 25 had 50 % nitrous oxide and 50 % oxygen ( Entonox ) . There was no evidence of renal dysfunction in either group , nor were there any significant differences between the groups . In a further 200 mothers , of whom 100 had methoxyflurane and 100 had nitrous oxide analgesia , the urinary and blood urea concentrations were measured on the morning of discharge from hospital . There were no significant differences between the groups . These results suggest that methoxyflurane is not nephrotoxic when used as a self-administered analgesic", "The effectiveness of transcutaneous electric nerve stimulation ( TENS ) for pain relief in labour was compared to inhalation analgesia consisting of 50 % nitrous oxide and 50 % oxygen ( ENTONOX ) . In the first part of the study 101 patients in early labour were allocated to using TENS ( Group A ) or ENTONOX ( Group B ) for pain relief . Our results did not show any beneficial effect on pain relief in labour with the use of TENS over ENTONOX ; 18.8 % of patients in Group A went through labour without any further form of analgesia as opposed to 17.0 % in Group B. In the second part of the study 20 nulliparous patients having induced labour were r and omly allocated to use TENS ( Group C ) or ENTONOX ( Group D ) as the first modality of pain relief . A switchover was made when labour pains were no longer tolerable . The results showed that both TENS and ENTONOX could be used in early labour up to 5 - 6 cm cervical dilatation till the frequency of contractions was nearly 5 in 10 min or the first 3 - 4 hr from the time patients first requested pain relief in labour when frequency of contractions was nearly 4 in 10 min . TENS could be used in early labour for patients who wish to be ambulant and is as effective as ENTONOX . Either modality of pain relief was not adequate for pain relief throughout labour", "The authors studied the neonatal neurobehavioral effects of nitrous oxide : oxygen and enflurane : oxygen inhalation analgesia for vaginal delivery . Parturients were assigned r and omly to receive no inhalation agent ( Group 1 , n = 21 ) ; enflurane , 0.3 to 0.8 per cent , and oxygen ( Group 2 , n = 22 ) ; or nitrous oxide , 30 to 50 per cent , and oxygen ( Group 3 , n = 18 ) . Infants were tested at 15 min , 2 h , and 24 h of age using the Neurologic and Adaptive Capacity Score ( NACS ) ; and at 2 and 24 h using the Early Neonatal Neurobehavioral Scale ( ENNS ) . No significant differences in neurobehavioral status occurred . For all groups , scores tended to be lowest at two hours of age . We conclude that neither enflurane nor nitrous oxide analgesia adversely affects neonatal neurobehavioral status at 15 min , 2 h , or 24 h of age", "Objectives To investigate possible short and long term side effects of epidural analgesia , compared with non‐epidural analgesia for pain relief in labour", "Entonox ( 50 % nitrous oxide premixed in oxygen ) was compared with a mixture of Entonox and approximately 0.25 % isoflurane ( Entonox-isoflurane ) for pain relief in the first stage of labour in 39 mothers . An Oxford Miniature Vaporizer was incorporated as the draw-over vaporizer for adding isoflurane to Entonox . The mixture was self-administered via the Entonox on-dem and valve . The two mixtures were given in r and om sequence for five consecutive contractions of labour to each patient . Linear analogue pain relief scores were significantly higher ( P=0.001 ) with Entonox-isoflurane . Fourteen patients continued using Entonox-isoflurane until delivery . No adverse effect from prolonged use was noted . Entonox-isoflurane is considered worthy of further investigation", "Log^n , R. F. L. , and Eimerl , T. S. ( 1965 ) . Millbank mem . Fd Quart . , 43 , No. 2 , Pt . 2 , pp . 302 - 310 . Logan , W. P. D. , and Cushion , A. A. ( 1958 ) . G.R.O. Stud , on Med . and Pop . Subj . No. 14 , vol . 1 , Morbidity Statistics from General Practice . H.M.S.O. , London . Ministry of Health ( 1965 ) . Annual Report for 1964 . H.M.S.O. , London . Peterson , O. L. , And rews , L. T. , Spain , R. F. , and Greenberg , B. G ( 1956 ) . J. med . Educ , 31 , No. 12 , Pi . 1 , pp . 1 - 165 . Querido , A. ( 1963 ) . The Efficiency of Medical Cjve . Stenfert-Kroese , Leiden . van der Wielen , V. ( 1960 ) . M.D. Thesis : \" The General Practitioner and the Effectiveness of his Share in the Care of Health . \" Leiden", "A comparison of the analgesic efficacy of enfrurane 1 % in air with Entonox ( 50 % nitrous oxide in oxygen ) was performed in 20 consenting women during the first stage of labour . The two drugs were given in a r and om sequence to each woman , who also acted as her own control . Pain scores were significantly lower with enfrurane than Entonox , although drowsiness scores were higher . No untoward effects were reported with either agent . The use of enflurane as an analgesic in the first stage of labour warrants further investigation", "We investigated the association between hormone replacement therapy ( HRT ) , primarily conjugated estrogens with or without medroxyprogesterone acetate , and colon cancer risk in a nested case-control study among women ages 55 - 79 years enrolled in Group Health Cooperative , a health maintenance organization in Washington state . Cases were diagnosed between 1984 and 1993 . We selected controls r and omly from enrollment files . HRT use was ascertained from a computerized data base containing virtually all prescriptions dispensed since 1977 . Among subjects with at least 5 years of pharmacy data base information before reference date ( 1 year before diagnosis date ) , there were 341 cases of incident colon cancer and 1,679 controls . Estrogen use during the 5 years before reference date was not associated with risk of colon cancer [ odds ratio ( OR ) = 0.85 and 95 % confidence interval ( CI ) = 0.57 - 1.27 for 1 - 749 estrogen tablets ; OR = 0.97 and 95 % CI = 0.68 - 1.40 for > or = 750 estrogen tablets ] . An analysis including only women with at least 10 years of pharmacy data base coverage found no association with use during the 10 years before reference date [ OR = 1.07 ( 95 % CI = 0.61 - 1.86 ) for 1 - 749 estrogen tablets ; OR = 1.11 ( 95 % CI = 0.69 - 1.80 ) for 750 or more estrogen tablets ] . These results do not support the hypothesis that recent HRT use substantially reduces risk of colon cancer", "Labor analgesia with nitrous oxide was studied in 34 parturients , and another 50 women taking no drug as the control group . The analgesic effect was satisfactory . By Mulleetr 's pain in labor score , 91.18 % women had score of 0 - 1 , and their respiratory and circulatory functions were not affected . During inhalational analgesia the parturients remained conscious . Uterine contraction , progress of labor and neonatal Apgar score were not interferred , and postpartum bleeding was not increased . There was no complications in the treatment group . This study suggests that nitrous oxide with enough oxygen inhalation is one of the good drug for obstetric analgesia , but its concentration must be strictly controlled" ]

[ "4120317", "22555112", "11448327", "20538634", "27457470", "24777708", "15513444", "19669678", "25227499", "17976724", "2443361", "4431059", "15947806", "24084500", "19948277", "4855017", "24461586", "22289279", "17978682", "19167602" ]

[ "Cost-effectiveness of ranibizumab and bevacizumab for age-related macular degeneration: 2-year findings from the IVAN randomised trial", "Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results.", "Development of the 25-item National Eye Institute Visual Function Questionnaire.", "Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study", "The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus Aflibercept in the UK", "The cost-utility of aflibercept for the treatment of age-related macular degeneration compared to bevacizumab and ranibizumab and the influence of model parameters", "Cost of care for patients with age-related macular degeneration in Switzerland and cost-effectiveness of treatment with verteporfin therapy", "Cost-effectiveness of ranibizumab compared with pegaptanib in neovascular age-related macular degeneration", "Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol.", "A value-based medicine analysis of ranibizumab for the treatment of subfoveal neovascular macular degeneration.", "Cost-effectiveness of ranibizumab for neovascular age-related macular degeneration", "The cost-effectiveness of initiating ranibizumab therapy in eyes with neovascular AMD with good vision: an economic model using real-world outcomes", "Drug pricing for a novel treatment for wet macular degeneration: using incremental cost-effectiveness ratios to ensure societal value.", "Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies.", "Verteporfin photodynamic therapy cohort study: report 2: clinical measures of vision and health-related quality of life.", "Different Strategies for the Treatment of Age-Related Macular Degeneration in China: An Economic Evaluation", "The neovascular age-related macular degeneration database: multicenter study of 92 976 ranibizumab injections: report 1: visual acuity.", "Cost-effectiveness analysis of ranibizumab versus verteporfin photodynamic therapy, pegaptanib sodium, and best supportive care for the treatment of age-related macular degeneration in Greece.", "[Cost-effectiveness of photodynamic therapy with verteporfin for choroidal neovascularization in age-related macular degeneration in routine clinical practice in Switzerland].", "Cost-effectiveness of ranibizumab compared with photodynamic treatment of neovascular age-related macular degeneration." ]

[ "Objective To assess the incremental cost and cost-effectiveness of continuous and discontinuous regimens of bevacizumab ( Avastin ) and ranibizumab ( Lucentis ) for neovascular age-related macular degeneration ( nAMD ) from a UK National Health Service ( NHS ) perspective . Design A within-trial cost-utility analysis with a 2-year time horizon , based on a multicentre factorial , non-inferiority r and omised controlled trial . Setting 23 hospital ophthalmology clinics . Participants 610 patients aged ≥50 years with untreated nAMD in the study eye . Interventions 0.5 mg ranibizumab or 1.25 mg bevacizumab given continuously ( monthly ) or discontinuously ( as-needed ) for 2 years . Main outcome measures Quality -adjusted life-years ( QALYs ) . Results Total 2-year costs ranged from £ 3002/patient ( $ 4700 ; 95 % CI £ 2601 to £ 3403 ) for discontinuous bevacizumab to £ 18 590/patient ( $ 29 106 ; 95 % CI £ 18 258 to £ 18 922 ) for continuous ranibizumab . Ranibizumab was significantly more costly than bevacizumab for both continuous ( + £ 14 989/patient ( $ 23 468 ) ; 95 % CI £ 14 522 to £ 15 456 ; p<0.001 ) and discontinuous treatment ( + £ 8498 ( $ 13 305 ) ; 95 % CI £ 7700 to £ 9295 ; p<0.001 ) , with negligible difference in QALYs . Continuous ranibizumab would only be cost-effective compared with continuous bevacizumab if the NHS were willing to pay £ 3.5 million ( $ 5.5 million ) per additional QALY gained . Patients receiving continuous bevacizumab accrued higher total costs ( + £ 599 ( $ 938 ) ; 95 % CI £ 91 to £ 1107 ; p=0.021 ) than those receiving discontinuous bevacizumab , but also accrued non-significantly more QALYs ( + 0.020 ; 95 % CI −0.032 to 0.071 ; p=0.452 ) . Continuous bevacizumab therefore cost £ 30 220 ( $ 47 316 ) per QALY gained versus discontinuous bevacizumab . However , bootstrapping demonstrated that if the NHS is willing to pay £ 20 000/QALY gained , there is a 37 % chance that continuous bevacizumab is cost-effective versus discontinuous bevacizumab . Conclusions Ranibizumab is not cost-effective compared with bevacizumab , being substantially more costly and producing little or no QALY gain . Discontinuous bevacizumab is likely to be the most cost-effective of the four treatment strategies evaluated in this UK trial , although there is a 37 % chance that continuous bevacizumab is cost-effective . Trial registration number IS RCT N92166560", "OBJECTIVE To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment . DESIGN Multicenter , r and omized clinical trial . PARTICIPANTS Patients ( n = 1107 ) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial . INTERVENTIONS At enrollment , patients were assigned to 4 treatment groups defined by drug ( ranibizumab or bevacizumab ) and dosing regimen ( monthly or as needed ) . At 1 year , patients initially assigned to monthly treatment were reassigned r and omly to monthly or as-needed treatment , without changing the drug assignment . MAIN OUTCOME MEASURES Mean change in visual acuity . RESULTS Among patients following the same regimen for 2 years , mean gain in visual acuity was similar for both drugs ( bevacizumab-ranibizumab difference , -1.4 letters ; 95 % confidence interval [ CI ] , -3.7 to 0.8 ; P = 0.21 ) . Mean gain was greater for monthly than for as-needed treatment ( difference , -2.4 letters ; 95 % CI , -4.8 to -0.1 ; P = 0.046 ) . The proportion without fluid ranged from 13.9 % in the bevacizumab-as-needed group to 45.5 % in the ranibizumab monthly group ( drug , P = 0.0003 ; regimen , P < 0.0001 ) . Switching from monthly to as-needed treatment result ed in greater mean decrease in vision during year 2 ( -2.2 letters ; P = 0.03 ) and a lower proportion without fluid ( -19 % ; P < 0.0001 ) . Rates of death and arteriothrombotic events were similar for both drugs ( P > 0.60 ) . The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab ( 39.9 % vs. 31.7 % ; adjusted risk ratio , 1.30 ; 95 % CI , 1.07 - 1.57 ; P = 0.009 ) . Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor ( VEGF ) . CONCLUSIONS Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period . Treatment as needed result ed in less gain in visual acuity , whether instituted at enrollment or after 1 year of monthly treatment . There were no differences between drugs in rates of death or arteriothrombotic events . The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF", "OBJECTIVE To develop and test the psychometric properties of a 25-item version of the National Eye Institute Visual Function Question naire ( NEI VFQ-25 ) . DESIGN Prospect i ve observational cohort study of persons with 1 of 5 chronic eye diseases or low vision who were scheduled for nonurgent visits in ophthalmology practice s and a reference sample of persons without eye disease . SETTING Eleven university-based ophthalmology practice s and the NEI Clinical Center . PATIENTS Eligible participants had to have 1 of the following eye conditions : age-related cataracts , age-related macular degeneration , diabetic retinopathy , primary open-angle glaucoma , cytomegalovirus retinitis , or low vision from any cause . Seven of the 12 sites also enrolled persons in a reference sample . Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error . All eligible persons had to be 21 years or older , English speaking , and cognitively able to give informed consent and participate in a health status interview . MEASUREMENTS AND MAIN RESULTS To provide the data needed to create the NEI VFQ-25 , all subjects completed an interview that included the 51-item NEI VFQ . Estimates of internal consistency indicate that the subscales of the NEI VFQ-25 are reliable . The validity of the NEI VFQ-25 is supported by high correlations between the short- and long-form versions of the measure , observed between-group differences in scores for persons with different eye diseases of varying severity , and the moderate-to-high correlations between the NEI VFQ-25 subscales that have the most to do with central vision and measured visual acuity . CONCLUSIONS The reliability and validity of the NEI VFQ-25 are comparable to those of the 51-item NEI VFQ field test version of the survey . This shorter version will be more feasible in setting s such as clinical trials where interview length is a critical consideration . In addition , preliminary analyses indicate that the psychometric properties of the NEI VFQ-25 are robust for the eye conditions studied ; this suggests that the measure will provide reproducible and valid data when used across multiple conditions of varying severity", "Objectives To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration . Design Prospect i ve , double masked , multicentre , r and omised controlled trial . Setting Three ophthalmology centres in the United Kingdom . Participants 131 patients ( mean age 81 ) with wet age related macular degeneration r and omised 1:1 to intervention or control . Interventions Intravitreous bevacizumab ( 1.25 mg , three loading injections at six week intervals followed by further treatment if required at six week intervals ) or st and ard treatment available at the start of the trial ( photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration , or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration ) . Main outcome measures Primary outcome : proportion of patients gaining ≥15 letters of visual acuity at one year ( 54 weeks ) . Secondary outcomes : proportion of patients with stable vision and mean change in visual acuity . Results Of the 131 patients enrolled in the trial , five patients did not complete the study because of adverse events , loss to follow-up , or death . In the bevacizumab group , 21 ( 32 % ) patients gained 15 or more letters from baseline visual acuity compared with two ( 3 % ) in the st and ard care group ( P<0.001 ) ; the estimated adjusted odds ratio was 18.1 ( 95 % confidence interval 3.6 to 91.2 ) and the number needed to treat was 4 ( 3 to 6 ) . In addition , the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment ( 91 % ( 59 ) v 67 % ( 44 ) in st and ard care group ; P<0.001 ) . Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the st and ard care group ( P<0.001 ) , and the initial improvement at week 18 ( plus 6.6 letters ) was sustained to week 54 . Among 65 patients treated with bevacizumab , there were no cases of endophthalmitis or serious uveitis related to the intervention . All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over st and ard care . Conclusions Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to st and ard care ( pegaptanib sodium , verteporfin , sham ) , with low rates of serious ocular adverse events . Treatment improved visual acuity on average at 54 weeks . Trial registration number Current controlled trials IS RCT", "Introduction Wet age-related macular degeneration ( AMD ) is a chronic eye condition that causes severe deterioration of vision and even blindness . Current wet AMD treatment in the UK involves the vascular endothelial growth factor inhibitors ranibizumab and aflibercept . Patients with wet AMD require frequent and long-term monitoring for treatment to be effective , contributing to a substantial re source burden at wet AMD centers . The European license for ranibizumab was recently up date d with an individualized ‘ treat and extend ’ ( T&E ) regimen , comprising a structured monitoring and treatment protocol . This study evaluated the cost-effectiveness of ranibizumab T&E versus aflibercept within a UK setting . Methods An individual patient-level simulation model was developed utilizing treatment effects from a network meta- analysis of r and omized controlled trials . The model was conducted from a UK National Health Service ( NHS ) perspective over a lifetime horizon and the base case utilized probabilistic sensitivity analysis to assess uncertainty in the model . Additional scenario analyses were conducted to assess the impact of changes to the model inputs . Results Ranibizumab T&E was found to be more effective and less costly than aflibercept , providing , on average , an additional 1.058 quality -adjusted life years ( QALYs ) and a cost-saving of £ 19,604 over a lifetime horizon . At list price , ranibizumab T&E was found to be cost-effective versus aflibercept in 100 % of simulations at a willingness-to-pay threshold of £ 20,000 per QALY . The robustness of the results was tested in several scenario analyses ; ranibizumab T&E was found to be more effective , and less costly , than aflibercept in the vast majority of cases . Conclusion This evaluation suggests that treating patients with ranibizumab according to the T&E regimen could be a better use of NHS re sources than aflibercept , and could , therefore , be considered as a first-line regimen for patients with wet AMD in the UK . Funding Novartis Pharmaceuticals UK Limited", "Background Age-related macular degeneration ( AMD ) is a blinding disease placing considerable burden on society due to blindness-associated costs . Intravitreal anti — vascular endothelial growth factors ( anti-VEGFs ) are effective in reducing the incidence of blindness , but at potentially high costs , depending on the cost of the drug used . Aflibercept has been introduced as an anti-VEGF equally effective to ranibizumab , but less costly . For this new drug , new cost-effectiveness analyses are needed , and AMD models used today give biased results . We investigated the cost-effectiveness of aflibercept compared to bevacizumab , ranibizumab , and no treatment and studied the influence of commonly used model parameters . Methods A patient-level , visual acuity-based , 2-eye model was developed . Data on effectiveness were derived from r and omized controlled trials evaluating the outcomes of aflibercept , bevacizumab , and ranibizumab . Utility and re source utilization were assessed in interviews with AMD patients . Costs were based on st and ard health care cost prices . Time horizons were two and five years . A societal perspective was employed . Results Over five years , costs associated with aflibercept treatment were € 36,030 , with 2.15 QALYs . Costs associated with the bevacizumab regimens , ABC study as-needed ( PRN ) ; CATT study PRN ; and CATT study 1 × /month , were € 19,367 ; € 26,746 ; and € 30,520 , with 2.16 ; 2.17 ; and 2.15 QALYs , respectively . Costs associated with ranibizumab PRN and 1 × /month were € 45,491 and € 74,837 with 2.16 and 2.15 QALYs , respectively . ‘ No treatment ’ was associated with € 9530 and 1.96 QALYs . The incremental cost-effectiveness ratios versus ‘ no treatment ’ were : aflibercept—€140,274 ; bevacizumab—€51,062 ( ABC PRN ) , € 83,256 ( CATT PRN ) and € 110,361 ( 1 × /month ) ; ranibizumab—€181,667 ( PRN ) and € 349,773 ( 1 × /month ) . Results were highly dependent on whether only one or both eyes were included , length of time horizon , and whether the costs of blindness and low-vision were included in the analysis . Conclusions Aflibercept is a cost-effective treatment for AMD over ranibizumab . However , aflibercept is not a cost-effective treatment when compared to bevacizumab . Application of inappropriate model assumptions leads to a biased cost-saving estimate of the cost-effectiveness of aflibercept . Therefore , cost-effectiveness analyses should be conducted with appropriate models", "The cost-effectiveness of photodynamic therapy with verteporfin in the treatment of patients with predominantly classic subfoveal choroidal neovascularization secondary to age-related macular degeneration was investigated by a Markov Model over a time horizon of three years in Switzerl and . This model describes patients moving between three levels of visual acuity ( e.g. , good vision , impaired vision , highly impaired vision ) and death in terms of transition probabilities . Transition probabilities as well as effectiveness values were derived from a r and omized , controlled , double-masked clinical trial . Effectiveness for verteporfin therapy and for placebo was calculated in terms of vision years : 1.068 and 0.494 , respectively . Cost per level of visual acuity was assessed in ascending order by expert panels from a societal perspective . Cost strongly increased parallel with vision loss on a patient-per-year basis from 4683 CHF at good vision to 8443 CHF at impaired vision , and was highest with 15231 CHF at highly impaired vision . The model-calculated cost per visionyear were 14907 CHF for patients in the verteporfin therapy group , versus 21047 CHF for patients in the placebo group . The incremental cost per vision-year additionally saved through verteporfin therapy was 9624 CHF . The study demonstrated that greater effectiveness of verteporfin therapy versus placebo compensated for the cost of the therapy so that verteporfin therapy was clearly costeffective . Therefore , for the indicated patients with AMD that causes severe vision loss , verteporfin therapy can be recommended as the therapy of choice , on both clinical and economic grounds", "Objective To assess the cost-effectiveness of ranibizumab compared with pegaptanib in the treatment of patients with minimally classic/occult neovascular age-related macular degeneration ( AMD ) , from a societal perspective in Spain . Methods We constructed a Markov model with five states defined by visual acuity ( VA ) in the better-seeing eye ( Snellen scale ) : VA > 20/40 , ≤20/40 to > 20/80 , ≤20/80 to > 20/200 , ≤20/200 to > 20/400 , ≤20/400 , and an additional death state . Two cohorts of patients were distributed along the VA states , and treated with either ranibizumab or pegaptanib . Transition probabilities assigned for movement between these states with both drugs were obtained from published r and omized clinical trials . Medical costs related to AMD treatment and follow-up , medical costs related to AMD comorbidities , and non-medical-related costs were taken into account . Costs ( 2008 Euro ) , health outcomes ( Quality -adjusted life years — QALYs ) , both discounted at a 3.5 % annual rate , and incremental cost-effectiveness ratios ( ICER : € /QALY ) , were determined for a lifetime horizon in the base case analysis . Sensitivity analyses were conducted to explore different scenarios and assumptions in the model . Results Treating patients with varying degrees of visual impairment with monthly ranibizumab instead of pegaptanib was € 71,206 more costly and provided 2.437 additional QALYs ( € 29,224/QALY ) . When administered on an as-needed basis , as in the Prospect i ve Optical Coherence Tomography Imaging of Patients with Neovascular AMD Treated with Intraocular Ranibizumab ( PrONTO ) trial , the cost per QALY gained with ranibizumab was reduced to € 4,623 . Conclusions The cost per QALY gained with monthly ranibizumab compared with pegaptanib in the minimally classic/occult neovascular AMD population is just below the € 30,000 threshold below which new drugs are sometimes regarded as cost-effective strategies in Spain . In this model , the key variables with greater impact on the cost-effectiveness results were the selected time horizon and the chosen extrapolation method , the source for data on pegaptanib efficacy and the number of ranibizumab injections . When administered on an as-needed basis , ranibizumab was a cost-effective strategy compared to pegaptanib in this population", "PURPOSE To compare the efficacy and safety of bevacizumab versus ranibizumab when administered according to a treat- and -extend protocol for the treatment of neovascular age-related macular degeneration ( AMD ) . DESIGN Multicenter , r and omized , noninferiority trial with a noninferiority limit of 5 letters . PARTICIPANTS Patients aged ≥ 50 years with previously untreated neovascular AMD in 1 eye and best-corrected visual acuity ( BCVA ) between 20/25 and 20/320 . METHODS Patients were r and omly assigned to receive ranibizumab 0.5 mg or bevacizumab 1.25 mg intravitreal injections . Monthly injections were given until inactive disease was achieved . The patients were then followed with a gradual extension of treatment interval by 2 weeks at a time up to a maximum of 12 weeks . If signs of recurrent disease appeared , the treatment interval was shortened by 2 weeks at a time . MAIN OUTCOME MEASURES Change in visual acuity at 1 year . RESULTS Between March 2009 and July 2012 , 441 patients were r and omized at 10 ophthalmological centers in Norway . The 1-year visit was completed by 371 patients . In the per protocol analysis at 1 year , bevacizumab was equivalent to ranibizumab , with 7.9 and 8.2 mean letters gained , respectively ( 95 % confidence interval [ CI ] of mean difference , -2.4 to 2.9 ; P = 0.845 ) . The intention-to-treat analysis was concordant . There was no significant difference in measured central retinal thickness ( CRT ) , with a mean decrease of -112 μm for bevacizumab and -120 μm for ranibizumab ( 95 % CI of mean difference , -13 to 28 ; P = 0.460 ) . There was a statistically significant difference ( P = 0.001 ) between the drugs regarding the number of treatments : 8.9 for bevacizumab and 8.0 for ranibizumab . There were fewer arteriothrombotic events in the bevacizumab group ( 1.4 % ) than in the ranibizumab group ( 4.5 % ) ( P = 0.050 ) and significantly more cardiac events in the ranibizumab group ( P = 0.036 ) . However , patients treated with ranibizumab more often had a history of myocardial infa rct ion ( P = 0.021 ) . CONCLUSIONS Bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year when administered according to a treat- and -extend protocol . The visual acuity results at 1 year were comparable to those of other clinical trials with monthly treatment . The numbers of serious adverse events were small", "OBJECTIVE To assess the conferred value and average cost-utility ( cost-effectiveness ) for intravitreal ranibizumab used to treat occult/minimally classic subfoveal choroidal neovascularization associated with age-related macular degeneration ( AMD ) . DESIGN Value-based medicine cost-utility analysis . PARTICIPANTS MARINA ( Minimally Classic/Occult Trial of the Anti-Vascular Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular AMD ) Study patients utilizing published primary data . METHODS Reference case , third-party insurer perspective , cost-utility analysis using 2006 United States dollars . MAIN OUTCOME MEASURES Conferred value in the forms of ( 1 ) quality -adjusted life-years ( QALYs ) and ( 2 ) percent improvement in health-related quality of life . Cost-utility is expressed in terms of dollars expended per QALY gained . All outcomes are discounted at a 3 % annual rate , as recommended by the Panel on Cost-effectiveness in Health and Medicine . Data are presented for the second-eye model , first-eye model , and combined model . RESULTS Twenty-two intravitreal injections of 0.5 mg of ranibizumab administered over a 2-year period confer 1.039 QALYs , or a 15.8 % improvement in quality of life for the 12-year period of the second-eye model reference case of occult/minimally classic age-related subfoveal choroidal neovascularization . The reference case treatment cost is $ 52652 , and the cost-utility for the second-eye model is $ 50691/QALY . The quality -of-life gain from the first-eye model is 6.4 % and the cost-utility is $ 123887 , whereas the most clinical ly simulating combined model yields a quality -of-life gain of 10.4 % and cost-utility of $ 74169 . CONCLUSIONS By conventional st and ards and the most commonly used second-eye and combined models , intravitreal ranibizumab administered for occult/minimally classic subfoveal choroidal neovascularization is a cost-effective therapy . Ranibizumab treatment confers considerably greater value than other neovascular macular degeneration pharmaceutical therapies that have been studied in r and omized clinical trials", "Background Intravitreal ranibizumab prevents vision loss and improves visual acuity in patients with neovascular age-related macular degeneration , but it is expensive , and efficacy beyond 2 years is uncertain . Methods We assessed the cost-effectiveness of ranibizumab compared with no ranibizumab over 10 years , using r and omized trial efficacy data for the first 2 years , post-trial efficacy assumptions , and ranibizumab acquisition costs ranging from the wholesale price ( $ 1,950 per dose ) to the price of bevazicumab ( $ 50 ) , a similar molecule which may be equally efficacious . We used a computer simulation model to estimate the probability of blindness , the number of quality -adjusted life-years ( QALYs ) , direct costs ( in 2004 U.S. dollars ) , and cost-effectiveness ratios for a 67-year old woman . Costs and QALYs were discounted at 3 % per year . Results The probability of blindness over 10 years was reduced from 56 % to 34 % if ranibizumab was efficacious for only 2 years , 27 % if efficacy was maintained for a further 2 years only ( base-case scenario ) , and 17 % if visual acuity at 4 years was then sustained . It was cost-saving under all price assumptions , when caregiver costs were included . When caregiver costs were excluded , the cost per QALY for the base-case ranged from $ 5,600 , assuming the bevazicumab price , to $ 91,900 assuming the wholesale ranibizumab price . The cost per QALY was < $ 50,000 when the cost of ranibizumab was less than $ 1000 . Conclusion From a societal perspective , ranibizumab was cost-saving . From a health care funder 's perspective , ranibizumab was an efficient treatment when it cost less than $ 1000 per dose", "Objectives To evaluate the cost-effectiveness of immediate treatment with ranibizumab in patients with neovascular age-related macular degeneration ( nAMD ) with good ( better than 6/12 ) starting visual acuity compared with current UK clinical guidance of waiting until vision falls below 6/12 to begin treatment , using real-world outcomes data . Design A patient-level health economic state transition model based on levels of visual acuity in the better seeing eye was constructed to simulate the costs and consequences of treating patients with nAMD with ranibizumab . Setting The model took the perspective of the UK National Health Service ( NHS ) . Participants The model was populated with real-world outcomes and re source use from a prospect i ve multicentre national nAMD data base study containing 92 976 ranibizumab treatment episodes . Interventions Two treatment approaches were compared : immediate intervention with 0.5 mg ranibizumab pro re nata , PRN ( on detection of nAMD ) or delayed intervention ( waiting until vision fell to 6/12 before beginning treatment ) . Main outcome measures Quality -adjusted life years ( QALYs ) for health states and healthcare costs were accrued for each strategy , and an incremental cost-effectiveness ratio ( ICER ) was calculated . One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model . Results Over a 2-year time horizon , based on 10 000 Monte Carlo simulations , the early treatment arm accumulated 1.59 QALYs and £ 8469.79 cost . The delayed treatment arm accumulated 1.35 QALYs and £ 7460.21 cost . The central ICER estimate was £ 4251.60 . Conclusions A model based on real-world data is likely to be a realistic reflection of the health gains and re source use of ranibizumab for nAMD in the UK NHS . Initiating treatment immediately with ranibizumab PRN regimen is a cost-effective strategy compared with current guidance of initiating treatment at a level of 6/12 or worse vision", "OBJECTIVE Health economic models can assist policy-makers in determining the value of novel treatments from the viewpoint of society . In this context , value is defined as the benefit of treatment , given its cost . A new treatment for wet age-related macular degeneration ( AMD ) , juxtascleral administration of anecortave acetate , 15 mg for depot suspension ( Retaane ) , is now in a late-phase clinical trial . In a theoretical analysis , we sought to determine the cost at which this treatment might offer economic value to society , using incremental cost-effectiveness ratios ( ICERs ) . METHODS A series of 1-year cost-utility models was created for the investigational treatment and st and ard treatment ( photodynamic therapy [ PDT ] with verteporfin [ Visudyne ] ) . Value to society was defined in terms of theoretical associated ICERs ( in US dollars ) : $ 100,000 per quality -adjusted life-year ( QALY ) , $ 50,000/QALY , $ 20,000/QALY and $ 0/QALY , the point of economic indifference . Models were created from the societal perspective and included a patient-derived utility assessment involving regression equations to estimate time trade-off preferences , event probabilities derived from a r and omized clinical trial comparing the safety and efficacy of anecortave administration and PDT with verteporfin , decision analysis and relevant costing information . RESULTS An ICER of $ 100,000/QALY would be associated with an anecortave cost of $ 3022/vial , an ICER of $ 50,000/QALY with an anecortave cost of $ 2986/vial and an ICER of $ 20,000/QALY with an anecortave cost of $ 2964/vial . The point of economic indifference between anecortave administration and st and ard therapy would occur with an anecortave cost of $ 2950/vial . INTERPRETATION In theory , an anecortave cost of $ 2986/vial is associated with an ICER of $ 50,000/QALY , the threshold used by many health technology assessment and reimbursement agencies", "PURPOSE To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration ( AMD ) during a second year of variable dosing after a first-year fixed-dosing period . DESIGN Two r and omized , double-masked , active-controlled , phase 3 trials . PARTICIPANTS Two thous and four hundred fifty-seven patients with neovascular AMD . METHODS From baseline to week 52 , patients received 0.5 mg intravitreal ranibizumab every 4 weeks ( Rq4 ) , 2 mg aflibercept every 4 weeks ( 2q4 ) , 0.5 mg aflibercept every 4 weeks ( 0.5q4 ) , or 2 mg aflibercept every 8 weeks ( 2q8 ) after 3 monthly injections . During weeks 52 through 96 , patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and m and atory dosing at least every 12 weeks . MAIN OUTCOME MEASURES Proportion of eyes at week 96 that maintained best-corrected visual acuity ( BCVA ; lost < 15 letters from baseline ) ; change from baseline in BCVA . RESULTS Proportions of eyes maintaining BCVA across treatments were 94.4 % to 96.1 % at week 52 and 91.5 % to 92.4 % at week 96 . Mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96 . Proportions of eyes without retinal fluid decreased from week 52 ( 60.3 % to 72.4 % ) to week 96 ( 44.6 % to 54.4 % ) , and more 2q4 eyes were without fluid at weeks 52 and 96 than Rq4 eyes ( difference of 10.4 % [ 95 % confidence interval { CI } , 4.9 - 15.9 ] and 9.0 % [ 95 % CI , 3.0 - 15.1 ] ) . Patients received on average 16.5 , 16.0 , 16.2 , and 11.2 injections over 96 weeks and 4.7 , 4.1 , 4.6 , and 4.2 injections during weeks 52 through 96 in the Rq4 , 2q4 , 0.5q4 , and 2q8 groups , respectively . The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group ( differences of -0.64 [ 95 % CI , -0.89 to -0.40 ] and -0.55 [ 95 % CI , -0.79 to -0.30 ] ; P < 0.0001 , post hoc analysis ) . Incidences of Antiplatelet Trialists ' Collaboration-defined arterial thromboembolic events were similar across groups ( 2.4 % to 3.8 % ) from baseline to week 96 . CONCLUSIONS All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks . The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks , but with an average of 5 fewer injections . Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing", "PURPOSE To quantify decreases in health-related quality of life ( HRQoL ) for given deterioration in clinical measures of vision ; to describe the shape of these relationships ; and to test whether the gradients of these relationships change with duration of visual loss . DESIGN A prospect i ve , longitudinal study of patients treated with verteporfin photodynamic therapy in the United Kingdom National Health Service . PARTICIPANTS Patients with neovascular age-related macular degeneration ( AMD ) treated in 18 ophthalmology departments in the United Kingdom with expertise in management of neovascular AMD . METHODS Responses to HRQoL question naires ( Short Form 36 [ SF-36 ] and National Eye Institute Visual Functioning Question naire [ NEIVFQ ] ) and clinical measures of vision were recorded at baseline and at follow-up visits . Mixed regression models were used to characterize the relationships of interest . MAIN OUTCOME MEASURES Measures of vision were best-corrected visual acuity ( BCVA ) and contrast sensitivity ( CS ) . The SF-36 physical and mental component scores ( PCS and MCS ) , SF-6D utility , and distance , near , and composite NEIVFQ scores were derived to characterize HRQoL. RESULTS The SF-6D , PCS , and MCS were linearly associated with BCVA ; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 0.0058 , 0.245 , and 0.546 , respectively ( all P<0.0001 ) . Gradients were not influenced by duration of follow-up . Models predicting distance , near , and composite NEIVFQ scores from BCVA were quadratic ; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 5.08 , 5.48 , and 3.90 , respectively ( all P<0.0001 ) . The BCVA predicted HRQoL scores more strongly than CS . CONCLUSIONS Clinical ly significant deterioration in clinical measures of vision is associated with small decreases in generic and vision-specific HRQoL. Our findings are important for further research modeling the cost effectiveness of current and future interventions for neovascular AMD", "Purpose . To assess the cost-effectiveness of bevacizumab compared to ranibizumab , verteporfin photodynamic therapy ( PDT ) , and usual care for the treatment of age-related macular degeneration ( AMD ) in China . Methods . A Markov model was developed according to patient visual acuity ( VA ) in the better-seeing eye ( Snellen scale ) . Four cohorts of patients were treated with one of the following therapies : bevacizumab , ranibizumab , PDT , or usual care . Clinical data related to treatments were obtained from published r and omized clinical trials . Direct medical costs and re source utilization in the Chinese health care setting were taken into account . Health and economic outcomes were evaluated over a lifetime horizon . Sensitivity analyses were performed . Results . Treatment with ranibizumab provided the greatest gains in quality -adjusted life-years ( QALYs ) . The cost per marginal QALY gained with bevacizumab over usual care was $ 1,258 , $ 3,803 , and $ 2,066 for the predominantly classic , minimally classic , and occult lesions , respectively . One-way sensitivity analysis showed considerably influential factors , such as utility values and effectiveness data . Probabilistic sensitivity analysis indicated that , compared to usual care , PDT and ranibizumab most cases would be cost-effective in the bevacizumab arm at a threshold of $ 7,480/QALY . Conclusion . Bevacizumab can be a cost-effective option for the treatment of AMD in the Chinese setting", "PURPOSE To study real-world ranibizumab therapy for treatment-naïve eyes with neovascular age-related macular degeneration ( nAMD ) and to benchmark st and ards of care . DESIGN Multicenter , national nAMD data base study . PARTICIPANTS A total of 92 976 treatment episodes from 12 951 eyes of 11 135 patients . METHODS Up to 5 years of routinely collected , anonymized data were extracted remotely from 14 United Kingdom centers to a central data base using an electronic medical record ( EMR ) system . Participating centers used ranibizumab to treat nAMD using a loading phase of 3 monthly injections and a pro re nata retreatment regimen . The minimum data set defined before first patient data entry and m and ated by the EMR system included age , Early Treatment Diabetic Retinopathy Study visual acuity ( VA ) at all visits , and injection episodes . MAIN OUTCOME MEASURES Baseline VA , change in VA , number of treatments and clinic visits , and baseline characteristics affecting VA change . RESULTS Information from more than 300 000 clinic visits ( 2.8 million data points ) were collated . Mean age at first treatment was 79.1 years , with a female preponderance of 1.7:1 . Mean VA ( letters ) for eyes followed up for at least 3 years from a baseline of 55 letters was 57 ( + 2 ) letters at 1 year , 56 ( + 1 ) letters at 2 years , and 53 ( -2 ) letters at 3 years . The proportion of eyes that avoided moderate vision loss at years 1 , 2 , and 3 were 90 % , 84 % , and 82 % , respectively . The proportion of eyes with VA of 20/40 or better were : baseline , 16 % ; year 1 , 30 % ; year 2 , 30 % ; and year 3 , 29 % . The median number of treatments for eyes followed up for at least 3 years in years 1 , 2 and 3 was 5 , 4 , and 4 , respectively , and the median number of outpatient visits was 9.2 , 8.2 , and 8.2 , respectively . Baseline VA was related inversely to mean vision gain at 3 months . Older age was associated with lower presenting VA . CONCLUSIONS Real-world visual outcomes achieved at a large number of centers across the United Kingdom do not match the results achieved in most r and omized trials , but they were delivered with substantially fewer injections and hospital visits . This study provides important benchmark results that should be of interest to patients , retina specialists , and commissioners of health care . This study demonstrates the EMR system 's potential usefulness for future phase 4 and 5 clinical trials", "BACKGROUND Age-related macular degeneration ( AMD ) is a progressive disease that results in loss of central vision , significant functional impairment , and a subsequent heavy socioeconomic burden . AMD treatments delay disease progression , improve patient outcomes , and reduce re source use associated with visual impairment , however , in a varying way concerning costs and effects . OBJECTIVE The purpose of this study was to investigate the cost effectiveness of ranibizumab compared with verteporfin photodynamic therapy , pegaptanib sodium , and best supportive care for the treatment of AMD in Greece . METHODS A 6-state Markov model was constructed according to patient visual acuity in the better-seeing eye . Data on effectiveness were derived from r and omized controlled trials evaluating the outcomes of ranibizumab versus alternative AMD treatments . Re source utilization reflected the Greek health care setting and was defined by a panel of experts . All treatments were administered for a 2-year period and evaluated during a 10-year time frame from a third-party payer perspective and discounted at 3.5 % per annum . RESULTS Estimated mean 10-year direct costs of treatment in the ranibizumab arm ranged from € 23,733 to € 31,795 ( 2011 Euros ) , with a projected gain of 4.50 to 4.74 quality -adjusted life years ( QALYs ) or 2.97 to 4.47 vision years , depending on type of lesion . For predominantly classic lesions , the cost per QALY gained with ranibizumab was estimated at € 6444/QALY ( 95 % uncertainty interval [ UI ] , € -30,403/QALY to € 44,524/QALY ) , € 15,344 ( 95 % UI , € -11,433 to € 53,554 ) and dominant relative to photodynamic therapy , best supportive care , and pegaptanib , respectively . Corresponding ratios for patients with minimally classic lesions were € 24,580/QALY ( 95 % UI , € -5580/QALY to € 76,229/QALY ) and € 13,112/QALY ( 95 % UI , € -3839/QALY to € 37,527/QALY ) for ranibizumab relative to best supportive care and pegaptanib , and for patients with occult lesions were estimated at € 19,407/QALY ( 95 % UI , € -1486 to € 46,434 ) and € 28,561/QALY ( 95 % UI , € 6143 to 73,431 ) , respectively . Sensitivity analysis provided robust results in all cases . CONCLUSION Ranibizumab can be a cost-effective option for the treatment of AMD compared with selected alternatives in the Greek health care setting", "OBJECTIVES Age-related macular degeneration is the leading cause of legal blindness in older people . Choroidal neovascularization ( CNV ) is treatable with photodynamic therapy with verteporfin ( PDT ) but is expensive . The aim of this study was to assess the cost-effectiveness of PDT in routine clinical practice in Switzerl and . MATERIAL S AND METHODS A Markov model was used to analyze the costs of PDT in routine clinical practice . It described patients moving between good or impaired vision ( visual acuity [VA]>0.1 ) and highly impaired vision ( VA<0.1 ) . Costs for PDT were based on the results of the Donati open-labeled prospect i ve clinical study . Costs for medical and social management of AMD patients were defined according to Grainer 's study . RESULTS The cost of PDT varied from 8,800 to 10,969 euros/patient/year . Ninety percent of the patients retained a VA > or = 0.1 . Health costs saved by keeping patients from moving to the highly impaired vision group was 4,248 euros/patient/year . Incremental costs per vision-year saved varied from 8,239 to 10,271 euros . Cost per quality -adjusted life year ( QALY ) gained at 5 years was 65,150 euros . DISCUSSION PDT was found to be moderately cost-effective in Switzerl and . The longer the follow-up , the more cost-effective Visudyne was . Cost-effectiveness is a country-dependent assessment and analyses should be done for each health care system . CONCLUSION PDT was found to be cost-effective in Switzerl and ( category C of Laupaci 's classification )", "OBJECTIVE This study compared the cost-effectiveness of ranibizumab with that of photodynamic therapy ( PDT ) in the treatment of predominantly classic choroidal neovascularization secondary to age-related macular degeneration ( AMD ) from the perspective of a third-party payer in a Spanish setting . METHODS We constructed a Markov model with 5 states defined by visual acuity ( VA ) in the better-seeing eye ( Snellen scale ) , as follows : VA > 20/40 , < or=20/40 to > 20/80 , 20/200 , < or=20/200 to > 20/400 , and < or=20/400 . A death state was also included . We took transition probabilities , number of ranibizumab injections , and number of PDT treatments from the ANCHOR ( Anti-Vascular Endothelial Growth Factor Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration ) trial . Utilities were taken from a published study of patients ' preferences . We used unit costs from our hospital and drug costs from a national data base . Re source utilization was determined by an ophthalmologist according to current clinical practice . We performed univariate , threshold , and probabilistic sensitivity analyses . Incremental costs ( 2007 euro ) and quality -adjusted life-years ( QALYs ) , both discounted at a 3 % annual rate , and incremental cost-effectiveness ratios ( ICERs ; euro/QALY ) were determined for the 2-year and life-expectancy time horizons . RESULTS Treating patients with varying degrees of visual impairment with ranibizumab instead of PDT , with a 2-year time horizon , was found to be euro18,328 more costly and to confer 0.140 additional QALY ( euro131,275/QALY ) . This ICER was reduced to euro39,398/ QALY for the longer life-expectancy time horizon . According to the probabilistic sensitivity analysis , PDT is the therapy of choice in all cases below the threshold of euro30,000/QALY for the 2-year time horizon . Ranibizumab was the optimal intervention in 26 % of cases in the longer lifetime horizon . When the initial VA was < or=20/400 , the ICER increased to euro255,477 over 2 years . When ranibizumab was administered on an as-needed basis , as in the PrONTO ( Prospect i ve Optical coherence tomography imaging of patients with Neovascular AMD Treated with intra-Ocular ranibizumab ) trial , the ICERs were reduced to euro29,566/QALY and euro11,469/QALY in the 2-year and life-expectancy horizons , respectively . CONCLUSIONS Based on these results , ranibizumab was not cost-effective when administered on a monthly basis . When administered as needed , ranibizumab was cost-effective compared with PDT for the treatment of AMD" ]

[ "3541894", "5282722", "4299527", "20387334", "3541877", "3274442", "3541909", "3606619", "19840350", "4629737", "3541898", "3541918", "4635827", "16185242", "16202594", "28105304" ]

[ "Community-based control of Aedes aegypti by adoption of eco-health methods in Chennai City, India", "Malaria control and prevention towards elimination: data from an eleven-year surveillance in Shandong Province, China", "Development of a community-based intervention for the control of Chagas disease based on peridomestic animal management: an eco-bio-social perspective", "Community involvement in dengue vector control: cluster randomised trial", "Building and analyzing an innovative community-centered dengue-ecosystem management intervention in Yogyakarta, Indonesia", "The effect of household heads training about the use of treated bed nets on the burden of malaria and anaemia in under-five children: a cluster randomized trial in Ethiopia", "Community mobilization and household level waste management for dengue vector control in Gampaha district of Sri Lanka; an intervention study", "Health impact and cost-effectiveness of a private sector bed net distribution: experimental evidence from Zambia", "Intersectoral coordination, community empowerment and dengue prevention: six years of controlled interventions in Playa Municipality, Havana, Cuba.", "An Assessment of Participatory Integrated Vector Management for Malaria Control in Kenya", "Community-centred eco-bio-social approach to control dengue vectors: an intervention study from Myanmar", "Application of eco-friendly tools and eco-bio-social strategies to control dengue vectors in urban and peri-urban settings in Thailand", "Integrated Schistosomiasis and Soil-Transmitted Helminthiasis Control over Five Years on Kome Island, Tanzania", "Improving access to early treatment of malaria: a trial with primary school teachers as care providers.", "School-based interventions to enhance knowledge and improve case management of schistosomiasis: a case study from Hunan, China.", "Preliminary results on the control of Aedes spp. in a remote Guatemalan community vulnerable to dengue, chikungunya and Zika virus: community participation and use of low-cost ecological ovillantas for mosquito control." ]

[ "Abstract Background : Dengue is highly endemic in Chennai city , South India , in spite of continuous vector control efforts . This intervention study was aim ed at establishing the efficacy as well as the favouring and limiting factors relating to a community-based environmental intervention package to control the dengue vector Aedes aegypti . Methods : A cluster r and omized controlled trial was design ed to measure the outcome of a new vector control package and process analysis ; different data collection tools were used to determine the performance . Ten r and omly selected intervention clusters ( neighbourhoods with 100 houses each ) were paired with ten control clusters on the basis of ecological/entomological indices and sociological parameters collected during baseline studies . In the intervention clusters , Aedes control was carried out using a community-based environmental management approach like provision of water container covers through community actors , clean-up campaigns , and dissemination of dengue information through schoolchildren . The main outcome measure was reduction in pupal indices ( pupae per person index ) , used as a proxy measure of adult vectors , in the intervention clusters compared to the control clusters . Results : At baseline , almost half the respondents did not know that dengue is serious but preventable , or that it is transmitted by mosquitoes . The stakeholder analysis showed that dengue vector control is carried out by vertically structured programmes of national , state , and local administrative bodies through fogging and larval control with temephos , without any involvement of community-based organizations , and that vector control efforts were conducted in an isolated and irregular way . The most productive container types for Aedes pupae were cement tanks , drums , and discarded containers . All ten intervention clusters with a total of 1000 houses and 4639 inhabitants received the intervention while the ten control clusters with a total of 1000 houses and 4439 inhabitants received only the routine government services and some of the information education and communication project material s. The follow-up studies showed that there was a substantial increase in dengue underst and ing in the intervention group with only minor knowledge changes in the control group . Community involvement and the partnership among stakeholders ( particularly women ’s self-help groups ) worked well . After 10 months of intervention , the pupae per person index was significantly reduced to 0·004 pupae per person from 1·075 ( P = 0·020 ) in the intervention clusters compared to control clusters . There were also significant reductions in the Stegomyia indices : the house index was reduced to 4·2 % , the container index to 1·05 % , and the Breteau index to 4·3 from the baseline values of 19·6 , 8·91 , and 30·8 in the intervention arm . Conclusion : A community-based approach together with other stakeholders that promoted interventions to prevent dengue vector breeding led to a substantial reduction in dengue vector density", "Background Sh and ong Province experienced a declining malaria trend of local-acquired transmission , but the increasing imported malaria remains a challenge . Therefore , underst and ing the epidemiological characteristics of malaria and the control and elimination strategy and interventions is needed for better planning to achieve the overall elimination goal in Sh and ong Province . Methods A retrospective study was conducted and all individual cases from a web-based reporting system were review ed and analysed to explore malaria-endemic characteristics in Sh and ong from 2005 to 2015 . Annual malaria incidence reported in 2005–2015 were geo-coded and matched to the county-level . Spatial cluster analysis was performed to evaluate any identified spatial disease clusters for statistical significance . The space – time cluster was detected with high rates through the retrospective space – time analysis scanning using the discrete Poisson model . Results The overall malaria incidence decreased to a low level during 2005–2015 . In total , 1564 confirmed malaria cases were reported , 27.1 % of which ( n = 424 ) were indigenous cases . Most of the indigenous case ( n = 339 , 80.0 % ) occurred from June to October . However , the number and scale of imported cases have been increased but no significant difference was observed during months . Sh and ong is endemic for both Plasmodium vivax ( n = 730 ) and Plasmodium falciparum ( n = 674 ) . The disease is mainly distributed in Southern ( n = 710 ) and Eastern region ( n = 424 ) of Sh and ong , such as Jinning ( n = 214 [ 13.7 % ] ) , Weihai ( n = 151 [ 9.7 % ] ) , and Yantai ( n = 107 [ 6.8 % ] ) . Furthermore , the spatial cluster analysis of malaria cases from 2005 to 2015 indicated that the diseased was not r and omly distributed . For indigenous cases , a total of 15 and 2 high-risk counties were determined from 2005 to 2009 ( control phase ) and from 2010 to 2015 ( elimination phase ) , respectively . For imported cases , a total of 26 and 29 high-risk counties were determined from 2005 to 2009 ( control phase ) and from 2010 to 2015 ( elimination phase ) , respectively . The method of spatial scan statistics identified different 13 significant spatial clusters between 2005 and 2015 . The space – time clustering analysis determined that the most likely cluster included 14 and 19 counties for indigenous and imported , respectively . Conclusions In order to cope with the requirements of malaria elimination phase , the surveillance system should be strengthened particularity on the frequent migration regions as well as the effective multisectoral cooperation and coordination mechanisms . Specific response packages should be tailored among different types of cities and capacity building should also be improved mainly focus on the emergence response and case management . Fund guarantees for scientific research should be maintained both during the elimination and post-elimination phase to consoli date the achievements of malaria elimination", "Background Integrated vector management strategies depend on local eco-bio-social conditions , community participation , political will and inter-sectorial partnership . Previously identified risk factors for persistent Triatoma dimidiata infestation include the presence of rodents and chickens , tiled roofs , dirt floors , partial wall plastering and dog density . Methods A community-based intervention was developed and implemented based on cyclical stakeholder and situational analyses . Intervention implementation and evaluation combined participatory action research and cluster r and omized pre-test post-test experimental design s. The intervention included modified insecticide application , education regarding Chagas disease and risk factors , and participatory rodent control . Results At final evaluation there was no significant difference in post-test triatomine infestation between intervention and control , keeping pre-test rodent and triatomine infestations constant . Knowledge levels regarding Chagas disease and prevention practice s including rodent control , chicken management and health service access increased significantly only in intervention communities . The odds of nymph infection and rat infestation were 8.3 and 1.9-fold higher in control compared to intervention communities , respectively . Conclusion Vector control measures without reservoir control are insufficient to reduce transmission risk in areas with persistent triatomine infestation . This integrated vector management program can complement house improvement initiatives by prioritizing households with risk factors such as tiled roofs . Requirement for active participation and multi-sectorial coordination poses implementation challenges", "Objective To assess the effectiveness of an integrated community based environmental management strategy to control Aedes aegypti , the vector of dengue , compared with a routine strategy . Design Cluster r and omised trial . Setting Guantanamo , Cuba . Participants 32 circumscriptions ( around 2000 inhabitants each ) . Interventions The circumscriptions were r and omly allocated to control clusters ( n=16 ) comprising routine Aedes control programme ( entomological surveillance , source reduction , selective adulticiding , and health education ) and to intervention clusters ( n=16 ) comprising the routine Aedes control programme combined with a community based environmental management approach . Main outcome measures The primary outcome was levels of Aedes infestation : house index ( number of houses positive for at least one container with immature stages of Ae aegypti per 100 inspected houses ) , Breteau index ( number of containers positive for immature stages of Ae aegypti per 100 inspected houses ) , and the pupae per inhabitant statistic ( number of Ae aegypti pupae per inhabitant ) . Results All clusters were subjected to the intended intervention ; all completed the study protocol up to February 2006 and all were included in the analysis . At baseline the Aedes infestation levels were comparable between intervention and control clusters : house index 0.25 % v 0.20 % , pupae per inhabitant 0.44 × 10−3 v 0.29 × 10−3 . At the end of the intervention these indices were significantly lower in the intervention clusters : rate ratio for house indices 0.49 ( 95 % confidence interval 0.27 to 0.88 ) and rate ratio for pupae per inhabitant 0.27 ( 0.09 to 0.76 ) . Conclusion A community based environmental management embedded in a routine control programme was effective at reducing levels of Aedes infestation . Trial registration Current Controlled Trials IS RCT N88405796", "Abstract Background and Objectives : Dengue is an important public health problem in Yogyakarta city , Indonesia . The aim of this study was to build an innovative community-centered dengue-ecosystem management intervention in the city and to assess the process and results . Methods : For describing the baseline situation , entomological surveys and household surveys were carried out in six r and omly selected neighborhoods in Yogyakarta city , documents were analyzed and different stakeholders involved in dengue control and environmental management were interviewed . Then a community-centered dengue-ecosystem management intervention was built up in two of the neighborhoods ( Demangan and Giwangan ) whereas two neighborhoods served as controls with no intervention ( Tahunan and Bener ) . Six months after the intervention follow up surveys ( household interviews and entomological ) were conducted as well as focus group discussion s and key informant interviews . FIindings : The intervention results included : better community knowledge , attitude and practice s in dengue prevention ; increased household and community participation ; improved partnership including a variety of stakeholders with prospect s for sustainability ; vector control efforts refocused on environmental and health issues ; increased community ownership of dengue vector management including broader community development activities such as solid waste management and recycling . Conclusion : The community-centred approach needs a lot of effort at the beginning but has better prospect s for sustainability than the vertical “ top-down ” approach", "Background Long-lasting insecticide-treated bed nets ( LLITN ) have demonstrated a significant effect in reducing malaria-related morbidity and mortality . However , barriers on the utilization of LLITN have hampered the desired outcomes . The aim of this study was to assess the effect of community empowerment on the burden of malaria and anaemia in under-five children in Ethiopia . Methods A cluster r and omized trial was done in 22 ( 11 intervention and 11 control ) villages in south-west Ethiopia . The intervention consisted of tailored training of household heads about the proper use of LLITN and community network system . The burden of malaria and anaemia in under-five children was determined through mass blood investigation at baseline , six and 12 months of the project period . Cases of malaria and anaemia were treated based on the national protocol . The burden of malaria and anaemia between the intervention and control villages was compared using the complex logistic regression model by taking into account the clustering effect . Eight Focus group discussion s were conducted to complement the quantitative findings . Results A total of 2,105 household heads received the intervention and the prevalence of malaria and anaemia was assessed among 2410 , 2037 and 2612 under-five children at baseline , six and 12 months of the project period respectively . During the high transmission/epidemic season , children in the intervention arm were less likely to have malaria as compared to children in the control arm ( OR = 0.42 ; 95%CI : 0.32 , 0.57 ) . Symptomatic malaria also steadily declined in the intervention villages compared to the control villages in the follow up periods . Children in the intervention arm were less likely to be anaemic compared to those in the control arm both at the high ( OR = 0.84 ; 95%CI : 0.71 , 0.99 ) ) and low ( OR = 0.73 ; 95%CI : 0.60 , 0.89 ) transmission seasons . Conclusion Training of household heads on the utilization of LLITN significantly reduces the burden of malaria in under-five children . The Ministry of Health of Ethiopia in collaboration with other partners should design similar strategies in high-risk areas to control malaria in Ethiopia . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) :", "Abstract Introduction : Waste management through community mobilization to reduce breeding places at household level could be an effective and sustainable dengue vector control strategy in areas where vector breeding takes place in small discarded water containers . The objective of this study was to assess the validity of this assumption . Methods : An intervention study was conducted from February 2009 to February 2010 in the populous Gampaha District of Sri Lanka . Eight neighborhoods ( clusters ) with roughly 200 houses each were selected r and omly from high and low dengue endemic areas ; 4 of them were allocated to the intervention arm ( 2 in the high and 2 in the low endemicity areas ) and in the same way 4 clusters to the control arm . A baseline household survey was conducted and entomological and sociological surveys were carried out simultaneously at baseline , at 3 months , at 9 months and at 15 months after the start of the intervention . The intervention programme in the treatment clusters consisted of building partnerships of local stakeholders , waste management at household level , the promotion of composting biodegradable household waste , raising awareness on the importance of solid waste management in dengue control and improving garbage collection with the assistance of local government authorities . Results : The intervention and control clusters were very similar and there were no significant differences in pupal and larval indices of Aedes mosquitoes . The establishment of partnerships among local authorities was well accepted and sustainable ; the involvement of communities and households was successful . Waste management with the elimination of the most productive water container types ( bowls , tins , bottles ) led to a significant reduction of pupal indices as a proxy for adult vector densities . Conclusion : The coordination of local authorities along with increased household responsibility for targeted vector interventions ( in our case solid waste management due to the type of preferred vector breeding places ) is vital for effective and sustained dengue control", "Background Relatively few programmes have attempted to actively engage the private sector in national malaria control efforts . This paper evaluates the health impact of a large-scale distribution of insecticide-treated nets ( ITNs ) conducted in partnership with a Zambian agribusiness , and its cost-effectiveness from the perspective of the National Malaria Control Programme ( NMCP ) . Methods The study was design ed as a cluster-r and omized controlled trial . A list of 81,597 cotton farmers was obtained from Dunavant , a contract farming company in Zambia ’s cotton sector , in December 2010 . 39,963 ( 49 % ) were r and omly selected to obtain one ITN each . Follow-up interviews were conducted with 438 farmers in the treatment and 458 farmers in the control group in June and July 2011 . Treatment and control households were compared with respect to bed net ownership , bed net usage , self-reported fever , and self-reported confirmed malaria . Cost data was collected throughout the programme . Results The distribution effectively reached target beneficiaries , with approximately 95 % of households in the treatment group reporting that they had received an ITN through the programme . The average increase in the fraction of household members sleeping under an ITN the night prior to the interview was 14.6 percentage points ( p-value < 0.001 ) . Treatment was associated with a 42 percent reduction in the odds of self-reported fever ( p-value < 0.001 ) and with a 49 percent reduction in the odds of self-reported malaria ( p-value 0.002 ) . This was accomplished at a cost of approximately five US$ per ITN to Zambia ’s NMCP . Conclusions The results illustrate that existing private sector networks can efficiently control malaria in remote rural regions . The intra-household allocation of ITNs distributed through this channel was comparable to that of ITNs received from other sources , and the health impact remained substantial", "OBJECTIVE To document the process , outcome and effectiveness of a community-based intervention for dengue control . METHODS The primary intervention , focused on strengthening intersectoral coordination , was initiated by research ers in January 2000 in a pilot area in Playa municipality , Havana . In August 2002 health authorities extended the intervention to neighbouring areas , one of which was selected for evaluation . In August 2003 a complementary strategy , focused on community empowerment , was initiated in half of the pilot area . In our control area , routine dengue activities continued throughout the study period . Longitudinal process assessment was carried out using document analysis , interviews and group discussion s. R and om population surveys in 1999 , 2002 and 2005 assessed levels of participation and behavioural changes . Entomological surveillance data from 1999 to 2005 were used to determine effectiveness . RESULTS Mean scores for participation in the pilot area were 1.6 , 3.4 and 4.4 at baseline , and 2 years after initiating intersectoral coordination and intersectoral coordination plus community empowerment interventions , respectively . While in the control area little behavioural change was observed over time , changes were considerable in the pilot and extension areas , with 80 % of households involved in the community empowerment intervention showed adequate behavioural patterns . The pilot and extension areas attained comparable entomological effectiveness with significantly lower Breteau indices ( BIs ) than the control area . The pilot ( sub- ) area with the community empowerment intervention reached BIs below 0.1 that continued to be significantly lower than the one in the control area until the end of the study . CONCLUSION The study showed a trend in the levels and quality of participation , behavioural change and effectiveness of Aedes control from the routine activities only over an intervention with intersectoral coordination to one that combined intersectoral coordination and community empowerment approach", "Background The World Health Organization ( WHO ) recommends integrated vector management ( IVM ) as a strategy to improve and sustain malaria vector control . However , this approach has not been widely adopted . Objectives We comprehensively assessed experiences and findings on IVM in Kenya with a view to sharing lessons that might promote its wider application . Methods The assessment used information from a qualitative external evaluation of two malaria IVM projects implemented between 2006 and 2011 and an analysis of their accumulated entomological and malaria case data . The project sites were Malindi and Nyabondo , located in coastal and western Kenya , respectively . The assessment focused on implementation of five key elements of IVM : integration of vector control methods , evidence -based decision making , intersectoral collaboration , advocacy and social mobilization , and capacity building . Results IVM was more successfully implemented in Malindi than in Nyabondo owing to greater community participation and multistakeholder engagement . There was a significant decline in the proportion of malaria cases among children admitted to Malindi Hospital , from 23.7 % in 2006 to 10.47 % in 2011 ( p < 0.001 ) . However , the projects ’ operational research methodology did not allow statistical attribution of the decline in malaria and malaria vectors to specific IVM interventions or other factors . Conclusions Sustaining IVM is likely to require strong participation and support from multiple actors , including community-based groups , non-governmental organizations , international and national research institutes , and various government ministries . A cluster-r and omized controlled trial would be essential to quantify the effectiveness and impact of specific IVM interventions , alone or in combination . Citation Mutero CM , Mbogo C , Mwangangi J , Imbahale S , Kibe L , Orindi B , Girma M , Njui A , Lw and e W , Affognon H , Gichuki C , Mukabana WR . 2015 . An assessment of participatory integrated vector management for malaria control in Kenya . Environ Health Perspect 123:1145–1151 ;", "Abstract Objectives : To build up and analyse the feasibility , process , and effectiveness of a partnership-driven ecosystem management intervention in reducing dengue vector breeding and constructing sustainable partnerships among multiple stakeholders . Methods : A community-based intervention study was conducted from May 2009 to January 2010 in Yangon city . Six high-risk and six low-risk clusters were r and omized and allocated as intervention and routine service areas , respectively . For each cluster , 100 households were covered . Bi-monthly entomological evaluations ( i.e. larval and pupal surveys ) and household acceptability surveys at the end of 6-month intervention period were conducted , supplemented by qualitative evaluations . Intervention description : The strategies included eco-friendly multi-stakeholder partner groups ( Thingaha ) and ward-based volunteers , informed decision-making of householders , followed by integrated vector management approach . Findings : Pupae per person index ( PPI ) decreased at the last evaluation by 5·7 % ( 0·35–0·33 ) in high-risk clusters . But in low-risk clusters , PPI remarkably decreased by 63·6 % ( 0·33–0·12 ) . In routine service area , PPI also decreased due to availability of Temephos after Cyclone Nargis . As for total number of pupae in all containers , when compared to evaluation 1 , there was a reduction of 18·6 % in evaluation 2 and 44·1 % in evaluation 3 in intervention area . However , in routine service area , more reduction was observed . All intervention tools were found as acceptable , being feasible to implement by multi-stakeholder partner groups . Conclusions : The efficacy of community-controlled partnership-driven interventions was found to be superior to the vertical approach in terms of sustainability and community empowerment", "Abstract Background : Dengue is considered one of the most important vector-borne diseases in Thail and . Its incidence is increasing despite routine implementation of national dengue control programmes . This study , conducted during 2010 , aim ed to demonstrate an application of integrated , community-based , eco-bio-social strategies in combination with locally-produced eco-friendly vector control tools in the dengue control programme , emphasizing urban and peri-urban setting s in eastern Thail and . Methodology : Three different community setting s were selected and were r and omly assigned to intervention and control clusters . Key community leaders and relevant governmental authorities were approached to participate in this intervention programme . Ecohealth volunteers were identified and trained in each study community . They were selected among active community health volunteers and were trained by public health experts to conduct vector control activities in their own communities using environmental management in combination with eco-friendly vector control tools . These trained ecohealth volunteers carried out outreach health education and vector control during household visits . Management of public spaces and public properties , especially solid waste management , was efficiently carried out by local municipalities . Significant reduction in the pupae per person index in the intervention clusters when compared to the control ones was used as a proxy to determine the impact of this programme . Results : Our community-based dengue vector control programme demonstrated a significant reduction in the pupae per person index during entomological surveys which were conducted at two-month intervals from May 2010 for the total of six months in the intervention and control clusters . The programme also raised awareness in applying eco-friendly vector control approaches and increased intersectoral and household participation in dengue control activities . Conclusion : An eco-friendly dengue vector control programme was successfully implemented in urban and peri-urban setting s in Thail and , through intersectoral collaboration and practical action at household level , with a significant reduction in vector densities", "Integrated control strategies are important for sustainable control of schistosomiasis and soil-transmitted helminthiasis , despite their challenges for their effective implementation . With the support of Good Neighbors International in collaboration with National Institute of Medical Research , Mwanza , Tanzania , integrated control applying mass drug administration ( MDA ) , health education using PHAST , and improved safe water supply has been implemented on Kome Isl and over 5 years for controlling schistosomiasis and soil-transmitted helminths ( STHs ) . Baseline surveys for schistosomiasis and STHs was conducted before implementation of any integrated control strategies , followed by 4 cross-sectional follow-up surveys on r and omly selected sample s of schoolchildren and adults in 10 primary schools and 8 villages , respectively , on Kome isl and s. Those follow-up surveys were conducted for impact evaluation after introduction of control strategies interventions in the study area . Five rounds of MDA have been implemented from 2009 along with PHAST and improved water supply with pumped wells as other control strategies for complementing MDA . A remarkable steady decline of schistosomiasis and STHs was observed from 2009 to 2012 with significant trends in their prevalence decline , and thereafter infection rate has remained at a low sustainable control . By the third follow-up survey in 2012 , Schistosoma mansoni infection prevalence was reduced by 90.5 % and hookworm by 93.3 % among schoolchildren while in adults the corresponding reduction was 83.2 % and 56.9 % , respectively . Integrated control strategies have successfully reduced S. mansoni and STH infection status to a lower level . This study further suggests that monitoring and evaluation is a crucial component of any large-scale STH and schistosomiasis intervention", "The feasibility of improving access to early case detection and prompt and adequate management of acute episodes of malaria using school teachers was explored through an intervention trial in Ghana . Of all the ' fevers ' diagnosed as presumptive malaria by the trained teachers , 93 % met the case definition . However , a lower proportion ( 75 % ) of such correctly diagnosed cases were subsequently treated according to the treatment protocol provided . In a scaled up study , pre-packaging of the antimalarial drug improved the rate of adequate treatment to 97 % of cases correctly diagnosed as presumptive malaria . Pre-packaging of chloroquine ensured a high level of user compliance ( 96.6 % ) , even in the face of diminished supervision of the teachers . It is feasible for the health and education sectors to work in partnership to improve access to early case detection and adequate management of acute episodes of malaria", "This paper discusses an intersectoral health-related intervention , using cartoons and video-recording , print material s and face-to-face educational methods , to increase children 's knowledge of schistosomiasis , which in turn might improve the case management of early diagnosis and treatment . The main components of the project were ( i ) the collaboration between the departments of public health and education and ( ii ) a r and omized , controlled , school-based field trial conducted in the Dongting Lake region , China . Children in the experimental group ( n=604 ) and their parents participated in the educational programme . Control children ( n=527 ) received a 2 hour lecture about the disease . All participants were pre-tested , and retested five months after the conduct of the educational intervention . The results show significant changes among children and their parents in the experimental group related to knowledge about schistosomiasis and beliefs towards screening and treatment of the disease . Children in the experimental group also had better compliance than children in the control group for regular screening for schistosomiasis . These findings indicate that carefully design ed education programmes are useful for providing both children and their families with information about the prevention and treatment of schistosomiasis . Intersectoral collaboration holds promise to deliver research -based interventions for enhanced knowledge of schistosomiasis and improved case management", "Objective : To study the effectiveness of an integrated intervention of health worker training , a low-cost ecological mosquito ovitrap , and community engagement on Aedes spp . mosquito control over 10 months in 2015 in an urban remote community in Guatemala at risk of dengue , chikungunya and Zika virus transmission . Methods : We implemented a three-component integrated intervention consisting of : web-based training of local health personnel in vector control , cluster-r and omized assignment of an ecological modified ovitrap ( ovillantas : ovi = egg , llanta = tire ) or st and ard ovitraps to capture Aedes spp . mosquito eggs ( no efforts have been taken to determine the exact Aedes species at this moment ) , and community engagement to promote participation of community members and health personnel in the underst and ing and maintenance of ovitraps for mosquito control . The intervention was implemented in local collaboration with Guatemala 's Ministry of Health 's Vector Control Programme , and in international collaboration with the National Institute of Public Health in Mexico . Findings : Eighty percent of the 25 local health personnel enrolled in the training programme received accreditation of their improved knowledge of vector control . When ovillantas were used in a cluster of ovitraps ( several in proximity ) , significantly more eggs were trapped by ecological ovillantas than st and ard ovitraps over the 10 month ( 42 week ) study period ( t=5.2577 ; p<0.05 ) . Repetitive filtering and recycling of the attractant solution ( or water ) kept the ovillanta clean , free from algae growth . Among both community members and health workers , the levels of knowledge , interest , and participation in community mosquito control and trapping increased . Recommendations for enhancing and sustaining community mosquito control were identified . Conclusion : Our three-component integrated intervention proved beneficial to this remote community at risk of mosquito-borne diseases such as dengue , chikungunya , and Zika . The combination of training of health workers , cluster use of low-cost ecological ovillanta to destroy the second generation of mosquitoes , and community engagement ensured the project met local needs and fostered collaboration and participation of the community , which can help improve sustainability . The ovillanta intervention and methodology may be modified to target other species such as Culex , should it be established that such mosquitoes carry Zika virus in addition to Aedes" ]

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[ "Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia.", "Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study.", "Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study", "Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy.", "Very-Low-Density Lipoprotein–Associated Apolipoproteins Predict Cardiovascular Events and Are Lowered by Inhibition of APOC-III", "Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial", "Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia.", "Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial", "Changes in Mipomersen Dosing Regimen Provide Similar Exposure With Improved Tolerability in Randomized Placebo‐Controlled Study of Healthy Volunteers", "Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins", "Lipoprotein(a) as a cardiovascular risk factor: current status", "Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia.", "Potent Reduction of Apolipoprotein B and Low-Density Lipoprotein Cholesterol by Short-Term Administration of an Antisense Inhibitor of Apolipoprotein B", "Effect of mipomersen on LDL-cholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study).", "Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension", "Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia.", "Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia", "Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial", "Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis", "Corrigendum to: \"Effect of mipomersen on LDL-cholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study)\" [Atherosclerosis 259 (2017 Apr) 20-25].", "Safety and efficacy of mipomersen in patients with heterozygous familial hypercholesterolemia.", "Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial." ]

[ "AIMS Mipomersen , an apolipoprotein ( apo ) B synthesis inhibitor , has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers . A r and omized , double-blind , placebo-controlled , dose-escalation study was design ed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia . METHODS AND RESULTS Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 r and omization ratio of active to placebo . Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week . Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins . In the 200 and 300 mg/week dose cohorts , mean reductions from baseline in LDL cholesterol were -45 ± 10 % ( P= 0.000 ) and -61 ± 8 % ( P= 0.000 ) , corresponding to a -46 ± 11 % ( P= 0.000 ) and -61 ± 7 % ( P= 0.000 ) decrease in apoB levels . Triglyceride levels were also lowered with median reductions up to 53 % ( P= 0.021 ) . The most common adverse events were injection site reactions . Seven of 40 subjects ( 18 % ) showed consecutive transaminase elevations > 3 × upper limit of normal . Five of these subjects received 400 mg/week , four of whom had apoB levels below the limit of detection . As a consequence , the 400 mg/week cohort was discontinued . CONCLUSIONS Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins . Higher doses were associated with hepatic transaminase increases", "BACKGROUND Homozygous familial hypercholesterolaemia is a genetic disorder characterised by substantially raised LDL cholesterol , reduced LDL receptor function , xanthomas , and cardiovascular disease before age 20 years . Conventional therapy is with statins , ezetimibe , and apheresis . We aim ed to assess the long-term safety and efficacy of the proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) inhibitor evolocumab in a subset of patients with homozygous familial hypercholesterolaemia enrolled in an open-label , non-r and omised phase 3 trial . METHODS In this interim subset analysis of the TAUSSIG study , which was undertaken at 35 sites in 17 countries , we included patients aged 12 years or older with homozygous familial hypercholesterolaemia who were on stable LDL cholesterol-lowering therapy for at least 4 weeks ; all patients received evolocumab 420 mg subcutaneously monthly , or if on apheresis every 2 weeks . Dosing could be increased to every 2 weeks after 12 weeks in patients not on apheresis . The primary outcome of the TAUSSIG study was treatment-emergent adverse events ; secondary outcomes were the effects of evolocumab on LDL cholesterol and other lipids . We analysed patients on an intention-to-treat basis , and all statistical comparisons were done post hoc in this interim analysis . The TAUSSIG study is registered with Clinical Trials.gov , number NCT01624142 , and is ongoing . FINDINGS 106 patients were included in this analysis , 34 receiving apheresis at study entry and 14 younger than 18 years . The first patient was enrolled on June 28 , 2012 , and the cutoff date for the analysis was Aug 13 , 2015 ; mean follow-up was 1·7 years ( SD 0·63 ) . After 12 weeks , mean LDL cholesterol decreased from baseline by 20·6 % ( SD 24·4 ; mean absolute decrease 1·50 mmol/L [ SD 1·92 ] ) ; these reductions were maintained at week 48 . 47 of 72 patients not on apheresis at study entry increased evolocumab dosing to every 2 weeks , with an additional mean reduction in LDL cholesterol of 8·3 % ( SD 13·0 ; mean absolute decrease 0·77 mmol/L [ SD 1·38 ] ; p=0·0001 ) . In a post-hoc analysis , mean reductions in LDL cholesterol in patients on apheresis were significant at week 12 ( p=0·0012 ) and week 48 ( p=0·0032 ) , and did not differ from reductions achieved in patients not on apheresis ( p=0·38 at week 12 and p=0·09 at week 48 ) . We noted a small reduction ( median -7·7 % [ IQR -21·6 to 6·8 ] ) in lipoprotein(a ) at week 12 ( p=0·0015 ) , with some additional reduction at week 48 ( -11·9 % [ -28·0 to 0·0 ] ; p<0·0001 ) . HDL cholesterol was increased by a mean of 7·6 % ( SD 18·1 ) at week 12 ( p<0·0001 ) and 7·6 % ( SD 20·6 ) at week 48 ( p=0·0007 ) . Evolocumab was well tolerated ; 82 ( 77 % ) patients reported treatment-emergent adverse events , which were mostly minor . The most common were nasopharyngitis ( 14 patients [ 13 % ] ) , influenza ( 13 [ 12 % ] ) , headache ( 11 [ 10 % ] ) , and upper respiratory tract infection ( 11 [ 10 % ] ) . Serious adverse events occurred in 18 ( 17 % ) patients , with the most common being cardiovascular events ( four patients [ 4 % ] ) . There were no deaths and four positively adjudicated cardiovascular events , one ( 3 % ) among patients on apheresis and three ( 4 % ) among patients who did not receive apheresis . INTERPRETATION Our interim results suggest that evolocumab is an effective additional option to reduce LDL cholesterol in patients with homozygous familial hypercholesterolaemia , with or without apheresis . FUNDING Amgen", "BACKGROUND Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs . We aim ed to assess the efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in adults with this disease . METHODS We did a single-arm , open-label , phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia . Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26 . Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day . The primary endpoint was mean percent change in levels of LDL cholesterol from baseline to week 26 , after which patients remained on lomitapide through to week 78 for safety assessment . Percent change from baseline to week 26 was assessed with a mixed linear model . FINDINGS 29 men and women with homozygous familial hypercholesterolaemia , aged 18 years or older , were recruited from 11 centres in four countries ( USA , Canada , South Africa , and Italy ) . 23 of 29 enrolled patients completed both the efficacy phase ( 26 weeks ) and the full study ( 78 weeks ) . The median dose of lomitapide was 40 mg a day . LDL cholesterol was reduced by 50 % ( 95 % CI -62 to -39 ) from baseline ( mean 8·7 mmol/L [ SD 2·9 ] ) to week 26 ( 4·3 mmol/L [ 2·5 ] ; p<0·0001 ) . Levels of LDL cholesterol were lower than 2·6 mmol/L in eight patients at 26 weeks . Concentrations of LDL cholesterol remained reduced by 44 % ( 95 % CI -57 to -31 ; p<0·0001 ) at week 56 and 38 % ( -52 to -24 ; p<0·0001 ) at week 78 . Gastrointestinal symptoms were the most common adverse event . Four patients had aminotransaminase levels of more than five times the upper limit of normal , which resolved after dose reduction or temporary interruption of lomitapide . No patient permanently discontinued treatment because of liver abnormalities . INTERPRETATION Our study suggests that treatment with lomitapide could be a valuable drug in the management of homozygous familial hypercholesterolaemia . FUNDING FDA Office of the Orphan Product Development , Aegerion Pharmaceuticals", "OBJECTIVES The aim of this study was to evaluate the efficacy and safety of mipomersen in hypercholesterolemic subjects taking stable statin therapy . BACKGROUND Mipomersen is an apolipoprotein ( apo ) B synthesis inhibitor that has demonstrated significant reductions in apo B and low-density lipoprotein ( LDL ) cholesterol in Phase 1 clinical trials in healthy volunteers . METHODS A r and omized , placebo-controlled , dose-escalation Phase 2 study was design ed to evaluate the effects of mipomersen in hypercholesterolemic subjects taking stable statin therapy . Seventy-four subjects were enrolled sequentially into 1 of 6 dose cohorts at a 4:1 ( active/placebo ) ratio . Subjects received 7 doses of 30 to 400 mg over 5 weeks in the first 5 cohorts and 15 doses of 200 mg over 13 weeks in the sixth cohort . Pre-specified end points included percentage change from baseline in apo B and LDL cholesterol . Safety was assessed with laboratory test results and by the incidence and severity of adverse events . RESULTS The apo B and LDL cholesterol were reduced by 19 % to 54 % and 21 % to 52 % , respectively , at doses of 100 mg/week mipomersen and higher in the 5-week treatment cohorts . Efficacy seemed to increase upon treatment for 13 weeks at a dose of 200 mg/week . Injection site reactions ( mild to moderate erythema [ 90 % ] ) and hepatic transaminase increases ( 17 % ) were the most common adverse events , leading to discontinuation in 2 subjects and 1 subject , respectively . In the 13-week treatment cohort , 5 of 10 subjects ( 50 % ) had elevations > or=3x the upper limit of normal , 4 of which persisted on 2 consecutive occasions . CONCLUSIONS Mipomersen might hold promise for treatment of patients not reaching target LDL cholesterol levels on stable statin therapy . Further studies are needed to address the mechanisms and clinical relevance of transaminase changes after mipomersen administration . ( Dose-Escalating Safety Study in Subjects on Stable Statin Therapy ; NCT00231569 )", "Background Routine apolipoprotein ( apo ) measurements for cardiovascular disease ( CVD ) are restricted to apoA-I and apoB. Here , the authors measured an unprecedented range of apolipoproteins in a prospect i ve , population -based study and relate their plasma levels to risk of CVD . Objectives This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level underst and ing of the correlations of apolipoproteins with the plasma lipidome and proteome . Methods Associations of 13 apolipoproteins , 135 lipid species , and 211 other plasma proteins with incident CVD ( 91 events ) , defined as stroke , myocardial infa rct ion , or sudden cardiac death , were assessed prospect ively over a 10-year period in the Bruneck Study ( N = 688 ) using multiple-reaction monitoring mass spectrometry . Changes in apolipoprotein and lipid levels following treatment with volanesorsen , a second-generation antisense drug targeting apoC-III , were determined in 2 human intervention trials , one of which was r and omized . Results The apolipoproteins most significantly associated with incident CVD were apoC-II ( hazard ratio per 1 SD [ HR/SD ] : 1.40 ; 95 % confidence interval [ CI ] : 1.17 to 1.67 ) , apoC-III ( HR/SD : 1.38 ; 95 % CI : 1.17 to 1.63 ) , and apoE ( HR/SD : 1.31 ; 95 % CI : 1.13 to 1.52 ) . Associations were independent of high-density lipoprotein ( HDL ) and non-HDL cholesterol , and extended to stroke and myocardial infa rct ion . Lipidomic and proteomic profiles implicated these 3 very-low-density lipoprotein (VLDL)-associated apolipoproteins in de novo lipogenesis , glucose metabolism , complement activation , blood coagulation , and inflammation . Notably , apoC-II/apoC-III/apoE correlated with a pattern of lipid species previously linked to CVD risk . ApoC-III inhibition by volanesorsen reduced plasma levels of apoC-II , apoC-III , triacylglycerols , and diacylglycerols , and increased apoA-I , apoA-II , and apoM ( all p < 0.05 vs. placebo ) without affecting apoB-100 ( p = 0.73 ) . Conclusions The strong associations of VLDL-associated apolipoproteins with incident CVD in the general community support the concept of targeting triacylglycerol-rich lipoproteins to reduce risk of CVD", "BACKGROUND Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective , result ing in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease . This study investigated whether an antisense inhibitor of apolipoprotein B synthesis , mipomersen , is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease . METHODS This r and omised , double-blind , placebo-controlled , phase 3 study was undertaken in nine lipid clinics in seven countries . Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia , who were already receiving the maximum tolerated dose of a lipid-lowering drug , were r and omly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks . R and omisation was computer generated and stratified by weight ( < 50 kg vs > /=50 kg ) in a central ised blocked r and omisation , implemented with a computerised interactive voice response system . All clinical , medical , and pharmacy personnel , and patients were masked to treatment allocation . The primary endpoint was percentage change in LDL cholesterol concentration from baseline . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00607373 . FINDINGS 34 patients were assigned to mipomersen and 17 to placebo ; data for all patients were analysed . 45 patients completed the 26-week treatment period ( 28 mipomersen , 17 placebo ) . Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L ( SD 3.6 ) in the mipomersen group and 10.4 mmol/L ( 3.7 ) in the placebo group . The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen ( -24.7 % , 95 % CI -31.6 to -17.7 ) than with placebo ( -3.3 % , -12.1 to 5.5 ; p=0.0003 ) . The most common adverse events were injection-site reactions ( 26 [ 76 % ] patients in mipomersen group vs four [ 24 % ] in placebo group ) . Four ( 12 % ) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal . INTERPRETATION Inhibition of apolipoprotein B synthesis by mipomersen represents a novel , effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs , including high-dose statins . FUNDING ISIS Pharmaceuticals and Genzyme Corporation", "BACKGROUND Familial hypercholesterolemia ( FH ) is characterized by severely elevated LDL-cholesterol and up to a 20-fold increase in premature cardiovascular disease ( CVD ) . OBJECTIVE Mipomersen has been shown to lower the levels of these atherogenic lipoproteins , but whether it lowers major adverse cardiac events ( MACEs ) has not been addressed . METHODS This post hoc analysis of prospect ively collected data of three r and omized trials and an open-label extension phase included patients that were exposed to ≥12 months of mipomersen . MACE rates that occurred during 24 months before r and omization in the mipomersen group were compared to MACE rates after initiation of mipomersen . Data from the trials included in this report are registered in Clinical trials.gov ( NCT00607373 , NCT00706849 , NCT00794664 , NCT00694109 ) . The occurrence of MACE events , defined as cardiovascular death , nonfatal acute myocardial infa rct ion , hospitalization for unstable angina , coronary revascularization and nonfatal ischemic stroke , was obtained from medical history data pre-treatment and adjudicated by an independent adjudication committee for events occurring post-treatment with mipomersen . RESULTS MACEs were identified in 61.5 % of patients ( 64 patients with 146 events [ 39 myocardial infa rct ions , 99 coronary revascularizations , 5 unstable angina episodes , 3 ischemic strokes ] ) during 24 months before mipomersen treatment , and in 9.6 % of patients ( 10 patients with 13 events [ 1 cardiovascular death , 2 myocardial infa rct ions , 6 coronary interventions , 4 unstable angina episodes ] ) during a mean of 24.4 months after initiation of mipomersen ( MACE rate 25.7 of 1000 patient-months vs 3.9 of 1000 patient-months , OR = 0.053 [ 95 % CI , 0.016 - 0.168 ] , P < .0001 by the exact McNemar test ) . The reduction in MACE coincided with a mean absolute reduction in LDL-C of 70 mg/dL ( -28 % ) and of non-HDL cholesterol of 74 mg/dL ( -26 % ) as well as reduction in Lp(a ) of 11 mg/dL ( -17 % ) . CONCLUSION Long-term mipomersen treatment not only lowers levels of atherogenic lipoproteins but may also lead to a reduction in cardiovascular events in FH patients", "Aims A r and omized , double-blind , placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen , an apolipoprotein B-100 ( apoB ) synthesis inhibitor , in patients who are statin intolerant and at high risk for cardiovascular disease ( CVD ) . Methods and results Thirty-three subjects , not receiving statin therapy because of statin intolerance , received a weekly subcutaneous dose of 200 mg mipomersen or placebo ( 2:1 r and omization ) for 26 weeks . The primary endpoint was per cent change in LDL cholesterol ( LDL-c ) from the baseline to Week 28 . The other efficacy endpoints were per cent change in apoB and lipoprotein a [ Lp(a ) ] . Safety was determined using the incidence of treatment-emergent adverse events ( AEs ) and clinical laboratory evaluations . After 26 weeks of mipomersen administration , LDL-c was reduced by 47 ± 18 % ( P < 0.001 vs. placebo ) . apoB and Lp(a ) were also significantly reduced by 46 and 27 % , respectively ( P < 0.001 vs. placebo ) . Four mipomersen ( 19 % ) and two placebo subjects ( 17 % ) discontinued dosing prematurely due to AEs . Persistent liver transaminase increases ≥3 × the upper limit of normal were observed in seven ( 33 % ) subjects assigned to mipomersen . In selected subjects , liver fat content was assessed , during and after treatment , using magnetic resonance spectroscopy . Liver fat content in these patients ranged from 0.8 to 47.3 % . Liver needle biopsy was performed in two of these subjects , confirming hepatic steatosis with minimal inflammation or fibrosis . Conclusion The present data suggest that mipomersen is a potential therapeutic option in statin-intolerant patients at high risk for CVD . The long-term follow-up of liver safety is required . Clinical Trial Registration : Clinical Trials.gov identifier :", "Background Mipomersen , an apolipoprotein B synthesis inhibitor , demonstrated significant reductions in low‐density lipoprotein ( LDL ) cholesterol , non‐high density lipoprotein cholesterol , and apolipoprotein B in 4 phase 3 studies at the FDA ‐approved subcutaneous dose of 200 mg once weekly . Methods and Results A short‐term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability , safety , and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen . Eighty‐four adults were r and omized to 1 of 3 cohorts ( 30 mg once daily , 70 mg 3 times weekly , or 200 mg once weekly ) and then mipomersen or placebo ( 3:1 ratio ) for 3 weeks of treatment . Comparable mipomersen post‐distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure . Injection site reactions were reported , but did not lead to treatment discontinuation . The median incidence of these responses per injection was decreased by lowering the dose . Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment . The one exception was a modest transient post‐dose elevation of C‐reactive protein ( CRP ) in the mipomersen 200 mg weekly group . This elevation was not associated with an increase in other proinflammatory markers . Conclusions This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens . Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment . These results support assessment of alternative dose regimens in longer‐term studies . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT01061814", "Mipomersen , an antisense oligonucleotide that reduces hepatic production of apoB , has been shown in phase 2 studies to decrease plasma apoB , LDL cholesterol ( LDL-C ) , and triglycerides . ApoC-III inhibits VLDL and LDL clearance , and it stimulates inflammatory responses in vascular cells . Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease . We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a r and omized controlled dose-ranging phase 2 study of mipomersen receiving 100 , 200 , or 300 mg/wk , or placebo for 13 wk ( n = 8 each ) . ApoC-III – containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation . Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl ( 38–42 % ) compared with placebo group ( P < 0.01 ) , and it reduced apoC-III in both apoB lipoproteins and HDL . Mipomersen 100 , 200 , and 300 mg doses reduced apoB concentration of LDL with apoC-III ( 27 % , 38 % , and 46 % ; P < 0.05 ) . Mipomersen reduced apoC-III concentration in HDL . The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins . In summary , antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III – containing lipoproteins . Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease ( CHD ) in epidemiologic studies independent of traditional risk factors", "Aims The aims of the study were , first , to critically evaluate lipoprotein(a ) [ Lp(a ) ] as a cardiovascular risk factor and , second , to advise on screening for elevated plasma Lp(a ) , on desirable levels , and on therapeutic strategies . Methods and results The robust and specific association between elevated Lp(a ) levels and increased cardiovascular disease (CVD)/coronary heart disease ( CHD ) risk , together with recent genetic findings , indicates that elevated Lp(a ) , like elevated LDL-cholesterol , is causally related to premature CVD/CHD . The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels . Mechanistically , elevated Lp(a ) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a ) resembles both plasminogen and plasmin but has no fibrinolytic activity , or may accelerate atherosclerosis because , like LDL , the Lp(a ) particle is cholesterol-rich , or both . We advise that Lp(a ) be measured once , using an isoform-insensitive assay , in subjects at intermediate or high CVD/CHD risk with premature CVD , familial hypercholesterolaemia , a family history of premature CVD and /or elevated Lp(a ) , recurrent CVD despite statin treatment , ≥3 % 10-year risk of fatal CVD according to European guidelines , and /or ≥10 % 10-year risk of fatal + non-fatal CHD according to US guidelines . As a secondary priority after LDL-cholesterol reduction , we recommend a desirable level for Lp(a ) < 80th percentile ( less than ∼50 mg/dL ) . Treatment should primarily be niacin 1–3 g/day , as a meta- analysis of r and omized , controlled intervention trials demonstrates reduced CVD by niacin treatment . In extreme cases , LDL-apheresis is efficacious in removing Lp(a ) . Conclusion We recommend screening for elevated Lp(a ) in those at intermediate or high CVD/CHD risk , a desirable level < 50 mg/dL as a function of global cardiovascular risk , and use of niacin for Lp(a ) and CVD/CHD risk reduction", "BACKGROUND Patients with homozygous familial hypercholesterolemia have markedly elevated cholesterol levels , which respond poorly to drug therapy , and a very high risk of premature cardiovascular disease . Inhibition of the microsomal triglyceride transfer protein may be effective in reducing cholesterol levels in these patients . METHODS We conducted a dose-escalation study to examine the safety , tolerability , and effects on lipid levels of BMS-201038 , an inhibitor of the microsomal triglyceride transfer protein , in six patients with homozygous familial hypercholesterolemia . All lipid-lowering therapies were suspended 4 weeks before treatment . The patients received BMS-201038 at four different doses ( 0.03 , 0.1 , 0.3 , and 1.0 mg per kilogram of body weight per day ) , each for 4 weeks , and returned for a final visit after a 4-week drug washout period . Analysis of lipid levels , safety laboratory analyses , and magnetic resonance imaging of the liver for fat content were performed throughout the study . RESULTS All patients tolerated titration to the highest dose , 1.0 mg per kilogram per day . Treatment at this dose decreased low-density lipoprotein ( LDL ) cholesterol levels by 50.9 % and apolipoprotein B levels by 55.6 % from baseline ( P<0.001 for both comparisons ) . Kinetic studies showed a marked reduction in the production of apolipoprotein B. The most serious adverse events were elevation of liver aminotransferase levels and accumulation of hepatic fat , which at the highest dose ranged from less than 10 % to more than 40 % . CONCLUSIONS Inhibition of the microsomal triglyceride transfer protein by BMS-201038 result ed in the reduction of LDL cholesterol levels in patients with homozygous familial hypercholesterolemia , owing to reduced production of apolipoprotein B. However , the therapy was associated with elevated liver aminotransferase levels and hepatic fat accumulation", "Background — Apolipoprotein B ( apoB ) is an important structural component of low-density lipoprotein cholesterol ( LDL-C ) and plays a key role in LDL-C transport and removal . Reduction in apoB synthesis is expected to reduce circulating LDL-C , a proven risk factor of cardiovascular disease . In the present study , we describe the outcome of the first-in-humans study on the safety and efficacy of an antisense oligonucleotide inhibitor of apoB. Methods and Results — This study was a double-blind , r and omized , placebo-controlled , dose-escalation investigation conducted at a single site in 36 volunteers with mild dyslipidemia . The study utilized an initial single dose of 50 to 400 mg of ISIS 301012 , a 20-mer oligonucleotide , followed by a 4-week multiple-dosing regimen with the same assigned dose . Safety was assessed by the incidence , severity , and relationship of adverse events to dose . Efficacy was determined by changes in serum apoB and LDL-C relative to baseline and placebo . The most common adverse event was erythema at the injection site ( 21 of 29 subjects ) . ApoB was reduced by a maximum of 50 % ( P=0.002 ) from baseline in the 200-mg cohort . This decrease in apoB coincided with a maximum 35 % reduction of LDL-C ( P=0.001 ) . LDL-C and apoB remained significantly below baseline ( P<0.05 ) up to 3 months after the last dose . Conclusions — Administration of an antisense oligonucleotide to human apoB result ed in a significant , prolonged , and dose-dependent reduction in apoB and LDL-C. Although injection-site reactions were common , adherence to protocol was unaffected", "BACKGROUND AND AIMS In this study , we evaluated the effect of mipomersen in patients with severe LDL-hypercholesterolaemia and atherosclerosis , treated by lipid lowering drugs and regular lipoprotein apheresis . METHODS This prospect i ve , r and omized , controlled phase II single center trial enrolled 15 patients ( 9 males , 6 females ; 59 ± 9 y , BMI 27 ± 4 kg/m2 ) with established atherosclerosis , LDL-cholesterol ≥130 mg/dL ( 3.4 mmol/L ) despite maximal possible drug therapy , and fulfilling German criteria for regular lipoprotein apheresis . All patients were on stable lipid lowering drug therapy and regular apheresis for > 3 months . Patients r and omized to treatment ( n = 11 ) self-injected mipomersen 200 mg sc weekly , at day 4 after apheresis , for 26 weeks . Patients r and omized to control ( n = 4 ) continued apheresis without injection . The primary endpoint was the change in pre-apheresis LDL-cholesterol . RESULTS Of the patients r and omized to mipomersen , 3 discontinued the drug early ( < 12 weeks therapy ) for side effects . For these , another 3 were recruited and r and omized . Further , 4 patients discontinued mipomersen between 12 and 26 weeks for side effects ( moderate to severe injection site reactions n = 3 and elevated liver enzymes n = 1 ) . In those treated for > 12 weeks , mipomersen reduced pre-apheresis LDL-cholesterol significantly by 22.6 ± 17.0 % , from a baseline of 4.8 ± 1.2 mmol/L to 3.7 ± 0.9 mmol/L , while there was no significant change in the control group ( + 1.6 ± 9.3 % ) , with the difference between the groups being significant ( p=0.02 ) . Mipomersen also decreased pre-apheresis lipoprotein(a ) ( Lp(a ) ) concentration from a median baseline of 40.2 mg/dL ( 32.5,71 ) by 16 % ( -19.4,13.6 ) , though without significance ( p=0.21 ) . CONCLUSIONS Mipomersen reduces LDL-cholesterol ( significantly ) and Lp(a ) ( non-significantly ) in patients on maximal lipid-lowering drug therapy and regular apheresis , but is often associated with side effects", "Abstract Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia ( HC ) taking maximally tolerated lipid-lowering therapy . Methods and results A planned interim analysis of an ongoing , open-label extension trial in patients ( n = 141 ) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks . The mean changes in low-density lipoprotein cholesterol ( LDL-C ) from baseline to weeks 26 ( n = 130 ) , 52 ( n = 111 ) , 76 ( n = 66 ) , and 104 ( n = 53 ) were −28 , −27 , −27 , and −28 % ; and in apolipoprotein B −29 , −28 , −30 , and −31 % , respectively . Reductions in total cholesterol , non-high-density lipoprotein-cholesterol , and lipoprotein(a ) were comparable with decreases in LDL-C and apolipoprotein B levels . Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6 % at weeks 26 and 52 , respectively . The long-term safety profile of mipomersen was similar to that reported in the associated r and omized placebo-controlled Phase 3 trials . Adverse events included injection site reactions and flu-like symptoms . There was an incremental increase in the median liver fat during the initial 6–12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation . The median alanine aminotransferase level showed a similar trend over time . Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient population s. Clinical trials.gov NCT00694109", "A r and omized , double-blind , placebo-controlled , dose-escalation study was conducted to examine the efficacy and safety of mipomersen ( ISIS 301012 ) , an antisense inhibitor of apolipoprotein B , when added to conventional lipid-lowering therapy for patients with heterozygous familial hypercholesterolemia . A total of 44 patients were enrolled and were separated into 4 cohorts , with doses ranging from 50 to 300 mg ( 4:1 active treatment/placebo ratio ) . Patients received 8 doses subcutaneously during a 6-week treatment period . Patients assigned to the 300-mg dose continued for an additional 7 weeks with once-per-week dosing . The primary efficacy end point was the percentage of change from baseline to week 7 in low-density lipoprotein ( LDL ) cholesterol . Safety was assessed using the laboratory test results and according to the incidence , severity , and relation of adverse events to drug dose . Mipomersen produced significant reductions in LDL cholesterol and other atherogenic apolipoprotein B-containing lipoproteins . After 6 weeks of treatment , the LDL cholesterol level was reduced by 21 % from baseline in the 200-mg/week dose group ( p < 0.05 ) and 34 % from baseline in the 300-mg/week dose group ( p < 0.01 ) , with a concomitant reduction in apolipoprotein B of 23 % ( p < 0.05 ) and 33 % ( p < 0.01 ) , respectively . Injection site reactions were the most common adverse event . Elevations in liver transaminase levels ( > or =3 times the upper limit of normal ) occurred in 4 ( 11 % ) of 36 patients assigned to active treatment ; 3 of these patients were in the highest dose group . In conclusion , mipomersen has an incremental LDL cholesterol lowering effect when added to conventional lipid-lowering therapy", "To investigate the impact of mipomersen , an apolipoprotein B-100 ( apoB ) synthesis inhibitor , on intra-hepatic triglyceride content ( IHTG content ) , we conducted a r and omized , double-blind , placebo-controlled study in 21 patients with familial hypercholesterolemia ( FH ) . Subjects received a weekly subcutaneous dose of 200 mg mipomersen or placebo for 13 weeks while continuing conventional lipid lowering therapy . The primary endpoint was change in IHTG content from week 0 to week 15 as measured by localized proton magnetic resonance spectroscopy ( 1H-MRS ) . Thirteen weeks of mipomersen administration reduced LDL-cholesterol by 22.0 ( 17.8 ) % and apoB by 19.9 ( 17.4 ) % ( both P < 0.01 ) . One of 10 patients ( 10 % ) in the mipomersen-treated group developed mild hepatic steatosis at week 15 , which was reversible following mipomersen discontinuation . For the group , there was a trend toward an increase in IHTG content [ placebo ; baseline : 1.2 % and week 15 : 1.1 % ; change −0.1 ( 0.9 ) . Mipomersen ; baseline : 1.2 % and week 15 : 2.1 % ; change 0.8 ( 1.7 ) ( P = 0.0513 ) ] . Mipomersen administration for 13 weeks to subjects with FH is associated with a trend toward an increase in IHTG content . Future studies evaluating the effects of long-term use of mipomersen reaching more profound reductions in apoB are required prior to broader use of this compound", "BACKGROUND Homozygous familial hypercholesterolaemia is a rare , serious disorder caused by very low or absent plasma clearance of LDL , substantially raised LDL cholesterol , and accelerated development of cardiovascular disease . Conventional lipid-lowering treatments are modestly effective . Evolocumab , a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , reduced LDL cholesterol by 16 % in a pilot study . We now report results with evolocumab in a r and omised , double-blind , placebo-controlled phase 3 trial . METHODS This r and omised , double-blind , placebo-controlled phase 3 trial was undertaken at 17 sites in ten countries in North America , Europe , the Middle East , and South Africa . 50 eligible patients ( aged ≥12 years ) with homozygous familial hypercholesterolaemia , on stable lipid-regulating therapy for at least 4 weeks , and not receiving lipoprotein apheresis , were r and omly allocated by a computer-generated r and omisation sequence in a 2:1 ratio to receive subcutaneous evolocumab 420 mg or placebo every 4 weeks for 12 weeks . R and omisation was stratified by LDL cholesterol at screening ( < 11 mmol/L or ≥11 mmol/L ) and implemented by a computerised interactive voice-response system . Patients , study personnel , and the funder were masked to treatment and to the efficacy results by the central laboratory not returning LDL cholesterol or any lipid results to the clinical sites after the baseline visit . The primary endpoint was percentage change in ultracentrifugation LDL cholesterol from baseline at week 12 compared with placebo , analysed by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT01588496 . FINDINGS Of the 50 eligible patients r and omly assigned to the two treatment groups , 49 actually received the study drug and completed the study ( 16 in the placebo group and 33 in the evolocumab group ) . Compared with placebo , evolocumab significantly reduced ultracentrifugation LDL cholesterol at 12 weeks by 30·9 % ( 95 % CI -43·9 % to -18·0 % ; p<0·0001 ) . Treatment-emergent adverse events occurred in ten ( 63 % ) of 16 patients in the placebo group and 12 ( 36 % ) of 33 in the evolocumab group . No serious clinical or laboratory adverse events occurred , and no anti-evolocumab antibody development was detected during the study . INTERPRETATION In patients with homozygous familial hypercholesterolaemia receiving stable background lipid-lowering treatment and not on apheresis , evolocumab 420 mg administered every 4 weeks was well tolerated and significantly reduced LDL cholesterol compared with placebo . FUNDING Amgen", "Importance Human genetic studies have indicated that plasma lipoprotein(a ) ( Lp[a ] ) is causally associated with the risk of coronary heart disease ( CHD ) , but r and omized trials of several therapies that reduce Lp(a ) levels by 25 % to 35 % have not provided any evidence that lowering Lp(a ) level reduces CHD risk . Objective To estimate the magnitude of the change in plasma Lp(a ) levels needed to have the same evidence of an association with CHD risk as a 38.67-mg/dL ( ie , 1-mmol/L ) change in low-density lipoprotein cholesterol ( LDL-C ) level , a change that has been shown to produce a clinical ly meaningful reduction in the risk of CHD . Design , Setting , and Participants A mendelian r and omization analysis was conducted using individual participant data from 5 studies and with external validation using summarized data from 48 studies . Population -based prospect i ve cohort and case-control studies featured 20 793 individuals with CHD and 27 540 controls with individual participant data , whereas summarized data included 62 240 patients with CHD and 127 299 controls . Data were analyzed from November 2016 to March 2018 . Exposures Genetic LPA score and plasma Lp(a ) mass concentration . Main Outcomes and Measures Coronary heart disease . Results Of the included study participants , 53 % were men , all were of white European ancestry , and the mean age was 57.5 years . The association of genetically predicted Lp(a ) with CHD risk was linearly proportional to the absolute change in Lp(a ) concentration . A 10-mg/dL lower genetically predicted Lp(a ) concentration was associated with a 5.8 % lower CHD risk ( odds ratio [ OR ] , 0.942 ; 95 % CI , 0.933 - 0.951 ; P = 3 × 10−37 ) , whereas a 10-mg/dL lower genetically predicted LDL-C level estimated using an LDL-C genetic score was associated with a 14.5 % lower CHD risk ( OR , 0.855 ; 95 % CI , 0.818 - 0.893 ; P = 2 × 10−12 ) . Thus , a 101.5-mg/dL change ( 95 % CI , 71.0 - 137.0 ) in Lp(a ) concentration had the same association with CHD risk as a 38.67-mg/dL change in LDL-C level . The association of genetically predicted Lp(a ) concentration with CHD risk appeared to be independent of changes in LDL-C level owing to genetic variants that mimic the relationship of statins , PCSK9 inhibitors , and ezetimibe with CHD risk . Conclusions and Relevance The clinical benefit of lowering Lp(a ) is likely to be proportional to the absolute reduction in Lp(a ) concentration . Large absolute reductions in Lp(a ) of approximately 100 mg/dL may be required to produce a clinical ly meaningful reduction in the risk of CHD similar in magnitude to what can be achieved by lowering LDL-C level by 38.67 mg/dL ( ie , 1 mmol/L )", "Aims : In this study we evaluated the effect of mipomersen in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipid lowering drugs and regular lipoprotein apheresis . Methods : This prospect i ve , r and omized , controlled phase II single centre trial enrolled 15 patients ( 9 males , 6 females ; 59±9ys , BMI 27±4kg/m2 ) with established atherosclerosis , LDL-cholesterol ≥130mg/dL(3.4mmol/L ) despite maximal possible drug therapy , and fulfilling German criteria for regular lipoprotein apheresis . All patients were on stable lipid lowering drug therapy and regular apheresis for > 3 months . Patients r and omized to treatment ( n = 11 ) self-injected mipomersen 200 mg sc weekly at day 4 after apheresis for 26 weeks . Patients r and omized to control ( n = 4 ) continued apheresis without injection . The primary endpoint was the change in pre-apheresis LDL-cholesterol . Results : Of the patients r and omized to mipomersen 3 discontinued the drug early ( 12 weeks , mipomersen reduced pre-apheresis LDL-cholesterol significantly by 22.6 ± 17.0 % , from a baseline of 4.8 ± 1.2mmol/L to 3.7 ± 0.9mmol/L , while there was no significant change in the control group ( + 1.6 ± 9.3 % ) , with the difference between the groups being significant ( p=0.006 ) . Mipomersen also decreased pre-apheresis lipoprotein(a ) ( Lp(a ) ) concentration from a median baseline of 40.2mg/dL ( 32.5,71 ) by 15 % ( -19.4,3.6 ) though without significance ( p=0.3 ) . Conclusions : Mipomersen reduces LDL-cholesterol ( significantly ) and Lp(a ) ( non-significantly ) in patients on maximal lipid-lowering drug therapy and regular apheresis but often is associated with side effects", "BACKGROUND AND AIMS Heterozygous familial hypercholesterolemia ( HeFH ) is a common genetic disorder characterized by elevated low-density lipoprotein cholesterol ( LDL-C ) and increased cardiovascular disease risk . Despite multiple LDL-C-lowering therapies , many HeFH patients do not reach LDL-C targets . Mipomersen , an antisense oligonucleotide against apolipoprotein B ( apoB ) , might further lower LDL-C in HeFH patients . We assessed the efficacy and safety of two mipomersen dosing regimens in HeFH patients and explored whether thrice-weekly dosing improves the benefit-risk profile . METHODS In this double-blind trial , HeFH patients ( LDL-C > 160 mg/dL ) on maximal tolerated LDL-lowering therapy were r and omized to mipomersen 200 mg once weekly ( n = 104 ) , mipomersen 70 mg thrice weekly ( n = 102 ) , or placebo in matching frequency ( n = 103 ) for 60 weeks . Main outcomes were LDL-C , apoB , and lipoprotein(a ) levels after 60 weeks of treatment . RESULTS Mipomersen 200 mg once weekly and mipomersen 70 mg thrice weekly significantly lowered LDL-C compared with placebo by 21.0 % and 18.8 % , respectively , and apoB by 22.1 % and 21.7 % ( all p < 0.001 ) . Lipoprotein(a ) was significantly lowered by 27.7 % ( p < 0.001 ) with thrice-weekly dosing . Injection-site reactions and flu-like symptoms led to discontinuation in 21.2 % ( 200 mg ) , 17.6 % ( 70 mg ) , and 5.8 % ( placebo ) of participants . Alanine transaminase was elevated ( ≥3 × upper limit of normal at least once ) in 21.2 % , 21.6 % , and 1.0 % of subjects , respectively . CONCLUSIONS Mipomersen 200 mg once weekly and 70 mg thrice weekly are effective in lowering apoB-containing lipoproteins in HeFH patients . This is counterbalanced by limited tolerability and increased hepatic transaminase levels in about 21 % of patients . The thrice-weekly dosing regimen was associated with lower frequency of flu-like symptoms , which might help avert discontinuation in some patients , but otherwise had no major benefits", "OBJECTIVES This study sought to examine the efficacy and safety of mipomersen for reducing atherogenic lipids and lipoproteins in patients with hypercholesterolemia . BACKGROUND Many patients on lipid-lowering therapies remain unable to achieve target low-density lipoprotein ( LDL ) cholesterol levels . Mipomersen , an antisense oligonucleotide inhibitor of apolipoprotein B , reduces LDL cholesterol and atherogenic lipoproteins . METHODS This r and omized , double-blind , multicenter study enrolled 158 patients with baseline LDL cholesterol levels ≥100 mg/dl with , or at high risk for , coronary heart disease who were receiving maximally tolerated lipid-lowering therapy . Patients received weekly subcutaneous mipomersen 200 mg ( n = 105 ) or placebo ( n = 52 ) for 26 weeks , with a 24-week follow-up period . R and omization was stratified by type 2 diabetes status . RESULTS Sixty mipomersen and 44 placebo patients completed treatment . Mean baseline LDL cholesterol levels were 122.7 and 122.6 mg/dl in the placebo and mipomersen patients , respectively . Mipomersen reduced LDL cholesterol by -36.9 % compared with placebo at -4.5 % ( p < 0.001 ) . Target LDL cholesterol < 100 mg/dl was attained in 76 % of mipomersen and 38 % of placebo patients . Mipomersen also significantly reduced apolipoprotein B ( -38 % ) and lipoprotein(a ) ( -24 % ) ( p < 0.001 ) . Common adverse events included injection site reactions ( 78 % with mipomersen , 31 % with placebo ) and flu-like symptoms ( 34 % with mipomersen , 21 % with placebo ) . Elevations in transaminases and liver fat also occurred in some patients , and these levels returned toward baseline after treatment cessation . CONCLUSIONS Mipomersen significantly reduced LDL cholesterol , apolipoprotein B , and lipoprotein(a ) in patients with hypercholesterolemia with , or at risk for , coronary heart disease not controlled by existing therapies . ( Safety and Efficacy of Mipomersen [ ISIS 301012 ] as Add-On Therapy in High Risk Hypercholesterolemic Patients ; NCT00770146 )" ]

[ "3357223", "3906835", "4021426", "3825495", "4237547", "3654568", "4282288", "4900973", "25468945", "21457428", "22632452", "25495720" ]

[ "Dose-Ranging Effects of Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, as Add-On to Metformin in Subjects With Type 2 Diabetes", "Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, 12-week study†", "Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies", "Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial", "Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone", "Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease", "Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial", "Simultaneous Reduction in Both HbA1c and Body Weight with Canagliflozin Versus Glimepiride in Patients with Type 2 Diabetes on Metformin", "Efficacy and Safety of Canagliflozin, an Inhibitor of Sodium–Glucose Cotransporter 2, When Used in Conjunction With Insulin Therapy in Patients With Type 2 Diabetes", "Canagliflozin, a novel inhibitor of sodium glucose co‐transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects", "Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2 diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2 inhibitor", "Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes." ]

[ "OBJECTIVE To evaluate the effects of canagliflozin , a sodium-glucose cotransporter 2 inhibitor , in type 2 diabetes mellitus inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This was a double-blind , placebo-controlled , parallel-group , multicenter , dose-ranging study in 451 subjects r and omized to canagliflozin 50 , 100 , 200 , or 300 mg once daily ( QD ) or 300 mg twice daily ( BID ) , sitagliptin 100 mg QD , or placebo . Primary end point was change in A1C from baseline through week 12 . Secondary end points included change in fasting plasma glucose ( FPG ) , body weight , and overnight urinary glucose-to-creatinine ratio . Safety and tolerability were also assessed . RESULTS Canagliflozin was associated with significant reductions in A1C from baseline ( 7.6–8.0 % ) to week 12 : −0.79 , −0.76 , −0.70 , −0.92 , and −0.95 % for canagliflozin 50 , 100 , 200 , 300 mg QD and 300 mg BID , respectively , versus −0.22 % for placebo ( all P < 0.001 ) and −0.74 % for sitagliptin . FPG was reduced by −16 to −27 mg/dL , and body weight was reduced by −2.3 to −3.4 % , with significant increases in urinary glucose-to-creatinine ratio . Adverse events were transient , mild to moderate , and balanced across arms except for a non – dose-dependent increase in symptomatic genital infections with canagliflozin ( 3–8 % ) versus placebo and sitagliptin ( 2 % ) . Urinary tract infections were reported without dose dependency in 3–9 % of canagliflozin , 6 % of placebo , and 2 % of sitagliptin arms . Overall incidence of hypoglycemia was low . CONCLUSIONS Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss . The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females", "Aims We examined the efficacy , safety and tolerability of canagliflozin , a sodium glucose co-transporter 2 inhibitor , in Japanese patients with type 2 diabetes ( T2DM ) undergoing diet and exercise therapy . Methods Patients aged 20–80 years with T2DM diagnosed ≥3 months previously , and HbA1c of 6.9–9.9 % were r and omized to 50 , 100 , 200 or 300 mg canagliflozin or placebo once daily for 12 weeks . The primary and secondary endpoints were changes in HbA1c , fasting plasma glucose ( FPG ) , urinary glucose/creatinine and postpr and ial glycaemic parameters following a meal test . The safety assessment s included adverse events ( AEs ) and clinical laboratory tests . Results Overall , 383 patients were r and omized to receive either placebo ( n = 75 ) , or 50 mg ( n = 82 ) , 100 mg ( n = 74 ) , 200 mg ( n = 77 ) or 300 mg canagliflozin ( n = 75 ) . At week 12 , significant reductions in HbA1c were observed in all canagliflozin groups relative to placebo ( −0.61 , –0.80 , –0.79 and −0.88 % for 50 , 100 , 200 and 300 mg , respectively , versus + 0.11 % for placebo ; all , p < 0.01 ) . FPG and postpr and ial glycaemic parameters improved significantly in the canagliflozin groups . Body weight was significantly decreased by canagliflozin . No deaths or drug-related serious AEs were reported . There was no dose-dependent increase in the incidence of AEs in the canagliflozin groups . The incidence of hypoglycaemia was low ; episodes were not severe or dose dependent . Canagliflozin did not affect serum creatinine levels or the urinary albumin/creatinine ratio . Conclusions Treatment with canagliflozin for 12 weeks significantly improved glycaemic control and reduced body weight in Japanese patients with T2DM . Canagliflozin was well tolerated", "Background Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus ( T2DM ) . The efficacy and safety of canagliflozin were evaluated in patients with T2DM < 65 and ≥65 years of age . Methods Pooled data from 4 r and omised , placebo-controlled , 26-week , Phase 3 studies ( N = 2,313 ) evaluating canagliflozin 100 and 300 mg were analysed by age : < 65 years ( n = 1,868 ; mean age , 52.8 years ) or ≥65 years ( n = 445 ; mean age , 69.3 years ) . Efficacy evaluations included change from baseline in glycaemic parameters and systolic blood pressure ( BP ) , and percent change from baseline in body weight . Assessment of safety/tolerability included adverse event ( AE ) reports , incidence of documented hypoglycaemia , and percent change from baseline in fasting plasma lipids . Results Canagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients < 65 and ≥65 years of age . Both canagliflozin doses reduced body weight and systolic BP relative to placebo in patients < 65 and ≥65 years of age . Incidence of overall AEs was similar across all treatment groups in patients < 65 and ≥65 years of age . Incidences of serious AEs and AE-related discontinuations were similar across all treatment groups in patients < 65 years of age and higher with canagliflozin 100 mg than other groups in patients ≥65 years of age . As in patients < 65 years of age , incidences of genital mycotic infections and osmotic diuresis-related AEs were higher with canagliflozin relative to placebo in those ≥65 years of age . Incidences of urinary tract infections ( UTIs ) , renal-related AEs , AEs related to volume depletion , and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age ; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients < 65 years of age . Changes in lipid parameters with canagliflozin were similar in both age subsets . Conclusions Canagliflozin improved glycaemic control , body weight , and systolic BP , and was generally well tolerated in older patients with T2DM.Trial registration Clinical Trials.gov , NCT01081834 ; NCT01106677 ; NCT01106625 ; NCT01106690", "Aims /hypothesisThe aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin . Methods This r and omised , double-blind , four-arm , parallel-group , Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012 . Participants ( N = 1,284 ) with type 2 diabetes aged ≥18 and ≤80 years who had inadequate glycaemic control ( HbA1c ≥7.0 % [ 53 mmol/mol ] and ≤10.5 % [ 91 mmol/mol ] ) on metformin therapy received canagliflozin 100 mg or 300 mg , sitagliptin 100 mg , or placebo ( n = 368 , 367 , 366 , 183 , respectively ) for a 26 week , placebo- and active-controlled period followed by a 26 week , active-controlled period ( placebo group switched to sitagliptin [ placebo/sitagliptin ] ) and were included in the modified intent-to-treat analysis set . R and omisation was performed using a computer-generated schedule ; participants , study centres and the sponsor were blinded to group assignment . The primary endpoint was change from baseline in HbA1c at week 26 ; secondary endpoints included changes in HbA1c ( week 52 ) and fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( BP ; weeks 26 and 52 ) . Adverse events ( AEs ) were recorded throughout the study . Results At week 26 , canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo ( −0.79 % , –0.94 % , –0.17 % , respectively ; p < 0.001 ) . At week 52 , canagliflozin 100 mg and 300 mg demonstrated non-inferiority , and canagliflozin 300 mg demonstrated statistical superiority , to sitagliptin in lowering HbA1c ( −0.73 % , –0.88%,–0.73 % , respectively ) ; differences ( 95 % CI ) vs sitagliptin were 0 % ( −0.12 , 0.12 ) and −0.15 % ( −0.27 , –0.03 ) , respectively . Canagliflozin 100 mg and 300 mg reduced body weight vs placebo ( week 26 : –3.7 % , –4.2 % , –1.2 % , respectively ; p < 0.001 ) and sitagliptin ( week 52 : –3.8 % , –4.2 % , –1.3 % , respectively ; p < 0.001 ) . Both canagliflozin doses reduced FPG and systolic BP vs placebo ( week 26 ) and sitagliptin ( week 52 ) ( p < 0.001 ) . Overall AE and AE-related discontinuation rates were generally similar across groups , but higher with canagliflozin 100 mg . Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin ; few led to discontinuations . Hypoglycaemia incidence was higher with canagliflozin . Conclusions /interpretationCanagliflozin improved glycaemia and reduced body weight vs placebo ( week 26 ) and sitagliptin ( week 52 ) and was generally well tolerated in patients with type 2 diabetes on metformin . Clinical trial registry Clinical Trials.gov NCT01106677 Funding This study was supported by Janssen Research & Development , LLC", "Aim The efficacy and safety of canagliflozin , a sodium glucose co-transporter 2 inhibitor , was evaluated in patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled with metformin and pioglitazone . Methods In this r and omized , double-blind , phase 3 study , patients ( N = 342 ) received canagliflozin 100 or 300 mg during a 26-week , placebo-controlled , core period and a 26-week , active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg . Efficacy comparisons for canagliflozin versus placebo at week 26 are reported , with no comparisons versus sitagliptin at week 52 ( sitagliptin used to maintain double-blind and control for safety ) . Safety data are reported for canagliflozin and placebo/sitagliptin . Results Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c ( HbA1c ) compared with placebo at week 26 ( −0.89 % , −1.03 % and −0.26 % ; p < 0.001 ) ; reductions with canagliflozin 100 and 300 mg were maintained at week 52 ( −0.92 % and −1.03 % ) . Relative to placebo , both canagliflozin doses significantly reduced body weight ( −2.5 and −3.5 kg ) , fasting plasma glucose and systolic blood pressure ( BP ) at week 26 ( p < 0.05 for all ) , with reductions maintained at week 52 . Overall adverse event ( AE ) incidence over 52 weeks was 69.9 , 76.3 and 76.5 % with canagliflozin 100 and 300 mg and placebo/sitagliptin ; AE-related discontinuation and serious AE rates were low . Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin . Conclusion Canagliflozin improved glycaemic control , reduced body weight and systolic BP , and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks", "Canagliflozin is a sodium glucose co‐transporter 2 inhibitor in development for treatment of type 2 diabetes mellitus ( T2DM ) . This study evaluated the efficacy and safety of canagliflozin in subjects with T2DM and stage 3 chronic kidney disease [ CKD ; estimated glomerular filtration rate ( eGFR ) ≥30 and < 50 ml/min/1.73 m2 ]", "Aims Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus ( T2DM ) . This r and omised , double-blind , placebo-controlled , Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM . Methods Patients ( N = 469 ) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension . Prespecified primary end-point was change in HbA1c at 26 weeks . Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c < 7.0 % , change in fasting plasma glucose ( FPG ) and systolic blood pressure , and per cent change in body weight , high-density lipoprotein cholesterol , and triglycerides ( weeks 26 and 52 ) . Results HbA1c was significantly reduced with canagliflozin 100 and 300 mg vs. placebo at week 26 ( –0.85 % , –1.06 % , and –0.13 % ; p < 0.001 ) ; these reductions were maintained at week 52 ( –0.74 % , –0.96 % , and 0.01 % ) . Both canagliflozin doses reduced FPG and body weight vs. placebo at week 26 ( p < 0.001 ) and week 52 . Overall adverse event ( AE ) rates were similar across groups over 52 weeks , with higher rates of genital mycotic infections and osmotic diuresis-related AEs seen with canagliflozin vs. placebo ; these led to few discontinuations . Increased incidence of documented , but not severe , hypoglycaemia episodes was seen with canagliflozin vs. placebo . Conclusions Canagliflozin improved glycaemic control , reduced body weight , and was generally well tolerated in T2DM patients on metformin plus sulphonylurea over 52 weeks", "Introduction Canagliflozin , a sodium glucose co-transporter 2 ( SGLT2 ) inhibitor , has demonstrated sustained improvements in glycemic control and body weight reductions with treatment for up to 104 weeks in a broad range of patients with type 2 diabetes mellitus ( T2DM ) . Methods This was a post hoc analysis of individual patient data ( N = 1450 ) from a r and omized , double-blind , placebo-controlled , Phase 3 study comparing canagliflozin with glimepiride as add-on to metformin in patients with T2DM during a 52-week core period followed by a 52-week extension period . The number of patients who achieved a reduction from baseline in both HbA1c and body weight with canagliflozin 100 and 300 mg and glimepiride was assessed at Weeks 52 and 104 . Safety was recorded as adverse events ( AEs ) during the study . Results Canagliflozin 100 and 300 mg provided durable glycemic improvements and body weight reductions compared with glimepiride over 104 weeks . At Week 52 , the proportion of patients who achieved reductions in both HbA1c and body weight was 72.4 % with canagliflozin 100 mg , 78.5 % with canagliflozin 300 mg , and 26.8 % with glimepiride ; similar results were observed at Week 104 ( 65.5 % , 71.1 % , and 26.8 % with canagliflozin 100 and 300 mg and glimepiride , respectively ) . The AE profile of canagliflozin was comparable to that observed in previous studies , with increased incidence of AEs related to the mechanism of SGLT2 inhibition ( e.g. , genital mycotic infections , urinary tract infections , and osmotic diuresis – related AEs ) and a low risk of hypoglycemia . Conclusion More patients treated with canagliflozin experienced reductions in both HbA1c and body weight compared with glimepiride for up to 104 weeks . Canagliflozin was generally well tolerated in patients with T2DM when used in combination with metformin . Clinical Trial Registration Clinical Trials.gov identifier , NCT00968812 . Funding Janssen Research & Development , LLC", "OBJECTIVE There are limited data about the effects of sodium – glucose cotransporter 2 inhibitors when used with insulin . We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin . RESEARCH DESIGN AND METHODS The CANagliflozin CardioVascular Assessment Study is a double-blind , placebo-controlled study that r and omized participants to placebo , canagliflozin 100 mg , or canagliflozin 300 mg once daily , added to a range of therapies . The primary end point of this sub study was the change in HbA1c from baseline at 18 weeks among patients using insulin ; 52-week effects were also examined . RESULTS Individuals receiving insulin at baseline were r and omized to receive placebo ( n = 690 ) , canagliflozin 100 mg ( n = 692 ) , or canagliflozin 300 mg ( n = 690 ) . These individuals were 66 % male and had a median age of 63 years , mean HbA1c of 8.3 % ( 67 mmol/mol ) , BMI of 33.1 kg/m2 , estimated glomerular filtration rate of 75 mL/min/1.73 m2 , fasting plasma glucose of 9.2 mmol/L , and a median daily insulin dose of 60 IU . Most individuals were using basal/bolus insulin . Reductions in HbA1c with canagliflozin 100 and 300 mg versus placebo were −0.62 % ( 95 % CI −0.69 , −0.54 ; −6.8 mmol/mol [ 95 % CI −7.5 , −5.9 ] ; P < 0.001 ) and −0.73 % ( 95 % CI −0.81 , −0.65 ; −8.0 mmol/mol [ 95 % CI −8.9 , −7.1 ] ; P < 0.001 ) at 18 weeks and −0.58 % ( 95 % CI −0.68 , −0.48 ; −6.3 mmol/mol [ 95 % CI −7.4 , −5.2 ] ) and −0.73 % ( 95 % CI −0.83 , −0.63 ; −8.0 mmol/mol [ 95 % CI −9.1 , −6.9 ] ) at 52 weeks . There were significant falls in fasting plasma glucose , body weight , and blood pressure at both time points and there was a greater incidence of hypoglycemia , genital mycotic infections , and hypovolemia with both canagliflozin doses . CONCLUSIONS Canagliflozin added to insulin therapy improved glycemic control and decreased body weight . There was a greater frequency of several anticipated side effects , although few led to discontinuation of treatment", "Canagliflozin , a potent , selective sodium glucose co‐transporter 2 inhibitor in development for treatment of type 2 diabetes , lowers plasma glucose ( PG ) by lowering the renal threshold for glucose ( RTG ) and increasing urinary glucose excretion ( UGE ) . An ascending single oral‐dose phase 1 study investigated safety , tolerability and pharmacodynamics of canagliflozin in healthy men ( N = 63 ) r and omized to receive canagliflozin ( n = 48 ) or placebo ( n = 15 ) . Canagliflozin ( 10 , 30 , 100 , 200 , 400 , 600 or 800 mg q.d . or 400 mg b.i.d . ) was administered to eight cohorts ( six subjects/cohort : canagliflozin ; two subjects/cohort : placebo ) . Dose dependently , canagliflozin decreased calculated 24‐h mean RTG with maximal reduction to approximately 60 mg/dl , and increased mean 24‐h UGE . At doses > 200 mg administered before breakfast , canagliflozin reduced postpr and ial PG and serum insulin excursions at that meal . Canagliflozin was generally well tolerated ; most adverse events were mild and no hypoglycaemia was reported . These results support further study of canagliflozin", "Abstract Background / objective : Women with type 2 diabetes mellitus ( T2DM ) are at increased risk for vaginal C and ida colonization , perhaps because of glucosuria . Sodium glucose co-transporter 2 ( SGLT2 ) inhibitors , in development for the treatment of T2DM , improve glycemic control by increasing urinary glucose excretion . Vaginal C and ida colonization and symptomatic vulvovaginal adverse events ( VVAE ) were assessed in females with T2DM treated with canagliflozin , a SGLT2 inhibitor . Methods : In a double-blind study , subjects with T2DM and inadequate glycemic control on metformin were r and omized to placebo ; canagliflozin 50 , 100 , 200 , 300 mg daily or 300 mg twice daily ; or sitagliptin 100 mg daily for 12 weeks . Vaginal swabs for C and ida culture were collected from 198 female subjects at baseline and week 12 , and during the trial if symptoms consistent with vulvovaginal c and idiasis occurred . Results : At baseline , 23/198 ( 12 % ) females had vaginal cultures positive for C and ida ( C. glabrata : 14 ; C. albicans : 5 ; other : 4 ) , with age ≤55 years associated with increased risk ( odds ratio [ OR ] , 3.5 ; 95 % confidence interval [ CI ] , 1.1–10.7 ) . Of those with negative cultures at baseline , 31 % of canagliflozin and 14 % of placebo/sitagliptin subjects converted to positive at week 12 ( OR , 2.8 ; 95 % CI , 1.0–7.3 for canagliflozin vs. placebo/sitagliptin ) . Two placebo/sitagliptin ( 3 % ) and 16 canagliflozin subjects ( 10 % ) experienced VVAE . Positive vaginal culture for C and ida species at baseline was a risk factor for VVAE ( OR , 9.1 ; 95 % CI , 2.4–34.0 ) . All 9/9 subjects in the canagliflozin group with a vaginal culture taken at the time of the VVAE were positive for C and ida species . Most VVAE were treated with antifungal therapy and resolved without study drug interruption ; none led to discontinuation . Study limitations include small population , short duration , and not obtaining cultures in all women with VVAE . Conclusion : Canagliflozin treatment was associated with an increase in vaginal colonization with C and ida species and in VVAE in women with T2DM . Trial registration : Clinical Trials.gov identifier : NCT00642278", "AIMS The long-term efficacy and safety of canagliflozin , a sodium glucose co-transporter 2 inhibitor , was evaluated over 104 weeks in patients aged 55 - 80 years with type 2 diabetes mellitus ( T2DM ) inadequately controlled on a stable antihyperglycaemic agent regimen . METHODS In this r and omized , double-blind , phase III study , patients received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period ( N = 714 ) and a 78-week extension period ( n = 624 ) . Efficacy endpoints at week 104 included change from baseline in glycated haemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) and systolic blood pressure , and percent change from baseline in body weight and fasting plasma lipids . Safety was assessed by adverse event ( AE ) reports . RESULTS At week 104 , canagliflozin 100 and 300 mg were associated with reductions in HbA1c versus placebo ( -0.32 and -0.43 % vs 0.17 % , respectively ; overall mean baseline , 7.7 % ) and more patients achieved HbA1c < 7.0 % with canagliflozin 100 and 300 mg than with placebo ( 35.8 and 41.9 % vs 20.3 % , respectively ) . Reductions in FPG , body weight and systolic blood pressure , and increases in high-density lipoprotein cholesterol ( HDL-C ) and low-density lipoprotein cholesterol ( LDL-C ) were seen with canagliflozin compared with placebo . The overall incidence rates of AEs over 104 weeks were 88.0 , 89.8 and 86.1 % with canagliflozin 100 and 300 mg and placebo , respectively ; serious AE rates were low across treatment groups . The incidence rates of urinary tract infections , genital mycotic infections and osmotic diuresis- and volume depletion-related AEs were higher with canagliflozin than with placebo . CONCLUSION Canagliflozin improved glycaemic control , reduced body weight and systolic blood pressure , and was generally well tolerated in patients aged 55 - 80 years with T2DM over 104 weeks" ]

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[ "A randomized study of the effects of t'ai chi on muscle strength, bone mineral density, and fear of falling in women with osteoarthritis.", "Effects of a Sun-style Tai Chi exercise on arthritic symptoms, motivation and the performance of health behaviors in women with osteoarthritis.", "Effectiveness and efficiency of an 11-week exercise intervention for patients with hip or knee osteoarthritis: a protocol for a controlled study in the context of health services research", "Simplified Tai Chi Resistance Training versus Traditional Tai Chi in Slowing Bone Loss in Postmenopausal Women", "Assessing the comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: design and rationale for a randomized trial", "A randomised controlled trial of Tai Chi and resistance exercise on bone health, muscle strength and balance in community-living elderly people.", "Tai Chi Qigong for the quality of life of patients with knee osteoarthritis: a pilot, randomized, waiting list controlled trial", "Tai Chi Improves Physical Function in Older Chinese Women With Knee Osteoarthritis", "Tai Chi is effective in treating knee osteoarthritis: a randomized controlled trial.", "A pilot cluster-randomized trial of a 20-week Tai Chi program in elders with cognitive impairment and osteoarthritic knee: effects on pain and other health outcomes.", "A supplemental report to a randomized cluster trial of a 20-week Sun-style Tai Chi for osteoarthritic knee pain in elders with cognitive impairment.", "Physical activity for osteoarthritis management: a randomized controlled clinical trial evaluating hydrotherapy or Tai Chi classes.", "Effects of tai chi exercise on pain, balance, muscle strength, and perceived difficulties in physical functioning in older women with osteoarthritis: a randomized clinical trial.", "A randomized, prospective study of the effects of Tai Chi Chun exercise on bone mineral density in postmenopausal women." ]

[ "PURPOSE Individuals with osteoarthritis can experience difficulty walking and poor strength , possibly leading to falls and fractures . Exercise has been found to increase strength and bone mineral density . The purpose of this study was to determine the effects of 6 months of t'ai chi on knee muscle strength , bone mineral density , and fear of falling in older women with osteoarthritis . METHODS Eighty-two ( 82 ) women with osteoarthritis , recruited from outpatient clinics and community health centers , were r and omly assigned to either a t'ai chi group and took part in a t'ai chi program , or a control group . Of these , 30 subjects ( mean age = 63 years ) in the t'ai chi group and 35 ( mean age = 61 years ) in the control group completed post-test measures at 6 months . RESULTS After the 6-month study period , subjects in the t'ai chi program had significantly greater knee extensor endurance ( pre- to post-test mean increase = 36.4 W/kg , versus 1.1 W/kg for the controls ) , and significantly greater bone mineral density in the neck of the proximal femur ( mean change = 0.09 , versus -0.10 for the controls ) , Ward 's triangle ( mean change = 0.04 , versus -0.04 for the controls ) , and trochanter ( mean change = 0.07 , versus -0.05 for the controls ) than the controls . However , knee extensor and flexor strength did not differ significantly between the groups . The fear of falling during daily activities reduced significantly more in the t'ai chi group ( mean change = -2.40 , versus 0.66 for the controls ) . CONCLUSIONS T'ai chi increased knee extensor muscle endurance and bone mineral density in older women with osteoarthritis , and decreased their fear of falling during daily activities . Further study with long-term follow-up is needed to substantiate the role of t'ai chi exercise in the prevention of fall and its related fracture", "PURPOSE Tai Chi exercise , an ancient Chinese martial art , has drawn more and more attention for its health benefits . The purpose of the study was to identify the effects of a Sun-style Tai Chi exercise on arthritic symptoms ( joint pain and stiffness ) , motivation for performing health behaviors , and the performance of health behaviors among older women with osteoarthritis . METHODS Total of 72 women with the mean age of 63 years old were recruited from out patients clinic or public health centers according to the inclusion criteria and assigned r and omly to either the Tai Chi exercise group or the control . A Sun-style Tai Chi exercise has been provided three times a week for the first two weeks , and then once a week for another 10 weeks . In 12 weeks of study period , 22 subjects in the Tai Chi exercise group and 21 subjects in the control group completed the posttest measure with the dropout rate of 41 % . Outcome variables included arthritic symptoms measured by K-WOMAC , motivation for health behavior , and health behaviors . RESULTS At the completion of the 12 week Tai Chi exercise , the Tai Chi group perceived significantly less joint pain ( t=-2.19 , p=0.03 ) and stiffness ( t=-2.24 , p=0.03 ) , perceived more health benefits ( t=2.67 , p=0.01 ) , and performed better health behaviors ( t=2.35 , p=0.02 ) , specifically for diet behavior ( t=2.06 , p=0.04 ) and stress management ( t=2.97 , p=0.005 ) . CONCLUSION A Sun-style Tai Chi exercise was found as beneficial for women with osteoarthritis to reduce their perceived arthritic symptoms , improve their perception of health benefits to perform better health behaviors", "Background Osteoarthritis is the most common reason for pain in older adults , and the individual and economic burden of this disease is immense . The chronic character of osteoarthritis requires a long-term therapeutic treatment . In this regard life-style interventions such as physical exercises that can be carried out by the patient himself are recommended as first line treatment . There is evidence for the short-term benefit of exercise therapy in terms of pain reduction and physical functioning . Nonetheless research agendas highlight the need for multifaceted interventions that incorporate exercise strategies into patient care . Studies should be conducted with appropriate sample sizes and should allow statements on long-term effects as well as cost-utility and safety . These open questions are under the scope of this study . Methods / design This is a controlled study in the context of health services research . The study population consists of n = 1400 subjects with hip or knee osteoarthritis . The intervention group will be recruited from participants of a country-wide health insurance offer for people with hip or knee osteoarthritis . Potential participants for the control group ( ratio 10:1 ( control vs. intervention ) will be filtered out from the insurance data base according to pre-defined matching criteria and asked by letter for their participation . The final statistical twins from the responders ( 1:1 ) will be determined via propensity score matching . The progressive training intervention comprises 8 supervised group sessions , supplemented by home exercises ( 2/week over 11 weeks ) . Exercises include mobilization , strengthening and training of postural control . Primary outcomes are pain and function measured with the WOMAC Index immediately after the intervention period . Among other things , health related quality of life , self-efficacy , cost utility and safety will be evaluated as secondary outcomes . Participants will be followed up 6 , 12 and 24 month after baseline . Discussion Results of this trial will document the effects of clinical as well as economic outcomes in a regular health care setting on the basis of a large sample size . As such , results of this trial might have great impact on future implementations of group- and home-based exercises in hip or knee osteoarthritis . Trail registration German Clinical Trial Register DRKS00009251 . Registered 10 September 2015", "Background . This study examined whether simplified Tai Chi resistance training is superior to traditional Tai Chi in slowing bone loss in postmenopausal women . Methods . This prospect i ve trial included 119 postmenopausal women ( age : 52–65 years ) . Subjects were r and omly assigned to participate in a traditional Tai Chi program ( TTC , n = 40 ) , a simplified Tai Chi resistance training program ( TCRT , n = 40 ) , or a blank control group ( routine activity , n = 39 ) . The TTC involved traditional Yang Style Tai Chi . The primary outcome was the change of lumbar bone mass density ( L2–L4 ) at 12 months over the baseline . Femoral neck and Ward 's triangle were also measured using dual-energy X-ray absorptiometry . Results . The L2–L4 density was significantly lower at 12 months in comparison to the baseline in the blank control group . In both the TCRT and TTC groups , the L2–L4 density was comparable to the baseline . There was a trend for less bone loss in the TCRT than in the TTC group . Similar findings were observed with femoral neck and Ward 's triangle . Conclusion . Simplified Tai Chi resistance training could slow bone loss in menopausal women . The results also suggested , but did not confirm , superiority to traditional Tai Chi", "Background Knee osteoarthritis ( OA ) causes pain and long-term disability with annual healthcare costs exceeding $ 185 billion in the United States . Few medical remedies effectively influence the course of the disease . Finding effective treatments to maintain function and quality of life in patients with knee OA is one of the national priorities identified by the Institute of Medicine . We are currently conducting the first comparative effectiveness and cost-effectiveness r and omized trial of Tai Chi versus a physical-therapy regimen in a sample of patients with symptomatic and radiographically confirmed knee OA . This article describes the design and conduct of this trial . Methods / Design A single-center , 52-week , comparative effectiveness r and omized controlled trial of Tai Chi versus a st and ardized physical-therapy regimen is being conducted at an urban tertiary medical center in Boston , Massachusetts . The study population consists of adults ≥ 40 years of age with symptomatic and radiographic knee OA ( American College of Rheumatology criteria ) . Participants are r and omly allocated to either 12 weeks of Tai Chi ( 2x/week ) or Physical Therapy ( 2x/week for 6 weeks , followed by 6 weeks of rigorously monitored home exercise ) . The primary outcome measure is pain ( Western Ontario and McMaster Universities WOMAC ) subscale at 12 weeks . Secondary outcomes include WOMAC stkiffness and function domain scores , lower extremity strength and power , functional balance , physical performance tests , psychological and psychosocial functioning , durability effects , health related quality of life , and healthcare utilization at 12 , 24 and 52 weeks . Discussion This study will be the first r and omized comparative-effectiveness and cost-effectiveness trial of Tai Chi versus Physical Therapy in a large symptomatic knee OA population with long-term follow up . We present here a robust and well- design ed r and omized comparative-effectiveness trial that also explores multiple outcomes to eluci date the potential mechanisms of mind-body effect for a major disabling disease with substantial health burdens and economic costs . Results of this study are expected to have important public health implication s for the large and growing population with knee OA.Trial registration Clinical Trials.gov identifier :", "BACKGROUND The beneficial role of exercise in improving bone mineral density , muscle strength and balance , has been documented predominantly in younger population s. These findings may not apply to elderly population s with limited ability to perform exercises of high intensity . OBJECTIVE To examine the effects of Tai Chi ( TC ) and resistance exercise ( RTE ) on bone mineral density ( BMD ) , muscle strength , balance and flexibility in community living elderly people . DESIGN R and omised controlled trial , using blocked r and omization with stratification by sex . SETTING A community in the New Territories Region of Hong Kong , China . SUBJECTS One hundred eighty subjects ( 90 men , 90 women ) aged 65 - 74 , were recruited through advertisements in community centres . METHODS Subjects were assigned to participate in TC , RTE three times a week , or no intervention ( C ) for 12 months . Measurements were carried out at baseline , 6 and 12 months . Analyses of covariance ( ANCOVA ) adjusted for age , and baseline values of variables that were significantly different between groups : i.e. smoking and flexibility for men ; quadriceps strength for women . RESULTS Compliance was high ( TC 81 % , RTE 76 % ) . In women , both TC and RTE groups had less BMD loss at total hip compared with controls . No effect was observed in men . No difference in either balance , flexibility or the number of falls was observed between either intervention or controls after 12 months . CONCLUSION The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes", "Objective : To evaluate the effects of Tai Chi Qigong training on the quality of life and physical function of patients with osteoarthritis of the knee . Design : A preliminary , single-blind , r and omized controlled trial . Setting : General community , performed at Hwaseong City Health Center . Participants : Forty-four elderly subjects ( mean age , 69.1 ± 5.4 years ) with knee osteoarthritis . Intervention : The patients were r and omized ( 2:1 ) to : ( 1 ) an eight-week Tai Chi Qigong training programme or ( 2 ) a waiting list control group . The programme involved eight weeks of group Tai Chi Qigong sessions , with 60 minutes per session twice a week . Main outcome measures : The primary outcome was quality of life measured with the Short Form 36 ( SF-36 ) at baseline and week 8 . Secondary outcomes included the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) and 6-m walking time . Results : The training group had statistically significant improvements in the quality of life ( changes of SF-36 , Qigong versus control : 21.6 ± 16.8 versus 9.8 ± 13.6 , P<0.05 ) and 6-m walking test ( change in walking time , Qigong versus control : —1.6 ± 1.7 versus —0.2 ± 0.8 s , P<0.01 ) . The WOMAC scores in the training group were markedly improved , although the differences were not statistically significant . Conclusions : Tai Chi Qigong training appears to have beneficial effects in terms of the quality of life and physical functioning of elderly subjects with knee osteoarthritis . However , more rigorous trials are needed to confirm the efficacy of this training for patients with osteoarthritis of the knee", "Background : Tai chi ( TC ) is proposed as a potential option for the management of osteoarthritis ( OA ) , however , its beneficial effect on patients with knee OA has not been convincing . Objectives : To evaluate the effect of a 24-week TC program on physical functions in older Chinese women with knee OA . Methods : Thirty-five older Chinese women with knee OA were r and omized into TC group ( n = 18 ) and attention control ( wellness education and stretching ) group ( n = 17 ) . Subjects in the TC group practice d the 24-form simplified Yang-style TC 2 to 4 times a week for 24 weeks with frequency gradually increased . Physical function was assessed using the Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) , 6-minute walk distance and stair climb time . Results : Compared with the control group , the participants in TC group had statistically significant improvements in changes of the WOMAC total score ( 6.18 ± 2.13 vs. 1.71 ± 2.73 , P = 0.000 ) , the WOMAC pain subscale ( 1.36 ± 0.22 vs. 0.07 ± 1.00 , P = 0.001 ) , the WOMAC stiffness subscale ( 0.66 ± 0.25 vs. 0.05 ± 0.38 , P = 0.043 ) , the WOMAC function subscale ( 6.17 ± 1.96 vs. 1.72 ± 2.63 , P = 0.000 ) , the 6-minute walk distance ( 32.43 ± 14.20 vs. 6.67 ± 16.76 , P = 0.003 ) , and the stair climb time ( 2.27 ± 0.74 vs. 0.27 ± 1.24 , P = 0.001 ) . Conclusions : This study suggests that TC provides a safe , feasible and useful exercise option for older Chinese female patients with knee OA", "OBJECTIVE To evaluate the effectiveness of Tai Chi in the treatment of knee osteoarthritis ( OA ) symptoms . METHODS We conducted a prospect i ve , single-blind , r and omized controlled trial of 40 individuals with symptomatic tibiofemoral OA . Patients were r and omly assigned to 60 minutes of Tai Chi ( 10 modified forms from classic Yang style ) or attention control ( wellness education and stretching ) twice weekly for 12 weeks . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain score at 12 weeks . Secondary outcomes included WOMAC function , patient and physician global assessment s , timed chair st and , depression index , self-efficacy scale , and quality of life . We repeated these assessment s at 24 and 48 weeks . Analyses were compared by intent-to-treat principles . RESULTS The 40 patients had a mean age of 65 years and a mean body mass index of 30.0 kg/m(2 ) . Compared with the controls , patients assigned to Tai Chi exhibited significantly greater improvement in WOMAC pain ( mean difference at 12 weeks -118.80 mm [ 95 % confidence interval ( 95 % CI ) -183.66 , -53.94 ; P = 0.0005 ] ) , WOMAC physical function ( -324.60 mm [ 95 % CI -513.98 , -135.22 ; P = 0.001 ] ) , patient global visual analog scale ( VAS ; -2.15 cm [ 95 % CI -3.82 , -0.49 ; P = 0.01 ] ) , physician global VAS ( -1.71 cm [ 95 % CI -2.75 , -0.66 ; P = 0.002 ] ) , chair st and time ( -10.88 seconds [ 95 % CI -15.91 , -5.84 ; P = 0.00005 ] ) , Center for Epidemiologic Studies Depression Scale ( -6.70 [ 95 % CI -11.63 , -1.77 ; P = 0.009 ] ) , self-efficacy score ( 0.71 [ 95 % CI 0.03 , 1.39 ; P = 0.04 ] ) , and Short Form 36 physical component summary ( 7.43 [ 95 % CI 2.50 , 12.36 ; P = 0.004 ] ) . No severe adverse events were observed . CONCLUSION Tai Chi reduces pain and improves physical function , self-efficacy , depression , and health-related quality of life for knee OA", "CONTEXT Because Tai Chi ( TC ) is beneficial to elders without cognitive impairment ( CI ) , it also may benefit elders with CI . But elders with CI have generally been excluded from TC studies because many measurement tools require verbal reports that some elders with CI are unable to provide . OBJECTIVES To test the efficacy of a TC program in improving pain and other health outcomes in community-dwelling elders with knee osteoarthritis ( OA ) and CI . METHODS This pilot cluster-r and omized trial was conducted between January 2008 and June 2010 ( Clinical Trials.gov Identifier : NCT01528566 ) . The TC group attended Sun style TC classes , three sessions a week for 20 weeks ; the control group attended classes providing health and cultural information for the same length of time . Measures included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain , physical function and stiffness subscales ; the Get Up and Go test ; the Sit-to-St and test ; and the Mini-Mental State Examination ( MMSE ) , administered at baseline , every four weeks during the intervention and at the end of the study ( post-test ) . RESULTS Eight sites participated in either the TC group ( four sites , 28 participants ) or control group ( four sites , 27 participants ) . The WOMAC pain ( P = 0.006 ) and stiffness scores ( P = 0.010 ) differed significantly between the two groups at post-test , whereas differences between the two groups in the WOMAC physical function score ( P = 0.071 ) and the MMSE ( P = 0.096 ) showed borderline significance at the post-test . WOMAC pain ( P = 0.001 ) , physical function ( P = 0.021 ) , and stiffness ( P ≤ 0.001 ) scores improved significantly more over time in the TC group than in controls . No adverse events were found in either group . CONCLUSION Practicing TC can be efficacious in reducing pain and stiffness in elders with knee OA and CI", "OBJECTIVE This was a secondary data analysis of a cluster-r and omized clinical trial that tested the efficacy of a 20-week Sun-style Tai Chi ( TC ) program in reducing pain in community-dwelling elders with cognitive impairment and knee osteoarthritis ( OA ) . The study also examined whether elders ' level of cognitive function was related to the outcomes of the TC program . METHOD Elders ( N=55 ) were recruited from 8 study sites . Each site was r and omly assigned to participate in either a 20-week TC or an education program . Verbal report of pain was measured by a Verbal Descriptor Scale ( VDS ) at weeks 1 , 5 , 9 , 13 , 17 and 21 ( design ated as times 1 - 6 ) . Pain behaviors and analgesic intake were also recorded at times 1 - 6 . RESULTS At post-test , scores on the VDS and observed pain behaviors were significantly better in the TC group than in the control group ( p=0.008 - 0.048 ) . The beneficial effects of TC were not associated with cognitive ability . CONCLUSION These results suggest that TC can be used as an adjunct to pharmacological intervention to relieve OA pain in elders with cognitive impairment . TRIAL REGISTRATION Clinical Trial.gov NCT01528566", "OBJECTIVE To determine whether Tai Chi or hydrotherapy classes for individuals with chronic symptomatic hip or knee osteoarthritis ( OA ) result in measurable clinical benefits . METHODS A r and omized controlled trial was conducted among 152 older persons with chronic symptomatic hip or knee OA . Participants were r and omly allocated for 12 weeks to hydrotherapy classes ( n = 55 ) , Tai Chi classes ( n = 56 ) , or a waiting list control group ( n = 41 ) . Outcomes were assessed 12 and 24 weeks after r and omization and included pain and physical function ( Western Ontario and McMaster Universities Osteoarthritis Index ) , general health status ( Medical Outcomes Study Short Form 12 Health Survey [ SF-12 ] , version 2 ) , psychological well-being , and physical performance ( Up and Go test , 50-foot walk time , timed stair climb ) . RESULTS At 12 weeks , compared with controls , participants allocated to hydrotherapy classes demonstrated mean improvements ( 95 % confidence interval ) of 6.5 ( 0.4 , 12.7 ) and 10.5 ( 3.6 , 14.5 ) for pain and physical function scores ( range 0 - 100 ) , respectively , whereas participants allocated to Tai Chi classes demonstrated improvements of 5.2 ( -0.8 , 11.1 ) and 9.7 ( 2.8 , 16.7 ) , respectively . Both class allocations achieved significant improvements in the SF-12 physical component summary score , but only allocation to hydrotherapy achieved significant improvements in the physical performance measures . All significant improvements were sustained at 24 weeks . In this almost exclusively white sample , class attendance was higher for hydrotherapy , with 81 % attending at least half of the available 24 classes , compared with 61 % for Tai Chi . CONCLUSION Access to either hydrotherapy or Tai Chi classes can provide large and sustained improvements in physical function for many older , sedentary individuals with chronic hip or knee OA", "OBJECTIVE Twelve forms of Sun-style tai chi exercise have been developed specifically to reduce the symptoms and improve the physical functioning of arthritic patients , and this r and omized study examined the changes in symptoms and physical characteristics in older women with osteoarthritis ( OA ) at the completion of a 12-week tai chi exercise program . METHODS Seventy-two patients with OA were r and omly assigned into 2 groups . Due to a 41 % overall dropout rate , 22 experimental subjects and 21 controls completed pre- and post-test measures over a 12 week interval . Outcome variables were physical symptoms and fitness , body mass index , cardiovascular functioning , and perceived difficulties in physical functioning . The independent t test was used to examine group differences . RESULTS The homogeneity test confirmed that there were no significant group differences in demographic data and pretest measures . Mean comparisons of the change scores revealed that the experimental group perceived significantly less pain ( t = -2.19 , p = 0.034 ) and stiffness ( t = -2.13 , p = 0.039 ) in their joints , and reported fewer perceived difficulties in physical functioning ( t = -2.81 , p = 0.008 ) , while the control group showed no change or even deterioration in physical functioning after 12 weeks . In the physical fitness test , there were significant improvements in balance ( t = 3.34 , p = 0.002 ) and abdominal muscle strength ( t = 2.74 , p = 0.009 ) for the tai chi exercise group . No significant group differences were found in flexibility and upper-body or knee muscle strength in the post-test scores . CONCLUSION Older women with OA were able to safely perform the 12 forms of Sun-style tai chi exercise for 12 weeks , and this was effective in improving their arthritic symptoms , balance , and physical functioning . A longitudinal study with a larger sample size is now needed to confirm the potential use of tai chi exercise in arthritis management", "OBJECTIVE To evaluate the potential benefits of programmed Tai Chi Chun ( TCC ) exercise on the weight-bearing bones of early postmenopausal women . DESIGN Age-matched and r and omized prospect i ve intervention . SETTING University medical school . PARTICIPANTS One hundred thirty-two healthy postmenopausal women ( mean age , 54.0+/-3.5y ) within 10 years of menopause onset were recruited and r and omized into the TCC exercise group ( n=67 ) or the sedentary control group ( n=65 ) . INTERVENTION Supervised TCC exercise was performed by the TCC group for 45 minutes a day , 5 days a week , for 12 months ; control subjects retained a sedentary life style . Main outcome measures Bone mineral density ( BMD ) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography ( pQCT ) . All BMD measurements were repeated after 12 months in both groups . Fracture rate was also documented . RESULTS Baseline measurements showed homogeneity in age , anthropometric variables , and menstruation status between the TCC and control groups . Exactly 81.6 % of the subjects in the TCC group and 83.1 % of subjects in the control group completed the 12-month follow-up study . BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites , but with a reportedly slower rate in the TCC group . A significant 2.6- to 3.6-fold retardation of bone loss ( P<.01 ) was found in both trabecular and cortical compartments of the distal tibia in the TCC group as compared with the controls , as measured by pQCT . A total of 4 fracture cases were documented during follow-up , including 3 subjects in the control group and 1 in the TCC group . CONCLUSIONS This is the first prospect i ve and r and omized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women . Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture" ]

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[ "Effect of a standardized nurse case-management telephone intervention on resource use in patients with chronic heart failure.", "Reducing the Cost of Frequent Hospital Admissions for Congestive Heart Failure: A Randomized Trial of a Home Telecare Intervention", "The comparative impact of video-consultation on neurosurgical health services", "What we can really expect from telemedicine in intensive diabetes treatment: results from 3-year study on type 1 pregnant diabetic women.", "Randomised controlled trial of telemedicine for new neurological outpatient referrals", "Cost analysis of telehomecare.", "Cost Implications of Outpatient Teleneurology", "The impact of telemedicine on outcomes of chronic wounds in the home care setting.", "The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.", "Telemedicine in the treatment of diabetic pregnancy.", "Improvement in diabetes control with a monitoring system based on a hand-held, touch-screen electronic diary", "Patient referral by telemedicine: effectiveness and cost analysis of an intranet system", "A randomized controlled trial assessing the health economics of realtime teledermatology compared with conventional care: an urban versus rural perspective", "A cost-minimization study of telemedicine. The case of telemonitored polysomnography to diagnose obstructive sleep apnea syndrome.", "[Tele-medicine system for high-risk asthmatic patients].", "Perioperative cataract OP management by means of teleconsultation", "The effect of telepharmacy counseling on metered-dose inhaler technique among adolescents with asthma in rural Arkansas.", "Compliance and effectiveness of 1 year's home telemonitoring. The report of a pilot study of patients with chronic heart failure", "Effects of home telemonitoring and community-based monitoring on blood pressure control in urban African Americans: a pilot study.", "A prospective satisfaction study and cost analysis of a pilot child telepsychiatry service in Newfoundland", "A cost-minimization analysis of the societal costs of realtime teledermatology compared with conventional care: results from a randomized controlled trial in New Zealand", "Telehealth: Reaching Out to Newly Injured Spinal Cord Patients", "Telemedicine improved diabetic management.", "[Hospitalization reduction by an asthma tele-medicine system]." ]

[ "BACKGROUND Case management is believed to promote continuity of care and decrease hospitalization rates , although few controlled trials have tested this approach . OBJECTIVE To assess the effectiveness of a st and ardized telephonic case-management intervention in decreasing re source use in patients with chronic heart failure . METHODS A r and omized controlled clinical trial was used to assess the effect of telephonic case management on re source use . Patients were identified at hospitalization and assigned to receive 6 months of intervention ( n = 130 ) or usual care ( n = 228 ) based on the group to which their physician was r and omized . Hospitalization rates , readmission rates , hospital days , days to first rehospitalization , multiple readmissions , emergency department visits , inpatient costs , outpatient re source use , and patient satisfaction were measured at 3 and 6 months . RESULTS The heart failure hospitalization rate was 45.7 % lower in the intervention group at 3 months ( P = .03 ) and 47.8 % lower at 6 months ( P = .01 ) . Heart failure hospital days ( P = .03 ) and multiple readmissions ( P = .03 ) were significantly lower in the intervention group at 6 months . Inpatient heart failure costs were 45.5 % lower at 6 months ( P = .04 ) . A cost saving was realized even after intervention costs were deducted . There was no evidence of cost shifting to the outpatient setting . Patient satisfaction with care was higher in the intervention group . CONCLUSIONS The reduction in hospitalizations , costs , and other re source use achieved using st and ardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches", "Background .The high cost of caring for patients with congestive heart failure ( CHF ) results primarily from frequent hospital readmissions for exacerbations . Home nurse visits after discharge can reduce readmissions , but the intervention costs are high . Objectives .To compare the effectiveness of three hospital discharge care models for reducing CHF-related readmission charges : 1 ) home telecare delivered via a 2-way video-conference device with an integrated electronic stethoscope ; 2 ) nurse telephone calls ; and 3 ) usual outpatient care . Research Design . One-year r and omized trial . Subjects . English-speaking patients 40 years of age and older with a primary hospital admission diagnosis of CHF . Measures .Our primary outcome was CHF-related readmission charges during a 6-month period after r and omization . Secondary outcomes included all-cause readmissions , emergency department ( ED ) visits , and associated charges . Results .Thirty-seven subjects were r and omized : 13 to home telecare , 12 each telephone care and 12 to usual care . Mean CHF-related readmission charges were 86 % lower in the telecare group ( $ 5850 , SD $ 21,094 ) and 84 % lower in the telephone group ( $ 7320 , SD $ 24,440 ) than in the usual care group ( $ 44,479 , SD $ 121,214 ) . However , the between-group difference was not statistically significant . Both intervention groups had significantly fewer CHF-related ED visits ( P = 0.0342 ) and charges ( P = 0.0487 ) than the usual care group . Trends favoring both interventions were noted for all other utilization outcomes . Conclusions .Substantial reductions in hospital readmissions , emergency visits , and cost of care for patients with CHF might be achieved by widespread deployment of distance technologies to provide posthospitalization monitoring . Home telecare may not offer incremental benefit beyond telephone follow-up and is more expensive", "This study evaluated the impact of telemedicine technology on the provision of neurosurgical health services . We focused on the differences between the use of real time audio-visual teleconferencing and teleradiology versus conventional telephone consultations in the referral of neurosurgical patients from a large district general hospital . All patients requiring emergency neurosurgical consultation were included for r and omization into telephone consultation only ( Mode A ) , teleradiology and telephone consultation ( Mode B ) and video-consultation ( Mode C ) . Measures of effectiveness included diagnostic accuracy and adverse events during the transfer and Glasgow Outcome Score . In a 10-month period , 327 patients were recruited and r and omized into the study : the male/female ratio was 2:1 and the number of patients required to be transferred to the neurosurgical unit was 125 ( 38 % ) . There was a trend towards a more favourable outcome in the video-consultation mode ( 44 % , Mode C ) , versus teleradiology ( 31 % , Mode B ) , versus telephone consultation ( 38 % , Mode A ) . The interim data of this prospect i ve r and omized trial suggests that video-consultation may have a favourable impact on emergency neurosurgical consultations", "Existing st and ards of the management of the diabetic patients are not efficient enough , and further improvement is needed . The major objective of this paper is to present and discuss the therapeutic effectiveness of an intensive care telematic system design ed and applied for intensive treatment of pregnant type 1 diabetic women . The developed system operates automatically , every night transferring all the data recorded during the day in the patient 's glucometer memory to a central clinical unit . In order to assess the efficiency of the design ed and developed system , a 3-year r and omized prospect i ve clinical trial was conducted , using the study group and the control group , each consisting of 15 pregnant type 1 diabetic women . All patients were treated by the same diabetologist . In the presented analysis , two indices calculated weekly were used for the assessment of glycemic control : MBG represents mean blood glucose level , and the universal J-index is sensitive to the glycemic level and glycemic variations . The most important results from the study concern : ( a ) better glycemic control in the study group in comparison with the control group during the course of treatment , as assessed by the average differences of the MBG and J indices calculated weekly ( n = 24 ) ( deltaMBG = -3.2 + /- 4.3 mg/dL , p = 0.0016 , deltaJ = -1.4 + /- 2.3 , p = 0.0065 ) ; ( b ) much more similar results in glycemic control among members of the study group compared to each other , than among members of the control group compared to each other , as indicated by significantly lower variations of the applied glycemic control indices ( SDMBG : 11.9 vs. 18.7 mg/dL , p = 0.0498 ; SDJ : 6.5 vs. 10.9 , p = 0.0318 ) ; ( c ) the observed tendency of a better glycemic control for patients with a lower level of intelligence ( IQ < 100 ) supported by the telematic system in comparison with all other assessed groups of patients . The last result was not statistically significant ( p > 0.05 ) . This telematic intensive care system improved the effectiveness of diabetes treatment during pregnancy . It also allows the diabetologist 's strategy to be much more precise than if it were conducted without telematic support . This telematic system is inexpensive and simple in use", "OBJECTIVE To test the hypothesis that telemedicine for new patient referrals to neurological out patients is as efficient and acceptable as conventional face to face consultation . METHODS A r and omised controlled trial between two groups : face to face ( FF ) and telemedicine ( TM ) . This study was carried out between a neurological centre and outlying clinics at two distant hospitals linked by identical medium cost commercial interactive video conferencing equipment with ISDN lines transmitting information at 384 kbits/s . The same two neurologists carried out both arms of the study . Of the 168 patients who were suitable for the study , 86 were r and omised into the telemedicine group and 82 into the face to face group . Outcome measures were ( 1 ) consultation process : ( a ) number of investigations ; ( b ) number of drugs prescribed ; ( c ) number of patient review s and ( 2 ) patient satisfaction : ( a ) confidence in consultation ; ( b ) technical aspects of consultation ; ( c ) aspects surrounding confidentiality . Diagnostic categories were also measured to check equivalence between the groups : these were structural neurological , structural non-neurological , non-structural , and uncertain . RESULTS Diagnostic categories were similar ( p>0.5 ) between the two groups . Patients in the telemedicine group had significantly more investigations ( p=0.001 ) . There was no difference in the number of drugs prescribed ( p>0.5 ) . Patients were generally satisfied with both types of consultation process except for concerns about confidentiality and embarrassment in the telemedicine group ( p=0.017 and p=0.005 respectively ) . CONCLUSION Telemedicine for new neurological out patients is possible and feasible but generates more investigations and is less well accepted than face to face examination", "The dem and for home health care has skyrocketed in recent years . The aging population and the push for more efficient delivery of hospital services have fueled this growing dem and . However , health care financing reforms have constrained the industry 's growth . Home health agencies struggle to deliver high- quality services while staying within the financial limitations imposed by reimbursement changes . Telehomecare is one way to provide cost-effective care in the current environment . Personal computers and video equipment can transmit data over ordinary telephone lines and allow home health providers to monitor patients and provide care at a much lower cost than earlier technologies that required wider b and width telephone lines and more complex equipment . But can telehomecare yield cost-savings for home health agencies ? This article addresses the costs associated with a telehomecare intervention in a large , urban , home health agency . The purpose of the study was two-fold : ( 1 ) to test the effects of telehomecare on clinical outcomes , and ( 2 ) to estimate the financial costs associated with providing telehomecare services . Our results show that , while telehomecare imposes additional expenses for care delivery , it contributes substantial savings without compromising quality . Additionally , we found that the financial benefit increases exponentially as the duration of the patient care episode increases", "A r and omized controlled trial was conducted to compare the costs of realtime teleneurology with the cost of conventional neurological care . Two district hospitals in Northern Irel and were equipped with videoconferencing units and were connected to the regional neurological centre by ISDN at 384 kbit/s . Of 168 patients r and omized to the study , 141 kept their appointments ( 76 male , 65 female ) . Sixty-five patients were r and omized to a conventional consultation while 76 were r and omized to a teleconsultation . The average age was 44 years of those seen conventionally and 42 years of those seen by telemedicine . The groups had similar diagnoses . The telemedicine group required more investigations and review s than the conventional group . The average cost of the conventional consultation was £ 49 compared with £ 72 for the teleconsultation . Realtime teleneurology was not as cost-effective as conventional care", "Since 1997 , more than 2,700 home care agencies have closed due to changes in reimbursement . With the implementation of a prospect i ve payment system , there is concern -- not only regarding the survival of the remaining home care agencies , but also whether adequate care can be provided to the patient . Chronic wound care is both prevalent and costly in home care . Factors contributing to cost include inconsistency of wound assessment and documentation and low usage of advanced wound products . These factors lead to lengthened healing time , more frequent visits by practitioners , and low healing rates . Involving a wound specialist can improve patient outcomes while decreasing cost . The authors examined the utilization of telemedicine in situations where wound specialists consulted with the home health nurse in the patient 's home regarding care of chronic wounds . During the two-way video visit , the wound specialist assessed the patient and the wounds and made recommendations for treatment . The wound specialist also collected outcome data during the visits . This data was then compared with like data collected as a baseline prior to the telemedicine intervention . Results revealed improved healing rates , decreased healing time , decreased number of home health visits , and a decreased number of hospitalizations related to wound complications . Telemedicine was deemed a viable option for delivering quality , cost-effective care to chronic wound patients in the home care setting", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "Good diabetic control requires that treatment be continuously adapted to the patient behavior . We investigated whether the use of telemedicine could present an advantage to the management of the diabetic woman during pregnancy . A system completely automatic ( DIANET system ) was used . Twenty IDDM women participated in the study : 10 treated by telemedicine and 10 by conventional system , at times \" entry \" ( 9.5 weeks ) , \" basal \" ( 9.5 - 16.8 weeks ) , \" 1st month \" of investigation , and \" end \" ( near delivery ) . All women used intensified protocol s of insulin administration . The treatment with DIANET vs conventional showed a better metabolic control as estimated by profile of blood glucose absolute values ( at time \" end \" : values significantly lower before breakfast : 87 + /- 6 vs 104 + /- 4 mg , lunch : 85 + /- 5 vs 104 + /- 4 mg , and after dinner : 102 + /- 5 vs 124 + /- 6 mg ) . These results were associated with higher insulin doses in the DIANET vs conventional treatment , and a significant reduction of hypoglycemic reaction in both group . Our results suggest that telemedicine-DIANET is a practical way of providing specialist care in the pregnancy area", "We conducted a six-month prospect i ve interventional crossover study examining a computerized diabetes monitoring system ( DMS ) that conveyed dietary information . The objectives were to compare glycaemic control between intervention and control periods , and to assess patients ' acceptance of the DMS . Nineteen patients were r and omized into two groups , each using the DMS for three months and serving as the control group for another three months . The patients recorded information about their meal portions and blood glucose readings in a h and -held electronic diary . After transmitting the data to the DMS through a telephone modem , the patients received immediate feedback about the carbohydrate , protein and fat content of the meal , as well as the calorie content . A significant improvement in glycaemic control was achieved during intervention compared with control periods ( mean HbA1C reduction of 0.825 % ) . The DMS was also highly acceptable : 95 % patients found it easy to operate while 63 % found it useful . The DMS was thus a feasible model of telemedicine in diabetes care and a larger study is warranted to examine its cost-effectiveness", "The clinical effectiveness and costs of telemedicine in improving the referral process from primary to secondary care were examined in an eight-month prospect i ve , comparative study with one-year follow-up . The internal-medicine outpatient clinics of two Finnish district hospitals were compared - Peijas Hospital ( PH ) with telemedicine and Hyvinkää Hospital ( HH ) without it . The three primary -care centres studied referred a total of 292 adult patients to the outpatient clinics . The population -based number of referrals to PH ( 7.5/1000 ) from primary -care centres was twice that to HH ( 3.8/1000 ) . Thirty-seven per cent of referrals to PH included requests from general practitioners for on-line medical advice ( teleconsultation ) . Forty-three per cent of the total number of intranet referrals result ed in outpatient visits at PH , compared with 79 % in the outpatient clinic at HH . Only 18 % of the patients receiving a teleconsultation ended up in the outpatient department of PH within one year . These visits were mainly due to progression of chronic disease . No deaths or missed diagnoses could be attributed to telemedicine , but one diagnosis was delayed . The direct costs of an outpatient clinic visit in internal medicine ( EU211 ) were seven times greater per patient than for an email consultation ( EU32 ) , with a marginal cost decrease of EU179 for every new intranet consultation . A cost-minimization analysis of the alternative interventions showed a net benefit of EU7876 in favour of the teleconsultation process . General practitioners sought an outpatient visit for 130 of their patients , and advice only for another 77 . On-line advice was nonetheless given in 108 cases , and only 88 patient visits were arranged . Eleven referrals were declined . The cost difference between giving on-line medical advice for the 108 cases and a visit to the outpatient clinic for the other 88 was less costly ( by EU4140 ) than investigating the 124 patients whose original clinic referrals to the PH were not declined . Productivity in the hospital increased over threefold by using email consultations instead of traditional outpatient visits . The wide interactive use of the intranet referral system between secondary and primary care improved clinical effectiveness , lowered direct costs , increased productivity and was cost-effective", "A r and omized controlled trial was carried out to measure the cost-effectiveness of realtime teledermatology compared with conventional outpatient dermatology care for patients from urban and rural areas . One urban and one rural health centre were linked to a regional hospital in Northern Irel and by ISDN at 128 kbit/s . Over two years , 274 patients required a hospital outpatient dermatology referral - 126 patients ( 46 % ) were r and omized to a telemedicine consultation and 148 ( 54 % ) to a conventional hospital outpatient consultation . Of those seen by telemedicine , 61 % were registered with an urban practice , compared with 71 % of those seen conventionally . The clinical outcomes of the two types of consultation were similar - almost half the patients were managed after a single consultation with the dermatologist . The observed marginal cost per patient of the initial realtime teledermatology consultation was 52.85 for those in urban areas and 59.93 per patient for those from rural areas . The observed marginal cost of the initial conventional consultation was 47.13 for urban patients and 48.77 for rural patients . The total observed costs of teledermatology were higher than the costs of conventional care in both urban and rural areas , mainly because of the fixed equipment costs . Sensitivity analysis using a real-world scenario showed that in urban areas the average costs of the telemedicine and conventional consultations were about equal , while in rural areas the average cost of the telemedicine consultation was less than that of the conventional consultation", "OBJECTIVES In a context where sleep laboratories are overwhelmed by a growing dem and to diagnose obstructive sleep apnea syndrome ( OSAS ) , efficient substitutive solutions to in-laboratory polysomnography should be found . To compare the effectiveness and costs of home unattended polysomnography ( Hpsg ) and telemonitored polysomnography ( TMpsg ) , a cost minimization study was performed . METHODS In a crossover trial , 99 patients underwent on two consecutive nights TMpsg and Hpsg according to a r and omized order . A legibility recording criterion was retained to measure effectiveness . A microcosting study of TMpsg and Hpsg was performed . The risks to adopt home strategy or telemonitored strategy , according to different scenario chosen to reach the diagnosis in case of failure of Hpsg or TMpsg , were analyzed . RESULTS The recording was considered to be ineffective in 11.2 % of TMpsg ( 95 % CI , 4.9 - 17.4 ) and in 23.4 % ( 95 % CI , 19.12 - 27.68 ) of Hpsg . The effectiveness differential was 12.2 % ( 95 % CI , 1.8 - 22.6 ) ( p = .02 ) . Assuming that in case of failure PSGs would be re-realized in the same condition to reach the diagnosis , then TMpsg could be selected if Hc/TMc ( cost of Hpsg/cost of TMpsg ) > 0.97 ; Hpsg could be selected if Hc/TMc < 0.76 . If 0.76 < or = Hc/TMc < or = 0.97 , the choice of TMpsg would be ambiguous . TMc was estimated to be $ 244 , while Hc was $ 153 ( Hc/TMc = 0.63 ) . CONCLUSION Unless some specific geographical situations generate significant transport costs , the implementation of a strategy based on unattended polysomnography at home is cost-saving compared to a telemonitoring strategy", "We have developed a tele-medicine system to monitor the airway status at home for patients with poorly controlled asthma , whereby a nurse provides instructions to individuals via the telephone to help them manage exacerbation under the supervision of their physicians . We examined the effectiveness of this system with a r and omized control study . Patients with high hospitalization risk were enrolled in the study by screening patients for those with multiple previous emergency room visits and r and omly assigned to either the tele-medicine or control group . After six months of participation in the program , the number of emergency room visits decreased significantly and the activities of daily living were improved in the tele-medicine group . Most of the patients in the tele-medicine group were able to continue measuring and transmitting peak expiratory flow ( PEF ) value successfully , and at six months had noticed an improvement in PEF . We therefore conclude that the system effectively contributes to the management of poorly controlled asthma . In addition , further consideration suggests that the reduction of emergency room visits may lead to reduction in hospitalization since we found a good correlation between number of emergency room visits and hospitalization from the studies published previously", "Abstract . Background : Teleconsultation services have the potential to improve the communication among different medical care providers and between them and the patient . Increasing effectiveness in the shape of a savings in time or cost is often the result of better communication . Methods : A study was performed in order to demonstrate the feasibility of teleconsultation services , using the perioperative management of cataract patients as an example , and to provide data on the quality , acceptance and effectiveness of these services in comparison with a control group experiencing normal treatment . Results : Over a period of 3 months 42 patients of the teleconsultation group and 20 controls were studied . There were two referring ophthalmologists and three surgeons . The teleconsultation group had one consultation fewer with the ophthalmic surgeon because of the teleconsultation service . Patient satisfaction was slightly higher using the new technology . Patients would like to see this technique used again should surgery on the second eye become necessary . Conclusions : Teleconsultation services are ready to support and improve perioperative cataract management . Patients ' confidence in their medical treatment was increased by using teleconsultation services . Physicians will exp and the use of teleconsultation", "The increased prevalence , morbidity , mortality , and health costs associated with asthma among children suggest the need for accessible asthma education . This study examined the effect of telepharmacy counseling , using interactive compressed video , on metered-dose inhaler ( MDI ) technique and patient satisfaction among adolescents with asthma in rural Arkansas . The telepharmacy counseling provided accessible education regarding MDI technique for adolescents in this study . Twenty percent of the adolescents who participated had never been shown the appropriate use of an MDI . The study used an experimental design with r and om assignment of participants to a telepharmacy counseling group ( n = 15 ) or a control group ( n = 21 ) . Both groups participated in pre-test , post-test , and 2- to 4-week follow-up assessment s for MDI technique and patients satisfaction ( follow-up assessment only ) via interactive compressed video . Results indicated that from pre-test to follow-up the telepharmacy counseling group showed more improvement in MDI technique than participants in the control group ( p < 0.001 ) . There was no significant difference between the telepharmacy counseling group and control group in satisfaction with the instructional sessions ( p = 0.132 ) . Both groups had high levels of satisfaction with the telepharmacy sessions . The study findings demonstrated that patient education provided by pharmacists via interactive compressed video was superior to education provided via written instructions on an inhaler package insert . Interactive compressed video is an effective medium for teaching and improving MDI technique in this rural , adolescent , predominantly African-American population", "Patients with a diagnosis of heart failure , registered at the study practice , were recruited into the study . First , they had a cardiologist 's assessment . They were then r and omised into telemonitored patients who measured pulse , BP , weight and video consulted , and controls", "BACKGROUND African Americans have a higher prevalence and greater severity of hypertension than do other minorities and whites . This fact is particularly problematic when one realizes that the rate of control and treatment of hypertension in the US population is getting worse rather than better . Alternative strategies to promote blood pressure control need to be tested . OBJECTIVES The purpose of this pilot study was to test the following hypothesis : Persons who participate in nurse-managed home telemonitoring ( HT ) plus usual care or who participate in nurse-managed community-based monitoring ( CBM ) plus usual care will have greater improvement in blood pressure from baseline to 3 months ' follow-up than will persons who receive usual care only . METHODS This study used a r and omized controlled design ; participants were r and omly assigned to 1 of 3 groups that were stratified by use or nonuse of antihypertension medication . One-way analysis of variance ( ANOVA ) and analysis of covariance ( ANCOVA ) controlling for age and body weight were used to determine changes in blood pressure from baseline to 3 months . The sample contained 26 African Americans with a mean age of 59 years . RESULTS Both the HT group and the CBM group had clinical ly and statistically significant ( P < .05 ) drops in systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) at 3 months ' follow-up , with participants in the HT group demonstrating the greatest improvement ( HT : baseline SBP 148.8 + /- 13.8 , DBP 90.2 + /- 5.79 ; 3 months ' follow-up SBP 124.1 + /- 13.82 , DBP 75.58 + /- 11.4 ; CBM : baseline SBP 155.25 + /- 17.014 , DBP 89.42 + /- 10.95 ; 3 months ' follow-up SBP 142.3 + /- 12.1 , DBP 78.25 + /- 6.86 ) . There was little change in SBP or DBP at 3 months ' follow-up in the usual care only group . CONCLUSION These are important pilot results , which if replicated in a larger sample will significantly improve care for urban African Americans with hypertension", "We evaluated user satisfaction with a PC-based videoconferencing system used for child psychiatry assessment s and performed a cost analysis . Thirty patients ( aged 5 - 16 years ) , accompanied by a parent , completed a psychiatric assessment using the videoconferencing system . One of five child psychiatrists was r and omly assigned to each assessment . Satisfaction question naires were completed after each assessment by the psychiatrist , patient and parent . Parents also completed a cost question naire . The telecommunications b and width was 336 kbit/s . The psychiatrists stated that they were either ' very satisfied ' or ' satisfied ' with the telepsychiatry assessment s. On a five-point Likert scale ( 1 = lowest , 5 = highest ) , 28 of the 30 parents ( 93 % ) rated their satisfaction level as 5 ; the other two rated it 4 . All 30 parents ( 100 % ) stated that they ' liked ' the telepsychiatry assessment and would use the system again . Twenty-nine parents ( 97 % ) indicated that they would prefer to use the telepsychiatry system to travelling to see a child psychiatrist in person . Eleven children ( aged 5 - 12 ) participated and all ( 100 % ) said they ' liked ' using the telepsychiatry system . Five out of nine children ( 56 % ) stated they liked the ' television doctor ' better than the ' real ' doctor ; four said they had no preference . Nineteen adolescents ( aged 13 - 16 years ) participated and most were very satisfied or satisfied with the system . Seventeen of the 19 adolescents ( 89 % ) said they would prefer to see the psychiatrist on the videoconferencing system to travelling for an assessment , and the same number said that they would use telepsychiatry again . The estimated total travel cost for the 30 patients was $ 12,849 , an average of $ 428 per patient . The total cost of the telepsychiatry service for the three-month pilot was $ 12,575 , or $ 419 per patient", "A r and omized controlled trial was carried out to measure the societal costs of realtime teledermatology compared with those of conventional hospital care in New Zeal and . Two rural health centres were linked to a specialist hospital via ISDN at 128 kbit/s . Over 10 months , 203 patients were referred for a specialist dermatological consultation and 26 were followed up , giving a total of 229 consultations . Fifty-four per cent were r and omized to the teledermatology consultation and 46 % to the conventional hospital consultation . A cost-minimization analysis was used to calculate the total costs of both types of dermatological consultation . The total cost of the 123 teledermatology consultations was NZ$34,346 and the total cost of the 106 conventional hospital consultations was NZ$30,081 . The average societal cost of the teledermatology consultation was therefore NZ$279.23 compared with NZ$283.79 for the conventional hospital consultation . The marginal cost of seeing an additional patient was NZ$135 via teledermatology and NZ$284 via conventional hospital appointment . From a societal viewpoint , and assuming an equal outcome , teledermatology was a more cost-efficient use of re sources than conventional hospital care", "Objectives . The authors present preliminary results on health-related outcomes of a r and omized trial of telehealth interventions design ed to reduce the incidence of secondary conditions among people with mobility impairment result ing from spinal cord injury ( SCI ) . Methods . Patients with spinal cord injuries were recruited during their initial stay at a rehabilitation facility in Atlanta , They received a video-based intervention for nine weeks , a telephone-based intervention for nine weeks , or st and ard follow-up care . Participants are followed for at least one year , to monitor days of hospitalization , depressive symptoms , and health-related quality of life . Results . Health-related quality of life was measured using the Quality of Well-Being ( QWB ) scale . QWB scores ( n = 111 ) did not differ significantly between the three intervention groups at the end of the intervention period . At year one post discharge , however , scores for those completing one year of enrollment ( n = 47 ) were significantly higher for the intervention groups compared to st and ard care . Mean annual hospital days were 3.00 for the video group , 5.22 for the telephone group , and 7.95 for the st and ard care group . Conclusions . Preliminary evidence suggests that in-home telephone or video-based interventions do improve health-related outcomes for newly injured SCI patients . Telehealth interventions may be cost-saving if program costs are more than offset by a reduction in rehospitalization costs , but differential advantages of video-based interventions versus telephone alone warrant further examination", "Effective control of diabetes is known to delay or prevent the end-organ complications of this disease . Can telemedicine improve a patient 's ability to self-manage diabetes ? Twenty-eight patients entered a study comparing home telemedicine consultation with st and ard outpatient care . A nurse case manager contacted the telemedicine group once a week under the direction of a primary care physician , who contacted the telemedicine group once a month . Laboratory studies and total body weight were measured at the beginning and at the end of the 3-month study . The hemoglobin A1c ( HbA1c ) and total body weight improved significantly in the intervention ( telemedicine ) group , as shown by a 16 % reduction in mean HbA1c level ( from 9.5 to 8.2 % ) and a 4 % mean weight reduction ( from 214.3 to 206.7 pounds ) . Based on our experience , we present a functionally based telemedicine classification system to improve the application of electronic medicine in future studies", "We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site r and omized control study . In this program , a nurse under physician supervision monitors the patient 's airway status at home and provides instructions to individuals via the telephone , helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan . Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and r and omly assigned to either the telemedicine or control group . After a six-month study period , an 83 % reduction in hospitalization was demonstrated in the telemedicine group versus the control group , with a P value of 0.01 . Improvement of peak expiratory flow and symptoms were also shown in the study group . We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring , compliance with prescribed daily prophylactic anti-inflammatory steroid medications , and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration" ]

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[ "The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial", "Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial", "A randomized controlled trial of prenatal physical activity to prevent gestational diabetes: design and methods.", "A randomized controlled trial of yoga for pregnant women with symptoms of depression and anxiety.", "Physical activity as an aid to smoking cessation during pregnancy (LEAP) trial: study protocol for a randomized controlled trial", "Adherence to physical activity guidelines in mid-pregnancy does not reduce sedentary time: an observational study", "A pilot walking program promotes moderate-intensity physical activity during pregnancy.", "Safety and efficacy of a lifestyle intervention for pregnant women to prevent excessive maternal weight gain: a cluster-randomized controlled trial", "The long-term effect of screening and lifestyle counseling on changes in physical activity and diet: the Inter99 Study – a randomized controlled trial", "Developing a complex intervention for diet and activity behaviour change in obese pregnant women (the UPBEAT trial); assessment of behavioural change and process evaluation in a pilot randomised controlled trial", "Optimizing healthy gestational weight gain in women at high risk of gestational diabetes: a randomized controlled trial.", "The effect of a personalized intervention on weight gain and physical activity among pregnant women in China.", "Improving diet and exercise in pregnancy with Video Doctor counseling: a randomized trial.", "Cost-effectiveness of an exercise program during pregnancy to prevent gestational diabetes: Results of an economic evaluation alongside a randomised controlled trial", "Effects of a Partially Home‐Based Exercise Program for Women With Gestational Diabetes", "Design of FitFor2 study: the effects of an exercise program on insulin sensitivity and plasma glucose levels in pregnant women at high risk for gestational diabetes", "Lifestyle intervention on diet and exercise reduced excessive gestational weight gain in pregnant women under a randomised controlled trial", "Feasibility and Efficacy of a Physical Activity Intervention Among Pregnant Women: The Behaviors Affecting Baby and You (B.A.B.Y.) Study.", "Pragmatic controlled trial to prevent childhood obesity in maternity and child health care clinics: pregnancy and infant weight outcomes (The VACOPP Study)", "Limiting postpartum weight retention through early antenatal intervention: the HeLP-her randomised controlled trial", "Does regular exercise during pregnancy influence lumbopelvic pain? A randomized controlled trial", "Exercise during pregnancy improves maternal glucose screen at 24–28 weeks: a randomised controlled trial", "Evaluation of a birth preparation program on lumbopelvic pain, urinary incontinence, anxiety and exercise: a randomized controlled trial", "Promoting smoking abstinence in pregnant and postpartum patients: a comparison of 2 approaches.", "The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial", "Effects of lifestyle intervention on dietary intake, physical activity level, and gestational weight gain in pregnant women with different pre-pregnancy Body Mass Index in a randomized control trial", "Physical activity for smoking cessation in pregnancy: randomised controlled trial", "Behavioral counseling to prevent childhood obesity – study protocol of a pragmatic trial in maternity and child health care", "Home-based exercise training improves capillary glucose profile in women with gestational diabetes.", "Effect of lifestyle intervention on dietary habits, physical activity, and gestational weight gain in obese pregnant women: a randomized controlled trial.", "A pregnancy lifestyle intervention to prevent gestational diabetes risk factors in overweight Hispanic women: a feasibility randomized controlled trial.", "Pregnancy: a \"teachable moment\" for weight control and obesity prevention.", "Randomized controlled trial to prevent excessive weight gain in pregnant women", "Evidence-based public health: moving beyond randomized trials.", "Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy? A randomised controlled trial", "Effect of a Physical Exercise Program During Pregnancy on Uteroplacental and Fetal Blood Flow and Fetal Growth: A Randomized Controlled Trial", "Health coaching to prevent excessive gestational weight gain: A randomized-controlled trial.", "Using a combined protection motivation theory and health action process approach intervention to promote exercise during pregnancy", "Regular Exercise During Pregnancy to Prevent Gestational Diabetes: A Randomized Controlled Trial", "Impact of an exercise intervention on physical activity during pregnancy: the behaviors affecting baby and you study.", "Prevention of Gestational Diabetes", "A community-based parish nurse intervention program for Mexican American women with gestational diabetes.", "Maternal-fetal disease information as a source of exercise motivation during pregnancy.", "Exercise throughout pregnancy does not cause preterm delivery: a randomized, controlled trial.", "Simple lifestyle recommendations and the outcomes of gestational diabetes. A 2×2 factorial randomized trial", "Strategies to Promote Physical Activity During Pregnancy", "Weight-related SMS texts promoting appropriate pregnancy weight gain: a pilot study." ]

[ "Background Overweight and obesity is a significant health concern during pregnancy . Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity . Methods We conducted a r and omised controlled trial , in which pregnant women with a body mass index ≥25 kg/m2 , and singleton gestation between 10 + 0 to 20 + 0 weeks were recruited and r and omised to Lifestyle Advice ( involving a comprehensive dietary and lifestyle intervention over their pregnancy ) or St and ard Care . Within the intervention group , we conducted a nested r and omised trial in which a subgroup of women were further r and omised to receive access to supervised group walking sessions in addition to the st and ard information presented during the intervention contacts ( the Walking group ) or st and ard information only . The outcome measures were maternal dietary intake , ( including food groups , macronutrient and micronutrient intake , diet quality ( using the Healthy Eating Index ; HEI ) , dietary glycaemic load , and glycaemic index ) and maternal physical activity . Women completed the Harvard Semi-Structured Food Frequency Question naire , and the Short Question naire to Assess Health-enhancing Physical Activity ( SQUASH ) , at trial entry , 28 and 36 weeks ’ gestational age , and 4 months postpartum . Analyses were performed on an intention-to-treat basis , using linear mixed effects models with adjustment for the stratification variables . Results Women r and omised to Lifestyle Advice demonstrated a statistically significant increase in the number of servings of fruit and vegetables consumed per day , as well as increased consumption of fibre , and reduced percentage energy intake from saturated fats ( P < 0.05 for all ) . Maternal HEI was significantly improved at both 28 ( 73.35 ± 6.62 versus 71.86 ± 7.01 ; adjusted difference in means 1.58 ; 95 % CI 0.89 to 2.27 ; P < 0.0001 ) and 36 ( 72.95 ± 6.82 versus 71.17 ± 7.69 ; adjusted difference in means 1.77 ; 95 % CI 1.01 to 2.53 ; P < 0.0001 ) weeks . There were no differences in dietary glycaemic index or glycaemic load . Women r and omised to Lifestyle Advice also demonstrated greater total physical activity ( adjusted difference in means 359.76 metabolic equivalent task units ( MET ) minutes/week ; 95 % CI 74.87 to 644.65 ; P = 0.01 ) compared with women receiving St and ard Care . The supervised walking group was poorly utilised . Conclusions For women who are overweight or obese , antenatal lifestyle advice improves maternal diet and physical activity during pregnancy . Please see related articles : http://www.biomed central .com/1741 - 7015/12/163 and http://www.biomed central .com/1741 - 7015/12/201.Trial registration Australian and New Zeal and Clinical Trials Registry ( http://ACTRN12607000161426", "Background Obesity is a significant global health problem , with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50 % . Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant , however there is more limited information available regarding effective interventions to improve health outcomes .The aims of this r and omised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal , fetal and infant health outcomes . Methods / Design Design : Multicentred r and omised , controlled trial . Inclusion Criteria : Women with a singleton , live gestation between 10 + 0 - 20 + 0 weeks who are obese or overweight ( defined as body mass index greater than or equal to 25 kg/m2 ) , at the first antenatal visit . Trial Entry & R and omisation : Eligible , consenting women will be r and omised between 10 + 0 and 20 + 0 weeks gestation using a central telephone r and omisation service , and r and omisation schedule prepared by non- clinical research staff with balanced variable blocks . Stratification will be according to maternal BMI at trial entry , parity , and centre where planned to give birth . Treatment Schedules : Women r and omised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain , and will include a combination of dietary , exercise and behavioural strategies . Women r and omised to the St and ard Care Group will continue to receive their pregnancy care according to local hospital guidelines , which does not currently include routine provision of dietary , lifestyle and behavioural advice . Outcome assessors will be blinded to the allocated treatment group . Primary Study Outcome : infant large for gestational age ( defined as infant birth weight ≥ 90th centile for gestational age ) . Sample Size : 2,180 women to detect a 30 % reduction in large for gestational age infants from 14.40 % ( p = 0.05 , 80 % power , two-tailed ) . Discussion This is a protocol for a r and omised trial . The findings will contribute to the development of evidence based clinical practice guidelines .Trial Registration Australian and New Zeal and Clinical Trials Registry", "BACKGROUND Women diagnosed with gestational diabetes mellitus ( GDM ) are at substantially increased risk of developing type 2 diabetes and obesity , currently at epidemic rates in the United States . GDM , therefore , identifies a population of women at high risk of developing type 2 diabetes and provides an opportunity to intervene before the development of this disorder . It is well recognized that acute as well as chronic physical activity improves glucose tolerance in type 2 diabetes . To date , however , primary prevention trials have not been conducted to test whether an increase in physical activity reduces risk of developing GDM among women at high risk of this disorder . METHODS The aims of this study are to investigate the effects of a motivationally targeted , individually tailored 12-week physical activity intervention on ( 1 ) development of GDM , ( 2 ) serum biomarkers associated with insulin resistance , and ( 3 ) the adoption and maintenance of exercise during pregnancy . Women at high risk of GDM are recruited in early pregnancy and r and omized to either an individually tailored exercise intervention or a comparison health and wellness intervention . RESULTS The overall goal of the exercise intervention is to encourage pregnant women to achieve the American College of Obstetricians and Gynecologists guidelines for physical activity during pregnancy through increasing walking and developing a more active lifestyle . CONCLUSIONS The intervention takes into account the specific social , cultural , economic , and physical environmental challenges faced by pregnant women of diverse socioeconomic and ethnic background", "BACKGROUND Yoga may be well suited for depressed and anxious pregnant women , given reported benefits of meditation and physical activity and pregnant women 's preference for nonpharmacological treatments . METHODS We r and omly assigned 46 pregnant women with symptoms of depression and anxiety to an 8-week yoga intervention or treatment-as-usual ( TAU ) in order to examine feasibility and preliminary outcomes . RESULTS Yoga was associated with high levels of credibility and satisfaction as an intervention for depression and anxiety during pregnancy . Participants in both conditions reported significant improvement in symptoms of depression and anxiety over time ; and yoga was associated with significantly greater reduction in negative affect as compared to TAU ( β = -0.53 , SE = 0.20 , p = .011 ) . CONCLUSION Prenatal yoga was found to be a feasible and acceptable intervention and was associated with reductions in symptoms of anxiety and depression ; however , prenatal yoga only significantly outperformed TAU on reduction of negative affect", "Background Many women try to stop smoking in pregnancy but fail . One difficulty is that there is insufficient evidence that medications for smoking cessation are effective and safe in pregnancy and thus many women prefer to avoid these . Physical activity ( PA ) interventions may assist cessation ; however , trials examining these interventions have been too small to detect or exclude plausible beneficial effects . The London Exercise And Pregnant smokers ( LEAP ) trial is investigating whether a PA intervention is effective and cost-effective when used for smoking cessation by pregnant women , and will be the largest study of its kind to date . Methods / design The LEAP study is a pragmatic , multi-center , two-arm , r and omized , controlled trial that will target pregnant women who smoke at least one cigarette a day ( and at least five cigarettes a day before pregnancy ) , and are between 10 and 24 weeks pregnant . Eligible patients are individually r and omized to either usual care ( that is , behavioral support for smoking cessation ) or usual care plus a intervention ( entailing supervised exercise on a treadmill plus PA consultations ) . The primary outcome of the trial is self-reported and biochemically vali date d continuous abstinence from smoking between a specified quit date and the end of pregnancy . The secondary outcomes , measured at 1 and 4 weeks after the quit date , and at the end of pregnancy and 6 months after childbirth , are PA levels , depression , self-confidence , and cigarette withdrawal symptoms . Smoking status will also be self-reported at 6 months after childbirth . In addition , perinatal measures will be collected , including antenatal complications , duration of labor , mode of delivery , and birth and placental weight . Outcomes will be analyzed on an intention-to-treat basis , and logistic regression models used to compare treatment effects on the primary outcome . Discussion This trial will assess whether a PA intervention is effective when used for smoking cessation during pregnancy . Trial registration IS RCT", "Background Physical activity ( PA ) interventions design ed to prevent prenatal complications have focused on increasing moderate PA yielding conflicting results . Minimal attention has focused on the evaluation of sleep , sedentary behavior ( SB ) , light activity or total daily PA during pregnancy . The purpose of this prospect i ve , longitudinal study was to 1 ) objective ly quantify and compare habitual PA and SB during the 2nd and 3rd trimester ; and 2 ) evaluate differences in activity patterns for women meeting prenatal PA guidelines versus those that did not . Methods Forty-six participants wore 2 PA monitors ( SenseWear ® Mini and activPAL ™ ) during week 18 and week 35 of pregnancy . We compared differences in sleep duration , postural allocation , daily steps , and PA between the 2nd and 3rd trimester and for women who met and did not meet PA guidelines . Results During the 2nd trimester , 30 % of the women ’s day ( 24-hours ) was total sleep ; 52 % SB ; 13 % light ; 3 % moderate ; and 0 % vigorous PA . Light ( P = 0.05 ) , vigorous ( P = 0.02 ) , and moderate-vigorous PA ( MET-minutes ; P = 0.02 ) , decreased with a trend in increased SB ( P = 0.07 ) . Activity of other intensities and sleep duration did not significantly change . Only 39 % and 37 % of participants slept between 7–9 hours/night at week 18 and 35 , respectively . Forty-six percent ( n = 21 ) and 28 % ( n = 13 ) of participants met prenatal PA guidelines during the 2nd and 3rd trimester , respectively . At week 18 , no differences in total sleep , SB , or light PA existed for women who met PA guidelines versus those who did not ; total PA was significantly greater for women who met guidelines . At week 35 , women that met PA guidelines had significantly less SB ( P < 0.005 ) than women who did not . Conclusions This study demonstrates that pregnant women spend the majority of their day in SB . Significant reductions in total activity across pregnancy may be attributed , in part to shifts in light PA and increased SB . Based on the lifestyle of our sample , regardless of meeting PA guidelines in mid-pregnancy , no significant difference exists in time spent in SB , however meeting PA recommendations in late pregnancy may reduce SB . Future interventions should target reducing SB by increasing light and moderate PA beyond volitional exercise", "INTRODUCTION Walking may be a strategy for increasing moderate-intensity physical activity ( MPA ) during pregnancy . PURPOSE This study aim ed to promote MPA among overweight and obese pregnant women , via walking , and to evaluate the effect of the intervention on maternal and birth outcomes . METHODS Thirty-seven overweight or obese pregnant women were r and omly assigned to a walking intervention or control group . Anthropometric and objective PA ( StepWatch ™ Activity Monitor ) data were collected for four 1-wk periods : weeks 10 - 14 ( V1 ) , weeks 17 - 19 ( V2 ) , weeks 27 - 29 ( V3 ) , and weeks 34 - 36 ( V4 ) of gestation . Participants provided information about maternal and birth outcomes . A cadence of ≥ 80 steps per minute was defined as MPA , and \" meaningful walking \" was defined as moderate walking in ≥ 8-min bouts . ANOVA was used to determine the differences in walking amount and meaningful walks , the Kolmogorov-Smirnov test was used for walking intensity distribution analysis , and Fisher 's exact test was used for maternal and infant outcomes analyses . Pearson correlation was used to examine the association between prepregnancy body mass index and gestational weight gain ( GWG ) . RESULTS There was significantly more MPA among women in the intervention group compared with those in the control group at V2 ( overweight , P < 0.0001 ; obese , P < 0.025 ) , V3 ( overweight , P < 0.0001 ) , and V4 ( overweight , P < 0.0001 ; obese , P < 0.025 ) . Women in the intervention group significantly increased their meaningful walks at V2 ( P = 0.054 ) , V3 ( P = 0.01 ) , and V4 ( P = 0.014 ) . There were trends for intervention group women to have more favorable maternal and birth outcomes compared with the control group . Rates of GWG at measurement points during pregnancy were significantly associated with preceding rates of GWG . CONCLUSION The pilot , unsupervised walking intervention increased the MPA of overweight and obese women during pregnancy", "Background Excessive gestational weight gain ( GWG ) is associated with short- and long-term health problems among mothers and their offspring . There is a strong need for effective intervention strategies targeting excessive GWG to prevent adverse outcomes . Methods We performed a cluster-r and omized controlled intervention trial in eight gynecological practice s evaluating the feasibility and effectiveness of a lifestyle intervention presented to all pregnant women ; 250 healthy , pregnant women were recruited for the study . The intervention program consisted of two individually delivered counseling sessions focusing on diet , physical activity , and weight monitoring . The primary outcome was the proportion of pregnant women exceeding weight gain recommendations of the Institute of Medicine ( IOM ) . Secondary outcome variables were maternal weight retention and short-term obstetric and neonatal outcomes . Results The intervention result ed in a lower proportion of women exceeding IOM guidelines among women in the intervention group ( 38 % ) compared with the control group ( 60 % ) ( odds ratio ( OR ) : 0.5 ; 95 % confidence interval ( CI ) : 0.3 to 0.9 ) without prompting an increase in the proportion of pregnancies with suboptimal weight gain ( 19 % vs. 21 % ) . Participants in the intervention group gained significantly less weight than those in the control group . Only 17 % of the women in the intervention group showed substantial weight retention of more than 5 kg compared with 31 % of those in the control group at month four postpartum ( pp ) ( OR : 0.5 ; 95 % CI : 0.2 to 0.9 ) . There were no significant differences in obstetric and neonatal outcomes . Conclusions Lifestyle counseling given to pregnant women reduced the proportion of pregnancies with excessive GWG without increasing suboptimal weight gain , and may exert favorable effects on pp weight retention . Trial registration German Clinical Trials Register DRKS00003801", "Background Multi-factorial intervention studies have been found to be successful in the initiation of lifestyle changes . However , little is known about the longer-term maintenance of health behavior improvements . The purpose of this study was to investigate whether improvements in physical activity and dietary habits achieved in a population -based multi-factorial lifestyle intervention of five years duration were maintained five years after intervention activities have ended . Methods The study was a population -based r and omized controlled trial , Inter99 ( 1999–2006 ) , Copenhagen , Denmark . Over five years , all participants in the intervention group ( n = 6,091 ) received individual lifestyle counseling ; participants at high risk of ischemic heart disease – according to pre-specified criteria – were also offered group-based counseling . The control group ( n = 3,324 ) was followed by question naires . Both groups were followed one , three , five , and ten years after baseline . Changes in physical activity and dietary habits ( intake of vegetables , fruit , fish , and saturated fat ) during and after the intervention were investigated using r and om-coefficient models . Results Five years after the intervention , women in the intervention group reported greater improvements in the intake of fruit ( MΔ = 90.2 g/week , p = 0.041 ) and less intake of saturated fat ( OR = 0.30 , 95 % CI : 0.17–0.54 ) than the control group . Men in the intervention group reported greater improvements in physical activity ( MΔ = 19.6 min/week , p = 0.003 ) and less intake of saturated fat ( OR = 0.31 , 95 % CI : 0.17–0.56 ) than the control group . Improvements in the intake of vegetables and fish achieved during the intervention were not maintained in the longer-term . Conclusions Screening and lifestyle counseling had sustained effects on physical activity and dietary habits five years after its discontinuation . The patterns of long-term changes in lifestyle differed across behaviors and between men and women . Trial registration Clinical Trials.gov ( NCT00289237", "Background Complex interventions in obese pregnant women should be theoretically based , feasible and shown to demonstrate anticipated behavioural change prior to inception of large r and omised controlled trials ( RCTs ) . The aim was to determine if a ) a complex intervention in obese pregnant women leads to anticipated changes in diet and physical activity behaviours , and b ) to refine the intervention protocol through process evaluation of intervention fidelity . Methods We undertook a pilot RCT of a complex intervention in obese pregnant women , comparing routine antenatal care with an intervention to reduce dietary glycaemic load and saturated fat intake , and increase physical activity . Subjects included 183 obese pregnant women ( mean BMI 36.3 kg/m2).Diet was assessed by repeated triple pass 24-hour dietary recall and physical activity by accelerometry and question naire , at 16 + 0 to 18 + 6 and at 27 + 0 to 28 + 6 weeks ’ gestation in women in control and intervention arms . Attitudes to behaviour change and quality of life were assessed and a process evaluation undertaken . The full RCT protocol was undertaken to assess feasibility . Results Compared to women in the control arm , women in the intervention arm had a significant reduction in dietary glycaemic load ( 33 points , 95 % CI −47 to −20 ) , ( p < 0.001 ) and saturated fat intake ( −1.6 % energy , 95 % CI −2.8 to −0 . 3 ) at 28 weeks ’ gestation . Objective ly measured physical activity did not change . Physical discomfort and sustained barriers to physical activity were common at 28 weeks ’ gestation . Process evaluation identified barriers to recruitment , group attendance and compliance , leading to modification of intervention delivery . Conclusions This pilot trial of a complex intervention in obese pregnant women suggests greater potential for change in dietary intake than for change in physical activity , and through process evaluation illustrates the considerable advantage of performing an exploratory trial of a complex intervention in obese pregnant women before undertaking a large RCT .Trial registration Trial Registration Number : IS RCT", "OBJECTIVE Optimizing gestational weight gain ( GWG ) in early pregnancy is of clinical and public health importance , especially in higher risk pregnancies . DESIGN AND METHODS In a robustly design ed , r and omized controlled trial , 228 pregnant women at risk of developing gestational diabetes mellitus ( GDM ) were allocated to either control ( written health information only ) or intervention ( four-session lifestyle program ) . All women received st and ard maternal care . Measures were completed at 12 - 15 and 26 - 28 weeks gestation . Measures included anthropometrics ( weight and height ) , physical activity ( pedometer and International Physical Activity Question naire ) , question naires ( risk perception ) , and GDM screening . RESULTS The mean ( SD ) age [ 31.7 ( 4.5 ) and 32.4 ( 4.7 ) years ] and body mass index [ BMI ; 30.3 ( 5.9 ) and 30.4 ( 5.6 ) kg/m(2 ) ] were similar between control and intervention groups , respectively . By 28 weeks , GWG was significantly different between control and intervention groups [ 6.9 ( 3.3 ) vs. 6.0 ( 2.8 ) kg , P < 0.05 ] . When stratified according to baseline BMI , overweight women in the control group gained significantly more weight compared to overweight women in the intervention group [ 7.8 ( 3.4 ) vs. 6.0 ( 2.2 ) kg , P < 0.05 ] , yet in obese women , GWG was similar in both groups . Physical activity levels declined by 28 weeks gestation overall ( P < 0.01 ) ; however , the intervention group retained a 20 % higher step count compared to controls [ 5,203 ( 3,368 ) vs. 4,140 ( 2,420 ) steps/day , P < 0.05 ] . Overall , GDM prevalence was 22.8 % [ Corrected ] , with a trend toward less cases in the intervention group ( P = 0.1 ) . CONCLUSIONS Results indicate that a low-intensity lifestyle intervention , integrated with antenatal care , optimizes healthy GWG and attenuates physical activity decline in early pregnancy . Efficacy in limiting weight gain was greatest in overweight women and in high-risk ethnically diverse women", "OBJECTIVE To examine whether personalized interventions could improve dietary intake and physical activity among pregnant women . METHODS A r and omized controlled trial was conducted at a center in Chengdu , China , between September 2012 and February 2013 . Women with a singleton pregnancy ( aged ≥18years , could underst and written Chinese , did not have pre-existing diabetes ) were enrolled at approximately 12weeks of pregnancy . They were r and omly assigned ( 1:1 ) to an intervention group ( received personalized educational material s ) or a control group ( conventional interventions only ) . Data for dietary intake and physical activity were recorded via question naires . Only pregnant women who completed the study were included in the analysis . RESULTS Analyses included 106 women in the control group and 115 in the intervention group . After intervention , the intake of energy , protein , fruit , milk , seafood , and nuts differed significantly between groups ( P<0.05 ) , with intakes closer to the recommended amounts in the intervention group . Women in the intervention group spent significantly less time resting ( P=0.033 ) and more time doing mild activity ( P=0.016 ) . Mean weight gain per week was significantly lower in the intervention group ( P=0.023 ) , and significantly fewer women in this group developed gestational diabetes ( P=0.043 ) . CONCLUSION Personalized educational interventions can improve dietary behavior and physical activity levels , and reduce prevalence of gestational diabetes among pregnant women in China . Chinese Clinical Trial Register : ChiCTR-IPR-15005809", "OBJECTIVE To determine if an interactive , computerized Video Doctor counseling tool improves self-reported diet and exercise in pregnant women . METHODS A r and omized trial comparing a Video Doctor intervention to usual care in ethnically diverse , low-income , English-speaking pregnant women was conducted . Brief messages about diet , exercise , and weight gain were delivered by an actor-portrayed Video Doctor twice during pregnancy . RESULTS In the Video Doctor group ( n=158 ) , there were statistically significant increases from baseline in exercise ( + 28 min ) , intake of fruits and vegetables , whole grains , fish , avocado and nuts , and significant decreases in intake of sugary foods , refined grains , high fat meats , fried foods , solid fats , and fast food . In contrast , there were no changes from baseline for any of these outcomes in the usual care group ( n=163 ) . Nutrition knowledge improved significantly over time in both groups but more so in the Video Doctor group . Clinician-patient discussion s about these topics occurred significantly more frequently in the Video Doctor group . There was no difference in weight gain between groups . CONCLUSION A brief Video Doctor intervention can improve exercise and dietary behaviors in pregnant women . PRACTICE IMPLICATION S The Video Doctor can be integrated into prenatal care to assist clinicians with effective diet and exercise counseling", "Background The prevalence of gestational diabetes mellitus ( GDM ) is increasing worldwide . GDM and the risks associated with GDM lead to increased health care costs and losses in productivity . The objective of this study is to evaluate whether the FitFor2 exercise program during pregnancy is cost-effective from a societal perspective as compared to st and ard care . Methods A r and omised controlled trial ( RCT ) and simultaneous economic evaluation of the FitFor2 program were conducted . Pregnant women at risk for GDM were r and omised to an exercise program to prevent high maternal blood glucose ( n = 62 ) or to st and ard care ( n = 59 ) . The exercise program consisted of two sessions of aerobic and strengthening exercises per week . Clinical outcome measures were maternal fasting blood glucose levels , insulin sensitivity and infant birth weight . Quality of life was measured using the EuroQol 5-D and quality -adjusted life-years ( QALYs ) were calculated . Re source utilization and sick leave data were collected by question naires . Data were analysed according to the intention-to-treat principle . Missing data were imputed using multiple imputations . Bootstrapping techniques estimated the uncertainty surrounding the cost differences and incremental cost-effectiveness ratios . Results There were no statistically significant differences in any outcome measure . During pregnancy , total health care costs and costs of productivity losses were statistically non-significant ( mean difference € 1308 ; 95%CI € -229 - € 3204 ) . The cost-effectiveness analyses showed that the exercise program was not cost-effective in comparison to the control group for blood glucose levels , insulin sensitivity , infant birth weight or QALYs . Conclusion The twice-weekly exercise program for pregnant women at risk for GDM evaluated in the present study was not cost-effective compared to st and ard care . Based on these results , implementation of this exercise program for the prevention of GDM can not be recommended . Trial registration", "Objective To examine the effectiveness of a partially homebased , moderate-intensity aerobic exercise program for women with gestational diabetes . Methods This was a r and omized experimental design . Thirty-three women with gestational diabetes were r and omly assigned to the exercise or the no-exercise group . Subjects underwent hemoglobin A1C assay and submaximal cycle ergometer fitness tests at baseline and at study conclusion . Subjects kept diaries of home fasting and 2-hour postpr and ial blood glucose determinations . Exercise subjects were asked to exercise for 30 minutes three to four times weekly at 70 % of estimated maximal heart rate for the weeks of study participation . Two exercise sessions weekly were supervised by the investigator , and two were unsupervised at home . Control-group subjects were asked to maintain their current activity level . Results Daily fasting and postpr and ial blood glucose levels , hemoglobin A1C , incidence of exogenous insulin therapy , and incidence of newborn hypoglycemia were not different between the groups . There was a training effect in the exercise group ( P = .005 ) but not in the control group ( P = .25 ) . A significant decline in daily grams of carbohydrate consumed was observed in the control group ( P = .03 ) , but not in the exercise group ( P = .97 ) . No complications were found in the subjects who exercised . Conclusions A partially home-based exercise program did not reduce blood glucose levels , but did result in a modest increase in cardiorespiratory fitness . The intervention appeared safe", "Background Pregnancy is a period in the life of women that is often associated with decreased daily physical activity and /or exercise . However , maintaining adequate levels of daily physical activity during pregnancy is important for mother and child . Studies suggest that moderate daily physical activity and exercise during pregnancy are associated with reductions in the risk of gestational diabetes mellitus ( GDM ) . However , at present , physical activity is not routinely advised to pregnant women at risk for gestational diabetes in the Netherl and s. In FitFor2- study we aim to assess whether an exercise program can improve insulin sensitivity and fasting plasma glucose levels of women at high risk for gestational diabetes , assuming that this will lower their risk of gestational diabetes . Methods The FitFor2- study is a r and omised controlled trial . Women who visit one of the participating hospitals or midwifery practice s and who are at risk for gestational diabetes are eligible to participate . After baseline measurement they are r and omly allocated to in the intervention or control group . The intervention group receives an exercise program twice a week in addition to usual care . The exercise program consist of aerobic and strength exercises and takes place under close supervision of a physiotherapist . Data are collected at 15 , 24 and 32 weeks of pregnancy and 12 weeks after delivery . Primary maternal outcome measures are fasting plasma glucose and relative increase in insulin resistance . Primary neonatal outcome is birth weight . Secondary outcome measures are : maternal serum triglycerides , HDL , cholesterol , HbA1c , maternal weight gain during pregnancy , maternal physical activity level , foetal growth . Discussion If the FitFor2 intervention program proves to be effective , obstetricians and midwives should refer women at risk for GDM to a special exercise program . Exercise programs for pregnant women under supervision of an experienced trainer are already available in the Netherl and s , and these programs could be adjusted easily for this target group . Furthermore , the costs of these programs should be refunded by including them in the basic health care cost reimbursement schemes . Trial registration", "Please cite this paper as : Hui A , Back L , Ludwig S , Gardiner P , Sevenhuysen G , Dean H , Sellers E , McGavock J , Morris M , Bruce S , Murray R , Shen G. Lifestyle intervention on diet and exercise reduced excessive gestational weight gain in pregnant women under a r and omised controlled trial . BJOG 2012;119:70–77", "BACKGROUND Physical activity during pregnancy is associated with reduced risk of adverse maternal and fetal outcomes . However , the majority of pregnant women are inactive and interventions design ed to increase exercise during pregnancy are sparse . We evaluated the feasibility and preliminary efficacy of an exercise intervention among a diverse sample of pregnant women . METHODS The B.A.B.Y. ( Behaviors Affecting Baby and You ) Study is conducted at a large tertiary care facility in Western Massachusetts . We r and omized 110 prenatal care patients ( 60 % Hispanic ) to an individually tailored 12-week exercise intervention arm ( n = 58 ) or to a health and wellness control arm ( n = 52 ) at mean = 11.9 weeks gestation . Physical activity was assessed via the Pregnancy Physical Activity Question naire ( PPAQ ) . RESULTS After the 12-week intervention , the exercise arm experienced a smaller decrease ( -1.0 MET-hrs/wk ) in total activity vs. the control arm ( -10.0 MET-hrs/wk ; P = .03 ) , and a higher increase in sports/exercise ( 0.9 MET-hrs/wk ) vs. the control arm ( -0.01 MET-hrs/wk ; P = .02 ) . Intervention participants ( 95 % ) reported being satisfied with the amount of information received and 86 % reported finding the study material s interesting and useful . CONCLUSIONS Findings support the feasibility and preliminary efficacy of a tailored exercise intervention in increasing exercise in a diverse sample of pregnant women", "Background According to current evidence , the prevention of obesity should start early in life . Even the prenatal environment may expose a child to unhealthy weight gain ; maternal gestational diabetes is known to be among the prenatal risk factors conducive to obesity . Here we report the effects of antenatal dietary and physical activity counselling on pregnancy and infant weight gain outcomes . Methods The study was a non-r and omised controlled pragmatic trial aim ing to prevent childhood obesity , the setting being municipal maternity health care clinics . The participants ( n = 185 ) were mothers at risk of developing gestational diabetes mellitus and their offspring . The children of the intervention group mothers were born between 2009 and 2010 , and children of the control group in 2008 . The intervention started between 10–17 gestational weeks and consisted of individual counselling on diet and physical activity by a public health nurse , and two group counselling sessions by a dietician and a physiotherapist . The expectant mothers also received a written information leaflet to motivate them to breastfeed their offspring for at least 6 months . We report the proportion of mothers with pathological glucose tolerance at 26–28 weeks ’ gestation , the mother ’s gestational weight gain ( GWG ) and newborn anthropometry . Infant weight gain from 0 to 12 months of age was assessed as weight-for-length st and ard deviation scores ( SDS ) and mixed effect linear regression models . Results Intervention group mothers had fewer pathological oral glucose tolerance test results ( 14.6 % vs. 29.2 % ; 95 % CI 8.9 to 23.0 % vs. 20.8 to 39.4 % ; p-value 0.016 ) suggesting that the intervention improved gestational glucose tolerance . Mother ’s GWG , newborn anthropometry or infant weight gain did not differ significantly between the groups . ConclusionS ince the intervention reduced the prevalence of gestational diabetes mellitus , it may have the potential to diminish obesity risk in offspring . However , results from earlier studies suggest that the possible effect on the offspring ’s weight gain may manifest only later in childhood . Trial registration Clinical Trials gov :", "Background Pregnancy is a recognised high risk period for excessive weight gain , contributing to postpartum weight retention and obesity development long-term . We aim ed to reduce postpartum weight retention following a low-intensity , self-management intervention integrated with routine antenatal care during pregnancy . Methods 228 women at increased risk of gestational diabetes , < 15 weeks gestation were r and omised to intervention ( 4 self-management sessions ) or control ( generic health information ) . Outcomes , collected at baseline and 6 weeks postpartum , included anthropometrics ( weight and height ) , physical activity ( pedometer ) and question naires ( health behaviours ) . Results Mean age ( 32.3 ± 4.7 and 31.7 ± 4.4 years ) and body mass index ( 30.4 ± 5.6 and 30.3 ± 5.9 kg/m2 ) were similar between intervention and control groups , respectively at baseline . By 6 weeks postpartum , weight change in the control group was significantly higher than the intervention group with a between group difference of 1.45 ± 5.1 kg ( 95 % CI : -2.86,-0.02 ; p < h0.05 ) overall , with a greater difference in weight found in overweight , but not obese women . Intervention group allocation , higher baseline BMI , GDM diagnosis , country of birth and higher age were all independent predictors of lower weight retention at 6 weeks postpartum on multivariable linear regression . Other factors related to weight including physical activity , did not differ between groups . Conclusions A low intensity intervention , integrated with st and ard antenatal care is effective in limiting postpartum weight retention . Implementation research is now required for scale-up to optimise antenatal health care . Trial registration Australian New Zeal and Clinical Trial Registry Number : ACTRN12608000233325 . Registered 7/5/2008", "Objective . To study lumbopelvic pain in women r and omized to a regular exercise program during pregnancy in comparison to women receiving st and ard antenatal care . Design . A two‐armed , two‐center , r and omized controlled trial . Setting . St Olavs Hospital , Trondheim University Hospital and Stavanger University Hospital . Population . A total of 855 pregnant women were r and omized to intervention or control groups . Methods . The intervention was a 12 week exercise program , including aerobic and strengthening exercises , conducted between 20 and 36 weeks of pregnancy . One weekly group session was led by physiotherapists , and home exercises were encouraged twice a week . The control group received st and ard antenatal care . Main outcome measures . Self‐reports of lumbopelvic pain and sick leave due to lumbopelvic pain . The data were analysed according to the “ intention‐to‐treat ” principle . Results . There were no significant differences between groups of women reporting lumbopelvic pain at 36 weeks ( 74 vs. 75 % , p=0.76 ) . The proportion of women on sick leave due to lumbopelvic pain was lower in the intervention group ( 22 % vs 31 % , p=0.01 ) . Conclusions . Exercise during pregnancy does not influence the prevalence of lumbopelvic pain , but women offered a regular exercise course seem to h and le the disorder better", "Objective The influence of an exercise programme performed by healthy pregnant women on maternal glucose tolerance was studied . Study design A physical activity ( PA , l and /aquatic activities ) programme during the entire pregnancy ( three sessions per week ) was conducted by a qualified instructor . 83 healthy pregnant women were r and omly assigned to either an exercise group ( EG , n=40 ) or a control ( CG , n=43 ) group . 50 g maternal glucose screen ( MGS ) , maternal weight gain and several pregnancy outcomes were recorded . Results Significant differences were found between study groups on the 50 g MGS . Values corresponding to the EG ( 103.8±20.4 mg/dl ) were better than those of the CG ( 126.9±29.5 mg/dl ) , p=0.000 . In addition , no differences in maternal weight gain and no cases of gestational diabetes in EG versus 3 in CG ( 7 % ) ( p>0.05 ) were found . Conclusion A moderate PA programme performed during pregnancy improves levels of maternal glucose tolerance", "Background Antenatal preparation programmes are recommended worldwide to promote a healthy pregnancy and greater autonomy during labor and delivery , prevent physical discomfort and high levels of anxiety . The objective of this study was to evaluate effectiveness and safety of a birth preparation programme to minimize lumbopelvic pain , urinary incontinence , anxiety , and increase physical activity during pregnancy as well as to compare its effects on perinatal outcomes comparing two groups of nulliparous women . Methods A r and omized controlled trial was conducted with 197 low risk nulliparous women aged 16 to 40 years , with gestational age ≥ 18 weeks . Participants were r and omly allocated to participate in a birth preparation programme ( BPP ; n=97 ) or a control group ( CG ; n=100 ) . The intervention was performed on the days of prenatal visits , and consisted of physical exercises , educational activities and instructions on exercises to be performed at home . The control group followed a routine of prenatal care . Primary outcomes were urinary incontinence , lumbopelvic pain , physical activity , and anxiety . Secondary outcomes were perinatal variables . Results The risk of urinary incontinence in BPP participants was significantly lower at 30 weeks of pregnancy ( BPP 42.7 % , CG 62.2 % ; relative risk [ RR ] 0.69 ; 95 % confidence interval [ CI ] 0.51 - 0.93 ) and at 36 weeks of pregnancy ( BPP 41.2 % , CG 68.4 % ; RR 0.60 ; 95%CI 0.45 - 0.81 ) . Participation in the BPP encouraged women to exercise during pregnancy ( p=0.009 ) . No difference was found between the groups regarding to anxiety level , lumbopelvic pain , type or duration of delivery and weight or vitality of the newborn infant . Conclusions The BPP was effective in controlling urinary incontinence and to encourage the women to exercise during pregnancy with no adverse effects to pregnant women or the fetuses . Trial registration Clinical trials.gov , ( NCT01155804", "OBJECTIVE To compare the implementation , delivery , and implication s for dissemination of 2 different maternal smoking-cessation/relapse-prevention interventions in managed care environments . STUDY DESIGN Healthy Options for Pregnancy and Parenting ( HOPP ) was a r and omized , controlled efficacy trial of an intervention that bypassed the clinical setting . Stop Tobacco for OuR Kids ( STORK ) was a quasi-experimental effectiveness study of a point-of-service intervention . Both incorporated prenatal and postnatal components . PATIENTS AND METHODS Subjects in both studies were pregnant women who either smoked currently or had quit recently . The major intervention in HOPP was telephone counseling delivered by trained counselors , whereas the STORK intervention was delivered by providers and staff during prepartum , inpatient postpartum , and well-baby visits . RESULTS In HOPP , 97 % of telephone intervention participants reported receiving 1 or more counselor calls . The intervention delayed but did not prevent postpartum relapse to smoking . Problems with intervention delivery related primarily to identification of the target population and acceptance of repeated calls . STORK delivered 1 or more cessation contacts to 91 % of prenatal smokers in year 1 , but the rate of intervention delivery declined in years 2 and 3 . Modest differences were obtained in sustained abstinence between 6 and 12 months postpartum , but not in point prevalence abstinence at 12 months . CONCLUSIONS The projects were compared using 4 of the 5 dimensions of the RE- AIM model including reach , adoption , implementation , and maintenance . It was difficult to apply the fifth dimension , efficacy , because of the differences in study design and purpose of the interventions . The strengths and limitations of each project were identified , and it was concluded that a combined intervention that incorporates elements of both HOPP and STORK would be optimal if it could be implemented at reasonable cost", "Background Overweight and obesity during pregnancy is common , although robust evidence about the economic implication s of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking . We conducted a health economic evaluation in parallel with the LIMIT r and omised trial . Women with a singleton pregnancy , between 10 + 0 - 20 + 0 weeks , and BMI ≥25 kg/m2 were r and omised to Lifestyle Advice ( a comprehensive antenatal dietary and lifestyle intervention ) or St and ard Care . The economic evaluation took the perspective of the health care system and its patients , and compared costs encountered from the additional use of re sources from time of r and omisation until six weeks postpartum . Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis . Mean costs and effects in the treatment groups allocated at r and omisation were compared , and incremental cost effectiveness ratios ( ICERs ) and confidence intervals ( 95 % ) calculated . Bootstrapping was used to confirm the estimated confidence intervals , and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight , and respiratory distress syndrome . Analyses utilised intention to treat principles . Results Overall , the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes , rendering the intervention cost neutral ( Lifestyle Advice Group $ 11261.19±$14573.97 versus St and ard Care Group $ 11306.70±$14562.02 ; p=0.094 ) . Using a monetary value of $ 20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg , the probability that the antenatal intervention is cost-effective is 0.85 , which increases to 0.95 when the threshold monetary value increases to $ 45,000 . Conclusions Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings , but is associated with a high probability of cost effectiveness . Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed , short-term endpoints , to more accurately estimate the value of the intervention on risk of obesity , and associated costs and health outcomes .Trials registration Australian and New Zeal and Clinical Trials Registry ( ACTRN12607000161426 )", "Background The objectives of this study were to assess the efficacy of lifestyle intervention on gestational weight gain in pregnant women with normal and above normal body mass index ( BMI ) in a r and omized controlled trial . Methods A total of 116 pregnant women ( < 20 weeks of pregnancy ) without diabetes were enrolled and 113 pregnant women completed the program . Participants were r and omized into intervention and control groups . Women in the intervention group received weekly trainer-led group exercise sessions , instructed home exercise for 3 - 5-times/week during 20 - 36 weeks of gestation , and dietary counseling twice during pregnancy . Participants in the control group did not receive the intervention . All participants completed a physical activity question naire and a 3-day food record at enrolment and 2 months after enrolment . Results The participants in the intervention group with normal pre-pregnancy BMI ( ≤24.9 kg/M2 , n = 30 ) had lower gestational weight gain ( GWG ) , offspring birth weight and excessive gestational weight gain ( EGWG ) on pregnancy weight gain compared to the control group ( n = 27 , p < 0.05 ) . Those weight related-changes were not detected between the intervention ( n = 27 ) and control group ( n = 29 ) in the above normal pre-pregnancy BMI participants . Intervention reduced total calorie , total fat , saturated fat and cholesterol intake were detected in women with normal or above normal pre-pregnancy BMI compared to the control group ( p < 0.05 or 0.01 ) . Increased physical activity and reduced carbohydrate intake were detected in women with normal ( p < 0.05 ) , but not above normal , pre-pregnancy BMI at 2 months after the onset of the intervention compared to the control group . Conclusion The results of the present study demonstrated that the lifestyle intervention program decreased EGWG , GWG , offspring birth weight in pregnant women with normal , but not above normal , pre-pregnancy BMI , which was associated with increased physical activity and decreased carbohydrate intake . Trial registration", "Objective To determine the effectiveness of a physical activity intervention for smoking cessation during pregnancy . Design Parallel group , r and omised controlled , multicentre trial . Setting 13 hospitals in Engl and , April 2009 to January 2014 . Participants 789 pregnant smokers , aged 16 - 50 years and at 10 - 24 weeks ’ gestation , who smoked at least one cigarette daily and were prepared to quit smoking one week after enrollment were r and omised ( 1:1 ) ; 785 were included in the intention to treat analyses , with 392 assigned to the physical activity group . Interventions Interventions began one week before a target quit date . Participants were r and omised to six weekly sessions of behavioural support for smoking cessation ( control ) or to this support plus 14 sessions combining supervised treadmill exercise and physical activity consultations . Main outcome measures The primary outcome was continuous smoking abstinence from the target quit date until end of pregnancy , vali date d by exhaled carbon monoxide or salivary cotinine levels . To assess adherence , levels of moderate-vigorous intensity physical activity were self reported and in a 11.5 % ( n=90 ) r and om sub sample of participants , physical activity was objective ly measured by an accelerometer . Results No significant difference was found in rates of smoking abstinence at end of pregnancy between the physical activity and control groups ( 8 % v 6 % ; odds ratio 1.21 , 95 % confidence interval 0.70 to 2.10 ) . For the physical activity group compared with the control group , there was a 40 % ( 95 % confidence interval 13 % to 73 % ) , 34 % ( 6 % to 69 % ) , and 46 % ( 12 % to 91 % ) greater increase in self reported minutes carrying out physical activity per week from baseline to one week , four weeks , and six weeks post-quit day , respectively . According to the accelerometer data there was no significant difference in physical activity levels between the groups . Participants attended a median of four treatment sessions in the intervention group and three in the control group . Adverse events and birth outcomes were similar between the two groups , except for significantly more caesarean births in the control group than in the physical activity group ( 29 % v 21 % , P=0.023 ) . Conclusion Adding a physical activity intervention to behavioural smoking cessation support for pregnant women did not increase cessation rates at end of pregnancy . During pregnancy , physical activity is not recommended for smoking cessation but remains indicated for general health benefits . Trial registration Current Controlled Trials IS RCT N48600346", "Background Prevention is considered effective in combating the obesity epidemic . Prenatal environment may increase offspring 's risk for obesity . A child starts to adopt food preferences and other behavioral habits affecting weight gain during preschool years . We report the study protocol of a pragmatic lifestyle intervention aim ing at primary prevention of childhood obesity . Methods / Design A non-r and omized controlled pragmatic trial in maternity and child health care clinics . The control group was recruited among families who visited the same clinics one year earlier . Eligibility criteria was mother at risk for gestational diabetes : body mass index ≥ 25 kg/m2 , macrosomic newborn in any previous pregnancy , immediate family history of diabetes and /or age ≥ 40 years . All maternity clinics in town involved in recruitment . The gestational intervention consisted of individual counseling on diet and physical activity by a public health nurse , and of two group counseling sessions . Intervention continues until offspring ’s age of five years . An option to participate a group counseling at child ’s age 1 to 2 years was offered . The intervention includes advice on healthy diet , physical activity , sedentary behavior and sleeping pattern . The main outcome measure is offspring BMI z-score and its changes by the age of six years . Discussion Early childhood is a critical time period for prevention of obesity . Pragmatic trials targeting this period are necessary in order to find effective obesity prevention programs feasible in normal health care practice .Trial registration Clinical Trials gov", "PURPOSE Regular maternal exercise may play an important role in the management of gestational diabetes mellitus ( GDM ) , yet specific exercise guidelines to achieve glycemic control have not been established . Furthermore , many women remain sedentary during pregnancy because of perceived barriers to exercise participation . This study examined the effectiveness of a home-based cycling program commenced upon diagnosis of GDM on daily fasting and postpr and ial blood glucose levels , glycosylated hemoglobin ( HbA1c ) , and the response of glucose and insulin to a 75-g oral glucose load . METHODS Forty sedentary women ( 28.8 ± 0.9 wk of gestation ) were r and omized to either home-based exercise training in combination with conventional management ( EX , n = 20 ) or to conventional management alone ( CON , n = 20 ) until week 34 of pregnancy . RESULTS Mean compliance to the supervised exercise training was 96 % , and no adverse effects were reported . Capillary glucose concentration was acutely reduced in response to each cycling session ( 6.3 ± 0.8 mM to 4.9 ± 0.7 mM , P < 0.001 ) . Overall , the EX group had lower mean daily postpr and ial glucose concentrations throughout the intervention compared with that in the CON group ( P < 0.05 ) despite consuming a greater proportion of dietary carbohydrate ( P < 0.05 ) . No differences were observed between groups with respect to HbA1c or the glucose and insulin response to oral glucose ingestion postintervention ( P > 0.05 ) . CONCLUSIONS A home-based cycling program may help to maintain daily postpr and ial normoglycemia in women with diet-controlled GDM", "BACKGROUND Maternal obesity and excessive gestational weight gain ( GWG ) are major short- and long-term risk factors for maternal and fetal complications . OBJECTIVE The objective was to study whether a lifestyle intervention based on a brochure or on active education can improve dietary habits , increase physical activity ( PA ) , and reduce GWG in obese pregnant women . DESIGN In this r and omized controlled trial , 195 white , obese pregnant women [ age : 29 + or - 4 y ; body mass index ( in kg/m(2 ) ) ; 33.6 + or - 4.2 ] were r and omly assigned into 3 groups : a group that received nutritional advice from a brochure , a group that received the brochure and lifestyle education by a nutritionist , and a control group . Nutritional habits were evaluated every trimester through 7-d food records . PA was evaluated with the Baecke question naire . RESULTS Energy intake did not change during pregnancy and was comparable in all groups . Fat intake , specifically saturated fat intake , decreased and protein intake increased from the first to the third trimester in the passive and active groups compared with an opposite change in the control group . Calcium intake and vegetable consumption increased during pregnancy in all groups . PA decreased in all groups , especially in the third trimester . No significant differences in GWG and obstetrical or neonatal outcome could be observed between the groups . CONCLUSIONS Both lifestyle interventions improved the nutritional habits of obese women during pregnancy . Neither PA nor GWG was affected", "AIMS To pilot the feasibility of a prenatal lifestyle intervention to modify physical activity and diet among pregnant overweight and obese Hispanic women , with the aim of reducing risk factors for gestational diabetes mellitus . METHODS Women were r and omized either to a lifestyle intervention ( n = 33 , 48.5 % ) , consisting of a culturally and linguistically modified , motivationally targeted , individually tailored 6-month prenatal programme , or to st and ard care ( n = 35 , 51.5 % ) . Bilingual and bicultural health educators encouraged women to achieve guidelines for physical activity , decrease saturated fat and increase dietary fibre . Outcomes included gestational weight gain , infant birth weight and biomarkers associated with insulin resistance . RESULTS Patient retention up to delivery was 97 % in both study groups . The lifestyle intervention attenuated the pregnancy-associated decline in moderate-intensity physical activity , but differences between groups were not significant ( mean ± se -23.4 ± 16.6 vs -27.0 ± 16.2 metabolic equivalent of task h/week ; P = 0.88 ) . Vigorous-intensity activity increased during the course of pregnancy in the lifestyle intervention group ( mean ± se 1.6 ± 0.8 metabolic equivalent of task h/week ) and declined in the st and ard care group ( -0.8 ± 0.8 metabolic equivalent of task h/week ; P = 0.04 ) . The lifestyle intervention group also had slightly lower gestational weight gain and infant birth weights compared with the st and ard care group ; however , these differences were not statistically significant . There were no statistically significant differences in biomarkers of insulin resistance between groups . CONCLUSIONS Findings suggest that a motivationally matched lifestyle intervention is feasible and may help attenuate pregnancy-related decreases in vigorous physical activity in a population of overweight and obese Hispanic women . The intervention protocol can readily be translated into clinical practice in underserved and minority population", "Excessive gestational weight gain has been shown to relate to high-postpartum weight retention and the development of overweight and obesity later in life . Because many women are concerned about the health of their babies during pregnancy and are in frequent contact with their healthcare providers , pregnancy may be an especially powerful \" teachable moment \" for the promotion of healthy eating and physical activity behaviors among women . Initial research suggests that helping women gain the recommended amount during pregnancy through healthy eating and physical activity could make a major contribution to the prevention of postpartum weight retention . However , more r and omized controlled trials with larger sample sizes are needed to identify the most effective and disseminable intervention . Providers have the potential to prevent high postpartum weight retention and future obesity by monitoring weight gain during pregnancy and giving appropriate advice about recommended amounts of gestational weight gain", "BACKGROUND : The Institute of Medicine ( IOM ) recommends that normal‐weight women ( BMI ( body mass index ) of 19.8–26.0 ) gain 25–35 lb ( 11.4–15.9 kg ) during pregnancy , and that overweight women ( BMI of 26.1–29.0 ) gain 15–25 lbs ( 6.8–11.4 kg ) . A significant number of normal‐weight women and an even greater proportion of overweight women exceed these guidelines , which increases postpartum weight retention and may contribute to the development of obesity . OBJECTIVE : To determine whether a stepped care , behavioral intervention will decrease the percentage of women who gain more than the IOM recommendation . DESIGN : R and omized controlled trial comparing a stepped-care behavioral intervention with usual care . Women ( n=120 ) who had a BMI > 19.8 , age>18 and < 20 weeks gestation were recruited from a hospital-based clinic serving low-income women and r and omized by race and BMI category to the intervention or control group . The intervention group received education about weight gain , healthy eating , and exercise and individual graphs of their weight gain . Those exceeding weight gain goals were given more intensive intervention . Women were followed through pregnancy to their first postpartum clinic visit . The main outcome measure was weight gain during pregnancy categorized as above the IOM recommendations vs below or within the IOM recommendations . RESULTS : The intervention significantly decreased the percentage of normal-weight women who exceeded the IOM recommendations ( 33 vs 58 % , P<0.05 ) . There was a non-significant ( P=0.09 ) effect in the opposite direction among overweight women ( 59 % of intervention and 32 % of control gained more than recommended ) . Postpartum weight retention was strongly related to weight gain during pregnancy ( r=0.89 ) . CONCLUSIONS : The intervention reduced excessive weight gain during pregnancy among normal weight women", "R and omized controlled trials ( RCTs ) are essential for evaluating the efficacy of clinical interventions , where the causal chain between the agent and the outcome is relatively short and simple and where results may be safely extrapolated to other setting s. However , causal chains in public health interventions are complex , making RCT results subject to effect modification in different population s. Both the internal and external validity of RCT findings can be greatly enhanced by observational studies using adequacy or plausibility design s. For evaluating large-scale interventions , studies with plausibility design s are often the only feasible option and may provide valid evidence of impact . There is an urgent need to develop evaluation st and ards and protocol s for use in circumstances where RCTs are not appropriate", "Please cite this paper as : Stafne S , Salvesen K , Romundstad P , Torjusen I , Mørkved S. Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy ? A r and omised controlled trial . BJOG 2012;119:1270–1280", "OBJECTIVE : To estimate the effect of supervised physical exercise on maternal physical fitness , fetoplacental blood flow , and fetal growth . METHODS : This was a r and omized controlled trial comparing three groups of pregnant women . Groups were as follows : exercise initiated at 13 weeks ( group A ) ; exercise initiated at 20 weeks ( group B ) ; and a control group ( no supervised exercise ; group C ) . The women in groups A and B walked at moderate intensity three times weekly . Physical fitness level was evaluated at weeks 13 , 20 , and 28 . Fetal growth and uteroplacental blood flow were evaluated monthly . Birth weight was registered . Analysis of variance for repeat measures was used for outcomes evaluated throughout pregnancy . Risk ratio was used as a measure of the relative risk of preeclampsia , fetal growth restriction , macrosomia , small-for-gestational-age newborns , and large-for-gestational-age newborns . RESULTS : All the women analyzed completed more than 85 % of the program . According to the evaluation conducted at week 28 , physical fitness improved , with mean maximal oxygen consumptions ( VO2max ) of 27.3±4.3 ( group A ) , 28±3.3 ( group B ) , and 25.5±3.8 ( group C ; P=.03 ) . Mean birth weights were 3,279±453 g ( group A ) , 3,285±477 g ( group B ) , and 3,378±593 g ( group C ; P=.53 ) , with no difference in the frequency of large for gestational age or small for gestational age . No association was found between the practice of physical activity and the variables investigated ( preeclampsia , fetal weight , blood pressure , and pulsatility index of the uterine , umbilical , and middle cerebral arteries ) . CONCLUSION : Moderate-intensity walking improved the physical fitness level of healthy , pregnant , previously sedentary women without affecting fetoplacental blood flow or fetal growth . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00641550 . LEVEL OF EVIDENCE :", "OBJECTIVES The objectives of this study were to evaluate the efficacy of a health coaching ( HC ) intervention design ed to prevent excessive gestational weight gain ( GWG ) , and promote positive psychosocial and motivational outcomes in comparison with an Education Alone ( EA ) group . DESIGN R and omized-controlled trial . METHODS Two hundred and sixty-one women who were < 18 weeks pregnant consented to take part . Those allocated to the HC group received a tailored HC intervention delivered by a Health Coach , whilst those in the EA group attended two education sessions . Women completed measures , including motivation , psychosocial variables , sleep quality , and knowledge , beliefs and expectations concerning GWG , at 15 weeks of gestation ( Time 1 ) and 33 weeks of gestation ( Time 2 ) . Post-birth data were also collected at 2 months post-partum ( Time 3 ) . RESULTS There was no intervention effect in relation to weight gained during pregnancy , rate of excessive GWG or birth outcomes . The only differences between HC and EA women were higher readiness ( b = 0.29 , 95 % CIs = 0.03 - 0.55 , p < .05 ) and the importance to achieve a healthy GWG ( b = 0.27 , 95 % CIs = 0.02 - 0.52 , p < .05 ) , improved sleep quality ( b = -0.22 , 95 % CIs = -0.44 to -0.03 , p < .05 ) , and increased knowledge for an appropriate amount of GWG that would be best for their baby 's health ( b = -1.75 , 95 % CI = -3.26 to -0.24 , p < .05 ) reported by the HC at Time 2 . CONCLUSIONS Whilst the HC intervention was not successful in preventing excessive GWG , several implication s for the design of future GWG interventions were identified , including the burden of the intervention commitment and the use of weight monitoring . STATEMENT OF CONTRIBUTION What is already known on the subject ? Design ing interventions to address gestational weight gain ( GWG ) continues to be a challenge . To date , health behaviour change factors have not been the focus of GWG interventions . What does this study add ? Our health coaching ( HC ) intervention did not reduce GWG more so than education alone ( EA ) . There was an intervention effect on readiness and importance to achieve healthy GWG . Yet there were no group differences regarding confidence to achieve healthy GWG post-intervention", "Despite the benefits of exercise during pregnancy , many expectant mothers are inactive . This study examined whether augmenting a protection motivation theory ( PMT ) intervention with a Health Action Process Approach can enhance exercise behavior change among pregnant women . Sixty inactive pregnant women were r and omly assigned to one of three treatment groups : PMT-only , PMT + action-planning , and PMT + action- and -coping-planning . Week-long objective ( accelerometer ) and subjective ( self-report ) exercise measures were collected at baseline , and at 1- and 4-weeks post-intervention . Repeated- measures ANOVAs demonstrated that while all participants reported increased exercise from baseline to 1-week post-intervention , participants in both planning groups were significantly more active ( p < .001 ) than those in the PMT-only group by 4-weeks post-intervention ( η2 = .13 and .15 for accelerometer and self-report data , respectively ) . In conclusion , augmenting a PMT intervention with action or action- and -coping-planning can enhance exercise behavior change in pregnant women", "OBJECTIVE : To assess whether exercise during pregnancy can prevent gestational diabetes and improve insulin resistance . METHODS : A total of 855 women in gestational week 18–22 were r and omly assigned to receiving a 12-week st and ard exercise program ( intervention group ) or st and ard antenatal care ( control group ) . The exercise program followed st and ard recommendations and included moderate-intensity to high-intensity activity 3 or more days per week . Primary outcomes were gestational diabetes and insulin resistance estimated by the homeostasis model assessment method . For the power calculation , we assumed a gestational diabetes prevalence of 9 % in the control group and a prevalence of 4 % in the exercise group ( risk difference of 5 % ) . Under these assumptions , a two- sample comparison with a 5 % level of significance and power of 0.80 gave a study population of 381 patients in each group . RESULTS : At 32–36 weeks of gestation there were no differences between groups in prevalence of gestational diabetes : 25 of 375 ( 7 % ) in the intervention group compared with 18 of 327 ( 6 % ) in the control group ( P=.52 ) . There were no differences in insulin resistance between groups when adjusting for baseline values . Only 55 % of women in the intervention group managed to follow the recommended exercise protocol . No serious adverse events related to physical exercise were seen , and the outcomes of pregnancy were similar in the two groups . CONCLUSION : There was no evidence that offering women a 12-week st and ard exercise program during the second half of pregnancy prevents gestational diabetes or improves insulin resistance in healthy pregnant women with normal body mass indexes . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00476567 . LEVEL OF EVIDENCE :", "OBJECTIVES We examined the impact of a prenatal exercise intervention on physical activity in 260 women at risk for gestational diabetes mellitus . METHODS We r and omized participants in the Behaviors Affecting Baby and You ( BABY ) Study , which took place from 2007 to 2012 , to either a 12-week individually tailored , motivationally matched exercise intervention ( n=132 ) or to a comparison health and wellness intervention ( n=128 ) . We assessed physical activity with the Pregnancy Physical Activity Question naire . We used linear mixed models to evaluate the impact of the interventions on change in physical activity according to intensity and type , total walking , and sedentary behavior . RESULTS Compared with the health and wellness arm , the exercise arm had significantly greater increases in sports or exercise activity ( 0.3 vs 5.3 metabolic equivalent of task [ MET ] hours/week ; P<.001 ) , and smaller declines in total activity ( -42.7 vs -2.1 MET hours/week ; P=.02 ) and activities of moderate to vigorous intensity ( -30.6 vs -10.6 MET hours/week ; P=.05 ) , and was more likely to achieve recommended guidelines for physical activity ( odds ratio=2.12 ; 95 % confidence interval=1.45 , 3.10 ) . CONCLUSIONS These findings extend the previous literature by demonstrating the benefits of a clinical ly feasible exercise intervention in an ethnically and socio-economically diverse population . Given the increased risk of adverse maternal health outcomes in ethnic minority groups , these findings may have important implication s for reducing health disparities", "OBJECTIVE To examine the feasibility of an individualized exercise program to prevent gestational diabetes mellitus ( GDM ) in obese pregnant women . RESEARCH DESIGN AND METHODS The study was a pilot r and omized controlled trial with obese pregnant women ( intervention group , individualized exercise program [ n = 25 ] ; control group , usual care [ n = 25 ] ) . Average weekly energy expenditure ( MET hours per week and kilocalories per week ) of exercise-specific activity was assessed during pregnancy using the Pregnancy Physical Activity Question naire . Fasting glucose and insulin and homeostasis model assessment of insulin resistance ( HOMA-IR ) were assessed at baseline and 20 , 28 , and 36 weeks ' gestation . RESULTS Of the women in the intervention group , 16 of 22 ( 73 % ) achieved more than 900 kcal/week of exercise-based activity at 28 weeks compared with 8 of 19 women in the control group ( 42 % ) , P = 0.047 . However , insulin resistance ( HOMA-IR ) did not differ between the groups . CONCLUSION This intervention was feasible and prompted a modest increase in physical activity . However , we are not confident that this intervention would be sufficient to prevent GDM", "OBJECTIVE To examine the effects of a Parish Nurse Intervention Program ( PNIP ) on maternal health behaviors , glycemic control , and neonatal outcomes among Mexican American women with gestational diabetes . DESIGN A r and omized controlled trial comparing care as usual ( CAU ) with a supplementary 1-hour education session for diabetes education reinforcement by a Parish Nurse . SETTING An outpatient treatment clinic for gestational diabetes within a 250-bed tertiary care , non-profit hospital with a Parish Nurse partnership . PARTICIPANTS One hundred Mexican American women were included in the study with r and omization into Parish Nurse Intervention Program ( n=49 ) and care as usual ( n=51 ) groups . MAIN OUTCOME MEASURES The Health Promoting Lifestyle Profile II ( HPLP II ) and two measures of glycemic control pre- and post-intervention , as well as newborn size , and days of maternal and neonatal hospitalization . RESULTS Outcomes indicate significantly improved Health Promoting Lifestyle Profile II scores in the Parish Nurse Intervention Program group post-intervention compared with the Care As Usual group . No significant differences between groups regarding glycemic control , macrosomia , or days of maternal or neonatal hospitalization were found . CONCLUSIONS A Parish Nurse Intervention Program for pregnant women of Mexican descent with gestational diabetes is effective in leading to improved self-reported health promoting behaviors", "OBJECTIVE A Protection Motivation Theory ( PMT ) framework was used to examine whether information about the role of exercise in preventing maternal-fetal disease served as a meaningful source of exercise motivation . DESIGN Pregnant women ( n = 208 ) were r and omly assigned into one of three conditions : PMT , attention control , and noncontact control . Women in the PMT group read a brochure about the benefits of exercise during pregnancy incorporating the major components of PMT ; perceived vulnerability ( PV ) , perceived severity ( PS ) , response efficacy ( RE ) , and self-efficacy ( SE ) . Participants in the attention-control condition read a brochure about diet . Following treatment , all participants completed measures of their beliefs toward maternal-fetal disease and exercise , goal intention ( GI ) , and implementation intention ( IMI ) . One week later , a measure of self-reported exercise behavior was collected . MAIN OUTCOME MEASURES Main outcome measures were PMT variables ( PV , PS , RE , and SE ) , GI , IMI , and follow-up physical activity . RESULTS Participants assigned to the PMT-present group reported significantly higher PS , RE , SE , GI , and increased exercise behavior . PS , RE , and SE predicted GI , GI predicted IMI , and IMI predicted exercise behavior . CONCLUSION Information grounded in PMT is effective in influencing pregnant women 's beliefs and intentions as well as changing their initial behavior", "BACKGROUND In spite of an extensive knowledge of the physiologic features of exercise during pregnancy , we still lack a comprehensive underst and ing of the effects of different types , intensities and duration of exercise throughout pregnancy on maternal and fetal well being . The aim of the current study was to examine the influence of an aerobic exercise program throughout pregnancy on gestational age at the moment of delivery . METHODS This study was a r and omized controlled trial . Three hundred and twenty Caucasian ( Spanish ) healthy pregnant women with singleton gestation were r and omly assigned to either an exercise ( n = 160 ) or a control ( n = 160 ) group . Gestational age ( weeks ) and other outcomes were measured . The exercise program included 85 sessions ( general fitness class , 3 times/week , 55 - 60 min/session from weeks 8 - 10 to weeks 38 - 39 of pregnancy ) . RESULTS Two hundred and ninety women were analyzed ( exercise group EG , n = 138 , control group CG , n = 152 ) . The mean gestational age did not differ between groups ( EG= 39.7 ± 1.3 vs CG= 39.6 ± 1.1 weeks , P = .81 ) . Relative to preterm deliveries in EG we found 6 ( 4.3 % ) and 11 ( 7.2 % ) in CG , ( P = .73 ) . CONCLUSIONS A supervised program of moderate exercise performed throughout pregnancy is not a risk of preterm delivery for healthy pregnant women", "The benefits of exercise and behavioural recommendations in gestational diabetes mellitus ( GDM ) are controversial . In a r and omized trial with a 2 × 2 factorial design , we examined the effect of exercise and behavioural recommendations on metabolic variables , and maternal/neonatal outcomes in 200 GDM patients . All women were given the same diet : group D received dietary recommendations only ; group E was advised to briskly walk 20‐min/day ; group B received behavioural dietary recommendations ; group BE was prescribed the same as B + E. Dietary habits improved in all groups . In a multivariable regression model , fasting glucose did not change . Exercise , but not behavioural recommendations , was associated with the reduction of postpr and ial glucose ( p < 0001 ) , glycated haemoglobin ( HbA1c ; p < 0.001 ) , triglycerides ( p = 0.02 ) and C‐reactive protein ( CRP ; p < 0.001 ) and reduced any maternal/neonatal complications ( OR = 0.50 ; 95%CI=0.28–0.89;p = 0.02 ) . In GDM patients a simple exercise programme reduced maternal postpr and ial glucose , HbA1c , CRP , triglycerides and any maternal/neonatal complications , but not fasting glucose values", "Physical activity during pregnancy has been associated with significant health benefits ; however , most women in the United States do not meet the current guidelines . This systematic review evaluates evidence for interventions to improve physical activity during pregnancy in order to identify best practice s and inform future research . Electronic data bases ( PubMed , CINAHL , SportD ISCUS , Embase , ERIC , Psych Info , and ISI Web of Science ) were search ed in July 2011 for peer- review ed journal articles . Studies were included if they were English- language r and omized control trials that measured the efficacy of an intervention targeted at pregnant women and were design ed to change physical activity as a primary or secondary outcome . Out of 777 studies identified through the systematic search , 9 interventions were selected for inclusion by multiple review ers . Data were abstract ed using an abstract ion form modeled after the “ Guide to Community Preventive Services . ” Of the 9 interventions included in the review , 3 reported statistically significant positive results for physical activity . Although the interventions included a variety of strategies and techniques , none were uniquely associated with positive outcomes . Overall , this review suggests that little is known about the efficacy of interventions for physical activity during pregnancy . This study provides several recommendations for future research and intervention design", "OBJECTIVES Excessive gestational weight gain ( GWG ) puts women and children at risk of obesity . We piloted an SMS-texting intervention to promote healthy GWG among overweight and obese women . METHODS We recruited 35 women and r and omized them in a 2:1 fashion to : a tailored SMS-texting intervention ( Preg CHAT ) vs. a generic texting intervention ( Txt4baby ) . Preg CHAT texts provided personalized feedback based on women 's intake of sweetened beverages , fruits and vegetables , fast food , daily steps taken , and weight . We abstract ed women 's weights from charts and surveyed women at baseline and 32 weeks gestation . RESULTS Few women refused the study ; many ( 30 % ) did not complete the study , however . Of those in the Preg CHAT arm , 86 % responded to texts , and 80 % said they would recommend this program to a friend . For women who completed the surveys ( n=23 ) , those in the Preg CHAT arm had a mean gain of 6 less pounds than women in the Txt4Baby arm ( 95 % CI -15.9 , 4.0 ; p=0.24 ) . CONCLUSIONS This pilot study shows feasibility , acceptability , and potential efficacy of a low-intensity and disseminable intervention to help overweight and obese women reduce GWG . PRACTICE IMPLICATION S An SMS texting program might help overweight women reduce excessive GWG" ]

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[ "Prognostic factors for patellofemoral pain: a multicentre observational analysis", "Patellofemoral pain caused by overactivity. A prospective study of risk factors in infantry recruits.", "A Prospective Investigation of Biomechanical Risk Factors for Patellofemoral Pain Syndrome", "A Prospective Study on Gait-related Intrinsic Risk Factors for Patellofemoral Pain", "Motor Control of the Vastus Medialis Oblique and Vastus Lateralis Muscles is Disrupted during Eccentric Contractions in Subjects with Patellofemoral Pain", "Clinical predictors of foot orthoses efficacy in individuals with patellofemoral pain.", "The Effects of Quadriceps Strengthening on Pain, Function, and Patellofemoral Joint Contact Area in Persons with Patellofemoral Pain", "Gait-related intrinsic risk factors for patellofemoral pain in novice recreational runners", "Is Knee Pain During Adolescence a Self-limiting Condition?", "Knee Angular Impulse as a Predictor of Patellofemoral Pain in Runners", "Delayed Vastus Medialis Obliquus to Vastus Lateralis Onset Timing Contributes to the Development of Patellofemoral Pain in Previously Healthy Men", "Articular cartilage lesions and anterior knee pain.", "Outcomes of a weight-bearing rehabilitation program for patients diagnosed with patellofemoral pain syndrome.", "Intrinsic Risk Factors for the Development of Anterior Knee Pain in an Athletic Population: A Two-Year Prospective Study *", "Etiologic factors associated with anterior knee pain in distance runners.", "In vivo noninvasive evaluation of abnormal patellar tracking during squatting in patients with patellofemoral pain." ]

[ "Objectives Describe proportions of individuals with patellofemoral pain ( PFP ) with an unfavourable recovery over 12 months ; identify clinical predictors of poor recovery at 3 and 12 months ; and determine baseline values of predictors that identify those with poor 12-month prognosis . Methods An observational analysis utilised data from 310 individuals with PFP enrolled in two r and omised clinical trials . Thirteen baseline variables ( participant , PFP , study characteristics ) were investigated for their prognostic ability . Pain , function and global recovery were measured at 3 and 12 months . Multivariate backward stepwise regression analyses ( treatment-adjusted , p<0.10 ) were performed for each follow-up measure . Receiver operator characteristic curves identified cut-points associated with unfavourable recovery at 12 months . Results 55 % and 40 % of participants had an unfavourable recovery at 3 and 12 months , respectively . Longer baseline pain duration was significantly associated with poor 3-month and 12-month recovery on measures of pain severity ( β 11.36 to 24.94 ) , Anterior Knee Pain ( AKP ) Scale ( −4.44 to −11.33 ) and global recovery ( OR : 2.32 to 6.11 ) . Greater baseline pain severity and lower AKP Scale score were significantly associated with poor recovery on multiple measures ( p<0.05 ) . Baseline duration > 2 months and AKP Scale score < 70/100 were associated with unfavourable 12-month recovery . Conclusions A substantial number of individuals with PFP have an unfavourable recovery over 12 months , irrespective of intervention . Knee pain duration > 2 months is the most consistent prognostic indicator , followed by AKP Scale score < 70 . Sports medicine practitioners should utilise interventions with known efficacy in reducing PFP , and promote early intervention to maximise prognosis . Trial registration Australian study : Australian Clinical Trials Registry ( ACTRN012605000463673 ) , Clinical Trials.gov ( NCT00118521 ) ; Dutch study : International St and ard R and omised Controlled Trial Number Register ( IS RCT N83938749", "A prospect i ve study of 390 infantry recruits revealed that the medial tibial intercondylar distance and that the isometric strength of the quadriceps , tested at 85 degrees of flexion of the knee , had a statistically significant correlation with the incidence of patellofemoral pain caused by overactivity . Increased medial tibial intercondylar distance and increased strength of the quadriceps were therefore deemed to be risk factors for this syndrome", "Background Patellofemoral pain syndrome is one of the most common chronic knee injuries ; however , little research has been done to determine the risk factors for this injury . Hypothesis Altered lower extremity kinematics and kinetics , decreased strength , and altered postural measurements will be risk factors . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods A total of 1597 participants were enrolled in this investigation and prospect ively followed from the date of their enrollment ( July 2005 , July 2006 , or July 2007 ) through January 2008 , a maximum of 2.5 years of follow-up . Each participant underwent baseline data collection during their pre-freshman summer at the United States Naval Academy . Baseline data collection included 3-dimensional motion analysis during a jump-l and ing task , 6 lower extremity isometric strength tests , and postural alignment measurements ( navicular drop and Q angle ) . Results Risk factors for the development of patellofemoral pain syndrome included decreased knee flexion angle , decreased vertical ground-reaction force , and increased hip internal rotation angle during the jump-l and ing task . Additionally , decreased quadriceps and hamstring strength , increased hip external rotator strength , and increased navicular drop were risk factors for the development of patellofemoral pain syndrome . Conclusion Multiple modifiable risk factors for patellofemoral pain syndrome pain have been identified in this investigation . To decrease the incidence of this chronic injury , the risk factors for patellofemoral pain syndrome need to be targeted in injury prevention programs . Clinical Relevance Prevention programs should focus on increasing strength of the lower extremity musculature along with instructing proper mechanics during dynamic movements to decrease the incidence of patellofemoral pain syndrome", "Objective : To prospect ively determine gait-related risk factors for patellofemoral pain . Design : A prospect i ve cohort study . Setting : Male and female recruits of the Belgian Royal Military Academy during a 6-week basic military training period . Participants : Eighty-four officer cadets ( 65 men , 19 women ) , who entered the Military Academy and were without a history of any knee or lower-leg complaints , participated in the study . Interventions : Before the start of the 6-week basic military training period , plantar pressure measurements during walking were performed . During the basic military training period , patellofemoral complaints were diagnosed and registered by a sports medicine physician . Main Outcome Measurements : Plantar pressure measurements during walking were performed using a footscan pressure plate ( RsScan International ) . Results : During the 6-week training period , 36 subjects developed patellofemoral pain ( 25 male and 11 female ) . Logistic regression analysis revealed that subjects who developed patellofemoral pain had a significantly more laterally directed pressure distribution at initial contact of the foot , a significantly shorter time to maximal pressure on the fourth metatarsal , and a significantly slower maximal velocity of the change in lateromedial direction of the center of pressure during the forefoot contact phase . Conclusions : Our findings suggest that the feet of the persons who developed anterior knee pain have a heel strike in a less pronated position and roll over more on the lateral side compared with the control group . The results of this study can be considered valuable in identifying persons at risk for patellofemoral pain", "Background Inappropriate control of the vastus medialis oblique and vastus lateralis muscles by the central nervous system can contribute to maltracking of the patella . Hypothesis The activation timing and amplitude of the vastus medialis oblique and vastus lateralis muscles will be different between normal subjects and patients with patellofemoral pain . Study Design Controlled laboratory study . Methods Subjects with patellofemoral pain and asymptomatic control subjects performed maximum voluntary knee extension contractions initiated from a flexed and an extended position . The activation timing and amplitude of the vastus lateralis and vastus medialis oblique muscles were quantified from the recorded electromyographic signals . Results There were no between-group differences in activation timing . The activation amplitude of the vastus medialis oblique and vastus lateralis muscles of the patellofemoral pain subjects was altered to the greatest extent during eccentric contractions and differed significantly from that of control subjects . Conclusions The activation amplitudes of the vastus medialis oblique and vastus lateralis muscles of subjects with patellofemoral pain are consistent with a laterally tracking patella during eccentric contractions . Clinical Relevance The findings suggest the clinical importance of determining whether altered activation patterns are sensitive to rehabilitation , and , if so , if subjective reports of knee joint pain and function parallel changes in the activation patterns as a result of rehabilitation", "PURPOSE There is emerging evidence that foot orthoses are effective in the management of patellofemoral pain syndrome ( PFPS ) . However , the identification of those most likely to benefit from foot orthoses has not been adequately explored . The aim of this study was to develop a preliminary clinical prediction rule to help identify individuals with PFPS who are most likely to benefit from foot orthoses . METHODS A total of 60 individuals with PFPS were issued with noncustomized prefabricated foot orthoses containing built-in arch supports and 4 ° rear foot varus wedging . Patient-reported level of improvement was documented at 12 wk . Potential baseline predictor variables of interest included patient demographics , pain characteristics , footwear motion control properties , foot and ankle characteristics , and functional performance measures . RESULTS Fourteen ( 25 % ) participants reported marked improvement at 12 wk . The number of participants with marked improvement increased to 78 % if three of the following four criteria were met : footwear motion control properties score of < 5.0 ( indicative of less supportive footwear ) , usual pain < 22.0 mm , ankle dorsiflexion range of motion ( knee flexed ) < 41 ° , and reduced single-leg squat pain when wearing the orthoses . CONCLUSIONS Individuals with PFPS who wear less supportive footwear , report lower levels of pain , exhibit less ankle dorsiflexion range of motion , and report an immediate reduction in pain with foot orthoses when performing a single-leg squat are more likely to benefit from foot orthoses", "Objective Patellar malalignment is a major cause of patellofemoral pain syndrome ( PFPS ) , but the relationship between clinical symptoms and changes in patellar position and knee muscle strength has not been confirmed . This study examined the effect of weight training on hip and knee muscle strength , patellofemoral joint contact area , and patellar tilt on subjects with and without PFPS , hoping to develop an optimal rehabilitation protocol for subjects with PFPS . Design The study uses a prospect i ve independent group comparison . Fifteen subjects with and without PFPS were assessed for knee strength , patellofemoral joint contact area , and patellar tilt angle using magnetic resonance imaging . The subjects with PFPS were also examined and given a numeric pain rating score and a Kujala patellofemoral score . The subjects performed lower-limb weight training 3 times/wk for 8 wks , and the outcomes were assessed both before and after training . Results Subjects with PFPS have increased their patellofemoral joint contact area after weight training ( P < 0.001 ) . No statistical significant change was found on the patellar tilt angle . The isometric and isokinetic knee strength in subjects with and without PFPS have increased after weight training ( P value increased from 0.007 to 0.05 ) . Both numeric pain rating and Kujala patellofemoral score in the PFPS group improved after training ( P < 0.001 ) . Conclusions Weight-training exercise increased knee muscle strength and the patellofemoral joint contact area , which could reduce mechanical stress in the joint , improving pain and function in subjects with PFPS", "Objective : To determine prospect ively gait-related intrinsic risk factors for patellofemoral pain ( PFP ) in a population of novice recreational runners . Design : Prospect i ve cohort study . Participants : 102 novice recreational runners ( 89 women ) with no history of knee or lower leg complaints . Interventions : The st and ing foot posture of the subjects was examined and plantar pressure measurements during running were collected . The subjects then participated in a 10-week “ start to run ” programme . During this period all sports injuries were registered by a sports medicine physician . Main outcome measurements : The relationship between the st and ing foot posture and PFP was investigated and gait-related intrinsic risk factors for PFP were determined . Results : The 17 runners who developed PFP exerted a significantly higher vertical peak force underneath the lateral heel and metatarsals 2 and 3 . Logistic regression analysis showed that a significantly higher vertical peak force underneath the second metatarsal and shorter time to the vertical peak force underneath the lateral heel were predictors for PFP . No significant evidence was found for an association between an excessively pronated or supinated foot posture and the development of PFP . Conclusions : The findings suggest that an excessive impact shock during heel strike and at the propulsion phase of running may contribute to an increased risk of developing PFP . The hypothesis that persons at risk for PFP show an altered static foot posture in comparison with non-afflicted persons is not supported by the results of this study", "Background : The prevalence of adolescent knee pain is 33 % , and patellofemoral pain ( PFP ) is the most common diagnosis with a nontraumatic onset . The 2-year prognosis of adolescent PFP compared with other types of knee pain is unknown . Purpose : To investigate the 2-year prognosis of knee pain among adolescents with and without a diagnosis of PFP . Study Design : Cohort study ; Level of evidence , 2 . Methods : In 2011 , a cohort of 2200 adolescents aged 15 to 19 years answered an online question naire on musculoskeletal pain . Of these , 504 reported knee pain , and 153 of these were clinical ly diagnosed with PFP . After 2 years , the 504 adolescents , as well as 252 r and omly selected adolescents who did not report knee pain in 2011 , were contacted again . Primary outcome at follow-up was the proportion of adolescents with knee pain during the last week prior to follow-up . Results : Overall , 55.9 % ( 95 % CI , 50.8%-60.9 % ) of those reporting knee pain at baseline also reported pain 2 years later . Adolescents diagnosed with PFP had a 1.26 ( 95 % CI , 1.05 - 1.50 ) higher relative risk ( RR ) of knee pain at follow-up compared with other types of knee pain . Adolescents with PFP were significantly more likely to reduce or stop sports participation compared with adolescents with other types of knee pain . Of those without knee pain at baseline , 12.8 % ( 95 % CI , 8.4%-17.2 % ) reported knee pain at follow-up in 2013 . Adolescents with knee pain at baseline had a 4.51 ( 95 % CI , 3.15 - 6.45 ) higher RR of knee pain at follow-up compared with adolescents without knee pain at baseline . Conclusion : Knee pain during adolescence , and PFP in particular , is in most cases present after 2 years and thus may not be self-limiting . A greater focus on early detection and prevention of knee pain during adolescence is needed", "Background Identification of mechanical factors associated with patellofemoral pain , the most prevalent running injury , is necessary to help in injury prevention , but unfortunately they remain elusive . Hypothesis Runners who develop patellofemoral pain have increased knee joint angular impulse in the frontal plane . Study Design Case control study ; Level of evidence , 3 . Methods A retrospective study compared knee abduction impulses of 20 patellofemoral pain patients with those of 20 asymptomatic patients . A second prospect i ve study quantified knee angular impulses during the stance phase of running of 80 runners at the beginning of the summer running season . Epidemiologic data were then collected , recording the type and severity of injury of these runners during a 6-month running period . Results The patellofemoral pain patients in the retrospective study had significantly higher ( P = . 026 ) knee abduction impulses ( 17.0 ± 8.5 Nms ) than did the asymptomatic patients ( 12.5 ± 5.5 Nms ) . Six patients developed patellofemoral pain during the prospect i ve study . The prospect i ve data showed that patients who developed patellofemoral pain had significantly higher ( P = . 042 ) knee abduction impulses ( 9.2 ± 3.7 Nms ) than did matched patients who remained uninjured ( 4.7 ± 3.5 Nms ) . Conclusion The data indicate that increased knee abduction impulses should be deemed risk factors that play a role in the development of patellofemoral pain in runners . Clinical Relevance Footwear and running style can influence knee angular impulse , and the appropriate manipulation of these variables may play a preventive role for patients who are predisposed to patellofemoral pain", "Background Delayed onset of vastus medialis obliquus activity has been described in patellofemoral pain patients . No prospect i ve study investigating the development of patellofemoral pain has tested the onset timing of electromyographic activity of the vastus medialis obliquus and vastus lateralis muscles during a functional task . Hypothesis Before the development of patellofemoral pain , subjects demonstrate an altered firing order of the vastus medialis obliquus and vastus lateralis muscles compared with healthy subjects during a functional task . Study Design Cohort study ; Level of evidence , 2 . Methods The onset of vastus medialis obliquus and vastus lateralis activity was measured with surface electromyography during a functional task ( rocking back on the heels ) in 79 healthy subjects subsequently su bmi tted to a 6-week strenuous basic military training . Afterward , these subjects were reassessed . Results Thirty-two percent of the recruits developed patellofemoral pain during training . Patellofemoral pain subjects demonstrated a significant delay of onset of vastus medialis obliquus electromyographic activity compared with the healthy controls ( P = .023 ) , even before basic military training . In healthy subjects , no significant differences in electromyographic activity onset of the vastus medialis obliquus compared with the vastus lateralis could be identified before and after basic military training . A significant ( P < .001 ) delay could be demonstrated in the patellofemoral pain group after basic military training . A binary logistic regression could be constructed wherein the onset of the electromyographic activity of the vastus medialis obliquus and vastus lateralis was withheld in the model . The most optimal cutoff value , which is based on the receiver operating characteristic curve , is a timing difference of −0.67 milliseconds ( vastus medialis obliquus – vastus lateralis ) . The area under the receiver operating characteristic curve is considered as fair ( 0.68 ) . Conclusion Delayed onset of electromyographic activity of the vastus medialis obliquus – vastus lateralis is one of the contributing risk factors to the development of patellofemoral pain", "The present case-control study included as cases 24 athletes with anterior knee pain , and 17 controls , matching the cases according to gender and age . All cases had their most symptomatic knee examined by magnetic resonance imaging ( MRI ) . Among controls one knee was chosen for examination at r and om . The MRI of the patella showed articular cartilage lesions in 17 out of 24 cases , whereas among the controls 4 out of 17 had articular cartilage lesions . ( Odds Ratio 7.9 ( 95 % confidence interval 1.9 - 33 ) ) . However , presence of articular cartilage lesions was not associated with duration of symptoms or intensity of the anterior knee pain . The present study showed a significant positive association between presence of articular cartilage lesions in the patella and presence of anterior knee pain , but further studies are needed to examine the relationship in detail", "OBJECTIVE To determine the effects of a weight-bearing rehabilitation program on quadriceps and gluteus medius electromyographic activity , pain , and function in subjects diagnosed with patellofemoral pain syndrome ( PFPS ) . DESIGN Pretest and posttest 6-week intervention study . SETTING Musculoskeletal research laboratory . PARTICIPANTS Fourteen subjects diagnosed with PFPS and 14 healthy control subjects volunteered to participate in this study . No subjects withdrew from the study because of adverse effects . INTERVENTION Subjects diagnosed with PFPS participated in a 6-week rehabilitation program . The rehabilitation program consisted of weight-bearing exercises that focused on strengthening the quadriceps and hip abductor musculature . MAIN OUTCOME MEASURES Electromyographic onsets of the vastus medialis oblique ( VMO ) and vastus lateralis and onset and duration of the gluteus medius were collected during a stair-stepping task that was performed during the pretest and posttest . A visual analog scale ( VAS ) and Functional Index Question naire ( FIQ ) were administered at pretest and posttest and each week of the intervention . RESULTS Vastus lateralis and VMO onset timing differences ( vastus lateralis electromyographic onset minus VMO electromyographic onset ) and VAS and FIQ scores significantly improved for patients diagnosed with PFPS . Vastus lateralis and VMO onset timing in the PFPS group were significantly different from those in the control group at baseline and were not significantly different from the control group after the intervention . We did not find differences in gluteus medius onsets or duration of activity . CONCLUSIONS Subjects diagnosed with PFPS responded favorably and quickly to a therapeutic exercise program that incorporated quadriceps and hip musculature strengthening . The efficacy of the therapeutic exercise program used in this study should be further investigated in a larger subject population", "Many variables have retrospectively been associated with the presence of anterior knee pain . Very few prospect i ve data exist , however , to determine which of these variables will lead to the development of anterior knee pain . It was our purpose in this study to determine the intrinsic risk factors for the development of anterior knee pain in an athletic population over a 2-year period . Before the start of training , 282 male and female students enrolled in physical education classes were evaluated for anthropometric variables , motor performance , general joint laxity , lower leg alignment characteristics , muscle length and strength , static and dynamic patellofemoral characteristics , and psychological parameters . During this 2-year follow-up study , 24 of the 282 students developed patellofemoral pain . Statistical analyses revealed a significant difference between those subjects who developed patellofemoral pain and those who did not concerning quadriceps and gastrocnemius muscle flexibility , explosive strength , thumb-forearm mobility , reflex response time of the vastus medialis obliquus and vastus lateralis muscles , and the psychological parameter of seeking social support . However , only a shortened quadriceps muscle , an altered vastus medialis obliquus muscle reflex response time , a decreased explosive strength , and a hypermobile patella had a significant correlation with the incidence of patellofemoral pain . We concluded that the latter four parameters play a dominant role in the genesis of anterior knee pain and we therefore deem them to be risk factors for this syndrome", "PURPOSE The objectives of this study were 1 ) to examine the differences between a noninjured ( C ) cohort of runners ( N = 70 ) and runners afflicted with anterior knee pain ( AKP ) according to selected training , anthropometric , rearfoot motion , ground reaction force , and muscular strength and endurance variables ; 2 ) to explore multivariate relationships among these measures in the well and injured groups ; and 3 ) to develop specific hypotheses concerning risk factors for injury that will later be tested in a prospect i ve clinical study . METHODS High speed videography ( 200 frames x s(-1 ) ) , a force platform ( 500 Hz ) , and a Cybex II+ isokinetic dynamometer were used to assess rearfoot motion , ground reaction forces , and knee muscular strength and endurance , respectively . A linear discriminant function was performed on each of the five categories of variables and revealed 19 significant ( P < or = 0.05 ) predictors . These variables were then combined and a final discriminant function analysis was performed . RESULTS Pronation through the first 10 % of stance , arch index , shoe mileage , and extension peak torque were the best overall ( P < or = 0.05 ) predictors . The AKP group had smaller mean values on all four significant predictors . CONCLUSION With the exception of shoe mileage , which is likely a response to rather than a risk factor for AKP , these results should prove useful to clinicians in identifying runners at risk for anterior knee pain", "BACKGROUND Patellofemoral pain syndrome is one of the most common knee problems and may be related to abnormal patellar tracking . Our purpose was to compare , in vivo and noninvasively , the patellar tracking patterns in symptomatic patients with patellofemoral pain and those in healthy subjects during squatting . We tested the hypothesis that patients with patellofemoral pain exhibit characteristic patterns of patellar tracking that are different from those of healthy subjects . METHODS Three-dimensional patellar kinematics were recorded in vivo with use of a custom-molded patellar clamp and an optoelectronic motion capture system in ten healthy subjects and nine subjects with patellofemoral pain . The position of osseous knee l and marks was digitized while subjects stood upright , and then patellofemoral kinematics were recorded during squatting . The tracking technique was vali date d with use of both in vitro and in vivo method ologies , and the average absolute error was < 1.2 degrees and < 1.1 mm . RESULTS At 90 degrees of knee flexion , the patella showed lateral spin ( the distal pole of the patella rotated laterally ) in subjects with patellofemoral pain ( mean and st and ard deviation , -10.13 degrees + /- 2.24 degrees ) and medial spin in healthy subjects ( mean , 4.71 degrees + /- 1.17 degrees ) ( p < 0.001 ) . At 90 degrees of knee flexion , the patella demonstrated significantly more lateral translation in subjects with patellofemoral pain ( mean , 5.05 + /- 3.73 mm ) than in healthy subjects ( mean , -4.93 + /- 3.93 mm ) ( p < 0.001 ) . CONCLUSIONS Kinematic differences between healthy subjects and subjects with patellofemoral pain were demonstrated through a large , dynamic range of knee flexion angles . Increased lateral patellar translation and lateral patellar spin in subjects with patellofemoral pain suggest that the patella is not adequately balanced during functional activities in this group . Prospect i ve studies are needed to identify when patellofemoral pain-related changes begin to occur and to determine the risk for the development of patellofemoral pain in individuals with abnormal kinematics" ]

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[ "Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.", "Lapatinib Activity in Premalignant Lesions and HER-2–Positive Cancer of the Breast in a Randomized, Placebo-Controlled Presurgical Trial", "United States Food and Drug Administration Drug Approval Summary", "Effects of lapatinib monotherapy: results of a randomised phase II study in therapy-naive patients with locally advanced squamous cell carcinoma of the head and neck", "Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.", "Phase II trial of capecitabine plus erlotinib versus capecitabine alone in patients with advanced colorectal cancer.", "Gefitinib versus placebo in completely resected non-small-cell lung cancer: results of the NCIC CTG BR19 study.", "Targeting epidermal growth factor receptor/human epidermal growth factor receptor 2 signalling pathway by a dual receptor tyrosine kinase inhibitor afatinib for radiosensitisation in murine bladder carcinoma.", "Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status.", "First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial", "Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial.", "Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)", "Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial.", "Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial." ]

[ "BACKGROUND Neratinib , an irreversible tyrosine-kinase inhibitor of HER1 , HER2 , and HER4 , has clinical activity in patients with HER2-positive metastatic breast cancer . We aim ed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer . METHODS We did this multicentre , r and omised , double-blind , placebo-controlled , phase 3 trial at 495 centres in Europe , Asia , Australia , New Zeal and , and North and South America . Eligible women ( aged ≥18 years , or ≥20 years in Japan ) had stage 1 - 3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before r and omisation . Inclusion criteria were amended on Feb 25 , 2010 , to include patients with stage 2 - 3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously . Patients were r and omly assigned ( 1:1 ) to receive oral neratinib 240 mg per day or matching placebo . The r and omisation sequence was generated with permuted blocks stratified by hormone receptor status ( hormone receptor-positive [ oestrogen or progesterone receptor-positive or both ] vs hormone receptor-negative [ oestrogen and progesterone receptor-negative ] ) , nodal status ( 0 , 1 - 3 , or ≥4 ) , and trastuzumab adjuvant regimen ( sequentially vs concurrently with chemotherapy ) , then implemented central ly via an interactive voice and web-response system . Patients , investigators , and trial sponsors were masked to treatment allocation . The primary outcome was invasive disease-free survival , as defined in the original protocol , at 2 years after r and omisation . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00878709 . FINDINGS Between July 9 , 2009 , and Oct 24 , 2011 , we r and omly assigned 2840 women to receive neratinib ( n=1420 ) or placebo ( n=1420 ) . Median follow-up time was 24 months ( IQR 20 - 25 ) in the neratinib group and 24 months ( 22 - 25 ) in the placebo group . At 2 year follow-up , 70 invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group ( stratified hazard ratio 0·67 , 95 % CI 0·50 - 0·91 ; p=0·0091 ) . The 2-year invasive disease-free survival rate was 93·9 % ( 95 % CI 92·4 - 95·2 ) in the neratinib group and 91·6 % ( 90·0 - 93·0 ) in the placebo group . The most common grade 3 - 4 adverse events in patients in the neratinib group were diarrhoea ( grade 3 , n=561 [ 40 % ] and grade 4 , n=1 [ < 1 % ] vs grade 3 , n=23 [ 2 % ] in the placebo group ) , vomiting ( grade 3 , n=47 [ 3 % ] vs n=5 [ < 1 % ] ) , and nausea ( grade 3 , n=26 [ 2 % ] vs n=2 [ < 1 % ] ) . QT prolongation occurred in 49 ( 3 % ) patients given neratinib and 93 ( 7 % ) patients given placebo , and decreases in left ventricular ejection fraction ( ≥ grade 2 ) in 19 ( 1 % ) and 15 ( 1 % ) patients , respectively . We recorded serious adverse events in 103 ( 7 % ) patients in the neratinib group and 85 ( 6 % ) patients in the placebo group . Seven ( < 1 % ) deaths ( four patients in the neratinib group and three patients in the placebo group ) unrelated to disease progression occurred after study drug discontinuation . The causes of death in the neratinib group were unknown ( n=2 ) , a second primary brain tumour ( n=1 ) , and acute myeloid leukaemia ( n=1 ) , and in the placebo group were a brain haemorrhage ( n=1 ) , myocardial infa rct ion ( n=1 ) , and gastric cancer ( n=1 ) . None of the deaths were attributed to study treatment in either group . INTERPRETATION Neratinib for 12 months significantly improved 2-year invasive disease-free survival when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer . Longer follow-up is needed to ensure that the improvement in breast cancer outcome is maintained . FUNDING Wyeth , Pfizer , Puma Biotechnology", "Dual epidermal growth factor receptor ( EGFR ) and HER2 targeting with the tyrosine kinase inhibitor lapatinib is approved for treating advanced HER2-positive breast cancer and can prevent estrogen receptor (ER)-negative mammary tumors in HER2 transgenic mouse models . Ki-67 labeling index ( LI ) has prognostic and predictive value and can be used to screen drugs ' therapeutic and preventive potential in a clinical model of short-term presurgical therapy of breast cancer . We conducted a r and omized , placebo-controlled trial of lapatinib ( 1500 mg/d ) administered orally for three weeks between biopsy and surgery in 60 women with HER-2–positive breast cancer to assess lapatinib biomarker ( including the primary endpoint , Ki-67 LI ) and clinical activity in invasive breast cancer , adjacent ductal intraepithelial neoplasia ( DIN , which comprises ductal carcinoma in situ and atypical ductal hyperplasia ) , and distant ductal hyperplasia without atypia ( DH ) . Ki-67 LI increased progressively in association with disease stage , increasing in the placebo arm , for example , by medians of 3 % in DH to 20 % in DIN to 30 % in invasive cancer . Ki-67 LI in cancer tissue decreased by a mean ( ±SD ) of 9.3 % ( ±34.2 ) in the lapatinib arm and increased by 15.1 % ( ±30.9 ) in the placebo arm ( P = 0.008 ) . Compared with placebo , lapatinib reduced Ki-67 significantly more in ER-negative tumors ( by 34.8 % ; P = 0.01 ) but not significantly more in ER-positive tumors ( by 12.3 % ; P = 0.2 ) and reduced Ki-67 more ( nonsignificantly ) in cytosol PTEN-overexpressing tumors ( P = 0.057 ) . The prevalence of DIN in post-treatment surgical specimens of both arms was similar ( 70%–76 % ) , with a median Ki-67 of 15 % ( range , 5%–35 % ) on lapatinib versus 20 % ( 5%–60 % ) on placebo ( P = 0.067 ) . The prevalence of DH also was similar in both arms ( > 90 % ) , with a median Ki-67 of 1 % ( 1%–7 % ) on lapatinib versus 3 % ( 1%–5 % ) on placebo ( P = 0.006 ) . Other results of lapatinib versus placebo , respectively , were as follows : Median tumor diameter at surgery of 18 mm ( 11 mm–57 mm ) versus 24 mm ( 10 mm–37 mm ; P = 0.009 ) ; partial response of 13.6 % versus 3.7 % , stable disease of 59.1 % versus 40.7 % , and progression of 27.3 % versus 55.6 % ( P-trend = 0.035 ) . In conclusion , short-term lapatinib decreased cell proliferation in DIN , DH , and invasive HER-2–positive ( especially ER-negative ) breast cancer , thus providing the rationale for further clinical development of lapatinib for breast cancer prevention in high-risk patients , including those with HER-2–positive DIN . Cancer Prev Res ; 4(8 ) ; 1181–9 . © 2011 AACR", "On May 5 , 2003 , gefitinib ( Iressa ; ZD1839 ) 250-mg tablets ( AstraZeneca Inc. ) received accelerated approval by the United States Food and Drug Administration as monotherapy for patients with locally advanced or metastatic non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapies . Information provided in this summary includes chemistry manufacturing and controls , clinical pharmacology , and clinical trial efficacy and safety results . Gefitinib is an anilinoquinazoline compound with the chemical name 4-quinazolinamine , N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy ] . It has the molecular formula C22H24ClFN4O3 . Gefitinib is often referred to as a “ specific ” or “ selective ” inhibitor of epidermal growth factor receptor . Studies demonstrate , however , that gefitinib inhibits the activity of other intracellular transmembrane tyrosine-specific protein kinases at concentrations similar to those at which it inhibits the epidermal growth factor signal . Maximum plasma concentrations result ing from clinical ly relevant doses are 0.5–1 μm or more , well within the IC50 values of several tyrosine kinases . No clinical studies have been performed that demonstrate a correlation between epidermal growth factor receptor expression and response to gefitinib . Gefitinib is 60 % available after oral administration and is widely distributed throughout the body . Gefitinib is extensively metabolized in the liver by cytochrome P450 3A4 enzyme . Over a 10-day period , approximately 86 % of an orally administered radioactive dose is recovered in the feces , with < 4 % of the dose in the urine . After daily oral administration , steady-state plasma levels are reached in 10 days and are 2-fold higher than those achieved after single doses . Gefitinib effectiveness was demonstrated in a r and omized , double-blind , Phase II , multicenter trial comparing two oral doses of gefitinib ( 250 versus 500 mg/day ) . A total of 216 patients were enrolled . The 142 patients who were refractory to or intolerant of a platinum and docetaxel comprised the evaluable population for the efficacy analysis . A partial tumor response occurred in 14 % ( 9 of 66 ) of patients receiving 250 mg/day gefitinib and in 8 % ( 6 of 76 ) of patients receiving 500 mg/day gefitinib . The overall objective response rate ( RR ) for both doses combined was 10.6 % ( 15 of 142 patients ; 95 % confidence interval , 6.0–16.8 % ) . Responses were more frequent in females and in nonsmokers . The median duration of response was 7.0 months ( range , 4.6–18.6 + months ) . Other su bmi tted data included the results of two large trials conducted in chemotherapy-naive , stage III and IV non-small cell lung cancer patients . Patients were r and omized to receive gefitinib ( 250 or 500 mg daily ) or placebo , in combination with either gemcitabine plus cisplatin ( n = 1093 ) or carboplatin plus paclitaxel ( n = 1037 ) . Results from this study showed no benefit ( RR , time to progression , or survival ) from adding gefitinib to chemotherapy . Consequently , gefinitib is only recommended for use as monotherapy . Common adverse events associated with gefitinib treatment included diarrhea , rash , acne , dry skin , nausea , and vomiting . Interstitial lung disease has been observed in patients receiving gefitinib . Worldwide , the incidence of interstitial lung disease was about 1 % ( 2 % in the Japanese post-marketing experience and about 0.3 % in a United States exp and ed access program ) . Approximately one-third of the cases have been fatal . Gefitinib was approved under accelerated approval regulations on the basis of a surrogate end point , RR . No controlled gefitinib trials , to date , demonstrate a clinical benefit , such as improvement in disease-related symptoms or increased survival . Accelerated approval regulations require the sponsor to conduct additional studies to verify that gefitinib therapy produces such benefit", "Background : Lapatinib is a dual inhibitor of epidermal growth factor receptor ( EGFR ) and human EGFR-2 ( HER-2 ) tyrosine kinases . This study investigated the pharmacodynamic and clinical effects of lapatinib in patients with locally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . Methods : In total , 107 therapy-naive patients with locally advanced SCCHN were r and omised ( 2 : 1 ) to receive lapatinib or placebo for 2–6 weeks before chemoradiation therapy ( CRT ) . Endpoints included apoptosis and proliferation rates , clinical response , and toxicity . Results : Versus placebo , lapatinib monotherapy did not significantly increase apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling or caspase-3 assays . A statistically significant decrease in proliferation using Ki67 assay was observed ( P=0.030 ) . In a subset of 40 patients that received ⩾4 weeks of lapatinib or placebo , objective response rate ( ORR ) was 17 % ( n=4/24 ) vs 0 % ( n=0/16 ) . In the lapatinib single-agent responders , all had EGFR overexpression , 50 % had EGFR amplification , and 50 % had HER2 expression by immunohistochemistry ( including one patient with HER2 amplification ) . However , these patients showed variable modulation of apoptosis , proliferation , and phosphorylated EGFR on drug treatment . Following CRT , there was a statistically non-significant difference in ORR between lapatinib ( 70 % ) and placebo ( 53 % ) . There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation . Mucosal inflammation , asthenia , odynophagia , and dysphagia were the most commonly reported adverse events with lapatinib . Conclusion : Short-term lapatinib monotherapy did not demonstrate apoptotic changes , but provided evidence of clinical activity in locally advanced SCCHN , and warrants further investigation in this disease", "PURPOSE This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer ( NSCLC ) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy . PATIENTS AND METHODS Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were r and omly assigned to observation or to gemcitabine ( 1,250 mg/m(2 ) days 1 and 8 of a 3-week cycle ) or daily erlotinib ( 150 mg/day ) study arms . On disease progression , patients in all three arms received pemetrexed ( 500 mg/m(2 ) once every 21 days ) as predefined second-line therapy . The primary end point was progression-free survival ( PFS ) . RESULTS PFS was significantly prolonged by gemcitabine ( median , 3.8 v 1.9 months ; hazard ratio [ HR ] , 0.56 ; 95 % CI , 0.44 to 0.72 ; log-rank P < .001 ) and erlotinib ( median , 2.9 v 1.9 months ; HR , 0.69 ; 95 % CI , 0.54 to 0.88 ; log-rank P = .003 ) versus observation ; this benefit was consistent across all clinical subgroups . Both maintenance strategies result ed in a nonsignificant improvement in overall survival ( OS ) ; patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit . Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance . Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events . CONCLUSION Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy . Response to induction chemotherapy may affect OS only for continuation maintenance", "Aim & methods : Capecitabine monotherapy as palliation for advanced colorectal cancer ( CRC ) is generally well tolerated . Adding erlotinib , an EGFR-tyrosine kinase inhibitor , might improve efficacy versus capecitabine alone . 82 patients received capecitabine alone ( Arm 1 ) or capecitabine with erlotinib ( Arm 2 ) . RESULTS Median time-to-progression ( TTP ) in Arm 1 was 7.9 months versus 9.2 in Arm 2 . In KRAS-wild type ( WT ) patients TTP was 8.4 and 11.7 months in Arms 1 and 2 , respectively . In KRAS-mutated patients TTP was 7.4 and 1.9 months in Arms 1 and 2 , respectively ( p = 0.023 ) . Arm 2 KRAS-WT patients , left-sided primaries , had an overall survival of 16.0 versus 12.1 months in right-sided primaries . CONCLUSION Adding erlotinib to capecitabine increased TTP by 3.2 months in KRAS-WT patients . This study suggests that erlotinib harms patients with KRAS-mutated advanced CRC while it may provide benefit to those with KRAS-WT CRC . Further study of EGFR-tyrosine kinase inhibitors in patients with left-sided KRAS-WT CRC is warranted", "PURPOSE Survival of patients with completely resected non-small-cell lung cancer ( NSCLC ) is unsatisfactory , and in 2002 , the benefit of adjuvant chemotherapy was not established . This phase III study assessed the impact of postoperative adjuvant gefitinib on overall survival ( OS ) . PATIENTS AND METHODS Patients with completely resected ( stage IB , II , or IIIA ) NSCLC stratified by stage , histology , sex , postoperative radiotherapy , and chemotherapy were r and omly assigned ( 1:1 ) to receive gefitinib 250 mg per day or placebo for 2 years . Study end points were OS , disease-free survival ( DFS ) , and toxicity . RESULTS As a result of early closure , 503 of 1,242 planned patients were r and omly assigned ( 251 to gefitinib and 252 to placebo ) . Baseline factors were balanced between the arms . With a median of 4.7 years of follow-up ( range , 0.1 to 6.3 years ) , there was no difference in OS ( hazard ratio [ HR ] , 1.24 ; 95 % CI , 0.94 to 1.64 ; P = .14 ) or DFS ( HR , 1.22 ; 95 % CI , 0.93 to 1.61 ; P = .15 ) between the arms . Exploratory analyses demonstrated no DFS ( HR , 1.28 ; 95 % CI , 0.92 to 1.76 ; P = .14 ) or OS benefit ( HR , 1.24 ; 95 % CI , 0.90 to 1.71 ; P = .18 ) from gefitinib for 344 patients with epidermal growth factor receptor ( EGFR ) wild-type tumors . Similarly , there was no DFS ( HR , 1.84 ; 95 % CI , 0.44 to 7.73 ; P = .395 ) or OS benefit ( HR , 3.16 ; 95 % CI , 0.61 to 16.45 ; P = .15 ) from gefitinib for the 15 patients with EGFR mutation-positive tumors . Adverse events were those expected with an EGFR inhibitor . Serious adverse events occurred in ≤ 5 % of patients , except infection , fatigue , and pain . One patient in each arm had fatal pneumonitis . CONCLUSION Although the trial closed prematurely and definitive statements regarding the efficacy of adjuvant gefitinib can not be made , these results indicate that it is unlikely to be of benefit", "Given the promising control of bladder cancer achieved by combined chemotherapy/radiotherapy with selective transurethral resection , obstacles remain to the treatment of unresectable bladder cancer . The aim of this study was to determine whether targeting epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 ( HER2 ) can radiosensitise a murine bladder tumour ( MBT-2 ) cell line . Cell survival , expression of signal proteins and cell cycle changes in MBT-2 cells treated in vitro and in vivo with afatinib , an irreversible EGFR/HER2 inhibitor , plus radiotherapy were investigated by colony formation assay , Western blot assay and flow cytometry , respectively . Ectopic xenografts were established by subcutaneous injection of MBT-2 cells in C3H/HeN mice . Mice were r and omised into 4 groups to receive afatinib ( 10mg/kg/day on day 1 - 7 ) and /or radiotherapy ( 15Gy on day 4 ) . Positron emission tomography ( PET ) on day 8 was used to evaluate the early treatment response . Afatinib ( 200 - 1000nM ) increased cell killing by radiation ( 0 - 10Gy ) . Pre-treatment of irradiated cells with afatinib inhibited radiation-activated HER2 and EGFR phosphorylation . As compared to either treatment alone , the combination increased the level of the cleavage form of poly ( ADP-ribose ) polymerase , the expression of phospho-γH2AX and the percentage of cells in subG1 phase ( indicating enhanced induction of apoptosis ) , and decreased tumour metabolism and inhibited tumour growth by 64 % . Afatinib has therapeutic value as a radiosensitiser of murine bladder cancer cells . The synergism between afatinib and radiation likely enhances DNA damage , leading to increased cell apoptosis", "PURPOSE To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer ( NSCLC ) and poor performance status . PATIENTS AND METHODS NSCLC patients ( chemotherapy naïve , WHO performance status 2 or 3 ; unfit for chemotherapy ; stage IIIB/IV ) were r and omly assigned to gefitinib ( 250 mg/d ) plus best supportive care ( BSC ; n = 100 ) or placebo plus BSC ( n = 101 ) . The primary end point was progression-free survival ( PFS ) . Secondary end points included overall survival ( OS ) , objective response rate ( ORR ) , quality of life ( QOL ) , pulmonary symptom improvement ( PSI ) , and safety . Correlation of gefitinib efficacy with EGFR gene copy number ( fluorescent in situ hybridization [ FISH ] ) was explored . RESULTS Hazard ratios ( HRs ; gefitinib : placebo ) were 0.82 ( 95 % CI , 0.60 to 1.12 ; P = .217 ) for PFS and 0.84 ( 95 % CI , 0.62 to 1.15 ; P = .272 ) for OS . As expected for this patient population , OS for both arms was poor , at about 3 months . ORRs were 6.0 % ( gefitinib ) and 1.0 % ( placebo ) . QOL and PSI rates were 21.1 % and 28.3 % ( gefitinib ) and 20.0 % and 28.3 % ( placebo ) , respectively . In EGFR FISH-positive patients ( n = 32 ) , HRs were 0.29 ( 95 % CI , 0.11 to 0.73 ) for PFS and 0.44 ( 95 % CI , 0.17 to 1.12 ) for OS . No unexpected adverse events occurred . CONCLUSION There was no statistically significant difference in PFS , OS , and ORRs after treatment with gefitinib or placebo , in the overall population ; improvements in QOL and symptoms were similar in both groups . Tolerability profile of gefitinib was consistent with previous studies . PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors", "Summary Background Many patients with advanced non-small-cell lung cancer ( NSCLC ) receive only active supportive care because of poor performance status or presence of several comorbidities . We investigated whether erlotinib improves clinical outcome in these patients . Methods TOPICAL was a double-blind , r and omised , placebo-controlled , phase 3 trial , done at 78 centres in the UK . Eligibility criteria were newly diagnosed , pathologically confirmed NSCLC ; stage IIIb or IV ; chemotherapy naive ; no symptomatic brain metastases ; deemed unsuitable for chemotherapy because of poor ( ≥2 ) Eastern Cooperative Oncology Group performance status or presence of several comorbidities , or both ; and estimated life expectancy of at least 8 weeks . Patients were r and omly assigned ( by phone call , in a 1:1 ratio , stratified by disease stage , performance status , smoking history , and centre , block size 10 ) to receive oral placebo or erlotinib ( 150 mg per day ) until disease progression or unacceptable toxicity . Investigators , clinicians , and patients were masked to assignment . The primary endpoint was overall survival . Analyses were by intention to treat , and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment . This study is registered , number IS RCT N 77383050 . Findings Between April 14 , 2005 , and April 1 , 2009 , we r and omly assigned 350 patients to receive erlotinib and 320 to receive placebo . We followed up patients until March 31 , 2011 . 657 patients died ; median overall survival did not differ between groups ( erlotinib , 3·7 months , 95 % CI 3·2–4·2 , vs placebo , 3·6 months , 3·2–3·9 ; unadjusted hazard ratio [ HR ] 0·94 , 95 % CI 0·81–1·10 , p=0·46 ) . 59 % ( 178 of 302 ) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash , which was the only independent factor associated with overall survival . Patients with first-cycle rash had better overall survival ( HR 0·76 , 95 % CI 0·63–0·92 , p=0·0058 ) , compared with placebo . Compared with placebo , overall survival seemed to be worse in the group that did not develop first-cycle rash ( 1·30 , 1·05–1·61 , p=0·017 ) . Grade 3 or 4 diarrhoea was more common with erlotinib than placebo ( 8 % [ 28 of 334 ] vs 1 % [ four of 313 ] , p=0·0001 ) , as was high- grade rash ( 23 % [ 79 of 334 ] vs 2 % [ five of 313 ] , p<0·0001 ) ; other adverse events were much the same between groups . Interpretation Patients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib . Patients who develop a first-cycle rash should continue to receive erlotinib , whereas those who do not have a rash after 28 days should discontinue erlotinib , because of the possibility of decreased survival . Funding Cancer Research UK , Roche", "PURPOSE Epidermal growth factor receptor ( EGFR ) -tyrosine kinase inhibitors have proven efficacy in advanced non-small-cell lung cancer ( NSCLC ) . We hypothesized that erlotinib would be efficacious in the adjuvant setting . PATIENTS AND METHODS An international r and omized , double-blind , placebo-controlled study was conducted in patients with completely resected IB to IIIA NSCLC whose tumors expressed EGFR protein by immunohistochemistry or EGFR amplification by fluorescence in situ hybridization . Patients were assigned 2:1 to erlotinib 150 mg once per day or placebo for 2 years . Stratification factors were stage , histology , previous adjuvant chemotherapy , smoking status , EGFR amplification status , and country . The primary end point was disease-free survival ( DFS ) ; key secondary end points were overall survival ( OS ) and DFS and OS in patients whose tumors had EGFR-activating mutations ( EGFRm-positive ) . RESULTS A total of 973 patients were r and omly assigned ( November 26 , 2007 , to July 7 , 2010 ) . There was no statistically significant difference in DFS ( median , 50.5 months for erlotinib and 48.2 months for placebo ; hazard ratio , 0.90 ; 95 % CI , 0.74 to 1.10 ; P = .324 ) . Among the 161 patients ( 16.5 % ) in the EGFRm-positive subgroup , DFS favored erlotinib ( median , 46.4 v 28.5 months ; hazard ratio , 0.61 ; 95 % CI , 0.38 to 0.98 ; P = .039 ) , but this was not statistically significant because of the hierarchical testing procedure . OS data are immature . Rash and diarrhea were common adverse events occurring in 528 ( 86.4 % ) and 319 ( 52.2 % ) patients treated with erlotinib , respectively , versus 110 ( 32.1 % ) and 54 ( 15.7 % ) patients receiving placebo . The most common grade 3 adverse events in patients treated with erlotinib were rash ( 22.3 % ) and diarrhea ( 6.2 % ) . CONCLUSION Adjuvant erlotinib did not prolong DFS in patients with EGFR-expressing NSCLC or in the EGFRm-positive subgroup . Further evaluation of erlotinib is warranted in the EGFRm-positive subgroup", "BACKGROUND This placebo-controlled phase III study investigated the effect on survival of gefitinib as second-line or third-line treatment for patients with locally advanced or metastatic non-small-cell lung cancer . METHODS 1692 patients who were refractory to or intolerant of their latest chemotherapy regimen were r and omly assigned in a ratio of two to one either gefitinib ( 250 mg/day ) or placebo , plus best supportive care . The primary endpoint was survival in the overall population of patients and those with adenocarcinoma . The primary analysis of the population for survival was by intention to treat . This study has been su bmi tted for registration with Clinical Trials.gov , number 1839IL/709 . FINDINGS 1129 patients were assigned gefitinib and 563 placebo . At median follow-up of 7.2 months , median survival did not differ significantly between the groups in the overall population ( 5.6 months for gefitinib and 5.1 months for placebo ; hazard ratio 0.89 [ 95 % CI 0.77 - 1.02 ] , p=0.087 ) or among the 812 patients with adenocarcinoma ( 6.3 months vs 5.4 months ; 0.84 [ 0.68 - 1.03 ] , p=0.089 ) . Preplanned subgroup analyses showed significantly longer survival in the gefitinib group than the placebo group for never-smokers ( n=375 ; 0.67 [ 0.49 - 0.92 ] , p=0.012 ; median survival 8.9 vs 6.1 months ) and patients of Asian origin ( n=342 ; 0.66 [ 0.48 - 0.91 ] , p=0.01 ; median survival 9.5 vs 5.5 months ) . Gefitinib was well tolerated , as in previous studies . INTERPRETATION Treatment with gefitinib was not associated with significant improvement in survival in either co primary population . There was pronounced heterogeneity in survival outcomes between groups of patients , with some evidence of benefit among never-smokers and patients of Asian origin", "BACKGROUND Evidence is scarce for the effectiveness of therapies for oesophageal cancer progressing after chemotherapy , and no r and omised trials have been reported . We aim ed to compare gefitinib with placebo in previously treated advanced oesophageal cancer . METHODS For this phase 3 , parallel , r and omised , placebo-controlled trial , eligible patients were adults with advanced oesophageal cancer or type I/II Siewert junctional tumours , histologically confirmed squamous-cell carcinoma or adenocarcinoma , who had progressed after chemotherapy , with WHO performance status 0 - 2 , and with measurable or evaluable disease on CT scan . Participants were recruited from 48 UK centres and r and omly assigned ( 1:1 ) to gefitinib ( 500 mg ) or matching placebo by simple r and omisation with no stratification factors . Patients , clinicians , and trial office staff were masked to treatment allocation . Treatment continued until disease progression , unacceptable toxicity , or patient choice . The primary outcome was overall survival , analysed by intention to treat . This trial is registered , number IS RCT N29580179 . FINDINGS Between March 30 , 2009 , and Nov 18 , 2011 , 450 patients were r and omly assigned to treatment groups ( one patient withdrew consent ; 224 patients allocated gefitinib and 225 allocated placebo included in analyses ) . Overall survival did not differ between groups ( median 3·73 months , 95 % CI 3·23 - 4·50 , for gefitinib vs 3·67 months , 95 % CI 2·97 - 4·37 , for placebo ; hazard ratio [ HR ] 0·90 , 95 % CI 0·74 - 1·09 , p=0·29 ) . Among the prespecified patient-reported outcomes ( 110 patients on gefitinib and 121 on placebo completed both baseline and 4 week question naires and were included in analyses ) , odynophagia was significantly better in the gefitinib group ( adjusted mean difference -8·61 , 95 % CI -14·49 to -2·73 ; n=227 ; p=0·004 ) , whereas the other outcomes were not significantly improved compared with placebo : global quality of life ( 2·69 , 95 % CI -2·33 to 7·72 , n=231 , p=0·293 ) , dysphagia ( -3·18 , 95 % CI -8·36 to 2·00 , n=231 , p=0·228 ) , and eating ( -4·11 , 95 % CI -9·96 to 1·75 , n=229 , p=0·168 ) . Median progression-free survival was marginally longer with gefitinib than it was with placebo ( 1·57 months , 95 % CI 1·23 - 1·90 in the gefitinib group vs 1·17 months , 95 % CI 1·07 - 1·37 in the placebo group ; HR 0·80 , 95 % CI 0·66 - 0·96 , p=0·020 ) . The most common toxicities were diarrhoea ( 36 [ 16 % ] of 224 patients on gefitinib vs six [ 3 % ] of 225 on placebo ) and skin toxicity ( 46 [ 21 % ] vs two [ 1 % ] ) , both mostly grade 2 . The commonest grade 3 - 4 toxicities were fatigue ( 24 [ 11 % ] vs 13 [ 6 % ] patients ) and diarrhoea ( 13 [ 6 % ] vs two [ 1 % ] ) . Serious adverse events were reported in 109 ( 49 % ) of 224 patients assigned to gefitinib and 101 ( 45 % ) of 225 on placebo . 54 ( 24 % ) of patients in the gefitinib group achieved disease control at 8 weeks , as did 35 ( 16 % ) of patients on placebo ( p=0·023 ) . INTERPRETATION The use of gefitinib as a second-line treatment in oesophageal cancer in unselected patients does not improve overall survival , but has palliative benefits in a subgroup of these difficult-to-treat patients with short life expectancy . Future research should focus on identification of predictive biomarkers to identify this subgroup of benefiting patients . FUNDING Cancer Research UK", "BACKGROUND Worldwide , many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the st and ard adjuvant treatment . We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer , started at any time after diagnosis . METHODS This study was a placebo-controlled , multicentre , r and omised phase 3 trial . Women out patients from 405 [ corrected ] centres in 33 countries [ corrected ] with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were r and omly assigned ( 1:1 ) to receive daily lapatinib ( 1500 mg ) or daily placebo for 12 months . R and omisation was done with a computer-generated sequence , stratified by time since diagnosis , lymph node involvement at diagnosis , and tumour hormone-receptor status . Investigators , site staff , and patients were masked to treatment assignment . The primary endpoint was disease-free survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00374322 . FINDINGS Between August , 2006 , and May , 2008 , 3161 women were enrolled and 3147 were assigned to lapatinib ( n=1571 ) or placebo ( n=1576 ) . After a median follow-up of 47·4 months ( range 0·4 - 60·0 ) in the lapatinib group and 48·3 ( 0·7 - 61·3 ) in the placebo group , 210 ( 13 % ) disease-free survival events had occurred in the lapatinib group versus 264 ( 17 % ) in the placebo group ( hazard ratio [ HR ] 0·83 , 95 % CI 0·70 - 1·00 ; p=0·053 ) . Central review of HER2 status showed that only 2490 ( 79 % ) of the r and omised women were HER2-positive . 157 ( 13 % ) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 ( 17 % ) of 1260 in the placebo group had a disease-free survival event ( HR 0·82 , 95 % 0·67 - 1·00 ; p=0·04 ) . Serious adverse events occurred in 99 ( 6 % ) of 1573 patients taking lapatinib and 77 ( 5 % ) of 1574 patients taking placebo , with higher incidences of grade 3 - 4 diarrhoea ( 97 [ 6 % ] vs nine [ < 1 % ] ) , rash ( 72 [ 5 % ] vs three [ < 1 % ] ) , and hepatobiliary disorders ( 36 [ 2 % ] vs one [ < 1 % ] ) . INTERPRETATION Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population . However , exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival . Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or can not receive adjuvant trastuzumab . FUNDING GlaxoSmithKline" ]

[ "24142687", "4887703", "22727976", "5393084", "17161256", "19018081", "26866364", "17262115", "16035077", "12767102", "10471456", "20872550", "23583763", "25410653" ]

[ "Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: A prospective randomized controlled study with six-month follow-up.", "Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol", "Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study.", "Preventive role of carvedilol in adriamycin-induced cardiomyopathy", "Protective effects of carvedilol against anthracycline-induced cardiomyopathy.", "American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants.", "Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial", "Left ventricular systolic function assessed by echocardiography in children and adolescents with osteosarcoma treated with doxorubicin alone or in combination with dexrazoxane.", "Cardioprotective effect of dexrazoxane during treatment with doxorubicin: a study using low-dose dobutamine stress echocardiography.", "Congestive heart failure in patients treated with doxorubicin", "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.", "Cardioprotective effect of metoprolol and enalapril in doxorubicin‐treated lymphoma patients: A prospective, parallel‐group, randomized, controlled study with 36‐month follow‐up", "Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of", "Protective effects of spironolactone against anthracycline-induced cardiomyopathy." ]

[ "BACKGROUND The use of antracycline ( ANT ) in breast cancer has been associated with adverse cardiac events . Two-dimensional ( 2D ) strain imaging ( SI ) can provide a more sensitive measure of altered left ventricular ( LV ) systolic function . We aim ed to evaluate the preventive effect of carvedilol administration assessed by SI in a patient with breast cancer treated with ANT . METHODS Patients receiving ANT were r and omly assigned to the carvedilol- or placebo-receiving group . Each received an echocardiographic examination with conventional 2D echocardiography , pulsed tissue Doppler , and 2D SI prior to and 6 months post ANT treatment . RESULTS During the 6-month follow-up period there were no patient deaths or interrupted chemotherapy treatments due to doxorubicin-induced cardiotoxicity . Both left ventricular ejection fraction ( LVEF ) and fractional shortening ( FS ) were within normal limits for all patients before and after ANT therapy . EF , FS and LV dimensions were measured using M-mode echocardiography and found to be similar in both groups before and after ANT therapy . The mean EF , FS , and LV echocardiograph baseline and control dimensions were similar in both groups after 6 months . Though baseline SI parameters were similar between the groups , there was a significant decrease in LV basal septal and basal lateral peak systolic strain in the control group compared to the carvedilol group . CONCLUSIONS These results indicate that carvedilol has a protective effect against the cardiotoxicity induced by ANT", "Abstract Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction . We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker c and esartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction ( LVEF ) associated with adjuvant , anthracycline-containing regimens with or without trastuzumab and radiation . Methods and results In a 2 × 2 factorial , r and omized , placebo-controlled , double-blind trial , we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker c and esartan cilexetil , the β-blocker metoprolol succinate , or matching placebos in parallel with adjuvant anticancer therapy . The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging . A priori , a change of 5 percentage points was considered clinical ly important . There was no interaction between c and esartan and metoprolol treatments ( P = 0.530 ) . The overall decline in LVEF was 2.6 ( 95 % CI 1.5 , 3.8 ) percentage points in the placebo group and 0.8 ( 95 % CI −0.4 , 1.9 ) in the c and esartan group in the intention-to-treat analysis ( P-value for between-group difference : 0.026 ) . No effect of metoprolol on the overall decline in LVEF was observed . Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation , concomitant treatment with c and esartan provides protection against early decline in global left ventricular function", "BACKGROUND We aim ed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients . METHODS In this small , prospect i ve , double-blind study , we r and omly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5 mg daily ( n=27 ) or placebo ( n=18 ) . Echocardiographic measurements and N-terminal pro-brain natriuretic peptide ( NT-pro-BNP ) levels were obtained at baseline and at 6-month of chemotherapy . RESULTS Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline . At 6-month , the left ventricular ( LV ) end-systolic and end-diastolic diameters increased in the placebo group ( LVESD : 29.7 ± 3.4 to 33.4 ± 4.5 mm ; LVEDD : 47.2 ± 3.8 to 52.0 ± 4.6 mm , p=0.01 for both ) but remained unchanged in the nebivolol group ( LVESD : 30.4 ± 3.5 to 31.0 ± 3.6 mm , p=0.20 ; LVEDD : 47.0 ± 4.4 to 47.1 ± 4.0 mm , p=0.93 ) . The placebo group also had lower LVEF than the nebivolol group ( 57.5 ± 5.6 % vs. 63.8 ± 3.9 % , p=0.01 ) at 6-month . NT-pro-BNP level remained static in the nebivolol group ( 147 ± 57 to 152 ± 69 pmol/l , p=0.77 ) while it increased in the placebo group ( 144 ± 66 to 204 ± 73 pmol/l , p=0.01 ) . CONCLUSIONS Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients", "Background & objectives : Adriamycin though considered as an effective anticancer drug , leads to irreversible cardiomyopathy ( CMP ) and congestive heart failure ( CHF ) . The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy ( CMP ) in cancer patients . Methods : Patients with lymphoreticular malignancy in whom ADR therapy was planned were r and omized into two groups : carvedilol and control . Twenty seven patients each were enrolled in carvedilol and control groups . In the carvedilol group , 12.5 mg once daily oral carvedilol was given during six months . The patients were evaluated by echocardiography before and after chemotherapy . Left ventricular ejection fraction ( EF ) and systolic and diastolic diameters were calculated . Results : At six months of follow up , six patients in the carvedilol group and five in the control group had died . The mean EF ( 63.19 vs. 63.88 % ) and fraction shortening ( FS ) ( 34 vs. 34.6 ) of the carvedilol group were similar at follow up , but in the control group , the mean EF ( 67.27 vs. 60.82 % , P=0.003 ) and FS ( 38.48 vs. 34.6 , P<0.05 ) at control echocardiography were significantly lower . In carvedilol group , both systolic and diastolic diameters were not changed , but in control group , systolic diameters were significantly increased compared with basal measures ( left ventricular end systolic diameter = 28.26±5.50 mm vs. 31.25± 6.50 mm ; P < 0.05 ) . Interpretation & conclusions : Prophylactic use of carvedilol in patients receiving anthracycline protected systolic functions of the left ventricle . Carvedilol can be a potential drug which can ameliorate ADR-induced CMP", "OBJECTIVES The aim of this study was to determine the protective effect of carvedilol in anthracycline (ANT)-induced cardiomyopathy ( CMP ) . BACKGROUND Despite its broad effectiveness , ANT therapy is associated with ANT-induced CMP . Recent animal studies and experimental observations showed that carvedilol prevented development of CMP due to chemotherapeutics . However , there is no placebo-controlled clinical trial concerning prophylactic carvedilol use in preventing ANT-induced CMP . METHODS Patients in whom ANT therapy was planned were r and omized to administration of carvedilol or placebo . We enrolled 25 patients in carvedilol and control groups . In the carvedilol group , 12.5 mg once-daily oral carvedilol was given during 6 months . The patients were evaluated with echocardiography before and after chemotherapy . Left ventricular ejection fraction ( EF ) and systolic and diastolic diameters were calculated . RESULTS At the end of 6 months of follow-up , 1 patient in the carvedilol group and 4 in the control group had died . Control EF was below 50 % in 1 patient in the carvedilol group and in 5 in the control group . The mean EF of the carvedilol group was similar at baseline and control echocardiography ( 70.5 vs. 69.7 , respectively ; p = 0.3 ) , but in the control group the mean EF at control echocardiography was significantly lower ( 68.9 vs. 52.3 ; p < 0.001 ) . Both systolic and diastolic diameters were significantly increased compared with basal measures in the control group . In Doppler study , whereas E velocities in the carvedilol group decreased , E velocities and E/A ratios were significantly reduced in the control group . CONCLUSIONS Prophylactic use of carvedilol in patients receiving ANT may protect both systolic and diastolic functions of the left ventricle", "PURPOSE To up date a clinical practice guideline on the use of chemotherapy and radiation therapy protectants for patients with cancer . METHODS An up date committee review ed literature published since the last guideline up date in 2002 . RESULTS Thirty-nine reports met the inclusion criteria : palifermin and dexrazoxane , three reports ( two studies ) each ; amifostine , 33 reports ( 31 studies ) ; and mesna , no published r and omized trials identified since 2002 . RECOMMENDATIONS Dexrazoxane is not recommended for routine use in breast cancer ( BC ) in adjuvant setting , or metastatic setting with initial doxorubicin-based chemotherapy . Consider use with metastatic BC and other malignancies , for patients who have received more than 300 mg/m(2 ) doxorubicin who may benefit from continued doxorubicin-containing therapy . Cardiac monitoring should continue in patients receiving doxorubicin . Amifostine may be considered for prevention of cisplatin-associated nephrotoxicity , reduction of grade 3 to 4 neutropenia ( alternative strategies are reasonable ) , and to decrease acute and late xerostomia with fractionated radiation therapy alone for head and neck cancer . It is not recommended for protection against thrombocytopenia , prevention of platinum-associated neurotoxicity or ototoxicity or paclitaxel-associated neuropathy , prevention of radiation therapy-associated mucositis in head and neck cancer , or prevention of esophagitis during concurrent chemoradiotherapy for non-small-cell lung cancer . Palifermin is recommended to decrease severe mucositis in autologous stem-cell transplantation ( SCT ) for hematologic malignancies with total-body irradiation ( TBI ) conditioning regimens , and considered for patients undergoing myeloablative allogeneic SCT with TBI-based conditioning regimens . Data are insufficient to recommend use in the non-SCT setting", "Objective : The aim of this study is to evaluate the preventive effects of carvedilol on doxorubicin-induced cardiotoxicity . Methods : In this trial , 70 female patients with breast cancer who were c and i date s to receive doxorubicin were enrolled , from which 30 were selected r and omly to receive carvedilol 6.25 mg daily during chemotherapy , with the rest receiving placebo as the control group . Both groups were evaluated 1 week before and 1 week after chemotherapy by measuring the left ventricular ejection fraction and strain/strain rate . Results : Data analysis showed that the case group presented no significant reduction in strain and strain-rate parameters after intervention , while there was a significant reduction in these parameters in the control group ( all p values < 0.001 ) . Also , the mean differences of strain parameters in the case group were significantly less than in the control group in all evaluated heart walls ( basal septal strain , p = 0.005 , basal lateral strain , p = 0.001 , basal inferior strain , p < 0.001 , and basal anterior strain , p < 0.001 ) ; the same was true for the strain-rate parameters ( the p values for basal septal , basal lateral , basal inferior and basal anterior strain rate were 0.037 , 0.037 , 0.002 and < 0.001 , respectively ) . Conclusion : This study shows that carvedilol can prevent doxorubicin-induced cardiotoxicity . Whether this prophylaxis should be considered as the preferred method needs further investigation", "OBJECTIVE To evaluate left ventricular ( LV ) systolic function by means of echocardiography in patients with osteosarcoma treated with doxorubicin alone or in combination with dexrazoxane . METHODS The study analyzed 55 patients with osteosarcoma , with or without metastasis , undergoing a six-cycle chemotherapy regimen of doxorubicin , who were divided into two groups according to dexrazoxane use . Group I : Thirty-seven patients who did not receive dexrazoxane ( 28 males , average age 15.4 years ) . Group II : Eighteen patients who did receive dexrazoxane ( 15 males , average age 15.1 years ) . Four echocardiographic evaluations were performed : 1 ) before the beginning of the chemotherapy ( initial evaluation ) ; 2 ) up to two weeks after the third cycle ; 3 ) up to two weeks after the fifth cycle ; and 4 ) up to four weeks after the sixth cycle of chemotherapy ( final evaluation ) . The left ventricular systolic function was assessed by the fractional percentage of systolic shortening ( FS% ) on echocardiography . Alterations in the contractile function or cardiac toxicity were defined as FS% values equal to or lower than 29 % , and /or by a drop in FS% by an absolute value equal to or greater than 10 units of the baseline value of each patient . RESULTS No significant difference as to age , gender , and race was observed between the groups . The cumulative dose of doxorubicin was significantly higher in group II throughout all phases of the treatment : 174 x 203 mg/m(2 ) ; 292 x 338 mg/m(2 ) and 345 x 405 mg/(2 ) ( p < 0.0001 ) . According to previously established criteria , the incidence of LV systolic dysfunction was not significantly different ( p=0.248 ) between patients in group I ( 18.92 % ) and patients in group II ( 11.1 % ) . The variance analysis with repeated measurements did not show significant differences in the means of fractional percentage of systolic percentage ( FS% ) throughout the study ( p=0.967 ) . However , a significant difference ( p=0.029 ) was observed between the FS% means in groups I and II at evaluations 2 ( 35.67 x 37.21 % ) , 3 ( 34.95 x 38.47 % ) and 4 ( 35.26 x 38.22 % ) . CONCLUSION Data in this study show that in patients with osteosarcoma treated with doxorubicin alone or combined with dexrazoxane , the LV systolic function , as assessed by the fractional percentage of systolic shortening mean , showed a better performance in the group that received dexrazoxane . On the other h and , the occurrence of systolic dysfunction was similar in both groups", "AIM To assess the late cardioprotective effect of dexrazoxane associated with doxorubicin during treatment of osteosarcoma by means of low-dose dobutamine stress echocardiography ( LDDSE ) in non-relapsed asymptomatic children and teenagers . PATIENTS AND METHODS The study population included 58 patients with osteosarcoma divided in three groups , with equivalent age range , gender proportion and body surface area . Group I ( 21 patients , 14 males , 15 + /- 4 years ) was analyzed before chemotherapy and considered the control group ; Group II ( 19 patients , 11 males , 19.7 + /- 4 years ) was treated with 348.4 + /- 18 mg/m2 of doxorubicin only and Group III ( 18 patients , 14 male , 16.8 + /- 5 years ) treated with 396.5 + /- 55 mg/m2 of doxorubicin with dexrazoxane in the ratio 10:1 . The patients were su bmi tted to LDDSE ( maximal dose 5 microg/kg/min ) . No major side effects were observed . Heart rate , blood pressure , left ventricular diameters , end systolic wall stress ( ESWS ) , and other diastolic and systolic function indexes were assessed at rest conditions and during LDDSE and compared between the three groups . RESULTS Group III received a doxorubicin dose significantly greater than Group II ( P = 0.001 ) . During LDDSE there were no significant changes in the diastolic function indexes in any of the groups , but there was a significant increase of systolic indexes and a decrease of ESWS in Group III compared to group II . There was no significant difference of any systolic functional parameters between Group I and III . Considering the ejection fraction ( EF ) at rest or at LDDSE , 13 patients ( 69.4 % ) in Group II and 5 patients ( 27.7 % ) in Group III were considered to have systolic dysfunction . ( P = 0.02 ) . CONCLUSION Myocardial response to LDDSE in patients treated with doxorubicin and dexrazoxane was similar to patients without chemotherapy and better than those treated with doxorubicin only , suggesting less cardiotoxicity", "Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug . A large‐scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7 % of patients developed doxorubicin‐related congestive heart failure ( CHF ) after a cumulative dose of 550 mg/m2 . To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting , the authors evaluated data from three prospect i ve studies to determine both the incidence of doxorubicin‐related CHF and the accumulated dose of doxorubicin at which CHF occurs", "BACKGROUND AND METHODS Aldosterone is important in the pathophysiology of heart failure . In a doubleblind study , we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor , a loop diuretic , and in most cases digoxin . A total of 822 patients were r and omly assigned to receive 25 mg of spironolactone daily , and 841 to receive placebo . The primary end point was death from all causes . RESULTS The trial was discontinued early , after a mean follow-up period of 24 months , because an interim analysis determined that spironolactone was efficacious . There were 386 deaths in the placebo group ( 46 percent ) and 284 in the spironolactone group ( 35 percent ; relative risk of death , 0.70 ; 95 percent confidence interval , 0.60 to 0.82 ; P<0.001 ) . This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes . The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group ( relative risk of hospitalization , 0.65 ; 95 percent confidence interval , 0.54 to 0.77 ; P<0.001 ) . In addition , patients who received spironolactone had a significant improvement in the symptoms of heart failure , as assessed on the basis of the New York Heart Association functional class ( P<0.001 ) . Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone , as compared with 1 percent of men in the placebo group ( P<0.001 ) . The incidence of serious hyperkalemia was minimal in both groups of patients . CONCLUSIONS Blockade of aldosterone receptors by spironolactone , in addition to st and ard therapy , substantially reduces the risk of both morbidity and death among patients with severe heart failure", "Anthracyclines have contributed to a marked increase in survival in different types of cancer [ 1,2 ] . Unfortunately , they are associated with dose-dependent cardiotoxicity and heart failure ( HF ) [ 3–8 ] . Change to a weekly dosage schedule with slow infusions has been tested , a strategy that requires more frequent hospital visits and increased storage re sources [ 7,9 ] . Liposomal anthracycline formulations with reduced drug exposure and lower plasma concentrations may still be cardiotoxic at higher cumulative doses [ 10 ] . Beta-blockers and angiotensin converting enzyme(ACE ) inhibitors have been shown to reduce anthracycline-induced cardiotoxicity , but have not been tested in long-term prospect i ve , r and omized , controlled studies with well defined cardiotoxicity criteria and careful cardiac function monitoring [ 11–16 ] . We investigated doxorubicin-induced clinical or sub clinical cardiotoxicity in lymphoma patients after concomitant prophylactic therapy with metoprolol or enalapril or no concomitant treatment . We examined whether cardiotoxicity was related to the treatment or any other variable . We found that HF was less frequent under concomitant treatment than no treatment , especially in the metoprolol group , but the differences were not significant . No association was found between the presence of cardiotoxicity and concomitant treatment or other variable apart of age that had a significant impact . The marginal benefit seen with metoprolol should be investigated further", "OBJECTIVES This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction ( LVSD ) in patients with hematological malignancies . BACKGROUND Current chemotherapy may induce LVSD . Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy . METHODS In this r and omized , controlled study , 90 patients with recently diagnosed acute leukemia ( n = 36 ) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation ( HSCT ) ( n = 54 ) and without LVSD were r and omly assigned to a group receiving enalapril and carvedilol ( n = 45 ) or to a control group ( n = 45 ) . Echocardiographic and cardiac magnetic resonance ( CMR ) imaging studies were performed before and at 6 months after r and omization . The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction ( LVEF ) . RESULTS The mean age of patients was 50 ± 13 years old , and 43 % were women . At 6 months , LVEF did not change in the intervention group but significantly decreased in controls , result ing in a -3.1 % absolute difference by echocardiography ( p = 0.035 ) and -3.4 % ( p = 0.09 ) in the 59 patients who underwent CMR . The corresponding absolute difference ( 95 % confidence interval [ CI ] ) in LVEF was -6.38 % ( 95 % CI : -11.9 to -0.9 ) in patients with acute leukemia and -1.0 % ( 95 % CI : -4.5 to 2.5 ) in patients undergoing autologous HSCT ( p = 0.08 for interaction between treatment effect and disease category ) . Compared to controls , patients in the intervention group had a lower incidence of the combined event of death or heart failure ( 6.7 % vs. 22 % , p = 0.036 ) and of death , heart failure , or a final LVEF < 45 % ( 6.7 % vs. 24.4 % , p = 0.02 ) . CONCLUSIONS Combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy . The clinical relevance of this strategy should be confirmed in larger studies . ( Prevention of Left Ventricular Dysfunction During Chemotherapy [ OVERCOME ] ; NCT01110824 )", "AIMS The protective effect of beta-blockers , ACE inhibitors , and ARBs on anthracycline cardiotoxicity has already been demonstrated , but the effect of aldosterone antagonism , which inhibits the last step of the renin-angiotensin-aldosterone system ( RAAS ) , was question ed . This study sought to investigate whether spironolactone protects the heart against anthracycline-induced cardiotoxicity . METHODS AND RESULTS Eighty-three female patients who were diagnosed with breast cancer were included in the study . The study population was r and omized into spironolactone and control groups . A dose of 25 mg/day spironolactone was administered to the patients in the spironolactone group . There were 43 patients ( mean age 50 ± 11 years ) in the spironolactone group and 40 patients ( mean age 51 ± 10 years ) in the control group . LVEF decreased from 67.0 ± 6.1 to 65.7 ± 7.4 ( P = 0.094 ) in the spironolactone group , and from 67.7 ± 6.3 to 53.6 ± 6.8 in the control group ( P < 0.001 ) . When the general linear model was applied , the interaction of LVEF decrease between groups was significantly lower in the spironolactone group than in the control group ( P < 0.001 ) . The diastolic functional grade of subjects in the spironolactone group was protected ( P = 0.096 ) , whereas it deteriorated in the control group ( P < 0.001 ) . CONCLUSION We showed that spironolactone administration used simultaneously with anthracycline group chemotherapeutics protects both myocardial systolic and diastolic functions . Spironolactone can be used to protect against anthracycline-induced cardiotoxicity . TRIAL REGISTRATION NCT02053974" ]

[ "19293786", "5576224", "27507905", "27214731", "20658527", "4371630", "8942775", "5473580", "11772964", "4599169", "22493463", "23921906", "22052062", "17570205", "8238690", "26067224", "8942774", "5479998", "26811150" ]

[ "Using a Multifaceted Approach to Improve the Follow-Up of Positive Fecal Occult Blood Test Results", "Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex?", "A randomised comparison of two faecal immunochemical tests in population-based colorectal cancer screening", "Population-Based Colonoscopy Screening for Colorectal Cancer: A Randomized Clinical Trial.", "A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate. A prospective, controlled, feasibility study", "Mailed participant reminders are associated with improved colonoscopy uptake after a positive FOBT result in Ontario’s ColonCancerCheck program", "Randomised controlled trial of faecal-occult-blood screening for colorectal cancer", "Association between socioeconomic deprivation and colorectal cancer screening outcomes: Low uptake rates among the most and least deprived people", "Protective effect of faecal occult blood test screening for colorectal cancer: worse prognosis for screening refusers.", "Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland", "Adherence to colorectal cancer screening: a randomized clinical trial of competing strategies.", "Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial.", "Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up", "Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening.", "Screening for colorectal neoplasia: physicians' adherence to complete diagnostic evaluation.", "Colorectal cancer screening in a low-incidence area: general invitation versus family risk targeting a comparative study from Montenegro", "Randomised study of screening for colorectal cancer with faecal-occult-blood test", "Clinical impact of the immunochemical fecal occult blood test for colorectal cancer screening in Brazil", "Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening" ]

[ "OBJECTIVES : Inadequate follow-up of abnormal fecal occult blood test ( FOBT ) results occurs in several types of practice setting s. Our institution implemented multifaceted quality improvement ( QI ) activities in 2004–2005 to improve follow-up of FOBT-positive results . Activities addressed precolonoscopy referral processes and system-level factors such as electronic communication , provider education , and feedback . We evaluated their effects on timeliness and appropriateness of positive-FOBT follow-up and identified factors that affect colonoscopy performance . METHODS : Retrospective electronic medical record review was used to determine outcomes before and after QI activities in a multispecialty ambulatory clinic of a tertiary care Veterans Affairs facility and its affiliated satellite clinics . From 1869 FOBT-positive cases , 800 were r and omly selected from time periods before and after QI activities . Two review ers used a pretested st and ardized data collection form to determine whether colonoscopy was appropriate or indicated based on predetermined criteria and if so , the timeliness of colonoscopy referral and performance before and after QI activities . RESULTS : In cases where a colonoscopy was indicated , the proportion of patients who received a timely colonoscopy referral and performance were significantly higher post-implementation ( 60.5 % vs. 31.7 % , P<0.0001 and 11.4 % vs. 3.4 % , P=0.0005 ) . A significant decrease also result ed in median times to referral and performance ( 6 vs. 19 days , P<0.0001 and 96.5 vs. 190 days , P<0.0001 ) and in the proportion of positive-FOBT test results that had received no follow-up by the time of chart review ( 24.3 % vs. 35.9 % , P=0.0045 ) . Significant predictors of absence of the performance of an indicated colonoscopy included performance of a non-colonoscopy procedure such as barium enema or flexible sigmoidoscopy ( OR=16.9 ; 95 % CI , 1.9–145.1 ) , patient non-adherence ( OR=33.9 ; 95 % CI , 17.3–66.6 ) , not providing an appropriate provisional diagnosis on the consultation ( OR=17.9 ; 95 % CI , 11.3–28.1 ) , and gastroenterology service not rescheduling colonoscopies after an initial cancellation ( OR=11.0 ; 95 % CI , 5.1–23.7 ) . CONCLUSIONS : Multifaceted QI activities improved rates of timely colonoscopy referral and performance in an electronic medical record system . However , colonoscopy was not indicated in over one third of patients with positive FOBTs , raising concerns about current screening practice s and the appropriate denominator used for performance measurement st and ards related to colon cancer screening", "Background The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test ( FIT ) . Although , colorectal cancer ( CRC ) screening with biannual ( FIT ) has shown to reduce CRC mortality , the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy , and thus , harms related to false results might not be underestimated . Current CRC screening programmes use a single faecal haemoglobin concentration ( f-Hb ) cut-off for colonoscopy referral for both sexes and all ages . We aim ed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion . Methods Prospect i ve cohort study using a single- sample faecal immunochemical test ( FIT ) on 444,582 invited average-risk subjects aged 50–69 years . A result was considered positive at ≥20 μg Hb/g faeces . Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs . Results We analysed 17,387 positive participants in the programme who underwent colonoscopy . Participation rate was 66.5 % . Men had a positivity rate for f-Hb of 8.3 % and women 4.8 % ( p < 0.0001 ) . The detection rate for advanced neoplasia ( cancer plus advanced adenoma ) was 44.0‰ for men and 15.9‰ for women ( p < 0.0001 ) . The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off . However , the loss in CRC detection increased by up to 28.1 % in men and 22.9 % in women . CRC missed were generally at early stages ( Stage I-II : from 70.2 % in men to 66.3 % in women ) . Conclusions This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs . We found differences in positivity rates , neoplasia detection rate , number needed to screen , and interval cancers in men and women and in younger and older groups . However , there are factors other than sex and age to consider when consideration is given to setting the f-Hb cut-off", "Objective Colorectal cancer screening programmes are implemented worldwide ; many are based on faecal immunochemical testing ( FIT ) . The aim of this study was to evaluate two frequently used FITs on participation , usability , positivity rate and diagnostic yield in population -based FIT screening . Design Comparison of two FITs was performed in a fourth round population -based FIT-screening cohort . R and omly selected individuals aged 50–74 were invited for FIT screening and were r and omly allocated to receive an OC -Sensor ( Eiken , Japan ) or faecal occult blood (FOB)-Gold ( Sentinel , Italy ) test ( March – December 2014 ) . A cut-off of 10 µg haemoglobin (Hb)/g faeces ( ie , 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold ) was used for both FITs . Results In total , 19 291 eligible invitees were included ( median age 61 , IQR 57–67 ; 48 % males ) : 9669 invitees received OC-Sensor and 9622 FOB-Gold ; both tests were returned by 63 % of invitees ( p=0.96 ) . Tests were non-analysable in 0.7 % of participants using OC-Sensor vs 2.0 % using FOB-Gold ( p<0.001 ) . Positivity rate was 7.9 % for OC-Sensor , and 6.5 % for FOB-Gold ( p=0.002 ) . There was no significant difference in diagnostic yield of advanced neoplasia ( 1.4 % for OC-Sensor vs 1.2 % for FOB-Gold ; p=0.15 ) or positive predictive value ( PPV ; 31 % vs 32 % ; p=0.80 ) . When comparing both tests at the same positivity rate instead of cut-off , they yielded similar PPV and detection rates . Conclusions The OC-Sensor and FOB-Gold were equally acceptable to a screening population . However , FOB-Gold was prone to more non-analysable tests . Comparison between FIT br and s is usually done at the same Hb stool concentration . Our findings imply that for a fair comparison on diagnostic yield between FIT 's positivity rate rather than Hb concentration should be used . Trial registration number NTR5385 ; Results", "IMPORTANCE Although some countries have implemented widespread colonoscopy screening , most European countries have not introduced it because of uncertainty regarding participation rates , procedure-related pain and discomfort , endoscopist performance , and effectiveness . To our knowledge , no r and omized trials on colonoscopy screening currently exist . OBJECTIVE To investigate participation rate , adenoma yield , performance , and adverse events of population -based colonoscopy screening in several European countries . DESIGN , SETTING , AND POPULATION A population -based r and omized clinical trial was conducted among 94 959 men and women aged 55 to 64 years of average risk for colon cancer in Pol and , Norway , the Netherl and s , and Sweden from June 8 , 2009 , to June 23 , 2014 . INTERVENTIONS Colonoscopy screening or no screening . MAIN OUTCOMES AND MEASURES Participation in colonoscopy screening , cancer and adenoma yield , and participant experience . Study outcomes were compared by country and endoscopist . RESULTS Of 31 420 eligible participants r and omized to the colonoscopy group , 12 574 ( 40.0 % ) underwent screening . Participation rates were 60.7 % in Norway ( 5354 of 8816 ) , 39.8 % in Sweden ( 486 of 1222 ) , 33.0 % in Pol and ( 6004 of 18 188 ) , and 22.9 % in the Netherl and s ( 730 of 3194 ) ( P < .001 ) . The cecum intubation rate was 97.2 % ( 12 217 of 12 574 ) , with 9726 participants ( 77.4 % ) not receiving sedation . Of the 12 574 participants undergoing colonoscopy screening , we observed 1 perforation ( 0.01 % ) , 2 postpolypectomy serosal burns ( 0.02 % ) , and 18 cases of bleeding owing to polypectomy ( 0.14 % ) . Sixty-two individuals ( 0.5 % ) were diagnosed with colorectal cancer and 3861 ( 30.7 % ) had adenomas , of which 1304 ( 10.4 % ) were high-risk adenomas . Detection rates were similar in the proximal and distal colon . Performance differed significantly between endoscopists ; recommended benchmarks for cecal intubation ( 95 % ) and adenoma detection ( 25 % ) were not met by 6 ( 17.1 % ) and 10 of 35 endoscopists ( 28.6 % ) , respectively . Moderate or severe abdominal pain after colonoscopy was reported by 601 of 3611 participants ( 16.7 % ) examined with st and ard air insufflation vs 214 of 5144 participants ( 4.2 % ) examined with carbon dioxide ( CO2 ) insufflation ( P < .001 ) . CONCLUSIONS AND RELEVANCE Colonoscopy screening entails high detection rates in the proximal and distal colon . Participation rates and endoscopist performance vary significantly . Postprocedure abdominal pain is common with st and ard air insufflation and can be significantly reduced by using CO2 . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00883792", "Immunochemical fecal occult blood test ( FIT ) is a new colorectal cancer ( CRC ) screening method already recommended by the American screening guidelines . We aim ed to test the feasibility of FIT as compared to guaiac fecal occult blood test ( G‐FOBT ) in a large urban population of Tel Aviv . Average‐risk persons , aged 50–75 years , were offered FIT or G‐FOBT after r and omization according to the socioeconomic status of their clinics . Participants with positive tests underwent colonoscopy . Participants were followed through the Cancer Registry 2 years after the study . Hemoccult SENSA ™ and OC‐MICRO ™ ( three sample s , 70 ng/ml threshold ) were used . FIT was offered to 4,657 persons ( Group A ) and G‐FOBT to 7,880 persons ( Group B ) . Participation rate was 25.9 % and 28.8 % in Group A and B , respectively ( p < 0.001 ) . Positivity rate in Group A and B was 12.7 % and 3.9 % , respectively ( p < 0.001 ) . Cancer found in six ( 0.49 % ) and eight ( 0.35 % ) patients of Group A and B , respectively ( NS ) . Cancer registry follow‐up found missed cancer in five ( 0.22 % ) cases of Group B and none in Group A ( NS ) . The sensitivity , specificity , negative and positive predictive value for cancer in Group A and B were 100 % , 85.9 % , 100 % , 3.9 % and 61.5 % , 96.4 % , 99.8 % , 9.1 % , respectively . There was increased detection of advanced adenomatous polyp ( AAP ) by FIT , irrespective of age , gender , and socioeconomic status ( Per Protocol : odds ratio 2.69 , 95 % confidence interval 1.6–4.5 ; Intention to Screen : odds ratio 3.16 , 95 % confidence interval 1.8–5.4 ) . FIT is feasible in urban , average‐risk population , which significantly improved performance for detection of AAP and CRC , despite reduced participation", "Background Timely follow-up of fecal occult blood screening with colonoscopy is essential for achieving colorectal cancer mortality reduction . This study evaluates the effectiveness of two ongoing interventions design ed to improve colonoscopy uptake after a positive fecal occult blood test ( FOBT ) result within Ontario ’s population -wide ColonCancerCheck program . The first was a revision of mailed FOBT lab results to physicians to explicitly define a positive FOBT and to recommend colonoscopy . The second was a letter to participants informing them of the positive FOBT and urging them to seek appropriate follow-up . Methods Prospect i ve cohort study using Ontario ’s ColonCancerCheck program data sets ( 2008–2011 ) , linked to provincial administrative health data bases . Crude rate ratios were calculated to assess determinants of colonoscopy uptake among an Ontario-wide FOBT-positive cohort with rolling enrolment , followed from October 2008 through February 2011 . Segmented time-series regression was used to assess the average additional change in colonoscopy uptake after FOBT-positive status following the introduction of two ongoing interventions among the same cohort . Results A notification mailed directly to FOBT-positive screening participants was observed to increase colonoscopy uptake , beyond the modest average underlying increase throughout the study period , by an average of 3 % per month ( multivariable-adjusted RR : 1.03 , 95 % CI : 1.00–1.06 ) . However , revision of the existing FOBT result notification to physicians was observed to have no effect . Conclusions Direct participant notification of a positive FOBT result improved adherence with follow-up colonoscopy in Ontario ’s population -wide ColonCancerCheck program . Further participant-directed interventions may be effective means of maximizing adherence in population -wide screening", "BACKGROUND There is growing evidence that faecal-occult-blood ( FOB ) screening may reduce colorectal cancer ( CRC ) mortality , but this reduction in CRC mortality has not been shown in an unselected population -based r and omised controlled trial . The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting . METHODS Between February , 1981 , and January , 1991 , 152,850 people aged 45 - 74 years who lived in the Nottingham area of the UK were recruited to our study . Participants were r and omly allocated FOB screening ( 76,466 ) or no screening ( controls ; 76,384 ) . Controls were not told about the study and received no intervention . Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor . FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results . Individuals with negative FOB tests at the first screening , together with those who tested positive but in whom no neoplasia was found on colonoscopy , were invited to take part in further screening every 2 years . Screening was stopped in February , 1995 , by which time screening-group participants had been offered FOB tests between three and six times . Screening-group participants who had a positive test were offered full colonoscopy . All participants were followed up until June , 1995 . The primary outcome measure was CRC mortality . FINDINGS Of the 152,850 individuals recruited to the study , 2599 could not be traced or had emigrated and were excluded from the analysis . Thus , there were 75,253 participants in the screening group and 74,998 controls . 44,838 ( 59.6 % ) screening-group participants completed at least one screening . 28,720 ( 38.2 % ) of these individuals completed all the FOB tests they were offered and 16,118 ( 21.4 % ) completed at least one screening but not all the tests they were offered . 30,415 ( 40.4 % ) did not complete any test . Of 893 cancers ( 20 % stage A ) diagnosed in screening-group participants ( CRC incidence of 1.49 per 1000 person-years ) , 236 ( 26.4 % ) were detected by FOB screening , 249 ( 27.9 % ) presented after a negative FOB test or investigation , and 400 ( 44.8 % ) presented in non-responders . The incidence of cancer in the control group ( 856 cases , 11 % stage A ) was 1.44 per 1000 person-years . Median follow-up was 7.8 years ( range 4.5 - 14.5 ) . 360 people died from CRC in the screening group compared with 420 in the control group-a 15 % reduction in cumulative CRC mortality in the screening group ( odds ratio=0.85 [ 95 % ; CI 0.74 - 0.98 ] , p = 0.026 ) . INTERPRETATION Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population", "Background Screening with faecal occult blood tests reduces colorectal cancer-related mortality ; however , age , sex and socioeconomic factors affect screening outcomes and could lead to unequal mortality benefits . The aim of this study was to describe the main outcomes of the population -based Barcelona colorectal cancer screening programme ( BCRCSP ) by deprivation . Methods Retrospective study of the eligible population of the first round of the BCRCSP . Participants ’ postal addresses were linked with the MEDEA data base to obtain the deprivation quintiles ( Dq ) . Chi-squared tests were used to compare proportions across variables and logistic regression was used to estimate the adjusted effects of age , sex and deprivation on uptake , FIT positivity , colonoscopy adherence and advanced neoplasia detection rate . Results Overall uptake was 44.7 % , higher in Dq2 , 3 and 4 ( OR 1.251 , 1.250 and 1.276 , respectively ) than in the least deprived quintile ( Dq 1 ) , and lowest in Dq5 ( OR 0.84 ) . Faecal immunochemical test ( FIT ) positivity and the percentage of people with detectable faecal haemoglobin below the positivity threshold increased with deprivation . The advanced neoplasia detection rate was highest in Dq4 . Conclusion Unlike most regions where inequalities are grade d along the socioeconomic continuum , inequalities in the uptake of colorectal cancer screening in Spain seem to be concentrated first in the most disadvantaged group and second in the least deprived group . The correlation of deprivation with FIT-positivity and faecal haemoglobin below the positivity threshold is worrying due to its association with colorectal cancer and overall mortality", "BACKGROUND AND AIMS Screening for colorectal cancer ( CRC ) by faecal occult blood testing ( FOBT ) decreases CRC mortality by 15 - 33 % . Compliance remains an obstacle to maximising the benefit of FOBT screening . We tested the hypothesis that individuals offered FOBT screening but refused would have an increased incidence and worse prognosis for CRC compared with those tested and with controls . METHODS Annual screening was offered to 3548 average risk individuals , > or = 40 years of age , from a highly stable population . A total of 2538 agreed to testing ( group 1 ) and 1010 ( 28 % ) refused ( group 2 ) . Another 1376 individuals were never offered the test and served as controls ( group 3 ) . The groups were followed for 11 years : a three year screening period ( 1985 - 1987 ) and an eight year follow up period at the end of the screening programme ( 1988 - 1995 ) . Incidence , stage , and mortality were compared . Characterisation of refusers was completed in 188 and 130 subjects of groups 1 and 2 , respectively . RESULTS In the screening phase , mortality from CRC was significantly lower in group 1 than in groups 2 and 3 . The cumulative incidence of CRC in the eight year follow up period was 21 ( 0.88 % ) , 23 ( 2.28 % ) , and 13 ( 0.94 % ) in groups 1 , 2 , and 3 , respectively . This shows a reduction of 61.4 % in group 1 compared with group 2 ( relative risk 0.28 ( 95 % confidence interval ( CI ) 0.19 - 0.32 ) ) ( p<0.001 ) and 6.4 % compared with group 3 ( relative risk 0.93 ( 95 % CI 0.93 - 1.00 ) ) ( NS ) . During follow up , group 1 subjects also demonstrated a decrease in advanced Dukes ' stage and mortality rate by 80 % and 64 % , and 79 % and 62 % , compared with groups 2 and 3 , respectively . Refusers were more likely to be male , of Asian-African descent , and more likely to smoke , consume more coffee , and less tea or dairy foods . CONCLUSIONS When accepted , FOBT may protect against CRC for prolonged periods . Individuals who refuse FOBT have a significantly higher CRC incidence and mortality rates than those who accept testing", "Background Screening for colorectal cancer ( CRC ) with guaiac-based faecal occult-blood test ( FOBT ) has been reported to reduce CRC mortality in r and omised trials in the 1990s , but not in routine screening , so far . In Finl and , a large r and omised study on biennial FOB screening for CRC was gradually nested as part of the routine health services from 2004 . We evaluate the effectiveness of screening as a public health policy in the largest population so far reported . Methods We r and omly allocated ( 1:1 ) men and women aged 60–69 years to those invited for screening and those not invited ( controls ) , between 2004 and 2012 . This result ed in 180 210 subjects in the screening arm and 180 282 in the control arm . In 2012 , the programme covered 43 % of the target age population in Finl and . Results The median follow-up time was 4.5 years ( maximum 8.3 years ) , with a total of 1.6 million person-years . The CRC incidence rate ratio between the screening and control arm was 1.11 ( 95 % CI 1.01 to 1.23 ) . The mortality rate ratio from CRC between the screening and control arm was 1.04 ( 0.84 to 1.28 ) , respectively . The CRC mortality risk ratio was 0.88 ( 0.66 to 1.16 ) and 1.33 ( 0.94 to 1.87 ) in males and females , respectively . Conclusions We did not find any effect in a r and omised health services study of FOBT screening on CRC mortality . The substantial effect difference between males and females is inconsistent with the evidence from r and omised clinical trials and with the recommendations of several international organisations . Even if our findings are still inconclusive , they highlight the importance of r and omised evaluation when new health policies are implemented . Trial registration 002_2010_august", "BACKGROUND Despite evidence that several colorectal cancer ( CRC ) screening strategies can reduce CRC mortality , screening rates remain low . This study aim ed to determine whether the approach by which screening is recommended influences adherence . METHODS We used a cluster r and omization design with clinic time block as the unit of r and omization . Persons at average risk for development of CRC in a racially/ethnically diverse urban setting were r and omized to receive recommendation for screening by fecal occult blood testing ( FOBT ) , colonoscopy , or their choice of FOBT or colonoscopy . The primary outcome was completion of CRC screening within 12 months after enrollment , defined as performance of colonoscopy , or 3 FOBT cards plus colonoscopy for any positive FOBT result . Secondary analyses evaluated sociodemographic factors associated with completion of screening . RESULTS A total of 997 participants were enrolled ; 58 % completed the CRC screening strategy they were assigned or chose . However , participants who were recommended colonoscopy completed screening at a significantly lower rate ( 38 % ) than participants who were recommended FOBT ( 67 % ) ( P < .001 ) or given a choice between FOBT or colonoscopy ( 69 % ) ( P < .001 ) . Latinos and Asians ( primarily Chinese ) completed screening more often than African Americans . Moreover , nonwhite participants adhered more often to FOBT , while white participants adhered more often to colonoscopy . CONCLUSIONS The common practice of universally recommending colonoscopy may reduce adherence to CRC screening , especially among racial/ethnic minorities . Significant variation in overall and strategy -specific adherence exists between racial/ethnic groups ; however , this may be a proxy for health beliefs and /or language . These results suggest that patient preferences should be considered when making CRC screening recommendations . Trial Registration clinical trials.gov Identifier : NCT00705731", "IMPORTANCE Colorectal cancer ( CRC ) screening saves lives , but participation rates are low among underserved population s. Knowledge on effective approaches for screening the underserved , including best test type to offer , is limited . OBJECTIVE To determine ( 1 ) if organized mailed outreach boosts CRC screening compared with usual care and ( 2 ) if FIT is superior to colonoscopy outreach for CRC screening participation in an underserved population . DESIGN , SETTING , AND PARTICIPANTS We identified uninsured patients , not up to date with CRC screening , age 54 to 64 years , served by the John Peter Smith Health Network , Fort Worth and Tarrant County , Texas , a safety net health system . INTERVENTIONS Patients were assigned r and omly to 1 of 3 groups . One group was assigned to fecal immunochemical test ( FIT ) outreach , consisting of mailed invitation to use and return an enclosed no-cost FIT ( n = 1593 ) . A second was assigned to colonoscopy outreach , consisting of mailed invitation to schedule a no-cost colonoscopy ( n = 479 ) . The third group was assigned to usual care , consisting of opportunistic primary care visit – based screening ( n = 3898 ) . In addition , FIT and colonoscopy outreach groups received telephone follow-up to promote test completion . MAIN OUTCOME MEASURES Screening participation in any CRC test within 1 year after r and omization . RESULTS Mean patient age was 59 years ; 64 % of patients were women . The sample was 41 % white , 24 % black , 29 % Hispanic , and 7 % other race/ethnicity . Screening participation was significantly higher for both FIT ( 40.7 % ) and colonoscopy outreach ( 24.6 % ) than for usual care ( 12.1 % ) ( P < .001 for both comparisons with usual care ) . Screening was significantly higher for FIT than for colonoscopy outreach ( P < .001 ) . In stratified analyses , screening was higher for FIT and colonoscopy outreach than for usual care , and higher for FIT than for colonoscopy outreach among whites , blacks , and Hispanics ( P < .005 for all comparisons ) . Rates of CRC identification and advanced adenoma detection were 0.4 % and 0.8 % for FIT outreach , 0.4 % and 1.3 % for colonoscopy outreach , and 0.2 % and 0.4 % for usual care , respectively ( P < .05 for colonoscopy vs usual care advanced adenoma comparison ; P > .05 for all other comparisons ) . Eleven of 60 patients with abnormal FIT results did not complete colonoscopy . CONCLUSIONS AND REVELANCE : Among underserved patients whose CRC screening was not up to date , mailed outreach invitations result ed in markedly higher CRC screening compared with usual care . Outreach was more effective with FIT than with colonoscopy invitation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01191411", "Background Three large r and omised trials have shown that screening for colorectal cancer ( CRC ) using the faecal occult blood test ( FOBt ) can reduce the mortality from this disease . The largest of these trials , conducted in Nottingham since 1981 , r and omised 152 850 individuals between the ages of 45 and 74 years to an intervention arm receiving biennial Haemoccult ( FOB ) test kit or to a control arm . In 2006 , the National Bowel Cancer Screening Programme was launched in Engl and using the FOBt , with the expectation that it will reduce CRC mortality . Aims To compare the CRC mortality and incidence in the intervention arm with the control arm after long-term follow-up . Methods The 152 850 r and omised individuals were followed up through local health records and central flagging ( Office for National Statistics ) . Results At a median follow-up of 19.5 years there was a 13 % reduction in CRC mortality ( 95 % CI 3 % to 22 % ) in the intervention arm despite an uptake at first invitation of approximately 57 % . The CRC mortality reduction in those accepting the first screening test , adjusted for the rate of non-compliers , was 18 % . There was no significant difference in mortality from causes other than CRC between the intervention and control arms . Despite removing 615 adenomas > 10 mm in size from the intervention arm , there was no significant difference in CRC incidence between the two arms . Conclusions Although the reduction in CRC mortality was sustained , further follow-up of the screened population has not shown a significant reduction in the CRC incidence . Moreover , despite the removal of many large adenomas there was no reduction in the incidence of invasive cancer which was independent of sex and site of the tumour", "BACKGROUND & AIMS We conducted a study to estimate population coverage and detection rate ( DR ) achievable through different strategies of colorectal cancer ( CRC ) screening . METHODS A population -based multicenter r and omized trial comparing 3 strategies was used : ( 1 ) biennial immunologic fecal occult blood test ( FIT ) , ( 2 ) \" once only \" sigmoidoscopy ( FS ) , and ( 3 ) \" once only \" colonoscopy ( TC ) . A r and om sample of men and women , aged 55 to 64 years , was drawn from general practitioners ' ( GP ) rosters . Eligible subjects , r and omized within GP , were mailed a personal invitation . Nonresponders in groups 2 and 3 were invited again at 12 and 24 months . Screenees with \" high-risk \" distal polyps ( villous component > 20 % , high- grade dysplasia , CRC , size > or=10 mm , > 2 adenomas ) at FS , or with positive FIT , were referred for TC . RESULTS The attendance rate was 32.3 % ( 1965/6075 ) for FIT , 32.3 % ( 1944/6018 ) for FS , 26.5 % ( 1597/6021 ) for TC . FIT detected 2 patients with CRC ( 0.1 % ) and 21 with an advanced adenoma ( 1.1 % ) . The corresponding figures were as follows : 12 ( 0.6 % ) and 86 ( 4.5 % ) patients , respectively , for FS ; 13 ( 0.8 % ) and 100 ( 6.3 % ) patients , respectively , for TC . To detect 1 advanced neoplasm , it would be necessary to invite 264 people with FIT , 60 with FS , 53 with TC . FS would have detected 27.3 % of the proximal advanced neoplasms detected at TC . Assuming the same participation rate at TC as at FS , 48 TCs would be necessary to detect 1 additional advanced neoplasm missed by FS . CONCLUSIONS When participants are offered 1 screening test , participation is lower in a TC than in an FS program . However , DR of advanced neoplasia is higher with TC", "This prospect i ve study was done in a health maintenance organization colorectal cancer screening program to determine whether 166 persons found to have abnormal fecal occult blood test results typically underwent complete diagnostic evaluation ( i.e. , either colonoscopy or barium enema x-ray plus flexible sigmoidoscopy ) . Chart audit data show that 137 ( 82 % ) subjects contacted a physician to discuss follow-up . A complete diagnostic evaluation was recommended to only 52 ( 38 % ) patients who talked with a physician . Forty-two ( 81 % ) patients who were advised to get a complete diagnostic evaluation actually complied . Significant differences in clinical findings were observed for patients who did and did not have a complete diagnostic evaluation", "Objectives Colorectal cancer ( CRC ) is one of the most common malignancies worldwide . The aim of this study was to compare the outcomes of two different screening approaches in a small country ( Montenegro , 650 000 inhabitants ) with a CRC incidence lower than the European average . Methods Two structured invitation programs were compared with respect to compliance and neoplasia yield : ( i ) program A focused on first-degree relatives of CRC patients diagnosed in two hospitals ( n=206 ) , inviting them for colonoscopy ; ( ii ) program B was an invitation program for fecal occult blood testing , followed by colonoscopy if positive , conducted in University Hospital , Podgorica , Montenegro , on 2760 r and omly selected average-risk persons , age 50–74 years , living in a single municipality . Results Of 710 first-degree relatives of 206 CRC patients approached , 540 presented for colonoscopy ( 76.05 % uptake ) . Overall , 31 were diagnosed with a cancer , 58 with advanced adenoma , and 151 with adenoma in general . In the general screening program , of 2760 individuals invited , 920 underwent fecal immunochemical test ( 33.3 % uptake ) and colonoscopy was performed in all 95 positive cases ( 10.3 % ) ; six cancers was found in five patients ( one patient had two cancers ) , 19 patients were diagnosed with advanced adenoma , and 26 with any adenomas . The risk-targeted screening program had a significantly higher yield for cancers in both per invited ( 31/710 vs. 5/2760 , P<0.001 ) and per eligible person analysis ( 31/540 vs. 5/920 , P<0.001 ) . Conclusion In a low-incidence country with limited re sources , it may be advisable to start with CRC screening targeted to risk groups", "BACKGROUND Case-control studies and a voluntary-based follow-up study have suggested that repeated screening with faecal-occult-blood ( FOB ) tests can lead to a reduction in mortality from colorectal cancer ( CRC ) . The aim of this r and omised study was to compare mortality rates after FOB tests every 2 years during a 10-year period with those of unscreened similar controls . METHODS 140,000 people aged 45 - 75 years lived in Funen , Denmark , in August , 1985 , and were considered for inclusion in our study . Before r and omisation we excluded individuals who had CRC or precursor adenomas and those who had taken part in a previous pilot study . R and omisation of 137,485 people in blocks of 14 allocated three per 14 to the screening group ( 30,967 ) , three per 14 to the control group ( 30,966 ) , and eight not to be enrolled in the study ( 75,552 ) . Controls were not told about the study and continued to use health-care facilities as normal . Hemoccult-II blood tests ( with dietary restrictions but without rehydration ) were sent to screening-group participants . Only those participants who completed the first screening round were invited for further screening -- five rounds of screening during a 10-year period . Participants with positive tests were asked to attend to full examination and were offered colonoscopy whenever possible . The primary endpoint was death from CRC . FINDINGS Of the 30,967 screening-group participants , 20,672 ( 67 % ) completed the first screening round and were invited for further screening ; more than 90 % accepted repeated screenings . During the 10-year study , 481 people in the screening group had a diagnosis of CRC , compared with 483 unscreened controls . There were 205 deaths attributable to CRC in the screening group , compared with 249 deaths in controls . CRC mortality , including deaths attributable to complications from CRC treatment , was significantly lower in the screening group than in controls ( mortality ratio 0.82 [ 95 % CI 0.68 - 0.99 ] ) p = 0.03 ) . INTERPRETATION Our findings indicate that biennial screening by FOB tests can reduce CRC mortality . This study is being continued to improve its statistical power and to assess the effect of the removal of more precursor adenomas in the screening-group participants than in controls on CRC incidence", "Background Colorectal cancer ( CRC ) screening programs based on the fecal occult blood test ( FOBT ) reduce CRC mortality . We carried out an observational prospect i ve study to determine the accuracy of immunochemical FOBTs for the detection of CRC in individuals at average risk for the disease . Methods This population -based study was performed between April 2015 and January 2016 in two gastroenterology referral centers in Southern Brazil . It included 1039 average-risk volunteers aged 50 - 75 years who were symptom-free for colonic disease . Participants underwent OC-Light immunochemical fecal occult blood test ( i-FOBT , EIKEN chemical Co. , Tokyo , Japan ) as well as screening colonoscopy . Results Nine hundred forty-eight ( 91.2 % ) of the 1039 participants completed and returned the i-FOBT ( 95 % confidence interval [ CI ] 89.4 - 92.9 ) . Among the 73 participants with a positive i-FOBT who underwent colonoscopy , advanced CRC was detected in 9 ( 12.3 % ) . Two ( 2.7 % ) early CRCs , 7 ( 9.5 % ) high- grade dysplasia adenomas and 25 ( 34.2 % ) low- grade dysplasia adenomas were also diagnosed . Among the 243 negative i-FOBT cases who underwent colonoscopy , one ( 0.4 % ) advanced CRC and 91 ( 37.6 % ) low- grade dysplasia adenomas were detected . The detection rate of CRC considering the whole screened population ( n=1039 ) was 1.05 % ( 11/1039 ) . Conclusions The i-FOBT test in the CRC screening programs in Brazil showed a high compliance and high detection rates for cancers and high-risk adenomas . The i-FOBT test is feasible for CRC screening in an average-risk population", "Context The fecal immunochemical test is an effective way to screen for colorectal cancer , but we know more about how well it does the first time it is used and less about how well it does in later years with repeated testing . Contribution The research ers show that , after 4 years of repeated testing , patients continued to use the test and it continued to identify colorectal cancer . Caution This study did not measure whether identification of cancer changed outcomes . Implication The fecal immunochemical test is acceptable and effective for repeated testing . Colorectal cancer ( CRC ) is the second leading cause of cancer death in the United States ( 13 ) , and screening with fecal occult blood tests ( FOBTs ) reduces CRC incidence and mortality ( 46 ) . In r and omized trials ( 711 ) , annual or biennial guaiac-based FOBTs reduced CRC incidence by 17 % to 20 % and CRC mortality by 15 % to 33 % . Thus , the U.S. Preventive Services Task Force ( 4 ) and U.S. Multi-Society Task Force on Colorectal Cancer ( 12 ) recommend annual FOBT as an option for CRC screening for average-risk patients , defined as those aged 50 to 75 years with no history of CRC or adenoma , with no first-degree relatives with CRC , and who are not up to date with CRC screening according to other methods ( that is , sigmoidoscopy within 5 years or colonoscopy within 10 years ) . Annual highly sensitive FOBTs are believed to be as effective as screening colonoscopy performed every 10 years if levels of adherence are high ( 13 ) , although colonoscopy is recommended for those with a family history of CRC . Fecal blood tests are noninvasive and can be delivered by mail ( 14 ) . In contrast to guaiac-based stool tests , fecal immunochemical test ( FIT ) screening can be done without dietary or medication restrictions , which allows it to achieve higher patient acceptance in organized CRC screening programs ( 15 ) . This test also has higher detection rates for CRC and advanced adenomas than guaiac-based stool tests ( 1517 ) . In a recent meta- analysis ( 18 ) , the sensitivity of a single FIT application was 79 % for CRC diagnosed within 2 years of testing ; however , little is known about performance characteristics over several rounds of annual screening , particularly in community practice . The present study was conducted to evaluate FIT sensitivity for CRC and other performance characteristics over 4 rounds of annual testing in a U.S. community-based CRC screening program . Methods Study Population This retrospective longitudinal study was performed in a fixed cohort of Kaiser Permanente Northern California ( KPNC ) and Southern California ( KPSC ) health plan members . These integrated health care delivery organizations serve approximately 7 million persons in urban , suburban , and semirural regions throughout California . Kaiser Permanente health plan membership in California is diverse and similar in socioeconomic characteristics to the region 's census demographics ( 1921 ) . Study Oversight The study was approved by the institutional review boards of KPNC and KPSC , both of which waived the requirement for informed consent . The listed authors had sole responsibility for the study design , data collection , decision to su bmi t the manuscript for publication , and drafting of the manuscript . This study was conducted within the National Cancer Institutefunded Population -based Research Optimizing Screening through Personalized Regimens ( PROSPR ) consortium , which conducts multisite , coordinated , transdisciplinary research to evaluate and improve cancer-screening processes . Organized CRC Screening Program The KPNC and KPSC initiated similar organized FIT screening programs between 2006 and 2008 ; the KPNC program has been described previously ( 14 ) . Briefly , each year , the programs mail a FIT kit to eligible health plan members aged 50 to 75 years without a record of a colonoscopy within 10 years , sigmoidoscopy within 5 years , or fecal blood test within the prior year . The kit includes the FIT ( OC FIT-CHEK ; Polymedco ) , a st and ardized letter from the patient 's primary care provider , directions for completing and mailing the test , and a preprinted laboratory requisition order form . Outreach includes in-person , mail , secure e-mail , and telephone reminders as needed . The kits are returned by mail to regional laboratories and analyzed on or shortly after the return date using an OC-Sensor Diana automated system ( Polymedco ) with a cutoff level of 20 g of hemoglobin/g of buffer for a positive result . Patients with a positive FIT result are referred for follow-up colonoscopy . Study Eligibility Criteria and Participant Tracking The study cohort included CRC screening program participants aged 50 to 70 years on the date an initial kit was mailed to them in 2007 or 2008 . Patients were excluded if they had been enrolled in the health plan for less than 1 year before the round 1 FIT mail date ( to allow for the recording of prior out-of-system endoscopy procedures ) . They were also excluded if they were mailed a kit but subsequently had sigmoidoscopy or colonoscopy , were diagnosed with CRC , died , or terminated membership in the health plan before returning the initial FIT or within 1 year after their round 1 mail date if no FIT was returned . A total of 670841 health plan members was mailed the initial kit in 2007 or 2008 and met the study eligibility criteria ; 323349 ( 48.2 % ) returned a FIT within 1 year after the mail date ( Figure ) . The analytic cohort comprised these round 1 participants who were tracked from their baseline mail date ( cohort entry ) through up to 4 rounds of testing for mail date s ; result date s ; results ( positive or negative ) ; whether follow-up colonoscopy was performed within 1 year after a positive FIT result ; and diagnoses of adenoma , adenoma with advanced histology , and CRC . Cohort members were followed for CRC through the follow-up screening rounds , even if they subsequently became ineligible for screening because of sigmoidoscopy or colonoscopy . Patients were censored at the time of CRC diagnosis , death , or termination of membership in the health plan if they did not rejoin . Figure . Study flow diagram . * The figure includes 1192 patients with CRC who were screened by FIT the year before diagnosis . Further , there were 118 additional patients with CRC diagnosed more than 1 y beyond the FIT screening date and 101 additional patients diagnosed with CRC who either crossed over to endoscopy in subsequent rounds or terminated health plan membership but then rejoined . CRC = colorectal cancer ; FIT = fecal immunochemical test . * Shading indicates where patients were censored or became ineligible for subsequent FIT screening . Patients were eligible for the initial FIT mailing if they were aged 50 to 70 y and had 1 y of membership . See Methods section for exclusions . Number censored because of CRC and includes patients with CRC diagnosed within 1 y after their FIT result . Defining Annual Screening Episodes For each patient , the initial kit mail date in 2007 or 2008 was the anchor date for round 1 and for each subsequent round of testing . However , because subsequent mailing date s varied each round , mail date s within 3 months before to 12 months after each subsequent round 's anchor date were counted as having been distributed during that specific round . For example , a patient with a round 1 mail date of 15 March 2007 had subsequent anchor date s of 15 March for rounds 2 through 4 ( 2008 , 2009 , and 2010 , respectively ) . If their next FIT was mailed on 15 January 2008 , the test was considered to be distributed in round 2 because the second mail date occurred within 3 months of the round 2 anchor date . The FIT results recorded within 1 year of each mail date , and colonoscopies performed and adenomas or CRC diagnosed within 1 year after FIT results , were considered part of a single screening episode for the round when the FIT was distributed . Among round 1 participants , FITs with no recorded mail date s returned in rounds 2 through 4 were assumed to be distributed through in-reach methods ( such as a clinic visit ) and were counted in the follow-up round returned . In general , the first result per patient was counted in any given round . The earliest possible date of cohort entry ( first mail date ) was 1 January 2007 , and the last possible date of follow-up was 31 December 2013 ( 12 months after the last possible FIT result date of 31 December 2012 ) . Data Sources The FIT-related date s and results were obtained from the CRC screening program and laboratory data bases for each region , respectively . Endoscopy procedures were identified using Current Procedural Terminology codes ( 22 ) . Adenoma diagnoses used Systematized Nomenclature of Medicine codes . Prior validation studies have confirmed high levels of sensitivity and accuracy for capture of colonoscopy examinations and assignment of adenoma status ( 23 ) . Colorectal adenocarcinomas and disease stage were obtained from the KPNC and KPSC cancer registries , which report to the SEER ( Surveillance , Epidemiology , and End Results ) registry . Cancer data bases capture more than 98 % of cancer diagnoses within the KPNC and KPSC population s. Advanced-stage cancer was defined as stage III ( regional disease with spread to regional lymph nodes only ) or stage IV ( distant metastasis ) according to the American Joint Committee on Cancer staging system ; for patients who did not have such staging , advanced-stage cancer was defined as code 3 ( disease in the regional lymph nodes ) , code 4 ( regional disease with direct extension and spread to regional lymph nodes ) , or code 7 ( distant metastasis ) according to the SEER Program Coding and Staging Manual 2013 ( 24 ) . Data Analysis The following performance characteristics were calculated for each round of screening and overall : 1 ) participation ( percentage of eligible patients who were distributed and completed a FIT within 1 year of their mailing date ) , 2 ) FIT positivity ( percentage of participants who completed FITs and had positive results ) , 3 ) follow-up colonoscopy (" ]

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[ "The effect on cardiorespiratory fitness after an 8-week period of commuter cycling--a randomized controlled study in adults.", "A Fit-Fat Index for Predicting Incident Diabetes in Apparently Healthy Men: A Prospective Cohort Study", "Grip strength is not associated with incident type 2 diabetes mellitus in healthy adults: The CoLaus study.", "Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form.", "Effects of active commuting and leisure-time exercise on fat loss in women and men with overweight and obesity: a randomized controlled trial", "Effect of handgrip on coronary artery disease and myocardial infarction: a Mendelian randomization study", "Muscular and performance fitness and the incidence of type 2 diabetes: prospective study of Japanese men.", "Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial.", "Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants", "Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study", "Resist diabetes: A randomized clinical trial for resistance training maintenance in adults with prediabetes", "Associations of Cardiorespiratory Fitness and Obesity With Risks of Impaired Fasting Glucose and Type 2 Diabetes in Men", "Cardiorespiratory fitness and the incidence of type 2 diabetes: prospective study of Japanese men.", "Handgrip strength does not represent an appropriate measure to evaluate changes in muscle strength during an exercise intervention program in frail older people.", "Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.", "Risk factors for Type 2 (non-insulin-dependent) diabetes mellitus. Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913", "The Association between Cardiorespiratory Fitness and Impaired Fasting Glucose and Type 2 Diabetes Mellitus in Men", "Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men.", "Muscular strength in male adolescents and premature death: cohort study of one million participants", "Reference Values for Cardiorespiratory Fitness and Incidence of Type 2 Diabetes", "Fitness, Body Habitus, and the Risk of Incident Type 2 Diabetes Mellitus in Korean Men.", "Prediction of Type 2 diabetes in healthy middle-aged men with special emphasis on glucose homeostasis. Results from 22.5 years' follow-up.", "Effect of fitness on incident diabetes from statin use in primary prevention." ]

[ "OBJECTIVE This study investigated the effect of commuter cycling on cardiorespiratory fitness in men and women . Secondary outcomes included body fat and blood pressure measurements . METHODS In February 2009 , 48 volunteers from the Isl and of Funen , Denmark were r and omly assigned to either \" no change in lifestyle \" or to \" minimum 20 minutes of daily commuter cycling during 8 weeks \" . Maximal oxygen uptake was assessed directly during a progressive cycle-ergometer-test , sum of skinfolds was used as an estimate of body fat , and blood pressure was measured using a Dinamap monitor . Measurements were obtained at baseline and at the conclusion of the 8-week intervention program . RESULTS Six cyclists dropped out . After 8 weeks VO(2)max ( mL O(2 ) min(-1 ) ) and cardiorespiratory fitness ( mL O(2 ) kg(-1 ) min(-1 ) ) were significantly improved in the cycling group when compared to the control group . Delta change in VO(2)max between groups equaled 206 mL O(2 ) min(-1 ) ( p=0.005 ) and delta change in cardiorespiratory fitness equaled 2.6 mL O(2 ) kg(-1 ) min(-1 ) ( p=0.003 ) . Body fatness changed more noticeable ( p=0.026 ) in the cyclists ( -12.3±7.3 mm ) than in the controls ( -0.2±7.1 mm ) . CONCLUSIONS VO(2)max and cardiorespiratory fitness were significantly improved and body fat reduced as a result of people engaging in 8 weeks of commuter cycling", "Background The purpose of this study was to examine the impact of combined cardiorespiratory fitness and waist-to-height ratio in the form of a fit-fat index on incident diabetes risk . Additionally , the independent predictive performance of cardiorespiratory fitness , waist-to-height ratio , and body mass index also were estimated and compared . Methods This was a prospect i ve cohort study of 10,381 men who had a normal electrocardiogram and no history of major chronic disease at baseline from 1979 to 2005 . R and om survival forest models and traditional Cox proportional hazards models were used to predict diabetes at 5- , 10- , and 15-year incidence horizons . Results Overall , 4.8 % of the participants developed diabetes . Receiver operating characteristic curve analyses for incidence risk demonstrated good discrimination using r and om survival forest models across fitness and fatness measures ; Cox models were poor to fair . The differences between fitness and fatness measures across horizons were clinical ly negligible . Smoothed r and om survival forest estimates demonstrated the impact of each fitness and fatness measure on incident diabetes was intuitive and grade d. Conclusions Although fitness and fatness measures showed a similar discriminative ability in predicting incident diabetes , unique to the study was the ability of the fit-fat index to demonstrate a better indication of incident risk when compared to fitness or fatness alone . A single index combining cardiorespiratory fitness and waist-to-height ratio may be more useful because it can indicate improvements in either or both of the measures", "AIMS We examined the association of grip strength with incident type 2 diabetes mellitus ( T2DM ) in healthy subjects initially aged 50 to 75years after a follow-up of 5.5years and 10.7years . METHODS This was a prospect i ve , population -based study derived from the CoLaus ( Cohorte Lausannoise ) study including 2318 participants ( aged 60.2y ; 1354 women ) free from T2DM at baseline . Grip strength was assessed using a h and held dynamometer . The effect of grip strength on the incidence of T2DM was analyzed by logistic regression . RESULTS After a follow-up of 5.5years , 190 ( 8.2 % ) T2DM cases were identified . In bivariate analysis , participants who developed T2DM had a higher absolute grip strength ( 35.3±10.6 versus 33.2±10.7 kg , P=0.013 ) . Analysis between grip strength expressed in 5 kg increment and incident TD2 M showed a negative association when adjusted for age and sex [ ORs ( 95 % CI ) : 0.88 ( 0.79 , 0.98 ) ] , or for age , sex and body mass index ( BMI ) [ ORs ( 95 % CI ) : 0.87 ( 0.78 , 097 ) ] . After a follow-up of 10.7years , 131 supplemental ( 7.3 % ) T2DM cases were identified , but there was no association between grip strength and incident T2DM in bivariate and multivariable analysis , potentially due to a lack of statistical power . CONCLUSIONS In non elderly healthy adults , the risk of incident T2DM is overall not associated with grip strength over a maximum follow-up of 10.7years . Future studies are warranted to better assess the association between grip strength and incident T2DM in bigger and even younger cohorts", "A major problem in review ing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways . The purpose of this paper is to exemplify methods by which results expressed either as risks ( or rates ) according to quantlle groups of the quantitative variable or as results derived from a logistic regression analysis can be reexpressed in a uniform manner , as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study . An important assumption of the methods is that the quantitative variable has an approximately normal distribution , and a way of investigating the appropriateness of this assumption is given . The methods can be applied to both prospect i ve and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality . In some applications , these methods can be used as a precursor to formal meta- analysis , for example , when differential control of potential confounding factors is not a problem . At the least , the methods can be useful either in quantitatively review ing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones", "Background : Aerobic exercise is recommended for weight management but energy balance is often less negative than predicted from exercise energy expenditure ( ExEE ) . Objective : To examine effects of active commuting and leisure-time exercise on fat loss in women and men with overweight and obesity . Methods : We r and omized 130 younger , physically inactive women and men with overweight and obesity ( body mass index : 25–35 kg m−2 ) to 6 months of habitual lifestyle ( control ; CON , n=18 ) , active commuting ( BIKE , n=35 ) or leisure-time exercise of moderate ( MOD , 50 % VO2peak reserve , n=39 ) or vigorous intensity ( VIG , 70 % VO2peak reserve , n=38 ) . The primary outcome was change in fat mass measured by dual-energy X-ray absorptiometry , which was analyzed intention-to-treat . Accumulated energy balance was calculated based on changes in body composition , and ExEE was calculated based on heart rate monitoring during exercise . Results : Testing at 3 and 6 months was completed by 95 and 90 participants , respectively . Fat mass was reduced after 3 and 6 months in BIKE ( 3 months : −3.6 ( −5.5 ; −1.7 ) kg ( mean ( 95 % CI ) ) ; 6 months : −4.2 ( −6.6 ; −1.9 ) kg ; both : P<0.001 ) , MOD ( 3 months : −2.2 ( −3.9 ; −0.4 ) kg ; 6 months : −2.6 ( −4.8 ; −0.5 ) kg , both : P<0.02 ) and VIG ( 3 months : −3.4 ( −5.2 ; −1.7 ) kg ; 6 months : −4.5 ( −6.6 ; −2.3 ) kg ; both : P<0.001 ) compared with CON . Furthermore , fat loss was greater in VIG compared with MOD ( 6 months : −1.8 ( −3.6 ; −0.1 ) kg , P=0.043 ) . Based on the ExEE and the accumulated energy balance MOD compensated for the ExEE ( 77 ( 48 ; 106 ) % ) but not BIKE ( 38 ( −18 ; 95 ) % ) and VIG ( 21 ( −14 ; 55 ) % ) . Conclusions : A meaningful fat loss was obtained by 6 months of active commuting and leisure-time exercise , but fat loss was greater with vigorous compared with moderate intensity exercise . Active commuting is an alternative to leisure-time exercise in the management of overweight and obesity . The trial was registered at clinical trials.gov as NCT01962259 ( main trial ) and NCT01973686 ( energy metabolism sub- study )", "Observational studies have reported an association of h and grip strength with risk of cardiovascular disease . However , residual confounding and reverse causation may have influenced these findings . A Mendelian r and omization ( MR ) study was conducted to examine whether h and grip is causally associated with cardiovascular disease . Two single nucleotide polymorphisms ( SNPs ) , rs3121278 and rs752045 , were used as the genetic instruments for h and grip . The effect of each SNP on coronary artery disease/myocardial infa rct ion ( CAD/MI ) was weighted by its effect on h and grip strength , and estimates were pooled to provide a summary measure for the effect of increased h and grip on risk of CAD/MI . MR analysis showed that higher grip strength reduces risk for CAD/MI , with 1-kilogram increase in genetically determined h and grip reduced odds of CAD by 6 % ( odds ratio ( OR ) = 0.94 , 95 % confidence interval ( CI ) 0.91–0.99 , P = 0.01 ) , and reduced odds of MI by 7 % ( OR = 0.93 , 95 % CI 0.89–0.98 , P = 0.003 ) . No association of grip strength with type 2 diabetes , body mass index , LDL- and HDL-cholesterol , triglycerides and fasting glucose was found . The inverse causal relationship between h and grip and the risk of CAD or MI suggests that promoting physical activity and resistance training to improve muscle strength may be important for cardiovascular health", "BACKGROUND Limited data are available on the relationship between muscular and performance fitness ( MPF ) and the incidence of type 2 diabetes . METHODS A cohort of 3792 Japanese men completed a medical examination that included MPF and cardiorespiratory fitness tests . MPF index composite score was calculated using Z-scores from vertical jump , sit-ups , side step , and functional reach tests . RESULTS The mean follow-up period was 187 months ( 15.6 years ) . There were 240 patients who developed type 2 diabetes during follow-up . Relative risks and 95 % confidence intervals ( CI ) for incidence of diabetes across baseline quartiles of MPF index composite score were obtained using the Cox proportional hazards model while adjusting for age , BMI , diastolic blood pressure , cigarette smoking , alcohol intake , and family history of diabetes . The relative risks for developing diabetes across quartiles of MPF index composite scores ( lowest to highest ) were 1.0 ( referent ) , 1.15 ( 95 % CI 0.83 - 1.60 ) , 1.10 ( 0.78 - 1.55 ) , and 0.57 ( 0.37 - 0.90 ) ( P for trend = .061 ) . These results were attenuated after adjustment for cardiorespiratory fitness ( P for trend = .125 ) . CONCLUSIONS This prospect i ve study suggests that MPF is a predictor of type 2 diabetes , although its predictive ability was attenuated after adjusting for cardiorespiratory fitness", "CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination . OBJECTIVE To examine the benefits of aerobic training alone , resistance training alone , and a combination of both on hemoglobin A(1c ) ( HbA(1c ) ) in individuals with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c ) levels of 6.5 % or higher were enrolled in the 9-month exercise program between April 2007 and August 2009 . INTERVENTION Forty-one participants were assigned to the nonexercise control group , 73 to resistance training 3 days a week , 72 to aerobic exercise in which they expended 12 kcal/kg per week ; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week . Main Outcome Change in HbA(1c ) level . Secondary outcomes included measures of anthropometry and fitness . RESULTS The study included 63.0 % women and 47.3 % nonwhite participants who were a mean ( SD ) age of 55.8 years ( 8.7 years ) with a baseline HbA(1c ) level of 7.7 % ( 1.0 % ) . Compared with the control group , the absolute mean change in HbA(1c ) in the combination training exercise group was -0.34 % ( 95 % confidence interval [ CI ] , -0.64 % to -0.03 % ; P = .03 ) . The mean changes in HbA(1c ) were not statistically significant in either the resistance training ( -0.16 % ; 95 % CI , -0.46 % to 0.15 % ; P = .32 ) or the aerobic ( -0.24 % ; 95 % CI , -0.55 % to 0.07 % ; P = .14 ) groups compared with the control group . Only the combination exercise group improved maximum oxygen consumption ( mean , 1.0 mL/kg per min ; 95 % CI , 0.5 - 1.5 , P < .05 ) compared with the control group . All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group . The resistance training group lost a mean of -1.4 kg fat mass ( 95 % CI , -2.0 to -0.7 kg ; P < .05 ) and combination training group lost a mean of -1.7 ( -2.3 to -1.1 kg ; P < .05 ) compared with the control group . CONCLUSIONS Among patients with type 2 diabetes mellitus , a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c ) levels . This was not achieved by aerobic or resistance training alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00458133", "Abstract Objective To investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score . Design Prospect i ve population based study . Setting UK Biobank . Participants 502 293 participants ( 54 % women ) aged 40 - 69 years . Main outcome measures All cause mortality as well as incidence of and mortality from cardiovascular disease , respiratory disease , chronic obstructive pulmonary disease , and cancer ( all cancer , colorectal , lung , breast , and prostate ) . Results Of the participants included in analyses , 13 322 ( 2.7 % ) died over a mean of 7.1 ( range 5.3 - 9.9 ) years ’ follow-up . In women and men , respectively , hazard ratios per 5 kg lower grip strength were higher ( all at P<0.05 ) for all cause mortality ( 1.20 , 95 % confidence interval 1.17 to 1.23 , and 1.16 , 1.15 to 1.17 ) and cause specific mortality from cardiovascular disease ( 1.19 , 1.13 to 1.25 , and 1.22 , 1.18 to 1.26 ) , all respiratory disease ( 1.31 , 1.22 to 1.40 , and 1.24 , 1.20 to 1.28 ) , chronic obstructive pulmonary disease ( 1.24 , 1.05 to 1.47 , and 1.19 , 1.09 to 1.30 ) , all cancer ( 1.17 , 1.13 to 1.21 , 1.10 , 1.07 to 1.13 ) , colorectal cancer ( 1.17 , 1.04 to 1.32 , and 1.18 , 1.09 to 1.27 ) , lung cancer ( 1.17 , 1.07 to 1.27 , and 1.08 , 1.03 to 1.13 ) , and breast cancer ( 1.24 , 1.10 to 1.39 ) but not prostate cancer ( 1.05 , 0.96 to 1.15 ) . Several of these relations had higher hazard ratios in the younger age group . Muscle weakness ( defined as grip strength < 26 kg for men and < 16 kg for women ) was associated with a higher hazard for all health outcomes , except colon cancer in women and prostate cancer and lung cancer in both men and women . The addition of h and grip strength improved the prediction ability , based on C index change , of an office based risk score ( age , sex , diabetes diagnosed , body mass index , systolic blood pressure , and smoking ) for all cause ( 0.013 ) and cardiovascular mortality ( 0.012 ) and incidence of cardiovascular disease ( 0.009 ) . Conclusion Higher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score . Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility", "BACKGROUND Reduced muscular strength , as measured by grip strength , has been associated with an increased risk of all-cause and cardiovascular mortality . Grip strength is appealing as a simple , quick , and inexpensive means of stratifying an individual 's risk of cardiovascular death . However , the prognostic value of grip strength with respect to the number and range of population s and confounders is unknown . The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries . METHODS The Prospect i ve Urban-Rural Epidemiology ( PURE ) study is a large , longitudinal population study done in 17 countries of varying incomes and sociocultural setting s. We enrolled an unbiased sample of households , which were eligible if at least one household member was aged 35 - 70 years and if household members intended to stay at that address for another 4 years . Participants were assessed for grip strength , measured using a Jamar dynamometer . During a median follow-up of 4.0 years ( IQR 2.9 - 5.1 ) , we assessed all-cause mortality , cardiovascular mortality , non-cardiovascular mortality , myocardial infa rct ion , stroke , diabetes , cancer , pneumonia , hospital admission for pneumonia or chronic obstructive pulmonary disease ( COPD ) , hospital admission for any respiratory disease ( including COPD , asthma , tuberculosis , and pneumonia ) , injury due to fall , and fracture . Study outcomes were adjudicated using source documents by a local investigator , and a subset were adjudicated central ly . FINDINGS Between January , 2003 , and December , 2009 , a total of 142,861 participants were enrolled in the PURE study , of whom 139,691 with known vital status were included in the analysis . During a median follow-up of 4.0 years ( IQR 2.9 - 5.1 ) , 3379 ( 2 % ) of 139,691 participants died . After adjustment , the association between grip strength and each outcome , with the exceptions of cancer and hospital admission due to respiratory illness , was similar across country-income strata . Grip strength was inversely associated with all-cause mortality ( hazard ratio per 5 kg reduction in grip strength 1.16 , 95 % CI 1.13 - 1.20 ; p<0.0001 ) , cardiovascular mortality ( 1.17 , 1.11 - 1.24 ; p<0.0001 ) , non-cardiovascular mortality ( 1.17 , 1.12 - 1.21 ; p<0.0001 ) , myocardial infa rct ion ( 1.07 , 1.02 - 1.11 ; p=0.002 ) , and stroke ( 1.09 , 1.05 - 1.15 ; p<0.0001 ) . Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure . We found no significant association between grip strength and incident diabetes , risk of hospital admission for pneumonia or COPD , injury from fall , or fracture . In high-income countries , the risk of cancer and grip strength were positively associated ( 0.916 , 0.880 - 0.953 ; p<0.0001 ) , but this association was not found in middle-income and low-income countries . INTERPRETATION This study suggests that measurement of grip strength is a simple , inexpensive risk-stratifying method for all-cause death , cardiovascular death , and cardiovascular disease . Further research is needed to identify determinants of muscular strength and to test whether improvement in strength reduces mortality and cardiovascular disease . FUNDING Full funding sources listed at end of paper ( see Acknowledgments )", "Objective To determine whether a social cognitive theory (SCT)-based intervention improves resistance training ( RT ) maintenance and strength , and reduces prediabetes prevalence . Research design and methods Sedentary , overweight/obese ( BMI : 25–39.9 kg/m2 ) adults aged 50–69 ( N = 170 ) with prediabetes participated in the 15-month trial . Participants completed a supervised 3-month RT ( 2 × /wk ) phase and were r and omly assigned ( N = 159 ) to one of two 6-month maintenance conditions : SCT or st and ard care . Participants continued RT at a self-selected facility . The final 6-month period involved no contact . Assessment s occurred at baseline and months 3 , 9 , and 15 . The SCT faded-contact intervention consisted of nine tailored transition ( i.e. , supervised training to training alone ) and nine follow-up sessions . St and ard care involved six generic follow-up sessions . Primary outcomes were prevalence of normoglycemia and muscular strength . Results The retention rate was 76 % . Four serious adverse events were reported . After 3 months of RT , 34 % of participants were no longer prediabetic . This prevalence of normoglycemia was maintained through month 15 ( 30 % ) , with no group difference . There was an 18 % increase in the odds of being normoglycemic for each % increase in fat-free mass . Increases in muscular strength were evident at month 3 and maintained through month 15 ( P<0.001 ) , which represented improvements of 21 % and 14 % for chest and leg press , respectively . Results did not demonstrate a greater reduction in prediabetes prevalence in the SCT condition . Conclusions Resistance training is an effective , maintainable strategy for reducing prediabetes prevalence and increasing muscular strength . Future research which promotes RT initiation and maintenance in clinical and community setting s is warranted . Trial Registration Clinical Trials.gov NCT01112709", "OBJECTIVE —The purpose of this study was to examine the associations of cardiorespiratory fitness ( hereafter fitness ) and various obesity measures with risks of incident impaired fasting glucose ( IFG ) and type 2 diabetes . RESEARCH DESIGN AND METHODS —This was a prospect i ve cohort study of 14,006 men ( 7,795 for the analyses of IFG ) , who did not have an abnormal electrocardiogram or a history of heart attack , stroke , cancer , or diabetes . RESULTS —Of the men , 3,612 ( 39,610 person-years ) and 477 ( 101,419 person-years ) developed IFG and type 2 diabetes , respectively . Compared with the least fit 20 % in multivariate analyses , IFG and type 2 diabetes risks in the most fit 20 % were 14 and 52 % lower , respectively ( both P < 0.001 ) . Men with BMI ≥30.0 kg/m2 , waist girth > 102.0 cm , or percent body fat ≥25 had 2.7- , 1.9- , and 1.3-fold higher risks for type 2 diabetes , respectively , compared with those for nonobese men ( all P < 0.01 ) , and the results for IFG were similar . In the combined analyses , obese unfit ( least fit 20 % ) men had a 5.7-fold higher risk for type 2 diabetes compared with normal-weight fit ( most fit 80 % ) men . We observed similar trends for the joint associations of BMI and fitness with IFG and those of waist girth or percent body fat and fitness with both IFG and type 2 diabetes . CONCLUSIONS —Low fitness and obesity increased the risks of IFG and type 2 diabetes by approximately similar magnitudes . When considered simultaneously , fitness attenuated but did not eliminate the increased risks of IFG and type 2 diabetes associated with obesity , and the highest risk was found in obese and unfit men", "OBJECTIVE To investigate the association between cardiorespiratory fitness and the incidence of type 2 diabetes among Japanese men . RESEARCH DESIGN AND METHODS This prospect i ve cohort study was conducted in 4747 nondiabetic Japanese men , aged 20 - 40 years at baseline , enrolled in 1985 with follow-up to June 1999 . Cardiorespiratory fitness was measured using a cycle ergometer test , and Vo(2max ) was estimated . During a 14-year follow-up , 280 men developed type 2 diabetes . RESULTS The age-adjusted relative risks of developing type 2 diabetes across quartiles of cardiorespiratory fitness ( lowest to highest ) were 1.0 ( referent ) , 0.56 ( 95 % CI 0.42 - 0.75 ) , 0.35 ( 0.25 - 0.50 ) , and 0.25 ( 0.17 - 0.37 ) ( for trend , P < 0.001 ) . After further adjustment for BMI , systolic blood pressure , family history of diabetes , smoking status , and alcohol intake , the association between type 2 diabetes risk and cardiorespiratory fitness was attenuated but remained significant ( 1.0 , 0.78 , 0.63 , and 0.56 , respectively ; for trend , P = 0.001 ) . CONCLUSIONS These results indicate that a low cardiorespiratory fitness level is an important risk factor for incidence of type 2 diabetes among Japanese men", "INTRODUCTION Although h and grip strength is considered a strong predictor of negative health outcomes , it is unclear whether h and grip strength represents a useful measure to evaluate changes in muscle strength following resistance-type exercise training in older people . We assessed whether measuring h and grip strength provides proper insight in the efficacy of resistance-type exercise training to increase muscle mass , strength , and physical performance in frail older people . METHODS Prefrail and frail older people ( ≥ 65 y ) were either conducting a 24-week resistance-type exercise training or no exercise training . Before , during , and after the intervention , h and grip strength ( JAMAR ) , lean body mass ( DXA ) , leg strength ( 1-RM ) , and physical performance ( SPPB ) were assessed . RESULTS H and grip strength correlated with appendicular lean mass ( r = 0.68 ; p < .001 ) and leg strength ( r = 0.67 ; p < .001 ) . After 24 weeks of whole body resistance-type exercise training , leg extension strength improved significantly better when compared with the control group ( 57 ± 2 - 78 ± 3 kg vs 57 ± 3 - 65 ± 3 kg : p < .001 ) . Moreover , physical performance improved significantly more in the exercise group ( 8.0 ± 0.4 - 9.3 ± 0.4 points ) when compared with the control group ( 8.3 ± 0.4 - 8.9 ± 0.4 points : p < .05 ) . These positive changes were not accompanied with any significant changes in h and grip strength ( 26.3 ± 1.2 - 27.6 ± 1.2 kg in the exercise group vs 26.6 ± 1.2 - 26.3 ± 1.3 kg in the control group : p = .71 ) . CONCLUSION Although h and grip strength strongly correlates with muscle mass and leg strength in frail older people , h and grip strength does not provide a valid means to evaluate the efficacy of exercise intervention programs to increase muscle mass or strength in an older population", "BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects", "Summary This report presents data on antecedents of Type 2 ( non-insulin-dependent ) diabetes mellitus in a homogeneous sample of r and omly selected 54-year-old men from an urban Swedish population with a diabetes incidence of 6.1 % during 13.5 years of follow-up . The increased risk leading to diabetes for those in the top quintile compared to the lowest quintile of the distribution of statistically significant risk factors were : body mass index = 21.7 , triglycerides = 13.5 , waist-to-hip circumference ratio = 9.6 , diastolic blood pressure = 6.7 , uric acid = 5.8 , glutamic pyruvic transaminase = 3.9 , bilirubin = 3.2 , blood glucose = 2.7 , lactate = 2.4 and glutamic oxaloacetic transaminase = 2.0 . Those with a positive family history of diabetes had 2.4-fold higher risk for developing diabetes than those without such a history . In a multivariate analysis glutamic pyruvic transaminase , blood glucose , body mass index , bilirubin , systolic blood pressure , uric acid and a family history of diabetes were all significantly associated with the development of diabetes . Our study demonstrates the great importance of adiposity and body fat distribution for the risk of diabetes . A number of established risk factors for coronary heart disease are risk factors for diabetes as well . Disturbed liver function and increased levels of lactate are early risk factors for diabetes — presumably indicators of the presence of impaired glucose tolerance and /or hyperinsulinaemia", "Type 2 diabetes is a common disease in industrialized countries . It is a major cause of cardiovascular disease and all-cause mortality ( 1 - 6 ) , and its prevalence has increased continuously over the past few decades ( 1 ) . The American Diabetes Association currently defines impaired fasting glucose as a fasting plasma glucose level from 6.1 to 6.9 mmol/L ( 110 to 125 mg/dL ) and type 2 diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Data from several prospect i ve studies show an inverse association between physical activity and diabetes ( 7 - 13 ) . However , these studies are limited by the use of self-reporting of physical activity and presence of type 2 diabetes ( 7 - 12 ) . Self-reporting of physical activity tends to be imprecise , and type 2 diabetes is undiagnosed in about 50 % of the prevalent cases ( 14 ) . This leads to misclassification on both exposure and outcome measures ( 15 ) . These limitations may result in underestimation of the true association between sedentary habits and risk for type 2 diabetes . Impaired fasting glucose is a strong predictor of type 2 diabetes , cardiovascular disease , and other diabetic complications ( 6 , 16 - 18 ) . The underlying cause of impaired fasting glucose is unknown , and no prospect i ve study of the association between physical activity and impaired fasting glucose has been published . We examined the relation of cardiorespiratory fitness , objective ly determined by a maximal exercise test on a treadmill , to the incidence of impaired fasting glucose and type 2 diabetes . Cases of impaired fasting glucose and diabetes at baseline and follow-up were determined by using the American Diabetes Association 's current guidelines ( 1 ) . Methods Patients In our population -based prospect i ve study , we included 8633 men 30 to 79 years of age at baseline ( mean , 43.5 years ) who completed at least two medical evaluations at the Cooper Clinic in Dallas , Texas , from 1970 to 1995 . Patients come to the Cooper Clinic for preventive medical examinations and health promotion counseling . Many are sent by their employers for these services , some are referred by their personal physicians , and others are self-referred . More than 97 % of the patients are white , and most are employed in executive or professional occupations . More than 75 % are college graduates . Although study participants came from middle and upper socioeconomic strata , they were similar to other well-characterized population -based cohorts in terms of blood pressure , cholesterol level , body weight , and cardiorespiratory fitness ( 19 ) . The study was review ed and approved annually by the institutional review board at the Cooper Institute for Aerobics Research . Additional details of the study methods and population characteristics of the cohort have been published elsewhere ( 20 , 21 ) . Because clinical or sub clinical heart disease and other conditions associated with type 2 diabetes may alter the level of physical activity and thus cardiorespiratory fitness , we excluded men with an abnormal resting or exercise electrocardiogram or a history of heart attack , stroke , or cancer at the baseline clinical examination ( n=2350 ) . The baseline evaluation was performed after participants gave written informed consent for the initial medical examination and registration in the follow-up study . Examinations were done after patients had fasted for at least 12 hours and included personal and family health histories , a question naire on demographic characteristics and health habits , a physical examination , an exercise test , anthropometric measurement , electrocardiography , blood chemistry analyses , and blood pressure measurement . Technicians who followed a st and ard manual of operations administered all procedures . Impaired fasting glucose and type 2 diabetes were diagnosed according to American Diabetes Association criteria that define impaired fasting glucose as a fasting plasma glucose level of 6.1 to 6.9 mmol/L ( 110 mg/dL to 125 mg/dL ) and diabetes as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or more ( 1 ) . Patients who did not meet these criteria but who reported a history of diabetes or current therapy with oral antidiabetic agents or insulin were also considered to have diabetes . We excluded patients who had diabetes at baseline according to any of these criteria ( n=377 ) . Cardiorespiratory fitness was assessed with a maximal exercise test that followed a modified Balke protocol ( 22 ) . Details of treadmill speed and elevation have been described elsewhere ( 20 , 21 ) . Briefly , the test began with the patient walking on a horizontal treadmill at 88 m/min . After the first minute , the elevation increased to 2 % ; the elevation then increased 1 % each minute up to 25 minutes . For the few patients who were still able to continue , the elevation was held constant after 25 minutes and the speed was increased by 5.4 m/min until the patient reached volitional fatigue . Use of this protocol for the exercise test correlates highly ( r=0.92 ) with measured maximal oxygen uptake ( 23 ) . All patients in our study achieved at least 85 % of their age-predicted maximal heart rate ; average maximal heart rates ( SD ) in each age group were 186 11 beats/min for patients 30 to 39 years of age , 179 12 beats/min for those 40 to 49 years of age , 172 13 beats/min for those 50 to 59 years of age , and 162 17 beats/min for those 60 years of age or older . Average maximal heart rates in each age group exceeded the age-predicted rate ( 220 beats/min age in years ) , which indicates that the exercise test can be considered maximal performance . We defined level of fitness by total time on the treadmill at the baseline examination , as in our previous studies ( 20 , 21 ) . Treadmill times were placed in frequency distributions for specific age groups ( 30 to 39 , 40 to 49 , 50 to 59 , or 60 or more years of age ) . The least fit 20 % of the participants in each age group were classified as low fitness , the next 40 % as moderate fitness , and the remaining 40 % as high fitness . The respective cut-points for total treadmill time in the low- , moderate- , and high-fitness groups were 945 seconds or less , 946 to 1259 seconds , and 1260 seconds or more for patients 30 to 39 years of age ; 849 seconds or less , 850 to 1020 seconds , and 1021 seconds or more for patients 40 to 49 years of age ; 750 seconds or less , 751 to 1035 seconds , and 1036 seconds or more for patients 50 to 59 years of age ; and 644 seconds or less , 645 to 953 seconds , and 954 seconds or more for patients 60 years of age or older . These cut-points at the 20th and 60th percentiles to define fitness levels were used in previous studies ( 20 , 21 ) and were selected before analysis for our investigation . However , we calculated these cut-points with patients in the current study , from which unhealthy persons were excluded . Therefore , they differ somewhat from the cut-points derived from the entire cohort of the Aerobics Center Longitudinal Study ( 21 ) . For some analyses , such as the models that included change in fitness from baseline to follow-up , cardiorespiratory fitness was expressed as maximal metabolic units ( metabolic equivalents [ METs ] , calculated as the working metabolic rate/resting metabolic rate ; 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg1 ) achieved on the exercise test . In other analyses , time on the treadmill was used as a continuous variable . Serum sample s were analyzed by using automated techniques in a laboratory that participates in the Centers for Disease Control and Prevention Lipid St and ardization Program . Blood pressure was measured by using auscultatory methods with a mercury sphygmomanometer . We defined high blood pressure as systolic blood pressure of at least 140 mm Hg , diastolic blood pressure of at least 90 mm Hg , or a history of hypertension . Height and weight were measured with a st and ard physician 's scale and stadiometer , and body mass index was calculated as weight in kg/height in m2 . Waist circumference was measured with a st and ard anthropometric tape . Statistical Analysis We used SAS statistical software for data analyses ( 24 ) . The incidence of impaired fasting glucose was calculated for men with normal fasting glucose at baseline , and the incidence of diabetes was based on data from all 8633 patients . For analyses with impaired fasting glucose as the outcome , we excluded 1122 men who had impaired fasting glucose at baseline and an additional 69 men who had normal fasting plasma glucose at baseline but developed diabetes during follow-up . Rates of impaired fasting glucose or diabetes were calculated by dividing the number of incident cases during the study period by the number of person-years over the same period . We defined the study period as the interval between the baseline examination and the last follow-up visit . We used logistic regression to estimate the association between dependent variables and independent variables after adjustment for possible confounding factors . We used general linear models to study the cross-sectional association of fitness level and parental history of diabetes ( 24 , 25 ) . To account for the possible cohort effect of baseline year , we examined the relation between incident cases and baseline year and found no association . We used tests for ordinal linear trend to evaluate the possible relation of higher treadmill time with risk for impaired fasting glucose or diabetes after dividing the sample into the three fitness groups . All P values are two-sided , and those less than 0.05 were considered statistically significant . Role of the Funding Source The funding agencies did not participate in the collection , analysis , or interpretation of data presented in this report or in the decision to su bmi t the manuscript for publication . Results During an average follow-up of 6.1 4.8 years ( range , 1 to 24.8 years ) that included 52 588 person-years , 593 men developed impaired fasting glucose and 149 developed diabetes . Of the men with incident diabetes , 139 ( 93 % ) were not aware of", "BACKGROUND Physical activity has been advocated as an important factor in the primary prevention of non-insulin-dependent diabetes mellitus ( NIDDM ) , but information concerning the specific intensities and duration s that are protective has been unavailable . OBJECTIVE To examine prospect ively the association between self-reported levels of the intensity and duration of physical activities , and cardiorespiratory fitness ( assessed by respiratory gas exchange ) and incident cases of NIDDM ( assessed by the oral glucose tolerance test ) in a population -based sample of 897 middle-aged Finnish men . RESULTS After adjustment for age , baseline glucose values , body mass index , serum triglyceride levels , parental history of diabetes , and alcohol consumption , moderately intense physical activities ( > or = 5.5 metabolic units ) that were undertaken for at least a 40-minute duration per week were associated with a reduced risk of NIDDM ( odds ration [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.22 - 0.88 ) . Activities with less than an intensity of 5.5 metabolic units , regardless of their duration , were not protective . Cardiorespiratory fitness levels greater than 31.0 mL of oxygen per kilogram per minute were protective against NIDDM ( OR , 0.26 ; 95 % CI , 0.08 - 0.82 ) . A subgroup of men at high risk of NIDDM , because they were overweight and were hypertensive and had a positive parental history of NIDDM , who engaged in moderately intense physical activities above the 40-min/wk duration reduced their risk of NIDDM by 64 % compared with men who did not participate in such activities . CONCLUSIONS After adjustment for age , baseline glucose levels , and known risk factors , physical activities with an intensity of 5.5 metabolic units or greater and a duration of 40 minutes or greater per week protected against the development of NIDDM . These protective effects were even more pronounced in a subgroup of men who were at high risk for the development of the disease", "Objectives To explore the extent to which muscular strength in adolescence is associated with all cause and cause specific premature mortality ( < 55 years ) . Design Prospect i ve cohort study . Setting Sweden . Participants 1 142 599 Swedish male adolescents aged 16 - 19 years were followed over a period of 24 years . Main outcome measures Baseline examinations included knee extension , h and grip , and elbow flexion strength tests , as well as measures of diastolic and systolic blood pressure and body mass index . Cox regression was used to estimate hazard ratios for mortality according to muscular strength categories ( tenths ) . Results During a median follow-up period of 24 years , 26 145 participants died . Suicide was a more frequent cause of death in young adulthood ( 22.3 % ) than was cardiovascular diseases ( 7.8 % ) or cancer ( 14.9 % ) . High muscular strength in adolescence , as assessed by knee extension and h and grip tests , was associated with a 20 - 35 % lower risk of premature mortality due to any cause or cardiovascular disease , independently of body mass index or blood pressure ; no association was observed with mortality due to cancer . Stronger adolescents had a 20 - 30 % lower risk of death from suicide and were 15 - 65 % less likely to have any psychiatric diagnosis ( such as schizophrenia and mood disorders ) . Adolescents in the lowest tenth of muscular strength showed by far the highest risk of mortality for different causes . All cause mortality rates ( per 100 000 person years ) ranged between 122.3 and 86.9 for the weakest and strongest adolescents ; corresponding figures were 9.5 and 5.6 for mortality due to cardiovascular diseases and 24.6 and 16.9 for mortality due to suicide . Conclusions Low muscular strength in adolescents is an emerging risk factor for major causes of death in young adulthood , such as suicide and cardiovascular diseases . The effect size observed for all cause mortality was equivalent to that for well established risk factors such as elevated body mass index or blood pressure", "Background In “ Physical Activity Reference for Health Promotion 2013 ” the Japan Ministry of Health , Labour and Welfare publication gives reference values for cardiorespiratory fitness ( CRF ) required for good health . We examined the associations between the CRF reference values and incidence of type 2 diabetes . Methods This prospect i ve cohort study enrolled 4633 nondiabetic Japanese men aged 20 to 39 years at baseline . CRF was measured using the cycle ergometer test , and maximal oxygen uptake was estimated . On the basis of the CRF reference value , participants were classified into 2 groups : those with values less than the reference value ( under-RV ) and those with values equal to or greater than reference value ( over-RV ) . Hazard ratios ( HRs ) and 95 % CIs for incident type 2 diabetes were estimated using a Cox proportional hazards model . Results A total of 266 participants developed type 2 diabetes during the 14 years of follow-up . As compared with the under-RV group , the over-RV group had a significantly lower multivariable-adjusted HR for type 2 diabetes ( HR 0.67 ; 95 % CI , 0.51–0.89 ) . In receiver operating characteristic analysis , the optimal CRF cut-off value for predicting incident type 2 diabetes was 10.8 metabolic equivalents ( sensitivity , 0.64 ; specificity , 0.64 ) , which was close to the CRF reference value of 11.0 metabolic equivalents . Conclusions The reference CRF value appears to be reasonably valid for prevention of type 2 diabetes , especially among Japanese men younger than 40 years . Development of type 2 diabetes can be prevented by maintaining a CRF level above the reference value", "The relative contributions of cardiorespiratory fitness ( CRF ) and body habitus to predict incident type 2 diabetes mellitus ( T2DM ) remain unclear . We prospect ively investigated the relation of CRF and body habitus on the risk of developing T2DM in men . Participants included 3,770 apparently healthy men who initially presented without baseline evidence of diabetes , cardiovascular disease , and hypertension . Participants were divided into 3 groups as normal weight ( 18.5 to 24.9 kg/m(2 ) ) , obese I ( 25.0 to 29.9 kg/m(2 ) ) , and obese II ( ≥30.0 kg/m(2 ) ) . CRF was directly measured by peak oxygen uptake ( VO2peak ) and categorized into unfit and fit cohorts based on the median value of age-specific VO2peak . Diabetes was defined as a glycated hemoglobin > 6.5 % and /or a fasting glucose > 126 mg/dl at baseline and follow-up examinations . During a median follow-up of 5 years , 170 men ( 4.5 % ) developed diabetes . After adjusting for age and fasting glucose , the relative risk and 95 % confidence interval ( CI ) for incident T2DM were 1.52 ( 95 % CI 1.11 to 2.07 ) for obese I and 3.11 ( 95 % CI 1.35 to 7.16 ) for obese II versus normal weight and 0.69 ( 95 % CI 0.51 to 0.95 ) for fit versus unfit . However , these associations were no longer statistically significant after adjusting for potential confounders with VO2peak ( 1.32 ; 95 % CI 0.96 to 1.83 for obese I and 1.61 , 95 % CI 0.64 to 4.06 for obese II vs normal weight ) or body mass index ( 0.75 , 95 % CI 0.54 to 1.05 for fit vs unfit ) . In the joint analysis , obese-unfit men had 1.81 times ( 95 % CI 1.22 to 2.69 ) greater risk of incident T2DM , but obese-fit men were not at increased risk of incident T2DM ( 0.95 , 95 % CI 0.57 to 1.58 ) compared with fit-normal weight men . In conclusion , these results suggest that both CRF and obesity predict the incidence of T2DM independent of potential confounders ; however , CRF appears to attenuate the risk of developing diabetes in obese men", "AIMS To study the glucose disappearance rate and fasting blood glucose as predictors of Type 2 diabetes in a 22.5-year prospect i ve follow-up of 1947 healthy non-diabetic men . SUBJECTS AND METHODS Of a cohort of 2014 Caucasian men , the 1947 who had both fasting blood glucose < 110 mg/dl and an intravenous glucose tolerance test were included . A number of other physiological parameters were also determined at baseline . Multivariate Cox regression analyses were used to investigate the possible significance of the glucose disappearance rate and fasting blood glucose as predictors of Type 2 diabetes . RESULTS After 22.5 years ' follow-up , 143 cases of Type 2 diabetes had developed . Glucose disappearance rate and fasting blood glucose were moderately correlated ( r = -0.32 ) . Men in the lowest quartile of glucose disappearance rate and highest quartile of fasting blood glucose had markedly higher diabetes rates than all other men ( P < 0.0001 ) . After adjusting for each other , age , diabetes heredity , body mass index , physical fitness , triglycerides , cholesterol and blood pressure ( Cox model ) , both glucose disappearance rate and fasting blood glucose remained major predictors of diabetes CONCLUSIONS Glucose disappearance rate and fasting blood glucose are , in spite of low intercorrelation , major long-term predictors of Type 2 diabetes in healthy non-diabetic Caucasian men", "OBJECTIVE To assess the effect of cardiorespiratory fitness on the association between the initiation of statin therapy and incident diabetes . PATIENTS AND METHODS In a prospect i ve observational study , we studied 6519 generally healthy men and 2334 women with two preventive health examinations from December 15 , 1998 through December 18 , 2013 which included measurement of fitness levels , statin therapy , risk factors for diabetes , and incident diabetes . RESULTS 93 cases of incident diabetes occurred during an average follow-up of 3.0 years . After multivariable adjustment , an increased odds of incident diabetes with statin use was observed in those patients with impaired fasting glucose at baseline ( odds ratio [ OR ] : 2.15 , [ 95 % CI:1.26 to 3.67 ] ) , but not among individuals with normal glucose levels ( OR:1.85 , [ 95 % CI : 0.76 to 4.52 ] ) . Cardiorespiratory fitness attenuated but did not eliminate the increased risk of incident diabetes with statin use . CONCLUSION In a population of relatively healthy patients , statin use was not associated with incident diabetes in patients with normal fasting glucose at baseline . However , it was associated with incident diabetes in those patients with impaired fasting glucose at baseline , though this risk was substantially reduced by increasing fitness . In addition , increasing cardiorespiratory fitness was inversely associated with incident diabetes whether or not a patient was treated with a statin" ]

[ "20362457", "24327455", "27959712", "29708851", "16872965", "15564545", "26282605", "11996262" ]

[ "Slower progression of atherosclerosis in vein grafts harvested with 'no touch' technique compared with conventional harvesting technique in coronary artery bypass grafting: an angiographic and intravascular ultrasound study.", "Pedicled no-touch saphenous vein graft harvest limits vascular smooth muscle cell activation: the PATENT saphenous vein graft study.", "Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts.", "Radial‐Artery or Saphenous‐Vein Grafts in Coronary‐Artery Bypass Surgery", "Harvesting the saphenous vein with surrounding tissue for CABG provides long-term graft patency comparable to the left internal thoracic artery: results of a randomized longitudinal trial.", "A randomized comparison of radial-artery and saphenous-vein coronary bypass grafts.", "The no-touch saphenous vein for coronary artery bypass grafting maintains a patency, after 16 years, comparable to the left internal thoracic artery: A randomized trial.", "Improved patency in vein grafts harvested with surrounding tissue: results of a randomized study using three harvesting techniques." ]

[ "OBJECTIVES In a long-term r and omised coronary artery bypass grafting ( CABG ) study , the patency rate using a new ' no touch ' ( NT ) vein-graft preparation technique was superior to the conventional ( C ) technique . This cineangiographic and intravascular ultrasound ( IVUS ) sub study examined possible mechanisms . METHODS A total of 45 patients ( 118 grafts ) in the NT group and 46 patients ( 112 grafts ) in the C group had patent grafts at short-term follow-up after 18 months . Thirty-seven patients ( 91 grafts ) in the NT group and 37 patients ( 77 grafts ) in the C group had patent grafts at long-term follow-up after 8.5 years , and were evaluated on a scale from 0 ( normal ) to 2 ( significant stenosis ) by cineangiogram . IVUS was performed in 15 NT grafts and 14 C grafts in the short-term follow-up , and 27 NT grafts and 26 C grafts in the long-term follow-up , in grafts considered normal by the cineangiogram . The grafts were evaluated with respect to lumen volume , intimal thickness , incidence of plaque and plaque components . RESULTS In the short-term follow-up , the cineangiogram showed more normal grafts ( 89.0 % in the NT group compared with 75.0 % in the C group ) , and the number of grafts with stenosis was 11.0 % in the NT group compared with 25.0 % in the C group ( p=0.006 ) . IVUS showed less mean intimal thickness ( 0.43 (0.07)mm vs 0.52 (0.08)mm ; p=0.03 ) , less grafts with considerable intimal hyperplasia ( ≥ 0.9 mm ; 20 % vs 78.6 % ; p=0.011 ) and fewer patients with considerable hyperplasia ( ≥ 0.9 mm ; 25 % vs 100 % ; p=0.007 ) . In the long-term follow-up , the cineangiogram showed more normal grafts , with 91.2 % in the NT group compared with 83.1 % in the C group ; there were fewer grafts with significant stenosis , with 7.7 % in the NT group compared with 15.6 % in the C group ( p=0.14 ) . IVUS showed fewer grafts containing multiple plaques ( 14.8 % vs 50 % ; p=0.008 ) , less advanced plaque with lipid ( 11.8 % vs 63.9 % ; p=0.0004 ) and less maximal plaque thickness ( 1.04 (0.23)mm vs 1.32 (0.25)mm ; p=0.02 ) in the NT group compared with the C group . CONCLUSION The superior long-term patency rate using the NT vein-graft technique at CABG could be explained by a significantly slower progression of atherosclerosis", "OBJECTIVE Neointimal hyperplasia secondary to vascular smooth muscle cell ( VSMC ) activation limits the long-term patency of saphenous vein grafts ( SVGs ) . We compared markers of vascular injury and VSMC activation in SVGs harvested using the pedicled ' no-touch ' ( NT ) vs the conventional ( CON ) technique . METHODS Patients undergoing coronary artery bypass surgery were enrolled in the PATENT SVG trial ( clinical trials.gov NCT01488084 ) . Patients were r and omly allocated to have SVGs harvested with the NT technique from one leg and the CON method from the other . SVG segments underwent morphometry , histological and electron microscopy assessment s and transcript measurements of VSMC activation and differentiation markers . Leg wound functional recovery and harvest site complications were assessed using a quality -of-life question naire . RESULTS A total of 17 patients ( 65.3 ± 7.3 years ) were enrolled . SVGs harvested using the NT vs CON technique exhibited preserved intimal , medial and adventitial architecture . CON harvest was associated with greater medial Kruppel-like factor 4 transcript levels ( 0.26 ± 0.05 vs 0.11 ± 0.02 , P < 0.05 ) . CON sample s had significantly lower medial serum response factor ( 0.53 ± 0.11 vs 1.44 ± 0.50 , P < 0.05 ) and myocardin ( 0.59 ± 0.08 vs 1.33 ± 0.33 , P < 0.05 ) transcript levels . MicroRNA-145 , an inhibitor of VSMC activation and differentiation , was higher in the NT vs CON sample s ( 1.84 ± 1.03 vs 0.50 ± 0.19 , P < 0.05 ) . Leg assessment scores were worse in the NT legs at 3 months , but similar to CON scores at 12 months . CONCLUSIONS SVGs harvested using the ' NT ' technique exhibit an early molecular and morphological pattern consistent with decreased VSMC activation compared with CON harvesting . Functional leg recovery was similar in both groups at 12 months . Larger studies are required to corroborate these findings", "BACKGROUND The use of bilateral internal thoracic ( mammary ) arteries for coronary-artery bypass grafting ( CABG ) may improve long-term outcomes as compared with the use of a single internal-thoracic-artery plus vein grafts . METHODS We r and omly assigned patients scheduled for CABG to undergo single or bilateral internal-thoracic-artery grafting in 28 cardiac surgical centers in seven countries . The primary outcome was death from any cause at 10 years . The composite of death from any cause , myocardial infa rct ion , or stroke was a secondary outcome . Interim analyses were prespecified at 5 years of follow-up . RESULTS A total of 3102 patients were enrolled ; 1554 were r and omly assigned to undergo single internal-thoracic-artery grafting ( the single-graft group ) and 1548 to undergo bilateral internal-thoracic-artery grafting ( the bilateral-graft group ) . At 5 years of follow-up , the rate of death was 8.7 % in the bilateral-graft group and 8.4 % in the single-graft group ( hazard ratio , 1.04 ; 95 % confidence interval [ CI ] , 0.81 to 1.32 ; P=0.77 ) , and the rate of the composite of death from any cause , myocardial infa rct ion , or stroke was 12.2 % and 12.7 % , respectively ( hazard ratio , 0.96 ; 95 % CI , 0.79 to 1.17 ; P=0.69 ) . The rate of sternal wound complication was 3.5 % in the bilateral-graft group versus 1.9 % in the single-graft group ( P=0.005 ) , and the rate of sternal reconstruction was 1.9 % versus 0.6 % ( P=0.002 ) . CONCLUSIONS Among patients undergoing CABG , there was no significant difference between those receiving single internal-thoracic-artery grafts and those receiving bilateral internal-thoracic-artery grafts with regard to mortality or the rates of cardiovascular events at 5 years of follow-up . There were more sternal wound complications with bilateral internal-thoracic-artery grafting than with single internal-thoracic-artery grafting . Ten-year follow-up is ongoing . ( Funded by the British Heart Foundation and others ; ART Current Controlled Trials number , IS RCT N46552265 . )", "BACKGROUND The use of radial‐artery grafts for coronary‐artery bypass grafting ( CABG ) may result in better postoperative outcomes than the use of saphenous‐vein grafts . However , r and omized , controlled trials comparing radial‐artery grafts and saphenous‐vein grafts have been individually underpowered to detect differences in clinical outcomes . We performed a patient‐level combined analysis of r and omized , controlled trials to compare radial‐artery grafts and saphenous‐vein grafts for CABG . METHODS Six trials were identified . The primary outcome was a composite of death , myocardial infa rct ion , or repeat revascularization . The secondary outcome was graft patency on follow‐up angiography . Mixed‐effects Cox regression models were used to estimate the treatment effect on the outcomes . RESULTS A total of 1036 patients were included in the analysis ( 534 patients with radial‐artery grafts and 502 patients with saphenous‐vein grafts ) . After a mean ( ±SD ) follow‐up time of 60±30 months , the incidence of adverse cardiac events was significantly lower in association with radial‐artery grafts than with saphenous‐vein grafts ( hazard ratio , 0.67 ; 95 % confidence interval [ CI ] , 0.49 to 0.90 ; P=0.01 ) . At follow‐up angiography ( mean follow‐up , 50±30 months ) , the use of radial‐artery grafts was also associated with a significantly lower risk of occlusion ( hazard ratio , 0.44 ; 95 % CI , 0.28 to 0.70 ; P<0.001 ) . As compared with the use of saphenous‐vein grafts , the use of radial‐artery grafts was associated with a nominally lower incidence of myocardial infa rct ion ( hazard ratio , 0.72 ; 95 % CI , 0.53 to 0.99 ; P=0.04 ) and a lower incidence of repeat revascularization ( hazard ratio , 0.50 ; 95 % CI , 0.40 to 0.63 ; P<0.001 ) but not a lower incidence of death from any cause ( hazard ratio , 0.90 ; 95 % CI , 0.59 to 1.41 ; P=0.68 ) . CONCLUSIONS As compared with the use of saphenous‐vein grafts , the use of radial‐artery grafts for CABG result ed in a lower rate of adverse cardiac events and a higher rate of patency at 5 years of follow‐up . ( Funded by Weill Cornell Medicine and others .", "OBJECTIVE Conventional harvesting of the saphenous vein in coronary artery bypass surgery produces vessel damage that contributes to graft failure . A novel \" no touch \" technique provides high short- and long-term patency rates . METHOD This r and omized longitudinal trial compares graft patency of two patient groups undergoing coronary artery bypass surgery . Conventional : 52 patients had their veins stripped , distended , and stored in saline solution . No-touch : 52 patients had veins removed with surrounding tissue , not distended , and stored in heparinized blood . Angiographic assessment was performed at mean time 18 months after the operation in 46 patients in the conventional group and 45 patients in the no-touch group and repeated at mean time 8.5 years in 37 patients from both groups . RESULTS The distribution of the grafts to the recipient coronary arteries regarding their size and quality was similar in both groups . The angiographic assessment at 18 months postoperatively showed 89 % conventional versus 95 % no-touch grafts were patent . Repeated angiography at 8.5 years showed a patency rate for the conventional group of 76 % and 90 % for the no-touch group ( P = .01 ) . The multivariate analysis showed that the most important surgical factors for graft patency were the technique of harvesting ( odds ratio= 3.7 , P = .007 ) for the no-touch versus the conventional technique and the vein quality before implantation ( odds ratio = 3.2 , P = .007 ) for veins that were of good quality . By comparison the patency of the thoracic artery grafts was 90 % . CONCLUSION Harvesting the saphenous vein with surrounding tissue provides high short- and long-term patency rates comparable to the left internal thoracic artery", "BACKGROUND In the past decade , the radial artery has frequently been used for coronary bypass surgery despite concern regarding the possibility of graft spasm . Graft patency is a key predictor of long-term survival . We therefore sought to determine the relative patency rate of radial-artery and saphenous-vein grafts in a r and omized trial in which we controlled for bias in the selection of patients and vessels . METHODS We enrolled 561 patients at 13 centers . The left internal thoracic artery was used to bypass the anterior circulation . The radial-artery graft was r and omly assigned to bypass the major vessel in either the inferior ( right coronary ) territory or the lateral ( circumflex ) territory , with the saphenous-vein graft used for the opposing territory ( control ) . The primary end point was graft occlusion , determined by angiography 8 to 12 months postoperatively . RESULTS Angiography was performed at one year in 440 patients : 8.2 percent of radial-artery grafts and 13.6 percent of saphenous-vein grafts were completely occluded ( P=0.009 ) . Diffuse narrowing of the graft ( the angiographic \" string sign \" ) was present in 7.0 percent of radial-artery grafts and only 0.9 percent of saphenous-vein grafts ( P=0.001 ) . The absence of severe native-vessel stenosis was associated with an increased risk of occlusion of the radial-artery graft and diffuse narrowing of the graft . Harvesting of the radial artery was well tolerated . CONCLUSIONS Radial-artery grafts are associated with a lower rate of graft occlusion at one year than are saphenous-vein grafts . Because the patency of radial-artery grafts depends on the severity of native-vessel stenosis , such grafts should preferentially be used for target vessels with high- grade lesions", "OBJECTIVES This study investigates whether the no-touch ( NT ) vein graft , at a mean time of 16 years , maintains a significantly higher patency rate than conventional ( C ) vein grafts and still has patency comparable to that of the left internal thoracic artery ( LITA ) . METHODS A total of 156 patients accepted for coronary artery bypass grafting were r and omly allocated to 1 of 3 groups . In the C group , the saphenous vein ( SV ) was stripped and distended . In the intermediate group , the SV was stripped but not distended . In the NT group , the SV was neither stripped nor distended , but rather harvested with a fat pedicle . This study is an angiographic follow-up of the C and NT groups , at a mean time of 16 years postoperatively . RESULTS Fifty-four patients were included ( C group = 27 ; NT group = 27 ) . In all , 72 and 75 vein grafts were completed in groups C and NT , respectively . Crude SV graft patency was 64 % in the C group versus 83 % in the NT group ( P = .03 ) , which was similar to the patency of the LITA ( 88 % ) . The harvesting technique had a major impact on the patency with a hazard ratio for occlusion of 1.83 for the C group ( P = .04 ) . CONCLUSIONS Harvesting the SV with the NT technique conferred , at a mean time of 16 years , a significantly higher patency than the conventional technique that was still comparable to that of the LITA", "BACKGROUND The technique of harvesting the saphenous vein for coronary artery bypass grafting influences the fate of vein grafts . The patency rate of a novel \" no-touch \" technique in which the vein is harvested with a pedicle of surrounding tissue and not distended was compared with two other techniques . METHODS One hundred fifty-six patients who underwent coronary artery bypass grafting were r and omized to three saphenous vein harvesting groups : group C (conventional)--the vein was stripped , distended , and stored in saline ; group I (intermediate)--the vein was stripped , local application of papaverine was used instead of distention , and the vessel was then stored in heparinized blood ; and group NT (no-touch)--the vein was harvested with surrounding tissue , not distended , and stored in heparinized blood . Surgical and clinical factors that might influence graft occlusion were recorded . One hundred twenty-seven vein grafts in group C , 116 in group I , and 124 in group NT , as well as 118 left internal mammary artery grafts , were angiographically assessed at 18 months mean follow-up time . RESULTS The vein graft patency was 88.9 % in group C , 86.2 % in group I , and 95.4 % in group NT . There was a statistically significant difference between the patency of the single-vein grafts in NT and the other two groups ( p = 0.025 ) . The higher the flow , the better the patency irrespective of the technique used . A higher attrition rate was found in vein segments taken from the knee area in group I. Poor vein quality affected patency in all groups . Forty-seven of all 51 sequential grafts ( 92.2 % ) were patent . The patency of left internal mammary artery grafts was 108 of 118 ( 91.5 % ) . CONCLUSIONS We conclude that preservation of the surrounding tissue of the saphenous vein using this no-touch technique abolishes venospasm intraoperatively and plays an important role in maintaining vein graft function and patency" ]

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[ "Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial", "Early dexamethasone treatment for septic shock patients: a prospective randomized clinical trial.", "The influence of competing-risks setting on the choice of hypothesis test for treatment effect.", "Undue reliance on I2 in assessing heterogeneity may mislead", "How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis", "Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine", "Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock*", "Immunologic and hemodynamic effects of \"low-dose\" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study.", "Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.", "Prednisolone Dose-Dependently Influences Inflammation and Coagulation during Human Endotoxemia1", "Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock*", "The Cardiopulmonary Response to Massive Doses of Steroids in Patients with Septic Shock", "Bayesian statistical inference enhances the interpretation of contemporary randomized controlled trials.", "The evidence provided by a single trial is less reliable than its statistical analysis suggests.", "Ineffectiveness of high-dose methylprednisolone in preventing parenchymal lung injury and improving mortality in patients with septic shock.", "Triple anti-TNF-alpha therapy in early sepsis: a preliminary report.", "Reversal of late septic shock with supraphysiologic doses of hydrocortisone.", "Hydrocortisone therapy for patients with septic shock.", "Effectiveness of betamethasone in management of severe infections. A double-blind study.", "Low-dose hydrocortisone during severe sepsis: Effects on microalbuminuria", "The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study.", "Steroids in the Treatment of Clinical Septic Shock", "Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.", "A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock." ]

[ "Abstract Introduction Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock . The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered . Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach . Methods In this prospect i ve r and omized study , we compared the blood glucose profiles , insulin requirements , amount of nursing workload needed , and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose ( 200 mg/day ) . Duration of hydrocortisone treatment was five days . Results The mean blood glucose levels were similar in the two groups , but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy ( 15.7 ± 8.5 versus 10.5 ± 8.6 episodes per patient , p = 0.039 ) . Also , more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group ( 4.7 ± 2.2 versus 3.4 ± 1.9 adjustments per patient per day , p = 0.038 ) . Hypoglycemic episodes were rare in both groups . No difference was seen in shock reversal . ConclusionS trict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion . This approach also reduces nursing workload needed to maintain tight blood glucose control . Trial Registration Number IS RCT", "CONTEXT AND OBJECTIVE Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome ( MODS ) and death . Our purpose was to investigate the efficacy of early administration of dexamethasone for patients with septic shock , with the aim of halting the progression towards MODS and death . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , single-center study , developed in a surgical intensive care unit at Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo . METHODS The study involved 29 patients with septic shock . All eligible patients were prospect ively r and omized to receive either a dose of 0.2 mg/kg of dexamethasone ( group D ) or placebo ( group P ) , given three times at intervals of 36 hours . The patients were monitored over a seven-day period by means of the sequential organ failure assessment score . RESULTS Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group ( p = 0.043 ) . Seven-day mortality was 67 % in group P ( 10 out of 15 ) and 21 % in group D ( 3 out of 14 ) ( relative risk = 0.31 , 95 % confidence interval 0.11 to 0.88 ) . Dexamethasone enhanced the effects of vasopressor drugs . CONCLUSIONS Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality", "There is considerable debate regarding the choice of test for treatment difference in a r and omized clinical trial in the presence of competing risks . This question arose in the study of st and ard and new antiepileptic drugs ( SANAD ) trial comparing new and st and ard antiepileptic drugs . This paper provides simulation results for the log-rank test comparing cause-specific hazard rates and Gray 's test comparing cause-specific cumulative incidence curves . To inform the analysis of the SANAD trial , competing-risks setting s were considered where both events are of interest , events may be negatively correlated , and the degree of correlation may differ in the 2 treatment groups . In setting s where there are effects in opposite directions for the 2 event types , a likely situation for the SANAD trial , Gray 's test has greater power to detect treatment differences than log-rank analysis . For the epilepsy application , conclusions were qualitatively similar for both log-rank and Gray 's tests", "Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose", "Context Clinicians rely on systematic review s for current , evidence -based information . Contribution This survival analysis of 100 meta-analyses indexed in ACP Journal Club from 1995 to 2005 found that new evidence that substantively changed conclusions about the effectiveness or harms of therapies arose frequently and within relatively short time periods . The median survival time without substantive new evidence for the meta-analyses was 5.5 years . Significant new evidence was already available for 7 % of the review s at the time of publication and became available for 23 % within 2 years . Implication Clinical ly important evidence that alters conclusions about the effectiveness and harms of treatments can accumulate rapidly . The Editors Systematic review s have become increasingly common in recent years ( 1 ) and are recommended by many as the best sources of evidence to guide both clinical decisions ( 2 ) and health care policy ( 3 ) . For systematic review s to fulfill these roles , their findings must remain relatively stable for at least several years or effective mechanisms must exist for alerting end users to important changes in evidence . Yet , surprisingly little research has assessed the extent to which systematic review s become out of date or the rate at which this occurs ( 47 ) . Some organizations , such as the Cochrane Collaboration , recommend updating systematic review s every 2 years , but few empirical data guide this or other recommendations about updating . We sought to determine how quickly systematic review s meet explicitly defined criteria for changes in evidence of sufficient importance to warrant updating . We also sought to identify predictors of survival time , the time to such important changes in evidence . Survival time might vary depending on many factors , including the type of question posed by the original review ( for example , therapeutic or diagnostic ) , the types of studies included ( for example , r and omized trials or observational studies ) , and whether the systematic review provided quantitative synthesis . To limit such variation , we focused on systematic review s of r and omized , controlled trials that evaluated therapeutic benefit or harm by providing quantitative synthesis ( meta- analysis ) for at least 1 outcome . Methods Study Design and Sample We used a quasi-r and om process ( alphabetical sort order by author ) to select 100 systematic review s that were indexed in ACP Journal Club with an accompanying commentary between January 1995 and December 2005 ( with a search date no later than 31 December 2004 to ensure at least 1 full year for new evidence to appear ) . We chose this sampling frame because ACP Journal Club selects systematic review s that meet explicit quality st and ards and are deemed directly relevant to clinical practice ( 8) . We regarded the sample size of 100 as sufficiently large to achieve suitably narrow confidence intervals and to permit evaluation of up to 5 potential predictors of survival . Eligibility Criteria Eligible review s evaluated the benefit or harm of a specific drug , class of drug , device , or procedure ( invasive procedure or surgery ) and included r and omized or quasi-r and omized , controlled trials . We excluded evaluations of alternative and complementary medicines because the stability of review s of such therapies might differ substantially from review s of conventional therapies . We required that review s provide a point estimate and 95 % confidence interval for at least 1 outcome in the form of a relative risk , odds ratio , or absolute risk difference for binary outcomes and weighted mean differences for continuous outcomes . We excluded meta-analyses of individual-patient data , meta-regressions , and indirect meta-analyses because of the difficulty of determining whether new data would alter previous quantitative results . Two team members independently assessed eligibility , with disagreements resolved by consensus involving a third review er . When more than 1 review on the same topic was identified , only the earliest was included . Search ing For each review , search es for new trials included identifying new systematic review s on the same topic , su bmi tting relevant content terms to the Clinical Queries function in Ovid , applying the Related Articles function in PubMed to the 3 largest and the 3 most recent trials in the original review ( up to 6 trials in total ) , and using Scopus ( www . scopus .com/ scopus /home.url ) to identify new r and omized trials that cited the original review . When these search strategies yielded no eligible new trials , we conducted more comprehensive electronic search es and review ed relevant chapters in such sources as Clinical Evidence and UpTo Date to ensure that we had not missed new trials . Team members who had background s in both medicine and clinical research screened citations retrieved by the preceding methods to identify trials that would have met the inclusion criteria in the original review . Retrieved articles were screened in chronological order to ascertain quantitative or qualitative signals for the need for updating . The review protocol stopped when any criteria for updating were met . Each systematic review was discussed in detail , with the final statussignal for updating was or was not detectedadjudicated by consensus ( Figure 1 ) . Figure 1 . Overall process for determining updating status . ACP Journal Club Signals for the Need to Up date Systematic Review s In design ing criteria for comparing new findings with those in a previous review , we adapted methods used by other investigators to address similar problems with comparing 2 sets of results relating to the same question ( 913 ) , such as r and omized and nonr and omized studies of the same intervention . These investigators identified conflicting findings among different publications using a combination of quantitative thresholds for differences in effect magnitude and qualitative judgments about the language used to describe the results . We have similarly conceptualized quantitative and qualitative signals of potential changes in evidence that are sufficiently important to warrant updating previous systematic review s. Quantitative Signals Quantitative signals consisted of a change in statistical significance or relative change in effect magnitude of at least 50 % . We restricted these changes to those involving 1 of the primary outcomes of the original review or any mortality outcome . We also ignored trivial changes in statistical significance when the original and up date d meta-analytic results both had P values between 0.04 and 0.06so that quantitative signals of changes in evidence would represent robust indicators of the need to up date previous review s. Quantitative signals were detected by combining data from eligible new trials with the previous results using a fixed-effects approach . Use of fixed-effect models allowed pooling of the new trials with the previous meta-analytic result , as opposed to having to obtain original data from all of the included trials in each of 100 systematic review s. Although r and om-effects models are usually preferred to avoid spurious precision in the face of heterogeneity , our goal was to detect potential changes in evidence that would warrant a formal up date , not produce exact estimates of the up date d results . Qualitative Signals Qualitative signals included new information about harm sufficient to affect clinical decision making , important caveats to the original results , emergence of a superior alternate therapy , and important changes in certainty or direction of effect . Qualitative signals were detected by using explicit criteria for comparing the language in the original review with descriptions of findings in new systematic review s that addressed the same topic , pivotal trials , clinical practice guidelines , or recent editions of major textbooks ( for example , UpTo Date ) . Pivotal trials were defined as trials that had a sample size at least 3 times larger than that of the previous largest trial or were published in 1 of the 5 highest-impact general medical journals ( The New Engl and Journal of Medicine , Lancet , Journal of the American Medical Association , Annals of Internal Medicine , and the British Medical Journal ) . We defined 2 levels of importance for qualitative signals : potentially invalidating changes in evidence , which would make one no longer want clinicians or policymakers to base decisions on the original findings ( such as a pivotal trial that characterized treatment effectiveness in terms opposite of those in the original systematic review ) , and major changes in evidence , which would affect clinical decision making in important ways without invalidating the previous results ( such as the identification of patient population s for whom treatment is more or less beneficial ) . Major changes also included differing characterizations of effectiveness that were less extreme than those for potentially invalidating signals but that would still affect clinical decision making ( for example , a change from possibly beneficial to definitely beneficial ) . Of importance , such characterizations as possibly effective , probably effective , and promising , were all categorized as possibly effective . Thus , qualitative signals for changes in evidence captured substantive differences in the characterization of treatment effects , not merely semantic differences . Full definitions for each of the specific signals can be found at www.ohri.ca/UpdatingSystRevs . Data Collection For each review , we characterized the clinical content area , eligibility criteria for included trials , definitions of reported outcomes , number of included trials and participants , meta-analytic result for each outcome , identification of statistical heterogeneity , and excerpted quotations of the authors ' characterizations of the main results . We also abstract ed whether a given outcome was explicitly identified as 1 of the primary or main outcomes . We discounted identification of more than 3 such outcomes as inconsistent with the", "Objective : To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients . Participants : A multidisciplinary , multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine . In addition , international experts in endocrinology were invited to participate . Design / Methods : The task force members review ed published literature and provided expert opinion from which the consensus was derived . The consensus statements were developed using a modified Delphi methodology . The strength of each recommendation was quantified using the Modified GRADE system , which classifies recommendations as strong ( grade 1 ) or weak ( grade 2 ) and the quality of evidence as high ( grade A ) , moderate ( grade B ) , or low ( grade C ) based on factors that include the study design , the consistency of the results , and the directness of the evidence . Results : The task force coined the term critical illness – related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness . Critical illness – related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response . Critical illness – related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents , particularly in the setting of sepsis . At this time , the diagnosis of tissue corticosteroid resistance remains problematic . Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 & mgr;g/dL after adrenocorticotrophic hormone ( 250 & mgr;g ) administration or a r and om total cortisol of < 10 & mgr;g/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome ( Pao2/Fio2 of < 200 and within 14 days of onset ) . The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids . Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day ( 10 mg/hr ) for ≥7 days is recommended for septic shock . Methylprednisolone in a dose of 1 mg·kg−1·day−1 for ≥14 days is recommended in patients with severe early acute respiratory distress syndrome . Glucocorticoids should be weaned and not stopped abruptly . Reinstitution of treatment should be considered with recurrence of signs of sepsis , hypotension , or worsening oxygenation . Dexamethasone is not recommended to treat critical illness – related corticosteroid insufficiency . The role of glucocorticoids in the management of patients with community-acquired pneumonia , liver failure , pancreatitis , those undergoing cardiac surgery , and other groups of critically ill patients requires further investigation . Conclusion : Evidence -linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary , multispecialty task force", "Objective : Vasopressin and corticosteroids are often added to support cardiovascular dysfunction in patients who have septic shock that is nonresponsive to fluid resuscitation and norepinephrine infusion . However , it is unknown whether vasopressin treatment interacts with corticosteroid treatment . Design : Post hoc sub study of a multicenter r and omized blinded controlled trial of vasopressin vs. norepinephrine in septic shock . Setting : Twenty-seven Intensive Care Units in Canada , Australia , and the United States . Patients : Seven hundred and seventy-nine patients who had septic shock and were ongoing hypotension requiring at least 5 & mgr;g/min of norepinephrine infusion for 6 hours . Interventions : Patients were r and omized to blinded vasopressin ( 0.01–0.03 units/min ) or norepinephrine ( 5–15 & mgr;g/min ) infusion added to open-label vasopressors . Corticosteroids were given according to clinical judgment at any time in the 28-day postr and omization period . Measurements : The primary end point was 28-day mortality . We tested for interaction between vasopressin treatment and corticosteroid treatment using logistic regression . Secondary end points were organ dysfunction , use of open-label vasopressors and vasopressin levels . Main Results : There was a statistically significant interaction between vasopressin infusion and corticosteroid treatment ( p = 0.008 ) . In patients who had septic shock and were also treated with corticosteroids , vasopressin , compared to norepinephrine , was associated with significantly decreased mortality ( 35.9 % vs. 44.7 % , respectively , p = 0.03 ) . In contrast , in patients who did not receive corticosteroids , vasopressin was associated with increased mortality compared with norepinephrine ( 33.7 % vs. 21.3 % , respectively , p = 0.06 ) . In patients who received vasopressin infusion , use of corticosteroids significantly increased plasma vasopressin levels by 33 % at 6 hours ( p = 0.006 ) to 67 % at 24 hours ( p = 0.025 ) compared with patients who did not receive corticosteroids . Conclusions : There is a statistically significant interaction between vasopressin and corticosteroids . The combination of low-dose vasopressin and corticosteroids was associated with decreased mortality and organ dysfunction compared with norepinephrine and corticosteroids", "Within the last few years , increasing evidence of relative adrenal insufficiency in septic shock evoked a re assessment of hydrocortisone therapy . To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation , 40 patients with septic shock were r and omized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 ( n = 20 ) or placebo ( n = 20 ) , followed by the opposite medication until Day 6 . Hydrocortisone infusion induced an increase of mean arterial pressure , systemic vascular resistance , and a decline of heart rate , cardiac index , and norepinephrine requirement . A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support . The inflammatory response ( interleukin-6 and interleukin-8 ) , endothelial ( soluble E-selectin ) and neutrophil activation ( expression of CD11b , CD64 ) , and antiinflammatory response ( soluble tumor necrosis factor receptors I and II and interleukin-10 ) were attenuated . In peripheral blood monocytes , human leukocyte antigen-DR expression was only slightly depressed , whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased . Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects . In conclusion , hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression", "We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications . In a multicenter trial , patients admitted to the Intensive Care Unit ( ICU ) with severe community-acquired pneumonia received protocol -guided antibiotic treatment and were r and omly assigned to hydrocortisone infusion or placebo . Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days . Primary end-points of the study were improvement in Pa(O(2)):FI(O(2 ) ) ( Pa(O(2)):FI(O(2 ) ) > 300 or > /= 100 increase from study entry ) and multiple organ dysfunction syndrome ( MODS ) score by Study Day 8 and reduction in delayed septic shock . Forty-six patients entered the study . At study entry , the hydrocortisone group had lower Pa(O(2)):FI(O(2 ) ) , and higher chest radiograph score and C-reactive protein level . By Study Day 8 , treated patients had , compared with control subjects , a significant improvement in Pa(O(2)):FI(O(2 ) ) ( p = 0.002 ) and chest radiograph score ( p < 0.0001 ) , and a significant reduction in C-reactive protein levels ( p = 0.01 ) , MODS score ( p = 0.003 ) , and delayed septic shock ( p = 0.001 ) . Hydrocortisone treatment was associated with a significant reduction in length of hospital stay ( p = 0.03 ) and mortality ( p = 0.009 )", "The effects of steroids on the outcome of sepsis are dose dependent . Low doses appear to be beneficial , but high doses do not improve outcome for reasons that are insufficiently understood . The effects of steroids on systemic inflammation as a function of dose have not previously been studied in humans . To determine the effects of increasing doses of prednisolone on inflammation and coagulation in humans exposed to LPS , 32 healthy males received prednisolone orally at doses of 0 , 3 , 10 , or 30 mg ( n = 8 per group ) at 2 h before i.v . injection of Escherichia coli LPS ( 4 ng/kg ) . Prednisolone dose-dependently inhibited the LPS-induced release of cytokines ( TNF-α and IL-6 ) and chemokines ( IL-8 and MCP-1 ) , while enhancing the release of the anti-inflammatory cytokine IL-10 . Prednisolone attenuated neutrophil activation ( plasma elastase levels ) and endothelial cell activation ( von Willebr and factor ) . Most remarkably , prednisolone did not inhibit LPS-induced coagulation activation , measured by plasma concentrations of thrombin-antithrombin complexes , prothrombin fragment F1 + 2 , and soluble tissue factor . In addition , activation of the fibrinolytic pathway ( tissue-type plasminogen activator and plasmin-α2-antiplasmin complexes ) was dose-dependently enhanced by prednisolone . These data indicate that prednisolone dose-dependently and differentially influences the systemic activation of different host response pathways during human endotoxemia", "Objectives : To investigate the effect of low-dose hydrocortisone on time to shock reversal , the cytokine profile , and its relation to adrenal function in patients with early septic shock . Design : Prospect i ve , r and omized , double-blind , single-center study . Setting : Medical intensive care unit of a university hospital . Patients : Forty-one consecutive patients with early hyperdynamic septic shock . Interventions : After inclusion and a short adrenocorticotropic hormone test , all patients were r and omized to receive either low-dose hydrocortisone ( 50-mg bolus followed by a continuous infusion of 0.18 mg/kg body of weight/hr ) or matching placebo . After shock reversal , the dose was reduced to 0.06 mg/kg/hr and afterward slowly tapered . Severity of illness was estimated using Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score . Measurements and Main Results : Time to cessation of vasopressor support ( primary end point ) was significantly shorter in hydrocortisone-treated patients compared with placebo ( 53 hrs vs. 120 hrs , p < .02 ) . This effect was more profound in patients with impaired adrenal reserve . Irrespective of endogenous steroid production , cytokine production was reduced in the treatment group with lower plasma levels of interleukin-6 and a diminished ex vivo lipopolysaccharide-stimulated interleukin-1 and interleukin-6 production . Interleukin-10 levels were unaltered . Adverse events were not more frequent in the treatment group . Conclusions : Treatment with low-dose hydrocortisone accelerates shock reversal in early hyperdynamic septic shock . This was accompanied by reduced production of proinflammatory cytokines , suggesting both hemodynamic and immunomodulatory effects of steroid treatment . Hemodynamic improvement seemed to be related to endogenous cortisol levels , whereas immune effects appeared to be independent of adrenal reserve", "The effects of massive doses of steroids on septic shock were tested in 48 patients being treated for extensive cellulitis , wet gangrene , or severe peritonitis . From diagnosis until maximum weight gain ( average , 47 hours ) , they received an average of 17.7 L of crystalloid solution and 1.0 L of blood and voided 3.1 L of urine . Of the 48 patients , 23 were selected in r and om fashion to receive dexamethasone sodium phosphate ( 6 mg/kg ) over 48 hours . The average age ( 55 years ) , duration of shock ( 36 minutes ) , and insult were similar for both groups . Each group received similar volumes of fluid and blood . Steroid therapy was associated with a statistically significant rise in diastolic pressure ( 88 v 78 mm Hg ) , mean arterial pressure ( 105 v 95 mm Hg ) , and central venous pressure ( 16 v 10 cm H2O ) . Concomitant blood volume was lower in patients treated with steroids ( 5.2 v 6.1 L ) . All differences between the two groups disappeared after 48 hours when steroid therapy was discontinued . No differences were noted in morbidity and five patients in each group died", "OBJECTIVE R and omized trials generally use \" frequentist \" statistics based on P-values and 95 % confidence intervals . Frequentist methods have limitations that might be overcome , in part , by Bayesian inference . To illustrate these advantages , we re-analyzed r and omized trials published in four general medical journals during 2004 . STUDY DESIGN AND SETTING We used Medline to identify r and omized superiority trials with two parallel arms , individual-level r and omization and dichotomous or time-to-event primary outcomes . Studies with P<0.05 in favor of the intervention were deemed \" positive \" ; otherwise , they were \" negative . \" We used several prior distributions and exact conjugate analyses to calculate Bayesian posterior probabilities for clinical ly relevant effects . RESULTS Of 88 included studies , 39 were positive using a frequentist analysis . Although the Bayesian posterior probabilities of any benefit ( relative risk or hazard ratio<1 ) were high in positive studies , these probabilities were lower and variable for larger benefits . The positive studies had only moderate probabilities for exceeding the effects that were assumed for calculating the sample size . By comparison , there were moderate probabilities of any benefit in negative studies . CONCLUSION Bayesian and frequentist analyses complement each other when interpreting the results of r and omized trials . Future reports of r and omized trials should include both", "OBJECTIVE To investigate whether a single trial can provide sufficiently robust evidence to warrant clinical implementation of its results . Trial-specific factors , such as subject selection , study design , and execution strategy , have an impact on the outcome of trials . In multiple trials , they may lead to heterogeneity that can be taken into account in the ( r and om effects ) meta- analysis . Single trials lack this method of estimating the impact of such factors , and this affects the credibility of the results . STUDY DESIGN AND SETTING To indicate how much the precision of the results of a single trial might be overestimated , we calculated the ratio of the widths of the confidence intervals when heterogeneity was taken into account and when it was not . RESULTS The ratios of the widths of the confidence intervals with and without between- study variability were 1.15 , 1.41 , and 2.00 , when the heterogeneity I(2 ) values were 0.25 , 0.50 , and 0.75 , respectively . CONCLUSION The results of a single trial should be interpreted with caution . When it is difficult to predict or determine how trial-specific factors influence the results , the best way to evaluate the performance of a treatment is to use multiple , possibly smaller , trials", "We conducted a prospect i ve , r and omized , double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury , including the adult respiratory distress syndrome ( ARDS ) , or improve mortality when administered early in septic shock . All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1 , 1983 and August 29 , 1986 were eligible for admission to the study if they had either ( 1 ) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values ( in already hospitalized patients ) , or ( 2 ) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg ( in newly admitted patients ) . Patients meeting these criteria were excluded if they ( 1 ) had severe immunodeficiency , ( 2 ) were less than 18 or greater than 76 yr of age , ( 3 ) had multilobar roentgenographic infiltrates , or ( 4 ) were already receiving corticosteroids . Eighty-seven patients enrolled in the study received either methylprednisolone , 30 mg/kg per dose , or mannitol placebo for a total of 4 doses every 6 h , following the presumptive diagnosis of septic shock . Of these patients , 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry . Thirteen of the patients who received methylprednisolone developed ARDS , compared to 14 patients who received placebo . Lesser degrees of parenchymal lung injury did not differ between the 2 groups . ( ABSTRACT TRUNCATED AT 250 WORDS", "Ten of 26 patients with sepsis were given a combination of dexamethasone ( 0.15 mg/kg , intravenously , once on admission ) , colchicine ( 0.5 mg , orally , daily , for 3 days ) and pentoxifylline ( DCP ) ( 400 mg , orally , daily , for 3 days ) , together with best medical therapy . Serum tumour necrosis factor-alpha ( TNF-alpha ) levels were undetectable at 24 h compared with about 4 IU/ml ( mean ) in 16 similar control patients who were not given DCP ( P < 0.06 ) . Although the clinical course in the two groups was not significantly different , this simple , well-tolerated and inexpensive regimen should be further evaluated as a possible means of preventing the deleterious effects of TNF-alpha in sepsis", "OBJECTIVES Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines . We examined the effect of hydrocortisone on shock reversal , hemodynamics , and survival in this particular setting . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Two intensive care units of a University hospital . PATIENTS Forty-one patients with septic shock requiring catecholamine for > 48 hrs . INTERVENTIONS Patients were r and omly assigned either hydrocortisone ( 100 mg i.v . three times daily for 5 days ) or matching placebo . MEASUREMENTS AND MAIN RESULTS Reversal of shock was defined by a stable systolic arterial pressure ( > 90 mm Hg ) for > or = 24 hrs without catecholamine or fluid infusion . Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients , 15 ( 68 % ) and 4 ( 21 % ) achieved 7-day shock reversal , respectively , a difference of 47 % ( 95 % confidence interval 17 % to 77 % ; p = .007 ) . Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups . At 28-day follow-up , reversal of shock was higher in the hydrocortisone group ( p = .005 ) . Crude 28-day mortality was 7 ( 32 % ) of 22 treated patients and 12 ( 63 % ) of 19 placebo patients , a difference of 31 % ( 95 % confidence interval 1 % to 61 % ; p = .091 ) . Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival . There were no significant differences in outcome in responders and nonresponders to a short corticotropin test . The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups . CONCLUSIONS Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of > 96 hrs result ed in a significant improvement in hemodynamics and a beneficial effect on survival . These beneficial effects do not appear related to adrenocortical insufficiency", "BACKGROUND Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin . METHODS In this multicenter , r and omized , double-blind , placebo-controlled trial , we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days ; the dose was then tapered during a 6-day period . At 28 days , the primary outcome was death among patients who did not have a response to a corticotropin test . RESULTS Of the 499 patients in the study , 233 ( 46.7 % ) did not have a response to corticotropin ( 125 in the hydrocortisone group and 108 in the placebo group ) . At 28 days , there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin ( 39.2 % in the hydrocortisone group and 36.1 % in the placebo group , P=0.69 ) or between those who had a response to corticotropin ( 28.8 % in the hydrocortisone group and 28.7 % in the placebo group , P=1.00 ) . At 28 days , 86 of 251 patients in the hydrocortisone group ( 34.3 % ) and 78 of 248 patients in the placebo group ( 31.5 % ) had died ( P=0.51 ) . In the hydrocortisone group , shock was reversed more quickly than in the placebo group . However , there were more episodes of superinfection , including new sepsis and septic shock . CONCLUSIONS Hydrocortisone did not improve survival or reversal of shock in patients with septic shock , either overall or in patients who did not have a response to corticotropin , although hydrocortisone hastened reversal of shock in patients in whom shock was reversed . ( Clinical Trials.gov number , NCT00147004 .", "STEROIDS might be of benefit to the patient with a serious infection.1 In 1961 a Cooperative double-blind study of the effects of administering a dose of 300 mg of hydrocortisone to patients with s", "Objective : The aim of this study was to investigate the effect of low-dose hydrocortisone on glomerular permeability measured by the microalbuminuria to creatinine ratio ( MACR ) and on other markers of sepsis in severe septic patients . Design : R and omized prospect i ve study . Setting : University intensive care unit . Patients : The study involved 40 patients with severe sepsis r and omized into the hydrocortisone group ( n = 20 ) and the st and ard therapy group ( n = 20 ) . Interventions : The hydrocortisone group received st and ard therapy plus a continuous infusion of hydrocortisone for 6 days , whereas the st and ard therapy group received only st and ard therapy . Measurements and Main Results : MACR , serum C-reactive protein , and procalcitonin concentrations were recorded every day from the day before the steroid therapy ( T0 ) until the 6 days after ( T1 , T2 , T3 , T4 , T5 , and T6 ) . Concentrations in the hydrocortisone group and the st and ard therapy group were compared using Mann-Whitney test at each time . We also compared with Wilcoxon signed rank test the values determined in each group at T0 with those at each subsequent time . Median MACR decreased from T0 to T6 in both patient groups ; however , values were significantly lower in the hydrocortisone group from T3 through to T6 . Median serum C-reactive protein also decreased from T0 in both patient groups , with significantly lower values in the hydrocortisone group from T3 through to T6 . There were no significant differences in procalcitonin between groups compared with baseline values or at any individual time point . Conclusions : Low-dose hydrocortisone seems to reduce MACR and serum C-reactive protein but not procalcitonin in patients with severe sepsis . Further studies are needed to confirm these results and to underst and the underlying molecular mechanisms", "To determine whether corticosteroids are efficacious in severe septic shock , we conducted a prospect i ve study of 59 patients r and omly assigned to a methylprednisolone , dexamethasone , or control group . Patients were treated 17.5 + /- 5.4 hours ( mean + /- S.E.M. ) after the onset of shock , and 55 patients required vasopressor agents . Early in the hospital course , reversal of shock was more likely in patients who received corticosteroids than in those who did not . Four ( 19 per cent ) of 21 methylprednisolone-treated , 7 ( 32 per cent ) of 22 dexamethasone-treated , and none of 16 control patients had reversal of shock 24 hours after drug administration ( corticosteroid groups vs. control group , P less than 0.05 ) . Patients treated with corticosteroids within four hours after the onset of shock had a higher incidence of shock reversal ( P less than 0.05 ) . At 133 hours after drug administration , 17 ( 40 per cent ) of 43 corticosteroid-treated patients had died , and 11 ( 69 per cent ) of 16 control patients had died ( P less than 0.05 ) . However , these differences in reversal of shock and survival disappeared later in the course . Overall , 16 ( 76 per cent ) of 21 patients receiving methylprednisolone , 17 ( 77 per cent ) of 22 patients receiving dexamethasone , and 11 ( 69 per cent ) of 16 controls in the hospital died . We conclude that corticosteroids do not improve the overall survival of patients with severe , late septic shock but may be helpful early in the course and in certain subgroups of patients", "A prospect i ve ( Part I ) and a retrospective ( Part II ) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock . In Part 1 , 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline : 43 received dexamethasone ( DMP ) , 43 received methylprednisolone ( MPS ) , and 86 received saline . The study was double-blind and r and omized , and the three groups were compared for age , severity of shock , presence of underlying disease , and year of study . In the 86 saline-treated patients , the mortality rate was 38.4 % ( 33/86 ) ; in the steroid-treated patients , it was 10.4 % ( 9/86 ) . With MPS the mortality rate was 11.6 % ( 5/43 ) , and with DMP it was 9.3 % ( 4/43 ) . Thus , overall mortality was significantly less in the steroid-treated group than in the control group . Further , there was no significant difference in mortality rate between the DMP- and the MPS-treated patients . In Part II , 328 patients were studied retrospectively . One-hundred sixty were treated without steroid , and 168 were treated with either DMP or MPS . Again , the two groups of patients were compared for severity of shock , underlying disease , age , and year of study . Mortality among patients treated without steroid was 42.5 % ( 68/160 ) and among patients treated with steroid was 14 % ( 24/168 ) ; there was no significant difference in mortality rate between DMP- and MPS-treated patients . In Parts I and II combined , complications occurred in 6 % of steroid-treated patients with no significant difference between DMP- and MPS-treated groups", "OBJECTIVE To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock . DESIGN Prospect i ve , r and omized , double-blind , single-center study . SETTING Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital . PATIENTS Forty consecutive patients who met the ACCP/SCCM criteria for septic shock . An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of > 4 L/min/m2 after fluid resuscitation ( pulmonary capillary wedge pressure : 12 - 15 mm Hg ) and without the use of positive inotropes such as dobutamine or dopexamine . The primary study end point was the time to cessation of vasopressor support ( norepinephrine or epinephrine in any dose , dopamine > or = 6 microg/kg/min ) . Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome ( MODS ) . The severity of illness at recruitment was grade d using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems . MODS was described by the Sepsis-related Organ Failure Assessment score . INTERVENTIONS All eligible patients were prospect ively r and omized to receive either stress doses of hydrocortisone or placebo . Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr . When septic shock had been reversed , the dose of hydrocortisone was reduced to 0.08 mg/kg/hr . This dose was kept constant for 6 days . As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to > 155 mmol/L , the hydrocortisone infusion was tapered in steps of 24 mg/day . Physiologic saline solution was the placebo . MEASUREMENTS AND MAIN RESULTS Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days . Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction . Baseline data at recruitment did not differ between the two groups . Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo . Hydrocortisone significantly reduced the time to cessation of vasopressor support . The median time of vasopressor support was 2 days ( 1st and 3rd Quartiles , 1 and 6 days ) in the hydrocortisone-treated group and 7 days ( 1st and 3rd Quartiles , 3 and 19 days ) in the placebo group ( p = .005 Breslow test ) . There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group . CONCLUSIONS Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock . This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions . Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study", "The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial . Our study was design ed as a prospect i ve , r and omized , double-blind , placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock . Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia ( rectal temperature greater than 38.3 degrees C [ 101 degrees F ] or less than 35.6 degrees C [ 96 degrees F ] ) , tachypnea ( greater than 20 breaths per minute ) , tachycardia ( greater than 90 beats per minute ) , and the presence of one of the following indications of organ dysfunction : a change in mental status , hypoxemia , elevated lactate levels , or oliguria . Three hundred eighty-two patients were enrolled . Treatment -- either methylprednisolone sodium succinate ( 30 mg per kilogram of body weight ) or placebo -- was given in four infusions , starting within two hours of diagnosis . No significant differences were found in the prevention of shock , the reversal of shock , or overall mortality . In the subgroup of patients with elevated serum creatinine levels ( greater than 2 mg per deciliter ) at enrollment , mortality at 14 days was significantly increased among those receiving methylprednisolone ( 46 of 78 [ 59 percent ] vs. 17 of 58 [ 29 percent ] among those receiving placebo ; P less than 0.01 ) . Among patients treated with methylprednisolone , significantly more deaths were related to secondary infection . We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock" ]

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[ "Innovative techniques to address retention in a behavioral weight-loss trial.", "Reach, Engagement, and Retention in an Internet-Based Weight Loss Program in a Multi-Site Randomized Controlled Trial", "A Church-based Diabetes Self-management Education Program for African Americans With Type 2 Diabetes", "Implementation and evaluation of a low-literacy diabetes education computer multimedia application.", "Depression and glycemic control in elderly ethnically diverse patients with diabetes: the IDEATel project.", "Diabetes self-management among low-income spanish-speaking patients: A pilot study", "Who Participates in Diabetes Self-management Interventions?", "Design and methods for a randomized clinical trial of a diabetes self-management intervention for low-Income Latinos: Latinos en Control", "Translating the Chronic Care Model Into the Community: Results From a Randomized Controlled Trial of a Multifaceted Diabetes Care Intervention", "Quantitative assessment of recruitment efforts for prevention trials in two diverse black populations.", "Culturally competent diabetes self-management education for Mexican Americans: the Starr County border health initiative.", "Spanish Diabetes Self-Management With and Without Automated Telephone Reinforcement", "Effects of a brief computer-assisted diabetes self-management intervention on dietary, biological and quality-of-life outcomes", "A randomized controlled trial of the effects of nurse case manager and community health worker team interventions in urban African-Americans with type 2 diabetes.", "Recruitment and participation in clinical trials: socio-demographic, rural/urban, and health care access predictors." ]

[ "Given that retention rates for weight-loss trials have not significantly improved in the past 20 years , identifying effective techniques to enhance retention is critical . This paper describes a conceptual and practical advance that may have improved retention in a behavioral weight-loss trial-the novel application of motivational interviewing techniques to diffuse ambivalence during interactive group-based orientation sessions prior to r and omization . These orientation sessions addressed ambivalence about making eating and exercise behavior changes , ambivalence about joining a r and omized controlled trial , and unrealistic weight-loss expectations . During these sessions , overweight and obese men and women learned about the health benefits of modest weight loss as well as trial design , the importance of a control condition , r and om assignment and the impact of dropouts . Participants were then divided into groups of three or four , and asked to generate two pros and two cons of being assigned to a control condition and an active condition . Participants shared their pros and cons with the larger group , while the investigator asked open-ended questions , engaged in reflective listening and avoided taking a ' pro-change ' position . Retention was high , with 96 % of the participants ( N = 162 ) completing 18-month clinic visits", "Background Research increasingly supports the conclusion that well- design ed programs delivered over the Internet can produce significant weight loss compared to r and omized controlled conditions . Much less is known about four important issues addressed in this study : ( 1 ) which recruitment methods produce higher eHealth participation rates , ( 2 ) which patient characteristics are related to enrollment , ( 3 ) which characteristics are related to level of user engagement in the program , and ( 4 ) which characteristics are related to continued participation in project assessment s. Methods We recruited overweight members of three health maintenance organizations ( HMOs ) to participate in an entirely Internet-mediated weight loss program developed by HealthMedia , Inc. Two different recruitment methods were used : personal letters from prevention directors in each HMO , and general notices in member newsletters . The personal letters were sent to members diagnosed with diabetes or heart disease and , in one HMO , to a general membership sample in a particular geographic location . Data were collected in the context of a 2 × 2 r and omized controlled trial , with participants assigned to receive or not receive a goal setting intervention and a nutrition education intervention in addition to the basic program . Results A total of 2311 members enrolled . Bivariate analyses on aggregate data revealed that personalized mailings produced higher enrollment rates than member newsletters and that members with diabetes or heart disease were more likely to enroll than those without these diagnoses . In addition , males , those over age 60 , smokers , and those estimated to have higher medical expenses were less likely to enroll ( all P < .001 ) . Males and those in the combined intervention were less likely to engage initially , or to continue to be engaged with their Web program , than other participants . In terms of retention , multiple logistic regressions revealed that enrollees under age 60 ( P < .001 ) and those with higher baseline self-efficacy were less likely to participate in the 12-month follow-up ( P = .03 ) , but with these exceptions , those participating were very similar to those not participating in the follow-up . Conclusions A single personalized mailing increases enrollment in Internet-based weight loss . eHealth programs offer great potential for recruiting large numbers of participants , but they may not reach those at highest risk . Patient characteristics related to each of these important factors may be different , and more comprehensive analyses of determinants of enrollment , engagement , and retention in eHealth programs are needed", "Introduction Diabetes self-management education interventions in community gathering places have been moderately effective , but very few studies of intervention effectiveness have been conducted among African Americans with type 2 diabetes . This paper describes a church-based diabetes self-management education intervention for African Americans , a r and omized controlled trial to evaluate the intervention , and baseline characteristics of study participants . Methods A New DAWN : Diabetes Awareness & Wellness Network was conducted among 24 churches of varying size in North Carolina . Each church recruited congregants with type 2 diabetes and design ated a diabetes advisor , or peer counselor , to be part of the intervention team . Participants were enrolled at each church and r and omized as a unit to either the special intervention or the minimal intervention . The special intervention included one individual counseling visit , twelve group sessions , three postcard messages from the participant 's diabetes care provider , and twelve monthly telephone calls from a diabetes advisor . Baseline data included measures of weight , hemoglobin A1c , blood pressure , physical activity , dietary and diabetes self-care practice s , and psychosocial factors . The study to evaluate the intervention ( from enrollment visit to last follow-up ) began in February 2001 and ended in August 2003 . Results Twenty-four churches ( with 201 total participants ) were r and omized . Sixty-four percent of the participants were women . On average , the participants were aged 59 years and sedentary . They had an average of 12 years of education , had been diagnosed with diabetes for 9 years , had a body mass index of 35 , had a hemoglobin A1c level of 7.8 % , and had a reported dietary intake of 39 % of calories from fat . Conclusion A New DAWN is a culturally sensitive , church-based diabetes self-management education program for African Americans with type 2 diabetes that is being evaluated for effectiveness in a r and omized controlled trial . The outcomes of A New DAWN will contribute to the literature on community-based interventions for minority population s and help to inform the selection of approaches to improve diabetes care in this population", "OBJECTIVE To evaluate a clinic-based multimedia intervention for diabetes education targeting individuals with low health literacy levels in a diverse population . RESEARCH DESIGN AND METHODS Five public clinics in Chicago , Illinois , participated in the study with computer kiosks installed in waiting room areas . Two hundred forty-four subjects with diabetes were r and omized to receive either supplemental computer multimedia use ( intervention ) or st and ard of care only ( control ) . The intervention includes audio/video sequences to communicate information , provide psychological support , and promote diabetes self-management skills without extensive text or complex navigation . HbA(1c ) ( A1C ) , BMI , blood pressure , diabetes knowledge , self-efficacy , self-reported medical care , and perceived susceptibility of complications were evaluated at baseline and 1 year . Computer usage patterns and implementation barriers were also examined . RESULTS Complete 1-year data were available for 183 subjects ( 75 % ) . Overall , there were no significant differences in change in A1C , weight , blood pressure , knowledge , self-efficacy , or self-reported medical care between intervention and control groups . However , there was an increase in perceived susceptibility to diabetes complications in the intervention group . This effect was greatest among subjects with lower health literacy . Within the intervention group , time spent on the computer was greater for subjects with higher health literacy . CONCLUSIONS Access to multimedia lessons result ed in an increase in perceived susceptibility to diabetes complications , particularly in subjects with lower health literacy . Despite measures to improve informational access for individuals with lower health literacy , there was relatively less use of the computer among these participants", "OBJECTIVE The purpose of the study was to investigate the effect of comorbid depression on glycemic control and on response to a telemedicine case management intervention for elderly , ethnically diverse diabetic patients . RESEARCH DESIGN AND METHODS Medicare beneficiaries in underserved areas were participants ( n = 1,665 ) in the Informatics for Diabetes Education and Telemedicine ( IDEATel ) project and r and omized to a telemedicine case management intervention or usual care . The data analyzed include baseline demographics ( age , sex , race/ethnicity , marital status , insulin use , years of education , years of diabetes , and pack-years smoked ) and measures of glycemic control ( HbA(1c ) [ A1C ] ) , comorbidity , diabetes symptom severity , functional disability and depression , and 1-year ( n = 1,578 ) A1C . The association between depression and glycemic control was analyzed cross-sectionally and prospect ively . RESULTS At baseline , there was a significant correlation between depression and A1C and a trend for depression to predict A1C when other factors were controlled . However , in prospect i ve analyses , depression did not predict change in A1C , either in the control or intervention group . CONCLUSIONS In this large sample of elderly diabetic patients , a weak relationship between depression and A1C was found , but depression did not prospect ively predict change in glycemic control . Thus , there is no evidence that depression should be used to exclude patients from interventions . Also , we should evaluate the impact of depression on outcomes other than glycemic control", "Background : The prevalence of type 2 diabetes and diabetesrelated morbidity and mortality is higher among low-income Hispanics when compared to that of Whites . However , little is known about how to effectively promote self-management in this population . Purpose : The objectives were first to determine the feasibility of conducting a r and omized clinical trial of an innovative self-management intervention to improve metabolic control in low-income Spanish-speaking individuals with type 2 diabetes and second to obtain preliminary data of possible intervention effects . Methods : Participants for this pilot study were recruited from a community health center , an elder program , and a community-wide data base developed by the community health center , in collaboration with other agencies serving the community , by surveying households in the entire community . Participants were r and omly assigned to an intervention ( n = 15 ) or a control ( n = 10 ) condition . Assessment s were conducted at baseline and at 3 months and 6 months postr and omization . The intervention consisted of 10 group sessions that targeted diabetes knowledge , attitudes , and self-management skills through culturally specific and literacysensitive strategies . The intervention used a cognitivebehavioral theoretical framework . Results : Recruitment rates at the community health center , elder program , and community registry were 48 % , 69 % , and 8 % , respectively . Completion rates for baseline , 3-month , and 6-month assessment s were 100 % , 92 % , and 92 % , respectively . Each intervention participant attended an average of 7.8 out of 10 sessions , and as a group the participants showed high adherence to intervention activities ( 93 % turned in daily logs , and 80 % self-monitored glucose levels at least daily ) . There was an overall Group × Time interaction ( p = .02 ) indicating group differences in glycosylated hemoglobin over time . The estimated glycosylated hemoglobin decrease at 3 months for the intervention group was −0.8 % ( 95 % confidence intervals = −1.1 % , −0.5 % ) compared with the change in the control group ( p = .02 ) . At 6 months , the decrease in the intervention group remained significant , −0.85 % ( 95 % confidence intervals = −1.2 , −0.5 ) , and the decrease was still significantly different from that of the controls ( p = .005 ) . There was a trend toward increased physical activity in the intervention group as compared to that of the control group ( p = .11 ) and some evidence ( nonsignificant ) of an increase in blood glucose self-monitoring in the intervention participants but not the control participants . Adjusting for baseline depressive scores , we oberved a significant difference in depressive symptoms between intervention participants and control participants at the 3-month assessment ( p = .02 ) . Conclusions : Low-income Spanish-speaking Hispanics are receptive to participate in diabetes-related research . This study shows that the pilot-tested diabetes self-management program is promising and warrants the conduct of a r and omized clinical trial", "PURPOSE The purpose of this study was to examine reasons for nonparticipation and drop out in a diabetes self-management intervention . METHODS A total of 468 recently screen-detected patients , receiving usual care or intensive pharmacological treatment , were invited and r and omized into either a control or intervention condition , consisting of a brief self-management course . A nonresponse survey was conducted , and participants , non participants , and dropouts were compared on sociodemographic variables , diabetes attitudes , and self-care . RESULTS A total of 227 patients consented and were allocated to the control ( n=108 ) or intervention group ( n=119 ) . Two hundred forty-one patients declined participation , 41 dropped out , and 78 completed the intervention . Major reasons for refusal and drop out were hesitancy toward research and practical barriers . Non participants were less educated and reported higher self-management , while participation also varied by treatment and disease duration : intensively treated patients were more likely to participate in their first year , and usual-care patients participated more often 2 to 3 years after diagnosis . Dropouts had a lower education level but did not differ on any other measure . CONCLUSION Participants , non participants , and dropouts did not differ in their attitudes toward diabetes , but the intervention did attract patients with lower self-care . Variations in participation by treatment and disease duration suggest that patients prefer self-management interventions at different times depending on their medical treatment . Finally , education appears to be the most important factor determining participation . Alternative strategies are needed to attract and retain patients with low education", "Background US Latinos have greater prevalence of type 2 diabetes ( diabetes ) , uncontrolled diabetes and diabetes co-morbidities compared to non-Latino Whites . They also have lower literacy levels and are more likely to live in poverty . Interventions are needed to improve diabetes control among low-income Latinos . Methods and design This r and omized clinical trial tested the efficacy of a culturally- and literacy-tailored diabetes self-management intervention ( Latinos en Control ) on glycemic control among low-income Latinos with diabetes , compared to usual care ( control ) . Participants were recruited from five community health centers ( CHCs ) in Massachusetts . The theory-based intervention included an intensive phase of 12 weekly sessions and a follow-up maintenance phase of 8 monthly sessions . Assessment s occurred at baseline , and at 4 and 12 months . The primary outcome was glycosylated hemoglobin ( HbA1c ) . Secondary outcomes were self-management behaviors , weight , lipids and blood pressure . Additional outcomes included diabetes knowledge , self-efficacy , depression and quality of life . The study was design ed for recruitment of 250 participants ( estimated 20 % dropout rate ) to provide 90 % power for detecting a 7 % or greater change in HbA1c between the intervention and control groups . This is a difference in change of HbA1c of 0.5 to 0.6 % . Discussion Low-income Latinos bear a great burden of uncontrolled diabetes and are an understudied population . Theory-based interventions that are tailored to the needs of this high-risk population have potential for improving diabetes self-management and reduce health disparities . This article describes the design and methods of a theory driven intervention aim ed at addressing this need . Trial registration http://www . clinical trials.gov #", "OBJECTIVE To determine whether using the chronic care model ( CCM ) in an underserved community leads to improved clinical and behavioral outcomes for people with diabetes . RESEARCH DESIGN AND METHODS This multilevel , cluster- design , r and omized controlled trial examined the effectiveness of a CCM-based intervention in an underserved urban community . Eleven primary care practice s , along with their patients , were r and omized to three groups : CCM intervention ( n = 30 patients ) , provider education only ( PROV group ) ( n = 38 ) , and usual care ( UC group ) ( n = 51 ) . RESULTS A marked decline in HbA(1c ) was observed in the CCM group ( -0.6 % , P = 0.008 ) but not in the other groups . The magnitude of the association remained strong after adjustment for clustering ( P = 0.01 ) . The same pattern was observed for a decline in non-HDL cholesterol and for the proportion of participants who self-monitor blood glucose in the CCM group ( non-HDL cholesterol : -10.4 mg/dl , P = 0.24 ; self-monitor blood glucose : + 22.2 % , P < 0.0001 ) , with statistically significant between-group differences in improvement ( non-HDL cholesterol : P = 0.05 ; self-monitor blood glucose : P = 0.03 ) after adjustment . The CCM group also showed improvement in HDL cholesterol ( + 5.5 mg/dl , P = 0.0004 ) , diabetes knowledge test scores ( + 6.7 % , P = 0.07 ) , and empowerment scores ( + 2 , P = 0.02 ) . CONCLUSIONS These results suggest that implementing the CCM in the community is effective in improving clinical and behavioral outcomes in patients with diabetes", "BACKGROUND Prevention efforts to reduce the morbidity and mortality disparity between blacks and whites in the United States present a national health priority . However , participation of blacks in prevention trials has been low . The present study reports successful recruitment processes from two economically diverse black population s. METHODS The two studies were independent projects , but both were part of a nationally funded collaboration on cardiovascular health . \" Hip Hop to Health \" is a 4-year r and omized controlled trial aim ed at dietary fat reduction and increased exercise among inner-city black families . The Fat Reduction Intervention Trial in African-Americans project is a 5-year trial to reduce total fat , saturated fat , and cholesterol intake among black families from a working class community . RESULTS The two population s differed on demographic characteristics . Direct presentation was the most effective recruitment strategy in the \" Hip Hop to Health \" program . In contrast , telephone recruitment and neighborhood canvassing were the more successful strategies for FRITAA . CONCLUSIONS Although both population s were black and at comparable cardiovascular disease risk , the differing demographics between the groups made different recruitment strategies necessary . This study documented the labor-intensive quality of successful recruitment , and results suggest that successful recruitment requires strategies tailored to the needs , experiences , and environment of the target group", "OBJECTIVE To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve , r and omized , repeated measures study was conducted on the Texas-Mexico border in Starr County . A total of 256 r and omly selected individuals with type 2 diabetes between 35 and 70 years of age , diagnosed with type 2 diabetes after 35 years of age , and accompanied by a family member or friend were included . The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses , dietitians , and community workers . The intervention involved 3 months of weekly instructional sessions on nutrition , self-monitoring of blood glucose , exercise , and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes . The approach was culturally competent in terms of language , diet , social emphasis , family participation , and incorporation of cultural health beliefs . Outcomes included indicators of metabolic control ( HbA(1c ) and fasting blood glucose ) , diabetes knowledge , and diabetes-related health beliefs . RESULTS Experimental groups showed significantly lower levels of HbA(1c ) and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores . At 6 months , the mean HbA(1c ) of the experimental subjects was 1.4 % below the mean of the control group ; however , the mean level of the experimental subjects was still high ( > 10 % ) . CONCLUSIONS This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans , particularly for those individuals with HbA(1c ) levels > 10 %", "OBJECTIVE —To determine 1 ) whether participants in the Spanish Diabetes Self-Management Program ( SDSMP ) , when compared at 6 months to r and omized control subjects , would demonstrate improvements in health status , health behaviors , and self-efficacy ; and 2 ) whether SDSMP participants receiving monthly automated telephone reinforcement would maintain improvements at 18 months better than those not receiving reinforcement . RESEARCH DESIGN AND METHODS —A total of 567 Spanish-speaking adults with type 2 diabetes were r and omized to a usual-care control group or 6-week community-based , peer-led SDSMP . SDSMP participants were re-r and omized to receive 15 months of automated telephone messages or no reinforcement . A1C was measured at baseline and 6 and 18 months . All other data were collected by self-administered question naires . RESULTS —At 6 months SDSMP participants compared with control subjects demonstrated improvements in A1C ( −0.4 % ) , health distress , symptoms of hypo- and hyperglycemia , and self-efficacy ( P < 0.05 ) . At 18 months all improvements persisted ( P < 0.05 ) . SDSMP participants also demonstrated improvements in self-rated health and communication with physicians , had fewer emergency room visits ( −0.18 visits in 6 months , P < 0.05 ) , and trended toward fewer visits to physicians . At 18 months the only difference between reinforced and nonreinforced participants was increased glucose monitoring for the reinforcement group . CONCLUSIONS —The SDSMP demonstrated effectiveness in lowering A1C and improving health status . Reinforcement did not add to its effectiveness . Given the high needs of the Spanish-speaking population , the SDSMP deserves consideration for implementation", "Objective : There is a need for practical , efficient and broad-reaching diabetes self-management interventions that can produce changes in lifestyle behaviours such as healthy eating and weight loss . The objective of this study was to evaluate such a computer-assisted intervention . Methods : Type 2 diabetes primary care patients ( n=335 ) from fee-for-service and health maintenance organization setting s were r and omized to social cognitive theory-based tailored self-management ( TSM ) or computer-aided enhanced usual care ( UC ) . Intervention consisted of computer-assisted self-management assessment and feedback , tailored goal - setting , barrier identification , and problem-solving , followed by health counsellor interaction and follow-up calls . Outcomes were changes in dietary behaviours ( fat and fruit/vegetable intake ) , haemoglobin A1c ( HbA1c ) , lipids , weight , quality of life , and depression . Results : TSM patients reduced dietary fat intake and weight significantly more than UC patients at the 2-month follow-up . Among patients having elevated levels of HbA1c , lipids or depression at baseline , there were consistent directional trends favouring intervention , but these differences did not reach significance . The intervention proved feasible and was implemented successfully by a variety of staff . Conclusions : This relatively low-intensity intervention appealed to a large , generally representative sample of patients , was well implemented , and produced improvement in targeted behaviours . Implication s of this practical clinical trial for dissemination are discussed", "The objective of the study was to determine the effectiveness and cost-effectiveness of primary care and community-oriented interventions in managing HbA1c , blood pressure , and lipids , and reducing hospitalizations and emergency room visits over 2 years . We describe an ongoing , r and omized controlled trial of 542 urban African-Americans with type 2 diabetes ages 25 years and older who are members of a university-affiliated managed-care organization in Baltimore , MD . The participants are 74 % female , have a mean age of 58 years , and 35 % have yearly incomes greater than 7500 US dollars . Participants were r and omized to one of two intervention groups for a period of 2 years : ( 1 ) usual medical care plus minimal telephone intervention implemented by a trained lay health educator ( control group ) or ( 2 ) usual medical care plus intensive intervention implemented by a nurse case manager (NCM)/community health worker ( CHW ) team . The intensive NCM/CHW team executes individual plans of care using evidence -based algorithms that focus on traditional diabetes self-management , screening and management of diabetes-related complications , and social issues surrounding diabetes care . Face-to-face NCM visits are conducted in the clinic once per year and CHW visits are conducted in the participant 's home one to three times per year , both with additional follow-up contacts as needed . Written and verbal feedback ( when necessary ) is provided to the participant 's primary care physician . All participants are expected to attend a 24-month follow-up visit where data are collected by interviewers blinded to intervention assignment . As of May 1 , 2003 , recruitment is complete , interventions are being fully implemented , and 24-month follow-up visits are beginning . Baseline sociodemographic characteristics , health-care utilization , health behaviors , and clinical characteristics of the study population are reported . This study is design ed to test the hypothesis that a primary -care-based NCM plus CHW team approach is an effective , practical , and economically feasible strategy for translating current knowledge about type 2 diabetes into high- quality health care for urban African-Americans", "BACKGROUND Recruitment and participation in clinical trials by minorities , particularly African Americans and rural underserved population s , are low . This report examines predictors of clinical trial recruitment and participation for adult Maryl and ers . METHODS A cross-sectional design was used to survey 5154 adults ( 18 years and older ) residing in 13 of the 24 jurisdictions in Maryl and , including urban Baltimore City , and the rural regions of Western Maryl and and the Eastern Shore . The survey , conducted between December 2001 and March 2003 , used Computer-Assisted Telephone Interviewing and r and om-digit dialing procedures . Primary dependent variables included \" ever asked to participate \" ( i.e. , recruited ) and \" participated \" in clinical trials . RESULTS 11.1 % of the respondents had been recruited to clinical trials . In addition , 59.4 % of the respondents recruited to clinical trials actually participated in a clinical trial . Among respondents recruited to clinical trials , black and middle income respondents were significantly less likely to actually participate in clinical trials ; whereas , respondents who received information about clinical trials from their health care provider , who were knowledgeable about clinical trials , and those who had the time commitment were significantly more likely to participate in clinical trials . CONCLUSIONS These results suggest serious gaps in efforts to recruit racial/ethnic minorities and residents of rural regions into clinical trials . The findings provide the basis for the development and implementation of community-based educational programs for both the general public and health care professionals , and to enhance availability of community-based clinical trials , especially in the rural areas of the state" ]

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[ "Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo", "Efficacy of azithromycin in the treatment of bronchiectasis.", "Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial.", "The bronchiectasis severity index. An international derivation and validation study.", "How well documented are testing strategies and outcome measurement methods in trials of tests? A comparison of reporting quality in test-treatment and monitoring RCTS", "Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study.", "Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial.", "A pilot study of low-dose erythromycin in bronchiectasis.", "The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial.", "The burden of disease in pediatric non-cystic fibrosis bronchiectasis.", "The Disease-Modifying Effects of Twice-Weekly Oral Azithromycin in Patients with Bronchiectasis", "Effects of long-term azithromycin therapy on airway oxidative stress markers in non-cystic fibrosis bronchiectasis.", "Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial", "Corrections. The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial.", "Effect of a short course of clarithromycin therapy on sputum production in patients with chronic airway hypersecretion.", "Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial.", "Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial.", "[Impact of treatment with low dose roxithromycin on stable bronchiectasis].", "New Zealand national incidence of bronchiectasis “too high” for a developed country", "Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis." ]

[ "Although long-term azithromycin decreases exacerbation frequency in bronchiectasis , increased macrolide resistance is concerning . We investigated macrolide resistance determinants in a secondary analysis of a multicenter r and omized controlled trial . Indigenous Australian children living in remote regions and urban New Zeal and Māori and Pacific Isl and er children with bronchiectasis were r and omized to weekly azithromycin ( 30 mg/kg ) or placebo for up to 24 months and followed post-intervention for up to 12 months . Nurses administered and recorded medications given and collected nasopharyngeal swabs 3–6 monthly for culture and antimicrobial susceptibility testing . Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups , while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher . Australian children , compared to New Zeal and children , had higher carriage overall , significantly higher carriage of macrolide-resistant bacteria at baseline ( 16/38 versus 2/40 children ) and during the intervention ( 69/152 versus 22/239 swabs ) , and lower mean adherence to study medication ( 63 % versus 92 % ) . Adherence ≥70 % ( versus < 70 % ) in the Australian azithromycin group was associated with lower carriage of any pathogen [ odds ratio ( OR ) 0.19 , 95 % confidence interval ( CI ) 0.07–0.53 ] and fewer macrolide-resistant pathogens ( OR 0.34 , 95 % CI 0.14–0.81 ) . Post-intervention ( median 6 months ) , macrolide resistance in S. pneumoniae declined significantly in the azithromycin group , from 79 % ( 11/14 ) to 7 % ( 1/14 ) of positive swabs , but S. aureus strains remained 100 % macrolide resistant . Azithromycin treatment , the Australian remote setting , and adherence < 70 % were significant independent determinants of macrolide resistance in children with bronchiectasis . Adherence to treatment may limit macrolide resistance by suppressing carriage", "BACKGROUND AND OBJECTIVE We evaluated the efficacy of a 12-week oral treatment with azithromycin in adult patients with bronchiectasis . The objectives were to demonstrate that this treatment reduces sputum volume , improves quality of life and to assess the lengths of effects after cessation of therapy . METHODS Seventy-eight patients with bronchiectasis confirmed by high-resolution computed tomography were included in this study . Subjects received oral azithromycin or placebo in a r and omized manner for 12 weeks followed by placebo for another 12 weeks . Sputum volume , St George 's Respiratory Question naire ( SGRQ ) score and spirometry were recorded at baseline , 12 weeks and 24 weeks , respectively . End-point measurements were compared from baseline to the end of each study phase . RESULTS Sixty-eight subjects were included in the analysis . Mean 24-h sputum volume significantly decreased ( P < 0.01 ) during the active treatment phase and remained low during the control phase ( P < 0.01 ) . The mean SGRQ total score with azithromycin decreased ( i.e. improved health status ) from baseline by more than the 4 points at the end of 12 and 24 weeks . Lung functions remained stable during oral azithromycin therapy and the subsequent control phase . CONCLUSIONS Twelve weeks administration of azithromycin in bronchiectasis produces significant reductions in mean sputum volume , health status and stabilization of lung function values . Sputum volume reduction and the improvement of quality of life were sustained for 12 weeks after cessation of azithromycin . ( Clinical trials.gov number NCT02107274 )", "IMPORTANCE Macrolide antibiotics have been shown beneficial in cystic fibrosis ( CF ) and diffuse panbronchiolitis , and earlier findings also suggest a benefit in non-CF bronchiectasis . OBJECTIVE To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis . DESIGN , SETTING , AND PARTICIPANTS The BAT ( Bronchiectasis and Long-term Azithromycin Treatment ) study , a r and omized , double-blind , placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherl and s among 83 out patients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year . INTERVENTIONS Azithromycin ( 250 mg daily ) or placebo for 12 months . MAIN OUTCOME MEASURES Number of infectious exacerbations during 12 months of treatment . Secondary end points included lung function , sputum bacteriology , inflammatory markers , adverse effects , symptom scores , and quality of life . RESULTS Forty-three participants ( 52 % ) received azithromycin and 40 ( 48 % ) received placebo and were included in the modified intention-to-treat analysis . At end of study , the median number of exacerbations in the azithromycin group was 0 ( interquartile range [ IQR ] , 0 - 1 ) , compared with 2 ( IQR , 1 - 3 ) in the placebo group ( P < .001 ) . Thirty-two ( 80 % ) placebo-treated vs 20 ( 46 % ) azithromycin-treated individuals had at least 1 exacerbation ( hazard ratio , 0.29 [ 95 % CI , 0.16 - 0.51 ] ) . In a mixed-model analysis , change in forced expiratory volume in the first second of expiration ( percent of predicted ) over time differed between groups ( F1,78.8 = 4.085 , P = .047 ) , with an increase of 1.03 % per 3 months in the azithromycin group and a decrease of 0.10 % per 3 months in the placebo group . Gastrointestinal adverse effects occurred in 40 % of patients in the azithromycin group and in 5 % in the placebo group ( relative risk , 7.44 [ 95 % CI , 0.97 - 56.88 ] for abdominal pain and 8.36 [ 95 % CI , 1.10 - 63.15 ] for diarrhea ) but without need for discontinuation of study treatment . A macrolide resistance rate of 88 % was noted in azithromycin-treated individuals , compared with 26 % in the placebo group . CONCLUSIONS AND RELEVANCE Among adults with non-CF bronchiectasis , the daily use of azithromycin for 12 months compared with placebo result ed in a lower rate of infectious exacerbations . This could result in better quality of life and might influence survival , although effects on antibiotic resistance need to be considered . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00415350", "RATIONALE There are no risk stratification tools for morbidity and mortality in bronchiectasis . Identifying patients at risk of exacerbations , hospital admissions , and mortality is vital for future research . OBJECTIVES This study describes the derivation and validation of the Bronchiectasis Severity Index ( BSI ) . METHODS Derivation of the BSI used data from a prospect i ve cohort study ( Edinburgh , UK , 2008 - 2012 ) enrolling 608 patients . Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up . The score was vali date d in independent cohorts from Dundee , UK ( n = 218 ) ; Leuven , Belgium ( n = 253 ) ; Monza , Italy ( n = 105 ) ; and Newcastle , UK ( n = 126 ) . MEASUREMENTS AND MAIN RESULTS Independent predictors of future hospitalization were prior hospital admissions , Medical Research Council dyspnea score greater than or equal to 4 , FEV1 < 30 % predicted , Pseudomonas aeruginosa colonization , colonization with other pathogenic organisms , and three or more lobes involved on high-resolution computed tomography . Independent predictors of mortality were older age , low FEV1 , lower body mass index , prior hospitalization , and three or more exacerbations in the year before the study . The derived BSI predicted mortality and hospitalization : area under the receiver operator characteristic curve ( AUC ) 0.80 ( 95 % confidence interval , 0.74 - 0.86 ) for mortality and AUC 0.88 ( 95 % confidence interval , 0.84 - 0.91 ) for hospitalization , respectively . There was a clear difference in exacerbation frequency and quality of life using the St. George 's Respiratory Question naire between patients classified as low , intermediate , and high risk by the score ( P < 0.0001 for all comparisons ) . In the validation cohorts , the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88 . CONCLUSIONS The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality , hospitalization , and exacerbations across healthcare systems", "Background Given the advantages of the r and omised controlled trial ( RCT ) design for the evaluation of therapeutic interventions , it is tempting to assume that the same approach must be the gold st and ard for the evaluation of testing strategies . Such trials present considerable challenges , due to the complex nature of the decision – making process . To interpret how changes in testing strategies create observed effects , trials must pre – specify how test results should inform diagnostic and management decisions and treatment plans", "Increased airway responsiveness ( AR ) is frequently associated with bronchiectasis . Roxithromycin is a new semisynthetic macrolide antibiotic that also has anti-inflammatory activities . This study was design ed to see whether roxithromycin could favourably alter the degree of AR in patients with bronchiectasis and increased AR . Twenty five children with bronchiectasis , who had an increased AR ( defined as a provocative concentration of methacholine causing a 20 % fall in forced expiratory volume in one second ( FEV1 ) ( PC20 ) < 25 mg x mL(-1 ) evaluated by the dosimeter method ) , were r and omized , double-blind into two parallel groups . Thirteen of the children were treated with roxithromycin ( 4 mg x kg(-1 ) b.i.d . ) for 12 weeks and 12 received placebo . FEV1 , sputum purulence and leucocyte scores were assessed every 3 weeks . To estimate AR , high-dose methacholine challenge tests were performed before and after treatment . On the dose-response curve to methacholine , PD20 and maximal response ( two indices of AR ) were measured . Changes in FEV1 were not observed during the course of the study in both groups . A significant improvement in sputum features was noted after 6 weeks of treatment in the roxithromycin group . After 12 weeks of roxithromycin therapy , the geometric mean ( range of 1 SD ) of provocative cumulative dose producing a 20 % fall in FEV1 ( PD20 ) increased significantly ( p<0.01 ) to 169.2 ( 83.2 - 344.2 ) breath units ( BU ) ( 1 BU denotes one inhalation of 1 mg x mL(-1 ) methacholine ) and the mean+/-SD of maximal response decreased significantly ( p<0.01 ) to 32.5+/-6.8 % , as compared with the initial values ( PD20 87.1 ( 47.3 - 160.4 ) BU ; maximal response 40.9+/-7.4 % ) . No significant changes in either parameter were observed in the placebo group . Our results indicate that roxithromycin may decrease the degree of airway responsiveness in patients with bronchiectasis and increased airway responsiveness . Further study is necessary to determine the mechanism by which roxithromycin reduces airway responsiveness in bronchiectasis and its clinical impact", "CONTEXT Treatment strategies for cystic fibrosis ( CF ) lung disease include antibiotics , mucolytics , and anti-inflammatory therapies . Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF . OBJECTIVE To determine if an association between azithromycin use and pulmonary function exists in patients with CF . DESIGN AND SETTING A multicenter , r and omized , double-blind , placebo-controlled trial conducted from December 15 , 2000 , to May 2 , 2002 , at 23 CF care centers in the United States . PARTICIPANTS Of the 251 screened participants with a diagnosis of CF , 185 ( 74 % ) were r and omized . Eligibility criteria included age 6 years or older , infection with Pseudomonas aeruginosa for 1 or more years , and a forced expiratory volume in 1 second ( FEV1 ) of 30 % or more . Participants were stratified by FEV1 ( > or = 60 % predicted vs < 60 % predicted ) , weight of less than 40 kg vs 40 kg or more , and CF center . INTERVENTION The active group ( n = 87 ) received 250 mg ( weight < 40 kg ) or 500 mg ( weight > or = 40 kg ) of oral azithromycin 3 days a week for 168 days ; placebo group ( n = 98 ) received identically packaged tablets . MAIN OUTCOME MEASURES Change in FEV1 from day 0 to completion of therapy at day 168 and determination of safety . Secondary outcomes included pulmonary exacerbations and weight gain . RESULTS The azithromycin group had a mean 0.097-L ( SD , 0.26 ) increase in FEV1 at day 168 compared with 0.003 L ( SD , 0.23 ) in the placebo group ( mean difference , 0.094 L ; 95 % confidence interval [ CI ] , 0.023 - 0.165 ; P = .009 ) . Nausea occurred in 17 % more participants in the azithromycin group ( P = .01 ) , diarrhea in 15 % more ( P = .009 ) , and wheezing in 13 % more ( P = .007 ) . Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group ( hazard ratio , 0.65 ; 95 % CI , 0.44 - 0.95 ; P = .03 ) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo ( 95 % CI , 0.1 - 1.4 kg ; P = .02 ) . CONCLUSION Azithromycin treatment was associated with improvement in clinical ly relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa", "Patients with bronchiectasis suffer from sputum production , recurrent exacerbations , and progressive airway destruction . Erythromycin is effective in diffuse panbronchiolitis , another suppurative airway disorder , although its efficacy is unknown in idiopathic bronchiectasis . A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin ( 500 mg b.i.d . ) in steady-state idiopathic bronchiectasis . Patients in the erythromycin group ( n=11 , 8 female , mean age 50+/-15 yrs ) , but not the placebo group ( n=10 , 8 female , mean age 59+/-16 yrs ) had significantly improved forced expiratory volume in one second , forced vital capacity and 24-h sputum volume after 8 weeks ( p<0.05 ) . There was no parallel improvement in sputum pathogens , leukocytes , interleukin (IL)-1alpha and IL-8 , tumour necrosis factor-alpha , or leukotriene B4 . The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis . Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis", "BACKGROUND Long-term macrolide treatment has proven benefit in inflammatory airways diseases , but whether it leads to changes in the composition of respiratory microbiota is unknown . We aim ed to assess whether long-term , low-dose erythromycin treatment changes the composition of respiratory microbiota in people with non-cystic fibrosis bronchiectasis . METHODS Microbiota composition was determined by 16S rRNA gene sequencing of sputum sample s from participants in the BLESS trial , a 12-month , double-blind , placebo-controlled trial of twice-daily erythromycin ethylsuccinate ( 400 mg ) in adult patients with non-cystic fibrosis bronchiectasis and at least two infective exacerbations in the preceding year . The primary outcome was within-patient change in respiratory microbiota composition ( assessed by Bray-Curtis index ) between baseline and week 48 , comparing erythromycin with placebo . The BLESS trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12608000460303 . FINDINGS The BLESS trial took place between Oct 15 , 2008 , and Dec 14 , 2011 . Paired sputum sample s were available from 86 r and omly assigned patients , 42 in the placebo group and 44 in the erythromycin group . The change in microbiota composition between baseline and week 48 was significantly greater with erythromycin than with placebo ( median Bray-Curtis score 0·52 [ IQR 0·14 - 0·78 ] vs 0·68 [ 0·46 - 0·93 ] ; median difference 0·16 , 95 % CI 0·01 - 0·33 ; p=0·03 ) . In patients with baseline airway infection dominated by Pseudomonas aeruginosa , erythromycin did not change microbiota composition significantly . In those with infection dominated by organisms other than P. aeruginosa , erythromycin caused a significant change in microbiota composition ( p=0·03 [ by analysis of similarity ] ) , representing a reduced relative abundance of Haemophilus influenzae ( 35·3 % [ 5·5 - 91·6 ] vs 6·7 % [ 0·8 - 74·8 ] ; median difference 12·6 % , 95 % CI 0·4 - 28·3 ; p=0·04 ; interaction p=0·02 ) and an increased relative abundance of P aeruginosa ( 0·02 % [ 0·00 - 0·33 ] vs 0·13 % [ 0·01 - 39·58 ] ; median difference 6·6 % , 95 % CI 0·1 - 37·1 ; p=0·002 ; interaction p=0·45 ) . Compared with placebo , erythromycin reduced the rate of pulmonary exacerbations over the 48 weeks of the study in patients with P. aeruginosa-dominated infection ( median 1 [ IQR 0 - 3 ] vs 3 [ 2 - 5 ] ; median difference -2 , 95 % CI -4 to -1 ; p=0·01 ) , but not in those without P. aeruginosa-dominated infection ( 1 [ 0 - 2 ] vs 1 [ 0 - 3 ] ; median difference 0 , -1 to 0 ; p=0·41 ; interaction p=0·04 ) . INTERPRETATION Long-term erythromycin treatment changes the composition of respiratory microbiota in patients with bronchiectasis . In patients without P. aeruginosa airway infection , erythromycin did not significantly reduce exacerbations and promoted displacement of H. influenzae by more macrolide-tolerant pathogens including P. aeruginosa . These findings argue for a cautious approach to chronic macrolide use in patients without P. aeruginosa airway infection . FUNDING Mater Adult Respiratory Research Trust Fund", "BACKGROUND The burden of disease in children with non-cystic fibrosis ( non-CF ) bronchiectasis is unknown . Our study aim ed to identify the determinants of quality of life ( QOL ) and parental mental health in this group of patients and their parents and to evaluate the effect of exacerbations on these parameters . METHODS Parents of 69 children ( median age 7 years ) with non-CF bronchiectasis prospect ively completed two question naires ( parent-proxy cough-specific quality of life [ PC-QOL ] and the Depression , Anxiety , and Stress Scale [ DASS ] ) at stable and exacerbation states . Data on clinical , investigational , and lung function parameters were also collected . RESULTS During the stable state , the median interquartile range ( IQR ) PC-QOL score was 6.5 ( 5.3 - 6.9 ) and the DASS 21-item question naire score was 6 ( 0 - 20 ) . Being of a young age correlated with a worse QOL ( r(5 ) = 0.242 , P = .04 ) but radiologic extent , lung function , underlying cause , environmental tobacco smoke exposure , and chronic upper-airway disease did not influence these scores . Exacerbations caused significant worsening in the PC-QOL scores ( median [ IQR ] , 4.6 [ 3.8 - 5.4 ] ; P = .001 ) and DASS scores ( median [ IQR ] , 22 [ 9 - 42 ] ; P < .001 ; 38 % with elevated anxiety , 54 % with abnormal depression/stress scores during exacerbation ) . The presence of viral infection , hypoxia , and hospitalization did not influence the exacerbation PC-QOL and DASS scores . CONCLUSIONS There is a significant burden of disease , especially during exacerbation , on parents of children with bronchiectasis . Prevention , early detection , and appropriate treatment of exacerbations are likely to reduce psychologic morbidity in this group", "Introduction Bronchiectasis is a chronic pulmonary process characterized by recurrent respiratory infections leading to destruction of airways secondary to inflammation . We investigated whether the addition of 6-months ’ twice-weekly azithromycin to the existing treatment regimen in patients with pulmonary bronchiectasis decreased the number of exacerbations and improved pulmonary function compared with a similar period of time without concurrent azithromycin . Methods Thirty patients with high-resolution computed tomography scan-confirmed bronchiectasis were to be recruited . In r and om order , patients received usual medications for 6 months , and usual medications plus oral azithromycin 500 mg twice weekly for 6 months . Patients receiving azithromycin first had a 1-month washout period prior to entering the second phase . Patients recorded weekly peak flow ( PF ) measurements . Pulmonary function tests ( PFTs ) , 24-hour sputum volume , and needs for intervention with medication or ancillary support were collected at baseline and every 3 months . Exacerbation incidence and sputum volume measurements were compared from baseline to the end of each study phase . Results Twelve patients were enrolled ; 11 were included in the analysis . Owing to r and omization , most patients received the azithromycin first , which was fairly well tolerated . PFTs did not change significantly during either study phase and PFs appeared to remain stable during azithromycin therapy and throughout the subsequent control phase . Azithromycin significantly decreased the incidence of exacerbations compared with usual medications ( 5 vs 16 ; p = 0.019 ) . Mean 24-hour sputum volume significantly decreased ( 15 % [ p = 0.005 ] ) during the active treatment phase , and remained decreased during the control phase ( p = 0.028 ) . Subjectively , patients reported increased energy and quality of life while receiving treatment with azithromycin . Conclusions The addition of twice-weekly azithromycin significantly decreased the incidence of exacerbation and 24-hour sputum volume and may have stabilized the PFTs and PFs in this 11-patient pilot study . The results of this study justify further investigation of adding azithromycin to the treatment regimens of patients with bronchiectasis for its disease-modifying effects", "BACKGROUND AND OBJECTIVE To explore the effect of long-term therapy with azithromycin in regards to airway oxidative stress markers in exhaled breath condensate ( EBC ) of adult patients with stable non-cystic fibrosis ( CF ) bronchiectasis . METHODS Open-label prospect i ve study of 30 patients r and omized to azithromycin 250 mg three times per week during 3 months ( 16 patients ) or control ( 14 patients ) . Primary outcome were changes in nitric oxide , 8-isoprostane , pH , nitrites and nitrates in EBC . Secondary outcomes were changes in exacerbation rates , dyspnoea ( Borg scale ) , sputum volume ( cc ) , sputum colour ( 15-point scale ) , bacterial infection , health-related quality of life ( St George 's Respiratory Question naire ) , lung function and radiological extension . RESULTS Azithromycin produced a significant decrease in sputum volume ( 8.9 ( 1.8 ) mL vs 2.1 ( 3.4 ) mL ) and number of exacerbations ( 0.1 ( 0.6 ) vs 1.2 ( 0.9 ) ) . Dyspnoea ( 0.4 ( 0.1 ) vs 0.1 ( 0.2 ) ) and health-related quality of life also improved after therapy . However , oxidative stress markers in EBC , systemic inflammatory markers as well as functional respiratory tests did not differ from the control group after therapy . A post-hoc analysis comparing patients infected or not with Pseudomonas aeruginosa revealed that these effects were more pronounced in infected patients . In this subgroup , treatment was followed by a significant reduction in sputum volume , number of exacerbations , dyspnoea and St George 's Respiratory Question naire total score . Of all airway oxidative stress markers , only nitrates in EBC were reduced after therapy . CONCLUSIONS Long-term azythromicin treatment has some clinical benefits in patients with non-CF stable bronchiectasis , but it does not affect airway oxidative stress markers", "BACKGROUND Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties . We tested the hypothesis that azithromycin would decrease the frequency of exacerbations , increase lung function , and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis . METHODS We undertook a r and omised , double-blind , placebo-controlled trial at three centres in New Zeal and . Between Feb 12 , 2008 , and Oct 15 , 2009 , we enrolled patients who were 18 years or older , had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year , and had a diagnosis of bronchiectasis defined by high-resolution CT scan . We r and omly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio , with a permuted block size of six and sequential assignment stratified by centre . Participants , research assistants , and investigators were masked to treatment allocation . The co primary endpoints were rate of event-based exacerbations in the 6-month treatment period , change in forced expiratory volume in 1 s ( FEV(1 ) ) before bronchodilation , and change in total score on St George 's respiratory question naire ( SGRQ ) . Analyses were by intention to treat . This study is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12607000641493 . FINDINGS 71 patients were in the azithromycin group and 70 in the placebo group . The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period ( rate ratio 0·38 , 95 % CI 0·26 - 0·54 ; p<0·0001 ) . Prebronchodilator FEV(1 ) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group , but the difference was not significant ( 0·04 L , 95 % CI -0·03 to 0·12 ; p=0·251 ) . Additionally , change in SGRQ total score did not differ between the azithromycin ( -5·17 units ) and placebo groups ( -1·92 units ; difference -3·25 , 95 % CI -7·21 to 0·72 ; p=0·108 ) . INTERPRETATION Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year . FUNDING Health Research Council of New Zeal and and Auckl and District Health Board Charitable Trust", "Castro M , Zangrilli J , Wechsler ME , et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts : results from two multicentre , parallel , double-blind , r and omised , placebo-controlled , phase 3 trials . Lancet Respir Med 2015 ; published online Feb 23 . http://dx.doi.org/10.1016/S22132600(15)00042-9—In table 1 of this Article , the footnote linked to || should read “ Historical CAE was defi ned as having at least one asthma exacerbation requiring oral , intramuscular , or intravenous corticosteroid use for at least 3 days over the 12 months before screening ” and in the Declaration of interests section GGB ’s competing interests should have read “ GGB has received speaker and consultancy fees from AstraZeneca , Boehringer Ingelheim , Chiesi , Novartis , and Pfi zer . ” These corrections have been made to the online version as of March 17 and will be made to the printed Article", "STUDY OBJECTIVE Long-term administration of macrolide antibiotics reduces sputum production in patients with chronic airway diseases , probably by inhibiting airway inflammation . The objective of the present study was to determine the acute effects of a macrolide on airway chloride secretion and sputum production . METHODS We first investigated the effect of erythromycin treatment on chloride diffusion potential difference ( CPD ) across tracheal mucosa in vivo . Next , we conducted a double-blind , parallel-group study examining the effect of 7 days of treatment with clarithromycin ( 400 mg/d ) , amoxicillin ( 1,500 mg/d ) , or cefaclor ( 750 mg/d ) in patients with chronic bronchitis or bronchiectasis without apparent respiratory infection . RESULTS IV administration of erythromycin decreased the CPD of rabbit tracheal mucosa in a dose-dependent manner . Treatment of patients with clarithromycin decreased sputum production , whereas amoxicillin and cefaclor treatment had no effect . The percentage of patients whose sputum decreased > 30 % from baseline ( responders ) was 38 % in the clarithromycin group , 7 % in the amoxicillin group , and 0 % in the cefaclor group . During treatment with clarithromycin , the sputum solid composition increased and chloride concentration decreased in responders , but these changes were not observed in nonresponders . CONCLUSION Short-term administration of 14-membered macrolide reduces chronic airway hypersecretion , presumably by inhibiting chloride secretion and the result ant water secretion across the airway mucosa", "IMPORTANCE Macrolide antibiotics such as erythromycin may improve clinical outcomes in non-cystic fibrosis ( CF ) bronchiectasis , although associated risks of macrolide resistance are poorly defined . OBJECTIVE To evaluate the clinical efficacy and antimicrobial resistance cost of low-dose erythromycin given for 12 months to patients with non-CF bronchiectasis with a history of frequent pulmonary exacerbations . DESIGN , SETTING , AND PARTICIPANTS Twelve-month , r and omized ( 1:1 ) , double-blind , placebo-controlled trial of erythromycin in currently nonsmoking , adult patients with non-CF bronchiectasis with a history of 2 or more infective exacerbations in the preceding year . This Australian study was undertaken between October 2008 and December 2011 in a university teaching hospital , with participants also recruited via respiratory physicians at other centers and from public radio advertisements . INTERVENTIONS Twice-daily erythromycin ethylsuccinate ( 400 mg ) or matching placebo . MAIN OUTCOME MEASURES The primary outcome was the annualized mean rate of protocol -defined pulmonary exacerbations ( PDPEs ) per patient . Secondary outcomes included macrolide resistance in commensal oropharyngeal streptococci and lung function . RESULTS Six-hundred seventy-nine patients were screened , 117 were r and omized ( 58 placebo , 59 erythromycin ) , and 107 ( 91.5 % ) completed the study . Erythromycin significantly reduced PDPEs both overall ( mean , 1.29 [ 95 % CI , 0.93 - 1.65 ] vs 1.97 [ 95 % CI , 1.45 - 2.48 ] per patient per year ; incidence rate ratio [ IRR ] , 0.57 [ 95 % CI , 0.42 - 0.77 ] ; P = .003 ) , and in the prespecified subgroup with baseline Pseudomonas aeruginosa airway infection ( mean difference , 1.32 [ 95 % CI , 0.19 - 2.46 ] ; P = .02 ) . Erythromycin reduced 24-hour sputum production ( median difference , 4.3 g [ interquartile range [ IQR ] , 1 to 7.8 ] , P = .01 ) and attenuated lung function decline ( mean absolute difference for change in postbronchodilator forced expiratory volume in the first second of expiration , 2.2 percent predicted [ 95 % CI , 0.1 % to 4.3 % ] ; P = .04 ) compared with placebo . Erythromycin increased the proportion of macrolide-resistant oropharyngeal streptococci ( median change , 27.7 % [ IQR , 0.04 % to 41.1 % ] vs 0.04 % [ IQR , -1.6 % to 1.5 % ] ; difference , 25.5 % [ IQR,15.0 % to 33.7 % ] ; P < .001 ) . CONCLUSION AND RELEVANCE Among patients with non-CF bronchiectasis , the 12-month use of erythromycin compared with placebo result ed in a modest decrease in the rate of pulmonary exacerbations and an increased rate of macrolide resistance . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12609000578202", "BACKGROUND Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis . We aim ed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease . METHODS Between Nov 12 , 2008 , and Dec 23 , 2010 , we enrolled Indigenous Australian , Maori , and Pacific Isl and children aged 1 - 8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre , double-blind , r and omised , parallel-group , placebo-controlled trial . Eligible children had had at least one pulmonary exacerbation in the previous 12 months . Children were r and omised ( 1:1 ratio , by computer-generated sequence with permuted block design , stratified by study site and exacerbation frequency [ 1 - 2 vs ≥3 episodes in the preceding 12 months ] ) to receive either azithromycin ( 30 mg/kg ) or placebo once a week for up to 24 months . Allocation concealment was achieved by double-sealed , opaque envelopes ; participants , caregivers , and study personnel were masked to assignment until after data analysis . The primary outcome was exacerbation ( respiratory episodes treated with antibiotics ) rate . Analysis of the primary endpoint was by intention to treat . At enrolment and at their final clinic visits , children had deep nasal swabs collected , which we analysed for antibiotic-resistant bacteria . This study is registered with the Australian New Zeal and Clinical Trials Registry ; ACTRN12610000383066 . FINDINGS 45 children were assigned to azithromycin and 44 to placebo . The study was stopped early for feasibility reasons on Dec 31 , 2011 , thus children received the intervention for 12 - 24 months . The mean treatment duration was 20·7 months ( SD 5·7 ) , with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group . Compared with the placebo group , children receiving azithromycin had significantly lower exacerbation rates ( incidence rate ratio 0·50 ; 95 % CI 0·35 - 0·71 ; p<0·0001 ) . However , children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria ( 19 of 41 , 46 % ) than those receiving placebo ( four of 37 , 11 % ; p=0·002 ) . The most common adverse events were non-pulmonary infections ( 71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group ) and bronchiectasis-related events ( episodes or investigations ; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group ) ; however , study drugs were well tolerated with no serious adverse events being attributed to the intervention . INTERPRETATION Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease . However , this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria , the clinical consequences of which are uncertain , and will need careful monitoring and further study . FUNDING National Health and Medical Research Council ( Australia ) and Health Research Council ( New Zeal and )", "OBJECTIVE To investigate the impact of treatment with low dose roxithromycin on clinical symptoms and CT scores in patients with stable bronchiectasis . METHODS Fifty patients with bronchiectasis in stable condition were r and omly assigned to a control group and a treatment group . Patients in the control group received ambroxol hydrochloride tablet 90 mg 3 times a day . Patients in the treatment group received roxithromycin disperse tablet 0.15 g every day and ambroxol hydrochloride tablet 90 mg 3 times a day . The course of treatment lasted for 6 months . Quality of life was assessed using St. George 's respiratory question naire ( SGRQ ) . The British Medical Research Council ( MRC ) dyspnea scale was used to assess the degree of dyspnea . The score for CT evaluation of the thorax , quality of life and SGRQ were performed for all patients before and after the treatment . RESULTS After 6 months , the scores for quality of life ( 48 ± 13 ) were lower compared to that ( 58 ± 15 ) before treatment in the control group ; however , the scores for bronchial wall thickening of bronchiectasis ( 1.8 ± 0.5 ) were higher than that ( 1.8 ± 0.4 ) before study . The scores for the extent of bronchiectasis ( 2.7 ± 1.6 ) , the bronchial wall thickening of bronchiectasis ( 1.3 ± 0.4 ) and the global CT score ( 6.7 ± 2.5 ) were reduced after treatment as compared to those before treatment [ ( 4.8 ± 2.3 ) , ( 1.8 ± 0.5 ) , ( 9.5 ± 3.3 ) ] in the treatment group , ( all P < 0.01 ) . The degree of dyspnea ( 1.3 ± 0.4 ) and quality of life ( 42 ± 12 ) were lower than those before treatment [ ( 1.89 ± 0.45 ) , ( 56 ± 15 ) ] in the treatment group . Furthermore , the scores for extent of bronchiectasis ( 2.7 ± 1.6 ) , the scores for the bronchial wall thickening of bronchiectasis ( 1.3 ± 0.4 ) and the global CT score ( 6.7 ± 2.5 ) in the treatment group were significantly improved as compared with those [ ( 4.8 ± 2.0 ) , ( 1.8 ± 0.5 ) , ( 9.7 ± 3.6 ) ] in the control group respectively after treatment . At the same time , the degree of dyspnea ( 1.3 ± 0.4 ) in the treatment group was significantly improved as compared with that ( 1.7 ± 0.4 ) in the control group after treatment . CONCLUSIONS The scores for the bronchial wall thickening of bronchiectasis were increased in patients with stable bronchiectasis . Low dose roxithromycin combined with ambroxol hydrochloride significantly improved degree of dyspnea , reduced scores for extent of bronchiectasis , scores for the bronchial wall thickening of bronchiectasis and the global CT score as compared to treatment with ambroxol hydrochloride alone in patients with bronchiectasis in stable condition", "Aims : To prospect ively estimate the incidence of bronchiectasis among New Zeal and ( NZ ) children , to consider aetiology and severity , and to evaluate regional and ethnic variation . Methodology : NZ paediatricians were surveyed monthly for new cases of bronchiectasis during 2001 and 2002 via the NZ paediatric surveillance unit ( with coverage of > 94 % of NZ paediatricians ) . Notified cases had their computed tomography scans review ed and scored for severity . Confirmed cases were followed up by postal question naire one year after diagnosis . Demographic , aetiological , and severity data were collected . Results : Ninety nine notifications were received . Sixty five cases were confirmed . An overall incidence of 3.7 per 100 000 under 15 year old children per year was estimated . Incidence was highest in Pacific children at 17.8 compared with 4.8 in Maori , 1.5 in NZ European , and 2.4 other per 100 000 per year . Incidence varied significantly by region . The median age at diagnosis was 5.2 years ; the majority had symptoms for more than two years . Eighty three per cent had bilateral disease , with a median of three lobes affected , mean FEV1 of 77 % predicted , and modified Bhalla H RCT score of 18 . Conclusions : The incidence of bronchiectasis is high in NZ children , nearly twice the rate for cystic fibrosis and seven times that of Finl and , the only other country reporting a childhood national rate . Incidence varied substantially between ethnicities . Most cases developed disease in early childhood and had delayed diagnosis", "BACKGROUND The effects of the macrolides can not be ascribed to their antibacterial action alone . Their immunoregulatory and anti-inflammatory functions are significant too . They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis ( CF ) . AIM To evaluate the effects of a macrolide antibiotic [ clarithromycin ( CAM ) ] on the process of inflammation [ by measuring IL-8 , TNF-alpha , IL-10 levels and cell profiles in bronchoalveolar lavage ( BAL ) fluid ] , pulmonary function and sputum production in children with steady-state bronchiectasis , secondary to causes other than CF or primary immunodeficiencies . METHODS Seventeen patients r and omized to the treatment group received CAM and supportive therapies for 3 months and 17 patients in the control group were given supportive therapies only . RESULTS Compared with the control group , the treatment group showed a significant decrease in IL-8 levels , total cell count , neutrophil ratios in BAL fluid and daily sputum production at the end of the third month . There was also a significant increase in the treatment group 's BAL fluid macrophage ratios . The differences in pulmonary function test parameters were not significant . CONCLUSION Use of CAM in children with steady-state bronchiectasis results in laboratory improvement by reducing the inflammatory processes in the lungs . No corresponding clinical improvement could be shown but although this is possible with long-term use , trial validation is necessary" ]

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[ "Parity, Mode of Delivery, and Pelvic Floor Disorders", "Fecal Incontinence During the First 12 Months Postpartum: Complex Causal Pathways and Implications for Clinical Practice", "Effects of carrying a pregnancy and of method of delivery on urinary incontinence: a prospective cohort study", "Urinary incontinence in middle aged women: childhood enuresis and other lifetime risk factors in a British prospective cohort.", "Pelvic organ support in pregnancy and postpartum", "Maternal outcomes at 2 years after planned cesarean section versus planned vaginal birth for breech presentation at term: the international randomized Term Breech Trial.", "The effect of pregnancy and mode of delivery on the prevalence of urinary and fecal incontinence.", "Effect of postpartum pelvic floor muscle training in prevention and treatment of urinary incontinence: a one‐year follow up", "Planned cesarean section versus planned vaginal delivery: comparison of lower urinary tract symptoms", "Antenatal prediction of postpartum urinary and fecal incontinence.", "Fecal and Urinary Incontinence in Primiparous Women", "Symptomatic Pelvic Organ Prolapse: Prevalence and Risk Factors in a Population-Based, Racially Diverse Cohort", "The effect of mode of delivery, parity, and birth weight on risk of urinary incontinence", "Faecal incontinence after first instrumental vaginal delivery using Thierry’s spatulas", "Obstetric anal sphincter injury, risk factors and method of delivery – an 8-year analysis across two tertiary referral centers", "Anal incontinence after childbirth." ]

[ "OBJECTIVE : This study aim ed to assess the associations between parity , mode of delivery , and pelvic floor disorders . METHODS : The prevalence of pelvic organ prolapse , stress urinary incontinence , overactive bladder , and anal incontinence was assessed in a r and om sample of women aged 25–84 years by using the vali date d Epidemiology of Prolapse and Incontinence Question naire . Women were categorized as nulliparous , vaginally parous , or only delivered by cesarean . Adjusted odds ratios and 95 % confidence intervals ( CIs ) for each disorder were calculated with logistic regression , controlling for age , body mass index , and parity . RESULTS : In the 4,458 respondents the prevalence of each disorder was as follows : 7 % prolapse , 15 % stress urinary incontinence , 13 % overactive bladder , 25 % anal incontinence , and 37 % for any one or more pelvic floor disorders . There were no significant differences in the prevalence of disorders between the cesarean delivery and nulliparous groups . The adjusted odds of each disorder increased with vaginal parity compared with cesarean delivery : prolapse = 1.82 ( 95 % CI 1.04–3.19 ) , stress urinary incontinence = 1.81 ( 95 % CI 1.25–2.61 ) , overactive bladder = 1.53 ( 95 % CI 1.02–2.29 ) , anal incontinence = 1.72 ( 95 % CI 1.27–2.35 ) , and any one or more pelvic floor disorders = 1.85 ( 95 % CI 1.42–2.41 ) . Number-needed-to-treat analysis revealed that 7 women would have to deliver only by cesarean delivery to prevent one woman from having a pelvic floor disorder . CONCLUSION : The risk of pelvic floor disorders is independently associated with vaginal delivery but not with parity alone . Cesarean delivery has a protective effect , similar to nulliparity , on the development of pelvic floor disorders when compared with vaginal delivery . LEVEL OF EVIDENCE :", "OBJECTIVES : To investigate whether postpartum fecal incontinence is less common in women who had a cesarean delivery and more common in women who had an operative vaginal birth compared with women who had a spontaneous vaginal birth for their first newborn , and whether postpartum fecal incontinence is more common in women who report intimate-partner violence . METHODS : This was a multicenter , prospect i ve , nulliparous pregnancy cohort ( n=1,507 ) using st and ardized measures to assess frequency and severity of fecal incontinence in pregnancy and at 3 , 6 , 9 , and 12 months postpartum . RESULTS : Approximately 17 % reported fecal incontinence at some point in the first 12 months postpartum , with 12.8 % reporting fecal incontinence beyond the first 3 months postpartum . Fecal incontinence at 4 to12 months postpartum was significantly more common among women who had experienced emotional violence , physical violence , or both in the first 12 months postpartum ( 18.8 % compared with 11.5 % , adjusted odds ratio [ OR ] 1.62 , 95 % confidence interval [ CI ] 1.05–2.50 ) . Compared with spontaneous vaginal birth , cesarean delivery ( 13.1 % compared with 11.3 % , adjusted OR 0.99 , 95 % CI 0.65–1.53 ) , and operative vaginal birth ( 15.0 % compared with 11.3 % , adjusted OR 1.33 , 95 % CI 0.86–2.07 ) did not significantly alter the likelihood of fecal incontinence beyond the first 3 months postpartum . CONCLUSION : Underst and ing causal pathways for postpartum fecal incontinence requires attention to the interplay of pregnancy and birth events and upstream factors such as intimate-partner violence . This has implication s for how clinicians present evidence and discuss risks associated with vaginal birth and cesarean delivery . In this nulliparous cohort , method of birth was not a major determinant of fecal incontinence status beyond 3 months postpartum . LEVEL OF EVIDENCE :", "Background This study was carried out to identify risk factors associated with urinary incontinence in women three months after giving birth . Methods Urinary incontinence before and during pregnancy was assessed at study enrolment early in the third trimester . Incontinence was re-assessed three months postpartum . Logistic regression analysis was used to assess the role of maternal and obstetric factors in causing postpartum urinary incontinence . This prospect i ve cohort study in 949 pregnant women in Quebec , Canada was nested within a r and omised controlled trial of prenatal perineal massage . Results Postpartum urinary incontinence was increased with prepregnancy incontinence ( adjusted odds ratio [ adj0R ] 6.44 , 95 % CI 4.15 , 9.98 ) , incontinence beginning during pregnancy ( adjOR 1.93 , 95 % CI 1.32 , 2.83 ) , and higher prepregnancy body mass index ( adjOR 1.07/unit of BMI , 95 % CI 1.03,1.11 ) . Caesarean section was highly protective ( adjOR 0.27 , 95 % CI 0.14 , 0.50 ) . While there was a trend towards increasing incontinence with forceps delivery ( adjOR 1.73 , 95 % CI 0.96 , 3.13 ) this was not statistically significant . The weight of the baby , episiotomy , the length of the second stage of labour , and epidural analgesia were not predictive of urinary incontinence . Nor was prenatal perineal massage , the r and omised controlled trial intervention . When the analysis was limited to women having their first vaginal birth , the same risk factors were important , with similar adjusted odds ratios . Conclusions Urinary incontinence during pregnancy is extremely common , affecting over half of pregnant women . Urinary incontinence beginning during pregnancy roughly doubles the likelihood of urinary incontinence at 3 months postpartum , regardless whether delivery is vaginal or by Caesarean section", "STUDY OBJECTIVE : To investigate the prevalence and lifetime risk factors for urinary incontinence in middle aged women . DESIGN : Nationally representative birth cohort study with prospect i ve data on childhood enuresis , measured adult height and weight , childbearing histories and measures of socioeconomic status up date d at regular contacts , and measures of menopausal status , symptomatology and health care in midlife . SETTING : Engl and , Scotl and and Wales . PARTICIPANTS : General population sample of 1333 women aged 48 years . MAIN RESULTS : Fifty per cent reported symptoms of stress incontinence and 22 % reported symptoms of urge incontinence in the previous year . Eight per cent had severe symptoms . Women who at age 6 years had wet in the day or several nights a week were more likely to suffer severe incontinence and report urge symptoms but occasional bedwetting was not associated with an increased risk in adult life . Those who were older at the birth of their children and who had vaginal deliveries had an excess risk of stress symptoms . Heavier adult body weight was also a risk factor for these symptoms and for severe incontinence . Postmenopausal women were less likely to report stress symptoms . These risk factors remained significant after taking account of the increased reporting of incontinence among women with high levels of general symptomatology and general practitioner visits , and of stress symptoms among better educated women . CONCLUSIONS : Urinary incontinence is a common problem among middle aged women . This is the first prospect i ve study of a general population sample to support the postulated link between childhood enuresis and adult incontinence . Child-bearing has long term adverse effects , particularly for older mothers . Overweight is a common risk factor", "The purpose of this study was to evaluate pelvic organ support during pregnancy and following delivery . This was a prospect i ve observational study . Pelvic organ prolapse quantification ( POPQ ) examinations were performed during each trimester of pregnancy and in the postpartum . Statistical comparisons of POPQ stage and of the nine measurements comprising the POPQ between the different time intervals were made using Wilcoxon ’s signed rank and the paired t-test . Comparison of POPQ stage by mode of delivery was made using Fisher ’s exact test . One hundred thirty-five nulliparous women underwent 281 pelvic organ support evaluations . During both the third trimester and postpartum , POPQ stage was significantly higher compared to the first trimester ( p<0.001 ) . In the postpartum , POPQ stage was significantly higher in women delivered vaginally compared to women delivered by cesarean ( p=0.02 ) . In nulliparous pregnant women , POPQ stage appears to increase during pregnancy and does not change significantly following delivery . In the postpartum , POPQ stage may be higher in women delivered vaginally compared to women delivered by cesarean", "OBJECTIVE This study was undertaken to compare maternal outcomes at 2 years postpartum after planned cesarean section and planned vaginal birth for the singleton fetus in breech presentation at term . STUDY DESIGN In selected centers in the Term Breech Trial , mothers completed a structured question naire at 2 or more years postpartum to determine their health in the previous 3 to 6 months . RESULTS A total of 917 of 1159 ( 79.1 % ) mothers from 85 centers completed a follow-up question naire at 2 years postpartum . There were no differences between groups in breast feeding , relationship with child or partner , pain , subsequent pregnancy , incontinence , depression , urinary , menstrual or sexual problems , fatigue , or distressing memories of the birth experience . Planned cesarean section was associated with a higher risk of constipation ( P = .02 ) . CONCLUSION Maternal outcomes at 2 years postpartum are similar after planned cesarean section and planned vaginal birth for the singleton breech fetus at term", "OBJECTIVE The purpose of this study was to determine the relative effects of pregnancy and mode of delivery on the prevalence of urinary and fecal incontinence . STUDY DESIGN This was a prospect i ve , observational multicenter study of women presenting to 6 gynecology clinics . Demographic data collected included : height , weight , gravidity , parity , and number of vaginal deliveries . Patients were diagnosed with incontinence by question naire . St and ard univariate logistic regression analyses ' were performed to determine the contribution of pregnancy , mode of delivery , and BMI on the prevalence of urinary and fecal incontinence . RESULTS One thous and and four women were enrolled over an 18-month period . Two hundred and thirty-seven and 128 subjects had urinary and fecal incontinence , respectively . Odds ratio ( 95 % CI ) calculated for the prevalence of urinary incontinence by pregnancy and mode of delivery were : any term pregnancy vs no term pregnancy was 2.46 ( 1.53 - 3.95 ) , any term pregnancy but no vaginal deliveries ( cesarean section only ) vs no term pregnancy was 1.95 ( 0.99 - 3.80 ) , any term pregnancy and at least 1 vaginal delivery vs no term pregnancy was 2.53 ( 1.57 - 4.07 ) , and any term pregnancy but no vaginal delivery ( cesarean section only ) vs any term pregnancy , and at least 1 vaginal delivery was 1.30 ( 0.77 - 3.95 ) . Odds ratio ( 95 % CI ) calculated for the prevalence of fecal incontinence by pregnancy and mode of delivery were : any term pregnancy vs no term pregnancy was 2.26 ( 1.22 - 4.19 ) , any term pregnancy but no vaginal deliveries ( cesarean section only ) vs no term pregnancy was 1.13 ( 0.43 - 2.96 ) , any term pregnancy and at least 1 vaginal delivery vs no term pregnancy was 2.41 ( 1.30 - 4.49 ) , and any term pregnancy but no vaginal deliveries ( cesarean section only ) vs any term pregnancy , and at least 1 vaginal delivery was 2.15 ( 0.97 - 4.77 ) . BMI and age did not impact these results . CONCLUSION Pregnancy increases the risk of urinary and fecal incontinence . Cesarean section does not decrease the risk of urinary or fecal incontinence compared to pregnancy with a vaginal delivery", "Objective To evaluate the long term effect of a postpartum pelvic floor muscle training course in prevention and treatment of urinary incontinence", "We compared the prevalence and risk of lower urinary tract symptoms in healthy primiparous women in relation to vaginal birth or elective cesarean section 9 months after delivery . We performed a prospect i ve controlled cohort study including 220 women delivered by elective cesarean section and 215 by vaginal birth . All subjects received an identical question naire on lower urinary tract symptoms in late pregnancy , at 3 and 9 months postpartum . Two hundred twenty subjects underwent elective cesarean section , and 215 subjects underwent vaginal delivery . After childbirth , the 3-month question naire was completed by 389/435 subjects ( 89 % ) and the 9-month question naire by 376/435 subjects ( 86 % ) . In the vaginal delivery cohort , all lower urinary tract symptoms increased significantly at 9 months follow-up . When compared to cesarean section , the prevalence of stress urinary incontinence ( SUI ) after vaginal delivery was significantly increased both at 3 ( p < 0.001 ) and 9 months ( p = 0.001 ) follow-up . In a multivariable risk model , vaginal delivery was the only obstetrical predictor for SUI [ relative risk ( RR ) 8.9 , 95 % confidence interval ( CI ) 1.9–42 ] and for urinary urgency ( RR 7.3 95 % CI 1.7–32 ) at 9 months follow-up . A history of SUI before pregnancy ( OR 5.2 , 95 % CI 1.5–19 ) and at 3 months follow-up ( OR 3.9 , 95 % CI 1.7–8.5 ) were independent predictors for SUI at 9 months follow-up . Vaginal delivery is associated with an increased risk for lower urinary tract symptoms 9 months after childbirth when compared to elective cesarean section", "OBJECTIVE To investigate the effect of pregnancy and delivery on continence and to assess whether physical markers of collagen weakness can predict postpartum urinary and fecal incontinence ( including incontinence of flatus ) . METHODS In a prospect i ve , longitudinal study in a London teaching hospital , 549 nulliparas were interviewed after 34 weeks ' gestation and again 3 months postpartum regarding urinary and fecal symptoms before and during pregnancy and after delivery . Family histories of incontinence , prolapse , and collagen abnormalities were recorded also . Physical examination was done to assess markers of collagen weakness such as striae , hernia , varicose veins , and joint mobility . RESULTS The prevalence of urinary incontinence before , during , and after pregnancy was 3.6 % , 43.7 % , and 14.6 % , and rates of fecal incontinence were 0.7 % , 6.0 % , and 5.5 % , respectively . Fecal urgency was more common in women who had spontaneous and instrument-assisted vaginal deliveries ( n = 413 ) compared with cesareans ( n = 131 ) ( 7.3 % versus 3.1 % ; P = .046 ) . Postnatal urinary or fecal dysfunction was not related to antenatal body mass index , smoking , race , striae , varicose veins , hemorrhoids , or family history of incontinence . Higher joint-mobility scores were associated with incontinence of flatus ( P = .021 ) but not with other urinary or fecal symptoms . CONCLUSION Although collagen weakness was previously implicated in the pathogenesis of incontinence , physical markers in this study could not predict postpartum urinary and fecal incontinence . Either those markers were not representative of collagen weakness , or a larger study with longer follow-up is necessary", "OBJECTIVE : To prospect ively investigate the relationship between anal sphincter tears and postpartum fecal and urinary incontinence . METHODS : The Childbirth and Pelvic Symptoms study was a prospect i ve cohort study performed by the Pelvic Floor Disorders Network to estimate the prevalence of postpartum fecal and urinary incontinence in primiparous women : 407 with clinical ly recognized anal sphincter tears during vaginal delivery , 390 without recognized sphincter tears ( vaginal controls ) , and 124 delivered by cesarean before labor . Women were recruited postpartum while hospitalized and interviewed by telephone 6 weeks and 6 months postpartum . We assessed fecal and urinary incontinence symptoms using the Fecal Incontinence Severity Index and the Medical , Epidemiological , and Social Aspects of Aging Question naire , respectively . Odds ratios were adjusted for age , race , and clinical site . RESULTS : Compared with the vaginal control group , women in the sphincter tear cohort reported more fecal incontinence ( 6 weeks , 26.6 % versus 11.2 % ; adjusted odds ratio [ AOR ] 2.8 , 95 % confidence interval [ CI ] 1.8–4.3 ; 6 months , 17.0 % versus 8.2 % ; AOR 1.9 , 95 % CI 1.2–3.2 ) , more fecal urgency and flatal incontinence , and greater fecal incontinence severity at both times . Urinary incontinence prevalence did not differ between the sphincter tear and vaginal control groups . Six months postpartum , 22.9 % of women delivered by cesarean reported urinary incontinence , whereas 7.6 % reported fecal incontinence . CONCLUSION : Women with clinical ly recognized anal sphincter tears are more than twice as likely to report postpartum fecal incontinence than women without sphincter tears . Cesarean delivery before labor is not entirely protective against pelvic floor disorders . LEVEL OF EVIDENCE :", "OBJECTIVE : To estimate the prevalence of and identify risk factors associated with symptomatic pelvic organ prolapse and level of distress in racially diverse women aged older than 40 years . METHODS : The Reproductive Risks for Incontinence Study at Kaiser is a population -based study of 2,001 r and omly selected women . Symptomatic prolapse was determined by self-report of a feeling of bulge , pressure , or protrusion or a visible bulge from the vagina . Risk factors were assessed by self-report , interview , physical examination , and record review . Distress was assessed by self-report . Multivariable logistic regression analysis was used to identify independent risk factors . RESULTS : Symptomatic prolapse was reported by 118 ( 6 % ) women . Almost 50 % of these women reported moderate or great distress , and 35 % reported that the symptoms affected at least one physical , social or sexual activity . In multivariable analysis , the risk of prolapse was significantly increased in women with one ( odds ratio [ OR ] 2.8 , 95 % confidence interval [ CI ] 1.1–7.2 ) , two ( OR 4.1 , 95 % CI 1.8–9.5 ) , and three or more ( OR 5.3 , 95 % CI 2.3–12.3 ) vaginal deliveries compared with nulliparous women . Irritable bowel syndrome , constipation , and self-reported fair or poor health status were strongly associated with prolapse , with ORs of 2.8 ( 95 % CI 1.7–4.6 ) , 2.5 ( 95 % CI 1.7–3.7 ) , and 2.3 ( 95 % CI 1.1–4.9 ) , respectively . African-American women were significantly less likely to report symptomatic prolapse compared with white women ( OR 0.4 , 95 % CI 0.2–0.8 ) . CONCLUSION : Symptomatic prolapse is less common among African-American women and more common among women with a prior vaginal delivery , poor health status , constipation , or irritable bowel syndrome . Nearly one half of women with symptomatic prolapse are substantially bothered by their symptoms . LEVEL OF EVIDENCE :", "To examine the relationship between symptoms of urinary incontinence ( UI ) and mode of delivery , parity , and birth weight , data were obtained from a population -based r and om sample of 3,205 black , Hispanic , and white women age 30–79 in the Boston Area Community Health Survey . Measures include UI symptoms [ ≥3 ( moderate/severe ) S and vik ’s severity index ] ; reproductive history [ live birth(s ) , no live births , never pregnant ] ; mode of delivery for live births ( ≥1 vaginal birth , cesarean delivery only ) ; parity ( 1 , 2 , ≥3 ) ; and maximum birth weight of live births ( < 4,000 g , ≥4,000 g ) . Using logistic regression , women having ≥1 vaginal delivery had twice the odds of UI compared to women with no pregnancies ( P = 0.002 ) or only cesarean deliveries ( P = 0.032 ) . There was no difference in odds of UI between cesarean delivery only and never pregnant , by parity or birth weight . Vaginal delivery contributes to risk of UI for black , Hispanic , and white women", "Objective The purpose of this study is to estimate the prevalence of faecal incontinence after first vaginal delivery and to assess the impact of Thierry ’s spatulas-assisted delivery . Methods A prospect i ve observational study of primiparas who underwent a vaginal delivery at term was conducted . Faecal incontinence was assessed at 2 and 6 months postpartum by a question naire ( Wexner score ≥5 was considered significant ) . Univariate and multivariate analyses were performed . Results Five hundred thirty-eight women were recruited with undergoing 176 spatulas-assisted deliveries and 362 spontaneous vaginal deliveries . The response rate was 85.9 % ( 2 months ) and 80.5 % ( 6 months ) . The prevalence of faecal incontinence was similar between the two groups at 2 months ( 14.3 % and 9.7 % ) . Episiotomy ( odds ratio [ OR ] = 5.0 ) and maternal age over 35 years ( OR = 4.1 ) were independently associated with faecal incontinence after adjustment . Conclusions Anal symptoms are common after the first vaginal delivery . Thierry ’s spatulas do not increase the prevalence of faecal incontinence after delivery given that an episiotomy is performed", "Abstract Objective : Obstetric anal sphincter injury ( OASIS ) represents a major cause of maternal morbidity and is a risk factor for the development of fecal incontinence . We set out to analyze the incidence of OASIS and its association with mode of delivery in two large obstetric hospitals across an 8-year study period . Methods : This was a prospect i ve observational study carried out at two large tertiary referral centers serving a single urban population , from 2003 to 2010 . Incidence of OASIS was examined as well as the influence of parity and mode of delivery on the occurrence of OASIS . Results : During the study period , there were 100 307 vaginal deliveries at the two hospitals . There was a total of 2121 cases of OASIS from 2003 to 2010 , giving an incidence of 2.1 % of vaginal deliveries . Patients were more likely to suffer an OASIS when having a forceps delivery than when having a normal vaginal delivery ( 8.6 % versus 1.3 % , p < 0.0001 , OR : 7.1 , CI : 6.4–7.9 ) . Vacuum delivery also carried an increased risk of sphincter injury compared with normal delivery ( 3.7 % versus 1.3 % , p < 0.0001 , OR : 2.9 , CI : 2–2.6 ) . About 16.7 % of infants delivered were macrosomic ( birthweight > 4 kg ) . The rate of episiotomy during the study was 19.1 % . Conclusion : These results demonstrate that OASIS remains an important cause of maternal morbidity in contemporary obstetric practice . These results will likely be of value in risk management planning and patient debriefing in what is a highly litigious area of obstetrics", "BACKGROUND Incontinence of stool and flatus are frequent complications of childbirth . We examined the prevalence and possible causes of these adverse outcomes in a large cohort of women . METHODS We studied 949 pregnant women who gave birth in 5 hospitals in 1995/96 in the province of Quebec . These women , participants in a r and omized controlled trial of prenatal perineal massage , completed a self-administered question naire 3 months after giving birth . RESULTS Three months after delivery 29 women ( 3.1 % ) reported incontinence of stool , and 242 ( 25.5 % ) had involuntary escape of flatus . Incontinence of stool was more frequent among women who delivered vaginally and had third- or fourth-degree perineal tears than among those who delivered vaginally and had no anal sphincter tears ( 7.8 % v. 2.9 % ) . Forceps delivery ( adjusted risk ratio [ RR ] 1.45 , 95 % confidence interval [ CI ] 1.01 - 2.08 ) and anal sphincter tears ( adjusted RR 2.09 , 95 % CI 1.40 - 3.13 ) were independent risk factors for incontinence of flatus or stool or both . Anal sphincter injury was strongly and independently associated with first vaginal birth ( RR 39.2 , 95 % CI 5.4 - 282.5 ) , median episiotomy ( adjusted RR 9.6 , 95 % CI 3.2 - 28.5 ) , forceps delivery ( adjusted RR 12.3 , 95 % CI 3.0 - 50.4 ) and vacuum-assisted delivery ( adjusted RR 7.4 , 95 % CI 1.9 - 28.5 ) but not with birth weight ( adjusted RR for nirth weight 4000 g or more : 1.4 , 95 % CI 0.6 - 3.0 ) or length of the second stage of labour ( adjusted RR for second stage 1.5 hours or longer compared with less than 0.5 hours : 1.2 , 95 % CI 0.5 - 2.7 ) . INTERPRETATION Anal incontinence is associated with forceps delivery and anal sphincter laceration . Anal sphincter laceration is strongly predicted by first vaginal birth , median episiotomy , and forceps or vacuum delivery but not by birth weight or length of the second stage of labour" ]

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[ "Timing of Antioxidant Vitamin Ingestion Alters Postprandial Proatherogenic Serum Markers", "Vitamin E Reduction of Protein Glycosylation in Diabetes: New Prospect for Prevention of Diabetic Complications?", "Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes.", "Effects of alpha-tocopherol supplementation and continuous subcutaneous insulin infusion on oxidative stress in Korean patients with type 2 diabetes.", "Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.", "The Impact of Vitamins and/or Mineral Supplementation on Blood Pressure in Type 2 Diabetes", "Vitamin E Supplementation Reduces Cardiovascular Events in a Subgroup of Middle-Aged Individuals With Both Type 2 Diabetes Mellitus and the Haptoglobin 2-2 Genotype: A Prospective Double-Blinded Clinical Trial", "Comparison of the effects of vitamins and/or mineral supplementation on glomerular and tubular dysfunction in type 2 diabetes.", "Long term effects of oral vitamin E supplement in type II diabetic patients.", "Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type II diabetic patients.", "Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes.", "Pro-oxidant effect of α-tocopherol in patients with Type 2 Diabetes after an oral glucose tolerance test – a randomised controlled trial", "Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial.", "The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients.", "Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled diabetes.", "The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia.", "Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus.", "Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy.", "Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study.", "The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial", "The impact of vitamin and/or mineral supplementation on lipid profiles in type 2 diabetes.", "Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects.", "RRR-alpha-tocopheryl acetate supplementation at pharmacologic doses decreases low-density-lipoprotein oxidative susceptibility but not protein glycation in patients with diabetes mellitus.", "Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of alpha-tocopherol supplementation.", "Effect of tocopherol on platelet aggregation in non-insulin-dependent diabetes mellitus: ex vivo and in vitro studies.", "Effects of Vitamin E on Susceptibility of Low-Density Lipoprotein and Low-Density Lipoprotein Subfractions to Oxidation and on Protein Glycation in NIDDM", "Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes.", "Measurement feasability of advanced glycated end-products from skin samples after antioxidant vitamin supplementation in patients with type 2 diabetes.", "[Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation]." ]

[ "Background This study was design ed to determine the optimal timing of vitamins E and C to prevent oxidative stress induced by a high‐fat evening meal in type 2 diabetes . Methods and Results Eleven subjects were admitted on 4 occasions . Euglycemia was maintained for 24 hours by insulin infusion . Participants were fed a high‐fat test supper equivalent to a McDonald 's Big Mac Meal . Blood was drawn for measurement of C‐reactive protein ( CRP ) , interleukin 6 ( IL‐6 ) , plasminogen activator inhibitor‐1 ( PAI‐1 ) , malonyldialdehyde ( MDA ) , and total radical antioxidant parameter ( TRAP ) before and during the 4 hours after the test meal . Studies were performed in r and om sequence with vitamin E 800 IU and vitamin C 1 g given either before breakfast or before supper in a double‐blind manner on the day of the test meal . Control studies were performed with no vitamins and no test meal administered . There was a significant rise in CRP and PAI‐1 after the test supper ( P<0.05 compared with “ no meal ” ) . Either presupper or prebreakfast vitamins E and C prevented the meal‐induced rise in CRP ( P=0.03 ) , although presupper vitamins were more effective ( P=0.03 compared with prebreakfast vitamins ) . Only prebreakfast vitamins prevented the meal‐induced rise in PAI‐1 ( P=0.006 ) . There were no significant meal‐related changes in the concentrations of IL‐6 , MDA , or TRAP . Conclusions The timing of administration of antioxidant vitamins has variable effects on markers of meal‐induced inflammation and fibrinolysis . This observation may be one reason why cardiovascular disease prevention trials using these vitamins have reported conflicting results . ( Circulation . 2003;108:24‐31 .", "Objective This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E. Research Design and Methods Two groups of 10 insulin-requiring diabetic patients , matched for duration of disease and metabolic control , received daily vitamin E supplementation of 1200 and 600 mg , respectively , for 2 mo . A third group of 10 diabetic patients , matched for duration of disease and metabolic control , served as the control group and received placebo . Fasting plasma glucose , mean daily plasma glucose , fasting labile HbA1 , and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment . In addition , hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients . Results Glycemic indices did not show any significant changes during the study , whereas fasting labile HbA , and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration . Stable HbA1 decreased after 2 mo . Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment , whereas a significant reduction in mean labile HbA1 incremental area was found after vitamin E supplementation . A significant difference was also found in both fasting and incremental labile HbA1 levels , stable HbA1 , and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E ; the diabetic patients who received the higher dose of vitamin E showed the greater reduction . No significant changes in these parameters were observed in diabetic patients on placebo administration . Conclusions These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose , an effect that may be due to the inhibition of labile glycosylation , the first step of the Maillard reaction . Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications", "BACKGROUND Type 2 diabetes is associated with elevated oxidative stress and declines in antioxidant defense . The disease is also characterized by an imbalance in the ratio of cardiac sympathetic to parasympathetic tone . Antioxidants , vitamin E in particular , may have beneficial effects on the cardiac autonomic nervous system through a decline in oxidative stress . OBJECTIVE We investigated the possible effects of vitamin E on the cardiac autonomic nervous system , as assessed by analysis of heart rate variability , in patients with type 2 diabetes and cardiac autonomic neuropathy . DESIGN In a double-blind r and omized controlled trial , 50 patients with type 2 diabetes were assigned to treatment with vitamin E ( 600 mg/d ) or placebo for 4 mo . RESULTS The anthropometric characteristics of the patients remained unchanged throughout the study . Chronic vitamin E administration was associated with decreases in concentrations of glycated hemoglobin ( P < 0.05 ) , plasma insulin ( P < 0.05 ) , norepinephrine ( P < 0.03 ) , and epinephrine ( P < 0.02 ) ; a lower homeostasis model assessment index ( P < 0.05 ) ; and improved indexes of oxidative stress . Furthermore , vitamin E administration was associated with increases in the R-R interval ( P < 0.05 ) , total power ( P < 0.05 ) , and the high-frequency component of heart rate variability ( HF ; P < 0.05 ) and decreases in the low-frequency component ( LF ; P < 0.05 ) and the ratio of LF to HF ( P < 0.05 ) . Finally , change in the plasma vitamin E concentration was correlated with change in the LF-HF ratio ( r = -0.43 , P < 0.04 ) independently of changes in the homeostasis model assessment index and plasma catecholamines concentrations . CONCLUSIONS Chronic vitamin E administration improves the ratio of cardiac sympathetic to parasympathetic tone in patients with type 2 diabetes . Such an effect might be mediated by a decline in oxidative stress", "BACKGROUND Most Koreans with type 2 diabetes are insulin deficient and insulin resistant . Continuous subcutaneous insulin infusion ( CSII ) provides a suitable amount of insulin to overcome insulin deficiency and achieve near-normal blood glucose concentrations . Our previous study showed , however , that CSII does not reduce oxidative stress even though it normalizes blood glucose concentrations . OBJECTIVE The purpose of this study was to determine whether CSII plus alpha-tocopherol supplementation for 2 mo would alter oxidative stress in Korean patients with type 2 diabetes . DESIGN Ninety-eight subjects received CSII plus either 200 mg alpha-tocopherol/d ( n = 48 ) or a placebo ( n = 50 ) for 2 mo . The general characteristics ( age , duration of diabetes , body mass index , and blood glucose concentrations ) of the 2 groups were not significantly different . RESULTS Fasting and postpr and ial blood glucose concentrations of all subjects were normalized after CSII . Fasting plasma insulin concentrations did not differ significantly between the 2 groups after CSII . Lipid peroxide concentrations in plasma and red blood cells decreased and alpha-tocopherol concentrations in plasma and red blood cells increased after alpha-tocopherol supplementation . However , these changes were not affected significantly by CSII . Plasma vitamin C concentrations increased significantly after CSII plus alpha-tocopherol supplementation . However , the activities of antioxidant enzymes in red blood cells did not change significantly after CSII plus alpha-tocopherol supplementation . CONCLUSION alpha-Tocopherol supplementation was beneficial in decreasing blood lipid peroxide concentrations without altering antioxidant enzyme activities in Korean patients with type 2 diabetes treated with CSII", "BACKGROUND Some studies have shown potential benefit of vitamin E on platelet function , but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation . Gamma-tocopherol , a major dietary form of vitamin E , may have protective properties different from those of alpha-tocopherol . OBJECTIVE We compared the effects of supplementation with alpha-tocopherol ( 500 mg ) and a gamma-tocopherol-rich compound ( 500 mg , containing 60 % gamma-tocopherol ) on serum and cellular tocopherol concentrations , urinary tocopherol metabolite excretion , and in vivo platelet activation in subjects with type 2 diabetes . DESIGN Fifty-eight subjects were r and omly assigned to receive either 500 mg alpha-tocopherol/d , 500 mg mixed tocopherols/d , or matching placebo . Serum , erythrocyte , and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention . Soluble CD40 lig and , urinary 11-dehydro-thromboxane B2 , serum thromboxane B2 , soluble P-selectin , and von Willebr and factor were measured as biomarkers of in vivo platelet activation . RESULTS Serum alpha-tocopherol increased with both tocopherol treatments . Serum and cellular gamma-tocopherol increased 4-fold ( P < 0.001 ) in the mixed tocopherol group , whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation . Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols . Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol , which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver . Neither treatment had any significant effect on markers of platelet activation . CONCLUSIONS Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol , whereas mixed tocopherols increased both serum alpha-tocopherol and serum and cellular gamma-tocopherol . Changes in serum tocopherol closely reflect changes in cellular concentrations of tocopherols after supplementation", "Objective : The present study design ed to assess the effect of Mg+Zn , vitamin C+E , and combination of these micronutrients on blood pressure in type 2 diabetic patients . Material s and Methods : In a r and omized , double-blind , placebo controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for three months ; group M : 200 mg Mg and 30 mg Zn ( n = 16 ) , group V : 200 mg vitamin C and 150 mg vitamin E ( n = 18 ) , group MV : minerals plus vitamins ( n = 17 ) , group P : placebo ( n = 18 ) . Blood pressure was measured at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . Results : Results indicate that after three months of supplementation levels of systolic , diastolic and mean blood pressure decreased significantly in the MV group by 8 mmHg ( 122 ± 16 vs. 130 ± 19 mmHg ) , 6 mmHg ( 77 ± 9 vs. 83 ± 11 mmHg ) , and 7 mmHg ( 92 ± 9 vs. 99 ± 13 mmHg ) , respectively ( p < 0.05 ) . Also combination of vitamin and mineral supplementation had significantly effects in increasing serum potassium ( p < 0.05 ) and in decreasing serum malondialdehyde ( p < 0.05 ) . There was no significant change in the levels of these parameters in the other three groups . Conclusion : The results of the present study indicated that in type 2 diabetic patients a combination of vitamins and minerals , rather than vitamin C and E or Mg and Zn , might decrease blood pressure", "Objective — Clinical trials of vitamin E have failed to demonstrate a decrease in cardiovascular events . However , these studies did not address possible benefit to subgroups with increased oxidative stress . Haptoglobin ( Hp ) , a major antioxidant protein , is a determinant of cardiovascular events in patients with Type 2 diabetes mellitus ( DM ) . The Hp gene is polymorphic with 2 common alleles , 1 and 2 . The Hp 2 allelic protein product provides inferior antioxidant protection compared with the Hp 1 allelic product . We sought to test the hypothesis that vitamin E could reduce cardiovascular events in DM individuals with the Hp 2 - 2 genotype , a subgroup that comprises 2 % to 3 % of the general population . Methods and Results —1434 DM individuals ≥55 years of age with the Hp 2 - 2 genotype were r and omized to vitamin E ( 400 U/d ) or placebo . The primary composite outcome was myocardial infa rct ion , stroke , and cardiovascular death . At the first evaluation of events , 18 months after initiating the study , the primary outcome was significantly reduced in individuals receiving vitamin E ( 2.2 % ) compared with placebo ( 4.7 % ; P=0.01 ) and led to early termination of the study . Conclusions —Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2 - 2 genotype ( Clinical Trials.gov NCT00220831 )", "OBJECTIVE The present study was design ed to assess the effect of magnesium plus zinc , vitamins C plus E , and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients . RESEARCH DESIGN AND METHODS In a r and omized , double-blind , placebo-controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months : group M ( n = 16 ) , 200 mg Mg and 30 mg Zn ; group V ( n = 18 ) , 200 mg vitamin C and 100 IU vitamin E ; group MV ( n = 17 ) , minerals plus vitamins ; and group P ( n = 18 ) , placebo . Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity ( NAG ) in urine were determined at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . RESULTS Results indicate that after 3 months of supplementation , levels of urinary albumin excretion decreased in the V and MV groups ( P = 0.034 and P = 0.005 , respectively ) . Urinary NAG activity did not significantly change in any treatment groups . Levels of systolic , diastolic , and mean blood pressure significantly decreased in the MV group ( P = 0.008 , P = 0.017 , and P = 0.009 , respectively ) . Also , combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose ( P = 0.035 ) and malondialdehyde concentrations ( P = 0.004 ) and in increasing HDL cholesterol and apolipoprotein A1 levels ( P = 0.019 ) . There was no significant change in the levels of these parameters in the other three groups . CONCLUSIONS In conclusion , the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium , zinc , and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients", "This triple-blind , placebo-controlled clinical trial was conducted to determine the effect of the vitamin E on fasting blood sugar ( FBS ) , serum insulin , and glycated hemoglobin ( GHb ) in type 11 diabetic patients ( NIDDM ) . A total of 100 patients , with no complications , aged 20 - 60 years old were chosen from those consulting the Isfahan Social Security Service Diabetes Clinic and divided r and omly into two treated and placebo groups , and matched for age , sex , level of education , and occupation . The treated and placebo groups were given vitamin E tablets ( 200 IU/day ) and placebo respectively . Serum vitamin E , total cholesterol ( TC ) , triglycerides ( TG ) , FBS , insulin , and GHb were measured at the beginning and at the end of the study ( a period of 27 weeks ) ; FBS , GHb and insulin levels were also determined several times during the period . Blood lipids and FBS were measured using the ELAN 2000 autoanalyzer at the Isfahan Cardiovascular Research Center , while for measuring insulin the enzyme-linked immunosorbent assay ( ELISA ) method was used ; GHb was determined calorimetrically ( thiobarbituric acid ) , and for vitamin E measurements the Hansen and Warwick method was used , by which the vitamin E was determined fluorometrically . The findings of this study show no effect of vitamin E supplementation in the patients : GHb did not change appreciably , FBS was reduced nonsignificantly ( -4.3 % in the treated group vs. -14.0 % in the placebo group , p < 0.05 ) . In the case of insulin , no increase was seen ; instead , a decrease was observed ( slightly more than 17 % in the two groups , p = 0.15 ) . No changes were observed in the levels of blood lipids . It was concluded that a daily vitamin E supplement of 200 IU for a period of 27 weeks does not affect insulin , GHb , or FBS in type II diabetic patients . However , since this antioxidant vitamin is beneficial in other ways in these patients , it would seem justified to recommend its use . Certainly , more extensive research is necessary to draw definite conclusions", "Vascular disease accounts for the majority of the clinical complications in diabetes mellitus . As an exaggerated oxidative stress degree has been postulated as the link between diabetes mellitus and endothelial function , a possible positive effect of plasma vitamin E ( Vit . E ) administration on brachial reactivity could be postulated . Our study aims at investigating the possible effect of chronic Vit . E administration on brachial reactivity , oxidative stress indexes , and intracellular magnesium and calcium content in type II diabetic patients free of diabetic complications . Forty adult , type II diabetic patients were enrolled in the study , which was deigned as a double blind , r and omized vs. placebo trial . At baseline all patients underwent the following tests : 1 ) anthropometric and metabolic examinations , 2 ) evaluation of oxidative stress indexes , 3 ) intracellular magnesium and calcium measurements , and 4 ) determination of arterial compliance and distensibility . Then , all patients were r and omly assigned to Vit . E treatment at a dose of 600 mg/day ( Evion Forte ; n = 20 ) or placebo ( n = 20 ) over 8 weeks . At the end of this treatment period , a complete reevaluation of the patients was made . Vit . E treatment was associated with a significant improvement in the percent change in brachial artery diameter ( P<0.03 ) and oxidative stress indexes ( P < 0.005 ) . In the Vit . E group , the percent change in brachial artery diameter correlated positively with the percent change in oxidative stress indexes ( oxidized/reduced glutathione , Trolox-equivalent antioxidant capacity , thiobarbituric acid reaction products , lipid peroxides ) and intracellular cation content ( magnesium and calcium ) . After adjustment for age , sex , body mass index , and wait/hip ratio , all of these correlations remained significant ( P<0.03 for all ) . Furthermore , adjusting for glycosylated hemoglobin , plasma total cholesterol , and homeostatic model index , brachial artery diameter was still correlated with the percent change in oxidative stress indexes ( P<0.04 for all ) . Nevertheless , the relationship between the percent change in brachial artery diameter and oxidative stress indexes was no longer significant after adjustment for intracellular Mg and Ca2 + . In conclusion , our study demonstrates that chronic administration of Vit . E improves brachial artery reactivity in patients with type II diabetes mellitus . Such an effect seems mediated by a reduction in oxidative stress and a regulation of intracellular calcium and magnesium contents", "OBJECTIVE To compare the effects of short-term dietary supplementation with tomato juice , vitamin E , and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein ( C-RP ) and cell adhesion molecules in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS There were 57 patients with well-controlled type 2 diabetes aged < 75 years treated with placebo for 4 weeks and then r and omized to receive tomato juice ( 500 ml/day ) , vitamin E ( 800 U/day ) , vitamin C ( 500 mg/day ) , or continued placebo treatment for 4 weeks . Susceptibility of LDL to oxidation ( lag time ) and plasma concentrations of lycopene , vitamin E , vitamin C , C-RP , vascular cell adhesion molecule 1 , and intercellular adhesion molecule 1 were measured at the beginning of the study , after the placebo phase , and at the end of the study . RESULTS Plasma lycopene levels increased nearly 3-fold ( P = 0.001 ) , and the lag time in isolated LDL oxidation by copper ions increased by 42 % ( P = 0.001 ) in patients during supplementation with tomato juice . The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E ( 54 % ) . Plasma C-RP levels decreased significantly ( -49 % , P = 0.004 ) in patients who received vitamin E. Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study . CONCLUSIONS This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E , which also decreases plasma levels of C-RP , a risk factor for myocardial infa rct ion , in patients with diabetes . These findings may be relevant to strategies aim ed at reducing risk of myocardial infa rct ion in patients with diabetes", "Background As a part of a larger study investigating the effects of α-tocopherol on gene expression in type 2 diabetics we observed a pro-oxidant effect of α-tocopherol which we believe may be useful in interpreting outcomes of large intervention trials of α-tocopherol . Methods 19 type 2 diabetes subjects were r and omised into two groups taking either 1200 IU/day of α-tocopherol or a matched placebo for 4 weeks . On day 0 and 29 of this study oxidative DNA damage was assessed in mononuclear cells from fasted blood sample s and following a 2 h glucose tolerance test ( GTT ) . Results On day 0 there was no significant difference in oxidative DNA damage between the two groups or following a GTT . On day 29 there was no significant difference in oxidative DNA damage in fasted blood sample s , however following a GTT there was a significant increase in oxidative DNA damage in the α-tocopherol treatment group . Conclusion High dose supplementation with α-tocopherol primes mononuclear cells from patients with type 2 diabetes for a potentially damaging response to acute hyperglycaemia", "OBJECTIVE We investigated in general practice the efficacy of antiplatelets and antioxidants in primary prevention of cardiovascular events in people with type 2 diabetes . RESEARCH DESIGN AND METHODS The Primary Prevention Project ( PPP ) is a r and omized , open trial with a two-by-two factorial design aim ed to investigate low-dose aspirin ( 100 mg/day ) and vitamin E ( 300 mg/day ) in the prevention of cardiovascular events in patients with one or more cardiovascular risk factors . The primary end point was a composite end point of cardiovascular death , stroke , or myocardial infa rct ion . A total of 1,031 people with diabetes in the PPP , aged > /=50 years , without a previous cardiovascular event were enrolled by 316 general practitioners and 14 diabetes outpatient clinics . RESULTS The PPP trial was prematurely stopped ( after a median of 3.7 years ) by the independent data safety and monitoring board because of a consistent benefit of aspirin compared with the control group in a population of 4,495 patients with one or more major cardiovascular risk factors . In diabetic patients , aspirin treatment was associated with a nonsignificant reduction in the main end point ( relative risk [ RR ] = 0.90 , 95 % CI 0.50 - 1.62 ) and in total cardiovascular events ( 0.89 , 0.62 - 1.26 ) and with a nonsignificant increase in cardiovascular deaths ( 1.23 , 0.69 - 2.19 ) . In nondiabetic subjects , RRs for the main end point , total cardiovascular events , and cardiovascular deaths were 0.59 ( 0.37 - 0.94 ) , 0.69 ( 0.53 - 0.90 ) , and 0.32 ( 0.14 - 0.72 ) , respectively . No significant reduction in any of the end points considered could be found with vitamin E in either diabetic or nondiabetic subjects . CONCLUSIONS Our data suggest a lower effect of primary prevention of cardiovascular disease ( CVD ) with low-dose aspirin in diabetic patients as opposed to subjects with other cardiovascular risk factors . If confirmed , these findings might indicate that the antiplatelet effects of aspirin in diabetic patients are overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation , thus making the balance between benefits and harms of aspirin treatment unfavorable . Further large-scale trials investigating the role of aspirin in the primary prevention of CVD in diabetic patients are urgently needed", "We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients . Subjects ( n = 89 ) were r and omized to vitamin E ( 1,800 IU daily ) or placebo and were followed for 12 months . High-resolution ultrasound images were used to measure the flow-mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( NID ; endothelium independent ) of the brachial artery . Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin . Left ventricular function was evaluated using transthoracic echocardiogram . At the end of the 6-month period , a worsening in endothelium-dependent skin vasodilation ( P = 0.02 ) and rise in endothelin levels ( P = 0.01 ) were found in the vitamin E compared with the placebo group . At the end of the 12-month period , a worsening was observed in NID ( P = 0.02 ) and a marginal worsening was seen in systolic blood pressure ( P = 0.04 ) and FMD ( P = 0.04 ) in the vitamin E compared with the placebo group . In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group ( P = 0.05 ) . No changes were observed in left ventricular function . We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients . Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects , the use of high dosages of vitamin E can not be recommended", "OBJECTIVE To examine the effects of vitamin E on total serum protein glycation ( fructosamine ) , hemoglobin glycation ( HbA1c ) , and serum levels of glucose , total cholesterol , triglycerides , LDL-C , HDL-C , apolipoprotein A1 and apolipoprotein B. MATERIAL AND METHODS Sixty poorly controlled diabetic patients were r and omly assigned to receive either 1200 mg/day of vitamin E or identical placebo capsules during a two month period following a double blind cross-over design with a four week wash-out period between regimens . RESULTS Seven patients were excluded from the study because of reasons not related to the medication . In the remaining 53 patients , the levels of serum glucose , fructosamine , HbA1c , total cholesterol , HDL-C , LDL-C , Apo A1 and Apo B did not vary significantly with vitamin E as compared with placebo . CONCLUSIONS No significant effects of vitamin E on any of the parameters evaluated were observed in poorly controlled diabetic patients", "In type 2 diabetics , the progression of atherosclerosis is more rapid than the general population and 80 % of these patients will die of an atherosclerotic event . Since in these patients hyperglycemia per se confers increased risk for cardiovascular disease ( CVD ) , the presence of even borderline-high-risk LDL-C signals the need for more aggressive LDL-lowering therapy . Most of the lipid lowering agents , currently in use in the treatment of dyslipidemia in type 2 diabetics , have a host of side effects . In contrast , dietary tocotrienols are Vitamin E and have effective lipid lowering property in addition to their potent antioxidant activity . In this study , we have investigated the therapeutic impacts of tocotrienols on serum and lipoprotein lipid levels in type 2 diabetic patients . Based on known tocotrienol rich fraction (TRF)-mediated decrease on elevated blood glucose and glycated hemoglobin A(1C ) ( HbA(1C ) ) in diabetic rats , we have also investigated the effect of TRF on these parameters . A r and omized , double blind , placebo-controlled design involving 19 type 2 diabetic subjects with hyperlipidemia was used . After 60 days of TRF treatment , subjects showed an average decline of 23 , 30 , and 42 % in serum total lipids , TC , and LDL-C , respectively . The goal in type 2 diabetics is to reduce LDL-C levels < or = 100mg/dl . In the present investigation tocotrienols mediated a reduction of LDL-C from an average of 179 mg/dl to 104 mg/dl . However , hypoglycemic effect of TRF was not observed in these patients because they were glycemically stable and their glucose and HbA(1 ) levels were close to normal values . In conclusion , daily intake of dietary TRF by type 2 diabetics will be useful in the prevention and treatment of hyperlipidemia and atherogenesis", "AIMS Vascular endothelial dysfunction , an early marker of atherosclerosis , has been demonstrated in Type 2 diabetes mellitus ( DM ) . Vitamin E preserves endothelial function in animal models of diabetes and reduces cardiovascular risk . We examined endothelial function and the effect of vitamin E supplements in uncomplicated Type 2 DM . METHODS Forty-eight subjects with Type 2 DM and 21 controls had endothelial function assessed using forearm venous occlusion plethysmography with endothelium-independent ( sodium nitroprusside ) and dependent ( acetylcholine , bradykinin ) vasodilators . Those with diabetes received 1600 i.u . daily oral alpha-tocopherol or placebo , double-blind for 8 weeks , and had endothelial function reassessed . RESULTS The diabetic group had higher HbA1c ( 6.9+/-1.4 vs 4.8+/-0.6 % ; P<0.01 ) and systolic ( 145+/-15 vs. 130+/-16 mm Hg ; P<0.01 ) but not diastolic blood pressure ( 79+/-8 vs. 76+/-9 mm Hg ; P = 0.15 ) . There was blunted vasodilation to acetylcholine ( 15 microg/min ; P<0.01 ) in subjects with diabetes . Vasodilation to sodium nitroprusside and bradykinin was similar ( all P>0.1 ) . Alpha-tocopherol did not affect vasodilation to nitroprusside ( P>0.1 ) , acetylcholine ( P>0.1 ) or bradykinin ( P>0.1 ) . CONCLUSIONS There may be receptor-specific endothelial dysfunction in subjects with uncomplicated Type 2 DM . This is not improved by treatment with alpha-tocopherol", "OBJECTIVES Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular ( CV ) events and of microvascular complications in people with diabetes . However , data from r and omized clinical trials are limited . Therefore , we evaluated the effects of vitamin E supplementation on major CV outcomes and on the development of nephropathy in people with diabetes . RESEARCH DESIGN AND METHODS The Heart Outcomes Prevention Evaluation ( HOPE ) trial is a r and omized clinical trial with a 2 x 2 factorial design , which evaluated the effects of vitamin E and of ramipril in patients at high risk for CV events . Patients were eligible for the study if they were 55 years or older and if they had CV disease or diabetes with at least one additional coronary risk factor . The study was design ed to recruit a large number of people with diabetes , and the analyses of the effects of vitamin E in this group were preplanned . Patients were r and omly allocated to daily treatment with 400 IU vitamin E and with 10 mg ramipril or their respective placebos and were followed for an average of 4.5 years . The primary study outcome was the composite of myocardial infa rct ion , stroke , or CV death . Secondary outcomes included total mortality , hospitalizations for heart failure , hospitalizations for unstable angina , revascularizations , and overt nephropathy . RESULTS There were 3,654 people with diabetes . Vitamin E had a neutral effect on the primary study outcome ( relative risk = 1.03 , 95 % CI 0.88 - 1.21 ; P = 0.70 ) , on each component of the composite primary outcome , and on all predefined secondary outcomes . CONCLUSIONS The daily administration of 400 IU vitamin E for an average of 4.5 years to middle-aged and elderly people with diabetes and CV disease and /or additional coronary risk factor(s ) has no effect on CV outcomes or nephropathy", "OBJECTIVE The present study has examined the effect of vitamin E , the principal modulator of free radical activity , on electrophysiological parameters in patients with diabetic peripheral sensorimotor polyneuropathy , matched for duration of disease and metabolic control . RESEARCH DESIGN AND METHODS A total of 21 subjects with type 2 diabetes were enrolled in this double-blind r and omized placebo-controlled study ( vitamin E , 11 patients ; placebo , 10 patients ) . Patients were r and omly assigned to receive either 900 mg vitamin E or placebo for 6 months . The average dietary vitamin E consumption of the subjects was similar during the study . The main outcome measure was the electrophysiological tests assessing nerve conduction . Fasting plasma glucose , HbA1 , postpr and ial plasma glucose , and electrophysiological parameters in the basal state and after 6 months of treatment were studied . RESULTS Glycemic indexes did not show any significant changes during the study , whereas nerve conduction improved significantly in 2 of the 12 studied electrophysiological parameters after 6 months in patients on vitamin E supplementation . The changes in the electrophysiological parameters were obvious in the median motor nerve fibers and tibial motor nerve fibers . Nerve conduction velocity in the median motor nerve fibers ( P = 0.0019 ) and tibial motor nerve distal latency ( P = 0.0284 ) improved significantly after 6 months of vitamin E supplementation . CONCLUSIONS This study shows that defective nerve conduction in diabetic subjects with mild-to-moderate peripheral neuropathy may be improved by pharmacological doses of vitamin E supplementation . Further studies with a larger number of patients for longer periods of time are needed", "Objective Oxidative stress has been suggested to play a role in the development of diabetes , hypertension and vascular dysfunction . Vitamin E , a major lipid-soluble dietary antioxidant , has two major dietary forms , α-tocopherol and γ-tocopherol . The potential importance of γ-tocopherol has largely been overlooked . Our aim was to investigate the effect of α-tocopherol and γ-tocopherol supplementation on 24-h ambulatory blood pressure ( BP ) and heart rate , vascular function and oxidative stress in individuals with type 2 diabetes . Method Fifty-eight individuals with type 2 diabetes were r and omized in a double-blind , placebo-controlled trial . Participants were r and omized to a daily dose of 500 mg/day RRR-α-tocopherol , 500 mg/day mixed tocopherols ( 60 % γ-tocopherol ) or placebo for 6 weeks . Primary endpoints were 24-h ambulatory BP and heart rate , endothelium-dependent and independent vasodilation and plasma and urinary F2-isoprostanes . Results Treatment with α-tocopherol significantly increased systolic BP [ 7.0 ( 5.2 , 8.8 ) mmHg , P < 0.0001 ] , diastolic BP [ 5.3 ( 4.0 , 6.5 ) mmHg , P < 0.0001 ] , pulse pressure [ 1.8 ( 0.6 , 3.0 ) mmHg , P < 0.005 ] and heart rate [ 2.0 ( 0.6 , 3.3 ) bpm , P < 0.005 ] versus placebo . Treatment with mixed tocopherols significantly increased systolic BP [ 6.8 ( 4.9 , 8.6 ) mmHg , P < 0.0001 ] , diastolic BP [ 3.6 ( 2.3 , 4.9 ) mmHg , P < 0.0001 ] , pulse pressure [ 3.2 ( 2.0 , 4.4 ) mmHg , P < 0.0001 ] and heart rate [ 1.8 ( 0.5 , 3.2 ) bpm , P < 0.01 ] versus placebo . Treatment with α-tocopherol or mixed tocopherols significantly reduced plasma F2-isoprostanes versus placebo , but had no effect on urinary F2-isoprostanes . Endothelium-dependent and independent vasodilation was not affected by either treatment . Conclusion In contrast to our initial hypothesis , treatment with either α- or mixed tocopherols significantly increased BP , pulse pressure and heart rate in individuals with type 2 diabetes", "OBJECTIVE The purpose of the present study was to assess the impact of Mg + Zn , Vitamins C + E , and combination of these micronutrients on serum lipid and lipoprotein profiles in type 2 diabetic patients . MATERIAL S AND METHODS In a r and omized , double-blind , placebo controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months ; group M : 200 mg Mg and 30 mg Zn ( n = 16 ) , group V : 200 mg Vitamin C and 150 mg Vitamin E ( n = 18 ) , group MV : minerals plus vitamins ( n = 17 ) , group P : placebo ( n = 18 ) . Fasting blood and urine sample s were collected at the beginning and at the end of the trial . Serum triglyceride , total cholesterol , high density lipoprotein cholesterol ( HDL-c ) and low density lipoprotein cholesterol ( LDL-c ) were measured enzymatically . Apolipoproteins ( apo ) A1 and B were measured by immunoturbidimetric method . Adjustment for differences in baselines covariates and changes in variables during study were performed by analysis of covariance using general linear models . RESULTS Results indicate that after 3 months of supplementation mean serum levels of HDL-c and apo A1 increased significantly in the MV group by 24 % ( 50.4 + /-19.3 mg/dl versus 40.6 + /- 10.8 mg/dl ) and 8.8 % ( 169.8 + /- 33.8 mg/dl versus 156.1 + /- 23.9 mg/dl ) , respectively ( P < 0.01 ) . There were no significant changes in the levels of these parameters in the other three groups . Serum levels of total cholesterol , LDL-c , triglyceride , and apo B were not altered after supplementation in all four groups . CONCLUSION It is concluded that since co-supplementation of Mg , Zn , Vitamins C and E significantly increases HDL-c and apo A1 , supplementation of these micronutrients could be recommended for the type 2 diabetic patients based on their daily requirements", "OBJECTIVE Markers of oxidative stress and plasma alanine transferase ( ALT ) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance . Vitamin E improves glycemic control in people with diabetes . We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals . RESEARCH DESIGN AND METHODS Eighty overweight individuals ( BMI > 27 kg/m(2 ) ) were r and omly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months . The dose of vitamin E was increased to 1,200 IU per day for a further 3 months . RESULTS Plasma peroxides decreased by 27 % at 3 months and by 29 % at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point . At 3 months , fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased . These changes were not apparent at 6 months . Plasma ALT concentrations declined significantly throughout the study period . CONCLUSIONS In conclusion , these findings indicate that vitamin E improves oxidative stress and hepatocellular function . Although insulin resistance also improves , this effect appears transient", "Patients with diabetes mellitus have an increased risk of premature atherosclerosis , which may be due in part to increased oxidizability of low-density lipoprotein ( LDL ) . Numerous studies have shown that alpha-tocopherol can reduce the oxidative susceptibility of LDL in normoglycemic subjects ; however , there are few studies in persons with diabetes . In addition , alpha-tocopherol may reduce the extent of protein glycation . Therefore , the objective of the present study was to assess the effect of RRR-alpha-tocopheryl acetate supplementation on LDL oxidizability and protein glycation in persons with diabetes without evidence of vascular disease . Twenty-eight persons with insulin-dependent diabetes mellitus ( IDDM ) and non-insulin-dependent diabetes mellitus ( NIDDM ) were r and omly assigned to receive either placebo or 1632 mg ( 1200 IU ) RRR-alpha-tocopherol/d , as tocopheryl acetate , for 8 wk . Plasma and LDL antioxidant concentrations and LDL oxidizability were assessed at both 0 and 8 wk . Plasma and LDL concentrations of alpha-tocopherol were significantly increased in the supplemented group only . Compared with the placebo group , the alpha-tocopherol-supplemented group had significant reductions in LDL oxidizability at 8 wk , as shown by the time-course curves of conjugated diene and lipid peroxide formation . Also , alpha-tocopherol supplementation produced a significant prolongation in the lag phases of both assays , which was evident in both the NIDDM and IDDM subgroups . However , there were no significant changes in glycated hemoglobin or in glycated plasma proteins after alpha-tocopherol supplementation . Thus , alpha-tocopherol supplementation may be beneficial in reducing LDL oxidizability in patients with diabetes", "In vivo supplementation studies of the antioxidant alpha-tocopherol in human Type II diabetes have used surrogate , rather than direct , markers of oxidative damage/antioxidant protection and have used higher doses of alpha-tocopherol than used in coronary secondary prevention trials . We tested the hypothesis that oral alpha-tocopherol in a dosage regimen used in secondary prevention trials would reduce directly observed oxidatively induced single-str and breaks in lymphocyte DNA in Type II diabetes . We studied 40 people with Type II diabetes and 30 controls in a r and omized , double-blind , placebo-controlled trial of 400 i.u . of oral alpha-tocopherol daily for 8 weeks . Lymphocyte DNA single-str and breaks and low-density lipoprotein ( LDL ) particle size and oxidizability were measured at baseline , after 8 weeks , and after 4 weeks washout . Polymorphisms in the gene for the antioxidant enzyme paraoxonase-1 gene ( position 192 ) were measured . The diabetics had increased DNA oxidative susceptibility ( P=0.008 ) , without increased LDL oxidative susceptibility . There was a direct relationship between DNA oxidative susceptibility and baseline plasma alpha-tocopherol in the diabetes group alone ( r=0.421 , r(2)=0.177 and P=0.023 ) , but DNA and LDL oxidative susceptibility were not influenced by alpha-tocopherol supplementation in either group in this regimen . Paraoxonase-1 gene polymorphisms did not contribute to LDL or DNA oxidative susceptibility or response to alpha-tocopherol . Increased DNA oxidative susceptibility , therefore , can occur in Type II diabetes without increased LDL oxidative susceptibility , but alpha-tocopherol supplementation in this regimen has no influence on DNA or LDL oxidative susceptibility in Type II diabetes or controls . Polymorphisms in the paraoxonase gene ( position 192 ) are not associated with differences in oxidative susceptibility or responses to alpha-tocopherol", "Tocopherol has been shown to have antiplatelet effects in insulin-dependent diabetes mellitus . However , its antiplatelet effect in non-insulin-dependent diabetes mellitus ( NIDDM ) remains to be established . In this report , the antiplatelet effect of tocopherol was assessed in a r and omized , double-blind and crossover study of 15 NIDDM subjects . Each subject received tocopherol ( dl-alpha-tocopherol nicotinate , 200 mg , tid ) and a placebo for two six-week treatment periods separated by a three-week period in between for wash-out . The mechanisms of the antiplatelet effect of tocopherol were also studied in vitro . A significant decrease in platelet reactivity was observed after tocopherol treatment as compared with the pretest , and the magnitude of the decrease during tocopherol treatment was significantly evident when compared with that of the placebo treatment , as assessed by collagen ( 5 , 10 micrograms/mL)-induced platelet aggregation of whole blood . A dose-dependent reduction in both ADP- and collagen-induced platelet aggregation was observed with tocopherol from 0.1 to 3.0 mM in vitro . No corresponding changes in ATP secretion and thromboxane synthesis were observed . Tocopherol also significantly inhibited fibrinogen-induced aggregation of elastase-treated platelets at a concentration of 0.1 mM. We demonstrated that platelet aggregation of whole blood ex vivo , among 15 NIDDM subjects was suppressed in tocopherol treatment , so tocopherol may have an antiplatelet effect in NIDDM subjects . The inhibitory effect of the platelet aggregation of tocopherol may be partially accomplished through interference with fibrinogen binding towards its receptor", "OBJECTIVE To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein ( LDL ) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus ( NIDDM ) . RESEARCH DESIGN AND METHODS Twenty-one men with NIDDM ( HbA1c = 6 - 10 % ) , ages 50–70 , were r and omly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period . LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy . Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation ( lag time ) and formation of thiobarbituric acid-reactive substances ( TBARS ) . Fasting serum glucose , mean weekly blood glucose , HbA1c , and glycated plasma protein concentrations were also determined at these time points . RESULTS Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold , respectively , in the vitamin E-treated group . Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo ( lag time , 243 ± 46 vs. 151 ± 22 min , P < 0.01 ; 3 h TBARS , 24 ± 12 vs. 66 ± 18 nmol malondialdehyde/mg LDL , P < 0.05 ) . Vitamin E content also increased significantly in both buoyant and dense LDL subfractions , and their oxidation was dramatically reduced . The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions ( r = 0.69–0.92 ) . Glycemic indexes did not change significantly in either group during the study . Protein glycation , including glycated hemoglobin , glycated albumin , glycated total plasma proteins , and glycated LDL were unchanged in the vitamin E group . CONCLUSIONS Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation . Despite a greater percentage increase in vitamin E content in small dense LDL , it remained substantially more susceptible to oxidation than was buoyant LDL . This suggests that dense , LDL may gain less protection against oxidation from antioxidant supplementation than does larger , more buoyant LDL . In contrast to previous reports , vitamin E supplementation did not reduce glycation of intracellular or plasma proteins", "BACKGROUND Vitamin E isomers may protect against atherosclerosis . The aim of this study was to compare the effects of supplementation with either alpha-tocopherol ( alphaT ) or mixed tocopherols rich in gamma-tocopherol ( gammaT ) on markers of oxidative stress and inflammation in patients with type 2 diabetes . METHODS In a double-blind , placebo-controlled trial , 55 patients with type 2 diabetes were r and omly assigned to receive ( 500 mg/day ) ( a ) alphaT , ( b ) mixed tocopherols , or ( c ) placebo for 6 weeks . Cellular tocopherols , plasma and urine F(2)-isoprostanes , erythrocyte antioxidant enzyme activities , plasma inflammatory markers , and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation . RESULTS Neutrophil alphaT and gammaT increased ( both P < 0.001 ) with mixed tocopherol supplementation , whereas alphaT ( P < 0.001 ) increased and gammaT decreased ( P < 0.005 ) after alphaT supplementation . Both alphaT and mixed tocopherol supplementation result ed in reduced plasma F(2)-isoprostanes ( P < 0.001 and P = 0.001 , respectively ) but did not affect 24-h urinary F(2)-isoprostanes or erythrocyte antioxidant enzyme activities . Neither alphaT nor mixed tocopherol supplementation affected plasma C-reactive protein , interleukin 6 , tumor necrosis factor-alpha , or monocyte chemoattractant protein-1 . Stimulated neutrophil leukotriene B(4 ) production decreased significantly in the mixed tocopherol group ( P = 0.02 ) but not in the alphaT group ( P = 0.15 ) . CONCLUSIONS The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes . In population s with well-controlled type 2 diabetes , supplementation with either alphaT or mixed tocopherols rich in gammaT is unlikely to confer further benefits in reducing inflammation", "PURPOSE To determine the feasibility of measuring advanced glycated end-products (AGEs)from skin sample s and to evaluate the effects of a combination of vitamins E and C on measures of glycemic control and AGEs in patients with type 2 diabetes mellitus . METHODS Twenty-two patients with type 2 diabetes from a Family Medicine clinic were r and omly assigned to receive a daily dietary supplement containing either a combination of 400 mg of vitamin E and 500 mg of vitamin C or matching placebo for a period of one year . AGEs were measured from skin sample s taken from the buttock . RESULTS Nineteen subjects completed this one-year pilot study . There were no major problems found in measuring AGEs from skin sample s taken from the butttock . Neither the treatment or placebo group had significant changes in glycemic control , protein glycosylation or AGEs . DISCUSSION Skin sample s taken from the buttock area may be an appropriate site for the determination of AGE levels as this procedure appeared to be well-tolerated . Daily vitamin E and C supplementation did not improve measures of glycemic control or AGE levels in this small sample of patients with type 2 diabetes . Because antioxidant vitamins are inexpensive and free of side effects , additional research using a variety of antioxidant vitamin combinations and dosing regimens is needed", "Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads . The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis . 80 patients affected with a long term diabetic late syndrome were r and omised and arranged to 4 groups of n = 20 each . In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium ( sodium selenite ) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months . In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates . The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner . The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications" ]

[ "8841320", "3143832", "21511111", "7697840", "21836143", "21872946" ]

[ "Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases.", "Prognostic utility of plasma neutrophil gelatinase-associated lipocalin in patients with acute heart failure: The NGAL EvaLuation Along with B-type NaTriuretic Peptide in acutely decompensated heart failure (GALLANT) trial", "The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies.", "Identification of 92-kD gelatinase in human coronary atherosclerotic lesions. Association of active enzyme synthesis with unstable angina.", "Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery.", "Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart failure." ]

[ "BACKGROUND AND PURPOSE Leukocytes have been implicated in the development of ischemic atherosclerotic vascular diseases . In a prospect i ve study we investigated whether the plasma concentrations of inflammatory mediators , ie , proteases and cytokines , as markers for systemic leukocyte activation , are increased in patients with acute ischemic cerebrovascular diseases . METHODS Using enzyme-linked immunosorbent assays , we measured the plasma levels of neutrophil gelatinase-associated lipocalin ( NGAL ) , neutrophil proteinase 4 ( NP4 ) , tumor necrosis factor-alpha ( TNF ) , and soluble TNF receptor protein-1 p55 ( sTNFR-1 ) in 120 patients with acute ischemic cerebrovascular insult ( 72 with stroke and 48 with transient ischemic attack [ TIA ] ) and in 35 age- and sex-matched healthy subjects . RESULTS Compared with the control group , plasma NGAL levels were higher in the stroke group ( P < .0001 ) and the TIA group ( P < .01 ) ; plasma NP4 levels were higher in the stroke group ( P < .0001 ) and the TIA group ( P < .01 ) ; and plasma sTNFR-1 levels were higher in the stroke group ( P < .04 ) . There was significant correlation between the plasma levels of fibrinogen and those of both sTNFR-1 ( r = .32 ; P = .005 ) and NGAL ( r = .40 ; P = .0001 ) and between the erythrocyte sedimentation rate and the plasma levels of both sTNFR-1 ( r = .35 ; P = .001 ) and NGAL ( r = .34 ; P = .002 ) . CONCLUSIONS Our study demonstrated that markers for systemic leukocyte activation , ie , plasma levels of cytokines and proteases , were higher in patients with acute ischemic cerebrovascular disease than in healthy control subjects . Activated leukocytes and leukocytic mediators may have an important role in acute cerebrovascular ischemia and its consequences", "Neutrophil gelatinase‐associated lipocalin ( NGAL ) is a measure of acute kidney injury . Renal dysfunction portends significant risk after discharge from acute heart failure ( AHF ) . Thus , a sensitive marker of renal injury might also help to risk stratify HF patients", "OBJECTIVES The aim of this study was to test the hypothesis that , without diagnostic changes in serum creatinine , increased neutrophil gelatinase-associated lipocalin ( NGAL ) levels identify patients with sub clinical acute kidney injury ( AKI ) and therefore worse prognosis . BACKGROUND Neutrophil gelatinase-associated lipocalin detects sub clinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function . METHODS We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospect i ve observational studies of NGAL . We used the terms NGAL(- ) or NGAL(+ ) according to study -specific NGAL cutoff for optimal AKI prediction and the terms sCREA(- ) or sCREA(+ ) according to consensus diagnostic increases in serum creatinine defining AKI . A priori-defined outcomes included need for renal replacement therapy ( primary endpoint ) , hospital mortality , their combination , and duration of stay in intensive care and in-hospital . RESULTS Of study patients , 1,296 ( 55.8 % ) were NGAL(-)/sCREA(- ) , 445 ( 19.2 % ) were NGAL(+)/sCREA(- ) , 107 ( 4.6 % ) were NGAL(-)/sCREA(+ ) , and 474 ( 20.4 % ) were NGAL(+)/sCREA(+ ) . According to the 4 study groups , there was a stepwise increase in subsequent renal replacement therapy initiation-NGAL(-)/sCREA(- ) : 0.0015 % versus NGAL(+)/sCREA(- ) : 2.5 % ( odds ratio : 16.4 , 95 % confidence interval : 3.6 to 76.9 , p < 0.001 ) , NGAL(-)/sCREA(+ ) : 7.5 % , and NGAL(+)/sCREA(+ ) : 8.0 % , respectively , hospital mortality ( 4.8 % , 12.4 % , 8.4 % , 14.7 % , respectively ) and their combination ( 4-group comparisons : all p < 0.001 ) . There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity : NGAL(-)/sCREA(- ) : 4.2 and 8.8 days ; NGAL(+)/sCREA(- ) : 7.1 and 17.0 days ; NGAL(-)/sCREA(+ ) : 6.5 and 17.8 days ; NGAL(+)/sCREA(+ ) : 9.0 and 21.9 days ; 4-group comparisons : p = 0.003 and p = 0.040 , respectively . Urine and plasma NGAL indicated a similar outcome pattern . CONCLUSIONS In the absence of diagnostic increases in serum creatinine , NGAL detects patients with likely sub clinical AKI who have an increased risk of adverse outcomes . The concept and definition of AKI might need re- assessment", "BACKGROUND Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque , leading to intracoronary thrombosis and clinical sequelae . The proximate cause of plaque rupture is unknown . Accordingly , we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family in acute coronary ischemia . METHODS AND RESULTS Coronary atherectomy specimens from patients with atherosclerosis and an acute ischemic syndrome consistent with recent plaque rupture ( unstable angina ) ( n = 12 ) were immunostained for the presence of 92-kD gelatinase ; the results were compared with those obtained by identical study of atherectomy specimens from patients with atherosclerosis and angina but without acute ischemia ( stable angina ) ( n = 12 ) . Positive immunostaining for 92-kD gelatinase was present in 83 % of specimens from both unstable and stable angina patients . However , intracellular localization of enzyme ( indicating active synthesis ) was documented in 10 of 10 positively stained specimens from patients with unstable angina compared with 3 of 10 positively stained specimens from patients with stable angina . Macrophages and smooth muscle cells were the major sources of 92-kD gelatinase in all specimens examined by immunostaining of adjacent sections . CONCLUSIONS 92-kD gelatinase is commonly expressed in coronary arterial atherosclerotic lesions . Active synthesis of 92-kD gelatinase by macrophages and smooth muscle cells in atherosclerotic lesions may play a pathogenic role in the development of acute coronary ischemia", "Acute kidney injury ( AKI ) is a frequent complication of cardiac surgery and increases morbidity and mortality . The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions . Here , we conducted a prospect i ve , multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18 , urine neutrophil gelatinase-associated lipocalin ( NGAL ) , or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes . Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery . After multivariable adjustment , the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI , respectively , compared with the lowest quintiles . Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay , longer intensive care unit stay , and higher risk for dialysis or death . The clinical prediction model for AKI had an area under the receiver-operating characteristic curve ( AUC ) of 0.69 . Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75 , respectively . Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement ( NRI ) and integrated discrimination improvement ( IDI ) . In conclusion , urine IL-18 , urine NGAL , and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery", "BACKGROUND The identification of patients at risk for worse outcome is still a challenge . We hypothesized that cystatin C , a marker of renal function , and neutrophil gelatinase-associated lipocalin ( NGAL ) , a marker of acute renal injury , would have a role in the prognostic stratification of these patients . METHODS We prospect ively evaluated 121 patients admitted for acute HF . Serum NGAL and cystatin C levels were measured on the first morning after admission . The outcome measures used were the occurrence of death from all causes , and the combined endpoint defined as the first occurrence of either death or hospital admission . Patients were followed for up to 3 months . RESULTS The variables associated with a higher occurrence of death in a univariate approach were older age and higher levels of BNP , cystatin C and NGAL , and those associated with the occurrence of the combined endpoint were older age , Diabetes mellitus , lower GFR , type 1 cardio-renal syndrome , BNP , cystatin C and NGAL . BNP and NGAL remained independent predictors of the occurrence of both all-cause death and the combined endpoint . NGAL levels in the 75th percentile ( > 167.5 ng/mL ) were associated with a 2.7-fold increase in the risk of death and a 2.9-fold increase in the risk of the first occurrence of either death or hospitalization . CONCLUSIONS Serum NGAL , a marker of acute renal injury , is an independent predictor of worse short term prognosis in patients with acute HF . This suggests a role of renal damage , apart from renal function , in the prognosis of these patients" ]

[ "20722686", "3554285", "3177728", "20818193", "10691160", "2292420", "2892348", "20973735", "12502654", "21098771", "2652459", "2963489", "22676205", "15920042", "3354853", "20819415", "19002314", "21767722", "19945929" ]

[ "The effects of total energy expenditure from all levels of physical activity vs. physical activity energy expenditure from moderate-to-vigorous activity on visceral fat and insulin sensitivity in obese Type 2 diabetic women.", "The Effects of Free-Living Interval-Walking Training on Glycemic Control, Body Composition, and Physical Fitness in Type 2 Diabetic Patients", "Effect of 3-Month Yoga on Oxidative Stress in Type 2 Diabetes With or Without Complications", "Effects of Nordic Walking and Exercise in Type 2 Diabetes Mellitus: A Randomized Controlled Trial", "Leisure-time physical activity at weekends and the risk of Type 2 diabetes mellitus in Japanese men: the Osaka Health Survey.", "Brisk walking compared with an individualised medical fitness programme for patients with type 2 diabetes: a randomised controlled trial", "Yoga Practice for the Management of Type II Diabetes Mellitus in Adults: A systematic review", "Effect of t'ai chi exercise on biochemical profiles and oxidative stress indicators in obese patients with type 2 diabetes.", "Randomized controlled community-based nutrition and exercise intervention improves glycemia and cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica.", "Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial.", "Community based yoga classes for type 2 diabetes: an exploratory randomised controlled trial", "Supervised Walking Groups to Increase Physical Activity in Type 2 Diabetic Patients", "Effects of a regular walking exercise program on behavioral and biochemical aspects in elderly people with type II diabetes.", "Make your diabetic patients walk: long-term impact of different amounts of physical activity on type 2 diabetes.", "Comprehensive yogic breathing program improves quality of life in patients with diabetes", "Resistance Exercise Did Not Alter Intramuscular Adipose Tissue but Reduced Retinol-binding Protein-4 Concentration in Individuals with Type 2 Diabetes Mellitus", "Improving glycaemic and BP control in type 2 diabetes. The effectiveness of tai chi.", "Qi-gong mind-body therapy and diabetes control. A randomized controlled trial.", "Effectiveness of an aerobic walking program using heart rate monitor and pedometer on the parameters of diabetes control in Asian Indians with type 2 diabetes." ]

[ "AIMS We examined the effects of physical activity with or without dietary restriction for 3 months on regional fat and insulin sensitivity and compared the effect of total energy expenditure from all levels of physical activity with that of physical activity energy expenditure from moderate-to-vigorous exercise in obese women with Type 2 diabetes . METHODS In this r and omized , controlled trial , we assessed change of body weight , abdominal visceral fat area , subcutaneous fat area and insulin sensitivity , expressed as K(ITT ) , and monitored total energy expenditure and physical activity energy expenditure using an accelerometer during a 12-week intervention in four groups : control , diet , exercise and diet plus exercise . RESULTS The mean body mass index was 28.0 + /- 2.7 kg/m(2 ) and the mean duration of diabetes was 8 + /- 6 years . Both the diet and diet plus exercise groups showed significant body weight loss compared with the control group ( P < 0.05 ) . However , the visceral fat area was reduced only in the diet and exercise group ( P = 0.017 ) and the subcutaneous fat area was reduced only in the diet group ( P = 0.009 ) . Mean energy intake was an independent determinant of the change in subcutaneous fat area ( P = 0.020 ) and mean total anergy expenditure was an independent determinant of visceral fat area ( P = 0.002 ) . Insulin sensitivity K(ITT ) was associated with physical activity energy expenditure ( P = 0.006 ) , energy intake ( P = 0.047 ) and the change in fructosamine level ( P = 0.016 ) but not with changes in body weight , subcutaneous fat area , visceral fat area or adipokine level . CONCLUSIONS Exercise had an additive effect to dietary restriction on visceral fat reduction . Visceral fat area was associated with total energy expenditure , but insulin sensitivity was associated with physical activity energy expenditure", "OBJECTIVE To evaluate the feasibility of free-living walking training in type 2 diabetic patients and to investigate the effects of interval-walking training versus continuous-walking training upon physical fitness , body composition , and glycemic control . RESEARCH DESIGN AND METHODS Subjects with type 2 diabetes were r and omized to a control ( n = 8) , continuous-walking ( n = 12 ) , or interval-walking group ( n = 12 ) . Training groups were prescribed five sessions per week ( 60 min/session ) and were controlled with an accelerometer and a heart-rate monitor . Continuous walkers performed all training at moderate intensity , whereas interval walkers alternated 3-min repetitions at low and high intensity . Before and after the 4-month intervention , the following variables were measured : VO2max , body composition , and glycemic control ( fasting glucose , HbA1c , oral glucose tolerance test , and continuous glucose monitoring [ CGM ] ) . RESULTS Training adherence was high ( 89 ± 4 % ) , and training energy expenditure and mean intensity were comparable . VO2max increased 16.1 ± 3.7 % in the interval-walking group ( P < 0.05 ) , whereas no changes were observed in the continuous-walking or control group . Body mass and adiposity ( fat mass and visceral fat ) decreased in the interval-walking group only ( P < 0.05 ) . Glycemic control ( elevated mean CGM glucose levels and increased fasting insulin ) worsened in the control group ( P < 0.05 ) , whereas mean ( P = 0.05 ) and maximum ( P < 0.05 ) CGM glucose levels decreased in the interval-walking group . The continuous walkers showed no changes in glycemic control . CONCLUSIONS Free-living walking training is feasible in type 2 diabetic patients . Continuous walking offsets the deterioration in glycemia seen in the control group , and interval walking is superior to energy expenditure – matched continuous walking for improving physical fitness , body composition , and glycemic control", "OBJECTIVE To assess the effect of yoga on anthropometry , blood pressure , glycemic control , and oxidative stress in type 2 diabetic patients on st and ard care in comparison with st and ard care alone . RESEARCH DESIGN AND METHODS The study involved 123 patients stratified according to groups with microvascular complications , macrovascular complications , and peripheral neuropathy and without complications and assigned to receive either st and ard care or st and ard care along with additional yoga for 3 months . RESULTS In comparison with st and ard care alone , yoga result ed in significant reduction in BMI , glycemic control , and malondialdehyde and increase in glutathione and vitamin C. There were no differences in waist circumference , waist-to-hip ratio , blood pressure , vitamin E , or superoxide dismutase in the yoga group at follow-up . CONCLUSIONS Yoga can be used as an effective therapy in reducing oxidative stress in type 2 diabetes . Yoga in addition to st and ard care helps reduce BMI and improve glycemic control in type 2 diabetic patients", "Objective : Both Nordic walking and Exercise on Prescription have potential as elements in the management of type 2 diabetes mellitus . These programs are recommended , but their effectiveness has not yet been established . The aim was to evaluate the efficacy of these 2 interventions compared with st and ard information on physical activity . Design : Single-blinded , r and omized , controlled intervention study . Setting : Sixty-eight patients ( 37 men and 31 women ) were r and omized into 3 groups : Nordic walking ( NW ; n = 22 ) , Exercise on Prescription ( EP ; n = 24 ) , and control ( CG ; n = 22 ) . Patients : Patients were recruited from a diabetes outpatient clinic and via newspaper advertisement . Interventions : Consisted of a 4-month intervention period followed by an 8-month follow-up , during which the participants were recommended to train on their own . Main Outcome Measures : HbA1c . Results : There was no difference in HbA1c when comparing the intervention groups relative to the control group : ΔNW = −0.4 % [ 95 % confidence intervals ( CI ) , −0.9 % to 0.1 % ] and ΔEP = −0.2 % ( 95 % CI , −0.6 % to 0.2 % ) after 4 months ; ΔNW = 0.0 % ( 95 % CI , −0.6 % to 0.5 % ) and ΔEP = 0.3 % ( 95 % CI , −0.3 % to 0.9 % ) after 12 months . However , fat mass assessed by dual energy X-ray absorptiometry ( DXA ) decreased significantly in the NW group after 4 months [ −1.0 kg ( 95 % CI , −1.7 to 0.1 ) ] and after 12 months in both NW [ −1.8 kg ( 95 % CI , −3.2 to −0.4 ) ] and EP [ −1.5 kg ( 95 % CI , −2.9 to −0.05 ) ] groups . No significant changes in other variables . Conclusions : Four-month exercise programs at moderate intensity of either Nordic walking or Exercise on Prescription did not significantly improve HbA1c in patients with type 2 diabetes either at the end of the program or at the follow-up", "AIMS To investigate association between leisure-time physical activity at weekends and the risk of developing Type 2 diabetes mellitus ( DM ) . METHODS Prospect i ve examination of 6,013 Japanese men aged 35 - 60 years who were free of DM , impaired fasting glycaemia , or hypertension at study entry . Type 2 DM was defined by a fasting plasma glucose level > or = 7.0 mmol/l or a 2-h post-load plasma glucose level > or = 11.1 mmol/l . Data on physical activity obtained from question naires consisted of overall leisure-time physical activity weekly and leisure-time physical activity at weekends . RESULTS During the 59,966 person-years follow-up , 444 cases developed Type 2 DM . Regular physical exercise at least once a week was associated with a reduced risk of Type 2 DM . After adjustments for age , body mass index , daily alcohol consumption , smoking habits , blood pressure levels and a parental history of Type 2 DM , men who engaged in regular physical exercise at least once a week had a relative risk of Type 2 DM of 0.75 ( 95 % CI , 0.61 - 0.93 ) compared with men engaging in exercise less often . Even vigorous activity only once a week at weekends was associated with a reduced risk of Type 2 DM . Men who engaged in vigorous activity at least once a week at weekends had a multiple-adjusted relative risk of Type 2 DM of 0.55 ( 95 % CI , 0.35 - 0.88 ) compared with sedentary men . CONCLUSIONS Regular physical exercise at least once a week and vigorous activity even only once a week at weekends are associated with a decreased risk of Type 2 DM", "Aims /hypothesisStructured exercise is considered a cornerstone in type 2 diabetes treatment . However , adherence to combined resistance and endurance type exercise or medical fitness intervention programmes is generally poor . Group-based brisk walking may represent an attractive alternative , but its long-term efficacy as compared with an individualised approach such as medical fitness intervention programmes is unknown . We compared the clinical benefits of a 12-month exercise intervention programme consisting of either brisk walking or a medical fitness programme in type 2 diabetes patients . Methods We r and omised 92 type 2 diabetes patients ( 60 ± 9 years old ) to either three times a week of 60 min brisk walking ( n = 49 ) or medical fitness programme ( n = 43 ) . Primary outcome was the difference in changes in HbA1c values at 12 months . Secondary outcomes were differences in changes in blood pressure , plasma lipid concentrations , insulin sensitivity , body composition , physical fitness , programme adherence rate and health-related quality of life . Results After 12 months , 18 brisk walking and 19 medical fitness participants were still actively participating . In both programmes , 50 and 25 % of the dropout was attributed to overuse injuries and lack of motivation , respectively . Intention-to-treat analyses showed no important differences between brisk walking and medical fitness programme in primary or secondary outcome variables . Conclusions /interpretationThe prescription of group-based brisk walking represents an equally effective intervention to modulate glycaemic control and cardiovascular risk profile in type 2 diabetes patients when compared with more individualised medical fitness programmes . Future exercise intervention programmes should anticipate the high attrition rate due to overuse injuries and motivation problems", "The effect of practicing yoga for the management of type II Diabetes was assessed in this systematic review through search ing related electronic data bases and the grey literature to the end of May 2007 using Ovid . All r and omized controlled clinical trials ( RCTs ) comparing yoga practice with other type of intervention or with regular practice or both , were included regardless of language or type of publication . Each study was assessed for quality by two independent review ers . Mean difference was used for summarizing the effect of each study outcomes with 95 % confidence intervals . Pooling of the studies did not take place due to the wide clinical variation between the studies . Publication bias was assessed by statistical methods . Five trials with 363 participants met the inclusion criteria with medium to high risk of bias and different intervention characteristics . The studies ’ results show improvement in outcomes among patients with diabetes type II . These improvements were mainly among short term or immediate diabetes outcomes and not all were statistically significant . The results were inconclusive and not significant for the long-term outcomes . No adverse effects were reported in any of the included studies . Short-term benefits for patients with diabetes may be achieved from practicing yoga . Further research is needed in this area . Factors like quality of the trials and other method ological issues should be improved by large r and omized control trials with allocation concealment to assess the effectiveness of yoga on diabetes type II . A definitive recommendation for physicians to encourage their patients to practice yoga can not be reached at present", "OBJECTIVE This study aim ed to vali date the effects of a simplified , gentle form of t'ai chi chuan in patients with type 2 diabetes and who are also obese . DESIGN The study was design ed to be a r and omized controlled trial . SETTING This study was conducted in the department of metabolism and endocrinology at Cheng Ching Hospital , in Taichung , Taiwan . SUBJECTS The study subjects were hospital-based patients with type 2 diabetes and who were also obese ( ages 40 - 70 , with a body-mass index [ BMI ] range of 30 - 35 ) . The patients were r and omly selected and grouped into t'ai chi exercise ( TCE ) and conventional exercise ( CE ) groups . INTERVENTIONS After receiving instruction in t'ai chi , the TCE group and the CE group practice d three times per week , including one practice session lasting up to 1 hour , for 12 weeks . OUTCOME MEASURES Hemoglobin A1C , serum lipid profile , serum malondialdehyde , and C-reactive protein were measured . Physical parameters of body weight and BMI were also measured . Diet and medications of participants were monitored carefully while biochemical and physical conditions were analyzed . RESULTS After 12 weeks , hemoglobin A1C values of the TCE group did not decrease ( 8.9 ± 2.7 % : 8.3 ± 2.2 % ; p = 0.064 ) . BMI ( 33.5 ± 4.8 : 31.3 ± 4.2 ; p = 0.038 ) and serum lipids , including triglyceride ( 214 ± 47 mg/dL : 171 ± 34 mg/dL ; p = 0.012 ) and high density lipoprotein cholesterol ( 38 ± 16 mg/dL : 45 ± 18 mg/dL ; p = 0.023 ) had significant improvements . Serum malondialdehyde tended to decrease from baseline ( 2.66 ± 0.78 μmol/L : 2.31 ± 0.55 μmol/L ; p = 0.035 ) , and C-reactive protein also decreased ( 0.39 ± 0.19 mg/dL : 0.22 ± 0.15 mg/dL ; p = 0.014 ) . No improvements occurred in BMI , lipids , and oxidative stress profiles in the CE group . CONCLUSIONS T'ai chi exercise practice d by patients who are obese and have type 2 diabetes is efficient and safe when supervised by professionals and helps improve parameters , such as BMI , lipid profile , C-reactive protein , and malondialdehyde . Periodic monitoring of blood glucose , blood pressure , heart rate , breathing , physical fitness , and symptoms of discomfort of patients who exercise helps prevent injury . Simple , gentle TCE can be applied as regular daily exercise for patients with type 2 diabetes even when such patients are obese", "OBJECTIVE The prevalence of type 2 diabetes , especially in developing countries , has grown over the past decades . We performed a controlled clinical study to determine whether a community-based , group-centered public health intervention addressing nutrition and exercise can ameliorate glycemic control and associated cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica . RESEARCH DESIGN AND METHODS A total of 75 adults with type 2 diabetes , mean age 59 years , were r and omly assigned to the intervention group or the control group . All participants received basic diabetes education . The subjects in the intervention group participated in 11 weekly nutrition classes ( 90 min each session ) . Subjects for whom exercise was deemed safe also participated in triweekly walking groups ( 60 min each session ) . Glycosylated hemoglobin , fasting plasma glucose , total cholesterol , triglycerides , HDL and LDL cholesterol , height , weight , BMI , and blood pressure were measured at baseline and the end of the study ( after 12 weeks ) . RESULTS The intervention group lost 1.0 + /- 2.2 kg compared with a weight gain in the control group of 0.4 + /- 2.3 kg ( P = 0.028 ) . Fasting plasma glucose decreased 19 + /- 55 mg/dl in the intervention group and increased 16 + /- 78 mg/dl in the control group ( P = 0.048 ) . Glycosylated hemoglobin decreased 1.8 + /- 2.3 % in the intervention group and 0.4 + /- 2.3 % in the control group ( P = 0.028 ) . CONCLUSIONS Glycemic control of type 2 diabetic patients can be improved through community-based , group-centered public health interventions addressing nutrition and exercise . This pilot study provides an economically feasible model for programs that aim to improve the health status of people with type 2 diabetes", "CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination . OBJECTIVE To examine the benefits of aerobic training alone , resistance training alone , and a combination of both on hemoglobin A(1c ) ( HbA(1c ) ) in individuals with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c ) levels of 6.5 % or higher were enrolled in the 9-month exercise program between April 2007 and August 2009 . INTERVENTION Forty-one participants were assigned to the nonexercise control group , 73 to resistance training 3 days a week , 72 to aerobic exercise in which they expended 12 kcal/kg per week ; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week . Main Outcome Change in HbA(1c ) level . Secondary outcomes included measures of anthropometry and fitness . RESULTS The study included 63.0 % women and 47.3 % nonwhite participants who were a mean ( SD ) age of 55.8 years ( 8.7 years ) with a baseline HbA(1c ) level of 7.7 % ( 1.0 % ) . Compared with the control group , the absolute mean change in HbA(1c ) in the combination training exercise group was -0.34 % ( 95 % confidence interval [ CI ] , -0.64 % to -0.03 % ; P = .03 ) . The mean changes in HbA(1c ) were not statistically significant in either the resistance training ( -0.16 % ; 95 % CI , -0.46 % to 0.15 % ; P = .32 ) or the aerobic ( -0.24 % ; 95 % CI , -0.55 % to 0.07 % ; P = .14 ) groups compared with the control group . Only the combination exercise group improved maximum oxygen consumption ( mean , 1.0 mL/kg per min ; 95 % CI , 0.5 - 1.5 , P < .05 ) compared with the control group . All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group . The resistance training group lost a mean of -1.4 kg fat mass ( 95 % CI , -2.0 to -0.7 kg ; P < .05 ) and combination training group lost a mean of -1.7 ( -2.3 to -1.1 kg ; P < .05 ) compared with the control group . CONCLUSIONS Among patients with type 2 diabetes mellitus , a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c ) levels . This was not achieved by aerobic or resistance training alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00458133", "Background Yoga is a popular therapy for diabetes but its efficacy is contested . The aim of this study was to explore the feasibility of research ing community based yoga classes in Type 2 diabetes with a view to informing the design of a definitive , multi-centre trial Methods The study design was an exploratory r and omised controlled trial with in-depth process evaluation . The setting was two multi-ethnic boroughs in London , UK ; one with average and one with low mean socio-economic deprivation score . Classes were held at a sports centre or GP surgery . Participants were 59 people with Type 2 diabetes not taking insulin , recruited from general practice lists or opportunistically by general practice staff . The intervention group were offered 12 weeks of a twice-weekly 90-minute yoga class ; the control group was a waiting list for the yoga classes . Both groups received advice and leaflets on healthy lifestyle and were encouraged to exercise . Primary outcome measure was HbA1c . Secondary outcome measures included attendance , weight , waist circumference , lipid levels , blood pressure , UKPDS cardiovascular risk score , diabetes-related quality of life ( ADDQoL ) , and self-efficacy . Process measures were attendance at yoga sessions , self-reported frequency of practice between taught sessions , and qualitative data ( interviews with patients and therapists , ethnographic observation of the yoga classes , and analysis of documents including minutes of meetings , correspondence , and exercise plans ) . Results Despite broad inclusion criteria , around two-thirds of the patients on GP diabetic registers proved ineligible , and 90 % of the remainder declined to participate . Mean age of participants was 60 + /- 10 years . Attendance at yoga classes was around 50 % . Nobody did the exercises regularly at home . Yoga teachers felt that most participants were unsuitable for ' st and ard ' yoga exercises because of limited flexibility , lack of basic fitness , co-morbidity , and lack of confidence . There was a small fall in HbA1c in the yoga group which was not statistically significant and which was not sustained six months later , and no significant change in other outcome measures . Conclusion The benefits of yoga in type 2 diabetes suggested in some previous studies were not confirmed . Possible explanations ( apart from lack of efficacy ) include recruitment challenges ; practical and motivational barriers to class attendance ; physical and motivational barriers to engaging in the exercises ; inadequate intensity and /or duration of yoga intervention ; and insufficient personalisation of exercises to individual needs . All these factors should be considered when design ing future trials . Trial registration National Research Register ( 1410 ) and Current Controlled Trials ( IS RCT N63637211 )", "OBJECTIVE To evaluate the impact of an exercise program organized into supervised walking groups in subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS Fifty-nine diabetic subjects were r and omized to a control group receiving st and ard lifestyle recommendations or an intervention group assigned to three supervised walking sessions per week and counseling . Changes in metabolic features , weight , 6-min walk test , prescription of antidiabetic medications , and overall physical activity were assessed . RESULTS Functional capacity and overall physical activity were higher in the intervention group , whereas metabolic changes were not different between groups after 4 months . However , in subjects who attended at least 50 % of scheduled walking sessions , changes in A1C and fasting glucose were greater than in control subjects . Discontinuation or reduction of antidiabetic drugs occurred in 33 % of these patients versus 5 % of control subjects ( P < 0.05 ) . CONCLUSIONS Supervised walking may be beneficial in diabetic subjects , but metabolic improvement requires adequate compliance", "The present study examined the effects of a regular walking exercise program on behavioral ( daily physical activity , physical strength , energy consumption ) and biochemical ( fasting blood glucose [ FBG ] , glycated hemoglobin [ HbA1c ] , total cholesterol , triglycerides [ TG ] , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol ) aspects of elderly people with type II diabetes . A r and omized and stratified experimental design was used with experimental and control groups . The experimental group was subjected to a 6 month walking exercise program , involving walking exercise three times per week for 50 min , and a 4 week education program on diet control and the prevention of complications , once per week for 20 min . Post-test was conducted after 3 and 6 months to examine short- and long-term behavioral and biochemical effects . The regular walking exercise program effectively increased daily physical activity , physical strength , and energy consumption ( behavioral aspects ) , and decreased FBG , HbA1c , and TG levels ( biochemical aspects ) in elderly people with type II diabetes . The incidence of type II diabetes complications might be reduced by implementing a regular walking exercise program", "OBJECTIVE To establish the impact of different amounts of increased energy expenditure on type 2 diabetes care . RESEARCH DESIGN AND METHODS Post hoc analysis of long-term effects of different amounts of increased energy expenditure ( metabolic equivalents [ METS ] per hour per week ) through voluntary aerobic physical activity was performed in 179 type 2 diabetic subjects ( age 62 + /- 1 years [ mean + /- SE ] ) r and omized to a physical activity counseling intervention . Subjects were followed for 2 years and divided into six groups based on their increments in METs per hour per week : group 0 ( no activity , n = 28 ) , group 1 - 10 ( 6.8 + /- 0.3 , n = 27 ) , group 11 - 20 ( 17.1 + /- 0.4 , n = 31 ) , group 21 - 30 ( 27.0 + /- 0.5 , n = 27 ) , group 31 - 40 ( 37.5 + /- 0.5 , n = 32 ) , and group > 40 ( 58.3 + /- 1.8 , n = 34 ) . RESULTS At baseline , the six groups did not differ for energy expenditure , age , sex , diabetes duration , and all parameters measured . After 2 years , in group 0 and in group 1 - 10 , no parameter changed ; in groups 11 - 20 , 21 - 30 , 31 - 40 , and > 40 , HbA(1c ) , blood pressure , total serum cholesterol , triglycerides , and estimated percent of 10-year coronary heart disease risk improved ( P < 0.05 ) . In group 21 - 30 , 31 - 40 , and > 40 , body weight , waist circumference , heart rate , fasting plasma glucose , serum LDL and HDL cholesterol also improved ( P < 0.05 ) . METs per hour per week correlated positively with changes of HDL cholesterol and negatively with those of other parameters ( P < 0.001 ) . After 2 years , per capita yearly costs of medications increased ( P = 0.008 ) by USD393 in group 0 , did not significantly change in group 1 - 10 ( USD 206 , P = 0.09 ) , and decreased in group 11 - 20 ( USD -196 , P = 0.01 ) , group 21 - 30 ( USD -593 , P = 0.009 ) , group 31 - 40 ( USD -660 , P = 0.003 ) , and group > 40 ( USD -579 , P = 0.001 ) . CONCLUSIONS Energy expenditure > 10 METs . h(-1 ) . week(-1 ) obtained through aerobic leisure time physical activity is sufficient to achieve health and financial advantages , but full benefits are achieved with energy expenditure > 20 METs . h(-1 ) . week(-1 )", "Objective : To assess the effect of a comprehensive yogic breathing program on glycemic control and quality of life ( QOL ) in patients with diabetes . Material s and Methods : This is a prospect i ve r and omized controlled intervention trial . Patients having HbA1c between 6 and 9 % for at least 3 months with lifestyle modification and oral antidiabetic medication were included . They were followed-up and r and omized at 6 months into two groups : one group receiving st and ard treatment of diabetes and the other group receiving st and ard treatment of diabetes and taught and told to regularly practice the comprehensive yogic breathing program ( Sudarshan Kriya Yoga and Pranayam ) . Change in fasting and post-pr and ial blood sugars , glycated hemoglobin and QOL as assessed by the World Health Organization QOL WHOQOL BREF question naire were assessed . Results : There was a trend toward improvement in glycemic control in the group practicing the comprehensive yogic breathing program compared with the group following st and ard treatment alone , although this was not significant . There was significant improvement in physical , psychological and social domains and total QOL post-intervention in the group practicing the comprehensive yogic breathing program as compared with the group following st and ard treatment alone . Conclusion : There was significant improvement in the QOL and a non-significant trend toward improvement in glycemic control in the group practicing the comprehensive yogic breathing program compared with the group that was following st and ard treatment alone", "Lipid accumulation in muscle is associated with diminished insulin sensitivity . It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 ( RBP4 ) , which is linked to adipose tissue and insulin sensitivity in diabetics . Forty-four women with type 2 diabetes were r and omly assigned to three groups for a period of 12 weeks : control ( asked to maintain a sedentary lifestyle ) ; resistance exercise ( elastic b and exercise at moderate intensity five times per week ) ; and aerobic exercise ( walking for 60 min at moderate intensity five times per week ) . Subcutaneous ( SCAT ) , subfascial ( SFAT ) and intramuscular ( IMAT ) adipose tissues at mid-thigh level were assessed using computed tomography , and RBP4 level and insulin sensitivity ( fractional disappearance rate of insulin , k ITT ) were assessed before and after intervention . Changes in SCAT , SFAT , IMAT , RBP4 and k ITT were similar among the three groups . Within-group analysis revealed that body mass index and waist circumference decreased significantly in both exercise groups , but RBP4 decreased significantly only with resistance exercise . Resistance exercise did not alter muscular adipose tissue or improve insulin sensitivity", "BACKGROUND This study assessed the effect of tai chi on glycosylated haemoglobin ( HbA1c ) , blood pressure and health status ( SF-36 ) in adults with type 2 diabetes . METHODS A r and omised controlled trial of tai chi classes for 6 months versus wait list control for adults with type 2 diabetes and a baseline HbA1c of 7 % or more . RESULTS A total of 53 patients were recruited to the study and r and omised to tai chi ( 28 ) or control group ( 25 ) . There were improvements in HbA1c ; 6 m walk test , and total cholesterol between baseline and follow up but the difference between the two treatment groups was not statistically significant . Health status results showed improvements in three domains for the tai chi group . DISCUSSION There was no significant improvement in metabolic control or cardiovascular risk at follow up compared to the control group . Patients in the tai chi group showed improvements in physical and social functioning", "BACKGROUND Previous studies have shown that qi-gong , a form of mind-body movement therapy , may be beneficial for people with type 2 diabetes ; however , no controlled studies have been conducted to examine the predictors and mediators of qi-gong effects on indicators of diabetes control . This study examined the effects of qi-gong on diabetes control and identified the predictors and mediators of these effects . DESIGN RCT . SETTING / PARTICIPANTS The study included forty-one participants ( 16 men and 25 women ; aged 41 - 71 years ) with elevated blood glucose levels . INTERVENTIONS Participants were r and omized to qi-gong intervention or a usual medical care control group . Physical and hematologic measures were assessed at baseline and after 12 weeks . MAIN OUTCOME MEASURES The outcomes were indicators of diabetes control ( HbA1c , insulin resistance , fasting blood glucose and insulin , and 2-hour blood glucose and insulin ) and potential mediators of these ( body weight , waist circumference , and leg strength ) . Data were collected in 2006 and analyzed in 2007 to 2009 . RESULTS Linear regression analyses showed significant between-group differences in favor of the intervention group in weight ( p<0.01 ) ; waist circumference ( p<0.01 ) ; leg strength ( p<0.01 ) ; HbA1c ( p<0.05 ) ; insulin resistance ( p<0.01 ) ; and fasting blood insulin ( p<0.01 ) at 12 weeks . Logistic regression analyses showed that the qi-gong intervention was a significant predictor of reduced weight ( odds for decreasing by -2 kg=11.14 , p<0.01 ) ; waist circumference ( by -5 cm=22.50 , p<0.01 ) ; insulin resistance ( by -0.2 unit=3.75 , p<0.05 ) ; and improved leg strength ( odds for increasing by 4 st and s in 30 seconds=7.00 , p<0.01 ) . The effect of the qi-gong intervention on improved insulin resistance was mediated by reduced weight . CONCLUSIONS The qi-gong intervention was associated with improvements in weight , waist circumference , leg strength , and insulin resistance . The mediation analyses highlight the importance of weight reduction in the control of diabetes . TRIAL REGISTRATION # : Australian New Zeal and Clinical Trials Registry : ACTRN12607000528459", "AIMS To analyze the effects of 8 weeks of aerobic walking using a heart rate monitor ( HRM ) and pedometer for monitoring exercise intensity on glycemic outcomes , fasting blood glucose ( FBG ) , cardiovascular fitness and well-being in type 2 diabetes patients . METHODS Forty adults with type 2 diabetes were r and omly allocated to an 8-week supervised program of walking using heart rate monitor and pedometer ( group A=20 ) and control group ( group B=20 ) . All outcomes were determined at baseline and after the 8-week training period . RESULTS The exercise training program result ed in a 9.7 % ( P<0.05 ) improvement in group A. Fasting blood glucose level decreased significantly by 37 % in group A ( P<0.05 ) . Body mass index ( BMI ) ratio decreased by 3.9 % in group A and increased by 2.2 % in group B. General well-being ( GWB ) improved by 28.8 % ( P<0.05 ) in the exercising group and there was an improvement in all parameters associated with cardiovascular health . CONCLUSION Monitoring an exercise program using a heart rate monitor and pedometer was effective and decreased the level of HbA1c , FBG , BMI and improved general well-being . Further using HRM helped us to attribute all improvements to the exercise intensity that we used in our study" ]

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[ "The effect of preoperative acetaminophen or a combination of acetaminophen and Ibuprofen on the success of inferior alveolar nerve block for teeth with irreversible pulpitis.", "Comparison of anesthetic efficacy of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:80,000 epinephrine for inferior alveolar nerve block in patients with irreversible pulpitis", "Efficacy of supplementary buccal infiltrations and intraligamentary injections to inferior alveolar nerve blocks in mandibular first molars with asymptomatic irreversible pulpitis: a randomized controlled trial.", "4% articaine buccal infiltration versus 2% lidocaine inferior alveolar nerve block for emergency root canal treatment in mandibular molars with irreversible pulpits: a randomized clinical study.", "A Comparison of Different Volumes of Articaine for Inferior Alveolar Nerve Block for Molar Teeth with Symptomatic Irreversible Pulpitis.", "A comparison of the anesthetic efficacy of articaine and lidocaine in patients with irreversible pulpitis.", "Efficacy of articaine versus lidocaine in block and infiltration anesthesia administered in teeth with irreversible pulpitis: a prospective, randomized, double-blind study.", "Comparison of Effect of Oral Premedication with Ibuprofen or Dexamethasone on Anesthetic Efficacy of Inferior Alveolar Nerve Block in Patients with Irreversible Pulpitis: A Prospective, Randomized, Controlled, Double-blind Study.", "Comparison of local anesthetic efficacy of tramadol hydrochloride (with adrenaline) versus plain tramadol hydrochloride in the extraction of upper molar teeth.", "Efficacy of preoperative ibuprofen and meloxicam on the success rate of inferior alveolar nerve block for teeth with irreversible pulpitis.", "Anaesthetic efficacy of lidocaine/clonidine for inferior alveolar nerve block in patients with irreversible pulpitis", "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", "The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis.", "Evaluation of the effect of locally administered amitriptyline gel as adjunct to local anesthetics in irreversible pulpitis pain.", "Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with irreversible pulpitis.", "The effect of orally administered ketamine on requirement for anesthetics and postoperative pain in mandibular molar teeth with irreversible pulpitis.", "The effect of preoperative submucosal administration of tramadol on the success rate of inferior alveolar nerve block on mandibular molars with symptomatic irreversible pulpitis: a randomized, double‐blind placebo‐controlled clinical trial", "Comparison of anesthetic efficacy between lidocaine with and without magnesium sulfate USP 50% for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis.", "Efficacy of Ketorolac Buccal Infiltrations and Inferior Alveolar Nerve Blocks in Patients with Irreversible Pulpitis: A Prospective, Double-blind, Randomized Clinical Trial.", "Anesthetic Efficacy of Articaine and Ketamine for Inferior Alveolar Nerve Block in Symptomatic Irreversible Pulpitis: A Prospective Randomized Double-Blind Study", "Comparative evaluation of effect of preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis: a prospective, double-blind, randomized clinical trial.", "Comparison of the anaesthetic efficacy of epinephrine concentrations (1 : 80 000 and 1 : 200 000) in 2% lidocaine for inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a randomized, double-blind clinical trial.", "Efficacy of preoperative ibuprofen on the success of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a randomized clinical trial.", "Effect of sublingual triazolam on the success of inferior alveolar nerve block in patients with irreversible pulpitis.", "Effect of nitrous oxide on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis.", "Pain Reduction in Untreated Symptomatic Irreversible Pulpitis Using Liposomal Bupivacaine (Exparel): A Prospective, Randomized, Double-blind Trial.", "Articaine hydrochloride: a study of the safety of a new amide local anesthetic.", "Effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients with irreversible pulpitis.", "Comparative evaluation of local infiltration of articaine, articaine plus ketorolac, and dexamethasone on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis.", "Effect of preoperative acetaminophen/hydrocodone on the efficacy of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a prospective, randomized, double-blind, placebo-controlled study.", "Effect of preoperative alprazolam on the success of inferior alveolar nerve block for teeth with irreversible pulpitis.", "A Comparison Between Lidocaine Alone and Lidocaine With Meperidine for Continuous Spinal Anesthesia", "The efficacy of pre-operative oral medication of lornoxicam and diclofenac potassium on the success of inferior alveolar nerve block in patients with irreversible pulpitis: a double-blind, randomised controlled clinical trial.", "Effect of combination of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve block in patients with symptomatic irreversible pulpitis.", "Effect of a Combination of Intranasal Ketorolac and Nitrous Oxide on the Success of the Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis: A Prospective, Randomized, Double‐blind Study", "Endodontic anesthesia in mandibular molars: a clinical study.", "Effect of preoperative medications on the efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: A placebo-controlled clinical study", "Comparison of Preoperative Oral Ketorolac on Anesthetic Efficacy of Inferior Alveolar Nerve Block and Buccal and Lingual Infiltration with Articaine and Lidocaine in Patients with Irreversible Pulpitis: A Prospective, Randomized, Controlled, Double-blind Study.", "Reducing fear of pain associated with endodontic therapy.", "Effect of Oral Premedication on the Efficacy of Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis: A Prospective, Double-Blind, Randomized Controlled Clinical Trial.", "Anesthetic efficacy of combinations of 0.5 mol/L mannitol and lidocaine with epinephrine for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis.", "Effect of bupivacaine on postoperative pain for inferior alveolar nerve block anesthesia after single-visit root canal treatment in teeth with irreversible pulpitis." ]

[ "This study compared preoperative administration of acetaminophen or a combination of acetaminophen and ibuprofen versus placebo for potential increased effectiveness of inferior alveolar nerve ( IAN ) block anesthesia . There were 40 patients with irreversible pulpitis r and omly assigned to a drug or placebo group . Thirty minutes after ingestion of medication , an IAN block was administered . A cold test was done 15 minutes after the block , and if the patients had no sensitivity , endodontic therapy was initiated . If the patient had no pain on access , the IAN was recorded as successful . If the patient had sensitivity to cold or to the access procedure , it was recorded as a failure . Overall success was 60 % for all three groups . Success was 71.4 % for the acetaminophen group , 75.9 % for the acetaminophen and ibuprofen group , and 46.2 % for the placebo group . There was no significant difference between the groups ; however , there was a trend toward higher success in the medication groups", "Objectives : This study was done to compare the anesthetic efficacy of 4 % articaine with 1:100,000 epinephrine with that of 2 % lidocaine with 1:80,000 epinephrine during pulpectomy in patients with irreversible pulpitis for inferior alveolar nerve block in m and ibular posterior teeth . Material and Methods : Patients with irreversible pulpitis referred to the Department of Conservative Dentistry and Endodontics , K.D. Dental College , r and omly received a conventional inferior alveolar nerve block containing 1.8 mL of either 4 % articaine with 1:100,000 epinephrine or 2 % lidocaine with 1:80,000 epinephrine . After the patient ’s subjective assessment of lip anesthesia , the absence/presence of pulpal anesthesia through electric pulp stimulation was recorded and the absence/presence of pain was recorded through visual analogue scale . Results : The pulpal anesthesia success for articaine ( 76 % ) was slightly more than with lidocaine ( 58 % ) as measured with pulp tester as well as for the pain reported during the procedure the success rate of articaine ( 88 % ) was slightly more than that of lidocaine ( 82 % ) although the difference between the two solutions was not statistically significant . Conclusions : Both the local anesthetic solutions had similar effects on patients with irreversible pulpitis when used for inferior alveolar nerve block . Key words : Anesthesia , articaine , lignocaine , pulpitis", "AIM This r and omized double-blinded controlled trial was performed to compare the efficacy of inferior alveolar nerve block ( IANB ) injection for m and ibular first molar teeth with irreversible pulpitis with or without supplementary buccal infiltration and intraligamentary injection . METHODOLOGY Eighty-two patients with asymptomatic irreversible pulpitis received either a combination of intraligamentary injection + buccal infiltration+ IANB or with traditional IANB injection in m and ibular first molar teeth with irreversible pulpitis . Each patient recorded their pain score on a Heft-Parker visual analogue scale before commencing treatment , in response to a cold test 15 min after the design ated anaesthetic injection , during access cavity preparation and during root canal instrumentation . No or mild pain at any stage was considered a success . Data were analysed by chi-square test . RESULTS At the final stage of treatment , 69 of the 82 patients were eligible to be included in the study . No significant difference was found between age ( P = 0.569 ) and gender ( P = 0.570 ) amongst the patients in the two groups . The success rate of anaesthesia in the IANB and the combination groups were 22 % and 58 % , respectively . The success rate of anaesthesia in the combination group was significantly higher than the traditional IANB injection ( P = 0.003 ) . CONCLUSION A combination of anaesthetic techniques can improve the success rate of anaesthesia for m and ibular first molar teeth with irreversible pulpitis", "AIM To compare the anaesthetic efficacy of inferior alveolar nerve blocks ( IANB ) with 1.8 mL of 2 % lidocaine ( LI ) to a buccal infiltration ( BI ) with 1.8 mL of 4 % articaine ( AR ) , both with 1 : 100 000 epinephrine , in patients with symptomatic irreversible pulpits in a r and omized controlled trial . METHODOLOGY Volunteers presenting at the Emergency Centre ( FOP-UNICAMP ) were r and omly divided into two groups ( 30 for AR and 20 for LI ) . Operator and patient were not blinded . Success was recorded when complete pain-free treatment was achieved after a single injection ( IANB or BI ) or when one supplemental injection was needed for emergency endodontic procedures . Success rate of supplemental injection was evaluated between and within groups using Fisher 's exact test and chi-square test . RESULTS A higher success rate ( P = 0.03/Fisher 's exact test ) was observed with AR ( 40 % ) than with LI ( 10 % ) . No significant difference was found when a single injection plus one supplemental injection was compared between groups ( P = 1.0 ; AR = 70 % ; LI = 80 % ) . However , supplemental injection increased the anaesthetic success rates ( AR , P = 0.04 ; LI , P = 0.0001 ) within groups . CONCLUSIONS Single anaesthesia techniques ( IANB or BI ) were not able to achieve pain-free emergency endodontic treatment . Supplemental anaesthetic techniques should be considered prior to treatment procedures in order to increase success rate ( consort : registration number - NCT01912755/Fapesp : # 2009/10834 - 4 )", "INTRODUCTION Achieving anesthesia in m and ibular molar teeth with irreversible pulpitis is very difficult . The aim of this study was to compare the efficacy of 1.8 mL and 3.6 mL articaine for an inferior alveolar nerve block ( IANB ) when treating molars with symptomatic irreversible pulpitis . METHODS In a r and omized , double-blind clinical trial , 82 first m and ibular molar teeth with symptomatic irreversible pulpitis r and omly received conventional IANB injection either with 1 ( 1.8 mL ) or 2 cartridges ( 3.6 mL ) of 4 % articaine with 1:100,000 epinephrine . The patients recorded their pain before and during access cavity preparation as well as during root canal instrumentation using a Heft-Parker visual analog scale . No or mild pain was considered as successful anesthesia . Data were analyzed by t and chi-square tests . RESULTS Eighty patients were eligible to participate in this study , which showed that 3.6 mL articaine provided a significantly higher success rate ( 77.5 % ) of IANBs compared with 1.8 mL of the same anesthetic solution ( 27.5 % ) although neither group had 100 % successful anesthesia ( P < .001 ) . CONCLUSIONS Increasing the volume of articaine provided a significantly higher success rate of IANBs in m and ibular first molar teeth with symptomatic irreversible pulpitis , but it did not result in 100 % anesthetic success", "The purpose of the present study was to compare the anesthetic efficacy of 4 % articaine with 1:100,000 epinephrine with that of 2 % lidocaine with 1:100,000 epinephrine during pulpectomy in patients with irreversible pulpitis in m and ibular posterior teeth . Forty volunteers , patients with irreversible pulpitis admitted to the Emergency Center of the School of Dentistry at the University of São Paulo , r and omly received a conventional inferior alveolar nerve block containing 3.6 mL of either 4 % articaine with 1:100,000 epinephrine or 2 % lidocaine with 1:100,000 epinephrine . During the subsequent pulpectomy , we recorded the patients ' subjective assessment s of lip anesthesia , the absence/presence of pulpal anesthesia through electric pulp stimulation , and the absence/presence of pain through a verbal analogue scale . All tested patients reported lip anesthesia after the application of either inferior alveolar nerve block . Regarding pulpal anesthesia success as measured with the pulp tester , the lidocaine solution had a higher success rate ( 70 % ) than the articaine solution ( 65 % ) . For patients reporting none or mild pain during pulpectomy , the success rate of the articaine solution ( 65 % ) was higher than that of the lidocaine solution ( 45 % ) . Yet , none of the observed differences between articaine and lidocaine were statistically significant . Apparently , therefore , both local anesthetic solutions had similar effects on the patients with irreversible pulpitis in m and ibular posterior teeth . Neither of the solutions , however , result ed in an effective pain control during irreversible pulpitis treatments", "INTRODUCTION Profound pulpal anesthesia in posterior m and ibular teeth with irreversible pulpitis usually requires administering an inferior alveolar nerve block ( IANB ) plus other supplemental injections . The purpose of this prospect i ve , r and omized , double-blind study was to compare the anesthetic success rate of buccal infiltration injections of articaine and lidocaine when supplemented with an IANB . METHODS One hundred twenty-five emergency patients who had their first or second m and ibular molar diagnosed with irreversible pulpitis participated in the study and received the IANB by using either 2 % lidocaine with 1:100,000 epinephrine or 4 % articaine with 1:100,000 epinephrine . One hundred two of the patients reported moderate-to-severe pain upon initiation of their endodontic treatment or through filing of their tooth canals and received supplemental buccal infiltration injections by using the same anesthetic that the IANB had been performed . After the block or the supplemental buccal infiltration injections , success was achieved with no or mild pain during instrumentation of the tooth canals . RESULTS The success rate after the administration of the infiltration injections after an incomplete IANB by using lidocaine was 29 % , whereas by using articaine it was 71 % ( P < .001 ) . No statistical differences were detected in the success rates between the 2 anesthetics after the block injections . CONCLUSIONS Supplementing an incomplete articaine IANB with articaine infiltration raises the anesthetic success more effectively compared with lidocaine in m and ibular molars with irreversible pulpitis", "The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine the effect of preoperative oral administration of ibuprofen or dexamethasone on the success rate of inferior alveolar nerve block ( IANB ) in patients with symptomatic irreversible pulpitis . Seventy-eight patients with irreversible pulpitis were r and omly divided into 3 groups ( 26 per group ) and given one of the following at 1 hr prior to performing local anesthesia : a placebo ; 400 mg ibuprofen ; or 4 mg dexamethasone . Each patient recorded their pain level on a visual analog scale before taking the medication or placebo , at 15 min after completion of IANB , and during treatment if pain occurred . The success of the anesthesia was defined as no or mild pain at any stage during the endodontic procedure . The success rate of the IANB was 38.5 , 73.1 , and 80.8 % with the placebo , ibuprofen , and dexamethasone , respectively . Both ibuprofen and dexamethasone were significantly more effective than the placebo . No significant difference was observed , however , between the two experimental medications in terms of effectiveness . The results of the present study suggest that premedication with ibuprofen or dexamethasone increases the success rate of an IANB in patients with symptomatic irreversible pulpitis in the m and ibular molars", "PURPOSE To evaluate the efficacy of local anesthesia using tramadol hydrochloride ( HCl ) with versus without adrenaline in the extraction of upper molar teeth . PATIENTS AND METHODS This was a double-blinded study that included 100 patients who required extraction of 1 upper molar by the conventional method and were allocated r and omly into 1 of 2 groups : in group A ( n = 50 ) , each patient received an initial dose of drug A ( tramadol HCl 50 mg and adrenalin 0.0225 mg diluted to 1.8 mL by distilled water ) ; in group B ( n = 50 ) , each patient received an initial dose of drug B ( tramadol HCl 50 mg diluted to 1.8 mL by distilled water ) . Degree of pain during tooth extraction , duration of surgery , and total number of cartridges used were recorded intraoperatively . Postoperatively , patients were instructed to record any adverse effects , such as nausea or vomiting , on the first day of the operation . RESULTS There were significant differences in the number of cartridges used and the degree of intraoperative pain . However , there was no significant difference in duration of surgery or side effects . CONCLUSIONS The results of this study suggest that tramadol HCl in combination with adrenaline can be used as an alternative local anesthetic in oral and maxillofacial surgery when , for some unusual reason , a patient can not receive a conventional local anesthetic", "OBJECTIVE The purpose of this study was to determine whether premedication with ibuprofen or meloxicam increases the success rate of anaesthesia in teeth with irreversible pulpitis . MATERIAL S AND METHODS In this parallel , double-blind clinical trial , 92 patients diagnosed with irreversible pulpitis were r and omly divided into four groups of 23 patients . The first group ( the no-premedication group ) received no premedication , the second group ( the meloxicam group ) received 7.5 mg of meloxicam , the third group ( the ibuprofen group ) received 600 mg of ibuprofen , and the fourth group ( the placebo group ) received placebo 1 hour before intervention . Before taking the medication , electrical pulp testing ( EPT ) and the Heft-Parker visual analogue scale ( VAS ) were used to evaluate sensitivity and pain at baseline . Then , local anaesthesia was injected , and after 15 minutes , EPT was used again to evaluate tooth sensitivity . The pain during access preparation was also recorded using the Heft-Parker VAS . RESULTS Ninety-two patients were analysed . The success rates of local anaesthesia were 21.7 % , 34.8 % , 78.3 % and 73.9 % in the no-premedication , placebo , ibuprofen and meloxicam groups , respectively , according to the EPT values . Considering the Heft-Parker VAS values , no premedication gave a 21.7 % success rate , placebo gave a 34.8 % success rate , ibuprofen gave an 82.6 % success rate and meloxicam gave a 65.2 % success rate . The ibuprofen and meloxicam groups showed significantly better results than the placebo and no-premedication groups ( P < 0.001 ) . However , the difference between meloxicam and ibuprofen groups was not significant . CONCLUSIONS Premedication with meloxicam and ibuprofen significantly increased the success rates of inferior alveolar nerve block anaesthesia for teeth with irreversible pulpitis ; however , neither drug provided profound anaesthesia", "AIMS This prospect i ve , r and omized , double-blind study aim ed to compare the efficacy of lidocaine with epinephrine versus lidocaine with clonidine for inferior alveolar nerve block ( IANB ) and hemodynamic stability ( heart rate , systolic blood pressure , diastolic blood pressure and mean arterial pressure ) in patients with irreversible pulpitis . METHODOLOGY One hundred patients with irreversible pulpitis in m and ibular molar teeth r and omly received 1.8 mL of 2 % lidocaine with clonidine ( 15 μg mL-1 ) or 1.8 mL of 2 % lidocaine with epinephrine ( 12.5 μg mL-1 ) , using a conventional IANB technique . Endodontic access cavities were prepared 15 min after solution deposition , and all patients were required to have profound lip numbness . Success was defined as no or mild pain ( visual analog scale recording ) upon endodontic access cavity preparation or initial canal instrumentation . The hemodynamic parameters were measured before , during and 5 , 10 and 30 min after administration . Finally , the collected data were subjected to independent t-test , chi-square and Fisher 's exact test using spss software ver.20 at a significant level of 0.05 . RESULTS The success rates for IANB using lidocaine with epinephrine and lidocaine with clonidine solutions were 29 % and 59 % , respectively . The clonidine group exhibited a significantly higher success rate ( P < 0.05 ) . Five minutes after drug administration , systolic blood pressure and heart rate significantly increased in the lidocaine with epinephrine group and insignificantly decreased in lidocaine with clonidine group . CONCLUSION For m and ibular molars with irreversible pulpitis , addition of clonidine to lidocaine improved the success rate of IANB compared to a st and ard lidocaine/epinephrine solution", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "INTRODUCTION Achieving pulp anesthesia with irreversible pulpitis is difficult . This study evaluated whether nonsteroidal anti-inflammatory drugs assist local anesthesia . METHODS In a r and omized double-blinded clinical trial , 150 patients ( 50 per group ) with irreversible pulpitis were given placebo , 600 mg ibuprofen , or 75 mg indomethacin 1 hour before local anesthesia . Each patient recorded their pain score on a visual analog scale before taking the medication , 15 minutes after anesthesia in response to a cold test , during access cavity preparation and during root canal instrumentation . No or mild pain at any stage was considered a success . Data were analyzed by the chi-square and analysis of variance tests . RESULTS Overall success rates for placebo , ibuprofen , and indomethacin were 32 % , 78 % , and 62 % , respectively ( p < 0.001 ) . Ibuprofen and indomethacin were significantly better than placebo ( p < 0.01 ) . There was no difference between ibuprofen and indomethacin ( p = 0.24 ) . CONCLUSIONS Premedication with ibuprofen and indomethacin significantly increased the success rates of inferior alveolar nerve block anesthesia for teeth with irreversible pulpitis", "BACKGROUND Amitriptyline is one of the most common tricyclic antidepressants , which binds to pain sensory nerve fibers close to the sodium channel ; hence , it could interact to some degree with receptors of local anesthetics . This study was design ed to assess the additional analgesic effects of 2 % Amitriptyline local gel administration in irreversible pulpitis pain of the molars . MATERIAL S AND METHODS This study was a r and omized , double-blind clinical trial that was performed on 56 consented adult patients who did not receive enough analgesia after a lidocaine nerve block for their tooth pulpitis pain . Patients were treated with 0.2 ml of either 2 % amitriptyline or placebo , which was directly injected into their m and ibular molar pulp chamber after they had received two routine lidocaine injections . Patients were asked to score their pain as a mark on a 10-cm Visual Analogue Scale ( VAS ) at different timepoints : 0 ( just before gel administration ) , 1 , 3 , 5 , 7 , and 9 minutes after the treatments . RESULTS There was a 92.5 % decrease in VAS scores of patients 9 minutes after amitriptyline administration compared to Time 0 , while in the placebo group this difference was only 13.5 % . Further , in the amitriptyline group , the VAS score at all timepoints was statistically different from Time 0 ( P < 0.01 ) . The overall pain reduction and its trend was significantly higher in the amitriptyline group compared with the placebo group ( P < 0.001 ) . CONCLUSION Inter-pulp space administration of amitriptyline 2 % gel for completing analgesia in irreversible pulpitis pain could be effective and useful as a conjunctive therapy to injections of local anesthetics", "The purpose of this prospect i ve , r and omized , double-blind study was to compare the anesthetic efficacy of 4 % articaine with 1:100,000 epinephrine to 2 % lidocaine with 1:100,000 epinephrine for inferior alveolar nerve blocks in patients experiencing irreversible pulpitis in m and ibular posterior teeth . Seventy-two emergency patients diagnosed with irreversible pulpitis of a m and ibular posterior tooth r and omly received , in a double-blind manner , 2.2 ml of 4 % articaine with 1:100,000 epinephrine or 2.2 ml of 2 % lidocaine with 1:100,000 epinephrine using a conventional inferior alveolar nerve block . Endodontic access was begun 15 min after solution deposition , and all patients were required to have profound lip numbness . Success was defined as none or mild pain ( Visual Analogue Scale recordings ) on endodontic access or initial instrumentation . The success rate for the inferior alveolar nerve block using articaine was 24 % and for the lidocaine solution success was 23 % . There was no significant difference ( p = 0.89 ) between the articaine and lidocaine solutions . Neither solution result ed in an acceptable rate of anesthetic success in patients with irreversible pulpitis", "Achieving successful anesthesia and pain control in a predictable , efficient manner is a challenge in the endodontic treatment of vital inflamed lower molars . The aim of this study was to evaluate the effect of oral ketamine on the dosage of local anesthetics required and postoperative pain management for irreversibly inflamed m and ibular molars . In this r and omized double-blind placebo-controlled clinical trial , 36 patients with irreversibly inflamed m and ibular molars were r and omly divided into two groups of 18 . Ten mg of ketamine dissolved in 20 ml of fruit juice was administered orally to patients in the experimental group . The control group was given 20 ml of fruit juice alone as a placebo . After 30 min , inferior alveolar nerve block ( IANB ) anesthesia was induced using one cartridge of 2 % lidocaine and 1:100000 epinephrine . Teeth were tested after 5 to 10 min using an electrical pulp tester . In patients showing a positive response , another IANB injection was applied , and the total number of anesthetic cartridges used was recorded . Postoperative pain was evaluated using a visual analogue scale ( VAS ) . In addition , use of analgesic in the first 24 h after treatment was monitored using a question naire . Data were analyzed by t test using SPSS software . There were no significant differences in age or gender between the two groups . The number of anesthetic cartridges used in the ketamine group was significantly less than that in the control group ( P = 0.003 ) . Furthermore , postoperative pain in the ketamine group was significantly lower ( P = 0.019 ) . Also the number of analgesic tablets taken in the ketamine group was significantly lower ( P = 0.011 ) . It can be concluded that a low dose of ketamine might be beneficial for enhancing the effect of local anesthetics", "AIM This r and omized , double-blind , placebo-controlled , clinical trial was design ed to improve the success of inferior alveolar nerve blocks ( IANB ) in m and ibular molars with symptomatic irreversible pulpitis ( SIP ) by means of preoperative submucosal administration of 50 mg tramadol . METHODOLOGY Forty-two patients with a m and ibular molar diagnosed with SIP took part in the trial . Patients were assigned r and omly to one of two groups : tramadol group ( n = 21 ) , who received 50 mg tramadol in 1 mL by m and ibular infiltration , and a placebo group ( n = 21 ) , who received 1 mL of normal saline administered to the affected tooth by the same means . Ten minutes later , all patients received an IANB with 4 % articaine with epinephrine 1 : 100 000 . A 10-min waiting time was established after local anaesthetic ( LA ) administration before carrying out three consecutive tests to assess anaesthesia of the pulp , that is two consecutive negative responses to an electric pulp test , positive or negative response to a cold test and no pain during access cavity preparation . IANB was considered successful only if the patient did not experience pain arising from these tests . Data were analysed by the Chi-squared frequency test and the Fisher 's exact test , for qualitative variables , Mann-Whitney U-test for independent sample s and two-way anova for more than two independent sample s. RESULTS In the tramadol group IANB was achieved successfully in 57 % of the sample , whilst the placebo group obtained 29 % . The difference between groups was not significant ( P = 0.06 ) . When performing endodontic access , the anaesthetic success rate was significantly in favour of tramadol ( P = 0.03 ) . CONCLUSIONS Preoperative submucosal administration of 50 mg tramadol in m and ibular molars with SIP significantly improved the success of IANB using 4 % articaine with 1 : 100 000 epinephrine during access cavity preparation in comparison with a placebo", "INTRODUCTION The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to compare the anesthetic efficacy between lidocaine with and without magnesium sulfate USP 50 % for inferior alveolar nerve ( IAN ) blocks in patients with symptomatic irreversible pulpitis . METHODS One hundred patients with symptomatic irreversible pulpitis of m and ibular posterior teeth were selected for the study . The patients received 1 mL magnesium sulfate USP 50 % or distilled water ( placebo ) 1 hour before administration of conventional IAN block . Endodontic access cavity preparation was initiated 15 minutes after the IAN block injection . Lip numbness was recorded for all the patients . Success of IAN block was defined as no or mild pain on the visual analogue scale during access cavity preparation and initial instrumentation . RESULTS The success rate for the IAN block was 58 % for magnesium sulfate group and 32 % for the placebo group , with statistically significant difference between the 2 groups ( P = .016 ) . CONCLUSIONS In m and ibular posterior teeth diagnosed with symptomatic irreversible pulpitis , preoperative administration of 1 mL magnesium sulfate USP 50 % result ed in statistically significant increase in success of IAN block compared with placebo", "INTRODUCTION The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine whether ketorolac buccal infiltrations ( BIs ) helped to improve the success of inferior alveolar nerve blocks ( IANBs ) in patients with acute irreversible pulpitis ( AIP ) . METHODS Forty adult volunteers with AIP in a m and ibular molar were included in this study . Patients were instructed to evaluate their pain by using a Heft-Parker visual analog scale . They were r and omly divided into 2 groups ( n = 20 ) . All patients received st and ard IANB injection and after that a BI of 4 % articaine with 1:100,000 epinephrine . After 5 minutes , 20 patients received a BI of 30 mg/mL ketorolac , and the other received a BI of normal saline ( control group ) . Endodontic access cavity preparation ( ACP ) was initiated 15 minutes after the IANB when the patient reported lip numbness and had 2 electric pulp tests with no responses . The patient 's pain during caries and dentin removal , ACP , and canal length measurements ( CLM ) was recorded by using Heft-Parker visual analog scale . Successful anesthesia was defined as no or mild pain during any of these steps , without the need for additional injection . Data were statistically analyzed by using Mann-Whitney U and χ(2 ) tests . RESULTS Successful anesthesia after an IANB plus BI of articaine was obtained in 15 % of patients in the control group at the end of CLM . Adding BI of ketorolac significantly increased the success rate to 40 % ( P < .05 ) . Patient 's pain during ACP and CLM was significantly lower in the ketorolac group ( P < .05 ) . CONCLUSIONS Ketorolac BI can increase the success rate of anesthesia after IANB and BI with articaine in patients with AIP", "Introduction : The aim of this prospect i ve , r and omized , double-blind study was to investigate the effect of articaine combined with ketamine on the success rate of inferior alveolar nerve block ( IANB ) in posterior m and ible teeth with symptomatic irreversible pulpitis . Methods and Material s : Forty two adult patients with diagnosis of symptomatic irreversible pulpitis of a m and ibular posterior tooth were selected . The patients received two cartridges of either containing 3.2 mL 4 % articaine with epinephrine 1:200000 and 0.4 mL 50 mg/mL ketamine hydrochloride ( A-ketamine group ) or 3.2 mL 4 % articaine with epinephrine 1:200000 and 0.4 mL normal saline ( A-saline group ) using conventional IANB injections . Access cavity preparation started 15 min after injection . Lip numbness was required for all the patients . Success was considered as no or mild pain on the basis of Heft-Parker visual analog scale recordings upon access cavity preparation or initial instrumentation . Data were analyzed by independent student t , Mann-Whitney and Chi-square tests . Results : The success rates were 55 % and 42.9 % for A-ketamine and A-saline group , respectively , with no significant differences between the two groups ( P=0.437 ) . Conclusion : Adding 0.4 mL 50 mg/mL ketamine hydrochloride to the articaine local anesthetic did not increase the efficacy of IANB for posterior m and ibular teeth with symptomatic irreversible pulpitis", "INTRODUCTION Anesthetic efficacy of inferior alveolar nerve block decreases in patients with irreversible pulpitis . It was hypothesized that premedication with nonsteroidal anti-inflammatory drugs might improve the success rates in patients with inflamed pulps . METHODS Sixty-nine adult volunteers who were actively experiencing pain participated in this prospect i ve , r and omized , double-blind study . The patients were divided into 3 groups on a r and om basis and were r and omly given 1 of the 3 drugs including ibuprofen , ketorolac , and placebo 1 hour before anesthesia . All patients received st and ard inferior alveolar nerve block of 2 % lidocaine with 1:200,000 epinephrine . Endodontic access preparation was initiated after 15 minutes of initial inferior alveolar nerve block . Pain during treatment was recorded by using a Heft Parker visual analog scale . Success was recorded as none or mild pain . RESULTS Statistical analysis with nonparametric chi2 tests showed that placebo gave 29 % success rate . Premedication with ibuprofen gave 27 % , and premedication with ketorolac gave 39 % success rate . There was no significant difference between the 3 groups . CONCLUSIONS Preoperative administration of ibuprofen or ketorolac has no significant effect on success rate of inferior alveolar nerve block in patients with irreversible pulpitis", "AIM The aim of this r and omized controlled , double-blind trial was to comparatively evaluate the anaesthetic efficacy and injection pain of 1.8 mL of 2 % lidocaine with different concentrations of epinephrine ( 1 : 80 000 and 1 : 200 000 ) in patients with symptomatic irreversible pulpitis . METHODOLOGY Sixty-two adult volunteers , actively experiencing pain , were r and omly allocated into 2 groups and received 1.8 mL of 2 % lidocaine with either 1 : 80 000 or 1 : 200 000 epinephrine concentration . Endodontic access preparation was initiated 15 min after the initial IANB . Pain during treatment was recorded using the Heft-Parker visual analogue scale ( HP VAS ) . The primary outcome measure , and the definition of ' success ' , was the ability to undertake pulp access and canal instrumentation with no or mild pain ( HP VAS score < 55 mm ) . Secondary outcome measure was the pain experienced during LA solution deposition . Statistical analysis was performed using Mann-Whitney U-test and chi-square test . RESULTS The anaesthetic success rates of 2 % lidocaine solutions containing 1 : 80 000 and 1 : 200 000 epinephrine concentrations were 20 % and 28 % , respectively . The difference was not statistically significant . There was also no significant difference in the pain experienced during deposition of the solutions . CONCLUSIONS Two percent lidocaine solution used for IANB achieved similar success rates when used with 1 : 80 000 or 1 : 200 000 epinephrine concentration", "AIM To evaluate the effect of preoperative oral ibuprofen ( IBU ) on the success of inferior alveolar nerve blocks ( IANBs ) with mepivacaine containing 1 : 100 000 epinephrine for patients with symptomatic irreversible pulpitis ( SIP ) . METHODOLOGY The present study was a double-blind , r and omized , placebo-controlled clinical trial . The study included two study groups each consisting of 25 patients who exhibited symptomatic irreversible pulpitis of a m and ibular posterior tooth . The patients presented prolonged moderate or severe pain ( > 10 s ) after cold testing and indicated their pain scores on a Heft-Parker visual analogue scale . The patients received identically appearing capsules containing either 600 mg IBU ( IBUg ) or gelatin ( placebo , PLAg ) 1 h before administration of IANB with 2 % mepivacaine containing 1 : 100 000 epinephrine . After 15 min , the anaesthetic blockade was assessed by a three-step examination ( lip numbness , positive/negative response to cold testing and clinical discomfort during endodontic access ) . IANB success was defined as the absence of pain during any of these evaluations . The data were analysed using the chi-squared test . RESULTS All of the patients reported moderate or severe pain before the preoperative procedure . Statistically significant differences were observed between the IBUg and PLAg ( P < 0.05 ) ; the success rates for the IANB were 72 % ( IBUg ) and 36 % ( PLAg ) . CONCLUSIONS Preoperative oral administration of IBU significantly improved the efficacy of IANB in patients with symptomatic irreversible pulpitis", "The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine the effect of the administration of sublingual triazolam on the success of the inferior alveolar nerve ( IAN ) block in patients experiencing irreversible pulpitis . Fifty-eight emergency patients diagnosed with irreversible pulpitis of a m and ibular posterior tooth r and omly received , in a double-blind manner , an identical sublingual tablet of either 0.25 mg of triazolam or a placebo 30 minutes before administration of a conventional IAN block . Access was begun 15 minutes after completion of the IAN block , and all patients had profound lip numbness . Success was defined as no or mild pain ( visual analog scale recordings ) on access or initial instrumentation . The success rate for the IAN block was 43 % with triazolam and 57 % with the placebo , with no significant difference ( P = .43 ) between the 2 groups . For m and ibular posterior teeth , triazolam in a sublingual dose of 0.25 mg did not result in an increase in success of the IAN block in patients with irreversible pulpitis . Therefore , when using conscious sedation , profound local anesthesia is still required to eliminate the sensation of pain during endodontic treatment for patients with irreversible pulpitis", "INTRODUCTION The inferior alveolar nerve ( IAN ) block does not always result in successful pulpal anesthesia . Anesthetic success rates might be affected by increased anxiety . Nitrous oxide has been shown to have both anxiolytic and analgesic properties . Therefore , the purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine the effect of nitrous oxide on the anesthetic success of the IAN block in patients experiencing symptomatic irreversible pulpitis . METHODS One hundred emergency patients diagnosed with symptomatic irreversible pulpitis of a m and ibular posterior tooth were enrolled in this study . Each patient was r and omly assigned to receive an inhalation regimen of nitrous oxide/oxygen mix or room air/oxygen mix ( placebo ) 5 minutes before the administration of the IAN block . Endodontic access was begun 15 minutes after completion of the IAN block , and all patients had profound lip numbness . Success was defined as no or mild pain ( visual analog scale recordings ) on access or instrumentation . RESULTS The success rate for the IAN block was 50 % for the nitrous oxide group and 28 % for the placebo group . There was a statistically significant difference between the 2 groups ( P = .024 ) . CONCLUSIONS For m and ibular teeth diagnosed with symptomatic irreversible pulpitis , administration of 30%-50 % nitrous oxide result ed in a statistically significant increase in the success of the IAN block compared with room air/oxygen", "INTRODUCTION In the treatment of patients with symptomatic irreversible pulpitis , endodontic debridement is a predictable method to relieve pain . However , there are clinical situations in which emergency care can not be provided immediately . An unexplored treatment option in these cases may be the use of a long-acting anesthetic to reduce pain in untreated irreversible pulpitis . Some medical studies have shown potential for infiltrations of liposomal bupivacaine ( Exparel ; Pacira Pharmaceuticals , San Diego , CA ) to prolong pain relief and reduce opioid use postoperatively . The Food and Drug Administration has approved Exparel only for infiltrations ; therefore , the purpose of this study was to compare an infiltration of liposomal bupivacaine versus bupivacaine for pain control in untreated , symptomatic irreversible pulpitis . METHODS Ninety-five emergency patients received 2 % lidocaine with 1:100,000 epinephrine via infiltration or an inferior alveolar nerve block to relieve their initial presenting pain . Patients then r and omly received either 4 mL liposomal bupivacaine ( 13.3 mg/mL ) or 4 mL 0.5 % bupivacaine with 1:200,000 epinephrine by infiltration . Patients received a diary for the day of the appointment and 3 days postinjection to record soft tissue numbness , pain levels , and analgesic ( non-narcotic and narcotic ) use . RESULTS No significant differences ( P < .05 ) were found between the 2 anesthetic formulations for pain or the use of pain medications . A statistically higher level of soft tissue numbness was found on days 1 to 3 for the liposomal bupivacaine group . CONCLUSIONS Although liposomal bupivacaine had some effect on soft tissue anesthesia , it did not reduce pain to manageable clinical levels in patients presenting with untreated , symptomatic irreversible pulpitis", "BACKGROUND Articaine is an amide local anesthetic introduced clinical ly in Germany in 1976 and subsequently throughout Europe , Canada and , in 2000 , the United States . METHODS The authors report on three identical single-dose , r and omized , double-blind , parallel-group , active-controlled multicenter studies that were conducted to compare the safety and efficacy of articaine ( 4 percent with epinephrine 1:100,000 ) with that of lidocaine ( 2 percent with epinephrine 1:100,000 ) . RESULTS A total of 1,325 subjects participated in these studies , 882 of whom received articaine 4 percent with epinephrine 1:100,000 and 443 of whom received lidocaine 2 percent with epinephrine 1:100,000 . The overall incidence of adverse events in the combined studies was 22 percent for the articaine group and 20 percent for the lidocaine group . The most frequently reported adverse events in the articaine group , excluding postprocedural dental pain , were headache ( 4 percent ) , facial edema , infection , gingivitis and paresthesia ( 1 percent each ) . The incidence of these events was similar to that reported for subjects who received lidocaine . The adverse events most frequently reported as related to articaine use were paresthesia ( 0.9 percent ) , hypesthesia ( 0.7 percent ) , headache ( 0.55 percent ) , infection ( 0.45 percent ) , and rash and pain ( 0.3 percent each ) . CONCLUSIONS Articaine is a well-tolerated , safe and effective local anesthetic for use in clinical dentistry", "INTRODUCTION The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine the effect of the administration of preoperative ibuprofen on the success of the inferior alveolar nerve block ( IAN ) in patients with irreversible pulpitis . METHODS One hundred endodontic emergency patients diagnosed with irreversible pulpitis of a m and ibular posterior tooth r and omly received , in a double-blind manner , identical capsules of either 800 mg ibuprofen or placebo 45 minutes before the administration of a conventional IAN block . Access was begun 15 minutes after completion of the IAN block , and all patients had profound lip numbness . Success was defined as no or mild pain ( visual analogue scale recordings ) on access or initial instrumentation . RESULTS AND CONCLUSIONS The success rate for the IAN block was 41 % with ibuprofen and 35 % with placebo , with no significant difference ( P=.57 ) between the 2 groups . For m and ibular posterior teeth , a dose of 800 mg of ibuprofen given 45 minutes before the administration of the IAN block did not result in a statistically significant increase in anesthetic success in patients with irreversible pulpitis", "INTRODUCTION The inferior alveolar nerve block ( IANB ) has a poor success rate in patients with irreversible pulpitis . The purpose of this study was to evaluate the effect of ketorolac and dexamethasone infiltration along with st and ard IANB on the success rate . METHODS Ninety-four adult volunteers who were actively experiencing pain participated in this prospect i ve , r and omized , double-blind study . All patients received st and ard IANB of 2 % lidocaine with 1:200,000 epinephrine . Twenty-four patients did not receive any supplemental infiltrations ( control ) . Twenty-four patients received supplemental buccal infiltration of 4 % articaine with 1:100,000 ephinephrine , and 24 patients received supplemental buccal infiltration of 1 mL/4 mg of dexamethasone . It was planned to give supplemental buccal infiltration of 1 mL/30 mg of ketorolac tromethamine in 26 patients , but the first 2 patients experienced severe injection pain after ketorlac infiltration and were excluded from the study . In the subsequent patients , 0.9 mL of 4 % articaine was infiltrated before injecting ketorolac . Endodontic access preparation was initiated after 15 minutes of initial IANB . Pain during treatment was recorded by using a Heft-Parker visual analog scale . Success was recorded as none or mild pain . RESULTS Statistical analysis was done by using nonparametric χ(2 ) tests . Control IANB gave 39 % success rate . Buccal infiltration of articaine and articaine plus ketorolac significantly increased the success rate to 54 % and 62 % , respectively ( P < .05 ) . Supplementary dexamethasone infiltration gave 45 % success rate , which was insignificant with control IANB . CONCLUSIONS Articaine and ketorolac infiltration can increase the success rate of IANB in patients with irreversible pulpitis . None of the tested techniques gave 100 % success rate", "INTRODUCTION The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine the effect of the administration of the combination acetaminophen/hydrocodone on the anesthetic success of m and ibular posterior teeth in patients experiencing symptomatic irreversible pulpitis . METHODS One hundred emergency patients in moderate to severe pain diagnosed with symptomatic irreversible pulpitis of a m and ibular posterior tooth r and omly received , in a double-blind manner , identical capsules of either a combination dose of 1000 mg acetaminophen/10 mg hydrocodone or placebo 60 minutes before the administration of a conventional inferior alveolar nerve ( IAN ) block . Endodontic access was begun 15 minutes after completion of the block , and all patients used for data analysis had profound lip numbness . Success was defined as no or mild pain ( visual analog scale recordings ) on pulpal access or instrumentation . RESULTS The success rate for the IAN block was 32 % for the combination dose of 1000 mg acetaminophen/10 hydrocodone and 28 % for the placebo dose , with no statistically significant difference between the 2 groups ( P = .662 ) . CONCLUSIONS A combination dose of 1000 mg acetaminophen/10 mg hydrocodone given 60 minutes before the administration of the IAN block did not result in a statistically significant increase in anesthetic success for m and ibular posterior teeth in patients experiencing symptomatic irreversible pulpitis", "INTRODUCTION Success of inferior alveolar nerve ( IAN ) block decreases in patients with irreversible pulpitis . The purpose of this study was to evaluate the effect of preoperative administration of alprazolam on the success of the IAN block for teeth with irreversible pulpitis . METHODS Sixty patients with irreversible pulpitis of a m and ibular molar were selected for this prospect i ve , r and omized , double-blind , placebo-controlled study . The patients received identical capsules of either 0.5 mg of alprazolam or placebo 45 minutes before the administration of a conventional IAN block . Access cavity preparation was initiated 15 minutes after the IAN block injection . Lip numbness was recorded for all the patients . Success was defined as no or mild pain on the basis of visual analogue scale recordings during access cavity preparation and initial instrumentation . Data were analyzed by t test , Mann-Whitney , and χ(2 ) tests . RESULTS The success rate was 53 % for alprazolam group and 40 % for placebo group , with no significant difference between the 2 groups ( P = .301 ) . CONCLUSIONS Within the scope of the current study , preoperative oral administration of 0.5 mg of alprazolam did not improve the success of the IAN block in m and ibular molars in patients with irreversible pulpitis , and the success rate was not adequate to ensure profound pulpal anesthesia", "Background and Objectives . Experimental investigations have demonstrated a synergistic interaction between opioids and local anesthetics . This study aims to assess the effective benefit-risk ratio of continuous spinal anesthesia ( CSA ) induced with either 1.6 % lidocaine alone or in combination with 1 % meperidine . Methods . Thirty-four elderly patients ( 80.7 ± 7.3 years ) operated on for fracture of the neck of the femur were r and omly allocated to two groups . In the first group ( n = 15 ) , CSA was induced with lidocaine 1.6 % plain , whereas in the second group ( n = 19 ) 1 % meperidine was added . Reinjections were performed in both groups using lidocaine 1.6 % alone . Results . In the lidocaine group , 43 ± 13 mg was used for induction whereas in the other group the addition of 18 ± 5 mg of meperidine significantly reduced the dose of lidocaine required to 28 ± 8 mg ( p < 0.001 ) . Delay between two reinjections was increased to 51 ± 7 minutes in the lidocaine plus meperidine group , compared to 35 ± 6 minutes in the lidocaine group ( p < 0.001 ) . Ephedrine was required for 9 out of the 19 patients in the lidocaine plus meperidine group , whereas it was required for only two patients in the other group ( p = 0.05 ) . Mean plasma concentrations of meperidine 1 hour and 3 hours after induction was 45.5 ± 12 ng/ml and 59 ± 22 ng/ml , respectively , and drowsiness was observed in 95 % of the patients in the second group . Delay before requirement for pain medication was 2.2 ± 2 hours in the lidocaine group and 14.1 ± 8 hours in the lidocaine plus meperidine group ( p < 0.001 ) . Conclusions . The association of 1 % meperidine with 1.6 % lidocaine during the induction of CSA decreases the initial induction dose , prolongs analgesia , produces initial drowsiness , and provides long-lasting pain relief . However , such benefits are offset by some impairment of hemodynamic stability that is likely to make this combination of drugs unacceptable as an enhanced analgesic technique", "AIM To determine the effect of administration of pre-operative lornoxicam ( LNX ) or diclofenac potassium ( DP ) on the success of inferior alveolar nerve blocks ( IANB ) in patients with irreversible pulpitis in a double-blind r and omised controlled trial . METHODOLOGY One hundred and fourteen patients with irreversible pulpitis of a m and ibular posterior tooth participated . Patients indicated their pain scores on a Heft Parker visual analogue scale , after which they were r and omly divided into three groups ( n = 38 ) . The subjects received identical capsules containing 8 mg LNX , 50 mg DP or cellulose powder ( placebo , PLAC ) , 1 h before administration of IANB with 2 % lidocaine containing 1 : 200 000 epinephrine . Lip numbness was assessed after 15 min , following which the teeth were tested with cold spray and their responses ( negative or positive ) were recorded . Access cavities were then prepared and success of IANB was defined as the absence of pain during access preparation and root canal instrumentation . The data were analysed using chi-squared tests . RESULTS The percentages of teeth giving a negative response to cold test were 42.8 % ( PLAC ) , 78.5 % ( LNX ) and 67.8 % ( DP ) , with no significant differences amongst the groups ( P > 0.05 ) . The success rates for the IANB in descending order were 71.4 % ( LNX ) , 53.5 % ( DP ) and 28.5 ( PLAC ) . A significant ( P < 0.001 ) difference was found between the LNX and the PLAC groups only . CONCLUSIONS Pre-operative administration of LNX significantly improved the efficacy of IANB in patients with irreversible pulpitis , whilst the effect of pre-medication with DP was not significantly different from the PLAC", "INTRODUCTION The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to determine the effect of the administration of the combination of preoperative ibuprofen/acetaminophen on the success of the inferior alveolar nerve ( IAN ) block in patients with symptomatic irreversible pulpitis . METHODS One hundred endodontic emergency patients in moderate to severe pain diagnosed with irreversible pulpitis of a m and ibular posterior tooth r and omly received , in a double-blind manner , identical capsules of either a combination of 800 mg ibuprofen and 1000 mg acetaminophen or placebo 45 minutes before the administration of a conventional IAN block . Access was begun 15 minutes after completion of the IAN block , and all patients had profound lip numbness . Success was defined as no or mild pain ( visual analog scale recordings ) on access or initial instrumentation . RESULTS AND CONCLUSIONS The success rate for the IAN block was 32 % for the combination ibuprofen/acetaminophen group and 24 % for the placebo , with no significant difference ( P = .37 ) between the 2 groups . For m and ibular posterior teeth , a combination dose of 800 mg ibuprofen and 1000 mg acetaminophen given 45 minutes before administration of the IAN block did not result in a statistically significant increase in anesthetic success in patients with symptomatic irreversible pulpitis", "Introduction : Previous studies in patients with irreversible pulpitis have reported increased success of the inferior alveolar nerve block ( IANB ) using premedication with ketorolac . Preemptive nitrous oxide administration has also shown an increase in the success of the IANB . Recently , ketorolac has been made available for intranasal delivery . Perhaps combining ketorolac and nitrous oxide would increase success . Therefore , the purpose of this prospect i ve , r and omized , double‐blind study was to determine the effect of a combination of intranasal ketorolac and nitrous oxide/oxygen on the anesthetic success of the IANB in patients presenting with symptomatic irreversible pulpitis . Methods : One hundred two patients experiencing spontaneous moderate to severe pain with symptomatic irreversible pulpitis in a m and ibular posterior tooth participated . Patients were r and omly divided into 2 groups and received either 31.5 mg intranasal ketorolac or intranasal saline placebo 20 minutes before the administration of nitrous oxide/oxygen . Ten minutes after the administration of nitrous oxide/oxygen , the IANB was given . After profound lip numbness , endodontic treatment was performed . Success was defined as the ability to perform endodontic access and instrumentation with no pain or mild pain . Results : The odds of success for the IANB was 1.631 in the intranasal saline/nitrous oxide group versus the intranasal ketorolac/nitrous oxide group with no significant difference between the groups ( P = .2523 ) . Conclusions : Premedication with intranasal ketorolac did not significantly increase the odds of success for the IANB over the use of nitrous oxide/oxygen alone . Supplemental anesthesia will still be needed to achieve adequate anesthesia", "Sixty-one m and ibular molar teeth with clinical ly manifest pulpitis , which required endodontic therapy , were studied . Twenty-seven subjects received st and ard inferior alveolar nerve block ( IANB ) with 2 % lidocaine HCI with 1:100,000 epinephrine and 34 subjects received IANB with 3 % mepivacaine with no vasoconstrictor . Pulpal anesthesia was assessed with dichlorodifluormethane ( DDM ) . Subjects who gave a positive response to DDM were given a periodontal ligament injection with 2 % lidocaine with 1:100,000 epinephrine . This study showed that 3 % mepivacaine HCI is as effective as 2 % lidocaine HCI in achieving pulpal anesthesia in m and ibular molars with IANB . Of a total 61 IANB with lip anesthesia , 23 subjects required periodontal ligament injection to achieve a negative response to DDM . It was concluded that lip anesthesia is not a reliable indicator of pulpal anesthesia . The use of DDM is a reliable method of determining true pulpal anesthesia", "Background : The purpose of this prospect i ve , r and omized , double-blind , placebo-controlled study was to compare the effect of the administration of preoperative ibuprofen , ketorolac , combination of etodolac with paracetamol and combination of aceclofenac with paracetamol versus placebo for the potential increased effectiveness of the inferior alveolar nerve block [ IANB ] anesthesia . Material s and Methods : A total of 100 endodontic emergency patients in moderate to severe pain diagnosed with irreversible pulpitis of a m and ibular posterior tooth r and omly received , in a double-blind manner , either a drug or placebo 30 minutes before the administration of a conventional IANB . Cold testing was done before administration of anesthesia to determine level of pain using Heft-Parker Visual Analogue Scale ( VAS ) score . Success was defined as no pain or pain ( VAS ) on access or initial instrumentation . Results : Overall success was 54 % for all the groups . Success was highest ( 70 % ) for the ketorolac group , 55 % for both ibuprofen group and combination of aceclofenac with paracetamol group , 50 % for combination of etodolac with paracetamol group , and 40 % for the placebo group . Conclusions : Under the conditions of this study , the use of preoperative medication did improve the anesthetic efficacy of IANB for the treatment of teeth diagnosed with irreversible pulpitis but not significantly", "INTRODUCTION Irreversible pulpitis ( IP ) commonly results in decreased anesthetic efficacy of the inferior alveolar nerve block ( IANB ) for m and ibular molar . It has been shown that supplementary buccal and /or lingual infiltration as well as premedication with ketorolac result in improved efficacy of the IANB . METHODS One hundred fifty emergency patients who had their lower first or/ and second molar diagnosed with IP participated in the study . All patients were r and omly divided into 2 major IANB groups : 1 group received 4 % articaine with 1:100,000 epinephrine , and the other group received 2 % lidocaine with 1:80,000 epinephrine . Each group was further divided into 3 subgroups of 25 each : ( 1 ) buccal and lingual infiltration with articaine and lidocaine , respectively ; ( 2 ) preoperative oral medication of ketorolac ; and ( 3 ) preoperative oral medication of ketorolac followed by buccal and lingual infiltration with articaine and lidocaine , respectively . Endodontic access was initiated 15 minutes after solution deposition , and all patients were required to have profound lip numbness . Success of the anesthetic was defined as none or mild pain on endodontic access and initial instrumentation . RESULTS Statistical analysis was performed using multiple-comparison analysis of variance ( Kruskal-Wallis ) and t tests . Articaine IANB with infiltrations plus oral ketorolac premedication significantly increased the success rate to 76 % . The success rate after the administration of an articaine IANB with infiltration injections was 64 % , whereas with lidocaine it was 32 % ( P < .05 ) . CONCLUSIONS Premedication with ketorolac significantly increases the anesthetic efficacy of articaine IANB plus infiltration in m and ibular molars with IP", "AIM To provide subjects with positive information about endodontic treatment ( ET ) to reduce fear of pain associated with ET . METHODOLOGY A large sample ( n = 437 ) was r and omly allocated to read one of five informative paragraphs and afterwards asked to complete two question naires ( dental anxiety and fear of dental pain ) . The paragraphs consisted of dental information obtained from patient brochures . One ( experimental ) paragraph consisted of positive information about pain during ET . Analysis of variance followed by post hoc analysis was used to detect differences in mean score . RESULTS Subjects who were given the positive information regarding ET indicated they were less fearful of pain associated with ET . CONCLUSIONS The clinical implication of this experiment is that patients should be accurately informed about pain associated with ET . In this way , the patient may be more at ease before and during treatment , decrease avoidance behaviour and make decisions regarding treatment choice , based on common sense rather than fearful expectations", "INTRODUCTION It is generally accepted that achieving complete anaesthesia with an Inferior Alveolar Nerve Block ( IANB ) in m and ibular molars with symptomatic irreversible pulpitis is more challenging than for other teeth . Therefore , administration of Non-Steroidal Anti-Inflammatory Agents ( NSAIDs ) 1 hour prior to anaesthetic administration has been proposed as a means to increase the efficacy of the IANB in such patients . AIM The purpose of this prospect i ve , double-blind , r and omized clinical trial was to determine the effect of administration of oral premedication with ketorolac ( KETO ) and diclofenac potassium ( DP ) on the efficacy of IANB in patients with irreversible pulpitis . MATERIAL S AND METHODS One hundred and fifty patients with irreversible pulpitis were evaluated preoperatively for pain using Heft Parker visual analogue scale , after which they were r and omly divided into three groups . The subjects received identical tablets of ketorolac , diclofenac pottasium or cellulose powder ( placebo ) , 1 hour prior to administration of IANB with 2 % lidocaine containing 1:200 000 epinephrine . Lip numbness as well as positive and negative responses to cold test were ascertained . Additionally pain score of each patient was recorded during cavity preparation and root canal instrumentation . Success was defined as the absence of pain or mild pain based on the visual analog scale readings . The data was analysed using One-Way Anova , Post-Hoc Tukey pair wise , Paired T - Test and chi-square test . Trial Registery Number is 4722/2015 for this clinical trial study . RESULTS There were no significant differences with respect to age ( p = 0.098 ) , gender ( p = 0.801 ) and pre-VAS score ( DP-KETO p=0.645 , PLAC-KETO p = 0.964 , PLAC-DP p = 0.801 ) between the three groups . All patients had subjective lip anaesthesia with the IAN blocks . Patients of all the three groups reported a significant decrease in active pain after local anaesthesia ( p < 0.05 ) . The post injection VAS Score was least in group 1 ( KETO ) followed by group II ( DP ) & maximum in group III ( PLACEBO ) . CONCLUSION Oral pre-medication with 10 mg KETO result ed in significantly higher percentage of successful inferior alveolar block in patients with irreversible pulpitis than pre-medication with 50 mg DP & PLAC", "INTRODUCTION The purpose of these 2 prospect i ve , r and omized , single-blind studies was to determine the anesthetic efficacy of lidocaine with epinephrine compared with a combination lidocaine with epinephrine plus 0.5 mol/L mannitol for inferior alveolar nerve ( IAN ) blocks in patients experiencing symptomatic irreversible pulpitis . METHODS In study one , 55 emergency patients r and omly received IAN blocks by using a 3.18-mL formulation containing 63.6 mg of lidocaine with 31.8 μg epinephrine or a 5-mL formulation containing 63.6 mg of lidocaine with 31.8 μg epinephrine ( 3.18 mL ) plus 1.82 mL of 0.5 mol/L mannitol . In study two , 51 emergency patients r and omly received IAN blocks by using a 1.9-mL formulation containing 76.4 mg of lidocaine with 36 μg epinephrine or a 3-mL formulation containing 76.4 mg of lidocaine with 36 μg epinephrine ( 1.9 mL ) plus 1.1 mL of 0.5 mol/L mannitol . Endodontic access was begun 15 minutes after the IAN block , and all patients had profound lip numbness . Success was defined as no or mild pain ( visual analogue scale recordings ) on endodontic access or instrumentation . RESULTS The 1.9 mL of lidocaine ( 76.4 mg ) with epinephrine plus 0.5 mol/L mannitol had a significantly ( P = .04 ) better success rate of 39 % when compared with the lidocaine formulation without mannitol ( 13 % success rate ) . CONCLUSIONS For m and ibular posterior teeth in patients with symptomatic irreversible pulpitis , the addition of 0.5 mol/L mannitol to 1.9 mL of lidocaine ( 76.4 mg ) with epinephrine result ed in a statistically higher success rate . However , the combination lidocaine/mannitol formulation would not result in predictable pulpal anesthesia", "INTRODUCTION Pain control after root canal treatment is of great importance in endodontic practice . The aim of the present study was to investigate the effect of a long-acting anesthetic ( bupivacaine ) on postoperative pain and the use of analgesics after root canal treatment . METHODS In a r and omized double-blinded clinical trial , 60 patients ( 30 per group ) having first or second m and ibular molars with irreversible pulpitis r and omly received either 0.5 % bupivacaine with 1:200,000 epinephrine or 2 % lidocaine with 1:80,000 epinephrine as the anesthetic solutions for inferior alveolar nerve blocks . After single-visit root canal treatment , each patient recorded their pain score on a visual analogue scale at 6 , 12 , 24 , 36 , 48 , and 72 hours after treatment . Data were analyzed by Mann-Whitney , χ(2 ) , Cochrane Q , and t tests as well as Pearson correlation analysis . RESULTS The results indicate that patients who received bupivacaine had significantly lower pain scores at 6 and 12 hours after root canal treatment compared with the patients who received lidocaine ( P < .05 ) . The use of analgesics in the bupivacaine patients was significantly lower than in the lidocaine group ( P < .05 ) . CONCLUSIONS Patients who received bupivacaine as the anesthetic agent for single-visit endodontic treatment of irreversible pulpitis in m and ibular molars had significantly less early postoperative pain and used fewer analgesics than those who had lidocaine as the anesthetic" ]

[ "18094377", "27228054", "15446319", "9428817", "9652559", "16386522", "19461489", "27364616", "26518948", "20595929", "25979971", "11907427" ]

[ "Reduced exposure to calcineurin inhibitors in renal transplantation.", "Usefulness of Tacrolimus without Basiliximab in Well-Matched Living-Donor Renal Transplant Recipients in Korea.", "Sequential Protocols using Basiliximab versus Anti-Thymocyte Globulins in Renal-Transplant Patients Receiving Mycophenolate Mofetil and Steroids", "Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.", "Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients", "Anti-CD25 monoclonal antibody sequential immunosuppressive induction therapy in renal transplants with high risk of delayed graft function.", "Early Outcomes of Thymoglobulin and Basiliximab Induction in Kidney Transplantation: Application of Statistical Approaches to Reduce Bias in Observational Comparisons", "Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate.", "Tacrolimus, Mycophenolate Mofetil, and Low-Dose Steroids With or Without Interleukin-2 Receptor Antibody Induction Therapy: A Retrospective Cohort Analysis.", "The Impact of IL2ra Induction Therapy in Kidney Transplantation Using Tacrolimus- and Mycophenolate-Based Immunosuppression", "Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance.", "A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years." ]

[ "BACKGROUND Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients . This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens . METHODS We r and omly assigned 1645 renal-transplant recipients to receive st and ard-dose cyclosporine , mycophenolate mofetil , and corticosteroids , or daclizumab induction , mycophenolate mofetil , and corticosteroids in combination with low-dose cyclosporine , low-dose tacrolimus , or low-dose sirolimus . The primary end point was the estimated glomerular filtration rate ( GFR ) , as calculated by the Cockcroft-Gault formula , 12 months after transplantation . Secondary end points included acute rejection and allograft survival . RESULTS The mean calculated GFR was higher in patients receiving low-dose tacrolimus ( 65.4 ml per minute ) than in the other three groups ( range , 56.7 to 59.4 ml per minute ) . The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus ( 12.3 % ) than in those receiving st and ard-dose cyclosporine ( 25.8 % ) , low-dose cyclosporine ( 24.0 % ) , or low-dose sirolimus ( 37.2 % ) . Allograft survival differed significantly among the four groups ( P=0.02 ) and was highest in the low-dose tacrolimus group ( 94.2 % ) , followed by the low-dose cyclosporine group ( 93.1 % ) , the st and ard-dose cyclosporine group ( 89.3 % ) , and the low-dose sirolimus group ( 89.3 % ) . Serious adverse events were more common in the low-dose sirolimus group than in the other groups ( 53.2 % vs. a range of 43.4 to 44.3 % ) , although a similar proportion of patients in each group had at least one adverse event during treatment ( 86.3 to 90.5 % ) . CONCLUSIONS A regimen of daclizumab , mycophenolate mofetil , and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function , allograft survival , and acute rejection rates , as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with st and ard-dose cyclosporine without induction . ( Clinical Trials.gov number , NCT00231764 [ Clinical Trials.gov ] . )", "OBJECTIVES Basiliximab is used alongside tacrolimus-based immunosuppression for routine induction therapy , even for well-matched living-donor renal transplant recipients . Because tacrolimus is a different drug from cyclosporine , this study examined the utility of tacrolimus-based immunosuppression without basiliximab for well-matched living-donor renal transplant recipients . MATERIAL S AND METHODS This prospect i ve study evaluated 36 patients who underwent 1 to 3 human leukocyte antigens mismatched living-donor renal transplants without basiliximab induction therapy between April 2012 and March 2015 ( group 1 ) . All transplants were ABO compatible and T-flow negative and were followed until April 2015 . Tacrolimus-based triple therapy was used for maintenance immunosuppression . The control group comprised 72 age- and sex-matched patients who underwent 1 to 3 human leukocyte antigens mismatched living-donor renal transplants with basiliximab induction therapy during the same period ( group 2 ) . RESULTS Two patients in group 1 and 12 patients in group 2 had infection , with cytomegalovirus infection and Pneumocystis pneumonia infection occurring only in group 2 and BK virus and urinary tract infection reported in both groups , with a similar incidence . One patient from group 2 had sepsis . Although the incidence of infection tended to be lower in group 1 than in group 2 ( 5.6 % vs 16.7 % ) , the overall incidence of infection was not significantly different ( P=.135 ) . In addition , there were no significant differences in incidence of acute rejection between groups 1 and 2 ( 2.8 % vs 4.2 % ; P=.699 ) . All patients showed stable renal function after treatment . CONCLUSIONS Tacrolimus-based triple drug maintenance immunosuppression without basiliximab might be an optimal treatment choice for individuals undergoing well-matched living-donor renal transplant", "Background . Sequential anti-thymocyte globulins (ATG)/cyclosporine immunosuppression has two main advantages : delayed introduction of the nephrotoxic drug cyclosporine and prevention of acute rejection . Basiliximab , a recently developed chimeric monoclonal antibody that selectively depletes the minor sub population of activated T lymphocytes , has been shown to reduce the incidence of acute rejection when used with cyclosporine introduced on day 1 . Methods . This open , r and omized , multicenter study was undertaken to compare the safety and efficacy of ATG versus basiliximab induction therapy ( IT ) with delayed introduction of cyclosporine for microemulsion ( Neoral ) in 105 low immunologic risk renal-transplant patients receiving mycophenolate mofetil and steroids . Results . One-year patient and graft survival rates were 98.1 % and 94.2 % , respectively , in the basiliximab group ( n=52 ) , and 98.1 % and 96.2 % in the ATG group ( n=53 ) . The incidence of biopsy-confirmed acute rejection was comparable ( basiliximab 9.6 % , ATG 9.4 % ) , as were key parameters of renal function , notably serum creatinine levels , time-to-nadir serum creatinine , and the number of patients requiring posttransplantation dialysis ( basiliximab 28.8 % , ATG 30.2 % ) . However , significantly fewer patients in the basiliximab group experienced cytomegalovirus ( CMV ) infection , leukopenia , and thrombocytopenia , and this without any significant difference in any other key safety parameters ( including the incidences of serum sickness , fever , lymphoma , and infections in general ) . Conclusions . Both ATG and basiliximab , when used for IT in a sequential protocol , are equally effective in terms of graft and patient survival as well as at preventing acute rejection . However , basiliximab is associated with a lower incidence of certain key adverse events , namely CMV infection , leukopenia , and thrombocytopenia", "BACKGROUND Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression . Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation . METHODS We administered daclizumab ( 1.0 mg per kilogram of body weight ) or placebo intravenously before transplantation and once every other week afterward , for a total of five doses , to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine , azathioprine , and prednisone . The patients were followed at regular intervals for 12 months . The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation . RESULTS Of the 126 patients given daclizumab , 28 ( 22 percent ) had biopsy-confirmed episodes of acute rejection , as compared with 47 of the 134 patients ( 35 percent ) who received placebo ( P=0.03 ) . Graft survival at 12 months was 95 percent in the daclizumab-treated patients , as compared with 90 percent in the patients given placebo ( P=0.08 ) . The patients given daclizumab did not have any adverse reactions to the drug , and at six months , there were no significant differences between the two groups with respect to infectious complications or cancers . The serum half-life of daclizumab was 20 days , and its administration result ed in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes . CONCLUSIONS Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients", "BACKGROUND Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30 % to 50 % of these patients . In the phase III study described here we assessed the ability of basiliximab , a chimeric interleukin (IL)-2 receptor monoclonal antibody , to prevent acute-rejection episodes in renal allograft recipients . METHODS 380 adult recipients of a primary cadaveric kidney transplant were r and omly allocated , in this double-blind trial , to receive a 20 mg infusion of basiliximab on day 0 ( day of surgery ) and on day 4 , to provide IL-2-receptor suppression for 4 - 6 weeks ( n=193 ) , or to receive placebo ( n=187 ) . Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study . The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation . Safety and tolerability were monitored over the 12 months of the study . FINDINGS 376 patients were eligible for intention-to-treat analysis ( basiliximab , n=190 ; placebo , n=186 ) . No significant differences in patient characteristics were apparent . The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 ( 29.8 % ) of 171 in the basiliximab group compared with 73 ( 44.0 % ) of 166 in the placebo group ( 32 % reduction ; 14.2 % difference [ 95 % Kaplan-Meier CIs 3 % to 24 % ] , p=0.012 ) . The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group ( 10 % vs 23.1 % , 13.1 % difference [ 5.4 % to 20.8 % ] , p<0.001 ) . At weeks 2 and 4 post-transplantation , the mean daily dose of steroids was significantly higher in the placebo group ( p<0.001 with one-way analysis of variance ) . The incidence of graft loss at 12 months post-transplantation was 23 ( 12.1 % ) of 190 in the basiliximab group and 25 ( 13.4 % ) of 186 in the placebo group ( 1.3 % difference [ -5 % to 9 % ] , p=0.591 ) . The incidence of infection and other adverse events was similar in the two treatment groups . The acute tolerability of basiliximab was excellent , with no evidence of cytokine-release syndrome . 14 deaths ( basiliximab n=9 ; placebo n=5 ; -2.0 % difference [ -6 % to 2 % ] , p=0.293 ) occurred during the 12-month study and a further three deaths ( basiliximab n=1 ; placebo n=2 ) occurred within the 380-day cut-off period . One post-transplantation lymphoproliferative disorder was recorded in each group . INTERPRETATION Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly , with no clinical ly relevant safety or tolerability concerns", "There is little experience on the use of monoclonal antibodies that block the high-affinity interleukin-2 receptor ( basiliximab and daclizumab ) in sequential therapy in renal transplants with risk of delayed graft function . This study sougth to test the efficacy and safety of the substitution of anticalcineurins with two doses of basiliximab or daclizumab in the immediate posttransplant period for recipients at risk of delayed renal graft function . Immunosuppression consisted of steroids , mycophenolate mofetil , and two doses of basiliximab ( 20 mg/day ) on days 0 and 4 posttransplant or daclizumab ( 1 mg/kg per day ) on days 0 and 15 posttransplant . Anticalcineurins were not administered until the beginning of graft function . Among 49 recipients ( mean age 63.5 + /- 10.5 years ) , 40 received a kidney from a donor over 60 years of age , three from a non-heart-beating donor , and six from donors with an acute elevation of serum creatinine to 2.4 + /- 0.86 ( 1.7 - 3.7 ) . At a mean follow-up of 14.2 + /- 8.4 months , five patients experienced acute rejection episodes . Only 15 patients needed posttransplant dialysis ( 2.7 + /- 1.6 ) . In 11 patients , cyclosporine ( CsA ) was introduced at 6 + /- 2.9 days posttransplant and in 37 , tacrolimus on 8.6 + /- 3.6 days posttransplant . The incidence of kidney graft loss was 16.3 % . Patient survival was 96 % . Thirty-nine recipients are alive with functioning grafts , with mean serum creatinine of 1.4 mg/dL. In conclusion , substitution for anticalcineurins with interleukin-2-receptor blockade in the immediate posttransplant period for patients at risk of delayed graft function minimizes nephrotoxicity and reduces tubular necrosis , without increasing the risk of an acute rejection episode", "Background . Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching . Methods . We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin , basiliximab , or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil . The primary outcome was the 6 month , Food and Drug Administration-approved composite endpoint of rejection , graft failure , or death . Outcomes according to induction exposure were compared using logistic regression analysis , exposure likelihood matching , and outcome risk score matching . Results . All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present , with approximately 22 % adjusted , relative reduction by logistic regression analysis and 3 % absolute reductions by matching approaches . When steroids were absent , risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance . Triple endpoint incidence was lower with both induction regimens compared with no induction across methods . Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospect i ve trial ranged from 1600 to nearly 7000 patients . Conclusions . Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era . As the sample sizes necessary to power a prospect i ve superiority trial are likely prohibitive , studies such as these provide clinical ly relevant information that may not be otherwise attainable", "BACKGROUND AND OBJECTIVES IL-2 receptor antagonist ( IL2-RA ) is recommended as a first-line agent for induction therapy in renal transplantation . However , this remains controversial in deceased donor renal transplantation ( DDRT ) maintained on tacrolimus (TAC)/mycophenolic acid ( MPA ) with or without steroids . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge ( n=74,627 ) to compare outcomes of IL2-RA and other induction agents . We initially divided the cohort into two groups on the basis of steroid use at the time of discharge : steroid ( n=59,010 ) versus no steroid ( n=15,617 ) . Each group was stratified into induction categories : IL2-RA , rabbit antithymocyte globulin ( r-ATG ) , alemtuzumab , and no induction . The main outcomes were incidence of acute rejection within the first year and overall graft failure ( defined as graft failure and /or death ) post-transplantation . Propensity score ( PS ) , specifically inverse probability of treatment weight , analysis was used to minimize selection bias caused by nonr and om assignment of induction therapies . RESULTS Median ( 25th , 75th percentiles ) follow-up times were 3.9 ( 1.1 , 5.9 ) and 3.2 ( 1.1 , 4.9 ) years for steroid and no steroid groups , respectively . Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category ( 13.3 % ; P<0.001 and 28 % ; P=0.01 , respectively ) in the steroid group and the IL2-RA category ( 11.1 % ; P=0.16 and 27.4 % ; P<0.001 , respectively ) in the no steroid group . Compared with IL2-RA , PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories , except that acute rejection was significantly lower with r-ATG ( odds ratio [ OR ] , 0.68 ; 95 % confidence interval [ 95 % CI ] , 0.62 to 0.74 ) . In the no steroid group , compared with IL2-RA , odds of acute rejection with r-ATG ( OR , 0.80 ; 95 % CI , 0.60 to 1.00 ) and alemtuzumab ( OR , 0.68 ; 95 % CI , 0.53 to 0.88 ) were lower , and r-ATG was associated with better graft survival ( hazard ratio , 0.86 ; 95 % CI , 0.75 to 0.99 ) . CONCLUSIONS In DDRT , compared with IL2-RA induction , no induction was associated with similar outcomes when TAC/MPA/steroids were used . r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocol", "BACKGROUND Selective interleukin-2 receptor ( IL2R ) blockade is one option to decrease acute rejection rates in kidney transplant recipients . However , there are little data on the impact of basiliximab in a triple immunosuppressive regimen ( tacrolimus , mycophenolate mofetil , and low-dose steroids ) . Thus , this analysis aims at investigating the impact of basiliximab induction on rejection rates and immediate graft function following kidney transplantation . METHODS Basiliximab was introduced in our center according to our center 's policy in the beginning of 2011 . Patients who received basiliximab ( n = 83 ) were compared with patients without induction therapy ( n = 65 ) transplanted before the introduction of IL2R antibody induction . RESULTS The use of basiliximab as induction therapy decreased the incidence of biopsy-proven acute rejection ( BPAR ) within the 1st year after transplantation ( 21.5 % vs 14.5 % ; P = .283 ) . Overall rejection episodes ( including BPAR and borderline rejection ) were significantly reduced in patients with basiliximab compared with patients without ( 41.5 % vs 24.1 % ; P = .033 ) . However , graft function ( incidence of delayed graft function , primary nonfunction , slow graft function , and serum creatinine decline ) and overall outcome ( patient and graft survivals ) were similar in both groups . CONCLUSIONS We found a favorable impact of basiliximab induction therapy on early acute rejection rate . The impact on long-term outcome must be addressed in further r and omized controlled trials", "Background . IL2 receptor antagonist ( IL2ra ) induction therapy has gained favor due to an excellent safety profile and improved outcomes in r and omized trials using cyclosporine-based immunosuppression . However , there have been no large r and omized trials or retrospective analyses examining the effect of IL2ra versus no induction using tacrolimus and mycophenolate (TAC/MPA)-based therapy . Methods . A retrospective analysis from the Scientific Renal Transplant Registry of adult , primary kidney transplant recipients from 2000 to 2008 with initial immunosuppression of TAC/MPA and prednisone , who received IL2ra induction therapy or no induction therapy ( n=28,686 ) was performed . The primary outcome was acute rejection at 1 year , and secondary outcomes were graft and patient survival at 1 and 3 years . Multivariable analysis was used to control for factors shown to influence the incidence of acute rejection , and separate analyses were performed for deceased versus living donors . Results . Acute rejection at 1 year was significantly lower with IL2ra ( 11.6 % ) versus no induction therapy ( 13.0 % ; P=0.001 ) . One-year ( 95.7 % vs. 95.8 % ) and 3-year ( 87.5 % vs. 87.8 % ) graft survival , and 1-year ( 97.4 % vs. 97.5 % ) and 3-year ( 92.8 % vs. 93.2 % ) patient survival , was not different between those receiving IL2ra and no induction therapy . On multivariable analysis , the relative risk of acute rejection with IL2ra was 0.90 ( 95 % CI , 0.85–0.96 ; P=0.001 ) , and the effect was greater in living donors ( relative risk , 0.82 ; P<0.001 ) than deceased donors ( relative risk , 0.95 ; P=0.23 ) . Conclusion . The benefit of IL2ra induction with TAC/MPA/prednisone maintenance immunosuppression is less than previously reported due to a low baseline incidence of acute rejection", "BACKGROUND AND OBJECTIVES Induction therapy with IL-2 receptor antagonist ( IL2-RA ) is recommended as a first line agent in living donor renal transplantation ( LRT ) . However , use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid ( MPA ) with or without steroids . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge ( n=36,153 ) to compare effectiveness of IL2-RA to other induction options . The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge : steroid ( n=25,996 ) versus no-steroid ( n=10,157 ) . Each group was further stratified into three categories according to commonly used antibody induction approach : IL2-RA , rabbit anti-thymocyte globulin ( r-ATG ) , and no-induction in the steroid group versus IL2-RA , r-ATG and alemtuzumab in the no-steroid group . The main outcomes were the risk of acute rejection at 1 year and overall allograft failure ( graft failure or death ) post-transplantation through the end of follow-up . Propensity score-weighted regression analysis was used to minimize selection bias due to non-r and om assignment of induction therapies . RESULTS Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction ( odds ratio [ OR ] , 0.96 ; 95 % confidence interval [ 95 % CI ] , 0.86 to 1.08 for acute rejection ; and hazard ratio [ HR ] , 0.99 ; 95 % CI , 0.90 to 1.08 for overall allograft failure ) and IL2-RA categories . In the no-steroid group , odds of acute rejection with r-ATG ( OR , 0.73 ; 95 % CI , 0.59 to 0.90 ) and alemtuzumab ( OR , 0.53 ; 95 % CI , 0.42 to 0.67 ) were lower ; however , overall allograft failure risk was higher with alemtuzumab ( HR , 1.27 ; 95 % CI , 1.03 to 1.56 ) but not with r-ATG ( HR , 1.19 ; 95 % CI , 0.97 to 1.45 ) , compared with IL2-RA induction . CONCLUSIONS Compared with no-induction therapy , IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients . r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocol", "BACKGROUND The 1-year results of the Phase III U.S. Multicenter Trial comparing tacrolimus (FK506)- and cyclosporine (CsA)-based immunosuppressive therapy in kidney transplantation revealed a significant reduction in the incidence and severity of acute rejection episodes among patients maintained on tacrolimus . The present report at 5 years of follow-up focuses on the long-term impact of tacrolimus treatment on kidney allograft outcome . METHODS The study protocol permitted crossover of patients to the alternate treatment arm under stringent conditions . The effect of crossover on graft survival was analyzed . Cardiovascular risk factors and serious adverse events were also monitored over 5 years . RESULTS Intent-to-treat analysis revealed equivalent patient and graft survival between treatment arms at 5 years of follow-up ( 79.1 % vs. 81.4 % ; P=0.472 and 64.3 % vs. 61.6 % ; P=0.558 among tacrolimus and CsA-treated patients , respectively ) . However , the rate of crossover was significantly higher among patients r and omized to receive CsA-based therapy ( 27.5 % vs. 9.3 % ; P<0.001 ) . The incidence of treatment failure ( 43.8 % vs. 56.3 % ; P=0.008 ) was significantly lower among tacrolimus-treated patients . Graft survival was significantly improved in the tacrolimus treatment arm when crossover due to rejection was counted as graft failure ( 63.8 % vs. 53.8 % ; P=0.014 ) . Tacrolimus therapy was also associated with a significantly reduced requirement for medications to control hypertension and hyperlipidemia . There was a substantial rate of reversal of tacrolimus-associated insulin dependence . CONCLUSION Tacrolimus-based therapy result ed in significantly reduced risk of graft failure , without an increase in the incidence of adverse events associated with long-term immunosuppression" ]

[ "28271623", "10468696", "5192275", "4993960", "24979556", "25092036", "24588932", "27725652", "15765388", "25488056", "28625832" ]

[ "A double‐blind, placebo‐controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea‐predominant IBS", "Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5‐HT3 receptor antagonist", "Irritable bowel syndrome symptom severity improves equally with probiotic and placebo", "A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation", "Therapeutic effects, tolerability and safety of a multi-strain probiotic in Iranian adults with irritable bowel syndrome and bloating.", "Melatonin Regulation as a Possible Mechanism for Probiotic (VSL#3) in Irritable Bowel Syndrome: A Randomized Double-Blinded Placebo Study", "Randomized clinical trial on the effect of a multispecies probiotic on visceroperception in hypersensitive IBS patients.", "A Randomized Controlled Trial Comparing the Low FODMAP Diet vs. Modified NICE Guidelines in US Adults with IBS-D", "Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.", "A randomized clinical trial of Saccharomyces cerevisiae versus placebo in the irritable bowel syndrome.", "A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial." ]

[ "BACKGROUND Micro-inflammation is considered an element in the pathogenesis of irritable bowel syndrome ( IBS ) . High-sensitivity C reactive protein ( hs-CRP ) was previously shown to be higher in IBS compared to healthy controls , albeit within the normal range . Since probiotics may suppress micro-inflammation in the gut , we tested if they reduce symptoms and inflammatory markers ( hs-CRP and fecal calprotectin ( FC ) in diarrhea-predominant IBS ( IBS-D ) . The aim of this study was to assess the clinical and laboratory effects of BIO-25 , a multispecies probiotic , in women with IBS-D. METHODS A double-blind , placebo-controlled study . Following a 2-week run-in , eligible women were assigned at r and om to a probiotic capsule or an indistinguishable placebo , twice daily for 8 weeks . IBS symptoms and stool consistency were rated daily by Visual Analogue Scales ( VAS ) and the Bristol Stool Scale ( BSS ) . High-sensitivity C reactive protein was tested at baseline , 4 and 8 weeks . FC was tested at baseline and 8 weeks . KEY RESULTS One hundred and seventy-two IBS-D patients were recruited and 107 eligible patients were allocated to the intervention ( n=54 ) or placebo ( n=53 ) group . All symptoms improved in both groups with no significant difference between them in symptom improvement , hs-CRP or FC levels . CONCLUSIONS & INFERENCES An 8-week treatment with BIO-25 improved symptoms in women with IBS-D , but was not superior to placebo . This rigorously design ed and executed study supports the findings of other studies that did not demonstrate superiority of probiotics over placebo in IBS . High quality clinical studies are necessary to examine the efficacy of other specific probiotics in IBS-D patients since data are still conflicting", ": No currently available treatment provides consistent relief of irritable bowel syndrome . Colonic sensory and motor function are modulated partly through 5HT3‐receptors", "AIM To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome ( IBS ) symptoms and quality of life ( QoL ) . METHODS In this r and omized triple-blind trial , adult IBS volunteers who were recruited according to Rome III criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk . IBS Symptom Severity Score ( IBS-SSS ) , which constituted the primary outcome , and secondary outcomes , including individual IBS symptoms , IBS-related QoL question naire , anxiety and depression , defecation frequency , and stool consistency , were assessed at baseline at the end of the 8-wk run-in period , after 4 and 12 wk of intervention , and after a 4-wk washout . RESULTS A total of 340 of 391 r and omized volunteers completed the trial . IBS-SSS improved over 12 wk of treatment in all treatment groups , decreasing by a mean ± SD of 44.0 ± 80.2 , 50.8 ± 82.4 , and 48.3 ± 72.2 in the placebo , active low-dose , and active high-dose groups , respectively . Similarly , secondary outcomes did not differ between treatment groups . However , in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline ( VAS > 35/100 ) , the treatment significantly reduced the sensation of abdominal pain . Pain scores fell by 20.8 ± 22.8 , 29.4 ± 17.9 , and 31.2 ± 21.9 in the placebo , active low-dose , and active high-dose groups , respectively ( P value for placebo vs combined active doses = 0.0460 ) . CONCLUSION NCFM alleviates moderate to severe abdominal pain , consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression", "Background and Aim . The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated . Methods . A r and omized , double-blind , three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups ( F_1 , F_2 , and F_3 ) . Each group received a daily oral administration of probiotic mixtures ( for 60 days ) F_1 or F_2 or placebo F_3 , respectively . Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics . Results . The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period ( t60 ) and was maintained quite similar during the follow-up period ( t90 ) . Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3 , and the same level was maintained during the follow-up period . Conclusions . Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota . This clinical study is registered with the clinical study registration number IS RCT N15032219", "BACKGROUND Irritable bowel syndrome ( IBS ) is a common disorder in Iran with challenging treatment . Although trials have suggested that probiotics alleviate the complaints of patients with minimal side effects , they have not been investigated in Iranian adults . METHODS In a r and omized double-blind study , 108 eligible IBS patients ( Rome III Criteria ) aged 20 - 70 years who referred consecutively to a clinical center in Tehran with abdominal bloating from 2010 to 2012 received a combination probiotics or placebo twice daily for 4 weeks . The objective was to evaluate the efficacy and safety of a multi-strain probiotics combination . One week prior to and throughout the treatment , the participants recorded their abdominal symptoms on a daily basis , using visual analogue scale and reported satisfactory relief of general symptoms at the end of each week . Adverse events were evaluated by self-reporting and physical examination . Continuous variables were analyzed by independent t-test and chi-square was used for binomials . RESULTS The baseline characteristics were balanced ( 60 % female , mean age 36.7 ± 11.5 ) . A total of 97 ( 51 intervention , 46 control ) completed the treatment . Intention to treat analysis was done on 108 allocated subjects . 85 % of the probiotic group reported satisfactory relief of general symptoms compared with 47 % in the control group ( P < 0.01 ) . A reduction in abdominal bloating and pain with probiotic was superior to placebo [ -13.0 vs. -3.7 ( P < 0.01 ) , -8.2 vs. -2.1 ( P = 0.02 ) , respectively ] . No severe adverse drug reaction was seen in either group . CONCLUSIONS A 4-week period of treatment with the combination probiotics twice daily was safe , well tolerated , and effective in our patients . Further investigation is recommended for other subgroups of IBS . Trial Registration : I RCT .ir I RCT 2012071010230N1", "Background Probiotics have treatment efficacy in irritable bowel syndrome ( IBS ) , but the exact mechanism remains obscure . One hypothesis is the mediation of melatonin levels , leading to changes in IBS symptoms . Aim The purpose of this study was to evaluate the effects of a probiotic , VSL#3 , on symptoms , psychological and sleep parameters , and pain sensitivity in IBS , and relate these parameters to in vivo melatonin levels . Methods Forty-two IBS patients were r and omly assigned to receive VSL#3 or placebo for 6 weeks . Subjects completed bowel and psychological question naires , underwent rectal sensitivity testing and saliva melatonin assays . Results Abdominal pain duration and distension intensity decreased significantly in the probiotic group , along with an increase in rectal distension pain thresholds . A correlation between increase in pain tolerance and improvement in abdominal pain scores ( r = 0.51 , p = 0.02 ) was seen with probiotic . There was an increase in salivary morning melatonin levels in males treated with VSL#3 , which correlated ( r = 0.61 ) with improved satisfaction in bowel habits . When grouped based on baseline diurnal melatonin levels , patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment , which significantly correlated with improved satisfaction in bowel habits ( r = 0.68 ) . They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3 , as well as satisfaction with bowel movements and quality -of-life . Conclusions VSL#3 improved symptoms and increased rectal pain thresholds . Symptom improvement correlated with a rise in morning melatonin , significant in males and subjects with normal circadian rhythm . This suggests that probiotics may act by influencing melatonin production , hence modulating IBS symptoms , in individuals with a normal circadian rhythm", "BACKGROUND Irritable bowel syndrome ( IBS ) is characterized by heterogeneous pathophysiology and low response to treatment . Up to 60 % of IBS patients suffers from visceral hypersensitivity , which is associated with symptom severity and underlying pathophysiological mechanisms . Recently , positive effects of probiotics in IBS have been reported , but overall the response was modest . We performed a study in IBS patients , characterized by visceral hypersensitivity measured with the rectal barostat , aim ing to assess the effect of 6 weeks of multispecies probiotic mix on visceral pain perception . METHODS We conducted a r and omized , placebo-controlled , double-blind trial in forty Rome III IBS patients with visceral hypersensitivity . Prior to intake , patients kept a 2-week symptom diary and underwent a rectal barostat measurement . When hypersensitivity was confirmed , participation was allowed and patients received a multispecies probiotic with in vitro proven potential beneficial effects on mechanisms contributing to visceral hypersensitivity ( six different probiotic strains ; 10(9 ) cfu/g ) , or a placebo product of one sachet ( 5 g ) per day for 6 weeks . At the end of the intervention period , visceroperception and symptoms were reassessed . KEY RESULTS Thirty-five patients completed the trial . The percentage of patients with visceral hypersensitivity decreased significantly in the probiotic and placebo group ( 76.5 % and 71.4 % , respectively ; N.S. between groups ) . Improvement in pain scores and mean symptom score did not differ between the probiotic and placebo group . CONCLUSIONS & INFERENCES In this placebo-controlled trial in IBS patients with visceral hypersensitivity , no significant effect of a multispecies probiotic on viscerperception was observed . The study has been registered in the US National Library of Medicine ( http://www . clinical trials.gov , NCT00702026 )", "Objectives : There has been an increasing interest in the role of fermentable oligo- , di- , and monosaccharides and polyols ( FODMAPs ) in irritable bowel syndrome ( IBS ) . We report results from the first r and omized controlled trial of the low FODMAP diet in US adults with IBS and diarrhea ( IBS-D ) . The objectives were to compare the efficacy of the low FODMAP diet vs. a diet based upon modified National Institute for Health and Care Excellence guidelines ( mNICE ) on overall and individual symptoms in IBS-D patients . Methods : This was a single-center , r and omized-controlled trial of adult patients with IBS-D ( Rome III ) which compared 2 diet interventions . After a 2-week screening period , eligible patients were r and omized to a low FODMAP or mNICE diet for 4 weeks . The primary end point was the proportion of patients reporting adequate relief of IBS-D symptoms ≥50 % of intervention weeks 3–4 . Secondary outcomes included a composite end point which required response in both abdominal pain ( ≥30 % reduction in mean daily pain score compared with baseline ) and stool consistency ( decrease in mean daily Bristol Stool Form of ≥1 compared with baseline ) , abdominal pain and stool consistency responders , and other key individual IBS symptoms assessed using daily question naires . Results : After screening , 92 subjects ( 65 women , median age 42.6 years ) were r and omized . Eighty-four patients completed the study ( 45 low FODMAP , 39 mNICE ) . Baseline demographics , symptom severity , and nutrient intake were similar between groups . Fifty-two percent of the low FODMAP vs. 41 % of the mNICE group reported adequate relief of their IBS-D symptoms ( P=0.31 ) . Though there was no significant difference in the proportion of composite end point responders ( P=0.13 ) , the low FODMAP diet result ed in a higher proportion of abdominal pain responders compared with the mNICE group ( 51 % vs. 23 % , P=0.008 ) . Compared with baseline scores , the low FODMAP diet led to greater reductions in average daily scores of abdominal pain , bloating , consistency , frequency , and urgency than the mNICE diet . Conclusions : In this US trial , 40–50 % of patients reported adequate relief of their IBS-D symptoms with the low FODMAP diet or a diet based on modified NICE guidelines . The low FODMAP diet led to significantly greater improvement in individual IBS symptoms , particularly pain and bloating , compared with the mNICE diet", "BACKGROUND & AIMS The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome ( IBS ) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain . METHODS Seventy-seven subjects with IBS were r and omized to receive either Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624 , each in a dose of 1 x 10 10 live bacterial cells in a malted milk drink , or the malted milk drink alone as placebo for 8 weeks . The cardinal symptoms of IBS were recorded on a daily basis and assessed each week . Quality of life assessment , stool microbiologic studies , and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase . RESULTS For all symptoms , with the exception of bowel movement frequency and consistency , those r and omized to B infantis 35624 experienced a greater reduction in symptom scores ; composite and individual scores for abdominal pain/discomfort , bloating/distention , and bowel movement difficulty were significantly lower than for placebo for those r and omized to B infantis 35624 for most weeks of the treatment phase . At baseline , patients with IBS demonstrated an abnormal IL-10/IL-12 ratio , indicative of a proinflammatory , Th-1 state . This ratio was normalized by B infantis 35624 feeding alone . CONCLUSIONS B infantis 35624 alleviates symptoms in IBS ; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine , suggesting an immune-modulating role for this organism , in this disorder", "BACKGROUND We aim ed to evaluate clinical symptoms in subjects with irritable bowel syndrome receiving Saccharomyces cerevisiae in a r and omized double-blind placebo-controlled clinical trial . METHODS Overall , 179 adults with irritable bowel syndrome ( Rome III criteria ) were r and omized to receive once daily 500 mg of Saccharomyces cerevisiae , delivered by one capsule ( n = 86 , F : 84 % , age : 42.5 ± 12.5 ) , or placebo ( n = 93 , F : 88 % , age : 45.4 ± 14 ) for 8 weeks followed by a 3-week washout period . After a 2-week run-in period , cardinal symptoms ( abdominal pain/discomfort , bloating/distension , bowel movement difficulty ) and changes in stool frequency and consistency were recorded daily and assessed each week . A safety assessment was carried out throughout the study . RESULTS The proportion of responders , defined by an improvement of abdominal pain/discomfort , was significantly higher ( p = 0.04 ) in the treated group than the placebo group ( 63 % vs 47 % , OR = 1.88 , 95 % , CI : 0.99 - 3.57 ) in the last 4 weeks of treatment . A non-significant trend of improvement was observed with Saccharomyces cerevisiae for the other symptoms . Saccharomyces cerevisiae was well tolerated and did not affect stool frequency and consistency . CONCLUSION Saccharomyces cerevisiae is well tolerated and reduces abdominal pain/discomfort scores without stool modification . Thus , Saccharomyces cerevisiae may be a new promising c and i date for improving abdominal pain in subjects with irritable bowel syndrome", "BACKGROUND & AIMS Dietary restriction of fermentable carbohydrates ( a low FODMAP diet ) has been reported to reduce symptoms in some patients with irritable bowel syndrome ( IBS ) . We performed a r and omized , placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS . METHODS We performed a 2 × 2 factorial trial of 104 patients with IBS ( 18 - 65 years old ) , based on the Rome III criteria , at 2 hospitals in the United Kingdom . Patients were r and omly assigned ( blinded ) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks , along with a placebo or multistrain probiotic formulation , result ing in 4 groups ( 27 receiving sham diet/placebo , 26 receiving sham diet/probiotic , 24 receiving low FODMAP diet /placebo , and 27 receiving low FODMAP diet/probiotic ) . The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet ; the diets had similar degrees of difficulty to follow . Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected . The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period ; along with stool frequency and consistency . At baseline , global and individual symptoms were measured , along with generic and disease-specific health-related quality of life , using st and ard scoring systems . All data were collected again at 4 weeks , and patients answered questions about adequate symptom relief . Fecal sample s were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing . The co- primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks . RESULTS There was no significant interaction between the interventions in adequate relief of symptoms ( P = .52 ) or Bifidobacterium species ( P = .68 ) . In the intention-to-treat analysis , a higher proportion of patients in the low FODMAP diet had adequate symptom relief ( 57 % ) than in the sham diet group ( 38 % ) , although the difference was not statistically significant ( P = .051 ) . In the per- protocol analysis , a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief ( 61 % ) than in the sham diet group ( 39 % ) ( P = .042 ) . Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet ( 173 ± 95 ) than the sham diet ( 224 ± 89 ) ( P = .001 ) , but not different between those given probiotic ( 207 ± 98 ) or placebo ( 192 ± 93 ) ( P = .721 ) Abundance of Bifidobacterium species was lower in fecal sample s from patients on the low FODMAP diet ( 8.8 rRNA genes/g ) than patients on the sham diet ( 9.2 rRNA genes/g ) ( P = .008 ) , but higher in patients given probiotic ( 9.1 rRNA genes/g ) than patients given placebo ( 8.8 rRNA genes/g ) ( P = .019 ) . There was no effect of the low FODMAP diet on microbiota diversity in fecal sample s. CONCLUSIONS In a placebo-controlled study of patients with IBS , a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo . It is not clear whether changes result ed from collective FODMAP restriction or removal of a single component , such as lactose . Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species , compared with placebo , and might be given to restore these bacteria to patients on a low FODMAP diet . Trial registration no : IS RCT N02275221" ]

[ "9544745", "12088787" ]

[ "Influence of genotype at the low density lipoprotein (LDL) receptor gene locus on the clinical phenotype and response to lipid-lowering drug therapy in heterozygous familial hypercholesterolaemia. The Familial Hypercholesterolaemia Regression Study Group.", "Relation of peripheral flow-mediated vasodilatation and coronary arterial calcium in young patients with heterozygous familial hypercholesterolemia." ]

[ "The relationship between molecular defect and clinical phenotype has been examined in 42 patients with heterozygous familial hypercholesterolaemia ( FH ) and premature coronary heart disease . The defined defects included mutations in the low density lipoprotein (LDL)-receptor gene ( 23/42 ) or the apolipoprotein B Arg3500Gln mutation ( 5/42 ) . Mean LDL-cholesterol was higher , both before and during treatment with simvastatin and bile acid sequestrants , in patients predicted as having a ' severe ' mutation than in those with a ' mild ' mutation ( 8.72 + /- 2.02 mmol/l vs 6.63 + /- 1.8 , P = 0.05 before and 4.51 + /- 0.90 mmol/l vs 3.19 + /- 0.58 , P = 0.05 during treatment ) . Maximum inducible LDL-receptor activity in cultured lymphoblasts was inversely correlated with LDL-cholesterol before ( r2 = 0.499 , P = 0.002 ) and during ( r2 = 0.478 , P = 0.004 ) treatment in patients with a defined mutation in the LDL-receptor gene , but not in the 14 patients with no detectable molecular defect . LDL-cholesterol concentrations before and during treatment were significantly correlated in patients with a defined LDL-receptor gene mutation ( r2 = 0.548 , P = 0.0001 ) , but not in those with no detectable genetic defect . All these correlations were weak , however and there were no differences in the response to treatment in terms of either relative reduction or absolute decrease in LDL-cholesterol concentration between patients with different LDL-receptor defects . We conclude that only part of the variable phenotype of heterozygous FH patients is explained by different LDL-receptor defects and that other factors determine the severity of their hypercholesterolaemia and the onset of coronary disease", "The relation of peripheral flow-mediated vasodilation and coronary arterial calcium was studied in young patients with heterozygous familial hypercholesterolemia ( FH ) using high-resolution ultrasound and multi-detector computed tomography ( MDCT ) . We found that peripheral flow mediated vasodilation , a precursor of atherosclerosis , is altered in young heterozygous patients with FH . This alteration occurs before coronary arterial or aortic root calcium can be detected by MDCT and is independently related to hypercholesterolemia" ]

[ "11870119", "22464806", "4963579", "12036083", "20089454", "22540635", "7851109", "3447676", "24355050", "4248143", "17364286", "18487215", "3722087", "15705376", "15251831", "24813752", "24158736", "3388435", "4071761", "17335818", "16831439", "17218230", "26315303", "22138521", "9363727", "18339123", "26613790", "5011206", "15790610", "3941370", "10402369", "17624345", "21770829", "12884545", "22334228", "25482371", "20180042", "26267328", "16679164", "25015747", "18803944", "17952759", "21123447", "18462730", "19574176", "14715857", "20712264", "26507336", "15134155", "20799592", "27186859", "4156817", "20385511", "24989721", "18990381", "17336970", "26291797", "24302192", "20939675", "18262146", "22500844", "20222840" ]

[ "Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study.", "Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency.", "A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women", "Ascorbic Acid Supplement During Luteal Phase in IVF", "Effect of N-acetyl-cysteine after ovarian drilling in clomiphene citrate-resistant PCOS women: a pilot study.", "N-Acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome.", "Is double data entry necessary? The CHART trials. CHART Steering Committee. Continuous, Hyperfractionated, Accelerated Radiotherapy.", "CONCERN: Does ovary need D-chiro-inositol?", "Female dietary antioxidant intake and time to pregnancy among couples treated for unexplained infertility.", "Effect of vitamin D insufficiency treatment on fertility outcomes in frozen-thawed embryo transfer cycles: A randomized clinical trial", "N‐Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross‐over trial", "Combined laparoscopic surgery and pentoxifylline therapy for treatment of endometriosis-associated infertility: a preliminary trial.", "Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial", "N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome.", "Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome.", "Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome.", "Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial", "Diamel Therapy in Polycystic Ovary Syndrome Reduces Hyperinsulinaemia, Insulin Resistance, and Hyperandrogenaemia", "Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF–ICSI Treatment", "N-acetyl cysteine vs. metformin in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective randomized controlled study.", "Clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate for augmenting ovulation in the management of unexplained infertility: a randomized double-blind controlled trial.", "Pentoxifylline therapy after laparoscopic surgery for different stages of endometriosis: a prospective, double-blind, randomized, placebo-controlled study.", "Effects of Zinc Supplementation on Endocrine Outcomes in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial", "Prospective randomized trial of multiple micronutrients in subfertile women undergoing ovulation induction: a pilot study.", "Pentoxifylline versus placebo in the treatment of infertility associated with minimal or mild endometriosis: a pilot randomized clinical trial.", "Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate.", "The Effects of Chromium Supplementation on Endocrine Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial", "Prospective Randomized Study on the Influence of Myoinositol in PCOS Women Undergoing IVF in the Improvement of Oocyte Quality, Fertilization Rate, and Embryo Quality", "Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial.", "The effect of omega-3 supplementation on androgen profile and menstrual status in women with polycystic ovary syndrome: A randomized clinical trial", "Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients.", "Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility.", "The efficacy of melatonin administration on oocyte quality", "Ascorbic acid and infertility treatment.", "[Diet, metformin and inositol in overweight and obese women with polycystic ovary syndrome: effects on body composition].", "N-Acetylcysteine improves oocyte and embryo quality in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection: an alternative to metformin.", "Effects of Multivitamin/Mineral Supplementation on Trace Element Levels in Serum and Follicular Fluid of Women Undergoing in Vitro Fertilization (IVF)", "Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome.", "Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study", "Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial.", "Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome.", "Myo-inositol in patients with polycystic ovary syndrome: A novel method for ovulation induction", "Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation.", "Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial.", "The effects of calcium-vitamin D and metformin on polycystic ovary syndrome: a pilot study.", "Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome.", "Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial.", "Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome", "A nutritional supplement for improving fertility in women: a pilot study.", "Evaluation of effect of silymarin on granulosa cell apoptosis and follicular development in patients undergoing in vitro fertilization.", "Vitamin D Status Relates to Reproductive Outcome in Women With Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial.", "A pilot double-blind randomised placebo-controlled dose–response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol", "N-acetyl cysteine: could it be an effective adjuvant therapy in ICSI cycles? A preliminary study.", "Oral antioxidants supplementation for women with unexplained infertility undergoing ICSI/IVF: Randomized controlled trial", "Pentoxifylline and antioxidants improve sperm quality in male patients with varicocele.", "Prospective, randomized trial of metformin and vitamins for the reduction of plasma homocysteine in insulin-resistant polycystic ovary syndrome.", "The adjuvant effect of metformin and N-acetylcysteine to clomiphene citrate in induction of ovulation in patients with Polycystic Ovary Syndrome", "Inositol: effects on oocyte quality in patients undergoing ICSI. An open study.", "N-acetyl cysteine plus clomiphene citrate versus metformin and clomiphene citrate in treatment of clomiphene-resistant polycystic ovary syndrome: a randomized controlled trial.", "Pentoxifylline after conservative surgery for endometriosis: a randomized, controlled trial.", "Therapeutic effects of calcium & vitamin D supplementation in women with PCOS.", "Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women" ]

[ "BACKGROUND Enhanced vascularization appears to be important for follicular selection and maturation in both spontaneous and stimulated IVF cycles . Nitric oxide , formed in vivo from L-arginine , may play a key role in follicular maturation and ovulation . METHODS To evaluate the role of L-arginine supplementation in controlled ovarian hyperstimulation , 37 IVF patients were divided into two groups according to ovarian stimulation protocol s : group I , GnRH agonist plus pure (p)FSH plus oral L-arginine ( n = 18 ) ; and group II , GnRH agonist plus pFSH plus placebo ( n = 19 ) . Hormonal , ultrasonographic and Doppler evaluations were performed , and plasma and follicular fluid nitrite/nitrate concentrations were monitored . RESULTS Thirty-two patients completed the study . In group I ( n = 16 ) , plasma L-arginine concentrations increased from ( basal ) 87 + /- 12 micromol to 279 + /- 31 micromol ( P = 0.002 ) on the day of beta-HCG administration . In this group , pFSH treatment was shorter ( P = 0.039 ) than in group II ( n = 16 ) . The number of the follicles > or = 17 mm was lower ( P = 0.038 ) in group I than group II . The \" good quality \" embryos were fewer in number ( P = 0.034 ) and pregnancy rate , both per patient ( P = 0.024 ) and per embryo transfer ( P = 0.019 ) , was lower in group I. In the L-arginine group , an increased follicular fluid concentration of nitrite/nitrate was observed . On day 8 of the cycle , elevated plasma estradiol levels were associated with decreased blood flow resistances of perifollicular arteries . Follicular fluid concentrations of nitrite/nitrate were inversely correlated with embryo quality ( r = -0.613 ; P = 0.005 ) and perifollicular artery pulsatility index ( r = -0.609 ; P = 0.021 ) . CONCLUSIONS L-Arginine supplementation may be detrimental to embryo quality and pregnancy rate during controlled ovarian hyperstimulation cycles", "Insulin resistance is one of the most common features of polycystic ovary syndrome ( PCOS ) . Some studies suggest that vitamin D deficiency may have a role in insulin resistance ; thus , the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency . We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency . The current study was a r and omized , placebo-controlled , double-blinded trial with 50 women with PCOS and a vitamin D deficiency , 20 to 40 years old , assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo ( 1 every 20 days ) for 2 months ( vitamin D , n = 24 ; placebo , n = 26 ) . The fasting blood glucose , insulin , 25-hydroxyvitamin D , and parathyroid hormone levels , as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment . In the vitamin D group , the serum level of 25-hydroxyvitamin D increased ( 6.9 ± 2.8 to 23.4 ± 6.1 ng/mL , P < .0001 ) , and the parathyroid hormone level decreased ( 70.02 ± 43.04 to 50.33 ± 21.99 μ IU/mL , P = .02 ) . There were no significant changes in the placebo group . There was a significant increase in insulin secretion in the vitamin D group ( P = .01 ) , but this was not significant compared with the placebo group . The fasting serum insulin and glucose levels and the insulin sensitivity and homeostasis model assessment of insulin resistance did not change significantly by the end of the study . We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency", "Introduction . We evaluated the effects of a therapy that combines myo-inositol ( MI ) and D-chiro-inositol ( DCI ) in young overweight women affected by polycystic ovary syndrome ( PCOS ) , characterized by oligo- or anovulation and hyper and rogenism , correlated to insulin resistance . Methods . We enrolled 46 patients affected by PCOS and , r and omly , we assigned them to two groups , A and B , treated , respectively , with the association of MI plus DCI , in a 40 : 1 ratio , or with placebo ( folic acid ) for six months . Thus , we analyzed pretreatment and posttreatment FSH , LH , 17-beta-Estradiol , Sex Hormone Binding Globulin , and rostenedione , free testosterone , dehydroepi and rosterone sulphate , HOMA index , and fasting glucose and insulin . Results . We recorded a statistically significant reduction of LH , free testosterone , fasting insulin , and HOMA index only in the group treated with the combined therapy of MI plus DCI ; in the same patients , we observed a statistically significant increase of 17-beta-Estradiol levels . Conclusions . The combined therapy of MI plus DCI is effective in improving endocrine and metabolic parameters in young obese PCOS affected women", "Purpose : To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospect i ve , r and omized , placebo-controlled , group comparative , double-blind study . Methods : Voluntary daily oral intake of either ascorbic acid ( 1 , 5 , or 10 g/day ) or Placebo for 14 days after follicle aspiration for IVF-ET procedure . Data was obtained on 620 cases of women , age < 40 years , undergoing first IVF-embryo transfer cycles in two private out-patient infertility clinics . All women were stimulated by the same protocol . The mean age was 31.73 ( ±4.4 SD ) years . Results : No differences in clinical pregnancy rate and implantation rate were noted in statistical logistic regression analysis between the four intake groups . Conclusions : There was no clinical evidence of any beneficial effect , as defined by main outcome measures , of ascorbic acid on IVF-ET . Our data suggest there is no obvious value of high dosed intake of vitamin C during luteal phase in infertility treatment", "The aim of this r and omized double-blind placebo-controlled pilot study was to evaluate N-acetyl-cysteine ( NAC ) as an adjunctive therapy following unilateral laparoscopic ovarian drilling ( LOD ) for clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . A total of 60 patients with clomiphene citrate-resistant PCOS who underwent unilateral LOD were assigned r and omly to receive either NAC 1.2 g/d ( group A=30 ) or placebo ( group B=30 ) for 5 days starting at day 3 of the cycle for 12 consecutive cycles . The primary outcome was pregnancy rate ; secondary outcomes were ovulation rates , endometrial thickness and pregnancy outcome . Baseline clinical , endocrine , and sonographic characteristics were similar in the two groups . A significant increase in both ovulation and pregnancy rates was observed in the NAC group , compared with placebo [ 87 % versus 67 % ( RR 1.3 ; 95 % CI 1.2 - 2.7 ) and 77 % versus 57 % ( RR 1.4 ; 95 % CI 1.1 - 2.7 ) , respectively , P<0.01 ] . Moreover , miscarriage rates were significantly lower and live birth rates were significantly higher in the NAC group [ 8.7 % versus 23.5 % ( RR 0.4 ; 95 % CI 0.1 - 3.7 ) and 67 % versus 40 % ( RR 1.7 ; 95 % CI 0.3 - 3.5 ) , respectively , P<0.01 ] . In conclusion , NAC is a novel adjuvant therapy after unilateral LOD which might help improve overall reproductive outcome", "AIM The aim of this study was to evaluate the effect of oral N-acetylcysteine ( NAC ) administration as an adjuvant to clomiphene citrate ( CC ) on induction of ovulation outcomes in patients with polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS In this placebo-controlled double-blind r and omized clinical trial , 180 PCOS infertile patients were r and omly divided into two groups for induction of ovulation . Patients in group 1 received CC 100 mg/d plus NAC 1.2 g/d and patients in group 2 received CC plus placebo for 5 days starting at day 3 of the cycle . On the 12th day of the menstrual cycle in the presence of at least one follicle with an 18 - 20-mm diameter in ultrasound evaluation , 10,000 U hCG was injected intramuscularly and timed intercourse was advised 36 h after hCG injection . Serum β-hCG level was measured on the 16th day after hCG injection . RESULTS The number of follicles > 18 mm and the mean endometrial thickness on the day of hCG administration were significantly higher among the CC+NAC group ( P-value = 0.001 ) . The ovulation and pregnancy rates were also significantly higher in the CC+NAC group ( P-value = 0.02 and 0.04 , respectively ) . No adverse side-effects and no cases of ovarian hyperstimulation syndrome were observed in the group receiving NAC . CONCLUSION NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients . It may also have some beneficial impacts on endometrial thickness", "There is some controversy over the need for double data entry in clinical trials . In particular , does the number and types of errors identified with this approach justify the extra effort involved ? We report the results of a study carried out to address this question . Our main outcome measure was the frequency and types of errors involved in the entry of data for the CHART ( continuous , hyperfractionated , accelerated radiotherapy ) trials . Data were reentered for a sample of 44 patients by a data manager other than the one making the initial entry . The second entry was then compared with the first entry . The error rate for the two entries combined was 14 per 10,000 data items ( fields ) ( 95 % confidence interval 10 , 19 ) . The error rate for the initial entry alone was 15 per 10,000 fields ( 95 % confidence interval 9.5 , 22 ) , and the vital/important error rate ( defined as any error on a principal outcome measure or a major error on any other endpoint or variable ) was 2.5 per 10,000 fields ( 95 % confidence interval 0.68 , 6.4 ) . On this evidence double data entry is not performed for the CHART trials", "BackgroudPolycystic Ovary Syndrome ( PCOS ) is a multifactorial pathology that affects 10 % of the women in reproductive age being the main cause of infertility due to menstrual dysfunction . Since 1980 , it is known that PCOS is associated with insulin resistance ( IR ) . The recognition of this association has prompted extensive investigation on the relationship between insulin and gonadal function , and has turned insulin sensitizer agent as the main therapeutic choice . In particular two different polyalcohol myo-inositol and D-chiro-inositol have been shown to improve insulin resistance , hyper and rogenism and to induce ovulation in PCOS women . In particular , while data on myo-inositol and restored ovulation were consistent , data on D-chiro-inositol were not . Recently , a comparative study , proposed a D-chiro-inositol paradox in the ovary of PCOS patients hypothesizing that only myo-inositol has a specific ovarian action . In the present study we aim to further study the role played by D-chiro-inositol at ovarian level . Methods A total of 54 women , aged < 40 years and diagnosed with PCOS were enrolled in this study . Patients with insulin resistance and /or hyperglycaemia were excluded from the study . Patients were r and omly divided into 5 groups ( n=10 - 12 ) : a placebo group , and 4 groups ( A-D ) that received 300 - 600 - 1200 - 2400 mg of DCI daily respectively . All treatments were carried out for 8 weeks before follicle stimulating hormone ( rFSH ) administration . Results Total r-FSH units increased significantly in the two groups that received the higher doses of DCI . The number of immature oocytes was significantly increased in the three groups that received the higher doses of DCI . Concurrently , the number of MII oocytes was significantly lower in the D group compared to placebo group . Noteworthy , the number of grade I embryos was significantly reduced by DCI supplementation . Conclusions Indeed , increasing DCI dosage progressively worsens oocyte quality and ovarian response", "OBJECTIVE To determine whether increased antioxidant intake in women is associated with shorter time to pregnancy ( TTP ) among a cohort of couples being treated for unexplained infertility . DESIGN Secondary data analysis of a r and omized controlled trial . SETTING Academic medical center associated with a private infertility center . PATIENTS Females with unexplained infertility . INTERVENTIONS None . MAIN OUTCOME MEASURE(S ) The time it took to establish a pregnancy that led to a live birth . RESULT ( S ) Mean nutrient intake exceeded the estimated average requirement ( EAR ) for vitamins C and E. No differences in mean intake of any of the antioxidants were noted between women who delivered a live-born infant during the study period vs. those who did not . In multivariable models , intake of β-carotene from dietary supplements was associated with shorter TTP among women with body mass index ( BMI ) ≥25 kg/m(2 ) ( hazard ratio [ HR ] 1.29 , 95 % confidence interval [ CI ] 1.09 - 1.53 ) and women < 35 y ( HR 1.19 , 95 % CI 1.01 - 1.41 ) . Intake of vitamin C from dietary supplements was associated with shorter TTP among women with BMI < 25 kg/m(2 ) ( HR 1.09 , 95 % CI 1.03 - 1.15 ) and women < 35 y ( HR 1.10 , 95 % CI 1.02 - 1.18 ) . Intake of vitamin E from dietary supplements among women ≥35 y also was associated with shorter TTP ( HR 1.07 , 95 % CI 1.01 - 1.13 ) . CONCLUSION ( S ) Shorter TTP was observed among women with BMI < 25 kg/m(2 ) with increasing vitamin C , women with BMI ≥25 kg/m(2 ) with increasing β-carotene , women < 35 y with increasing β-carotene and vitamin C , and women ≥35 y with increasing vitamin E. CLINICAL TRIAL REGISTRATION NUMBER NCT00260091", "Background : Frozen- thawed embryo transfer is an essential part of ART treatment and outcomes of this procedure are associated with several clinical factors . Several studies have showed an increase level of IVF outcomes in women with sufficient vitamin D. Objective : whether treatment of vitamin D insufficiency can improve pregnancy rates in frozen-thawed embryo transfer cycles . Material s and Methods : This is an interventional , r and omized clinical trial . Serum 25-(OH ) vitamin D level of 128 women who had undergone IVF/ICSI with cryopreservation of embryos was checked . One hundred fourteen infertile women with insufficient serum vitamin D ( less than 30 ng/ml ) were included in the study . Fifty seven women were treated with supplementary vitamin D , 50000 IU weekly , for 6 - 8 weeks and fifty seven women were received no supplementation . One hundred six women completed frozen thawed embryo transfer cycles and included in the final analysis . Primary and secondary outcomes were chemical and clinical pregnancy respectively . Results : Our study did not show any significant difference between vitamin D insufficient and treated women in term of chemical ( 29.40 % vs. 29.10 % respectively , p=1.00 ) or clinical ( 25.50 % vs. 21.80 % respectively , p=0.81 ) pregnancy rates . Conclusion : Vitamin D insufficiency treatment is not associated with higher pregnancy rate in frozen-thawed embryo transfer cycles", "Objective . To compare clomiphene citrate plus N‐acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome . Design . Prospect i ve cross‐over trial . Setting . University teaching hospital and a private practice setting . Patients . Five hundred and seventy‐three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N‐acetyl cysteine for another cycle . All women suffered from polycystic ovary syndrome . Interventions . Patients had clomiphene citrate 50‐mg tablets twice daily alone or with N‐acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle . Outcome measures . Primary outcomes were number of mature follicles , serum E2 , serum progesterone , and endometrial thickness . Secondary outcome was the occurrence of pregnancy . Results . Ovulation rate improved significantly after the addition of N‐acetyl cysteine ( 17.9 % versus 52.1 % ) . Although the number of mature follicles was more in the N‐acetyl cysteine group ( 2.1±0.88 versus 3.2±0.93 ) , the difference was not statistically significant . The mean E2 levels ( pg/ml ) at the time of human chorionic gonadotropine injection , serum progesterone levels ( ng/ml ) on days 21–23 of the cycle , and the endometrial thickness were significantly improved in the N‐acetyl cysteine group . The overall pregnancy rate was 11.5 % in the N‐acetyl cysteine group . Insulin resistance occurred in 260 patients ( 55.4 % ) . There was no significant difference between the insulin resistance group ( n = 260 ) and non‐insulin resistance group ( n = 210 ) as regards ovulation rate , number of follicles , serum E2 ( pg/ml ) , serum progesterone ( ng/ml ) , endometrial thickness ( mm ) , or pregnancy rate . Conclusion . N‐Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients", "BACKGROUND Surgical treatment has modest efficacy for the treatment of infertility associated with early-stage endometriosis . Immunomodulation with pentoxifylline is considered as a new strategy potentially useful in treating endometriosis . Thus , this study investigated the usefulness of combined laparoscopic surgery and pentoxifylline therapy in the treatment of infertility associated with minimal to mild endometriosis . METHODS A prospect i ve , r and omized , controlled blind trial was conducted . Patients entered the study immediately after laparoscopic surgery and were r and omly assigned to the treatment with either oral pentoxifylline ( 800 mg/day ) ( pentoxifylline group , n = 51 ) or an oral placebo ( placebo group , n = 53 ) . Patients were then observed for pregnancy for 6 months . RESULTS Among 98 patients finally considered in the evaluation of the results , the 6 month overall pregnancy rates were 28 and 14 % in the pentoxifylline and placebo groups , respectively . Thus , an absolute difference of 14 % ( 95 % CI -2 to 30 ) ( Chi-squared test , P = 0.1 ) in the cumulative probability of pregnancy in 6 months after laparoscopic surgery in patients receiving pentoxifylline versus placebo post-operatively was observed . CONCLUSION Our findings provide preliminary clinical evidence to suggest the new experimental treatment approaches , toward endometriosis , that are based on immunomodulation deserve further attention . Well- design ed multicenter trials are warranted to confirm or refute our results", "Background Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome ( PCOS ) , which is characterized by hyper and rogenism , ovulatory dysfunction , and presence of polycystic ovaries on pelvic scanning . Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease . Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated . In this paper , we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS . Methods / design This is a multicenter , r and omized , placebo-controlled and double-blind trial . A total of 120 patients will be enrolled in this study and will be r and omized into two groups . Berberine or placebo will be taken orally for 12 weeks . The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp . Discussion We postulate that women with PCOS will have improved insulin resistance following berberine administration . Trial registration This study is registered at Clinical Trials.gov , NCT01138930", "OBJECTIVE To evaluate the effect of N-acetyl-cysteine ( NAC ) , a mucolytic drug with insulin sensitizing properties , as an adjuvant therapy in subjects with polycystic ovary syndrome ( PCOS ) resistant to clomiphene citrate ( CC ) . DESIGN Placebo-controlled , double-blind r and omized trial . SETTING University-based hospital and private infertility practice . PATIENT(S ) One hundred fifty women diagnosed with CC-resistant PCOS , aged 18 - 39 years undergoing therapy for infertility were included . INTERVENTION(S ) The patients were assigned r and omly to receive either NAC 1.2 g/d ( group I ) or placebo ( group II ) with CC 100 mg/d for 5 days starting at day 3 of the cycle . MAIN OUTCOME MEASURE(S ) Ovulation rate and pregnancy rate ( PR ) . RESULT ( S ) Combination of CC and NAC significantly increased both ovulation rate and PR in women with CC-resistant PCOS ( 49.3 % vs. 1.3 % and 21.3 % vs. 0 % , respectively ) . No cases of ovarian hyperstimulation syndrome ( OHSS ) were reported in the NAC group ; two cases of miscarriage ( 12.5 % ) were reported . CONCLUSION ( S ) The NAC as an adjuvant to CC was more effective than placebo for CC-resistant patients with PCOS . It is safe and well tolerated", "OBJECTIVE To determine whether the administration of D-chiro-inositol , a putative insulin-sensitizing drug , would affect the concentration of circulating insulin , the levels of serum and rogens , and the frequency of ovulation in lean women with the polycystic ovary syndrome . METHODS In 20 lean women ( body mass index , 20.0 to 24.4 kg/m 2 ) who had the polycystic ovary syndrome , treatment was initiated with either 600 mg of D-chiro-inositol or placebo orally once daily for 6 to 8 weeks . We performed oral glucose tolerance tests and measured serum sex steroids before and after therapy . To monitor for ovulation , we determined serum progesterone concentrations weekly . RESULTS In the 10 women given D-chiro-inositol , the mean ( + /- st and ard error ) area under the plasma insulin curve after oral administration of glucose decreased significantly from 8,343 + /- 1,149 mU/mL per min to 5,335 + /- 1,792 mU/mL per min in comparison with no significant change in the placebo group ( P = 0.03 for difference between groups ) . Concomitantly , the serum free testosterone concentration decreased by 73 % from 0.83 + /- 0.11 ng/dL to 0.22 + /- 0.03 ng/dL , a significant change in comparison with essentially no change in the placebo group ( P = 0.01 ) . Six of the 10 women ( 60 % ) in the D-chiro-inositol group ovulated in comparison with 2 of the 10 women ( 20 % ) in the placebo group ( P = 0.17 ) . Systolic ( P = 0.002 ) and diastolic ( P = 0.001 ) blood pressures , as well as plasma triglyceride concentrations ( P = 0.001 ) , decreased significantly in the D-chiro-inositol group in comparison with the placebo group , in which these variables either increased ( blood pressure ) or decreased minimally ( triglycerides ) . CONCLUSION We conclude that , in lean women with the polycystic ovary syndrome , D-chiro-inositol reduces circulating insulin , decreases serum and rogens , and ameliorates some of the metabolic abnormalities ( increased blood pressure and hypertriglyceridemia ) of syndrome", "This prospect i ve r and omized controlled trial evaluated the effect of combined oral coenzyme Q10 ( CoQ10 ) and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome ( PCOS ) . A total of 101 infertile women with PCOS resistant to clomiphene citrate were r and omized either to combined CoQ10 and clomiphene citrate ( 51 patients , 82 cycles ) or to clomiphene citrate alone ( 50 patients , 71 cycles ) . The outcome measures were number of follicles , serum oestradiol , serum progesterone , endometrial thickness and ovulation , clinical pregnancy and miscarriage rates . Numbers of follicles > 14 mm and ≥18 mm were significantly higher in the CoQ10 group . Endometrial thickness on the day of human chorionic gonadotrophin was significantly greater in the CoQ10 group ( 8.82 ± 0.27 mm versus 7.03 ± 0.74 mm ) . Ovulation occurred in 54/82 cycles ( 65.9 % ) in the CoQ10 group and 11/71 cycles ( 15.5 % ) in the control group . Clinical pregnancy rate was significantly higher in the CoQ10 group ( 19/51 , 37.3 % ) versus the control group ( 3/50 , 6.0 % ) . Combination of CoQ10 and clomiphene citrate in the treatment of clomiphene-citrate-resistant PCOS patients improves ovulation and clinical pregnancy rates . It is an effective and safe option and can be considered before gonadotrophin therapy or laparoscopic ovarian drilling", "Abstract Purpose To determine whether administration of vitamin D affects the success rates of intra uterine insemination ( IUI ) in infertile polycystic ovarian syndrome ( PCOS ) women and their endometrial thickness . Methods This r and omized , double-blind , placebo-controlled trial was conducted in an infertility clinic of Women ’s Hospital , and 110 infertile PCOS patients undergoing IUI were r and omly divided to receive vitamin D or placebo . Endometrial thickness , IUI results , number of dominant follicles , duration of IUI cycle , and dose of HMG used in IUI were determined . Results The endometrial thickness was significantly different in the group treated with vitamin D versus the placebo group ( p = 0.003 ) . There was no statistical difference in pregnancy out come between the two groups ( RR = 1.167 , CI 95 % 0.70–1.93 ) . No statistical difference was found in number of dominant follicles ( p = 0.96 ) , duration of IUI cycles ( p = 0.70 ) and dose of HMG used for IUI ( p = 0.95 ) . Conclusions It seems that administration of vitamin D induces endometrial proliferation in PCOS women during IUI cycle", "For to determine the effect of Diamel on the insulin resistance , insulin sensitivity , and sexual hormones results in women with polycystic ovary syndrome ( PCOS ) . A study was carried out on 37 patients with this disorder . A triple-blind clinical trial was design ed in which the Diamel food supplement was compared with a placebo . The women with reproductive ages were r and omly distributed in two groups , with 18 and 19 women respectively , and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation . A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel . The insulin sensitivity improved considerably in this group . The rate of menstrual recovery was higher in the group with Diamel , and two patients from this group obtained pregnancy . The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group . The LH also decreases in the same group when comparing the start with 6 months . We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS , with improvement in the levels of LH and testosterone", "Background The age-related reduction in live-birth rate is attributed to a high rate of aneuploidy and follicle depletion . We showed in an animal model that treatment with Coenzyme Q10 ( CoQ10 ) markedly improved reproductive outcome . The aim of this study was to compare the post-meiotic oocyte aneuploidy rate in in vitro fertilization ( IVF ) and intra cytoplasmic sperm injection ( ICSI ) patients treated with CoQ10 or placebo . Methods We conducted a double blind placebo controlled r and omized trial that included IVF-ICSI patients 35 - 43 years of age . The patients were treated with either 600 mg of CoQ10 or an equivalent number of placebo caps . We compared the post-meiotic aneuploidy rate using polar body biopsy ( PBBX ) and comparative genomic hybridization ( CGH ) . According to the power calculation , 27 patients were needed for each arm . Results Owing to safety concerns regarding the effects of polar body biopsy on embryo quality and implantation , the study was terminated before reaching the target number of participants . A total of 39 patients were evaluated and r and omized ( 17 CoQ10 , 22 placebo ) , 27 were given the study medication ( 12 CoQ10 , 15 placebo ) , and 24 completed an IVF-ICSI cycle including PBBX and embryo transfer ( 10 CoQ10 , 14 placebo ) . Average age , base line follicle stimulating hormone ( FSH ) , peak estradiol and progesterone serum level , as well as the total number of human menopausal gonadotropin ( hMG ) units–-did not differ between the groups . The rate of aneuploidy was 46.5 % in the CoQ10 group compared to 62.8 % in the control . Clinical pregnancy rate was 33 % for the CoQ10 group and 26.7 % for the control group . Conclusion No significant differences in outcome were detected between the CoQ10 and placebo groups . However , the final study was underpowered to detect a difference in the rate of aneuploidy", "OBJECTIVE To compare the effect of N-acetyl cysteine and metformin on hormonal profile ( insulin and T ) and ovulation rate in women with clomiphene citrate-resistant polycystic ovary syndrome . DESIGN Prospect i ve r and omized controlled study . SETTING Department of obstetrics and gynecology in a university hospital in Egypt . PATIENT(S ) Sixty-one infertile women with clomiphene citrate-resistant polycystic ovary syndrome were assigned r and omly to receive either metformin ( 1,500 mg/d ) or N-acetyl cysteine ( 1.8 g/d ) for 6 weeks . INTERVENTION(S ) Hormonal profile was determined before and after the course of treatment . Folliculometry was performed to assess ovulation . MAIN OUTCOME MEASURE(S ) Ovulation rate and insulin and T changes . RESULT ( S ) In the metformin group , there was a significant decrease in the fasting glucose , fasting insulin , and total T. In the N-acetyl cysteine group , there was no significant difference in the fasting glucose or fasting insulin and there was a significant decrease in total T. There was no significant difference in the fasting glucose-fasting insulin ratio in both groups . In the metformin group , the rate of ovulation was 51.6 % ( 16/31 ) , vs. 6.7 % ( 2/30 ) in the N-acetyl cysteine group , which was statistically significant . CONCLUSION ( S ) Metformin alone is an effective drug in inducing ovulation in clomiphene citrate-resistant polycystic ovary syndrome , whereas N-acetyl cysteine alone is not . Further large studies are required to confirm our results", "OBJECTIVE To compare clomiphene citrate with N-acetyl cysteine vs. clomiphene citrate alone for augmenting ovulation in management of unexplained infertility . DESIGN Prospect i ve r and omized double-blind controlled trial . SETTING Department of obstetrics and gynecology in a university medical faculty in Egypt . PATIENT(S ) Four hundred four patients as a study group ( clomiphene citrate plus N-acetyl cysteine group ) and 400 patients as a control group ( clomiphene citrate-alone group ) . All women had unexplained infertility . INTERVENTION(S ) Patients in the study group were treated with clomiphene citrate ( 50-mg tablets ) twice per day and with N-acetyl cysteine ( 1,200 mg/d orally ) for 5 days starting on day 2 of the cycle . Patients in the control group were treated with clomiphene citrate with sugar powder . MAIN OUTCOME MEASURE(S ) The primary outcomes were number and size of growing follicles , serum E(2 ) , serum P , and endometrial thickness . The secondary outcome was the occurrence of pregnancy . RESULT ( S ) There were no statistically significant differences between the two groups in the number of follicles sized > 18 mm , mean E(2 ) levels , serum P , or endometrial thickness . Pregnancy rate was comparable in both groups ( 22.2 % vs. 27 % ) . Miscarriage rate was comparable in both groups ( 6.7 % in the study group vs. 7.4 % in the control group ) . CONCLUSION ( S ) N-Acetyl cysteine is ineffective in inducing or augmenting ovulation in patients with unexplained infertility and can not be recommended as an adjuvant to clomiphene citrate in such patients", "STUDY OBJECTIVE To evaluate the effects of pentoxifylline administration on patients with different stages of endometriosis on whom laparoscopy was performed . DESIGN Prospect i ve , double-blind , r and omized , placebo-controlled clinical ( Canadian Task Force classification I ) . SETTING University and private hospitals . PATIENTS Eighty-eight women , all with infertility , some with dysmenorrhea , dyspareunia , or pelvic pain , on whom a laparoscopic diagnosis of endometriosis was made . INTERVENTIONS The treatment group received 800 mg pentoxifylline daily for 6 months immediately after surgery . The control group received placebo capsules . All patients were followed-up for 1 year thereafter . MEASUREMENTS AND MAIN RESULTS A comparison of pregnancy rate and recurrence of signs and symptoms in the 2 groups was performed . Forty-three patients were studied in the pentoxifylline group and 45 in the placebo group . The cumulative pregnancy rate was 39.5 % and 35.6 % in the treatment and control groups , respectively . The overall recurrence of signs and symptoms was 14 % in the former group and 15.6 % in the latter . There were no statistically significant differences between the 2 groups in rates of pregnancy and recurrence ( p = .700 and .832 , respectively ) . Nor was there any significant statistical difference between the same stages in the 2 groups regarding immunomodulation . CONCLUSIONS According to the results of this study , and while keeping in mind that appropriate surgery is the main aspect of endometriosis treatment , there is no evidence that immunomodulation with pentoxifylline aids fertility or lessens recurrence of signs and symptoms in women with different stages of endometriosis ( i.e. , minimal , mild , moderate , or severe )", "The current study was conducted to evaluate the effects of zinc supplementation on endocrine outcomes , biomarkers of inflammation , and oxidative stress in patients with polycystic ovary syndrome ( PCOS ) . This study was a r and omized double-blind , placebo-controlled trial . Forty-eight women ( 18–40 years ) with PCOS diagnosed according to Rotterdam criteria were r and omly assigned to receive either 220 mg zinc sulfate ( containing 50 mg zinc ) ( group 1 ; n = 24 ) and /or placebo ( group 2 ; n = 24 ) for 8 weeks . Hormonal profiles , biomarkers of inflammation , and oxidative stress were measured at study baseline and after 8-week intervention . After 8 weeks of intervention , alopecia ( 41.7 vs. 12.5 % , P = 0.02 ) decreased compared with the placebo . Additionally , patients who received zinc supplements had significantly decreased hirsutism ( modified Ferriman-Gallwey scores ) ( −1.71 ± 0.99 vs. −0.29 ± 0.95 , P < 0.001 ) and plasma malondialdehyde ( MDA ) levels ( −0.09 ± 1.31 vs. + 2.34 ± 5.53 μmol/L , P = 0.04 ) compared with the placebo . A trend toward a significant effect of zinc intake on reducing high-sensitivity C-reactive protein ( hs-CRP ) levels ( P = 0.06 ) was also observed . We did observe no significant changes of zinc supplementation on hormonal profiles , inflammatory cytokines , and other biomarkers of oxidative stress . In conclusion , using 50 mg/day elemental zinc for 8 weeks among PCOS women had beneficial effects on alopecia , hirsutism , and plasma MDA levels ; however , it did not affect hormonal profiles , inflammatory cytokines , and other biomarkers of oxidative stress", "This study investigated whether subfertile women undergoing ovulation induction using st and ard treatment regimens with clomiphene citrate/gonadotrophins have higher pregnancy rates when on an adjuvant multiple micronutrient ( MMN ) nutritional supplement compared with folic acid alone . A prospect i ve r and omized controlled trial was conducted in a teaching-hospital fertility clinic on 58 subfertile women , of which 56 women completed the study . Women undergoing ovulation induction were allocated to either receive adjuvant MMN supplementation or folic acid . Clinical pregnancy rates and blood nutrient concentrations were assessed after the third treatment attempt or as soon as the women achieved pregnancy . Using intention-to-treat analysis , it was observed that women on adjuvant MMN supplementation had a significantly higher cumulative clinical pregnancy rate ( 66.7 % ) compared with those on folic acid ( 39.3 % ; P = 0.013 ) . The ongoing pregnancy rate in women on MMN supplementation was 60.0 % versus 25.0 % ( P < 0.02 ) in the folic-acid group . Further , women who were on MMN supplementation had significantly fewer attempts to achieve pregnancy compared with women on folic acid ( P < 0.001 ) . The results of this pilot study suggest that women who take adjuvant MMN supplementation during ovulation induction have a higher chance of pregnancy compared with women on folic acid", "The present study is the first prospect i ve r and omized controlled trial of the effect of pentoxifylline on future fertility in infertile women with asymptomatic minimal or mild endometriosis . After completion of a basic infertility workup and laparoscopy , patients were entered into the study and r and omly allocated to receive either a 12 month course of oral pentoxifylline ( 800 mg/day ) ( n = 30 ) or an oral placebo ( n = 30 ) . Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be non-contributory . Life-table analysis was used to compare pregnancy rates between the two groups over a 12 month period that started immediately after laparoscopy . The 12 month actuarial overall pregnancy rates were 31 and 18.5 % in the pentoxifylline and placebo groups respectively . However , this difference was not statistically significant by the chi(2)-test . Similarly , the Cox regression method showed no differences between the hazard of pregnancy in the two groups studied ( odds ratio , 0.56 ; 95 % confidence interval , 0.18 - 1.67 ) . Therefore , there is no evidence from this study that immunomodulation with pentoxifylline aids fertility in those women with minimal or mild endometriosis . Further studies including more infertile patients with endometriosis are desirable in order to confirm our results", "We investigated the relationship between oxidative stress and poor oocyte quality and whether the antioxidant melatonin improves oocyte quality . Follicular fluid was sample d at oocyte retrieval during in vitro fertilization and embryo transfer ( IVF-ET ) . Intrafollicular concentrations of 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) in women with high rates of degenerate oocytes were significantly higher than those with low rates of degenerate oocytes . As there was a negative correlation between intrafollicular concentrations of 8-OHdG and melatonin , 18 patients undergoing IVF-ET were given melatonin ( 3 mg/day ) , vitamin E ( 600 mg/day ) or both melatonin and vitamin E. Intrafollicular concentrations of 8-OHdG and hexanoyl-lysine adduct were significantly reduced by these antioxidant treatments . One hundred and fifteen patients who failed to become pregnant with a low fertilization rate ( < or = 50 % ) in the previous IVF-ET cycle were divided into two groups during the next IVF-ET procedure ; 56 patients with melatonin treatment ( 3 mg/day ) and 59 patients without melatonin treatment . The fertilization rate was improved by melatonin treatment compared to the previous IVF-ET cycle . However , the fertilization rate was not significantly changed without melatonin treatment . Oocytes recovered from preovulatory follicles in mice were incubated with H2O2 for 12 hr . The percentage of mature oocytes with a first polar body was significantly reduced by addition of H2O2 ( 300 microm ) . The inhibitory effect of H2O2 was significantly blocked by simultaneous addition of melatonin . In conclusion , oxidative stress causes toxic effects on oocyte maturation and melatonin protects oocytes from oxidative stress . Melatonin is likely to improve oocyte quality and fertilization rates", "Limited data are available indicating the effects of chromium administration on endocrine profiles , biomarkers of inflammation , and oxidative stress among women with polycystic ovary syndrome ( PCOS ) . This study was done to assess the effects of chromium administration on endocrine profiles , biomarkers of inflammation , and oxidative stress in women with PCOS . Participants of this r and omized , double-blind , placebo-controlled trial consisted of 60 patients with PCOS who received either 200 μg chromium supplements ( n = 30 ) or placebo daily ( n = 30 ) for 8 weeks . Endocrine profiles , inflammatory factors , and biomarkers of oxidative stress were assessed at study baseline and at the end of intervention . After 8 weeks of intervention , pregnancy rate in chromium group was higher than that in the placebo group : 16.7 % ( 5/30 ) vs. 3.3 % ( 1/30 ) , P = 0.08 . In addition , prevalence of acne ( 20.0 vs. 3.3 % , P = 0.04 ) decreased following the administration of chromium supplements compared with the placebo . Taking chromium led to a significant reduction in hirsutism ( −1.8 ± 2.5 vs. −0.2 ± 0.8 , P = 0.002 ) , serum high-sensitivity C-reactive protein ( hs-CRP ) ( −717.0 ± 1496.1 vs. + 227.1 ± 1669.6 ng/mL , P = 0.02 ) , plasma malondialdehyde ( MDA ) ( −0.1 ± 0.7 vs. + 1.1 ± 1.5 μmol/L , P < 0.001 ) , and a significant increase in plasma total antioxidant capacity ( TAC ) concentrations ( + 250.7 ± 265.2 vs. + 13.0 ± 201.6 mmol/L , P < 0.001 ) . We failed to find any significant effect of chromium administration on endocrine profiles and nitric oxide ( NO ) and glutathione ( GSH ) levels . Overall , taking chromium for 8 weeks among women with PCOS had beneficial effects on acne , hirsutism , hs-CRP , TAC , and MDA levels , but it did not affect endocrine profiles , NO , and GSH . Clinical trial registration number : I RCT 201506105623N44 ( www.i rct .ir", "Polycystic ovarian syndrome ( PCOS ) is one of the pathological factors involved in the failure of in vitro fertilization ( IvF ) . The aim of the present study was to investigate if the combination of myoinositol + folic acid was able to improve the oocyte quality , the ratio between follicles and retrieved oocytes , the fertilization rate , and the embryo quality in PCOS patients undergoing IvF treatments . 29 patients with PCOS underwent IvF protocol s for infertility treatment and were r and omized prospect ively into two groups . Group A ( placebo ) with 15 patients and group B ( 4000 mg myoinositol + 400 μg folic acid per day ) with 14 patients . The patients of group B used for two months myoinositol + folic acid before starting the IvF protocol and data were obtained concerning number of follicles , number of oocytes , quality of oocytes , fertilization rates , and embryo quality in both groups . The ratio follicle/retrieved oocyte was better in the myoinositol group (= group B ) . Out of the 233 oocytes collected in the myoinositol group 136 were fertilized , whereas only 128 out of 300 oocytes in the placebo group were fertilized . More metaphase II and I oocytes were retrieved in relation to the total amount of oocytes in the myoinositol . More embryos of grade I quality were obtained in the myoinositol . The duration of stimulation was 9,7 days ( ±3,3 ) in the myoinositol group and 11,2 ( ±1,8 ) days in the placebo group and the number of used FSH units was lower in the myoinositol group : 1750 FSH units ( mean ) versus 1850 units ( mean ) . Our evidence suggests that myoinositol therapy in women with PCOS results in better fertilization rates and a clear trend to a better embryo quality . As the number of retrieved oocytes was smaller in the myoinositol group , the risk of hyper stimulation syndrome can be reduced in these patients", "BACKGROUND The aim of the current study was to assess the effects of B-group vitamins and folic acid administration on serum levels of homocysteine ( Hcy ) in patients with polycystic ovarian syndrome ( PCOS ) on short-term metformin treatment . METHODS Patients were r and omly assigned to one of three treatment groups . Group 1 patients ( n = 20 ) received metformin ( 850 mg twice daily ) ; group 2 patients ( n = 20 ) received metformin ( 850 mg twice daily ) and B-group vitamins ( vitamin B1 , 250 mg ; vitamin B6 , 250 mg ; vitamin B12 , 1000 microg twice daily ) ; and group 3 patients ( n = 20 ) received metformin ( 850 mg twice daily ) and folic acid ( 174 microg twice daily ) . In all groups , lipid profiles and plasma total Hcy , vitamin B12 , folic acid and glucose levels were recorded at baseline and at 3 months . RESULTS A 26.5 % increase in Hcy levels was seen after 12 weeks of metformin therapy , while 21.17 and 8.33 % decreases in Hcy levels were detected when B-group vitamins or folic acid plus metformin were given respectively . There were no statistically significant differences recorded in insulin sensitivity using homeostasis model assessment in the three groups . CONCLUSION These findings suggest that B-group vitamins and folic acid administration counteract the Hcy-increasing effect seen with metformin therapy", "Background : There is some evidence regarding the effect of poly unsaturated fatty acid intake on and rogen levels and gonadal function in polycystic ovary syndrome ( PCOS ) . Objective : This study was conducted to determine the effect of omega-3 supplementation on sex hormone-binding protein ( SHBG ) , testosterone , free and rogen index ( FAI ) and menstrual status in women with PCOS . Material s and Methods : This double-blind r and omized clinical trial was conducted on 78 overweight/obese women with PCOS . Participants were r and omized to receive omega-3 ( 3gr/day ) or placebo for 8 weeks . Data about weight , height and nutrient intake as well as blood sample s were collected before and after intervention . Serum concentrations of testosterone ( nmol/L ) and SHBG ( nmol/L ) were measured . FAI was also calculated as the ratio of testosterone to SHBG . Results : Seventy eight patients ( age : 26.92±5.46 yrs , Body Mass Index : 31.69±4.84 Kg/m2 ) completed the study . There was no significant difference in mean age , weight , height , Body Mass Index and intake of energy , and macronutrients between 2 study groups before and after treatment . All the participants had irregular periods . After the trial the percentage of regular menstruation in the omega-3 group was more than the placebo group ( 47.2 % vs. 22.9 % , p=0.049 ) . Furthermore , testosterone concentration was significantly lower in the omega-3 group compared with placebo , after supplementation ( p=0.04 ) . SHBG and FAI did not change in either group . Conclusion : Omega-3 supplementation could reduce serum concentrations of testosterone and regulate menstrual cycle without significant effect on SHBG and FAI . Future studies with longer period of supplementation are warranted . This article extracted from M.Sc . thesis . ( Niloufar Vaziri ) Registretion ID in I RCT : I RCT", "The objective of the present study was prospect ively and r and omly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women . A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocol s : ( i ) flare-up gonadotrophin-releasing hormone analogue ( GnRHa ) plus elevated pure follicle stimulating hormone ( pFSH ) ( n = 17 ) ; and ( ii ) flare-up GnRHa plus elevated pFSH plus oral L-arginine ( n = 17 ) . During the ovarian stimulation regimen , the patients were su bmi tted to hormonal ( oestradiol and growth hormone ) , ultrasonographic ( follicular number and diameter , endometrial thickness ) and Doppler ( uterine and perifollicular arteries ) evaluations . Furthermore , the plasma and follicular fluid concentrations of arginine , citrulline , nitrite/nitrate ( NO2-/NO3- ) , and insulin-like growth factor-1 ( IGF-1 ) were assayed . All 34 patients completed the study . In the L-arginine treated group a lower cancellation rate , an increased number of oocytes collected , and embryos transferred were observed . In the same group , increased plasma and follicular fluid concentrations of arginine , citrulline , NO2-/NO3- , and IGF-1 was observed . Significant Doppler flow improvement was obtained in the L-arginine supplemented group . Three pregnancies were registered in these patients . No pregnancies were observed in the other group . It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response , endometrial receptivity and pregnancy rate", "OBJECTIVE To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility . DESIGN A prospect i ve cohort study . SETTING The Nurses ' Health Study II . PATIENT(S ) Eighteen thous and five hundred fifty-five married , premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999 . INTERVENTION(S ) None , observational study . MAIN OUTCOME MEASURE(S ) Incident reports of infertility caused by anovulation . RESULT ( S ) During 8 years of follow-up , 438 women reported infertility caused by ovulatory disorder . There was an inverse association between frequency of multivitamin use and ovulatory infertility . The multivariate-adjusted relative risk ( 95 % confidence interval ) of ovulatory infertility was 0.88 ( 0.60 , 1.28 ) for women consuming two tablets per week or less , 0.69 ( 0.51 , 0.95 ) for women consuming three to five tablets per week , and 0.59 ( 0.46 , 0.75 ) for women consuming six or more tablets per week , when compared with women who did not use these supplements ( P , trend < .001 ) . Folic acid appeared to explain part of the association between multivitamin supplement use and risk of ovulatory infertility . CONCLUSION ( S ) Regular use of multivitamin supplements may decrease the risk of ovulatory infertility", "The aim of the study was to evaluate the efficacy of melatonin administration on oocyte quality in women underwent in vitro fertilization ( IVF ) cycles . Eighty-five women undergoing IVF cycles were r and omized in two groups during IVF – embryo transfer ( ET ) procedure , 40 women with melatonin treatment ( A ) and 45 women without melatonin treatment ( B ) . Primary endpoint was the number of morphologically mature oocytes retrieved ( MII oocytes ) . Secondary endpoints were fertilization rate per number of mature oocytes , embryo quality and pregnancy rate . There were no differences between two groups according to age , and peak estradiol levels . The mean number of oocytes ( 15.33 vs. 14.27 ) and the mean number of mature oocytes did not differ between the two groups ( 12.63 vs. 10.94 ) , whereas the percentage of mature oocytes ( M2/oocytes retrieved ) was significantly different in melatonin-treated group ( p < 0.05 ) . Fertilization rate ( 72.75 vs. 71.16 ) did not differ between the two groups . The mean number of class 1 embryos result ed higher in the group A ( 3.28 vs. 2.53 ) ( p < 0.05 ) . Clinical pregnancy rate was in tendency higher in the group treated with melatonin , although the differences did not reach statistical significance . Melatonin is likely to improve oocyte and embryo quality in women undergoing IVF or intracytoplasmic sperm insemination ( ICSI )", "AIM OF THE STUDY To assess the ascorbic acid ( AA ) in the follicular fluid in women treated by in vitro fertilization and embryonic transfer levels ( IVF/ET ) and to analyse the influence of vitamin C supplementation on the results of infertility treatment . TYPE OF THE STUDY Prospect i ve study in women treated by IVF/ET . METHODS The influence of vitamin C supplementation on the outcome of infertility treatment in the assisted reproduction programme in 76 women ( 38 of them smokers , 38 non-smokers ) was studied . Half the women ( 19 smokers and 19 non-smokers ) were administered vitamin C in daily doses of 500 mg in so-called pellets allowing for gradual release over 8 to 12 hours . The control group consisted of the same number of smokers and non-smokers . In all the women , ascorbic acid levels were determined in two urine sample s ( prior to supplementation and at follicle retrieval ) and in follicular fluid by means of a colorimetric method . Ovarian response to hormonal stimulation with gonadotropins ( hMG , FSH ) at a dosage of 150 - 225 IU per day combined with GnRH analogues in the short ( buserelin ) or long ( triptorelin ) protocol s , and 5,000 - 10,000 IU of human chorionic gonadotropin was evaluated based on the number of follicles created and number of retrieved oocytes . Fertilisation was assessed , based on the number of successfully fertilised oocytes ( fertilisation rate ) and based on the number of cultivated embryos . The success of the infertility treatment was evaluated based on the number of pregnancies . RESULTS Ascorbic acid levels in follicles were significantly higher ( p < 0.001 ) in women with vitamin C supplementation than in the control group ( 8.98 + /- 5.09 vs. 5.04 + /- 2.85 mg/l ) . The administration of vitamin C during the period of hormonal stimulation showed a statistically insignificant impact in terms of the higher number of pregnancies ( 34.2 % vs. 23.7 % ) . Vitamin supplementation had a greater impact on the number of pregnancies in the non-smokers ' group ( 57.9 % vs. 31.6 % ) . The pregnancy rate was significantly higher ( p < 0.01 ) in non-smoking women than in smokers--44.7 % vs. 13.2 % , which appears to be a reason for asking women to cease smoking prior to infertility treatment", "AIM The aim of this study was to evaluate the effects of diet alone , and in association with metformin in monotherapy or in cotreatment with myoinositol ( MYO ) on menstrual irregularities , hirsutism , body weight and composition in overweight/obese women with polycystic ovary syndrome ( PCOS ) . METHODS Twenty-seven PCOS overweight/obese patients were r and omly treated : nine with only diet ( D ) ; nine with diet and metformin 1000 mg/day continuously ( D+M ) ; nine with diet , metformin 500 mg/day and MYO 4 g/day plus 400 µg folic acid daily , continuously ( D+M+I ) . Menstrual cycle , Ferriman-Gallwey score , body mass index ( BMI ) , waist hip rate ( WHR ) , body composition by BIA 101 of AKERN SRL , were measured on basal condition and at 3 months . RESULTS Regularity of menstrual cycle was restored in a significantly number of patients of group D+M+I ( P<0.05 ) ; Ferriman score was significantly improved by weight loss ( P<0.05 ) . Body weight , BMI , waist and hip circumferences decreased significantly in all groups without WHR modification ; body weight loss significantly depended on adding metformin to diet . Fat mass ( FM ) kg and % was significantly reduced in groups D and D+M+I ; fat free mass ( FFM ) kg was slightly reduced by diet ( P<0.05 ) and correlated with Ferriman score . CONCLUSION Body weight loss in obese PCOS patients improves symptoms and body composition ; weight loss was dependent on adding metformin to diet ; MYO was more effective in restoring regularity of menstrual cycle . Further investigation occurs to confirm metformin and MYO rule on body composition improvement , specially regarding FFM that is likewise FM correlated to cardiovascular risk", "Polycystic ovary syndrome ( PCOS ) is associated with low- quality oocytes . The aim of the present study was to investigate the effects of metformin ( MET ) , N-acetylcysteine ( NAC ) and their combination on follicular fluid parameters , oocytes and embryo quality in PCOS patients . A prospect i ve r and omised placebo-controlled pilot study on 60 Iranian women with PCOS ( aged 25 - 35 years ) undergoing intracytoplasmic sperm injection ( ICSI ) was design ed . Women were divided into four groups ( n=15 in each ) : ( 1 ) an MET , administered 1500 mg day(-1 ) MET ; ( 2 ) an NAC group , administered 1800 mg day(-1 ) NAC ; ( 3 ) an NAC + MET group ; and ( 4 ) a placebo group . Drugs were administered from the 3rd day of previous cycle until the day of oocyte aspiration ( 6 weeks treatment in total ) . Data were analysed by one-way ANOVA , with significance set at P<0.05 . The number of immature and abnormal oocytes decreased significantly in the NAC compared with placebo group , with a concomitant increase in the number of good- quality embryos in the NAC group ( P<0.05 ) . Malondialdehyde levels decreased significantly in the NAC and NAC + MET groups compared with the placebo-treated group ( P<0.02 ) . In addition , there were significant decreases in leptin levels in the NAC , MET and NAC + MET groups compared with the placebo group ( P<0.001 ) . Insulin and LH levels were significantly lower in the MET and NAC groups compared with the placebo-treated group ( P<0.02 ) . We concluded that NAC improves oocyte and embryo quality and could be administered as an alternative to MET", "We investigated effects of multivitamin/mineral supplementation on element levels in serum and follicular fluid of women undergoing IVF . We used three groups in this study . The first group was used as an age-matched and nonpregnant control ( n = 13 ) . Group 2 ( n = 30 ) constituted the IVF group and women in the third group who were undergoing IVF also received a multivitamin/mineral tablet daily for 45 days . Follicular fluid and serum selenium and zinc levels and follicular fluid copper levels were lower in IVF patients than in controls although follicular fluid aluminum and iron levels were higher in IVF patients than in controls . However , follicular fluid and serum aluminum , copper , zinc and selenium levels , and serum magnesium levels were higher in the multivitamin/mineral group than in the IVF group although follicular fluid iron levels were lower in the multivitamin/mineral group than in the IVF group . In conclusion , we observed that copper , zinc , and selenium in serum and follicular fluid decreased in women undergoing IVF . Multivitamin/mineral supplementation in serum and follicular fluid of women undergoing IVF normalized the trace element levels", "Selenium supplementation could be effective on reproductive outcomes , biomarkers of inflammation , and oxidative stress among women with polycystic ovary syndrome ( PCOS ) . The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes , biomarkers of inflammation , and oxidative stress in PCOS patients . The present r and omized double-blind , placebo-controlled trial was conducted on 64 women aged 18 - 40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences , Ardabil , Iran . The participants were r and omly assigned to 2 groups receiving either 200 μg selenium daily ( n=32 ) or placebo ( n=32 ) for 8 weeks . Hormonal profiles , biomarkers of inflammation , and oxidative stress were measured and compared both before and after the treatment . After 8 weeks of intervention , pregnancy rate in the selenium group was higher than in the placebo group : 18.8 ( 6/32 ) vs. 3.1 % ( 1/32 ) , p=0.04 . In addition , alopecia ( 40.6 vs. 9.4 % , p=0.004 ) and acne ( 46.9 vs. 12.5 % , p=0.003 ) decreased following the consumption of selenium supplements compared with placebo . Additionally , patients who received selenium supplements had significantly decreased serum dehydroepi and rosterone ( DHEA ) levels ( p=0.02 ) , hirsutism ( modified Ferriman-Gallwey scores ) ( p<0.001 ) , serum high sensitivity C-reactive protein ( hs-CRP ) ( p=0.02 ) , and plasma malondialdehyde ( MDA ) levels ( p=0.01 ) compared with placebo . We did not observe any significant effects of taking selenium supplements on other hormonal profiles , nitric oxide ( NO ) , and other biomarkers of oxidative stress . Taken together , selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes , DHEA , hs-CRP , and MDA levels . Supporting Information for this article is available online at http://www.thieme-connect.de/products", "BACKGROUND There is a need to underst and what affects the success of in-vitro fertilisation ( IVF ) and the rate of result ing twin births so that pregnancy rates can be improved and multiple gestations avoided . Our aim was to assess the role of B vitamins and genetics . METHODS We did a prospect i ve cohort study of 602 women undergoing fertility treatment . We assessed intake of folate and vitamin B12 with a question naire and measured their plasma and red-blood-cell concentrations by radioimmunoassay . We measured five B-vitamin-related gene variants in women who received treatment and in 932 women who conceived naturally . FINDINGS The likelihood of a twin birth after IVF rose with increased concentrations of plasma folate ( 1.52 , 1.01 - 2.28 ; p=0.032 ) and red-cell folate ( 1.28 , 1.00 - 1.65 ; p=0.039 ) . There was no association between folate and vitamin B12 levels and likelihood of a successful pregnancy . Women homozygous for the 1298 CC variant of methylenetetrahydro-folate reductase ( MTHFR ) , rather than the AA variant , were less likely to produce a livebirth after IVF ( 0.24 , 0.08 - 0.71 ; p=0.003 ) or to have had a previous pregnancy ( 0.42 , 0.21 - 0.81 ; p=0.008 ) . INTERPRETATION Our findings suggest that MTHFR genotype is linked to a woman 's potential to produce healthy embryos ( possibly through interaction with genes related to DNA methylation ) . In women likely to have a successful IVF pregnancy , high folate status increases the likelihood of twin birth after multiple embryo transfer . Proposals to fortify the UK diet with folic acid could lead to an increase in the number of twins born after IVF", "OBJECTIVE To evaluate the effectiveness of L-carnitine on improving the ovulation and pregnancy rates as well as adverse metabolic indices in clomiphene-resistant PCOS . DESIGN Single center , double blinded , superiority , r and omized controlled clinical trial . SETTING Women 's Health Hospital , Assiut University . METHODS One hundred and seventy women diagnosed with PCOS were found to be clomiphene resistant . The women were r and omly allocated into two groups : Group A ( n=85 ) , where patients received 250 mg clomiphene citrate from day three until day seven of the cycle plus L-carnitine ( LC ) 3 g daily ; and Group B ( n=85 ) received 250 mg clomiphene citrate with placebo . OUTCOME Primary outcome is cumulative clinical pregnancy rate . Secondary outcomes are changes in serum glucose level and lipid profile . RESULTS The combination of L-carnitine and CC significantly improve both the ovulation and the cumulative pregnancy rates in clomiphene resistant PCOS ( 55 ( 64.4 % ) vs. 15 ( 17.4 % ) and 44 ( 51.5 ) % vs. 5 ( 5.8 ) % ) . The number of stimulated follicles reaching ≥17 mm diameter was significantly more in Group A to Group B ( 2.2 ± 0.77 vs. 0.16 ± 0.79 ; p<0.0001 ) . Group A needed significantly fewer days for adequate follicular maturation , had a thicker endometrium and higher oestradiol concentration at the time of human chorionic gonadotrophin injection ( 10.1 ± 0.1 mm vs. 6.8 ± 0.4 mm ; p<0.0001 ) . The same group had a higher mean luteal-phase serum progesterone compared with the control group ( 13.55 ± 0.99 vs. 10.6 ± 0.98 ng ; p<0.0001 ) . A significant difference was found regarding the clinical pregnancy rates ( 42 ( 49.4 % ) vs. ( 1 ) 1.1 % respectively p value < 0.0001 ) . CONCLUSION Adding L-carnitine when treating clomiphene-resistant PCOS patients not only improved the quality of ovulation and the pregnancy rate with an acceptable patient tolerability , but also enhanced the patient lipid profile and body mass index", "Some actions of insulin are mediated by inositolphosphoglycan ( IPG ) mediators . Deficient release of a putative D-chiro-inositol-containing ( DCI ) IPG mediator may contribute to insulin resistance in women with polycystic ovary syndrome ( PCOS ) . Previously , we demonstrated that oral DCI supplementation improved ovulation and metabolic parameters in women with PCOS . However , whether oral DCI mediates an increase in the release of the DCI-IPG mediator and an improvement in insulin sensitivity in women with PCOS is unknown . We conducted a r and omized controlled trial of DCI supplementation vs placebo in 11 women with PCOS who were assessed at 2 time points 6 weeks apart . Plasma DCI , DCI-IPG release during oral glucose tolerance test ( AUC(DCI-IPG ) ) , and insulin sensitivity ( S(i ) ) by frequently sample d intravenous glucose tolerance test were assessed at baseline and end of study . The study was terminated early because of a sudden unavailability of the study drug . However , in all subjects without regard to treatment assignment , there was a positive correlation between the change in AUC(DCI-IPG)/AUC(insulin ) ratio and the change in S(i ) during the 6-week period ( r = 0.69 , P = .02 ) , which remained significant after adjustment for body mass index ( P = .022 ) and after further adjustment for body mass index and treatment allocation ( P = .0261 ) . This suggests that , in women with PCOS , increased glucose-stimulated DCI-IPG release is significantly correlated with improved insulin sensitivity . The significant relationship between DCI-IPG release and insulin sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic interventions in PCOS", "Background . Polycystic ovary syndrome ( PCOS ) is often characterized by chronic oligo- or anovulation ( usually manifested as oligo- or amenorrhea ) , and hyper and rogenism . In addition , 30–40 % of PCOS women have impaired glucose tolerance , and a defect in the insulin signaling pathway ( inositol-containing phosphoglycan mediators ) seems to be implicated in the pathogenesis of insulin resistance . PCOS patients are subfertile as a consequence of such ovulatory disorders and often need drugs , such as clomiphene citrate or follicle-stimulating hormone , for ovulation induction , which increases the risk of multiple pregnancy and ovarian hyperstimulation syndrome . We hypothesized that the administration of an isoform of inositol ( myo-inositol ) , belonging to the vitamin B complex , would improve the insulin-receptor activity , restoring normal ovulatory function . Material s and methods . Twenty-five PCOS women of childbearing age with oligo- or amenorrhea were enrolled in the study . Ovulatory disorder due to PCOS was apparently the only cause of infertility ; no tubal defect or deficiency of male semen parameters was found . Myo-inositol combined with folic acid ( Inofolic ® ) 2 g twice a day was administered continuously . During an observation period of 6 months , ovulatory activity was monitored with ultrasound scan and hormonal profile , and the numbers of spontaneous menstrual cycles and eventually pregnancies were assessed . Results . Twenty-two out of the 25 ( 88 % ) patients restored at least one spontaneous menstrual cycle during treatment , of whom 18 ( 72 % ) maintained normal ovulatory activity during the follow-up period . A total of 10 singleton pregnancies ( 40 % of patients ) were obtained . Nine clinical pregnancies were assessed with fetal heart beat at ultrasound scan . Two pregnancies evolved in spontaneous abortion . Conclusion . Myo-inositol is a simple and safe treatment that is capable of restoring spontaneous ovarian activity and consequently fertility in most patients with PCOS . This therapy did not cause multiple pregnancy", "BACKGROUND Folate is a methyl donor . Availability of folate affects DNA methylation profiles and thereby gene expression profiles . We investigated the effects of low-dose folic acid use ( 0.4 mg/d ) on the ovarian response to mild and conventional ovarian stimulation in women . METHODS In a r and omized trial among subfertile women , 24 and 26 subjects received conventional and mild ovarian stimulation , respectively . Blood sample s were taken during the early follicular phase of the cycle prior to treatment and on the day of human chorionic gonadotropin administration for determination of serum total homocysteine , anti-Müllerian hormone ( AMH ) , estradiol , and folate . Folic acid use was vali date d by question naire and serum folate levels . Preovulatory follicles were visualized , counted , and diameters recorded using transvaginal ultrasound . The relation between folic acid use and ovarian response was assessed using linear regression analysis . RESULTS Folic acid use modified the ovarian response to ovarian stimulation treatment . The estradiol response was higher in nonfolic acid users receiving conventional treatment [ β(interaction ) = 0.52 ( 0.07 - 0.97 ) ; P = 0.03 ] , and this effect was independent of serum AMH levels and the preovulatory follicle count . In the conventional treatment , the mean follicle number was also greater in nonusers compared with the users group ( 14.1 vs. 8.9 , P = 0.03 ) . CONCLUSION Low-dose folic acid use attenuates follicular and endocrine responses to conventional stimulation , independent of AMH and follicle count . The nature of this observation suggests that the effect of folic acid is most prominent during early follicle development , affecting immature follicles . Deleterious effects of folate deficiency , like DNA hypomethylation and oxidative stress , can help to explain our observations", "OBJECTIVE To determine the effects of myo-inositol on oocyte quality in polycystic ovary syndrome ( PCOS ) patients undergoing intracytoplasmic sperm injection ( ICSI ) cycles . DESIGN A prospect i ve , controlled , r and omized trial . SETTING Assisted reproduction centers . PATIENT(S ) Sixty infertile PCO patients undergoing ovulation induction for ICSI . INTERVENTION(S ) All participants underwent st and ard long protocol . Starting on the day of GnRH administration , 30 participants received myo-inositol combined with folic acid ( Inofolic ) 2 g twice a day and 30 control women received folic acid alone , administrated continuously . MAIN OUTCOME MEASURE(S ) Primary end points were number of morphologically mature oocytes retrieved , embryo quality , and pregnancy and implantation rates . Secondary end points were total number of days of FSH stimulation , total dose of gonadotropin administered , E(2 ) level on the day of hCG administration , fertilization rate per number of retrieved oocytes , embryo cleavage rate , live birth and miscarriage rates , cancellation rate , and incidence of moderate or severe ovarian hyperstimulation syndrome . RESULT ( S ) Total r-FSH units ( 1,958 + /- 695 vs. 2,383 + /- 578 ) and number of days of stimulation ( 11.4 + /- 0.9 vs. 12.4 + /- 1.4 ) were significantly reduced in the myo-inositol group . Furthermore , peak E(2 ) levels ( 2,232 + /- 510 vs. 2,713 + /- 595 pg/mL ) at hCG administration were significantly lower in patients receiving myo-inositol . The mean number of oocytes retrieved did not differ in the two groups , whereas in the group cotreated with myo-inositol the mean number of germinal vesicles and degenerated oocytes was significantly reduced ( 1.0 + /- 0.9 vs. 1.6 + /- 1.0 ) , with a trend for increased percentage of oocytes in metaphase II ( 0.82 + /- 0.11 % vs. 0.75 + /- 0.15 % ) . CONCLUSION ( S ) These data show that in patients with PCOS , treatment with myo-inositol and folic acid , but not folic acid alone , reduces germinal vesicles and degenerated oocytes at ovum pick-up without compromising total number of retrieved oocytes . This approach , reducing E(2 ) levels at hGC administration , could be adopted to decrease the risk of hyperstimulation in such patients", "OBJECTIVE The aim of this study was to evaluate the effects of calcium-vitamin D and metformin on the menstrual cycle and ovulation in patients with polycystic ovary syndrome ( PCOS ) . MATERIAL S AND METHODS In this pilot study , 60 infertile PCOS patients were enrolled in a r and omized clinical trial and divided into three equal groups . Group 1 received 1,000 mg of calcium and 400 IU of vitamin D per day , orally . Group 2 received the same as Group 1 , plus 1,500 mg/day of metformin . Group 3 received 1,500 mg/day of metformin . The patients were treated for 3 months and followed up for a further 3 months . Regularity of menses , number of large follicles ( > or = 14 mm ) and pregnancy rates were compared among the three groups . RESULTS Generalized estimating equation tests showed that the number of dominant follicles ( > or = 14 mm ) during the 2 - 3 months of follow-up was higher in the calcium-vitamin D plus metformin group than in either of the other two groups ( p = 0.03 ) . CONCLUSION The effects of metformin and calcium-vitamin D in regulating the menstrual cycle suggest that they could also be effective for the treatment of anovulation and oligomenorrhea , with possible consequences for pregnancy rates in PCOS patients", "Some actions of insulin are mediated by putative inositolphosphoglycan mediators , and a deficiency in D-chiro-inositol-containing inositolphosphoglycan ( DCI-IPG ) may contribute to insulin resistance in women with polycystic ovary syndrome ( PCOS ) . Furthermore , similar effects of DCI and metformin , an insulin-sensitizing drug , have been demonstrated in PCOS women . To determine whether metformin improves insulin actions by increasing biologically active DCI-IPG in women with PCOS , we analyzed DCI-IPG during an oral glucose tolerance test in 19 obese women with PCOS before and after 4 - 8 wk of metformin or placebo . After treatment , the mean ( + /-SE ) area under the curve ( AUC ) during the oral glucose tolerance test of insulin ( AUC(insulin ) ) decreased significantly more in the metformin group , compared with the placebo group [ -3574 + /- 962 vs. + 1367 + /- 1021 micro IU/min.ml ( -26 + /- 7 vs. + 10 + /- 7 nmol/min.liter ) , P = 0.003 ] , but the AUC of DCI-IPG ( AUC(DCI-IPG ) ) decreased similarly in both groups ( -1452 + /- 968 vs. -2207 + /- 1021%/min , P = 0.60 ) . However , the ratio of AUC(DCI-IPG)/AUC(insulin ) increased by 160 % after metformin and decreased by 29 % after placebo ( P = 0.002 between groups ) . Moreover , metformin seemed to improve the positive correlation between AUC(DCI-IPG ) and AUC(insulin ) but not placebo ( r = 0.32 , P = 0.68 at baseline ; r = 0.52 , P = 0.12 after metformin ; and r = -0.39 , P = 0.30 after placebo ) . We conclude that in obese women with PCOS , metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators , as evidence d by increased bioactive DCI-IPG released per unit of insulin", "OBJECTIVE The aim of the study was to evaluate the efficacy of a treatment with myo-inositol plus folic acid plus melatonin compared with myo-inositol plus folic acid alone on oocyte quality in women underwent in vitro fertilization ( IVF ) cycles . DESIGN A prospect i ve , clinical trial . MATERIAL S AND METHODS Starting on the day of GnRH administration , 65 women undergoing IVF cycles were r and omized in two groups to receive myo-inositol plus folic acid plus melatonin ( 32 women , group A ) , and myo-inositol plus folic acid ( 33 women , group B ) , administered continuously . Primary endpoints were number of morphologically mature oocytes retrieved ( MII oocytes ) , embryo quality , and pregnancy rate . Secondary endpoints were the total number of oocytes retrieved ( immature and mature oocytes ) , fertilization rate per number of retrieved oocytes and embryo cleavage rate . RESULTS The mean number of oocytes retrieved did not differ between the two groups ( 7.88 + /- 1.76 vs 7.67 + /- 1.88 ; P=0.65 ) . Whereas the group cotreated with melatonin reported a significantly greater mean number of mature oocytes ( 6.56 + /- 1.64 vs 5.76 + /- 1.56 ; P=0.047 ) and a lower mean number of immature oocytes ( 1.31 + /- 0.74 vs. 1.91 + /- 0.68 ; P=0.001 ) . The mean number of embyos of top- quality ( class 1 and 2 ) result ed higher in the group A ( 1.69 + /- 0.64 vs 1.24 + /- 0.75 ; P=0.01 ) . Fertilization rate did not differ between the two groups . A total of 22 pregnancies were obtained ( 13 in group A and 9 in group B ; P=0.26 ) . Clinical pregnancy rate and implantation rate were in tendency higher in the group cotreated with melatonin , although the differences did not reach statistical significance . Biochemical pregnancy rate and abortion rate were similar in both groups . CONCLUSION melatonin ameliorates the activity of myo-inositol and folic acid by improving oocyte quality and pregnancy outcome in women with low oocyte quality history", "Abstract Polycystic ovarian syndrome ( PCOS ) induces anovulation in women of reproductive age , and is one of the pathological factors involved in the failure of in vitro fertilization ( IVF ) . Indeed , PCOS women are characterized by poor quality oocytes . Therefore , a treatment for enhancing oocyte quality becomes crucial for these patients . Myo-Inositol and melatonin proved to be efficient predictors for positive IVF outcomes , correlating with high oocyte quality . We tested the synergistic effect of myo-inositol and melatonin in IVF protocol s with PCOS patients in a r and omized , controlled , double-blind trial . Five-hundred twenty-six PCOS women were divided into three groups : Controls ( only folic acid : 400 mcg ) , Group A ( Inofolic ® plus , a daily dose of myo-inositol : 4000 mg , folic acid : 400 mcg , and melatonin : 3 mg ) , and Group B ( Inofolic ® , a daily dose of myo-inositol : 4000 mg , and folic acid : 400 mcg ) . The main outcome measures were oocyte and embryo quality , clinical pregnancy and implantation rates . The treatment lasted from the first day of the cycle until 14 days after embryo transfer . Myo-inositol and melatonin have shown to enhance , synergistically , oocyte and embryo quality . In consideration of the beneficial effect observed in our trial and on the bases of previous studies , we decided to integrate routinely MI and M supplementation in the IVF protocol s. The same treatment should be taken carefully in consideration in all procedures of this kind", "OBJECTIVE To determine the impact of nutritional supplementation on optimization of reproductive health in women . STUDY DESIGN A double-blind , placebo-controlled pilot study was initiated to determine the effects of FertilityBlend ( Daily Wellness Co. , Sunnyvale , California ) , a proprietary nutritional supplement containing chasteberry and green tea extracts , L-arginine , vitamins ( including folate ) and minerals . Changes in progesterone level , basal body temperature , menstrual cycle , pregnancy rate and side effects were monitored . RESULTS Thirty women aged 24 - 46 years who had tried unsuccessfully to conceive for 6 - 36 months completed the study . After 3 months , the supplement group ( n = 15 ) demonstrated a trend toward an increase in mean midluteal phase progesterone level ( from 8.2 to 12.8 ng/mL , P = .08 ) and a significant increase in the average number of days in the cycle with basal temperatures > 37 degrees C during the luteal phase ( 6.8 - 9.7 days , P = .04 ) . The placebo group ( n = 15 ) did not show any notable changes after treatment in any of the parameters studied . After 5 months , 5 of the 15 women in the supplement group were pregnant ( 33 % ) , and none of the 15 women in the placebo group were ( P < .01 ) . No significant side effects were noted . CONCLUSION Nutritional supplementation may provide an attractive alternative or complement to conventional fertility therapy", "To investigate the effects of silymarin on follicular development , we enrolled 40 healthy women undergoingin vitro fertilization ( IVF ) due to male factor infertility in this trial . They underwent ovulation induction and on a r and om and blind basis , patients were assigned to receive silymarin ( 70 mg x 3/day ) or placebo from the beginning of the induction cycle . The number and quality of oocytes retrieved were evaluated and apoptosis of > or = granolusa cells was studied . There was no significant difference between the groups for mean number of follicles 18 mm ( P = 0.131 ) , mean number of oocytes retrieved ( P = 0.209 ) or endometrial thickness ( P = 0.673 ) . However , the proportion of total apoptosis in the study group was significantly lower than in the placebo group ( P = 0.032 ) . These data suggest that administration of silymarin in IVF patients concomitantly with gonadotropin results in reduction of granolusa cell apoptosis but does not have any effect in promotion of follicular development , oocyte retrieval or endometrial thickness", "CONTEXT Experimental evidence supports a relevance of vitamin D ( VitD ) for reproduction ; however , data in humans are sparse and inconsistent . OBJECTIVE To assess the relationship of VitD status with ovulation induction ( OI ) outcomes in women with polycystic ovary syndrome ( PCOS ) . DESIGN A retrospective cohort . SETTING Secondary analysis of r and omized controlled trial data . PARTICIPANTS Participants in the Pregnancy in PCOS I ( PPCOS I ) r and omized controlled trial ( n = 540 ) met the National Institutes of Health diagnostic criteria for PCOS . INTERVENTIONS Serum 25OHD levels were measured in stored sera . MAIN OUTCOME MEASURES Primary , live birth ( LB ) ; secondary , ovulation and pregnancy loss after OI . RESULTS Likelihood for LB was reduced by 44 % for women if the 25OHD level was < 30 ng/mL ( < 75 nmol/L ; odds ratio [ OR ] , 0.58 [ 0.35 - 0.92 ] ) . Progressive improvement in the odds for LB was noted at thresholds of ≥38 ng/mL ( ≥95 nmol/L ; OR , 1.42 [ 1.08 - 1.8 ] ) , ≥40 ng/mL ( ≥100 nmol/L ; OR , 1.51 [ 1.05 - 2.17 ] ) , and ≥45 ng/mL ( ≥112.5 nmol/L ; OR , 4.46 [ 1.27 - 15.72 ] ) . On adjusted analyses , VitD status was an independent predictor of LB and ovulation after OI . CONCLUSIONS In women with PCOS , serum 25OHD was an independent predictor of measures of reproductive success after OI . Our data identify reproductive thresholds for serum 25OHD that are higher than recommended for the nonpregnant population", "Introduction High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation ( IVF ) . Recent studies have reported that melatonin , a neurohormone secreted from the pineal gl and in response to darkness , has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos . Early studies of oral melatonin ( 3–4 mg/day ) in IVF have suggested favourable outcomes . However , most trials were poorly design ed and none have addressed the optimum dose of melatonin . We present a proposal for a pilot double-blind r and omised placebo-controlled dose – response trial aim ed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology . Methods and analyses We will recruit 160 infertile women into one of four groups : placebo ( n=40 ) ; melatonin 2 mg twice per day ( n=40 ) ; melatonin 4 mg twice per day ( n=40 ) and melatonin 8 mg twice per day ( n=40 ) . The primary outcome will be clinical pregnancy rate . Secondary clinical outcomes include oocyte number/ quality , embryo number/ quality and fertilisation rate . We will also measure serum melatonin and the oxidative stress marker , 8-hydroxy-2′-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up . We will investigate follicular blood flow with Doppler ultrasound , patient sleepiness scores and pregnancy complications , comparing outcomes between groups . This protocol has been design ed in accordance with the SPIRIT 2013 Guidelines . Ethics and dissemination Ethical approval has been obtained from Monash Health HREC ( Ref : 13402B ) , Monash University HREC ( Ref : CF14/523 - 2014000181 ) and Monash Surgical Private Hospital HREC ( Ref : 14107 ) . Data analysis , interpretation and conclusions will be presented at national and international conferences and published in peer- review ed journals . Trial registration number ACTRN12613001317785", "This r and omized controlled trial tested the hypothesis that addition of N-acetyl cysteine ( NAC ) can increase the probability of pregnancy in intracytoplasmic sperm injection ( ICSI ) cycles using the long agonist protocol . Women undergoing ICSI cycles due to male factor were r and omly assigned to receive either long protocol ( group A , 38 women ) or long protocol plus NAC ( group B , 38 women ) . Clinical pregnancy was the primary outcome . Granulosa cell apoptosis , fertilization rate , number of grade -one embryos and ongoing pregnancy were the secondary outcomes . Clinical pregnancy rate was insignificantly higher in NAC group ( 52.6 % ) than control ( 47.4 % ) . Early and late apoptosis were also insignificantly lower in group B than in group A. Irrespective of the used protocol , there was significant negative correlation between both early and late apoptosis and fertilization rate ( both P<0.001 ) and the number of good- quality embryos ( P=0.007 and P<0.001 , respectively ) . Pregnant patients had significantly lower early and late apoptosis than those who did n't achieve pregnancy ( P<0.001 ) . In conclusion , NAC supplementation did not significantly increase the probability of pregnancy in ICSI cycles using long agonist protocol . It appears that granulosa cell apoptosis may be an important prognosticator for ICSI cycle outcome", "Abstract Objective : Good oocyte quality and maturity are important prerequisites for high fertilization and implantation rates in IVF/ICSI treatment cycles . Reactive oxygen species ( ROS ) are produced within ovarian follicles , especially during the ovulation process , and increased ROS activity may be a cause of impaired oocyte maturation and higher rate of failure of IVF/ICSI cycles . Study design : RCT evaluating the effect of antioxidant supplementation on ICSI/IVF outcomes . Two hundred and eighteen women with unexplained subfertility undergoing IVF/ICSI were r and omized into two groups . The study group ( n = 112 ) received daily oral antioxidants in the form of multivitamins and minerals ( amino acid chelated ) while the control group ( n = 106 ) did not . Main outcomes were number of mature metaphase II ( MII ) oocytes and clinical pregnancy rate . Results : There were no significant changes between the groups as regards age , BMI , basal FSH , number of mature ( MII ) oocytes ( 12.7 ± 9.4 vs. 13.2 ± 8.6 , P = 0.7 ) and clinical pregnancy rate per woman r and omized ( 38 % vs. 34 % ; [ OR = 1.2 ; 95 % CI , 0.70–2.11 ] . Conclusion : Oral antioxidants in the form of a combination of multivitamins and minerals ( amino acid chelated ) did not improve oocyte quality and pregnancy rates in women with unexplained infertility undergoing IVF/ICSI treatment", "We examined the effect of 12 weeks of daily oral administration of pentoxifylline with zinc and folic acid on the semen quality of 36 men with varicocele-associated infertility in an open , uncontrolled study . After 4 weeks of treatment , the proportion of morphologically normal sperm cells was significantly increased ; these changes persisted until at least 4 weeks after the end of treatment", "One hundred and two women with insulin-resistant polycystic ovary syndrome were r and omized to treatment with a vitamin B preparation , metformin , or both , in conjunction with st and ard infertility treatment . Plasma homocysteine levels were significantly reduced by both B vitamins and metformin , but to a greater degree by B vitamins , and higher pregnancy rates were associated with vitamin B treatment", "Abstract Objectives : To assess the adjuvant effect of metformin and N-acetylcysteine ( NAC ) to clomiphene citrate ( CC ) in induction of ovulation in Polycystic Ovary Syndrome ( PCOS ) patients . Study design : 120 women with PCOS were r and omly divided into three equal groups : group I received CC only , group II received CC plus NAC and group III received CC plus metformin . Results : There was a significant difference between group II and other two groups regarding average number of ovulatory follicles > 18 mm ( 2.25 versus 1.75 and 1.89 , respectively ) , but no significant difference between the three study groups regarding number of intermediate follicles 14–18 mm ( 4 , 10 and 4 , respectively ) . There was no significant difference between the three study groups regarding occurrence and laterality of ovulation , pregnancy rate per cycle but a significant difference between group II and other two groups regarding pregnancy rate per patient ( 20 % versus 10 % and 10 % , respectively , p value 0.05 ) . There was a highly statistically significant difference between group II and other two groups regarding peak endometrial thickness ( 7.3 ± 1.1 versus 5.4 ± 0.6 and 5.3 ± 0.6 , respectively ) . Conclusions : NAC as an adjuvant to CC for induction of ovulation improves ovulation and pregnancy rates in PCOS patients with beneficial impacts on endometrial thickness . Chinese abstract 目的：评估多囊卵巢综合症（PCOS）患者采用枸橼酸氯米芬（CC）促排卵过程中，二甲双胍和N-乙酰半胱氨酸的辅助作用 。 实验设计：120名PCOS女性随机分为三组：组I仅接受CC治疗，组II接受CC+NAC治疗，组III接受CC+二甲双胍 。 结果：组II与其它两组在直径＞18mm的卵泡数均值方面有显著差异（分别为2.25、1.75、1.89），但三组在中等大小卵泡（14–18mm）的数目方面无显著差异（分别为4、10、4）。三组在排卵发生和哪侧排卵，以及周期妊娠率均无明显差异，但组II在患者妊娠率方面显著不同于其它两组（分别为20%、10%、10%，p=0.05）。组II和其他组在子宫内膜峰值厚度方面有显著统计学差异（分别为7.3 ± 1.1、5.4 ± 0.6和5.3 ± 0.6 ） 。 结论：NAC作为CC促排卵的辅助用药可提高PCOS患者的排卵率和妊娠率，且对子宫内膜厚度有良好的影响", "OBJECTIVES Nuclear and cytoplasmic competence of human oocyte is critical for future competence of the embryo upon which ultimately depends the outcome of an ART ( Assisted Reproductive Technology ) treatment . Follicular microenvironment in which the oocyte develops is crucial , and this must be taken into account particularly with the use of hormonal ovarian stimulation protocol s. Inositol is an important element of the follicular environment and data support that its higher level in follicular fluid correlates with the development of a good oocyte . Aim of this study is to underst and the effects of treatment with inositol on oocyte quality in a sample of patients undergoing ICSI ( Intracytoplasmic Sperm Injection ) . PATIENTS AND METHODS Assessment of oocyte/embryo quality and pregnancy rates in 149 patients divided , according to a controlled r and omized pattern , into two groups : study group 1 treated with folic acid and inositol and control group 2 treated with folic acid alone . RESULTS The number of patients with excellent and good oocyte quality appears to be significantly higher in group 1 ( p = 0.02 ) , as shown , they significantly increased the number of embryos of grade A transferred in the group 1 ( p = 0.02 ) compared to group 2 , despite being completely similar averages of total embryos transferred ( total mean ± SD = 2.4 ± 0.8 , group 1 mean ± SD = 2.4 ± 0.8 , group 2 mean ± SD = 2.4 ± 0.8 ) . There is not any significant difference between groups 1 and 2 in the number of positivity to β-hCG and in the number of biochemical pregnancies detected although it has a tendency to increase in the first and to decrease in the second for group 1 . The increase in percentage of clinical pregnancies in group 1 was statistically significant ( p = 0.02 ) , whereas there was no apparent significance in the difference between the biochemical and clinical pregnancies in the two groups despite the positive trend in the study group . CONCLUSIONS Relying on \" inositol help \" to solidify our efforts , seems to be an easy path to help to deepen the effectiveness of its use in all patients still under 40 but with prior failed attempts at ICSI or diagnosed with PCOS or as \" poor responders \"", "OBJECTIVE To compare the effects of combined N-acetyl cysteine ( NAC ) and clomiphene citrate ( CC ) and of combined metformin and CC on ovulation induction in anovulatory CC-resistant women with polycystic ovary syndrome ( PCOS ) . METHODS One hundred ninety-two women were r and omized to receive either the NAC-CC drug combination ( group A , n = 95 ) or the combined metformin-CC therapy ( group B , n = 97 ) for three treatment cycles . The primary outcome measure was ovulation ; secondary outcomes were number of follicles , serum estrogen and progesterone levels , posttreatment endometrial thickness , pregnancy , and miscarriage . RESULTS Over a 3-month follow-up period , women in group B had significantly higher ovulation and pregnancy rates compared with women in group A ( 69.1 % vs. 20.0 % , p = 0.002 , and 22.7 % vs. 5.3 % , p = 0.020 , respectively ) . The level of serum estrogen , the endometrial thickness on the day of human chorionic gonadotropin ( hCG ) administration , and the serum progesterone level on cycle days 21 - 23 were all significantly higher for women in group B than for those in group A. Additionally , a lower miscarriage rate was observed among women in group B than among those in group A. CONCLUSIONS The efficacy of metformin-CC combination therapy is higher than that of NAC-CC for inducing ovulation and achieving pregnancy among CC-resistant PCOS patients", "STUDY OBJECTIVE To compare outcomes after conservative surgery for endometriosis with and without pentoxifylline and to assess the efficacy of pentoxifylline in preventing recurrence of endometriosis after conservative surgery . DESIGN Parallel-group , r and omized , controlled trial ( Canadian Task Force classification I ) . SETTING Tertiary care hospital . PATIENTS Women undergoing conservative surgery for endometriosis . INTERVENTIONS Laparoscopic conservative surgery for endometriosis was completed by a single surgeon ( J.A.T. ) , and all suspected endometriotic lesions were widely excised using monopolar coagulation and scissors . All specimens were su bmi tted to pathology for confirmation of the diagnosis . R and omization to the treatment or control groups was completed preoperatively in the outpatient surgery unit by drawing colored marbles . A preoperative visual analog pain scale ( VAS ) was completed . After surgery , patients were discharged home with prescriptions for naproxen , hydromorphone , and pentoxifylline . MEASUREMENTS AND MAIN RESULTS Visual analog scale scoring was completed monthly by each patient , and each patient was seen monthly for review and pelvic examination . Analgesic use was recorded daily using an individual medication log . Ongoing treatment choice after completion of the 3-month follow-up was recorded . The relationship between the group receiving pentoxifylline and the control group as well as analysis of the VAS scores at time of surgery and 1 , 2 , and 3 months postoperatively was determined using a covariate mixed-model ANOVA . Forty-nine patients were enrolled in the trial . One patient became pregnant before surgery , and 1 patient 's chart was not available for analysis . Of the 47 who underwent conservative surgery for endometriosis , 9 ( 19 % ) had no endometriosis noted in the pathology specimens su bmi tted . Two patients withdrew from the trial after surgery , and 2 patients were lost to follow-up after relocating to a different city . Nineteen women completed the 3-month follow-up in the control group , 15 in the group receiving pentoxifylline . The mean age , gravidity , parity , body mass index , previous surgery for endometriosis , menstrual cycle , and preoperative analgesic use did not differ significantly between the control and treatment groups . The time to complete the conservative surgery did not vary between the 2 groups . There were no intraoperative complications : two patients were admitted postoperatively , one for nausea and vomiting , one for pain that resolved 24 hours after admission . The VAS scores did not differ at the time of surgery ; and in both the control and the pentoxifylline groups , there was significant improvement at each monthly interval ( p < .05 ) . The patients receiving pentoxifylline had significantly better VAS scores at 2 and 3 months after surgery ( p < .03 ) . CONCLUSIONS The use of pentoxifylline after conservative surgery for endometriosis result ed in improved VAS scores at 2 and 3 months after the procedure when compared with patients having conservative surgery only . The longer-term use of pentoxifylline after conservative surgery may improve long-term outcomes after surgical treatment for endometriosis", "OBJECTIVE To evaluate the efficacy of calcium & vitamin D supplementation in infertile women suffering from polycystic ovary syndrome ( PCOS ) , and to assess levels of 25-hydroxy vitamin D in these patients . METHODS In a case control study , 100 infertile PCOS women based on a r and omly divided into two groups . Group I ( n = 50 ) were treated with metformin 1500 mg/day , and group II ( n = 50 ) treated with metformin 1500 mg/day plus Calcium 1000 mg/day and Vitamin D 100000 IU/month for 6 months . Patients were followed by transvaginal sonography at first , 3 and 6 months later for evaluating dominant follicle . BMI , menstrual regularity , follicle diameter , pregnancy , serum 25-OH-vitamin D level were matured and compared in two groups . RESULTS BMI decreased almost significantly ( 25.49 ± 1.88 vs 26.28 ± 2.15 , p : 0.054 ) in group II . A better improvement was gained in regulating menstrual abnormalities ( 70 % vs 58 % , p : 0.211 ) , follicle maturation ( 28 % vs 22 % , p : 0.698 ) , and infertility ( 18 % vs 12 % , p : 0.401 ) in group II compared with group I , but these results were not statistically significant . Eighty three percent of all the PCOS patients showed vitamin D deficiency while 35 % were severely deficient . The serum 25-OH-vitamin D mean levels were 13.38 ± 6.48 ng/ml . Vitamin D deficiency was recompensed in 74 % of the PCOS patients who had taken calcium & vitamin D supplementation . There was no correlation between BMI and 25-OH-VD before and after the treatment ( p ≥ 0.01 ) . CONCLUSION This study showed the positive effects of calcium & vitamin D supplementation on weight loss , follicle maturation , menstrual regularity , and improvement of hyper and rogenism , in infertile women with PCOS", "Abstract Objective . The aim of this study was to compare the effectiveness of myo-inositol ( MYO ) and metformin , in monotherapy or in association with recombinant follicle stimulating hormone ( r-FSH ) , in the treatment of menstrual irregularities , chronic anovulation , and female infertility in patients with polycystic ovary syndrome ( PCOS ) . Material s and methods . One hundred twenty patients were r and omly treated with metformin 1500 mg/day orally ( n = 60 ) , or 4 g MYO plus 400 μg folic acid daily ( n = 60 ) , continuously . If no pregnancy occurred , r-FSH ( 37.5 units/day ) was added to the treatment for a maximum of three attempts . Results . Fifty percent of the patients who assumed metformin restored spontaneous ovulation , 18.3 % of these obtained pregnancy . The remaining 42 patients were treated with metformin plus r-FSH . Pregnancy occurred in a total of 11 women ( 26.1 % ) . The total pregnancy rate was 36.6 % . Sixty-five percent of the patients treated with MYO plus folic acid restored spontaneous ovulation activity , 30 % of these obtained pregnancy . The remaining 38 patients were treated with MYO , folic acid plus r-FSH . Pregnancy occurred in a total of 11 women ( 28.9 % ) . The total pregnancy rate was 48.4 % . Conclusions . Both metformin and MYO , can be considered as first line treatment for restoring normal menstrual cycles in most patients with PCOS , even if MYO treatment seems to be more effective than metformin" ]

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[ "Aerobic Exercise Reduces Blood Pressure in Resistant Hypertension", "The effect of the addition of resistance training to a dietary education intervention on apolipoproteins and diet quality in overweight and obese older adults", "Enhanced blood pressure response to dietary salt in elderly women, especially those with small waist:hip ratio", "Effects of exercise on neurobehavioral function in community-dwelling older people more than 75 years of age.", "Decreased exercise blood pressure in older adults after exercise training: contributions of increased fitness and decreased fatness", "Rayyan—a web and mobile app for systematic reviews", "Improving cardiovascular fitness by strength or endurance training in women aged 76-78 years. A population-based, randomized controlled trial.", "Cardiovascular adaptations to resistance training in elderly postmenopausal women.", "Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension.", "The Effects of Resistance Training and Walking on Functional Fitness in Advanced Old Age", "The impact of aerobic exercise on blood pressure variability", "Moderate- and high-intensity exercise lowers blood pressure in normotensive subjects 60 to 79 years of age.", "Low to moderate intensity endurance training in healthy older adults: physiological responses after four months.", "Effects of exercise in overweight Japanese with multiple cardiovascular risk factors.", "Effects of exercise training on arterial stiffness in older hypertensive females", "Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol concentration in healthy elderly subjects.", "The effect of a short-term exercise programme on haemodynamic adaptability; a randomised controlled trial with newly diagnosed transient ischaemic attack patients", "The Hypotensive Effects of Isometric Handgrip Training Using an Inexpensive Spring Handgrip Training Device", "Strength Training Improves Submaximum Cardiovascular performance in Older Men", "High intensity deep water training can improve aerobic power in elderly women", "Regulation of blood volume during training in post-menopausal women.", "The Effect of Music on Hypertensive Patients", "Walking with its training effects on the fitness and activity patterns of 79-91 year old females.", "Aerobic Training Restores Arterial Baroreflex Sensitivity in Older Adults With Type 2 Diabetes, Hypertension, and Hypercholesterolemia", "Cardiovascular and behavioral effects of aerobic exercise training in healthy older men and women.", "[Cost and effectiveness of exercise therapy for patients with essential hypertension].", "Improving physical function and blood pressure in older adults through cobblestone mat walking: a randomized trial.", "Salzburg Skiing for the Elderly Study: changes in cardiovascular risk factors through skiing in the elderly.", "Stress management versus lifestyle modification on systolic hypertension and medication elimination: a randomized trial.", "Isometric training lowers resting blood pressure and modulates autonomic control.", "The effects of endurance exercise training on ambulatory blood pressure in normotensive older adults.", "The effects of aerobic exercise and T'ai Chi on blood pressure in older people: results of a randomized trial.", "Physical activity preferences, preferred sources of assistance, and perceived barriers to increased activity among physically inactive Australians.", "Effect of yoga on arterial stiffness in elderly subjects with increased pulse pressure: A randomized controlled study.", "2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)." ]

[ "Regular physical exercise is broadly recommended by current European and American hypertension guidelines . It remains elusive , however , whether exercise leads to a reduction of blood pressure in resistant hypertension as well . The present r and omized controlled trial examines the cardiovascular effects of aerobic exercise on resistant hypertension . Resistant hypertension was defined as a blood pressure ≥140/90 mm Hg in spite of 3 antihypertensive agents or a blood pressure controlled by ≥4 antihypertensive agents . Fifty subjects with resistant hypertension were r and omly assigned to participate or not to participate in an 8- to 12-week treadmill exercise program ( target lactate , 2.0±0.5 mmol/L ) . Blood pressure was assessed by 24-hour monitoring . Arterial compliance and cardiac index were measured by pulse wave analysis . The training program was well tolerated by all of the patients . Exercise significantly decreased systolic and diastolic daytime ambulatory blood pressure by 6±12 and 3±7 mm Hg , respectively ( P=0.03 each ) . Regular exercise reduced blood pressure on exertion and increased physical performance as assessed by maximal oxygen uptake and lactate curves . Arterial compliance and cardiac index remained unchanged . Physical exercise is able to decrease blood pressure even in subjects with low responsiveness to medical treatment . It should be included in the therapeutic approach to resistant hypertension", "Objectives The aim of the study was to examine the additive effect of resistance training ( RT ) to a dietary education ( DE ) intervention on emerging coronary heart disease ( CHD ) risk factors , concentration of apolipoproteins B ( apoB ) and A-I ( apoA-I ) , and Dietary Approaches to Stop Hypertension ( DASH ) Diet Index scores in overweight and obese older adults . Patients and methods This was an ancillary study of a r and omized clinical trial held in the Fall of 2008 at the University of Rhode Isl and . Participants were overweight or obese subjects ( mean body mass index [ BMI ] of 31.7 kg/m2 ) r and omized into two groups , one participating in DE only ( n = 12 ) and the other participating in DE plus RT ( DERT ) ( n = 15 ) . The intervention involved all subjects participating in 30 minutes of DE per week for 10 weeks . Subjects in the DERT group participated in an additional 40 minutes of RT three times per week for 10 weeks . Measurements taken were anthropometric ( height , weight , waist circumference , and body composition using the BOD POD ® [ Body Composition System , v 2.14 ; Life Measurement Instruments , Concord , CA ] ) , clinical ( blood pressure ) , and biochemical ( lipid profile and apoB and apoA-I concentrations ) , and the DASH Diet Index was used to measure diet quality . Results 27 subjects ( 11 males , 16 females ) , with a mean age of 66.6 ± 4.3 years , were included in analyses . The DERT subjects had significantly better triacylglycerol and apoB concentrations and DASH Diet Index scores than the DE subjects post-intervention . Improvements were seen within the DE group in energy intake , fat-free mass , and systolic blood pressure and within the DERT group in body weight , percentage of body fat , BMI , diastolic blood pressure , and oxidized low-density lipoprotein ( all P < 0.05 ) . Conclusion The addition of RT effectively reduced CHD risk factors , body composition , and diet quality in overweight and obese older adults ; DERT was more effective than DE alone in improving DASH Diet Index scores and lowering apoB concentrations but was not more effective in increasing apoA-I concentrations . Future research is needed to determine if apolipoproteins are superior to lipoprotein cholesterol concentrations in predicting CHD risk", "Objective : To determine the blood pressure responses in elderly normotensive men and women to dietary sodium and to the diunsaturated fatty acid dihomogammalinolenic acid ( DGLA ) , which is derived from linoleic acid Design : Blood pressure responses were assessed in 66 subjects ( 36 male , 30 female ; mean age 65 years ) on two diets differing by approximately 70mmol/day sodium , combined with daily supplements of either 1 g DGLA or 1 g safflower oil , giving a four-group parallel design . After a common period of salt restriction and salt supplementation , two sets of parallel groups continued with either salt or placebo tablets . The study was blinded , except for dietary adjustments based on 24-h urinary sodium excretion values measured once every 2 weeks . Blood pressures were also measured automatically once every 2 weeks Results : Urinary sodium excretion ( sodium intake ) correlated significantly with systolic and diastolic blood pressures . A strong interaction with sex ( P < 0.001 for systolic blood pressure ) reflected greater responsiveness in women to changing sodium intake . A second major determinant of blood pressure responsiveness was the waist : hip ratio , an index of central obesity ; this correlation was independent of the initial sodium intake , initial blood pressure or body mass index . The waist : hip ratio was a powerful predictor of blood pressure changes with sodium intake in women only ; women with and roid fat distribution were , similarly to men , less sensitive to dietary sodium . Daily supplements of 1 g DGLA doubled the concentration of DGLA in plasma but did not influence blood pressure Conclusions : Among elderly normotensive subjects , women responded to changes in sodium intake with greater changes in blood pressure than men did . Furthermore , this response was strongly related to the gynaecoid distribution of body", "OBJECTIVE We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age . DESIGN A r and omized controlled trial with 6-month follow-up was conducted . SETTING The study was performed in the rural town of Kahoku , Japan , the population of which is considered representative of the older population of Japan . PARTICIPANTS We studied 42 healthy volunteers ( 18 men and 24 women ; mean age , 79 years ( range 75 to 87 years ) ) who were r and omly assigned to one of two groups , exercise or control . INTERVENTION Subjects assigned to the exercise group were instructed to exercise for 60 minutes twice a week for 6 months . Subjects in the control group were not instructed to engage in an specific exercise regimen . MEASUREMENTS The following measurements were recorded for both groups at baseline and at 6-month follow-up : ( 1 ) Neurobehavioral function as determined by the following tests : Mini-Mental State Exam ( MMSE ) , Hasegawa Dementia Scale Revised ( HDSR ) , Visuospatial Cognitive Performance Test ( VCP-test ) , Button score , Up & Go test , and Functional Reach ; and ( 2 ) Body mass index and blood pressure . RESULTS The effects of exercise were shown in the Up & Go test , and Functional Reach ( ANOVA with repeated measures ) . CONCLUSION This study demonstrates the acceptability and effectiveness of exercise on neurobehavioral function , even in older people more than 75 years of age", "Objective : To describe the contribution of changes in fitness and fatness result ing from exercise training on changes in submaximal exercise blood pressure ( BP ) during treadmill testing . Design and setting : Prospect i ve , r and omised , controlled trial . Participants : Sedentary older adults ( n = 115 ) with untreated prehypertension or mild hypertension . Intervention : Six-month supervised aerobic and strength training . Main outcome measurement : Systolic BP ( SBP ) was assessed at rest and during each stage of a maximal grade d exercise test ( GXT ) that determined Vo2peak . General and regional fatness was assessed by anthropometry , dual-energy x-ray absorptiometry and MRI . BP changes were calculated for each GXT stage , and multivariate regression models were used to describe the association of changes in exercise BP with changes in fitness and fatness . Results : After training , exercisers versus controls had significantly increased Vo2peak and significantly lower measures of general and regional fatness . Also , stage-specific SBP was significantly lower at stage 3 ( −9.4 vs −1.6 mm Hg , p = 0.03 ) and stage 4 ( −7.9 vs −1.2 mm Hg , p = 0.03 ) . Pooled regression analysis across all stages showed that exercisers had a 7.1 mm Hg reduction in SBP , but this reduction fell short of statistical significance ( p = 0.12 ) compared with controls . A 1.0 ml/kg/min increase in Vo2peak and a 1.0 cm decrease in waist circumference independently predicted a 1.0 mm Hg decrease in exercise SBP ( p = 0.04 and p = 0.001 , respectively ) . Conclusions : Decreased exercise SBP was independently associated with decreased waist circumference , a marker of abdominal obesity and increased fitness . These findings suggest that exercise training improves multiple factors that have an independent influence on SBP", "Background Synthesis of multiple r and omized controlled trials ( RCTs ) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions . Filtering of search es is time consuming , and no single method fulfills the principal requirements of speed with accuracy . Automation of systematic review s is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making . We developed Rayyan ( http://rayyan.qcri.org ) , a free web and mobile app , that helps expedite the initial screening of abstract s and titles using a process of semi-automation while incorporating a high level of usability . For the beta testing phase , we used two published Cochrane review s in which included studies had been selected manually . Their search es , with 1030 records and 273 records , were uploaded to Rayyan . Different features of Rayyan were tested using these two review s. We also conducted a survey of Rayyan ’s users and collected feedback through a built-in feature . Results Pilot testing of Rayyan focused on usability , accuracy against manual methods , and the added value of the prediction feature . The “ taster ” review ( 273 records ) allowed a quick overview of Rayyan for early comments on usability . The second review ( 1030 records ) required several iterations to identify the previously identified 11 trials . The “ suggestions ” and “ hints , ” based on the “ prediction model , ” appeared as testing progressed beyond five included studies . Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements . The survey respondents reported 40 % average time savings when using Rayyan compared to others tools , with 34 % of the respondents reporting more than 50 % time savings . In addition , around 75 % of the respondents mentioned that screening and labeling studies as well as collaborating on review s to be the two most important features of Rayyan . As of November 2016 , Rayyan users exceed 2000 from over 60 countries conducting hundreds of review s totaling more than 1.6 M citations . Feedback from users , obtained mostly through the app web site and a recent survey , has highlighted the ease in exploration of search es , the time saved , and simplicity in sharing and comparing include-exclude decisions . The strongest features of the app , identified and reported in user feedback , were its ability to help in screening and collaboration as well as the time savings it affords to users . Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of review ers", "BACKGROUND there have been few population -based , r and omized controlled trials on the effects of strength or endurance training on cardiovascular fitness in older women . OBJECTIVE to study the effects of strength or endurance training on cardiovascular fitness in women aged 76 - 78 years . DESIGN a population -based , r and omized controlled trial . SETTING exercise laboratory in a university faculty of sport and health sciences . SUBJECTS we r and omly assigned 42 medically-screened women aged 76 - 78 years , drawn from the population register to strength ( n=16 ) , endurance ( n=15 ) or control ( n=11 ) groups . METHODS subjects in the two exercise groups performed a supervised , individually tailored 18-week strength or endurance training programme . Controls continued with physical activity at their normal level . RESULTS the strength training group showed an increase in cycle ergometer peak power from 68.1 to 70.3 W ( P=0.035 compared with controls ) . Their peak power per kg body weight increased from 1.02 to 1.05 , while that of the endurance training group increased from 0.91 to 0.93 ( P=0.027 and P=0.049 respectively ) . Peak oxygen uptake increased from 18.1 to 19.7 ml x kg(-1 ) x min(-1 ) in the strength and from 17.1 to 18.2 in the endurance group ( non-significant ) . Six subjects ( 19 % ) in the exercise groups withdrew from the study because of health problems . CONCLUSIONS even with its limitations , the study suggests that the effect of 18-week strength or endurance training on cardiovascular fitness among women aged > /=75 is relatively small . Furthermore , health problems can emerge during training programmes in medically-screened elderly women", "The purpose of this study was to investigate the effect of resistance training on resting blood pressure and heart rate variability in elderly postmenopausal women . 29 untrained , non-hypertensive elderly women were r and omly assigned to 2 groups : an intervention group ( n=15 , 65.5±5.0 years , 57.3±6.5 kg , 156.7±5.1 cm ) that underwent a supervised resistance training program ( 8 exercises , 2 sets , 10 - 15 repetitions , 3 times/week ) or a control group ( n=14 , 66.2±4.1 years , 61.1±11.7 kg , 157.5±7.1 cm ) that participated in a supervised stretching program ( 25 - 30 min/session , 2 times/week ) . Resting auscultatory blood pressure , heart rate variability , evaluated from short recordings in a seated position , and maximal dynamic strength ( 1-RM test ) were measured at baseline and after 12 weeks . A group x time ANOVA revealed that muscular strength increased significantly in the resistance training group ( + 10.2 % for bench press and + 12.7 % for leg extension , P<0.05 ) . Systolic blood pressure was reduced significantly in the resistance training group from pre- to post-intervention period ( - 5 mmHg ; P<0.05 ) , while no significant effect was noted for diastolic blood pressure and heart rate variability indexes ( P>0.05 ) . None of these variables changed in the control group throughout the study . In conclusion , a supervised resistance training program improved muscular strength and reduced systolic blood pressure without affecting diastolic blood pressure and heart rate variability in elderly postmenopausal women", "BACKGROUND Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults , surprisingly little data exist to confirm the efficacy of these interventions in older persons . METHODS We conducted a r and omized , controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg . The experimental arm was a nonpharmacologic intervention combining weight reduction , sodium restriction , and increased physical activity . The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase , followed by four monthly group sessions during the maintenance phase . The control group received no treatment during the study . Blood pressure was assessed by certified technicians ( blinded to group assignment ) using r and om zero sphygmomanometers . RESULTS Of 56 participants r and omized , 47 completed the entire 6-month trial ( 21 in the intervention group and 26 in the control group ) . Attendance at the intervention sessions was excellent . The intervention group lost more weight ( -2.1 kg ) over 6 months than the control group ( + 0.3 kg ) . Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups , with greater trend in the intervention group , were not statistically significant . The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group ( mean differences between groups at 6 months , 4.2/4.9 mm Hg , respectively ) . CONCLUSIONS Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure", "The authors assessed the effects of resistance training and walking exercise on measures of functional fitness . Sixty-four volunteers ( average age 83.5 years ) from an independent-living facility were r and omly assigned to walking , resistance training , or control groups . Participants in the walking and resistance-training groups engaged in two exercise sessions per week for 16 weeks . Measures of functional fitness included upper and lower body strength , hip and shoulder flexibility , agility and balance , coordination , blood pressure , and resting heart rate . Repeated measures analysis of variance was used to examine pretest to posttest differences . Both exercise groups showed significant improvements relative to control group in upper and lower body strength , shoulder flexibility , and agility and balance exercise . Findings demonstrate that exercise can lead to improvements in multiple domains of functional fitness even among very old , previously sedentary individuals , possibly making activities of daily living easier to perform", "There is increasing evidence that blood pressure variability ( BPV , variation of blood pressure over time ) constitutes a strong and independent marker of cardiovascular risk . The all-cause mortality is > 50 % greater in subjects with a st and ard deviation of inter-visit blood pressure > 5 mm Hg . Regular aerobic exercise reduces blood pressure and is recommended by current hypertension guidelines as a basic lifestyle modification . It remains elusive , however , whether aerobic exercise is able to reduce BPV as well . In total , 72 hypertensive subjects were r and omly assigned to an 8–12-week treadmill exercise program ( target lactate 2.0±0.5 mmol l−1 ) or sedentary control . Blood pressure was measured by 24 h-ambulatory blood pressure monitoring ( ABP ) . Two aspects of BPV were assessed : the variability of ABP and the variability of blood pressure on exertion . The coefficient of variation ( CV ) was used as a statistical measure of BPV . The CV of systolic daytime ABP was defined as primary outcome . The exercise program significantly decreased systolic and diastolic daytime ABP by 6.2±10.2 mm Hg ( P<0.01 ) and 3.0±6.3 mm Hg ( P=0.04 ) , respectively . Moreover , it reduced blood pressure on exertion and increased physical performance ( P<0.05 each ) . Exercise had no impact , however , on the CV of daytime ( 10.2±2.7 vs. 9.8±2.6 % , P=0.30 ) and night-time systolic ( 8.9±3.2 vs. 10.5±4.1 % , P=0.10 ) and diastolic ABP ( daytime 11.5±3.3 vs. 11.5±3.1 % , night-time 12.0±4.3 vs. 13.8±5.2 % ; P>0.05 each ) . Regular aerobic exercise is a helpful adjunct to control blood pressure in hypertension , but it has no effect on 24 h- BPV , an independent predictor of cardiovascular risk", "To investigate the effects of exercise intensity on resting blood pressure ( BP ) in normotensive elderly subjects , 44 sedentary healthy subjects aged 60 to 79 years of age were studied during 6 months of walking exercise . Subjects were ranked according to maximal oxygen consumption and r and omly stratified to groups that trained at 70 % ( n = 19 ) or 80 % to 85 % ( n = 14 ) of maximal heart rate reserve , or to a control group ( n = 11 ) that did not train . Initial BP was established during a 2- to 3-week control period . During the first 3 months , both exercise groups progressed to 70 % of heart rate reserve for 40 minutes 3 times each week . The moderate-intensity group continued to train at 70 % ( 45-minute duration ) for an additional 3 months , whereas the high-intensity group progressed to training at 85 % of heart rate reserve ( 35-minute duration ) . Maximal oxygen consumption increased ( p < or = 0.05 ) during the initial 3 months in both exercise groups ( 25.2 to 28.1 ml.kg-1.min-1 and 26.3 to 29.3 ml.kg-1.min-1 ) and continued to increase ( p < or = 0.05 ) after 3 additional months of training , but the increase was greater ( p < or = 0.05 ) in the high-intensity group ( 28.1 to 29.4 ml.kg-1.min-1 and 29.3 to 32.8 ml.kg-1.min-1 ) . Systolic BP decreased ( p < or = 0.05 ) similarly at 6 months in both training groups ( 120 to 111 mm Hg and 120 to 112 mm Hg ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE To determine the physiological adaptations in previously sedentary healthy older men and women ( mean age = 68 ) to a 16-week low-to-moderate-intensity exercise program . DESIGN R and omized , controlled trial . SETTING An exercise facility and testing laboratory in a gerontological research institute . PARTICIPANTS Two-hundred forty-seven community-dwelling older persons free of significant cardiovascular , pulmonary , or uncontrolled metabolic disease , anemia , electrolyte abnormality , resting BP of 165/90 or greater , or chronic disease affecting the ability to exercise on a bicycle . INTERVENTION Subjects were r and omly assigned to either an exercise ( n = 166 ) or attention control group ( n = 81 ) . Exercisers trained thrice weekly for 40 minutes on a cycle ergometer ( 5-minute warm up , 30 minutes at training heart rate ( THR ) , 5-minute cool down ) . THR was set at 70 % of peak heart rate attained on a maximal exercise test ( mean = 115 + /- 15 ) . Control subjects attended weekly group talks . Testing took place before and after the program . RESULTS Peak attained oxygen uptake ( VO2max ) increased 8.5 % in exercisers and decreased slightly in controls ( p less than .001 ) and oxygen uptake at ventilatory threshold ( VeT VO2 ) increased by 3.5 % in exercisers and decreased by 3 % in controls ( p less than .001 ) . This pattern of a greater increase in VO2max than VeT VO2 is different from that seen in young and middle-aged subjects . CONCLUSION This study demonstrated that a large scale training program is feasible for healthy older people , that physiologic improvements can be measured after 16 weeks of low-to-moderate-intensity training , and that mechanisms of adaptation to exercise may be different in elderly subjects from those in younger ones", "PURPOSE The effects of exercise in subjects with multiple cardiovascular risk factors ( RF ) have never been tested in a large-scale r and omized controlled trial . The favorable results from our observational study led to this r and omized controlled trial . METHODS The participants , recruited from a community , were overweight , with two of the following three risk factors : hypertension , hyperlipidemia , or glucose intolerance ( N=561 ; 44 % male ; mean age ( SD ) 67 ( 6 ) ; mean BMI 26.4 ( 2.0 ) ) . All participants received a st and ard health exam with counseling , followed by r and omization . The intervention group ( INT ) was to exercise two to four times per week for 6 months at a fitness club . RESULTS Dropout rate was 11 % for INT and 10 % for the controls . INT exercised an average of 2.6 times per week . Among primary outcome measures , there was a marginally significant between-group difference in changes in systolic blood pressure ( intervention minus control , -2.46 mm Hg ) . Reductions in LDL cholesterol ( -1.9 mg.dL ) and hemoglobin A1c ( -0.042 % ) were not significant . Among secondary outcomes , between-group differences were significantly greater ( P<0.05 ) for INT in mean body weight ( -1.60 kg ) , waist circumference ( -1.8 cm ) , triglyceride ( -7 mg.dL ) , hsCRP ( -0.063 mg . L ) , and estimated VO2peak ( 2.0 mL.kg.min ) . All directional mean RF changes consistently favored INT . A cardiovascular risk reduction estimated from the changes in RF was about 24 % . A greater improvement was also found in health-related quality -of-life measures ( SF-36 ) in INT . No difference was found in the adverse event rate . CONCLUSIONS Exercising an average of 2.6 times per week for 6 months produced a significant improvement in cardiovascular risk profile in subjects with multiple cardiovascular risk factors through cumulative results of modest yet pervasive changes in all conventional risk factors , without increased adverse effects", "Purpose Regular physical exercise is recommended for the prevention and treatment of cardiovascular disease . However , it is unclear whether the effects of exercise training on arterial stiffness are the same in older hypertensive individuals as those observed in older healthy subjects . The aim of this study was to compare the effects of exercise training on arterial stiffness between older hypertensive and healthy females . Methods Ninety-two females with untreated hypertension and 108 healthy females were r and omly assigned to either the control group or to participate in a 12-week training program . In the training groups , the subjects engaged in 90 min of training twice a week for 12 weeks . Each training program included recreational activities , six to eight resistance exercises for circuit training and chair-based exercise for the lower extremities . The systolic/diastolic blood pressure ( SBP/DBP ) and brachial to ankle pulse wave velocity ( baPWV ) were obtained in the supine position using an automatic pulse wave form analyzer . Results Compared with that observed in the control group , greater reductions in the baPWV and SBP/DBP were achieved in both training groups ( P < 0.05 ) . Furthermore , a significant difference in the delta baPWV values obtained before and after training was noted between the hypertensive ( −72.5 ± 8.1 cm s−1 ) and healthy females ( −131.5 ± 107.3 cm s−1 ) who participated in the training program ( P < 0.05 ) . Conclusions These data indicate that exercise training produces fewer improvements in arterial stiffness in older hypertensive females than in older healthy females", "The concentration of high-density lipoprotein cholesterol ( HDL-C ) is inversely correlated with the risk of coronary heart disease . The effects of low-intensity aerobic training on serum HDL-C and other lipoprotein concentrations were examined in healthy elderly subjects . The subjects were r and omly assigned to two groups matched for sex , age , height , and weight . The training group ( n = 20 , 10 men and 10 women aged 67 + /- 4 years ) participated in a supervised physical exercise regimen using a bicycle ergometer at an intensity of 50 % estimated maximal oxygen consumption ( VO2max ) for 60 minutes two to four times per week for 5 months . In contrast , the control group ( n = 20 , 10 men and 10 women aged 68 + /- 4 years ) did not perform any particular physical training . The training protocol result ed in significant increases in the VO2max ( P < .05 ) , HDL-C , HDL2-C , and HDL2-C/HDL3-C ratio ( P < .01 ) . The change in HDL2-C ( r = .57 , P < .01 ) and HDL2-C/HDL3-C ( r = .63 , P < .01 ) was positively associated with an increase in the total exercise duration per week . In addition , the total weekly exercise duration also showed a significant positive relationship with HDL-C ( r = .75 , P < .01 ) , HDL2-C ( r = .81 , P < .01 ) , and HDL2-C/HDL3-C ( r = .71 , P < .01 ) after the training period . The changes in body weight and the VO2max were not significantly correlated with any lipid parameters . Low-intensity aerobic training may improve the profile of HDL-C and its subfractions in healthy elderly subjects . Also , the total exercise duration may be an important factor for improving HDL-C and HDL2-C in elderly subjects", "This study assessed the effect of a short-term , 8-week exercise programme on resting and exercise blood pressure ( systolic ( SBP ) ; diastolic ( DBP ) ) , and other haemodynamic responses ( heart rate ( HR ) , pulse pressure ( PP ) , double product ( DP ) ) , of newly diagnosed transient ischaemic attack ( TIA ) patients . Sixty-eight TIA patients completed a continuous and incremental exercise test within 2 weeks of symptom diagnosis . HR , SBP and DBP were regularly measured at rest , during exercise and in recovery . Participants were then r and omised to either an 8-week exercise programme or to a usual care control group prior to completing an identical post-intervention ( PI ) re- assessment . Individuals r and omised to the exercise condition experienced a significantly greater reduction in resting HR ( −5.4±10.2 % ) , SBP ( −6.7±8.1 % ) and DBP ( −2.8±7.2 % ) than the control group at the PI assessment ( all P<0.05 ) . Similar findings were demonstrated at the PI assessment when comparing haemodynamic responses during exercise ( P<0.05 ) , with significantly larger decrements observed for SBP and HR ( both 10–14 % ) , PP ( 17–24 % ) and DP ( 26–32 % ) for those r and omised to the exercise intervention ( all P<0.05 ) . This study demonstrates that structured physical activity soon after TIA diagnosis will improve haemodynamic responses . The early implementation of exercise following TIA diagnosis may be an important secondary prevention strategy for this population", "PURPOSE Research has demonstrated the efficacy of isometric h and grip ( IHG ) training to attenuate resting blood pressure . These studies have relied on the use of programmable digital h and grips for training . This study aim ed to determine the effectiveness of simple , inexpensive spring-loaded h and grip devices in producing hypotensive effects . METHODS The study was a r and omized controlled trial of 49 normotensive participants ( 66.4 ± 0.9 years ; 57 % women ) . Participants in the exercise group ( n = 25 ) trained and had blood pressure measured twice weekly for 8 weeks . Control participants ( n = 24 ) completed weekly blood pressure measurements . Pre- and posttraining measurements were each assessed over 3 visits . Statistical analysis of the pre-post data involved analyses of variance and hierarchical linear modeling was used to examine changes over time . RESULTS Following 8 weeks , IHG participants demonstrated significant reductions in resting blood pressure . Systolic and diastolic blood pressures were reduced from 122 ± 3 mm Hg to 112 ± 3 mm Hg ( P < .001 ) and from 70 ± 1 mm Hg to 67 ± 1 mm Hg ( P < .05 ) , respectively . Hierarchical linear modeling analysis also revealed a significant cross-level ( ie , group ÷ time ) interaction , with an estimated reduction in systolic blood pressure of 5.4 mm Hg ( P < .001 ) over the training period in the IHG group . CONCLUSIONS In agreement with previous studies , IHG training reduced resting arterial pressure following 8 weeks of training . Hypotensive effects linked to IHG training may be achieved using simple , inexpensive spring h and grip training devices and may provide a convenient and affordable therapeutic alternative or adjunctive therapy for lowering blood pressure", "ABSTRACT Purpose : To determine if 16 weeks of strength training can improve the cardiovascular function of older men during sub‐maximum aerobic exercise . Methods : Twenty four men aged 70‐80 yr were r and omly assigned to a strength training ( ST ; n = 12 ) and control group ( C ; n = 12 ) . Training consisted of 3 sets of 6 ‐ 10 repetitions at 70 % to 90 % of 1RM , 3 times per week , on an incline squat machine for 16 weeks , followed by 4 weeks detraining . Leg strength and maximum oxygen consumption ( VO2 max ) were assessed every 4 weeks of the 20‐week study . Cardiovascular function was assessed during submaximum cycle exercise at 40 Watts , 50 % and 70 % of VO2 max before training , after 16 weeks training , and after 4 weeks detraining . Results : At 40 Watts , heart rate ( HR ) , systolic blood pressure , and rate pressure product ( RPP ) were lower and stroke volume ( SV ) significantly higher after 16 weeks training and 4 weeks detraining : at 50 % VO2 max , HR and RPP were lower after 16 weeks training and 4 weeks detraining : at 70 % VO2 max , cycle ergometry power , VO2 and arterio‐venous oxygen difference ( a ‐ & OV0456;O2 ) were higher after 16 weeks training . Leg strength and VO2 max increased after 16 weeks training , with leg strength remaining above pre‐training levels after 4‐weeks detraining . Conclusions : Sixteen weeks of strength training significantly improves the cardiovascular function of older men . Therefore strength training not only increases muscular strength and hypertrophy but also provides significant cardiovascular benefits for older individuals", "Deep water running with wet vest is a safe form of exercise for elderly with mobility limitations . However , it is not known to what extent their aerobic power may be improved . Therefore , the aim was to assess the effects of high intensity deep water interval training with vest in elderly women . Twenty-nine healthy women 69 ± 4 years old participated . They performed a grade d maximal exercise test on the cycle ergometer . They were r and omly assigned to a control or to a training group . A submaximal exercise test on the cycle ergometer was executed only by the training group . They trained in deep water running/walking wearing a vest two times a week for 8 weeks . The target heart rate was 75 % of maximal heart rate and the training consisted of several short working periods and resting intervals . After the intervention the heart rate at rest was 8 % lower for the training group ( P<0.01 ) . Their heart rate at submaximal exercise was 3 % less ( P<0.01 ) , their maximal oxygen uptake was raised by 10 % ( P<0.01 ) , and their maximal ventilation was increased 14 % ( P<0.01 ) . The values for the control group were unaltered after the period of intervention . In conclusion , high intensity deep water running with vest improves submaximal work capacity , maximal aerobic power , and maximal ventilation with the effects transferable to l and -based activities in elderly women", "UNLABELLED In younger people the increase in aerobic capacity following training is related , in part , to blood volume ( BV ) expansion and the consequent improvements in maximal cardiac output . This training-induced hypervolemia is associated with a decrease in cardiopulmonary baroreflex ( CPBR ) control of peripheral vascular tone . PURPOSE To test the hypothesis that improvement in peak oxygen consumption ( VO2peak ) during training in older women is associated with specific central adaptations , such as BV expansion and a reduction in CPBR control of vascular tone . METHODS Seventeen healthy older women were r and omized into training ( N = 9 , 71 + /- 2 yr ) and control ( N = 8 , 73 + /- 3 yr ) groups . The training group exercised three to four times per wk for 30 min at 60 % peak heart rate for 12 wk and then 40 - 50 min at 75 % peak heart rate for 12 wk . The control group participated in yoga exercises over the same time period . We measured resting BV ( Evans blue dye ) , VO2peak , and the forearm vascular resistance response to unloading low pressure mechanoreceptors during low levels of lower body negative pressure ( through -20 mm Hg ) before and after aerobic training . The slope of the increase in forearm vascular resistance ( response ) per unit decrease in central venous pressure ( stimulus ) was used to assess CPBR responsiveness . RESULTS Aerobic training increased VO2peak 14.2 % from 24.2 mL x kg(-1 ) x min(-1 ) to 27.7 mL x kg(-1 ) x min(-1 ) ( P < 0.05 ) , a smaller improvement than typically seen in younger subjects . Blood volume ( 59.9 + /- 1.9 and 60.9 + /- 1.9 mL x kg[-1 ] ) and CPBR function ( -3.98 + /- 0.92 and -3.46 + /- 0.94 units x mm(-1 ) Hg ) were similar before and after training . CONCLUSIONS These data indicate that the inability to induce adaptations in CPBR function may limit BV expansion during training in older women . In addition , the absence of these specific adaptations may contribute to the relatively poor improvements in VO2peak in older women during short ( 10 - 12 wk ) periods of training", "The aim of this study is to examine if , and to what extent , daily listening to a certain type of music can help hypertensive patients lower their blood pressure ( BP ) . Experiments were conducted at an elderly home . Thirty subjects aged 63 - 93 years participated in the study and were r and omly assigned into either a music group ( n=15 ) or a control group ( n=15 ) . There were no significant differences between the two groups in initial BP values , age , gender , or medication status . Subjects in the music group listened to selected music , 25 min every day for 4 weeks . BP was measured twice a week by a registered nurse with a sphygmomanometer during the 4-week study period and after the completion of the study . Four subjects dropped from the experiment due to a change of medical conditions or to personal reasons . After 4 weeks , the average decrease for the music group ( n=12 ) in systolic BP ( SBP ) and diastolic BP ( DBP ) was 11.8 mmHg ( />=0.008 ) and 4.7 mmHg ( />=0.218 ) , respectively , whereas there was no significant changes in SBP or DBP for the control group ( n=14 ) . The results suggest that listening to a certain type of music serves to reduce high SBP and therefore music therapy may be an alterative for hypertension treatment", "BACKGROUND Information is lacking about the physiological and psychosocial effects of exercise among very old persons . AIM To investigate the effect of a twice-weekly , six-month progressive walking programme on 38 healthy women in their ninth decade , for evidence of the benefits of exercise . METHODS Aerobic fitness , blood pressure , skinfold thickness and habitual activity patterns were studied in a r and omised controlled trial . Women were chosen , as this is a group of increasing demographic importance for which studies are lacking . RESULTS The training group and control group were not significantly different at baseline . However , after six months of progressive exercise the training group showed lower resting ( p < 0.05 ) and working ( p < 0.005 ) heart rates compared with non-exercising controls . ANCOVA analyses indicated higher scores for the training group compared with the control group for Maximum Current Activity and Normative Impairment Index ( both p < 0.001 ) , which are both components of the Habitual Activity Profile . Morale also significantly improved within the training group ( p < 0.01 ) . CONCLUSIONS These data show the trainability of very old women and the positive impact a low frequency , progressive exercise programme can have on cardiorespiratory fitness and daily living activity patterns . Such improvements are likely to be indicative of an enhanced outlook for independence", "Objective : Lowered baroreflex sensitivity ( BRS ) predicts mortality and occurs with increasing age and diabetes . We examined whether aerobic exercise could restore arterial BRS in adults at high cardiovascular risk ( diabetes , geriatric age group , hypercholesterolemia , and hypertension ) . Design : R and omized , controlled , single-blind study . Setting : VITALiTY ( Vancouver Initiative to Add Life to Years ) Research Laboratory . Participants : Thirty-nine older adults ( mean age , 71.5 ± 0.7 years ) with diet-controlled or oral hypoglycemic-controlled type 2 diabetes , hypertension , and hypercholesterolemia . Interventions : Subjects were recruited to each of 2 groups : an aerobic group ( 3 months of vigorous aerobic exercise as defined by 80 % to 85 % of maximal heart rate ) , and a nonaerobic ( no aerobic exercise ) group . Exercise sessions were supervised by a certified exercise trainer 3 times per week . Main Outcome Measures : Baroreflex function was assessed using the spontaneous baroreflex method . Main outcome measures included BRS , BRSup , BRSdown , and & OV0312;o2max . Results : The aerobic group demonstrated an increase in BRS that was not demonstrated in the nonaerobic group ( + 60.9 ± 23.5 vs + 2.2 ± 7.9 % ; P = 0.010 ) . Conclusions : Our findings indicate that a relatively short aerobic exercise intervention can reverse functional impairments of the arterial baroreflex function in older adults at high cardiovascular risk", "The cardiovascular and behavioral adaptations associated with a 4-month program of aerobic exercise training were examined in 101 older men and women ( mean age = 67 years ) . Subjects were r and omly assigned to an Aerobic Exercise group , a Yoga and Flexibility control group , or a Waiting List control group . Prior to and following the 4-month program , subjects underwent comprehensive physiological and psychological evaluations . Physiological measures included measurement of blood pressure , lipids , bone density , and cardiorespiratory fitness including direct measurements of peak oxygen consumption ( VO2 ) and anaerobic threshold . Psychological measures included measures of mood , psychiatric symptoms , and neuropsychological functioning . This study demonstrated that 4 months of aerobic exercise training produced an overall 11.6 % improvement in peak VO2 and a 13 % increase in anaerobic threshold . In contrast , the Yoga and Waiting List control groups experienced no change in cardiorespiratory fitness . Other favorable physiological changes observed among aerobic exercise participants included lower cholesterol levels , diastolic blood pressure levels , and for subjects at risk for bone fracture , a trend toward an increase in bone mineral content . Although few significant psychological changes could be attributed to aerobic exercise training , participants in the two active treatment groups perceived themselves as improving on a number of psychological and behavioral dimensions", "PURPOSE While exercise therapy is established as an appropriate treatment for essential hypertension , its economic profile has not been fully evaluated . The purpose of this study is to evaluate cost and effectiveness in comparison with drug therapy . SUBJECTS AND METHODS The study subjects were hypertensive patients under treatment at an outpatient clinic . Fifty-seven were selected on a non-r and omized manner for exercise therapy and the same number of patients was chosen for drug therapy after matching age , sex , medication and complications . The following data were collected during three months of intervention . 1 ) Effectiveness : Change of systolic blood pressure before and after the intervention . 2 ) Cost : equipment , personnel expenses for exercise therapy and fees for health check-ups ( exercise therapy ) ; fees for consultation , laboratory examination and medications ( drug therapy ) , 3 ) Cost-effectiveness : cost per 1 mmHg systolic blood pressure reduction . We evaluated the variance of cost-effectiveness by controlling the number of program participants , personnel expenses , and equipment expenses of exercise therapy . We also simulated how the cost-effectiveness of exercise therapy would improve by modifying the number of exercise participants , personnel and equipment expenses . RESULTS The cost-effectiveness per 1 mmHg systolic blood pressure reduction was yen 11,268 for exercise therapy and yen 2,441 for drug therapy . Extending program facilities and increasing the number of participants would improve the cost-effectiveness of exercise therapy , but there were limitations to how far this could be achieved in the hospital setting . CONCLUSION Differences in cost-effectiveness between exercise and drug therapies are attributed to differences in personnel expenses . Although they could be reduced by managerial effort of the hospital to some extent , outsourcing of exercise therapy to community-based facilities should be considered", "OBJECTIVES To determine the relative effects of cobblestone mat walking , in comparison with regular walking , on physical function and blood pressure in older adults . DESIGN R and omized trial with allocation to cobblestone mat walking or conventional walking . SETTING General community in Eugene , Oregon . PARTICIPANTS One hundred eight physically inactive community-dwelling adults aged 60 to 92 ( mean age+/-st and ard deviation=77.5+/-5.0 ) free of neurological and mobility-limiting orthopedic conditions . INTERVENTION Participants were r and omized to a cobblestone mat walking condition ( n=54 ) or regular walking comparison condition ( n=54 ) and participated in 60-minute group exercise sessions three times per week for 16 consecutive weeks . MEASUREMENTS Primary endpoint measures were balance ( functional reach , static st and ing ) , physical performance ( chair st and s , 50-foot walk , Up and Go ) , and blood pressure ( systolic , diastolic ) . Secondary endpoint measures were Short Form-12 physical and mental health scores and perceptions of health-related benefits from exercise . RESULTS At the 16-week posttest , differences between the two exercise groups were found for balance measures ( P=.01 ) , chair st and s ( P<.001 ) , 50-foot walk ( P=.01 ) , and blood pressure ( P=.01 ) but not for the Up and Go test ( P=.14 ) . Although significant within-group changes were observed in both groups for the secondary outcome measures , there were no differences between intervention groups . CONCLUSION Cobblestone mat walking improved physical function and reduced blood pressure to a greater extent than conventional walking in older adults . Additional benefits of this walking program included improved health-related quality of life . This new physical activity may provide a therapeutic and health-enhancing exercise alternative for older adults", "Numerous studies have shown that treatment of the modifiable cardiovascular risk factors ( CVRF ) results in a decreased risk to suffer from stroke or myocardial infa rct ion . Despite the fact that exercise training is a potent treatment choice for CVRF , this is the first r and omized study to assess the effects of alpine skiing on CVRF in elderly skiers . Subjects ( n=42 ) were r and omized into an intervention group ( IG ; n=22 ; 12 males/10 females ; age : 66.6 ± 2.1 years ) completing 12 weeks of guided skiing or a control group ( CG ; n=20 ; 10 males/10 females ; age : 67.3 ± 4.4 years ) . CVRF were assessed before and after the intervention period . No cardiovascular event occurred within a total of 795.1 h of skiing . A significant increase in exercise capacity in IG ( ΔVO(2 max ) : + 2.0 mL/kg/min , P=0.005 ) but not in CG ( ΔVO(2 max ) : -0.1 mL/kg/min , P=0.858 ; IG vs CG : P=0.008 ) as well as a decrease in body fat mass [ IG : -2.3 % , P<0.0001 ; CG : ± 0.0 % , P=0.866 ; IG vs CG : P<0.0001 ] was achieved . Blood pressure , blood lipids , heart rate and everyday physical activity remained essentially unchanged . Alpine skiing in the elderly is safe with respect to cardiovascular events , and improves some , but not all CVRF", "Isolated systolic hypertension is common in the elderly , but decreasing systolic blood pressure ( SBP ) without lowering diastolic blood pressure ( DBP ) remains a therapeutic challenge . Although stress management training , in particular eliciting the relaxation response , reduces essential hypertension its efficacy in treating isolated systolic hypertension has not been evaluated . We conducted a double-blind , r and omized trial comparing 8 weeks of stress management , specifically relaxation response training ( 61 patients ) , versus lifestyle modification ( control , 61 patients ) . Inclusion criteria were > or=55 years , SBP 140 - 159 mm Hg , DBP < 90 mm Hg , and at least two antihypertensive medications . The primary outcome measure was change in SBP after 8 weeks . Patients who achieved SBP < 140 mm Hg and > or=5 mm Hg reduction in SBP were eligible for 8 additional weeks of training with supervised medication elimination . SBP decreased 9.4 ( st and ard deviation [ SD ] 11.4 ) and 8.8 ( SD 13.0 ) mm Hg in relaxation response and control groups , respectively ( both ps < 0.0001 ) without group difference ( p=0.75 ) . DBP decreased 1.5 ( SD 6.2 ) and 2.4 ( SD 6.9 ) mm Hg ( p=0.05 and 0.01 , respectively ) without group difference ( p=0.48 ) . Forty-four ( 44 ) in the relaxation response group and 36 in the control group were eligible for supervised antihypertensive medication elimination . After controlling for differences in characteristics at the start of medication elimination , patients in the relaxation response group were more likely to successfully eliminate an antihypertensive medication ( odds ratio 4.3 , 95 % confidence interval 1.2 - 15.9 , p=0.03 ) . Although both groups had similar reductions in SBP , significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control", "PURPOSE This study examined the effects of isometric h and grip training on resting arterial blood pressure , heart rate variability , and blood pressure variability in older adults with hypertension . METHODS Nine subjects performed four 2-min isometric h and grip contractions at 30 % of the maximum voluntary contraction force , 3 d.wk(-1 ) for 10 wk , and eight subjects served as controls . RESULTS After training , there was a significant reduction in resting systolic pressure and mean arterial pressure . In addition , power spectral analysis of heart rate variability demonstrated that the low frequency : high frequency area ratio tended to decrease . CONCLUSIONS It is concluded that isometric training at a moderate intensity elicits a hypotensive response and a simultaneous increase in vagal modulation in older adults with hypertension", "This study investigated the effects of 16-weeks of endurance exercise training ( EET ) on ambulatory blood pressure in older adults . Twenty-one men and women , 68.5 + /- 4.7 ( mean + /- SD ) years of age were r and omly assigned to an exercise group ( EG , n = 11 ) or to a control group ( CG , n = 10 ) . Subjects were normotensive ( mean resting BP 132.0 + /- 8.6/80.1 + /- 6.6 mm Hg ) , free from overt cardiovascular or renal diseases , and were taking no vasoactive or diuretic medications . Maximal oxygen uptake ( VO2max ) , body composition , resting BP , and 24-hr ambulatory systolic ( ASBP ) and diastolic ( ADBP ) blood pressures were measured in all subjects before and after the study period . The EG completed 16 weeks ( 3 , 1-hour bouts/wk ) of EET , progressing in intensity from 50 % to 85 % of maximal workload . The CG did not exercise . In the EG , although body composition and resting BP did not change ( p > 0.05 ) , VO2max increased by 14 % ( p = 0.001 ) , mean 24-hr ASBP decreased 7.9 mm Hg ( p = 0.0001 ) , and mean 24-hr ADBP decreased 3.6 mm Hg ( p = 0.002 ) . In the CG , there were no significant changes in these variables ( p > 0.05 ) . These data suggest that EET can improve both aerobic fitness and \" real-life \" blood pressures in healthy older adults and may help inhibit increases in blood pressure associated with normal aging", "OBJECTIVE To compare the effects on blood pressure of a 12-week moderate-intensity aerobic exercise program and a T'ai Chi program of light activity . DESIGN A r and omized clinical trial . SETTING A suburban clinic in the Baltimore , MD , area . PARTICIPANTS Sixty-two sedentary older adults ( 45 % black , 79 % women , aged > or = 60 years ) with systolic blood pressure 130 - 159 mm Hg and diastolic blood pressure < 95 mm Hg ( not on antihypertensive medication ) . INTERVENTION Participants were r and omized to a 12-week aerobic exercise program or a light intensity T'ai Chi program . The goal of each condition was to exercise 4 days per week , 30 minutes per day . MEASUREMENTS Blood pressure was measured during three screening visits and every 2 weeks during the intervention . Estimated maximal oxygen uptake and measures of physical activity level were determined at baseline and at the end of the intervention period . RESULTS Mean ( SD ) baseline systolic and diastolic blood pressures were 139.9 ( 9.3 ) mm Hg and 76.0 ( 7.3 ) mm Hg , respectively . For systolic blood pressure , adjusted mean ( SE ) changes during the 12-week intervention period were -8.4 ( 1.6 ) mm Hg and -7.0 ( 1.6 ) mm Hg in the aerobic exercise and T'ai Chi groups , respectively ( each within-group P < .001 ; between-group P = .56 ) . For diastolic blood pressure , corresponding changes were -3.2 ( 1.0 ) mm Hg in the aerobic exercise group and -2.4 ( 1.0 ) mm Hg in the T'ai Chi group ( each within-group P < .001 ; between-group P = .54 ) . Body weight did not change in either group . Estimated maximal aerobic capacity tended to increase in aerobic exercise ( P = .06 ) but not in T'ai Chi ( P = .24 ) . CONCLUSIONS Programs of moderate intensity aerobic exercise and light exercise may have similar effects on blood pressure in previously sedentary older individuals . If additional trials confirm these results , promoting light intensity activity could have substantial public health benefits as a means to reduce blood pressure in older aged persons", "BACKGROUND Participation in regular moderate or vigorous physical activity substantially reduces risk for all-cause and cardiovascular-disease mortality and confers other health benefits . Efforts to decrease the population prevalence of inactivity will have a greater impact if they are tailored to the needs and preferences of the community . METHODS In the Pilot Survey of the Fitness of Australians , a question naire was administered to a r and omly selected sample of 2,298 adults and included questions on the preferred sources of assistance or support to become physically active , preferred activities , and barriers to regular participation . The responses of those who were identified as insufficiently physically active ( n = 1,232 ; 53.6 % ) were examined for men and women separately and for those aged 18 to 39 , 40 to 59 , and 60 to 78 years . RESULTS The most-preferred activity was walking ( 38 and 68 % of the youngest and oldest age groups , respectively ) . The most frequently cited barriers to more-regular participation in the youngest age group were insufficient time , lack of motivation and child care responsibilities . Among those aged 60 to 78 years , injury or poor health were the most frequently cited barriers to activity . The most-preferred source of advice or assistance changed with age : more than 50 % of the oldest age group wanted advice from a health professional ( compared with 22 % of the youngest group ) and the opportunity to exercise with a group was the most preferred source of support for the youngest age group . CONCLUSIONS The physical activity-related attributes of men and women and of younger and older age groups described in this study may be used to provide more relevant and appealing options for those who might otherwise be missed by \" one-size-fits-all \" physical activity promotion strategies", "OBJECTIVE We aim ed to determine the effect of yoga on arterial function in elderly with increased pulse pressure ( PP ) . DESIGN R and omized controlled study with two parallel groups . PARTICIPANTS Elderly subjects with PP≥60 mmHg ( n=60 ) . INTERVENTIONS Yoga group ( n=30 ) was assigned for yoga training and brisk-walking ( BW ) group ( n=30 ) for brisk-walk with stretching exercise for 1h in the morning for 6 days in a week for 12 weeks . MAIN OUTCOME MEASURES Arterial stiffness measures : Brachial-ankle pulse wave velocity ( baPWV ) , Carotid-femoral pulse wave velocity ( c-f PWV ) , aortic augmentation index ( AIx@75 ) , arterial stiffness index at brachial ( bASI ) and tibial arteries ( aASI ) . Total serum nitric oxide concentration ( NOx ) as an index of endothelial function . Heart rate variability ( HRV ) measures : Low frequency and high frequency in normalized units ( LFnu , HFnu ) and LF/HF ratio . RESULTS The mean between-group change ( with 95 % CI ) in arterial stiffness : c-f PWV(m/s ) [ 1.25(0.59 - 1.89 ) ; p<0.001 ] , baPWV(m/s ) [ 1.96(0.76 - 3.16 ) , p<0.01 ] , AIx@75 [ 3.07(0.24 - 5.89 ) , p=0.066 ] , aASI [ 8.3(4.06 - 12.53 ) , p<0.001 ] ; endothelial function index : NO(μmol/L ) [ -9.03(-14.57 to -3.47 ) , p<0.001 ] ; SBP(mmHg ) [ 14.23(12.03 - 16.44 ) , p<0.001 ] , DBP(mmHg ) [ 0.1(-1.95 - 2.15 ) , p=0.38 ] , PP(mmHg ) [ 14.07(11.2 - 16.92 ) , p<0.001 ] , MAP(mmHg ) [ 4.7(3.08 - 6.32 ) , p<0.001 ] ; and cardiac autonomic function : LF(nu ) [ 4.81(1.54 - 8.08 ) , p<0.01 ] , HF(nu ) [ -4.13(-7.57 to -0.69 ) , p<0.01 ] , LF/HF ratio [ 0.84(0.3 - 1.37 ) , p<0.001 ] , indicate significant difference in effects of two intervention on arterial stiffness , endothelial function , BP and cardiac autonomic activity . There was significant change within-yoga group in vascular function , BP and autonomic function , while no significant change within-BW group was observed . CONCLUSION Our findings suggest that yoga program offered was more effective than brisk-walk in reducing arterial stiffness along with BP in elderly individuals with increased PP . Yoga can also significantly reduce sympathetic activity and improve endothelial function with enhancement in bioavailability of NO", "ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology" ]

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[ "Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort", "Fasting serum glucose level and cancer risk in Korean men and women.", "Haematopoietic cancer and medical history: a multicentre case control study", "Cancer incidence in type 2 diabetes patients - first results from a feasibility study of the D2C cohort", "Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias", "A Prospective Study of the Associations Between Treated Diabetes and Cancer Outcomes", "Medical history risk factors for non-Hodgkin's lymphoma in older women.", "History of diabetes mellitus and risk of prostate cancer in physicians.", "Physical activity, diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies", "Preliminary communication: glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: a prospective analysis from the European prospective investigation into cancer-Norfolk study.", "Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis", "Type 2 diabetes mellitus and medications for type 2 diabetes mellitus are associated with risk for and mortality from cancer in a German primary care cohort.", "Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan.", "History of Diabetes and Risk of Head and Neck Cancer: A Pooled Analysis from the International Head and Neck Cancer Epidemiology Consortium", "Glycosylated Hemoglobin and Risk of Colorectal Cancer in Men and Women, the European Prospective Investigation into Cancer and Nutrition", "Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts", "Association of diabetes with prostate cancer risk in the multiethnic cohort.", "Variation in TCF7L2 and Increased Risk of Colon Cancer", "Diabetes mellitus and subsite-specific colorectal cancer risks in the Iowa Women's Health Study.", "Risk factors for colon cancer in 150,912 postmenopausal women", "Diabetes and Risk of Prostate Cancer", "The association of diabetes with colorectal cancer risk: the Multiethnic Cohort", "The role of diabetes in hepatocellular carcinoma: a case-control study among United States veterans", "Prospective Study of Self-Reported Diabetes and Risk of Upper Gastrointestinal Cancers", "Diabetes and the risk of non-Hodgkin’s lymphoma and multiple myeloma in the European Prospective Investigation into Cancer and Nutrition", "Self reported non-insulin dependent diabetes, family history, and risk of prevalent colorectal cancer: population based, cross sectional study", "Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial", "The Impact of Type 2 Diabetes on the Development of Hepatocellular Carcinoma in Different Viral Hepatitis Statuses", "Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women.", "Dietary factors and the incidence of cancer of the urinary bladder.", "Nonradiation risk factors for thyroid cancer in the US Radiologic Technologists Study.", "Risk of Malignant Neoplasm of the Pancreas in Relation to Diabetes", "Diabetes and endometrial cancer in the Iowa women's health study.", "Type 2 diabetes and hepatocellular carcinoma: A cohort study in high prevalence area of hepatitis virus infection.", "The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients.", "Risk of malignant neoplasms of liver and biliary tract in diabetic patients with different age and sex stratifications", "A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers.", "Risk factors for urinary bladder carcinoma in postmenopausal women", "Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990-2006.", "Diabetes and Risk of Endometrial Cancer: A Population-Based Prospective Cohort Study", "Is diabetes mellitus associated with prostate cancer incidence and survival?", "Diabetes and thyroid cancer risk in the National Institutes of Health-AARP Diet and Health Study.", "Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study", "DOES BODY FAT DISTRIBUTION PROMOTE FAMILIAL AGGREGATION OF ADULT ONSET DIABETES MELLITUS AND POSTMENOPAUSAL BREAST CANCER?", "Diabetes and the risk of prostate cancer: the role of diabetes treatment and complications", "Type 2 diabetes and subsequent incidence of breast cancer in the Nurses' Health Study.", "History of diabetes mellitus and the risk of prostate cancer: the Ohsaki Cohort Study", "Diabetes mellitus and risk of colorectal cancer in the Singapore Chinese Health Study.", "Type II Diabetes Mellitus and the Incidence of Epithelial Ovarian Cancer in the Cancer Prevention Study-II Nutrition Cohort", "Diabetes mellitus, body size and bladder cancer risk in a prospective study of Swedish men.", "Anthropometrics, Physical Activity, Related Medical Conditions, and the Risk of Non-Hodgkin Lymphoma", "Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a case-control study in China.", "Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis.", "Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.", "Antidiabetes drugs correlate with decreased risk of lung cancer: a population-based observation in Taiwan.", "Cigarette smoking, elevated fasting serum glucose, and risk of pancreatic cancer in Korean men", "Prospective study reveals associations between colorectal cancer and type 2 diabetes mellitus or insulin use in men.", "Common immune-related risk factors and incident non-Hodgkin lymphoma: the multiethnic cohort.", "Association of diabetes mellitus with prostate cancer: nested case-control study (Prostate testing for cancer and treatment study)." ]

[ "Aims /hypothesisThere has been long-st and ing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development . Prospect i ve epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism , overall and as a function of lag times between marker measurements ( blood donation ) and date of tumour diagnosis . Methods Pre-diagnostic levels of HbA1c and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospect i ve Investigation into Cancer and Nutrition . Conditional logistic regression models were used to estimate ORs for pancreatic cancer . Results Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA1c levels up to an OR of 2.42 ( 95 % CI 1.33 , 4.39 highest [ ≥6.5 % , 48 mmol/mol ] vs lowest [ ≤5.4 % , 36 mmol/mol ] category ) , even for individuals with HbA1c levels within the non-diabetic range . C-peptide levels showed no significant relationship with pancreatic cancer risk , irrespective of fasting status . Analyses showed no clear trends towards increasing hyperglycaemia ( as marked by HbA1c levels ) or reduced pancreatic beta cell responsiveness ( as marked by C-peptide levels ) with decreasing time intervals from blood donation to cancer diagnosis . Conclusions /interpretationOur data on HbA1c show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA1c levels , relatively independently of obesity and insulin resistance — the classic and major risk factors for type 2 diabetes . While there is no strong difference by lag time , more data are needed on this in order to reach a firm conclusion", "CONTEXT Diabetes is a serious and costly disease that is becoming increasingly common in many countries . The role of diabetes as a cancer risk factor remains unclear . OBJECTIVE To examine the relationship between fasting serum glucose and diabetes and risk of all cancers and specific cancers in men and women in Korea . DESIGN , SETTING , AND PARTICIPANTS Ten-year prospect i ve cohort study of 1,298,385 Koreans ( 829,770 men and 468,615 women ) aged 30 to 95 years who received health insurance from the National Health Insurance Corp and had a biennial medical evaluation in 1992 - 1995 ( with follow-up for up to 10 years ) . MAIN OUTCOME MEASURES Death from cancer and registry-documented incident cancer or hospital admission for cancer . RESULTS During the 10 years of follow-up , there were 20,566 cancer deaths in men and 5907 cancer deaths in women . Using Cox proportional hazards models and controlling for smoking and alcohol use , the stratum with the highest fasting serum glucose ( > or = 140 mg/dL [ > or = 7.8 mmol/L ] ) had higher death rates from all cancers combined ( hazard ratio [ HR ] , 1.29 ; 95 % confidence interval [ CI ] , 1.22 - 1.37 in men and HR , 1.23 ; 95 % CI , 1.09 - 1.39 in women ) compared with the stratum with the lowest level ( < 90 mg/dL [ < 5.0 mmol/L ] ) . By cancer site , the association was strongest for pancreatic cancer , comparing the highest and lowest strata in men ( HR , 1.91 ; 95 % CI , 1.52 - 2.41 ) and in women ( HR , 2.05 ; 95 % CI , 1.43 - 2.93 ) . Significant associations were also found for cancers of the esophagus , liver , and colon/rectum in men and of the liver and cervix in women , and there were significant trends with glucose level for cancers of the esophagus , colon/rectum , liver , pancreas , and bile duct in men and of the liver and pancreas in women . Of the 26,473 total cancer deaths in men and women , 848 were estimated as attributable to having a fasting serum glucose level of less than 90 mg/dL. For cancer incidence , the general patterns reflected those found for mortality . For persons with a diagnosis of diabetes or a fasting serum glucose level greater than 125 mg/dL ( 6.9 mmol/L ) , risks for cancer incidence and mortality were generally elevated compared with those without diabetes . CONCLUSION In Korea , elevated fasting serum glucose levels and a diagnosis of diabetes are independent risk factors for several major cancers , and the risk tends to increase with an increased level of fasting serum glucose", "BACKGROUND Viruses ( such as Epstein-Barr virus ) and pathological conditions ( mainly involving immunosuppression ) have been shown to increase the risk of haematolymphopoietic malignancies . Other associations ( diabetes , tonsillectomy , autoimmune diseases ) have been inconsistently reported . METHODS The association between different haematolymphopoietic malignancies ( lymphomas , myelomas and leukaemias ) and the previous medical history has been studied in a population -based case-control investigation conducted in Italy , based on face to face interviews to 2669 cases and 1718 population controls ( refusal rates 10 % and 19 % , respectively ) . Controls were a r and om sample of the general population . RESULTS Previous findings were confirmed concerning the association between non-Hodgkin 's lymphoma ( NHL ) and lupus erythematosus ( odds ratio , OR=8.4 ; 95 % CI 1.6 , 45 ) , tuberculosis ( OR=1.6 ; 1.05 , 2.5 ) and hepatitis ( 1.8 ; 1.4 , 2.3 ) . An association was found also between NHL and maternal ( OR=2.8 ; 1.1 , 6.9 ) or paternal tuberculosis ( OR=1.7 ; 0.7 , 3.9 ) . Odds ratios of 4.0 ( 1.4 , 11.8 ) and 4.4 ( 1.1 , 6.6 ) were detected for the association between NHL and Hodgkin 's disease , respectively , and previous infectious mononucleosis , but recall bias can not be ruled out . No association was found with diabetes , tonsillectomy and adenoidectomy . An association with malaria at young age and “ low grade ” lymphatic malignancies is suggested . One interesting finding was the observation of four cases of poliomyelitis among NHL patients , one among Hodgkin 's disease and one among myeloid leukaemia patients , compared with none among the controls ( Fisher 's exact test for NHL and Hodgkin 's disease , p= 0.03 , one tail ) . CONCLUSIONS Some of these findings are confirmatory of previous evidence . Other observations , such as the putative role of the polio virus and of malaria are new . A unifying theory on the mechanisms by which previous medical history may increase the risk of haematolymphopoietic malignancies is still lacking", "Background A large prospect i ve study in patients with type 2 diabetes ( T2D ) , the German D2C cohort , is presently being enumerated to investigate risk factors of incident cancer in diabetic patients . Study setting A disease management program was offered , on a voluntary basis , to all T2D patients who were members of a statutory health insurance fund in Germany . This first feasibility report uses data from 26.742 T2D patients , who were 40 to 79 years old , resided in the Muenster District , and who were enrolled between June 2003 and July 2008 . Cancer cases were identified through the regional Cancer Registry . Methods Invasive cancer cases were identified using probabilistic record linkage procedures and pseudonymised personal identifiers . Censoring date was December 31 , 2008 . We included only first cancers , leaving 12.650 male and 14.092 female T2D with a total of 88.778 person-years ( py ) . We computed st and ardised incidence ratios ( SIR ) for external comparisons and we employed Cox regression models and hazard ratios ( HR ) within the cohort . Results We identified 759 first cancers among male T2D patients ( 18.7 per 1,000 py ) and 605 among females ( 12.7 per 1,000 py ) . The risk of any incident cancer in T2D was raised ( SIR = 1.14 ; 95 % confidence interval [ 1.10 - 1.21 ] ) , in particular for cancer of the liver ( SIR = 1.94 [ 1.15 - 2.94 ] ) and pancreas ( SIR = 1.45 [ 1.07 - 1.92 ] ) . SIRs decreased markedly with time after T2D diagnosis . In Cox models , adjusting for diabetes duration , body mass index and sex , insulin therapy was related to higher cancer risk ( HR = 1.25 [ 1.17 - 1.33 ] ) . No effect was seen for metformin . Discussion Our study demonstrates feasibility of record linkage between DMP and cancer registries . These first cohort results confirm previous reports . It is envisaged to enhance this cohort by inclusion of further regions of the state , expansion of the follow-up times , and collection of a more detailed medication history", "Aims /hypothesisDespite the vast body of epidemiological literature on the risk of cancer in people with diabetes , few studies have examined the pattern of cancer risk during different time windows following diabetes onset . The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset . Methods This was a population -based retrospective cohort study . The study period was 1 April 1994 to 31 March 2006 ; censoring occurred at 31 March 2006 , at death or on departure from British Columbia , Canada . Using linked health data bases , we identified incident cohorts with and without diabetes , who were matched by age , sex and index year . Following a minimum 2-year cancer washout period , first site-specific cancers were identified prospect ively in both cohorts . Results Within 3 months following diabetes onset , participants with diabetes had significantly increased risks of colorectal , lung , liver , cervical , endometrial , ovarian , pancreatic and prostate cancers . After the initial 3-month period , the risks for colorectal ( HR 1.15 , 95 % CI 1.05 , 1.25 ) , liver ( HR 2.53 , 95 % CI 1.93 , 3.31 ) and endometrial ( HR 1.58 , 95 % CI 1.28 , 1.94 ) cancers remained significantly elevated compared with those without diabetes . The diabetes cohort remained at increased risk of pancreatic cancer in later years , but followed a different pattern : HR 3.71 at 3 months–1 year , 2.94 at 1–2 years , 1.78 at 2–3 years and 1.65 at 3–10 years ( p value for all < 0.01 ) . After an initial period of elevated risk , men with type 2 diabetes subsequently had a decreased risk of prostate cancer ( HR 0.82 , 95 % CI 0.76 , 0.88 ) . Conclusions /interpretationPeople with type 2 diabetes are at increased risk of select cancers ; this risk is particularly elevated at the time of diabetes onset , which is likely to be due to increased ascertainment", "OBJECTIVE To quantify the association of treated diabetes with cancer incidence and cancer mortality as well as cancer case fatality and all-cause mortality in adults who subsequently develop cancer and to calculate attributable fractions due to diabetes on various cancer outcomes . RESEARCH DESIGN AND METHODS Prospect i ve data on 599 diabetic and 17,681 nondiabetic adults from the CLUE II ( Give Us a Clue to Cancer and Heart Disease ) cohort in Washington County , Maryl and , were analyzed . Diabetes was defined by self-reported use of diabetes medications at baseline . Cancer incidence was ascertained using county and state cancer registries . Mortality data were obtained from death certificates . RESULTS From 1989 to 2006 , 116 diabetic and 2,365 nondiabetic adults developed cancer , corresponding to age-adjusted incidence of 13.25 and 10.58 per 1,000 person-years , respectively . Adjusting for age , sex , education , BMI , smoking , hypertension treatment , and high cholesterol treatment using Cox proportional hazards regression , diabetes was associated with a higher risk of incident cancer ( hazard ratio 1.22 [ 95 % CI 0.98–1.53 ] ) and cancer mortality ( 1.36 [ 1.02–1.81 ] ) . In individuals who developed cancer , adults with diabetes had a higher risk of cancer case fatality ( 1.34 [ 1.002–1.79 ] ) and all-cause mortality ( 1.61 [ 1.29–2.01 ] ) . For colorectal , breast , and prostate cancers , the attributable fractions result ing from diabetes were larger for cancer fatality and mortality than cancer incidence . CONCLUSIONS In this prospect i ve cohort , diabetes appears to exert a greater influence downstream on the risk of mortality in people with cancer than on upstream risk of incident cancer", "BACKGROUND It has been suggested that certain medical conditions and drug exposures might suppress the immune system and increase the risk of developing non-Hodgkin 's lymphoma ( NHL ) . PURPOSE We investigated whether specific medical conditions and drug exposures were associated with the risk of NHL in a cohort of older women who were enrolled in the Iowa Women 's Health Study . METHODS A cohort of 41837 women , 55 - 69 years of age at baseline , was followed prospect ively for the development of cancer from 1986 through 1992 . These women had completed a baseline question naire in January 1986 that inquired about the occurrence and age at onset of specific medical conditions , about family history of cancer , and about the use of selected medications . Follow-up question naires were mailed to the women in 1987 , 1989 , and 1992 . Incident cancers and deaths were ascertained through linkages to state and national data bases . For most analyses , women with a self-reported history of cancer at baseline ( n = 3903 ) were excluded . Relative risks ( RRs ) and 95 % confidence intervals ( CIs ) , adjusted for age or for age and other variables , were used as a measure of the association between NHL and medical history factors . Reported P values are two-sided . RESULTS One hundred fourteen incident cases of NHL were identified in the cohort during follow-up . A history of adult-onset diabetes mellitus ( i.e. , first diagnosed after the age of 30 years ) was associated with an increased risk of developing NHL ( age-adjusted RR = 2.18 ; 95 % CI = 1.22 - 3.90 ) . In addition , there was an association between the duration of adult-onset diabetes and increasing risk of NHL ( P for trend = .004 ) , with an age-adjusted RR of 2.90 ( 95 % CI = 1.07 - 7.90 ) for women with a diagnosis of diabetes for 15 or more years compared with women with no diagnosis of diabetes . Women with a history of blood transfusion were also at increased risk for the development of NHL ( age-adjusted RR = 1.95 ; 95 % CI = 1.33 - 2.85 ) . The risk estimates for diabetes and transfusion history were independent of each other and were not changed substantially after adjustment for other risk factors . History of a previous cancer ( excluding hematopoietic and lymphatic cancers ) was associated with an increased risk of NHL ( age-adjusted RR = 1.92 ; 95 % CI = 1.21 - 3.06 ) ; this risk estimate was attenuated somewhat after adjustment for a history of diabetes , transfusion history , and other major risk factors ( RR = 1.66 ; 95 % CI = 1.02 - 2.69 ) . No statistically significant associations were found between NHL and a history of chronic colitis , nonestrogen steroid use , use of exogenous estrogens , or use of thyroid medications . CONCLUSIONS AND IMPLICATION S A history of adult-onset diabetes mellitus , blood transfusion , and a history of cancer ( or its treatment ) appear to be independent risk factors for NHL in older women", "Some studies have suggested that diabetes mellitus may decrease the risk of prostate cancer because of lower insulin levels . To further investigate the relation between diabetes and prostate cancer , a nested case-control study was conducted within the US Physicians ' Health Study . Cases ( n = 1,110 ) had been diagnosed with prostate cancer , confirmed on medical record review , during follow-up in 1982 - 1995 . Controls ( n = 1,110 ) were selected r and omly from men free of prostate cancer and were matched on age and date of r and omization . Information on personal history of diabetes and other diseases , lifestyle habits , and body weight/height was self-reported . Logistic regression analysis showed that the odds ratio for prostate cancer was 0.64 ( 95 % confidence interval ( CI ) : 0.43 , 0.95 ) for men with diabetes , relative to those without the disease , after adjustment for potential confounders . Odds ratio estimates were 0.63 ( 95 % CI : 0.35 , 1.14 ) , 0.77 ( 95 % CI : 0.35 , 1.72 ) , 0.59 ( 95 % CI : 0.21 , 1.66 ) , and 0.59 ( 95 % CI : 0.27 , 1.27 ) for diabetes diagnosed 1 - 5 , 6 - 10 , 11 - 15 , and > or = 16 years prior to prostate cancer diagnosis ( p for trend < 0.05 ) . Adjusted odds ratios were 1.44 ( 95 % CI : 0.34 , 6.17 ) for stage A prostate cancer and 0.48 ( 95 % CI : 0.28 , 0.83 ) for stages B-D. Results suggest that history of diabetes may be associated with a decreased risk of prostate cancer , especially late-stage tumors", "Purpose Although many studies have linked obesity with increased risk of thyroid cancer , few have investigated the role of obesity-related lifestyle characteristics and medical conditions in the etiology of this disease . We examined the associations of self-reported physical activity and diabetes history with thyroid cancer risk in a large pooled analysis of prospect i ve cohort studies . Methods Data from five prospect i ve studies in the U.S. ( n = 362,342 men , 312,149 women ) were coded using st and ardized exposure , covariate , and outcome definitions . Hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for thyroid cancer were estimated using age as the time metric and adjusting for sex , education , race , marital status , cigarette smoking , body mass index , alcohol intake , and cohort . Effect modification by other risk factors ( e.g. , age , sex , and body mass index ) and differences by cancer subtype ( e.g. , papillary , follicular ) were also examined . Results Over follow-up ( median = 10.5 years ) , 308 men and 510 women were diagnosed with a first primary thyroid cancer . Overall , subjects reporting the greatest amount of physical activity had an increased risk of the disease ( HR = 1.18 , 95 % CI:1.00–1.39 ) ; however , this association was restricted to participants who were overweight/obese ( ≥25 kg/m2 ; HR = 1.34 , 95 % CI:1.09–1.64 ) as opposed to normal-weight ( < 25 kg/m2 ; HR = 0.92 , 95 % CI:0.69–1.22 ; P-interaction = 0.03 ) . We found no overall association between self-reported history of diabetes and thyroid cancer risk ( HR = 1.08 , 95 % CI:0.83–1.40 ) . Conclusion Neither physical inactivity nor diabetes history was associated with increased risk of thyroid cancer . While it may have been a chance finding , the possible increased risk associated with greater physical activity warrants further investigation", "BACKGROUND Increasing evidence suggests that abnormal glucose metabolism may be associated with increased risk of colorectal cancer . METHODS We examined the relationship between known diabetes and glycated hemoglobin ( HbA1c ) concentrations measured in 1995 to 1997 and subsequent incident colorectal cancer after 6 years follow-up in 9,605 men and women ages 45 to 79 years in the European Prospect i ve Investigation into Cancer-Norfolk Study . RESULTS Among individuals not known to have cancer at the baseline survey , there were 67 incident colorectal cancers . HbA1c concentration appeared continuously related to incident colorectal cancer risk , with lowest rates observed in those with HbA1c below 5 % . Known diabetes was also associated with incident colorectal cancer , with relative risk ( RR ) 3.18 and 95 % confidence interval ( CI ) 1.36 - 7.40 ( P < 0.01 ) adjusting for age and sex and RR 2.78 and 95 % CI 1.10 - 7.00 ( P = 0.03 ) adjusting for age , sex , body mass index , and smoking compared with those without known diabetes . The RR ( 95 % CI ) of incident colorectal cancer per 1 % absolute increase in HbA1c was 1.34 ( 1.12 - 1.59 ; P < 0.001 ) . HbA1c concentrations appeared to explain the increased colorectal cancer risk associated with diabetes in multivariate models . CONCLUSIONS Known diabetes was associated with approximately 3-fold risk of colorectal cancer in this analysis ; this increased risk was largely explained by HbA1c concentrations , which appears continuously related to colorectal cancer risk across the population distribution", "A sedentary lifestyle , obesity , and a Westernized diet have been implicated in the aetiology of both colorectal cancer and non-insulin dependent diabetes mellitus , leading to the hypothesis that hyperinsulinaemia may promote colorectal cancer . We prospect ively examined the association between colorectal cancer risk and factors related to insulin resistance and hyperinsulinaemia , including BMI , physical activity , diabetes mellitus , and blood glucose , in a cohort of 75 219 Norwegian men and women . Information on incident cases of colorectal cancer was made available from the Norwegian Cancer Registry . ReportedPvalues are two-sided . During 12 years of follow up , 730 cases of colorectal cancer were registered . In men , but not in women , we found a negative association with leisure-time physical activity ( Pfor trend = 0.002 ) , with an age-adjusted RR for the highest versus the lowest category of activity of 0.54 ( 95 % CI = 0.37–0.79 ) . Women , but not men , with a history of diabetes were at increased risk of colorectal cancer ( age-adjusted RR = 1.55 ; 95 % CI = 1.04–2.31 ) , as were women with non-fasting blood glucose ≥8.0 mmol l–1(age-adjusted RR = 1.98 ; 95 % CI = 1.31–2.98 ) compared with glucose < 8.0 mmol l–1 . Overall , we found no association between BMI and risk of colorectal cancer . Additional adjustment including each of the main variables , marital status , and educational attainment did not material ly change the results . We conclude that the inverse association between leisure-time physical activity and colorectal cancer in men , and the positive association between diabetes , blood glucose , and colorectal cancer in women , at least in part , support the hypothesis that insulin may act as a tumour promoter in colorectal carcinogenesis . © 2001 Cancer Research Campaign", "There is growing evidence that patients with type 2 diabetes mellitus have increased cancer risk . We examined the association between diabetes , cancer , and cancer-related mortality and hypothesized that insulin sensitizers lower cancer-related mortality . Participants in the Diabetes Cardiovascular Risk and Evaluation : Targets and Essential Data for Commitment of Treatment study , a nationwide cross-sectional and prospect i ve epidemiological study , were recruited from German primary care practice s. In the cross-sectional study , subjects with type 2 diabetes mellitus had a higher prevalence of malignancies ( 66/1308 , 5.1 % ) compared to nondiabetic subjects ( 185/6211 , 3.0 % ) ( odds ratio , 1.64 ; 95 % confidence interval , 1.12 - 2.41 ) before and after adjustment for age , sex , hemoglobin A(1c ) , smoking status , and body mass index . Patients on metformin had a lower prevalence of malignancies , comparable with that among nondiabetic patients , whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders ; inclusion of metformin in these regimens decreased the prevalence of malignancies . In the prospect i ve analyses , diabetic patients in general and diabetic patients treated with insulin ( either as monotherapy or in combination with other treatments ) had a 2- and 4-fold , respectively , higher mortality rate than nondiabetic patients , even after adjustment for potential confounders ( incidence of cancer deaths in patients with type 2 diabetes mellitus [ 2.6 % ] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [ 1.2 % ] ) . Our results suggest that diabetes and medications for diabetes , with the exception of the insulin sensitizer metformin , increase cancer risk and mortality", "BACKGROUND An association between diabetes mellitus ( DM ) and cancer has long been speculated , but no conclusive evidence has been obtained . METHODS We prospect ively examined the association between a history of DM and subsequent risk of cancer in the Japan Public Health Center-Based Prospect i ve Study . A total of 97 771 general Japanese persons ( 46 548 men and 51 223 women ) aged 40 to 69 years who responded to the baseline question naire , from January 1990 to December 1994 , were followed up for cancer incidence through December 31 , 2003 . At baseline , 6.7 % of men and 3.1 % of women had a history of DM . RESULTS A total of 6462 cases of newly diagnosed cancer were identified . In men , a 27 % increase in the risk of total cancer incidence was observed in those with a history of DM ( n = 3907 [ 366 with DM ] ; hazard ratio [ HR ] , 1.27 ; 95 % confidence interval [ CI ] , 1.14 - 1.42 ) . The HR was especially high for those with cancer of the liver ( n = 312 [ 52 with DM ] ; HR , 2.24 ; 95 % CI , 1.64 - 3.04 ) , pancreas ( n = 118 [ 16 with DM ] ; HR , 1.85 ; 95 % CI , 1.07 - 3.20 ) , and kidney ( n = 99 [ 13 with DM ] ; HR , 1.92 ; 95 % CI , 1.06 - 3.46 ) . We also observed a moderately increased risk of colon cancer ( n = 491 [ 46 with DM ] ; HR , 1.36 ; 95 % CI , 1.00 - 1.85 ) and of stomach cancer with borderline significance ( n = 977 [ 87 with DM ] ; HR , 1.23 ; 95 % CI , 0.98 - 1.54 ) . In women , a borderline significant increase in risk was observed for the incidence of total cancer ( n = 2555 [ 104 with DM ] ; HR , 1.21 ; 95 % CI , 0.99 - 1.47 ) , while statistical significance was observed for the incidence of stomach cancer ( n = 362 [ 20 with DM ] ; HR , 1.61 ; 95 % CI , 1.02 - 2.54 ) and liver cancer ( n = 120 [ 10 with DM ] ; HR , 1.94 ; 95 % CI , 1.00 - 3.73 ) and borderline significance was observed for the incidence of ovarian cancer ( n = 74 [ 5 with DM ] ; HR , 2.42 ; 95 % CI , 0.96 - 6.09 ) . CONCLUSION Patients with DM drawn from the general Japanese population may be at increased risk of total cancer and of cancer in specific sites", "Background : A history of diabetes is associated with an increased risk of several types of cancers . Whether diabetes is a risk factor for head and neck cancer ( HNC ) has received little attention . Methods : We pooled data from 12 case – control studies including 6,448 cases and 13,747 controls , and estimated OR and 95 % CI for the associations between diabetes and HNC , adjusted for age , education level , sex , race/ethnicity , study center , cigarette smoking , alcohol use , and body mass index . Results : We observed a weak association between diabetes and the incidence of HNC overall ( OR , 1.09 ; 95 % CI : 0.95–1.24 ) . However , we observed a modest association among never smokers ( OR , 1.59 ; 95 % CI : 1.22–2.07 ) , and no association among ever smokers ( OR , 0.96 ; 95 % CI : 0.83–1.11 ) ; likelihood ratio test for interaction P = 0.001 . Conclusion : A history of diabetes was weakly associated with HNC overall , but we observed evidence of effect modification by smoking status , with a positive association among those who never smoked cigarettes . Impact : This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population . Prospect i ve studies incorporating biomarkers are needed to improve our underst and ing of the relationship between diabetes and HNC risk , possibly providing new strategies in the prevention of HNC . Cancer Epidemiol Biomarkers Prev ; 21(2 ) ; 294–304 . © 2011 AACR", "Although large-scale prospect i ve cohort studies have related hyperglycemia to increased risk of cancer overall , studies specifically on colorectal cancer have been generally small . We investigated the association between prediagnostic levels of glycosylated hemoglobin ( HbA1c ) , a marker for average glucose level in blood , and colorectal cancer risk in a case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition cohort . One thous and and twenty-six incident colorectal cancer cases ( 561 men and 465 women ) and 1,026 matched controls were eligible for the study . Multivariate conditional logistic regression was used to estimate odds ratios ( ORS ) adjusted for possible confounders . Increasing HbA1c percentages were statistically significantly associated with a mild increase in colorectal cancer risk in the whole population [ OR , 1.10 ; 95 % confidence interval ( CI ) , 1.01,1.19 for a 10 % increase in HbA1c ] . In women , increasing HbA1c percentages were associated with a statistically significant increase in colorectal cancer risk ( OR , 1.16 ; 95 % CI , 1.01 , 1.32 for a 10 % increase in HbA1c ) and with a borderline statistically significant increase in rectum cancer ( OR , 1.22 ; 95 % CI , 0.99,1.50 for a 10 % increase in HbA1c ) . No significant association with cancer risk was observed in men . The results of the current study suggest a mild implication of hyperglycemia in colorectal cancer , which seems more important in women than in men , and more for cancer of the rectum than of the colon . ( Cancer Epidemiol Biomarkers Prev 2008;17(11):3108–15", "We examined the associations of body mass index ( BMI ) , waist circumference , a history of diabetes , and cigarette smoking with risk of pancreatic cancer among 37 147 women and 45 906 men followed up during 560 666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men ; 136 incident cases of pancreatic cancer were diagnosed . The multivariate rate ratio ( RR ) of pancreatic cancer for obese women and men ( BMI ⩾30 kg/m2 ) was 1.81 ( 95 % CI : 1.04–3.15 ) compared to those with a BMI of 20–25 kg/m2 . For a difference of 20 cm ( about two st and ard deviations ) in waist circumference , the multivariate RRs were 1.32 ( 95 % CI : 0.73–2.37 ) among women and 1.74 ( 95 % CI : 1.00–3.01 ) among men . Pancreatic cancer risk was associated with history of diabetes ( multivariate RR : 1.88 ; 95 % CI : 1.09–3.26 ) and cigarette smoking ( multivariate RR for current compared with never smokers : 3.06 ; 95 % CI : 1.99–4.72 ) . Current smokers of ⩾40 pack-years had a five-fold elevated risk compared with never smokers . Risk among past smokers approached the RR for never smokers within 5–10 years following smoking cessation . Findings from this prospect i ve study support positive relationships of overall obesity , abdominal adiposity , diabetes and smoking with risk of pancreatic cancer", "Among men of European ancestry , diabetics have a lower risk of prostate cancer than do nondiabetics . The biologic basis of this association is unknown . The authors have examined whether the association is robust across population s in a population -based prospect i ve study . The analysis included 5,941 prostate cancer cases identified over a 12-year period ( 1993 - 2005 ) among 86,303 European-American , African-American , Latino , Japanese-American , and Native Hawaiian men from the Multiethnic Cohort . The association between diabetes and prostate-specific antigen ( PSA ) levels ( n = 2,874 ) and PSA screening frequencies ( n = 46,970 ) was also examined . Diabetics had significantly lower risk of prostate cancer than did nondiabetics ( relative risk = 0.81 , 95 % confidence interval ( CI ) : 0.74 , 0.87 ; P < 0.001 ) , with relative risks ranging from 0.65 ( 95 % CI : 0.50 , 0.84 ; P = 0.001 ) among European Americans to 0.89 ( 95 % CI : 0.77 , 1.03 ; P = 0.13 ) among African Americans . Mean PSA levels were significantly lower in diabetics than in nondiabetics ( mean PSA levels , 1.07 and 1.28 , respectively ; P = 0.003 ) as were PSA screening frequencies ( 44.7 % vs. 48.6 % ; P < 0.001 ) ; however , this difference could explain only a small portion ( approximately 20 % ) of the inverse association between these diseases . Diabetes is a protective factor for prostate cancer across population s , suggesting shared risk factors that influence a common mechanism", "OBJECTIVE —The purpose of this study was to determine whether a variation in the transcription factor 7-like 2 ( TCF7L2 ) gene , which influences diabetes risk , is associated with incidence of cancers . RESEARCH DESIGN AND METHODS —We related diabetes and TCF7L2 variation with occurrence of several common cancers in a prospect i ve cohort study of 13,117 middle-aged adults initially free of cancer in 1987–1989 . We assessed five single nucleotide polymorphisms ( SNPs ) in TCF7L2 including the putative SNP ( rs7903146 ) for diabetes . We identified incident cancers through 2000 via cancer registries , supplemented by hospital records . RESULTS —Diabetes was associated marginally inversely with incidence of prostate cancer but not with incidence of colorectal , colon , lung , or breast cancer . The T allele of rs7903146 ( frequency 30 % ) was associated with increased risk of colorectal cancer and , more specifically , colon cancer , with adjusted hazard ratios ( 95 % CI ) of 1.0 for CC , 1.25 ( 0.85–1.83 ) for CT , and 2.15 ( 1.27–3.64 ) for TT genotypes ( Ptrend = 0.009 ) . TCF7L2 variation also was associated with lung cancer incidence in whites but not blacks , but residual confounding by smoking may be present . CONCLUSIONS —Subjects who were initially cancer-free and carrying certain genetic variants of TCF7L2 , most notably the T allele of rs7903146 , have an increased risk of colon cancer . This association appears to be an independent gene effect not explained by diabetes . Because the T allele of rs7903146 is common , if a causal link is established , this variant could account for a sizable proportion ( ∼17 % here ) of cases of colon cancer in the general population", "OBJECTIVE Controversy remains regarding the association between type 2 diabetes mellitus ( DM ) and colorectal cancer ( CRC ) risk . To clarify and extend the existing data , we prospect ively evaluated the association between self-reported type 2 DM ( onset at > 30 years of age ) and incident CRC , overall and by anatomic subsite , among postmenopausal women in the Iowa Women 's Health Study ( n = 35,230 ) . METHODS After 14 years of follow-up , a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry . DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up . CRC risks were estimated using Cox proportional hazards regression models . RESULTS After adjusting for age , body mass index and other potential confounding variables , the relative risk ( RR ) for women with DM versus women without DM was modestly increased at 1.4 [ 95 % confidence interval ( 95 % CI ) , 1.1 - 1.8 ] . By anatomic subsite , the RR for proximal colon cancer was statistically significantly increased ( RR , 1.9 ; 95 % CI , 1.3 - 2.6 ) , whereas the RRs for distal colon ( RR , 1.1 ; 95 % CI , 0.6 - 1.8 ) and rectal cancer ( RR , 0.8 ; 95 % CI , 0.4 - 1.6 ) were not statistically different from unity . Analyses that included DM ascertained at baseline and follow-up yielded similar results . CONCLUSION In this large , prospect i ve study of postmenopausal women , the association between DM and incident CRC was found to be subsite specific . If confirmed by others , this finding implies that CRC prevention strategies among type 2 DM patients should include examination of the proximal colon", "Background Prospect i ve data from the Women ’s Health Initiative were analyzed to evaluate more than 800 possible risk factors for an association with colon cancer in postmenopausal women . Methods Data included 150,912 postmenopausal women between the ages of 50 and 79 . The Cox proportional hazard regression analysis was used to identify risk factors independently associated with the development of colon cancer during a median follow-up time of 8 years . Results A total of 1,210 women developed colon cancer and 282 developed rectal cancer . Eleven risk factors were independently associated with an increased risk of colon cancer at the p < 0.001 level . In decreasing order of associated χ2 values , they were age , waist girth ( especially for subjects without diabetes ) , use of hormone therapy at baseline ( protective ) , years smoked , arthritis ( protective presumably because of medications used for treatment ) , relatives with colorectal cancer , lower hematocrit levels , fatigue , diabetes , less use of sleep medication , and cholecystectomy . Of the 11 factors , three were significantly associated with an increased risk of rectal cancer : age , waist , and not taking hormone therapy . Conclusions The results provide additional support for the importance of waist girth , hormone therapy , smoking , NSAID use , diabetes , and cholecystectomy as risk factors for colon cancer . Some factors previously identified as influencing risk ( exercise and black race ) did not have a strong independent association with colon cancer in this analysis", "OBJECTIVE The link between diabetes and prostate cancer is rarely studied in Asians . RESEARCH DESIGN AND METHODS The trend of age-st and ardized prostate cancer incidence in 1995–2006 in the Taiwanese general population was calculated . A r and om sample of 1,000,000 subjects covered by the National Health Insurance in 2005 was recruited . A total of 494,630 men for all ages and 204,741 men ≥40 years old and without prostate cancer at the beginning of 2003 were followed to the end of 2005 . Cumulative incidence and risk ratio between diabetic and nondiabetic men were calculated . Logistic regression estimated the adjusted odds ratios for risk factors . RESULTS The trend of prostate cancer incidence increased significantly ( P < 0.0001 ) . The cumulative incidence markedly increased with age in either the diabetic or nondiabetic men . The respective risk ratio ( 95 % CI ) for all ages and age 40–64 , 65–74 , and ≥75 years was 5.83 ( 5.10–6.66 ) , 2.09 ( 1.60–2.74 ) , 1.35 ( 1.07–1.71 ) , and 1.39 ( 1.12–1.71 ) . In logistic regression for all ages or for age ≥40 years , age , diabetes , nephropathy , ischemic heart disease , dyslipidemia , living region , and occupation were significantly associated with increased risk , but medications including insulin and oral antidiabetic agents were not . CONCLUSIONS Prostate cancer incidence is increasing in Taiwan . A positive link between diabetes and prostate cancer is observed , which is more remarkable in the youngest age of 40–64 years . The association between prostate cancer and comorbidities commonly seen in diabetic patients suggests a more complicated scenario in the link between prostate cancer and diabetes at different disease stages", "Background : Diabetics have been found to have a greater risk of colorectal cancer than non-diabetics . Methods : We examined whether this relationship differed by ethnic group , cancer site or tumour stage in a population -based prospect i ve cohort , including 3549 incident colorectal cancer cases identified over a 13-year period ( 1993–2006 ) among 199 143 European American , African American , Native Hawaiian , Japanese American and Latino men and women in the Multiethnic Cohort . Results : Diabetics overall had a significantly greater risk of colorectal cancer than did non-diabetics ( relative risk (RR)=1.19 , 95 % confidence interval (CI)=1.09–1.29 , P-value (P)<0.001 ) . Positive associations were observed for colon cancer , cancers of both the right and left colon , and cancers diagnosed at a localised and regional/distant stage . The association with colorectal cancer risk was significantly modified by smoking status ( PInteraction=0.0044 ) , with the RR being higher in never smokers ( RR=1.32 , 95 % CI=1.15–1.53 , P<0.001 ) than past ( RR=1.19 , 95 % CI=1.05–1.34 , P=0.007 ) and current smokers ( RR=0.90 , 95 % CI=0.70–1.15 , P=0.40 ) . Conclusion : These findings provide strong support for the hypothesis that diabetes is a risk factor for colorectal cancer", "OBJECTIVE : Diabetes mellitus ( DM ) has been reported to increase the risk of hepatocellular carcinoma ( HCC ) . We carried out a case-control study to examine the role of DM while controlling for several known risk factors of HCC . METHODS : All hospitalized patients with primary liver cancer ( PLC ) during 1997–1999 were identified in the computerized data base of the Department of Veterans Affairs , the Patient Treatment File . Controls without cancer were r and omly assigned from the Patient Treatment File during the same time period . The inpatient and outpatient files were search ed for several conditions including DM , hepatitis C virus ( HCV ) , hepatitis B virus ( HBV ) , alcoholic cirrhosis , autoimmune hepatitis , hemochromatosis , and nonspecific cirrhosis . Adjusted odds ratios ( OR ) were calculated in a multivariable logistic regression model . RESULTS : We identified 823 patients with PLC and 3459 controls . The case group was older ( 62 yr [ ±10 ] vs 60 [ ±11 ] , p < 0.0001 ) , had more men ( 99 % vs 97 % , 0.0004 ) , and a greater frequency of nonwhites ( 66 % vs 71 % , 0.0009 ) compared with controls . However , HCV- and HBV-infected patients were younger among cases than controls . Risk factors that were significantly more frequent among PLC cases included HCV ( 34 % vs 5 % , p < 0.0001 ) , HBV ( 11 % vs 2 % , p < 0.0001 ) , alcoholic cirrhosis ( 47 % vs 6 % , p < 0.0001 ) , hemochromatosis ( 2 % vs 0.3 % , p < 0.0001 ) , autoimmune hepatitis ( 5 % vs 0.5 % , p < 0.0001 ) , and diabetes ( 33 % vs 30 % , p = 0.059 ) . In the multivariable logistic regression , diabetes was associated with a significant increase in the adjusted OR of PLC ( 1.57 , 1.08–2.28 , p = 0.02 ) in the presence of HCV , HBV , or alcoholic cirrhosis . Without markers of chronic liver disease , the adjusted OR for diabetes and PLC was not significantly increased ( 1.08 , 0.86–1.18 , p = 0.4 ) . There was an increase in the HCV adjusted OR ( 17.27 , 95 % CI = 11.98–24.89 ) and HBV ( 9.22 , 95 % CI = 4.52–18.80 ) after adjusting for the younger age of HCV- and HBV-infected cases . The combined presence of HCV and alcoholic cirrhosis further increases the risk with an adjusted OR of 79.21 ( 60.29–103.41 ) . The population attributable fraction for HCV among hospitalized veterans was 44.8 % , whereas that of alcoholic cirrhosis was 51 % . CONCLUSION : DM increased the risk of PLC only in the presence of other risk factors such as hepatitis C or B or alcoholic cirrhosis . Hepatitis C infection and alcoholic cirrhosis account for most of PLC among veterans", "Background : Although gastric noncardia adenocarcinoma ( GNCA ) incidence rates in the United States have decreased , the rates of gastric cardia adenocarcinoma ( GCA ) and esophageal adenocarcinoma ( EADC ) have increased . Obesity increases the risks of GCA and EADC , and the associations may be partially mediated by insulin resistance . A few case-control studies have shown an association between diabetes and an increased risk of EADC . Methods : We prospect ively examined the association between diabetes and upper gastrointestinal ( UGI ) cancers in a cohort of 469,448 people in the United States , ages 50 to 71 at baseline . Cox proportional hazards regression was used to estimate the HR and 95 % CI for diabetes and UGI cancers , controlling for multiple potential confounders , including body mass index ( BMI ) . Results : We observed no association of self-reported diabetes with risk of EADC , HR ( 95 % CI ) = 0.98 ( 0.73–1.31 ) , esophageal squamous cell carcinoma ( ESCC ) , HR ( 95 % CI ) = 1.02 ( 0.60–1.74 ) , or GNCA , HR ( 95 % CI ) = 0.98 ( 0.70–1.37 ) . However , diabetes was significantly associated with an increased risk of GCA , HR ( 95 % CI ) = 1.89 ( 1.43–2.50 ) . The significant association between diabetes and risk of GCA remained after adjustment for BMI , HR ( 95 % CI ) = 1.70 ( 1.28–2.26 ) and did not differ by BMI strata ( Pinteraction = 0.83 ) . The significant association was unchanged when restricting to only overweight subjects ( BMI 25 to ≤30 ) , HR ( 95 % CI ) = 1.83 ( 1.18–2.85 ) . Conclusions : We found a significant association between self-reported diabetes and increased risk of GCA . Impact : Our results suggest that the metabolic and hormonal changes related to diabetes may play a role in the etiology of GCA independently from BMI . Cancer Epidemiol Biomarkers Prev ; 20(5 ) ; 954–61 . © 2011 AACR", "Background Non-Hodgkin ’s lymphomas are a heterogeneous group of neoplasms arising from the lymphopoietic system including a wide range of subtypes of either B-cell or T-cell lymphomas . The few established risk factors for the development of these neoplasms include viral infections and immunological abnormalities , but their etiology remains largely unknown . Evidence suggests that certain medical conditions may be linked , through immunosuppression , to the risk of non-Hodgkin ’s lymphoma . Multiple myeloma is a neoplasm of plasma cells that accounts for approximately 15 % of lymphopoietic cancers . Increases in the incidence of non-Hodgkin ’s lymphoma and multiple myeloma in the past implicate environmental factors as potential causal agents . Design and Methods In the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) , 1,213 histologically confirmed incident cases of non-Hodgkin ’s lymphoma and multiple myeloma ( 594 men ; 619 women ) were identified during a follow-up of 8.5 years . Cox proportional hazard models were used to explore the association between self-reported diabetes , diagnosed after 30 years of age , and the risk of non-Hodgkin ’s lymphoma overall and multiple myeloma and various lymphoma subtypes . Results We found no association between a personal history of diabetes and the risk of non-Hodgkin ’s lymphoma overall in men ( HR : 1.28 , 95 % CI : 0.89–1.84 ) , in women ( HR : 0.71 , 95 % CI : 0.41– 1.24 ) , or in men and women combined ( HR : 1.09 , 95 % CI : 0.80–1.47 ) . Among the B-non-Hodgkin ’s lymphoma subtypes , we observed a statistically significant increased risk of B-cell chronic lymphocytic leukemia ( HR : 2.0 , 95 % CI : 1.04–3.86 ) in men , but not in women ( HR : 1.07 , 95 % CI : 0.33–3.43 ) . Conclusions This prospect i ve study did not provide evidence for a role of self-reported diabetes in the etiology of non-Hodgkin ’s lymphoma overall or multiple myeloma . We found an increased risk of B-cell chronic lymphocytic leukemia among men with diabetes , but not among women . We hypothesize that diabetes may not play a causal role in the etiology of B-cell chronic lymphocytic leukemia , though the underlying pathogenic mechanisms of both disorders may include shared genetic , host and /or environmental susceptibility factors", "Several studies have shown positive associations between non-insulin dependent diabetes ( NIDDM ) and incidence of colorectal cancer.1 - 3 This relation , as well as the marked similarity of dietary and lifestyle risk factors for the two conditions , has led investigators to propose that hyperinsulinaemia may be the underlying link between NIDDM and colorectal cancer.3 It is thought that raised insulin levels , either indirectly or directly , may promote the growth of colorectal tumours.1 3 Thus people with an inherited susceptibility to colorectal cancer and who also have NIDDM may be expected to be at even greater risk of colorectal cancer than from either risk factor alone . One measure of inherited susceptibility is family history of disease — an established risk factor for colorectal cancer.4 5 We therefore examined the relation between NIDDM , family history and risk of prevalent colorectal cancer among middle aged and older British adults using data from a large population based study . Participants for this analysis were recruited between 1993 and 1997 as part of the East Anglian component of the European Prospect i ve Investigation into Cancer ( EPIC – Norfolk ) . The detailed", "Objective A history of diabetes has been fairly consistently related to a reduced prostate cancer risk , but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass , variables closely related to glucose metabolism . Methods We prospect ively examined the diabetes – prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial . Results During 8.9 years follow-up , we ascertained 2,058 incident prostate cancer cases . Diabetes history was related to decreased risk of total prostate cancer ( RR = 0.80 , 95 % CI = 0.68–0.95 ) . The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease ( i.e. , the combination of low grade ( Gleason sum < 8) and low stage ( clinical stages I or II ) ; RR = 0.75 ; 95 % CI = 0.62–0.91 ) . In contrast , no association was noted between diabetes and aggressive disease ( i.e. , high grade or high stage ( Gleason sum ≥8 or clinical stages III or IV ) ; RR = 1.04 , 95 % CI = 0.74–1.45 ) . In further analyses , the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean ( RR = 1.64 , 95 % CI = 0.87–3.07 ; BMI < 25 kg/m2 ) and it was positive for men who were the most physically active ( RR = 1.63 ; 95 % CI = 1.07–2.62 ; 3 + hours vigorous activity/week ) . By comparison , no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts ( p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity , respectively ) . Conclusion In this study , diabetes showed divergent relations with prostate cancer by tumor aggressiveness . Specifically , diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer . Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI", "Background : The risk of type 2 diabetes on the development of hepatocellular carcinoma remains inconclusive in different hepatitis statuses . Methods : We prospect ively followed a community-based cohort with 5,929 persons in southern Taiwan from January 1997 through December 2004 , made up of 4,117 seronegative , 982 anti – hepatitis C virus – positive [ HCV(+ ) ] , 696 hepatitis B surface antigen – positive [ HBsAg(+ ) ] , and 134 coinfected persons . Before the study , 546 participants had developed diabetes . Hepatocellular carcinoma diagnoses were from the National Cancer Registry . Results : After 50,899 person-years of follow-up , 111 individuals had developed hepatocellular carcinoma . The highest risk of hepatocellular carcinoma , compared with seronegative individuals without diabetes , was in anti-HCV(+ ) individuals with diabetes [ incidence rate ratio ( IRR ) , 76.0 ] , then coinfected ( IRR , 46.0 ) , anti-HCV(+ ) without diabetes ( IRR , 26.1 ) , HBsAg(+ ) with diabetes ( IRR , 21.4 ) , and seronegative with diabetes ( IRR , 7.2 ; P < 0.001 ) . Anti-HCV(+ ) ( n = 132 ) and seronegative individuals ( n = 352 ) with diabetes had a higher cumulative incidence rate of hepatocellular carcinoma than those without diabetes ( log-rank test , P < 0.001 ) . Multivariate Cox proportional hazards analysis showed that gender , age , body mass index ≥30 , HBsAg(+ ) [ hazards ratio ( HR ) , 12.6 ] , anti-HCV(+ ) ( HR , 18.8 ) , coinfection ( HR , 25.9 ) , and diabetes [ HR , 2.7 ; 95 % confidence interval ( 95 % CI ) , 1.7 - 4.3 ] were independent predictors of hepatocellular carcinoma ( P < 0.05 ) . After stratifying hepatitis status in multivariate Cox analysis , diabetes was significant for seronegative ( HR , 5.4 ; 95 % CI , 1.7 - 17.1 ) and anti-HCV(+ ) individuals ( HR , 3.1 ; 95 % CI , 1.7 - 5.4 ) . Body mass index ≥30 was significant for HBsAg(+ ) individuals ( HR , 3.3 ; 95 % CI , 1.3 - 8.1 ) . Conclusion : Type 2 diabetes is a strong independent predictor of hepatocellular carcinoma in anti-HCV(+ ) and seronegative individuals but not in HBsAg(+ ) individuals . ( Cancer Epidemiol Biomarkers Prev 2009;18(7):2054–60", "BACKGROUND The remarkable similarity of lifestyle and environmental risk factors for type 2 ( non-insulin-dependent ) diabetes mellitus and colon cancer has led to the hypothesis that diabetes may increase the risk of this cancer . We prospect ively examined the relationship between diabetes and risk of colorectal cancer in a cohort of 118403 women aged 30 through 55 years who were without previously diagnosed cancer at baseline in 1976 . METHODS The women , who were enrolled in the Nurses ' Health Study , were assessed for history of diabetes at baseline and during follow-up by use of biennial question naires . Self-reported diabetes was vali date d by information obtained from a supplemental question naire on symptoms and treatment and was confirmed by medical record review in a sample of the participants . Incident cases of colorectal cancer were ascertained through medical record review . All reported P values are two-sided . RESULTS During 18 years of follow-up ( 201061 person-years ) , we documented 892 new cases of colorectal cancer . After adjustment for age , body mass index ( weight in kg/height in m2 ) , physical activity , and other covariates , relative risks ( RRs ) were 1.43 ( 95 % confidence interval [ CI ] = 1.10 - 1.87 ; P = .009 ) for colorectal cancer , 1.49 ( 95 % CI = 1.09 - 2.06 ; P = .01 ) for colon cancer , 1.11 ( 95 % CI = 0.56 - 2.21 ; P = .76 ) for rectal cancer , 1.56 ( 95 % CI = 1.07 - 2.28 ; P = .02 ) for advanced colorectal cancer , and 2.39 ( 95 % CI = 1.46 - 3.92 ; P = .0005 ) for fatal colorectal cancer . CONCLUSION Our data provide support for the hypothesis that diabetes is associated with an increased risk of colorectal cancer in women", "A case-control study of diet and bladder cancer was conducted during 1979 - 1982 in Edmonton , Calgary , Toronto , and Kingston , Canada . A total of 826 histologically verified cancer cases were individually matched by age , sex , and area of residence to 792 r and omly selected population controls . Subjects were interviewed concerning their histories of exposure to a number of dietary factors , including table-top artificial sweeteners , low calorie foods and drinks , beverages containing caffeine or ethanol , and certain other food items . Also , subjects provided information on their past medical , occupational , and residential histories , in addition to their exposures to tobacco and other life-style factors . For the analysis , conditional logistic regression methods were used . Under adjustment for cumulative lifetime amount of cigarette smoking , the dietary factors , with little exception , were not associated with significant alteration of risk for bladder cancer . In particular , ever regular use of artificial sweeteners did not appear to be associated with increased risk , either among men ( odds ratio = 0.95 , p = 0.70 ) or among women ( odds ratio = 1.15 , p = 0.53 ) . However , daily intake of cholesterol , calculated from reported frequencies of consumption of nine relevant food items , suggested a mild increase in risk ; the odds ratio estimate of trend was 1.07/100 mg average daily intake ( i.e. , 1.07(5.5 ) = 1.45 for 550 mg cholesterol per day , as might be consumed in one egg ; p = 0.009 ) . A history of diabetes mellitus of onset after age 20 years also seemed to be associated with increased risk of bladder cancer ( odds ratio = 1.65 , p = 0.019 ) , but this increase did not appear to be the result of use of insulin or other medications , or use of artificial sweeteners or low calorie foods . Thus , this study tends to confirm reports of a lack of association between use of artificial sweeteners and subsequent risk of bladder cancer", "The incidence of thyroid cancer has been rapidly increasing in the United States , but few risk factors have been established . The authors prospect ively examined the associations of self-reported medical history , anthropometric factors , and behavioral factors with thyroid cancer risk among 90,713 US radiologic technologists ( 69,506 women and 21,207 men ) followed from 1983 through 2006 . Incident thyroid cancers in 242 women and 40 men were reported . Elevated risks were observed for women with benign thyroid conditions ( hazard ratio ( HR ) = 2.35 , 95 % confidence interval ( CI ) : 1.73 , 3.20 ) , benign breast disease ( HR = 1.56 , 95 % CI : 1.08 , 2.26 ) , asthma ( HR = 1.68 , 95 % CI : 1.00 , 2.83 ) , and body mass index > or = 35.0 versus 18.5 - 24.9 kg/m(2 ) ( HR = 1.74 , 95 % CI : 1.03 , 2.94 ; P-trend = 0.04 ) . Current smoking was inversely associated with thyroid cancer risk ( HR = 0.54 ) . No clear associations emerged for reproductive factors , other medical conditions , alcohol intake , or physical activity . Despite few thyroid cancers in men , men with benign thyroid conditions had a significantly increased risk of thyroid cancer ( HR = 4.65 , 95 % CI : 1.62 , 13.34 ) , and results for other risk factors were similar to those for women . Consistent with prior studies , obesity and benign thyroid conditions increased and current smoking decreased the risk of thyroid cancer . The novel findings for benign breast disease and asthma warrant further investigation", "OBJECTIVE We prospect ively assessed the age- and sex-specific incidence and relative risk of malignant neoplasm of the pancreas in Taiwan ’s diabetic population . RESEARCH DESIGN AND METHODS A total of 615,532 diabetic patients and 614,871 age- and sex-matched control subjects were linked to inpatient cl aims ( 2000–2006 ) to identify the admissions for malignant neoplasm of the pancreas ( ICD-9 : 157 ) . The Cox proportional hazards regression model was used to estimate the age- and sex-specific relative risk of pancreatic neoplasm . RESULTS Compared with the control group , the diabetic patients had a significantly increased risk of pancreatic cancer ( hazard ratio [ HR ] 1.54 [ 95 % CI 1.39–1.71 ] ) . The higher and significant age-specific HRs were observed in diabetic men ( 1.91 ) and women ( 1.80 ) aged 45–65 years . CONCLUSIONS Middle-aged diabetic men and women were associated with the most increased risk of malignant neoplasm of the pancreas", "Diabetes has been associated with increased risk of endometrial cancer in some epidemiological studies . Body mass index ( BMI ) and other measures of obesity have been associated positively with both diabetes and endometrial cancer . It is not clear whether or not the association of diabetes with endometrial cancer is explained entirely by obesity . Thus , we sought to test the hypothesis that diabetes is not associated with endometrial cancer independent of obesity . We examined the association between self-reported diabetes ( onset at > 30 years of age ) and incident endometrial cancer in a prospect i ve cohort study of 24,664 postmenopausal women in Iowa . Over 12 years of follow-up , 346 cases occurred among the cohort at risk . Data were analyzed using proportional hazards regression models . Diabetes was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up . After adjustment for BMI , waist : hip ratio , and other covariates , the relative risk ( RR ) for women with diabetes versus women without diabetes was 1.43 [ 95 % confidence interval ( CI ) , 0.98 - 2.1 ] . The diabetes association was confined to women in the upper two BMI quintiles ( RR , 1.47 ; 95 % CI , 0.98 - 2.20 ) , but a formal test of interaction was not statistically significant . Analyses that included diabetes ascertained at baseline and at follow-up gave similar results ; the diabetes-associated RR in the higher BMI strata was 1.64 ( 95 % CI , 1.16 - 2.31 ) . We conclude that after adjustment for other risk factors , diabetes is associated with a modestly increased risk for endometrial cancer among women in this cohort", "This study aim ed to eluci date the relationship of type 2 diabetes , other known risk factors , and primary hepatocellular carcinoma ( HCC ) in countries with a high prevalence of hepatitis infection . We followed a prospect i ve cohort of 54,979 subjects who participated in the Keelung Community-Based Integrated Screening program between 1999 and 2002 . A total of 5,732 subjects with type 2 diabetes cases were identified at enrollment on the basis of fasting blood glucose level , and a total of 138 confirmed HCC cases were identified either through two-stage liver cancer screening or linkage with the National Cancer Registry . The independent effect of type 2 diabetes on the incidence of HCC and the interaction between type 2 diabetes and hepatitis infection or lipids profile were assessed using the Cox proportional hazards regression model . After controlling for age , sex , hepatitis B virus ( HBV ) , hepatitis C virus ( HCV ) , smoking , and alcohol consumption , the association between type 2 diabetes and incidence of HCC ( excluding 33 prevalent cases identified at enrollment ) was modified by HCV status and cholesterol level . The associations were only statistically significant ( adjusted hazard ratio [ HR ] = 2.08 [ 1.03 - 4.18 ] ) for being HCV negative and for having hypercholesterolemia ( adjusted HR = 2.81 [ 1.20 - 6.55 ] ) . These statistically significant findings remained even excluding cases of diabetes newly diagnosed at enrollment . In conclusion , in an area with a high prevalence of hepatitis virus infection , type 2 diabetes increases the risk of developing HCC in those who are HCV negative or have a high level of total cholesterol", "Studies have shown an association between diabetes and cancer in Western countries ; but this , as well as the influence of associated metabolic factors , must be confirmed by a prospect i ve study in other population groups . This study aim ed to investigate whether the strong association of cancer and diabetes is independent from the influence of hypertension , dyslipidemia , and gout in the Taiwanese population . A total of 985,815 study subjects were identified from the National Health Insurance in 1997 and followed up from 1998 to 2009 . The demographic characteristics between patients with diabetes and cancer , including age , sex , hypertension , dyslipidemia , and gout , were analyzed using the χ(2 ) test . Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risks of cancer . A total of 104,343 diabetic patients were followed up from 1998 to 2009 . After adjusting for sex , age , hypertension , dyslipidemia , and gout , the incidences of cancer at any site and in the liver , colon , lungs , and prostate in diabetic patients were independently higher , with risk ratios of 1.56 ( 95 % confidence interval [ CI ] , 1.43 - 1.71 ) , 1.67 ( 95 % CI , 1.39 - 2.01 ) , 1.75 ( 95 % CI , 1.49 - 2.06 ) , 1.54 ( 95 % CI , 1.26 - 1.88 ) , and 1.56 ( 95 % CI , 1.19 - 2.04 ) , respectively . Only breast cancer did not show any clinical significance . There was an increased incidence of cancer at any site in the diabetic patients compared with nondiabetic subjects . The most common cancers were liver , colon , lung , breast , and prostate cancer ; and except for breast cancer , their incidences increased independently of hypertension , dyslipidemia , and gout in patients with diabetes", "We prospect ively investigated 615,532 diabetic patients and 614,871 age‐matched and sex‐matched control subjects selected from National Health Insurance cl aims for malignant neoplasms of liver and biliary tract ( International Statistical Classification of Diseases and Related Health Problems , 9th edition , codes 155 and 156 , respectively ) between 2000 and 2006 . The person‐year approach with Poisson assumption was used to estimate the hazard rates . We also evaluated the age‐specific and sex‐specific relative risks of these two malignancies in relation to diabetes with Cox proportional hazard regression model with adjustment for potential confounders . The overall hazard rate of malignant neoplasm of the liver was 32.76 and 17.41 per 10,000 patient‐years , respectively , for diabetic men and women ; the corresponding figures for biliary tract neoplasm were much lower at 1.42 and 1.60 per 10,000 patient‐years . Compared with control subjects , diabetic patients had a two‐fold increased risk of malignant neoplasm of the liver , but this risk was attenuated by adjusting for selected clinical risk factors ( hazard ratio [ HR ] 1.21 ; 95 % confidence interval [ CI ] 1.17‐1.25 ) . Additionally , diabetic patients were associated with increased risk of biliary neoplasms with an approximate magnitude of 20%‐30 % , but the HR was attenuated and became insignificant after adjustment for clinical risk factors ( HR 1.07 ; 95 % CI 0.95‐1.21 ) . Diabetic patients with cirrhosis had the highest relative risk of liver neoplasm ( HR 85.25 ; 95 % CI 76.84‐94.58 ) , whereas those with cholangitis had the highest risk of biliary tract neoplasm ( HR 70.30 ; 95 % CI 51.95‐95.12 ) compared with control subjects without any clinical risk factors . Conclusion : This population ‐based study confirms the association of diabetes with liver neoplasm and suggests that diabetic patients with certain clinical risk factors should be educated for strict adherence of liver neoplasm screening . ( HEPATOLOGY 2010", "Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer . Anthropometric measures ( height , weight , and body mass index ( weight (kg)/height (m)(2 ) ) and metabolic abnormalities associated with insulin resistance syndrome ( IRS ) ( abnormalities in measured blood pressure , high density lipoprotein ( HDL ) cholesterol , and total cholesterol ) were prospect ively evaluated for associations with incident colon ( n = 227 ) , rectal ( n = 183 ) , and colorectal ( n = 410 ) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study . Cox proportional hazards models were used to calculate hazard ratios and 95 % confidence intervals . In comparison with the lowest quintile , the highest quintile of body mass index was significantly associated with colorectal cancer ( hazard ratio ( HR ) = 1.70 , 95 % confidence interval ( CI ) : 1.01 , 2.85 ; p-trend = 0.01 ) , particularly colon cancer . Subjects with a cluster of three IRS-related conditions ( hypertension , body mass index > /=25 kg/m(2 ) , and HDL cholesterol level < 40 mg/dl ( < 1.55 mmol/liter ) ) , compared with those with fewer conditions , had a significantly increased risk of colorectal cancer ( HR = 1.40 , 95 % CI : 1.12 , 1.74 ) , particularly colon cancer ( HR = 1.58 , 95 % CI : 1.18 , 2.10 ) , but not rectal cancer . These results support the hypothesis that the significant association observed between IRS-defining metabolic abnormalities and colorectal cancer is determined primarily by adiposity", "We evaluated prospect ively the association of smoking and other potential risk factors with bladder carcinoma incidence in postmenopausal women .", "Diabetes is a risk factor for many cancers ; chronic hyperglycemia is hypothesized to be , in part , explanatory . We evaluated the association between glycated hemoglobin , a time-integrated glycemia measure , and cancer incidence and mortality in nondiabetic and diabetic men and women . We conducted a prospect i ve study of 12,792 cancer-free participants attending the second visit ( 1990 - 1992 ) of the Atherosclerosis Risk in Communities ( ARIC ) Study . We measured glycated hemoglobin in whole-blood sample s using HPLC . Incident cancers were ascertained from registries and hospital records through 2006 . We estimated multivariable-adjusted hazard ratios ( HR ) of cancer incidence and mortality for nondiabetic participants with values ≥ 5.7 % ( elevated ) , nondiabetic participants with < 5.0 % ( low ) and diabetic participants all compared with nondiabetic participants with 5.0 - 5.6 % ( normal ) . We ascertained 2,349 incident cancer cases and 887 cancer deaths . Compared with nondiabetic women with normal glycated hemoglobin , nondiabetic women with elevated values had an increased risk of cancer incidence ( HR:1.24 ; 95 % CI:1.07,1.44 ) and mortality ( HR:1.58 ; 95 % CI:1.23,2.05 ) as did diabetic women ( incidence , HR:1.30 ; 95 % CI:1.06,1.60 , mortality , HR:1.96 ; 95 % CI:1.40,2.76 ) . Nondiabetic women with low values also had increased risk . Diabetic women with good glycemic control ( < 7.0 % ) had a lower cancer risk than those with higher values . Glycated hemoglobin in nondiabetic and diabetic men , and diabetes were not statistically significantly associated with total cancer risk . Our findings support the hypothesis that chronic hyperglycemia , even in the nondiabetic range , increases cancer risk in women . Maintaining normal glycated hemoglobin overall , and good glycemic control among diabetic adults , may reduce the burden of cancer , especially in women", "Although there is accumulating evidence that hyperinsulinemia in the context of insulin resistance is associated with carcinogenesis , only one prospect i ve study of endometrial cancer incidence , in relation to diabetes , addressed this issue and showed no significant positive association . No previous study has investigated whether physical activity can modify the association between diabetes and endometrial cancer . We examined the association between diabetes and incidence of endometrial cancer and the potential effect modification by obesity and physical activity in the Swedish Mammography Cohort , a prospect i ve cohort of 36,773 women , including 225 incident endometrial adenocarcinoma cases . After adjustments , the relative risk ( RR ) for endometrial cancer among women with diabetes comparing with nondiabetic women was 1.94 [ 95 % confidence interval ( 95 % CI ) , 1.23 - 3.08 ] . Among obese diabetics , the RR was 6.39 ( 95 % CI , 3.28 - 12.06 ) compared with nonobese nondiabetic women . Among diabetics with low physical activity , the RR for endometrial cancer was 2.80 ( 95 % CI , 1.62 - 4.85 ) compared with physically active nondiabetic women . Obese diabetics with low physical activity had a RR of 9.61 ( 95 % CI , 4.66 - 19.83 ) compared with normal weight nondiabetic women with high physical activity . Diabetes was associated with a 2-fold increased risk , and combination of diabetes with obesity and low physical activity was associated with a further increased risk for endometrial cancer . Interventions to reduce body weight and increase physical activity may have important implication s in terms of prevention of endometrial cancer and future management of diabetic subjects . ( Cancer Epidemiol Biomarkers Prev 2007;16(2):268–72", "Results of two recent prospect i ve incidence studies have suggested that certain subgroups of men with diabetes mellitus may be protected from developing prostate cancer . Two earlier studies , however , concluded that diabetes increased the risk of mortality from prostate cancer . With hundreds of thous and s of male respondents , the 1959 - 1972 Cancer Prevention Study provided a unique opportunity to explore whether men with diabetes were more likely to develop prostate cancer during a 13-year follow-up period than were men without diabetes . After adjusting for factors associated with prostate cancer in previous studies , we found little association between diabetes at baseline and prostate cancer incidence [ incidence density ratio ( IDR ) = 1.05 ; 95 % confidence interval ( CI ) = 0.81 - 1.36 ] . Men who had diabetes mellitus for 5 or more years , however , had a higher incidence of prostate cancer than did men without diabetes ( IDR = 1.56 ; 95 % CI = 1.02 - 2.38 ) . Among all study participants who were diagnosed with prostate cancer , men with diabetes were only slightly more likely to die from prostate cancer than were men without diabetes ( IDR = 1.11 ; 95 % CI = 0.76 - 1.62 )", "BACKGROUND We hypothesized that diabetes may play a role in thyroid cancer risk due to the parallel secular rise in diabetes prevalence and morbidity in the United States , the higher prevalence of thyroid disorders among diabetics compared with the general population , and the potential roles of metabolic syndrome , obesity , and diabetes as precipitating factors in cancer development . METHODS We assessed the association between self-reported diabetes and the risk of differentiated thyroid cancer in the NIH-AARP Diet and Health Study , a prospect i ve cohort of 200,556 women and 295,992 men , 50 - 71 years of age , in 1995 - 1996 . Diabetes status and information on potential confounders was ascertained using a self-administered question naire . During an average of 10 years of follow-up , 585 thyroid cancer cases were identified . Cox proportional hazards models were used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for thyroid cancer and thyroid cancer subtypes in men and women according to diabetes status . RESULTS Nine percent of the total baseline cohort reported a history of diabetes ( 7 % of women , 10 % of men ) . A nonsignificant 25 % increase in thyroid cancer risk ( HR = 1.25 ; 95 % CI : 0.95 - 1.64 ) was associated with diabetes . Among women , the risk was significantly increased ( HR = 1.46 , 95 % CI : 1.01 - 2.10 ) . The risk was not elevated among men ( HR = 1.04 , 95 % CI : 0.69 - 1.58 ) . In this cohort , diabetic women with differentiated thyroid cancer were at somewhat higher risk of follicular thyroid cancer ( HR = 1.92 ; 95 % CI : 0.86 - 4.27 ) than papillary thyroid cancer ( HR = 1.25 ; 95 % CI : 0.80 - 1.97 ) . CONCLUSION This study lends support to the hypothesis that diabetes increases the risk of differentiated thyroid cancer", "Background : Diabetes has been associated with an increased risk of hepatocellular carcinoma ( HCC ) in studies of referred patients . This is the first population based case control study in the USA to examine this association while adjusting for other major risk factors related to HCC . Methods : We used the Surveillance Epidemiology and End- Results Program (SEER)-Medicare linked data base to identify patients aged 65 years and older diagnosed with HCC and r and omly selected non-cancer controls between 1994 and 1999 . Only cases and controls with continuous Medicare enrolment for three years prior to the index date were examined . Inpatient and outpatient cl aims files were search ed for diagnostic codes indicative of diabetes , hepatitis C virus ( HCV ) , hepatitis B virus ( HBV ) , alcoholic liver disease , and haemochromatosis . HCC patients without these conditions were categorised as idiopathic . Unadjusted and adjusted odds ratios were calculated in logistic regression analyses . Results : We identified 2061 HCC patients and 6183 non-cancer controls . Compared with non-cancer controls , patients with HCC were male ( 66 % v 36 % ) and non-White ( 34 % v 18 % ) . The proportion of HCC patients with diabetes ( 43 % ) was significantly greater than non-cancer controls ( 19 % ) . In multiple logistic regression analyses that adjusted for demographics features and other HCC risk factors ( HCV , HBV , alcoholic liver disease , and haemochromatosis ) , diabetes was associated with a threefold increase in the risk of HCC . In a subset of patients without these major risk factors , the adjusted odds ratio for diabetes declined but remained significant ( adjusted odds ratio 2.87 ( 95 % confidence interval 2.49–3.30 ) ) . A significant positive interaction between HCV and diabetes was detected ( p<0.0001 ) . Similar findings persisted in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis . Conclusions : Diabetes is associated with a 2–3-fold increase in the risk of HCC , regardless of the presence of other major HCC risk factors . Findings from this population based study suggest that diabetes is an independent risk factor for HCC", "Noninsulin-dependent diabetes mellitus and postmenopausal breast cancer share a number of risk factors , including obesity , increased waist-to-hip ratio , and a positive family history . If risk for these diseases is mediated through a familial tendency for abdominal obesity , then one might expect to see familial clustering of both diseases . We analyzed data from a prospect i ve cohort study of 41,837 Iowa women age 55–69 years . Diabetes was not associated with incidence of breast cancer [ relative risk ( RR ) = 0.97 ] . The association between family history of breast cancer and breast cancer incidence , however , was slightly modified by individual history of diabetes : a positive family history of breast cancer in the absence of baseline diabetes was associated with a relative risk of 1.36 [ 95 % confidence interval ( CI ) = 1.08–1.70 ] , whereas the presence of both factors was associated with a RR of 1.87 ( 95 % CI = 0.93–3.76 ) . Adjustment for waist-to-hip ratio greatly diminished this difference . Conversely , a family history of breast cancer was associated with a RR of 5-year diabetes mortality of 1.94 ( 95 % CI = 1.17–3.24 ) that persisted after stratification by tertile of waist-to-hip ratio . No clear association of family history of breast cancer and waist-to-hip ratio for self-reported diabetes incidence was evident . These data are indicative of a complex interrelation between waist-to-hip ratio , familial predisposition , diabetes , and breast cancer", "Epidemiologic evidence suggests diabetic men have a slightly lower prostate cancer risk than non-diabetic men . We examined this association in a prospect i ve cohort study of 35 239 men , 50–76 years old , in Washington State who completed a baseline question naire between 2000 and 2002 . Incident prostate cancers as of 31 December 2004 were identified through the SEER registry . Diabetic men had a slightly lower risk of prostate cancer than non-diabetic men ( hazard ratio ( HR ) 0.83 , 95 % confidence interval ( CI ) 0.64–1.07 ) . Insulin users overall and insulin users with diabetic complications had decreased risks , compared to non-diabetic men ( HR 0.49 , 95 % CI 0.26–0.92 ) and ( HR 0.36 , 95 % CI 0.15–0.87 ) , respectively . Oral medication use for diabetes was not associated with prostate cancer . Insulin is likely a marker of severity of diabetes . Future studies of this association should consider diabetes type , treatment , severity , complications and biomarkers", "OBJECTIVE Hyperinsulinemia may promote mammary carcinogenesis . Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes . We prospect ively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses ' Health Study . RESEARCH DESIGN AND METHODS A total of 116,488 female nurses who were 30 - 55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer , verified by medical records and pathology reports . RESULTS During 2.3 million person-years of follow-up , we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer . Women with type 2 diabetes had a modestly elevated incidence of breast cancer ( hazard ratio [ HR ] = 1.17 ; 95 % CI 1.01 - 1.35 ) compared with women without diabetes , independent of age , obesity , family history of breast cancer , history of benign breast disease , reproductive factors , physical activity , and alcohol consumption . This association was apparent among postmenopausal women ( 1.16 ; 0.98 - 1.62 ) but not premenopausal women ( 0.83 ; 0.48 - 1.42 ) . The association was predominant among women with estrogen receptor-positive breast cancer ( 1.22 ; 1.01 - 1.47 ) . CONCLUSIONS Women with type 2 diabetes may have a slightly increased risk of breast cancer", "Objective The association between diabetes mellitus and the risk of prostate cancer has been tested in previous prospect i ve cohort studies in western population s. However , no evidence from cohort studies is available for Asian population s , whose lifestyle is very different from that of westerners . Methods The authors examined the relationship between diabetes mellitus and the risk of prostate cancer in the Ohsaki cohort followed from 1995 to 2003 , in which 230 new cases of prostate cancer were identified among 22,458 Japanese men . Baseline information including diabetes mellitus status was collected using a self-administered question naire . The Cox proportional hazards regression model was used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Results Although a history of diabetes mellitus was not associated with the risk of total prostate cancer in this population , after stratification based on the clinical stage of prostate cancer , patients with diabetes mellitus showed a higher risk of advanced prostate cancer with a multivariate adjusted HR = 1.89 ( 95 % CI : 1.02–3.50 ) . The relationship remained robust when we excluded from the analysis cases arising in the first 2 years . Conclusion This population -based prospect i ve cohort study indicates that a history of diabetes mellitus is associated with an increased incidence of advanced prostate cancer", "The incidence of colorectal cancer is highest in population s that consume an energy-dense diet , have low intakes of vegetables and fruit , or lead a sedentary lifestyle . These factors may influence colorectal carcinogenesis via insulin pathways . We examined whether diabetes mellitus was associated with colorectal cancer in Singapore Chinese , whose body type and lifestyle profiles are distinct from those of Western population s. Between April 1993 and December 1998 , 63,257 Singapore Chinese men and women aged 45 to 74 years were enrolled in a prospect i ve study of diet and cancer . Each subject provided dietary , medical , and lifestyle information through an in-person interview . As of December 31 , 2002 , 636 incident colorectal cancer cases had been diagnosed . A history of physician-diagnosed diabetes was statistically significantly associated with colorectal cancer risk in both men ( relative risk [ RR ] = 1.5 , 95 % confidence interval [ CI ] = 1.2 to 2.1 ) and women ( RR = 1.4 , 95 % CI = 1.0 to 1.9 ) . In stratified analyses , this association remained statistically significant among the subset of diabetics with high total calorie intake and low physical activity levels . Our results support the hypothesis that hyperinsulinemia may play a role in colorectal carcinogenesis , even in a relatively lean population", "Background : Despite consistent associations of type II diabetes mellitus with hormonally related cancers such as breast and endometrium , the relation between type II diabetes mellitus and ovarian cancer risk is unclear . Methods : Associations of type II diabetes mellitus status , duration , and insulin use with epithelial ovarian cancer overall , and with serous and nonserous histologic subtypes were examined in the Cancer Prevention Study -II Nutrition Cohort , a prospect i ve study of U.S. men and women predominantly aged 50 years and older . Between 1992 and 2007 , 524 incident epithelial ovarian cancer cases were identified among 63,440 postmenopausal women . Multivariable-adjusted relative risks ( RR ) and 95 % confidence intervals ( CI ) were computed using extended Cox regression to up date diabetes status and bilateral oophorectomy status during follow-up . Results : Type II diabetes mellitus status ( RR = 1.05 ; 95 % CI , 0.75–1.46 ) and duration were not associated with epithelial ovarian cancer risk . Although not statistically significantly different ( Pdifference = 0.39 ) , the RR was higher for type II diabetes mellitus with insulin use ( RR = 1.28 ; 95 % CI , 0.74–2.24 ) than for type II diabetes mellitus without insulin use ( RR = 0.96 ; 95 % CI , 0.64–1.43 ) . Diabetes seemed to be more strongly associated with nonserous ( RR = 1.41 ; 95 % CI , 0.70–2.85 ) than serous ( RR = 0.71 ; 95 % CI , 0.41–1.23 ) histologic subtypes . Conclusions : Type II diabetes mellitus was not associated with risk of epithelial ovarian cancer , although higher risks with nonserous subtypes and among insulin users can not be ruled out . Impact : Larger studies are needed to clarify associations of type II diabetes mellitus with or without insulin use with risk of ovarian cancer overall and by histologic subtypes . Cancer Epidemiol Biomarkers Prev ; 21(11 ) ; 2000–5 . © 2012 AACR", "Epidemiologic studies on diabetes and body size in relation to risk of bladder cancer have yielded inconsistent results . We examined prospect ively the associations between a history of diabetes , height , weight , body mass index and waist circumference , and the incidence of bladder cancer in the Cohort of Swedish Men , a prospect i ve study of 45,906 men aged 45 - 79 years at baseline . During follow-up from 1998 through December 2007 , 414 incident cases of bladder cancer were ascertained . A history of diabetes was not associated with risk of bladder cancer ( multivariate rate ratio=1.16 ; 95 % confidence interval=0.81 - 1.64 ) . Similarly , no associations were observed for height , weight , body mass index or waist circumference . These findings in men do not support a role for diabetes , height or excess body mass in the aetiology of bladder cancer", "Background : Recent reports suggest that obesity , or conditions associated with obesity , might be risk factors for non-Hodgkin lymphoma ( NHL ) , a cancer with dramatically increasing incidence in western countries over the last several decades . Physical inactivity increases the risk of obesity and of type 2 diabetes , but there are few data on the association of physical activity with risk of NHL . Methods : We evaluated these factors in a population -based case – control study conducted in Detroit , Iowa , Los Angeles , and Seattle from 1998 to 2000 . Incident HIV-negative NHL cases aged 20–74 years were rapidly reported in each area ( n = 1321 ) . Controls were identified through r and om digit dialing and Medicare files , and were frequency matched to cases on sex , age , race , and study site ( n = 1057 ) . Risk factor data were collected by in-person interviews and self-administered question naires . Unconditional logistic regression was used to estimate the odds ratio ( OR ) and 95 % confidence intervals ( CI ) , adjusted for age , sex , race and study center . Results : High body mass index ( OR = 1.73 for 35 + versus < 25 kg/m2 ; 95 % CI 1.15–2.59 ) and history of gallstones ( OR = 1.95 , 95 % CI 1.11–3.40 ) were positively associated with diffuse NHL , but were not associated with follicular or all NHL combined . Height was positively associated with risk of all NHL combined ( OR = 1.38 for > 70 versus < 65 inches ; 95 % CI 0.98–1.94 ) , and positive associations were apparent for both diffuse and follicular NHL . Non-occupational physical activity was inversely associated with risk of all NHL combined ( ORs with increasing level : 1 , 0.75 , 0.71 , 0.55 , 0.68 ; p-trend = 0.04 ) and for diffuse and follicular NHL . We observed no association of total energy intake , type 2 diabetes , or hypertension with risk of NHL . In a multivariable model to predict risk of diffuse NHL , BMI ( OR = 2.15 for 35 + versus < 25 kg/m2 ; 95 % CI 1.09–4.25 ) and height ( OR = 1.63 for 71 + versus < 65 inches ; 95 % CI 0.75–3.57 ) were positively associated with risk while physical activity was weakly and inversely associated risk ( ORs with increasing level : 1 , 0.76 , 0.72 , 0.78 , 0.82 ; p-trend = 0.9 ) . Conclusion : BMI and history of gallstones were positively associated with risk of diffuse NHL , supporting a role for obesity in this NHL subtype . Height was positively associated with NHL risk across subtypes , and suggests a role for early life nutrition in NHL risk . Non-occupational physical activity was only weakly and inversely associated with NHL risk after adjustment for obesity , height and alcohol use", "BACKGROUND / AIMS The risk factors for cholangiocarcinoma are incompletely defined in China , especially for intrahepatic cholangiocarcinoma ( ICC ) . We evaluated the risk factors for both ICC and extrahepatic cholangiocarcinoma ( ECC ) . METHODS A case-control study in which cases were cholangiocarcinoma patients referred to Peking Union Medical College Hospital ( PUMCH ) between 1998 and 2008 and controls were healthy individuals . Controls were r and omly selected from an existing data base of healthy individuals at the Health Screening Center of PUMCH . Data on liver disease , family history , diabetes , smoking and drinking were collected by a retrospective review of the patients ' records and health examination reports or by interview . RESULTS A total of 190 patients ( 61 ICC ; 129 ECC ) and 380 age- and sex-matched controls were enrolled . HBsAg ( P<0.001 ) and anti-HBc without HBsAg ( P=0.001 ) were significantly related to ICC . The adjusted odds ratios ( OR ) and 95 % confidence intervals ( CI ) were 18.1 ( 95 % CI : 7.5 - 44.0 ) and 3.6 ( 95 % CI : 1.7 - 7.6 ) respectively . Diabetes mellitus ( P=0.007 ) , cholecystolithiasis ( P=0.004 ) and previous cholecystectomy ( P<0.001 ) were significantly associated with ECC . The prevalence of cirrhosis was higher in ICC than that in ECC ( P<0.001 ) . Furthermore , on excluding the ICC patients with cirrhosis , ICC patients showed significant independent associations with HBsAg ( OR : 7.3 ; 95 % CI : 3.1 - 17.2 ) and anti-HBc without HBsAg ( OR : 2.4 ; 95 % CI : 1.1 - 5.2 ) . CONCLUSION Cirrhosis and chronic hepatitis B virus infection are risk factors for ICC , while cholecystolithiasis , diabetes and previous cholecystectomy are risk factors for ECC", "BACKGROUND & AIMS Influence of being overweight and diabetes mellitus on the occurrence of hepatocellular carcinoma ( HCC ) in patients with cirrhosis has not been evaluated prospect ively . The aim of this study was to show the predictive value of these factors in a cohort of 771 patients with well-compensated alcohol- or hepatitis C (HCV)-related cirrhosis who were screened prospect ively for HCC . METHODS The predictive value for HCC occurrence was assessed by using the log-rank test and the Cox proportional hazards model . At enrollment , the mean age was 61.4 + /- 10 years and 431 patients were men . Cirrhosis was caused by alcohol ( n = 478 ) , HCV ( n = 220 ) , or the association of both factors ( n = 73 ) . The mean body mass index ( BMI ) was 25.4 kg/m(2 ) and 231 patients were diabetic . RESULTS During a mean follow-up period of 4.2 + /- 3 years , 220 patients developed HCC . In univariate analysis , a BMI of 25 kg/m(2 ) or more , diabetes , male sex , age older than 60 years , and HCV infection were risk factors for HCC . In multivariate analysis , predictive factors were a BMI between 25 - 30 kg/m(2 ) ( hazard ratio [ HR ] , 2.0 ; 95 % confidence interval [ CI ] , 1.4 - 2.7 ) , BMI of 30 kg/m(2 ) or more ( HR , 2.8 ; 95 % CI , 2.0 - 4.0 ) , diabetes ( HR , 1.6 ; 95 % CI , 1.2 - 2.1 ) , age 60 - 70 years ( HR , 2.4 ; 95 % CI , 1.3 - 4.3 ) , age older than 70 years ( HR , 3.0 ; 95 % CI , 1.7 - 5.5 ) , male sex ( HR , 2.0 ; 95 % CI , 1.4 - 2.7 ) , HCV ( HR , 1.6 ; 95 % CI , 1.1 - 2.2 ) , and mixed ( HR , 2.6 ; 95 % CI , 1.7 - 4.0 ) etiology . We found a positive linear relationship between BMI level and HCC incidence during follow-up evaluation . CONCLUSIONS Overweight and diabetes mellitus are associated with an increased risk of HCC occurrence in patients with HCV- or alcohol-related cirrhosis", "BACKGROUND & AIMS An association between diabetes and chronic liver disease has been reported . However , the temporal relationship between these conditions remains unknown . METHODS We identified all patients with a hospital discharge diagnosis of diabetes between 1985 and 1990 using the computerized records of the Department of Veterans Affairs . We r and omly assigned 3 patients without diabetes for every patient with diabetes . We excluded patients with concomitant liver disease . The remaining cohort was followed through 2000 for the occurrence of chronic nonalcoholic liver disease ( CNLD ) and hepatocellular carcinoma ( HCC ) . Hazard rate ratios ( HRR ) were determined in Cox proportional hazard survival analysis . RESULTS The study cohort comprised 173,643 patients with diabetes and 650,620 patients without diabetes . Most were men ( 98 % ) . Patients with diabetes were older ( 62 vs. 54 years ) than patients without diabetes . The incidence of chronic nonalcoholic liver disease was significantly higher among patients with diabetes ( incidence rate : 18.13 vs. 9.55 per 10,000 person-years , respectively , P < 0.0001 ) . Similar results were obtained for HCC ( incidence rate : 2.39 vs. 0.87 per 10,000 person-years , respectively , P < 0.0001 ) . Diabetes was associated with an HRR of 1.98 ( 95 % CI : 1.88 to 2.09 , P < 0.0001 ) of CNLD and an HRR of 2.16 ( 1.86 to 2.52 , P < 0.0001 ) of hepatocellular carcinoma . Diabetes carried the highest risk among patients with longer than 10 years of follow-up . CONCLUSIONS Among men with diabetes , the risk of CNLD and HCC is doubled . This increase in risk is independent of alcoholic liver disease , viral hepatitis , or demographic features", "BACKGROUND The risk of some forms of cancer has been found to be higher in patients with diabetes mellitus ( DM ) than in the general population . The aim of this study was to examine , with sufficient statistical power , the association between DM and lung cancer and the impact of antidiabetes drugs on lung cancer risk in Taiwan . MATERIAL S AND METHODS From a r and omly selected data set of 1 million National Health Insurance ( NHI ) cl aims in Taiwan from 2000 - 2005 , 19,624 cases ( patients ≥ 20 years of age ) of newly diagnosed DM were identified . From the same data set , 78,496 enrollees with no record of DM were selected as controls and were matched in sex and age to the first group . The incidence of newly diagnosed lung cancer was compared between patients with DM and controls for a period of 9 years ( 2000 - 2008 ) . RESULTS The multivariate Cox model analysis showed a slightly increased hazard ratio ( HR ) of 1.05 of lung cancer in patients with DM , but the association was not statistically significant . However the use of antidiabetes drugs , such as metformin , thiazolidinediones , or alpha-glucosidase inhibitors , correlates with a decreased lung cancer risk of 39%-45 % . A significant association was found between lung cancer risk and male sex ( HR , 2.23 ) , pulmonary tuberculosis ( HR , 1.60 ) , chronic obstructive pulmonary disease ( HR , 1.21 ) , and age ( HR , 1.07 ) . CONCLUSION Patients with DM are not at increased risk for the development of lung cancer , but the use of antidiabetes drugs would considerably decrease the risk . In this cohort , male sex , age , pulmonary tuberculosis , and chronic obstructive pulmonary disease were all associated with an increased risk of lung cancer , consistent with findings in the literature and indicative of the validity of our study", "Pancreatic cancer is one of the most fatal human cancers and continues to be a major unsolved health problem . The goal of this study was to estimate the independent effects and interactions between cigarette smoking and diabetes on the risk of pancreatic cancer in Korean male population . Cigarette smoking and the risk of incidence and death from pancreatic cancer were examined in a 10‐year prospect i ve cohort study of 446,407 Korean men aged 40 to 65 years who received health insurance from the National Health Insurance Corporation and who had a medical evaluation in 1992 . Relative risks ( RR ) and 95 % confidence intervals ( CI ) were calculated using a Cox proportional hazards model after adjusting for age , body mass index , exercise and alcohol use . Current smoking was associated with an increased risk of incidence ( RR = 1.7 , 95 % CI = 1.6–1.9 ) and mortality ( RR = 1.6 , 95 % CI = 1.4–1.7 ) from pancreatic cancer . The RR for pancreatic cancer increased with both duration and amount of smoking . Diabetes was also associated with an increased risk of both incidence ( RR = 1.8 , 95 % CI = 1.5–2.2 ) and mortality ( RR = 1.7 , 95 % CI = 1.4–2.1 ) from pancreatic cancer . There was no interaction between smoking and fasting serum glucose in terms of pancreatic cancer risk . Thus , our prospect i ve study has demonstrated that cigarette smoking and elevated fasting serum glucose are independently associated with an increased risk of pancreatic cancer in a large cohort of Korean males . © 2006 Wiley‐Liss ,", "BACKGROUND & AIMS Type 2 diabetes mellitus ( DM ) is associated with an increased risk of colorectal cancer ( CRC ) ; it is not clear if this association varies by sex or other factors . Insulin use might also be associated with CRC risk . We investigated associations of type 2 DM and insulin use with CRC risk . METHODS The Cancer Prevention Study II Nutrition Cohort is a prospect i ve study of cancer incidence . In 1992 or 1993 , adult participants ( n = 184,194 ) completed a detailed , self-administered question naire . Follow-up question naires were sent in 1997 and every 2 years thereafter . Cox proportional hazards regression analysis was used to calculate relative risks ( RR ) and 95 % confidence intervals ( CI ) , adjusting for covariates . RESULTS After exclusions , 73,312 men and 81,663 women remained in the final analytic cohort ; 1567 men ( 227 with type 2 DM ) and 1242 women ( 108 with type 2 DM ) were diagnosed with colon or rectal cancer by 2007 . Among men , type 2 DM was associated with increased risk of incident CRC compared to not having type 2 DM ( RR : 1.24 ; 95 % CI : 1.08 - 1.44 ) ; risk was higher for participants with type 2 DM using insulin ( RR : 1.36 ; 95 % CI : 1.05 - 1.78 ) , and participants with type 2 DM not using insulin ( RR : 1.22 , 95 % CI : 1.04 - 1.45 ) . Among women , type 2 DM and insulin use were not associated with risk of incident CRC ( RR : 1.01 ; 95 % CI : 0.82 - 1.23 and RR : 0.95 ; 95 % CI : 0.64 - 1.41 , respectively ) . CONCLUSIONS There is a modest association between type 2 DM and CRC among men , but not women . Insulin use is not associated with a substantially increased risk of CRC", "Severe immune dysfunction is an established risk factor of lymphoma , but the role of moderate alterations of immunity is not clear and prospect i ve investigations are needed . We examined several immune-related disorders and medications in relation to non-Hodgkin lymphoma ( NHL ) in the Multiethnic Cohort . Over 215,000 subjects of African American , Caucasian , Japanese American , Latino and Native Hawaiian ancestry aged 45 - 75 years completed a question naire , including information on medical history , in 1993 - 1996 . After exclusions , we performed Cox regression among 193,050 cohort members including 939 incident NHL cases while adjusting for sex , age , ethnicity , education , body mass index and alcohol intake . Self-reported diabetes was not associated with NHL overall , but was positively associated with risk among Japanese Americans [ hazard ratio ( HR ) = 1.55 ; 95 % confidence interval ( CI ) : 1.10 - 2.17 ] . Participants with a history of blood transfusion were at increased risk with HR = 1.39 ( 95 % CI : 1.06 - 1.84 ) in men and HR = 1.22 ( 95 % CI : 0.94 - 1.58 ) in women , especially for the diffuse large B-cell lymphoma subtype . History of asthma or other allergies was associated with elevated risk only among Latinos ( HR = 1.46 ; 95 % CI : 1.07 - 2.00 ) who also showed a significant relation between current use of antihistamines and NHL ( HR = 1.80 ; 95 % CI : 1.09 - 2.97 ) . Use of nonsteroidal anti-inflammatory drugs was not associated with NHL . Our findings from this large prospect i ve study support a moderate risk for NHL related to blood transfusions , current long-term antihistamine use and diabetes , but the associations were limited to certain ethnic groups and require further replications", "Observational studies suggest that diabetes is associated with a decreased risk of prostate cancer , but few are population based or have investigated associations with cancer stage or duration of diabetes . We report a case-control study nested within the population -based Prostate testing for cancer and Treatment ( ProtecT ) study IS RCT N20141297 . Men aged 50 - 69 years based around 9 UK cities were invited for a prostate-specific antigen ( PSA ) test between June 2002 and November 2006 . Amongst 55,215 PSA-tested men , 1,966 had histologically confirmed prostate cancer ; of these , 1,422 ( 72.3 % ) completed the question naire and 1,291 ( 65.7 % ) had complete data for analysis . We r and omly selected 6,479 age- ( within 5 years ) and general practice -matched controls . The prevalence of diabetes was 89/1,291 ( 6.9 % ) in cases and 555/6,479 ( 8.6 % ) in controls . Diabetes was associated with a reduced risk of prostate cancer ( odds ratio = 0.78 ; 95 % confidence interval : 0.61 - 0.99 ) . There was weak evidence that the inverse association was greater for well- versus poorly differentiated cancers ( p = 0.07 ) . The magnitude of the inverse association did not change with increasing duration of diabetes ( p for trend = 0.95 ) . Diabetes is associated with a decreased risk of PSA-detected prostate cancer . These data add to the evidence of the association of diabetes with prostate cancer in the PSA era" ]

[ "12011225", "10022415", "10203281", "9593409", "9923856", "12433720" ]

[ "Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China.", "Acute and short-term effects of growth hormone on insulin-like growth factors and their binding proteins: serum levels and hepatic messenger ribonucleic acid responses in humans.", "Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3.", "Circulating concentrations of insulin-like growth factor I and risk of breast cancer", "Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis.", "Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort." ]

[ "BACKGROUND Insulin-like growth factor I ( IGF-I ) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor . The major binding protein for IGF-I , insulin-like growth factor-binding protein 3 ( IGFBP-3 ) , modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor . In a prospect i ve study of men in Shanghai , China , we examined the association between serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer . METHODS From 1986 to 1989 , serum was collected from 18,244 men aged 45 - 64 years living in Shanghai without a history of cancer . We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects . RESULTS Among 230 case patients and 659 matched control subjects , increased IGF-I levels were not associated with increased risk of lung cancer . However , for subjects in the highest quartile relative to the lowest quartile of IGFBP-3 , the odds ratio ( OR ) for lung cancer , adjusted for smoking and IGF-I , was 0.50 ( 95 % confidence interval [ CI ] = 0.25 to 1.02 ) . When the analysis was restricted to ever smokers ( 184 case patients and 344 matched control subjects ) , the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile , adjusted for smoking and IGF-I , was 0.41 ( 95 % CI = 0.18 to 0.92 ) . CONCLUSIONS In this prospect i ve study of Chinese men , higher serum levels of IGF-I did not increase the risk of lung cancer . However , subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer . This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor", "We investigated the acute ( 4 - 5 h ) and short-term ( 5 days ) effects of GH treatment on hepatic messenger RNA ( mRNA ) levels of the genes for the insulin-like growth factors ( IGFs ) , insulin-like growth factor binding protein-1 , -2 , and -3 ( IGFBPs ) , and the acid labile subunit ( ALS ) , as well as serum levels of these proteins in humans . At the mRNA level , we observed an increase in IGF-1 transcription ( + 173 % ) following GH treatment in the acute group , which remained elevated in the short-term treatment group . IGFBP-2 mRNA decreased after short-term GH treatment , without changes in IGFBP-1 or -3 expression . The ALS transcript level increased after 5 days . In serum , we found increased levels of IGF-I and insulin , and decreased levels of IGF-II , in the short-term treatment group . IGFBP-1 decreased in both treatment groups , whereas IGFBP-2 was reduced after 5 days treatment . ALS increased in the short-term group . We observed increased IGFBP-3 serum levels after 5 days of GH treatment , likely due to increased formation of the ternary complex . Our results show that the metabolic effects by GH on the IGF axis are complex . In addition to a direct stimulation of IGF-I and ALS expression , GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner , possibly facilitating enhanced IGF bioavailability to target tissues", "BACKGROUND Insulin-like growth factor-I ( IGF-I ) is a potent mitogen for normal and neoplastic cells , whereas IGF-binding protein-3 ( IGFBP-3 ) inhibits cell growth in many experimental systems . Acromegalics , who have abnormally high levels of growth hormone and IGF-I , have higher rates of colorectal cancer . We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospect i ve case-control study nested in the Physicians ' Health Study . METHODS Plasma sample s were collected at baseline from 14916 men without diagnosed cancer . IGF-I , IGF-II , and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects . All P values are two-sided . RESULTS IGFBP-3 levels correlated with IGF-I levels ( r=.64 ) and with IGF-II levels ( r=.90 ) . After controlling for IGFBP-3 , age , smoking , body mass index ( weight in kg/[height in m]2 ) , and alcohol intake , men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile ( relative risk [RR]=2.51 ; 95 % confidence interval [CI]=1.15 - 5.46 ; P for trend = .02 ) . After controlling for IGF-I and other covariates , men with higher IGFBP-3 had a lower risk ( RR=0.28 ; 95 % CI=0.12 - 0.66 ; P for trend = .005 , comparing extreme quintiles ) . The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men . IGF-II was not associated with risk . CONCLUSIONS Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer", "BACKGROUND Insulin-like growth factor (IGF)-I , a mitogenic and antiapoptotic peptide , can affect the proliferation of breast epithelial cells , and is thought to have a role in breast cancer . We hypothesised that high circulating IGF-I concentrations would be associated with an increased risk of breast cancer . METHODS We carried out a nested case-control study within the prospect i ve Nurses ' Health Study cohort . Plasma concentrations of IGF-I and IGF binding protein 3 ( IGFBP-3 ) were measured in blood sample s collected in 1989 - 90 . We identified 397 women who had a diagnosis of breast cancer after this date and 620 age-matched controls . IGF-I concentrations were compared by logistic regression with adjustment for other breast-cancer risk factors . FINDINGS There was no association between IGF-I concentrations and breast-cancer risk among the whole study group . In postmenopausal women there was no association between IGF-I concentrations and breast-cancer risk ( top vs bottom quintile of IGF-I , relative risk 0.85 [ 95 % CI 0.53 - 1.39 ] ) . The relative risk of breast cancer among premenopausal women by IGF-I concentration ( top vs bottom tertile ) was 2.33 ( 1.06 - 5.16 ; p for trend 0.08 ) . Among premenopausal women less than 50 years old at the time of blood collection , the relative risk was 4.58 ( 1.75 - 12.0 ; p for trend 0.02 ) . After further adjustment for plasma IGFBP-3 concentrations these relative risks were 2.88 and 7.28 , respectively . INTERPRETATION A positive relation between circulating IGF-I concentration and risk of breast cancer was found among premenopausal but not postmenopausal women . Plasma IGF-I concentrations may be useful in the identification of women at high risk of breast cancer and in the development of risk reduction strategies . Additional larger studies of this association among premenopausal women are needed to provide more precise estimates of effect", "BACKGROUND Insulin-like growth factors ( IGFs ) , in particular IGF-I and IGF-II , strongly stimulate the proliferation of a variety of cancer cells , including those from lung cancer . To examine the possible causal role of IGFs in lung cancer development , we compared plasma levels of IGF-I , IGF-II , and an IGF-binding protein ( IGFBP-3 ) in patients with newly diagnosed lung cancer and in control subjects . METHODS From an ongoing hospital-based , case-control study , we selected 204 consecutive patients with histologically confirmed , primary lung cancer and 218 control subjects who were matched to the case patients by age , sex , race , and smoking status . IGF-I , IGF-II , and IGFBP-3 plasma levels were measured by enzyme-linked immunosorbent assay and then divided into quartiles , based on their distribution in the control subjects . Associations between the IGF variables and lung cancer risk were estimated by use of odds ratios ( ORs ) . Reported P values are two-sided . RESULTS IGF and IGFBP-3 levels were positively correlated ( all r>.27 ; all P<.001 ) . High plasma levels of IGF-I were associated with an increased risk of lung cancer ( OR = 2.06 ; 95 % confidence interval [ CI ] = 1.19 - 3.56 ; P = .01 ) , and this association was dose dependent in both univariate and multivariate analyses . Plasma IGFBP-3 showed no association with lung cancer risk unless adjusted for IGF-I level ; when both of these variables were analyzed together , high plasma levels of IGFBP-3 were associated with reduced risk of lung cancer ( OR = 0.48 ; 95 % CI = 0.25 - 0.92 ; P = .03 ) . IGF-II was not associated with lung cancer risk . CONCLUSIONS Plasma levels of IGF-I are higher and plasma levels of IGFBP-3 are lower in patients with lung cancer than in control subjects . If these findings can be confirmed in prospect i ve studies , measuring levels of IGF-I and IGFBP-3 in blood may prove useful in assessing lung cancer risk", "Recent prospect i ve studies have suggested that insulin-like growth factor (IGF)-I levels are related to risk of some epithelial cancers . We previously reported in a case-control study a significant association between IGF-I level and lung cancer risk , with a 2-fold increased risk in the highest quartile . We now report the results of a lung cancer case-control study nested in the placebo arm of the beta-Carotene and Retinol Efficacy Trial in heavy smokers . We identified 159 cases for whom sera had been collected at least 3 years before diagnosis and for whom 2 suitable controls/case ( final number , 297 ) could be matched from the same study arm on age ( within 5-year intervals ) , sex , ethnicity , year of enrollment into the beta-Carotene and Retinol Efficacy Trial , year of blood draw , and exposure category ( smoking or asbestos ) . The cases were significantly heavier smokers than the controls ( mean pack-years , 58.7 and 45.9 , respectively ; P < 0.001 ) . An inverse relationship between IGF-I level and age was evident only for former smokers , and not for those who were current smokers at the time of blood draw . Both IGF-I and IGF-binding protein (IGFBP)-3 levels were higher in cases than in controls , but none of the differences achieved statistical significance . The odds ratios for IGF-I were around unity , except for subsets of heaviest smokers and those who had quit smoking for the longest period of time , in whom there were elevated risks in the second to fourth quartiles of IGF-I relative to the first quartile ( odds ratios , 2.21 - 2.91 ) , although again , none achieved statistical significance . For younger subjects , IGF-I was inversely associated with lung cancer risk in the models that also controlled for IGFBP-3 . Elevated risks for lung cancer were noted in the highest quartile of IGFBP-3 level , and these tended to be higher in current smokers and more recent quitters . These results do not support the conclusions of our prior case-control study . It is possible that current smoking or recent cessation may exert a suppressive effect on IGF-I levels ( notably in younger subjects with higher baseline levels ) that may obscure a relatively modest association between IGF-I level and lung cancer risk . On the other h and , risks associated with elevated IGFBP-3 level tended to be higher in current smokers and more recent quitters . This trend toward a positive association with IGFBP-3 level is unexpected and requires further investigation . Finally , from these data , we can not exclude the possibility that risk of lung cancer in nonsmokers may be related to IGF-I levels" ]

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[ "Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling.", "A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain.", "Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome.", "Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.", "A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination.", "Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.", "Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin.", "Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome.", "Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial.", "The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome.", "Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study.", "Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial.", "The use of metformin for women with PCOS undergoing IVF treatment.", "Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.", "Medical vs. surgical treatment for clomiphene citrate-resistant women with polycystic ovary syndrome", "Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome.", "Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome.", "Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.", "Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization.", "Effects of metformin on clinical and biochemical parameters in polycystic ovary syndrome.", "Metformin therapy in women with polycystic ovary syndrome.", "The effect of metformin on ovarian stimulation and in vitro fertilization in insulin-resistant women with polycystic ovary syndrome: an open-label randomized cross-over trial", "Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial", "Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice.", "Role of metformin in correcting hyperinsulinemia, menstrual irregularity and anovulation in polycystic ovary syndrome.", "A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study.", "The effect of metformin treatment to ovarian response in cases with PCOS", "Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone.", "Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome", "The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome.", "Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome.", "Metformin improves ovulation and pregnancy rates in patients with polycystic ovary syndrome", "Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospective parallel randomized double-blind placebo-controlled trial.", "Presentation of polycystic ovary syndrome and its management with clomiphene alone and in combination with metformin.", "Does metformin induce ovulation in normoandrogenic anovulatory women?", "Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial.", "Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo-controlled double-blind assessment." ]

[ "AIM To evaluate the effects of metformin on insulin resistance , and rogen concentration , ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome ( PCOS ) . METHODS Forty-two infertile women with PCOS were selected in this r and omized clinical study . Basal steroid and gonadotropin levels were measured , and oral glucose tolerance test ( OGTT ) was performed . The patients were r and omly divided into group 1 ( n = 21 ) and group 2 ( n = 21 ) . Group 1 patients were treated with laparoscopic ovarian drilling ( LOD ) . Group 2 patients underwent laparoscopic ovarian drilling ( LOD ) and received 1700 mg per day of metformin for 6 months . LOD was performed in women with PCOS using a unipolar electrode . Serum progesterone ( P ) level > 5 ng/mL was considered as a confirmation of ovulation . Ovulation and pregnancy rates were determined after six cycles . RESULTS Serum and rogens and insulin response to OGTT decreased significantly after metformin therapy . Mean serum P levels and endometrial thickness were significantly higher in cycles treated with metformin plus LOD ( 34.6 + /- 25.4 ng/mL , 8.4 + /- 1.1 mm ) than in those treated with LOD alone ( 26.2 + /- 24.7 ng/mL , 7.9 + /- 2.8 mm ) ( P < 0.05 ) . The ovulation ( 56 of 65 cycles , 86.1 % vs 29 of 65 cycles , 44.6 % ) and pregnancy rates ( nine of 21 women , 47.6 % vs four of 21 women , 19.1 % ) were significantly higher in group 2 than in group I. CONCLUSIONS Metformin improves insulin resistance , reduces and rogen levels and significantly increases the ovulation and pregnancy rates in infertile women , following LOD", "We prospect ively estimated the prevalence of the polycystic ovary syndrome ( PCOS ) , as defined by the NIH/NICHHD 1990 endocrine criteria , in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation . Anthropometric data ; the presence of hirsutism , acne , and and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels . PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , and 3 ) exclusion of hyperprolactinemia , thyroid disorders , and nonclassic 21-hydroxylase deficiency . Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more , acne was considered as a sign of hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen index above the 95th percentile of the control values derived from the nonhirsute , nonacneic women having regular menses who were not receiving hormonal therapy . PCOS was present in 10(6.5 % ) , hirsutism was present in 11 ( 7.1 % ) , and acne was present in 19 ( 12.3 % ) of the 154 women . Our results demonstrate a 6.5 % prevalence of PCOS , as defined , in a minimally biased population of Caucasian women from Spain . The polycystic ovary syndrome , hirsutism , and acne are common endocrine disorders in women", "OBJECTIVE To evaluate the effect of ultra-short ( 12 days ) metformin pretreatment in clomiphene-citrate ( CC ) resistant polycystic ovary syndrome ( PCOS ) . METHOD Eighty women with CC-resistant PCOS were r and omly allocated to metformin pretreatment or usual treatment . Forty women received 1500 mg metformin daily for 12 days , followed by clomiphene 150 mg daily for 5 days along with metformin . Forty women ( control group ) received the same dose of clomiphene but no metformin pretreatment . RESULTS In the metformin group , 17 ( 42.5 % ) women ovulated , and 6 ( 15 % ) conceived . In the control group , 5 ( 12.5 % ) women ovulated but none conceived . Compared with the control group , the metformin group had significantly higher ovulation ( P = 0.03 ) and pregnancy rates ( P = 0.026 ) . CONCLUSION Twelve days of metformin pretreatment improves ovulation and pregnancy rates in women with CC-resistant PCOS", "BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo . Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin ovulated spontaneously or in response to clomiphene , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin", "BACKGROUND There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome ( PCOS ) . The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation ( COS ) followed by timed intercourse ( TI ) or intrauterine insemination ( IUI ) . METHODS Seventy insulin-resistant primary infertile women with PCOS were r and omized to receive metformin cloridrate ( 850 mg twice daily ; group A ) or placebo tablets ( two tablets daily ; group B ) for 3 months . Three trials of COS using highly purified urinary FSH ( hpFSH ) plus TI/IUI were performed . Number of ampoules of gonadotrophin used , duration of the ovarian stimulation , cycle cancellation , ovulation , pregnancy , abortion , live birth , mono-ovulatory cycles , multiple pregnancies and ovarian hyperstimulation syndrome ( OHSS ) rates were assessed . RESULTS No difference between groups was detected in ovulation , cycle cancellation , pregnancy , abortion , live birth , multiple pregnancies and OHSS rates . The mono-ovulatory cycle rates were significantly ( P = 0.002 ) more frequent in group A than in group B , whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly ( P < 0.001 ) higher in group A than in group B. CONCLUSION In insulin-resistant women with PCOS , metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles", "Estimates of the prevalence of the polycystic ovary syndrome ( PCOS ) in the general population have ranged from 2 - 20 % . The vast majority of these reports have studied White population s in Europe , used limited definitions of the disorder , and /or used bias population s , such as those seeking medical care . To estimate the prevalence of this disorder in the United States and address these limitations , we prospect ively determined the prevalence of PCOS in a reproductive-aged population of 369 consecutive women ( 174 White and 195 Black ; aged 18 - 45 yr ) , examined at the time of their preemployment physical . Body measures were obtained , and body hair was quantified by a modified Ferriman-Gallwey ( F-G ) method . All exams were initially performed by 2 trained nurses , and any subject with an F-G score above 3 was reexamined by a physician , the same for all patients . Of the 369 women , 277 ( 75.1 % ) also agreed to complete a question naire and have additional blood drawn . Subjects were studied regardless of current estrogen/progestin hormonal use ( 28.5 % ) . PCOS was defined as 1 ) oligoovulation , 2 ) clinical hyper and rogenism ( i.e. hirsutism ) and /or hyper and rogenemia , and 3 ) exclusion of other related disorders , such as hyperprolactinemia , thyroid abnormalities , and non-classic adrenal hyperplasia . Hirsutism was defined by a F-G score of 6 or more , and hyper and rogenemia was defined as a total or free testosterone , and rostenedione , and /or dehydroepi and rosterone sulfate level above the 95th percentile of control values [ i.e. all eumenorrheic women in the study , who had no hirsutism ( F-G < or = 5 ) or acne and were receiving no hormonal therapy ; n = 98 ] . Considering all 369 women studied , White and Black women had similar mean ages ( 29.4 + /- 7.1 and 31.1 + /- 7.8 yr , respectively ) , although White women had a lesser body mass than Black women ( 24.9 + /- 6.1 vs. 29.2 + /- 8.1 kg/m2 , respectively ; P < 0.001 ) . Of these 7.6 % , 4.6 % , and 1.9 % demonstrated a F-G score of 6 or more , 8 or 10 , respectively , and there was no significant racial difference , with hirsutism prevalences of 8.0 % , 2.8 % , and 1.6 % in Whites , and 7.1 % , 6.1 % , and 2.1 % in Blacks , respectively . Of the 277 women consenting to a history and hormonal evaluation , 4.0 % had PCOS as defined , 4.7 % ( 6 of 129 ) of Whites and 3.4 % ( 5 of 148 ) of Blacks . In conclusion , in our consecutive population of unselected women the prevalence of hirsutism varied from 2 - 8 % depending on the chosen cut-off F-G score , with no significant difference between White and Black women . Using an F-G score of 6 or more as indicative of hirsutism , 3.4 % of Blacks and 4.7 % of Whites had PCOS as defined . These data suggest that PCOS may be one of most common reproductive endocrinological disorders of women", "OBJECTIVES To evaluate the clinical features , endocrine and metabolic profiles in clomiphene ( CC ) responders and non-responders with polycystic ovarian disease ( PCOD ) , and to examine the effects of metformin ( MTF ) on the above parameters of CC resistance . METHODS A prospect i ve clinical trial was undertaken at the infertility division of a university teaching hospital . Forty-one CC responders were selected and their hormonal and clinical features were determined . Forty-one CC-resistant PCOD women were also selected and clinical features ; metabolic and hormonal profiles before and after treatment with MTF 1500 mg/day for 6 - 8 weeks were evaluated . Women who failed to conceive were treated by CC while continuing to take MTF . RESULTS CC responders had higher insulin levels while non-responders were hyperinsulinemic . Menstrual irregularities improved in 30 % . Mean+/-S.D. area under curve of insulin decreased from 297.58+/-191.33 to 206+/-0.1 mIU/ml per min ( P=0.005 ) . Only 39.39 % ovulated and 24.24 % conceived . CONCLUSION PCOD is associated with insulin resistance ( IR ) particularly in CC-resistant women . Insulin resistance and and rogen levels are significantly higher in obese patients . MTF therapy improved hyper and rogenemia , IR , and pregnancy rate", "BACKGROUND Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome . P450c17 alpha , which is involved in and rogen bio synthesis , has both 17 alpha-hydroxylase and 17,20-lyase activities . Increased activity of this enzyme results in exaggerated conversion of progesterone to 17 alpha-hydroxyprogesterone in response to stimulation by gonadotrophin . We hypothesized that hyperinsulinemia stimulates ovarian P450c17 alpha activity . METHODS We measured fasting serum steroid concentrations and the response of serum 17 alpha-hydroxyprogesterone to leuprolide , a gonadotrophin-releasing hormone agonist , and performed oral glucose-tolerance tests before and after oral administration of either metformin ( 500 mg three times daily ) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome . RESULTS In the 11 women given metformin , the mean ( + /- SE ) area under the serum insulin curve after oral glucose administration decreased from 9303 + /- 1603 to 4982 + /- 911 microU per milliliter per minute ( 56 + /- 10 to 30 + /- 6 nmol per liter per minute ) ( P = 0.004 ) . This decrease was associated with a reduction in the basal serum 17 alpha-hydroxyprogesterone concentration from 135 + /- 21 to 66 + /- 7 ng per deciliter ( 4.1 + /- 0.6 to 2.0 + /- 0.2 nmol per liter ) ( P = 0.01 ) and a reduction in the leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone concentration from 455 + /- 54 to 281 + /- 52 ng per deciliter ( 13.7 + /- 1.6 to 8.5 + /- 1.6 nmol per liter ) ( P = 0.01 ) . The serum 17 alpha-hydroxyprogesterone values increased slightly in the placebo group . In the metformin group , the basal serum luteinizing hormone concentration decreased from 8.5 + /- 2.2 to 2.8 + /- 0.5 mlU per milliliter ( P = 0.01 ) , the serum free testosterone concentration decreased from 0.34 + /- 0.07 to 0.19 + /- 0.05 ng per deciliter ( 12 + /- 3 to 7 + /- 2 pmol per liter ) ( P = 0.009 ) , and the serum sex hormone-binding globulin concentration increased from 0.8 + /- 0.2 to 2.3 + /- 0.6 microgram per deciliter ( 29 + /- 7 to 80 + /- 21 nmol per liter ) ( P < 0.001 ) . None of these values changed significantly in the placebo group . CONCLUSIONS In obese women with the polycystic ovary syndrome , decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyper and rogenism", "BACKGROUND Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome ( PCOS ) has led to the use of insulin sensitizers . METHODS A r and omized , controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins . Sixty clomiphene-resistant women with PCOS were r and omized to two groups ( n = 30 each ) , using computer-generated tables . Group I received metformin for 6 months , followed by ovulation induction with clomiphene citrate ; group II received hMG for ovulation induction . Hormonal profiles were evaluated at the onset and after completion of treatment . RESULTS There was no significant difference in pregnancy rates between the two groups ( 16.7 versus 23.3 % ) . In group I , there was a significant improvement in menstrual function and ovulation after treatment ( 40 % , P < 0.001 ; and 46.7 % , P < 0.001 ) , with a significant decrease in fasting insulin levels ( P < 0.05 ) . There were no changes in other biochemical parameters . The ovulation rate in group II was 43.3 % , with a high drop-out rate . The cost-effective analysis for medications per pregnancy in group I was US$ 71 + /- 3 versus US$ 277 + /- 171 in group II . CONCLUSIONS Sequential treatment with metformin and clomiphene citrate is an effective and safe option for clomiphene-resistant women with PCOS", "OBJECTIVE ( S ) To evaluate the effects of metformin on insulin resistance , ovarian and rogen production , and clomiphene-induced ovulation and pregnancy rates in infertile women with polycystic ovary syndrome ( PCOS ) . STUDY DESIGN Twenty-one infertile women with PCOS were selected in this prospect i ve r and omized clinical study . Basal steroid and gonadotropin levels were measured , and oral glucose tolerance test ( OGTT ) was performed . The patients were divided r and omly into group 1 ( n = 11 ) and group 2 ( n = 10 ) . Group 1 patients were treated with 1700 mg per day of metformin for 3 months . The basal tests and OGTT were repeated after metformin therapy . Group 2 patients did not receive metformin . The patients in both groups received 100 mg of clomiphene citrate ( CC ) daily for 5 days until either a pregnancy occurred , or six CC cycles were reached . Metformin administration continued during CC therapy until the day of hCG in group 1 . Serum progesterone ( P ) level > or=5 ng/ml was considered as confirmatory of ovulation . Ovulation and pregnancy rates after six cycles were determined . RESULTS Serum and rogens and insulin response to OGTT decreased significantly after metformin therapy . Midluteal serum P level was significantly higher in cycles treated with metformin plus CC ( P < 0.05 ) . The ovulation ( 38 of 51 cycles , 74.4 % versus 34 of 55 cycles , 61.8 % ) and pregnancy rates ( 5 of 11 women , 45.5 % versus 3 of 10 women , 30 % ) were higher , but not significantly , in the metformin plus CC group than in the CC alone group . All the patients who conceived had insulin resistance in group 1 whereas non-insulin resistance in group 2 . CONCLUSION ( S ) Metformin improves insulin resistance and reduces and rogen levels . Metformin did not increase significantly the ovulation and pregnancy rates", "BACKGROUND Our aim was to investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome ( PCOS ) scheduled for IVF stimulation . METHODS Seventy-three oligo/amenorrhoeic women with polycystic ovaries and at least one of the following criteria : hyper and rogenaemia , elevated LH/FSH ratio , hyperinsulinism , decreased SHBG levels or hirsutism , were studied . Normal weight and overweight patients were r and omized separately in a prospect i ve , r and omized , double blind study . All patients were treated for at least 16 weeks with metformin ( 1000 mg bid ) or placebo ending on the day of HCG injection . RESULTS No differences were found in the primary end-points : duration of FSH stimulation 14.4 ( 13.1 - 15.7 ) versus 14.2 ( 12.6 - 15.7 ) days or estradiol on the day of HCG injection 6.8 ( 5.3 - 8.2 ) versus 7.6 ( 5.6 - 9.6 ) nmol/l in the metformin and placebo groups , respectively . The secondary end-points number of oocytes , fertilization rates , embryo quality , pregnancy rates and clinical pregnancy rates were equal . However , in the normal weight subgroup ( BMI < 28 kg/m(2 ) , n = 27 ) , pregnancy rates following IVF were 0.71 ( 0.63 - 0.79 ) versus 0.23 ( 0.15 - 0.31 ) in the metformin and placebo groups , respectively ( P = 0.04 ) . Overall clinical pregnancy rates were equal : 0.51 ( 0.34 - 0.68 ) versus 0.44 ( 0.27 - 0.62 ) in the metformin and placebo groups , respectively . However , in the normal weight subgroup , clinical pregnancy rates were 0.67 ( 0.43 - 0.91 ) and 0.33 ( 0.06 - 0.60 ) , respectively ( P = 0.06 ) . CONCLUSIONS Pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome . However , among normal weight PCOS women , pre-treatment with metformin tends to improve pregnancy rates . Further studies in subgroups of PCOS women are required", "BACKGROUND This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome ( PCOS ) patients with normal glucose tolerance . METHODS AND RESULTS Thirty-two patients were r and omized to metformin ( n = 16 ) and placebo ( n = 16 ) groups . Hormonal assessment , a 75 g oral glucose tolerance test ( OGTT ) and a frequently sample d i.v . glucose tolerance test ( FSIGTT ) were performed before and after oral administration of metformin ( 850 mg twice daily ) or placebo for 6 weeks . Recombinant FSH treatment was undertaken , thereafter , in women who did not ovulate on metformin ( n = 10 ) or placebo ( n = 15 ) . There was no significant change in all insulin sensitivity indices in both groups . The only change noted was a decline in mean serum free testosterone concentration in the metformin group ( P = 0.049 ) . One patient on placebo and six patients on metformin ovulated spontaneously ( P < 0.05 ) . All parameters of ovarian response were comparable between the two groups during rFSH treatment . Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle , the overall ovulation rates were 75 and 94 % in the placebo and metformin groups respectively ( P > 0.05 ) . The respective figures for pregnancy were 6.3 and 31.3 % ( P > 0.05 ) . CONCLUSIONS Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance , but has no significant effect on ovarian response during rFSH treatment", "BACKGROUND Metformin appears to improve reproductive function in some women with polycystic ovary syndrome ( PCOS ) . We wished to explore the effect of metformin in women with PCOS undergoing IVF . METHODS A r and omized , placebo-controlled , double-blind study was carried out between 2001 and 2004 . Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were r and omized to receive metformin ( MET ) , 850 mg , or placebo ( PLA ) tablets twice daily from the start of the down-regulation process until the day of oocyte collection . The primary outcome was to be an improvement in the overall fertilization rate . RESULTS One-hundred and one IVF/ICSI cycles were r and omized to receive metformin ( 52 ) or to receive placebo ( 49 ) . There was no difference in the total dose of rFSH required per cycle ( median dose : MET = 1200 U , PLA = 1300 U ; P = 0.937 ) . The median number of oocytes retrieved per cycle ( MET = 17.2 , PLA = 16.2 ; P = 0.459 ) and the overall fertilization rates ( MET = 52.9 % , PLA = 54.9 % ; P = 0.641 ) did not differ . However , both the clinical pregnancy rates beyond 12 weeks gestation per cycle ( MET = 38.5 % , PLA = 16.3 % ; P = 0.023 ) and per embryo transfer ( MET = 44.4 % , PLA = 19.1 % ; P = 0.022 ) were significantly higher in those treated with metformin . Furthermore , a significant decrease in the incidence of severe ovarian hyperstimulation syndrome ( OHSS ) was observed ( MET = 3.8 % , PLA = 20.4 % ; P = 0.023 ) , and this was still significant after adjustment for BMI , total rFSH dose and age ( OR = 0.15 ; 95 % CI : 0.03 , 0.76 ; P = 0.022 ) . CONCLUSION Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS", "OBJECTIVE To evaluate the effect of metformin therapy on hyper and rogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT(S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3 - 7 of the second cycle in both groups . MAIN OUTCOME MEASURE(S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy result ed in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction result ed in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy rate in the metformin group ; however , there was no significant difference in the pregnancy rate between the two groups . CONCLUSION ( S ) Metformin therapy not only decreases hyper and rogenism and insulin resistance but also improves ovulation rates , cervical scores , and pregnancy rates in clomiphene citrate-resistant women with PCOS", "This study was conducted to evaluate the efficacy of metformin compared with ovarian drilling in the treatment of clomiphene citrate ( CC ) resistant women with polycystic ovary syndrome . A total of 161 infertile , CC-resistant women with PCOS aged 22 - 34 years ( mean 25.5 ± 4.4 ) were evaluated prospect ively during the period between January 2000 and December 2001 . Patients were allocated into two groups ; group 1 includes 64 women who received metformin , 850 mg twice daily throughout the cycle , and group 2 which includes 97 women who underwent laparoscopic ovarian drilling . If spontaneous ovulation or pregnancy was not achieved within 3 months after treatment , CC was added with increments of 50 mg ( up to 150 mg/day ) for both groups . Clinical and menstrual characteristics in addition to the hormonal profile were evaluated before and after the treatment . There were no significant differences between the two groups in terms of age , body weight , BMI , duration of infertility and serum hormone levels ( and rogens , gonadotrophins , insulin ) before starting the treatment . A significant improvement in the regularity of menstrual cycles ( P<0.05 ) and a significant reduction in the serum levels of testosterone ( P<0.01 ) , and rostenedione ( P<0.01 ) , DHEAS ( P<0.05 ) , LH ( P<0.01 ) and LH : FSH ratio ( P<0.05 ) were noted after the treatment . There were no significant differences between the metformin group compared with the drilling group in the rates of ovulation ( 79.7 % vs. 83.5 % ) and pregnancy ( 64.1 % vs. 59.8 % ) . It is concluded that CC-resistant patients with polycystic ovary syndrome can be treated effectively either by metformin or by laparoscopic ovarian drilling . Menstrual cycle pattern and the rates of ovulation and pregnancy are improved significantly , due most probably to the significant decrease in the levels of and rogens and luteinising hormone", "In 43 amenorrheic women with polycystic ovary syndrome ( PCOS ) , 31 ( 74 % ) with fasting hyperinsulinemia ( > or = 20 microU/mL ) , our aim was to determine whether Metformin ( Bristol-Myers Squibb , Princeton , NJ ) , which reduces hyperinsulinemia , would reverse the endocrinopathy of PCOS , allowing resumption of regular normal menses . A second aim was to assess the effects of weight loss versus other Metformin-induced effects on ovarian function , and to determine if there were different responses to Metformin between those who lost weight and those who did not . A third aim was to assess associations between PCOS , 4G/5 G polymorphism in the promoter sequence of the plasminogen activator inhibitor-1 gene ( PAI-1 gene ) , and PAI activity ( PAI-Fx ) . Of the 43 women , 40 ( 93 % ) had normal fasting blood glucose and 37 had normal hemoglobin A1C ( HgA1C ) ; onlythree ( 7 % ) had type 2 diabetes mellitus . Metformin ( 1.5 to 2.25 g/d ) was given for 6.1+/-5.1 months ( range , 1.5 to 24 ) , to 16 patients for less than 3 months , to 12 for 3 to 6 months , and to 15 for at least 6 months . On Metformin , 39 of 43 patients ( 91 % ) resumed normal menses . The percentage of women resuming normal menses did not differ among treatment duration groups ( P<.1 ) or among dose groups ( P>.1 ) . The body mass index ( BMI ) decreased from 36.4 + 7 Kg/m2 at study entry to 35.1+/-6.7 on Metformin ( P=.0008 ) . Of 43 patients , 28 ( 67 % ) lost weight ( 1 to 69 pounds ) , with nine ( 21 % ) losing at least 12 pounds . On Metformin , the median fasting serum insulin decreased from 26 microU/mL to 22 ( P=.019 ) , testosterone decreased from 61 ng/dL to 47 ( P=.003 ) , and estradiol increased from 41 pg/mL to 71 ( P=.0001 ) . Metformin-induced improvements in ovarian function were independent of weight loss ( testosterone decrease , P<.002 ; estradiol increase , P<.0004 ) . The change in response variables on Metformin did not differ ( P>.05 ) between those who lost weight and those who did not , excepting Lp(a ) , which increased 4 mg/dL in those who lost weight and decreased 9 mg/dL in those who did not ( P = .003 ) . The change in response variables on Metformin did not differ among the five quintiles of weight loss , excepting fasting glucose ( P<.05 ) , which increased 6 mg/dL in those who lost the least weight on Metformin versus those in the 60th to 80th percentile for weight loss , in whom glucose decreased 33 mg/dL. Although the pretreatment fasting serum insulin was not significantly correlated with testosterone ( r=.24 , P=.13 ) or and rostenedione ( r=.27 , P=.09 ) , on Metformin , the change in insulin correlated positively with the change in testosterone ( r=.35 , P=.047 ) and with the change in and rostenedione ( r=.48 , P=.01 ) . Patients were more likely than normal controls ( 83 % v 64 % , P=.016 ) to be heterozygous or homozygous for 4 G polymorphism of the PAI-1 gene and were also more likely to have high PAI-Fx ( > or = 22 U/mL , 28 % v3 % , chi(2)=10.1 , P=.001 ) . Metformin reduces the endocrinopathy of PCOS , allowing resumption of normal menses in most ( 91 % ) previously amenorrheic women with PCOS", "OBJECTIVE To evaluate whether pretreatment with metformin improves FSH-induced ovulation in women with clomiphene-resistant polycystic ovary syndrome ( PCOS ) . DESIGN R and omized prospect i ve trial . SETTING Department of Obstetrics and Gynecology , University of Siena . PATIENT(S ) Twenty women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) The women were divided r and omly into groups A and B ( 10 subjects each ) . Group B received 1,500 mg of metformin for at least a month before a single cycle of FSH stimulation . Group A underwent two cycles of FSH stimulation and then received metformin for a month before undergoing a third cycle . MAIN OUTCOME MEASURE(S ) The number of FSH ampules , days of treatment , E2 level on the day of hCG , number of follicles > 15 mm , number of hyperstimulation , and the number of cycles with hCG withheld . RESULT ( S ) The number of follicles > 15 mm in diameter on the day of hCG administration was significantly lower in cycles performed after metformin treatment . The percentage of cycles with hCG withheld because of excessive follicular development was significantly lower in cycles treated with metformin . Plasma levels of E2 were significantly higher in cycles treated with FSH alone than in those treated with FSH and metformin . CONCLUSION ( S ) By reducing hyperinsulinism , metformin determines a reduction in intraovarian and rogens . This leads to a reduction in E2 levels and favors orderly follicular growth in response to exogenous gonadotropins", "We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment . Serum glycodelin , a putative biomarker of endometrial function , is decreased in women with early pregnancy loss . Insulin-like growth factor-binding protein-1 may also play an important role in pregnancy by facilitating adhesion processes at the feto-maternal interface . We studied 48 women with polycystic ovary syndrome before and after 4 weeks of administration of 500 mg metformin ( n = 26 ) or placebo ( n = 22 ) 3 times daily . Oral glucose tolerance tests were performed , and serum glycodelin and insulin-like growth factor-binding protein-1 were measured during the follicular and clomiphene-induced luteal phases of menses . In the metformin group , the mean ( + /-SE ) area under the serum insulin curve after glucose administration decreased from 62 + /- 6 to 19 + /- 2 nmol/L.min ( P < 0.001 ) . Follicular phase serum glycodelin concentrations increased 20-fold from 150 + /- 46 to 2813 + /- 1192 pmol/L ( P < 0.001 ) , and serum insulin-like-growth factor-binding protein-1 concentrations increased from 936 + /- 152 to 2396 + /- 300 pmol/L ( P < 0.001 ) . Similarly , luteal phase serum glycodelin concentrations increased 3-fold from 3434 + /- 1299 to 10624 + /- 1803 pmol/L ( P < 0.001 ) , and serum insulin-like growth factor-binding protein-1 concentrations increased from 1220 + /- 136 to 4916 + /- 596 pmol/L ( P < 0.001 ) . Uterine vascular penetration also increased in the metformin group , as did blood flow of spiral arteries , as demonstrated by a 20 % decrease in the resistance index from 0.71 + /- 0.02 to 0.57 + /- 0.03 ( P < 0.001 ) . These variables did not change in the placebo group . We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome . These changes may reflect an improved endometrial milieu for the establishment and maintenance of pregnancy", "This study was design ed to determine if metformin therapy improves ovarian stimulation and IVF outcomes in coasted patients with clomiphene-resistant polycystic ovarian syndrome ( PCOS ) . A retrospective data analysis was performed on women with clomiphene citrate-resistant PCOS treated with or without metformin , who underwent 72 cycles of IVF-embryo transfer with intracytoplasmic sperm injection ( ICSI ) . In 59 cycles , patients were coasted to allow oestradiol concentrations to drop before human chorionic gonadotrophin administration . In patients undergoing coasting , the outcome of IVF with ICSI was compared in those who were treated and untreated . In patients treated with metformin , follicular fluid concentrations of testosterone and insulin were significantly lower ( 60.5 + /- 5 versus 79.1 + /- 6 ng/dl ; P < 0.05 and 18 + /- 2.5 versus 22 + /- 2.4 micro IU/ml ; P < 0.05 respectively ) , and the mean number of oocytes retrieved ( 22.3 + /- 2.4 versus 19.7 + /- 1.6 ) did not differ . The metformin-treated group showed an increase in the mean number of mature oocytes , oocytes fertilized and cleaving embryos ( 4-cell or greater by 72 h ) . However , in the group of patients undergoing coasting , maximum oestradiol concentrations and number of days of coasting were all lower in the metformin-treated group with increased clinical pregnancy rates ( 71 versus 30 % , P < 0.05 ) . Therefore , metformin use appears beneficial in improving IVF outcomes in clomiphene citrate-resistant PCOS patients", "OBJECTIVE To assess the effects of 6 months of metformin therapy on clinical and biochemical parameters in polycystic ovary syndrome ( PCOS ) and to evaluate those parameters in responders and nonresponders to identify the subjects who respond to an insulin sensitizer in PCOS . STUDY DESIGN Sixty-six diagnosed PCOS patients were recruited . Baseline characteristics ( menstrual history , hirsutism scoring , acne grading , body mass index [ BMI ] , serum luteinizing hormone and follicule-stimulating hormone [ LH/FSH ] ratio , testosterone , fasting insulin and glucose/insulin index ) were assessed initially and 6 months after metformin therapy . Three groups were constructed on the basis of menstrual symptoms : oligomenorrhea ( group I ) , amenorrhea ( group II ) and hypomenorrhea ( group III ) . Responders were those who had improvements in menstrual pattern or conceived . Response was compared in 3 groups , and biochemical parameters were compared in responders and nonresponders . RESULTS There were 44 ( 66.6 % ) oligomenorrheic , 17 ( 25.7 % ) amenorrheic and 5 ( 7.5 % ) hypomenorrheic cases and 31 ( 46.5 % ) infertile women . In total , 85.7 % responded to treatment ; the rest ( 14.3 % ) were nonresponders . Among responders , 62.29 % achieved regular periods , 22.95 % experienced improvements in their menstrual abnormalities , and 13 % conceived . Overall , a significant reduction occurred in BMI ( P = .04 ) , mean testosterone ( P = .03 ) and mean fasting insulin levels ( P = .01 ) , but no significant improvement was observed in hirsutism , acne , LH/FSH ratio or glucose/insulin index . A total of 9.75 % , 18.75 % and 30 % did not respond in the oligomenorrheic , amenorrheic and hypomenorrheic groups , respectively ( P = .04 ) . Testosterone and insulin were reduced significantly in responders ( P = .05 and .01 , respectively ) but not in nonresponders ( P = .26 and .73 ) . An initial high LH/FSH ratio and lower testosterone levels were associated with a better response . CONCLUSION Six months of metformin therapy improved menstrual cyclicity and fertility in women with PCOS . It result ed in a decline in testosterone and insulin levels . Oligomenorrheic patients with an increased LH/FSH ratio and lower testosterone levels responded better", "OBJECTIVE To determine the clinical , biochemical , hormonal , and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome ( PCOS ) and compare with pretherapy parameters . METHOD 50 Indian women with PCOS , 25 unmarried and 25 married , infertile women , were enrolled in this prospect i ve clinical study . After a baseline workup , including body mass index ( BMI ) , waist hip ratio ( WHR ) , Ferriman Gallwey hirsutism scoring , menstrual pattern , levels of fasting insulin , lipids , oral glucose tolerance test ( OGTT ) , serum gonadotropins , estradiol ( E2 ) , testosterone , and rostenedione , sex hormone binding globulin ( SHBG ) , and dehydroepi and rosterone sulphate ( DHEAS ) , patients were given 1000 gm of metformin for 6 months and then reevaluated . RESULT In 41 of 50 women who completed treatment , significant improvement in BMI , WHR , menstrual cyclicity ( 80.5 % ) , ovulation rate ( 66 % ) , and pregnancy rate ( 28 % ) was noted . Statistically significant decrease in lutenising hormone ( LH ) and LH/FSH ratio with an increase in follicle stimulating hormone ( FSH ) levels were seen . Levels of high-density lipoprotein ( HDL ) cholesterol ( Chol ) increased along with a decrease in total cholesterol . Improvement was noted in ovarian volume , stromal thickness , and number of follicles . There was no change in hirsutism , acne , levels of other sex steroid hormones , and lipids . CONCLUSION A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS", "Metformin effectively restores insulin sensitivity in insulin-resistant women with polycystic ovary syndrome ( PCOS ) . We examined whether metformin , given prior to and during ovarian stimulation for in vitro fertilization ( IVF ) , altered follicle stimulating hormone ( FSH ) requirement and increased the number of collected oocytes in these women . Seventeen insulin-resistant women with PCOS were recruited to our IVF unit to receive two consecutive cycles of ovarian stimulation with or without metformin co-treatment , the order of treatments being r and omized using a table of r and om numbers . Metformin treatment ( 1500 mg/day ) started 3 weeks before downregulation with buserelin acetate and was continued throughout ovarian stimulation with human recombinant FSH . Nine women completed both cycles , the results of eight women being excluded because of pregnancy after the first cycle ( n = 4 ) or because the protocol of the study was not followed ( n = 4 ) . Mean total FSH dose was 2301 IU ( range 1500 - 6563 IU ) in metformin cycles and 2174 IU ( range 1200 - 3900 IU ) in parallel control cycles , while the mean number of collected oocytes was 8.6 ( range 2 - 28 ) and 4.6 ( range 1 - 16 ) , respectively . Bayesian analysis showed probabilities of 0.05 that metformin reduces FSH requirement by at least 10 % , and of 0.61 that at least 10 % more oocytes are collected after metformin co-treatment . Co-administration of metformin is therefore likely to increase the number of oocytes collected after ovarian stimulation in insulin-resistant women with PCOS but is unlikely to reduce the requirement for FSH", "Abstract Objective To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome . Design R and omised clinical trial . Setting Multicentre trial in 20 Dutch hospitals . Participants 228 women with polycystic ovary syndrome . Interventions Clomifene citrate plus metformin or clomifene citrate plus placebo . Main outcome measure The primary outcome measure was ovulation . Secondary outcome measures were ongoing pregnancy , spontaneous abortion , and clomifene resistance . Results 111 women were allocated to clomifene citrate plus metformin ( metformin group ) and 114 women were allocated to clomifene citrate plus placebo ( placebo group ) . The ovulation rate in the metformin group was 64 % compared with 72 % in the placebo group , a non-significant difference ( risk difference − 8 % , 95 % confidence interval − 20 % to 4 % ) . There were no significant differences in either rate of ongoing pregnancy ( 40 % v 46 % ; − 6 % , − 20 % to 7 % ) or rate of spontaneous abortion ( 12 % v 11 % ; 1 % , − 7 % to 10 % ) . A significantly larger proportion of women in the metformin group discontinued treatment because of side effects ( 16 % v 5 % ; 11 % , 5 % to 16 % ) . Conclusion Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome . Trial registration Current Controlled Trials IS RCT N55906981 [controlled-trials.com][controlled-trials.com ]", "AIMS To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome ( PCOS ) in an infertility clinic . METHODS This was a r and omized placebo controlled double-blind crossover study of 3 months metformin ( 1500 mg day-1)/placebo , followed by 3 months metformin/placebo together with clomiphene ( 50 - 100 mg for 5 days ) for three cycles in clomiphene resistant women with PCOS . The primary outcomes were restoration of spontaneous menses , ovulation induction ( spontaneous or clomiphene induced ) and pregnancy . Secondary endpoints were changes in biochemical parameters related to and rogens and insulin . RESULTS Twelve women completed the metformin arm and 14 the placebo arm . Spontaneous menstruation resumed in five metformin treated patients and in six placebo treated women , P=0.63 . No women given metformin spontaneously ovulated , although one patient given placebo did , P=0.30 . There was no difference in the efficacy of clomiphene between the two groups with ovulation being induced in five ( out of 12 ) metformin treated women and four ( out of 14 ) placebo treated women , P=0.63 . Pregnancy occurred in three ( out of 12 ) women given metformin and two ( out of 14 ) women given placebo , P=0.59 . CONCLUSIONS Metformin is not always beneficial when given to clomiphene resistant infertile women with PCOS in clinical practice", "BACKGROUND Previous studies suggest that metformin by reducing hyperinsulinemia is clinical ly useful in the treatment of polycystic ovary syndrome ( PCOS ) . Our Objective was to observe the role of metformin in correcting oligomenorrhea/amenorrhea and anovulation within six month in hyperinsulinemic women with PCOS . Another aim was to assess the decrease in hyperinsulinemia and body weight by metformin in our population . METHODS This study was carried out at the Department of Obstetrics and Gynaecology , Islamic International Medical Complex ( IIMC ) Islamabad , from October 2001 to March 2003 . Fifty women fulfilling the clinical and biochemical criteria for PCOS and hyperinsulinemia were enrolled . Metformin was started at an oral dose of 500mg/day and maintained at 1500 mg for 6 months . Besides ultrasonography and body weight . serum FSH , LH , fasting insulin , fasting blood sugar and creatinine levels were performed . After six months menstrual cyclicity , fasting insulin levels , day 21 serum progesterone and body weights were assessed . RESULTS After six months of Metformin therapy , menstrual regularity was achieved in 19 out of 22 women ( 86 % ) . Out of these 11 women ( 50 % ) were ovulating at six months . On Metformin , the median fasting serum insulin decreased from 23.6 micro U/ml to 20.2 micro U/ml ( P<0.05 ) . There was no significant weight reduction ( p=0.096 ) with Metformin in six months . Data was analyzed using SPSS by paired t-test", "OBJECTIVE To obtain data from a pilot r and omized trial on the effect of metformin therapy and lifestyle modification on ovulation and and rogen concentrations in women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , placebo-controlled pilot trial . SETTING Academic medical center . PATIENT(S ) Thirty-eight overweight or obese women with PCOS . INTERVENTION(S ) All subjects were r and omized to one of four 48-week interventions : metformin 850 mg two times per day , lifestyle modification plus metformin 850 mg two times per day , lifestyle modification plus placebo , or placebo alone . MAIN OUTCOME MEASURE(S ) Recruitment , dropout , and compliance with a long-term lifestyle intervention in PCOS ; preliminary estimates of treatment effect on ovulation , as measured by weekly urinary pregnanediol glucuronide , and on total T and free and rogen index . RESULT ( S ) It was necessary to screen seven women to have one subject r and omized . The dropout rate was 39 % , with the majority of dropouts occurring within the first 24 weeks . Mean body mass index was > 39 mg/kg(2 ) . Modest weight reduction was found in all treatment groups , with the most significant reduction occurring with the combination of metformin and lifestyle intervention . Significant and rogen reduction occurred in the combination group only . Ovulation rates did not differ significantly between groups . However , when data were analyzed by presence or absence of weight reduction in subjects , independent of treatment group , the estimated odds ratio for weight loss was 9.0 ( 95 % confidence interval 1.2 - 64.7 ) with respect to regular ovulation . If weight loss occurred during metformin therapy , the odds ratio for regular ovulation was 16.2 ( 95 % confidence interval 4.4 - 60.2 ) . CONCLUSION ( S ) Key method ologic issues for a large-scale , r and omized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity . Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS", "Abstract Objective . To examine the effect of metformin therapy on ovarian response in clomiphene-resistant PCOS patients . Design . R and omized prospect i ve study . Setting . Zeynep Kamil Hospital IVF Center . Patients . Thirty-two female PCOS patients with clomiphene citrate resistance . Interventions . Test group A received 2 × 850 mg/day metformin therapy for 8 weeks , followed by gonadotropin induction . Only gonadotropin induction was applied to Control group B.Main outcome measures . Total gonadotropin dosage , duration of gonadotropin therapy , estradiol level on HCG-day , number of follicles with ≥16 mm diameter , number of cases with hyperstimulation development , number of cancelled cycles , endometrial thickness on HCG-day , pregnancy outcome , multiple pregnancy rate . Results . The total gonadotropin doses given to metformin- study group was significantly lower than the control group . In addition , duration of therapy , HCG level , plasma estradiol level on HCG-day in the study group was significantly lower than in the control group . Conclusions . Metformin therapy has led to a higher pregnancy outcome , as well as to a decrease in hyperstimulation risk , cycle cancellations , and multiple pregnancy rates with a lower gonadotropin dosage", "OBJECTIVE To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate ( CC ) in women who are resistant to CC alone . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Multicenter environment . PATIENT(S ) Anovulatory women with the polycystic ovary syndrome ( PCOS ) who were resistant to CC . INTERVENTION(S ) Participants received placebo or metformin , 500 mg three times daily , for 7 weeks . Information on reproductive steroids , gonadotropins , and oral glucose tolerance testing was obtained at baseline and after treatment . Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days . Serum P level > or = 4 ng/mL was considered to indicate ovulation . With ovulation , the daily CC dose was not changed , but with anovulation it was increased by 50 mg for the next cycle . Patients completed the study when they had had six ovulatory cycles , became pregnant , or experienced anovulation while receiving 150 mg of CC . MAIN OUTCOME MEASURE(S ) Ovulation and pregnancy rates . RESULT ( S ) In the metformin and placebo groups , 9 of 12 participants ( 75 % ) and 4 of 15 participants ( 27 % ) ovulated , and 6 of 11 participants ( 55 % ) and 1 of 14 participants ( 7 % ) conceived , respectively . Comparisons between the groups were significant . CONCLUSION ( S ) In anovulatory women with PCOS who are resistant to CC , metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment", "Most patients with polycystic ovary syndrome ( PCOS ) have hyperinsulinemia ; thus it has been postulated that insulin-lowering drugs , such as metformin , might be a useful long-term choice . We evaluated the effects of 6 months ' administration of metformin on clinical and endocrine indices in PCOS patients . Forty-two hyperinsulinemic women with PCOS were countinuously treated with metformin for 6 months . Gonadotropins , and rogens ( testosterone and and rostenedione ) , insulin , sex hormone binding globulin ( SHBG ) , lipid profile and clinical indices ( menstrual length , body mass index ( BMI ) , Ferriman-Gallwey score and waist/hip ratio ( WHR ) ) were studied before and after metformin treatment . All women experienced a normalization of menstrual cycle length ( reduction rate , 36.9 % ) , a significant decrease in luteinizing hormone , insulin and and rogen levels and an increase in SHBG plasma concentrations , with a concomitant decrease in cycle length and WHR . Significant changes were observed in the lipid profile . According to baseline and rogen levels , patients were divided into two groups : 20 normo and rogenic and 17 hyper and rogenic women . The greatest decline of and rogens , BMI and Ferriman-Gallwey score was observed in hyper and rogenic patients . Lowering of and rogenicity was independent of BMI . Significant changes in lipid profile were observed in both groups after metformin treatment . These results suggest that metformin is effective in decreasing hyper and rogenism , mainly by reducing insulin levels . This leads to an improvement of clinical manifestations of PCOS and , in particular , of hyper and rogenism", "OBJECTIVE To study the effect of metformin in combination with clomiphene citrate , as compared with placebo plus clomiphene citrate , on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome . METHODS This study was carried out at King Hussein Medical Center , Amman , Jordan , during the period January 2001 through to July 2001 . Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospect ively for 6 treatment cycles by receiving metformin , 850 mg twice daily throughout the cycle along with 50 mg clomiphene citrate , starting on day 5 - 9 of the same cycle ( N=16 ) , or by taking placebo with clomiphene citrate ( N=12 ) . During cycles 2 - 6 , clomiphene citrate was added with increments of 50 mg ( up to 200 mg/day ) for both groups . Progesterone level on day 21 and 28 > 5ng/dl was indicative of ovulation . RESULTS A statistically significant increase in the rates of ovulation ( 68.6 % versus 25 % , p<0.05 ) and pregnancy ( 56.3 % versus 16.6 % , p<0.05 ) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls . Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group . CONCLUSION Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates , and decreases the occurrence of ovarian hyperstimulation syndrome", "CONTEXT Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome ( PCOS ) , clomiphene citrate ( CC ) is still considered to be the first-line drug to induce ovulation in these patients . OBJECTIVE The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS . DESIGN We describe a prospect i ve parallel r and omized , double-blind , double-dummy controlled clinical trial . SETTING The study was conducted at the University \" Magna Graecia \" of Catanzaro , Catanzaro , Italy . PATIENTS One hundred nonobese primary infertile anovulatory women with PCOS participated . INTERVENTIONS We administered metformin cloridrate ( 850 mg twice daily ) plus placebo ( group A ) or placebo plus CC ( 150 mg for 5 d from the third day of a progesterone withdrawal bleeding ) ( group B ) for 6 months each . MEAN OUTCOME MEASURES The main outcome measures were ovulation , pregnancy , abortion , and live-birth rates . RESULTS The subjects of groups A ( n = 45 ) and B ( n = 47 ) were studied for a total of 205 and 221 cycles , respectively . The ovulation rate was not statistically different between either treatment group ( 62.9 vs. 67.0 % , P = 0.38 ) , whereas the pregnancy rate was significantly higher in group A than group B ( 15.1 vs. 7.2 % , P = 0.009 ) . The difference found between groups A and B regarding the abortion rate was significant ( 9.7 vs. 37.5 % , P = 0.045 ) , whereas a positive trend was observed for the live-birth rate ( 83.9 vs. 56.3 % , P = 0.07 ) . The cumulative pregnancy rate was significantly higher in group A than group B ( 68.9 vs. 34.0 % , P < 0.001 ) . CONCLUSIONS Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women", "Abstract We evaluated the fertility promoting effect of metformin in infertile patients with polycystic ovary syndrome . Twenty-nine infertile patients with polycystic ovary syndrome ( PCOS ) are included in our prospect ively design ed study and 15 normal menstruating women served as controls for reproductive hormones and ovarian volumes . All PCOS patients received a total of 78 cycles of clomiphene citrate ( CC ) in the beginning , then patients who could not get pregnant were switched to metformin plus clomiphene citrate . PCOS patients served as their own controls for the ovulation and pregnancy rates . At the end of the CC cycles 4.2 % of patients got pregnant and 65.2 % of the remaining group got pregnant with metformin plus CC cycles ( p=0.0001 ) . We have not observed any serious side effects of metformin . The high pregnancy rate of our study population is consistent with the hypothesis that insulin resistance plays an important role in the pathogenesis of anovulation in patients with PCOS", "At present , it is unclear what the role is of laparoscopic ovarian diathermy ( LOD ) and of metformin administration as second-line treatments for ovulation induction in women with polycystic ovary syndrome ( PCOS ) after failure of clomiphene citrate ( CC ) treatment . The aim of the present study was to compare in a r and omized double-blind placebo-controlled fashion the effectiveness of LOD with metformin administration in the treatment of CC-resistant women with PCOS . A total of 120 overweight primary infertile anovulatory CC-resistant women with PCOS were enrolled and r and omized into two groups of treatment . Group A underwent diagnostic laparoscopy , whereas group B underwent LOD . At hospital discharge , the patients were treated for 6 months with metformin cloridrate ( group A ; 850 mg twice daily ) or with multivitamins ( group B ) . The ovulation , pregnancy , abortion , and live-birth rates were evaluated . At the end of the study , the total ovulation rate was not statistically different between both treatment groups ( 54.8 vs. 53.2 % [ correction ] in groups A and B , respectively ) , whereas the pregnancy ( 21.8 [ correction ] vs. 13.4 % ) , the abortion ( 9.3 [ correction ] vs. 29.0 % ) , and the live-birth ( 86.0 [ correction ] vs. 64.5 % ) rates were significantly ( P < 0.05 ) different between the two groups . Our data show that metformin administration is more effective than LOD in overall reproductive outcomes in overweight infertile CC-resistant women with PCOS", "BACKGROUND This study was carried out to determine the pattern of presentation of Polycystic ovary syndrome ( PCOS ) in patients presenting at our unit and to compare effects of clomiphene alone and in combination with metformin in management of PCOS . METHODS This study was conducted from Jan 2001 - 2003 at Military Hospital , Rawalpindi . All patients presenting with infertility were evaluated with a view to select 100 patients of PCOS with the help of history of oligomenorrhoea , hirsuitism and acne . Diagnosis was confirmed by ultrasonography and hormone analysis ( LH , FSH , prolactin , testosterone along with LH : FSH>2 ) . The 100 selected patients were divided into two equal groups . One was given combined clomiphene citrate ( CC ) and metformin for ovulation induction and the other CC alone . These patients were followed for six cycles for ovulation and conception . Follicle tracking on ultrasonography and day-21 serum progesterone level were used to detect ovulation while conception was confirmed by urine pregnancy test , serum B-HCG level and ultrasonography for gestational sac . RESULTS Hirsuitism and oligomenorrhoea were the two most common clinical features of PCOS . In the first group 34 patients ( 68 % ) ovulated as compared with 18 ( 36 % ) in the second group . In the first group 18 out of 34 women ( 52.9 % ) conceived as compared with only 8 out of 18 ( 44 % ) in the second group . The difference was significant at > 0.05 when ovulatory and pregnancy responses were compared among two groups . All patients tolerated metformin well and no teratogenic effects were observed in patients who conceived after treatment with metformin . CONCLUSION A combination of metformin and clomiphene citrate significantly increases the ovulation and conception rates in these patients", "OBJECTIVE This study was undertaken to evaluate the efficacy of metformin in women with anovulation who do not have evidence for hyper and rogenism and classic polycystic ovary syndrome . STUDY DESIGN A r and omized trial of metformin ( 1500 mg daily ) and placebo in 24 anovulatory women was undertaken for 3 months . Assessment s of changes in hormone levels and insulin sensitivity were carried out . Abnormal hormonal values were defined by levels exceeding the range in normal ovulatory controls . RESULTS Anovulatory women had normal and rogen levels and luteinizing hormone but had higher serum insulin and lower insulin sensitivity compared with controls . Over 3 months , there were 16 ovulatory cycles with metformin and only 4 with placebo ( P < .05 ) . Success of ovulation did not correlate with changes in and rogen , insulin , or insulin sensitivity parameters . CONCLUSION Metformin may be useful for inducing ovulation in anovulatory women who do not have hyper and rogenism . This effect may be independent of a lowering of and rogen or insulin levels", "CONTEXT Metformin is successfully used in the treatment of cycle disorders and anovulation in women with polycystic ovary syndrome ( PCOS ) . No data of the exact point and the impact of insulin resistance ( IR ) on metformin 's efficacy exist . OBJECTIVE The objective of the study was to evaluate the early potential effects of metformin treatment , their time of onset , and the role of IR on metformin 's efficacy . DESIGN This was a prospect i ve r and omized , double-blind , placebo-controlled trial . SETTING The study was conducted at the University of Heidelberg , Heidelberg , Germany . PATIENTS The patient population was 45 oligo-/anovulatory PCOS women with typical ovaries . INTERVENTIONS Women were stratified for IR ( 32 of 13 ) and then r and omly allocated to receive either metformin ( n = 22 ) or placebo ( n = 23 ) and were assessed before and every 4 wk within a treatment period of 12 wk . MAIN OUTCOME MEASURES Menstrual disturbance and markers of insulin metabolism were measured . RESULTS The main outcome criterion menstrual disturbance was successfully improved in the metformin-treated group , depending on IR ( 12 of 15 vs. three of 17 ) , whereas women without IR ( four of seven vs. four of six ) had no significant amelioration of their menstrual irregularities ( P < 0.05 ) . Estradiol levels increased continuously only in the treatment group ( P < 0.005 ) , indicating an improvement of ovulatory function . Sixty-seven percent of metformin-treated women had at least one ovulation , compared with only 45 % in the placebo group , shown by biphasic body temperature curves . Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio , compared with baseline ( P < 0.005 ) . CONCLUSIONS IR is a baseline predictor of clinical efficacy in metformin treatment in PCOS women measured by improved menstrual cyclicity and ovulatory function", "OBJECTIVE To assess whether the addition of metformin to gonadotrophin ovulation induction in insulin-resistant , normogonadotrophic , anovulatory women alters ovarian responsiveness to exogenous FSH . DESIGN Placebo-controlled double-blind assessment in an academic hospital . RESULTS After a progestagen withdrawal bleeding , patients were r and omised for either metformin ( n = 11 ) or placebo ( n = 9 ) treatment . In cases of absent ovulation , exogenous FSH was subsequently administered to induce ovulation . Only during metformin treatment did body mass index and and rogen ( and rostenedione and testosterone ) levels decrease , whereas FSH and LH levels increased significantly . In the metformin group , a single patient ovulated before the initiation of exogenous FSH . Significantly more monofollicular cycles and lower preovulatory oestradiol concentrations were observed in women receiving FSH with metformin compared with FSH alone . CONCLUSIONS Metformin co-treatment in a group of insulin-resistant , normogonadotrophic , anovulatory patients result ed in normalization of the endocrine profile and facilitated monofollicular development during the FSH induction of ovulation" ]

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[ "HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm", "Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass", "Simple ultrasound-based rules for the diagnosis of ovarian cancer.", "Evaluation of the Diagnostic Accuracy of the Risk of Ovarian Malignancy Algorithm in Women With a Pelvic Mass", "Transvaginal ultrasonographic characterization of ovarian masses: comparison of five scoring systems in a multicenter study.", "Differential diagnosis of adnexal masses: sequential use of the risk of malignancy index and HistoScanning, a novel computer-aided diagnostic tool.", "Multicentre external validation of IOTA prediction models and RMI by operators with varied training", "Color and Pulsed Doppler Sonography, Gray‐Scale Imaging, and Serum CA 125 in the Assessment of Adnexal Disease", "Artificial neural network models for the preoperative discrimination between malignant and benign adnexal masses.", "Comparison of four malignancy risk indices in the detection of malignant ovarian masses", "Impact of a multiparameter, ultrasound-based triage on surgical management of adnexal masses.", "No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting.", "Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group", "The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass.", "Differentiation of small adnexal masses based on morphologic characteristics of transvaginal sonographic imaging: a multicenter study.", "The Utility of Human Epididymal Protein 4, Cancer Antigen 125, and Risk for Malignancy Algorithm in Ovarian Cancer and Endometriosis", "Risk of malignancy index used as a diagnostic tool in a tertiary centre for patients with a pelvic mass", "Sonographic prediction of malignancy in adnexal masses using multivariate logistic regression analysis.", "Mathematical Models to Discriminate Between Benign and Malignant Adnexal Masses: Potential Diagnostic Improvement Using Ovarian HistoScanning", "Ovarian crescent sign and sonomorphological indices in preoperative determination of malignancy in adnexal masses.", "[Diagnostic importance of the sonographic scoring system in differentiating between malignant and benign ovarian tumors].", "A prospective randomized study of laparoscopy and minilaparotomy in the management of benign adnexal masses.", "Prospective evaluation of the IOTA logistic regression model LR2 for the diagnosis of ovarian cancer.", "Diagnostic Formula for the Differentiation of Adnexal Tumors by Transvaginal Sonography", "[HE4 a biomarker of ovarian cancer].", "Transvaginal color Doppler assessment of venous flow in adnexal masses.", "Comparison of 'pattern recognition' and logistic regression models for discrimination between benign and malignant pelvic masses: a prospective cross validation.", "Evaluation of transvaginal color Doppler sonography, transvaginal sonography and CA 125 for prediction of ovarian malignancy.", "Prospective Evaluation of Logistic Regression Models for the Diagnosis of Ovarian Cancer", "Doppler flow and arterial location in ovarian tumors.", "Prospective Internal Validation of Mathematical Models to Predict Malignancy in Adnexal Masses: Results from the International Ovarian Tumor Analysis Study", "Assessment of a new logistic model in the preoperative evaluation of adnexal masses.", "A multicenter prospective external validation of the diagnostic performance of IOTA simple descriptors and rules to characterize ovarian masses.", "Effect of quality of gynaecological ultrasonography on management of patients with suspected ovarian cancer: a randomised controlled trial.", "Effectiveness of a Multivariate Index Assay in the Preoperative Assessment of Ovarian Tumors", "A proposal for a new scoring system to evaluate pelvic masses: Pelvic Masses Score (PMS).", "Differentiation of benign and malignant adnexal masses: value of a morphologic scoring system.", "[Sonographic characterization, Doppler ultrasonography and tumor markers in the diagnosis of malignancy of ovarian masses].", "Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses.", "Comparison of risk of malignancy indices in evaluating ovarian masses in a Southeast Asian population.", "Role of gray scale and color Doppler in differentiating benign from malignant ovarian masses", "A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass.", "Logistic regression model to distinguish between the benign and malignant adnexal mass before surgery: a multicenter study by the International Ovarian Tumor Analysis Group.", "The efficacy of a sonographic morphology index in identifying ovarian cancer: a multi-institutional investigation.", "How Relevant Are ACOG and SGO Guidelines for Referral of Adnexal Mass?", "Comparison of Lerner score, Doppler ultrasound examination, and their combination for discrimination between benign and malignant adnexal masses.", "A comparative study of the risk of malignancy index and the ovarian crescent sign for the diagnosis of invasive ovarian cancer.", "Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass.", "A comparison between an ultrasound based prediction model (LR2) and the risk of ovarian malignancy algorithm (ROMA) to assess the risk of malignancy in women with an adnexal mass.", "Prospective cross-validation of Doppler ultrasound examination and gray-scale ultrasound imaging for discrimination of benign and malignant pelvic masses.", "Distinguishing the benign and malignant adnexal mass: an external validation of prognostic models.", "Risk scoring for adnexal masses and endoscopic management.", "IOTA simple rules for discriminating between benign and malignant adnexal masses: prospective external validation." ]

[ "Background : Recently , a Risk of Ovarian Malignancy Algorithm ( ROMA ) utilising human epididymis secretory protein 4 ( HE4 ) and CA125 successfully classified patients as presenting a high or low risk for epithelial ovarian cancer ( EOC ) . We vali date d this algorithm in an independent prospect i ve study . Methods : Women with a pelvic mass , who were scheduled to have surgery , were enrolled in a prospect i ve study . Preoperative serum levels of HE4 and CA125 were measured in 389 patients . The performance of each of the markers , as well as that of ROMA , was analysed . Results : When all malignant tumours were included , ROMA ( receiver operator characteristic (ROC)-area under curve (AUC)=0.898 ) and HE4 (ROC-AUC)=0.857 ) did not perform significantly better than CA125 alone ( ROC – AUC=0.877 ) . Using a cutoff for ROMA of 12.5 % for pre-menopausal patients , the test had a sensitivity of 67.5 % and a specificity of 87.9 % . With a cutoff of 14.4 % for post-menopausal patients , the test had a sensitivity of 90.8 % and a specificity of 66.3 % . For EOC vs benign disease , the ROC – AUC of ROMA increased to 0.913 and for invasive EOC vs benign disease to 0.957 . Conclusion : This independent validation study demonstrated similar performance indices to those recently published . However , in this study , HE4 and ROMA did not increase the detection of malignant disease compared with CA125 alone . Although the initial reports were promising , measurement of HE4 serum levels does not contribute to the diagnosis of ovarian cancer", "Objective Women presenting with a large or complex ovarian cyst are referred to extensive surgical staging to ensure the correct diagnosis and treatment of a possible epithelial ovarian cancer . We hypothesized that measurement of the biomarkers HE4 and CA-125 preoperatively would improve the assignment of these patients to the correct level of care . Methods Patients diagnosed with a cystic ovarian mass and scheduled for an operation at our center of excellence for ovarian cancer surgery from 2001 to 2010 were prospect ively included ( n=394 ) and plasma was collected consecutively . Cut-off for HE4 was calculated at 75 % specificity ( 85 pM and 71.8 pM for post and premenopausal women ) . For CA-125 , 35 U/mL cut-off was used . The study population included women with malignant ( n=114 ) , borderline ( n=45 ) , and benign ( n=215 ) ovarian tumors . Results Receiver operator characteristic ( ROC ) area under the curve ( AUC ) in the benign versus malignant cohorts was 86.8 % for CA-125 and 84.4 % for HE4 . Negative predictive value was 91.7 % when at least one of the biomarkers was positive , with only early stage epithelial ovarian cancer showing false negative results . Sensitivity at set specificity ( 75 % ) was 87 % for risk of ovarian malignancy algorithm ( ROMA ) in the postmenopausal cohort ( cut-off point , 26.0 % ) and 81 % in the premenopausal cohort ( cut-off point , 17.3 % ) . ROC AUC in the benign versus stage I epithelial ovarian cancer was only 72 % for HE4 and 76 % for CA-125 . Conclusion In our study , population HE4 did not outperform CA-125 . Based on our data a prospect i ve trial with patients already diagnosed with an ovarian cyst may be conducted", "OBJECTIVE To derive simple and clinical ly useful ultrasound-based rules for discriminating between benign and malignant adnexal masses . METHODS In a multicenter study involving nine centers consecutive patients with persistent adnexal tumors underwent transvaginal gray-scale and Doppler ultrasound examination using a st and ardized examination technique and st and ardized terms and definitions . Information on 42 gray-scale ultrasound variables and six Doppler variables was collected and entered into a research protocol . When developing simple ultrasound-based rules to predict malignancy ( M-rules ) we chose the ultrasound variable or the combination of ultrasound variables that had the highest positive predictive value ( PPV ) with regard to malignancy ; when developing simple rules to predict a benign tumor ( B-rules ) we chose the ultrasound variable or the combination of ultrasound variables that had the lowest PPV with regard to malignancy . We selected ten rules that were in agreement with our clinical experience and were applicable to at least 30 tumors and then tested them prospect ively on 507 tumors examined in three of the nine centers . RESULTS 1066 patients with 1233 adnexal tumors were included . There were 903 benign tumors ( 73 % ) and 330 malignant tumors ( 27 % ) . In 167 patients the tumors were bilateral . We selected five simple rules to predict malignancy ( M-rules ) : ( 1 ) irregular solid tumor ; ( 2 ) ascites ; ( 3 ) at least four papillary structures ; ( 4 ) irregular multilocular-solid tumor with a largest diameter of at least 100 mm ; and ( 5 ) very high color content on color Doppler examination . We chose five simple rules to suggest a benign tumor ( B-rules ) : ( 1 ) unilocular cyst ; ( 2 ) presence of solid components where the largest solid component is < 7 mm in largest diameter ; ( 3 ) acoustic shadows ; ( 4 ) smooth multilocular tumor less than 100 mm in largest diameter ; and ( 5 ) no detectable blood flow on Doppler examination . These ten rules were applicable to 76 % of all tumors , where they result ed in a sensitivity of 93 % , specificity of 90 % , positive likelihood ratio ( LR+ ) of 9.45 and negative likelihood ratio ( LR- ) of 0.08 . When prospect ively tested the rules were applicable in 76 % ( 386/507 ) of the tumors , where they had a sensitivity of 95 % ( 106/112 ) , a specificity of 91 % ( 249/274 ) , LR+ of 10.37 , and LR- of 0.06 . CONCLUSION Most adnexal tumors in an ordinary tumor population can be correctly classified as benign or malignant using simple ultrasound-based rules . For tumors that can not be classified using simple rules , ultrasound examination by an expert examiner might be useful", "OBJECTIVE : It is often difficult to distinguish a benign pelvic mass from a malignancy and tools to help referring physician are needed . The purpose of this study was to vali date the Risk of Ovarian Malignancy Algorithm in women presenting with a pelvic mass . METHODS : This was a prospect i ve , multicenter , blinded clinical trial that included women who presented to a gynecologist , a family practitioner , an internist , or a general surgeon with an adnexal mass . Serum HE4 and CA 125 were determined preoperatively . A Risk of Ovarian Malignancy Algorithm score was calculated and classified patients into high-risk and low-risk groups for having a malignancy . The sensitivity , specificity , negative predictive value , and positive predictive value of the Risk of Ovarian Malignancy Algorithm were estimated . RESULTS : A total of 472 patients were evaluated with 383 women diagnosed with benign disease and 89 women with a malignancy . The incidence of all cancers was 15 % and 10 % for ovarian cancer . In the postmenopausal group , a sensitivity of 92.3 % and a specificity of 76.0 % and for the premenopausal group the Risk of Ovarian Malignancy Algorithm had a sensitivity of 100 % and specificity of 74.2 % for detecting ovarian cancer . When considering all women together , the Risk of Ovarian Malignancy Algorithm had a sensitivity of 93.8 % , a specificity of 74.9 % , and a negative predictive value of 99.0 % . CONCLUSION : The use of the serum biomarkers HE4 and CA 125 with the Risk of Ovarian Malignancy Algorithm has a high sensitivity for the prediction of ovarian cancer in women with a pelvic mass . These findings support the use of the Risk of Ovarian Malignancy Algorithm as a tool for the triage of women with an adnexal mass to gynecologic oncologists . LEVEL OF EVIDENCE :", "The aim of this work was to test and compare the accuracy of five different morphological scoring systems to identify malignant ovarian masses in a prospect i ve multicenter study . Four of the systems had previously been reported by Granberg , Sassone , De Priest and Lerner and the fifth is newly developed . A total of 330 ovarian neoplasms were collected in three different centers , which adopted the same diagnostic procedures . Of these , 261 masses were benign ( mean diameter 50 + /- 26 mm ) and 69 were malignant ( mean diameter 69 + /- 33 mm ) ( prevalence 21 % ) . The area under the receiver operating characteristic ( ROC ) curve for the multicenter score was 0.84 . This was significantly better than the areas of the other four scores which ranged from 0.72 to 0.75 . The cut-off levels derived from the five ROC curves achieved a sensitivity that ranged from 74 % ( Sassone score ) to 88 % ( De Priest score > or = 5 ) , and a specificity from 40 % ( De Priest ) to 67 % ( multicenter ) ; the highest positive predictive value was 41 % ( multicenter ) . With a cut-off level of 9 , the accuracy of the multicenter score was significantly better than the scores of Granberg and De Priest ( McNemar 's test p < 0.0001 ) . Similar results were obtained in 207 ovarian masses of < or = 5 cm in mean diameter , and when 19 borderline and 11 stage 1 cancers only were considered . For the clinical purpose s of a screening test we also checked a possible cut-off level of > or = 8 , which increased the sensitivity to 93 % with a drop of specificity to 56 % . With the use of the same criteria for the scores of the different authors , the following values were obtained for sensitivity : 96 % , 81 % , 93 % and 90 % ; and for specificity : 23 % , 56 % , 28 % and 49 % . The multicenter score performed well at distinguishing malignant from benign lesions , and was better than the other four traditional scores , for both large and small masses . This was mainly due to the introduction of two criteria that allowed correction for typical dermoids and endohemorrhagic corpora lutea . A completely reliable differentiation of benign from malignant masses can not be obtained by sonographic imaging alone", "OBJECTIVE To assess the value of ovarian Histo-Scanning ( ™ ) , a novel computerized technique for interpreting ultrasound data , in combination with the risk of malignancy index ( RMI ) in improving triage for women with adnexal masses . METHODS RMI indices were assessed in 199 women enrolled in a prospect i ve study to investigate the use of HistoScanning . Ultrasound scores were obtained by blinded analysis of archived images . The following sequential test was developed : HistoScanning was modeled as a second-line test for RMI between a lower cut-off and an upper cut-off . The optimal combination of these cut-offs that together maximized the Youden index ( Sensitivity + Specificity - 1 ) was determined . RESULTS Using RMI at the st and ard cut-off value of 250 result ed in a sensitivity of 74 % and a specificity of 86 % . When RMI was combined with HistoScanning , the highest accuracy was achieved by using HistoScanning as a sequential second-line test for patients with RMI values between 105 and 2100 . At these cut-off values , sequential use of RMI and HistoScanning result ed in mean sensitivity and specificity estimates of 88 % and 95 % , respectively . CONCLUSIONS Our data suggest that HistoScanning may have the potential to improve the diagnostic accuracy of RMI , which could result in better triage for women with adnexal masses . Further prospect i ve validation is warranted", "Background : Correct characterisation of ovarian tumours is critical to optimise patient care . The purpose of this study is to evaluate the diagnostic performance of the International Ovarian Tumour Analysis ( IOTA ) logistic regression model ( LR2 ) , ultrasound Simple Rules ( SR ) , the Risk of Malignancy Index ( RMI ) and subjective assessment ( SA ) for preoperative characterisation of adnexal masses , when ultrasonography is performed by examiners with different background training and experience . Methods : A 2-year prospect i ve multicentre cross-sectional study . Thirty-five level II ultrasound examiners contributed in three UK hospitals . Transvaginal ultrasonography was performed using a st and ardised approach . The final outcome was the surgical findings and histological diagnosis . To characterise the adnexal masses , the six-variable prediction model ( LR2 ) with a cutoff of 0.1 , the RMI with cutoff of 200 , ten SR ( five rules for malignancy and five rules for benignity ) and SA were applied . The area under the curves ( AUCs ) for performance of LR2 and RMI were calculated . Diagnostic performance measures for all models assessed were sensitivity , specificity , positive and negative likelihood ratios ( LR+ and LR− ) , and the diagnostic odds ratio ( DOR ) . Results : Nine-hundred and sixty-two women with adnexal masses underwent transvaginal ultrasonography , whereas 255 had surgery . Prevalence of malignancy was 29 % ( 49 primary invasive epithelial ovarian cancers , 18 borderline ovarian tumours , and 7 metastatic tumours ) . The AUCs for LR2 and RMI for all masses were 0.94 ( 95 % confidence interval ( CI ) : 0.89–0.97 ) and 0.90 ( 95 % CI : 0.83–0.94 ) , respectively . In premenopausal women , LR2−RMI difference was 0.09 ( 95 % CI : 0.03–0.15 ) compared with −0.02 ( 95 % CI : −0.08 to 0.04 ) in postmenopausal women . For all masses , the DORs for LR2 , RMI , SR+SA ( using SA when SR inapplicable ) , SR+MA ( assuming malignancy when SR inapplicable ) , and SA were 62 ( 95 % CI : 27–142 ) , 43 ( 95 % CI : 19–97 ) , 109 ( 95 % CI : 44–274 ) , 66 ( 95 % CI : 27–158 ) , and 70 ( 95 % CI : 30–163 ) , respectively . Conclusion : Overall , the test performance of IOTA prediction models and rules as well as the RMI was maintained in examiners with varying levels of training and experience", "Objective To compare color and pulsed Doppler sonography with gray-scale ultrasound imaging and serum CA 125 levels in establishing accurate preoperative diagnoses of adnexal masses . Methods Medical records of 109 patients referred with preexisting adnexal lesions were review ed retrospectively by comparing preoperative ultrasonic data ( gray-scale imaging and color and pulsed Doppler findings ) with serum CA 125 levels . Results Eighty-three masses were removed surgically , confirming seven malignancies and 76 benign tumors , and 26 masses were followed ; 15 regressed and 11 persisted . Color and pulsed Doppler sonography showed the highest sensitivity , followed by gray-scale imaging , whereas serum CA 125 levels revealed the highest specificity in distinguishing malignant from benign adnexal tumors . All three methods had high negative predictive values ( 96–100 % ) , whereas only serum CA 125 had a positive predictive value greater than 50 % . Conclusion Color and pulsed Doppler sonography , which demonstrate a tumor angiogenic activity , are as accurate as gray-scale imaging in the assessment of adnexal lesions . Together with serum CA 125 marker levels , they produce high negative predictive values , providing reassurance that an adnexal mass is benign", "OBJECTIVE The aim of this study was to generate and evaluate artificial neural network ( ANN ) models from simple clinical and ultrasound-derived criteria to predict whether or not an adnexal mass will have histological evidence of malignancy . DESIGN The data were collected prospect ively from 173 consecutive patients who were scheduled to undergo surgical investigations at the University Hospitals , Leuven , between August 1994 and August 1996 . The outcome measure was the histological classification of excised tissues as malignant ( including borderline ) or benign . METHODS Age , menopausal status and serum CA 125 levels and sonographic features of the adnexal mass were encoded as variables . The ANNs were trained on a r and omly selected set of 116 patient records and tested on the remainder ( n = 57 ) . The performance of each model was evaluated using receiver operating characteristic ( ROC ) curves and compared with corresponding data from an established risk of malignancy index ( RMI ) and a logistic regression model . RESULTS There were 124 benign masses , five of borderline malignancy and 44 invasive cancers ( of which 29 % were metastatic ) ; 37 % of patients with a malignant or borderline tumor had stage I disease . The best ANN gave an area under the ROC curve of 0.979 for the whole data set , a sensitivity of 95.9 % and specificity of 93.5 % . The corresponding values for the RMI were 0.882 , 67.3 % and 91.1 % , and for the logistic regression model 0.956 , 95.9 % and 85.5 % , respectively . CONCLUSION An ANN can be trained to provide clinical ly accurate information , on whether or not an adnexal mass is malignant , from the patient 's menopausal status , serum CA 125 levels , and some simple ultrasonographic criteria", "Objective The aim of this study was to evaluate the ability of four risk of malignancy indices ( RMI ) to detect malignant ovarian tumors . Methods This is a prospect i ve study of 100 women admitted to the Department of Obstetrics and Gynecology of Gulhane Military Medicine Academy for surgical exploration of pelvic masses . To diagnose malignant ovarian tumors , the sensitivity , specificity , negative and positive predictive values and diagnostic accuracy of four RMIs ( RMI 1 , RMI 2 , RMI 3 , and RMI 4 ) were obtained . Results In our study we found that there is no statistically significant difference in the performance of four different RMIs in discriminating malignancy . We think that malignancy risk indices is more reliable than the menopausal status , serum CA-125 levels , ultrasound features and tumor size separately in detecting malignancy . Conclusion We concluded that any of the four malignancy risk indices described can be used for selection of cases for optimal therapy . These methods are simple techniques that can be used even in less-specialized gynecology clinics to facilitate the selection of cases for referral to an oncological unit", "OBJECTIVE To prospect ively evaluate the accuracy of a multiparameter , ultrasound-based triage and its impact on surgical management of adnexal masses . METHODS Masses evaluated as normal according to Ferrazzi 's sonographic morphological score were considered as being at low risk of malignancy and eligible for laparoscopic treatment without further evaluation . Masses evaluated as abnormal , but without additional risk factors such as ascites , diameter > or = 10 cm , bilaterality , immobility , resistance index < or = 0.6 and serum CA 125 > 35 IU/mL were considered at moderate risk and eligible for laparoscopic evaluation and treatment . Masses with abnormal morphological score and any of these additional risk factors were considered at high risk and treated by laparotomy . The results of pathological examination were obtained for each mass . RESULTS Two hundred and four ( 87 % ) masses were benign and 30 ( 13 % ) were malignant . Among 182 low-risk , 19 moderate-risk and 33 high-risk masses , the odds of malignancy were 1 : 90 , 1 : 18 and 4.5 : 1 , respectively . To calculate the diagnostic accuracy of this algorithm , low- and moderate-risk groups were considered together : the sensitivity was 90 % , specificity 97 % , positive predictive value 82 % and negative predictive value 99 % . The new algorithm was significantly more accurate than was morphological score alone ( P = 0.0002 ) . Ninety-six percent of benign masses were treated by laparoscopy . All three patients with malignant masses that were incorrectly assigned to laparoscopy underwent laparoscopic adnexectomy and frozen section . CONCLUSIONS The accuracy of this new algorithm was higher than that of the sonographic morphological scoring system alone . In the present series , it allowed the treatment by laparoscopy of 96 % of benign adnexal masses without mismanagement of any cases of ovarian cancer", "OBJECTIVE About 70 % of epithelial ovarian cancer patients ( EOC ) are diagnosed at advanced stage with a five-year survival rate of only 30 % . Whilst CA125 detects peritoneally-spread disease , it has limited sensitivity for early cancers , many of which are potentially curable . METHODS We compared the new commercially available tumor marker HE4 with CA125 individually , in combination , within the risk of malignancy index ( RMI ) and the newly defined risk of malignancy algorithm ( ROMA ) . Our prospect ively-collected cohort of 160 patients consisted of healthy controls , benign diseases , and borderline tumors/adenocarcinomas of ovarian , tubal , peritoneal and endometrial origin . HE4 and CA125 were measured in serum using st and ardized ELISA . RESULTS Both markers showed similar diagnostic performance in the detection of EOC at clinical ly defined thresholds ( CA125 35U/ml ; HE4 70pM ) but HE4 was not elevated in endometriosis . Comparison of non-malignant diagnoses ( n=71 ) versus early stage ovarian and tubal cancers ( n=19 ) revealed that HE4 and ROMA displayed the best diagnostic performance ( AUC 0.86/0.87 , specificity 85.9%/87.3 % and sensitivity 78.9%/78.9 % , respectively ) . Whilst RMICA125 detects peritoneal cancer better than all other models ( AUC 0.99 , specificity 97.2 % , sensitivity 80.0 % ) , there is no other detection benefit from RMI compared to HE4 alone or included in ROMA . CONCLUSIONS The major advantage of HE4 lies in its specificity and improved detection of borderline tumors and early stage ovarian and tubal cancers . HE4 is superior to CA125 with or without RMI and ROMA indices . However , we see no benefit from combining both markers in clinical practice", "Objectives To prospect ively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index , two logistic regression models , and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result . Design Prospect i ve temporal and external validation of simple ultrasound rules to distinguish benign from malignant adnexal masses . The rules comprised five ultrasonic features ( including shape , size , solidity , and results of colour Doppler examination ) to predict a malignant tumour ( M features ) and five to predict a benign tumour ( B features ) . If one or more M features were present in the absence of a B feature , the mass was classified as malignant . If one or more B features were present in the absence of an M feature , it was classified as benign . If both M features and B features were present , or if none of the features was present , the simple rules were inconclusive . Setting 19 ultrasound centres in eight countries . Participants 1938 women with an adnexal mass examined with ultrasound by the principal investigator at each centre with a st and ardised research protocol . Reference st and ard Histological classification of the excised adnexal mass as benign or malignant . Main outcome measures Diagnostic sensitivity and specificity . Results Of the 1938 patients with an adnexal mass , 1396 ( 72 % ) had benign tumours , 373 ( 19.2 % ) had primary invasive tumours , 111 ( 5.7 % ) had borderline malignant tumours , and 58 ( 3 % ) had metastatic tumours in the ovary . The simple rules yielded a conclusive result in 1501 ( 77 % ) masses , for which they result ed in a sensitivity of 92 % ( 95 % confidence interval 89 % to 94 % ) and a specificity of 96 % ( 94 % to 97 % ) . The corresponding sensitivity and specificity of subjective assessment were 91 % ( 88 % to 94 % ) and 96 % ( 94 % to 97 % ) . In the 357 masses for which the simple rules yielded an inconclusive result and with available results of CA-125 measurements , the sensitivities were 89 % ( 83 % to 93 % ) for subjective assessment , 50 % ( 42 % to 58 % ) for the risk of malignancy index , 89 % ( 83 % to 93 % ) for logistic regression model 1 , and 82 % ( 75 % to 87 % ) for logistic regression model 2 ; the corresponding specificities were 78 % ( 72 % to 83 % ) , 84 % ( 78 % to 88 % ) , 44 % ( 38 % to 51 % ) , and 48 % ( 42 % to 55 % ) . Use of the simple rules as a triage test and subjective assessment for those masses for which the simple rules yielded an inconclusive result gave a sensitivity of 91 % ( 88 % to 93 % ) and a specificity of 93 % ( 91 % to 94 % ) , compared with a sensitivity of 90 % ( 88 % to 93 % ) and a specificity of 93 % ( 91 % to 94 % ) when subjective assessment was used in all masses . Conclusions The use of the simple rules has the potential to improve the management of women with adnexal masses . In adnexal masses for which the rules yielded an inconclusive result , subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate diagnostic test ; the risk of malignancy index and the two regression models were not useful", "OBJECTIVE The purpose of this study was to evaluate the performance of human epididymis protein 4 ( HE4 ) and the Risk of Ovarian Malignancy Algorithm ( ROMA ) for distinguishing between benign and malignant pelvis masses in Asian women . METHODS This was a prospect i ve , multicenter ( n=6 ) study with patients from six Asian countries . Patients had a pelvic mass on imaging and were scheduled to undergo surgery . Serum CA125 and HE4 were measured on preoperative sample s. CA125 , HE4 , and ROMA were evaluated for sensitivity , specificity , positive predictive value ( PPV ) and negative predictive value ( NPV ) . RESULTS A total of 414 women with an adnexal mass were evaluated , of which 65 had epithelial ovarian ( EOC ) cancer , 16 had borderline tumors and 11 had other malignant diseases . Compared to CA125 , HE4 had lower sensitivity ( 56.9 % vs 90.8 % ) and NPV ( 91.8 % vs 97.3 % ) , but improved specificity ( 96.9 % vs 67.1 % ) and PPV ( 78.7 % vs 35.8 % ) for differentiating between benign pelvic mass and EOC . ROMA had similar sensitivity ( 89.2 % vs 90.8 % ) and NPV ( 97.6 % vs 97.3 % ) as CA125 , but showed improved specificity ( 87.3 % vs 67.1 % ) and PPV ( 58.6 % vs 35.8 % ) . ROMA accurately predicted 87.3 % of benign cases as low risk , and 82.6 % of stage I/II EOC and 89.2 % of all EOC as high risk . CONCLUSION ROMA showed similar sensitivity as CA125 but improved specificity and PPV , especially in premenopausal women . Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning", "OBJECTIVE The purpose of this study was to assess the diagnostic accuracy of transvaginal sonographic examination of small adnexal masses by simple descriptive sonographic scoring . METHODS In a prospect i ve multicenter study , 4 teaching hospitals and 2 regional hospitals with homogeneous st and ard sonographic equipment and operator experience recruited 677 consecutive patients with small adnexal masses of less than 5 cm . Morphologic scoring was obtained for each mass and recorded . The management of the mass was based on local protocol s. The minimal requirement was that surgery had to be performed for complex masses scoring 8 or higher , and follow-up of at least 12 months had to be performed and recorded for patients not admitted to surgery . Sonographic results were compared with pathologic reports and follow-up findings . RESULTS Fifty-two malignant tumors ( 19 borderline , 15 stage I-II , 15 stage III-IV , 2 tubal carcinomas , and 1 ovarian lymphoma ) , 243 benign tumors at pathologic examination , and 382 masses defined as benign according to follow-up findings were observed . Malignant tumors had a significantly higher mean + /- SD morphologic score ( 11.2 + /- 2.7 ) than benign masses ( 6.2 + /- 2.5 ) ( P = .001 ) . No difference was observed in the scoring assignment of malignant masses in different centers ( P = .56 ) . With a score of 8 or higher , the likelihood ratio was 3.61 ( 95 % confidence interval , 3.09 - 4.21 ) ; sensitivity , 92 % ; specificity , 76.9 % ; and positive predictive value , 25.6 % . CONCLUSIONS Our results provide evidence that descriptive morphologic scoring may overcome the subjectivity of interpretation of morphologic characteristics in small masses , and , at the same time , it can incorporate criteria to avoid simplistic description of a complex mass", "Background In women with pelvic mass , cancer antigen 125 ( CA125 ) had not achieved satisfactory sensitivity and specificity in the detection of ovarian cancer , particularly in patients with underlying endometriosis . The aim of this study was to determine the diagnostic potential of human epididymal protein 4 ( HE4 ) , the combination of HE4+CA125 , and the Risk of Ovarian Malignancy Algorithm ( ROMA ) for patients with pelvic mass , particularly in differentiating endometriosis from carcinoma . Methods A prospect i ve cross-sectional study was conducted at the Clinic for Gynecology and Obstetrics , Clinical Center of Serbia . Serum sample s were obtained preoperatively from 108 women undergoing surgery for pelvic mass ; 29 of them had ovarian carcinoma , and 79 had a nonmalignant ovarian disease ( 39 with benign tumor , 20 with endometriosis , 20 healthy controls ) . Sera were analyzed for the levels of HE4 and CA125 and were then compared with the final pathologic results . The diagnostic performance of HE4 and CA125 was estimated using receiver operating characteristic curve and area under the receiver operating characteristic curve . Results The level of HE4 and CA125 was significantly higher among the patients with malignant tumors , compared with patients with nonmalignant disease . At the predefined specificity of 95 % , HE4 and CA125 showed sensitivity of 65.5 % and 58.6 % , respectively , whereas the combination of HE4+CA125 reached 68.9 % at the same specificity . Importantly , the level of HE4 did not differ significantly between the patients with endometriosis and with other nonmalignant diseases ( which was not the case with CA125 ) . Risk of Ovarian Malignancy Algorithm classified 96 % of benign premenopausal cases as at low risk for ovarian cancer . Conclusions HE4 showed satisfactory capability of distinguishing endometriosis from ovarian cancer , which CA125 lacked . The Risk of Ovarian Malignancy Algorithm score proved to be useful in excluding malignant diagnosis in premenopausal women", "Abstract Objective . Risk of malignancy index ( RMI ) , based on a serum cancer antigen 125 level , ultrasound findings and menopausal status , is used to discriminate ovarian cancer from benign pelvic mass . In Denmark , patients with pelvic mass and RMI ≥200 are referred to tertiary gynecologic oncology centers according to the national guidelines for ovarian cancer treatment . The guidelines include recalculation of RMI at the tertiary center and , if indicated , positron emission tomography/computed tomography and fast‐track surgery by specialists in cancer surgery . The aim of this study was to vali date the use of RMI ≥200 as a tool for preoperative identification of ovarian cancer at a tertiary center . Design . Prospect i ve observational study . Setting . A tertiary center in Copenhagen , Denmark . Population . One thous and one hundred and fifty‐nine women with pelvic mass . Methods . The RMI was calculated after ultrasound examination and blood sampling for serum cancer antigen 125 analysis within two weeks before surgery . Main outcome measures . Sensitivity , specificity , positive and negative predictive values were calculated to evaluate the ability of RMI to distinguish between ovarian cancer and benign pelvic mass . Results . There were 778 women diagnosed with benign pelvic mass , while 251 had ovarian cancer and 74 had borderline ovarian tumor . Fifty‐six women were diagnosed with other forms of cancer . Sensitivity and specificity for ovarian cancer vs. benign pelvic mass for RMI ≥200 were 92 and 82 % , respectively . Corresponding positive and negative predictive values were 62 and 97 % . Conclusions . Risk of malignancy index ≥200 is a reliable tool for identifying patients with ovarian cancer pelvic masses at a tertiary centre to select patients for further preoperative examinations", "The aim of the study was to assign a probability of malignancy for any patient with an adnexal tumor by the application of multivariate logistic regression analysis to variables recorded at the time of pelvic sonography . Sixty-seven women with known adnexal masses were examined using transvaginal B-mode and color Doppler imaging . For each patient the variables included : ( 1 ) age , ( 2 ) maximum tumor diameter , ( 3 ) tumor volume , ( 4 ) unilocularity ( presence ( 0 ) or absence(1 ) ) , ( 5 ) papillary projections ( presence ( 1 ) or absence ( 0 ) ) , ( 6 ) r and om echogenicity ( presence ( 1 ) or absence ( 0 ) ) , ( 7 ) highest peak systolic velocity ( PSV ) , ( 8) time-averaged maximum velocity ( TAMXV ) , ( 9 ) pulsatility index ( PI ) and ( 10 ) resistance index ( RI ) . The TAMXV , PI and RI were those associated with the highest PSV . These ten independent variables and the final histological diagnosis for each patient ( the dependent variable ) were used for the regression analysis . Approximately 75 % of the entire data set was r and omly selected for generating the regression model . The remaining 25 % was used as the testing set for cross-validation of the model . In the entire data set there were 52 women with benign , three with borderline and 12 with invasive ovarian tumors . Regression analysis on the ten variables result ed in the retention of only ' age ' , ' papillary projection score ' and ' TAMXV ' as significantly contributing to predicting the presence or absence of malignancy . The probability of malignancy for any patient was given by solving the equation : Probability = 1/(1 + e-z ) where e is the base value for natural logarithms and z = ( 0.1273 x Age ) + ( 0.2794 x TAMXV ) + ( 4.4136 x Papillary projections score ) - 14.2046 . Cross-validation of the model on the test set of data gave a 100 % sensitivity and specificity . However , for the entire data set the best sensitivity and specificity were 93.3 and 90.4 % , respectively , at a cut-off value of 25 % probability of malignancy . In conclusion , multivariate logistic regression analysis enables the calculation of probability of malignancy for any patient with a known adnexal mass . The accuracy of this prediction appears to be better than that of morphological or Doppler criteria when the latter are used independently . The value of this model needs to be tested prospect ively", "Purpose : Accurate preoperative clinical assessment of adnexal masses can optimize outcomes by ensuring appropriate and timely surgery . This article addresses whether a new technology , ovarian HistoScanning , has an additional diagnostic value in mathematical models developed for the differential diagnosis of adnexal masses . Patients and Methods : Transvaginal sonography-based morphological variables were obtained through blinded analysis of archived images in 199 women enrolled in a prospect i ve study to assess the performance of ovarian HistoScanning . Logistic regression ( LR ) and neural network ( NN ) models including these variables and clinical and patient data along with the HistoScanning score ( HSS ) ( range , 0 - 125 ; based on mathematical algorithms ) were developed in a learning set ( 60 % patients ) . The remaining 40 % patients ( evaluation set ) were used to assess model performance . Results : Of all morphological and clinical variables tested , serum CA-125 , presence of a solid component , and HSS were most significant and used to develop the LR model . The NN model included all variables . The novel variable , HSS , offered significant improvement in the LR and NN models ' performance . The LR and NN models in an independent evaluation set were found to have area under the receiver operating characteristic curve = 0.97 ( 95 % confidence interval [ CI ] , 94 - 99 ) and 0.93 ( 95 % CI , 88 - 98 ) , sensitivities = 83 % ( 95 % CI , 71%-91 % ) and 80 % ( 95 % CI , 67%-89 % ) , and specificities = 98 % ( 95 % CI , 89%-99 % ) and 86 % ( 95 % CI , 72%-95 % ) , respectively . In addition , these models showed an improved performance when compared with 3 other existing models ( all P < 0.05 ) . Conclusions : This initial report shows a clear benefit of including ovarian HistoScanning into mathematical models used for discriminating benign from malignant ovarian masses . These models may be specifically helpful to the less experienced examiner . Future research should assess performance of these models in prospect i ve clinical trials in different population", "OBJECTIVE To compare the value of ovarian crescent sign ( OCS ) and various sonomorphologic scoring systems in consolidating pre-operative suspicion of ovarian malignancy in adnexal masses . MATERIAL S AND METHODS A prospect i ve study was carried out in 60 consenting women with an undiagnosed adnexal mass requiring operative intervention . OCS was considered to be present if normal ovarian tissue was seen adjacent to the tumor area on ultrasound . Various other sonological parameters were noted to calculate five morphological scoring systems . Doppler velocimetry study values were available in 27 cases . The results were compared for correctness of suspicion with histopathologic examination report of the tumor obtained at surgery . RESULTS Eleven of 60 specimens showed histopathologic diagnosis of malignancy . OCS was identified in 97 % of the benign masses . The sign was not seen in 10 of the 11 cases with malignancy . Sensitivity and negative predictive value of crescent sign was better than values obtained for the compared sonomorphological indices and Doppler velocimetry studies . CONCLUSION Ovarian crescent sign is a reliable and simple sonographic indicator comparable to sonomorphological indices and Doppler flow velocimetric studies for the preoperative detection of malignancy in adnexal masses", "INTRODUCTION There have been several different sonographic scoring systems developed for evaluation of particular characteristics of ovarian tumors in order to classify malignant diseases in the most objective way . The aim of this study was to evaluate diagnostic significance of our own scoring system and possibilities of its application in differentiation of malignant and benign ovarian tumors . MATERIAL AND METHODS A prospect i ve study comprised 177 women with different ovarian tumors . All patients underwent ultrasound examination using a unit with a 5 MHz probe . Certain tumor characteristics ( size , morphology , septa , type of capsule and ascites ) were estimated by scores from 0 to 2 whereas the sum of all scores presented the total score . A final diagnosis was made after histopathologic examination : group A -- malignant ovarian tumors ( n = 71 ) and group B -- benign ovarian tumors ( n = 106 ) . RESULTS The highest value of reliability in differentiation of malignant and benign ovarian tumors was score 6 and more than six ( sensitivity 87.3 % , specificity 91.5 % , positive predictive value 87.3 % , negative predictive value 91.5 % and test accuracy 90.9 % ) . DISCUSSION A separate diagnostic problem during application of mentioned sonographic scoring system were solid malignant tumors with a low total score ( 4 and 5 scores ) and benign tumors of complex consistence of high total score ( 7 and 8 scores ) . The total score 1 - 3 eliminates malignant tumors and the score from 9 - 10 eliminates benign type of tumors . CONCLUSION High sensitivity ( 95.7 % ) is present at the total score of 5 and more than five , but low specificity ( 81.1 % ) and test accuracy ( 87 % ) gives advantage to the score 6 and more , where differences between separate statistical parameters are least present", "BACKGROUND Recent prospect i ve and r and omized studies have demonstrated that laparoscopy is better than laparotomy in the treatment of benign adnexal masses . The aim of this study is to analyse the perioperative outcomes of laparoscopy and minilaparotomy in these patients , in a prospect i ve and r and omized manner . METHODS Between January 2003 and August 2003 , 100 consecutive women with a diagnosis of presumed benign adnexal mass and requiring surgical treatment were r and omly assigned to minilaparotomy and laparoscopy . R and omization was central ized and computer-based . RESULTS All operative procedures were performed without conversion to laparotomy . In the group of patients su bmi tted to minilaparotomy , a shorter operating time than patients su bmi tted to operative laparoscopy ( mean+/-SD : 71.9+/-31.8 versus 87.0+/-44.8 min ; P<0.05 ) was found . On the other h and , there were significant differences in terms of postoperative ileus ( 1.1+/-0.4 days in laparoscopy and 1.4+/-0.6 in minilaparotomy P<0.023 ) , without affecting the day of discharge . No intraoperative or early complications were registered in either group . CONCLUSIONS Taking into account that laparoscopy has to be considered the first choice for benign adnexal surgery , our data suggest that minilaparotomy could offer the gynaecology surgeon a valid alternative in the minimally invasive surgery field , especially in specific setting", "OBJECTIVES To assess the accuracy of the IOTA logistic regression model LR2 for the diagnosis of ovarian cancer . METHODS This was a prospect i ve single-center study of women with an ultrasound diagnosis of an adnexal tumor . They were all examined by a single Level-II ultrasound operator , who had received training in the systematic examination of ovarian tumors in accordance with the IOTA guidelines . In all women the likelihood of the adnexal lesion being malignant was calculated using the IOTA LR2 model . All women underwent surgery within 120 days of ultrasound examination and the ultrasound findings were compared with operative findings and the final histological diagnosis . RESULTS One hundred and twenty-four women were included in the final analysis . The mean age was 53.2 ( range , 20 - 91 ) years and 61/124 ( 49.2 % ) women were postmenopausal . 66/124 ( 53.2 % ) women had malignant lesions on postoperative histological examination . The IOTA LR2 model had a sensitivity of 97.0 % ( 95 % CI , 89.5 - 99.6 % ) and a specificity of 69.0 % ( 95 % CI , 55.5 - 80.5 % ) . The area under the receiver-operating characteristics curve was 0.93 ( SE , 0.022 ; 95 % CI , 0.89 - 0.97 ) , which was not significantly different from 0.92 ( SE , 0.018 ) reported in the original study ( P > 0.05 ) . CONCLUSION When evaluated prospect ively , the accuracy of the IOTA LR2 model was similar to that reported in the original study", "Objective To create a strategy for sonographic differentiation of benign and malignant adnexal tumors in premenopausal and postmenopausal patients . Methods Multiple sonomorphologic criteria were analyzed prospect ively in 754 tumors . Four hundred were found in premenopausal and 354 in postmenopausal women . In a logistic regression model , relevant criteria were selected , and a diagnostic formula for tumor differentiation was derived . Results There were 165 malignant tumors , of which 37 ( 9.2 % ) were found in premenopausal and 128 ( 36.2 % ) in postmenopausal women . In both groups , the criteria of solid phase and ascites were the most significant . Further important diagnostic criteria were structure and tumor size in premenopausal women and cyst architecture and tumor surface in postmenopausal women . These results allowed an estimation of the probability of malignancy . Using a cutoff point of 10 % for the probability to classify tumors as malignant , the sensitivity and specificity in premenopausal patients were 86.5 % and 92.6 % , respectively , with an accuracy of 92 % . In postmenopausal women , the sensitivity , specificity , and accuracy were 93 % , 82.7 % , and 86.6 % , respectively . Assuming a prevalence as given in the study , the positive and negative predictive values were 54.4 % and 98.5 % in premenopausal and 75.3 % and 95.4 % in postmenopausal women . Conclusions With four binary criteria , a useful diagnostic formula for tumor differentiation was obtained . However , estimates for sensitivity , specificity , and accuracy may be too optimistic because they were derived from the same data that were already used for model selection", "OBJECTIVE Verification of the importance of determination of HE4 and calculation of ROMA index for increasing the efficiency of diagnosis of ovarian cancer in a population of Czech women . DESIGN Prospect i ve study . SETTING Department of Gynaecology and Obstetrics , Faculty Hospital in Pilsen . METHODS In the period from 06/24/2010 to 12/01/2011 was at the Department of Gynaecology and Obstetrics , University Hospital Pilsen examined 552 patients with abnormalities in the pelvis . Patients were divided into two groups . There were 30 women with histologically confirmed malignant ovarian tumors . Another 522 women had benign findings . According to the levels of FSH were women in both groups divided into premenopausal and postmenopausal . At all women were measured CA 125 , HE4 and FSH . HE4 and CA125 were determined using the chemiluminescent device Architect 1000 ( Abbott , USA ) , FSH chemiluminescent method on the device DXI 800 ( Beckman Coulter , USA ) . At all premenopausal women was calculated ROMA1 index and at all postmenopausal women ROMA2 index . SAS statistical software 9.2 were used for all statistical calculations . RESULTS The highest diagnostic efficiency was achieved by a combination of HE4 and CA125 markers with the calculation ROMA2 index for postmenopausal women . In determining of menopausal status according to the values of FSH cut-off for menopause 40 IU/L and cut-off at 26.4 % for ROMA2 reaches ROMA2 sensitivity of 92.3 % , specificity of 88.5 % and PV- of 99.3 % . If we reduce the cut-off for laboratory diagnosis of menopause using FSH at 22 IU/L , and cut-off for ROMA2 was 26.3 % reaches ROMA2 sensitivity of 95.2 % , specificity of 87.8 % and PV- of 99.5 % . CONCLUSION HE4 in combination with CA125 and current ROMA index calculation is a suitable methodology to improve the detection of ovarian cancer", "OBJECTIVE To analyze the usefulness of transvaginal color Doppler assessment of venous flow in the differential diagnosis of adnexal masses . MATERIAL AND METHODS Ninety-one consecutive patients ( mean age : 46.6 years , range : 16 - 81 years ) diagnosed as having an adnexal mass were evaluated by transvaginal color Doppler sonography prior to surgery . Color Doppler was used to detect and analyze the flow velocity waveform from arterial and venous blood flow within the tumor . For arterial signals the resistance index and peak systolic velocity , and for veins the maximum venous flow velocity , were calculated . Receiver operator characteristic curves were plotted to determine the best venous flow velocity cut-off . According to our previous study using arterial Doppler , a tumor was considered as malignant when flow was detected and the lowest resistance index was < or = 0.45 . Using venous Doppler a mass was considered as malignant when flow was detected and the venous flow velocity was > or = the best cut-off found on the receiver operator characteristic curve . Definitive histopathological diagnosis was obtained in all cases . Sensitivity , specificity , positive predictive value and negative predictive value for B-mode morphology ( evaluation performed according to Sassone 's scoring system ) , arterial Doppler , venous Doppler , and a combination of both arterial and venous Doppler were calculated . RESULTS Twenty-five masses ( 27.5 % ) were malignant and 66 ( 72.5 % ) benign . Arterial and venous flow was found more frequently in malignant than in benign masses ( 92 % vs. 41 % ( P < 0.001 ) and 72 % vs. 21 % ( P < 0.001 ) , respectively ) . The resistance index was significantly lower in malignant tumors ( 0.42 vs. 0.60 , P = 0.0003 ) . No differences were found in peak systolic velocity . Venous flow velocity was significantly higher in malignant masses ( 18.1 cm/s vs. 8.9 cm/s , P = 0.0006 ) . The best cut-off of venous flow velocity was 10 cm/s . Sensitivity , specificity , positive predictive value and negative predictive value for morphology , arterial Doppler , venous Doppler , and the combination of both arterial and venous Doppler were 92 % , 71 % , 45 % , 96 % ; 76 % , 95 % , 87 % , 91 % ; 68 % , 94 % , 81 % , 89 % ; and 88 % , 91 % , 79 % , 95 % , respectively . CONCLUSIONS Our results indicate that preoperative evaluation by venous flow assessment of adnexal masses may be useful to discriminate between malignant and benign tumors", "OBJECTIVES To test prospect ively the diagnostic performance of two logistic regression models for calculation of individual risk of malignancy in adnexal tumors ( the ' Tailor model ' and the ' Timmerman model ' ) , and to compare them to that of ' pattern recognition ' ( subjective evaluation of the gray-scale ultrasound image and color Doppler ultrasound examination ) . DESIGN Consecutive women with a pelvic mass judged clinical ly to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler examination . The same examination techniques and definitions as those used in the studies in which the logistic regression models had been created were used . The Tailor model was tested in 133 women ( 35 of whom hada malignancy ) and the Timmerman model in 82 women ( 29 of whom had a malignancy ) . A subset of 79 women ( 28 of whom had a malignancy ) was used to compare the performance of the Tailor model and the Timmerman model by calculating and comparing the areas under the receiver operating characteristics curves of the two models . Sensitivity and specificity with regard to malignancy were calculated for all three methods . RESULTS Pattern recognition performed better than the two logistic regression models ( sensitivity around 85 % , specificity around 90 % ) . Using a risk of malignancy of > 50 % to indicate malignancy ( as suggested in the original publications ) , the sensitivity of the Tailor model was 69 % and the specificity 88 % ( n = 133 ) . The corresponding values for the Timmerman model were 62 % and 79 % ( n = 82 ) . The receiver operating characteristics curves showed the two logistic regression models to have similar diagnostic properties ( area under the curve , 0.87 vs. 0.84 ; P = 0.25 ; n = 79 ) . The diagnostic performance of the mathematical models was much poorer in this study than in those in which the models had been created . CONCLUSION The poor diagnostic performance of the mathematical models can probably be explained by subtle differences in definitions and examination technique and by differences between the original tumor population s and the study population . For mathematical models to be generally useful , they probably need to be created on the basis of a very large number of tumors , and the variables in the model must be unequivocally defined and the examination technique meticulously st and ardized", "OBJECTIVES To evaluate the efficacy of color Doppler ultrasonography as the predictor of malignant ovarian tumors and to compare the results with CA 125 levels and ultrasonographic morphological patterns . METHODS We compared color Doppler ultrasound with sonographic findings and serum CA 125 levels for predicting ovarian malignancy in 16 patients with malignant and 12 patients with benign ovarian tumors . RESULTS There was a significant difference in pulsatility index ( PI ) value of ovarian vessel between benign and malignant tumors ( 2.42 + /- 0.67 for benign and 1.35 + /- 0.78 for malignant , respectively , P < 0.01 ) . The specificity of morphological findings and CA 125 was lower than that of PI measurements , but sensitivity was not different between the three methods . In addition , the combination of color Doppler and CA 125 or morphological assessment s result ed in a sensitivity of 100 % and a negative predictive value of 100 % , respectively . CONCLUSION PI measurements by transvaginal color Doppler ultrasound combined with CA 125 levels or morphological findings could be an accurate and appropriate screening method for ovarian tumors", "Objective To test the accuracy of three logistic regression models in diagnosing malignancy in women with adnexal masses . Methods This was a prospect i ve collaborative study . Women were recruited from three hospitals and all assessment s were performed at the Gynaecology Ultrasound Unit , King 's College Hospital . One hundred women with known adnexal masses were examined preoperatively . The demographic , biochemical , and sonographic data recorded for each patient included age , menopausal status , CA 125 levels , ultrasound morphology , and Doppler blood flow analysis . The diagnosis of malignancy was made for each woman using three logistic regression models previously described by Alcazar et al , Tailor et al , and Timmerman et al. Variables used in these models were then combined to form a new model . The results were compared with the final histopathologic diagnosis . Results Sixty-seven women had benign tumors and 33 had ovarian cancer . Women with malignant tumors were older than those with benign masses . There were significant differences in CA 125 levels , presence of papillary proliferations , and ascites between the two groups . The sensitivities and specificities achieved respectively by the models were as follows : 45 % and 93 % with Tailor et al 's model , 9 % and 99 % with Alcazar et al 's model , and 73 % and 91 % with Timmer-man et al 's model . There was no significant improvement over the performance of Timmerman et al 's model and the new combined model . Conclusion All models performed less well than originally reported . Combining the models did not lead to a significant improvement in performance . Larger sample sizes that incorporate all types of ovarian tumors are necessary to design more accurate diagnostic models", "OBJECTIVES This prospect i ve study investigated the clinical evaluation of transvaginal color Doppler ultrasonography in the diagnosis of ovarian tumors . METHODS Transvaginal ultrasonography ( morphological assessment , DePriest 's index ) and color Doppler analysis were performed for 31 malignant and 64 benign tumors ovarian tumors . Serum tumor markers such as CA125 , CA72 - 4 , and STN were measured . RESULTS Sensitivity , specificity , positive predictive value , negative predictive value , and accuracy were as follows : DePriest 's index , 90.3 % , 73.4 % , 62.2 % , 94.0 % , 78.9 % ; CA125 , 70.4 % , 87.7 % , 73.1 % , 86.2 % , 82.1 % ; minimum pulsatile index combined with detection of location of arterial blood flow , 83.9 % , 98.4 % , 96.3 % , 92.6 % , 93.7 % , respectively . In cases where arterial blood flow was recognized , malignant tumors had significantly fewer diastolic notches , while benign tumors had many diastolic notches . The difference in the presence of diastolic notch between malignant and benign tumors was significant ( P<0.0004 ) . CONCLUSIONS For diagnosis of ovarian tumors , transvaginal color Doppler analysis combined with detection of arterial location is more useful than other procedures", "Purpose : To prospect ively test the mathematical models for calculation of the risk of malignancy in adnexal masses that were developed on the International Ovarian Tumor Analysis ( IOTA ) phase 1 data set on a new data set and to compare their performance with that of pattern recognition , our st and ard method . Methods : Three IOTA centers included 507 new patients who all underwent a transvaginal ultrasound using the st and ardized IOTA protocol . The outcome measure was the histologic classification of excised tissue . The diagnostic performance of 11 mathematical models that had been developed on the phase 1 data set and of pattern recognition was expressed as area under the receiver operating characteristic curve ( AUC ) and as sensitivity and specificity when using the cutoffs recommended in the studies where the models had been created . For pattern recognition , an AUC was made based on level of diagnostic confidence . Results : All IOTA models performed very well and quite similarly , with sensitivity and specificity ranging between 92 % and 96 % and 74 % and 84 % , respectively , and AUCs between 0.945 and 0.950 . A least squares support vector machine with linear kernel and a logistic regression model had the largest AUCs . For pattern recognition , the AUC was 0.963 , sensitivity was 90.2 % , and specificity was 92.9 % . Conclusion : This internal validation of mathematical models to estimate the malignancy risk in adnexal tumors shows that the IOTA models had a diagnostic performance similar to that in the original data set . Pattern recognition used by an expert sonologist remains the best method , although the difference in performance between the best mathematical model is not large", "OBJECTIVE To assess a new logistic regression model developed to predict malignancy in adnexal masses . METHODS In the first part of this study , we developed a logistic model by applying logistic regression analysis in a series of 268 adnexal masses ( 203 benign and 65 malignant lesions ) in 248 patients ( mean age , 43.6 years ; SD , 14.2 years ) evaluated and treated at our institution . Eleven parameters were entered in the logistic regression analysis in a forward stepwise way . In the second part of the study , we evaluated the model 's diagnostic performance in a further set of 135 adnexal masses ( 103 benign and 32 malignant tumors ) in 129 patients ( mean age , 44.4 years ; SD , 14.6 years ) . This diagnostic performance was compared with that of age , tumor volume , Sassone 's and Ferrazzi 's B-mode ultrasonographic morphologic scoring systems , serum cancer antigen 125 level , and the tumor 's lowest resistive index . Comparison was done by calculating the area under the receiver operating characteristic curve . RESULTS In logistic analysis , only menopausal status , the presence of papillary projections , the logarithm of the cancer antigen 125 value , tumor blood flow location , and the lowest resistive index were retained in the model . The model had the best area under the curve ( 0.97 ) , significantly higher than patient age ( area under the curve , 0.78 ; P = .001 ) , tumor volume ( area under the curve , 0.68 ; P < .0001 ) , cancer antigen 125 ( area under the curve , 0.88 ; P = .008 ) , lowest resistive index ( area under the curve , 0.85 ; P = .011 ) , Ferrazzi 's scoring system ( area under the curve , 0.89 ; P = .01 ) , and maximal peak systolic velocity ( area under the curve , 0.71 ; P < .0001 ) . Comparison with Sassone 's scoring system ( area under the curve , 0.91 ) did not reach statistical significance , but a clear trend was found ( P = .116 ) . CONCLUSIONS The model had the best diagnostic performance for discriminating between benign and malignant adnexal masses . A clinical prospect i ve evaluation is needed to confirm its actual value", "OBJECTIVES To evaluate the diagnostic performance of the IOTA ( International Ovarian Tumor Analysis group ) ( clinical ly oriented three-step strategy for preoperative characterization of ovarian masses when ultrasonography is performed by examiners with different background training and experience . METHODS A 27-month prospect i ve multicenter cross-sectional study was performed . 36 level II ultrasound examiners contributed in three UK hospitals . Transvaginal ultrasonography was performed using a st and ardized approach . Step one uses simple descriptors ( SD ) , step two ultrasound simple rules ( SR ) and step three subjective assessment of ultrasound images ( SA ) by examiners . The final outcome was findings at surgery and the histological diagnosis of surgically removed masses . RESULTS 1165 women with adnexal masses underwent transvaginal ultrasonography , 301 had surgery . Prevalence of malignancy was 31 % ( n=92 ) . SD were able to classify 46 % of the masses into benign or malignant ( step one ) , with a sensitivity of 93 % and specificity of 97 % . Applying SD followed by SR to residual unclassified masses by SD enabled 89 % of all masses ( n=268 ) to be classified with a sensitivity 95 % of and specificity of 95 % . SA was then used to evaluate the rest of the masses . Compared to the risk of malignancy index ( RMI ) , the sensitivity and specificity for the three-step ( SD+SR+SA ) strategy were 93 % ( 95 % CI : 86 - 97 % ) and 92 % ( 95 % CI : 87 - 95 % ) vs. 72 % ( 95 % CI : 62 - 80 % ) and 95 % ( 95 % CI : 91 - 97 % ) for RMI , respectively . CONCLUSION The IOTA three-step strategy shows good test performance on external validation in the h and s of ultrasonography examiners with different background training and experience . This performance is considerably better than the RMI", "BACKGROUND The diagnostic accuracy of ultrasonography for differentiating between benign and malignant adnexal masses is proportional to the expertise of the operator . However , we do not know whether improved diagnostic accuracy will affect the management of these tumours . We assessed the effect of the quality of gynaecological ultrasonography on the management of patients with suspected ovarian cancer in a r and omised controlled trial . METHODS 165 patients who were referred to the regional gynaecological cancer centre at Guy 's and St Thomas ' NHS Foundation Trust ( London , UK ) , between June 7 , 2004 , and April 23 , 2006 , with suspected adnexal tumours met the inclusion criteria . Of these , 150 patients were r and omly assigned to either level II ( routine ) ultrasonography ( n=73 ) or to level III ( expert ) ultrasonography ( n=77 ) . The primary endpoint was the number of major surgical staging procedures ( including a laparotomy and at least an oophorectomy and omental biopsy ) in each group of the study . Secondary endpoints were : total number of surgical procedures ; number of minimally invasive procedures ( eg , operative laparoscopy or ultrasonography-guided cyst aspiration ) ; number of additional diagnostic tests ( eg , CT or laparoscopy ) ; number of follow-up scans ; diagnostic accuracy of level II and level III ultrasonography ; and duration of hospital stay . All analyses were by intention to treat . This study is registered on the Current Controlled Trials website http://www.controlled-trials.com/m rct /trial/230201/IS RCT N02631195 . FINDINGS More major surgical staging procedures for suspected ovarian cancer were done in the level II group than in the level III group of the study ( 27 of 73 [ 37 % ] vs 17 of 77 [ 22 % ] , respectively ; difference between groups 15 % [ 95 % CI 0 - 29 ] ; RR 1.68 [ 1.00 - 2.81 ] ; p=0.049 ) . The total number of surgical procedures was similar between the two groups : 35 of 73 ( 48 % ) in the level II group and 33 of 77 ( 43 % ) in the level III group ( RR 1.12 [ 0.79 - 1.59 ] ; p=0.53 ) . The median duration of hospital stay for patients who were operated on was 6 days ( range 3 - 13 ) in the level II group and 5 days ( range 1 - 9 ) in the level III group ( p=0.01 ) . A likely histological diagnosis was provided to clinicians after ultrasonography for 76 of 77 ( 99 % ) patients in the level III group compared with only 38 of 73 ( 52 % ) patients in the level II group . 18 of 150 ( 12 % ) patients recruited were eventually diagnosed with ovarian malignancy . The sensitivity and specificity of ultrasonography was 2 of 5 ( 40 % ; [ 95 % CI 6.5 - 84.6 ] ) and 10 of 10 ( 100 % ; [ 34 - 100 ] ) , respectively , in the level II group and 7 of 8 ( 88 % ; [ 47 - 98 ] ) and 27 of 28 ( 96 % ; [ 82 - 99 ] ) , respectively , in the level III group . INTERPRETATION Improved quality of ultrasonography has a measurable effect on the management of patients with suspected ovarian cancer in a tertiary gynaecology cancer centre , and results in a significant decrease in the number of major staging procedures and a shorter inpatient hospital stay", "OBJECTIVE : To compare the effectiveness of physician assessment with a new multivariate index assay in identifying high-risk ovarian tumors . METHODS : The multivariate index assay was evaluated in women scheduled for surgery for an ovarian tumor in a prospect i ve , multi-institutional trial involving 27 primary - care and specialty sites throughout the United States . Preoperative serum was collected , and results for the multivariate index assay , physician assessment , and CA 125 were correlated with surgical pathology . Physician assessment was documented by each physician before surgery . CA 125 cutoffs were chosen in accordance with the referral guidelines of the American College of Obstetricians and Gynecologists . RESULTS : The study enrolled 590 women , with 524 evaluable for the multivariate index assay and CA 125 , and 516 for physician assessment . Fifty-three percent were enrolled by nongynecologic oncologists . There were 161 malignancies and 363 benign ovarian tumors . Physician assessment plus the multivariate index assay correctly identified malignancies missed by physician assessment in 70 % of nongynecologic oncologists , and 95 % of gynecologic oncologists . The multivariate index assay also detected 76 % of malignancies missed by CA 125 . Physician assessment plus the multivariate index assay identified 86 % of malignancies missed by CA 125 , including all advanced cancers . The performance of the multivariate index assay was consistent in early- and late-stage cancers . CONCLUSION : The multivariate index assay demonstrated higher sensitivity and lower specificity compared with physician assessment and CA 125 in detecting ovarian malignancies . LEVEL OF EVIDENCE :", "OBJECTIVES Ovarian cancer is the fourth leading cause of death among neoplastic diseases in women . In spite of constant improvement in surgical , chemotherapeutic and immunologic techniques , which can induce long remission periods , the five-year survival rate has not really changed over the past thirty years . We tried to create a sonographic scoring system , called PMS , that could be helpful in diagnosis of pelvic masses . STUDY DESIGN The three most commonly used and vali date d indexes -- Sassone score , Ovarian Tumor Index ( OTI ) , and Risk of Malignancy Index 3 (RMI3)--were applied to a population of 102 women with adnexal masses . We developed a new scoring system , named Pelvic Masses Score ( PMS ) , that takes into account the ultrasound morphological pattern , the Doppler flowmetry of the pelvic mass , the CA125 serum level and the menopausal status . We then applied this scoring system to a population of 160 women for validation of the score . RESULTS Statistical analysis of the data obtained from the new scoring system reveals that sensitivity , specificity , positive and negative predictive values ( PPV and NPV ) are higher than in the case of data separately derived from the Sassone score , OTI index or RMI index . CONCLUSIONS Our preliminary data showed good results in term of sensitivity , specify and predictive values compared to other old scoring systems . A larger prospect i ve study is required to confirm these preliminary data . The number of cases will be exp and ed to permit a better evaluation of PMS", "OBJECTIVE The purpose of this study was to assess the value of conventional gray-scale ultrasonography , based on a morphologic scoring system , in the differential diagnosis of malignant and benign adnexal tumors . MATERIAL AND METHODS A total of 58 adnexal masses in 51 patients were classified prospect ively as suggestive of malignant or benign , on the basis of gray-scale ultrasonographic morphology . The results were correlated with histopathological diagnosis . RESULTS Histopathology of 42 masses was found to be benign and 16 masses were found to be malignant . On gray-scale analysis 15 of 16 malignant masses were classified as suggestive of malignant and 37 of 42 benign masses were classified as suggestive of benign . The sensitivity , specificity , positive predictive value and negative predictive value are calculated as 93 % , 88 % , 75 % , and 97 % , respectively . CONCLUSION Prediction of malignancy using gray scale ultrasonograhy based on a morphological scoring system was reliable ( NPV = 97 % , PPV = 93 % ) . However further investigations about the assessment of adnexal masses with ultrasonography are", "BACKGROUND The study analyses the diagnostic possibilities regarding ovarian neoplasms offered by different clinical approaches : B-mode morphological ultrasonographic examination , colour Doppler and Doppler pulsed ultrasonography , and lastly the assay of a number of tumour markers . METHODS A prospect i ve study was carried out in 125 selected patients attending the Ultrasonography unit of the Obstetrics and Gynecology Clinic at Parma University between June 1997 and June 1999 who presented an adnexal mass . All patients underwent transvaginal ultrasonography ( multifrequency vaginal probe 5.0 - 6.5 MHz , Esaote Idea , Genova ) to characterise the mass , applying 5 different ultrasonographic scores : Granberg , Sassone , Di Priest , Lerner , Ferrazzi . Colour Doppler imaging was then performed to analyse the vascularisation of the mass , also using pulsed Doppler to study a number of velocimetric parameters : pulsatility index , index of resistance , systolic and diastolic peak velocity , mean velocity . All the patients underwent surgery using laparotomy or video laparoscopy , accompanied by histological analysis . A number of different tumour markers were assayed prior to surgery : Cal25 , CA19 - 9 , CEA , beta-HCG , alpha-fetoprotein . RESULTS Out of 127 pelvic masses examined , histological analysis showed that 19 were malignant and 108 benign . The diagnostic accuracy of malignancy was comparable for the 5 scores studied , with a minimum of 57.48 % for Lerner and a maximum of 77.16 % for Di Priest . The central importance of vascularisation was the only significant parameter among those analysed using colour Doppler which was useful for the diagnosis of a malignant neoplasm , with a diagnostic accuracy of 82.95 % . No indicator obtained using pulsed Doppler was useful for diagnostic purpose s. CA125 was the only tumour marker that revealed a statistically significant difference emerged between the benign ( 21.6 U/ml ) and malignant ( 220.8 U/ml ) masses . Its diagnostic accuracy was 75.58 % . CONCLUSIONS This study confirmed that the three methods analysed do not differentiate substantially in their overall diagnostic capacity of malignant ovarian neoplasms . The best performances for ecographic scores ( Di Priest ) did not exceed a sensitivity of 89.47 % with a 21.25 % incidence of false positives ; this was comparable to CA125 with a sensitivity of 85.71 % and false positives in 22.09 % . In relation to the central importance of vascularisation , colour Doppler achieved a lower sensitivity ( 55.55 % ) , but this was confirmed by a low incidence of false positives ( 7.95 % ) . This revealed its importance as a useful method , especially for excluding the presence of malignant tumours", "PURPOSE The combination of two tumour markers , CA125 and HE4 , in the risk of ovarian malignancy assay ( ROMA ) has been shown to be successful in classifying patients into those who have a high or low risk of epithelial ovarian cancer . In the present study , the diagnostic accuracy of ROMA was assessed and compared to the diagnostic accuracy of the two most widely used ultrasound methods , namely the risk of malignancy index ( RMI ) and subjective assessment by ultrasound . METHODS From August , 2005 to March , 2009 , 432 women with a pelvic mass who were scheduled to have surgery were enrolled in a single-centre prospect i ve cohort study . A preoperative ultrasound was performed and preoperative CA125 and HE4 serum levels were measured . Once the final surgical pathology reports were obtained , the diagnostic accuracy and performance indices of ROMA , RMI and subjective assessment were calculated . RESULTS Of the 432 eligible patients , 374 could be analysed . Subjective assessment had the highest area under the receiver operator characteristic curve ( AUC ) ( 0.968 , 95%CI:0.945 - 0.984 ) , followed by the RMI ( 0.931 , 95%CI:0.901 - 0.955 ) . The subjective assessment and RMI both had significantly higher AUCs than the ROMA ( 0.893 , 95%CI:0.857 - 0.922 ; P<0.0001 and P=0.0030 , respectively ) . The pre- and postmenopausal population s generated similar results . CONCLUSION Although new tumour markers models are promising , they do not contribute significantly to the diagnosis of ovarian cancer . Ultrasound , especially subjective assessment by ultrasound , remains superior in discriminating malignant from benign ovarian masses", "INTRODUCTION The risk of malignancy index ( RMI ) is a scoring system used to triage benign from malignant ovarian masses . We compared the specificity and sensitivity of the four indices ( RMI 1 , RMI 2 , RMI 3 and RMI 4 ) to discriminate a benign ovarian mass from a malignant one in a Southeast Asian population . METHODS This was a five-year retrospective study of women who were admitted for surgery due to ovarian masses . RMI scores were calculated based on st and ardised preoperative cancer antigen (CA)-125 levels , ultrasonography findings , menopausal status and tumour size based on ultrasonography . Postoperative histopathologic diagnosis was regarded as the definite outcome . Data were analysed using the Statistical Package for the Social Sciences , and Mann-Whitney U test was used to compare the individual RMI scores between the benign and malignant cases . RESULTS Out of the 480 patients review ed , 228 women aged 10 - 65 years were included in the study . Of these , 17 ( 7.5 % ) had malignant disease and 211 ( 92.5 % ) had benign pathology . There was no statistical difference in the RMI 1 , 2 , 3 and 4 scores between the benign and malignant cases . Individual variables that were analysed showed significant differences in median CA-125 level and tumour size ( p = 0.044 and p < 0.0005 , respectively ) between the benign and malignant cases . CONCLUSION Our study shows that RMI is not a valuable triage tool for our Southeast Asian population . Further prospect i ve validation , with regard to st and ardising results in different patient population s and centres , is required", "Objectives : To evaluate prospect ively the relative usefulness of color Doppler and gray scale sonography in differentiating benign from malignant ovarian masses and evaluation of scoring systems Sassone and Alcazar for differentiating benign from malignant ovarian masses . Methods : Study was conducted during the period of Jan 2006 to Oct 2007 in department of obstetrics and gynaecology , New civil Hospital , Surat . The study was conducted mainly with the help of department of radio-diagnosis . The study include 100 patient clinical ly suspected to have ovarian neoplasm and referred to department of radio-diagnosis where evaluation with Ultrasonography and Doppler was done . The efficacy of scoring systems were evaluated by histopathological examination of mass or fine needle aspiration cytology or presence of malignant cells in ascetic fluid . Results : Sassone 's scoring system was able to identify 72 out of 78 benign masses and 18 out of 22 malignant masses.where as Alcazar system with use of colour Doppler was able to identify 75 out of 78 benign and 21 out of 22 malignant ovarian masses . Sensitivity and specificity of sassone is 81.8%,92.3 % respectively , where as that of Alcazar is 95.5 % , 96.2 % respectively . Conclusion : Using both gray scale and colour Doppler in differentiating benign from malignant ovariam masses is giving results with more accuracy and Alcazar system is better performing than sassone 's scoring systems", "INTRODUCTION Patients diagnosed with epithelial ovarian cancer ( EOC ) have improved outcomes when cared for at centers experienced in the management of EOC . The objective of this trial was to vali date a predictive model to assess the risk for EOC in women with a pelvic mass . METHODS Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospect i ve study . Preoperative serum levels of HE4 and CA125 were measured . Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC . RESULTS Twelve sites enrolled 531 evaluable patients with 352 benign tumors , 129 EOC , 22 LMP tumors , 6 non EOC and 22 non ovarian cancers . The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0 % ( 95 % CI 66.9 - 81.4 ) , and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3 % ( 95 % CI=85.9 - 96.4 ) . The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8 % ( 95 % CI=68.2 - 80.6 ) , and 18 EOC and 16 LMP tumors of which 26 were classified as high risk , providing a sensitivity of 76.5 % ( 95 % CI=58.8 - 89.3 ) . CONCLUSION An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8 % of EOC correctly classified as high risk . This model can be used to effectively triage patients to centers of excellence", "PURPOSE To collect data for the development of a more universally useful logistic regression model to distinguish between a malignant and benign adnexal tumor before surgery . PATIENTS AND METHODS Patients had at least one persistent mass . More than 50 clinical and sonographic end points were defined and recorded for analysis . The outcome measure was the histologic classification of excised tissues as malignant or benign . RESULTS Data from 1,066 patients recruited from nine European centers were included in the analysis ; 800 patients ( 75 % ) had benign tumors and 266 ( 25 % ) had malignant tumors . The most useful independent prognostic variables for the logistic regression model were as follows : ( 1 ) personal history of ovarian cancer , ( 2 ) hormonal therapy , ( 3 ) age , ( 4 ) maximum diameter of lesion , ( 5 ) pain , ( 6 ) ascites , ( 7 ) blood flow within a solid papillary projection , ( 8) presence of an entirely solid tumor , ( 9 ) maximal diameter of solid component , ( 10 ) irregular internal cyst walls , ( 11 ) acoustic shadows , and ( 12 ) a color score of intratumoral blood flow . The model containing all 12 variables ( M1 ) gave an area under the receiver operating characteristic curve of 0.95 for the development data set ( n = 754 patients ) . The corresponding value for the test data set ( n = 312 patients ) was 0.94 ; and a probability cutoff value of .10 gave a sensitivity of 93 % and a specificity of 76 % . CONCLUSION Because the model was constructed from multicenter data , it is more likely to be generally applicable . The effectiveness of the model will be tested prospect ively at different centers", "Transvaginal sonography ( TVS ) has been shown to be the most effective means to screen for ovarian cancer . TVS is associated with a high sensitivity and specificity . However , the positive predictive value associated with TVS in the diagnosis of malignancy is low . A morphologic scoring index for use with TVS has been used at the University of Kentucky since 1991 . The current study was performed to more fully evaluate the efficacy and interobserver variation in ultrasonographic morphology index scores attributed to ovarian tumors . Ultrasound records of 213 patients from five participating centers were review ed by three independent observers . Morphology index scores were assigned to each tumor in a blinded fashion . The morphology index scores were then compared with the final histopathologic findings . One hundred sixty-nine patients had benign tumors and 44 patients had ovarian malignancies . The mean morphology index scores were significantly higher in malignant ovarian tumors ( MI 7.3 + /- 1.9 ) than in benign ovarian tumors ( MI 3.3 + /- 1.8 ) . Statistical evaluation of the morphology index scores revealed a sensitivity of 89 % and a positive predictive value of 46 % . Interobserver variation was lowest in assessing ovarian volume and higher in the evaluation of wall structure and septal structure . A multilogistic regression model was used to evaluate the predictive power of each component of the morphology index . The use of a morphology index is an effective and cost-efficient method of increasing the positive predictive value of TVS screening for ovarian cancer . Use of this index in large numbers of patients will generate data which should help refine appropriate structural scoring categories and reduce interobserver variation", "OBJECTIVE : To evaluate referral guidelines published by American College of Obstetricians and Gynecologists ( ACOG ) and Society of Gynecologic Oncologists ( SGO ) , which provide guidance about when to refer a patient with a pelvic mass to a gynecologic oncologist . METHODS : Data from consecutive patients evaluated for pelvic mass were collected prospect ively over a 5-year period . The performance characteristics of the ACOG/SGO referral guidelines for detection of primary and metastatic ovarian cancer were calculated by using menopausal status , CA 125 level , imaging results , physical findings , and family history . RESULTS : Eight hundred thirty-seven patients met inclusion criteria . Forty-four percent ( 263/597 ) of postmenopausal women were diagnosed with ovarian cancer , whereas 20 % ( 48/240 ) of premenopausal women had ovarian cancer . Seventy-four percent of primary cancers were stage III or IV . The referral guidelines were 79.2 % sensitive and 69.8 % specific for premenopausal women , with a positive predictive value of 39.6 % . For postmenopausal women , the guidelines were 93.2 % sensitive and 59.9 % specific , and positive predictive value was 64.6 % . The referral guidelines performed better for late-stage than early-stage cancers in both sensitivity and positive predictive value , especially in postmenopausal women . Although only 28 patients would not have been referred by the guidelines , the majority of these had early stage ( I or II ) disease . Lowering the CA 125 cutoff level required for referral of premenopausal patients increased the sensitivity of the guidelines in this group . CONCLUSION : The ACOG/SGO guidelines perform well in predicting advanced-stage ovarian cancer , probably owing to the nature of advanced-stage disease . The guidelines perform poorly in identifying early-stage disease , especially in premenopausal women , primarily due to lack of early markers and signs of ovarian cancer . LEVEL OF EVIDENCE :", "OBJECTIVE To determine whether the combined use of Lerner 's morphologic score and color Doppler ultrasound examination results in better discrimination of benign and malignant adnexal masses than the use of Lerner 's score alone or Doppler variables alone . DESIGN One hundred and seventy-three consecutive women with a pelvic mass judged clinical ly to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler techniques . One hundred and forty-nine tumors were benign and 24 malignant . The sensitivity and false-positive rate with regard to malignancy were calculated for Lerner 's score , six Doppler variables and combinations of Lerner 's score and Doppler variables . Previously defined gray scale and Doppler criteria of malignancy were used and tested prospect ively . The best method was defined as that detecting most malignancies with the lowest false-positive rate . RESULTS Lerner 's score had a sensitivity of 92 % and a false-positive rate of 36 % . The best Doppler variable -- time-averaged maximum velocity -- had similar diagnostic properties with a sensitivity of 100 % and a false-positive rate of 41 % . Combining Lerner 's score with Doppler measurement of time-averaged maximum velocity -- i.e . requiring both Lerner 's score and time-averaged maximum velocity to indicate malignancy for a malignant diagnosis to be made -- had a sensitivity of 92 % and a false-positive rate of 19 % . CONCLUSIONS The combined use of Lerner 's score and measurement of time-averaged maximum velocity is a better method for discrimination of benign and malignant adnexal masses than the use of Lerner 's score alone or Doppler ultrasound examination alone . The clinical value of the combined method needs to be cross-vali date d prospect ively in a new series of tumors", "OBJECTIVE To compare the value of the risk of malignancy index ( RMI ) and the ovarian crescent sign ( OCS ) in the diagnosis of ovarian malignancy . METHODS This was a prospect i ve observational study of women with ultrasonographic diagnosis of an ovarian cyst . The RMI was calculated in all cases using a previously published formula ( RMI = U ( ultrasound score ) x M ( menopausal status ) x serum CA125 ( kU/L ) ) . A value > 200 was considered to be diagnostic of ovarian cancer . The OCS was defined as a rim of visible healthy ovarian tissue in the ipsilateral ovary . Its absence was taken as being diagnostic of invasive cancer . RESULTS A total of 106 consecutive women were included in the study , of whom 92 ( 86.8 % ) had a benign ovarian tumor , five ( 4.7 % ) had borderline lesions and nine ( 8.5 % ) had an invasive ovarian cancer . The absence of an OCS diagnosed invasive ovarian cancer with a sensitivity of 100 % ( 95 % CI , 70 - 100 % ) , specificity of 93 % ( 95 % CI , 86 - 96 % ) , positive predictive value ( PPV ) of 56 % , negative predictive value ( NPV ) of 100 % and positive likelihood ratio ( LR+ ) of 13.86 ( 95 % CI , 6.79 - 28.29 ) . This compared favorably with a sensitivity of 89 % ( 95 % CI , 57 - 98 % ) , specificity of 92 % ( 95 % CI , 85 - 96 % ) , PPV of 50 % , NPV of 99 % and LR+ of 10.78 ( 95 % CI , 5.34 - 21.77 ) , which were achieved using RMI > 200 ( P < 0.01 ) . CONCLUSIONS The RMI and the OCS are useful tests for discriminating between invasive and non-invasive ovarian tumors . The application of these tests in a sequential manner might improve the overall accuracy of ovarian cancer diagnosis", "OBJECTIVE Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index ( RMI ) in differentiating ovarian cancer ( OC ) from other pelvic masses , thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics . The aim was to evaluate serum Human Epididymis protein 4 ( HE4 ) and the risk of ovarian malignancy algorithm ( ROMA ) for these purpose s. METHODS Serum from 1218 patients in the prospect i ve ongoing pelvic mass study was collected prior to diagnosis . The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI . RESULTS 809 benign tumors , 79 borderline ovarian tumors , 252 OC ( 64 early and 188 late stage ) , 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated . Differentiating between OC and benign disease the specificity was 62.2 ( CA125 ) , 63.2 ( HE4 ) , 76.5 ( ROMA ) and 81.5 ( RMI ) at a set sensitivity of 94.4 which corresponds to RMI=200 . The areas under the curve ( AUC ) were 0.854 ( CA125 ) , 0.864 ( HE4 ) , 0,897 ( ROMA ) and 0.905 ( RMI ) for benign vs. early stage OC . For premenopausal benign vs. OC AUC were 0.925 ( CA125 ) , 0.905 ( HE4 ) , 0.909 ( ROMA ) and 0.945 ( RMI ) . CONCLUSION HE4 and ROMA helps differentiating OC from other pelvic masses , even in early stage OC . ROMA performs equally well as the ultrasound depending RMI and might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary center and further diagnostics . Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed , especially regarding premenopausal women", "OBJECTIVE The identification of novel biomarkers led to the development of the ROMA algorithm incorporating both HE4 and CA125 to predict malignancy in women with a pelvic mass . An ultrasound based prediction model ( LR2 ) developed by the International Ovarian Tumor Analysis ( IOTA ) study offers better diagnostic performance than CA125 alone . In this study we compared the diagnostic accuracy between LR2 and ROMA . METHODS This study included women with a pelvic mass scheduled for surgery and enrolled in a previous prospect i ve diagnostic accuracy study . Experienced ultrasound examiners , general gynecologists and trainees supervised by one of the experts performed the preoperative transvaginal ultrasound examinations . Serum biomarkers were taken prior to surgery . Accuracy of LR2 and ROMA was estimated at completion of this study and did not form part of the decision making process . Final outcome was histology of removed tissues and surgical stage if relevant . RESULTS In total 360 women were evaluated . 216 women had benign disease and 144 a malignancy . Overall test performance of LR2 ( AUC 0.952 ) with 94 % sensitivity and 82 % specificity was significantly better than ROMA ( AUC 0.893 ) with 84 % sensitivity and 80 % specificity . Difference in AUC was 0.059 ( 95 % CI : 0.026 - 0.091 ; P-value 0.0004 ) . Similar results were obtained when stratified for menopausal status . CONCLUSION LR2 shows a better diagnostic performance than ROMA for the characterization of a pelvic mass in both pre- and postmenopausal women . These findings suggest that HE4 and CA125 may not play an important role in the diagnosis of ovarian cancer if good quality ultrasonography is available", "OBJECTIVE To cross-vali date , prospect ively , the diagnostic performance of established ultrasound methods for discrimination of benign and malignant pelvic masses . METHODS A total of 173 consecutive women with a pelvic mass judged clinical ly to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler techniques . A total of 149 tumors were benign , and 24 were malignant . The sensitivity and false-positive rate with regard to malignancy were calculated for the following methods , using cut-off values recommended in previous publications : Lerner score ; ultrasound morphology , i.e. tumors without solid components being classified as benign and tumors with solid components as malignant ; tumor color score ; pulsatility index ; resistance index ; time-averaged maximum velocity ; peak systolic velocity ; the combined use of ultrasound morphology and tumor color score and the combined use of ultrasound morphology and peak systolic velocity . Sensitivity and false-positive rate were also calculated for subjective evaluation of the gray-scale ultrasound image and for subjective evaluation of the gray-scale ultrasound image supplemented with subjective evaluation of color Doppler ultrasound examination . The confidence with which the diagnosis was made , based on subjective evaluation , was rated on a visual analog scale . RESULTS Subjective evaluation of the gray-scale ultrasound image was by far the best method for distinguishing benign from malignant tumors ( sensitivity 88 % , false-positive rate 4 % ) , followed in descending order by subjective evaluation of the gray-scale ultrasound image supplemented with color Doppler examination , the Lerner score and the time-averaged maximum velocity . Adding Doppler examination to subjective evaluation of the gray-scale image did not increase the number of correct diagnoses , but it increased the confidence with which a correct diagnosis was made in 14 % of tumors . In 11 tumors ( 6 % of the series as a whole ) , the addition of Doppler examination changed the diagnosis based on subjective evaluation of the gray-scale ultrasound image from an incorrect ( n = 1 ) or uncertain ( n = 10 ) diagnosis to a correct and confident diagnosis . CONCLUSION In experienced h and s , subjective evaluation of the gray-scale ultrasound image is the best ultrasound method for discriminating between benign and malignant adnexal masses . The main advantage of adding Doppler examination to subjective evaluation of the gray-scale image is an increase in the confidence with which a correct diagnosis is made", "OBJECTIVE Because external validation of the present models has not been reported , the purpose of the present study was to assess existing diagnostic models that are used to distinguish malignant from benign masses . METHODS We tested the performance of existing models in a prospect ively assembled data set of 170 patients with an adnexal mass . Twenty-one models that have been reported previously were assessed . The models were based on combinations of ultrasound findings , color Doppler tests , CA-125 measurement , age , and /or menopausal status . For each model , we constructed ROC curves and calculated an area under the ROC curve . RESULTS Of the 170 adnexal masses that were operated on , 30 ( 18 % ) were malignant . The area under the ROC curve of 21 models that were externally vali date d varied between 0.69 and 0.90 . We found the performance of the existing models to be inferior to the performance reported in the initial studies . Even models that incorporated multiple diagnostic tools and that were developed using logistic regression models or neural networks had an area under the ROC curve of 0.86 at maximum . In the case where we focused on almost perfect sensitivity , the highest specificities varied between 0.45 and 0.60 . CONCLUSION Although diagnostic models might be of value in the preoperative assessment of the adnexal mass , their diagnostic performance is not as good as that reported in the original publications", "Endoscopic surgery is the treatment of choice for adnexal masses in premenopausal women . A prospect i ve observational study was conducted with 100 consecutive premenopausal women with adnexal masses who had been referred for endoscopic management to the University Hospital of Larissa , Larissa , Greece . The aim of the study was to compare the ability of the risk malignancy index ( RMI ) [ 1,2 ] and the Ferrazzi score [ 3 ] ( Table 1 ) to discriminate preoperatively between benign and malignant masses . Histopathologic diagnosis was regarded as the final arbiter . Patients with a RMI of 150 or greater or a Ferrazzi score of 8 or greater were referred to the oncology team and explorative laparotomy was performed . All other patients were treated endoscopically and a frozen-section biopsy was performed . The sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) of the Ferrazzi score and RMI were calculated at various cut-off points , separately or in combination , for different age groups . Of the 89 patients who had benign disease , 76 were treated endoscopically . The 10 patients found to have malignant disease underwent explorative laparotomy . The remaining patient ( who also had ovarian torsion ) underwent staging laparotomy after the results of her frozen-section biopsy indicated that she had a borderline tumor . Her serum concentration of cancer antigen (CA)-125 was 192 U/ mL , but the value had not been available preoperatively . Mean age was significantly higher for cancer patients ( 45.4 years ) than for patients with benign disease ( 30.8 years ) ( P<0.001 ) . Ferrazzi score , RMI , and CA-125 levels were significantly associated with cancer diagnosis , but the Ferrazzi score proved the more accurate predictor of malignancy ( Fig. 1 ) . Specificity was 86.5 % and NPV was 93.9 for a RMI of 150 or greater whereas specificity was 100 % and NPV was 92.7 for a Ferrazzi score of 8 or greater . These results suggest that the Ferrazzi score can be strongly recommended . Moreover , specificity was 100 % and NPV was 98 among patients aged 40 years or older who had both a RMI of 150 or greater and a Ferrazzi score of 8 or greater . A possible explanation is that the primary purpose of introducing RMI was to improve the referral of older patients with advanced ovarian cancer to oncology centers [ 1,2,4 ] . In this study 36 % of the patients younger than 40 years had endometriosis , a disease associated with higher CA-125 values , and this high proportion decreased the predictive performance of the RMI . The Ferrazzi score is a detailed morphometric ultrasonographic score that excludes dermoid cysts , which may explain its superior performance [ 3 ] ( Table 1 ) . Preoperative risk scoring for adnexal masses with both Ferrazzi score and RMI can be reliably performed by a generalist gynecologist and would allow for a more effective referral to experienced subspecialists", "OBJECTIVE To determine the diagnostic performance of International Ovarian Tumor Analysis ( IOTA ) ' simple ' rules for discriminating between benign and malignant adnexal masses . METHODS A prospect i ve study was performed between January 2011 and June 2012 . Eligible patients were women diagnosed with a persistent adnexal mass who presented to the participating centers . Four trainees evaluated the adnexal mass by transvaginal ultrasound under the supervision of an expert examiner . The trainee analyzed the mass according to IOTA simple rules and provided a diagnosis of benign , malignant or inconclusive . All women included in the study underwent surgery and tumor removal in the center of recruitment . Diagnostic performance was assessed by calculating sensitivity , specificity and positive ( LR+ ) and negative ( LR- ) likelihood ratios . RESULTS A total of 340 women were included ( mean patient age , 42.1 ( range , 13 - 79 ) years ) . Of the tumors , 55 ( 16.2 % ) were malignant and 285 ( 83.8 % ) were benign . The IOTA simple rules could be applied in 270 ( 79.4 % ) cases . In these cases , sensitivity was 87.9 % ( 95 % CI , 72.4 - 95.2 ) , specificity 97.5 % ( 95 % CI , 94.6 - 98.8 ) , LR+ 34.7 ( 95 % CI , 15.6 - 77.3 ) and LR- 0.12 ( 95 % CI , 0.05 - 0.31 ) . CONCLUSIONS Application of the IOTA simple rules yielded acceptable results in terms of specificity in the h and s of non-expert examiners . However , with non-expert examiners there was a 12 % false-negative rate , which is relatively high" ]

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[ "A trial of a test-and-treat strategy for Helicobacter pylori positive dyspeptic patients in general practice.", "Should obstetricians see women with normal pregnancies? A multicentre randomised controlled trial of routine antenatal care by general practitioners and midwives compared with shared care led by obstetricians", "Effect of information about waiting lists on referral patterns of general practitioners.", "Pragmatic randomised controlled trial to evaluate guidelines for the management of infertility across the primary care-secondary care interface", "A randomized controlled trial and economic evaluation of counselling in primary care.", "Do clinical guidelines improve general practice management and referral of infertile couples?", "Controlled trial of an open-access physiotherapy service.", "Impact of introducing near patient testing for standard investigations in general practice.", "A prospective controlled trial of computerized decision support for lipid management in primary care.", "In-house referral: a primary care alternative to immediate secondary care referral?", "Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care", "Randomised controlled trial of effect of Baby Check on use of health services in first 6 months of life", "Changing remuneration systems: effects on activity in general practice.", "Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study", "Investigation of benefits and costs of an ophthalmic outreach clinic in general practice.", "Management of joint and soft tissue injuries in three general practices: value of on-site physiotherapy.", "Improving foot care for people with diabetes mellitus – a randomized controlled trial of an integrated care approach", "Randomized controlled trial of the effect of the Royal College of Radiologists' guidelines on general practitioners' referrals for radiographic examination.", "Effectiveness of an educational strategy to improve family physicians' detection and management of depression: a randomized controlled trial.", "Controlled comparison of pharmacological and psychological treatment of generalized anxiety disorder in primary care.", "Randomised controlled trial of teaching general practitioners to carry out structured assessments of their long term mentally ill patients", "Prospective study of trends in referral patterns in fundholding and non-fundholding practices in the Oxford region, 1990-4", "Improving referrals for glue ear from primary care: are multiple interventions better than one alone?", "Cost effectiveness of initial endoscopy for dyspepsia in patients over age 50 years: a randomised controlled trial in primary care", "Counselling in primary care: a randomised controlled trial.", "The Costs of Alternative Types of Routine Antenatal Care for Low-Risk Women: Shared Care Vs Care by General Practitioners and Community Midwives" ]

[ "Computer models of different strategies for the management of dyspepsia in primary care indicate that a ' test- and -treat ' approach is likely to be associated with the lowest costs and acceptable clinical outcomes . We present information on computer modelling studies and report the findings of a r and omised trial comparing a Helicobacter pylori test- and -treat strategy with referral to direct access endoscopy in the management of dyspepsia in general practice . We compared costs and clinical outcomes in patients managed for one year in study ( test- and -treat ) and control ( endoscopy ) practice s in south London . Patients aged less than 45 years presenting with persistent dyspepsia without alarm symptoms ( 141 study patients , 91 control patients ) were studied . In the one-year follow-up period there were 17 endoscopies in the study group : all the control patients underwent initial endoscopy and five further endoscopies were performed . None revealed peptic ulcer or cancer . Forty-three ( 30 % ) of the study patients compared with 16 ( 17 % ) of the controls were referred to hospital clinics ( p < 0.025 ) . The cost of management per patient for one year in the study group was 205.67 Pounds , compared with 404.31 Pounds in the control group ( p < 0.0001 ) . Clinical outcomes in both groups at one year were comparable . An H. pylori test- and -treat strategy for dyspeptic patients aged less than 45 , employing office-based serology testing , appears to be associated with substantially lower costs than initial endoscopy and with similar clinical outcomes", "Abstract Objective : To compare routine antenatal care provided by general practitioners and midwives with obstetrician led shared care . Design : Multicentre r and omised controlled trial . Setting : 51 general practice s linked to nine Scottish maternity hospitals . Subjects : 1765 women at low risk of antenatal complications . Intervention : Routine antenatal care by general practitioners and midwives according to a care plan and protocol s for managing complications . Main outcome measures : Comparisons of health service use , indicators of quality of care , and women 's satisfaction . Results : Continuity of carer was improved for the general practitioner and midwife group as the number of carers was less ( median 5 carers v 7 for shared care group , P<0.0001 ) and the number of routine visits reduced ( 10.9 v 11.7 , P<0.0001 ) . Fewer women in the general practitioner and midwife group had antenatal admissions ( 27 % ( 222/834 ) v 32 % ( 266/840 ) , P<0.05 ) , non-attendances ( 7 % ( 57 ) v 11 % ( 89 ) , P<0.01 ) and daycare ( 12 % ( 102 ) v 7 % ( 139 ) , P<0.05 ) but more were referred ( 49 % ( 406 ) v 36 % ( 305 ) , P<0.0001 ) . Rates of antenatal diagnoses did not differ except that fewer women in the general practitioner and midwife group had hypertensive disorders ( pregnancy induced hypertension , 5 % ( 37 ) v 8 % ( 70 ) , P<0.01 ) and fewer had labour induced ( 18 % ( 149 ) v 24 % ( 201 ) , P<0.01 ) . Few failures to comply with the care protocol occurred , but more Rhesus negative women in the general practitioner and midwife group did not have an appropriate antibody check ( 2.5 % ( 20 ) v 0.4 % ( 3 ) , P<0.0001 ) . Both groups expressed high satisfaction with care ( 68 % ( 453/663 ) v 65 % ( 430/656 ) , P=0.5 ) and acceptability of allocated style of care ( 93 % ( 618 ) v 94 % ( 624 ) , P=0.6 ) . Access to hospital support before labour was similar ( 45 % ( 302 ) v 48 % ( 312 ) visited labour rooms before giving birth , P=0.6 ) . Conclusion : Routine specialist visits for women initially at low risk of pregnancy complications offer little or no clinical or consumer benefit . Key messages Key messages Care by general practitioners and midwives improved continuity of care : there were fewer carers , non-attendances , and hospital admissions , and marginally fewer routine visits than with specialist led shared care ; incidences of hypertension , proteinuria , pre-eclampsia , and induction of labour were also lower Overall there were few deviations from the care protocol , but a greater proportion of Rhesus negative women in the general practitioner and midwife group did not have an appropriate check for antibodies The women in both trial groups were equally highly satisfied with all aspects of their care ; only a small minority of women in the general practitioner and midwife group said they would have liked to have seen a hospital doctor but did not Although there was no net benefit from routine specialist antenatal visits , over half of women developed some complication during their pregnancy ; in the general practitioner and midwife model of care , low risk women see a specialist when required and not at predefined routine", "In a two year trial general practitioners in the West Midl and s were provided with extended waiting time information for hospital consultation and treatment in general surgery . Selected general practitioners were sent monthly bulletins on comparative times to wait for both outpatient appointment and inpatient treatment throughout the region . Their referrals to consultant general surgeons were monitored , alongside those of a matched control group not receiving such information . Differences were found between the two groups which indicate the willingness of general practitioners to change their referral practice when adequate information is available . In addition , patients referred to their local hospital had longer waiting times than patients matched for clinical condition and district of origin who were sent to hospitals where it was indicated that a shorter wait might be expected", "Abstract Objective : To investigate the effect of clinical guidelines on the management of infertility across the primary care- secondary care interface . Design : Cluster r and omised controlled trial . Setting : General practice s and NHS hospitals accepting referrals for infertility in the Greater Glasgow Health Board area . Participants : All 221 general practice s in Glasgow ; 214 completed the trial . Intervention : General practice s in the intervention arm received clinical guidelines developed locally . Control practice s received them one year later . Dissemination of the guidelines included educational meetings . Main outcome measures : The time from presentation to referral , investigations completed in general practice , the number and content of visits as a hospital outpatient , the time to reach a management plan , and costs for referrals from the two groups . Results : Data on 689 referrals were collected . No significant difference was found in referral rates for infertility . Fewer than 1 % of couples were referred inappropriately early . Referrals from intervention practice s were significantly more likely to have all relevant investigations carried out ( odds ratio 1.32 , 95 % confidence interval 1.00 to 1.75 , P=0.025 ) . 70 % of measurements of serum progesterone concentrations during the midluteal phase and 34 % of semen analyses were repeated at least once in hospital , despite having been recorded as normal when checked in general practice . No difference was found in the proportion of referrals in which a management plan was reached within one year or in the mean duration between first appointment and date of management plan . NHS costs were not significantly affected . Conclusions : Dissemination of infertility guidelines by commonly used methods results in a modest increase in referrals having recommended investigations completed in general practice , but there are no detectable differences in outcome for patients or reduction in costs . Clinicians in secondary care tended to fail to respond to changes in referral practice by doctors . Guidelines that aim to improve the referral process need to be disseminated and implemented so as to lead to changes in both primary care and secondary care . What is already known on this topic Most previous research into clinical guidelines has focused on their development and implementation Evidence is lacking about the outcomes and costs associated with the use of clinical guidelines What this study adds Clinical guidelines that may alter the balance of care between general practice and hospital setting s require more intensive implementation than guidelines aim ed at either setting on its own The cost effectiveness of clinical guidelines should not be", "BACKGROUND Counselling in primary care setting s remains largely unevaluated . Such evaluation has been strongly recommended . AIM To determine the relative effectiveness and cost-effectiveness of generic counselling and usual general practitioner ( GP ) care for patients with minor mental health problems . METHOD A r and omized controlled trial and health economic evaluation were carried out in nine general practice s. Access to generic counselling ( brief counselling , generally involving up to six 50-minute sessions ) was compared with usual GP care . A total of 162 patients aged 16 years and over with diverse mental health problems ( excluding phobic conditions and psychoses ) were r and omized . The Hospital Anxiety and Depression ( HAD ) scale , COOP/WONCA ( World Organization of Family Doctors ) functional health assessment charts , and the delighted-terrible faces scale were used to assess outcome four months after r and omization . RESULTS The two groups were similar at baseline . There were significant improvements in both groups between r and omization and follow-up for most outcome measures , but no significant differences between the study arms . The 95 % confidence limits were narrow and excluded clinical ly significant effects . Under various assumptions concerning the cost of secondary care referrals and of counselling time , no clear cost advantage was associated with either intervention . CONCLUSIONS This pragmatic trial demonstrates no difference in functional or mental health outcome at four months between subjects offered access to counselling and those given usual care by their GP . There is no clear difference in the cost-effectiveness of the two interventions . Purchasers should take account of these findings in allocating re sources within primary care", "OBJECTIVE --To evaluate guidelines for general practice management and referral of infertile couples . Guidelines were implemented with a disease specific reminder at the time of consultation ( the guidelines were embedded within a structured infertility management sheet for each couple ) . DESIGN --Pragmatic r and omised controlled trial . Participating practice s were r and omised to a group that received the guidelines and a control group . SETTING --82 general practice s in Grampian region . SUBJECTS--100 couples referred by general practitioners receiving the guideline and 100 couples referred by control general practitioners . MAIN OUTCOME MEASURES --Whether the general practitioner had taken a full sexual history and examined and investigated both partners appropriately . RESULTS --Characteristics of patients referred by study and control general practitioners did not differ significantly at baseline . Compliance with the guidelines increased for all targeted activities . General practitioners in the study group were more likely to take a sexual history ( for example , couples ' use of fertile period , 85 % v 69 % , p < 0.01 ) ; examine both partners ( female partner , 68 % v 52 % , p < 0.05 ; male partner 39 % v 13 % , p < 0.01 ) ; and investigate both partners ( day 21 progesterone , 72 % v 41 % , p < 0.001 ; semen analysis , 51 % v 41 % , p > 0.05 ) . Improvements were greater when general practitioners used the disease specific reminder . CONCLUSION --Receiving guidelines led to improvements in the process of care of infertile couples within general practice . This effect was enhanced when the guidelines were embedded in a structured infertility management sheet for each couple", "A r and omized controlled trial of outpatient open-access physiotherapy was carried out at West Cornwall Hospital during 1979/80 . The referral rate to consultant outpatient clinics for those patients offered open-access physiotherapy was considerably lower than for the control group ( 17 per cent and 56 per cent respectively ) . Patients using the service received physiotherapy promptly although this did not result in shorter treatments . Those of the control group who eventually received physiotherapy had faced considerable delays . An analysis of self-reported information showed that patients receiving open-access physiotherapy recovered more rapidly . Taken overall , the results support the concept of open-access physiotherapy", "OBJECTIVE --To assess the clinical and economic impact of surgery based near patient testing in general practice for six commonly used biochemical and bacteriological tests . DESIGN --After four months ' monitoring , equipment for two bacteriological and four biochemical tests was introduced without cost into 12 practice s using a crossover design . Structured request forms were used to monitor laboratory investigations . SETTING --12 general practice s in west midl and s and south west Thames with list sizes above 9000 . MAIN OUTCOME MEASURES --Investigation rates per 1000 consultations . Changes from baseline rates . Reasons for requesting investigations and provisional diagnoses . Cost per test and sensitivity of costs to rate of use . RESULTS --Investigation rates for the six tests rose by 16.5 % ( from 78.6/1000 consultations to 91.6/1000 ) when equipment was available in the surgery and reverted to baseline rates when it was withdrawn . The average weekly number of tests when equipment was available ranged from 0.5 to 10.5 ( mean 9.0 ) . Cholesterol tests were used as an addition to laboratory testing , usually for screening . Midstream urine analysis was often done in the surgery instead of in the laboratory , although 30 % of sample s were tested by both methods . Doctors ' reasons for investigation and conditions tested were largely unaffected by availability of surgery tests . Costs for surgery tests were higher for all tests except midstream urine . CONCLUSIONS --Availability of surgery based testing increased the number of tests performed . It was cost effective only for midstream urine analysis", "OBJECTIVES This study aim ed to assess the uptake and effect in primary care of a computerized decision support system ( DSS ) for the management of hyperlipidaemia . METHOD A prospect i ve controlled trial was conducted in 25 practice s covering a population of 150,000 in the city of Birmingham . The Primed system , a specialist developed , rule based DSS for general practice , was introduced prospect ively after a 3-month baseline data collection . The main outcome measures were nine months ' data on prescribing of lipid lowering agents ; use of laboratory tests ; and referrals to secondary care for the investigation of hyperlipidaemia . RESULTS System use was lower than expected . A shift was observed towards requests for appropriate follow-up of previously abnormal lipid results and a greater emphasis on full lipid profiles , in line with the DSS guidelines . Referrals showed a 55 % decrease on those expected ( NS ) . The prescribing evaluation revealed a large variation between practice s , but no significant alteration following system use . Views of users favoured decision support as a concept , but criticised technical problems with the system . CONCLUSIONS Greater integration of DSS software and practice based data h and ling systems is needed . The mode of data capture , and hence both the content and form of knowledge representation , in DSS must take greater account of the primary care consultation process if such systems are to be of use to practitioners", "BACKGROUND Methods are needed to ensure that those patients referred from primary to secondary care are those most likely to benefit . In-house referral is the referral of a patient by a general practitioner to another general practitioner within the same practice for a second opinion on the need for secondary care referral . OBJECTIVE To describe whether in-house referral is practical and acceptable to patients , and the health outcomes for patients . METHODS Practice s were r and omized into an intervention or a control group . In intervention practice s , patients with certain conditions who were about to be referred to secondary care were referred in-house . If the second clinician agreed referral was appropriate the patient was referred on to secondary care . In control practice s patients were referred in the usual fashion . Patient satisfaction and health status was measured at the time of referral , 6 months and one year . RESULTS Eight intervention and seven control practice s took part . For the 177 patients referred in-house , 109 ( 61 % ) were judged to need referral on to secondary care . For patient satisfaction , the only difference between the groups studied was that at 12 months patients who had been referred in-house reported themselves as being more satisfied than those referred directly to hospital . For health status , the only difference found was that at the time of referral , patients who had been referred in-house and judged to need hospital referral reported themselves as being less able on the ' Physical function ' subscale of the SF-36 than patients who were referred in-house and judged to not need hospital referral . CONCLUSION In-house referral is acceptable to patients and provides a straightforward method of addressing uncertainty over the need for referral from primary to secondary care", "Abstract Objective : To determine the cost effectiveness of a strategy of near patient Helicobacter pylori testing and endoscopy for managing dyspepsia . Design : R and omised controlled trial . Setting : 31 UK primary care centres . Participants : 478 patients under 50 years old presenting with dyspepsia of longer than four weeks duration . Interventions : Near patient testing for H pylori and open access endoscopy for patients with positive results . Control patients received acid suppressing drugs or specialist referral at general practitioner 's discretion . Main outcome measures : Cost effectiveness based on improvement in symptoms and use of re sources at 12 months ; quality of life . Results : 40 % of the study group tested positive for H pylori . 45 % of study patients had endoscopy compared with 25 % of controls . More peptic ulcers were diagnosed in the study group ( 7.4 % v 2.1 % , P=0.011 ) . Paired comparison of symptom scores and quality of life showed that all patients improved over time with no difference between study and control groups . No significant differences were observed in rates of prescribing , consultation , or referral . Costs were higher in the study group ( £ 367.85 v £ 253.16 per patient ) . Conclusions : The test and endoscopy strategy increases endoscopy rates over usual practice in primary care . The additional cost is not offset by benefits in symptom relief or quality of life . What is already known on this topic Patients younger than 50 without H pylori infection are unlikely to have treatable disease detected at endoscopy Such patients can be managed by acid suppression and reassurance alone Test and endoscopy ( referral of patients testing positive for H pyloriin primary care ) has been recommended as a way to reduce endoscopic workload What this paper adds Applying a test and endoscopy strategy increased the endoscopy referral rate from 25 % to 40 % The strategy produced no significant differences in symptoms or quality of life compared with usual management The increased costs of this strategy can not be", "Abstract Objective : To evaluate the effect of Baby Check , an illness scoring system for babies of 6 months or less , on parents ' use of health services for their baby . Design : R and omised controlled trial . Setting : 13 general practice s in Glasgow . Subjects : 997 newly delivered mothers , r and omised to receive either Baby Check and Play It Safe , an accident prevention leaflet ( n=497 ) , or Play It Safealone ( control group , n=500 ) . Main outcome measures : Data on consultations and referrals extracted from general practice notes after 6 months . Results : At the time of recruitment , maternal characteristics were similar for both groups ( mean maternal age 29 years ; deprivation categories 6 and 1 in both groups ; 424 ( 45 % ) mothers were primiparous ) . At 6 months , general practice notes were available for 467 ( 94 % ) of the Baby Check group and 468 ( 94 % ) of the control group . The number of general practitioner consultations did not differ between the groups : median number of consultations was 2 ( interquartile range 1 to 4 ) in the Baby Check group , and 2 ( 1 to 3 ) in the control group . Use of out of hours services did not differ significantly between the two groups ( 86 v 85 ; P=0.93 ) . Conclusion : Distributing Baby Check to an unselected group of mothers does not affect use of health services for infants up to 6 months of age", "OBJECTIVE --To investigate the effects on general practitioners ' activities of a change in their remuneration from a capitation based system to a mixed fee per item and capitation based system . DESIGN --Follow up study with data collected from contact sheets completed by general practitioners in one period before ( March 1987 ) a change in their remuneration system and two periods after ( March 1988 , November 1988 ) , with a control group of general practitioners with a mixed fee per item and capitation based system throughout . SETTING --General practice s in Copenhagen city ( index group ) and Copenhagen county ( control group ) . SUBJECTS--265 General practitioners in Copenhagen city , of whom 100 were selected r and omly from the 130 who agreed to participate ( 10 exclusions ) and 326 general practitioners in Copenhagen county . MAIN OUTCOME MEASURES --Number of consultations ( face to face and by telephone ) and renewals of prescriptions , diagnostic and curative services , and specialist and hospital referrals per 1000 enlisted patients in one week . RESULTS --Of the 75 general practitioners who completed all three sheets , four were excluded for incomplete data . Total contact rates per 1000 patients listed rose significantly compared with the rates before the change index in the city ( 100.0 before the change v 111.7 ( 95 % confidence interval 106.4 to 117.4 after the change ) and over the same time in the control group ( 100.0 v 106.0 ) , but within a year these rates fell ( to 104.2(99.1 to 109.6 ) and 104.0 respectively ) . There was an increase in consultations by telephone initially but not thereafter . Rates of examinations and treatments that attracted specific additional remuneration after the change rose significantly compared with those before ( diagnostic services , 138.1 ( 118.7 to 160.5 ) and 159.5 ( 137.8 to 184.7 ) and curative services 194.6 ( 152.2 to 248.9 ) and 194.8(152.3 to 249.2 ) for second and third data collection s respectively ) and with the control group ( diagnostic services 105.3 , 107.6 and curative services 106.0 , 115.0 ) whereas referral rates to secondary care fell ( specialist referrals 90.1 ( 80.7 to 100.6 ) and 77.0 ( 68.6 to 86.4 ) and hospital referrals 87.4 ( 71.1 to 107.5 ) and 68.4 ( 54.7 to 85.4 ] in doctors in the city . CONCLUSIONS --Introducing a partial fee for service system seemed to stimulate the provision of services by general practitioners , result ing in reduced referral rates . The concept of a \" target income \" which doctors aim at , rather than maximising their income seemed to play a part in adjustment to changing the system of remuneration", "Abstract Objective : To determine whether an educational package could influence the management of menorrhagia , increase the appropriateness of choice of non-hormonal treatment , and reduce referral rates from primary to secondary care . Design : R and omised controlled trial . Setting : General practice s in East Anglia . Subjects : 100 practice s ( 348 doctors ) in primary care were recruited and r and omised to intervention ( 54 ) and control ( 46 ) . Interventions : An educational package based on principles of “ academic detailing ” with independent academics was given in small practice based interactive groups with a visual presentation , a printed evidence based summary , a graphic management flow chart , and a follow up meeting at 6 months . Outcome measures : All practice s recorded consultation details , treatments offered , and outcomes for women with regular heavy menstrual loss ( menorrhagia ) over 1 year . Results : 1001 consultation data sheets for menorrhagia were returned . There were significantly fewer referrals ( 20 % v 29 % ; odds ratio 0.64 ; 95 % confidence interval 0.41 to 0.99 ) and a significantly higher use of tranexamic acid ( odds ratio 2.38 ; 1.61 to 3.49 ) in the intervention group but no overall difference in norethisterone treatment compared with controls . There were more referrals when tranexamic acid was given with norethisterone than when it was given alone . Those practice s reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid . Conclusions : The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs", "BACKGROUND With the advent of general practitioner fundholding , there has been growth in outreach clinics covering many specialties . The benefits and costs of this model of service provision are unclear . AIM A pilot study aim ed to evaluate an outreach model of ophthalmic care in terms of its impact on general practitioners , their use of secondary ophthalmology services , patients ' views , and costs . METHOD A prospect i ve study , from April 1992 to March 1993 , of the introduction of an ophthalmic outreach service in 17 general practice s in London was undertaken . An ophthalmic outreach team , comprising an ophthalmic medical practitioner and an ophthalmic nurse , held clinics in the practice s once a month . Referral rates to Edgware General Hospital ophthalmology outpatient department over one year from the study practice s were compared with those from 17 control practice s. General practitioners ' assessment s of the scheme and its impact on their knowledge and practice of ophthalmology were sought through a postal survey of all partners and interviews with one partner in each practice . Patient surveys were conducted using self-administered structured question naires . A costings exercise compared the outreach model with the conventional hospital ophthalmology outpatient clinic . RESULTS Of 1309 patients seen by the outreach team in the study practice s , 480 ( 37 % ) were referred to the ophthalmology outpatient department . The annual referral rate to this department from control practice s was 9.5 per 10,000 registered patients compared with 3.8 per 10,000 registered patients from study practice s. A total of 1187 patients were referred to the outpatient department from control practice s. An increase in knowledge of ophthalmology was reported by 18 of 47 general practitioners ( 38 % ) . Nineteen ( 40 % ) of 47 general practitioners took advantage of the opportunity for inservice training with the outreach team ; they were more likely to change their routine practice for ophthalmic care or referral criteria for patients with cataracts or diabetes than those who did not attend for inservice training . The outreach scheme was popular with patients , for whom ease of access and familiarity of surroundings were major advantages . The cost per patient seen in the outreach clinics ( 48.09 pounds ) was about three times the cost per patient seen in the outpatient department ( 15.71 pounds ) . CONCLUSION The model of ophthalmic outreach care in this pilot study was popular with patients and general practitioners and appeared to act as an effective filter of dem and for care in the hospital setting . However , the educational impact of the scheme was limited . Although the unit costs ( per patient ) of the outreach scheme compared unfavourably with those of conventional outpatient treatment , potential health gains from this more accessible model of care require further exploration", "A prospect i ve study was undertaken to determine the potential benefits in patient management and cost effectiveness of physiotherapists employed by general practitioners compared with direct hospital access and access via consultants . The study involved 401 patients from three rural general practice s in south Cheshire and north Staffordshire and took place over six months . On-site physiotherapy in general practice premises result ed in higher referral rates to the physiotherapist compared with the practice using direct hospital access or the practice with access via consultants . Both on site and direct access physiotherapy were associated with fewer prescriptions and lower overall prescribing costs per patient than access to physiotherapy via consultants . There was less time lost from work and normal duties for patients attending the practice with on site physiotherapy compared with those attending the practice which required referral via hospital consultants . Access to physiotherapy via hospital specialists result ed in considerably longer delays than on site physiotherapy and greatly increased the financial costs for the patient . Physiotherapy in general practice premises is a cost effective way of dealing with joint and soft tissue complaints . Direct access to the physiotherapy department within hospitals results in longer delays but provides a satisfactory service . There is little to recommend the utilization of hospital consultants as a means of access to physiotherapy", "SUMMARY", "BACKGROUND The Royal College of Radiologists ' guidelines aim to encourage more appropriate use of diagnostic radiology and so reduce the use of clinical ly unhelpful x-ray examinations . AIM The object of this study was to conduct a r and omized controlled trial of the introduction of the guidelines into general practice . METHOD A total of 62 practice s ( 170 general practitioners ) referring patients to St George 's Hospital , London for diagnostic radiology were r and omly allocated into two groups . Guidelines were sent to the 30 practice s in the intervention group . Radiological referral patterns were compared in both groups before and after the introduction of guidelines . RESULTS Practice s which had received guidelines requested significantly fewer examinations of the spine , and made a significantly higher proportion of requests which conformed to the guidelines compared with practice s which had not received the guidelines . There were no significant differences in the proportion of forms giving physical findings or in the proportion of positive findings at radiology . CONCLUSION Introduction of guidelines can influence general practitioners ' radiological referrals in the short term . Wider use of guidelines might help to reduce unnecessary irradiation of patients", "BACKGROUND Depression , a common disorder often treated by family physicians , may be both underdiagnosed and undertreated . The objective of this study was to determine whether the diagnosis and treatment of depression by family physicians could be improved through an educational strategy . METHODS In this study , conducted between July and December 1997 , 42 family physicians in Newfoundl and were r and omly assigned to an intervention group ( 3-hour case-based educational session on clinical practice guidelines [ CPGs ] for depression and access to a psychiatrist for consultation ) or to a control group ( receipt of CPGs without educational session or access to the psychiatrist ) . Physicians were asked to keep a log of patients with newly diagnosed depression and to record information on severity of depression , medications and referrals to mental health professionals . Patients were asked to complete the Centre for Epidemiologic Studies Depression ( CES-D ) scale before treatment and after 6 months of follow-up . The primary outcome measure was the \" gain \" score ( difference between first and last CES-D scores ) . RESULTS During the study period physicians in the intervention group diagnosed 91 new cases of depression ( mean 4.1 per physician ) and those in the control group diagnosed 56 ( mean 2.8 per physician ) ; the difference was not significant . Most patients ( 91.2 % in the intervention group and 89.3 % in the control group received a prescription for an antidepressant on their first visit . Similar proportions ( 46.2 % in the intervention group and 37.5 % in the control group ) took their medication for the full 6 months ; however , significantly more patients in the intervention group were taking an antidepressant at the 6-month follow-up ( 56 % v. 39.3 % , p = 0.02 ) . The mean number of visits per patient was similar in the 2 groups ( 7.7 in the intervention group and 7.6 in the control group ) . Physicians in the intervention group consulted the psychiatrist 9 times . The overall rate of referrals to psychiatrists and other mental health professionals was 10.9 % ; however , referrals were significantly higher in the intervention group ( 15.4 % v. 3.5 % , p = 0.05 ) . After 6 months of follow-up , a significant difference in gain scores was detected between the intervention and control groups for both the patient 's self-rated CES-D scores ( mean gain score 19.3 v. 15.5 respectively , p = 0.04 ) and the physicians ' ratings of depression severity before treatment and at 6 months ( mean gain 1.1 v. 0.7 respectively , p = 0.02 ) . INTERPRETATION The educational strategy had a modest beneficial effect on the outcomes of patients with depression , but there are still concerns regarding the low rates of drug treatment and referral to mental health professionals by family physicians", "A sample of 101 patients with generalized anxiety disorder were r and omly allocated to one of five groups -- diazepam , placebo , cognitive-behaviour therapy , diazepam plus cognitive-behaviour therapy , or placebo plus cognitive-behaviour therapy-- and treated over 10 weeks in a primary care setting . All groups received a similar amount of contact with the psychologist and general practitioner . The greatest improvement in ratings of severity of symptoms and overall change in symptoms occurred with cognitive-behaviour therapy combined with diazepam ; cognitive-behaviour therapy alone also performed well and cognitive-behaviour therapy plus placebo performed slightly less well . Diazepam alone showed improvement relative to placebo alone . There was a high level of agreement between ratings by the general practitioners , psychologist , and the patients of the response to treatment . At six months follow-up there was no difference between treatment groups in the proportion of patients receiving psychotropic medication after the end of the study . However , cognitive-behaviour therapy , either alone or in combination with drug or placebo , showed the lowest incidence of referral for psychological or psychiatric treatment at six months follow-up", "Abstract Objective : To assess the impact of teaching general practitioners to carry out structured assessment s of their long term mentally ill patients . Design : R and omised controlled trial . Setting : Sixteen group general practice s in South Thames ( west ) region . Subjects : 440 adults disabled by long term mental illness . Interventions : Patients were identified by using practice data with help from local psychiatric and social services . In eight practice s the practitioners were taught a structured assessment schedule to use with patients every six months for two years . Main outcome measures : Changes in drug treatments , referrals , consultation rates , and recording of preventive health data in the two years after intervention . Results : Follow up data were available on 373 patients ( 84.7 % ) . At least one structured assessment was recorded for 127 patients in the intervention group but only 29 had four assessment s recorded . Participating practitioners considered the structured assessment to be time consuming and reported that it did not often lead directly to changes in treatment or referrals . Changes in treatment with neuroleptic drugs and referrals to community psychiatric nurses , however , were significantly more frequent in the intervention group ( differences for intervention group minus control group adjusted for activity in two years before intervention were 14.3 % ( 95 % confidence interval 4.3 % to 24.33 % ; P<0.01 ) for neuroleptic drugs and 13.3 % ( 2.0 % to 24.6%;P<0.05 ) for referrals ) . There were no significant differences in psychiatric admissions , use of the Mental Health Act , drug overdoses , prescriptions , referrals or admissions for physical problems , consultation rates , continuity of care , or recording of preventive data . Conclusions : Teaching general practitioners about the problems of long term mentally ill patients may increase their involvement in patients ' psychiatric care . Regular structured assessment s do not seem feasible in routine surgery appointments . More training for general practitioners and increased re sources such as more nurse time may be necessary if improvements in care of long term mentally ill patients in general practice are to be generalised", "Abstract Objective : To compare outpatient referral patterns in fundholding and non-fundholding practice s before and after the NHS reforms in April 1991 . Design : Prospect i ve collection of data on general practitioners ' referrals to specialist outpatient clinics between June 1990 and January 1994 and detailed comparisons of three phases -- October 1990 to March 1991 ( phase 1 ) , October 1991 to March 1992 ( phase 2 ) , and October 1993 to January 1994 ( phase 3 ) . Setting : 10 first wave fundholding practice s and six non-fundholding practice s in the Oxford region . Subjects : Patients referred to consultant outpatient clinics . Results : NHS referral rates increased in fundholding practice s in phase 2 and phase 3 of the study by 8.1/1000 patients a year ( 95 % confidence interval 5.7 to 10.5 ) , anincrease of 7.5 % from phase 1 ( 107.3/1000 ) to phase 3 ( 115.4/1000 ) . Non-fundholders ' rates increased significantly , by 25.3/1000 patients ( 22.5 - 28.1 ) , an increase of 26.6 % from phase 1 ( 95.0/1000 ) to phase 3 ( 120.3/1000 ) . The fundholders ' referral rates to private clinics decreased by 8.8 % , whereas those from non-fundholding practice s increased by 12.2 % . The proportion of referrals going outside district boundaries did not change significantly . Three of the four practice s entering the third and fourth wave of fundholding increased their referral rates significantly in the year before becoming fundholders . Conclusions : No evidence existed that budgetary pressures caused first wave fundholders to reduce referral rates , although the method of budget allocation may have encouraged general practitioners to inflate their referral rates in the preparatory year . Despite investment in new practice based facilities , no evidence yet exists that fundholdingencourages a shift away from specialist care", "Objectives : To evaluate the effect of a risk factor checklist and training video for general practitioners in reducing inter- practice variation and improving the appropriateness of referrals ( assessed by their positive predictive value or PPV ) of patients with suspected otitis media with effusion ( OME or ' glue ear ' ) to secondary care . Methods : Fifty general practice s ( 177 practitioners ) from the NHS Trent region and the West of Scotl and were cluster-r and omised either to a control group ( n = 12 ) or to one of three intervention groups ( training video ( n = 16 ) , checklist ( n = 11 ) , or both ( n = 11 ) ) . Data on all paediatric ear , nose and throat ( ENT ) referrals and diagnostic results at ENT clinics were collected for a one-year period pre- and post-intervention . Referral rates for OME and for closely related conditions were calculated for children aged 0 - 15 years , based on each practice 's list size . PPV was defined as the proportion of referrals result ing in bilateral hearing loss ≥ 20 dB at the ENT outpatient department . Results : There was a significant improvement in the PPV , adjusted for patients ' waiting time between general practitioner ( GP ) referral and being seen at the ENT department . The improvement in PPV pre- and postintervention was 15 % ( 95 % confidence interval , CI : -12.1 % to 41.7 % ) for the practice s receiving both interventions , compared with a degradation of 20 % pre- and post-intervention ( 95 % CI : -32.9 % to -6.4 % ) for practice s receiving only one intervention and a degradation of 34 % for those receiving no intervention . Conclusions : Disseminating a risk factor checklist and training video on glue ear to GPs using a multi-channel approach can improve the quality of referrals to ENT", "BACKGROUND Dyspepsia can be managed by initial endoscopy and treatment based on endoscopic findings , or by empirical prescribing . We aim ed to determine the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years presenting to their primary care physician . METHODS 422 patients were recruited and r and omly assigned to initial endoscopy or usual management . Primary outcomes were effect of treatment on dyspepsia symptoms and cost effectiveness . Secondary outcomes were quality of life and patient satisfaction . Total costs were calculated from individual patient 's use of re sources with unit costs applied from national data . Statistical analysis of uncertainty on incremental cost-effectiveness ratio ( ICER ) was done along with a sensitivity analysis on unit costs with cost-effectiveness acceptability curves . FINDINGS In the 12 months following recruitment , 213 ( 84 % ) patients had an endoscopy compared with 75 ( 41 % ) controls . Initial endoscopy result ed in a significant improvement in symptom score ( p=0.03 ) , and quality of life pain dimension ( p=0.03 ) , and a 48 % reduction in the use of proton pump inhibitors ( p=0.005 ) . The ICER was Pound Sterling1728 ( UK Pound Sterling ) per patient symptom-free at 12 months . The ICER was very sensitive to the cost of endoscopy , and could be reduced to Pound Sterling165 if the unit cost of this procedure fell from Pound Sterling246 to Pound Sterling100 . INTERPRETATION Initial endoscopy in dyspeptic patients over age 50 might be a cost-effective intervention", "A r and omised controlled trial of the effectiveness of counselling ( In-House Counselled ( IHC ) group ) compared to routine advice from General Practitioners ( Routine Treatment ( RT ) group ) was conducted with three practice s and a total of 188 patients in East Sussex . Changes in interpersonal problems using the 32 item Inventory of Interpersonal Problems , symptoms of psychological distress using the Symptom Index and self esteem using Repertory Grids were compared between groups at four months and after a further four month follow-up . A question naire monitoring patient service satisfaction was given to those who had received In-House counselling . The number of counselling sessions , early withdrawals and refusers was also monitored . In order to facilitate interprofessional communication , the three counsellors and a GP representative from each practice met monthly for an Action Learning group , led by an external facilitator to provide a forum to discuss working practice s. The group met six times for two and a half hours . An audit of the participants ' medical notes was carried out at the end of the study to establish any changes in subsequent use of medical services and prescribing patterns . The results show that patients within both groups improved considerably , in line with similar studies . The IHC group was significantly less likely to be referred out to mental health services . However , there was no statistical difference between the groups on any of the measures or in changes in subsequent service use or prescribing patterns . This may have been a result of Action Learning Group producing more psychologically minded GPs . Patients in the IHC group were overwhelmingly in favour of counselling and stated that it had helped them with a variety of psychological problems", "Objectives : To compare the costs to the health service , women and their families of routine antenatal care provided by either traditional obstetrician-led shared care or general practitioner (GP)/community midwife care . Method : A multicentre r and omized controlled trial in 51 general practice s linked to nine maternity hospitals in Scotl and : 1667 low-risk pregnant women provided information on costs to the health service . 704 of these women provided information on non-health service costs . Results : GP/midwife antenatal care was found to cost statistically significantly less than shared care . This was the case for investigations carried out at routine antenatal visits ( GP/midwife = £ 87.25 , shared care = £ 91.15 , P = 0.05 ) , staffing costs at routine antenatal visits ( GP/midwife = £ 127.76 , shared care = £ 131.09 , P = 0.001 ) , and non-health service costs incurred by women and their companions ( GP/midwife = £ 118.53 , shared care = £ 133.49 , P = 0.001 ) . While non-routine care in the GP/midwife arm of the trial costs less than in the shared care arm , the difference was not statistically significant ( GP/midwife = £ 83.74 , shared care = £ 94.43 , P = 0.46 ) . The total societal cost of antenatal care was £ 417.28 per woman in the GP/midwife arm of the trial and £ 450.19 in the shared care arm of the trial . This difference was statistically significant ( P < 0.001 ) . The application of sensitivity analysis did not change these results . Conclusions : GP/midwife antenatal care is a satisfactory option for low-risk pregnant women in Scotl and provided that clinical outcomes and women 's satisfaction are at least the same as those of women with shared care" ]

[ "22878823", "10570423", "15764775", "24832000", "11265884", "22406960", "22610520" ]

[ "Optimal management of malignant pleural effusions (results of CALGB 30102).", "A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions", "Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.", "Comparing cost of indwelling pleural catheter vs talc pleurodesis for malignant pleural effusion.", "Treatment of malignant pleural effusions with tunneled long-term drainage catheters.", "Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion.", "Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial." ]

[ "The optimal strategy to achieve palliation of malignant pleural effusions ( MPEs ) is unknown . This multi-institutional , prospect i ve , r and omized trial compares 2 established methods for controlling symptomatic unilateral MPEs . Patients with unilateral MPEs were r and omized to either daily tunneled catheter drainage ( TCD ) or bedside talc pleurodesis ( TP ) . This trial is patterned after a previous r and omized trial that showed that bedside TP was equivalent to thoracoscopic TP ( CALGB 9334 ) . The primary end point of the current study was combined success : consistent/reliable drainage/pleurodesis , lung expansion , and 30-day survival . A secondary end point , survival with effusion control , was added retrospectively . This trial r and omized 57 patients who were similar in terms of age ( 62 years ) , active chemotherapy ( 28 % ) , and histologic diagnosis ( lung , 63 % ; breast , 12 % ; other/unknown cancers , 25 % ) to either bedside TP or TCD . Combined success was higher with TCD ( 62 % ) than with TP ( 46 % ; odds ratio , 5.0 ; P = .064 ) . Multivariate regression analysis revealed that patients treated with TCD had better 30-day activity without dyspnea scores ( 8.7 vs. 5.9 ; P = .036 ) , especially in the subgroup with impaired expansion ( 9.1 vs. 4.6 ; P = .042 ) . Patients who underwent TCD had better survival with effusion control at 30 days compared with those who underwent TP ( 82 % vs. 52 % , respectively ; P = .024 ) . In this prospect i ve r and omized trial , TCD achieved superior palliation of unilateral MPEs than TP , particularly in patients with trapped lungs", "The purpose of this study was to compare the effectiveness and safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via tube thoracostomy in the treatment of patients with recurrent symptomatic malignant pleural effusions ( MPE )", "STUDY OBJECTIVE To demonstrate the efficacy , safety , and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions ( MPEs ) . DESIGN A prospect i ve , r and omized trial was design ed to compare thoracoscopy with talc insufflation ( TTI ) to thoracostomy and talc slurry ( TS ) for patients with documented MPE . MEASUREMENTS The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-exp and ed > 90 % . Morbidity , mortality , and quality of life were also assessed . RESULTS Of 501 patients registered , those eligible were r and omized to TTI ( n = 242 ) or TS ( n = 240 ) . Patient demographics and primary malignancies were similar between study arms . Overall , there was no difference between study arms in the percentage of patients with successful 30-day outcomes ( TTI , 78 % ; TS , 71 % ) . However , the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS ( 82 % vs 67 % ) . Common morbidity included fever , dyspnea , and pain . Treatment-related mortality occurred in nine TTI patients and seven TS patients . Respiratory complications were more common following TTI than TS ( 14 % vs 6 % ) . Respiratory failure was observed in 4 % of TS patients and 8 % of TTI patients , accounting for five toxic deaths and six toxic deaths , respectively . Quality -of-life measurement demonstrated less fatigue with TTI than TS . Patient ratings of comfort and safety were also higher for TTI , but there were no differences on perceived value or convenience of the procedures . CONCLUSIONS Both methods of talc delivery are similar in efficacy ; TTI may be better for patients with either a lung or breast primary . The etiology and incidence of respiratory complications from talc need further exploration", "BACKGROUND Malignant pleural effusion is associated with short life expectancy and significant morbidity . A r and omized controlled trial comparing indwelling pleural catheters ( IPCs ) with talc pleurodesis found that IPCs reduced in-hospital time and the need for additional procedures but were associated with excess adverse events . METHODS Using data from the clinical trial , we compared costs associated with use of IPCs and with talc pleurodesis . Re source use and adverse events were captured through case report forms over the 1-year trial follow-up . Costs for outpatient and inpatient visits , diagnostic imaging , nursing , and doctor time were obtained from the UK National Health Service reference costs and University of Kent 's Unit Costs of Health and Social Care 2011 and inflated to 2013 using the UK Consumer Price Index . Procedure supply costs were obtained from the manufacturer . Difference in mean costs was compared using nonparametric bootstrapping . All costs were converted to US dollars using the Organisation for Economic Co-operation and Development Purchasing Power Parity Index . RESULTS Overall mean cost ( SD ) for managing patients with IPCs and talc pleurodesis was $ 4,993 ( $ 5,529 ) and $ 4,581 ( $ 4,359 ) , respectively . The incremental mean cost difference was $ 401 , with 95 % CI of -$1,387 to $ 2,261 . The mean cost related to ongoing drainage in the IPC group was $ 1,011 ( $ 732 ) vs $ 57 ( $ 213 ) in the talc pleurodesis group ( P = .001 ) . This included the cost of drainage bottles , dressing changes in the first month , and catheter removal . There was no significant difference in cost of the initial intervention or adverse events between the groups . For patients with survival < 14 weeks , IPC is significantly less costly than talc pleurodesis , with mean cost difference of -$1,719 ( 95 % CI , -$3,376 to -$85 ) . CONCLUSIONS There is no significant difference in the mean cost of managing patients with IPCs compared with talc pleurodesis . For patients with limited survival , IPC appears less costly . TRIAL REGISTRY is rct n.org ; No. : IS RCT N87514420 ; URL : www.is rct n.org", "PURPOSE To assess the effectiveness of tunneled pleural catheters ( TPCs ) in the treatment of malignant pleural effusions ( MPEs ) . MATERIAL S AND METHODS Twenty-eight patients with symptomatic MPEs had 31 hemithoraces treated with TPCs placed under image guidance . Chemical sclerotherapy had failed in two patients and two had symptomatic locules . Drainage was accomplished by intermittent connection to vacuum bottles . Pleurodesis was considered achieved when three consecutive outputs were scant and imaging showed no residual fluid . RESULTS All catheters were successfully placed . Dyspnea improved in 94 % ( 29 of 31 hemithoraces ) at 48 hours and 91 % ( 20 of 22 patients ) at 30 days . Control of the MPE was achieved in 90 % of hemithoraces ( 28/31 ) , although five required ancillary procedures . Pleurodesis occurred in 42 % ( 13 of 31 ) of hemithoraces , including both that underwent an earlier attempt at chemical sclerotherapy and one treated locule . Continued drainage without pleurodesis controlled the effusion in 48 % ( 15 of 31 ) . In only 7 % was hospital time necessary for care related to the TPC . Early , transient catheter-related pain was common , but only three complications ( in two patients ) occurred . Neither of these altered patient care . CONCLUSIONS Regardless of whether pleurodesis is achieved , TPCs provide effective long-term outpatient palliation of MPEs", "BACKGROUND Patients with malignant pleural effusion ( MPE ) have limited prognoses . They require long-lasting symptom relief with minimal hospitalization . Indwelling pleural catheters ( IPCs ) and talc pleurodesis are approved treatments for MPE . Establishing the implication s of IPC and talc pleurodesis on subsequent hospital stay will influence patient choice of treatment . Therefore , our objective was to compare patients with MPE treated with IPC vs pleurodesis in terms of hospital bed days ( from procedure to death or end of follow-up ) and safety . METHODS In this prospect i ve , 12-month , multicenter study , patients with MPE were treated with IPC or talc pleurodesis , based on patient choice . Key end points were hospital bed days from procedure to death ( total and effusion-related ) . Complications , including infection and protein depletion , were monitored longitudinally . RESULTS One hundred sixty patients with MPE were recruited , and 65 required definitive fluid control ; 34 chose IPCs and 31 pleurodesis . Total hospital bed days ( from any causes ) were significantly fewer in patients with IPCs ( median , 6.5 days ; interquartile range [ IQR ] = 3.75 - 13.0 vs pleurodesis , mean , 18.0 ; IQR , 8.0 - 26.0 ; P = .002 ) . Effusion-related hospital bed days were significantly fewer with IPCs ( median , 3.0 days ; IQR , 1.8 - 8.3 vs pleurodesis , median , 10.0 days ; IQR , 6.0 - 18.0 ; P < .001 ) . Patients with IPCs spent significantly fewer of their remaining days of life in hospital ( 8.0 % vs 11.2 % , P < .001 , χ(2 ) = 28.25 ) . Fewer patients with IPCs required further pleural procedures ( 13.5 % vs 32.3 % in pleurodesis group ) . There was no difference in rates of pleural infection ( P = .68 ) and protein ( P = .65 ) or albumin loss ( P = .22 ) . More patients treated with IPC reported immediate ( within 7 days ) improvements in quality of life and dyspnea . CONCLUSIONS Patients treated with IPCs required significantly fewer days in hospital and fewer additional pleural procedures than those who received pleurodesis . Safety profiles and symptom control were comparable", "CONTEXT Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy . Palliation is achieved by fluid drainage , but the most effective first-line method has not been determined . OBJECTIVE To determine whether indwelling pleural catheters ( IPCs ) are more effective than chest tube and talc slurry pleurodesis ( talc ) at relieving dyspnea . DESIGN Unblinded r and omized controlled trial ( Second Therapeutic Intervention in Malignant Effusion Trial [ TIME2 ] ) comparing IPC and talc ( 1:1 ) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals . Patients were screened from April 2007-February 2011 and were followed up for a year . INTERVENTION Indwelling pleural catheters were inserted on an outpatient basis , followed by initial large volume drainage , education , and subsequent home drainage . The talc group were admitted for chest tube insertion and talc for slurry pleurodesis . MAIN OUTCOME MEASURE Patients completed daily 100-mm line visual analog scale ( VAS ) of dyspnea over 42 days after undergoing the intervention ( 0 mm represents no dyspnea and 100 mm represents maximum dyspnea ; 10 mm represents minimum clinical ly significant difference ) . Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables . RESULTS Dyspnea improved in both groups , with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group ( 95 % CI , 19.3 - 30.1 mm ) and 24.4 mm ( 95 % CI , 19.4 - 29.4 mm ) in the talc group , with a difference of 0.16 mm ( 95 % CI , −6.82 to 7.15 ; P = .96 ) . There was a statistically significant improvement in dyspnea in the IPC group at 6 months , with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm ( 95 % CI , −25.2 to −2.8 mm ; P = .01 ) . Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days ( interquartile range [ IQR ] , 0 - 1 day ) and 4 days ( IQR , 2 - 6 days ) for the talc group , with a difference of −3.5 days ( 95 % CI , −4.8 to −1.5 days ; P < .001 ) . There was no significant difference in quality of life . Twelve patients ( 22 % ) in the talc group required further pleural procedures compared with 3 ( 6 % ) in the IPC group ( odds ratio [ OR ] , 0.21 ; 95 % CI , 0.04 - 0.86 ; P = .03 ) . Twenty-one of the 52 patients in the catheter group experienced adverse events vs 7 of 54 in the talc group ( OR , 4.70 ; 95 % CI , 1.75 - 12.60 ; P = .002 ) . CONCLUSION Among patients with malignant pleural effusion and no previous pleurodesis , there was no significant difference between IPCs and talc pleurodesis at relieving patient-reported dyspnea . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N87514420" ]

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[ "[Postoperative analgesia with nefopam and non-steroidal anti-inflammatory drugs in patients after surgery for tumors of head and neck].", "A prospective randomized trial to compare immediate and 24‐hour delayed catheter removal following total abdominal hysterectomy", "Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group.", "Patient education and informed consent in head and neck surgery.", "Closed-suction versus Penrose drainage after cholecystectomy. A prospective, randomized evaluation.", "Anesthetic techniques for pharyngeal flap surgery: effects on postoperative complications.", "Comparison of Perioperative Oral Multimodal Analgesia Versus IV PCA for Spine Surgery", "The Ideal Split-Thickness Skin Graft Donor-Site Dressing: A Clinical Comparative Trial of a Modified Polyurethane Dressing and Aquacel", "Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty", "The influence of an Enhanced Recovery Programme on clinical outcomes, costs and quality of life after surgery for colorectal cancer", "Timing of urinary catheter removal after uncomplicated total abdominal hysterectomy: a prospective randomized trial.", "Randomized clinical trial on enhanced recovery versus standard care following open liver resection", "Implementing Fast-Track Protocol for Colorectal Surgery: A Prospective Randomized Clinical Trial", "The effect of dobutamine on blood flow of free tissue transfer flaps during head and neck reconstructive surgery*", "Loxoprofen sodium and celecoxib for postoperative pain in patients after spinal surgery: a randomized comparative study", "Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance?", "Core temperature measurement in the intensive care unit", "Bilateral Superficial Cervical Plexus Block Combined with General Anesthesia Administered in Thyroid Operations", "Antimicrobial prophylaxis for contaminated head and neck surgery.", "[Gravity or suction drainage in thyroid surgery? Control of efficacy with ultrasound determination of residual hematoma].", "The efficacy of routine central venous monitoring in major head and neck surgery: a retrospective review.", "Multimodal Perioperative Rehabilitation in Elective Conventional Resection of Colonic Cancer: Results from the German Multicenter Quality Assurance Program ‘Fast-Track Colon II’", "Dexmedetomidine premedication of outpatients under IVRA.", "Pre‐operative carbohydrate loading may be used in type 2 diabetes patients", "Total Intravenous Anesthesia with Propofol Reduces Postoperative Nausea and Vomiting in Patients Undergoing Robot-Assisted Laparoscopic Radical Prostatectomy: A Prospective Randomized Trial", "Effect of Pregabalin and Dexamethasone on Postoperative Analgesia after Septoplasty", "Resistive-Heating and Forced-Air Warming Are Comparably Effective", "Effect of prewarming on post-induction core temperature and the incidence of inadvertent perioperative hypothermia in patients undergoing general anaesthesia.", "Comparison of Intramuscular Dexmedetomidine and Midazolam Premedication for Elective Abdominal Hysterectomy", "Management of superficial to partial-thickness wounds.", "Superficial selective cervical plexus block following total thyroidectomy: a randomized trial.", "Antiemetic effects of granisetron and dexamethasone combination therapy during cisplatin-containing chemotherapy for head and neck cancer: dexamethasone dosage verification trial", "Clinical assessment of venous thromboembolic risk in surgical patients.", "Morphine/ondansetron PCA for postoperative pain, nausea, and vomiting after skull base surgery", "The effects of warming intravenous fluids on intraoperative hypothermia and postoperative shivering during prolonged abdominal surgery", "HOW TO DRESS DONOR SITES OF SPLIT THICKNESS SKIN GRAFTS: A PROSPECTIVE, RANDOMISED STUDY OF FOUR DRESSINGS", "Post-Operative Nausea and Vomiting (PONV) after Thyroid Surgery: A Prospective, Randomized Study Comparing Totally Intravenous versus Inhalational Anesthetics", "Comparison of noninvasive cardiac output measurements using the Nexfin monitoring device and the esophageal Doppler.", "Analgesic efficacy of bilateral superficial cervical plexus block administered before thyroid surgery under general anaesthesia.", "Outcomes of intubation in difficult airways due to head and neck pathology.", "A Carbohydrate-Rich Drink Reduces Preoperative Discomfort in Elective Surgery Patients", "Percutaneous versus surgical tracheostomy: a double-blind randomized trial.", "Preoperative topical antimicrobial decolonization in head and neck surgery.", "Randomized clinical trial of intraoperative superficial cervical plexus block versus incisional local anaesthesia in thyroid and parathyroid surgery", "The Bilateral Superficial Cervical Plexus Block With 0.75% Ropivacaine Administered Before or After Surgery Does Not Prevent Postoperative Pain After Total Thyroidectomy", "Comparison of Sevoflurane versus Propofol under Auditory Evoked Potential Monitoring in Female Patients Undergoing Breast Surgery", "Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.", "A randomized controlled trial of early oral feeding in laryngectomized patients.", "Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery.", "Three-dose vs extended-course clindamycin prophylaxis for free-flap reconstruction of the head and neck.", "Antibiotic prophylaxis in clean-contaminated head and neck oncological surgery.", "Assessment of common nonsteroidal anti-inflammatory medications by whole blood aggregometry: a clinical evaluation for the perioperative setting.", "Preliminary report of associated factors in wound infection after major head and neck neoplasm operations--does the duration of prophylactic antibiotic matter?", "Clinical evaluation of two antiemetic combinations palonosetron dexamethasone versus ondansetron dexamethasone in chemotherapy of head and neck cancer.", "Tropisetron plus dexamethasone is more effective than tropisetron alone for the prevention of postoperative nausea and vomiting in children undergoing tonsillectomy.", "A controlled trial of intermittent positive pressure breathing, incentive spirometry, and deep breathing exercises in preventing pulmonary complications after abdominal surgery.", "Antibiotic Use During Major Head and Neck Surgery", "Analgesic effects of preoperative gabapentin after tongue reconstruction with the anterolateral thigh flap.", "Comparison of three prophylactic antibiotic regimens in clean‐contaminated head and neck surgery", "A Prospective Randomized Controlled Trial of Multimodal Perioperative Management Protocol in Patients Undergoing Elective Colorectal Resection for Cancer", "A fast-track program reduces complications and length of hospital stay after open colonic surgery.", "Multimedia Approach to Preoperative Adenotonsillectomy Counseling", "The role of topical antibiotic prophylaxis in patients undergoing contaminated head and neck surgery with flap reconstruction.", "Bilateral Superficial Cervical Plexus Block Reduces Postoperative Nausea and Vomiting and Early Postoperative Pain after Thyroidectomy", "Effect of cyclooxygenase-2-specific inhibitors on postoperative analgesia after major open abdominal surgery.", "Short‐term versus long‐term antimicrobial prophylaxis in oncologic head and neck surgery", "Predicting skin flap viability using a new intraoperative tissue oximetry sensor: a feasibility study in pigs.", "No reduction in complication rate by stay in the intensive care unit for patients undergoing surgery for head and neck cancer and microvascular reconstruction.", "Resistive-Heating or Forced-Air Warming for the Prevention of Redistribution Hypothermia", "The combined analgesic effect of gabapentin and transdermal fentanyl patch on acute and chronic pain after maxillary cancer surgeries" ]

[ "MATERIAL S AND METHODS 83 adult patients included in the study were divided into two groups . Patients of the group-1 ( n-49 ) had medium level of pain after cancer head and neck surgery . Patients of the group-2 ( n-34 ) had severe pain . Three first postoperative days their post-operative multimodal analgesia started with tenoxycam 20 mg i.m . after induction of anesthesia , then every 24 hour ( 58 patients ) . 25 patients got ketoprofen 100 mg i.m . every 8 - 12 hours instead of tenoxycam . All patients had nefopam 30 mg i.m . 30 min prior the end of surgery procedure , and every 8 hours afterwards . 7 patients of the group-1 had more than 4 pain scores ( day 1 ) , 4 patients --at the day 2 . They received tramadol or paracetamol additionally . 7 patients ( group-2 ) also had up to 5 pain scores on the day 1 , 5 patients had 4 pain scores on the day 2 , and 3 patients 4 pain scores on the day 3 . All that patients received additional analgesia with tramadol or trimeperidine once a day . 8.4 % of patients suffered from adverse reactions ( tachycardia , PONV and sweating ) . CONCLUSION This method of multimodal postoperative analgesia is very simple and fairly efficient", "Objective . To assess whether early or immediate removal of a 12F in‐dwelling Foley catheter after total abdominal hysterectomy affects the level of subjective pain assessment postoperatively . Design . R and omized controlled trial . Setting . University Hospital . Population . Seventy women underwent total abdominal hysterectomies for various benign gynecological diseases . Methods . Women were r and omized to have the urinary catheter removed in the operating room after the surgical procedure or to have it removed on postoperative day 1 . Main outcome measures . The primary outcome was patients ’ pain assessment and the secondary outcomes were rate of re‐catheterization and symptomatic urinary tract infection . Results . There was no difference in the pain assessment between the two groups . A significantly higher number of urinary retention episodes requiring re‐catheterization were found in the immediate removal group compared with the delayed removal group ( 20 vs. 0 % ; p= 0.011 ) . The incidence of symptomatic urinary tract infection did not differ between the two groups . Conclusions . There are pros and cons regarding the policy of one‐day in‐dwelling catheterization compared to immediate catheter removal", "BACKGROUND Mild perioperative hypothermia , which is common during major surgery , may promote surgical-wound infection by triggering thermoregulatory vasoconstriction , which decreases subcutaneous oxygen tension . Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen . Hypothermia also directly impairs immune function . We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization . METHODS Two hundred patients undergoing colorectal surgery were r and omly assigned to routine intraoperative thermal care ( the hypothermia group ) or additional warming ( the normothermia group ) . The patient 's anesthetic care was st and ardized , and they were all given cefam and ole and metronidazole . In a double-blind protocol , their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks ; wounds containing culture-positive pus were considered infected . The patients ' surgeons remained unaware of the patients ' group assignments . RESULTS The mean ( + /- SD ) final intraoperative core temperature was 34.7 + /- 0.6 degrees C in the hypothermia group and 36.6 + /- 0.5 degrees C in the normothermia group ( P < 0.001 ) Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia ( 19 percent ) but in only 6 of 104 patients assigned to normothermia ( 6 percent , P = 0.009 ) . The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia ( P = 0.002 ) , and the duration of hospitalization was prolonged by 2.6 days ( approximately 20 percent ) in hypothermia group ( P = 0.01 ) . CONCLUSIONS Hypothermia itself may delay healing and predispose patients to wound infections . Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations", "OBJECTIVE To examine the effects of an educational intervention , in the form of printed material , on patient knowledge and recall of possible risks from parotidectomy or thyroidectomy . DESIGN Prospect i ve , r and omized , controlled study conducted during a 9-month period . SETTING Head and neck surgery clinic of an academic tertiary care hospital . PATIENTS One hundred twenty-five consecutive patients older than 16 years who were undergoing thyroidectomy or parotidectomy at the head and neck surgery clinic were recruited . Four patients were excluded from analysis because their follow-up interview was not within the required limits . INTERVENTION At the preoperative visit during the routine consent process , both groups received a verbally delivered checklist of risks specific for the surgery to be performed . The intervention group was also given a pamphlet with written information accompanied by illustrations . MAIN OUTCOME MEASURES The effectiveness of the educational intervention was determined by comparing the average rate of risk recall between the intervention and control groups . The effects of age , sex , level of education , and time between the consent and recall interviews on recall rate were also assessed . RESULTS The overall risk recall rate for both procedures was 39.1 % . The recall rate of the intervention group was 50.3 % compared with 29.5 % for the control group ( P<.001 ) . CONCLUSIONS The intervention consistently improved risk recall for all patients regardless of age , sex , and level of education . Patients ' ability to recall potential risks was significantly increased by an educational intervention ; all patients would benefit from this intervention", "Closed-suction drainage was compared prospect ively to open , passive drainage ( Penrose drains ) in 128 patients undergoing cholecystectomy . Patients were r and omized at the time of operation to receive either closed-suction drains ( Group I , 67 patients ) or Penrose drains ( Group II , 61 patients ) . The preoperative clinical parameters of the two groups were similar . The patients in Group I when compared with those in Group II had a shorter duration of drainage ( 3.3 days and 4.1 days , respectively , p less than 0.01 ) , a lesser volume of drainage in the first 48 hours postoperatively ( 78 ml and 132 ml , respectively , p less than 0.001 ) , a decreased incidence of fever on the night of operation ( 24 of 67 patients and 39 of 61 patients , respectively , p less than 0.05 ) and on the first postoperative day ( 26 of 67 patients and 32 of 61 patients , respectively , p less than 0.05 ) , and a lower leukocyte count on the first postoperative day ( 12,000 cells/mm3 and 14,100 cells/mm3 , respectively , 0.05 less than p less than 0.1 ) . Patients in Group I tended to have a lower rate of wound infection ( 1 of 67 patients versus 5 of 61 patients in Group II , 0.05 less than p less than 0.1 ) and had a much lower incidence of drain site tenderness ( 8 of 67 patients in Group I versus 24 of 61 patients in Group II , p less than 0.05 ) . This study demonstrates the superiority of closed-suction drains over open , passive drains after cholecystectomy", "OBJECTIVE To assess the effects of 2 different anesthetic techniques on early complications after superior pharyngeal flap surgery . DESIGN R and omized , prospect i ve , single-blind study . SETTING Large referral hospital . PATIENTS One hundred patients undergoing superior pharyngeal flap surgery for the correction of velopharyngeal insufficiency were r and omly divided into 2 equal groups to receive either isoflurane or propofol-based anesthesia . INTERVENTIONS Following induction of anesthesia with fentanyl citrate and propofol , patients were r and omized to receive either isoflurane or propofol for the maintenance of general anesthesia . The inspired isoflurane concentration and propofol infusion rate were adjusted to maintain a stable depth of anesthesia as judged by clinical signs and hemodynamic responses to surgical stimuli . MAIN OUTCOME MEASURES Recovery from anesthesia , recovery from surgery , and early postoperative complications . RESULTS The groups were similar in age , weight , height , induction time , surgery time , extubation time , and anesthetic time . The time ( mean + /- SD ) required to achieve a maximal Steward Recovery Score was 7 + /- 14 minutes in the propofol group compared with 32 + /- 28 minutes in the isoflurane group ( P<.04 ) . No significant differences in postoperative patient satisfaction scores , time to first swallow , drinking time , and time to \" home readiness \" were noted . Overall , 17 patients ( 17 % ) developed airway-related complications and 2 of the patients ( 2 % ) were accounted as severe . Two patients ( 2 % ) bled from the operation site . However , there was no difference in the incidence of postoperative complications between the groups . CONCLUSIONS When compared with isoflurane administration for maintenance of general anesthesia , propofol-based anesthesia was associated with more rapid mental and psychomotor recovery . However , airway-related complications and \" home readiness \" were similar between the groups", "Study Design A preintervention and postintervention design was used to examine a total of 200 patients . Objective After successful implementation at our institution of a perioperative oral multimodal analgesia protocol in major joint arthroplasty , a modified regimen was provided to patients undergoing spine procedures . Summary of Background Data A proactive , multimodal approach is currently recommended for the management of acute postoperative pain . Inadequate postoperative analgesia can negatively influence surgical outcome and duration of rehabilitation . Routine use of intravenous patient controlled analgesia ( IV PCA ) after surgery can result in substantial functional interference , side effects , and lead to untoward events as a result of programming errors . Methods A preintervention and postintervention design was used to compare a historical control group of spine surgery patients who received conventional IV PCA ( N=100 ) with a prospect i ve group who received some form of perioperative oral multiodal analgesis ( N=100 ) . The new regimen included preoperative and postoperative scheduled extended-release oxycodone , gabapentin , and acetaminophen , intraoperative dolasetron and as-needed postoperative short-acting oral oxycodone . Patient surveys and chart audits were used to measure pain intensity , functional interference from pain , opioid consumption , analgesic-related side effects , and patient satisfaction over the first 24 hours postoperatively . Results Patients who received the new perioperative multimodal oral regimen had significantly less opioid consumption ( P<0.001 ) , lower ratings of Least Pain ( P<0.01 ) , and experienced less nausea ( P<.001 ) , drowsiness ( P<0.05 ) , interference with walking ( P=0.05 ) , and coughing and deep breathing ( P<0.05 ) compared with the IV PCA group . Conclusions This quality improvement study shows some safety and significant advantages of a multimodal perioperative oral analgesic regimen compared with st and ard IV PCA after spine surgery", "Background : The almost single disadvantage of conventional polyurethane film dressings , uncontrolled leakage , is probably as often described as its numerous advantages for split-thickness skin graft donor sites . This shortcoming can be overcome by perforating the polyurethane dressing , which permits controlled leakage into a secondary absorbent dressing . The study was conducted to compare the polyurethane dressing system and Aquacel , a hydrofiber wound dressing , which also seems to fulfill all criteria of an ideal donor-site dressing . Methods : This prospect i ve , r and omized , double-blind clinical trial included 50 adult patients . Skin graft donor sites were divided equally for the application of Aquacel and polyurethane dressing . The dressings were kept unchanged for 10 days . After removal of the dressing at day 10 , the epithelialization rate of both sites was evaluated . Pain scores were assessed according to a 0 to 5 numeric pain scale every postoperative day and during dressing removal . Results : On postoperative day 10 , 86.4 percent of the polyurethane dressing donor sites showed complete reepithelialization compared with 54.5 percent of the Aquacel-treated donor sites ( p < 0.001 ) . Polyurethane dressing was significantly less painful until and during removal of the dressing ( p < 0.001 ) . There was no significant difference with respect to scar formation . Conclusions : Overall , polyurethane dressing was superior to Aquacel . Further attributes of the polyurethane dressing such as ease of application , low labor input , high patient comfort , and protection against secondary wound infection qualify this dressing system as an ideal wound covering for donor sites . CLINICAL QUESTION /LEVEL OF EVIDENCE : Therapeutic , II", "BACKGROUND In-vitro studies indicate that platelet function and the coagulation cascade are impaired by hypothermia . However , the extent to which perioperative hypothermia influences bleeding during surgery remains unknown . Accordingly , we tested the hypothesis that mild hypothermia increases blood loss and allogeneic transfusion requirements during hip arthroplasty . METHODS Blood loss and transfusion requirements were evaluated in 60 patients undergoing primary , unilateral total hip arthroplasties who were r and omly assigned to normothermia ( final intraoperative core temperature 36.6 [ 0.4 ] degrees C ) or mild hypothermia ( 35.0 [ 0.5 ] degrees C ) . Crystalloid , colloid , scavenged red cells , and allogeneic blood were administered by strict protocol . FINDINGS Intra- and postoperative blood loss was significantly greater in the hypothermic patients : 2.2 ( 0.5 ) L vs 1.7 ( 0.3 ) L , p < 0.001 ) . Eight units of allogeneic packed red cells were required in seven of the 30 hypothermic patients , whereas only one normothermic patient required a unit of allogeneic blood ( p < 0.05 for administered volume ) . A typical decrease in core temperature in patients undergoing hip arthroplasty will thus augment blood loss by approximately 500 mL. INTERPRETATION The maintenance of intraoperative normothermia reduces blood loss and allogeneic blood requirements in patients undergoing total hip arthroplasty", "Objective Optimizing peri‐operative care using an enhanced recovery programme improves short‐term outcomes following colonic resection . This study compared a prospect i ve group of patients undergoing resection of colorectal cancer within an enhanced recovery programme , with a prospect ively studied historic cohort receiving conventional care", "OBJECTIVE To assess whether immediate ( 0h ) , intermediate ( after 6h ) or delayed ( after 24h ) removal of an indwelling urinary catheter after uncomplicated abdominal hysterectomy can affect the rate of re-catheterization due to urinary retention , rate of urinary tract infection , ambulation time and length of hospital stay . STUDY DESIGN Prospect i ve r and omized controlled trial conducted at Suez Canal University Hospital , Egypt . Two hundred and twenty-one women underwent total abdominal hysterectomy for benign gynecological diseases and were r and omly allocated into three groups . Women in group A ( 73 patients ) had their urinary catheter removed immediately after surgery . Group B ( 81 patients ) had the catheter removed 6h post-operatively while in group C ( 67 patients ) the catheter was removed after 24h . The main outcome measures were the frequency of urinary retention , urinary tract infections , ambulation time and length of hospital stay . RESULTS There was a significantly higher number of urinary retention episodes requiring re-catheterization in the immediate removal group compared to the intermediate and delayed removal groups ( 16.4 % versus 2.5 % and 0 % respectively ) . Delayed urinary catheter removal was associated with a higher incidence of urinary tract infections ( 15 % ) , delayed ambulation time ( 10.3h ) and longer hospital stay ( 5.6 days ) compared to the early ( 1.4 % , 4.1h and 3.2 days respectively ) and intermediate ( 3.7 % , 6.8h and 3.4 days respectively ) removal groups . CONCLUSIONS Removal of the urinary catheter 6h postoperatively appears to be more advantageous than early or late removal in cases of uncomplicated total abdominal hysterectomy", "Enhanced recovery programmes ( ERPs ) have been shown to reduce length of hospital stay ( LOS ) and complications in colorectal surgery . Whether ERPs have the same benefits in open liver resection surgery is unclear , and r and omized clinical trials are lacking", "Background Fast-track protocol s are followed by an enhanced recovery , early return to bowel function and to complete nutrition , and a reduced hospital stay . Our study was design ed to implement fast-track protocol in our university hospital . Methods The 96 consecutive patients with colorectal neoplasm included in the study were r and omized in two equal groups : group 1 ( FT ) included patients undergoing colorectal surgery in a fast-track protocol , and group 2 ( C ) included patients undergoing colorectal surgery with a conventional care protocol . As with other fast-track protocol s , our protocol included carbohydrate fluids load before operation , early mobilization and oral feeding , regular prokinetics , and multimodal postoperative analgesia . Time to restoration of bowel function , to complete mobilization and feeding , length of hospital stay , and incidence of complications and readmissions were monitored . Results Time to mobilization , restoring of bowel function , and complete oral feeding were significantly shorter with fast-track protocol ( p = 0.001 , p = 0.042 , and p = 0.01 , respectively ) . Hospital stay also was shorter in the fast-track group ( p = 0.001 ) . The incidence of complications did not significantly differ with the study groups . Conclusions In our study , fast-track protocol result ed in a shorter time to mobilization , complete feeding , and discharge from hospital . Fast-track protocol did not increase the incidence of complications . However , we consider that our data require further confirmation with powered multicenter national studies", "In view of the controversy over the use of inotropes in free tissue transfer surgery , we assessed the effect of different intra‐operative dobutamine infusion rates on blood flow in the anastomosed recipient artery . Twenty patients undergoing head and neck tumour resection and immediate reconstructive surgery with free tissue transfer were recruited . After completion of the microvascular anastomoses , patients received dobutamine infusions of 2 , 4 and 6 μg.kg−1.min−1 in a r and omised order . After steady state dobutamine concentration was achieved , mean and maximum blood flow in the arterial anastomosis was measured at each concentration , using the Medi‐Stim Butterfly Flowmeter system . Systemic haemodynamic parameters were simultaneously recorded using a pulse contour cardiac output system . Both mean and maximum blood flow increased significantly in the anastomosed artery at dobutamine infusions of 4 and 6 μg.kg−1.min−1 and this was accompanied by increased cardiac output . This may improve free flap perfusion", "Background Nonsteroidal anti-inflammatory drugs ( NSAIDs ) are often used to treat inflammation , pain , and fever , but no criterion st and ard exists for the management of postoperative pain following spinal surgery . In the present study , we compared the analgesic efficacy of loxoprofen sodium ( loxoprofen ) and celecoxib for the management of postoperative pain following spinal surgery . Methods One-hundred forty-one patients ( mean age 62.2 years ) were r and omly assigned to two groups before spinal surgery : a loxoprofen group ( n = 73 , 180 mg/day ) and a celecoxib group ( n = 68 , 200 mg/day ) . The drugs were administered from 1 day until 7 days after surgery . A numeric rating scale ( NRS ) was used to evaluate pain at nine predefined times every day and the findings were compared between the two groups . Laboratory data and adverse events were also recorded . Results There was no significant difference in the maximum and mean NRS scores on each day between loxoprofen and celecoxib , suggesting a comparable analgesic effect for these two NSAIDs . Greater improvement in the NRS score between preadministration ( baseline ) and 30 min or 2 h after administration was obtained for loxoprofen . This tendency was shown for both slight ( NRS score < 5 at baseline ) and severe pain ( NRS score ≥5 at baseline ) . Loxoprofen was discontinued in one patient on day 4 because of renal dysfunction . Celecoxib was discontinued in one patient on day 2 at the patient ’s request . Conclusions Both loxoprofen sodium and celecoxib were well tolerated for the relief of acute postoperative pain after spinal surgery . A single administration of loxoprofen showed superior and rapid effectiveness compared with celecoxib for both slight and severe postoperative pain", "BACKGROUND We aim ed to investigate whether fluid therapy with a goal of near-maximal stroke volume ( SV ) guided by oesophageal Doppler ( ED ) monitoring result in a better outcome than that with a goal of maintaining bodyweight ( BW ) and zero fluid balance in patients undergoing colorectal surgery . METHODS In a double-blinded clinical multicentre trial , 150 patients undergoing elective colorectal surgery were r and omized to receive fluid therapy after either the goal of near-maximal SV guided by ED ( Doppler , D group ) or the goal of zero balance and normal BW ( Zero balance , Z group ) . Stratification for laparoscopic and open surgery was performed . The postoperative fluid therapy was similar in the two groups . The primary endpoint was postoperative complications defined and divided into subgroups by protocol . Analysis was performed by intention-to-treat . The follow-up was 30 days . The trial had 85 % power to show a difference between the groups . RESULTS The number of patients undergoing laparoscopic or open surgery and the patient characteristics were similar between the groups . No significant differences between the groups were found for overall , major , minor , cardiopulmonary , or tissue-healing complications ( P-values : 0.79 ; 0.62 ; 0.97 ; 0.48 ; and 0.48 , respectively ) . One patient died in each group . No significant difference was found for the length of hospital stay [ median ( range ) Z : 5.00 ( 1 - 61 ) vs D : 5.00 ( 2 - 41 ) ; P=0.206 ] . CONCLUSIONS Goal -directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery", "Objective To compare three devices that measure core body temperature at the bedside in ICU patients . Design Prospect i ve , consecutive sample . Setting Voluntary community teaching hospital . Patients Fifteen patients , 78 ± 6 ( SD ) yrs of age , admitted to the medical ICU over a 5-month period who had pulmonary artery catheters inserted as part of their routine care were studied . Thirteen patients were studied once , one patient twice , and one patient six times for a total of 21 sets of measurements . Interventions All patients had urinary bladder thermistor catheters inserted just before pulmonary artery catheterization . Simultaneous core temperatures were measured for the duration of pulmonary artery catheterization every 4 hrs by the pulmonary artery thermistor catheter , the bladder thermistor catheter , and by a tympanic membrane infrared probe set on its core temperature setting . The three devices were then compared with each other in vitro using a specialized constant water bath setup . Finally , two of the tympanic membrane infrared probes were compared with each other in 20 ambulatory emergency department patients . Measurements and Main Results Over 32 hrs of pulmonary artery catheterization , the pulmonary artery thermistor catheters and bladder thermistor catheters showed excellent agreement , with a bias of only −0.04 ° C between the two . However , the bias comparing the tympanic membrane infrared probe with the pulmonary artery thermistor catheter was −0.38 ° C , and the bias was −0.34 ° C comparing the tympanic membrane infrared probe with the bladder thermistor catheter . The tympanic membrane infrared probe readings remained significantly higher than the pulmonary artery thermistor catheter or bladder thermistor catheter readings over the entire 32-hr period . The two tympanic membrane infrared probes compared with each other in emergency room patients showed excellent agreement ( p < .001 ) . In the in vivo water bath setup , the tympanic membrane infrared probe on most of its setting s again registered significantly ( p < .01 ) higher than both the pulmonary artery thermistor catheter and the bladder thermistor catheter . Conclusions Pulmonary artery thermistor catheters and bladder thermistor catheters appear to give consistent , highly reliable bedside measurements of core body temperature in ICU patients . The currently available device that measures core body temperature from the tympanic membrane appears to give erroneously high readings , and should be used with caution", "Background We investigated the analgesic efficacy of bilateral superficial cervical plexus block in patients undergoing thyroidectomy and to determine whether it reduces the adverse effects of general anesthesia . Methods We prospect ively recruited 162 patients who underwent elective thyroid operations from March 2006 to October 2007 . They were r and omly assigned to receive a bilateral superficial cervical block ( 12 ml per side ) with isotonic saline ( group A ; n = 56 ) , bupivacaine 0.5 % ( group B ; n = 52 ) , or levobupivacaine 0.5 % ( group C ; n = 54 ) after induction of general anesthesia . The analgesic efficacy of the block was assessed with : intraoperative anesthetics ( desflurane ) , numbers of patients needing postoperative analgesics , the time to the first analgesics required , and pain intensity by visual analog scale ( VAS ) . Postoperative nausea and vomiting ( PONV ) for 24 h were also assessed by the “ PONV grade . ” We also compared hospital stay , operative time , and discomfort in swallowing . Results There were no significant differences in patient characteristics . Each average end-tidal desflurane concentration was 5.8 , 3.9 , and 3.8 % in groups A , B , and C , respectively ( p < 0.001 ) . Fewer patients in groups B and C required analgesics ( A : B : C = 33:8:7 ; p < 0.001 ) , and it took longer before the first analgesic dose was needed postoperatively ( group A : B : C = 82.1:360.8:410.1 min ; p < 0.001 ) . Postoperative pain VAS were lower in groups B and C for the first 24 h postoperatively ( p < 0.001 ) . Incidences of overall and severe PONV were lower , however , there were not sufficient numbers of patients to detect differences in PONV among the three groups . Hospital stay was shorter in group B and group C ( p = 0.011 ) . There was no significant difference in operative time and postoperative swallowing pain among the three groups . Conclusions Bilateral superficial cervical plexus block reduces general anesthetics required during thyroidectomy . It also significantly lowers the severity of postoperative pain during the first 24 h and shortens the hospital stay", "The use of antibiotic prophylaxis in head and neck surgery is controversial . Most surgeons agree that when surgery requires entry into the aerodigestive tract through the skin the wound is by definition contaminated and antibiotic prophylaxis is indicated as it is in other contaminated wounds . There is no general agreement as to which antibiotic or combination of antibiotics to use or what the schedule of dosage administration should be . In order to obtain a meaningful data to help in decision making , a double blind , r and omized study was performed to investigate whether cefazolin alone or a combination of gentamicin and clindamycin was more effective in prophylaxis . All patients entered into the study underwent major oncologic head and neck surgery requiring entry into the upper aerodigestive tract through the skin . Patients were stratified at entry according to the stage of disease , surgical procedure , and the existence of a prior tracheotomy or prior radiation therapy . Subsequently , patients were r and omly assigned to 1 of 4 treatment groups . Group I : Cefazolin 1 day , placebo day 2 to 5 . Group II : Cefazolin days 1 to 5 , Group III : Gentamicin and clindamycin 1 day , placebo days 2 to 5 . Group IV : Gentamicin and clindamycin days 1 to 5 . Drugs were given intravenously beginning 3 hours preoperatively and continued postoperatively every 8 hours , according to the assigned schedule . All wounds were observed daily following surgery and were grade d on a predetermined scale by 3 unbiased observers . Significantly wound infections occurred in 15 % of all patients . Group I , 33 % ; Group II , 20 % ; Group III , 7 % ; Group IV , 4 % . In Group III and Group IV there was a statistically significant ( P less than .05 ) reduction in the rate of postoperative wound infection . Multifactorial analysis demonstrated that patients whose surgery included repair with a regional pectoral flap had a statistically significant increased chance of developing postoperative wound infection ( P less than .05 ) . Patients undergoing laryngectomy , with or without neck dissection , were at less risk of postoperative infection tham patients undergoing oropharyngeal resection ( P less than .05 ) . The preoperative existence of tracheotomy or prior radiation therapy had no demonstrable effect on the incidence of wound infection postoperatively in this study", "In a prospect i ve r and omized trial , the common high-vacuum drainage system according to Redon was compared with the nonsuction system according to Robinson in 80 patients undergoing elective thyroid surgery between January 1995 and August 1995 . Forty patients were provided with nonsuction , passive drains , and another 40 patients were allocated to a control group with the high-vacuum system . Twenty-four h postoperatively , the wound area was analyzed by sonography after drainage removal . The dimension of the remaining hematoma was determined by scanning the operation field in six to seven layers ( thickness per layer T = 1 cm ) . The area ( A ) of the hematoma was measured per layer , and thus the volume was determined by the formula : V = T x ( A1 + A2 .. + A(n ) ) . Simultaneously , the quantity of discharge was determined . Patients receiving nonsuction drainage had significantly lower median drainage volume ( 34 ml ; range : 0 - 175 ml vs-115 ml ; range : 40 - 346 ml ; P < 0.01 ) and a remaining hematoma , measured sonographically , of similar volume to that of the patients receiving high-vacuum treatment ( 4.4 ml ; range : 0 - 21.7 ml vs 5.3 ml ; range : 0.6 - 24.9 ml ; not significant ) . No complications were observed . An advantage to using the nonsuction device is seen with respect to similar resting wound hematoma , lower fluid evacuation , and painless drain removal . This study supports prophylacity routine nonsuction wound drainage after elective thyroid surgery", "STUDY OBJECTIVE To further define the efficacy of routine central venous catheter placement for major head and neck surgery from the st and point of fluid and blood administration , and various other parameters of perioperative management . DESIGN R and omized , retrospective chart review . SETTING University-affiliated medical center . PATIENTS 104 patients who had undergone major head and neck surgery ( defined as surgery lasting longer than 4 hours with a predicted blood loss of 500 ml or greater ) at the University of Iowa Hospitals and Clinics between 1985 and 1992 . MEASUREMENTS AND MAIN RESULTS Central venous monitoring was used in 51 of the 104 ( 49 % ) procedures . Patients with and without central monitors did not differ in age , weight , preoperative laboratory values [ i.e. , hemoglobin ( Hb ) , blood urea nitrogen ( BUN ) , creatinine ) , incidence of significant cardiac or renal disease , or a smoking history exceeding 30 pack years . In addition , these patients did not differ with respect to the following intraoperative characteristics : general type of anesthetic ; duration of surgery ; estimate of blood loss ; Hb values ; lowest urine output per hour ; development of oliguria ; total urine output ; amount of replacement of blood , colloid , or crystalloid ; development of systolic blood pressure less than 70 mmHg ; or use of a myocutaneous flap . Patients also did not differ with respect to the following postoperative characteristics : duration of stay in the surgical intensive care unit or hospital , BUN or creatinine values on days 1 and 2 , total urine output or the development of oliguria on days 1 through 3 , incidence of reintubation , fever on days 1 through 5 , wound dehiscence , death , myocardial infa rct ion , or the development of pneumonia , pulmonary edema , or sepsis . Patients with central monitors had a greater incidence of having a tracheostomy performed and a slightly lower Hb level on the first postoperative day than those without central monitors . CONCLUSIONS The study raises doubt about the efficacy of routine central venous catheter placement as a necessary guide for fluid and blood administration for these procedures , or as a necessary adjunct for several other parameters of perioperative management . It suggests the need for a r and omized , prospect i ve evaluation", "Aim : Multimodal perioperative rehabilitation in patients undergoing curative conventional colonic resection for cancer has not yet been studied in a multicenter setting . In 2005 , a nationwide quality assurance program was initiated in Germany in an unselected patient population . Methods : The prospect i ve multicenter data collection includes patients from 24 German hospitals . All hospitals had established ‘ fast-track ’ rehabilitation as the st and ard perioperative treatment in elective colonic resection , and all patients entered the registry . Results : 748 of 2,047 fast-track patients ( 36.5 % ) underwent open resection of colonic cancer . The median age of the 380 female and 368 male patients was 71 ( 26–96 ) years . Compliance was high for epidural analgesia ( 89 % ) , systemic basic nonopioid analgesia ( 93 % ) , ‘ restrictive ’ intraoperative intravenous fluids ( 81 % ) , oral feeding ( 73 % ) and enforced mobilization ( 84 % ) on the day of surgery . Surgical complications were diagnosed in 20 % , general morbidity occurred in only 13 % of all patients , and 3 patients ( 0.4 % ) died in the early postoperative period . Readmission within 30 days of discharge was necessary in 27 patients ( 4 % ) . Conclusions : Compliance with fast-track measures was high , and general morbidity was low in a population of patients undergoing multimodal perioperative rehabilitation for conventional colonic cancer resection", "PURPOSE Dexmedetomidine is approximately 8 times more selective toward the alpha-2-adrenoceptors than clonidine . It induces analgesia in patients and decreases anesthetic requirements by up to 90 % . The current study aim ed to evaluate the effects of dexmedetomidine premedication on tourniquet pain , intraoperative - postoperative analgesic requirements , sedation levels , quality of anesthesia , and the hemodynamic parameters when used as a single dose before intravenous regional anesthesia ( IVRA ) . MATERIAL AND METHODS Fifty-four patients undergoing h and surgery ( carpal tunnel and tendon release ) were r and omly divided into 2 groups for IVRA . IVRA was performed with 40 mL of 0.5 % lidocaine in both groups . A single dose of dexmedetomidine 0.5 microg/kg in 20 mL saline was administered to group D ( n = 27 ) and placebo solution 20 mL to group C ( n = 27 ) through the non-IVRA catheter 15 minutes before IVRA . Sensory and motor block onset and recovery time , hemodynamic variables , tourniquet pain , analgesic requirements according to verbal rating scale ( VRS ) and visual analog scale(VAS ) , sedation score , and anesthesia quality were recorded in the intraoperative and postoperative period . RESULTS Improved quality of anesthesia , reduced postoperative pain scores , and total analgesic requirements were found in group D during postoperative period . Additionally , the patients experienced a higher degree of sedation during intraoperative and postoperative period . CONCLUSION The premedication of 0.5 microg/kg low dose dexmedetomidine before IVRA improves the quality of anesthesia and decreases the postoperative analgesic requirement of out patients undergoing h and surgery without any serious side effects", "Background : Post‐operative insulin resistance and hyperglycaemia are associated with an impaired outcome after surgery . Pre‐operative oral carbohydrate loading ( CHO ) reduces post‐operative insulin resistance with a reduced risk of hyperglycaemia during post‐operative nutrition . Insulin‐resistant diabetic patients have not been given CHO because the effects on pre‐operative glycaemia and gastric emptying are unknown", "Purpose We investigated the effect of total intravenous anesthesia ( TIVA ) with propofol on postoperative nausea and vomiting ( PONV ) after robot-assisted laparoscopic radical prostatectomy ( RLRP ) in patients at low risk of developing PONV , in comparison to balanced anesthesia with desflurane . Material s and Methods Sixty two patients were r and omly assigned to the Des or TIVA group . Propofol and remifentanil were used for induction of anesthesia in both groups and for maintenance of the anesthesia in the TIVA group . In the Des group , anesthesia was maintained with desflurane and remifentanil . In both groups , postoperative pain was controlled using fentanyl-based intravenous patient controlled analgesia , and ramosetron 0.3 mg was administered at the end of surgery . The incidence of PONV , severity of nausea and pain , and requirements of rescue antiemetics and analgesics were recorded . Results The incidence of nausea in the post-anesthetic care unit was 22.6 % in the Des group and 6.5 % in the TIVA ( p=0.001 ) group . The incidence of nausea at postoperative 1 - 6 hours was 54.8 % in the Des group and 16.1 % in the TIVA group ( p=0.001 ) . At postoperative 6 - 48 hours , there were no significant differences in the incidence of nausea between groups . Conclusion In order to prevent PONV after RLRP in the early postoperative period , anesthesia using TIVA with propofol is required regardless of patient-related risk factors", "Objectives . The aim of this study was to explore effect of a combination of pregabalin and dexamethasone on pain control after septoplasty operations . Methods . In this study , 90 patients who were scheduled for septoplasty under general anesthesia were r and omly assigned into groups that received either placebo ( Group C ) , pregabalin ( Group P ) , or pregabalin and dexamethasone ( Group PD ) . Preoperatively , patients received either pregabalin 300 mg one hour before surgery , dexamethasone 8 mg intravenously during induction , or placebo according to their allocation . Postoperative pain treatment included tramadol and diclofenac sodium 30 minutes before the end of the operation . Numeric rating scale ( NRS ) for pain assessment , side effects , and consumption of tramadol , pethidine , and ondansetron were recorded . Results . The median NRS score at the postoperative 0 and the 2nd h was significantly higher in Group C than in Group P and Group PD ( P ≤ 0.004 for both ) . The 24 h tramadol and pethidine , consumptions were significantly reduced in Groups P and PD compared to Group C ( P < 0.001 and P < 0.001 ) . The incidence of blurred vision was significantly higher in Group PD compared to Group C within both 0–2 h and 0–24 h periods ( P = 0.002 and P < 0.001 , resp . ) . Conclusions . We conclude that administration of 300 mg pregabalin preoperatively may be an adequate choice for pain control after septoplasty . Addition of dexamethasone does not significantly reduce pain in these patients", "Serious adverse outcomes from perioperative hypothermia are well documented . Consequently , intraoperative warming has become routine . We thus evaluated the efficacy of a novel , nondisposable carbon-fiber resistive-heating system . Twenty-four patients undergoing open abdominal surgery lasting approximately 4 h were r and omly assigned to warming with 1 ) a full-length circulating water mattress set at 42 ° C , 2 ) a lower-body forced-air cover with the blower set on high , or 3 ) a three-extremity carbon-fiber resistive-heating blanket set to 42 ° C . Patients were anesthetized with a combination of continuous epidural and general anesthesia . All fluids were warmed to 37 ° C , and ambient temperature was kept near 22 ° C . Core ( tympanic membrane ) temperature changes among the groups were compared by using factorial analysis of variance and Scheffe[Combining Acute Accent ] F tests ; results are presented as means ± SD . Potential confounding factors did not differ significantly among the groups . In the first 2 h of surgery , core temperature decreased by 1.9 ° C ± 0.5 ° C in the circulating-water group , 1.0 ° C ± 0.6 ° C in the forced-air group , and 0.8 ° C ± 0.2 ° C in the resistive-heating group . At the end of surgery , the decreases were 2.0 ° C ± 0.8 ° C in the circulating-water group , 0.6 ° C ± 1.0 ° C in the forced-air group , and 0.5 ° C ± 0.4 ° C in the resistive-heating group . Core temperature decreases were significantly greater in the circulating-water group at all times after 150 elapsed minutes ; however , temperature changes in the forced-air and resistive-heating groups never differed significantly . Even during major abdominal surgery , resistive heating maintains core temperature as effectively as forced air . IMPLICATION S : Efficacy was similar for forced-air and resistive heating , and both maintained intraoperative core temperature far better than circulating-water mattresses . We thus conclude that even during major abdominal surgery , resistive heating maintains core temperature as effectively as forced air", "BACKGROUND Inadvertent perioperative hypothermia ( IPH ) occurs in many patients because warming techniques are insufficient to counteract thermal redistribution result ing from the ablation of thermoregulatory vasoconstriction associated with anaesthesia . We tested the efficiency of a preoperative forced-air warming ( FAW ) device ( Bair Paws ) in preventing IPH . METHODS Sixty-eight adult patients undergoing spinal surgery under general anaesthesia were r and omized to receive either normal care or prewarming for 60 min , at 38 degrees C , using the Bair Paws system . All patients received routine FAW intraoperatively . RESULTS Thirty-one patients were prewarmed and 37 patients were in the control group . There was a 0.3 degrees C smaller decrease in mean core temperature in the prewarmed group at 40 , 60 , and 80 min post-induction ( P < or = 0.05 ) . Temperature was maintained above the hypothermic threshold of 36 degrees C in 21 ( 68 % ) patients in the prewarmed group , compared with 16 ( 43 % ) patients in the control group ( P<0.05 ) . CONCLUSIONS Preoperative warming using the Bair Paws system results in smaller decreases in core temperature intraoperatively and less IPH in patients undergoing spinal surgery under general anaesthesia", "The purpose of this study was to compare the periop-erative effects of the intramuscular ( IM ) α2 agonist , dexmedetomidine ( DEX ) , and midazolam ( MID ) premedication . The study comprised 192 women ( 64 per group ) scheduled for abdominal hysterectomy . The doses of the study drugs were chosen to obtain equal sedative effects . The three groups were : 1 ) IM DEX ( 2.5 μ/kg ) and intravenous ( IV ) placebo ( DexPla group ) , 2 ) IM DEX and IV fentanyl ( FENT ) ( 1.5 μg/kg ) ( DexFent group ) , and 3 ) IM MID ( 0.08 mg/kg ) and IV FENT ( MidFent group ) . IM drugs were administered 45–90 min before induction of anesthesia . Preoperative sedation and anxiolysis after DEX was comparable to that after MID . The maximum arterial blood pressure response to endotracheal intubation was blunted in the DexFent group , while in the two other groups blood pressure increased 30–34 mm Hg after endotracheal intubation . The mean isoflurane concentration during surgery was 0.14 % in the DexFent group , 0.24 % in the DexPla group , and 0.34 % in the MidFent group ( P < 0.001 ) . During surgery , bradycardia ( heart rate < 40 bpm ) was observed in 6.2 % of DEX patients , and no MID patients , whereas postoperatively 14.1 % of DEX patients and 1.6 % of MID patients had bradycardia . Fewer patients suffered from postoperative shivering after DEX ( 10 % ) than after MID ( 52 % ) . We conclude that DEX has many desirable effects , but side effects such as bradycardia may limit its routine use in ASA physical status 111 patients", "REFERENCE/CITATION Wiechula R. The use of moist wound-healing dressings in the management of split-thickness skin graft donor sites : a systematic review . Int J Nurs Pract . 2003 ; 9:S9-S17 . CLINICAL QUESTION Do rates of healing , infection , and pain differ depending on whether nonmoist or moist dressings are used to manage superficial to partial-thickness wounds ? DATA SOURCES Investigations were identified by CINAHL , MEDLINE , Pre- MEDLINE , Cochrane Library , Current Contents , Health STAR , EMBASE , Exp and ed Academic Index , and Dissertation Abstract s International search es . The search terms included skin , graft , and donor . Additional search es were performed with reference lists and bibliographies of retrieved studies . STUDY SELECTION To be included in the review , each study had to fulfill the following criteria : it had to be an intraindividual or prospect i ve r and omized controlled trial of human subjects ; it had to include patients with postharvest split-thickness skin graft donor sites ; it had to evaluate the effectiveness of primary and secondary wound dressings ; and it had to have outcome measures that included healing ( objective ) , infection ( subjective ) , and pain ( objective ) . DATA EXTRACTION Data extraction and study quality assessment procedures were developed specifically for this review based on Cochrane Collaboration , Centre for Review s and Dissemination , and Joanna Briggs Institute protocol s and were performed independently by the author . Details of the procedures were not fully explained . The principal outcome measures were healing ( proportion of sites healed within the study period or time to complete healing ) , rate of infection , and pain scores . The studies were grouped according to broad dressing type ( nonmoist and moist ) and specific types of moist dressings ( hydrocolloids and polyurethane semipermeable transparent films ) . When comparable , study results were pooled and analyzed with a fixed-effects model . Data within broader dressing categories ( nonmoist and moist ) were analyzed with a r and om-effects model . chi ( 2 ) analysis was used to determine heterogeneity among the studies . RevMan software ( version 4.04 ; Cochrane Centre , Oxford , UK ) was used for statistical analysis . MAIN RESULTS The search es identified 111 studies and 1 integrative review , of which 58 studies met the inclusion and exclusion criteria . Inconsistency and variation in outcome measures and incomplete reporting of results prevented analysis of many studies . Wound healing was measured by days to complete healing ( when dressings could be removed without trauma and pain ) and wounds healed by day X ( removal of dressings at regular intervals ) . Wound infection was subjectively measured based on clinical signs of infection ( edema , heat , pain , or smell ) . Visual analog scales were used to measure pain levels . Among the broad categories of nonmoist ( sterile gauze , fine mesh gauze , Xerofoam [ Tyco Healthcare Group LP , Mansfield , MA ] ) and moist ( DuoDERM hydrocolloid [ ConvaTec , Princeton , NJ ] , Tegaderm transparent film [ 3 M Health Care , St Paul , MN ] , Opsite transparent film [ Smith & Nephew , London , UK ] ) dressings , the outcomes of healing , infection , and pain were analyzed . In 6 studies , the findings significantly favored moist dressings , compared with nonmoist dressings , for days to complete healing ( weighted mean difference [ WMD ] = -3.97 , 95 % confidence interval [ CI ] = -5.91 , -2.02 ) . In 9 studies , wounds healed by day X ( day 7 , 8 , 9 , 10 , or 12 ) were analyzed . The results were varied and inconclusive because of a small number of trials and subjects . Among 10 studies , no significant difference was noted in infection rates between nonmoist and moist dressings ( odds ratio [ OR ] = 0.41 , 95 % CI = 0.14 , 1.18 ) . Three studies using visual analog scales for the outcome of pain were converted into a uniform scale of 1 to 10 ( 10 representing most painful ) . The findings significantly favored moist dressings over nonmoist dressings ( WMD = -1.75 , 95 % CI = -2.94 , -0.56 ) . Among nonmoist and specific types of moist dressings , a subset analysis was performed to examine the outcomes of healing , infection , and pain . For days to complete healing , 2 investigations significantly favored hydrocolloid dressings over nonmoist dressings ( WMD = -2.19 , 95 % CI = -2.89 , -1.49 ) . Additionally , in 2 studies , hydrocolloid dressings were significantly favored over other moist dressings ( semiocclusive hydrocolloid and transparent film ) for days to complete healing ( WMD = -1.45 , 95 % CI = -2.17 , -0.74 ) . In 3 studies , the data significantly favored polyurethane semipermeable transparent film dressings over nonmoist dressings for days to complete healing ( WMD = -2.82 , 95 % CI = -3.58 , -2.07 ) . For infection rates , 4 studies significantly favored hydrocolloid dressings over nonmoist dressings ( OR = 0.21 , 95 % CI = 0.07 , 0.65 ) . In 4 other studies , polyurethane semipermeable transparent film dressings were significantly favored over nonmoist dressings with regard to infection rates ( OR = 0.28 , 95 % CI = 0.09 , 0.91 ) . For the outcome of pain , varied outcome measures and insufficient data prevented analysis among specific types of moist dressings . CONCLUSIONS Moist dressings decreased the days to complete healing and pain scores when compared with nonmoist dressings . Among the broad categories of nonmoist and moist dressings , no differences were found in infection rates . The data on specific types of moist dressings revealed that days to complete healing were decreased with hydrocolloid dressings compared with nonmoist and other moist dressings . Hydrocolloid dressings also decreased infection rates compared with nonmoist dressings . Polyurethane semipermeable transparent film dressings also decreased days to complete healing and infection rates compared with nonmoist dressings . Overall , the data indicated that hydrocolloid dressings are more effective than nonmoist dressings in terms of rates of healing , infection , and pain in the management of superficial to partial-thickness wounds . The variations in outcome measures among the included studies should be considered in interpreting these findings", "BACKGROUND Pain after thyroid surgery is of moderate intensity and short duration . Bilaterally superficial cervical plexus block ( BSCPB ) may reduce analgesic requirements . However , its effectiveness in decreasing pain after thyroidectomy is debated . METHODS This double-blind , r and omized placebo-controlled study in 100 patients undergoing total thyroidectomy evaluates the effects of BSCPB done with 20 mL of 0.75 % ropivacaine . Additional parecoxib was administrated immediately postoperatively and 12 hours later . RESULTS Postoperative pain was assessed by visual analogue rating scale . All parameters were recorded at 0 , 3 , 6 , 9 , 12 , and 24 hours after surgery . The control group had higher values than the ropivacaine group at all moments ( p < .05 ) except H12 ( p = .76 ) . Additional analgesia was needed for 7 patients ( 14 % ) in the control group and for 8 patients ( 16 % ) in the group with ropivacaine ( p = .96 ) . CONCLUSION Two-point bilateral BSCPB has a major analgesic effect on patients after total thyroidectomy , with a statistically significant reduction in postoperative pain scores . However , no significant difference was noted in the proportion of patients that required additional analgesics", "Background Chemotherapy-induced nausea and vomiting ( CINV ) remains a significant problem for patients and is associated with a substantial deterioration in quality of life ; appropriate use of antiemetic drugs is crucial in maintaining the quality of life in patients undergoing chemotherapy . Methods This r and omized , crossover trial evaluated the antiemetic efficacy and safety of 8 mg per day ( low-dose ) and 16 mg per day ( st and ard-dose ) dexamethasone , in combination with the 5-HT3 receptor antagonist granisetron , in 36 patients receiving cisplatin (CDDP)-containing chemotherapy for head and neck cancer . Following chemotherapy , the antinausea/vomiting inhibition rate for each dexamethasone dose was measured . Results During the 24-h period following administration of chemotherapy ( acute phase ) , the antinausea/vomiting inhibition rates ( no nausea and no episodes of vomiting ) for 8 mg and 16 mg dexamethasone were comparably high ( 58.3 % and 63.8 % , respectively ; P = 0.8092 ) . Similar results were seen on days 2–5 following chemotherapy . Efficacy during the acute phase , based on the number of instances of vomiting and degree of nausea , was also comparably high for the two dexamethasone doses ( overall efficacy rates were 94.4 % and 88.8 % , respectively , for 8 mg and 16 mg dexamethasone ; P = 0.7637 ) . Both doses maintained an 80 % or higher response rate until day 3 , and neither dose produced severe side effects . Conclusion The results suggest that granisetron and dexamethasone combination therapy is useful in controlling acute and delayed nausea and vomiting induced by CDDP-containing chemotherapy for head and neck cancer . Furthermore , 8 mg and 16 mg dexamethasone have equivalent antiemetic efficacy", "Prophylaxis against postoperative venous thromboembolism should be tailored according to the patient 's level of risk . However , risk assessment is not yet in widespread use in surgical practice . In this study , 538 general surgical patients were prospect ively assessed based on a scoring system containing 20 risk factors . Depending on the total risk factor score , the patients were grouped into low ( 0 to 1 , 34.5 % ) , moderate ( 2 to 4 , 48.5 % ) , or high risk ( more than 4 , 17.2 % ) categories . Statistically significant ( p less than 0.0001 ) correlation was found between our results and those of three existing risk assessment systems . Overall , of the 538 patients , 37.2 % received prophylaxis ; 10 % , 42.1 % , and 76 % received prophylaxis in the low- , moderate- , and high-risk categories , respectively . Mechanical prophylactic modalities ( graduated elastic compression and sequential intermittent compression ) were preferred over pharmacologic modalities . These results suggest that implementation of prophylaxis remains underutilized despite published reports , including NIH guidelines . Our results indicate that the majority of surgical patients seen in this suburban hospital have two or more risk factors for developing venous thromboembolism", "Objective Patients who underwent skull base procedures have been noted to experience appreciable pain . This study examines pain after surgery and the effectiveness of patient controlled analgesia ( PCA ) with combination morphine ondansetron for analgesia and control of emesis . Study Design and Setting A total of 120 skull base surgery patients were r and omized to receive placebo , morphine , or morphine ondansetron . Demographic and intraoperative variables were recorded along with pain , nausea , vomiting , and rescue analgesics . Total PCA use , hospital stay , satisfaction , and cost were also compared . Results Demographically the groups were similar . Pain was elevated with placebo PCA , and this group averaged twice as many analgesic rescues . Total usage time was lower with placebo PCA . Morphine ondansetron PCA had the lowest pain score with highest satisfaction . Nausea and vomiting was similar but female patients had more vomiting regardless of PCA group . Conclusions and Significance The use of morphine PCA reduced pain and did not appreciably increase nausea or vomiting . The addition of ondansetron produced no real benefit and its PCA use can not be justified . EBM rating : A-1b © 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation . All rights reserved", "Background : The infusion of several liters of crystalloid solution at room temperature may significantly contribute to intraoperative hypothermia because warming fluid to core temperature requires body heat . The aim of this study was to evaluate the effect of delivering warmed intravenous ( IV ) fluid to the patient on preventing intraoperative hypothermia", "We investigated the effects of four dressings on donor sites of split thickness skin grafts . Eighty patients undergoing elective split thickness skin grafting were r and omly allocated to one of four groups . The dressings were paraffin gauze , polyurethane foam , polyethane film , and polyurethane film . The main outcome measures were pain and discomfort , healing of donor sites , and time to remove dressings . Polyurethane film caused less pain and discomfort and was also easiest to remove . There were no differences in healing among the four groups", "The incidence of postoperative nausea and vomiting ( PONV ) after thyroidectomy and the association of Propofol versus Sevoflurane use for anesthesia maintenance were investigated during a r and omized , prospect i ve study . One hundred and ninety-eight patients underwent thyroidectomy receiving either Sevoflurane ( 0.5 - 1.3 % end-tidal ) or Propofol ( 50 - 200 mg/kg/min ) for anesthesia maintenance . All patients received Propofol for induction of anesthesia , Succinylcholine or Vecuronium , Nitrous Oxide , and Fentanyl . Prophylactic antiemetics were not administered . The combined incidence of PONV was 54.4 per cent over the 24-hour postoperative evaluation period . PONV was more common in patients receiving Sevoflurane than Propofol for maintenance of anesthesia ( 64.6 % vs 43.8 % ) . In women ( n = 117 ) , the incidence of PONV result ed higher when receiving inhalational Sevoflurane than Propofol for maintenance ( 70.6 % vs 42.4 % ) . However , in men ( n = 81 ) , there was no significant difference in PONV between anesthetic regimens ( 47.4 % with Sevoflurane vs 49.6 % with Propofol ) . Patients undergoing thyroid surgery are at high risk for the development of PONV . Propofol for maintenance of anesthesia , although more expensive than Sevoflurane , may reduce the rate of PONV", "STUDY OBJECTIVE To evaluate the validity of cardiac output ( CO ) measurements obtained using the Nexfin device in comparison to those obtained with the esophageal Doppler in steady-state conditions and after phenylephrine administration . DESIGN Prospect i ve observational study . SETTING Operating room of a North American academic medical center . PATIENTS 25 ASA physical status 1 , 2 , and 3 patients referred for abdominal or orthopedic surgeries . INTERVENTIONS After endotracheal intubation , patients who presented with a 20 % or greater decrease in mean arterial pressure ( MAP ) received an intravenous ( IV ) bolus of 100 μg of phenylephrine . If MAP was still 20 % lower than the patient 's baseline level at least 10 minutes after the first vasopressor treatment , a second bolus of 100 μg of phenylephrine was given . MEASUREMENTS CO was measured simultaneously by esophageal Doppler ( CO(ED ) ) and Nexfin ( CO(NXF ) ) at baseline and when blood pressure peaked after an IV 100 μg phenylephrine bolus . Comparisons were then made between the two devices to evaluate the ability of the Nexfin device to track changes in CO . MAIN RESULTS 66 pairs of data were obtained . Mean CO(ED ) and CO(NXF ) were 4.7 ± 1.8 L/min and 5.6 ± 2.0 L/min , respectively . There was a significant relationship between CO(ED ) and CO(NXF ) ( r(2 ) = 0.82 ; P < 0.001 ) . The agreement between CO(ED ) and CO(NXF ) was 0.88 ± 0.86 L/min ( Bl and Altman ) . The mean percent error ( Critchley and Critchley ) of CO(NXF ) versus CO(ED ) was 37 % . Trending analysis found a 94 % concordance between changes in CO(ED ) and CO(NXF ) after phenylephrine administration . CONCLUSIONS Intraoperative CO measurement using the Nexfin device has a strong correlation with CO measured by esophageal Doppler", "BACKGROUND The use of regional anaesthesia in thyroid surgery remains controversial . This double-blind , r and omized controlled study was conducted to evaluate the analgesic efficacy of bilateral superficial cervical plexus block ( BSCPB ) performed under general anaesthesia in patients undergoing total thyroidectomy . METHODS Eighty-seven consecutive consenting patients were r and omized to receive a BSCPB with saline ( Group P , n = 29 ) , ropivacaine 0.487 % ( Group R , n = 29 ) , or ropivacaine 0.487 % plus clonidine 5 microg ml(-1 ) ( Group RC , n = 29 ) . Sufentanil was given during the intraoperative period for a 20 % increase in arterial mean pressure or heart rate in a patient with a bispectral index between 40 and 60 . All patients received 4 g of acetaminophen during the first 24 h after operation . The pain score was checked every 4 h and nefopam was given for pain score > 4 on a numeric pain scale . RESULTS During surgery , the median sufentanil requirements were significantly reduced in Group RC compared with Groups R and P ( 0.32 vs 0.47 and 0.62 microg kg(-1 ) ; P < 0.0001 ) . After surgery , the number of patients requiring nefopam within 24 h of surgery was significantly lower in Groups R and RC than in Group P ( 16 and 19 vs 25 ; P = 0.03 ) . At post-anaesthetic care unit admission , median ( range ) pain scores were significantly lower in Groups R [ 3 ( 0 - 10 ) ] and RC [ 3 ( 0 - 8 ) ] than in Group P [ 5 ( 0 - 8 ) , P = 0.03 ] . No major complications of BSCPB occurred during study . CONCLUSIONS BSCPB with ropivacaine and clonidine improved intraoperative analgesia . BSCPB with ropivacaine or ropivaciane and clonidine was effective in reducing analgesic requirements after thyroid surgery", "The purpose of this study was to examine the impact of surgical pathology , anesthesiologist experience , and airway technique on surgically relevant outcomes in patients identified by preoperative laryngoscopy to have a difficult airway due to head and neck pathology . We prospect ively recorded a series of 152 difficult airway cases due to head and neck pathology out of 2,145 direct laryngoscopies undertaken between November 2005 and June 2008 . One of two senior anesthesiologists specializing in head and neck procedures intubated 101 ( 66.4 % ) of the 152 patients and did so 3.3 minutes faster ( p = 0.51 ) , with better oxygenation ( 87.3 vs. 81.8 % ; p = 0.02 ) and fewer airway plan changes ( p = 0.001 ) than did other , nonspecialist anesthesiologists . Predictors of failure of the first intubation plan included : cancer diagnosis ( p = 0.02 ) , previous radiotherapy ( p = 0.03 ) , and supraglottic lesions ( p = 0.03 ) . Glottic/subglottic lesions required the most intubation attempts ( p = 0.02 ) . Awake fiberoptic intubation was the most common method used ( 44.7 % ) but result ed in a change in the airway plan in 6 cases ( 8.8 % ) . Gas induction maintained the best oxygenation ( p = 0.01 ) . Awake tracheostomy was infrequent ( 1.3 % ) and took the longest ( p = 0.006 ) . We concluded that difficult airways due to head and neck pathology require teamwork and a backup plan . An anesthesiologist specializing in head and neck procedures may help to avoid adverse outcomes associated with cancer , especially previously irradiated supraglottic/glottic lesions , leading to a less frequent need for awake tracheostomy", "We studied the effects of different preoperative oral fluid protocol s on preoperative discomfort , residual gastric fluid volumes , and gastric acidity . Two-hundred-fifty-two elective abdominal surgery patients ( ASA physical status I – II ) were r and omized to preparation with a 12.5 % carbohydrate drink ( CHO ) , placebo ( flavored water ) , or overnight fasting . The CHO and Placebo groups were double-blinded and were given 800 mL to drink on the evening before and 400 mL on the morning of surgery . Visual analog scales were used to score 11 different discomfort variables . CHO did not increase gastric fluid volumes or affect acidity , and there were no adverse events . The visual analog scale scores in a control situation were not different between groups . During the waiting period before surgery , the CHO-treated group was less hungry and less anxious than both the other groups ( P ≤ 0.05 ) . CHO reduced thirst as effectively as placebo ( P < 0.0001 versus Fasted ) . Trend analysis showed consistently decreasing thirst , hunger , anxiety , malaise , and unfitness in the CHO group ( P < 0.05 ) . The Placebo group experienced decreasing unfitness and malaise , whereas nausea , tiredness , and inability to concentrate increased ( P < 0.05 ) . In the Fasted group , hunger , thirst , tiredness , weakness , and inability to concentrate increased ( P < 0.05 ) . In conclusion , CHO significantly reduces preoperative discomfort without adversely affecting gastric contents", "OBJECTIVE To compare surgical ( SgT ) and percutaneous ( PcT ) tracheostomies . BACKGROUND Percutaneous tracheostomy has been said to provide numerous advantages over classical SgT. METHODS A prospect i ve r and omized trial with a double-blind evaluation was used to compare SgT and PcT. SgT and PcT were performed according to established techniques ( n = 70 ) . The procedure was performed at the bedside in the intensive care unit in 21 cases ( 30 % ) . The outcome measures were divided into procedure-related variables , perioperative complications , and postoperative complications . The procedure-related variables ( location , duration , and difficulty ) were evaluated by the surgeon . The perioperative and postoperative complications were divided into serious , intermediate , and minor . Perioperative and early postoperative ( 14 days ) complications were evaluated daily by an intensive care unit nurse blinded to the technique used . Long-term postoperative complications were evaluated 3 months after decannulation by a surgeon blinded to the surgical technique . RESULTS There were no major complications in either group . Most variables studied were not statistically different between the PcT and SgT groups . The only variables to reach statistical significance were the size of the incision ( smaller with PcT , p < 0.0001 ) , minor perioperative complications ( greater with PcT , p = 0.02 ) , and difficult cannula changes ( greater with PcT ; p < 0.05 ) . Among nonsignificant differences , difficult procedures and false passages were more frequent with PcT , whereas long-term unesthetic scars were more frequent with SgT. CONCLUSIONS Both techniques are associated with a low rate of serious or intermediate complications when performed by experienced surgeons . There were more minor perioperative complications with PcT and more minor long term complications with", "OBJECTIVES /HYPOTHESIS Surgical site infections ( SSIs ) are an important cause of morbidity and mortality after head and neck surgery . Our primary objective was to determine the efficacy of preoperative topical antimicrobial decolonization before head and neck surgery . STUDY DESIGN Prospect i ve , r and omized controlled trial . METHODS This study was conducted among 84 patients presenting for head and neck surgery requiring admission to an academic medical center . Preoperative cultures were performed to identify Staphylococcus aureus carriers . Patients were r and omized to preoperative topical antimicrobial decolonization with a 5-day regimen of chlorhexidine skin rinses and intranasal mupirocin coupled with st and ard perioperative systemic antimicrobial prophylaxis , versus st and ard prophylaxis alone . The main outcome was the incidence of SSIs . RESULTS Despite a trend suggesting a decrease in SSIs with perioperative topical antimicrobial decolonization ( 24 % vs. 10 % ) , there was no significant difference ( odds ratio , 0.34 ; 95 % confidence interval , 0.10 - 1.18 ; P = .079 ) . Patients with a higher American Society of Anesthesiologists score ( 3 vs. 1 ; P = .02 ) , with more operative blood loss ( P = .05 ) , and who required operative takeback ( P = .04 ) had a higher rate of SSIs ; there was a trend suggesting a higher rate of SSIs among patients undergoing clean-contaminated surgery compared to clean cases ( P = .08 ) and among those having received prior radiation ( P = .07 ) or chemotherapy ( P = .06 ) . CONCLUSIONS Preoperative antimicrobial decolonization did not significantly decrease the incidence of SSIs after head and neck surgery , but might be considered for high-risk groups despite the lack of conclusive evidence confirming efficacy . Risk factors for SSIs after head and neck surgery are identified for the first time in a prospect i ve study", "Moderate wound pain and opiate analgesia requirement is reported following thyroid and parathyroid surgery . A r and omized clinical trial was performed to investigate whether intraoperative superficial cervical plexus block ( SCPB ) would decrease postoperative pain and analgesia use", "Patients undergoing thyroid surgery need postoperative pain management . Bilateral superficial cervical plexus block by administration of 0.25 % bupivacaine with 1:200000 epinephrine at the end of surgery has been shown to improve postoperative analgesia . The objective of this study was to assess the analgesic efficacy in the first 36 postoperative hours after total thyroidectomy of bilateral superficial cervical plexus block with 0.75 % ropivacaine administered before the incision or on completion of the surgical procedure . Methods : We performed a prospect i ve double-blinded , r and omized controlled trial that compared 3 parallel groups : the CONT group did not receive any block , the PRE group received bilateral superficial cervical plexus block before surgery while under general anesthesia , and the POST group received bilateral superficial cervical plexus block after surgery while under general anesthesia . The study included 111 patients ( 37 in each group ) . Postoperative pain was assessed every 4 hours by use of a 0 to 10 numeric rating scale . All patients received paracetamol every 6 hours . Morphine was administered following a st and ardized protocol if the numeric rating scale was 4 or higher . The main outcome variables were the proportion of patients given morphine during the 36 hours period , pain intensity scores , and morphine consumption . Results : No intergroup differences were observed in terms of percentage of patients who required morphine , morphine delivery , pain scores , and intraoperative opioid consumption . Conclusions : Bilateral superficial cervical plexus block with 0.75 % ropivacaine administered before or after surgery does not improve postoperative analgesia after total thyroidectomy", "Background : General anesthesia is used for most major surgeries , and the most common side effects include headache , nausea , vomiting , and sore throat . Major breast surgery is associated with a high incidence of postoperative nausea and vomiting ( PONV ) . We compared the postoperative nausea and vomiting of propofol-based total intravenous anesthesia ( TIVA ) and sevoflurane ( SEVO ) anesthesia under auditory evoked potential ( AEP ) monitoring in female patients undergoing breast surgery . Methods : A total of 84 patients scheduled to undergo elective breast surgery from 1 to 4 h in duration from March 2011 to December 2011 were prospect ively included in the study . All participants were r and omly assigned to TIVA or SEVO group . The AEP index was maintained at 15 - 25 . After completing the surgery , the duration of surgery , emergence time , and the side effects of PONV were recorded . Results : Patient characteristics , intraoperative and postoperative data , and the amounts of intraoperative analgesic drugs used were not significantly different between the TIVA and SEVO groups . The incidence of PONV was significantly higher in the SEVO group than in the TIVA group ( 50 % and 14.3 % , respectively ; p < 0.001 ) , and the total cost was significantly lower in the TIVA group than in the SEVO group ( 648 ± 185 and 850 ± 197 , respectively ) . Conclusion : We observed that when compared with sevoflurane , propofol given for the maintenance of general anesthesia improves the postoperative patient well-being and reduces the incidence of PONV . Furthermore , total intravenous anesthesia with propofol result ed in significant cost reductions", "BACKGROUND & AIMS Protocol s for enhanced recovery provide comprehensive and evidence -based guidelines for best perioperative care . Protocol implementation may reduce complication rates and enhance functional recovery and , as a result of this , also reduce length-of-stay in hospital . There is no comprehensive framework available for pancreaticoduodenectomy . METHODS An international working group constructed within the Enhanced Recovery After Surgery ( ERAS ® ) Society constructed a comprehensive and evidence -based framework for best perioperative care for pancreaticoduodenectomy patients . Data were retrieved from st and ard data bases and personal archives . Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group . The quality of evidence was rated \" high \" , \" moderate \" , \" low \" or \" very low \" . Recommendations were grade d as \" strong \" or \" weak \" . RESULTS Comprehensive guidelines are presented . Available evidence is summarised and recommendations given for 27 care items . The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations . CONCLUSIONS The present evidence -based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy . A unified protocol allows for comparison between centres and across national borders . It facilitates multi-institutional prospect i ve cohort registries and adequately powered r and omised trials", "OBJECTIVE To evaluate the safety and efficacy of early oral feeding by comparing it with feeding through primary tracheoesophageal puncture after total laryngectomy with primary pharyngeal closure . STUDY DESIGN A prospect i ve , r and omized , controlled study . METHODS Patients who underwent total laryngectomy with primary pharyngeal closure and who were c and i date s for primary voice restoration ( an in whose cases primary tracheoesophageal puncture [ TEP ] was created ) were included . After total laryngectomy , patients were r and omly assigned to either the oral group ( study group ) or the TEP group ( control group ) . Patients in the oral group were fed orally with a clear liquid diet on the first postoperative day , then advanced to a regular diet , whereas patients in the TEP group were fed through tracheoesophageal puncture and received nothing orally until the seventh postoperative day ; then they were fed orally if fistula had not occurred . St and ard criteria for discharge were used for all the patients . RESULTS During a 3-year period , 67 patients were enrolled in the trial , and complete data were available for 65 patients ( 32 patients in the oral group , 33 patients in the TEP group ) . The two groups were similar for factors reported to influence the rate of pharyngocutaneous fistula . In three ( 9 % ) patients in the TEP group , fistula occurred on the 5th , 7th , and 14th postoperative days , respectively . Two ( 6.2 % ) fistulas occurred in the oral group on the sixth and eighth postoperative days , respectively . In patients without fistula , the mean length of hospital stay was 7.6 days ( range , 4 - 19 d [ SD = 3.1 d ] ) for the oral group and 8.2 days ( range , 7 - 18 d [ SD = 2.6 d ) for the TEP group . There was no significant difference between two groups for either the incidence of fistula or the length of hospital stay . CONCLUSIONS Initiation of oral feeding on the first postoperative day in patients undergoing total laryngectomy with primary pharyngeal closure is a safe clinical practice . However , it does not shorten the length of hospital stay for these patients", "STUDY OBJECTIVE To assess the efficacy and safety of intravenous ( i.v . ) dexmedetomidine , an alpha-2 agonist , as a premedication before i.v . regional anesthesia . DESIGN R and omized , double-blind , placebo-controlled study with two parallel groups . SETTING Day-case surgery unit , Department of Surgery , Turku University Hospital , Turku , Finl and . PATIENTS 30 healthy ASA physical status I out patients scheduled for minor h and surgery with i.v . regional anesthesia . INTERVENTIONS Patients were assigned to one of two groups to receive either dexmedetomidine 1 microgram/kg i.v . ( n = 15 ) or saline placebo i.v . ( n = 15 ) 10 minutes before exsanguination and inflation of a tourniquet . Regional blockade was induced with 0.5 % lidocaine 3 mg/kg ( maximum 200 mg ) . Additional fentanyl 1 microgram/kg intraoperatively and oxycodone 0.05 mg/kg postoperatively were administered for analgesia if needed . MEASUREMENTS AND MAIN RESULTS Dexmedetomidine preoperatively induced 16 % to 20 % decreases in systolic blood pressure ( p < 0.001 ) , diastolic blood pressure ( p < 0.001 ) , and heart rate ( p < 0.001 ) , which were mainly abolished within the 4-hour postoperative follow-up period . A clinical ly significant decrease in arterial oxygen saturation was not observed . The subjective intensity of pain during tourniquet inflation was similar in both groups , but fewer intraoperative ( p = 0.009 ) opioid analgesics were needed in the dexmedetomidine group . Dexmedetomidine decreased sympathoadrenal responses : plasma norepinephrine concentration decreased to one-fourth of the baseline level ( p < 0.001 ) , and one of its main metabolites , 3,4-dihydroxyphenylglycol , decreased by 27 % ( p < 0.001 ) . Dexmedetomidine also prevented an increase in plasma epinephrine concentration following tourniquet inflation ( p = 0.003 ) . Dexmedetomidine induced subjective sedation ( p = 0.002 ) , but the Maddox Wing test did not show any statistically significant differences between the groups . General effectiveness was grade d superior in the dexmedetomidine group ( p < 0.001 ) . CONCLUSIONS Dexmedetomidine is an effective premedication before i.v . regional anesthesia because it reduces patient anxiety , sympathoadrenal responses , and opioid analgesic requirements", "BACKGROUND Twenty-four hours of perioperative antibiotics provides effective prophylaxis for most head and neck cancer resections . Many reconstructive surgeons have been hesitant to apply this st and ard to free-flap reconstruction of the head and neck . This prospect i ve clinical trial compared short-course and long-course clindamycin prophylaxis for wound infection in patients with head and neck cancer undergoing free-flap reconstruction . METHODS Seventy-four patients were r and omized to receive short-course ( 3 doses ) or long-course ( 15 doses ) clindamycin perioperatively . Wound infections , fistulas , and other postoperative complications were documented by faculty surgeons who were blinded as to treatment group . RESULTS The differences in wound infections and other complications were statistically insignificant . No other independent predictors of wound complications emerged in this series of patients . CONCLUSIONS Short-course clindamycin is as effective as long-course clindamycin in preventing wound infections after free-flap surgery for head and neck ablative defects", "BACKGROUND Perioperative antibiotic prophylaxis has significantly reduced wound infection rates in clean-contaminated head and neck surgical procedures but controversy still remains regarding the optimal antibiotic regime . OBJECTIVE To examine the efficacy of different antibiotics in head and neck oncological surgery prophylaxis . PATIENTS AND METHODS In this prospect i ve , double-blind clinical trial , 189 patients with carcinoma of the upper aerodigestive tract were r and omized to receive amoxicillin-clavulanate or cefazolin intravenously up to 1h before surgery and at 8-h intervals for an additional three doses . RESULTS An overall wound infection rate of 22 % was observed . The infection rate in patients receiving cefazolin was 24 % ( 22/92 ) vs. 21 % ( 20/97 ) in those receiving amoxicillin-clavulanate ; the difference was not statistically significant . Postoperative overall non-wound infection developed in 12 % ( 22/189 ) patients ; the rate of infection was 9.8 % ( 9/92 ) in patients receiving cefazolin vs. 13.4 % ( 13/97 ) in those receiving amoxicillin-clavulanate , without a statistically significant difference between the two groups . Gram-negative bacteria were more often isolated with Pseudomonas aeruginosa as the dominant species . The risk of postoperative infection was more influenced by the type of surgical procedure than by disease stage . CONCLUSION In clean-contaminated head and neck oncologic surgery amoxicillin-clavulanate prophylaxis was at least as efficient as cefazolin . However , when taking into account the fact that beta-lactamase containing strains have recently been spreading , amoxicillin-clavulanate should be the logical first choice", "OBJECTIVE To help define the perioperative risk related to commonly used non-aspirin NSAIDs with whole blood platelet aggregometry . METHODS Twelve healthy volunteers were recruited . Two cyclooxygenase (COX)-1 inhibitors ( ibuprofen and naproxen ) and two COX-2 inhibitors ( meloxicam and celecoxib ) were administered , and daily whole blood platelet aggregometry studies were obtained until studies showed no platelet inhibition . Aspirin was studied at the conclusion of the study . RESULTS Ibuprofen had no inhibitory effect on platelet aggregation in all women and no inhibitory effect in 83 % of men at 24 hours . All platelet function had returned to normal at 48 hours . The inhibitory effect of naproxen on platelets was absent at 48 hours in 83 % of the women and 50 % of men . By 72 hours all platelet studies had returned to normal . Meloxicam and celecoxib did not cause any overall inhibitory effect on platelet aggregation . CONCLUSIONS Ibuprofen and naproxen have a mild inhibitory effect on platelet aggregation compared with aspirin and this effect is undetectable by 48 hours and 72 hours , respectively . Meloxicam and celecoxib show essentially no inhibitory effect on platelet aggregation . These findings suggest that there is little bleeding risk related to platelet aggregation at 24 hours in patients who take COX-2 inhibitors and at 72 hours for those who take COX-1 inhibitor medications", "The aim of this study was to investigate whether an extended course of prophylactic antibiotic could reduce the wound infection rate in a subtropical country . Fifty-three consecutive cases scheduled to receive major head and neck operations were r and omised into one-day or three-day prophylactic antibiotic groups . Thirteen cases ( 24.5 per cent ) developed wound infections after operations . The duration of prophylactic antibiotic was not related to the surgical wound infection . However , pre-operative haemoglobulin less than 10.5 g/dl ( odds ratio : 7.24 , 95 per cent confidence interval : 1.28 - 41.0 ) and reconstruction with a free flap or pectoris major myocutaneous flap during the operation ( odds ratio : 11.04 , 95 per cent confidence interval : 1.17 - 104.7 ) were associated factors significantly influencing post-operative wound infection . Therefore , one day of prophylactic antibiotic was effective in major head and neck procedures but should not be substituted for proper aseptic and meticulous surgical techniques", "INTRODUCTION Palonosetron and ondansetron are two selective 5-hydroxytryptamine ( 5-HT3 ) receptor antagonists that have shown remarkable efficacy in controlling nausea and vomiting following administration of moderately emetic anticancer chemotherapy . Their efficacy is enhanced by the concurrent administration of dexamethasone . In the present study , we aim ed to compare the antiemetic efficacy of a palonosetron plus dexamethasone ( PD ) schedule versus an ondansetron plus dexamethasone ( OD ) schedule . METHODS A r and omised , crossover trial was conducted in 30 patients with head and neck cancer who were receiving moderately emetogenic chemotherapy . The patients were divided into two groups . In the first cycle , one group was given a PD schedule and the other , an OD schedule . For the subsequent cycle , crossover of the antiemetic schedules was done . The antiemetic effects were evaluated by recording the intensity of nausea and the frequency of vomiting in the acute and delayed phases . RESULTS Complete response in the acute phase was observed in 83.3 percent of the patients on the PD schedule and in 80 percent of those on the OD schedule . In the delayed phase , complete response was observed in 76.7 percent and 66.7 percent of the patients on the PD schedule and OD schedule , respectively . The overall rate of complete response was 66.7 percent in the PD group and 46.7 percent in the OD group . In the PD group , there were 73.3 percent of nausea-free patients as opposed to 66.7 percent in the OD group . CONCLUSION The results suggest that the PD schedule was superior to the OD schedule in controlling emesis in cancer chemotherapy , although this difference was not statistically significant", "The 5-HT3 antagonists are effective in reducing postoperative nausea and vomiting ( PONV ) associated with paediatric tonsillectomy . Although prophylactic tropisetron can reduce the incidence of PONV by half , the result ing level of over 40 % is still unacceptably high . The aim of this study was to evaluate the effect of adding dexamethasone to tropisetron . In a blinded study , 59 children ( mean age 6.1 years ) were administered 0.1 mg.kg-1 up to 2 mg of tropisetron and 66 children ( mean age 5.7 years ) received the same dose of tropisetron plus 0.5 mg.kg-1 up to 8 mg of dexamethasone . Both drugs were given intravenously during induction of anaesthesia for tonsillectomy . During the inpatient stay of 24 h , the incidence of postoperative vomiting in the tropisetron alone group was 53 % compared with 26 % in the combination group ( P=0.002 , chi-squared ) . A significant reduction in nausea from 53 % to 30 % was also observed ( P=0.02 ) . Parents completed a daily diary for 5 days following discharge . Delayed vomiting occurred in 27 % and 11 % of the tropisetron and combination therapy groups , respectively ( P=0.025 ) Sixteen percent and 9 % , respectively , required medical attention ( P=0.27 ) . Tropisetron plus dexamethasone is more effective than tropisetron alone in reducing the incidence of PONV following paediatric tonsillectomy", "Controversy exists regarding the routine use of aids to lung expansion in the prevention of pulmonary complications after abdominal surgery . We prospect ively r and omized 172 patients into 1 of 4 groups : the control group ( 44 patients ) received no respiratory treatment , the IPPB group ( 45 patients ) received intermittent positive pressure breathing therapy for 15 min 4 times daily , the IS group ( 42 patients ) was treated with incentive spirometry 4 times daily , and the DBE group ( 41 patients ) carried out deep breathing exercises under supervision for 15 min 4 times daily . Roentgenographic changes , observed 24 h after surgery , were comparable in the 4 groups ( 20.5 to 36.6 % ) . Pulmonary complications were defined as the development of 3 or more of 6 new findings : cough , phlegm , dyspnea , chest pain , temperature greater than 38 degrees C , pulse rate more than 100 beats/min . The frequency of development of pulmonary complications was 48 % in the control group , 22 % in the IPPB group ( p less than 0.05 ) , 21 % in the IS group ( p less than 0.05 ) , and 22 % in the DBE group ( p less than 0.05 ) . Side effects of respiratory treatment were observed only in the IPPB group ( 18 % ; p less than 0.05 ) . Hospital stay in patients undergoing upper abdominal surgery was significantly shorter in the IS group ( mean + /- SD , 8.6 + /- 3 days ) than in the control group ( 13 + /- 5 days ) . This difference was not observed for the other 2 treatment groups . ( ABSTRACT TRUNCATED AT 250 WORDS", "The appropriate use of prophylactic antimicrobial therapy in patients undergoing major contaminated surgery is an important issue for the head and neck surgeon . A series of five sequential , prospect i ve , r and omized , double-blind clinical trials of antibiotics for patients undergoing major contaminated oncologic head and neck surgery are review ed and summarized . The information generated from the study of these 547 patients indicates that a number of drugs or drug combinations have similar efficacy when employed in adequate dosage . The bacteriologic spectrum of the prophylactic drug should include oral microflora , especially anaerobic bacteria . The administration of antibiotics effective against gram-negative aerobic bacteria may be unnecessary . Perioperative antibiotic administration should be initiated prior to surgery . To date , no evidence exists to support prolonged administration of antibiotics beyond the first 24 hours following surgery", "OBJECTIVE To investigate gabapentin 's role in head and neck cancer surgery following the demonstration of the effectiveness of gabapentin in reducing postoperative pain . DESIGN Non-r and omised open-label trial . SETTING Prince of Wales Hospital , Hong Kong . MAIN OUTCOME MEASURES Pain scores , analgesic usage , and the frequency of adverse effects . PATIENTS In patients undergoing anterolateral thigh flap reconstruction after resection of tongue carcinoma , those who had an oral dose of gabapentin before surgery were compared to those who did not . RESULTS Postoperative pain was reduced in the gabapentin group ( 1.2 ) compared to the control group ( 1.7 ) [ P=0.05 ] . In the gabapentin group , mean morphine ( patient-controlled analgesia ) use ( 3.5 mg ) , sedation scores ( 1.0 ) , and antiemetic usage ( 0 mg metoclopramide ) were all significantly reduced in comparison to the controls with respective figures of 11.4 mg , 1.6 , and 12.2 mg . CONCLUSION Single preoperative doses of gabapentin led to significant reductions in postoperative pain and nausea with reduced analgesic and antiemetic usage , without additional side-effects or increases in operative complications", "Although appropriate perioperative antibiotic prophylaxis has significantly reduced wound infection rates in clean‐contaminated head and neck surgical procedures , controversy still remains regarding the optimal antibiotic regimen", "Objective : A prospect i ve r and omized controlled trial ( RCT ) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer . Aims : This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT . Methods : Patients for elective resection for colorectal cancer were offered trial entry . Participants were stratified by sex and requirement for a total mesorectal excision and central ly r and omized . Multimodal patients received intravenous fluid restriction , unrestricted oral intake with prokinetic agents , early ambulation , and fixed regimen epidural analgesia . Control patients received intravenous fluids to prevent oliguria , restricted oral intake until return of bowel motility , and weaning regimen epidural analgesia . Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets . Discharge decision was made using preagreed criteria . The primary endpoint was postoperative stay , and achievement of independence milestones . Secondary endpoints were postoperative complications , readmission rates , and mortality . Analysis was by intention to treat . Results : Seventy patients were recruited . Approximately one fourth underwent TME . Median ages were similar ( 69.3 vs. 73.0 years ) . The median stay was significantly reduced in the multimodal group ( 5 vs. 7 days ; P < 0.001 , Mann-Whitney U test ) . Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days . Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions . There were 2 deaths , both controls . Conclusions : This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery . Morbidity and mortality are not increased", "BACKGROUND & AIMS A fast-track program is a multimodal approach for patients undergoing colonic surgery that combines stringent regimens of perioperative care ( fluid restriction , optimized analgesia , forced mobilization , and early oral feeding ) to reduce perioperative morbidity , hospital stay , and cost . We investigated the impact of a fast-track protocol on postoperative morbidity in patients after open colonic surgery . METHODS A r and omized trial of patients in 4 teaching hospitals in Switzerl and included 156 patients undergoing elective open colonic surgery who were assigned to either a fast-track program or st and ard care . The primary end point was the 30-day complication rate . Secondary end points were severity of complications , hospital stay , and compliance with the fast-track protocol . RESULTS The fast-track protocol significantly decreased the number of complications ( 16 of 76 in the fast-track group vs 37 of 75 in the st and ard care group ; P = .0014 ) , result ing in shorter hospital stays ( median , 5 days ; range , 2 - 30 vs 9 days , respectively ; range , 6 - 30 ; P < .0001 ) . There was a trend toward less severe complications in the fast-track group . A multiple logistic regression analysis revealed fluid administration greater than the restriction limits ( odds ratio , 4.198 ; 95 % confidence interval , 1.7 - 10.366 ; P = .002 ) and a nonfunctioning epidural analgesia ( odds ratio , 3.365 ; 95 % confidence interval , 1.367 - 8.283 ; P = .008 ) as independent predictors of postoperative complications . CONCLUSIONS The fast-track program reduces the rate of postoperative complications and length of hospital stay and should be considered as st and ard care . Fluid restriction and an effective epidural analgesia are the key factors that determine outcome of the fast-track program", "Objective . The primary objective was to compare retention of knowledge of surgical risks in parents of children having an adenotonsillectomy who received a preoperative h and out or watched a video , in addition to st and ard counseling . A secondary objective was to determine whether time from counseling to day of surgery affects risk retention . Study Design . Prospect i ve r and omized control study . Setting . Tertiary referral center . Subjects and Methods . The study , conducted March 2010 through April 2011 , included participants who had children undergoing adenotonsillectomy . The preoperative and postoperative test scores of those undergoing verbal counseling , counseling with h and out , or counseling with video were compared . Results . Forty-five participants were tasked to identify 9 risks of adenotonsillectomy . Preoperatively , participants identified an average of 6.8 ( 95 % confidence interval [ CI ] , 6.2 - 7.3 ) in the counseling group , 7.3 ( 95 % CI , 6.4 - 8.3 ) in the counseling and h and out group , and 6.6 ( 95 % CI , 5.9 - 7.3 ) in the counseling and video group ( P = .32 ) . Postoperatively , participants identified an average of 5.8 ( 95 % CI , 4.9 - 6.7 ) in the counseling group , 6.5 ( 95 % CI , 5.3 - 7.6 ) in the counseling and h and out group , and 5.2 ( 95 % CI , 4.1 - 6.3 ) in the counseling and video group ( P = .19 ) . Time between preoperative counseling and day of surgery was inversely correlated with postoperative score ( β −.34 , P = .02 ) . Conclusion . Participants were not able to identify all of the risks associated with adenotonsillectomy . There was no difference in identification of risks associated with adenotonsillectomy among different modalities of counseling . Participants retained more information when there was less time between the preoperative counseling and day of surgery", "OBJECTIVES /HYPOTHESIS Patients undergoing contaminated head and neck surgery with flap reconstruction have wound infection rates of 20 % to 25 % with parenteral antibiotic prophylaxis . Studies suggest that perioperative antimicrobial mouthwash reduces oropharyngeal flora and may prevent wound infections . We hypothesized that the addition of topical antibiotics to a parenteral prophylactic regimen would reduce the incidence of wound infection in these high-risk patients . STUDY DESIGN We performed a r and omized , prospect i ve clinical trial . METHODS Patients received either 1 ) parenteral piperacillin/tazobactam ( 3.375 g every 6 hours for 48 h ) or 2 ) parenteral piperacillin/tazobactam plus topical piperacillin/tazobactam administered as a mouthwash immediately before surgery and once a day for 2 days postoperatively , with piperacillin/tazobactam added to the intraoperative irrigation solution . The wounds of all patients were evaluated daily using predefined objective criteria . RESULTS Sixty-two patients met inclusion criteria and were enrolled in the study . The overall wound infection rate was 8.1 % ( 95 % confidence interval [ CI ] , 2.7%-17.8 % ) . Two of 31 patients ( 6.4 % ) who received parenteral antibiotics alone developed a wound infection compared with 3 of 31 patients ( 9.7 % ) r and omly assigned to receive topical plus parenteral antibiotics . This difference was not statistically significant ( P = > .05 ) . Infection rate was not associated with flap type ( rotational vs. free tissue transfer ) , m and ibular reconstruction , age , gender , tumor site , stage , surgical duration , or blood loss . CONCLUSIONS These results suggest that piperacillin/tazobactam is a highly effective antibiotic for prevention of wound infection in patients undergoing flap reconstruction following contaminated head and neck surgery . However , the addition of topical piperacillin/tazobactam does not appear to enhance the prophylactic benefit of parenteral antibiotics alone", "OBJECTIVE : To compare the incidence of postoperative nausea and vomiting ( PONV ) and postoperative pain in thyroidectomy patients undergoing general anaesthesia , with or without bilateral superficial cervical plexus block ( BSCPB ) . METHODS : In this prospect i ve , r and omized , double-blind study , adult patients scheduled for thyroid surgery under general anaesthesia were r and omized to receive BSCPB with 20 ml 0.5 % ropivacaine ( ropivacaine group ) or placebo ( 20 ml saline ; saline group ) before surgery . The incidence of PONV and postoperative pain , and the need for rescue antiemetics were assessed at 0 – 24 h postoperatively . RESULTS : Data from 135 patients were evaluated and the incidence of PONV , the need for rescue antiemetics and the number of patients needing additional perioperative pain relief in the postanaesthetic care unit were significantly lower in the ropivacaine group compared with the saline group . Early postoperative ( 0 – 8 h ) visual analogue scale pain scores were significantly lower in the ropivacaine group compared with the saline group . CONCLUSIONS : BSCPB with 0.5 % ropivacaine administered before surgery can significantly reduce the incidence of PONV and early postoperative pain and also reduce perioperative opioid requirements in thyroidectomy patients undergoing general anaesthesia", "The aim of this study was to examine the effect of cyclooxygenase-2 (COX-2)-specific medications on postoperative analgesia after major open abdominal surgery . This is was a prospect i ve , r and omized controlled , double-blind study conducted on 90 patients who underwent major open abdominal surgery between September 2011 and June 2012 , in the General Surgery Department , Jinling Hospital . After written informed consent , patients were prospect ively and r and omly assigned to one of three treatment groups before surgery , and were scheduled to receive different analgesic drugs according to r and omization . We assessed the patients ' pain levels using pain intensity score and adverse events during our study period . The group that received intravenous parecoxib for 3 days , and continued oral celecoxib for 4 days had better postoperative analgesia than other groups . COX-2-specific inhibitors are safe and effective in reducing postoperative pain in patients who have undergone major open abdominal surgery . Additionally , sufficient postoperative analgesia , lasting for 1 week , was necessary for patients to obtain satisfactory pain control after major open abdominal surgery", "Although antimicrobial prophylaxis is m and atory in major clean‐contaminated oncologic surgery of the head and neck , both the choice of specific antimicrobial compounds and the treatment duration are still discussed", "BACKGROUND Operations for soft-tissue reconstruction , orthopedic , vascular , and other types of surgery can be complicated by unexpected skin flap necrosis . At present , surgeons utilize subjective clinical judgment and physical findings to estimate the potential for tissue compromise . As the validity of these subjective methods is question able , there is a need for objective , quantitative tools to determine the risk of flap necrosis during surgery . METHODS Three 9-month-old Yorkshire pigs were used for the study . Four laterally based r and om pattern fasciocutaneous flaps were dissected on each animal . After the flaps were elevated , a prototype oximeter ( ViOptix Inc. , Fremont , CA ) , was used to measure tissue oxygenation ( StO2 ) at 2 cm intervals along the flaps . Measurements were performed immediately after the flaps were dissected , and again at the same points after they were sutured . The animals were reevaluated 4 days later , and assessed for areas of tissue necrosis . RESULTS For each flap , StO2 at the base was compared with StO2 at the more distal points . The median delta StO2 , as measured immediately after dissection , was -3.9 % points for tissue that remained viable and -34.0 % points for tissue that became necrotic ( p = 0.039 ) . After the flaps were sutured back to the chest wall , the median delta StO2 for tissue that remained viable was -1.7 % points versus -24.7 % points for tissue that became necrotic ( p = 0.006 ) . CONCLUSIONS This new h and held surface sensor can be used to measure StO2 of skin flaps and may potentially reduce complications associated with unexpected tissue necrosis", "BACKGROUND The aim of this prospect i ve cohort study was to determine whether an immediate postoperative period of deep sedation and artificial respiration in an intensive care unit ( ICU ) leads to fewer complications and a reduced failure rate of microvascular flaps compared with a situation in which patients are allowed to breathe spontaneously without sedation in a recovery room . METHODS Each group comprised 50 patients . General medical complications and flap donor and recipient site complications were documented . RESULTS Significantly , more patients had problems with weaning from ventilation in the ICU group ( p = .022 ) . More cases of respiratory insufficiency ( p = .240 ) and pneumonia ( p = .081 ) occurred in the ICU group compared with the recovery room group without statistically significant differences . The number of flaps lost was comparable in both groups ( p = .646 ) . CONCLUSIONS Admission to an ICU did not reduce complications after microvascular reconstruction and , therefore , has only to be considered for selected cases", "BACKGROUND : We evaluated the efficacy of resistive-heating or forced-air warming versus no prewarming , applied before induction of anesthesia for prevention of hypothermia . METHODS : Twenty-seven patients scheduled for laparoscopic colorectal surgery were r and omized into 1 of 3 groups : no prewarming ; 30 minutes of prewarming with a carbon fiber total body cover at 42 ° C ; or 30 minutes of preoperative forced-air warming at 42 ° C . The forced-air warming cover excluded the shoulders , ankles , and feet . The prewarming period was exactly 30 minutes . At the 31st minute , a total IV anesthesia technique was initiated , and all patients were actively warmed with a lithotomy blanket . Tympanic and distal esophageal temperatures were measured . Categorical data were analyzed using & khgr;2 test , and continuous data were analyzed with analysis of variance . P < 0.05 was considered statistically significant . RESULTS : The mean esophageal temperatures differed significantly between the control and the carbon fiber group from 40 to 90 minutes of anesthesia . After 50 minutes of anesthesia , the mean esophageal temperatures in the control , carbon fiber , and forced-air groups were 35.9 ° C ± 0.3 ° C , 36.5 ° C ± 0.4 ° C , and 36.2 ° C ± 0.3 ° C , respectively . No statistically significant difference was found between the forced-air and control groups . After 30 minutes of prewarming with resistive heating , patients had an esophageal temperature that was significantly higher than the control group . CONCLUSIONS : Prewarming should be considered part of the anesthetic management when patients are at risk for postoperative hypothermia", "Abstract Purpose of this study was to evaluate the combined analgesic effect of gabapentin and transdermal fentanyl patch , on acute and chronic pain after surgery for maxillary cancer . Study design The Study was double blind and prospect i ve . 100 subjects belonging to ASA grade I and II , 30–50 years age group , scheduled for maxillary cancer surgery were r and omized into two groups ; treatment group ( GT ) : to receive gabapentin , transdermal fentanyl patch or control group © : two placebos . For acute postoperative pain ( Visual Analogue Score ) and analgesic requirements were assessed 2 , 4 , 8 hours and 7 days after surgery . Subjects were also assessed for chronic pain 2 , 4 , 6 months later . Results Subjects in treatment group required lesser dose of analgesic , as compared to control group , in the post operative period . Visual Analogue Scores were also significantly lower in the treatment group throughout the post operative period . Occurrence of side effects was non significant between both groups . 2 , 4 and 6 months after surgery , 40 , 35 and 28 subjects respectively , out of total 45 subjects of the control group , reported chronic pain . In comparison , 25 , 10 and 4 subjects out of 42 subjects in the treatment group reported chronic pain 2 , 4 , 6 months respectively after surgery . 15 , 10 and 6 out of 45 of the control group required analgesics , whereas 2 , 0 and 0 out of 42 in the treatment group , required analgesics respectively 2 , 4 and 6 months after surgery Conclusion Acute and chronic pain after maxillary cancer surgery is significantly reduced by multimodal analgesia" ]

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[ "Leuprolide in a 3-monthly versus a monthly depot formulation for the treatment of symptomatic endometriosis: a pilot study.", "An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team.", "Effects of triptorelin versus placebo on the symptoms of endometriosis.", "Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue.", "THE MEDICAL TREATMENT OF MILD ENDOMETRIOSIS", "On the origin and significance of serum CA-125 concentrations in 97 patients with endometriosis before, during, and after buserelin acetate, nafarelin, or danazol.", "Bone loss during gonadotropin releasing hormone agonist treatment and use of nasal calcitonin", "Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study.", "Equivalence of the 3-month and 28-day formulations of triptorelin with regard to achievement and maintenance of medical castration in women with endometriosis.", "A double-blind randomized study of the treatment of endometriosis with nafarelin or nafarelin plus norethisterone.", "Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group.", "Clinical experience treating endometriosis with nafarelin.", "Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study.", "Depot Goserelin and Danazol Pre‐Treatment Before Rollerball Endometrial Ablation for Menorrhagia", "Comparison of the gonadotropin-releasing hormone agonist goserelin acetate alone versus goserelin combined with estrogen-progestogen add-back therapy in the treatment of endometriosis.", "Vaginal patterns during danazol and buserelin acetate therapy for endometriosis: structural and ultrastructural study.", "Buserelin versus danazol in the treatment of endometriosis-associated infertility.", "Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. The Nafarelin European Endometriosis Trial Group (NEET).", "Buserelin acetate in the treatment of pelvic pain associated with minimal and mild endometriosis: a controlled study.", "Efficacy and safety of nafarelin in the treatment of endometriosis.", "Danazol but not gonadotropin-releasing hormone agonists suppresses autoantibodies in endometriosis.", "Prolonged GnRH Agonist and Add‐Back Therapy for Symptomatic Endometriosis: Long‐term Follow‐up", "Short-term Lupron or danazol therapy for pelvic endometriosis.", "Estrogenic suppression by different administration schedules of goserelin depot for treatment of endometriosis", "Pre‐ and postoperative therapy with GnRH agonist for endometrial resection", "A Randomized, Parallel, Comparative Study of the Efficacy and Safety of Nafarelin Versus Danazol in the Treatment of Endometriosis in Taiwan", "Effects of Sodium Etidronate in Combination With Low-Dose Norethindrone in Patients Administered a Long-Acting GnRH Agonist: A Preliminary Report", "Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain.", "Comparison of the effects of leuprorelin acetate and danazol treatments on serum CA-125 levels in women with endometriosis.", "Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results.", "Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone \"add-back\" therapy.", "Comparison between the effects of nafarelin and danazol on serum lipids and lipoproteins in patients with endometriosis.", "Efficacy of intranasal or subcutaneous luteinizing hormone-releasing hormone agonist inhibition of ovarian function in the treatment of endometriosis.", "A comparison of nafarelin acetate and danazol in the treatment of endometriosis.", "Administration of nasal Buserelin as compared with subcutaneous Buserelin implant for endometriosis.", "Depot leuprorelin acetate versus danazol in the treatment of infertile women with symptomatic endometriosis.", "Leuprorelin acetate depot vs danazol in the treatment of endometriosis: results of an open multicentre trial.", "Decrease in symptoms, blood loss and uterine size with nafarelin acetate before abdominal hysterectomy: a placebo-controlled, double-blind study.", "A Randomized Comparison of Danazol and Leuprolide Acetate Suppression of Serum‐Soluble CD23 Levels in Endometriosis", "Pain of endometriosis: effects of nafarelin and danazol therapy.", "The levonorgestrel-releasing intrauterine system and endometriosis staging.", "[Treatment of endometriosis].", "Nafarelin versus danazol in the treatment of endometriosis.", "Depot leuprolide acetate versus danazol in the treatment of women with symptomatic endometriosis: a multicenter, double-blind randomized clinical trial. II. Assessment of safety. The Lupron Endometriosis Study Group.", "Quantification of endometriosis-associated pain and quality of life during the stimulatory phase of gonadotropin-releasing hormone agonist therapy: a double-blind, randomized, placebo-controlled trial.", "Human issues and medical economics of endometriosis. Three- vs. six-month GnRH-agonist therapy.", "Effectiveness of tibolone on hypoestrogenic symptoms induced by goserelin treatment in patients with endometriosis.", "A randomized, comparative trial of triptorelin depot (D-Trp6-LHRH) and danazol in the treatment of endometriosis.", "Nafarelin vs. leuprolide acetate depot for endometriosis. Changes in bone mineral density and vasomotor symptoms. Nafarelin Study Group.", "Nafarelin in the treatment of pelvic pain caused by endometriosis.", "Ovarian suppression induced with Buserelin or danazol in the management of endometriosis: a randomized, comparative study.", "A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis.", "Treatment of endometriosis with a decreasing dosage of a gonadotropin-releasing hormone agonist (nafarelin): a pilot study with low-dose agonist therapy (\"draw-back\" therapy).", "Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial.", "[Medical treatment of endometriosis: comparative study of leuprolide acetate and danazol].", "Serum-soluble CD23 in patients with endometriosis and the effect of treatment with danazol and leuprolide acetate depot injection.", "A Comparative Treatment Trial of Endometriosis Using the Gonadotrophin‐releasing Hormone Agonist, Nafarelin, and the Synthetic Steroid, Danazol" ]

[ "An open-label r and omized pilot study was conducted to evaluate the efficacy and acceptability of 6 months treatment with leuprolide in a 3-monthly versus a monthly i.m . depot injection for the relief of chronic pelvic pain in women with endometriosis . A total of 30 women aged 18 - 38 years were allocated to the 3-monthly depot arm ( n = 15 ) or to the monthly depot arm ( n = 15 ) after laparoscopic diagnosis of pelvic endometriosis . Mean ( SD ) deep dyspareunia scores according to a 0 - 3 point verbal rating scale decreased from 1.8 ( 0.9 ) at baseline to 1.3 ( 0.7 ) at the end of treatment in the 3-monthly depot group and from 2.1 ( 1.2 ) to 1.3 ( 0.7 ) in the monthly depot group . Corresponding values in non-menstrual pain scores fell from 2.1 ( 0.6 ) to 1.1 ( 0.3 ) , and from 2.1 ( 0.8 ) to 1.2 ( 0.4 ) respectively , without statistically significant differences between the groups . Serum luteinizing hormone ( LH ) and 17 beta-oestradiol concentrations were significantly suppressed at 12 and 24 weeks compared with baseline values , without differences between the groups . The monthly depot caused a slightly more marked inhibition of serum follicle stimulating hormone ( FSH ) levels with respect to the 3-monthly preparation . Mean ( SD ) endometriosis scores at baseline and at 6-month follow-up laparoscopy were respectively 32.8 ( 25.1 ) and 12.2 ( 9.3 ) in the 3-monthly depot group and 29.0 ( 22.7 ) and 13.1 ( 15.3 ) in the monthly depot group ( paired t-test , P < 0.05 ) . Mean percentage decrease in lumbar spine bone mineral density was 5.2 % in the former and 4.9 % in the latter subjects . In the 3-monthly depot group , 13 women grade d the tolerability of their treatment schedule as \" good ' compared with seven in the monthly depot group ( chi 2 = 5.40 , P = 0.02 )", "OBJECTIVE To compare the efficacy and safety of goserelin depot and danazol for endometriosis . DESIGN Open , r and omized comparative trial . SETTING Multicenter European academic clinical institutions . PATIENTS A total of 307 patients with laparoscopically diagnosed endometriosis were r and omized to goserelin ( n = 204 ) or danazol ( n = 103 ) ; 249 patients underwent second look laparoscopy ( 175 received goserelin and 74 danazol ) and were analyzed for efficacy . INTERVENTIONS A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three times a day administered for 24 weeks . MAIN OUTCOME MEASURES Efficacy assessment s were based on changes in visible deposits at laparoscopy before and after treatment and subjective symptom scores at 4-week intervals during treatment and 8-week intervals after treatment for up to 24 weeks . Safety was assessed by adverse event reporting and clinical laboratory measures . RESULTS There were similar proportions of symptomatic ( 73 % ) and asymptomatic ( but infertile ) ( 27 % ) and comparable distribution of different severity of endometriosis r and omized to each treatment . Significantly fewer patients r and omized to goserelin ( 6.4 % ) withdrew during treatment compared with 20.4 % r and omized to danazol ( P less than 0.05 ) . There were significantly reduced visible deposits of endometriosis found post-treatment ( P less than 0.0001 ) within each group but no differences between the treatments . The mean total subjective symptoms scores remained significantly less than entry at 24 weeks post-treatment ( P less than 0.05 ) . Hypoestrogenic side effects were more common in those receiving goserelin , particularly hot flushes , but anabolic/ and rogenic side effects of weight gain and muscle cramps were more common in those receiving danazol . CONCLUSIONS The monthly administered 3.6-mg depot preparation of goserelin was highly effective at inducing resolution of endometriotic implants and relieving the symptoms of endometriosis with prevention of their return during 24 weeks follow-up in the majority of patients . However , results were not significantly different from those achieved with danazol 600 mg/d", "OBJECTIVE To compare the effect of a GnRH-agonist , triptorelin , versus placebo on the symptoms of endometriosis . DESIGN A prospect i ve , r and omized , double-blind study of 6 months of treatment followed by 12 months of follow-up . SETTING Departments of Obstetrics and Gynecology at two universities and one general hospital . PATIENT(S ) Forty-nine women with symptoms of laparoscopically verified endometriosis . INTERVENTION(S ) Triptorelin depot or placebo was given every 4 weeks . Clinical evaluation , including the Duration Intensity Behavior Scale and Visual Analogue Scale for pain , was performed before the injections and up to 12 months after treatment . A control laparoscopy was performed 4 - 6 weeks after the last injection . MAIN OUTCOME MEASURE(S ) Quantitation of pain . RESULT ( S ) Twenty-four patients had active treatment and 25 received placebo . Pain symptoms according to both scales were significantly more reduced after 2 months of triptorelin treatment compared to placebo . The extent of endometriotic lesions was reduced 50 % during triptorelin treatment and increased 17 % during placebo . The average area of endometriotic lesions was reduced 45 % during triptorelin treatment but was unchanged during placebo . Side effects , mainly hot flushes , were experienced by 80 % of the actively treated group but also by 33 % of patients in the placebo group . Because of recurrent symptoms , only five patients could be observed for 12 months after completion of treatment . CONCLUSION ( S ) Triptorelin reduces endometriotic lesions and pain to a significantly higher degree than placebo", "BACKGROUND The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system ( LNG-IUS ) compared with the GnRH analogue ( GnRHa ) leuprolide acetate on these risk markers after 6 months of treatment . STUDY DESIGN This was a r and omized , prospect i ve , open clinical study , with 44 patients with laparoscopically and histologically confirmed endometriosis . Patients were r and omized into two groups : the LNG-IUS group , composed of 22 patients who underwent LNG-IUS insertion , and the GnRHa group , composed of 22 patients who received a monthly GnRHa injection for 6 months . Body mass index ; systolic and diastolic arterial blood pressure ; heart rate ; and laboratory cardiovascular risk markers such as interleukin-6 ( IL-6 ) , tumor necrosis factor-alpha ( TNF-alpha ) , C-reactive protein ( CRP ) , homocysteine ( HMC ) , lipid profile , total leukocytes and vascular cell adhesion molecule ( VCAM ) were measured before and 6 months after treatment . RESULTS After 6 months of treatment , a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated . In the LNG-IUS group , from pretreatment to posttreatment period , there was a significant reduction in the levels ( mean+/-SD ) of VCAM ( 92.8+/-4.2 to 91.2+/-2.7 ng/mL , p=.04 ) , CRP ( 0.38+/-0.30 to 0.28+/-0.21 mg/dL , p=.03 ) , total cholesterol ( 247.0+/-85.0 to 180.0+/-31.0 mg/dL , p=.0002 ) , triglycerides ( 118.0+/- 76.0 to 86.5+/-41.5 mg/dL , p=.003 ) , low-density lipoprotein cholesterol ( 160.5+/-66.0 to 114.5+/-25.5 mg/dL , p=.0005 ) and high-density lipoprotein cholesterol ( 63.0+/-20.5 to 48.5+/-10.5 mg/dL , p=.002 ) . The GnRHa group showed an increase in HMC levels ( 11.5+/-2.9 to 13.0+/-2.7 mumol/L , p=.04 ) and a reduction in IL-6 levels ( 4.3+/-3.9 to 2.3+/-0.8 pg/mL , p=.005 ) , VCAM ( 94.0+/-3.8 to 92.0+/-1.6 ng/mL , p=.03 ) and total leukocytes ( 7330+/-2554 to 6350+/-1778 , p=.01 ) . In the GnRH group , the remaining variables , including lipid profile , did not show any statistical difference . CONCLUSIONS This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-IUS , but the latter had a greater positive impact on the lipid profile , which could lead to a favorable effect during long-term treatment", "Minor degrees of endometriosis have often been regarded as being of no import and hence remain untreated , but a study of the natural history of endometriosis has demonstrated that 47 % ( 95 % confidence limits , 23–71 % ) of patients ( n=35 ) given placebo in a double‐blind , r and omized controlled trial showed progression of the disease when assessed before and after treatment by laparoscopy . The active agent , the progestogen gestrinone , was given at a dose of 2.5 mg twice weekly and result ed in an improvement of the disease ( p < 0.004 ) . Furthermore , follow‐up over 12 months showed no significant difference between those patients treated with active agent or placebo , and none between those with persistent disease and those in whom it had been obliterated . These data suggest that a diagnosis of mild endometriosis should be followed by treatment to prevent progressive disease , but that the treatment does not influence subsequent fertility . They indicate that expectant treatment has no place and that even if fertility is not an immediate requirement , active treatment should be instituted , and that the new gestogen , gestrinone is efficacious . Other treatments , such as danazol or luteinizing hormone releasing hormone ( LHRH ) agonists , or the older contraceptive or pseudopregnancy regimens , must be set against spontaneous improvement ( in 5 of 17 patients i.e. 29 % ) or elimination ( in 4 of 17 patients i.e. 24 % ) in the placebo group . Infertile patients with mild endometriosis have disorders of follicular and luteal function , and in vitro fertilization suggests a reduced fertilization rate . Nevertheless , these patients require active treatment if these problems are not to be compounded by adhesions , possibly leading to ovarian enclosure , that would further reduce the untreated cumulative conception rate", "OBJECTIVE To further eluci date the origin and significance of serum CA-125 in pelvic endometriosis . DESIGN Retrospective . PATIENTS Ninety-seven women with endometriosis who participated in two trials : ( 1 ) open-label study on buserelin acetate ( n = 51 ) and ( 2 ) comparative , placebo-controlled study on nafarelin ( n = 31 ) versus danazol ( n = 15 ) ( 2:1 ratio ) . INTERVENTIONS ( 1 ) Buserelin acetate 900 micrograms/d intranasally ( IN ) ; ( 2 ) nafarelin 400 micrograms/d IN versus danazol 400 mg/d orally during 6 months . MAIN OUTCOME MEASURE(S ) Serum CA-125 and estradiol concentrations ; severity of endometriosis-related symptoms ; scores according to The American Fertility Society ( AFS ) classification for endometriosis and /or adhesions ( before and on last day of therapy ) . RESULTS Menstruation and adhesions appeared major factors influencing pretreatment serum CA-125 concentrations . Compared with nonmenstruating women without adhesions , both menses and adhesions induced a slight increase tending to significancy , whereas the elevating effect of adhesions and menses together was highly significant and more than expected . All three treatment regimens reduced CA-125 concentrations to the same extent ; cessation of therapy was followed by restoration to pretreatment concentrations . Of the AFS scores for implants and /or adhesions , only pretreatment scores for adhesions correlated significantly with CA-125 concentrations . Severity scores for endometriosis-related complaints did not correlate . CONCLUSIONS The findings indicate that adhesions play a major role in the presence of CA-125 in the systemic circulation and suggest that reductions of serum CA-125 concentrations during gonadotropin-releasing hormone agonist and danazol therapy are hormonally determined", "Gonadotropin releasing hormone ( GnRH ) agonists have shown to be effective in the treatment of several sex-hormone-dependent conditions . However , their use could be limited by the bone loss they induce . To evaluate the use of nasal salmon calcitonin ( sCT ) in preventing this bone loss , 40 patients with endometriosis were treated for 6 months with triptoreline ( 3.75 mg monthly ) and calcium ( 1 g daily ) , and r and omized in three groups — placebo , sCT 100 IU daily and sCT 200 IU daily — in a prospect i ve double-masked study . Dual-energy X-ray absorptiometry and biochemical parameters were used to evaluate the benefit of the treatment . At baseline , there were no statistically significant differences between the groups . After 6 months , estradiol and biochemical markers of bone metabolism were at postmenopausal levels , with no difference between the groups . There was no difference in bone loss in the three groups , at all sites . Mean lumbar bone loss was 4.01±2.59 % ( mean±SD ) in this population . In this study dosages of 100 IU and 200 IU daily of nasal sCT were insufficient to prevent bone loss during GnRH agonist treatment", "OBJECTIVES To study the effect of GnRH agonist ( GnRH-a ) treatment on memory and to assess the role of psychological factors . DESIGN A r and omized prospect i ve study . SETTING An academic teaching hospital . PARTICIPANTS Women with endometriosis and infertility or endometriosis alone . MAIN OUTCOME MEASURES Memory Observation Question naire , Profile of Mood States , Health Concerns scale , a weekly diary of adverse effects . RESULTS Perceived memory functioning decreased during GnRH-a administration and by the final week of treatment 44 % of women reported moderate to marked impairment in comparison to community norms . Prospect i ve memory was most affected and withdrawal of GnRH-a treatment result ed in a return to normal memory functioning . Impairment was not related to excessive health concerns or mood changes and was uncorrelated with other adverse effects . CONCLUSIONS Memory disruption may be a more common side effect of GnRH-a treatment than currently is recognized . Problems were temporary and more likely a result of rapid estrogen depletion than a consequence of mood , somatic distress , or personality factors", "OBJECTIVE The present study aims at demonstrating the equivalence of the 28-day and 3-month formulations of triptorelin SR ( sustained release ) in terms of percentage of patients achieving castration levels of estradiol ( < = = 50 pg/mL ) 84 days after treatment initiation . DESIGN A phase II , prospect i ve , r and omized , multicenter , open study was conducted in two parallel groups of women with endometriosis . SETTING Academic hospitals . PATIENT(S ) Seventy-two women with endometriosis . were treated with a single intramuscular injection of 3-month triptorelin SR , and 74 patients were treated with one intramuscular injection of 28-day triptorelin SR every 28 days for 3 months . INTERVENTION(S ) As part of two parallel treatment groups , 72 women were given a single intramuscular injection of 3-month triptorelin SR , and 74 women were given one intramuscular injection of 28-day triptorelin SR every 28 days for 3 months . MAIN OUTCOME MEASURE(S ) Percentage of patients achieving castration levels of estradiol at the end of the treatment period . RESULT ( S ) Patients participated in the study until resumption of menses . Ninety-seven percent of patients given the 3-month formulation and 94 % of those given the 28-day formulation were in a state of medical castration on day 84 . The mean time to achieve castration was shorter for the 3-month formulation , and the duration of castration was significantly longer . The FSH and LH parameters were comparable , though not always identical . CONCLUSION ( S ) The pharmacodynamic effects of the Decapeptyl SR 3-month formulation are equivalent to those of the 28-day formulation . The 3-month formulation provides the added advantage of a longer maintenance of medical castration in women who have endometriosis", "The objective of this study was to compare the efficacy of nafarelin 200 micrograms ( Group A ) , nafarelin 400 micrograms ( Group B ) and the combination of nafarelin 200 micrograms and norethisterone 1.2 mg ( Group C ) daily , in treating symptoms of endometriosis , American Fertility Society score and adverse events during 6 months of treatment . A prospect i ve , r and omized , double-blind parallel group study was performed in two centers and 49 women with endometriosis diagnosed laparoscopically were included . The patients were seen monthly for physical examination and records were taken for bleeding pattern , symptom score and adverse events . A control laparoscopy was performed at the end of 6 months of treatment . All patients were followed 6 months after treatment . At 3 and 6 months the pelvic examination total score had decreased significantly in all three groups . The total endometriosis score was significantly reduced in Groups B and C. After 2 months the total symptom score showed a significant decrease in Groups B and C. The frequency of hot flushes during the first month of treatment was lowest in Group C , but during the rest of treatment there were no differences between the groups . Best bleeding control was obtained in Group C. We conclude that nafarelin 200 micrograms daily has as good an effect on endometriosis symptoms as nafarelin 400 micrograms daily , and the addition of norethisterone 1.2 mg results in fewer hot flushes and better bleeding control", "The safety and efficacy of leuprolide acetate ( LA ) for depot suspension ( Lupron depot ; TAP Pharmaceuticals , North Chicago , IL ) , 3.75 mg versus placebo , in the treatment of pain associated with endometriosis was assessed in a r and omized , double-blind , multicenter study involving 52 patients . Dysmenorrhea , pelvic pain , and pelvic tenderness all responded significantly to LA treatment in comparison with placebo . Menses were suppressed in all of the LA patients . Estradiol decreased significantly to menopausal levels in the LA group . There were small to moderate changes in a variety of laboratory parameters , but these were not clinical ly significant . The most common adverse event was vasodilatation , occurring significantly more frequently in the LA group . Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis , result ing in alleviation of pain symptoms", "The preliminary results from an ongoing multicenter trial further support the efficacy and excellent tolerability of nafarelin in the management of endometriosis", "OBJECTIVES To evaluate the efficacy and safety of very low dose danazol in improving pelvic pain in women with endometriosis , the benefit of preceding the treatment by a short course of a GnRH agonist , symptoms recurrence after drug withdrawal , and variations in menstrual pattern . DESIGN Open-label , r and omized study . SETTING University hospital endometriosis center . PATIENTS Forty-two women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis . INTERVENTIONS Treatment with oral danazol , 50 mg/d , for 9 months ( group I , n = 21 ) or leuprolide depot for 3 months followed by oral danazol , 50 mg/d , for 6 months ( group II , n = 21 ) , and a 6-month follow-up . MAIN OUTCOME MEASURES Variations in severity of symptoms during treatment and at the end of follow-up as shown by a linear analog scale and a verbal rating scale ; menstrual blood loss as assessed by a pictorial chart . RESULTS Four patients withdrew from the study , one in each group at the fifth month of treatment ( for persistent pain ) and one in each group during follow-up ( they requested additional therapy ) ; one woman in group I was lost to follow-up . Significant improvements were obtained in dysmenorrhea , deep dyspareunia , and nonmenstrual pain in both treatment schedules without differences between the groups . Also menstrual blood loss was significantly reduced in both groups . A temporary fall in high and rise in low density lipoprotein cholesterol was observed in the study population . At the end of follow-up symptoms recurred without significant differences in median pain scores with respect to baseline . CONCLUSION Very low dose danazol may be an alternative for temporary relief of endometriosis-associated pain . Ovulation is not always inhibited and barrier contraception is needed . Side effects occur but are rarely severe . Further data are required to evaluate the influence of long-term administration on the lipid profile", "Objective To compare the safety and efficacy of a GnRH agonist , deport goserelin , and danazol as preoperative treatments before rollerball endometrial ablation . Methods We performed an open , r and omized study of women with clinical ly convincing histories of menorrhagia . Two treatment groups of equal size ( goserelin acetate , 3.6 mg subcutaneous implant given monthly , n = 30 ; and danazol , 200 mg two times per day , n = 30 ) were treated for 2 months before undergoing endometrial ablation , which entailed using the rollerball with 80–100 watts of coagulating current . Results Measured menstrual blood loss decreased dramatically after ablation , with 74 % of goserelin users and 62 % of danazol users achieving complete amenorrhea by the end of the 6-month follow-up period . Among women who did not achieve complete amenorrhea , those in the danazol group were more likely to experience occasional episodes of moderate or heavy bleeding . Mean measured blood loss decreased from 94.8 to 1.1 mL at 3 months and 1.0 mL at 6 months after goserelin , and 97.9 to 15.0 mL and 7.4 mL after danazol . Menstrual pain also improved markedly . The median duration of surgery was 20 minutes ( range 5–55 ) in both groups , median irrigation fluid deficit was 100 mL ( range 0–800 ) , and median operative blood loss was 20 mL ( range 1–50 ) . Endometrium was less than 2 mm thick in all goserelin and most danazol users . Side effects of goserelin and danazol therapy were all within the expected pattern for these drugs . Conclusion Depot goserelin and danazol both provide adequate endometrial preparation before rollerball endometrial ablation for treatment of menorrhagia due to ovulatory dysfunctional uterine bleeding", "OBJECTIVE To investigate whether the addition of low-dose estrogen-P combination hormone replacement therapy ( HRT ) to GnRH agonist ( GnRH-a ) treatment for endometriosis reduces the pharmacologic side effects of such treatment without reducing efficacy and to determine the endocrinologic changes during treatment . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled , comparative study of two drug regimens : 3.6 mg goserelin acetate in a 28-day SC depot formulation once monthly for 6 months plus either a combination of 2 mg 17 beta-E2 and 1 mg norethisterone acetate ( NET ) 1 mg or matching placebo tablets once daily for 6 months . SETTING Multicenter study in three tertiary referral centers at university teaching hospitals and two central hospitals . PATIENTS Women with laparoscopically confirmed symptomatic endometriosis were included in the study . RESULTS Of the total of 109 patients screened , 93 were recruited and 88 patients were r and omized to either the HRT or the placebo group . Four women were withdrawn because of various medical reasons , and 76 patients were followed-up for a total of 12 months . In terms of efficacy , there was no difference between the two drug regimens for objective or subjective response . There were significantly less postmenopausal symptoms in the patients treated with goserelin plus HRT compared with those treated with goserelin plus placebo . CONCLUSION Goserelin diminished significantly the symptoms and laparoscopic scores of endometriosis . The addition of HRT did not reduce the efficacy of goserelin but diminished the postmenopausal symptoms during treatment", "OBJECTIVE To evaluate histologic and ultrastructural changes of the vaginal mucosa in patients given buserelin acetate or danazol treatment for endometriosis . DESIGN Controlled clinical study . SETTING Infertility clinic of an academic unit . PATIENTS Infertile women with endometriosis r and omized to receive buserelin acetate or danazol and undergoing vaginal biopsies during treatment were selected . INTERVENTIONS Buserelin acetate was administered IN 400 micrograms three times per day and danazol orally 600 mg/d . Vaginal biopsies were performed baseline and at 3 and 6 months of treatment , and specimens were examined by light microscopy and scanning electron microscopy . 17 beta-Estradiol and P levels were determined in each patient at the time of each biopsy . MAIN OUTCOME MEASURE Structural and ultrastructural patterns of vaginal mucosa after 3 and 6 months of treatment . RESULTS Buserelin acetate treatment induced early , marked hypotrophy of the vaginal mucosa with aspects typical of the menopause . The modifications caused by danazol occurred mainly in the intermediate layer , which was weakly hypotrophic only at the end of the treatment . CONCLUSION Vaginal mucosa undergoes constant and well-defined modifications during both buserelin acetate and danazol treatment for endometriosis . The modifications are compatible with the biological effects of the drugs", "A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated r and omly to two treatment groups , one of which ( 32 patients ) received oral danazol 600 micrograms/day and the other ( 30 patients ) received intranasal buserelin 1200 micrograms/day for 6 months . Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment . Pain symptoms improved markedly during treatment in both groups . At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it ( 12 in the buserelin group and 13 in the danazol group ) , and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants . All of the patients were followed up for at least 12 months , during which pregnancy was attempted . At 18 months the cumulative pregnancy rate was 48 % in the patients treated with buserelin and 43 % in those treated with danazol . Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension . The side effects were more frequent and more severe in the danazol-treated patients , whereas those given buserelin generally reported only symptoms of hypoestrogenism . The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility , and its side effects are less severe", "OBJECTIVE To compare the efficacy and safety of nafarelin and danazol for endometriosis . DESIGN R and omized , double-blind , double-dummy . SETTING Multiple European institutions . PATIENTS In total , 307 patients with laparoscopically diagnosed endometriosis received nafarelin ( n = 206 ) or danazol ( n = 101 ) ; 263 ( 171 nafarelin , 92 danazol ) were analyzed for efficacy . INTERVENTIONS Intranasal nafarelin 200 micrograms two times a day or oral danazol 200 mg three times a day were administered for 6 months . MAIN OUTCOME MEASURES Efficacy assessment s were based on preadmission and end-of-treatment laparoscopic scores and subjective symptom scores at admission , end of treatment , 1 , 3 , 6 , and 12 months after treatment . Safety was evaluated by adverse events and clinical laboratory tests . RESULTS In each group , endometriosis growth and symptoms significantly improved during treatment ( P less than 0.001 ) . After treatment , symptoms returned in each group , but severity was less than at admission at all time points ( P less than or equal to 0.016 ) . Mean body weight increased in the danazol-treated group ( P less than 0.001 ) , serum glutamic oxaloacetic transaminase increased in both groups ( P less than 0.001 for both ) but significantly more in danazol users ( P less than 0.002 ) , and more nafarelin recipients had hot flushes ( P less than 0.001 ) . CONCLUSIONS Nafarelin and danazol were equally effective in reducing endometriosis growth and symptoms during treatment and in preventing the return of symptoms during 12-month follow-up", "OBJECTIVE To evaluate the changes of pain symptoms induced by buserelin acetate , a gonadotropin-releasing hormone agonist , in a group of patients with endometriosis . DESIGN Thirty-five infertile patients with one or more of the following symptoms ( dysmenorrhea , pelvic pain , deep dyspareunia , and endometriosis stage I or II ) were allocated r and omly to treatment with buserelin acetate 1,200 micrograms/d IN for 6 months ( n = 19 ) or expectant management ( n = 16 ) . Pain symptoms were recorded by the women themselves using a question naire that included two scales for pain evaluation : one analogue and one multidimensional . The treated and untreated patients were followed for a minimum of 18 and 12 months from the time of r and omization , respectively . RESULTS Buserelin acetate markedly reduced dysmenorrhea , pelvic pain , and dyspareunia during the treatment and also for the 12 subsequent months . During follow-up of the expectant management group , dysmenorrhea resolved in 19 % ( 3/16 ) of the cases , and pelvic pain did not recur after diagnostic laparoscopy in one of the three women affected nor did deep dyspareunia in two of the five who reported the symptom before laparoscopy . CONCLUSION Buserelin acetate induced a significant improvement of pain symptoms that persisted in approximately half of the patients even after withdrawal of the drug . However , symptoms associated with endometriosis showed a spontaneous remission in approximately one fifth of the untreated patients", "The efficacy and safety of the gonadotropin-releasing hormone agonist nafarelin for treatment of endometriosis were compared with those of danazol in two large-scale , double-blind trials . Assessment s of severity of symptoms , laparoscopic scores before and after therapy , and pregnancy rates showed that nafarelin , 400 and 800 micrograms administered intranasally , was as efficacious as oral danazol , 600 and 800 mg . The adverse effects seen with nafarelin , mainly hot flashes , were related to its mode of action , namely hypoestrogenemia induced by reversible inhibition of ovarian hormone production . Hypoestrogenemia was associated with a decrease of bone density in the lumbar vertebrae , but these changes were partially or completely reversible after treatment was discontinued . No significant changes in bone mass occurred in the distal radius . Danazol was associated with and rogenic and metabolic adverse effects , including weight gain , negative effects on the lipid profile , and elevated liver enzyme levels . Nafarelin was found to be as effective as danazol for the management of endometriosis , with a different and more favorable safety profile", "The effect of treatment with danazol ( n = 10 ) or gonadotropin-releasing hormone agonists ( GnRH-a ) ( n = 10 ) on autoantibody ( AA ) production ( IgG , IgM and , IgA to 6 phospholipids , 5 histones , and 4 polynucleotides ) in endometriosis was evaluated blindly in a longitudinal , prospect i ve , r and omized study . Clinical improvement , ovarian suppression , and resolution of endometriosis were comparable in both groups . Approximately 50 % of patients had significant AA abnormalities initially . During treatment with danazol but not GnRH-a , AA gradually decreased in concentration and in number/patient . Total immunoglobulin levels ( IgG , IgM , and IgA ) also decreased only in the danazol group . This study indicates that danazol , but not GnRH-a , lowers abnormal AA associated with endometriosis", "OBJECTIVE To assess post‐treatment effects in endometriosis patients of a 12‐month course of GnRH agonist alone or with one of three “ add‐back ” regimens . METHODS This is a post‐treatment follow‐up analysis of a r and omized , double‐masked , placebo‐controlled 52‐week trial . All patients had received monthly leuprolide acetate and were r and omized to one of four groups : A — daily placebo ; B — daily norethindrone acetate 5 mg ; C — daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg ; and D — daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg . Of 201 patients enrolled in the initial trial , 123 completed at least 280 days of therapy and entered the follow‐up period . Physical findings and symptoms were quantified , and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post‐therapy . RESULTS Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups ( P < .05 ) . Findings were not affected by endometriosis scores noted on screening laparoscopy . Mean bone mineral density values remained at or above baseline in all add‐back groups . The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow‐up visit ( P < .001 ) . CONCLUSION GnRH agonist and norethindrone acetate alone or combined with low‐dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy", "OBJECTIVE To compare the efficacy of a 3-month trial of leuprolide acetate ( LA ; Lupron ; TAP Pharmaceuticals , Deerfield , IL ) versus danazol ( Danocrine ; Scenofi Winthrup Pharmaceuticals , New York , NY ) therapy on laparoscopically proven endometriosis . DESIGN Endometriosis severity was assessed at the time of laparoscopy and patients were r and omized to receive 0.1 mg SC LA ( n = 22 ) or 800 mg danazol orally ( n = 18 ) daily for 3 months . A second laparoscopy and /or laparotomy was performed to assess the change in the extent of endometriosis and for surgical therapy . SETTING Private practice at a university-affiliated hospital . PATIENTS Forty patients with mild , moderate , or severe endometriosis . Ten patients were excluded . INTERVENTION Three-month treatment r and omly assigned to either LA or danazol . MAIN OUTCOME MEASURES Prospect i ve measurement of American Fertility Society endometriosis scores and size of ovarian endometriomata before and after therapy via laparoscopy . RESULTS The mean endometriosis score including adhesions decreased significantly from 36 + /- 4.9 to 29 + /- 5.0 ( mean + /- SEM ) with LA and from 34 + /- 6.4 to 29 + /- 6.5 with danazol . The mean laparoscopic endometriosis score not including adhesions decreased from 27 + /- 3.5 to 22 + /- 3.4 with LA and 22 + /- 3.5 to 19 + /- 3.1 with danazol . Seven of 18 ( 39 % ) endometriomata responded to LA and 6 of 15 ( 40 % ) endometriomata responded to danazol . CONCLUSION We conclude that both danazol and LA will reduce endometriosis scores after a 3-month course of therapy . Larger clinical trials are needed to compare short courses of therapy with the more established 6-month trials . A 3-month versus a 6-month course of therapy offers obvious benefits including decreased cost and decreased side effects", "Eighteen patients affected by laparoscopically confirmed endometriosis were r and omly assigned to three different schedules of treatment with gonadotropin-releasing hormone agonist ( GnRH-a ) ( goserelin depot formulation 3.6 mg ) every 28 days for 6 months . Six women received the first implant in early follicular phase , 4 in late luteal phase and 8 in 3rd and 17th day from onset of menses . Pretreatment and posttreatment laparoscopic score , performed according to the American Fertility Society scoring system , were compared ; a significant reduction in the extent of disease was observed in each group investigated ( A and C : p<0.01 ; B : p<0.05 ) . In each treatment group after the second GnRH-a implant the mean levels of estrone-3-glucuronide ( E1 - 3 G ) , daily measured in early morning urine specimens during the control cycle and the first three months of therapy , were suppressed to menopausal women range . In group B during the 2nd and 3rd month of therapy , the urinary mean levels of EI-3 G were significantly lower than in group A and C. In conclusion the different goserelin depot administration schedules gave similar laparoscopic improvement , in spite of the first GnRH-a administration in luteal phase allowed a more marked estrogenic suppression", "Background . To assess the value of endometrial preparation , with preoperative and pre‐ and postoperative GnRH agonist therapy in transcervical endometrial resection", "Background : The purpose of this study was to evaluate the efficacy and safety of nafarelin , a gonadotropin‐releasing hormone ( GnRH ) analogue , versus danazol in the treatment of women with endometriosis in Taiwan . Methods : Fifty‐nine women with laparoscopically and pathologically confirmed endometriosis were r and omized to receive nafarelin or danazol for 180 days . Efficacy was assessed from mean changes in laparoscopy score ( LS ) and total symptom severity score ( TSSS ) . Adverse events ( AEs ) and laboratory parameters , including hematology , hepatic function , blood pressure , and lipid levels , were monitored for safety evaluations . Results : All demographic and baseline factors , except body weight , were comparable between the 2 treatment groups . Both nafarelin and danazol satisfactorily resolved pelvic tenderness , in duration , pelvic pain , dysmenorrhea and dyspareunia . No significant differences were noted in efficacy endpoints between nafarelin and danazol regarding LS and TSSS at 90 and 180 days of treatment . No significant difference was observed between the 2 groups regarding the overall incidence of AEs , except for laboratory‐related AEs . However , nafarelin tended to have less impact than danazol on aspartate transaminase and alanine transaminase , and nafarelin was better tolerated than danazol regarding changes in lipid profiles . Both treatments had little or no effect on hematologic parameters . Conclusion : Nafarelin and danazol demonstrated similar clinical efficacy , but nafarelin was associated with fewer laboratory changes and a stable lipid profile , relative to danazol . Moreover , intranasally administered nafarelin is noninvasive , and may be a more comfortable and safer alternative to slow‐release injectable GnRH agonists . Based on this study , we suggest that nafarelin , like other GnRH analogues , may be a treatment of choice for Taiwanese women with endometriosis . However , direct comparative studies of nafarelin with slow‐release injectable GnRH agonists are now required", "Objective : To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone . Methods : Eleven patients enrolled in this r and omized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks . Six patients ( group I ) self-administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles . This regimen was supplemented by norethindrone 2.5 mg/day orally . Five patients ( group II ) self-administered norethindrone 10 mg/day orally . Two sets of controls were used . Group III consisted of ten previously reported patients who received the same GnRH agonist only . Group IV comprised 12 regularly cycling untreated controls . Bone mineral density , vasomotor symptoms , circulating estrogens , and lipids were assessed serially . Results : The significant vasomotor instability ( P<.01 ) and bone mineral density loss ( -4.8 ± 0.9 % ; P<.05 ) experienced by patients in group HI was prevented in those in groups I and II despite maintenance of a persistent hypoestrogenic state . Bone density changes in groups I and II were similar to those in untreated controls ( group IV ) . Persistent decreases in high-density lipoprotein ( HDL ) cholesterol ( P=.005 ) and increases in the low-density lipoprotein- to-HDL ratio ( P<.05 ) were noted only in group II patients receiving supplemental high-dose norethindrone . Conclusion : These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone", "OBJECTIVES To determine the effectiveness of a 3-month course of nafarelin and , furthermore , to determine the long-term efficacy in patients treated for 3 and 6 months with nafarelin for symptoms associated with endometriosis . DESIGN Double-blind , prospect i ve , multicenter , clinical trial . SETTING Fifteen reproductive endocrine clinics throughout the United States . PATIENTS One hundred seventy-nine women with pelvic pain and endometriosis . INTERVENTIONS Patients were assigned r and omly to 3 months nafarelin followed by 3 months of placebo ( n = 91 ) or to 6 months nafarelin ( n = 88 ) in a prospect i ve , r and omized , double-blind multicenter trial . Patients were followed for 12 months after cessation of therapy . MAIN OUTCOME MEASURES Patient-reported pain scores and physician-reported physical exam findings . RESULTS Pain scores dropped significantly by the end of treatment in both groups . Symptoms recurred in both groups , and pain scores gradually increased during the follow-up period but always remained below baseline in both groups . No significant difference in efficacy was noted between the groups . A total of 26 % of patients in each group underwent retreatment for recurrent symptoms . CONCLUSIONS A 3-month course of nafarelin provided effective symptom relief for endometriosis . One year follow-up demonstrated continued pain relief but with gradual return of symptoms", "OBJECTIVE To investigate the effects of danazol and leuprorelin acetate on CA-125 levels during treatment for endometriosis . PATIENTS AND METHODS Fifty women with laparoscopically diagnosed and treated endometriosis , and 50 women without pelvic disease as a control group . Following surgical treatment , 35 women with endometriosis were divided into two groups . The first group ( 20 women ) received 200 mg danazol three times daily for 6 months ; the second group ( 15 women ) received 3.75 mg leuprorelin acetate depot every 28 days for 6 months . Serum CA-125 levels were measured before medical treatment , during the last 15 days of the 6-month treatment course , and 3 months after treatment . RESULTS Serum CA-125 levels were significantly higher in women with endometriosis than in women in the control group . Before treatment , CA-125 levels in patients with stage III/IV endometriosis were significantly higher than those in stage I/II endometriosis . Six months of danazol or leuprorelin acetate depot treatment decreased serum CA-125 levels . Three months after stopping danazol , CA-125 levels remained significantly lower than pretreatment levels . On the other h and , 3 months after stopping leuprorelin acetate , CA-125 levels returned to pretreatment levels . CONCLUSIONS ( a ) Danazol and leuprorelin acetate are equally effective in the treatment of endometriosis . ( b ) Moreover , the results support the view that the determination of CA-125 levels may assist in evaluating progress of endometriosis treatment", "OBJECTIVE We aim ed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis . STUDY DESIGN A double-blind r and omized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis . Pretreatment and posttreatment endometriosis symptoms and signs were assessed with st and ardized methods . RESULTS When compared with danazol , leuprolide depot caused a more rapid and profound suppression of estradiol . Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis , as well as the pain and tenderness associated with endometriosis . CONCLUSION Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain", "OBJECTIVE To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist ( GnRH-a ) for prolonged therapy of symptomatic endometriosis . DESIGN Prospect i ve r and omized open label study . SETTING Tertiary care university-affiliated reproductive medicine program . PATIENTS Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis . INTERVENTIONS All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks . Group I patients ( n = 10 ) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily . Group II patients ( n = 9 ) received only supplemental 10 mg norethindrone daily . Group III volunteers ( n = 18 ) were untreated and followed for bone density changes . MAIN OUTCOME MEASURES Disease extent at follow-up laparoscopy ; pain , vasomotor , and vaginal symptom scores ; bone mineral density ( serial dual-energy roentgenogram absorptiometry scans ) ; serum estrogens , lipids , and glucose and insulin response to glucose challenge . RESULTS Painful symptoms and extent of endometriosis were reduced in both treatment groups . Despite maintenance of a chronically hypoestrogenic state for 48 weeks , no changes in bone density over time or in comparison to group III untreated controls were noted . Similarly , no evidence of significant vasomotor symptoms were reported in either treatment group . However , adverse changes over time in circulating low-density lipoprotein ( LDL ) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II . CONCLUSIONS The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis . Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved", "The effects of nafarelin ( 400 micrograms daily ; 12 patients ) and danazol ( 600 mg daily ; 6 patients ) on serum lipoproteins , high density lipoprotein ( HDL ) subfractions , and apoproteins-A-I and -A-II were studied . Lipoproteins were fractionated by sequential flotation from sample s taken before and after 1 , 3 , and 6 months of treatment as well as 3 months after cessation of medication . Serum concentrations of estradiol , total and free testosterone , and rostenedione , and sex hormone-binding globulin were also determined . On nafarelin treatment , serum total HDL and HDL2 cholesterol concentrations increased slightly , but total and low density lipoprotein ( LDL ) cholesterol levels were unchanged . There was no effect on apoproteins-A-I and -A-II or on total and very low density lipoprotein ( VLDL ) triglyceride concentrations . During treatment with danazol , the serum levels of total HDL and HDL2 cholesterol showed profound decrease , as did all the components of HDL2 , including apoprotein-A-I. Concomitantly , the total mass of LDL was increased by 25 % , accounted for by parallel rises in all of the components of LDL . Total and VLDL triglyceride concentrations decreased inconsistently . Both treatments result ed in hypoestrogenism of the same degree . The steep drop in the serum sex hormone-binding globulin level reflected the and rogenic effect of danazol , whereas during nafarelin treatment , serum concentrations of testosterone and and rostenedione were reduced . This difference in and rogenic milieu may well explain the differences in the lipid profiles . We conclude that , regarding lipid effects , nafarelin is a more favorable treatment for endometriosis than is danazol", "We have previously reported reversible hypogonadism induced by the intranasal administration of the luteinizing hormone-releasing hormone agonist buserelin as a new therapeutic approach for endometriosis . Thirteen patients were r and omized to receive intranasal buserelin ( 400 micrograms 3 times a day ) or subcutaneous buserelin injection ( 200 micrograms once daily ) for a 6- to 9-month period . Both routes of administration were effective in inhibiting serum estradiol levels to near the menopausal range after 1 month of treatment . The two dosage regimens had also a comparable efficacy in alleviating endometriosis symptoms and in reducing the revised American Fertility Society scoring at laparoscopic examination . The implant score mainly decreased by more than 70 % . The occurrence of side effects was similar in both groups , and side effects were mainly hot flushes , dyspareunia secondary to decreased vaginal secretion , and decreased libido . Results of hemogram , urinalysis , and serum biochemical and hormonal tests remained in the normal range . The ovulatory cycle rapidly returned after the cessation of treatment , and three pregnancies occurred in six previously infertile patients . Intranasal and subcutaneous buserelin were well accepted and equally effective in inhibiting the pituitary-ovarian function , which caused mild menopausal symptoms but an important regression of endometriosis", "Nafarelin 400 micrograms daily and danazol 600 mg daily were compared in a double-blind r and omized study . Eighty-two patients with endometriosis were treated for 6 months after an initial laparoscopy and 74 had a second laparoscopy . Twenty-two ( 30 % ) patients had complete disease regression , 42 ( 57 % ) patients had a partial regression , and in 10 ( 13 % ) patients disease was unchanged or worse . Both treatments led to significant regression of active disease but not of adhesions . At 3 months follow-up , 34 ( 64 % ) patients reported their symptoms were improved , 15 ( 28 % ) reported no change , and 4 ( 8 % ) were worse . Nafarelin was associated with more hot flushes and headaches , and danazol with more weight gain . No significant differences , however , were noted in treatment efficacy between the two groups", "One hundred infertile patients with laparoscopically confirmed ovarian endometriosis were treated with either intranasal ( IN ) Buserelin ( Hoechst , AG , Frankfurt am Main , West Germany ) ( 300 micrograms three times a day ) or subcutaneous ( SC ) Buserelin implant ( 6.6 mg Buserelin ) . Serum estradiol was suppressed in the menopausal range in both groups , but the inhibition of the pituitary ovarian axis appeared more profound and consistent in the SC group than in the IN group . Laparoscopic findings proved that the SC Buserelin emerged superior to the IN Buserelin . Indeed , the score of endometriotic lesions and the ovarian cyst diameter were more reduced in the SC group than in the IN group . Moreover , the histologic study showed a lower incidence of active endometriosis and a lower mitotic index of ovarian endometrial epithelium in the SC group than in the IN group . In conclusion , the release of a gonadotropin-releasing hormone agonist by a biodegradable implant achieved better efficacy in reducing endometriotic lesions than the IN mode of administration", "PURPOSE OF INVESTIGATION Endometriosis is a common finding in women with infertility , but the mechanism by which it renders a woman infertile remains unclear . The medical treatment of pelvic endometriosis includes hormonal therapy that directly attacks endometriosis lesions or indirectly by inhibiting endometrial proliferation through estrogenic deprivation . The aim of this study was to compare the efficacy and safety of leuprorelin acetate depot and danazol for endometriosis in infertile women . METHODS This r and omized trial involved 81 women 19 - 41 years old with regular menses and known pelvic endometriosis who were recruited from the Fertility Center of the Second University of Naples between 1992 and 1999 . Fifty-four women were given 3.75 mg of leuprolide acetate depot every 28 days for 24 weeks and the remaining 27 took 200 mg of danazol three times daily for 24 weeks . Efficacy assessment s were based on pre-admission and end-of-treatment laparoscopic scores and subjective symptoms scores at 4-week intervals during and after treatment . Safety was evaluated by adverse events and clinical laboratory tests . RESULTS In each group , endometriosis growth and symptoms significantly improved during treatment ( p < 0.001 ) . Significantly fewer patients r and omized to leuprorelin acetate ( 5.5 % ) withdrew during treatment compared with 18.5 % r and omized to danazol ( p < 0.05 ) . After treatment symptoms returned in each group , but severity was less than at admission at all time points ( p < 0.02 ) . Hypoestrogenic side-effects were more common in those receiving leuprorelin , particularly hot flushes , but anabolic/ and rogenic side-effects of weight gain and acne were more common in those receiving danazol . CONCLUSION Both leuprorelin acetate depot and danazol are effective in the treatment of endometriosis in infertile patients . The hypoestrogenic side-effects of leuprorelin may be better tolerated than the and rogenic , anabolic effects of danazol", "A national multicentre trial was organized in order to compare the efficacy and safety of leuprorelin acetate depot and danazol in the treatment of endometriosis . Sixty-seven patients with pelvic endometriosis of different severity at laparoscopy were included in the study and followed during the 24 weeks of treatment . Leuprorelin acetate depot 3.75 mg was injected every 24 days , while the daily dose of danazol was 600 - 800 mg . At the end of the study objective improvements induced by the two drugs were observed by a second laparoscopic examination . In addition , at regular intervals during the study semiquantitative evaluation of subjective symptoms were monitored . Scoring the final objective changes in the two patient groups revealed no significant difference , however the women treated with leuprorelin acetate depot registered significantly better control of pelvic pain . Due to its efficacy , tolerability and ease of use , leuprorelin acetate appears to be an excellent drug for the treatment of endometriosis", "To evaluate the efficacy and safety of nafarelin before hysterectomy in a prospect i ve placebo-controlled trial , we r and omized 188 pre-menopausal women with uterine fibroids ( n = 111 ) , menometrorrhagia ( n = 58 ) or pelvic pain ( n = 19 ) to receive either nafarelin ( 200 micrograms twice daily as a nasal spray ) or a placebo for 3 months before abdominal hysterectomy . The data analysis could be performed in 166 women , of whom 107 received nafarelin and 59 a placebo . Nafarelin led to a rise in blood haemoglobin ( 5.5 g/l ) and to a decrease in uterine volume ( 23.7 % ) . This , however , gave no objective benefit during surgery ( similar operative duration s and blood losses ) . The uteri from patients treated with nafarelin ( 255.5 + /- 12.6 g , mean + /- SD ) were significantly lighter ( P = 0.029 ) than those from patients treated with a placebo ( 346.2 + /- 35.7 g ) . Histological examination of the fibroids or uteri revealed changes typical for hypo-oestrogenism , but no specific histological pattern could be established . The endometrium was proliferative in 56 % and showed mild hyperplastic features in 10 % of patients given nafarelin , whereas the respective figures for the placebo group were 41 and 0 % . Hot flushes were the most common side-effects , being reported by 61 % in the nafarelin group and 35 % in the placebo group . Nafarelin can be useful as a pre-surgical adjunct in a patient scheduled for abdominal hysterectomy if there is a need to raise the haemoglobin concentration or to reduce the size of the uterus", "Objective To determine the effects of treatment with danazol and leuprolide acetate depot on serum-soluble CD23 concentrations in women with endometriosis . Methods This r and omized trial involved 20 women 18–42 years old with regular menses and known pelvic endometriosis who were recruited from a university hospital between 1993 and 1998 . Ten women took 200 mg of danazol three times daily for 6 months , and the remaining ten were given 3.75 mg of leuprolide acetate depot every 28 days for 6 months . Blood-soluble CD23 levels were measured before treatment , during the last 15 days of the 6-month treatment course , and 3 months after treatment . Only one blood sample was taken from ten women without endometriosis , between the 5th and 7th days of their menstrual cycles . For statistical analysis , we used independent and paired t tests with the Pearson correlation coefficient . Results Soluble CD23 levels were significantly higher in women with endometriosis before treatment than in ten normal controls . Levels decreased significantly during treatment with either danazol or leuprolide acetate . Three months after treatment , soluble CD23 values remained lower than before treatment . There was no correlation between soluble CD23 concentrations and severity of endometriosis . Conclusion Our findings suggest that endometriosis increases soluble CD23 levels , which can be suppressed with either danazol or leuprolide acetate injection", "OBJECTIVE To compare the efficacy of nafarelin acetate with danazol in the treatment of dysmenorrhea , dyspareunia , and pelvic pain associated with endometriosis . DESIGN Prospect i ve , r and omized double-blind controlled study . PATIENTS , SETTING , TREATMENTS : Two hundred thirteen patients aged 18 to 48 with laparoscopically confirmed pelvic endometriosis and dysmenorrhea , dyspareunia or pelvic pain were r and omly assigned to 6 months of treatment with either nafarelin acetate 800 micrograms per day or 400 micrograms per day , or danazol 800 micrograms per day . MAIN OUTCOME MEASURES The percentage of patients with dysmenorrhea , dyspareunia or pelvic pain before treatment who still had these symptoms after 6 months of treatment and 6 months following completion of treatment . RESULTS [ table : see text ] CONCLUSIONS Nafarelin acetate and danazol both provided significant relief of dysmenorrhea , dyspareunia , and pelvic pain during treatment and for 6 months following treatment in women with endometriosis", "This study aims to determine whether the levonorgestrel-releasing intrauterine system can influence American Society for Reproductive Medicine endometriosis staging scores , as assessed through second-look laparoscopies , and to compare the results with those obtained with a GnRH agonist . Both treatments reduced the extent of pelvic endometriotic lesions in patients with chronic pelvic pain", "In a r and omized study , the effect of gestrinone ( 2 x 2.5 mg/week ) was compared with the effect of danazol ( 3 x 200 mg/day ) in treating 30 patients with laparoscopically proven endometriotic implants for 6 months . Therapy was effective in 80%-90 % of cases and pregnancy rates were similar , but the incidence of side effects was different in the groups . In addition , buserelin ( 900 micrograms/day intranasally ) was investigated in a multinational , multicenter trial in 275 patients . In 80 % , GnRH agonist treatment induced the disappearance or reduction of endometriotic implants . The main side effects were due to estrogenic suppression . Presently , various methods of hormonal treatment are under investigation , especially to determine recurrency rates of endometriosis and long-term side effects", "A double-blind , double-dummy , 6-month multicenter study comparing the effects of nafarelin and danazol in the treatment of endometriosis was completed recently by investigators from 13 institutions in seven European countries . The 194 patients ( aged 18 to 45 years ) selected for the study were divided into two groups . One group received nafarelin , 200 micrograms twice daily , and placebo capsules identical to danazol , twice daily . The other group received danazol capsules , 200 mg twice daily , and a placebo nasal spray identical to nafarelin , twice daily . A comparison of decreases in both groups of American Fertility Society endometriosis scores and in severity scores developed by the investigators indicates that nafarelin and danazol are equally effective in the treatment of endometriosis", "OBJECTIVES This is the first multicenter , double-blind r and omized clinical trial that compares a depot gonadotropin-releasing hormone agonist with danazol in the treatment of endometriosis . Efficacy results have been previously reported ; this report focuses on safety data . STUDY DESIGN A total of 270 patients from 22 centers were r and omly selected to receive either leuprolide acetate depot ( 3.75 mg injected monthly ) or danazol ( 800 mg administered orally daily ) . Safety outcomes included adverse effects , clinical laboratory changes , and bone mineral density changes . RESULTS Most patients receiving either drug reported side effects , most of which were related to the hypoestrogenism of leuprolide ( e.g. , vasodilatation ) and relative hyper and rogenism of danazol ( e.g. , weight gain ) . Similarly small numbers of patients dropped out of the two treatment groups because of the side effects encountered . Leuprolide depot caused a greater decrease in bone density ; preliminary data suggest a return to baseline on cessation of the drug . Danazol was associated with alteration of serum lipids , specifically a significant decrease in high-density lipoprotein . CONCLUSIONS Although side effects were commonly reported in both groups , the drugs were similarly safe in terms of the absence of serious complications and the results of cessation of therapy . Side effects were largely reversible on discontinuation of medication . More longitudinal data are necessary before the possibility of long-term risks can be excluded , especially as they pertain to bone mineral density and lipids", "OBJECTIVE The purpose of this study was a quantification of changes in endometriosis-associated pain and quality of life during the stimulatory phase of gonadotropin-releasing hormone agonist therapy . STUDY DESIGN One hundred twenty women with significant endometriosis-associated pain participated in a 1-month double-blind , r and omized , placebo-controlled trial . Pain was measured at baseline and at 2 and 4 weeks with visual analog scales and the Endometriosis Symptom Severity score . Quality of life was measured with the SF-36 instrument . Group means and SEMs were calculated . Paired t tests were used after determination of data normality . RESULTS Compared with placebo-treated control subjects women treated with gonadotropin-releasing hormone agonist had a statistically ( P < . 0001 ) and clinical ly significant temporary increase in pain and a concomitant decrease in quality of life . CONCLUSION The stimulatory phase of gonadotropin-releasing hormone agonist therapy is associated with an increase in endometriosis-associated pain and a decrease in quality of life", "OBJECTIVE To project the efficacy and economic consequence of short-term intranasal gonadotropin-releasing hormone agonist ( GnRH-a ) for diagnosis of and therapy for endometriosis . STUDY DESIGN Multicenter , placebo-controlled clinical trials of GnRH-a comparing three vs. six months of treatment , three months of retreatment and three months of postoperative treatment for the symptoms and signs of laparoscopically diagnosed endometriosis . RESULTS The reduction in symptoms and signs of endometriosis was similar at the end of three months to the relief at six months . Retreatment was as effective as initial treatment , and the return of symptoms after laparoscopic surgery plus postoperative treatment for three months was delayed by approximately 18 months as compared to surgery alone . The projected charges for the surgical approaches ( laparoscopy or minilaparoscopy ) to diagnosis and therapy were 50 - 60 % greater than those for the medical approach . CONCLUSION GnRH-a administration for three months could be a cost-effective approach to the presumptive diagnosis and treatment of endometriosis among women with chronic pelvic pain", "OBJECTIVE To investigate the efficacy and safety of tibolone on hypoestrogenic vasomotor symptoms and bone parameters in patients treated with goserelin acetate . DESIGN Prospect i ve , r and omized placebo controlled double-blind study . SETTING Human volunteers in a university-based fertility clinic . PATIENT(S ) Twenty-nine women of mean age 29.2 + /- 4.8 years with mild to severe endometriosis undergoing 6 months of treatment with 3.6 mg goserelin acetate in an SC depot formulation were studied . INTERVENTION(S ) The patients were allocated r and omly to either 2.5 mg/d tibolone ( n = 15 ) or an iron pill ( n = 14 ) in a double-blinded fashion beginning in the third cycle . MAIN OUTCOME MEASURE(S ) Frequency and severity of hot flushes , sweating , irritability , loss of libido , nervousness , and sleeplessness were assessed by the patients using 0 to 6 point scoring system and compared . Sample s of urine were obtained for calcium and creatinine ( Ca : Cr ) ratios at the start of treatment and monthly there after . The vasomotor scoring for each symptom and Ca : Cr ratios before the treatment and at the end of 6th month were analyzed by parametric and nonparametric tests . RESULT ( S ) The mean age , weight , vasomotor scores , pelvic scores , and urine Ca : Cr ratios were similar in both placebo and tibolone group ( 28.7 + /- 4.8 versus 27.6 + /- 6.3 years , 50.9 + /- 5.3 versus 53.1 + /- 7.1 kg , 4.7 + /- 1.1 versus 4.2 + /- 0.8 , and 0.056 + /- 0.008 versus 0.059 + /- 0.006 , respectively ) . The decreases in vasomotor scoring as regards to hot flushing , sweating , and other associated symptoms were statistically significant in tibolone group compared with placebo ( 10.4 + /- 1.6 versus 24.6 + /- 4.9 ) . During the study significant reductions in urine Ca : Cr ratio was obtained in the tibolone patients compared with placebo ( 0.031 + /- 0.006 versus 0.0055 + /- 0.007 ) . The incidence of side effects ( weight change , vaginal bleeding ) was low and did not differ from the placebo group . CONCLUSION ( S ) Considering the beneficial effects of tibolone on vasomotor symptoms and bone loss , our data suggest that this synthetic steroid is an effective and safe option in relieving symptoms induced by GnRH-analogue", "To compare treatment efficacy and safety parameters a total of 55 premenopausal women with histologically proven endometriosis ( stage II-IV ) were r and omized to receive the LHRH-analogue depot triptorelin ( n = 30 ) or the steroid danazol ( n = 25 ) for a total of 24 weeks . Immediately after cessation of the endocrine therapy a second-look operation was performed . Four as well as 24 weeks after the end of treatment patients were seen for re-evaluation of clinical symptoms and safety parameters . Estradiol suppression was significantly more pronounced with triptorelin , while the free and rogenic index rose with danazol . Both substances were equally effective in reducing endometriotic implants ( 58 % and 51 % , respectively ) . Dysmenorrhea was absent at the end of medical therapy in both treatment groups . Dyspareunia and pelvic pain decreased at least by 50 % . Red blood count , thrombocytes , liver enzymes and the atherogenic index rose with danazol , while the urinary calcium/creatinine ratio showed a marked elevation with triptorelin . Adverse effects were mainly due to the hypoestrogenism of the LHRH analogue and the and rogenic/anabolic properties of the steroid . Triptorelin and danazol are equally effective in treating endometriosis . Therefore , choice of treatment should be based on the patient 's medical history and the pharmacological profile of each substance", "OBJECTIVE To compare intranasal nafarelin and intramuscular leuprolide acetate ( LA ) depot in the management of endometriosis . STUDY DESIGN A multicenter , prospect i ve , r and omized , double-placebo , double-blind study was conducted on subjects who had symptoms and signs of endometriosis and bone mineral density ( BMD ) within the age-appropriate normal range . For 6 months , 99 subjects received nafarelin , 200 micrograms twice daily , and placebo injections once monthly ; 93 subjects received LA depot injections , 3.75 mg once monthly , and placebo nasal spray , twice daily . Subjects were followed throughout treatment and for six months after treatment . The main outcome measures were changes in endometriosis symptoms and signs , BMD measurements , subject-reported and objective ly measured hot flushes and circulating estradiol concentrations . RESULTS Nafarelin was as effective as LA depot in alleviating symptoms and signs of endometriosis . LA depot recipients lost significantly more BMD , had more days with subjective hot flushes and more objective ly measured hot flushes than did nafarelin recipients . In the nafarelin group , estradiol levels were consistently higher than in the leuprolide depot group , with significant differences by month 3 of dosing . CONCLUSION Nafarelin and LA depot were equally effective despite higher estradiol levels in nafarelin recipients . Nafarelin-treated subjects lost less BMD , had fewer days with hot flushes and had fewer objective ly measured hot flushes", "As part of a large , multicenter trial , 82 patients with endometriosis were r and omized to 6 months of treatment with either nafarelin or danazol . Among 73 patients who had subjective symptoms ( dysmenorrhea , dyspareunia , or pelvic pain ) at baseline , 94 % of patients treated with nafarelin and 91 % of those treated with danazol had improvement . Resolution of physical findings also was observed in similar percentages of patients in each treatment group . Long-term studies are needed to determine whether these two agents are associated with different cure rates or times to recurrence of disease", "The effectiveness of Buserelin ( Hoechst-Roussel Pharmaceuticals , Inc. , Somerville , NJ ) ( 0.2 mg subcutaneously [ SC ] or 1.2 mg intranasally [ IN ] per day ) and danazol ( 800 mg per day ) in inducing ovarian suppression for the management of endometriosis was compared in a prospect i ve r and omized study . During 6 months of treatment , peripheral follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , and estradiol concentrations were suppressed to a similar degree in both groups . Symptomatic improvement and laparoscopically assessed regression of endometriotic lesions also were comparable . After treatment , 8 of 18 infertile women treated with Buserelin and 5 of 8 treated with danazol conceived . General and hypoestrogenic side effects were similar in both groups , while and rogenic and anabolic were more frequent with danazol . High density lipoprotein (HDL)-cholesterol increased in the Buserelin and decreased in the danazol group . The study indicates that at the dose tested , buserelin and danazol induce a similar degree of ovarian suppression result ing in a comparable clinical improvement and regression of endometriotic lesions", "A prospect i ve , r and omized trial compared hormonal changes induced with intranasal leuprolide 1.6 mg/day to danazol 800 mg/day for treatment of endometriosis . Both regimens induced anovulation and ovarian suppression in all subjects . Mean estradiol ( E2 ) and progesterone ( P ) levels were suppressed with both regimens , but were lower with leuprolide . There was no difference in cumulative follicle-stimulating hormone ( FSH ) and luteinizing hormone ( LH ) levels , although at times during treatment mean levels of these hormones were lower with leuprolide . Higher P levels in the danazol group , most likely of adrenal origin , indicated a suppressive effect on adrenal steroidogenesis . Symptomatic improvement was significant in both groups . Laparoscopy after treatment also demonstrated a decrease in endometriosis scores in both groups . At 12 months after treatment , cumulative pregnancy and live birth rates were similar in both groups . Leuprolide offers an attractive alternative to danazol for the medical treatment of endometriosis", "OBJECTIVE To evaluate the efficacy of half-dose GnRH agonist therapy for endometriosis . DESIGN Prospect i ve , longitudinal pilot study . SETTING Osaka University Hospital . PATIENT(S ) Patients with symptomatic endometriosis . INTERVENTION(S ) Fifteen patients were r and omized to receive either full-dose nafarelin treatment ( 200 microgram b.i.d . ) for 24 weeks ( n = 7 ) or full-dose nafarelin treatment for 4 weeks followed by half-dose nafarelin treatment ( 200 microgram daily ) for 20 weeks ( n = 8) . MAIN OUTCOME MEASURE(S ) Clinical symptoms and the results of physical examinations . Serum E(2 ) and carcinoma antigen 125 ( CA125 ) levels , lipid profiles , and urinary levels of the N-telopeptide of type I collagen . Bone mineral density of the lumbar spine . RESULT ( S ) Subjective and objective manifestations of endometriosis were decreased to a similar extent in both study groups . Adverse effects were markedly reduced with half-dose administration . In the half-dose group , the mean serum E(2 ) level was significantly suppressed by 4 weeks of treatment with full-dose nafarelin and remained at approximately 30 pg/mL with half-dose nafarelin . Loss of bone mineral density was significantly less with half-dose treatment . CONCLUSION ( S ) Half-dose administration of nafarelin after pituitary down-regulation with full-dose nafarelin ( \" draw-back \" therapy ) is a new protocol for the treatment of endometriosis that is effective and associated with fewer adverse effects", "Treatment with nafarelin , a gonadotropin-releasing hormone agonist , reversibly inhibits ovarian function and induces hypoestrogenemia . To determine the efficacy of such hormonal manipulation in the treatment of endometriosis , we r and omly assigned 213 patients with laparoscopically confirmed endometriosis to receive , for six months , either nafarelin by nasal spray ( 400 or 800 micrograms per day ) or oral danazol ( 800 mg per day ) . Placebo nasal spray and placebo tablets were used to double blind the study . Pretreatment and post-treatment laparoscopies were compared by means of the American Fertility Society 's scoring system . More than 80 percent of the patients in each treatment group had a reduction in the extent of disease as assessed by laparoscopy . The mean laparoscopic scores decreased from 21.9 to 12.6 with 800 micrograms of nafarelin , from 20.4 to 11.7 with 400 micrograms of nafarelin , and from 18.4 to 10.5 with danazol ( P = 0.0001 within each group ; there were no statistically significant differences between the groups ) . The percentage of women with severely painful symptoms of endometriosis decreased from about 40 percent to 5 to 10 percent , whereas the percentage with no or minimal discomfort rose from 25 to 70 percent . Of the 149 patients who tried to become pregnant , 58 ( 39 percent ) succeeded after the completion of treatment ; similar rates of pregnancy applied to the three treatment groups . Danazol use decreased high-density lipoprotein levels and increased low-density lipoprotein levels . These changes were not observed in nafarelin users , but a higher percentage of them reported hot flashes and decreased libido . We conclude that nafarelin is an effective agent for treating endometriosis and has few side effects other than hypoestrogenism", "Hypo-oestrogenaemia following surgical oophorectomy leads to a regression of the ectopic endometrial tissue . A medical and transitory oophorectomy can be obtained using leuprolide ac . , an analogue of LH-RH . In this study we compare the results of therapy with danazol or leuprolide in the treatment of endometriosis . Fifty patients affected by endometriosis were selected laparoscopically and recorded under the classification of American Fertility Society . 20 - 40 year old women who were admitted had not received any therapy for endometriosis within the previous 12 months . They were allocated at r and om to open treatment with intramuscular injection of leuprolide ( 3.75 mg/monthly ) or oral danazol . The dose regimen used for this last drug was 600 mg/daily in the majority of patients . 47 women completed a six months therapy , and 42 underwent to a second laparoscopy to evaluate the effects of the treatment . Both danazol and leuprolide were associated to a decreasing of clinical symptoms and to adverse effects that we described in this paper", "Activated B cells have recently been shown to produce soluble CD23 from their membranes . The serum-soluble CD23 concentration in 21 patients with pelvic pain diagnosed as having endometriosis and confirmed by histology , and in 18 patients without pelvic pain , who had a normal pelvis during laparoscopic sterilization , was studied by chemiluminescent enzyme-linked immunosorbent assay . The endometriosis patients were r and omized to 3 months of either danazol or leuprolide acetate injection . Serum was taken before and after 3 months of therapy . The serum-soluble CD23 concentration was significantly elevated in patients with endometriosis when compared with the controls ( P < 0.0001 ) . There was no correlation between soluble CD23 concentrations and the severity of endometriosis ( r = 0.48 , P > 0.05 ) . The serum concentration of soluble CD23 decreased significantly on treatment with danazol but not leuprolide acetate ( P < 0.05 ) . We conclude that the elevation of soluble CD23 in patients with endometriosis suggests that there is activation of B cells , which respond to danazol but not leuprolide acetate injection", "Summary : : A r and omized and double‐blind trial was carried out comparing intranasal nafarelin acetate ( 400 μg daily ) and oral danazol ( 600 mg daily ) , given over 6 months , in the treatment of 49 patients with laparoscopically proven endometriosis . Both drugs produced a highly significant and similar reduction ( of 60 to 70 % ) in objective American Fertility Society scoring , even in severe disease . No effect was seen on adhesions . Both drugs suppressed oestradiol levels to a similar extent , although nafarelin caused a substantial rise in the first 2 weeks after the initiation of therapy . Nafarelin suppressed LH substantially and FSH , testosterone and prolactin to a small degree , whereas FSH and LH increased slightly during danazol . Pregnancies occurred in 12 of 22 infertile women in the 12 months following nafarelin , and in 6 of 14 in the danazol group . Side‐effects were reported at a similar rate with both drugs , but the pattern was different . Hot flushes were the predominant side effect with nafarelin , although oestradiol levels were not suppressed to the extent expected . Small amounts of spotting or light bleeding were experienced with both drugs , but these tended to decrease with time with nafarelin and increase with danazol" ]

[ "22442172", "15687128", "16757495", "21911657", "22496337", "15016485" ]

[ "Association of Statins and Statin Discontinuation With Poor Outcome and Survival After Intracerebral Hemorrhage", "Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients.", "Serum cholesterol, haemorrhagic stroke, ischaemic stroke, and myocardial infarction: Korean national health system prospective cohort study", "Statins and intracerebral hemorrhage: a retrospective cohort study.", "Total and High-Density Lipoprotein Cholesterol and Stroke Risk", "Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions." ]

[ "Background and Purpose — Studies suggest a protective role for statins after intracerebral hemorrhage , but many failed to assess statin discontinuation , did not include postdischarge outcomes , or did not account for withdrawal of care . We studied the relationship between preintracerebral hemorrhage statin use and in-hospital statin discontinuation on stroke severity and 30-day mortality . Methods — We analyzed data from the Registry of the Canadian Stroke Network and determined the adjusted ORs for statin use and outcomes , controlling for stroke severity and other covariates . Results — We analyzed 2466 consecutive patients with intracerebral hemorrhage from 2003 to 2008 : median age was 71 years , 53.6 % were male , and 30-day mortality rate was 36.5 % . Overall , 537 ( 21.7 % ) were taking statins before presentation . Compared with nonusers , statin users were less likely to have severe strokes on presentation ( 54.7 % versus 63.3 % ) but had similar rates of poor outcome ( 70 % versus 67 % ) and 30-day mortality ( 36 % versus 37 % ) . Statins were discontinued on admission in 158 of 537 ( 29.4 % ) ; these patients were more likely to have severe stroke ( 65 % versus 27 % , P<0.01 ) , poor outcome ( 90 % versus 62 % , P<0.01 ) , and to have died by 30 days ( 71 % versus 21 % , P<0.01 ) . After adjusting for stroke severity , statin discontinuation was still associated with poor outcome ( adjusted OR , 2.4 ; 95 % CI , 1.13–4.56 ) and higher mortality ( adjusted OR , 2.0 ; 95 % CI , 1.30–3.04 ) . However , these associations were attenuated and no longer significant after excluding patients treated palliatively . Conclusions — We found no association between preadmission statin use and outcomes in intracerebral hemorrhage . Statin discontinuation may worsen outcomes or may simply be a marker of worse underlying prognosis", "BACKGROUND Soluble CD40L ( sCD40L ) , a substance that maximally reflects in vivo platelet activation , is increased in patients with hypercholesterolemia . We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin . METHODS AND RESULTS Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1 + 2 , a marker of thrombin generation , were investigated in 30 hypercholesterolemic patients and 20 healthy subjects . Hypercholesterolemic patients were then r and omized to either diet ( n=15 ; group A ) or atorvastatin 10 mg/d ( group B ) ; the aforementioned variables were measured at baseline and after 3 days of treatment . Compared with referents , hypercholesterolemic patients showed higher values of platelet CD40L ( P<0.005 ) , sCD40L ( P<0.005 ) , and F1 + 2 ( P<0.003 ) . Platelet CD40L was significantly correlated with sCD40L ( P<0.001 ) , and the latter was significantly correlated with F1 + 2 ( P<0.001 ) . The intervention trial showed no changes in group A but a significant decrease in platelet CD40L ( P<0.01 ) , sCD40L ( P<0.002 ) , and F1 + 2 ( P<0.03 ) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes ; also , atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes . CONCLUSIONS This study shows that , in hypercholesterolemia , platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1 + 2 . Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation , independently of its cholesterol-lowering effect", "Abstract Objective To investigate risk factors , such as heavy alcohol consumption , that might explain any increased risk of haemorrhagic stroke associated with low blood cholesterol . Design Prospect i ve cohort study . Setting Korea . Participants 787 442 civil servants ( 661 700 men , 125 742 women ) aged 30 - 64 . Main outcome measures Cardiovascular risk factors were assessed at biennial health check . Data on morbidity and mortality were ascertained from 1990 to 2001 using hospital admissions and mortality surveillance systems . Results 6328 cases of ischaemic stroke ( 6021 men , 307 women ) , 3947 cases of haemorrhagic stroke ( 3748 men , 199 women ) , 3170 cases of undefined stroke ( 2902 men , 268 women ) , and 4417 cases of myocardial infa rct ion ( 4305 men , 112 women ) occurred . Ischaemic stroke and myocardial infa rct ion were strongly and positively associated with blood cholesterol ( hazard ratio per 1 mmol/l cholesterol 1.20 ( 95 % confidence 1.16 to 1.24 ) and 1.48 ( 1.43 to 1.53 ) , respectively ) . Haemorrhagic stroke showed an inverse association in fully adjusted models ( 0.91 , 0.87 to 0.95 ) . This inverse association was confined to participants with hypertension . When stratified by concentration of γ glutamyl transferase ( GGT ) , an indicator of alcohol consumption , the association was not seen in participants with low concentrations of GGT , and it was independent of hypertension in those with high concentrations of GGT ( > 80 U/l ) . Conclusion High alcohol consumption may underlie the association between low blood cholesterol and increased risk of haemorrhagic stroke", "BACKGROUND A recent post hoc analysis of a large r and omized trial in patients with cerebrovascular disease suggested that statins may increase the risk of intracerebral hemorrhage ( ICH ) . OBJECTIVE To examine the association between statins and ICH in patients with recent ischemic stroke in a population -based setting . DESIGN Retrospective propensity-matched cohort study with accrual from July 1 , 1994 , to March 31 , 2008 . SETTING Ontario , Canada . PARTICIPANTS A total of 17 872 patients aged 66 years and older who initiated statin therapy following acute ischemic stroke and were followed for a median of 4.2 years ( interquartile range , 2.4 - 5.0 years ) . To enhance causal inference , we conducted several tests of specificity to exclude healthy user bias in this sample . Main Outcome Measure Hospitalization or emergency department visit for ICH defined using vali date d diagnosis coding . RESULTS Overall , 213 episodes of ICH occurred . In the primary analysis comparing statin users with nonusers , we found no association between statins and ICH ( hazard ratio = 0.87 ; 95 % confidence interval , 0.65 - 1.17 ) . Subgroup and dose-response analyses yielded similar results . In tests of specificity , statin therapy was not associated with bone mineral density testing , vitamin D or B(12 ) screening , gastrointestinal endoscopy , or elective knee arthroplasty , suggesting that results were not due to healthy user bias or differences in quality of care . CONCLUSION Statin exposure following ischemic stroke was not associated with ICH", "Background and Purpose — The association of total and high-density lipoprotein ( HDL ) cholesterol with stroke risk is unclear , especially regarding hemorrhagic stroke . Methods — We prospect ively investigated the associations of serum total and HDL cholesterol and total/HDL cholesterol ratio with total and type-specific stroke incidence among 58 235 Finnish people aged 25 to 74 years and free of coronary heart disease and stroke at baseline . Results — During a mean follow-up period of 20.1 years , 3914 participants developed stroke events ( 3085 ischemic , 497 intracerebral hemorrhage , and 332 subarachnoid hemorrhage ) . The multivariable-adjusted hazard ratios at different levels of total cholesterol ( < 5 [ reference ] , 5–5.9 , 6–6.0 , ≥7.0 mmol/L ) were 1.00 , 1.05 , 1.16 , and 1.22 for total stroke ( Ptrend=0.036 ) and 1.00 , 1.06 , 1.19 , and 1.27 for ischemic stroke ( Ptrend=0.02 ) in men and 1.00 , 0.58 , 0.61 , and 0.50 for intracerebral hemorrhagic stroke ( Ptrend=0.02 ) in women , respectively . Low levels of HDL cholesterol and high total/HDL cholesterol ratio were associated with increased risks of total and ischemic stroke in both men and women . These associations disappeared in men but remained significant in women after further adjustment for body mass index , blood pressure , and history of diabetes . Conclusions — The study showed a positive association between total cholesterol and total and ischemic stroke risks in men and an inverse association between total cholesterol and intrahemorrhagic stroke risk in women . The inverse association of HDL cholesterol and a positive association of total/HDL cholesterol ratio with total and ischemic stroke risks were found in men and women . These associations attenuated after adjustment for body mass index , blood pressure , and history of diabetes", "BACKGROUND Lower blood cholesterol concentrations have consistently been found to be strongly associated with lower risks of coronary disease but not with lower risks of stroke . Despite this observation , previous r and omised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke , but large-scale prospect i ve confirmation has been needed . METHODS 3280 adults with cerebrovascular disease , and an additional 17256 with other occlusive arterial disease or diabetes , were r and omly allocated 40 mg simvastatin daily or matching placebo . Subgroup analyses were prespecified of first \" major vascular event \" ( ie , non-fatal myocardial infa rct ion or coronary death , stroke of any type , or any revascularisation procedure ) in prior disease subcategories . Subsidiary outcomes included any stroke , and stroke sub-type . Comparisons are of all simvastatin-allocated versus all placebo-allocated participants ( ie , \" intention-to-treat \" ) , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( 39 mg/dL ) during the 5-year treatment period . FINDINGS Overall , there was a highly significant 25 % ( 95 % CI 15 - 34 ) proportional reduction in the first event rate for stroke ( 444 [ 4.3 % ] simvastatin vs 585 [ 5.7 % ] placebo ; p<0.0001 ) , reflecting a definite 28 % ( 19 - 37 ) reduction in presumed ischaemic strokes ( p<0.0001 ) and no apparent difference in strokes attributed to haemorrhage ( 51 [ 0.5 % ] vs 53 [ 0.5 % ] ; rate ratio 0.95 [ 0.65 - 1.40 ] ; p=0.8 ) . In addition , simvastatin reduced the numbers having transient cerebral ischaemic attacks alone ( 2.0 % vs 2.4 % ; p=0.02 ) or requiring carotid endarterectomy or angioplasty ( 0.4 % vs 0.8 % ; p=0.0003 ) . The reduction in stroke was not significant during the first year , but was already significant ( p=0.0004 ) by the end of the second year . Among patients with pre-existing cerebrovascular disease there was no apparent reduction in the stroke rate , but there was a highly significant 20 % ( 8 - 29 ) reduction in the rate of any major vascular event ( 406 [ 24.7 % ] vs 488 [ 29.8 % ] ; p=0.001 ) . The proportional reductions in stroke were about one-quarter in each of the other subcategories of participant studied , including : those with coronary disease or diabetes ; those aged under or over 70 years at entry ; and those presenting with different levels of blood pressure or lipids ( even when the pretreatment LDL cholesterol was below 3.0 mmol/L [ 116 mg/dL ] ) . INTERPRETATION Much larger numbers of people in the present study suffered a stroke than in any previous cholesterol-lowering trial . The results demonstrate that statin therapy rapidly reduces the incidence not only of coronary events but also of ischaemic strokes , with no apparent effect on cerebral haemorrhage , even among individuals who do not have high cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rate of ischaemic strokes by about one-quarter and so , after making allowance for non-compliance in the trial , actual use of this regimen would probably reduce the stroke rate by about a third . HPS also provides definitive evidence that statin therapy is beneficial for people with pre-existing cerebrovascular disease , even if they do not already have manifest coronary disease" ]

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[ "A prospective, randomized, pivotal trial of a novel extravascular collagen-based closure device compared to manual compression in diagnostic and interventional patients.", "A multicenter, randomized, controlled trial of totally percutaneous access versus open femoral exposure for endovascular aortic aneurysm repair (the PEVAR trial).", "Closure of the femoral artery after cardiac catheterization: A comparison of Angio‐Seal, StarClose, and manual compression", "Utilization of collagen-based vascular closure devices in patients with severe peripheral artery disease.", "A comparison of Percutaneous femoral access in Endovascular Repair versus Open femoral access (PiERO): study protocol for a randomized controlled trial", "Percutaneous closure devices for endovascular repair of infrarenal abdominal aortic aneurysms: a prospective, non-randomized comparative study.", "Prospective Comparison of Angio-Seal versus Manual Compression for Hemostasis after Neurointerventional Procedures under Systemic Heparinization", "Randomized comparison of effects of suture-based and collagen-based vascular closure devices on post-procedural leg perfusion", "A randomised controlled trial comparing StarClose and AngioSeal vascular closure devices in a district general hospital--the SCOAST study.", "Large-scale experience with an anchorless vascular closure device in a real-life clinical setting", "Comparison of Exo-Seal® and Angio-Seal® for arterial puncture site closure", "Predictors of Failure of Closure in Percutaneous EVAR Using the Prostar XL Percutaneous Vascular Surgery Device.", "The Angio-Seal™ femoral closure device allows immediate ambulation after coronary angiography and percutaneous coronary intervention.", "A randomised controlled trial comparing the routine use of an Angio-Seal STS device strategy with conventional femoral haemostasis methods in a district general hospital.", "A prospective randomized single-blind trial of patient comfort following vessel closure: extravascular synthetic sealant closure provides less pain than a self-tightening suture vascular compression device", "Randomised comparison of manual compression and FemoSeal™ vascular closure device for closure after femoral artery access coronary angiography: the CLOSure dEvices Used in everyday Practice (CLOSE-UP) study.", "MynxGrip for Closure of Antegrade Puncture After Peripheral Interventions With Same-Day Discharge", "A randomized trial comparing compression, perclose proglide™ and Angio‐Seal VIP™ for arterial closure following percutaneous coronary intervention: The cap trial", "A propensity analysis of the risk of vascular complications after cardiac catheterization procedures with the use of vascular closure devices.", "The safety and efficacy of an extravascular, water‐soluble sealant for vascular closure: Initial clinical results for Mynx™", "The StarClose® vascular closure system: Interventional results from the CLIP study", "Use of a novel access technology for femoral artery catheterization: results of the RECITAL trial.", "Percutaneous endovascular abdominal aortic aneurysm repair: methods and initial outcomes from the first prospective, multicenter trial.", "Total percutaneous endovascular aneurysm repair with the dual 6-F Perclose-AT preclosing technique: a case-control study.", "Cardiva Catalyst II Vascular Access Management Device in Percutaneous Diagnostic and Interventional Procedures with Same-Day Discharge (CATALYST II Trial)", "StarClose® vascular closure system (VCS) is safe and effective in patients who ambulate early following successful femoral artery access closure—results from the RISE clinical trial", "A modified “Preclosure” technique after percutaneous aortic valve replacement", "VIPER-2: A Prospective, Randomized Single-Center Comparison of 2 Different Closure Devices with a Hemostatic Wound Dressing for Closure of Femoral Artery Access Sites", "Comparison of vascular closure devices vs manual compression after femoral artery puncture: the ISAR-CLOSURE randomized clinical trial.", "Closure device or manual compression in patients undergoing percutaneous coronary intervention: a randomized comparison.", "Feasibility and clinical benefit of a suture-mediated closure device for femoral vein access after percutaneous edge-to-edge mitral valve repair.", "A randomized comparison of a novel bioabsorbable vascular closure device versus manual compression in the achievement of hemostasis after percutaneous femoral procedures: the ECLIPSE (Ensure's Vascular Closure Device Speeds Hemostasis Trial).", "Efficacy of a novel procedure sheath and closure device during diagnostic catheterization: the multicenter randomized clinical trial of the FISH device.", "The Angio-Seal Evolution registry: outcomes of a novel automated Angio-Seal vascular closure device." ]

[ "OBJECTIVES The RESPECT trial was aim ed at evaluating safety/efficacy of a new extravascular closure system in diagnostic ( Dx ) and interventional ( Ix ) procedures performed through 6 or 7 Fr introducer sheaths . BACKGROUND Although vascular closure devices ( VCDs ) have been available for two decades , manual compression ( MC ) remains the st and ard of care in many institutions . VCDs have not been shown to have greater safety than MC . METHODS The RESPECT trial was a multicenter , r and omized comparison of the Vascade VCD ( Cardiva Medical , Inc ) versus MC in Dx and Ix patients undergoing femoral access . Endpoints included time to hemostasis ( TTH ) , time to ambulation ( TTA ) , time to discharge eligibility ( TTDe ) , device and procedure success , major and minor complications . Subjects were r and omized 2:1 ( Vascade vs MC ) . RESULTS A total of 420 patients were enrolled ( 211 Dx , 209 Ix ) . Mean age was 62 ± 11 years and 29 % were female . For Ix Vascade/MC patients , 77%/69 % received bivalirudin , 27%/26 % received heparin , and 8%/3 % received glycoprotein IIb/IIIa inhibitors , respectively . Patients were followed for 30 ± 7 days . A total of 415 subjects ( 98.8 % ) completed follow-up . TTH was 3.0 minutes ( range , 0.6 - 31.6 minutes ) for Vascade vs 20.0 minutes ( range , 0.0 - 97.0 minutes ) for MC ; TTA was 3.2 hours ( range , 1.0 - 78.0 hours ) for Vascade vs. 5.2 hours ( range , 1.7 - 22.8 hours ) for MC ; and TTDe was 3.6 hours ( range , 1.4 - 78.4 hours ) for Vascade vs. 5.7 hours ( range , 2.2 - 23.2 hours ) for MC . Device and procedure success rates were 98 % for Vascade and 100 % for MC . Minor events were 1.1 % for Vascade and 7 % for MC . No major access-site related complications were reported in either arm . CONCLUSION Despite high percentage of bivalirudin use , there were no major access-site related complications in either arm . Vascade use reduced rates of minor access-site related complications , and significantly shortened TTH , TTA , and TTDe compared to MC", "OBJECTIVE The first multicenter r and omized controlled trial was design ed and conducted to assess the safety and effectiveness of totally percutaneous endovascular aortic aneurysm repair ( PEVAR ) with use of a 21F endovascular stent graft system and either an 8 F or 10 F suture-mediated closure system ( the PEVAR trial , NCT01070069 ) . A noninferiority trial design was chosen to compare percutaneous access with st and ard open femoral exposure . METHODS Between 2010 and 2012 , 20 U.S. institutions participated in a prospect i ve , Food and Drug Administration-approved r and omized trial to evaluate percutaneous femoral artery access and closure by a \" preclose \" technique in conjunction with endovascular abdominal aortic aneurysm repair . A total of 151 patients were allocated by a 2:1 design to percutaneous access/closure ( n = 101 ) or open femoral exposure ( n = 50 [ FE ] ) . PEVAR procedures were performed with either the 8 F Perclose ProGlide ( n = 50 [ PG ] ) or the 10 F Prostar XL ( n = 51 [ PS ] ) closure devices . All endovascular abdominal aortic aneurysm repair procedures were performed with the Endologix 21 F profile ( outer diameter ) sheath-based system . Patients were screened by computed tomography with three-dimensional reconstruction and independent physician review for anatomic suitability and adequate femoral artery anatomy for percutaneous access . The primary trial end point ( treatment success ) was defined as procedural technical success and absence of major adverse events and vascular complications at 30 days . An independent access closure sub study evaluated major access-related complications . Clinical utility and procedural outcomes , ankle-brachial index , blood laboratory analyses , and quality of life were also evaluated with continuing follow-up to 6 months . RESULTS Baseline characteristics were similar among groups . Procedural technical success was 94 % ( PG ) , 88 % ( PS ) , and 98 % ( FE ) . One-month primary treatment success was 88 % ( PG ) , 78 % ( PS ) , and 78 % ( FE ) , demonstrating noninferiority vs FE for PG ( P = .004 ) but not for PS ( P = .102 ) . Failure rates in the access closure sub study analyses demonstrated noninferiority of PG ( 6 % ; P = .005 ) , but not of PS ( 12 % ; P = .100 ) , vs FE ( 10 % ) . Compared with FE , PG and PS yielded significantly shorter times to hemostasis and procedure completion and favorable trends in blood loss , groin pain , and overall quality of life . Initial noninferiority test results persist to 6 months , and no aneurysm rupture , conversion to open repair , device migration , or stent graft occlusion occurred . CONCLUSIONS Among trained operators , PEVAR with an adjunctive preclose technique using the ProGlide closure device is safe and effective , with minimal access-related complications , and it is noninferior to st and ard open femoral exposure . Training , experience , and careful application of the preclose technique are of paramount importance in ensuring successful , sustainable outcomes", "Objectives : To compare Angio‐Seal ( AS ) and StarClose ( SC ) and manual compression ( MC ) on efficacy of hemostasis , complication rate , safety of early mobilization , and patient comfort . Background : Closure of the femoral artery after cardiac catheterization can be obtained through different methods . Today , physicians can choose from a number of different devices to achieve arterial closure . Methods : In a prospect i ve trial 450 patients were r and omized to AS , SC , or MC . Patients were mobilized 1 to 2 hr after device placement , and 6 hr after MC . Data were collected during hospital admission and by telephone at one month after hospital discharge . Results : Devices were used in 138/150 allocated to AS and 124/150 allocated to SC patients ( 92 % vs. 83 % , P = 0.015 ) Patients with MC experienced more pain during sheath removal than patients receiving a device , and rated their period of bed rest as less comfortable . Oozing and need for pressure b and age at the puncture site were observed in 37 AS patients and 57 SC patients ( 25 % vs. 38 % , P = 0.002 ) . Hematoma occurred in 15 AS patients , in 17 SC patients , and in 14 MC patients ( 11 vs. 14 vs. 9 % , ns ) . Conclusion : There is no difference in safety between the three methods of arterial closure . SC was more often not used or successfully deployed . SC patients more often had continuing oozing . On patient comfort , closure devices performed better than MC . Early ambulation in patients with a closure device is safe . AS is the preferred method of arterial closure after cardiac catheterization . © 2008 Wiley‐Liss ,", "BACKGROUND Collagen-based vascular closure devices ( VCD ) are commonly used after catheterization with femoral access . However , data about complication rates due to the utilization of VCDs in patients with known peripheral artery disease ( PAD ) of the lower limbs are inconsistent and patients with significant PAD are excluded in most VCD trials . In this study , we aim ed to assess complication rates of collagen-based VCDs in patients with significant PAD . METHODS Patients with significant PAD treated with a VCD ( Angio-Seal ; St Jude Medical , Inc ) after percutaneous therapeutic interventions of lower extremities were included in this study . Significant PAD was defined as Fontaine ≥2b . In-hospital complications ( bleeding , spurious aneurysm , vessel occlusion , dissection , surgical repair , vasovagal reaction ) were recorded . RESULTS A total of 121 patients ( 64.6 ± 11.3 years , 77 % male ) were included . PAD stage IIb was present in 99 patients ( stage III in 8 patients , stage IV in 14 patients ) . A total of 112 treatments ( 93.3 % ) processed without complications ( major complication rate , 1.7 % ; minor complication rate , 5.0 % ) . There was a trend toward higher prevalence of complications with increasing size of closure device and with the stage of PAD ; however , this trend was not statistically significant ( P>.05 for all ) . CONCLUSION We report moderate complication rates of collagen-based VCDs in patients with significant PAD . Our data suggest that Angio-Seal may be safe in patients with PAD after catheter intervention . Further r and omized trials with larger sample size comparing VCD with st and ard manual compression in patients with significant PAD are required", "Background Access for endovascular repair of abdominal aortic aneurysms ( EVAR ) is obtained through surgical cutdown or percutaneously . The only devices suitable for percutaneous closure of the 20 French arteriotomies of the common femoral artery ( CFA ) are the Prostar ™ and Proglide ™ devices ( Abbott Vascular ) . Positive effects of these devices seem to consist of a lower infection rate , and shorter operation time and hospital stay . This conclusion was published in previous reports comparing techniques in patients in two different groups ( cohort or r and omized ) . Access techniques were never compared in one and the same patient ; this research simplifies comparison because patient characteristics will be similar in both groups . Methods / Design Percutaneous access of the CFA is compared to surgical cutdown in a single patient ; in EVAR surgery , access is necessary in both groins in each patient . R and omization is performed on the introduction site of the larger main device of the endoprosthesis . The contralateral device of the endoprosthesis is smaller . When we use this type of r and omization , both groups will contain a similar number of main and contralateral devices . Preoperative nose cultures and perineal cultures are obtained , to compare colonization with postoperative wound cultures ( in case of a surgical site infection ) . Furthermore , patient comfort will be considered , using VAS-scores ( Visual analog scale ) . Punch biopsies of the groin will be harvested to retrospectively compare skin of patients who suffered a surgical site infection ( SSI ) to patients who did not have an SSI . Discussion The PiERO trial is a multicenter r and omized controlled clinical trial design ed to show the consequences of using percutaneous access in EVAR surgery and focuses on the occurrence of surgical site infections . Trial registration NTR4257 10 November 2013 , NL44578.042.13", "PURPOSE This study was design ed to describe and evaluate our preliminary results with a percutaneous arterial closure device as compared to those obtained with conventional femoral surgical cut down during endovascular repair of abdominal aortic aneurysms ( AAA ) . MATERIAL AND METHODS Between January 2004 and December 2006 , 40 of 86 AAA patients selected for endovascular repair met the criteria for inclusion in this study . Nineteen of these patients ( Group A ) received a bifurcated endograft placed by direct puncture of the femoral arteries ( 38 femoral triangles ) with closure by a Prostar((R ) ) percutaneous arterial closure device ( Abbott ) . The other 21 patients ( control group B ) were managed with a bifurcated endograft placed by conventional open surgery ( 42 femoral triangles ) . Data concerning all 40 patients were collected prospect ively and analyzed . RESULTS The technical success rate was 92 % ( group A ) vs 90 % ( group B ) , P=0.79 . The incidence of perioperative complications was 16 % ( 3/19 ) in group A and 14 % ( 3/21 ) in group B ( P=0.89 ) . The mean hospital stay was 5.8 days in group A and 7.8 days in group B ( P=0.05 ) . The difference in the length of hospitalisation was associated with reduced cost for the percutaneous group ( 5579.60 euros vs. 7503.60 euros ; P=0.04 ) , that counterbalanced the cost induced by the Prostar XL((R ) ) suture mediated device . Mean follow-up in both groups was 12 months . The overall incidence of locoregional complications after one year of follow-up was 11 % ( 2/19 ) in group A and 19 % ( 4/21 ) in group B ( P=0.45 ) . CONCLUSION This study confirms the feasibility and safety of total percutaneous endovascular AAA repair . Our preliminary results suggest that the costs paid by healthcare providers for endovascular AAA repair might not be increased with the selective use of percutaneous closure devices", "This article addresses the utility of Angio-Seal versus manual hemostasis in anticoagulated patients following neurointerventional procedures . In a study of 174 punctures , 104 were closed with Angio-Seal and the rest with manual compression . All patients had activated clotting time values between 250–500 seconds at the time of closure . Mean hemostasis times were significantly longer with manual compression and hematomas 3 times more common . Using Angio-Seal led to arterial occlusion in 1 patient who was successfully revascularized . Thus , Angio-Seal is fast and effective in this setting . BACKGROUND AND PURPOSE : The use of arterial closure device in patients with prolonged high ACT values has not been extensively studied . The aim of this study was to compare the safety and efficacy of an arterial closure device , Angio-Seal , with manual compression in patients on anticoagulation following neurointerventional procedures . MATERIAL S AND METHODS : This was a 2-center prospect i ve study approved by our institutional review boards . In total , 153 consecutive patients with 174 arteriotomies ( 86 men , 67 women ; mean age , 56.1 ± 16.2 years ) following femoral arterial puncture for neurointerventional procedures were enrolled in convenience sampling . All of the patients were systemically heparinized with an ACT between 250 and 500 seconds before removal of the sheath after the procedure . Group 1 consisted of 104 arteriotomies that were closed with an arterial closure device ( Angio-Seal ) , and group 2 consisted of 70 arteriotomies treated with manual compression . The ACT before sheath removal , time to hemostasis , and complications immediately and 24 hours after the procedure were recorded . RESULTS : The mean ACT before sheath removal was 284.8 ± 37.6 seconds ( range , 250–414 seconds ) . The mean hemostasis time was significantly shorter in group 1 ( 2.4 ± 11.7 minutes ) compared with group 2 ( 44.7 ± 27.4 minutes ) ( 95 % CI , 38.16–51.24 minutes ; P < .001 ) . Hematoma occurred in 9 patients in group 1 ( 8.6 % ) and 18 in group 2 ( 25.7 % ) . One patient developed an arterial occlusion after hemostasis with the closure device , but this was successfully revascularized . CONCLUSIONS : Angio-Seal was found to safely and effectively achieve rapid closure of the femoral access site in patients undergoing neuroendovascular procedures under systemic heparinization with an ACT in the range of 250–500 seconds", "Background Vascular closure devices ( VCD ) are well established to facilitate hemostasis after cardiac catheterization procedures . However , impairment of flow due to the reduction of femoral artery diameter remains a major concern . The present study aims to evaluate leg perfusion before and after application of collagen- and suture-based vascular closure devices . Methods A total of 366 patients ( age : 64.3 years±10.7 , male : 71.3 % ) were r and omized to receive femoral access site closure with either a collagen-based closure device ( group A ) ( n=214 ) or a suture-mediated device ( group B ) ( n=152 ) , immediately following coronary catheterization procedures . In all patients , the anklebrachial- index ( ABI ) was measured before and the day after closure device application . Results In group A , mean ABI at baseline was 1.09±0.2 , in group B 1.11±0.2 . In both groups , there was a significant , albeit clinical ly not relevant , reduction in post-procedural ABI ( group A : 1.04±0.2 , p<0.01 vs baseline , group B : 1.06±0.2 , p<0.01 vs baseline ) . ΔABI was not different between both VCD groups ( p=0.55 ) . In patients with peripheral vascular disease ( PVD ) , neither the Angioseal device ( mean ABI at baseline 0.76±0.1 ) nor the Perclose-device ( mean ABI at baseline 0.79±0.1 ) induced a remarkable impairment of leg perfusion ( Angioseal : 0.77±0.1 , p=0.9 vs baseline , Perclose : 0.78±0.1 , p=1.0 vs baseline ) . Clinical ly , no aggravation of claudication was observed in the PVD patient group . Conclusion Both vascular closure devices are not associated with clinical ly relevant reduction in ABI . There was no difference between the two groups with respect to the level of flow impairment . Both devices may be safely used in patients with reduced ABI", "AIMS AngioSeal and StarClose are vascular closure devices ( VCDs ) that can be used following cardiac catheterisation via the femoral artery to achieve haemostasis . Both devices have been demonstrated to be superior to conventional manual pressure , which reduce time to haemostasis and time to patient ambulation . We sought to compare these devices in a prospect i ve , r and omised trial . METHODS Patients undergoing elective coronary angiography were r and omised to receive either AngioSeal VIP or StarClose VCD with immediate postprocedure mobilisation . Bruising was recorded at 30 min , 60 min and at 1 week postprocedure . Patient satisfaction surveys were taken at 1 h and 1 week postprocedure . Complications for both groups were compared . RESULTS Four hundred and one patients were included . Arteriotomy closure was achieved in 144 of 208 ( 69.2 % ) patients r and omised to AngioSeal and 134 of 193 ( 69.3 % ) patients r and omised to StarClose ( p = ns ) . There was no significant bruising in either group at either 30 or 60 min postprocedure . However , at 1 week , there was significantly more bruising in the AngioSeal group than the StarClose group ( 63.1 vs. 38.5cm2 , p = 0.02 ) . Patient satisfaction and pain perception with the procedure at closure were not significantly different between the groups . Deployment success and instant mobilisation rates were significantly lower for junior , as compared with senior , operators . CONCLUSION Achievement of haemostasis is similar with both AngioSeal and StarClose . The StarClose vascular closure device results in significantly less bruising at 1 week postprocedure as compared with AngioSeal , with no significant differences in complication rates . Patients ' pain perception and satisfaction are similar with both VCDs", "Aims This study was design ed to evaluate safety and effectiveness of the vascular closure device Exoseal ( Cordis ) for hemostatic control following cardiac catheterization in a real-life clinical setting . Methods and results This prospect i ve , single-center study enrolled n = 2,031 consecutive patients who underwent coronary angiography via the femoral artery ± PCI ( n = 801 ) . Patients were excluded if they had radial access , percutaneous repair of structural heart disease , or if they had severe peripheral artery disease . If clinical abnormalities were discovered at the access site , color Doppler ultrasound was performed . The composite primary endpoint was defined as bleeding/vascular complications and device failure , and it was experienced by 5.4 % ( n = 110 ) of patients . The most frequent complications were pseudoaneurysm ( 2.9 % , n = 58 ) and access-site hematoma > 6 cm ( 1.8 % , n = 37 ) . The overall device failure rate was 0.7 % ( n = 14 ) . Multiple logistic regression analysis demonstrated that the strongest independent predictors of bleeding/vascular complications and /or device failure were procedure duration ( OR 2.1 , CI 1.4–3.2 ) , PCI ( OR 2.7 , CI 1.7–4.2 ) , GP IIb/IIIa inhibitors ( OR 2.9 , CI 1.5–5.7 ) , and age ( OR 2.2 , CI 1.4–3.5 ) . Conclusions These results indicate that Exoseal was safe in a broad collective of patients . However , lengthy procedures , PCIs , the use of GP IIb/IIIa inhibitors , and elderly patients require special attention", "Background The use of extravascular femoral closure devices in patients undergoing coronary angiography/intervention has not been sufficiently evaluated . We sought to define the impact of an extravascular polyglycolic acid ( PGA ) plug for the closure of a femoral access site in patients undergoing coronary angiography and /or percutaneous coronary intervention . Methods In this prospect i ve , single-blind , multicenter trial we r and omly assigned 319 patients to vessel closure with Angio-Seal ® or Exo-Seal ® . We hypothesized that the use of an extravascular closure device is not inferior to an anchor/plug-mediated device regarding the occurrence of the composite primary endpoint : hematoma > 5 cm , significant groin bleeding ( TIMI major bleed ) , false aneurysm , and device failure . Results There was no significant difference in patient baseline characteristics or procedural results . After 24 h the primary endpoint occurred in nine patients ( 5.6 % ) in the Angio-Seal ® group and in 13 patients ( 8.2 % ) inthe Exo-Seal ® group ( p = 0.38 ) . Hematoma > 5 cm was noted in three patients ( 1.9 % ) receiving Angio-Seal ® vs. two patients ( 1.3 % ) receiving Exo-Seal ® ( p = 0.99 ) . In one patient ( 0.6 % ) of the Exo-Seal ® group , TIMI major bleeding occurred , requiring transfusion ( p = 0.49 ) . There were four ( 2.5 % ) false aneurysms found in patients treated with Angio-Seal ® and two ( 1.3 % ) in patients treated with Exo-Seal ® ( p = 0.68 ) . There was a trend for a higher incidence of device failure in the Exo-Seal ® group ( 1.2 vs. 5.2 % , p = 0.06 ) . At telephone interview after 30 days , there was no significant difference found regarding the events readmission with surgery of puncture site , infection , bleeding , hematoma , or pain . Conclusion In the present study , there were no significant differences found regarding the occurrence of hematoma > 5 cm , major bleeding , false aneurysm , and device failure between Angio-Seal ® and Exo-Seal ® 24 h after device implantation . ZusammenfassungHintergrundDie Verwendung extravaskulärer Verschlusssysteme für die Femoralarterie bei Patienten mit Koronarangiographie/perkutaner Intervention wurde bisher nicht ausreichend untersucht . Ziel der Autoren war , den Einfluss eines extravaskulären Polyglykolsäure ( PGA ) Anker basierten Verfahrens auf den Verschluss des Zugangs in der Leiste bei Patienten zu ermitteln , bei denen eine Koronarangiographie und/oder eine perkutane Koronarintervention erfolgte . Method enIn der vorliegenden prospektiven , einfach verblindeten Multizenterstudie wurden 319 Patienten r and omisiert dem Gefäßverschluss mit Angio-Seal ™ oder Exo-Seal ® zugeteilt . Die Hypothese der Autoren best and darin , dass der Einsatz eines extravaskulären Verschlusssystems einem System auf PGA/Ankerbasis i m Hinblick auf das Auftreten des kombinierten primären Endpunkts aus Hämatom > 5 cm , erheblicher Blutung in der Leistenregion ( schwere Blutung nach TIMI-Kriterien ) , Aneurysma spurium und „ device“-Versagen nicht unterlegen sei . ErgebnisseEs f and sich kein signifikanter Unterschied bei den Ausgangsmerkmalen der Patienten oder den Ergebnissen der Prozedur . Nach 24 h trat der primäre Endpunkt bei 9 Patienten ( 5,6 % ) in der Angio-Seal ™ - und bei 13 Patienten ( 8,2 % ) der Exo-Seal ® -Gruppe auf ( p = 0,38 ) . Ein Hämatom > 5 cm wurde bei 3 Patienten ( 1,9 % ) unter Verwendung von Angio-Seal ™ vs. 2 Patienten ( 1,3 % ) unter Verwendung von Exo-Seal ® ( p = 0,99 ) festgestellt . Bei einem Patienten ( 0,6 % ) der Exo-Seal ® -Gruppe trat eine schwere Blutung nach TIMI-Kriterien auf , die eine Transfusion notwendig machte ( p = 0,49 ) . Es wurden 4 ( 2,5 % ) falsche Aneurysmen bei den mit Angio-Seal ™ beh and elten Patienten und 2 ( 1,3 % ) bei den mit Exo-Seal ® beh and elten Patienten ( p = 0,68 ) diagnostiziert . Eine Tendenz zu einer höheren Inzidenz von „ device“-Versagen best and in der Exo-Seal ® -Gruppe mit 1,2 vs. 5,2 % ( p = 0,06 ) . Bei einer telefonischen Befragung nach 30 Tagen war kein signifikanter Unterschied hinsichtlich der Ereignisse Wiederaufnahme mit chirurgischem Eingriff an der Punktionsstelle , Infektion , Blutung , Hämatom oder Schmerzen festzustellen . SchlussfolgerungIn der vorliegenden Studie wurden keine signifikanten Unterschiede in Bezug auf das Auftreten eines Hämatoms > 5 cm , einer schweren Blutung , eines falschen Aneurysmas und eines „ device“-Versagens zwischen Angio-Seal ™ und Exo-Seal ® 24 h nach Implantation des Systems festgestellt", "OBJECTIVE To identify predictors of failure in percutaneous endovascular aneurysm repair ( P-EVAR ) using the Prostar XL Percutaneous Vascular Surgery Device ( Abbot Vascular , Santa Clara , CA , USA ) and the need for conversion to conventional femoral cutdown ( O-EVAR ) . METHODS Consecutive patients who underwent P-EVAR with the Prostar XL device between January 2009 and April 2012 were included in this series . Patients with a circular calcified common femoral artery ( CFA ) oncomputed tomography angiography were operated using O-EVAR and were therefore excluded . To identify predictors of success of closure in P-EVAR , artery characteristics , sheath size used , and comorbidities were analyzed in a univariate logistic regression model . RESULTS Percutaneous access was achieved in 154 femoral access sites with conversion to O-EVAR was needed in10 ( 6.5 % ) . Significant predictors of conversion included sheath size ( continuous , relative risk [ RR ] 1.50 , p < .03 ) and the ratio between sheath size and CFA diameter > 0.75 ( RR 8.93 , p < .01 ) . Variables such as calcification quantity scores , CFA diameter , body mass index , and comorbidities were not significant . CONCLUSION The data demonstrate that sheath size , in particular , combined with CFA diameter predicts failure of closure in P-EVAR using the Prostar XL device . This ratio can be utilized to help in decision making with regard to the EVAR approach . A ratio of > 0.75 would favor a primary open groin approach", "AIMS To test the safety of immediate mobilisation of patients undergoing coronary angiography and percutaneous coronary intervention ( PCI ) closed with Angio-Seal ™ -a femoral vascular closure device . METHODS AND RESULTS First , a r and omised controlled trial of immediate mobilisation vs. delayed ambulation was performed followed by a prospect i ve validation registry to test the obtained results in a real-world situation . The r and omised trial comprised 300 patients ; the validation registry comprised 1,097 patients . Primary endpoints were complications defined as : small haematoma < 5 cm and /or minor bleeding/oozing from the puncture site , haematomas ≥ 5 cm , bleeding needing transfusion , bleeding needing surgical attention , pseudoaneurysm and vasovagal reaction . In the r and omised trial , overall complications were similar in both groups ( 16.0%vs.18.8 % ; p=0.53 ) . Small haematomas/small bleedings/oozing were the most frequent ( 12.2 % vs.15.3 ; p=0.44 ) . There were no bleedings needing transfusion or surgical attention , and no pseudoaneurysms occurred . The prospect i ve registry showed similar results . In the st and ard-care cohort , complications were similar to those in the implementation cohort ( 9.6 % vs.11.3 % ; p=0.41 ) , mainly consisting of small haematomas/minor bleedings/oozing ( 6.1 % vs.7.3 % ; p=0.49 ) . No bleedings needed transfusion or surgical attention . Pseudoaneurysms occurred in 1 ( 0.34 % ) vs. 3 ( 0.37 % ; p=0.94 ) and vasovagal reactions in three ( 1.0 % ) vs. four ( 0.5 % ; p=0.33 ) patients . It was possible to mobilise 87 % of patients in the implementation cohort . CONCLUSIONS In patients undergoing coronary angiography or PCI , the use of immediate mobilisation after Angio-Seal ™ deployment is safe . With routine use of a femoral vascular closure device , approximately 87 % of patients are suitable for immediate mobilisation", "Femoral artery closure devices reduce the time to haemostasis and ambulation . Most district general hospitals ( DGHs ) now perform day case angiography on site . The purpose of this study was to assess the Angio-Seal self-tightening suture ( STS ) device in comparison with manual compression in this environment . A prospect i ve r and omised controlled trial was undertaken comparing the Angio-Seal STS device with manual pressure recording complications , time from end of procedure and patient satisfaction in a DGH setting . Angiography lists of 206 patients undergoing day case diagnostic cardiac catheterisation with a five French sheath at a DGH were r and omised by intention to treat to receive either manual compression or a six French Angio-Seal STS device . Time from sheath removal to mobilisation , complication rate and patient satisfaction were compared . There were no significant differences between the two groups in terms of demographics ( manual compression : Angio-Seal ; male ( % ) 58 vs. 57 , age ( years ) 65.4 vs. 66.3 , body mass index ( kg/m(2 ) ) 27.7 vs. 27.5 ) . Despite r and omisation , only 74 of 107 patients in the Angio-Seal group actually had a device deployed . Angio-Seal use was associated with significantly shorter times to mobilisation ( 87.6 vs. 144.1 min ; p < 0.001 ) , significantly less bruising ( bruise size at 1 week ( 28.5 vs. 82.5 cm(3 ) ; p < 0.01 ) and no increase in vascular complications . In addition , patients were more satisfied with Angio-Seal devices in terms of length of immobility . The routine use of Angio-Seal closure devices result in earlier mobilisation , less bruising , increased patient satisfaction with no increase in other complications in comparison to manual pressure", "Background and purpose The Mynx M5 ( AccessClosure , Inc. , Mountain View , California , USA ) , a novel vascular closure device ( VCD ) utilizing extravascular synthetic sealant , may effectively seal the arteriotomy while reducing the pain associated with arteriotomy closure seen with other VCDs . To date , no studies exist comparing the pain associated with deployment between differing VCDs as a primary end point . Methods A blinded , r and omized controlled trial was performed comparing the Mynx and a popular VCD that utilizes a self-tightening suture , the Angio-Seal Evolution ( St Jude Medical , St Paul , Minnesota , USA ) . Subjects were all adult patients undergoing diagnostic cerebral angiography via femoral access . Local anesthesia and intraprocedural intravenous pain medication were st and ardized . Pain was assessed using a horizontal visual analog scale both before and after VCD deployment . Results 64 patients were enrolled with 32 in each treatment arm . Both pain at closure and pain increase from baseline to closure were significantly higher in the Angio-Seal group ( p=0.009 and 0.002 , respectively ) . 88 % of patients receiving an Angio-Seal reported closure as the most painful part of the procedure compared with only 34 % of patients receiving the Mynx ( p<0.001 ) . No adverse events were detected in either treatment arm . Conclusions In a blinded , r and omized trial comparing the Mynx with the Angio-Seal Evolution , pain with device deployment at arteriotomy closure was significantly lower with the Mynx . The reason for the large pain gradient between groups is likely due to the presence , and absence , of compression elements within the Angio-Seal and Mynx , respectively", "AIMS To compare in a r and omised trial the safety and efficacy of the FemoSeal vascular closure device ( VCD ) versus manual compression ( MC ) after femoral access coronary angiography ( CAG ) . METHODS AND RESULTS In 13 months , 1,014 patients were included and 1,001 patients entered analysis . Median [ interquartile range ] closure time was 8.0 [ 6 - 10 ] minutes after MC versus 1.0 [ 1 - 1 ] minute ( p<0.0001 ) for the FemoSeal VCD . Bed rest for one hour after the closure procedure was recommended in both groups . The primary endpoint of incidence of large groin haematoma was 6.7 % in the MC group vs. 2.2 % ( p=0.002 ) in the FemoSeal group . The combined endpoint of 14-day adverse vascular events occurred in 1.0 % in the MC group vs. 0.6 % in the FemoSeal VCD group ( p=0.7 ) . Manual compression ( OR 3.3 , 95 % CI : 1.5 - 7.2 , p=0.002 ) , female gender ( OR 2.1 , 95 % CI : 1.1 - 3.9 , p=0.018 ) , and multiple punctures ( OR 10.5 , 95 % CI : 3.2 - 34.3 , p=0.001 ) were identified as independent predictors of adverse events and large haematomas . CONCLUSIONS Closure of femoral access after coronary angiography by the FemoSeal vascular closure device was safe , faster , and associated with significantly fewer in-hospital large haematomas as compared to closure by manual compression", "Background : This was the first prospect i ve study to assess the safety and efficiency of MynxGrip vascular closure device ( VCD ) in peripheral interventions with ante grade access . Methods and Results : We enrolled 66 consecutive patients from 1 center . All patients were discharged home on the day of procedure and were observed for adverse events at 1 and 30 days of follow-up . No major complications were observed . The rate of minor complications ( conversion to manual or mechanical compression ) was 7.6 % . Postdischarge , 3 % of patients experienced minor complications — small abscess , ipsilateral deep vein thrombosis . In 1 patient , a second VCD was deployed after device failure . The derived device failure rate was 5.9 % . No patients required hospitalization . No late bleeding and no hematomas > 6 cm were noted . The mean time to discharge was 4 hours and 5 minutes . Conclusion : The MynxGrip was safe and effective in sealing access sites after ante grade femoral artery puncture with same-day discharge", "Objective : This prospect i ve r and omized trial compared the Angio‐Seal VIP ™ with Perclose Proglide ™ and to manual compression with respect to time to hemostasis and ambulation , patient satisfaction , and vascular complications following percutaneous coronary intervention ( PCI ) . Background : The use of arterial closure devices for the reduction of vascular complications following PCI remains controversial . There have been no head to head trials comparing these most commonly used arterial closure devices following PCI . Methods : Two hundred patients undergoing PCI were r and omized to manual compression , Perclose Proglide ™ or Angio‐Seal VIP ™ . Ambulation was allowed 3 hr after Perclose Proglide ™ or Angio‐Seal VIP ™ and 6 hr after compression . Results : There were 10 failures to deploy Perclose Proglide ™ and none for Angio‐Seal ™ ( P < 0.01 ) . Time to hemostasis was significantly shorter with Angio‐Seal VIP ™ compared with Perclose Proglide ™ ( 5.3 vs. 46.8 min , P < 0.01 ) . Time to ambulation was shorter with Angio‐Seal VIP ™ than with Perclose Proglide ™ ( 261 vs. 334 min , P < 0.05 ) and the time to ambulation , as expected , was longest with compression ( 943 min , P < 0.01 vs. Angio‐Seal VIP ™ and Perclose Proglide ™ ) . Delay in ambulation was higher with Perclose Proglide ™ than with Angio‐Seal VIP ™ ( 18 vs. 9 , P < 0.01 ) . There was no significant difference in major vascular complications between groups . Compared with compression , patient discomfort was significantly improved with Angio‐Seal ™ ( 1.5 vs. 2.0 , P < 0.01 ) , but not with Perclose Proglide ™ . Conclusion : The Angio‐Seal VIP ™ device has a high rate of deployment success , which is significantly better than that of Perclose Proglide ™ . Angio‐Seal VIP ™ allows for earlier hemostasis and ambulation compared with both compression and Perclose Proglide ™ and is associated with greater patient satisfaction compared with compression . © 2008 Wiley‐Liss ,", "BACKGROUND Complications of vascular access are one of the most common adverse events after coronary angiography and percutaneous coronary intervention ( PCI ) and are reported to occur in 1 % to 9 % of cases . There are conflicting reports of the association of vascular complications with the use of vascular closure devices ( VCDs ) . The purpose of this study was to assess femoral arterial access-related vascular outcomes after invasive cardiology procedures with the routine use of VCDs . METHODS A total of 12,937 consecutive patients were studied for inhospital outcomes through a prospect i ve registry from January 2002 to December 2005 . Of these , 6913 ( 53 % ) patients underwent PCI and 9996 ( 77 % ) patients received VCDs . Univariate and multivariate logistic regression analyses were used to determine the predictors of vascular complications . A propensity analysis of VCD use was performed to account for potential bias in the likelihood of using such devices . RESULTS Vascular complications occurred in 0.7 % of diagnostic angiography and 2.7 % of PCI patients . The risk of vascular complications was significantly lower with closure device use compared with manual compression in both diagnostic angiography ( 0.5 % vs 1.1 % , P = .01 * ) and PCI ( 2.4 % vs 4.9 % , P < .001 * ) groups . Multivariate logistic regression analysis , after accounting for the propensity to use such devices , revealed that VCD use was associated with a 58 % ( 95 % CI 19%-88 % ) reduction in the risk of vascular complications in diagnostic procedures catheterization and a 42 % ( 95 % CI 17%-59 % ) reduction in PCI patients . CONCLUSIONS In contemporary practice , VCDs offer reduced risk of vascular complications as compared with manual compression in appropriately selected patients undergoing diagnostic and therapeutic cardiac catheterizations", "Objective : The purpose of this study was to evaluate the hemostatic efficacy and safety of the Mynx extravascular sealant for femoral artery closure . Background : The Mynx device is an extra‐arterial vascular closure technology utilizing a water‐soluble , porous , polyethylene glycol matrix that immediately seals the arteriotomy by rapidly absorbing subcutaneous fluids and exp and ing in the tissue tract and then , resorbs within 30 days . Methods : The Mynx study was a prospect i ve , multicenter , single‐arm clinical investigation conducted at five European centers . The safety and effectiveness of the Mynx device was evaluated in patients following diagnostic or interventional endovascular procedures performed through 5 Fr , 6 Fr , or 7 Fr introducer sheaths in the common femoral artery . The primary safety endpoint was the combined rate of major complications within 30 days ( ±7 days ) . The primary efficacy endpoints were time to hemostasis and time to ambulation . Results : Patient enrollment included 190 patients with 50 % having undergone diagnostic catheterization and 50 % interventional procedures with a mean activated clotting time of 221 sec. One ( 0.5 % ) major vascular complication ( transfusion ) occurred in one patient . No device‐precipitated complications associated with serious clinical sequelae were reported . Mean ( ± st and ard deviation ) times to hemostasis and ambulation were 1.3 ± 2.3 min and 2.6 ± 2.6 hr , respectively . There was no significant difference in median times to hemostasis between diagnostic and interventional patients ( 0.5 vs. 0.6 min ) . Conclusions : The initial experience with the extra‐arterial Mynx closure technology supports hemostatic safety and efficacy in patients undergoing diagnostic and interventional catheterization procedures . © 2007 Wiley‐Liss ,", "Background : The StarClose ® Vascular Closure System is a femoral access site closure technology that uses a flexible nitinol clip to complete a circumferential , extravascular arteriotomy close . The Clip CLosure In Percutaneous Procedures study was initiated to study the safety and efficacy of the StarClose device in subjects undergoing diagnostic and interventional catheterization procedures . Methods : A total of 17 U.S. sites enrolled 596 subjects , with 483 subjects r and omized at a 2:1 ratio to receive StarClose or st and ard compression of the arteriotomy after the percutaneous procedure . The study included roll‐in ( n = 113 ) , diagnostic ( n = 208 ) , and interventional ( n = 275 ) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis . Results : The results of the diagnostic StarClose cohort have been reported separately . Results for the interventional arm revealed major vascular complications occurring in 1.1 % of StarClose subjects ( 2/184 ) and 1.1 % in manual compression subjects ( 1/91 ; P = 1.00 ) . No infections were seen in either cohort . Minor complications in the StarClose interventional group occurred at a rate of 4.3 % ( 8/184 ) and with compression at 9.9 % ( 9/91 ; P = 0.107 ) . Pseudoaneurysm or arteriovenous fistula was not seen with StarClose . With StarClose , procedural success was 100 % ( 136/136 ) for the diagnostic group and 98.9 % ( 181/183 ) in the interventional group . Device success for the treatment group was 86.8 % . In the interventional cohort , 87.3 % ( 158/181 ) of StarClose subjects reported a pain scale of 0–3 compared with 93.3 % ( 84/90 ) in the compression group , which was not statistically different . Conclusions : The clinical results of this study demonstrate that the StarClose Vascular Closure System is noninferior to manual compression with respect to the primary safety endpoint of major vascular events in subjects who undergo percutaneous interventional procedures . StarClose significantly reduced time to hemostasis , ambulation , and dischargeability when compared with compression . © 2006 Wiley‐Liss ,", "OBJECTIVE To present results of a registry of a novel vascular access device . BACKGROUND Arterial access has been largely unchanged for 60 years . The Arstasis device creates a novel shallow-angle arterial access design ed to facilitate hemostasis without use of a vascular closure device ( VCD ) or implantation of a foreign body for closure . This is the first publication to report the outcomes of Arstasis access . METHODS Patients ( n = 346 ) underwent routine diagnostic cardiac catheterization ( Dx ) at 8 sites in the United States . Patients were assessed for device success , time to hemostasis ( TTH ) , early sit up , time to ambulation ( TTA ) , time-to-discharge- eligibility ( TTDe ) as well as safety ; 249 patients had Dx only , 97 crossed over to PCI . RESULTS Device deployment was successful in 97 % ; the other 3 % converted to routine access . Mean TTH and TTA for Dx were 4.0 ± 2.5 minutes and 1.5 ± 1.2 hours , respectively ; for PCI it was 6.9 ± 5.1 minutes and 3.2 ± 3.3 hours . A subset of 245 patients ( 72.9 % ) sat up within 30 minutes after hemostasis ; early sit-up was successful in all but 1 ( 99.6 % ) . TTDe for Dx was 2.7 ± 1.6 hours . There were no major access-site related complications ; minor complications were primarily sub clinical hematomas in 1.2 % . CONCLUSIONS Arstasis access is associated with short TTH and TTA , early sit up after sheath pull , and accelerated TTDe , achieved without use of VCDs or implantation of a foreign body , with high success and minimal complication rates", "AIM A totally percutaneous approach to endovascular abdominal aortic aneurysm repair ( PEVAR ) has been shown in multiple single center reports to be feasible . Nonetheless , questions regarding the broader applicability of the approach remain due to the lack of a r and omized multicenter trial , thus preventing more widespread adoption . We report the methods and outcomes from the roll-in phase of the first prospect i ve , multicenter trial of PEVAR . METHODS Among 19 institutions participating in the PEVAR Trial ( NCT01070069 ) , 38 consecutive patients with abdominal aortic aneurysm were enrolled in a roll-in phase between April 2010 and May 2011 . PEVAR procedures with adjunctive \" pre-close \" of the common femoral arteries ( CFAs ) targeted for large sheath access using the ProGlide or Prostar XL closure devices were performed using the Endologix IntuiTrak System . All patients were followed periprocedurally and to 30 days for major adverse events and access-related vascular complications . RESULTS Patients presented at a mean age of 71 years with mean aneurysm sac diameter of 5.6 cm . Technical success of the pre-close procedure was 97 % ( 37/38 patients ) . In one patient , ProGlide devices failed to achieve ipsilateral CFA hemostasis , leading to bleeding requiring transfusion and surgical vascular repair . All endovascular repairs were successful . No mortality or major adverse events occurred . Other pre-close related complications occurring within 30 days included pseudoaneurysm , lower extremity ischemia , and blood transfusion . CONCLUSION PEVAR with adjunctive ' pre-close ' techniques using the ProGlide or Prostar XL devices is safe and feasible as applied in this multicenter experience . Continued evaluation in the prospect i ve , r and omized trial is warranted", "PURPOSE To determine the safety and efficacy of total percutaneous access closure for endovascular aortic aneurysm repair with a suture-mediated preclosing technique . MATERIAL S AND METHODS One hundred thirty-two femoral access sites in 70 patients who underwent endovascular aortic aneurysm repair were closed percutaneously with off-label use of two F-6 Perclose AT devices preapplied at a 90 degrees angle . Femoral access sizes ranged from 12 to 24 F. Technical success , complications , and procedure and access closure times were evaluated . Follow-up with computed tomography and /or magnetic resonance imaging was scheduled at 1 - 4 days and 3 , 6 , and 12 months and used to obtain groin hematoma and scar severity scores ( grade s 1 - 3 ) . Data were compared with those from a cohort of 67 patients who underwent endovascular aortic aneurysm repair with surgical femoral cutdown . RESULTS Technical success was achieved with the preclosing technique in 127 of the 132 arteries ( 96.2 % ) . Two to four closure devices were used per groin . Five technical failures were managed intraoperatively with surgical suture . There was no access-related mortality and no late groin complications . The mean procedure duration was 91 minutes + /- 32 , and the mean access closure time was 12 minutes + /- 9 . For surgical management , the mean procedure time was 153 minutes + /- 112 ( P < .05 ) , and the mean closure time was 12 minutes + /- 13 ( not statistically significant ) . Hematoma severity score at 1 - 4 days was 1.8 for total percutaneous endovascular aneurysm repair and 2.1 for surgical closure . Scar severity scores at 3 , 6 , and 12 months were 1.1 , 1.0 , and 1.0 for total percutaneous endovascular aneurysm repair and 2.4 , 2.4 , and 2.3 for surgical management , respectively . CONCLUSIONS Total percutaneous endovascular aneurysm repair with a dual 6-F-Perclose preclosing technique is safe and effective . Compared with femoral cutdown , there are fewer late groin complications and scar tissue formation is less severe", "Purpose : To present a prospect i ve , single-center trial of the Cardiva Catalyst II , a vascular closure device that provides temporary hemostasis after the procedure and is removed under manual compression , leaving no material behind . Methods : During a 16-month period between April 2008 and July 2009 , 400 procedures ( 100 interventions , 300 diagnostic procedures ) were performed on 351 nonconsecutive patients ( 185 men ; mean age 60.2±12.0 years , range 27–93 ) . All interventions were performed utilizing bivalirudin for anti-thrombin therapy . Initial follow-up was done at a mean 1.3±0.7 days after the index procedure in all patients . Final follow-up , for diagnostic procedures as well as interventions , was performed at a mean 15.4±7.1 days . The primary and secondary endpoints were the rate of major and minor vascular complications , respectively . Results : Successful deployment of the device was reported in 397 ( 99.3 % ) procedures , which were primarily in retro grade fashion ( 97.0 % ) from the right groin ( 92.5 % ) . In most cases ( 309 , 77.2 % ) , a 5-F sheath was used . A major vascular complication occurred after 1 intervention ; none was noted after diagnostic procedures . Minor vascular complications were recorded after 2 interventions and 5 diagnostic procedures . Overall vascular complication rates were 0.25 % for major sequelae and 1.75 % for minor events . Mean time to discharge after diagnostic procedures was 145.0621.2 minutes versus 295.1±44.1 minutes after interventional procedures ( p<0.05 ) . There was no death , stroke , myocardial infa rct ion , or urgent hospital transfer in the study cohort . Conclusion : Cardiva Catalyst is safe and effective device in achieving local hemostasis after percutaneous diagnostic procedures and interventions performed under bivalirudin anticoagulation . The use of this device with an appropriate protocol facilitates same-day discharge", "Objective : The RISE study was a prospect i ve , multicenter , single‐arm study evaluating the safety and efficacy of the StarClose ® Vascular Closure System ( VCS ) in the femoral artery in subjects who were ambulated early following percutaneous diagnostic coronary or peripheral catheterization procedures . Background : Previous studies have demonstrated that several vascular closure devices are able to safely decrease the amount of bedrest needed following angiography . To date , no device has been shown to be safe for immediate ambulation . Methods : Between April 2006 and November 2006 , 315 patients undergoing a catheterization via the femoral artery were enrolled ( intent‐to‐treat population , ITT ) . Of these , 171 subjects were not excluded by angiographic or clinical criteria and had a StarClose device placed to attain hemostasis . If hemostasis was immediately achieved , patients were ambulated within 20 min for 20 feet without assistance ( per‐ protocol population , PP ) . Patients were followed for 30 days after the index procedure . The primary endpoint of the study was time to ambulation ( TTA ) . Results : Immediate hemostasis was achieved in 156 patients ( 91.2 % ) . The mean TTA in the PP was 8.29 min , median 5.92 . There were no deaths or major vascular complications , and the rate of minor vascular complications was 1.9 % ( 3/156 ) . Conclusion : The StarClose ® VCS device is both safe and effective allowing immediate ambulation of patients who have undergone catheterization via the femoral artery . © 2011 Wiley Periodicals ,", "Objectives : To evaluate the feasibility , safety and efficacy of suture‐mediated closure devices using a modified “ preclosure ” technique for access site management after percutaneous aortic valve replacement ( PAVR ) . Background : PAVR using a retro grade transfemoral approach has recently evolved to an endovascular alternative to open surgery in high‐risk patients . However , large‐bore femoral artery access is required , commonly dem and ing surgical closure and general anesthesia . A truly percutaneous intervention would be desirable to reduce procedural complexity and diminish the need of vascular surgery and general anaesthesia . Methods : After direct puncture of the common femoral artery , three conventional suture‐mediated closure devices ( 6F Perclose ) were deployed . The preloaded sutures were tied at the end of the procedure . If no immediate hemostasis was achieved , an additional device was deployed thereafter . Results : PAVR with percutaneous access site closure was attempted in 15 consecutive patients and could successfully be achieved in all patients allowing conscious sedation in all but three cases . Following complications occurred : one retroperitoneal bleeding caused by removal of the valve delivery sheath requiring surgical repair , as well as two cases of femoral and iliac artery dissection caused by delivery sheath introduction and treated by stenting and vascular surgery , respectively . Vascular surgery became only necessary due to total vessel occlusion after suture closure and remains the only closure‐related complication . However , treatment led to recovery in all patients . Conclusions : The modified “ preclosure ” technique is a feasible and safe method for hemostasis after PAVR improving procedural management and diminishing the need for general anesthesia . © 2008 Wiley‐Liss ,", "Purpose : To report the outcome of a prospect i ve r and omized safety and performance trial of 2 access site closure devices versus a wound dressing . Methods : Between October 2005 and July 2006 , 852 consecutive patients ( 605 men ; mean age 67 years ) undergoing diagnostic or interventional catheterization procedures thru a 5- or 6-F femoral sheath were r and omized to one of the 3 closure methods : a collagen plug device ( Angio-Seal ) , a clip ( StarClose ) , or a wound dressing ( D-Stat Dry ) . The efficacy of the devices was assessed , as well as the complications occurring at the puncture site during the hospital stay . The primary endpoint of the study was the cumulative incidence of access site pseudoaneurysm , major access site bleeding requiring transfusion , access site vascular surgery , or death from all causes . Results : There were no significant differences in baseline characteristics between the 3 treatment groups . The primary endpoint was reached in 20 ( 7.1 % ) of 281 patients treated with D-Stat Dry and in 11 ( 1.9 % ) of 571 patients treated with the mechanical closure devices ( p<0.0001 ) . There was no significant difference among the mechanical closure devices concerning the incidence of the primary endpoint ( Angio-Seal 1.1 % versus StarClose 2.8 % ; p=0.13 ) . Conclusion : The collagen plug device had the lowest rates of major and minor access site — related complications after removal of 5- or 6-F femoral sheaths . The difference between the mechanical closure devices concerning the incidence of the primary endpoint did not reach statistical significance . The wound dressing showed significantly higher major and minor complication rates", "IMPORTANCE The role of vascular closure devices ( VCD ) for the achievement of hemostasis in patients undergoing transfemoral coronary angiography remains controversial . OBJECTIVE To compare outcomes with the use of 2 hemostasis strategies after diagnostic coronary angiography performed via transfemoral access-a VCD-based strategy with 2 types of devices , an intravascular device and an extravascular device , vs st and ard manual compression . The primary hypothesis to be tested was that femoral hemostasis achieved through VCD is noninferior to manual compression in terms of vascular access-site complications . A secondary objective was the comparison of the 2 types of VCD . DESIGN , SETTING , AND PARTICIPANTS R and omized , large-scale , multicenter , open-label clinical trial . We enrolled 4524 patients undergoing coronary angiography with a 6 French sheath via the common femoral artery from April 2011 through May 2014 in 4 centers in Germany . Last 30-day follow-up was performed in July 2014 . INTERVENTIONS After angiography of the access site , patients were r and omized to hemostasis with an intravascular VCD , extravascular VCD , or manual compression in a 1:1:1 ratio . MAIN OUTCOMES AND MEASURES Primary end point : the composite of access site-related vascular complications at 30 days after r and omization with a 2 % noninferiority margin . Secondary end points : time to hemostasis , repeat manual compression , and VCD failure . An α-level of .025 was chosen for primary and secondary comparisons . RESULTS Of the 4524 enrolled patients , 3015 were r and omly assigned to a VCD group ( 1509 received intravascular VCD and 1506 received extravascular VCD ) and 1509 patients were r and omly assigned to the manual compression group . Before hospital discharge , duplex sonography of the access site was performed in 4231 ( 94 % ) patients . The primary end point was observed in 208 patients ( 6.9 % ) assigned to receive a VCD and 119 patients ( 7.9 % ) assigned to manual compression ( difference , -1.0 % [ 1-sided 97.5 % CI , 0.7 % ] ; P for noninferiority<.001 ) . Time to hemostasis was significantly shorter in patients with VCD ( 1 minute [ interquartile range { IQR } , 0.5 - 2.0 ] ) , vs manual compression ( 10 minutes [ IQR , 10 - 15 ] ; P < .001 ) . Time to hemostasis was significantly shorter among patients with intravascular VCD ( 0.5 minute [ IQR , 0.2 - 1.0 ] ) , vs extravascular VCD ( 2.0 minutes [ IQR , 1.0 - 2.0 ] ; P < .001 ) and closure device failure was also significantly lower among those with intravascular vs extravascular VCD ( 80 patients [ 5.3 % ] , vs 184 patients [ 12.2 % ] ; P < .001 ) . CONCLUSIONS AND RELEVANCE In patients undergoing transfemoral coronary angiography , VCDs were noninferior to manual compression in terms of vascular access-site complications and reduced time to hemostasis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01389375", "AIMS Although closure devices may be comfortable for patients , the clinical benefits in patients with moderate-to-high risk of bleeding are not yet clear . We compared a closure device with manual compression in moderate- to high-risk bleeding patients undergoing percutaneous coronary intervention ( PCI ) . METHODS AND RESULTS A r and omized study was performed to compare a closure device ( Angio-Seal , St. Jude Medical , Inc. ) with manual compression in 627 patients treated with aspirin , clopidogrel , a glycoprotein IIb/IIIa inhibitor and heparin during PCI . The primary endpoint was the inhospital combined incidence of : 1 ) severe hematoma > 5 cm at the puncture site or groin bleeding result ing in prolonged hospital stay , transfusion and /or surgical intervention at the puncture site ; 2 ) arteriovenous fistula formation and /or surgical intervention at the puncture site . A total of 313 patients ( 49.9 % ) were r and omized to the closure device and 314 patients ( 50.1 % ) to manual compression . The combined primary endpoint was 2.6 % in the closure device group compared to 4.5 % in the manual compression group ( p = 0.195 ) . In the predefined subgroup of patients with a history of hypertension , however , the combined primary endpoint ( 0.8 % vs. 7.2 % ; p = 0.008 ) was significantly reduced after use of the closure device . CONCLUSION This trial did not show the superiority of using a closure device over manual compression in patients treated with triple antiplatelet therapy who underwent PCI . The fact that patients with a history of hypertension had a benefit from a closure device merits further investigation", "AIMS We assessed feasibility , efficacy and safety of a suture-mediated closure device , Perclose Proglide ( Abbott Vascular Devices , Santa Clara , CA , USA ) , for closure of the femoral vein access after percutaneous MitraClip ( Abbott Vascular Devices ) implantation . METHODS AND RESULTS Venous access of 80 consecutive patients undergoing percutaneous mitral valve repair using the MitraClip device was managed either by manual compression , \" figure eight \" suture and compression b and age for 12 hours , or by applying the Proglide device for haemostasis after the procedure ( 40 patients each group ) . Patients with Proglide closure showed complete immediate haemostasis in 92.5 % ( 37/40 ) and were immobilised with a compression b and age for only four hours . In the Proglide group , one arteriovenous fistula was observed and had to be treated by vascular surgery . The overall duration of stay on an intensive care unit was significantly reduced in the Proglide group ( 59.4±48.9 hours vs. 84.6±59.5 hours , p<0.005 ) . CONCLUSIONS Using a suture-mediated closure device for the femoral vein after percutaneous MitraClip implantation is feasible and safe . This allows earlier patient mobilisation and may reduce post-interventional duration of stay on an intensive care unit", "OBJECTIVES This trial compared the performance of a novel bioabsorbable vascular closure device ( VCD ) versus manual compression ( MC ) for access site hemostasis in patients undergoing percutaneous trans-femoral coronary or peripheral procedures . BACKGROUND From a patient 's perspective , access site management after percutaneous procedures remains challenging . METHODS Patients enrolled in this multicenter , nonblinded trial underwent 6-F diagnostic or interventional procedures were r and omly assigned 2:1 to VCD versus MC . The primary efficacy end points were time to hemostasis ( TTH ) and time to ambulation ( TTA ) , and the primary safety end points were periprocedural and 30-day incidence of arterial access-related complications . RESULTS The trial assigned 401 patients ( mean age 62.7 + /- 10.9 years , 66.1 % men ) to VCD ( n = 267 ) versus MC ( n = 134 ) after 87 \" roll-in \" patients treated at 17 participating institutions . The baseline characteristics of the groups were similar . Procedural success was 91.8 % in the VCD versus 91.0 % in the MC group ( p = NS ) . Mean TTH was 4.4 + /- 11.6 min in the VCD versus 20.1 + /- 22.5 min in the MC group ( 95 % confidence interval : 19.0 to 12.3 ; p < 0.0001 ) . Likewise , TTA was significantly shorter in the VCD ( 2.5 + /- 5.0 h ) than in the MC ( 6.2 + /- 13.3 h ) group ( 95 % confidence interval : 5.5 to 1.9 ; p = 0.0028 ) . No patient died or suffered a major access-site-related adverse event . Minor adverse events were few among all study groups . CONCLUSIONS After 6-F percutaneous invasive procedures , TTH and TTA were both significantly shorter in patients assigned to VCD than in patients managed with MC . The 30-day rates of access-site-related complications were remarkably low in all groups . ( Safety and Effectiveness Study of the Ensure Medical Vascular Closure Device ; NCT00345631 )", "BACKGROUND The aim of vascular closure devices is to safely secure the arterial access site at the conclusion of catheterization procedures , thereby increasing patient comfort and decreasing time to hemostasis and ambulation . The FISH ( femoral introducer sheath and hemostasis ) device is novel in that the access sheath and closure component are incorporated onto the same system . METHODS The FISH pivotal investigation was conducted at 8 catheterization laboratories throughout the United States . Eligible diagnostic patients were r and omized ( 2 to 1 ) to the FISH device versus manual compression and assessed for time to hemostasis and time to ambulation . Half of the participants underwent ultrasonographic evaluation at 30-day follow up . Enrollment for an interventional cohort is ongoing and will be reported at a later date ; however , the interventional patients enrolled to date were combined with the diagnostic patients to comprise the safety data of the trial . RESULTS Overall , 191 patients were r and omized to the FISH device and 106 patients to manual compression . Most patients received a 6 Fr sheath ( approximately 70 % ) , while the remaining patients received a 5 or 8 Fr sheath . Twenty-seven patients who received the FISH device were converted to manual compression due to anticipated suboptimal hemostasis . Among the diagnostic patients , the mean time to hemostasis was 8.9 minutes for the FISH device , compared to 17.2 minutes for manual compression ( p < 0.0001 ) . Similarly , the mean time to ambulation was 2.4 hours for the FISH device , compared to 4.3 hours for manual compression ( p < 0.0001 ) . Among the total cohort , there was 1 death and 1 episode of major access-site-related bleeding that required transfusion occurred in the FISH group ( 1.1 % ) , compared to no serious adverse safety events in the manual compression group ( p = 1.0 ) . For the FISH group , there were 5 minor adverse safety events ; 3 access-site hematomas and 2 pseudoaneurysms treated with thrombin injection , and in the manual compression group , there was 2 access-site hematomas and 1 pseudoaneurysm treated with thrombin injection ( p = 1.0 ) . CONCLUSION Among diagnostic patients with good sheath placement and favorable femoral anatomy , the FISH device is superior in achieving time to hemostasis and ambulation compared to manual compression . At 30 days , there is no apparent difference in serious or minor adverse vascular events with the use of the FISH device", "OBJECTIVES The objective of the study was to assess the efficacy and safety of a novel vascular closure device , the Angio-Seal Evolution ( EVCD ) , in patients undergoing routine cardiac catheterization ( CATH ) and intervention ( PCI ) via a retro grade femoral artery access . BACKGROUND Successful use of current-generation vascular closure devices is highly dependent on operator methodology . To reduce dependence on operator technique , the EVCD was modified to automate the closure process , specifically the compaction of the extravascular collagen sponge that creates a s and wich under pressure against the intra-arterial anchor . METHODS This was a prospect i ve ten-site registry including 1,004 patients undergoing 1,010 procedures with in-laboratory closure using the EVCD after CATH and PCI . The primary outcome measure was the rate of major vascular complications , and secondary outcomes were deployment success , time to hemostasis and in-hospital rates of minor vascular complications through 30 days . Clinical trial identifier NCT 00817349 . RESULTS There were 575 CATH ( 56.9 % ) and 435 PCI ( 43.1 % ) closures . Overall deployment success was 99.7 % ; 99.8 % for CATH and 99.5 % for PCI . Major vascular complications occurred in 0.4 % including 0.2 % in CATH and 0.7 % in PCI . Minor vascular complications occurred in 2.4 % , with 0.5 % for CATH and 4.9 % for PCI . CONCLUSIONS Automation of the anchor-collagen closure of femoral artery access sites with the Angio-Seal ECVD result ed in excellent efficacy and safety after routine cardiac catheterization and intervention" ]

[ "27721262", "26104943", "21073623", "5302991", "27418129", "11870157", "4156653", "22160648", "24609941", "23154078", "28034064", "26891913", "16298001", "24666012", "15936538", "7713792", "17189069", "21940159" ]

[ "The efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy for esophageal squamous cell carcinoma in Chinese population: A single institution experience.", "Expert Consensus Contouring Guidelines for Intensity Modulated Radiation Therapy in Esophageal and Gastroesophageal Junction Cancer.", "Phase I study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and pemetrexed, cisplatin for locally advanced esophageal squamous cell carcinoma.", "A phase II study of concurrent chemoradiotherapy and erlotinib for inoperable esophageal squamous cell carcinoma", "Comparison of dosimetric parameters and toxicity in esophageal cancer patients undergoing 3D conformal radiotherapy or VMAT", "INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy.", "Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer", "Analysis of dose–volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation therapy or IMRT", "Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma", "ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy.", "Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial.", "Phase I study of concurrent selective lymph node late-course accelerated hyperfractionated radiotherapy and S-1 plus cisplatin for locally advanced oesophageal squamous cell carcinoma.", "Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer.", "Phase II study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and pemetrexed and cisplatin for locally advanced oesophageal squamous cell carcinoma.", "Challenges in defining radiation pneumonitis in patients with lung cancer.", "Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)", "Prospective assessment of dosimetric/physiologic-based models for predicting radiation pneumonitis.", "Volumetric modulated arc radiotherapy for esophageal cancer." ]

[ "PURPOSE To evaluate the clinical efficacy and toxicity of simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in patients with esophageal squamous cell carcinoma ( ESCC ) in Chinese population . PATIENTS AND METHODS Patients with ESCC , who received SIB-IMRT from September 2011 to January 2013 were retrospectively analyzed . The SIB-IMRT plans were design ed to deliver primary gross tumor volume at 60 - 64.4 Gy in 28 - 30 fractions , and planning target volume at 50.4 - 56 Gy in 28 - 30 fractions . Treatment-related toxicities were estimated based on Common Terminology Criteria for Adverse Events version 4.0 , and tumor response after the treatment was estimated according to Response Evaluation Criteria in Solid Tumors version 1.0 . Overall survival ( OS ) , locoregional progression-free survival ( LPFS ) , and progression-free survival ( PFS ) were estimated with Kaplan-Meier . RESULTS All patients completed definitive radiotherapy , 54 ( 78.3 % ) received combined chemotherapy , of which 31 ( 44.9 % ) were concurrent chemoradiotherapy and 23 ( 33.3 % ) were sequential chemotherapy . The objective response rate is 82.6 % ( 56/69 ) , with complete response 11 ( 15.9 % ) , partial response 45 ( 65.2 % ) , stable disease 8 ( 11.6 % ) , and progressive disease 5 ( 7.2 % ) . The 1- , 2- and 3-year LPFS was 74.4 % , 57.8 % , and 55.6 % , respectively . The 1- , 2- and 3-year PFS was 62.3 % , 41.0 % , and 34.2 % , respectively , and the 1- , 2- , and 3-year OS was 73.8 % , 57.4 % , and 41.0 % , respectively , with a median OS of 27.1 months ( 4.5 - 54.9 m ) . For those who received concurrent chemotherapy , the 1- , 2- , and 3-year OS was 75.9 % , 69.0 % , and 55.2 % , respectively , better than those who had sequential chemotherapy or radiotherapy alone ( χ2 = 3.115 , P = 0.078 ) . Radiation esophagitis occurred in 63.8 % and 14.5 % with Grade 2 and 3 , respectively . No patients occurred ≥ Grade 3 radiation pneumonia . CONCLUSIONS It is safe and effective using SIB-IMRT technology to treat patients with ESCC . More prospect i ve clinical studies should be needed", "PURPOSE / OBJECTIVE ( S ) Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony l and marks , and they do not provide sufficient anatomic detail to ensure consistent contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy ( IMRT ) . Therefore , we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume ( CTV ) in esophageal or gastroesophageal junction ( GEJ ) cancer . METHODS AND MATERIAL S Eight expert academically based gastrointestinal radiation oncologists participated . Three sample cases were chosen : a GEJ cancer , a distal esophageal cancer , and a mid-upper esophageal cancer . Uniform computed tomographic ( CT ) simulation data sets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert , and the expert was instructed to generate gross tumor volume ( GTV ) and CTV contours for each case . All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours . The panel then refined these contours to generate the contouring atlas . RESULTS The κ statistics indicated substantial agreement between panelists for each of the 3 test cases . A consensus CTV atlas was generated for the 3 test cases , each representing common anatomic presentations of esophageal cancer . The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases . CONCLUSIONS This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas . This atlas will serve as a reference for IMRT contours for clinical practice and prospect i ve trial design . Subsequent patterns of failure analyses of clinical data sets using these guidelines may require modification in the future", "The optimized concurrent chemoradiotherapy has not been established for patients with advanced esophageal squamous cell carcinoma ( SCC ) . The aim of the present study was to evaluate the safety and efficacy of concurrent chemotherapy and selective lymph node ( SLN ) late course accelerated hyperfractionated ( LCAF ) intensity modulated radiotherapy ( IMRT ) for the patients with thoracic SCC . Twelve patients with T3 - 4N0 - 1M0 - 1a thoracic esophageal SCC were included . The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks . The concurrent chemotherapy protocol was as following : cisplatin 10 mg/m(2 ) on days 1 - 5 and 22 - 26 , pemetrexed in escalating doses , from the base level of 500 mg/m(2 ) once every 21 days . The primary objectives were to determine the maximum tolerated dose ( MTD ) , recommended dose ( RD ) , and dose limiting toxicities ( DLTs ) . Secondary end point included determination of preliminary radiographic response rates . As a result , three patients were enrolled in dose level 1 with pemetrexed 500 mg/m(2 ) and nine patients in dose level 0 with 400 mg/m(2 ) , respectively . At dose level 1 , DLTs occurred in two of three patients . However , only two of nine patients in Level 0 developed DLTs . The complete response and partial response were observed in eight and four patients , respectively . Furthermore , no patient experienced cancer progression with a median follow-up of 9 months . In conclusion , the concurrent SLN LCAF IMRT and chemotherapy is feasible . The MTD of pemetrexed in this regimen was 500 mg/m(2 ) and RD was 400 mg/m(2 ) . Although toxicities were common , the protocol was safe , well tolerated , and achieved an encouraging outcome", "Cisplatin-based concurrent chemoradiotherapy for patients with unresectable , locally advanced esophageal squamous cell carcinoma ( ESCC ) is associated with significant toxicities that are often intolerable . Prognosis for this subgroup of patients remains poor , and new therapeutic approaches are urgently needed . We investigated the efficacy and safety of paclitaxel combined with erlotinib and concurrent radiotherapy in patients with inoperable ESCC . Erlotinib ( 150 mg ) was administered daily for 60 days beginning at the start of radiotherapy , and paclitaxel ( 45 mg/m² ) was administered weekly along with intensity modulated conformal radiotherapy ( 60 Gy in 30 fractions ) . The median follow-up time was 21 months . The associations between EGFR and VEGF expression and treatment outcome were evaluated . Among the 21 patients treated , the overall response rate ( CR + PR ) was 85.6 % . The median LPFS , PFS and OS were : 17.5 , 14.3 , and 22.9 months , respectively . Treatment-related grade 3 toxicities included esophagitis ( two patients ) and hypoleukemia ( one patient ) . Grade 4 pulmonary toxicity was observed in one patient . Patients expressing EGFR had longer PFS , while those expressing VEGF or with a history of smoking had worse outcomes . Weekly paclitaxel combined with erlotinib and concurrent radiotherapy shows promise as an effective , tolerated regimen for patients with inoperable ESCC", "Purpose Volumetric-modulated arc therapy ( VMAT ) achieves high conformity to the planned target volume ( PTV ) and good sparing of organs at risk ( OAR ) . This study compares dosimetric parameters and toxicity in esophageal cancer ( EC ) patients treated with VMAT and 3D conformal radiotherapy ( 3D-CRT ) . Material s and methods Between 2007 and 2014 , 17 SC patients received neoadjuvant chemoradiation ( CRT ) with VMAT . Dose – volume histograms and toxicity were compared between these patients and 20 treated with 3D-CRT . All patients were irradiated with a total dose of 45 Gy . All VMAT patients received simultaneous chemotherapy with cisplatin and 5‑fluorouracil ( 5-FU ) in treatment weeks 1 and 5 . Of 20 patients treated with 3D-CRT , 13 ( 65 % ) also received CRT with cisplatin and 5‑FU , whereas 6 patients ( 30 % ) received CRT with weekly oxaliplatin and cetuximab , and a continuous infusion of 5‑FU ( OE-7 ) . Results There were no differences in baseline characteristics between the treatment groups . For the lungs , VMAT was associated with a higher V5 ( median 90.1 % vs. 79.7 % ; p = 0.013 ) and V10 ( 68.2 % vs. 56.6 % ; p = 0.014 ) , but with a lower V30 ( median 6.6 % vs. 11.0 % ; p = 0.030 ) . Regarding heart parameters , VMAT was associated with a higher V5 ( median 100.0 % vs. 91.0 % ; p = 0.043 ) , V10 ( 92.0 % vs. 79.2 % ; p = 0.047 ) , and Dmax ( 47.5 Gy vs. 46.3 Gy ; p = 0.003 ) , but with a lower median dose ( 18.7 Gy vs. 30.0 Gy ; p = 0.026 ) and V30 ( 17.7 % vs. 50.4 % ; p = 0.015 ) . Complete resection was achieved in 16 VMAT and 19 3D-CRT patients . Due to systemic progression , 2 patients did not undergo surgery . The most frequent postoperative complication was anastomosis insufficiency , occurring in 1 VMAT ( 6.7 % ) and 5 3D-CRT patients ( 27.8 % ; p = 0.180 ) . Postoperative pneumonia was seen in 2 patients of each group ( p = 1.000 ) . There was no significant difference in 3‑year overall ( 65 % VMAT vs. 45 % 3D-CRT ; p = 0.493 ) or 3‑year progression-free survival ( 53 % VMAT vs. 35 % 3D-CRT ; p = 0.453 ) . Conclusion Although dosimetric differences in lung and heart exposure were observed , no clinical ly relevant impact was detected in either patient group . In a real-life patient cohort , VMAT enables reduction of lung and heart V30 compared to 3D-CRT , which may contribute to reduced toxicity . ZusammenfassungZielDie volumetrisch modulierte Rotationstherapie ( VMAT ) erreicht eine hohe Abdeckung des Planungszielvolumens mit guter Schonung der Risikoorgane . Verglichen wurden dosimetrische Parameter und Toxizität zwischen VMAT und 3D-konformaler Strahlentherapie ( 3D-CRT ) bei Patienten mit Ösophaguskarzinom . Material und Method enZwischen 2007 und 2014 erhielten 17 Patienten während der neoadjuvanten Radiochemotherapie eine VMAT . Dosis-Volumen-Histogramme und Toxizität wurden mit 20 mit 3D-CRT beh and elten Patienten verglichen . Die Gesamtdosis aller Patienten betrug 45 Gy ( Tagesdosis 1,8 Gy ) . Die VMAT-Gruppe erhielt eine simultane Chemotherapie mit Cisplatin und 5‑Fluoruracil ( 5-FU ) in der 1 . und 5 . Woche . In der 3D-CRT-Gruppe bekamen 13 Patienten ( 65 % ) ebenfalls eine Chemotherapie mit Cisplatin und 5‑FU , 6 Patienten ( 30 % ) eine wöchentliche Chemotherapie mit Oxaliplatin und Cetuximab , sowie eine kontinuierliche Chemotherapie mit 5‑FU (OE-7).ErgebnisseHinsichtlich der Basischarakteristika zeigte sich kein Unterschied zwischen den Gruppen . Für die Lungen war VMAT mit einer höheren V5 ( Median 90,1 % vs. 79,7 % ; p = 0,013 ) und V10 ( 68,2 % vs. 56,6 % ; p = 0,014 ) , aber einer niedrigeren V30 assoziiert ( Median 6,6 % vs. 11,0 % ; p = 0,030 ) . Für das Herz waren für VMAT V5 ( Median 100 % vs. 91 % ; p = 0,043 ) , V10 ( 92 % vs. 79,2 % , p = 0,047 ) und Dmax ( 47,5 Gy vs. 46,3 Gy ; p = 0,003 ) höher , die mittlere Dosis ( 18,7 Gy vs. 30 Gy , p = 0,026 ) und V30 ( 17,7 % vs. 50,4 % ; p = 0,015 ) niedriger . Bei 16 VMAT- bzw . 19 3D-CRT-Patienten wurde der Tumor komplett reseziert . Aufgrund eines systemischen Progresses wurden 2 Patienten nicht operiert . Häufigste postoperative Komplikation war die Anastomoseninsuffizienz bei einem VMAT- ( 6,7 % ) und 5 3D-CRT-Patienten ( 27,8 % ; p = 0,180 ) . In jeder Gruppe entwickelten 2 Patienten eine postoperative Pneumonie ( p = 1,000 ) . Beim 3‑Jahres-Gesamt- ( 65 % vs. 45 % ; p = 0,493 ) und progressionsfreien Überleben ( 53 % vs. 35 % ; p = 0,453 ) zeigte sich kein Unterschied . Ein Lokalrezidiv wurde bei 6 3D-CRT- ( 30 % ) und bei einem VMAT-Patienten ( 6 % ) beobachtet ( p = 0,097).SchlussfolgerungDosimetrische Unterschiede der Dosisverteilung in Herz und Lungen waren klinisch nicht relevant . Verglichen mit 3D-CRT reduziert VMAT V30 für Lunge und Herz und somit möglicherweise die Toxizität", "PURPOSE To compare the local/regional control , survival , and toxicity of combined-modality therapy using high-dose ( 64.8 Gy ) versus st and ard-dose ( 50.4 Gy ) radiation therapy for the treatment of patients with esophageal cancer . PATIENTS AND METHODS A total of 236 patients with clinical stage T1 to T4 , N0/1 , M0 squamous cell carcinoma or adenocarcinoma selected for a nonsurgical approach , after stratification by weight loss , primary tumor size , and histology , were r and omized to receive combined-modality therapy consisting of four monthly cycles of fluorouracil ( 5-FU ) ( 1,000 mg/m(2)/24 hours for 4 days ) and cisplatin ( 75 mg/m(2 ) bolus day 1 ) with concurrent 64.8 Gy versus the same chemotherapy schedule but with concurrent 50.4 Gy . The trial was stopped after an interim analysis . The median follow-up was 16.4 months for all patients and 29.5 months for patients still alive . RESULTS For the 218 eligible patients , there was no significant difference in median survival ( 13.0 v 18.1 months ) , 2-year survival ( 31 % v 40 % ) , or local/regional failure and local/regional persistence of disease ( 56 % v 52 % ) between the high-dose and st and ard-dose arms . Although 11 treatment-related deaths occurred in the high-dose arm compared with two in the st and ard-dose arm , seven of the 11 deaths occurred in patients who had received 50.4 Gy or less . CONCLUSION The higher radiation dose did not increase survival or local/regional control . Although there was a higher treatment-related mortality rate in the patients assigned to the high-dose radiation arm , it did not seem to be related to the higher radiation dose . The st and ard radiation dose for patients treated with concurrent 5-FU and cisplatin chemotherapy is 50.4 Gy", "Background To report our experience with increased dose intensity-modulated radiation and concurrent systemic chemotherapy as definitive treatment of locally advanced esophageal cancer . Patients and methods We analyzed 27 consecutive patients with histologically proven esophageal cancer , who were treated with increased-dose IMRT as part of their definitive therapy . The majority of patients had T3/4 and /or N1 disease ( 93 % ) . Squamous cell carcinoma was the dominating histology ( 81 % ) . IMRT was delivered in step- and -shoot technique in all patients using an integrated boost concept . The boost volume was covered with total doses of 56 - 60 Gy ( single dose 2 - 2.14 Gy ) , while regional nodal regions received 50.4 Gy ( single dose 1.8 Gy ) in 28 fractions . Concurrent systemic therapy was scheduled in all patients and administered in 26 ( 96 % ) . 17 patients received additional adjuvant systemic therapy . Loco-regional control , progression-free and overall survival as well as acute and late toxicities were retrospectively analyzed . In addition , quality of life was prospect ively assessed according to the EORTC QLQs ( QLQ-OG25 , QLQ-H&N35 and QLQ-C30 ) . Results Radiotherapy was completed as planned in all but one patient ( 96 % ) , and 21 patients received more than 80 % of the planned concurrent systemic therapy . We observed ten locoregional failures , transferring into actuarial 1- , 2- and 3-year-locoregional control rates of 77 % , 65 % and 48 % . Seven patients developed distant metastases , mainly to the lung ( 71 % ) . The actuarial 1- , 2- and 3-year-disease free survival rates were 58 % , 48 % and 36 % , and overall survival rates were 82 % , 61 % and 56 % . The concept was well tolerated , both in the clinical objective examination and also according to the subjective answers to the QLQ question naire . 14 patients ( 52 % ) suffered from at least one acute CTC grade 3/4 toxicity , mostly hematological side effects or dysphagia . Severe late toxicities were reported in 6 patients ( 22 % ) , mostly esophageal strictures and ulcerations . Severe side effects to skin , lung and heart were rare . Conclusion IMRT with concurrent systemic therapy in the definitive treatment of esophageal cancer using an integrated boost concept with doses up to 60 Gy is feasible and yields good results with acceptable acute and late overall toxicity and low side effects to skin , lung and heart", "Purpose Multimodality therapy for esophageal cancer can cause various kinds of treatment-related sequelae , especially pulmonary toxicities . This prospect i ve study aims to investigate the clinical and dosimetric parameters predicting lung injury in patients undergoing radiation therapy for esophageal cancer . Methods Forty-five esophageal cancer patients were prospect ively analyzed . The pulmonary toxicities ( or sequelae ) were evaluated by comparing chest X-ray films , pulmonary function tests and symptoms caused by pulmonary damage before and after treatment . All patients were treated with either three-dimensional radiotherapy ( 3DCRT ) or with intensity-modulated radiotherapy ( IMRT ) . The planning dose volume histogram was used to compute the lung volumes receiving more than 5 , 10 , 20 and 30 Gy ( V5 , V10 , V20 , V30 ) and mean lung dose . Results V20 was larger in the IMRT group than in the 3DCRT group ( p = 0.002 ) . V20 ( > 15 % ) and V30 ( > 20 % ) result ed in a statistically significant increase in the occurrence of chronic pneumonitis ( p = 0.03 ) and acute pneumonitis ( p = 0.007 ) , respectively . Conclusions The study signifies that a larger volume of lung receives lower doses because of multiple beam arrangement and a smaller volume of lung receives higher doses because of better dose conformity in IMRT plans . Acute pneumonitis correlates more with V30 values , whereas chronic pneumonitis was predominantly seen in patients with higher V20 values", "Purpose The safety and efficacy of using simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) for patients with esophageal squamous cell carcinoma were evaluated in a single-institution phase II setting . Methods and material sBetween June 2007 and October 2009 , 45 patients underwent concurrent chemoradiotherapy ( n = 27 ) or radiotherapy alone ( n = 18 ) . Two planning target volumes ( PTV ) were defined for the SIB : PTVC and PTVG , with prescribed doses of 50.4 Gy to the PTVC ( 1.8 Gy/fraction ) and 63 Gy to the PTVG ( 2.25 Gy/fraction ) , both given in 28 fractions . Results At a median follow-up interval of 20.3 months , the 3-year overall survival ( OS ) and progression-free survival ( PFS ) rates were 42.2 and 40.7 % , respectively . The median overall survival time was 21 months ; locoregional control rates were 83.3 % at 1 year and 67.5 % at 3 years . According to CTCAE ( version 3.0 ) criteria , none of the patients developed grade 4–5 toxicity . The most common grade 2 and 3 radiation-related toxicity was radiation esophagitis , occurring in 64 % of all patients ( but only 13 % as grade 3 ) . No patient developed grade > 2 pulmonary complications . ConclusionS IB-IMRT is a feasible therapeutic approach for esophageal carcinoma patients and provides encouraging locoregional control with a low toxicity profile . Further investigations should focus on dose escalation and optimization of the combination with systemic therapies . ZusammenfassungZielDie Wirksamkeit und Effektivität einer intensitätsmodulierten Radiotherapie mit einem simultan integrierten Boost ( SIB-IMRT ) für Patienten mit Ösophaguskarzinom wurde in einer Single-Institution-Phase-II-Studie bewertet . Method en und Material Zwischen Juni 2007 und Oktober 2009 wurden 45 Patienten mit einer simultanen Radiochemotherapie ( n = 27 ) oder einer alleinigen Strahlentherapie ( n = 18 ) beh and elt . Zwei Planungszielvolumen ( PTV ) wurden für die SIB definiert : PTVC und PTVG , mit vorgeschriebenen Dosen von 50,4 Gy für PTVC ( 1,8 Gy/Fraktion ) und 63 Gy für PTVG ( 2,25 Gy/Fraktion ) , beide in 28 Fraktionen verabreicht . ErgebnisseBei einer mittleren Verlaufsbeobachtung von 20,3 Monaten lagen die 3-Jahres-Überlebensraten für das Gesamtüberleben ( OS ) und das progressionsfreie Überleben ( PFS ) bei jeweils 42,2 und 40,7 % . Das mediane OS betrug 21 Monate ; lokoregionäre Kontrollraten waren 83,3 % nach 1 Jahr und 67,5 % nach 3 Jahren . Bei keinem Patienten entwickelten sich eine Toxizität von Grad 4–5 gemäß der CTCAE-Kriterien ( Version 3.0 ) . Die häufigste strahlenbedingte Toxizität von Grad 2 und 3 war bei 64 % aller Patienten eine Ösophagitis ( aber nur 13 % mit Grad 3 ) . Bei keinem Patienten entwickelten sich pulmonale Komplikationen > Grad 2.SchlussfolgerungSIB-IMRT funktioniert grundsätzlich für Patienten mit Ösophaguskarzinom . Es bewirkt eine Förderung der lokoregionären Kontrolle mit akzeptabler Toxizität . Weitere Untersuchungen zur Dosissteigerung und Optimierung der Kombination sollten mit einer systemischen Therapie durchgeführt werden", "PURPOSE The ataxia telangiectasia mutated ( ATM ) gene mediates detection and repair of DNA damage . We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis ( RP ) . METHODS AND MATERIAL S We genotyped 3 potentially functional single nucleotide polymorphisms ( SNPs ) of ATM ( rs1801516 [ D1853N/5557G > A ] , rs189037 [ -111G > A ] and rs228590 ) in 362 patients with non-small cell lung cancer ( NSCLC ) , who received definitive (chemo)radiation therapy . The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis . The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered . RESULTS Of 362 patients ( 72.4 % of non-Hispanic whites ) , 56 ( 15.5 % ) experienced grade ≥3 RP . Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516 G ( G-T-G ) haplotype had a lower risk of severe RP ( rs189037 : GG/AG vs AA , adjusted hazard ratio [ HR ] = 0.49 , 95 % confidence interval [ CI ] , 0.29 - 0.83 , P=.009 ; rs228590 : TT/CT vs CC , HR=0.57 , 95 % CI , 0.33 - 0.97 , P=.036 ; haplotype : G-T-G vs A-C-G , HR=0.52 , 95 % CI , 0.35 - 0.79 , P=.002 ) . Such positive findings remained in non-Hispanic whites . CONCLUSIONS ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites . Large prospect i ve studies are required to confirm our findings", "Purpose Although intensity-modulated radiation therapy ( IMRT ) is increasingly used to treat locally advanced non-small-cell lung cancer ( NSCLC ) , IMRT and three-dimensional conformal external beam radiation therapy ( 3D-CRT ) have not been compared prospect ively . This study compares 3D-CRT and IMRT outcomes for locally advanced NSCLC in a large prospect i ve clinical trial . Patients and Methods A secondary analysis was performed to compare IMRT with 3D-CRT in NRG Oncology clinical trial RTOG 0617 , in which patients received concurrent chemotherapy of carboplatin and paclitaxel with or without cetuximab , and 60- versus 74-Gy radiation doses . Comparisons included 2-year overall survival ( OS ) , progression-free survival , local failure , distant metastasis , and selected Common Terminology Criteria for Adverse Events ( version 3 ) ≥ grade 3 toxicities . Results The median follow-up was 21.3 months . Of 482 patients , 53 % were treated with 3D-CRT and 47 % with IMRT . The IMRT group had larger planning treatment volumes ( median , 427 v 486 mL ; P = .005 ) ; a larger planning treatment volume/volume of lung ratio ( median , 0.13 v 0.15 ; P = .013 ) ; and more stage IIIB disease ( 30.3 % v 38.6 % , P = .056 ) . Two-year OS , progression-free survival , local failure , and distant metastasis-free survival were not different between IMRT and 3D-CRT . IMRT was associated with less ≥ grade 3 pneumonitis ( 7.9 % v 3.5 % , P = .039 ) and a reduced risk in adjusted analyses ( odds ratio , 0.41 ; 95 % CI , 0.171 to 0.986 ; P = .046 ) . IMRT also produced lower heart doses ( P < .05 ) , and the volume of heart receiving 40 Gy ( V40 ) was significantly associated with OS on adjusted analysis ( P < .05 ) . The lung V5 was not associated with any ≥ grade 3 toxicity , whereas the lung V20 was associated with increased ≥ grade 3 pneumonitis risk on multivariable analysis ( P = .026 ) . Conclusion IMRT was associated with lower rates of severe pneumonitis and cardiac doses in NRG Oncology clinical trial RTOG 0617 , which supports routine use of IMRT for locally advanced NSCLC", "OBJECTIVE This Phase I study aim ed to assess the safety and efficacy of concurrent selective lymph node ( SLN ) late-course accelerated hyperfractionated ( LCAF ) intensity-modulated radiotherapy ( IMRT ) and S-1 plus cisplatin ( CDDP ) for the locally advanced oesophageal squamous-cell carcinoma ( ESCC ) . METHODS The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks . The concurrent chemotherapy ( CCRT ) was administered as follows : CDDP 25 mg m(-2 ) on Days 1 - 3 and Days 22 - 24 ; S-1 was applied in a de-escalating dosage with a decrement of 10 mg m(-2 ) per day , from its full dose level of 80 mg m(-2 ) , orally twice daily on Days 1 - 14 and Days 22 - 35 . We inferred the maximum-tolerated dose ( MTD ) , dose-limiting toxicities ( DLTs ) and recommended dose , according to adverse reaction during CCRT . RESULTS Totally , 15 patients with ESCC with T2 - 4N0 - 1M0 - 1a were enrolled in Dose Level 1 ( 80 mg m(-2 ) ) . In the initial five patients , two patients developed DLTs . As MTD was not reached , five additional patients were treated with the same dose level , and DLTs occurred in only one patient . Similar results were found in the last five patients . After CCRT , the objective response rates were 100 % for primary tumours and 86.2 % for metastatic lymph nodes , respectively . Totally , the observed Grade 3 toxicities during CCRT were leukopenia ( 20 % ) , neutropenia ( 20 % ) and dermatitis ( 13.3 % ) , and no Grade 4 toxicity occurred . The Kaplan-Meier-estimated overall and progression survival rates were 86.7 % and 66.7 % ( 1 year ) , 73.3 % and 60 % ( 2 years ) and 73.3 % and 60 % ( 3 years ) . CONCLUSION The concurrent SLN LCAF IMRT and chemotherapy with S-1 and CDDP was well tolerated and showed promising efficacy . The dose of S-1 in this regimen was recommended with 80 mg m(-2 ) orally twice daily on Days 1 - 14 and Days 22 - 35 . ADVANCES IN KNOWLEDGE CCRT with S-1 plus CDDP exhibited encouraging results with milder toxicities , high objective response rates and ideal overall survival time", "BACKGROUND AND PURPOSE To evaluate the feasibility whether intensity-modulated radiotherapy ( IMRT ) can be used to reduce doses to normal lung than three-dimensional conformal radiotherapy ( 3 DCRT ) in treating distal esophageal malignancies . PATIENTS AND METHODS Ten patient cases with cancer of the distal esophagus were selected for a retrospective treatment-planning study . IMRT plans using four , seven , and nine beams ( 4B , 7B , and 9B ) were developed for each patient and compared with the 3 DCRT plan used clinical ly . IMRT and 3 DCRT plans were evaluated with respect to PTV coverage and dose-volumes to irradiated normal structures , with statistical comparison made between the two types of plans using the Wilcoxon matched-pair signed-rank test . RESULTS IMRT plans ( 4B , 7B , 9B ) reduced total lung volume treated above 10 Gy ( V(10 ) ) , 20 Gy ( V(20 ) ) , mean lung dose ( MLD ) , biological effective volume ( V(eff ) ) , and lung integral dose ( P<0.05 ) . The median absolute improvement with IMRT over 3DCRT was approximately 10 % for V(10 ) , 5 % for V(20 ) , and 2.5 Gy for MLD . IMRT improved the PTV heterogeneity ( P<0.05 ) , yet conformity was better with 7B-9B IMRT plans . No clinical ly meaningful differences were observed with respect to the irradiated volumes of spinal cord , heart , liver , or total body integral doses . CONCLUSIONS Dose-volume of exposed normal lung can be reduced with IMRT , though clinical investigations are warranted to assess IMRT treatment outcome of esophagus cancers", "OBJECTIVE To determine the clinical efficacy and toxicity of pemetrexed combined with low-dose cisplatin ( CDDP ) concurrent with late-course accelerated hyperfractionated ( LCAF ) intensity-modulated radiation therapy ( IMRT ) in patients with inoperable locally advanced oesophageal squamous cell carcinoma ( ESCC ) . METHODS Patients with locally advanced ESCC ( less than or equal to 75 years of age , clinical stages IIB-IVA and Karnofsky performance status ≥70 ) were enrolled into the study . A target group size of 22 was projected based on the estimation that 2-year overall survival ( OS ) would increase from 20 % to 40 % . Patients were treated with pemetrexed , low-dose CDDP and LCAF IMRT concurrently . The main objective of the study was for a 2-year OS , and the secondary objectives were progression-free survival ( PFS ) , objective response , locoregional failure rate , and acute and late toxicities . RESULTS 25 patients were recruited from October 2008 to July 2011 . The median OS was 21 months , with 2- and 5-year OS rates of 44 % and 44 % , respectively . The median PFS was 18.2 months . The objective response rate was 96 % ( 24/25 ) , with 11 complete responses and 13 partial responses . The locoregional failure rate was 16 % . Grade s 4 and 5 acute toxicity rates were 8 % and 4 % , respectively , while no Grade 3 or greater late toxicity was observed . CONCLUSION The findings of this Phase II study indicated that the therapeutic regimen appears to achieve an excellent response rate and favourable survival for locally advanced ESCC . However , the severe acute side effects should be considered cautiously in further studies . ADVANCES IN KNOWLEDGE To our knowledge , this is the first study that introduced pemetrexed and low-dose CDDP combined with LCAF IMRT to treat locally advanced ESCC . The 5-year OS rate was as high as 44 % , which was more favourable than other studies", "PURPOSE To assess the difficulty of assigning a definitive clinical diagnosis of radiation (RT)-induced lung injury in patients irradiated for lung cancer . METHODS Between 1991 and 2003 , 318 patients were enrolled in a prospect i ve study to evaluate RT-induced lung injury . Only patients with lung cancer who had a longer than 6-month follow-up ( 251 patients ) were considered in the current analysis . Of these , 47 of 251 patients had Grade > /=2 ( treated with steroids ) increasing shortness of breath after RT , thought possibly consistent with pneumonitis/fibrosis . The treating physician , and one to three additional review ing physicians , evaluated the patients or their medical records , or both . The presence or absence of confounding clinical factors that made the diagnosis of RT-induced uncertain lung injury were recorded . RESULTS Thirty-one of 47 patients ( 66 % ) with shortness of breath had \" classic \" pneumonitis , i.e. , they responded to steroids and had a definitive diagnosis of pneumonitis . In 13 of 47 patients ( 28 % ) , the diagnosis of RT-induced toxicity was confounded by possible infection ; exacerbation of preexisting lung disease ( chronic obstructive pulmonary disease ) ; tumor regrowth/progression ; and cardiac disease in 6 , 8 , 5 , and 1 patients , respectively ( some of the patients had multiple confounding factors and were counted more than once ) . An additional 3 patients ( 6 % ) had progressive shortness of breath and an overall clinical course more consistent with fibrosis . All 3 had evidence of bronchial stenosis by bronchoscopy . CONCLUSIONS Scoring of radiation pneumonitis was challenging in 28 % of patients treated for lung cancer owing to confounding medical conditions . Recognition of this uncertainty is needed and may limit our ability to underst and RT-induced lung injury", "The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells . From quite early in the history of radiation therapy , it was apparent that there were striking differences in effects in the panoply of normal tissues . Although there was early appreciation of some late effects in normal tissues , often not predicted by acute reactions , only in recent years has there been full documentation of the slow and progressive increase in severity of late damage . Pathophysiological mechanisms of acute and late radiation effects are better understood today ( 2 ) , but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae . The work of Stone ( 3 ) is a classic example of unanticipated late effects , which result ed from irradiation with ‘ fast neutrons . Acute reactions were moderate and tolerable , but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades . The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group ( RTOG ) staff . In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG . Recognizing the results of Stone , this committee , led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy . Investigators from the European Organization for Research and Treatment of Cancer ( EORTC ) , led by William Duncan of the Western General Hospital of Edinburgh , wished to have common toxicity criteria in anticipation of joint studies . RTOG Protocol 7929 , an international registry of patients treated with heavy particles , was started in 1980 . At the annual meetings of the international participants in particle studies , there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity , but no publications document these efforts . The first prospect i ve trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001 , a study of fast neutron therapy for malignant tumors arising in salivary gl and s. Although the RTOG began to use these criteria in reporting toxicity in patients enrolled in all studies from 198 1 ( beginning with RTOG Protocol 8 115 ) , the criteria only became a published part of protocol s in 1983 . At that time , statistical methods began to be used , which presented time-adjusted estimates of late effects , the rationale for which was described by Cox ( 1 ) . It is now considered st and ard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival . The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria . The National Cancer Institute promulgated st and ard toxicity criteria in 1990 , but late effects were not considered . An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the St and ard for Breast Conservation Treatment . The current RTOG Acute Radiation Morbidity Scoring Criteria are presented in Table 1 . The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2 . In both tables , 0 means an absence of radiation effects and 5 means the effects led to death . The", "PURPOSE Clinical and 3D dosimetric parameters are associated with symptomatic radiation pneumonitis rates in retrospective studies . Such parameters include : mean lung dose ( MLD ) , radiation ( RT ) dose to perfused lung ( via SPECT ) , and pre-RT lung function . Based on prior publications , we defined pre-RT criteria hypothesized to be predictive for later development of pneumonitis . We herein prospect ively test the predictive abilities of these dosimetric/functional parameters on 2 cohorts of patients from Duke and The Netherl and s Cancer Institute ( NKI ) . METHODS AND MATERIAL S For the Duke cohort , 55 eligible patients treated between 1999 and 2005 on a prospect i ve IRB-approved study to monitor RT-induced lung injury were analyzed . A similar group of patients treated at the NKI between 1996 and 2002 were identified . Patients believed to be at high and low risk for pneumonitis were defined based on : ( 1 ) MLD ; ( 2 ) OpRP ( sum of predicted perfusion reduction based on regional dose-response curve ) ; and ( 3 ) pre-RT DLCO . All doses reflected tissue density heterogeneity . The rates of grade > or = 2 pneumonitis in the \" presumed \" high and low risk groups were compared using Fisher 's exact test . RESULTS In the Duke group , pneumonitis rates in patients prospect ively deemed to be at \" high \" vs. \" low \" risk are 7 of 20 and 9 of 35 , respectively ; p = 0.33 one-tailed Fisher 's . Similarly , comparable rates for the NKI group are 4 of 21 and 6 of 44 , respectively , p = 0.41 one-tailed Fisher 's . CONCLUSION The prospect i ve model appears unable to accurately segregate patients into high vs. low risk groups . However , considered retrospectively , these data are consistent with prior studies suggesting that dosimetric ( e.g. , MLD ) and functional ( e.g. , PFTs or SPECT ) parameters are predictive for RT-induced pneumonitis . Additional work is needed to better identify , and prospect ively assess , predictors of RT-induced lung injury", "A treatment planning study was performed to evaluate the performance of volumetric arc modulation with RapidArc ( RA ) against 3D conformal radiation therapy ( 3D-CRT ) and conventional intensity-modulated radiation therapy ( IMRT ) techniques for esophageal cancer . Computed tomgraphy scans of 10 patients were included in the study . 3D-CRT , 4-field IMRT , and single-arc and double-arc RA plans were generated with the aim to spare organs at risk ( OAR ) and healthy tissue while enforcing highly conformal target coverage . The planning objective was to deliver 54 Gy to the planning target volume ( PTV ) in 30 fractions . Plans were evaluated based on target conformity and dose-volume histograms of organs at risk ( lung , spinal cord , and heart ) . The monitor unit ( MU ) and treatment delivery time were also evaluated to measure the treatment efficiency . The IMRT plan improves target conformity and spares OAR when compared with 3D-CRT . Target conformity improved with RA plans compared with IMRT . The mean lung dose was similar in all techniques . However , RA plans showed a reduction in the volume of the lung irradiated at V(₂₀Gy ) and V(₃₀Gy ) dose levels ( range , 4.62 - 17.98 % ) compared with IMRT plans . The mean dose and D(₃₅% ) of heart for the RA plans were better than the IMRT by 0.5 - 5.8 % . Mean V(₁₀Gy ) and integral dose to healthy tissue were almost similar in all techniques . But RA plans result ed in a reduced low-level dose bath ( 15 - 20 Gy ) in the range of 14 - 16 % compared with IMRT plans . The average MU needed to deliver the prescribed dose by RA technique was reduced by 20 - 25 % compared with IMRT technique . The preliminary study on RA for esophageal cancers showed improvements in sparing OAR and healthy tissue with reduced beam-on time , whereas only double-arc RA offered improved target coverage compared with IMRT and 3D-CRT plans" ]

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[ "The effects of weight reduction on the rehabilitation of patients with knee osteoarthritis and obesity.", "Can Trials of Physical Treatments Be Blinded?: The Example of Transcutaneous Electrical Nerve Stimulation for Chronic Pain", "Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.", "Temporary pain relief using transcranial electrotherapy stimulation: results of a randomized, double-blind pilot study", "Undue reliance on I2 in assessing heterogeneity may mislead", "TENS, electroacupuncture and ice massage: comparison of treatment for osteoarthritis of the knee.", "A pilot study on using acupuncture and transcutaneous electrical nerve stimulation (TENS) to treat knee osteoarthritis (OA)", "Acupuncture-like stimulation with codetron for rehabilitation of patients with chronic pain syndrome and osteoarthritis.", "The effects of electro-acupuncture and transcutaneous electrical nerve stimulation on patients with painful osteoarthritic knees: a randomized controlled trial with follow-up evaluation.", "Optimal stimulation duration of tens in the management of osteoarthritic knee pain.", "Transcutaneous electrical nerve stimulation in osteoarthrosis: a therapeutic alternative?", "Comparing Hot Pack, Short-Wave Diathermy, Ultrasound, and TENS on Isokinetic Strength, Pain, and Functional Status of Women with Osteoarthritic Knees: A Single-Blind, Randomized, Controlled Trial", "Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment", "The comparative analgesic efficacy of transcutaneous electrical nerve stimulation and a non-steroidal anti-inflammatory drug for painful osteoarthritis.", "The effectiveness of pulsed electrical stimulation (E-PES) in the management of osteoarthritis of the knee: a protocol for a randomised controlled trial", "Does Transcutaneous Electrical Nerve Stimulation Improve the Physical Performance of People With Knee Osteoarthritis?", "Optimal stimulation frequency of transcutaneous electrical nerve stimulation on people with knee osteoarthritis.", "Does four weeks of TENS and/or isometric exercise produce cumulative reduction of osteoarthritic knee pain?", "OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.", "The treatment of osteoarthritis of the knee with pulsed electrical stimulation.", "The effect of neuromuscular electrical stimulation on arthritis knee pain in older adults with osteoarthritis of the knee.", "Randomized Trial of Codetron for pain Control in Osteoarthritis of the Hip/Knee", "Short-term effects of electrical stimulation superimposed on muscular voluntary contraction in postural control in elderly women.", "Efficacy of periosteal stimulation therapy for the treatment of osteoarthritis-associated chronic knee pain: an initial controlled clinical trial.", "Treatment of osteoarthritis of the knee with transcutaneous electrical nerve stimulation", "A home-based protocol of electrical muscle stimulation for quadriceps muscle strength in older adults with osteoarthritis of the knee.", "Would the addition of TENS to exercise training produce better physical performance outcomes in people with knee osteoarthritis than either intervention alone?", "Comparative effectiveness of different stimulation modes in relieving pain. Part II. A double-blind controlled long-term clinical trial", "Evaluating the benefits of patterned stimulation in the treatment of osteoarthritis of the knee: a multi-center, randomized, single-blind, controlled study with an independent masked evaluator.", "[Low frequency electro-stimulation and ultrasonic therapy (author's transl)].", "Predicting outcome of TENS in chronic pain: A prospective, randomized, placebo controlled trial" ]

[ "OBJECTIVE To evaluate the effect of weight reduction on the rehabilitation of patients with knee osteoarthritis and obesity . METHODS A total of 126 patients with bilateral knee osteoarthritis and obesity were classified into 3 groups by their stages of osteoarthritis . Each group was divided into subgroups a , b , and c. The subjects in subgroup a received weight reduction treatment , those in subgroup b received weight reduction and electrotherapy modalities , and those in subgroup c received electrotherapy modalities to relieve pain . RESULTS Pain reduction , weight reduction , ambulation speed , and changes of Lequesne 's index were greater in patients in subgroups a and b than in subgroup c after treatment . Although the last pain scores in subgroup b were less than those in subgroup a , as measured by a visual analog scale ( VAS ) , there was no significant difference between their functional status . Significant pain relief ( VAS < 2 ) and an acceptable functional status ( Lequesne 's index < 7 ) were indicated when weight reduction was more than 15 % and 12 % , respectively , of the initial body weight of the individual . CONCLUSION Weight reduction was found to be a practical adjuvant treatment in the rehabilitation of patients with knee osteoarthritis", "Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion", "BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . )", "Results of a r and omized , double-blind pilot study indicate that transcranial electrotherapy stimulation may be an effective treatment for the temporary reduction of pain in osteoarthritis patients . Presently , the predominant method for pain management is medication . One very different approach is the application of micro- to milliamp current applied to specific areas of the head , result ing in a release of endogenous opioids from pain management regions of the brain . For the pilot study , 64 subjects suffering from osteoarthritis of the knee and /or hip were enrolled . For two weeks prior , then during and after treatment , subject pain was self-assessed using the visual scale ( VS ) . In addition , subjects were globally assessed by a physician . All subjects , device operators and physicians were blinded as to whether subjects were treated with an active or sham device . Data collected from the study indicate both a decrease in VS pain scores and a significant improvement ( p = 0.05 ) in physician assessment in subjects treated with active devices compared to those treated with the sham device", "Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose", "The purpose of this study was to compare the effectiveness of transcutaneous nerve stimulation ( TENS ) , electroacupuncture ( EA ) , and ice massage with placebo treatment for the treatment of pain . Subjects ( n = 100 ) diagnosed with osteoarthritis ( OA ) of the knee were treated with these modalities . The parameters for evaluating the effectiveness of treatment include pain at rest , stiffness , 50 foot walking time , quadriceps muscle strength , and knee flexion degree . The results showed ( a ) that all three methods could be effective in decreasing not only pain but also the objective parameters in a short period of time ; and ( b ) that the treatment results in TENS , EA and ice massage were superior to placebo", "Background The present study tests whether a combined treatment of acupuncture and transcutaneous electrical nerve stimulation ( TENS ) is more effective than acupuncture or TENS alone for treating knee osteoarthritis ( OA ) . Methods Thirty-two patients with knee OA were r and omly allocated to four groups . The acupuncture group ( ACP ) received only acupuncture treatment at selected acupoints for knee pain ; the TENS group ( TENS ) received only TENS treatment at pain areas ; the acupuncture and TENS group ( A&T ) received both acupuncture and TENS treatments ; the control group ( CT ) received topical poultice ( only when necessary ) . Each group received specific weekly treatment five times during the study . Outcome measures were pain intensity in a visual analogue scale ( VAS ) and knee function in terms of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Results The ACP , TENS and A&T groups reported lower VAS and WOMAC scores than the control group . Significant reduction in pain intensity ( P = 0.039 ) and significant improvement in knee function ( P = 0.008 ) were shown in the A&T group . Conclusion Combined acupuncture and TENS treatment was effective in pain relief and knee function improvement for the sample d patients suffering from knee OA", "Acupuncture is one of the oldest healing methods which is used in traditional medicine . In the modern medicine , we are witnessing a renaissance of this ancient treatment applied mainly in the management of chronic pain . A number of modern technological changes are being applied to replace , or modify , the classical needle treatment . Among many modalities used today is the novel addition in Transcutaneous Electrical Nerve Stimulation ( TENS ) called CODETRON which delivers acupuncture-like stimulation in a r and om order . CODETRON was developed by a Canadian Scientist and had been evaluated in a clinical trial in a multidisciplinary pain clinic on patients who came for acupuncture therapy over a period of two years . Indications , effectiveness and experiences with this form of treatment are presented . In addition , results obtained from a six week double-blind r and omized placebo controlled pilot trial of osteoarthritis of the hip/knee with CODETRON which was conducted later . The results were highly suggestive of the beneficial effect of this nonhabituating mode of therapy and confirmed our initial uncontrolled trial results", "OBJECTIVES To examine the relative effectiveness of electro-acupuncture ( EA ) and transcutaneous electrical nerve stimulation ( TENS ) in alleviating osteoarthritic (OA)-induced knee pain . DESIGN Single-blinded , r and omized controlled study . SUBJECTS Twenty-four ( 24 ) subjects ( 23 women and 1 man ) , mean age 85 , were recruited from eight subsidized Care & Attention Homes for the elderly . INTERVENTIONS Subjects were r and omly assigned to the EA , TENS , or control groups . Subjects in the EA group ( n = 8) received low-frequency EA ( 2 Hz ) on two acupuncture points ( ST-35 , Dubi and EX-LE-4 , Neixiyan ) of the painful knee for 20 minutes . Subjects in the TENS group ( n = 8) received low-frequency TENS of 2 Hz and pulse width of 200 micros on the same acupuncture points for 20 minutes . In both treatment groups , electrical treatment was carried out for a total of eight sessions in 2 weeks . Eight subjects received osteoarthritic knee care and education only in a control group . All subjects were evaluated before the first treatment , after the last treatment , and at 2-week follow-up periods . RESULTS After eight sessions of treatment , there was significant reduction of knee pain in both EA group and TENS group , as measured by the Numeric Rating Scale ( NRS ) of pain ( p < 0.01 ) . Prolonged analgesic effect was maintained in the EA and the TENS groups at a 2-week follow-up evaluation . The Timed Up- and -Go Test ( TUGT ) score of the EA group was significantly lower than that of the control group ( p < 0.05 ) , but such change was not observed in the TENS group . CONCLUSIONS Both EA and TENS treatments were effective in reducing OA-induced knee pain . EA had the additional advantage of enhancing the TUGT results as opposed to TENS treatment or no treatment , which did not produce such corollary effect", "OBJECTIVE This study examined the optimal stimulation duration of transcutaneous electrical nerve stimulation ( TENS ) for relieving osteoarthritic knee pain and the duration ( as measured by half-life ) of post-stimulation analgesia . SUBJECTS Thirty-eight patients received either : ( i ) 20 minutes ( TENS20 ) ; ( ii ) 40 minutes ( TENS40 ) ; ( iii ) 60 minutes ( TENS60 ) of TENS ; or ( iv ) 60 minutes of placebo TENS ( TENS(PL ) ) 5 days a week for 2 weeks . METHODS A visual analogue scale recorded the magnitude and pain relief period for up to 10 hours after stimulation . RESULTS By Day10 , a significantly greater cumulative reduction in the visual analogue scale scores was found in the TENS40 ( 83.40 % ) and TENS60 ( 68.37 % ) groups than in the TENS20 ( 54.59 % ) and TENS(PL ) ( 6.14 % ) groups ( p < 0.000 ) , such a group difference was maintained in the 2-week follow-up session ( p < 0.000 ) . In terms of the duration of post-stimulation analgesia period , the duration for the TENS40 ( 256 minutes ) and TENS60 ( 258 minutes ) groups was more prolonged than in the other 2 groups ( TENS20 = 168 minutes , TENS(PL ) = 35 minutes ) by Day10 ( p < 0.000 ) . However , the TENS40 group produced the longest pain relief period by the follow-up session . CONCLUSION 40 minutes is the optimal treatment duration of TENS , in terms of both the magnitude ( VAS scores ) of pain reduction and the duration of post-stimulation analgesia for knee osetoarthritis", "Thirty patients with chronic pain due to osteoarthrosis ( OA ) of the knee were enrolled in a r and omised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation ( TENS ) and placebo TENS . Medication was st and ardised to paracetamol tablets only . As measured on visual analogue scales for pain relief 46 % of patients responded to active therapy and 43 % to placebo . The length of pain relief during active therapy was significantly longer than that during placebo . At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication . Although most of the parameters observed favoured active TENS , it was not possible to establish its clear superiority over placebo , because the response rate to placebo TENS was high and sustained for at least 3 weeks . This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis", "Cetin N , Aytar A , Atalay A , Akman MN : Comparing hot pack , short-wave diathermy , ultrasound , and TENS on isokinetic strength , pain , and functional status of women with osteoarthritic knees : a single-blind , r and omized , controlled trial . Am J Phys Med Rehabil 2008;87:443–451 . Objective : To investigate the therapeutic effects of physical agents administered before isokinetic exercise in women with knee osteoarthritis . Design : One hundred patients with bilateral knee osteoarthritis were r and omized into five groups of 20 patients each : group 1 received short-wave diathermy + hot packs and isokinetic exercise ; group 2 received transcutaneous electrical nerve stimulation + hot packs and isokinetic exercise ; group 3 received ultrasound + hot packs and isokinetic exercise ; group 4 received hot packs and isokinetic exercise ; and group 5 served as controls and received only isokinetic exercise . Results : Pain and disability index scores were significantly reduced in each group . Patients in the study groups had significantly greater reductions in their visual analog scale scores and scores on the Lequesne index than did patients in the control group ( group 5 ) . They also showed greater increases than did controls in muscular strength at all angular velocities . In most parameters , improvements were greatest in groups 1 and 2 compared with groups 3 and 4 . Conclusions : Using physical agents before isokinetic exercises in women with knee osteoarthritis leads to augmented exercise performance , reduced pain , and improved function . Hot pack with a transcutaneous electrical nerve stimulator or short-wave diathermy has the best outcome", "It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect , as suggested by the gate control theory . Electrical stimulation ( by way of Interferential Current ) applied at the pain area ( segmental ) was administered to 4 groups of patients with osteoarthritis ( OA ) knee pain . Two groups were administered with noxious stimulation ( 30 % above pain threshold ) and two with innocuous stimulation ( 30 % below pain threshold ) . In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived . Group 5 and 6 received sham stimulation and no treatment , respectively . The outcome measures were : chronic pain intensity , morning stiffness , range of motion ( ROM ) , pain threshold and % pain reduction . Both noxious and innocuous stimulation significantly decreased chronic pain ( P<0.001 ) and morning stiffness ( P<0.01 ) and significantly increased pain threshold ( P<0.001 ) and ROM ( P<0.001 ) compared with the control groups . Nevertheless , noxious stimulation decreased pain intensity ( P<0.05 ) and increased pain threshold ( P<0.001 ) significantly more than innocuous stimulation . No differences in treatment outcomes were found between adjusted and unadjusted stimulation . ( a ) Interferential current is very effective for chronic OA knee pain , ( b ) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation , ( c ) the fading of sensation during treatment , does not decrease the analgesic effect . Possible mechanisms explaining the findings are discussed", "Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation ( TENS ) and naproxen , an NSAID . All pre-experiment treatment was withdrawn . Each subject experienced in some order three 3-week treatment phases : NSAID plus placebo TENS ; TENS plus placebo drug ; and double placebo . A broad range of pain measures was used , including daily diary ratings , and four-times-per-day ratings entered into a small electronic data logger ( the PIPER ) worn by the subject . A substantial placebo response occurred across all conditions , which may have masked treatment differences . Broad comparisons across subjects , combining the four main measures of pain , found no significant differences among the three experimental treatments . Analysis of diary and PIPER data for individuals suggested that , in a small minority of subjects , the NSAID plus placebo TENS combination may be more effective than double placebo . The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures , suggesting the value of very frequent pain assessment s , such as those entered by a subject into the PIPER , in the study of chronic pain", "Background Osteoarthritis ( OA ) of the knee is one of the main causes of musculoskeletal disability in the western world . Current available management options provide symptomatic relief ( exercise and self-management , medication and surgery ) but do not , in general , address the disease process itself . Moreover , adverse effects and complications with some of these interventions ( medication and surgery ) and the presence of co-morbidities commonly restrict their use . There is clearly a need to investigate treatments that are more widely applicable for symptom management and which may also directly address the disease process itself . In two r and omised controlled trials of four and 12 weeks duration , pulsed electrical stimulation was shown to be effective in managing the symptoms of OA of the knee . Laboratory and animal studies demonstrate the capacity of externally applied electric and electromagnetic fields to positively affect chondrocyte proliferation and extracellular matrix protein production . This latter evidence provides strong theoretical support for the use of electrical stimulation to maintain and repair cartilage in the clinical setting and highlights its potential as a disease-modifying modality . Methods / Design A double-blind , r and omised , placebo-controlled , repeated measures trial to examine the effectiveness of pulsed electrical stimulation in providing symptomatic relief for people with OA of the knee over 26 weeks . Seventy people will be recruited and information regarding age , gender , body mass index and medication use will be recorded . The population will be stratified for age , gender and baseline pain levels . Outcome measures will include pain ( 100 mm VAS and WOMAC 3.1 ) , function ( WOMAC 3.1 ) , stiffness ( WOMAC 3.1 ) , patient global assessment ( 100 mm VAS ) and quality of life ( SF-36 ) . These outcomes will be measured at baseline , four , 16 and 26 weeks . Activity levels will be measured at baseline and 16 weeks using accelerometers and the Human Activity Profile question naire . A patient global perceived effect scale ( 11-point Likert ) will be completed at 16 and 26 weeks . Discussion This paper describes the protocol for a r and omised , double-blind , placebo-controlled trial that will contribute to the evidence regarding the use of sub-sensory pulsed electrical stimulation in the management of OA of the knee . Trial registration Australian Clinical Trials Registry ACTRN12607000492459", "Background : According to a recent meta analysis study , there is strong evidence to support the view that transcutaneous electrical nerve stimulation ( TENS ) is an effective treatment for managing osteoarthritis ( OA ) knee pain . However , there is limited evidence showing its effectiveness in improving physical function . This study examined whether TENS alone can improve physical function in terms of range of knee motion and the Timed-Up- and -Go Test . Methods : Subjects were r and omly allocated into 2 groups receiving TENS at 100 Hz or a placebo TENS . Outcome measures included : 1 ) visual analog scale for measuring the intensity of the present pain , 2 ) Timed-Up- and -Go Test , and 3 ) range of knee motion ( ROM ) . Repeated- measures analysis of variance and Pearson correlation were used for data analyses . Results : By day 10 , TENS produced a significantly greater increase in maximum knee ROM than the placebo group ( P = 0.033 ) . TENS also significantly increased the pain-limited knee ROM across sessions , but the between-group difference was short of significance ( P = 0.067 ) . The decrease in time in performing the Timed-Up- and -Go Test was also not significantly different between the 2 groups . A moderate correlation was observed between the reduction in pain scores and the improvement in the Timed-Up- and -Go Test . Conclusions : Our findings suggested that TENS did improve some of the physical parameters but over 10 days was unable to produce significant improvement in functional performance among people with knee OA . A larger-scale study with the assessment of other functional outcomes may be required to clarify if TENS could improve function in people with knee OA . Also , exercise can be considered to be an important adjunct treatment to TENS to improve function significantly", "OBJECTIVE This is a double blind study that examined the optimal stimulation frequency of transcutaneous electrical nerve stimulation in reducing pain due to knee osteoarthritis . SUBJECTS Thirty-four subjects were r and omly allocated into 4 groups receiving transcutaneous electrical nerve stimulation at either : ( i ) 2 Hz ; ( ii ) 100 Hz ; ( iii ) an alternating frequency of 2 Hz and 100 Hz ( 2/100 Hz ) ; or ( iv ) a placebo transcutaneous electrical nerve stimulation . METHODS Treatment was administered 5 days a week for 2 weeks . The outcome measures included : ( i ) a visual analogue scale ; ( ii ) a timed up- and -go test ; and ( iii ) a range of knee motion . RESULTS The 3 active transcutaneous electrical nerve stimulation groups ( 2 Hz , 100 Hz , 2/100 Hz ) , but not the placebo group , significantly reduced osteoarthritic knee pain across treatment sessions . However , no significant between-group difference was found . Similarly , the 3 active transcutaneous electrical nerve stimulation groups , but not the placebo group , produced significant reductions in the amount of time required to perform the timed up- and -go test , and an increase in the maximum passive knee range of motion . CONCLUSION Our findings suggested that 2 weeks of repeated applications of transcutaneous electrical nerve stimulation at 2 Hz , 100 Hz or 2/100 Hz produced similar treatment effects for people suffering from osteoarthritic knee", "Objective : To evaluate the cumulative effect of repeated transcutaneous electrical nerve stimulation ( TENS ) on chronic osteoarthritic ( OA ) knee pain over a four-week treatment period , comparing it to that of placebo stimulation and exercise training given alone or in combination with TENS . Design : Sixty-two patients , aged 50–75 , were stratified according to age , gender and body mass ratio before being r and omly assigned to four groups . Interventions : Patients received either ( 1 ) 60 minutes of TENS , ( 2 ) 60 minutes of placebo stimulation , ( 3 ) isometric exercise training , or ( 4 ) TENS and exercise ( TENS & Ex ) five days a week for four weeks . Main outcome measures : Visual analogue scale ( VAS ) was used to measure knee pain intensity before and after each treatment session over a four-week period , and at the four-week follow-up session . Results : Repeated measures ANOVA showed a significant cumulative reduction in the VAS scores across the four treatment sessions ( session 1 , 10 , 20 and the follow-up ) in the TENS group ( 45.9 % by session 20 , p < 0.001 ) and the placebo group ( 43.3 % by session 20 , p = 0.034 ) . However , linear regression of the daily recordings of the VAS indicated that the slope in the TENS group ( slope = -2.415 , r = 0.943 ) was similar to the exercise group ( slope = -2.625 , r = 0.935 ) , which were steeper than the other two groups . Note that the reduction of OA knee pain was maintained in the TENS group and the TENS & Ex group at the four-week follow-up session , but not in the other two groups . Conclusions : The four treatment protocol s did not show significant between-group difference over the study period . It was interesting to note that isometric exercise training of the quadriceps alone also reduced knee pain towards the end of the treatment period", "BACKGROUND The OARSI St and ing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains ( pain , function , and patient 's global assessment ) as a single variable for clinical trials ( 1 ) . For each domain , a response was defined by both a relative and an absolute change , with different cut-offs with regard to the drug , the route of administration and the OA localization . OBJECTIVE To propose a simplified set of responder criteria with a similar cut-off , whatever the drug , the route or the OA localization . METHODS Data driven approach : ( 1 ) Two data bases were considered : the \" elaboration \" data base with which the formal OARSI sets of responder criteria were elaborated , and the \" revisit \" data base . ( 2 ) Six different scenarios were evaluated : The two formal OARSI sets of criteria ; Four proposed scenarios of simplified sets of criteria . Data from clinical r and omized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different data bases ( \" elaboration \" versus \" revisit \" ) and those of the four proposed simplified scenarios within the \" revisit \" data base . The placebo effect , active effect , treatment effect , and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios . Experts ' opinion approach : Results were discussed among the participants of the OMERACT VI meeting , who voted to select the definite OMERACT-OARSI set of criteria ( one of the six evaluated scenarios ) . RESULTS Data driven approach : Fourteen trials totaling 1886 OA patients and fifteen studies involving 8164 OA patients were evaluated in the \" elaboration \" and the \" revisit \" data bases respectively . The variability of the performances observed in the \" revisit \" data base when using the different simplified scenarios was similar to that observed between the two data bases ( \" elaboration \" versus \" revisit \" ) when using the formal scenarios . The treatment effect and the required sample arm size were similar for each set of criteria . Experts ' opinion approach : According to the experts , these two previous performances were the most important of an optimal set of responder criteria . They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response , with similar cut-offs whatever the drug , the route of administration or the OA localization . CONCLUSION This data driven and experts ' opinion approach is the basis for proposing an optimal simplified set of responder criteria for OA clinical trials . Other studies , using other sets of OA patients , are required in order to further vali date this proposed OMERACT-OARSI set of criteria", "OBJECTIVE The safety and effectiveness of pulsed electrical stimulation was evaluated for the treatment of osteoarthritis ( OA ) of the knee . METHODS A multicenter , double blind , r and omized , placebo controlled trial that enrolled 78 patients with OA of the knee incorporated 3 primary efficacy variables of patients ' pain , patients ' function , and physician global evaluation of patients ' condition , and 6 secondary variables that included duration of morning stiffness , range of motion , knee tenderness , joint swelling , joint circumference , and walking time . Measurements were recorded at baseline and during the 4 week treatment period . RESULTS Patients treated with the active devices showed significantly greater improvement than the placebo group for all primary efficacy variables in comparisons of mean change from baseline to the end of treatment ( p < 0.05 ) . Improvement of > or = 50 % from baseline was demonstrated in at least one primary efficacy variable in 50 % of the active device group , in 2 variables in 32 % , and in all 3 variables in 24 % . In the placebo group improvement of > or = 50 % occurred in 36 % for one , 6 % for 2 , and 6 % for 3 variables . Mean morning stiffness decreased 20 min in the active device group and increased 2 min in the placebo group ( p < 0.05 ) . No statistically significant differences were observed for tenderness , swelling , or walking time . CONCLUSION The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee . Studies for longterm effects are warranted", "The objective of this study was to examine the short- and long-term effects of a home-based , 12-week neuromuscular electrical stimulation ( NMES ) of the quadriceps femoris to decrease arthritis knee pain in older adults with osteoarthritis of the knee . The study sample ( N = 38 ) was r and omly assigned to the NMES treatment plus education group or the arthritis education-only group . Pain was measured in both groups with the McGill Pain Question naire ( MPQ ) at baseline , during the intervention at weeks 4 , 8 , 12 , and at follow-up and with the Arthritis Impact Measurement Scale 2-Pain Subscale ( AIMS 2-PS ) at baseline and week 12 . The NMES Pain Diary ( PD ) was completed 15 minutes before and after each stimulation session . There was a significant 22 % decline in pain 15 minutes after as compared with immediately before each NMES treatment ( p < .001 ) , as measured by the PD . No significant group differences were found between the 2 groups over the course of the intervention and follow-up . These findings indicate that a home-based NMES intervention reduced arthritis knee pain 15 minutes after a NMES treatment", "Patients suffering from pain due to osteoarthritis of the hip and knee participated in a double-blind placebo controlled trial using daily Codetron home care units for 6 weeks over the tibial , saphenous , popliteal and sciatic nerves , and tender points . Seventy-four percent of patients in the real Codetron ( Group A ) and 28 % of the patients in sham Codetron ( Group B ) improved their pain level more than 25 % as measured by visual analogue scale . The difference in pain improvement in the two groups was statistically significant ( p < 0.02 using Fisher 's exact probability ratio ) Other functional parameters proved to be insensitive to change in this study . This is highly suggestive of beneficial effect of chronic pain conditions such as osteoarthritis", "Thirty-two women between 62 and 75 years old were r and omized into 3 groups . Each group performed a program of 4 sessions a week over 6 weeks . Group SC ( n = 11 ) climbed up and down stairs , group ES ( n = 11 ) practice d electrostimulation , and group SC + ES ( n = 10 ) superimposed the 2 activities simultaneously . Using a force platform and a seesaw platform , static and dynamic balance in eyes-open and eyes-closed conditions were analyzed before and after the programs for each group . After the programs , the results indicated that dynamic balance improved for the 3 groups , but the contribution of visual information in the control of oscillation amplitude was lower in the SC group than in the ES and SC + ES groups . In the SC + ES group , the electrical stimulation interferes with neurophysiologic afference integration in postural control in relation to voluntary movement . Voluntary exercise appears to be more efficient than electrical stimulation and the superimposed techniques to change balancing tactics in the elderly", "OBJECTIVES To examine the efficacy of periosteal stimulation therapy ( PST , osteopuncture ) for the treatment of chronic pain associated with advanced knee osteoarthritis . DESIGN R and omized , controlled clinical trial . SETTING Outpatient pain clinic . PARTICIPANTS Eighty-eight community-dwelling older adults with moderate knee pain or greater for 3 months or longer and Kellgren-Lawrence ( K-L ) grade 2 through 4 radiographic severity ( 80 % had K-L 4 ) . INTERVENTION Participants were r and omized to receive PST or control PST once a week for 6 weeks . MEASUREMENTS Pain severity and self-reported function ( Western Ontario and McMasters University Osteoarthritis Index ( WOMAC ) ) and physical performance ( Short Physical Performance Battery ( SPPB ) ) were assessed at baseline , after the last PST session ( post ) , and 3 months later ( follow-up ) . Pain severity was also assessed monthly using the multidimensional pain inventory short form . RESULTS Pain was reduced significantly more in the PST group than in the control PST group at post ( P=.003 ; mean WOMAC pain subscale baseline 9.4 vs 6.4 ) and 1 month later ( P<.001 ) , but by 2 months , pain levels had regressed to pre-intervention levels . The group-by-time interaction for the WOMAC function scale was significant at post ( P=.04 ) but not at follow-up ( P=.63 ) . No significant group differences were found for the SPPB . Neither analgesic use nor global improvement differed between groups . There were four treatment dropouts . CONCLUSION PST affords short-term modest pain reduction for older adults with advanced knee OA . Future research should test the effectiveness of booster treatments in sustaining analgesic benefits and of combining PST with therapeutic exercise in ameliorating disability risk", "Abstract Ten patients with pain due to osteoarthritis of the knee were treated in a double‐blind cross‐over study with two weeks of transcutaneous electrical nerve stimulation ( TENS ) and placebo . There was statistically significant pain relief by TENS and half of the patients chose to continue using TENS for pain control after the test month . However , at one year 's follow‐up , only two patients had sufficient benefit to continue using the device", "OBJECTIVE To determine whether home-based neuromuscular electrical stimulation ( NMES ) applied to the quadriceps femoris ( QF ) muscle increases strength , physical activity , and physical performance in older adults with knee osteoarthritis ( OA ) . METHODS Thirty-four adults ( > 60 yrs ) with radiographically confirmed symptomatic knee OA were r and omized to NMES plus education or education only ( EDU ) . The primary outcome was isometric QF peak torque ( PTIso ) , with secondary outcomes of daily step counts , total activity vector magnitude , 100-foot walk-turn-walk , timed stair climb , chair rise , and pain . The NMES group used a portable electrical muscle stimulator 3 days a week for unilateral QF training with incremental increases in the intensity of isometric contraction to 30 - 40 % of maximum over 12 weeks . Both groups received the 12-week Arthritis Self-Management course and were followed an additional 12 weeks . RESULTS The stimulated knee-extensor showed a 9.1 % increase in 120 degrees PTIso compared to a 7 % loss in the EDU group ( time x group interaction for 120 degrees PTIso ; p = 0.04 ) . The chair rise time decreased by 11 % in the NMES group , whereas the EDU group saw a 7 % reduction ( p = 0.01 , time ; p = 0.9 , group ) . Similarly , both groups improved their walk time by approximately 7 % ( p = 0.02 , time ; p = 0.61 group ) . Severity of pain reported following intervention did not differ between groups . CONCLUSION In older adults with knee OA , a home-based NMES protocol appears to be a promising therapy for increasing QF strength in adults with knee OA without exacerbating painful symptoms", "Objective : To examine if the addition of transcutaneous electrical nerve stimulation ( TENS ) to exercise training would produce better physical outcomes than TENS or exercise alone in people with knee osteoarthritis . Design : Sixty-two subjects were r and omly allocated to four groups . Interventions : Patients received either ( 1 ) TENS , ( 2 ) placebo stimulation , ( 3 ) exercise training , or ( 4 ) TENS and exercise training five days a week for four weeks . Main outcome measures : The isometric peak torque , spatiotemporal gait parameters and range of knee movement were assessed in treatment session1 , session10 and session20 and the four-week follow-up . Results : By session20 , the TENS and exercise group demonstrated an average of 26.6 % cumulative gain in the knee extensor peak torque for the different knee positions ( all p < 0.05 ) . Although the between-group difference was short of being statistically significant , the gain found in the TENS and exercise group was greater than that found in the other three groups . The TENS and exercise group also tended to show greater cumulative increase in stride length ( 12.6 % , p-0.006 ) , walking cadence ( 9.3 % , p-0.098 ) and gait velocity ( 22.4 % , p-0.034 ) than the other groups . By session20 , it was the only group that produced a significant increase in the range of knee motion during walking ( 12.0%,p-0.000 ) . The TENS group and the exercise group both demonstrated some improvements in the above physical outcomes , but negligible change was found in the group receiving placebo stimulation ( all p > 0.05 ) . Conclusion : No significant difference was found among the four treatment protocol s , but the addition of TENS to exercise training tended to produce the best overall improvement in physical outcomes in people with knee osteoarthritis", "& NA ; Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms — frequency modulation and burst — rather than conventional continuous mode . To assess whether long‐term therapeutic effects vali date the immediate test results , this trial was performed in 14 patients with 21 pain conditions . Considering the results of the pilot study , the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were r and omly delivered to each patient who was blind to the modes of stimulation for 20 min . A second observer assessed the pain scores using visual analogue scales . The stimulation modes employed were : ( 1 ) conventional continuous stimulation ( continuous pulses with a constant frequency of 70 Hz ) , ( 2 ) burst stimulation ( 80 msec long trains of pulses , each train consisting of 8 pulses , with an internal frequency of 90 Hz repeated 1.3 times a second ) , ( 3 ) high‐rate frequency modulation , HRFM ( continuous pulses changed from 90 Hz to 55 Hz over 90 msec , 1.3 times a second ) , ( 4 ) low‐rate frequency modulation , LRFM ( continuous pulses changed from 60 Hz to 20 Hz over 90 msec , 1.3 times a second ) . After the test treatment of 4 sessions in the clinic , depending on the pain scores and duration of pain relief recorded , the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home , under our supervision , for 3 months . Fourteen pain conditions out of 21 ( 66 % ) responded well to the therapy ; the majority preferred was the HRFM and burst‐type stimulation . These results vali date the initial testing of different stimulation modes before assessing long‐term stimulation therapy", "OBJECTIVE This study investigated the benefits of the combination of interferential ( IF ) and patterned muscle stimulation in the treatment of osteoarthritis ( OA ) of the knee . DESIGN This was a multi-center , r and omized , single-blind , controlled study with an independent observer . The study r and omized 116 patients with OA of the knee to a test or control group . The test group received 15 min of IF stimulation followed by 20 min of patterned muscle stimulation . The control group received 35 min of low-current transcutaneous electrical nerve stimulation ( TENS ) . Both groups were treated for 8 weeks . Subjects completed question naires at baseline and after 2 , 4 and 8 weeks . Primary outcomes included the pain and physical function subscales of the Western Ontario MacMaster ( WOMAC ) OA Index and Visual Analog Scales ( VAS ) for pain and quality of life . RESULTS Compared to the control group , the test group showed reduced pain and increased function . The test group showed a greater decrease in the WOMAC pain subscale ( P=0.002 ) , function subscale ( P=0.003 ) and stiffness subscale ( P=0.004 ) . More than 70 % of the test group , compared to less than 50 % of the control group , had at least a 20 % reduction in the WOMAC pain subscale . When analyzing only patients who completed the study , the test group had a nominally significant greater decrease in overall pain VAS . No significant between-group differences were observed in incidence of adverse events . CONCLUSIONS In patients with OA of the knee , home-based patterned stimulation appears to be a promising therapy for relieving pain , decreasing stiffness , and increasing function", "In a prospect i ve study 1200 sequences of low frequency electrostimulation and ultrasonic therapy have been examined . The basics of the type of currents applied , the therapy scheme and the indication routine are presented . These parameters were kept constant in the course of the 2 years ' study . For the treatment 8 different apparatuses were available . The actual current shapes of the generators were measured , the influence of constant-current and constant-voltage output circuits were tested and were discussed in relation to the electrode types .-- Advantages and disadvantages of disposable-type , sponge-type , lead-type and vacuum-type electrodes are reported . Treatments were carried out with the current types DF and CP of the diadynamic currents alone , as combined therapy together with ultrasound , as mere ultrasound treatment , as ultrastimulation current , as iontophoresis and galvanic current . The results are compared with comparable examinations by other authors and they are discussed with respect to different influencing factors", "& NA ; Transcutaneous electrical nerve stimulation ( TENS ) is an easy to use non‐invasive analgesic intervention applied for diverse pain states . However , effects in man are still inconclusive , especially for chronic pain . Therefore , to explore the factors predicting result of TENS treatment in chronic pain we conducted a prospect i ve , r and omized , placebo‐controlled trial ( n = 163 ) , comparing high frequency TENS ( n = 81 ) with sham TENS ( n = 82 ) . Patients ’ satisfaction ( willingness to continue treatment ; yes or no ) and pain intensity ( VAS ) were used as outcome measures . The origin of pain and cognitive coping strategies were evaluated as possible predictors for result of TENS treatment . Results : Fifty‐eight percent of the patients in the TENS group and 42.7 % of the sham‐TENS group were satisfied with treatment result ( chi square = 3.8 , p = 0.05 ) . No differences were found for pain intensity . Patients diagnosed with osteoarthritis and related disorders ( especially of the vertebral column ) or peripheral neuropathic pain were less satisfied with high frequency TENS ( OR = 0.12 ( 95 % CI 0.04–0.43 ) and 0.06 ( 95 % CI 0.006–0.67 ) , respectively ) . Injury of bone and soft tissue ( especially postsurgical pain disorder ) provided the best results . Treatment modality or interactions with treatment modality did not predict intensity of pain as a result of treatment . We conclude , that predicting the effect of high frequency TENS in chronic pain depends on the choice of outcome measure . Predicting patients ’ satisfaction with treatment result is related to the origin of pain . Predicting pain intensity reflects mechanisms of pain behavior and perceived control of pain , independent of treatment modality . Pain catastrophizing did not predict TENS treatment outcome" ]

[ "24975729", "25109426", "23658436", "16990384", "4499169", "3890472", "17764767", "18583907", "19958962", "23651816", "19249426", "15219514", "23663817", "23129008", "25484310" ]

[ "The beneficial effects of intracoronary autologous bone marrow stem cell transfer as an adjunct to percutaneous coronary intervention in patients with acute myocardial infarction", "Cardiac magnetic resonance performs better in the detection of functionally significant coronary artery stenosis compared to single-photon emission computed tomography and dobutamine stress echocardiography.", "Intracoronary Infusion of Allogeneic Mesenchymal Precursor Cells Directly After Experimental Acute Myocardial Infarction Reduces Infarct Size, Abrogates Adverse Remodeling, and Improves Cardiac Function", "Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.", "Intracoronary infusion of Wharton’s jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial", "A Randomized, Open-Label, Multicenter Trial for the Safety and Efficacy of Adult Mesenchymal Stem Cells after Acute Myocardial Infarction", "Three-, 6-, and 12-month results of autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction.", "Intracoronary Delivery of Bone Marrow Cells to the Acutely Infarcted Myocardium", "A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction.", "A critical challenge: dosage-related efficacy and acute complication intracoronary injection of autologous bone marrow mesenchymal stem cells in acute myocardial infarction.", "Intracoronary administration of bone marrow-derived progenitor cells improves left ventricular function in patients at risk for adverse remodeling after acute ST-segment elevation myocardial infarction: results of the Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial", "Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction.", "Impact of timing and dose of mesenchymal stromal cell therapy in a preclinical model of acute myocardial infarction.", "Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial.", "Randomized, double-blind, phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction." ]

[ "The efficacy of post-percutaneous coronary intervention ( PCI ) intracoronary injection with bone marrow mesenchymal stem cells ( BMSCs ) in patients with acute myocardial infa rct ion ( AMI ) remains controversial . Here , 58 patients with AMI undergoing PCI were r and omly divided into two groups : BMSC and control groups . Autologous BSMCs were then generated in vitro from the BMSC patients . After transplantation , left ventricular ejection fraction ( LVEF ) , left ventricular end-diastolic dimensions ( LVDd ) , and infa rct size ( IS ) were evaluated in both groups . LVEF , LVDd , and IS improved after BMSC transplantation but the changes were not significantly different from those in the controls . The number of adverse events and rehospitalization rates after 1 month were significantly higher in the control group than in the BMSC group . BMSC transplantation thus benefits patients by decreasing the number of adverse events and reducing the rehospitalization rate in the early stages following PCI", "BACKGROUND Fractional flow reserve ( FFR ) measured on catheterization is now widely used for the diagnosis of functional myocardial ischemia in patients with coronary artery disease ( CAD ) . FFR , however , is invasive and carries potential procedural complications . Therefore , the aim of this study was to compare the diagnostic capability in functionally significant stenosis identified on FFR , between cardiac magnetic resonance myocardial perfusion imaging ( CMR-MPI ) , single-photon emission computed tomography MPI ( SPECT-MPI ) , and dobutamine stress echocardiography ( DSE ) in patients with CAD . METHODS AND RESULTS A total of 25 patients who had at least 1 angiographic stenosis ≥50 % on coronary angiography was studied . CMR-MPI , SPECT-MPI and DSE were done before FFR measurement . FFR was measured in all 3 major epicardial coronary arteries . Out of 71 vascular territories excluding 4 territories due to inadequate imaging , 29 ( 41 % ) had FFR < 0.80 . The sensitivity of CMR-MPI was significantly higher than that of SPECT-MPI and DSE ( P=0.02 and P=0.001 , respectively ) . The area under the receiver operating characteristic curve ( AUC ) for CMR-MPI ( AUC , 0.92 ) was significantly greater than for SPECT-MPI ( AUC , 0.73 ; P=0.006 ) and DSE ( AUC , 0.69 ; P<0.001 ) . CONCLUSIONS CMR-MPI performed well in the detection of functionally significant stenosis defined according to FFR , and had the highest diagnostic sensitivity among the 3 modalities tested in patients with CAD", "Rationale : Mesenchymal precursor cells ( MPCs ) are a specific Stro-3 + sub population of mesenchymal stem cells isolated from bone marrow . MPCs exert extensive cardioprotective effects , and are considered to be immune privileged . Objective : This study assessed the safety , feasibility , and efficacy of intracoronary delivery of allogeneic MPCs directly after acute myocardial infa rct ion in sheep . Methods and Results : Initially , intracoronary delivery conditions were optimized in 20 sheep . These conditions were applied in a r and omized study of 68 sheep with an anterior acute myocardial infa rct ion . Coronary flow was monitored during MPC infusion , and cardiac function was assessed using invasive hemodynamics and echocardiography at baseline and during 8 weeks follow-up . Coronary flow remained within thrombolysis in myocardial infa rct ion III definitions in all sheep during MPC infusion . Global left ventricular ejection fraction as measured by pressure – volume loop analysis deteriorated in controls to 40.7±2.6 % after 8 weeks . In contrast , MPC treatment improved cardiac function to 52.8±0.7 % . Echocardiography revealed significant improvement of both global and regional cardiac functions . Infa rct size decreased by 40 % in treated sheep , whereas infa rct and border zone thickness were enhanced . Left ventricular adverse remodeling was abrogated by MPC therapy , result ing in a marked reduction of left ventricular volumes . Blood vessel density increased by > 50 % in the infa rct and border areas . Compensatory cardiomyocyte hypertrophy was reduced in border and remote segments , accompanied by reduced collagen deposition and apoptosis . No microinfa rct ions in remote myocardial segments or histological abnormalities in unrelated organs were found . Conclusions : Intracoronary infusion of allogeneic MPCs is safe , feasible , and markedly effective in a large animal model of acute myocardial infa rct ion", "BACKGROUND Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infa rct ion . METHODS In a multicenter trial , we r and omly assigned 204 patients with acute myocardial infa rct ion to receive an intracoronary infusion of progenitor cells derived from bone marrow ( BMC ) or placebo medium into the infa rct artery 3 to 7 days after successful reperfusion therapy . RESULTS At 4 months , the absolute improvement in the global left ventricular ejection fraction ( LVEF ) was significantly greater in the BMC group than in the placebo group ( mean [ + /-SD ] increase , 5.5+/-7.3 % vs. 3.0+/-6.5 % ; P=0.01 ) . Patients with a baseline LVEF at or below the median value of 48.9 % derived the most benefit ( absolute improvement in LVEF , 5.0 % ; 95 % confidence interval , 2.0 to 8.1 ) . At 1 year , intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death , recurrence of myocardial infa rct ion , and any revascularization procedure ( P=0.01 ) . CONCLUSIONS Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infa rct ion . Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality", "Background The use of adult stem cells is limited by the quality and quantity of host stem cells . It has been demonstrated that Wharton ’s jelly – derived mesenchymal stem cells ( WJMSCs ) , a primitive stromal population , could integrate into ischemic cardiac tissues and significantly improve heart function . In this r and omized , controlled trial , our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infa rct ion ( AMI ) . Methods In a multicenter trial , 116 patients with acute ST-elevation MI were r and omly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infa rct artery at five to seven days after successful reperfusion therapy . The primary endpoint of safety : the incidence of adverse events ( AEs ) within 18 months , was monitored and quantified . The endpoint of efficacy : the absolute changes in myocardial viability and perfusion of the infa rct ed region from baseline to four months , global left ventricular ejection fraction ( LVEF ) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography ( F-18-FDG-PET ) and 99mTc-sestamibi single-photon emission computed tomography ( 99mTc-SPECT ) , and two-dimensional echocardiography , respectively . Results During 18 months follow-up , AEs rates and laboratory tests including tumor , immune , and hematologic indexes were not different between the two groups . The absolute increase in the myocardial viability ( PET ) and perfusion within the infa rct ed territory ( SPECT ) was significantly greater in the WJMSC group [ 6.9 ± 0.6 % ( 95 % CI , 5.7 to 8.2 ) ] and [ 7.1 ± 0.8 % ( 95 % CI , 5.4 to 8.8 ) than in the placebo group [ 3.3 ± 0.7 % ( 95 % CI , 1.8 to 4.7 ) , P < 0.0001 ] and 3.9 ± 0.6(95 % CI , 2.8 to 5.0 ) , P = 0.002 ] at four months . The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [ 7.8 ± 0.9 ( 6.0 to approximately 9.7 ) vs. 2.8 ± 1.2 ( 0.4 to approximately 5.1 ) , P = 0.001 ] . Concomitantly , the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group ( P = 0.0004 , P = 0.004 , respectively ) . Conclusions Intracoronary infusion of WJMSCs is safe and effective in patients with AMI , providing clinical ly relevant therapy within a favorable time window . This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy . Trial registration Clinical Trials NCT01291329 ( 02/05/2011 )", "Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells ( MSCs ) may improve left ventricular function in patients with acute myocardial infa rct ion ( AMI ) . However , there is still argumentative for the safety and efficacy of MSCs in the AMI setting . We thus performed a r and omized pilot study to investigate the safety and efficacy of MSCs in patients with AMI . Eighty patients with AMI after successful reperfusion therapy were r and omly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infa rct related artery at 1 month . During follow-up period , 58 patients completed the trial . The primary endpoint was changes in left ventricular ejection fraction ( LVEF ) by single-photon emission computed tomography ( SPECT ) at 6 month . We also evaluated treatment-related adverse events . The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group ( 5.9%±8.5 % vs 1.6%±7.0 % ; P=0.037 ) . There was no treatment-related toxicity during intracoronary administration of MSCs . No significant adverse cardiovascular events occurred during follow-up . In conclusion , the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT . ( Clinical Trials.gov registration number : NCT01392105", "BACKGROUND There are only few data on long-term effectiveness of the stem cell therapy . AIM We studied the time course of global and regional left ventricular function in patients with acute myocardial infa rct ion within 1 year after the autologous mononuclear bone marrow cell transplantation . METHODS Sixty patients with a first acute myocardial infa rct ion , who had been r and omized into 3 groups , completed a 12-month protocol . Two groups were intracoronarily given bone marrow cells in either higher ( 10(8 ) cells , HD group , n=20 ) or lower ( 10(7 ) cells , LD group , n=20 ) doses . Twenty patients without cell transplantation served as a control ( C ) group . Doppler tissue imaging and the gated technetium-99 m sestamibi single photon emission computed tomography were performed before cell transplantation and at 3 , 6 , and 12 months later . RESULTS The baseline peak systolic velocities of longitudinal contraction of the infa rct ed wall ( S(infa rct ) ) of 5.2 cm/s , 4.6 cm/s , and 4.4 cm/s in C , LD , and HD groups increased by 0.0 cm/s , 0.3 cm/s ( p = NS vs. C group ) , and by 0.7 cm/s ( p<0.05 vs. C group ) , respectively , at 3 months . At 12 months , however , the corresponding changes from baseline values of 0.1 cm/s , 0.2 cm/s , and 0.6 cm/s did not differ significantly ( all p = NS ) . In contrast , the post-transplant improvements in the left ventricular ejection fraction by 6 % , 7 % , and 7 % at months 3 , 6 , and 12 , respectively , were preserved in HD group patients during the whole 12-month follow-up and remained significantly better as compared to controls . CONCLUSIONS In our study , the autologous mononuclear bone marrow cell transplantation provided sustained improvement in global left ventricular systolic function in patients with acute myocardial infa rct ion . However , when evaluating regional systolic function of the infa rct ed wall , the short-term benefit was partially lost during the 12-month follow-up", "Objectives : Intracoronary cell transplantation during catheter balloon inflations may be associated with adverse events . We studied the effectiveness of an alternative transplantation technique – intracoronary cell infusion . Methods : Fourteen pigs , which had survived acute myocardial infa rct ion , were r and omized into 2 treatment groups and 2 controls . Three days after infa rct ion , 12 pigs underwent allogeneic intracoronary mononuclear bone marrow cell transplantation using either the st and ard technique ( short-term cell injections during repeat balloon inflations , technique A , n = 6 ) or continuous intracoronary cell infusion without balloon inflations ( technique B , n = 6 ) . Implanted cells were stained with fluorescent dye . After transplantation , the pigs were euthanized and myocardial sample s were analyzed by fluorescent microscopy . Results : The mean numbers of fluorescently labeled bone marrow cells in the infa rct ion border zone , in the infa rct ion mid-area and in the center of myocardial infa rct ion were 84 , 72 and 55 using technique A , and 29 , 57 and 46 using technique B , respectively . The mean cell retention in the infa rct ion border zone of 84 cells for technique A and 29 cells for technique B differed significantly ( p = 0.034 , two-tailed t test ) . Conclusion : The continuous intracoronary cell infusion technique is a less efficient cell delivery technique as compared with the st and ard technique using repeat intracoronary balloon inflations", "OBJECTIVES Our aim was to investigate the safety and efficacy of intravenous allogeneic human mesenchymal stem cells ( hMSCs ) in patients with myocardial infa rct ion ( MI ) . BACKGROUND Bone marrow-derived hMSCs may ameliorate consequences of MI , and have the advantages of preparation ease , allogeneic use due to immunoprivilege , capacity to home to injured tissue , and extensive pre- clinical support . METHODS We performed a double-blind , placebo-controlled , dose-ranging ( 0.5 , 1.6 , and 5 million cells/kg ) safety trial of intravenous allogeneic hMSCs ( Prochymal , Osiris Therapeutics , Inc. , Baltimore , Maryl and ) in reperfused MI patients ( n=53 ) . The primary end point was incidence of treatment-emergent adverse events within 6 months . Ejection fraction and left ventricular volumes determined by echocardiography and magnetic resonance imaging were exploratory efficacy end points . RESULTS Adverse event rates were similar between the hMSC-treated ( 5.3 per patient ) and placebo-treated ( 7.0 per patient ) groups , and renal , hepatic , and hematologic laboratory indexes were not different . Ambulatory electrocardiogram monitoring demonstrated reduced ventricular tachycardia episodes ( p=0.025 ) , and pulmonary function testing demonstrated improved forced expiratory volume in 1 s ( p=0.003 ) in the hMSC-treated patients . Global symptom score in all patients ( p=0.027 ) and ejection fraction in the important subset of anterior MI patients were both significantly better in hMSCs versus placebo subjects . In the cardiac magnetic resonance imaging sub study , hMSC treatment , but not placebo , increased left ventricular ejection fraction and led to reverse remodeling . CONCLUSIONS Intravenous allogeneic hMSCs are safe in patients after acute MI . This trial provides pivotal safety and provisional efficacy data for an allogeneic bone marrow-derived stem cell in post-infa rct ion patients . ( Safety Study of Adult Mesenchymal Stem Cells [ MSC ] to Treat Acute Myocardial Infa rct ion ; NCT00114452 )", "BACKGROUND Previous studies showed improvement in heart function by injecting bone marrow mesenchymal stem cells ( BMSCs ) after AMI . Emerging evidence suggested that both the number and function of BMSCs decline with ageing . We design ed a r and omized , controlled trial to further investigate the safety and efficacy of this treatment . METHODS Patients with ST-elevation AMI undergoing successful reperfusion treatment within 12 hours were r and omly assigned to receive an intracoronary infusion of BMSCs ( n=21 ) or st and ard medical treatment ( n=22 ) ( the numbers of patients were limited because of the complication of coronary artery obstruction ) . RESULTS There is a closely positive correlation of the number and function of BMSCs vs. the cardiac function reflected by LVEF at baseline ( r=0.679 , P=0.001 ) and at 12-month follow-up ( r=0.477 , P=0.039 ) . Six months after cell administration , myocardial viability within the infa rct area by 18-FDG SPECT was improved in both groups compared with baseline , but no significant difference in the BMSCs compared with control groups ( 4.0±0.4 % 95%CI 3.1 - 4.9 vs. 3.2±0.5 % 95%CI 2.1 - 4.3 , P=0.237 ) . 99mTc-sestamibi SPECT demonstrated that myocardial perfusion within the infa rct area in the BMSCs did not differ from the control group ( 4.4±0.5 % 95%CI 3.2 - 5.5 vs. 3.9±0.6 % 95%CI 2.6 - 5.2 , P=0.594 ) . Similarly , LVEF after 12 and 24 months follow-up did not show any difference between the two groups . In the BMSCs group , one patient suffered a serious complication of coronary artery occlusion during the BMSCs injection procedure . CONCLUSIONS The clinical benefits of intracoronary injection of autologous BMSCs in acute STEMI patients need further investigation and reevaluation", "BACKGROUND Serial cardiac magnetic resonance imaging ( CMR ) is the reference st and ard for evaluating left ventricular function , wall motion , and infa rct size in patients with acute myocardial infa rct ion , as well as remodeling during follow-up . The cardiac CMR sub study of the r and omized multicenter REPAIR-AMI trial ( Reinfusion of Enriched Progenitor cells And Infa rct Remodeling in Acute Myocardial Infa rct ion study ) aim ed at gaining insight into postinfa rct ion left ventricular remodeling processes . METHODS Consecutive patients with ST-segment elevation myocardial infa rct ion and primary percutaneous coronary intervention were enrolled ( n = 204 ) and r and omly assigned to either stem cell therapy ( bone marrow-derived progenitor cells [ BMC ] ) or placebo after bone marrow aspiration . In the magnetic resonance imaging sub study , 54 patients completed serial CMR ( baseline , 4 and 12 months , respectively ) after enrollment ( 27 BMC , 27 placebo ) . Image analysis was performed at a central core laboratory . RESULTS There were no significant differences between the 2 groups with respect to global ejection fraction ( EF ) , end-diastolic volume ( EDV ) , and end-systolic volume ( ESV ) at baseline . At 12 months , the treatment effect of BMC infusion on EF amounted to 2.8 absolute percentage points ( P = .26 ) , the progression of EDV at 12 months was less in the BMC group ( treatment effect 14 mL , P = .12 ) , and unlike placebo , ESV did not increase ( absolute treatment effect 13 mL , P = .08 ) , respectively . In patients with a baseline EF < median ( EF < or = 48.9 % ) , BMC administration was associated with a significantly improved EF ( + 6.6 % , P = .01 ) , reduced EDV increase ( treatment effect 29.1 mL , P = .02 ) , and abrogation of ESV increase ( treatment effect 29.4 mL , P = .01 ) after 12 months , respectively . CONCLUSION Intracoronary administration of BMC additionally improved left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infa rct ion despite optimal \" state-of-the-art \" reperfusion and pharmacologic treatment on 1-year follow-up and beneficially interfered with adverse postinfa rct ion left ventricular remodeling", "Sixty-nine patients who underwent primary percutaneous coronary intervention within 12 hours after onset of acute myocardial infa rct ion were r and omized to receive intracoronary injection of autologous bone marrow mesenchymal stem cell or st and ard saline . Several imagining techniques demonstrated that bone marrow mesenchymal stem cells significantly improved left ventricular function", "BACKGROUND Although mesenchymal stem/stromal cells ( MSC ) have shown therapeutic promise after myocardial infa rct ion ( MI ) , the impact of cell dose and timing of intervention remains uncertain . We compared immediate and deferred administration of 2 doses of MSC in a rat model of MI . METHODS AND RESULTS Sprague-Dawley rats were used . Allogeneic prospect ively isolated MSC ( \" low \" dose 1 × 10(6 ) or \" high \" dose 2 × 10(6 ) cells ) were delivered by transepicardial injection immediately after MI ( \" early-low , \" \" early-high \" ) , or 1 week later ( \" late-low , \" \" late-high \" ) . Control subjects received cryopreservant solution alone . Left ventricular dimensions and ejection fraction ( EF ) were assessed by cardiac magnetic resonance . All 4 MSC-treatment cohorts demonstrated higher EF than control animals 4 weeks after MI ( P values < .01 to < .0001 ) , with function most preserved in the early-high group ( absolute reduction in EF from baseline : control 39.1 ± 1.7 % , early-low 26.5 ± 3.2 % , early-high 7.9 ± 2.6 % , late-low 19.6 ± 3.5 % , late-high 17.9 ± 4.0 % ) . Cell treatment also attenuated left ventricular dilatation and fibrosis and augmented left ventricular mass , systolic wall thickening ( SWT ) , and microvascular density . Although early intervention selectively increased SWT and vascular density in the infa rct territory , delayed treatment caused greater benefit in remote ( noninfa rct ) myocardium . All outcomes demonstrated dose dependence for early MSC treatment , but not for later cell administration . CONCLUSIONS The nature and magnitude of benefit from MSC after acute MI is strongly influenced by timing of cell delivery , with dose dependence most evident for early intervention . These novel insights have potential implication s for cell therapy after MI in human patients", "CONTEXT While the delivery of cell therapy after ST-segment elevation myocardial infa rct ion ( STEMI ) has been evaluated in previous clinical trials , the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed . OBJECTIVES To determine the effect of intracoronary autologous bone marrow mononuclear cell ( BMC ) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery ( 3 days vs 7 days after reperfusion ) influences this effect . DESIGN , SETTING , AND PATIENTS A r and omized , 2 × 2 factorial , double-blind , placebo-controlled trial , Timing In Myocardial infa rct ion Evaluation ( TIME ) enrolled 120 patients with left ventricular dysfunction ( left ventricular ejection fraction [ LVEF ] ≤ 45 % ) after successful primary percutaneous coronary intervention ( PCI ) of anterior STEMI between July 17 , 2008 , and November 15 , 2011 , as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart , Lung , and Blood Institute . INTERVENTIONS Intracoronary infusion of 150 × 106 BMC s or placebo ( r and omized 2:1 ) within 12 hours of aspiration and cell processing administered at day 3 or day 7 ( r and omized 1:1 ) after treatment with PCI . MAIN OUTCOME MEASURES The primary end points were change in global ( LVEF ) and regional ( wall motion ) left ventricular function in infa rct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7 . The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infa rct size . RESULTS The mean ( SD ) patient age was 56.9 ( 10.9 ) years and 87.5 % of participants were male . At 6 months , there was no significant increase in LVEF for the BMC group ( 45.2 % [ 95 % CI , 42.8 % to 47.6 % ] to 48.3 % [ 95 % CI , 45.3 % to 51.3 % ) vs the placebo group ( 44.5 % [ 95 % CI , 41.0 % to 48.0 % ] to 47.8 % [ 95 % CI , 43.4 % to 52.2 % ] ) ( P = .96 ) . There was no significant treatment effect on regional left ventricular function observed in either infa rct or border zones . There were no significant differences in change in global left ventricular function for patients treated at day 3 ( −0.9 % [ 95 % CI , −6.6 % to 4.9 % ] , P = .76 ) or day 7 ( 1.1 % [ 95 % CI , −4.7 % to 6.9 % ] , P = .70 ) . The timing of treatment had no significant effect on regional left ventricular function recovery . Major adverse events were rare among all treatment groups . CONCLUSION Among patients with STEMI treated with primary PCI , the administration of intracoronary BMC s at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00684021", "BACKGROUND AIMS Cell therapy is promising as an exploratory cardiovascular therapy . We have recently developed an investigational new drug named Stempeucel ( bone marrow-derived allogeneic mesenchymal stromal cells ) for patients with acute myocardial infa rct ion ( AMI ) with ST-segment elevation . A phase I/II r and omized , double-blind , single-dose study was conducted to assess the safety and efficacy of intravenous administration of Stempeucel versus placebo ( multiple electrolytes injection ) . METHODS Twenty patients who had undergone percutaneous coronary intervention for AMI were r and omly assigned ( 1:1 ) to receive intravenous Stempeucel or placebo and were followed for 2 years . RESULTS The number of treatment-emergent adverse events observed were 18 and 21 in the Stempeucel and placebo groups , respectively . None of the adverse events were related to Stempeucel according to the investigators and independent data safety monitoring board . There was no serious adverse event in the Stempeucel group and there were three serious adverse events in the placebo group , of which one had a fatal outcome . Ejection fraction determined by use of echocardiography showed improvement in both Stempeucel ( 43.06 % to 47.80 % ) and placebo ( 43.44 % to 45.33 % ) groups at 6 months ( P = 0.26 ) . Perfusion scores measured by use of single-photon emission tomography and infa rct volume measured by use of magnetic resonance imaging showed no significant differences between the two groups at 6 months . CONCLUSIONS This study showed that Stempeucel was safe and well tolerated when administered intravenously in AMI patients 2 days after percutaneous coronary intervention . The optimal dose and route of administration needs further evaluation in larger clinical trials ( http:// clinical trials.gov/show/NCT00883727 )" ]

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[ "A Randomized Trial of Telemedicine-based Collaborative Care for Depression", "Feasibility of an eHealth Service to Support Collaborative Depression Care: Results of a Pilot Study", "Case Management for Depression by Health Care Assistants in Small Primary Care Practices", "Integration of Depression and Hypertension Treatment: A Pilot, Randomized Controlled Trial", "Nontricyclic antidepressants: predictors of nonadherence.", "Cost Effectiveness of a Pharmacy-Based Coaching Programme to Improve Adherence to Antidepressants", "Compliance with antidepressants in a primary care setting, 1: Beyond lack of efficacy and adverse events.", "The pilot study of a telephone disease management program for depression.", "Patient outcomes following an intervention involving community pharmacists in the management of depression.", "Improving antidepressant adherence and depression outcomes in primary care: the treatment initiation and participation (TIP) program.", "Impact of an antidepressant management program on medication adherence.", "Nine-month predictors and outcomes of SSRI antidepressant continuation in primary care.", "Randomized trial of pharmacist interventions to improve depression care and outcomes in primary care.", "Continuity is the main challenge in treating major depressive disorder in psychiatric care.", "A cohort study of adherence to antidepressants in primary care: the influence of antidepressant concerns and treatment preferences.", "Selective Serotonin Reuptake Inhibitor Discontinuation: Side Effects and Other Factors That Influence Medication Adherence", "Randomized Trial of Depression Follow-Up Care by Online Messaging", "Enhancing adherence to prevent depression relapse in primary care.", "Behavioural factors associated with symptom outcomes in a primary care-based depression prevention intervention trial.", "A cluster randomized trial comparing two interventions to improve treatment of major depression in primary care.", "Effects of an educational compliance enhancement programme and therapeutic drug monitoring on treatment adherence in depressed patients managed by general practitioners", "Treatment outcomes in depression: comparison of remote treatment through telepsychiatry to in-person treatment.", "A pharmacy-based coaching program to improve adherence to antidepressant treatment among primary care patients.", "Pharmacist telemonitoring of antidepressant use: effects on pharmacist-patient collaboration.", "A randomized trial of a specific adherence enhancement program in sertraline-treated adults with major depressive disorder in a primary care setting", "Beliefs About Depression and Depression Treatment Among Depressed Veterans" ]

[ "Background Evidence -based practice s design ed for large urban clinics are not necessarily portable into smaller isolated clinics . Implementing practice -based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists . Objective The purpose of the Telemedicine Enhanced Antidepressant Management ( TEAM ) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists . Design Matched sites were r and omized to the intervention or usual care . Participants Small VA Community-based outpatient clinics with no on-site psychiatrists , but access to telepsychiatrists . In 2003–2004 , 395 primary care patients with PHQ9 depression severity scores ≥12 were enrolled , and followed for 12 months . Patients with serious mental illness and current substance dependence were excluded . Measures Medication adherence , treatment response , remission , health status , health-related quality of life , and treatment satisfaction . Results The sample comprised mostly elderly , white , males with substantial physical and behavioral health comorbidity . At baseline , subjects had moderate depression severity ( Hopkins Symptom Checklist , SCL-20 = 1.8 ) , 3.7 prior depression episodes , and 67 % had received prior depression treatment . Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 ( odds ratio [ OR ] = 2.1 , p = .04 ) and 12 months ( OR = 2.7 , p = .01 ) . Intervention patients were more likely to respond by 6 months ( OR = 2.0 , p = .02 ) , and remit by 12 months ( OR = 2.4 , p = .02 ) . Intervention patients reported larger gains in mental health status and health-related quality of life , and reported higher satisfaction . Conclusions Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies", "Background Treatments and organizational changes supported by eHealth are beginning to play an important role in improving disease treatment outcome and providing cost-efficient care management . “ Improvehealth.eu ” is a novel eHealth service to support the treatment of patients with depressive disorder . It offers active patient engagement and collaborative care management by combining Web- and mobile-based information and communication technology systems and access to care managers . Objectives Our objective was to assess the feasibility of a novel eHealth service . Methods The intervention — the “ Improvehealth.eu ” service — was explored in the course of a pilot study comparing two groups of patients receiving treatment as usual and treatment as usual with eHealth intervention . We compared patients ’ medication adherence and outcome measures between both groups and additionally explored usage and overall perceptions of the intervention in intervention group . Results The intervention was successfully implemented in a pilot with 46 patients , of whom 40 were female . Of the 46 patients , 25 received treatment as usual , and 21 received the intervention in addition to treatment as usual . A total of 55 % ( 12/25 ) of patients in the former group and 45 % ( 10/21 ) in the latter group finished the 6-month pilot . Available case analysis indicated an improvement of adherence in the intervention group ( odds ratio [ OR ] = 10.0 , P = .03 ) . Intention-to-treat analysis indicated an improvement of outcome in the intervention group ( ORs ranging from 0.35 to 18 ; P values ranging from .003 to .20 ) , but confidence intervals were large due to small sample sizes . Average duration of use of the intervention was 107 days . The intervention was well received by 81 % ( 17/21 ) of patients who reported feeling actively engaged , in control of their disease , and that they had access to a high level of information . In all , 33 % ( 7/21 ) of the patients also described drawbacks of the intervention , mostly related to usability issues . Conclusions The results of this pilot study indicate that the intervention was well accepted and helped the patients in the course of treatment . The results also suggest the potential of the intervention to improve both medication adherence and outcome measures of treatment , including reduction of depression severity and patients becoming “ healthy .", "Context Few studies have evaluated whether health care assistants can improve care for depressed patients . Contribution Patients who were r and omly assigned to receive telephone case management by health care assistants reported slightly greater improvements in depression symptoms , better adherence to antidepressant therapies , and more favorable assessment s of the quality of their care than did patients r and omly assigned to receive usual care . Implication Telephone case management facilitated by health care assistants may be a feasible mechanism for small primary care practice s to improve care of their patients with depression . The Editors Depression causes a substantial disease burden ( 1 ) and is responsible for annual health care costs of about $ 83.1 billion in the United States ( 2 , 3 ) . Most patients with depression are treated in primary care ( 46 ) . Collaborative care can improve depression outcomes by providing decision support and clinical information for family physicians , as well as self-management support and follow-up for patients . However , evidence regarding collaborative depression care stems mostly from academic or managed care setting s in the United States ( 711 ) . In these trials , family physicians generally relied on mental health case managers and decision support from mental health specialists ( 12 ) . Case management is a patient-centered element of collaborative care that may be effective in primary care ( 13 ) . It comprises systematic tracking of patients , support for continuing the treatment , and taking action in the case of nonadherence or lack of improvement ( 14 ) . Collaborative depression care has generally yielded positive results in diverse primary care setting s ( 7 ) . The IMPACT ( Improving MoodPromoting Access to Collaborative Treatment ) trial found that care managers who were supervised by psychiatrists and who provided education and support for medication adherence reduced depression symptoms in older patients ( 15 ) . Dietrich and colleagues ( 16 ) found that telephone support , provided by a trained , central ly based mental health care manager who was supervised by a psychiatrist , improved depression symptoms . Dobscha and colleagues ( 17 ) evaluated a primary care decision-support team for depression ( comprising a psychiatrist and a mental health nurse ) and found improved care processes but no differences in depression symptoms ( 17 ) , possibly because of less intensive follow-up of patients . Small , isolated primary care setting s often have limited re sources ( 18 ) . In the United States , 26 % of primary care practice s are solo practice s or 2-person partnerships , in which extensive collaborative models would be difficult to implement , and 22 % are located in rural areas with limited access to mental health specialists ( 19 ) . Health care assistants are established professionals in primary care setting s. They have less training than U.S. physician assistants or nurse practitioners , who provide first-contact care , and need not be college graduates ( 20 ) . In Germany , health care assistants have 3 years of on-the-job training . They are mainly responsible for administrative tasks in general practice but provide basic clinical procedures ( 21 ) . Health care assistants are a potentially important re source for enhancing patient care in primary care setting s ( 20 ) . Our aim was to evaluate whether case management by a practice -based health care assistant can reduce depression symptoms and improve the process of care for patients with major depression in small primary care practice s. Methods We design ed a pragmatic , cluster r and omized , controlled trial that used practice as the unit of r and omization to avoid contamination ( 22 ) . The institutional review board of Goethe University Frankfurt am Main , Frankfurt am Main , Germany , approved the study protocol on 25 April 2005 ( 23 ) . We used written consent procedures for family physicians and patients . We recruited practice s between February 2005 and May 2005 and patients between May 2005 and July 2006 . We carried out the intervention between June 2005 and August 2007 . We completed the last follow-up for study patients in September 2007 . Setting and Participants After calculating the sample size ( 24 ) , we informed all 1600 family physicians registered with the medical association of the state of Hesse , Germany ( m and atory registration ) , about the trial and invited them by mail to participate in information meetings . As the registration list presents only names and addresses , we checked inclusion criteria only for those who participated in the meetings . We stopped recruiting when 74 practice s had enrolled , even though more practice s were interested in participating . Inclusion criteria for the practice s were acceptance of all major health plans ( 90 % of patients are covered by this type of insurance ) ( 25 ) ; provision of a primary care service , according to the definition of Starfield and colleagues ( 26 ) ; and management by a family physician . Patients were screened on special date s and referred to the trial by the family physician in the primary care practice . Inclusion criteria for patients were diagnosis of major depression with indication for any antidepressive treatment , age 18 to 80 years , access to a private telephone , ability to give informed consent , and ability to communicate in German . The diagnosis of major depression was based on a score of more than 9 points and a categorical diagnosis in the Patient Health Question naire-9 ( PHQ-9 ) ( 27 ) , and was confirmed by the family physician by using the checklists in the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , and International Classification of Diseases , Tenth Edition . New patients were double-screened with the same procedure within 2 weeks . Exclusion criteria were confirmed pregnancy , severe alcohol or illicit drug consumption , or acute suicidal ideation assessed by the family physician . R and omization and Interventions The data safety and monitoring board stratified the practice s according to the size of the city and performed computer-based r and omization . Patient r and om assignment status was nested within the practice status . The data safety and monitoring board was responsible for allocation concealment by keeping the r and omization results in a secure data base . Because of the practice staff training required for the behavioral intervention , patients , health care assistants , family physicians , and research ers were not blinded to assignment once the trial was started . We design ed our case management intervention in accordance with the Chronic Care Model ( 28 , 29 ) , which emphasizes proactive support for the patient by the entire practice team . We trained 1 health care assistant from each practice assigned to the intervention group in 2 workshops ( an 11-hour and a 6-hour workshop ) . This interactive training included information on depression , communication skills , telephone monitoring , and behavioral activation for the patient ( 3032 ) . The health care assistants contacted their patients by telephone twice a week in the first month and than once a month for the following 11 months . They monitored depression symptoms and adherence to medication by using the Depression Monitoring List ( 33 ) . Health care assistants also encouraged patients to follow self-management activities , such as medication adherence and activation for pleasant or social activities . The assistants provided this information to the family physician in a structured report that stratified the urgency of the contact by a robot scheme . Family physicians in both the intervention and control groups received training on evidence -based depression treatment guidelines ( 34 ) . During the trial , other forms of disease or case management programs were uncommon in Germany ( 35 ) . No study practice carried out case management for any other diseases . Outcomes and Follow-up Self-rating question naires were h and ed out to the patients at baseline and at 6 and 12 months after baseline . Patients filled in the question naires at home and sent them back to the practice . We collected the question naires in the practice s and collected data from patient records ( number of family physician and specialist contacts , hospitalization , and prescribed medication ) . Research staff carried out data input and management ( 36 ) . Serious adverse events were reported to the data safety and monitoring board . Clinical Outcomes The primary outcome was depression symptoms , which we assessed by using the primary carevali date d PHQ-9 ( 37 ) . Each item is scored from 0 ( not at all ) to 3 ( nearly every day ) , for a total score that ranges from 0 to 27 ( high scores indicate more severe depression ) . We assessed response ( 50 % improvement in PHQ-9 score ) and remission status ( PHQ-9 score<5 ) as secondary outcomes . We also report data for the following secondary outcomes : quality of life , patient assessment of chronic illness care , and medication adherence . We measured health-related quality of life by using the Medical Outcomes Study Short Form 36 ( SF-36 ) ( 38 , 39 ) and the EuroQol-5D ( 40 ) . The SF-36 allows the calculation of scores for physical health and mental health ( range , 0 to 100 ; higher scores indicate better status ) . The EuroQol-5D is a generic instrument that measures health-related quality of life with a visual analogue scale ( range , 0 to 100 ; higher ratings indicate higher quality of life ) . We determined the number of physical comorbid conditions by counting the documented diagnoses from different diagnostic groups listed in the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , and International Classification of Diseases , Tenth Edition , excluding all psychiatric diagnoses in the patient record . We assessed severity of chronic physical diseases by using the Chronic Disease Score , on the basis of prescription data from the patient record ( 41 ) . Process-of-Care Outcomes We assessed the number of family physician and mental health specialist contacts , as well as prescriptions for", "PURPOSE We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications , depression outcomes , and blood pressure control among older primary care patients . METHODS Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were r and omly assigned to an integrated care intervention or usual care . Outcomes were assessed at baseline , 2 , 4 , and 6 weeks using the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression , an electronic monitor to measure blood pressure , and the Medication Event Monitoring System to assess adherence . RESULTS In all , 64 participants aged 50 to 80 years participated . Participants in the integrated care intervention had fewer depressive symptoms ( CES-D mean scores , intervention 9.9 vs usual care 19.3 ; P < .01 ) , lower systolic blood pressure ( intervention 127.3 mm Hg vs usual care 141.3 mm Hg ; P < .01 ) , and lower diastolic blood pressure ( intervention 75.8 mm Hg vs usual care 85.0 mm Hg ; P < .01 ) compared with participants in the usual care group at 6 weeks . Compared with the usual care group , the proportion of participants in the intervention group who had 80 % or greater adherence to an antidepressant medication ( intervention 71.9 % vs usual care 31.3 % ; P < .01 ) and to an antihypertensive medication ( intervention 78.1 % vs usual care 31.3 % ; P < .001 ) was greater at 6 weeks . CONCLUSION A pilot , r and omized controlled trial integrating depression and hypertension treatment was successful in improving patient outcomes . Integrated interventions may be more feasible and effective in real-world practice s , where there are competing dem and s for limited re sources", "According to professionals , medication nonadherence is often attributed to adverse effects or early remission . There is , however , little evidence to support these attributions . Our aim was to study the predictors of nonadherence in primary care patients with a new antidepressant ( AD ) prescription . We used a prospect i ve cohort study with 6-month follow-up among 147 primary care patients who were newly prescribed with a nontricyclic AD for depression . They were recruited in 19 community pharmacies in the Netherl and s that were linked to 85 general practitioners . An electronic pill container ( medication event monitoring system ; Aardex Ltd , Untermüli , Switzerl and ) registered the adherence for 6 months . The predictive values of patient , prescriber , pharmacist , and drug-related characteristics were expressed in univariate and multivariate odds ratios with 95 % confidence intervals . Outcome measures showed nonadherence , as expressed in these factors ( all dichotomous ) : ( 1 ) incorrect intakes ( < 80 % period coverage ) ; ( 2 ) extra pill intakes ( > 1 per day ) ; ( 3 ) drug holidays ( > or=1 ) . We found that not only a positive drug attitude , the most important predictor , but also adverse effects , early treatment response , longer onset of depression , and a higher educational level predicted the correct intake of ADs . Extra intakes were predicted by ADs with a shorter half-life and by experience of adverse effects . Drug holidays were predicted by patients with less social support and a negative drug attitude . In conclusion , the predictors of adherence were multifactorial and varied across the 3 adherence types . A positive drug attitude emerged as the most important predictor for correct intakes and drug holidays", "Introduction The efficacy of antidepressants in the treatment of depression has been convincingly demonstrated in r and omised trials . However , non-adherence to antidepressant treatment is common . Objective To evaluate , from a societal perspective , the cost effectiveness of a pharmacy-based intervention to improve adherence to antidepressant therapy in adult patients receiving treatment in primary care . Methods An economic evaluation was performed alongside a 6-month r and omised controlled trial in The Netherl and s. Patients who came to 19 pharmacies with a new prescription for a non-tricyclic antidepressant , i.e. those who had not received any prescription for an antidepressant in the past 6 months , were invited to participate . They were then r and omly allocated to education and coaching by the pharmacist or to usual care . The coaching programme consisted of three contacts with the pharmacist , with a mean duration of between 13 and 20 minutes , and a take-home video review ing important facts on depression and antidepressant treatment . The clinical outcome measures were adherence to antidepressant treatment measured using an electronic pill container ( eDEM ) and improvement in depressive symptoms measured using the Hopkins Symptom Checklist ( SCL ) . Re source use was measured by means of question naires . The uncertainty around differences in costs and cost effectiveness between the treatment groups was evaluated using bootstrapping . Results Seventy patients were r and omised to the intervention group and 81 to the usual care group ; of these , 40 in the intervention group and 48 in the control group completed all of the follow-up question naires . There were no significant differences in adherence , improvements in the SCL depression mean item score and costs over 6 months between the two treatment groups . Mean total costs ( 2002 values ) were € 3275 in the intervention group and € 2961 in the control group ( mean difference € 315 ; 95 % CI —1922 , 2416 ) . The incremental cost-effectiveness ratio associated with the pharmacist intervention was € 149 per 1 % improvement in adherence and € 2550 per point improvement in the SCL depression mean item score . Cost-effectiveness planes and acceptability curves indicated that the pharmacist intervention was not likely to be cost effective compared with usual care . Conclusion In patients starting treatment with antidepressants , there were no significant differences in adherence , severity of depression , costs and cost effectiveness between patients receiving coaching by a pharmacist and patients receiving usual care after 6 months . Considering the re sources needed to implement an intervention like this in clinical practice , based on these results , the continuation of usual care is recommended", "BACKGROUND Treatment guidelines recommend antidepressant treatment be continued for at least 6 months to ensure maximal improvement and to prevent relapse . Naturalistic studies show that the average length of treatment is shorter than 6 months and that dropout rates are high . Factors leading patients to discontinuation of therapy are not well understood . This study investigates when and why patients stop treatment and whether they inform their doctors . METHOD Patients ( N = 272 ) receiving antidepressant therapy due to an episode of major depressive disorder ( DSM-IV ) were asked to complete an antidepressant compliance question naire . Patients were then telephoned monthly while they continued on antidepressant therapy , up to 6 months . During each call , patients were asked st and ard questions . RESULTS By endpoint , 53 % of patients had discontinued antidepressant treatment . The most common reason given was \" feeling better . \" However , different dropout reasons were prevalent at different times after initiation of therapy . Overall , 24 % of the patients did not inform their physician about stopping the antidepressant medication . The likelihood of patients ' informing their physicians differed according to the patients ' reasons for discontinuation and according to the patients ' perceptions of their relationship with their physicians . CONCLUSION These results provide new guidelines for improving compliance . Strategy should be adapted to the stage of treatment , as patients ' reasons for discontinuation vary as treatment progresses . The attitude of the physician and the information provided by the physician significantly influence whether patients inform the physician when they discontinue antidepressant therapy", "Most depressed patients are seen and treated exclusively by primary care clinicians . However , primary care patients with depression are often not adequately treated . The aims of this pilot study were to measure the impact of a telephone disease management program on patient outcome and clinician adherence to practice guidelines , measure the relationship of clinician adherence to patient outcome , and explore the measurement of patient adherence to clinician recommendations and its impact on patient outcomes . Thirty-five primary care practice s in the University of Pennsylvania Health System were r and omized to telephone disease management ( TDM ) or \" usual care \" ( UC ) . All patients received a baseline and a 16-week follow-up clinical evaluation performed over the telephone . Those from TDM practice s also received follow-up contact at least every 3 weeks , with formal evaluations at weeks 6 and 12 . These interval contacts were design ed to facilitate patient and clinician adherence to a treatment algorithm based on the Agency for Health Research and Quality ( AHRQ ) practice guidelines . Depressive symptoms evaluated with the Community Epidemiologic Survey of Depression ( CES-D ) scale as well as guideline adherence were the primary outcome measures . Sixty-one patients were enrolled in this pilot project . The overall effect for CES-D scores over time was significant , ( P < .001 ) , indicating that those participating in the trial ( both TDM and UC groups ) showed significant improvement . The interaction between intervention condition and time was also significant ( P < .05 ) , indicating that TDM patients improved significantly more over time than did UC patients . A greater proportion of TDM patients had CES-D scores < 16 by Week 16 ( 66.7 versus 33.3 % ; chi(2 ) , P < .05 ) . The improvement in depression outcome for the TDM group was related to its impact on improving clinician adherence to depression treatment algorithms . The TDM pilot did not show a statistically significant effect on improving patient adherence to clinician recommendations , however . This preliminary data suggests that TDM for depression improves both clinician guideline adherence and patient outcomes in the acute phase of depression . The effect on patient outcome is at least partially explained by the effect of TDM on clinician adherence to depression treatment algorithms", "OBJECTIVE Documentation and evaluation of patient outcomes in a pilot study into the role of rural community pharmacists in the management of depression . DESIGN Parallel groups design with a control and intervention group . SETTING Thirty-two community pharmacies in rural and remote New South Wales , Australia . PARTICIPANTS One hundred and six patient participants , mean age of 46 years , predominantly female , not currently employed , recruited by participating pharmacists . INTERVENTIONS Intervention pharmacists were given video-conference training on the nature and management of depression by a psychiatrist , psychologist and general practitioner and asked to dispense medication with extra advice and support . Control pharmacists were asked to provide usual care . MAIN OUTCOME MEASURES Adherence by self-report , K10 , Drug Attitude Index . RESULTS The results indicated that adherence to medications was high in both groups ( 95 % versus 96 % ) and that both groups had improved significantly in wellbeing ( a reduction K10 score of 4 ( control ) versus 4.7 ( intervention ) ) . No significant change was found in attitude to drug treatment once baseline scores were controlled for . CONCLUSIONS Because both groups improved in wellbeing it is not possible to cl aim that the training provided to the intervention pharmacists was responsible for the success . However , the improvements gained in such a short time ( two months ) suggest that the involvement of pharmacists has had a beneficial rather than negative effect . Further research into the most appropriate ways in which to integrate the skills of pharmacists into a model of mental health care delivery in rural communities is recommended", "OBJECTIVE To test the impact of a novel psychosocial intervention to improve antidepressant adherence and depression outcomes among older adults prescribed pharmacotherapy by their primary care physician ( PCP ) . DESIGN A r and omized controlled pilot study was conducted to examine the usefulness of the Treatment Initiation and Participation ( TIP ) program as an intervention to improve antidepressant adherence and depression outcomes . SETTING The study was conducted at two primary care clinics in New York city : one clinic served geriatric adults and the second clinic served a diverse group of mixed aged adults . PARTICIPANTS The sample consisted of adults aged 60 years and older with major depression who were recommended antidepressant therapy by their PCPs . INTERVENTION All participants were prescribed antidepressant therapy and r and omly assigned to either the intervention ( TIP ) or the treatment as usual ( TAU ) group . The TIP intervention identifies and targets psychological barriers to depression care , especially stigma , as well as fears and misconceptions of depression and its treatment . TIP participants are encouraged to develop a treatment goal and create an adherence strategy . MEASUREMENT Study participants were assessed at entry , 6 , 12 , and 24 weeks later . Adherence was measured based on self-report with chart verification . Depression severity was measured using the Hamilton Depression Rating Scale . RESULTS Participants in TIP were significantly more adherent to their antidepressant pharmacotherapy at all assessment time points and had a significantly greater decrease in depressive symptoms than older adults who received TAU . CONCLUSION The results provide support for the usefulness of TIP as a brief intervention to improve adherence to depression medication treatment provided in primary care setting", "OBJECTIVE To evaluate the impact of mail-based physician and member educational interventions on patient adherence to antidepressant medications . STUDY DESIGN The r and omized controlled prospect i ve design included patients followed for 6 months after filling a new prescription for an antidepressant . A pharmacy cl aims data base was used to identify patients and track medication adherence . PATIENTS AND METHODS Patients receiving a new prescription for an antidepressant and their prescribers were included . Prescribers were r and omly assigned to the intervention and control groups . Patient assignment was linked to their physician 's assignment . The control group received no intervention . The educational intervention consisted of monthly letters to patients and prescribers regarding the Health Plan Employer Data and Information Set ( HEDIS ) st and ards or educational information regarding the importance of medication adherence . The primary outcome was adherence as measured by the medication possession ratio and measurement as specified by HEDIS . The Student 's ttest , the chi2 test , and a logistic regression model were used to compare groups and the variables that affect adherence . Other secondary measurements of adherence were performed . RESULTS A total of 9564 patients were included . Patients in the intervention group demonstrated greater adherence compared with the control group at 90 and 180 days ( P < .05 ) . After adjusting for variables , the intervention variable stood alone in its significant impact on adherence ( P < .01 ; confidence interval , 1.003 - 1.197 ) . Adherence in the total population was significantly higher for selective serotonin reuptake inhibitors than for other agents ( P < .001 ) . CONCLUSION A monthly mail-based educational intervention program regarding antidepressant medications can positively influence patient adherence to therapy", "BACKGROUND This study aim ed to identify the predictors and outcomes of SSRI antidepressant continuation , discontinuation and switching over a 9-month period of naturalistic observation . METHODS Primary care patients ( n=573 ) with physician-diagnosed depression from 37 practice s were r and omized to an open-label trial of one of three selective serotonin reuptake inhibitors ( SSRIs ) managed in their primary care setting . Psychiatric characteristics and treatment course were assessed at baseline and at 1 , 3 , 6 and 9 months after medication initiation . RESULTS Nineteen percent of patients switched SSRIs , which occurred significantly sooner than discontinuation ( median : 41 vs.100 days ) . Time to discontinuation was primarily explained by baseline patient skepticism about taking an antidepressant ( 62 % increase in discontinuation risk ) . In contrast , time to switch was associated with greater impairment at baseline and lesser improvement in impairment during the first month on medication . Patients who discontinued were significantly less likely to be depressed 9 months after starting medication than those who either continued or switched medication , and were less symptomatic and impaired than patients who switched . CONCLUSIONS Baseline impairment may increase the risk for SSRI antidepressant switching . Additionally , patient skepticism about antidepressants predicts early SSRI discontinuation and may predict rapid recovery . Intent-to-treat analyses in nonr and omized clinical trials may paradoxically inflate antidepressant effect sizes", "PURPOSE The impact of pharmacist interventions on the care and outcomes of patients with depression in a primary care setting was evaluated . METHODS Patients diagnosed with a new episode of depression and started on anti-depressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) for one year . EC consisted of a pharmacist collaborating with primary care providers to facilitate patient education , the initiation and adjustment of antidepressant dosages , the monitoring of patient adherence to the regimen , the management of adverse reactions , and the prevention of relapse . The patients in the UC group served as controls . Outcomes were measured by the Hopkins Symptom Checklist , Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for major depression , health-related quality of life , medication adherence , patient satisfaction , and use of depression-related health care services . An intent-to-treat analysis was used . RESULTS Seventy-four patients were r and omized to EC or UC . At baseline , the EC group included more patients diagnosed with major depression than did the UC group ( p = 0.04 ) . All analyses were adjusted for this difference . In both groups , mean scores significantly improved from baseline for symptoms of depression and quality of life at three months and were maintained for one year . There were no statistically significant differences between treatment groups in depression symptoms , quality of life , medication adherence , provider visits , or patient satisfaction . CONCLUSION Frequent telephone contacts and interventions by pharmacists and UC in a primary care setting result ed in similar rates of adherence to antidepressant regimens and improvements in the outcomes of depression at one year", "OBJECTIVE Several evidence -based treatment guidelines for major depressive disorder ( MDD ) have been published . However , little is known about how recommendations for treatment are adhered to by patients in current usual psychiatric practice . METHOD The Vantaa Depression Study is a prospect i ve , naturalistic cohort study of 269 psychiatric patients with a new episode of DSM-IV MDD who were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and Structured Clinical Interview for DSM-III-R Personality Disorders between February 1 , 1997 , and May 31 , 1998 , and again at 6 and 18 months . Treatments provided , as well as adherence to and attitudes toward both antidepressants and psychotherapeutic support/psychotherapy , were investigated among the 198 unipolar patients followed for 18 months . RESULTS Most depression patients ( 88 % ) received antidepressants in the early acute phase , but about half ( 49 % ) terminated treatment prematurely . This premature termination was associated with worse outcome of major depressive episodes , and with negative attitudes , mainly explained by fear of dependence on or side effects of antidepressants . Nearly all patients ( 98 % ) received some psychosocial treatment in the acute phase ; about one fifth ( 16 % ) had weekly psychotherapy during the follow-up . About a quarter of patients admitted nonadherence to ongoing treatments . CONCLUSION Problems of psychiatric care seem most related to continuity of treatment . While adequate treatments are provided in the early acute phase , antidepressants are terminated too soon in about half of patients , often following their autonomous decisions . From a secondary and tertiary preventive point of view , improving continuity of treatment would appear a crucial task for improving the outcome of psychiatric patients with MDD", "OBJECTIVE Clinical guidelines recommend that antidepressant treatment should be continued for a minimum of 6 months following response in depression and anxiety disorders . However , adherence to antidepressants is low . This prospect i ve cohort study investigated the influence of patients ' antidepressant concerns , treatment preferences , and illness perceptions on adherence to antidepressants over a 6-month period . METHOD A cohort of 178 patients aged 18 to 74 years and newly issued with a prescription for antidepressants to treat any condition was followed up prospect ively at 5 primary care practice s in Southeast Engl and . Adherence was measured through self-report and prescription refill data . Patient perceptions were quantified using vali date d outcome measures , the Beliefs about Medicine Question naire and the Illness Perception Question naire , at 4 timepoints . Patient treatment preferences were recorded using a specially design ed question naire . Data collection took place between September 2000 and May 2002 . RESULTS Of 147 participants ( 83 % ) who completed the study , 19 % persisted with antidepressants in accordance with guideline recommendations throughout the 6-month period . Specific concern about antidepressant side effects ( OR = 3.30 , 95 % CI = 2.20 to 4.97 ) and general worry about taking antidepressants ( OR = 1.65 , 95 % CI = 1.13 to 2.40 ) were independent predictors of antidepressant nonuse . Preference for different treatment/uncertainty about preferred treatment was also a strong predictor ( OR = 3.82 , 95 % CI = 1.35 to 10.77 ) . However , illness perceptions were not associated with adherence . CONCLUSIONS Concerns about antidepressants and a mismatch between patients ' preferred and prescribed treatment act as significant barriers to sustained adherence . This study highlights the central role of the patient-physician partnership in exploring antidepressant concerns , working with treatment preferences , and providing supportive continued management . The findings may inform the development of interventions within primary care programs to enhance commitment to treatment for common mental disorders", "Objective : Patients with major depression discontinue taking their antidepressants for many reasons . Although side effects are often cited as the reason for discontinuation , few prospect i ve studies have addressed this question , and none has specifically examined discontinuation in patients with severe depression . Method : In patients and out patients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission . Three months later , patients were contacted and interviewed to determine antidepressant usage and the side effects experienced , including when these were experienced and their severity . Results : Between October 2001 and April 2003 , 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up . One in 4 patients discontinued the index antidepressant . Among specific side effects noted , only \" change in weight \" and \" anxiety \" were significant predictors of discontinuation after controlling for confounders . Experiencing 1 or more \" extremely \" bothersome side effects was associated with more than a doubling of the risk of discontinuation , but the presence of side effects and side effects less severe than \" extremely \" bothersome were not significant predictors . There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates . Conclusion : The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested . Disparate findings from earlier studies may reflect aspects of study design , such as examining population s whose severity of depression varied widely or not controlling for important confounding factors . Future research should separately examine high-risk groups ( or control for severity of depression ) and carefully rule out other potential contributors to discontinuation", "Background Quality of antidepressant treatment remains disturbingly poor . Rates of medication adherence and follow-up contact are especially low in primary care , where most depression treatment begins . Telephone care management programs can address these gaps , but reliance on live contact makes such programs less available , less timely , and more expensive . Objective Evaluate the feasibility , acceptability , and effectiveness of a depression care management program delivered by online messaging through an electronic medical record . Design R and omized controlled trial comparing usual primary care treatment to primary care supported by online care management Setting Nine primary care clinics of an integrated health system in Washington state Participants Two hundred and eight patients starting antidepressant treatment for depression . InterventionThree online care management contacts with a trained psychiatric nurse . Each contact included a structured assessment ( severity of depression , medication adherence , side effects ) , algorithm-based feedback to the patient and treating physician , and as-needed facilitation of follow-up care . All communication occurred through secure , asynchronous messages within an electronic medical record . Main Measures An online survey approximately five months after r and omization assessed the primary outcome ( depression severity according to the Symptom Checklist scale ) and satisfaction with care , a secondary outcome . Additional secondary outcomes ( antidepressant adherence and use of health services ) were assessed using computerized medical records . Key Results Patients offered the program had higher rates of antidepressant adherence ( 81 % continued treatment more than 3 months vs. 61 % , p = 0.001 ) , lower Symptom Checklist depression scores after 5 months ( 0.95 vs. 1.17 , p = 0.043 ) , and greater satisfaction with depression treatment ( 53 % “ very satisfied ” vs. 33 % , p = 0.004 ) . Limitations The trial was conducted in one integrated health care system with a single care management nurse . Results apply only to patients using online messaging . Conclusions Our findings suggest that organized follow-up care for depression can be delivered effectively and efficiently through online messaging", "We performed a r and omized trial to prevent depression relapse in primary care by evaluating intervention effects on medication attitudes and self-management of depression . Three hundred and eighty six primary care patients at high risk for recurrent depression were r and omized to receive a 12-month intervention . Interviews at baseline , 3 , 6 , 9 , and 12-months assessed attitudes about medication , confidence in managing side effects , and depression self-management . This depression relapse prevention program significantly increased : 1 ) favorable attitudes toward antidepressant medication [ Beta = .26 , 95 % C.I. = ( .18,.33 ) ] ; 2 ) self-confidence in managing medication side effects [ Beta = .53 , 95 % C.I. = ( .15,.91 ) ] ; 3 ) depressive symptom monitoring [ O.R. = 4.08 , 95 % C.I. = ( 2.80 , 5.94 ) ] ; 4 ) checking for early warning signs [ O.R. = 3.27 , 95 % C.I. = ( 2.32 , 4.61 ) ] ; and , 5 ) planful coping [ O.R. = 2.01 , 95 % C.I. = ( 1.49 , 2.72 ) ] . Significant predictors of adherence to long-term pharmacotherapy were : favorable attitudes toward antidepressant treatment [ OR = 2.20 , 95 % CI = ( 1.50 , 3.22 ) ] , and increased confidence in managing medication side effects [ OR = 1.10 , 95 % CI = ( 1.04 , 1.68 ) ] . Among primary care patients at high risk for depression relapse , enhanced attitudes towards antidepressant medicines and higher confidence in managing side effects were key factors associated with greater adherence to maintenance pharmacotherapy", "BACKGROUND A r and omized trial of a primary care-based intervention to prevent depression relapse result ed in improved adherence to long-term antidepressant medication and depression outcomes . We evaluated the effects of this intervention on behavioural processes and identified process predictors of improved depressive symptoms . METHOD Patients at high risk for depression recurrence or relapse following successful acute phase treatment ( N=386 ) were r and omly assigned to receive a low intensity 12-month intervention or continued usual care . The intervention combined education about depression , shared decision-making regarding use of maintenance pharmacotherapy and cognitive-behavioural strategies to promote self-management . Baseline , 3 , 6 , 9 and 12-month interviews assessed patients ' self-care practice s , self-efficacy for managing depression and depressive symptoms . RESULTS Intervention patients had significantly greater self-efficacy for managing depression ( P<0.01 ) and were more likely to keep track of depressive symptoms ( P<0.0001 ) , monitor early warning signs ( P<0.0001 ) , and plan for coping with high risk situations ( P<0.0001 ) at all time points compared to usual care control patients . Self-efficacy for managing depression ( P<0.0001 ) , keeping track of depressive symptoms ( P=0.05 ) , monitoring for early warning signs ( P=0.01 ) , engaging in pleasant activities ( P<0.0001 ) and engaging in social activities ( P<0.0001 ) positively predicted improvements in depression symptom scores . CONCLUSIONS A brief intervention design ed to target cognitive-behavioural factors and promote adherence to pharmacotherapy in order to prevent depression relapse was highly successful in changing several behaviours related to controlling depression . Improvements in self-efficacy and several self-management behaviours that were targets of the intervention were significantly related to improvements in depression outcome", "BACKGROUND Many patients with major depression are non-adherent to antidepressant medication and do not receive care according to current guidelines . There is increasing evidence that treatment of depression in primary care can be improved . Comparison between effective interventions may help to establish the active ingredients of such interventions . METHOD In a r and omized trial two interventions to improve treatment of major depression in primary care were compared ( 1 ) a depression care programme , targeting general practitioners ( GPs ) , patients , and systematic follow-up , and ( 2 ) a systematic follow-up programme . Thirty GPs were r and omized and 211 primary -care patients with current major depression were included . All patients were prescribed a selective serotonin reuptake inhibitor . Outcome measures included adherence to antidepressant medication , and depression outcome . RESULTS No significant differences in adherence rates and treatment outcome measures were demonstrated between interventions at week 10 or week 26 . Adherence rates were high and treatment outcome was favourable . CONCLUSIONS The depression care programme was not superior to the systematic follow-up programme . Systematic follow-up in depression treatment in primary care seems to be an intervention per se , having the potential to improve adherence and treatment outcome", "Medication non-adherence is a major obstacle in the treatment of affective disorders . The primary objective of this study was to evaluate two different interventions to improve adherence to antidepressant drugs . Secondary objectives included response to treatment , relation between adherence and response , patient satisfaction and tolerability . A r and omized controlled design was used to assess the effect of a patient educational compliance enhancing programme ( CP ) and therapeutic drug monitoring in 1031 major depressed patients treated with sertraline for 24 weeks and managed by their general practitioner . Adherence was measured by question ing , measurable serum levels of sertraline and desmethylsertraline , appointments kept and a composite index including all three methods . Treatment adherence was found in 37–70 % of patients , depending on the method used . Neither of the interventions result ed in a significant increase in adherence rate . However , significantly more patients in the CP group had responded at week 24 compared to patients in the control group . Overall , significantly more adherent patients responded to treatment compared to non-adherent patients , regardless of method used to determine adherence . This large study demonstrates that treatment response increases when using an educational compliance programme and that a strong relationship between treatment adherence and response exists", "OBJECTIVE Telepsychiatry is an increasingly common method of providing psychiatric care , but r and omized trials of telepsychiatric treatment compared to in-person treatment have not been done . The primary objective of this study was to compare treatment outcomes of patients with depressive disorders treated remotely by means of telepsychiatry to outcomes of depressed patients treated in person . Secondary objectives were to determine if patients ' rates of adherence to and satisfaction with treatment were as high with telepsychiatric as with in-person treatment and to compare costs of telepsychiatric treatment to costs of in-person treatment . METHOD In this r and omized , controlled trial , 119 depressed veterans referred for outpatient treatment were r and omly assigned to either remote treatment by means of telepsychiatry or in-person treatment . Psychiatric treatment lasted 6 months and consisted of psychotropic medication , psychoeducation , and brief supportive counseling . Patients ' treatment outcomes , satisfaction , and adherence and the costs of treatment were compared between the two conditions . RESULTS Hamilton Depression Rating Scale and Beck Depression Inventory scores improved over the treatment period and did not differ between treatment groups . The two groups were equally adherent to appointments and medication treatment . No between-group differences in dropout rates or patients ' ratings of satisfaction with treatment were found . Telepsychiatry was more expensive per treatment session , but this difference disappeared if the costs of psychiatrists ' travel to remote clinics more than 22 miles away from the medical center were considered . Telepsychiatry did not increase the overall health care re source consumption of the patients during the study period . CONCLUSIONS Remote treatment of depression by means of telepsychiatry and in-person treatment of depression have comparable outcomes and equivalent levels of patient adherence , patient satisfaction , and health care cost", "The effects on adherence and depressive symptoms of a community pharmacy-based coaching program , including a take-home videotape , were evaluated in a r and omized controlled trial in the Netherl and s. A total of 147 depressed primary care patients who had a new antidepressant prescription were included in the study . Adherence was measured with an electronic pill container and was also derived from pharmacy medication records ; the latter method was associated with an overestimation of adherence of only 5 percent . Intention-to-treat analyses showed no intervention effect on adherence ( 73 percent compared with 76 percent ) , whereas analyses of patients who received the intervention ( per protocol ) showed improved adherence ( 73 percent compared with 90 percent ) . Neither analysis showed effects on depressive symptoms", "OBJECTIVE To explore the impact of telephone-based education and monitoring by community pharmacists on multiple outcomes of pharmacist-patient collaboration . DESIGN A r and omized , controlled , unblinded , mixed experimental design . SETTING Eight Wisconsin community pharmacies within a large managed care organization . PATIENTS A total of 63 patients presenting new antidepressant prescriptions to their community pharmacies . INTERVENTIONS Patients were r and omized to receive either three monthly telephone calls from pharmacists providing pharmacist-guided education and monitoring ( PGEM ) or usual pharmacist 's care . Usual care is defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies . MAIN OUTCOME MEASURES Patient 's frequency of feedback with the pharmacist , antidepressant knowledge , antidepressant beliefs , antidepressant adherence at 3 and 6 months , improvement in depression symptoms , and orientation toward treatment progress . RESULTS Of the 60 patients who completed the study , 28 received PGEM and 32 received usual pharmacist 's care . Results showed that PGEM had a significant and positive effect on patient feedback , knowledge , medication beliefs , and perceptions of progress . There were no significant group differences in patient adherence or symptoms at 3 months ; however , PGEM patients who completed the protocol missed fewer doses than did the usual care group at 6 months ( P < or = .05 ) . CONCLUSION Antidepressant telemonitoring by community pharmacists can significantly and positively affect patient feedback and collaboration with pharmacists . Longer-term studies with larger sample s are needed to assess the generalizability of findings . Future research also needs to explore additional ways to improve clinical outcomes", "Adherence to drug therapy is a limitation in treatment success for major depressive disorder ( MDD ) . The influence of RHYTHMS , an information and ongoing interactive program design ed by Pfizer Pharmaceuticals , to address patient adherence to sertraline therapy was evaluated in a primary care setting using a r and omized , double-blind , parallel group controlled trial over 29 weeks . Remission was the primary outcome evaluated . At study completion , no statistically significance between group differences was noted for remission rates , treatment adherence or mean Hamilton Depression Rating Scale ( HDRS ) score . However , the RHYTHMS group reported significantly greater satisfaction with knowledge received about depression and its treatment and demonstrated significantly greater satisfaction with treatment received . We conclude that the application of RHYTHMS in a primary care setting has a substantial role in improving satisfaction with sertraline treatment by patients with MDD", "Introduction : Because of the misunderst and ing and stigmatization of mental health disorders and treatment , health beliefs may be important in treatment seeking for depression . It is important to underst and patients ’ beliefs about mental health disorders and mental health treatment to improve systems of care . Methods : We studied beliefs about depression and depression treatment among patients in a r and omized trial of a chronic care intervention to improve depression treatment in the Veterans Administration healthcare system ( n = 395 ) . The Depression Beliefs Inventory was used to assess beliefs regarding : ( 1 ) perceived need for depression treatment , ( 2 ) the efficacy of depression treatment , and ( 3 ) treatment barriers , including stigma , at baseline and 6 months . We calculated descriptive statistics on patients ’ baseline beliefs , and used multiple regression to investigate the extent to which beliefs changed in intervention and treatment as usual patients between baseline and 6-month assessment s. We used logistic regression to investigate the relationship between beliefs and antidepressant initiation , adherence and clinical response . Results : At baseline , 73 % of our sample believed that they had depression , and 66 % believed that taking antidepressants would be helpful for their depression . However , the depression intervention had few effects on beliefs , and individual beliefs were generally not associated with taking medication or clinical response . However , a summary measure of beliefs was found to have predictive validity with respect to initiating and adhering to antidepressant treatment . Discussion : Our results highlight the potential difficulty in modifying individuals ’ attitudes regarding depression and depression treatment in chronic care models for depression interventions" ]

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[ "Early intervention for relapse in schizophrenia: impact of cognitive behavioural therapy on negative beliefs about psychosis and self-esteem.", "Internet-Based Interventions to Promote Mental Health Help-Seeking in Elite Athletes: An Exploratory Randomized Controlled Trial", "Effects of school-based interventions on mental health stigmatization: a systematic review", "Public conceptions of mental illness: labels, causes, dangerousness, and social distance.", "Filmed v. live social contact interventions to reduce stigma: randomised controlled trial.", "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", "Systematic reviews of the effectiveness of quality improvement strategies and programmes", "Mental health first aid training for high school teachers: a cluster randomized trial", "Feasibility, acceptability, and initial efficacy of a knowledge-contact program to reduce mental illness stigma and improve mental health literacy in adolescents.", "Randomised trial of impact of school mental-health programme in rural Rawalpindi, Pakistan", "Effects of a Cognitive‐Behavioural Internet Program on Depression, Vulnerability to Depression and Stigma in Adolescent Males: A School‐Based Controlled Trial", "Effects of a psychoeducational intervention program on the attitudes and health perceptions of relatives of patients with schizophrenia", "A controlled trial of a school-based Internet program for reducing depressive symptoms in adolescent girls.", "A randomized controlled trial of telephone motivational interviewing to enhance mental health treatment engagement in Iraq and Afghanistan veterans.", "Mental Illness Training for Licensed Staff in Long-Term Care", "Stigma and the military: evaluation of a PTSD psychoeducational program.", "Reducing mental illness stigma in mental health professionals using a web-based approach.", "Testing the effectiveness of an educational intervention aimed at changing attitudes to self-harm.", "Randomized controlled trial of the self-stigma reduction program among individuals with schizophrenia", "Mental Health First Aid Training by e-Learning: A Randomized Controlled Trial" ]

[ "OBJECTIVES The study aim ed to test two hypotheses . Firstly , that participants who relapsed during the 12-month follow-up period of our r and omized controlled trial , would show increased negative beliefs about their illness and reduced self-esteem , in comparison to the non-relapsed participants . Secondly , that cognitive behavioural therapy ( CBT ) for early signs of relapse would result in a reduction in negative beliefs about psychosis and an improvement in self-esteem at 12 months . DESIGN AND METHODS A total of 144 participants with schizophrenia or a related disorder were r and omized to receive either treatment as usual ( TAU ; N=72 ) or CBT ( N=72 ) . Participants completed the Personal Beliefs about Illness Question naire ( PBIQ ; Birchwood , Mason , MacMillan , & Healy , 1993 ) and the Rosenberg Self-Esteem Scale ( RSES ; Rosenberg , 1965 ) at entry , 3 months , 6 months , and 12 months . RESULTS At 12 months , relapsers showed greater increase in scores for PBIQ entrapment compared with non-relapsers . In addition , after controlling for baseline covariates ( treatment group and PBIQ self versus illness ) , relapsers also showed greater increase in scores for PBIQ self versus illness at 12 months . Furthermore , in comparison to treatment as usual , participants who received CBT showed greater improvement in PBIQ loss and in Rosenberg self-esteem . CONCLUSIONS The study provides evidence that relapse is associated with the development of negative appraisal s of entrapment and self-blame ( self vs. illness ) . In addition , this is the first study to show that CBT reduces negative appraisal s of loss arising from psychosis and improvements in self-esteem . Implication s for future research and treatment are discussed", "Background Mental disorders are more common in young adults than at any other life stage . Despite this , young people have low rates of seeking professional help for mental health problems . Young elite athletes have less positive attitudes toward seeking help than nonathletes and thus may be particularly unlikely to seek help . Interventions aim ed at increasing help-seeking in young elite athletes are warranted . Objective To test the feasibility and efficacy of three Internet-based interventions design ed to increase mental health help-seeking attitudes , intentions , and behavior in young elite athletes compared with a control condition . Methods We conducted a r and omized controlled trial ( RCT ) of three brief fully automated Internet-based mental health help-seeking interventions with 59 young elite athletes recruited online in a closed trial in Australia . The interventions consisted of a mental health literacy and destigmatization condition , a feedback condition providing symptom levels , and a minimal content condition comprising a list of help-seeking re sources , compared with a control condition ( no intervention ) . We measured help-seeking attitudes , intentions and behavior using self-assessed surveys . Participation was open to elite athletes regardless of their mental health status or risk of mental illness . Results Of 120 athletes initially agreeing to participate , 59 ( 49 % ) su bmi tted a preintervention or postintervention survey , or both , and were included in the present study . Adherence was satisfactory , with 48 ( 81 % ) participants visiting both weeks of assigned intervention material . None of the interventions yielded a significant increase in help-seeking attitudes , intentions , or behavior relative to control . However , at postintervention , there was a trend toward a greater increase in help-seeking behavior from formal sources for the mental health literacy/destigmatization condition compared with control ( P = .06 ) . This intervention was also associated with increased depression literacy ( P = .003 , P = .005 ) and anxiety literacy ( P = .002 , P = .001 ) relative to control at postintervention and 3-month follow-up , respectively , and a reduction in depression stigma relative to control at postintervention ( P = .01 , P = .12 ) and anxiety stigma at 3-month follow-up ( P = .18 , P = .02 ) . The feedback and help-seeking list interventions did not improve depression or anxiety literacy or decrease stigmatizing attitudes to these conditions . However , the study findings should be treated with caution . Due to recruitment challenges , the achieved sample size fell significantly short of the target size and the study was underpowered . Accordingly , the results should be considered as providing preliminary pilot data only . Conclusions This is the first RCT of an Internet-based mental health help-seeking intervention for young elite athletes . The results suggest that brief mental health literacy and destigmatization improves knowledge and may decrease stigma but does not increase help-seeking . However , since the trial was underpowered , a larger trial is warranted . Trial Registration 2009/373 ( www . clinical trials.gov ID : NCT00940732 ) , cited at http://www.webcitation.org/5ymsRLy9r", "Stigmatizing , or discriminatory , perspectives and behaviour , which target individuals on the basis of their mental health , are observed in even the youngest school children . We conducted a systematic review of the published and unpublished , scientific literature concerning the benefits and harms of school-based interventions , which were directed at students 18 years of age or younger to prevent or eliminate such stigmatization . Forty relevant studies were identified , yet only a qualitative synthesis was deemed appropriate . Five limitations within the evidence base constituted barriers to drawing conclusive inferences about the effectiveness and harms of school-based interventions : poor reporting quality , a dearth of r and omized controlled trial evidence , poor methods quality for all research design s , considerable clinical heterogeneity , and inconsistent or null results . Nevertheless , certain suggestive evidence derived both from within and beyond our evidence base has allowed us to recommend the development , implementation and evaluation of a curriculum , which fosters the development of empathy and , in turn , an orientation toward social inclusion and inclusiveness . These effects may be achieved largely by bringing especially but not exclusively the youngest children into direct , structured contact with an infant , and likely only the oldest children and youth into direct contact with individuals experiencing mental health difficulties . The possible value of using educational activities , material s and contents to enhance hypothesized benefits accruing to direct contact also requires investigation . Overall , the curriculum might serve as primary prevention for some students and as secondary prevention for others", "OBJECTIVES The authors used nationwide survey data to characterize current public conceptions related to recognition of mental illness and perceived causes , dangerousness , and desired social distance . METHODS Data were derived from a vignette experiment included in the 1996 General Social Survey . Respondents ( n = 1444 ) were r and omly assigned to 1 of 5 vignette conditions . Four vignettes described psychiatric disorders meeting diagnostic criteria , and the fifth depicted a \" troubled person \" with sub clinical problems and worries . RESULTS Results indicate that the majority of the public identifies schizophrenia ( 88 % ) and major depression ( 69 % ) as mental illnesses and that most report multicausal explanations combining stressful circumstances with biologic and genetic factors . Results also show , however , that smaller proportions associate alcohol ( 49 % ) or drug ( 44 % ) abuse with mental illness and that symptoms of mental illness remain strongly connected with public fears about potential violence and with a desire for limited social interaction . CONCLUSIONS While there is reason for optimism in the public 's recognition of mental illness and causal attributions , a strong stereotype of dangerousness and desire for social distance persist . These latter conceptions are likely to negatively affect people with mental illness", "BACKGROUND Direct social contact interventions are known to reduce mental health stigma . Filmed social contact may be equally effective and have practical and cost advantages . AIMS To compare the effectiveness of a DVD , a live intervention and a lecture control , in reducing stigma , testing the hypotheses that : ( a ) DVD and live interventions will be equally effective ; and ( b ) the interventions with social contact ( DVD/live ) will be more effective than the lecture . Cost-effectiveness , process and acceptability are also assessed . METHOD Student nurses were r and omised to : ( a ) watch a DVD of service users/informal carers talking about their experiences , ( b ) watch a similar live presentation , or ( c ) attend a lecture . Primary outcomes were changes in attitudes ( using the Mental Illness : Clinicians Attitudes Scale , MICA ) , emotional reactions ( using the Emotional Reactions to Mental Illness Scale , ERMIS ) , intended proximity ( using the Reported and Intended Behaviour Scale , RIBS ) , and knowledge ( using the Social Contact Intended Learning Outcomes , SCILO ) , immediately after the intervention and at 4-month follow-up . RESULTS For the 216 participants , there were no differences between the DVD and live groups on MICA , ERMIS or RIBS scores . The DVD group had higher SCILO ( knowledge ) scores . The combined social contact group ( DVD/live ) had better MICA and RIBS scores than the lecture group , the latter difference maintained at 4 months . The DVD was the most cost-effective of the interventions , and the live session the most popular . CONCLUSIONS Our hypotheses were confirmed . This study supports the wider use of filmed social contact interventions to reduce stigma about mental illness", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Systematic review s provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies . The methods of systematic review of individual patient r and omised trials of healthcare interventions are well developed . We discuss method ological and practice issues that need to be considered when undertaking systematic review s of quality improvement strategies including developing a review protocol , identifying and screening evidence sources , quality assessment and data abstract ion , analytical methods , reporting systematic review s , and appraising systematic review s. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care ( EPOC ) review group", "Background Mental disorders often have their first onset during adolescence . For this reason , high school teachers are in a good position to provide initial assistance to students who are developing mental health problems . To improve the skills of teachers in this area , a Mental Health First Aid training course was modified to be suitable for high school teachers and evaluated in a cluster r and omized trial . Methods The trial was carried out with teachers in South Australian high schools . Teachers at 7 schools received training and those at another 7 were wait-listed for future training . The effects of the training on teachers were evaluated using question naires pre- and post-training and at 6 months follow-up . The question naires assessed mental health knowledge , stigmatizing attitudes , confidence in providing help to others , help actually provided , school policy and procedures , and teacher mental health . The indirect effects on students were evaluated using question naires at pre-training and at follow-up which assessed any mental health help and information received from school staff , and also the mental health of the student . Results The training increased teachers ' knowledge , changed beliefs about treatment to be more like those of mental health professionals , reduced some aspects of stigma , and increased confidence in providing help to students and colleagues . There was an indirect effect on students , who reported receiving more mental health information from school staff . Most of the changes found were sustained 6 months after training . However , no effects were found on teachers ' individual support towards students with mental health problems or on student mental health . Conclusions Mental Health First Aid training has positive effects on teachers ' mental health knowledge , attitudes , confidence and some aspects of their behaviour . Trial registration", "The purpose of this school-based cluster-r and omized trial was to determine the initial acceptability , feasibility , and efficacy of an existing community-based intervention , In Our Own Voice , in a sample of US adolescent girls aged 13 - 17 years ( n = 156 ) . In Our Own Voice is a knowledge-contact intervention that provides knowledge about mental illness to improve mental health literacy and facilitates intergroup contact with persons with mental illness as a means to reduce mental illness stigma . This longitudinal study was set in two public high schools located in a southern urban community of the U.S. Outcomes included measures of mental illness stigma and mental health literacy . Findings support the acceptability and feasibility of the intervention for adolescents who enrolled in the study . Findings to support the efficacy of In Our Own Voice to reduce stigma and improve mental health literacy are mixed . The intervention did not reduce mental illness stigma or improve mental health literacy at one week follow up . The intervention did not reduce mental illness stigma at 4 and 8 weeks follow up . The intervention did improve mental health literacy at 4 and 8 weeks follow up . Previous studies have assessed the preliminary efficacy In Our Own Voice among young adults ; rarely has In Our Own Voice been investigated longitudinally and with adolescents in the United States . This study provides initial data on the effects of In Our Own Voice for this population and can be used to further adapt the intervention for adolescents", "BACKGROUND A school mental-health programme has been developed as a component of the community mental-health programme in Rawalpindi , Pakistan . It has the objective of improving the underst and ing of disorders of mental health in the rural community . We aim ed to assess the impact of a school mental-health programme on the awareness of schoolchildren , their parents , friends who were not attending school , and neighbours . METHODS We chose two secondary schools for boys and two for girls that were similar in terms of size , staff-pupil ratio , and drop-out rates . 100 children aged 12 - 16 years ( 25 girls and 25 boys in each of the study and control groups ) , 100 parents ( one for each child ) , 100 friends who did not attend school ( one for each child ) , and 100 neighbours ( one for each child ) were given a 19-item question naire before and after the study group had had a 4-month programme of mental-health education . The maximum score for the question naire was 16 points . FINDINGS Before the school mental-health programme the awareness of mental-health issues was poor ( mean score 5.7 - 7.6 ) in the four groups of participants . In the study group there was a significant improvement in the mean scores after the school programme in the schoolchildren ( mean improvement 7.6 [ 95 % CI 6.7 - 8.5 ] , p<0.01 ) , their parents ( 5.3 [ 4.5 - 6.1 ] , p<0.01 ) , friends ( 5.1 [ 4.1 - 6.1 ] , p<0.01 ) , and neighbours ( 3.4 [ 2.6 - 4.2 ] , p<0.01 ) . In the control group the difference in awareness was significant only in schoolchildren ( 1.5 [ 0.5 - 2.3 ] , p=0.01 ) and their friends ( 0.8 [ 0.3 - 1.3 ] , p<0.01 ) . INTERPRETATION The school programme succeeded in improving awareness of mental health in schoolchildren and the community . The schoolchildren were receptive to the programme , and shared their new underst and ing with family , friends , and neighbours . Mental-health planners who wish to improve community awareness of mental health , particularly in areas with low literacy rates , should consider setting up school mental-health programmes", "This study evaluated the effectiveness of a cognitive behaviour therapy Internet program ( MoodGYM ) for depressive symptoms , attributional style , self‐esteem and beliefs about depression , and on depression and depression‐vulnerable status in male youth . A total of 78 boys age 15 and 16 years were allocated to either undertake MoodGYM or to st and ard personal development activities . Outcomes were measured before commencement , post‐program and 16 weeks post‐program . There were no significant between‐group differences in change scores pre‐ to post‐ or pre‐ to follow‐up using the intention to treat sample or for participants with post‐ and /or follow‐up data . For boys completing 3 or more modules there were small relative benefits of MoodGYM for depressive symptoms ( Effect Size , ES = 0.34 ) , attributional style ( ES = 0.17 ) and self‐esteem ( ES = 0.16 ) at post‐program , although only the effect for self‐esteem was sustained at follow‐up . Both groups showed improvement in their beliefs about depression at follow‐up , with the control group showing a moderate relative benefit ( ES = 0.40 ) . While the numbers are small , there was a reduction in the risk of being depressed in the MoodGYM group of 9 % at post‐treatment compared with a slightly increased risk for the control group . The risk of being classified as vulnerable to depression reduced by 17 % in the MoodGYM group at post‐treatment compared with no change in risk for the control group . These reductions in risk for the MoodGYM group were not sustained at follow‐up . The limitations of the study highlight several important challenges for MoodGYM and other self‐directed Internet cognitive behaviour therapy programs . These include how to ensure enough of the program is received and that people who could potentially benefit access the program and continue to remain engaged with it , and how to enhance the sustainability of any benefits", "Background In recent years there has been increased interest in the role played by families in the treatment of patients with schizophrenia . Some family interventions may significantly reduce clinical difficulties and may have a positive impact , both emotionally and economically . The aim of this study is to assess the efficacy of a family psychoeducational program in changing attitude and health perceptions in relatives of patients with schizophrenia . Methods Sample : 45 relatives , key caregivers of patients with schizophrenia seen at a public mental health outpatient centre in Arica (Chile).InstrumentsAttitudes of Relatives toward Schizophrenia Question naire and General Health Question naire SF-36.ProcedureThe sample was r and omly divided into a control group , in which caregivers received the usual treatment ( a monthly interview with a psychiatric nurse ) , and an experimental group , which participated in a family psychoeducational intervention program in addition to the usual treatment . Medication of patients remained unchanged in both groups . Results The psychoeducational program was effective in modifying caregivers ’ attitudes . However , it had no effect on their health perceptions . Conclusions This family psychoeducational treatment program modifies the negative attitudes of relatives towards schizophrenia . However , programs of this kind may not improve health problems ; alternatively , their effects may only be seen in the long term", "BACKGROUND This study evaluates the benefits of a self-directed Internet intervention for depression ( MoodGYM ) delivered as a part of the high school curriculum . METHOD One hundred and fifty-seven girls , aged 15 and 16 years , were allocated to undertake either MoodGYM or their usual curriculum . MoodGYM 's impact on depressive symptoms , risk of depression , attributional style , depression literacy and attitudes toward depression was examined using r and om effect regression . RESULTS MoodGYM produced a significantly faster rate of decline in depressive symptoms over the trial period than the control condition . The effect size for MoodGYM was not significant immediately after the intervention ( Cohen 's d=.19 , 95 % CI -.18-.56 ) but was moderate and significant 20 weeks after the intervention ( d=.46 , 95 % CI .10-.82 ) . Girls with high depression scores before intervention showed the strongest benefits on self-reported depression at follow-up ( d=.92 , 95 % CI .10 - 1.38 ) . There were no significant intervention effects on depression status , attributional style , depression literacy , and attitudes . Approximately 70 % of girls in the MoodGYM group completed less than three of its modules and completion of fewer modules was related to high depression score before intervention . CONCLUSIONS The findings suggest that there are benefits from MoodGYM on self-reported depressive symptoms but has low rates of completion highlight problems in ensuring adherence to Internet programs for depression", "OBJECTIVE To test the efficacy of telephone-administered motivational interviewing ( MI ) to enhance treatment engagement in Iraq and Afghanistan veterans with mental health ( MH ) problems . METHOD Between April 23 , 2008 , and February 25 , 2011 , 73 Iraq and Afghanistan veterans who screened positive for ≥1 MH problem(s ) on telephone-administered psychometric assessment , but were not engaged in treatment , were r and omized to either personalized referral for MH services and four sessions of telephone MI or st and ard referral and four neutral telephone check-in sessions ( control ) at baseline , 2 , 4 and 8 weeks . Blinded assessment occurred at 8 and 16 weeks . RESULTS In intent-to-treat analyses , 62 % assigned to telephone MI engaged in MH treatment compared to 26 % of controls [ relative risk (RR)=2.41 , 95 % confidence interval (CI)=1.33 - 4.37 , P=.004 ] , which represented a large effect size ( Cohen 's h=0.74 ) . Participants in the MI group also demonstrated significantly greater retention in MH treatment than controls [ MI mean visits (S.D.)=1.68 ( 2.73 ) and control mean visits (S.D.)=0.38 ( 0.81 ) , incidence rate ratio (IRR)=4.36 , 95 % CI=1.96 - 9.68 , P<.001 ] , as well as significant reductions in stigma and marijuana use at 8 weeks ( P<.05 ) . CONCLUSIONS Telephone MI enhances MH treatment engagement in Iraq and Afghanistan veterans with MH problems", "Licensed care staff working in long-term care facilities may be poorly prepared to work with residents with mental illness . This research reports on the program evaluation of Caring Skills : Working with Mental Illness , a training program delivered on the Internet . It was tested with a r and omized treatment-control design , with an eight-week follow-up . The training provided video-based behavioral skills and knowledge training . Measures included video situations testing and assessment of psycho-social constructs including empathy and stigmatization . ANCOVA analysis at 4-weeks posttest showed significant positive effects with medium-large effect sizes , which were largely maintained at the 8-week follow-up . The training was well-received by the users", "Trauma risk management ( TRiM ) is an intensive posttraumatic stress disorder ( PTSD ) psychoeducational management strategy based on peer-group risk assessment developed by the UK Royal Navy ( RN ) . TRiM seeks to modify attitudes about PTSD , stress , and help-seeking and trains military personnel to identify at-risk individuals and refer them for early intervention . This quasiexperimental study found that TRiM training significantly improved attitudes about PTSD , stress , and help-seeking from TRiM-trained personnel . There was a nonsignificant effect on attitudes to seeking help from normal military support networks and on general health . Within both the military and civilian population s , stigma is a serious issue preventing help-seeking and reducing quality of life . The results suggest that TRiM is a promising antistigma program within organizational setting", "OBJECTIVE This study was design ed to investigate the efficacy of a web-based mental disorder stigma education program for mental health professionals . METHODS The sample consisted of 205 individuals who were either residents or specialists in psychiatry . Participants were contacted through a national web-based e-mail group that consisted of professionals in psychiatry , who were r and omly assigned to experimental and control groups . The experimental group received an informative e-mail which contained a general account of \" stigma \" before they were asked to respond to an Internet-based question naire which was design ed to predict their stigmatizing attitudes towards individuals with mental disorders . Control subjects , on the other h and , were asked to respond to the same Internet-based question naire without having been given the aforementioned informative e-mail . RESULTS The experimental group , compared to the control group , demonstrated a lesser stigmatizing attitude towards individuals with mental illness , as measured by the Internet-based survey which utilized the \" social distance \" concepts of stigma . CONCLUSIONS These data suggest that such \" anti-stigma \" campaigns using the potential of the Internet might be an effective tool in the fight against the stigmatization of persons with mental illness", "Nurses ' attitudes toward service users who repeatedly self-harm can be negative and may interfere with the user 's willingness to engage with services . The effectiveness of an educational intervention aim ed at improving nurses ' attitudes in this area was tested in this study . The intervention consisted of attendance on an accredited course on self-harm over a period of 15 weeks and the outcome of interest was attitudes as measured by the Self Harm Antipathy Scale . When deployed in a before- and -after design with two non-r and omly allocated groups , there was evidence of a 20 % reduction in antipathy toward self-harm among course attenders maintained over a period of at least 18 months ( compared with a 9 % reduction in a comparison group ) . Three of the six Self Harm Antipathy Scale attitude dimensions showed significant short-term change with some further long-term effects . This is preliminary evidence for the effectiveness of the chosen intervention in reducing overall antipathy toward self-harm clients and enhancing a sense of competence , a valuing of the care process and an awareness of the factors contributing to self-harm", "Research evidence suggests that individuals with schizophrenia are prone to self-stigmatization , which reduces their psychosocial treatment adherence . A self-stigma reduction program was developed based on a theoretical framework proposed by our team . The effectiveness of such program to reduce self-stigma , enhance readiness for change , and promote adherent behaviors among individuals with schizophrenia was investigated . This program consisted of 12 group and four individual follow-up sessions . An integrative approach including psychoeductaion , cognitive behavioral therapy , motivational interviewing , social skills training , and goal attainment program was adopted . Sixty-six self-stigmatized individuals with schizophrenia were recruited . They were r and omly allocated to the self-stigma reduction program ( N=34 ; experimental protocol ) or the newspaper reading group ( N=32 ; comparison protocol ) . Measures on participants ' level of self-stigma , readiness for change , insight , general self-efficacy , and treatment adherence were taken for six assessment intervals . The findings suggested that the self-stigma reduction program has potential to reduce self-esteem decrement , promote readiness for changing own problematic behaviors , and enhance psychosocial treatment adherence among the self-stigmatized individuals with schizophrenia during the active interventional stage . However , there was a lack of therapeutic maintenance effects during the 6-month follow-up period . Recommendations for further improving the effectiveness of self-stigma reduction program are suggested", "Objective : Mental Health First Aid training is a course for the public that teaches how to give initial help to a person developing a mental health problem or in a mental health crisis . The present study evaluated the effects of Mental Health First Aid training delivered by e-learning on knowledge about mental disorders , stigmatizing attitudes and helping behaviour . Method : A r and omized controlled trial was carried out with 262 members of the Australian public . Participants were r and omly assigned to complete an e-learning CD , read a Mental Health First Aid manual or be in a waiting list control group . The effects of the interventions were evaluated using online question naires pre- and post-training and at 6-months follow up . The question naires covered mental health knowledge , stigmatizing attitudes , confidence in providing help to others , actions taken to implement mental health first aid and participant mental health . Results : Both e-learning and the printed manual increased aspects of knowledge , reduced stigma and increased confidence compared to waiting list . E-learning also improved first aid actions taken more than waiting list , and was superior to the printed manual in reducing stigma and disability due to mental ill health . Conclusions : Mental Health First Aid information received by either e-learning or printed manual had positive effects , but e-learning was better at reducing stigma" ]

[ "12608943", "15886235", "15739035", "10457270" ]

[ "Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes", "Vitamin D receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density.", "BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial", "FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women." ]

[ "objective To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor ( VDR ) genotypes", "CONTEXT Osteoporosis is a systemic disease with a strong genetic component . Vitamin D receptor ( VDR ) gene polymorphisms explain only a small part of the genetic influence on the level of bone mineral density ( BMD ) , whereas their effect on fracture remains uncertain . OBJECTIVE The objective of this study was to investigate the relationships between VDR genotypes and fracture risk . DESIGN A prospect i ve population -based cohort was studied . SUBJECTS A total of 589 postmenopausal women ( mean age , 62 yr ) were followed prospect ively during a median ( interquartile ) of 11 ( 1.1 ) yr . MAIN OUTCOME MEASURE The study measured incidents of vertebral and nonvertebral fractures . RESULTS VDR allele B was significantly and dose dependently overrepresented in women who fractured , including 34 and 86 women with first incident vertebral and nonvertebral fragility fractures , respectively . This corresponded to an odds ratio of 1.5 ( 95 % confidence interval , 0.95 - 2.40 ) for heterozygous carriers ( bB , n = 286 ) and 2.10 ( 95 % confidence interval , 1.16 - 3.79 ) for homozygous carriers ( BB , n = 90 ) of the B allele , compared with women with the bb genotype ( n = 213 ) . VDR genotype groups did not differ for demographics , physical activity , grip strength , personal and maternal history of fracture , and calcium intake . The association was independent of BMD of the spine , hip , and radius , and of the BMD loss at the radius . The relationship between VDR polymorphisms and fracture risk was not altered after adjustment for baseline circulating levels of bone turnover markers , estradiol , dehydroepi and rosterone sulfate , SHBG , IGF-I , intact PTH , and 25 hydroxyvitamin D. CONCLUSION VDR genotypes are associated with the risk of fracture in postmenopausal women independently of BMD , rate of postmenopausal forearm BMD loss , bone turnover , and endogenous hormones . The mechanisms by which VDR genotypes influence bone strength remain to be determined", "Vitamin D receptor ( VDR ) gene polymorphisms could be considered one of the factors influencing the efficacy of the anti-osteoporotic treatments . In this multicenter , prospect i ve , r and omized and controlled trial we evaluated whether BsmI vitamin D receptor ( VDR ) genotypes influence the efficacy of antiresorptive treatment regimes ( administered alone or in combination ) in postmenopausal osteoporotic women . Using restriction endonuclease , we identified the BsmI VDR polymorphism in 1,100 postmenopausal women with osteoporosis . The women were r and omized , taking account of genotype , into five treatment groups : ( 1 ) alendronate ( Aln , 10 mg/day ) plus raloxifene ( Rlx , 60 mg/day ) ; ( 2 ) Aln plus hormone replacement therapy ( HRT , 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate ) ; ( 3 ) Aln alone ; ( 4 ) HRT alone ; and ( 5 ) Rlx alone . Lumbar-spine bone mineral density ( BMD ) and bone turnover markers were measured at study entry and after 1 year of treatment . Using the general linear model ( GLM ) repeated- measures procedure , the means of BMD and bone turnover markers significantly differed from baseline after a period of treatment . In particular , the mean change from baseline for BMD was −0.034 ( 95 % confidence interval [ CI ] : −0.037 to −0.031 , P < 0.001 ) ; for serum osteocalcin ( OC ) it was 1.369 ( 95 % CI : 1.289 to 1.448 , P < 0.001 ) ; and for urinary deoxypyridinoline ( DPD ) it was 1.322 ( 95 % CI : 1.242 to 1.401 , P < 0.001 ) , indicating a considerable variation before and after treatment of these indicators . In all three cases these effects appeared significantly influenced by treatments , genotypes , and the treatments*genotypes interaction term ( P < 0.001 each , except for the BMD and genotype effect with P = 0.02 ) , and not by the investigational centers involved in the study . In conclusion , in postmenopausal osteoporotic women , BsmI VDR genotypes influence the efficacy of antiresorptive drugs particularly when used in combination", "A novel T/C polymorphism ( ATG to ACG ) at the translation initiation site of the vitamin D receptor ( VDR ) gene , defined by FokI restriction endonuclease , has been recently associated with variation in bone mineral density ( BMD ) and rates of bone loss in a group of postmenopausal Mexican-American women . The presence of the restriction site , design ated as f , allows protein translation to initiate from the first ATG , while the allele lacking the site , indicated as F , initiates translation at a second ATG . In this study , we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic ( n = 164 ) , osteopenic ( n = 117 ) , and normal ( n = 119 ) groups . There were 159 ( 41 % ) FF homozygotes , 55 ( 14 % ) ff homozygotes , and 186 ( 45 % ) Ff heterozygotes . In the whole population , we observed a weak association between FokI polymorphism and lumbar BMD ( p = 0.06 , analysis of covariance [ ANCOVA ] ) but not with femoral neck BMD ( p = 0.5 , ANCOVA ) . Interestingly , the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause ( p = 0.04 , ANCOVA ) , progressively declining afterward . In addition , a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed ( p = 0.04 , Chi-square test ) . Finally , ff genotype result ed significantly over-represented in the group of women with a vertebral fracture as compared with controls ( p = 0.003 , Chi-square test ) , equivalent to a relative risk of 2.58 ( 95 % confidence intervals 1.36 - 4.91 ) . We conclude that in this population , FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine" ]

[ "10023893", "2677107", "23117349", "3196245", "3766233", "16137297", "19651265", "14559955" ]

[ "Prevention of falls in the elderly trial (PROFET): a randomised controlled trial", "Incidence and Prediction of Falls in Dementia: A Prospective Study in Older People", "Feasibility, safety and preliminary evidence of the effectiveness of a home-based exercise programme for older people with Alzheimer’s disease: a pilot randomized controlled trial", "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", "A feasibility study and pilot randomised trial of a tailored prevention program to reduce falls in older people with mild dementia", "Development of a common outcome data set for fall injury prevention trials: the Prevention of Falls Network Europe consensus.", "Reducing risk of falling in older people discharged from hospital: a randomized controlled trial comparing seated exercises, weight-bearing exercises, and social visits.", "Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial." ]

[ "BACKGROUND Falls in elderly people are a common presenting complaint to accident and emergency departments . Current practice commonly focuses on the injury , with little systematic assessment of the underlying cause , functional consequences , and possibilities for future prevention . We undertook a r and omised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls . METHODS Eligible patients were aged 65 years and older , lived in the community , and presented to an accident and emergency department with a fall . Patients assigned to the intervention group ( n=184 ) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated ; those assigned to the control group ( n=213 ) received usual care only . The analyses were by intention to treat . Follow-up data were collected every 4 months for 1 year . FINDINGS At 12-month follow-up , 77 % of both groups remained in the study . The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group ( p=0.0002 ) . The risk of falling was significantly reduced in the intervention group ( odds ratio 0.39 [ 95 % CI 0.23 - 0.66 ] ) as was the risk of recurrent falls ( 0.33 [ 0.16 - 0.68 ] ) . In addition , the odds of admission to hospital were lower in the intervention group ( 0.61 [ 0.35 - 1.05 ] ) whereas the decline in Barthel score with time was greater in the control group ( p<0.00001 ) . INTERPRETATION The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment", "Background Falls are a major cause of morbidity and mortality in dementia , but there have been no prospect i ve studies of risk factors for falling specific to this patient population , and no successful falls intervention/prevention trials . This prospect i ve study aim ed to identify modifiable risk factors for falling in older people with mild to moderate dementia . Methods and Findings 179 participants aged over 65 years were recruited from outpatient clinics in the UK ( 38 Alzheimer 's disease ( AD ) , 32 Vascular dementia ( VAD ) , 30 Dementia with Lewy bodies ( DLB ) , 40 Parkinson 's disease with dementia ( PDD ) , 39 healthy controls ) . A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospect ively for 12 months . Dementia participants experienced nearly 8 times more incident falls ( 9118/1000 person-years ) than controls ( 1023/1000 person-years ; incidence density ratio : 7.58 , 3.11–18.5 ) . In dementia , significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder ( proportional hazard ratio ( HR ) adjusted for age and sex : 3.33 , 2.11–5.26 ) , and history of falls in the preceding 12 months ( HR : 2.52 , 1.52–4.17 ) . In multivariate analyses , significant potentially modifiable predictors were symptomatic orthostatic hypotension ( HR : 2.13 , 1.19–3.80 ) , autonomic symptom score ( HR per point 0–36 : 1.055 , 1.012–1.099 ) , and Cornell depression score ( HR per point 0–40 : 1.053 , 1.01–1.099 ) . Higher levels of physical activity were protective ( HR per point 0–9 : 0.827 , 0.716–0.956 ) . Conclusions The management of symptomatic orthostatic hypotension , autonomic symptoms and depression , and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia . R and omised controlled trials to assess such a strategy are a priority", "Objective : To evaluate the feasibility and safety of a home-based exercise programme for people with Alzheimer ’s disease , and to provide preliminary evidence of programme effectiveness in improving balance and mobility and reducing falls risk . Design : A r and omized controlled trial . Setting : Community . Participants : Forty people with mild to moderate Alzheimer ’s disease ( mean age 81.9 , SD 5.72 ; 62.5 % female ) . Interventions : Participants were r and omized to a six-month home-based individually tailored balance , strengthening and walking exercise programme ( physiotherapist ) or a six-month home-based education programme ( control ) ( occupational therapist ) . Both programmes provided six home-visits and five follow-up phone calls . Main measures : Balance , mobility , falls and falls risk were measured at baseline and programme completion . Intention-to-treat analysis using a generalized linear model with group allocation as a predictor variable was performed to evaluate programme effectiveness . Feasibility and adverse events were systematic ally recorded at each contact . Results : Fifty-eight per cent of the exercise group finished the programme , completing an average of 83 % of prescribed sessions , with no adverse events reported . Functional Reach improved significantly ( P = 0.002 ) in the exercise group ( mean ( SD ) , 2.28 ( 4.36 ) ) compared to the control group ( –2.99 ( 4.87 ) ) . Significant improvement was also observed for the Falls Risk for Older People – Community score ( P = 0.008 ) and trends for improvement on several other balance , mobility , falls and falls risk measures for the exercise group compared to the control group . Conclusions : The exercise programme was feasible and safe and may help improve balance and mobility performance and reduce falls risk in people with Alzheimer ’s disease", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Background People with dementia have a disproportionately high rate of falls and fractures and poorer outcomes , yet there is currently no evidence to guide falls prevention in this population . Methods A r and omised trial design was used to test feasibility of study components and acceptability of a home hazard reduction and balance and strength exercise fall prevention program . The program was tailored to participant ’s individual cognitive levels and implemented as a carer-supported intervention . Feasibility of recruitment , retention and implementation of intervention were recorded through observation and documented in field notes . Adherence , carer burden and use of task simplification strategies were also monitored . Outcome measures , collected at 12 weeks included physiological , fear of falling , cognitive and functional measures . Results Recruitment was achievable but may be more challenging in a multisite trial . Twenty two dyads of persons with mild dementia and their carers were r and omised to intervention or usual care control group . Of 38 dyads referred to the study , there was a high rate of willingness to participate , with 6 ( 16 % ) declining and 10 ( 26 % ) not meeting inclusion criteria . The intervention was well received by participants and carers and adherence to both program components was very good . All participants implemented some home safety recommendations ( range 19 - 80 % ) with half implementing 50 % or more . At the end of 12 weeks , 72 % of the intervention group were exercising . Both the rate of falling and the risk of a fall were lower in the intervention group but these findings were not significant ( RR= 0.50 ( 95 % CI 0.11 - 2.19 ) . There were no differences in physiological outcome measures between the control and intervention groups . However results were influenced by the small study size and incomplete data primarily in the intervention group at follow up . Conclusions The pilot study was feasible and acceptable to people with mild dementia and their carers . The lessons learnt included : recruitment for a larger trial will require multiple approaches ; home safety recommendations should provide a greater emphasis on environmental use compared with behavioural change ; strategies to ensure an adequate dosage of exercise should be further explored . We recommend that intervention delivery incorporate an integrated occupational therapy and physiotherapy approach and that carers be provided with an individualised session to enhance dementia-specific skills in management and communication . A refined intervention should be tested in a r and omised trial with an adequately powered sample size . Trial registration Australia and New Zeal and Clinical Trials Registry", "The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered", "OBJECTIVE To compare the efficacy of seated exercises and weight-bearing ( WB ) exercises with social visits on fall risk factors in older people recently discharged from hospital . DESIGN Twelve-week r and omized , controlled trial . SETTING Home-based exercises . PARTICIPANTS Subjects ( N=180 ) aged 65 and older , recently discharged from hospital . INTERVENTIONS Seated exercises ( n=60 ) , WB exercises ( n=60 ) , and social visits ( n=60 ) . MAIN OUTCOME MEASURES Primary outcome factors were Physiological Profile Assessment ( PPA ) fall risk score , and balance while st and ing ( Coordinated Stability and Maximal Balance Range tests ) . Secondary outcomes included the component parts of the PPA and other physical and psychosocial measures . RESULTS Subjects were tested at baseline and at completion of the intervention period . After 12 weeks of interventions , subjects in the WB exercise group had significantly better performance than the social visit group on the following : PPA score ( P=.048 ) , Coordinated Stability ( P<.001 ) , Maximal Balance Range ( P=.019 ) ; body sway on floor with eyes closed ( P=.017 ) ; and finger-press reaction time ( P=.007 ) tests . The seated exercise group performed better than the social visit group in PPA score ( P=.019 ) but for no other outcome factor . The seated exercise group had the highest rate of musculoskeletal soreness . CONCLUSIONS In older people recently discharged from the hospital , both exercise programs reduced fall risk score in older people . The WB exercises led to additional beneficial impacts for controlled leaning , reaction time , and caused less musculoskeletal soreness than the seated exercises", "CONTEXT Exercise training for patients with Alzheimer disease combined with teaching caregivers how to manage behavioral problems may help decrease the frailty and behavioral impairment that are often prevalent in patients with Alzheimer disease . OBJECTIVE To determine whether a home-based exercise program combined with caregiver training in behavioral management techniques would reduce functional dependence and delay institutionalization among patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 153 community-dwelling patients meeting National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer Disease and Related Disorders Association criteria for Alzheimer disease , conducted between June 1994 and April 1999 . INTERVENTIONS Patient-caregiver dyads were r and omly assigned to the combined exercise and caregiver training program , Reducing Disability in Alzheimer Disease ( RDAD ) , or to routine medical care ( RMC ) . The RDAD program was conducted in the patients ' home over 3 months . MAIN OUTCOME MEASURES Physical health and function ( 36-item Short-Form Health Survey 's [ SF-36 ] physical functioning and physical role functioning subscales and Sickness Impact Profile 's Mobility subscale ) , and affective status ( Hamilton Depression Rating Scale and Cornell Depression Scale for Depression in Dementia ) . RESULTS At 3 months , in comparison with the routine care patients , more patients in the RDAD group exercised at least 60 min/wk ( odds ratio [ OR ] , 2.82 ; 95 % confidence interval [ CI ] , 1.25 - 6.39 ; P = .01 ) and had fewer days of restricted activity ( OR , 3.10 ; 95 % CI , 1.08 - 8.95 ; P<.001 ) . Patients in the RDAD group also had improved scores for physical role functioning compared with worse scores for patients in the RMC group ( mean difference , 19.29 ; 95 % CI , 8.75 - 29.83 ; P<.001 ) . Patients in the RDAD group had improved Cornell Depression Scale for Depression in Dementia scores while the patients in the RMC group had worse scores ( mean difference , -1.03 ; 95 % CI , -0.17 to -1.91 ; P = .02 ) . At 2 years , the RDAD patients continued to have better physical role functioning scores than the RMC patients ( mean difference , 10.89 ; 95 % CI , 3.62 - 18.16 ; P = .003 ) and showed a trend ( 19 % vs 50 % ) for less institutionalization due to behavioral disturbance . For patients with higher depression scores at baseline , those in the RDAD group improved significantly more at 3 months on the Hamilton Depression Rating Scale ( mean difference , 2.21 ; 95 % CI , 0.22 - 4.20 ; P = .04 ) and maintained that improvement at 24 months ( mean difference , 2.14 ; 95 % CI , 0.14 - 4.17 ; P = .04 ) . CONCLUSION Exercise training combined with teaching caregivers behavioral management techniques improved physical health and depression in patients with Alzheimer disease" ]

[ "7963304", "1430964", "11828556", "10884075", "3885685", "9330145", "12002496", "2022828", "9111400", "7553006", "15249101", "8169480", "12954255", "15010154", "15142699", "9222908", "12107308", "8408148", "8543875", "15620502", "12954254", "3276422", "12809659", "12772108", "8732400", "11861728", "15720906" ]

[ "Outcome following epineurotomy in carpal tunnel syndrome: a prospective, randomized clinical trial.", "Endoscopic release of the carpal tunnel: a randomized prospective multicenter study.", "Carpal tunnel release by limited palmar incision vs traditional open technique: randomized controlled trial.", "Early Recovery After Endoscopic vs. Short‐Incision Open Carpal Tunnel Release", "Internal neurolysis or ligament division only in carpal tunnel syndrome—Results of a randomized study", "Ultrasonographically assisted carpal tunnel release.", "Endoscopic versus open carpal tunnel release in bilateral carpal tunnel syndrome. A prospective, randomised, blinded assessment.", "Internal neurolysis fails to improve the results of primary carpal tunnel decompression.", "The Role of Epineurotomy in the Operative Treatment of Carpal Tunnel Syndrome*", "The value of one-portal endoscopic carpal tunnel release: A prospective randomized study", "The quality of reporting and outcome measures in randomized clinical trials related to upper-extremity disorders.", "Endoscopic Carpal Tunnel Decompression", "Neurophysiological Recovery After Open Carpal Tunnel Decompression: Comparison of Simple Decompression and Decompression with Epineurotomy", "A Randomized Controlled Trial of Knifelight and Open Carpal Tunnel Release", "Carpal Tunnel Decompression. Is Lengthening of the Flexor Retinaculum Better than Simple Division?", "Local Symptoms After open Carpal Tunnel Release", "Single-Portal Endoscopic Carpal Tunnel Release Compared with Open Release: A Prospective, Randomized Trial", "Carpal tunnel release. A prospective, randomized assessment of open and endoscopic methods.", "Early Results of Conventional Versus Two-Portal Endoscopic Carpal Tunnel Release", "Prospective Randomized Trial Comparing Absorbable and Non-Absorbable Sutures in Open Carpal Tunnel Release", "Early Outcome and Cost-Effectiveness of Endoscopic Versus Open Carpal Tunnel Release: A Randomized Prospective Trial", "Interfascicular neurolysis in the severe carpal tunnel syndrome. A prospective, randomized, double-blind, controlled study.", "Evaluation of Carpal Tunnel Release Using the Knifelight® Instrument", "Endoscopic versus open carpal tunnel release: a randomized trial.", "A Prospective, Randomized Study with an Independent Observer Comparing Open Carpal Tunnel Release with Endoscopic Carpal Tunnel Release", "The Role of Flexor Tenosynovectomy in the Operative Treatment of Carpal Tunnel Syndrome", "Carpal tunnel syndrome, the search for a cost-effective surgical intervention: a randomised controlled trial." ]

[ "To assess the efficacy of an adjunctive epineurotomy in carpal tunnel syndrome , 36 wrists in 33 patients were prospect ively r and omized into epineurotomy and non-epineurotomy treatment groups . The operating surgeons and evaluating therapist were double-blinded . Patients were evaluated preoperatively and at either 6 or 12 months postoperatively , with 15 patients examined at both postoperative time points . Evaluation consisted of five sensory and four motor tests : static and moving two-point discrimination , Semmes-Weinstein monofilament testing , vibratory ( 30 and 256 cps ) sensibility , and dynamometer testing of grip strength and lateral , three-jaw , and tip pinch strengths . Sensory testing showed overall improvement within both groups postoperatively , but there was no difference between the two groups at either 6 or 12 months postoperatively . Motor testing revealed no improvement in the grip strength or lateral , three-jaw , or tip pinch of either group at 12 months when compared to preoperative levels . Twenty-four of 26 epineurotomy patients and all 10 control patients were satisfied with their clinical outcome 30 months after surgery . The addition of an adjunctive epineurotomy , although safe , offered no clinical benefit in the surgical treatment of carpal tunnel syndrome in this series", "A 10-center r and omized prospect i ve multicenter study of endoscopic release of the carpal tunnel was carried out . Surgery was performed with a new device for transecting the transverse carpal ligament while control h and s were treated with conventional open surgery . There were 122 patients in the study ; 25 had carpal tunnel surgery on both h and s and 97 had surgery on one h and . Of the surgical procedures , 65 were in the control group and 82 were in the device group . The endoscopic device was coupled to a fiberoptic light and a video camera . A trigger-activated blade was used to incise the transverse carpal ligament . After surgery , the best predictors of return to work and to activities of daily living were strength and tenderness variables . For patients in the device group with one affected h and , the median time for return to work was 21 1/2 days less than that for the control group . Two patients treated with the endoscopic device required reoperation by open surgical decompression ; only one of these had incomplete release with the device . Two patients in the device group experienced transient ulnar neurapraxia", "AIM To compare a limited palmar incision for carpal tunnel release ( CTR ) with a traditional open technique , which is still considered the gold st and ard . METHODS Seventy-two patients with a carpal tunnel syndrome were individually r and omized into the trial ( limited incision CTR ) ( n=36 ) and control group ( traditional technique CTR ) ( n=36 ) . In the trial group , skin incision parallel to the thenar crease was made up to 2.5 cm in length , under an operating microscope and endoscopic transillumination . Skin incision in the control group began at the distal border of the carpal ligament , followed the longitudinal crease of the palm , and crossed the base of the palm in a zigzag fashion . Three months after surgery , the patients were asked about symptomatic relief and intervals between the operation and return to their daily activities and work , and examined for scar tenderness and esthetic outcome . Distal motor latency , conduction velocity , scar length , scar width , and operation time were measured . RESULTS There were no differences between the two groups in symptomatic relief and electrophysiological parameters . Intervals between the operation and return to daily activities ( median 5 days , range 2 - 15 ) were shorter in the trial group than in the control group ( median 10 days , range 2 - 21 ; p<0.001 ) , as well as the intervals between the operation and return to work ( median 15 days , range 5 - 45 vs median 30 days , range 10 - 60 ; p<0.001 ) . Scar/pillar tenderness , scar length and width , esthetic outcome , and operation time were significantly better in the trial group . CONCLUSION Limited palmar incision CTR is as effective and safe as traditional CTR technique , but with better postoperative recovery and cosmetic results", "& NA ; Endoscopic carpal tunnel release has been cl aim ed to offer improvement in recovery time and postoperative discomfort over open carpal tunnel release . Short‐incision open carpal tunnel release has been cl aim ed to offer recoveries comparable with endoscopic techniques . Patients receiving carpal tunnel surgery were r and omized to short‐incision open release or single‐portal endoscopic release . Preoperative and postoperative evaluation included grip and pinch strength measurements and patient completion of a question naire regarding symptoms and function . Thirty‐six operated h and s completed evaluation , including 22 endoscopic and 14 open releases . Early grip and pinch strength after endoscopic carpal tunnel release were improved significantly over short‐incision open release ( p < 0.05 ) . Subjective evaluation indicated a trend toward improved symptoms and function with endoscopic over short‐incision open carpal tunnel release . Endoscopic carpal tunnel release provides faster recovery of strength than short‐incision open carpal tunnel release and improves early postoperative comfort and function to a small degree . Mackenzie DJ , Hainer R , Wheatley MJ . Early recovery after endoscopic vs. short‐incision open carpal tunnel release . Ann Plast Surg", "Summary In a series of patients with clinical ly and neurophysiologically well defined carpal tunnel syndrome a r and omization has been made into two groups , one for operation with internal neurolysis and a microscopical technique , and the other group for cutting of the carpal ligament ( flexor retinaculum ) alone . The two groups have been compared postoperatively regarding clinical and neurophysiological parameters . All patients improved , 89 % in both groups considered themselves totally free of symptoms at follow-up examinations but there was no significant difference in any parameter between the two groups . As a conclusion the use of internal neurolysis can not be recommended as a routine procedure in carpal tunnel syndrome", "An operative technique of carpal tunnel release using intraoperative ultrasonography is described . In this technique , \" safe line \" is defined in the transverse carpal ligament and the adjacent deep forearm fascia midway between the ulnar margin of the median nerve and the radial margin of the ulnar artery . After ultrasonographic design of a 1.0 to 1.5-cm skin incision along the safe line at the distal carpal tunnel , the distal ligament is released under direct vision . Proximal release is performed along this line under ultrasonographic monitoring using a device that consists of a basket punch and an outer metal tube . In a prospect i ve r and omized study , the outcomes were compared for carpal tunnel release using either this technique in 50 h and s of 50 patients or conventional open release in 53 h and s of 53 patients . Follow-up assessment at 3 , 6 , 13 , 26 , 52 , and 104 weeks showed no significant difference with respect to numbness and paresthesias , static two-point discrimination , findings on Semmes-Weinstein monofilament testing , findings on manual muscle testing of the abductor pollicis brevis , and electrophysiologic findings . The ultrasonographic-release group had better outcomes regarding pain , tenderness of the scar , and key-pinch strength at 3 , 6 , and 13 weeks , and grip strength at 3 and 6 weeks after surgery . The scar was more aesthetic in this group . There were no complications with either technique", "The advantages and disadvantages of endoscopic compared with open carpal tunnel release are controversial . We have performed a prospect i ve , r and omised , blinded assessment in a district general hospital in order to determine if there was any demonstrable advantage in undertaking either technique . Twenty-five patients with confirmed bilateral idiopathic carpal tunnel syndrome were r and omised to undergo endoscopic release by the single portal Agee technique to one h and and open release to the other . Independent preoperative and postoperative assessment was undertaken by a h and therapist who was blinded to the type of treatment . Follow-up was for 12 months . The operating time was two minutes shorter for the open technique ( p < 0.005 ) . At all stages of postoperative assessment , the endoscopic technique had no significant advantages in terms of return of muscle strength and assessment of h and function , grip strength , manual dexterity or sensation . In comparison with open release , single-portal endoscopic carpal tunnel release has a similar incidence of complications and a similar return of h and function , but is a slightly slower technique to undertake", "This prospect i ve , r and omized study compares two treatment methods in patients with primary carpal tunnel syndrome . Decompression of the transverse carpal ligament was done in thirty-two h and s ( thirty patients ) and decompression of the transverse carpal ligament with the addition of an internal neurolysis of the median nerve was done in thirty-one h and s ( twenty-nine patients ) . Relief of symptoms was described in eighty-eight percent of the patients with carpal ligament release and eighty-one percent of patients with carpal ligament release plus internal neurolysis . Improvement in h and sensibility testing , in thenar muscle strength , and atrophy was noted in both treatment groups with no statistical difference between groups . The addition of an internal neurolysis to division of the transverse carpal ligament does not add significant improvement in the sensory or motor outcome of patients with primary carpal tunnel syndrome", "We conducted a prospect i ve , r and omized study to evaluate the effect of epineurotomy on the outcome of operative treatment of established median-nerve compression in the carpal canal . Fifty h and s ( forty-four patients ) were r and omized into two groups : one group had a release of the transverse carpal ligament alone , and the other had a release and adjuvant epineurotomy of the median nerve . The groups were similar with regard to age , gender , duration of symptoms , and preoperative physical findings . All patients had electrophysiological evidence of sensory delays and fibrillations on preoperative testing . All of the operative procedures were performed by the same surgeon . The patients were evaluated preoperatively and at one year postoperatively . The follow-up examination revealed no detectable differences between the two groups with regard to symptoms , objective findings , or electrophysiological findings . This suggests that epineurotomy of the median nerve offers no benefit compared with sectioning of the transverse carpal ligament alone", "A r and omized prospect i ve study was carried out to compare one-portal endoscopic carpal tunnel release with an open procedure . There were 47 patients ( mean age 52.6 years ) : 25 underwent an endoscopic and 22 an open release . The aim of the study was to evaluate the risks against the benefits for pain , grip , key-pinch strength and ability to return to work . The distribution of age , occupation , sex , neurographic findings and operated h and was similar in both groups . We detected no serious nerve complications . One “ open ” patient developed a hypertrophic scar , a second “ open ” patient a disabling reflex sympathetic dystrophy , one “ endo ” patient a transient neurapraxia . The remaining patients experienced complete relief of symptoms . Improvement of grip strength is significantly better after endoscopic release ( P=0.0001 at 3 months ) . In contrast , the key-pinch showed a similar pattern of improvement in both groups . The ability to use the operated h and as effectively as the contralateral one developed after 24 days for the endoscopic group versus 42 for the open approach ( P=0.0000 ) . The carpal arch alteration was less important for the endoscopic group ( P= 0.013 ) , but without any correlation with the grip strength . Agee 's one-portal technique only allows correct placement of a knife , not an inspection of the structures being operated upon . This is a major limitation , reducing the surgeon to a technician . Further development of this procedure dem and s a device that will enable a fruitful inspection of the carpal tunnel", "PURPOSE R and omized clinical trials can provide strong evidence regarding effective treatment options . The quality of reporting and the type of outcome measures used are important when judging whether results justify change in clinical practice . The aim of this study was to assess the quality of reporting of r and omized clinical trials related to treatment of upper-extremity disorders , published in 4 h and surgical and orthopedic journals during an 11-year period , and assess the type of outcome measures used in the trials . METHODS Eligible articles were identified by review ing all abstract s published in the 4 journals from 1992 through 2002 . The quality of reporting was assessed by a modified Jadad scale that consisted of 3 items ( r and omization , blinding , and withdrawals/dropouts ) . A higher score ( 0 - 5 ) indicated higher quality . The outcome measures were classified according to the International Classification of Functioning , Disability and Health into the levels of body function and structure , activity , and participation . RESULTS Of 92 articles reporting r and omized clinical trials , 40 articles described appropriate r and omization method that implied they were truly r and omized studies , 31 articles did not describe the r and omization method , and 21 articles ( 23 % ) described inappropriate r and omization methods . Double or single blinding was reported in 33 articles . Absence or description of withdrawals/dropouts was shown in 77 articles . The median quality score calculated for all 92 articles was 2 ( range , 0 - 5 ) points . The median score for the 28 articles published 1992 through 1996 was 1 ( range , 0 - 5 ) points and for the 64 articles published from 1997 through 2002 was 3 ( range , 0 - 5 ) points . All trials used outcome measures on body function and structure level ; 41 % used measures of activity and /or participation . CONCLUSIONS There is a need to improve the quality of reporting of upper-extremity r and omized clinical trials and to increase the use of outcome measures covering different aspects of disability", "A study of endoscopic carpal tunnel release was carried out in three parts , consisting of initial cadaveric dissections , a prospect i ve pilot study of 20 patients and a prospect i ve , r and omized trial of 71 patients comparing endoscopic with open decompression . In the main trial , 25 patients with bilateral symptoms underwent simultaneous endoscopic and open release , with the remainder r and omized to one or other technique . Both techniques effectively decompressed the median nerve . A significant improvement in grip and pinch strength over 3 months was achieved in those undergoing endoscopic surgery . Average return to work was 14 days in the endoscopic series and 39 days in the open series . A complication rate of 35 % was achieved with the transbursal endoscopic technique , 3.7 % with the extrabursal endoscopic technique and 13.5 % in the open series", "Two hundred and seventy-three patients with carpal tunnel syndrome without advanced neurophysiological changes ( distal motor latency below 11 ms ) were r and omized to treatment by open carpal tunnel release with , or without , epineurotomy . Patients were examined clinical ly and by nerve conduction studies preoperatively and at 3 , 6 and 12 months postoperatively . We found no statistically significant difference between simple decompression and decompression combined with epineurotomy with regard to either the clinical or the neurophysiological outcome", "A r and omized controlled trial was done to compare the results of carpal tunnel decompression using the st and ard open approach and the Knifelight ® technique . Twenty-six patients with bilateral carpal tunnel syndrome requiring operation were selected for the study and the operative technique was r and omized for the first h and . Six weeks later , the second h and was operated upon using the alternate technique . There was little difference between the two techniques with regard to time taken to return to work , return of grip strength , symptom relief , complications , incidence of pillar pain and patient preference . However , the incidence of scar tenderness was significantly lower with the Knifelight ® technique", "This prospect i ve r and omized double-blind control trial compared lengthening and simple division of the flexor retinaculum in carpal tunnel decompression . Twenty-six patients with bilateral carpal tunnel syndrome were r and omly allocated to have the flexor retinaculum divided on one side and lengthened on the other . All 52 h and s were review ed at regular intervals up to 25 weeks . The patients , therapists and the final review er were unaware of treatment allocation . The Levine symptom and function scores were used to assess the severity of the carpal tunnel syndrome and showed that the two treatments were comparable for relief of carpal tunnel symptoms . The two treatments were also similar for function measured with the Jebsen – Taylor test . There is no identifiable benefit in lengthening the flexor retinaculum when decompressing the carpal tunnel . Moderate or severe pillar and scar pain is common , occurring in 13 of 52 h and s after surgery , but only in four by the 12th week and two by the 25th week", "We report a r and omized trial of two skin incisions for carpal tunnel decompression , namely a st and ard incision and an ulnar L incision . We looked particularly at the resolution of local symptoms namely pillar pain and scar sensitivity . There were 47 patients in the trial . No difference was found in pillar pain between the two incisions , but one had a lower incidence of scar sensitivity . These results give a baseline for comparison of local postoperative symptoms following open release with those following endoscopic release", "Background : Carpal tunnel syndrome is a common condition causing h and pain and numbness . Endoscopic carpal tunnel release has been demonstrated to reduce recovery time , although previous studies have raised concerns about an increased rate of complications . The purpose of this prospect i ve , r and omized study was to compare open carpal tunnel release with single-portal endoscopic carpal tunnel release . Methods : A prospect i ve , r and omized , multicenter center study was performed on 192 h and s in 147 patients . The open method was performed in ninety-five h and s in seventy-two patients , and the endoscopic method was performed in ninety-seven h and s in seventy-five patients . All of the patients had clinical signs or symptoms and electrodiagnostic findings consistent with carpal tunnel syndrome and had not responded to , or had refused , nonoperative management . Follow-up evaluations with use of vali date d outcome instruments and quantitative measurements of grip strength , pinch strength , and h and dexterity were performed at two , four , eight , twelve , twenty-six , and fifty-two weeks after the surgery . Complications were identified . The cost of the procedures and the time until return to work were recorded and compared between the groups . Results : During the first three months after surgery , the patients treated with the endoscopic method had better Carpal Tunnel Syndrome Symptom Severity Scores , better Carpal Tunnel Syndrome Functional Status Scores , and better subjective satisfaction scores . During the first three months after surgery , they also had significantly ( p < 0.05 ) greater grip strength , pinch strength , and h and dexterity . The open technique result ed in greater scar tenderness during the first three months after surgery as well as a longer time until the patients could return to work ( median , thirty-eight days compared with eighteen days after the endoscopic release ) . No technical problems with respect to nerve , tendon , or artery injuries were noted in either group . There was no significant difference in the rate of complications or the cost of surgery between the two groups . Conclusion : Good clinical outcomes and patient satisfaction are achieved more quickly when the endoscopic method of carpal tunnel release is used . Single-portal endoscopic surgery is a safe and effective method of treating carpal tunnel syndrome", "To define the role of two-portal endoscopic carpal-tunnel release as a method for the treatment of compression of the median nerve at the wrist , a prospect i ve , r and omized , multicenter study was performed on 169 h and s in 145 patients . Either open or endoscopic carpal-tunnel release was performed in all of the patients who had clinical signs and symptoms consistent with carpal tunnel syndrome , had not responded to or had refused non-operative management , and had had electrodiagnostic studies consistent with carpal tunnel syndrome . Follow-up evaluations were performed at twenty-one , forty-two , and eighty-four days . At the end of the follow-up period , both the open and endoscopic methods had result ed in high levels of achievement of the primary outcomes ( relief of pain and paresthesias ) . The numbness and paresthesias were relieved in eighty ( 98 per cent ) of eighty-two h and s in the open-release group compared with seventy-seven ( 99 per cent ) of seventy-eight h and s in the endoscopic-release group . This parameter was not recorded for three h and s in the open-release group or six h and s in the endoscopic-release group . The satisfaction of the patients with the procedure , grade d on a scale of 0 to 100 per cent , averaged 84 per cent in the open-release group compared with 89 per cent in the group that had had endoscopic release . We found no significant differences between the two groups with regard to the secondary quantitative- outcome measurements , including two-point discrimination , postoperative interstitial-pressure data for the carpal canal , Semmes-Weinstein monofilament testing , and motor strength . The open technique result ed in more tenderness of the scar than did the endoscopic method . Thirty-two ( 39 per cent ) of eighty-two h and s in the open-release group and fifty ( 64 per cent ) of seventy-eight h and s in the endoscopic-release group were not tender at eighty-four days . This parameter was not recorded for three h and s in the open-release group and six h and s in the endoscopic-release group . The open method also result ed in a longer interval until the patient could return to work ( median , twenty-eight days , compared with fourteen days for the open-release and endoscopic-release groups ) . Four complications occurred in the endoscopic carpal-tunnel release group : one partial transection of the superficial palmar arch , one digital-nerve contusion , one ulnar-nerve neuropraxia , and one wound hematoma . ( ABSTRACT TRUNCATED AT 400 WORDS", "The authors compare in a prospect i ve , r and omized study the early outcome of carpal tunnel release using either a conventional palmar open release ( n=40 ) or a two-portal endoscopic release ( n=56 ) . Both groups were similar . No statistically significant differences were found regarding pain , disappearing of paraesthesiae or time to return to work . However , better recovery of grip strength was observed in the endoscopic group at 1 and 3 months . No surgical complications were observed in either group", "A prospect i ve r and omized trial was undertaken to compare the influence of absorbable and non-absorbable sutures on pillar pain , scar tenderness , extent of wound inflammation and overall outcome of the surgery following open carpal tunnel release . Forty h and s in 33 patients ( mean age , 51 years ; range , 31–74 years ) were r and omized into group A ( absorbable sutures ) or group B ( non-absorbable sutures ) . Clinical assessment was done at 2 , 6 and 12 weeks follow-up . The outcome of surgery in terms of improvement of severity of symptoms and functional status of patients was assessed using a self-administered Boston Question naire . There was no significant difference between the two groups for any of our outcome measures at the final follow-up", "Proponents of endoscopic carpal tunnel release have been advocating the technique for more than 10 years but there is still debate about its efficacy , safety and cost-effectiveness . We have performed a r and omized , prospect i ve , blind trial to compare early outcome after single portal endoscopic or open carpal tunnel surgery and to assess the cost-effectiveness of the procedures . There were no significant differences in symptom and functional activity scores , grip strength or anterior carpal pain in the first 3 months . For those in employment , we found a statistically significant difference between the two treatment groups with the endoscopic group returning to work , on average , 8 ( 95 % CI , 2–13 days ) days sooner than the open group . This translates into a cost saving to industry . There were no major neurovascular complications in either group . On the basis of these findings , we recommend that endoscopic carpal tunnel release should be considered in the employed as a cost-effective procedure , but perhaps not in the general population as a whole", "There is significant difference of opinion whether an adjunctive interfascicular neurolysis will improve the results of lysis of the transverse carpal ligament in patients with severe carpal tunnel syndrome ( thenar atrophy and /or fixed sensory deficit ) . Fifty such cases were prospect ively and consecutively selected and then r and omized into two groups prior to surgery . Half were treated by st and ard ligament release alone ; the other half also had adjunctive interfascicular neurolysis . All patients had neurologic examination and nerve conduction studies performed by a \" blind \" examiner at one and three months postoperatively with comparison of these findings with preoperative data . Analysis of the data revealed no significant difference between the two groups and , therefore , demonstrated no benefit from adjunctive interfascicular neurolysis . Additionally , as the majority of patients in both groups improved significantly , the study demonstrated frequent benefit from transverse carpal ligament release even in the presence of fixed neurologic deficit in severe carpal tunnel syndrome", "We have performed a prospect i ve r and omized controlled trial to compare the results of open carpal tunnel release with those of carpal tunnel release using a Knifelight ® ( Stryker , Kalamazoo , MI ) . This is a new knife with its own battery-powered light source which enables the operation to be performed through a small incision in the palm of the h and . There were 43 patients in the open operation group and 39 in the Knifelight group . We found no difference in discomfort reported during surgery , in the operative time , in the grip strength measured at 2 and 6 weeks postoperatively or in the proportion of patients cured of their pre-operative symptoms . Patients in the Knifelight group had a statistically significant improvement in the time to return to work and in scar tenderness at 6 weeks post-operatively", "PURPOSE This study compared the outcomes in patients assigned to either endoscopic carpal tunnel release ( ECTR ) or traditional open carpal tunnel release ( OCTR ) . METHODS An unbalanced r and omized clinical trial ( 91 endoscopic , 32 open ) was conducted . Short-term and long-term outcomes were evaluated by a blinded assessor . The primary outcome measures were symptom severity measured on a self-report scale and nerve/vascular complications . Secondary outcomes included the McGill pain question naire , grip strength , pinch strength , sensory threshold ( NK PSSD device , NK Biotechnical Corp , Minneapolis , MN ) , and time to return to work . RESULTS Both groups improved on all outcomes . No differences were observed in primary outcomes between the groups at either baseline or follow-up at 1 week , 6 weeks , or 12 weeks after surgery . No significant complications occurred in either group . Grip strength and pain were significantly better at 1 and 6 weeks in the endoscopic group although differences dissipated by 12 weeks . No significant differences occurred in other secondary outcomes . Long-term satisfaction was lower in the endoscopic group , attributable to a 5 % rate of re-operation . Lower rates of endoscopic release have occurred at our center once these results were available to surgeons and patients . CONCLUSIONS No substantive difference in benefit was shown for these 2 methods of carpal tunnel release", "In order to define the role of two-portal endoscopic carpal tunnel release , a prospect i ve r and omised study with an independent observer was performed to compare endoscopic and open surgery . Thirty-two h and s in 29 patients , with symptoms , clinical signs and EMG changes consistent with idiopathic carpal tunnel syndrome were r and omised to either endoscopic carpal tunnel release or open release . No significant difference in sick leave between the two groups could be found , being a mean of 17 days ( range 0–31 days ) with endoscopic surgery , and 19 days ( range 0–42 days ) with open conventional surgery . No differences in surgical results were found , but three patients in the endoscopic group suffered transient numbness on the radial side of the ring finger", "Background : We conducted a prospect i ve , r and omized study to evaluate the effect of flexor tenosynovectomy as an adjunct to open carpal tunnel release for the treatment of idiopathic carpal tunnel syndrome and review ed the histological characteristics of the flexor tenosynovium to identify possible correlations between histopathology and symptoms . Methods : Eighty-eight wrists in eighty-seven patients with idiopathic carpal tunnel syndrome were r and omized to open carpal tunnel release with or without flexor tenosynovectomy . A vali date d self-administered question naire for the assessment of symptom severity and functional status was completed both before and after the operation to assess patient outcome . The study group included fifteen men and seventy-two women with a mean age of fifty-eight years . All patients were followed for a minimum of twelve months after the operation . Intraoperatively , the tenosynovium of all patients was grade d on the basis of its gross appearance . Half of the wrists were then treated with a flexor tenosynovectomy through the operative incision , and the tenosynovium was grade d histologically . Correlations were sought between the gross appearance of the tenosynovium and the preoperative and postoperative symptoms and functional status , between the histologic appearance of the tenosynovium and the preoperative and postoperative symptoms and functional status , and between the gross and the histologic findings . Results : After the operation , both groups improved significantly with respect to symptom severity and functional status ( paired t test ) , with no significant difference between the groups ( unpaired t test ) . No significant correlation was found between the gross appearance of the tenosynovium and the preoperative or postoperative symptoms and functional status , between the histologic appearance of the tenosynovium and the preoperative or postoperative symptoms and functional status , or between the gross and the histologic findings . Conclusions : We observed neither an added benefit nor an increased rate of morbidity in association with the performance of a flexor tenosynovectomy at the time of carpal tunnel release . We identified no clinical correlations that might predict which individuals would benefit from flexor tenosynovectomy on the basis of either the gross ( intraoperative ) or histologic evaluation of the flexor tenosynovium . Our findings suggest that routine flexor tenosynovectomy offers no benefit compared with sectioning of the transverse carpal ligament alone for the treatment of idiopathic carpal tunnel syndrome", "OBJECTIVE There is insufficient evidence regarding the clinical and cost-effectiveness of surgical interventions for carpal tunnel syndrome . This study evaluates the cost , effectiveness and cost-effectiveness of minimally invasive surgery compared with conventional open surgery . PATIENTS AND METHODS 194 sufferers ( 208 h and s ) of carpal tunnel syndrome were r and omly assigned to each treatment option . A self-administered question naire assessed the severity of patients ' symptoms and functional status pre- and postoperatively . Treatment costs were estimated from re source use and hospital financial data . RESULTS Minimally invasive carpal tunnel decompression is marginally more effective than open surgery in terms of functional status , but not significantly so . Little improvement in symptom severity was recorded for either intervention . Minimally invasive surgery was found to be significantly more costly than open surgery . The incremental cost effectiveness ratio for functional status was estimated to be 197 UK pounds , such that a one percentage point improvement in functioning costs 197 UK pounds when using the minimally invasive technique . CONCLUSIONS Minimally invasive carpal tunnel decompression appears to be more effective but more costly . Initial analysis suggests that the additional expense for such a small improvement in function and no improvement in symptoms would not be regarded as value-for-money , such that minimally invasive carpal tunnel release is unlikely to be considered a cost-effective alternative to the traditional open surgery procedure" ]

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[ "BACKGROUND Physical activity promotion is a priority , but contribution of physicians ' interventions is unclear . The effectiveness of the PEPAF ( \" Experimental Program for Physical Activity Promotion \" ) , which was implemented exclusively by physicians in routine primary care from October 2003 to December 2004 , was assessed . METHODS Fifty-six Spanish family physicians were r and omized to either the intervention ( n = 29 ) or st and ard care ( n = 27 ) arm of the trial . The physicians recruited 4317 physically inactive patients ( 2248 for intervention and 2069 for control protocol s ) from a systematic sample after assessing their physical activity in routine practice . Intervention physicians provided advice to all patients and a physical activity prescription to the subgroup attending an additional appointment ( 30 % ) . The main outcome measure was the change in physical activity measured by blinded nurses using the 7-Day Physical Activity Recall . Secondary outcomes included cardiorespiratory fitness and health-related quality of life . RESULTS At 6 months , intervention patients increased physical activity more than controls ( adjusted difference , 18 min/wk [ 95 % confidence interval , 6 - 31 min/wk ] ; metabolic equivalent tasks x hours per week , 1.3 [ 95 % CI , 0.4 - 2.2 ] ) . The proportion of the population achieving minimal physical activity recommendations was 3.9 % higher in the intervention group ( 1.2%-6.9 % ; number needed to treat , 26 ) . No differences were found in secondary outcomes . The effect of intervention was positively modified in subjects older than 50 years ( P < or = .01 ) and in the prescription subgroup ( P < .001 ) . CONCLUSIONS Family physicians were effective for increasing physical activity of primary care patients . Overall clinical effect was small but relevant for population public health . Within the intervention program , clinical ly relevant effects were seen in patients receiving a physical activity prescription . Trial Registration clinical trials.gov Identifier : NCT00131079", "Background A recent HTA review concluded that there was a need for RCTs of exercise referral schemes ( ERS ) for people with a medical diagnosis who might benefit from exercise . Overall , there is still uncertainty as to the cost-effectiveness of ERS . Evaluation of public health interventions places challenges on conventional health economics approaches . This economic evaluation of a national public health intervention addresses this issue of where ERS may be most cost effective through subgroup analysis , particularly important at a time of financial constraint . Method This economic analysis included 798 individuals aged 16 and over ( 55 % of the r and omised controlled trial ( RCT ) sample ) with coronary heart disease risk factors and /or mild to moderate anxiety , depression or stress . Individuals were referred by health professionals in a primary care setting to a 16 week national exercise referral scheme ( NERS ) delivered by qualified exercise professionals in local leisure centres in Wales , UK . Health-related quality of life , health care services use , costs per participant in NERS , and willingness to pay for NERS were measured at 6 and 12 months . Results The base case analysis assumed a participation cost of £ 385 per person per year , with a mean difference in QALYs between the two groups of 0.027 . The incremental cost-effectiveness ratio was £ 12,111 per QALY gained . Probabilistic sensitivity analysis demonstrated an 89 % probability of NERS being cost-effective at a payer threshold of £ 30,000 per QALY . When participant payments of £ 1 and £ 2 per session were considered , the cost per QALY fell from £ 12,111 ( base case ) to £ 10,926 and £ 9,741 , respectively . Participants with a mental health risk factor alone or in combination with a risk of chronic heart disease generated a lower ICER ( £ 10,276 ) compared to participants at risk of chronic heart disease only ( £ 13,060 ) . Conclusions Results of cost-effectiveness analyses suggest that NERS is cost saving in fully adherent participants . Though full adherence to NERS ( 62 % ) was higher for the economics sample than the main sample ( 44 % ) , results still suggest that NERS can be cost-effective in Wales with respect to existing payer thresholds particularly for participants with mental health and CHD risk factors . Trial registration Current Controlled Trials IS RCT", "Background Over the past decade , practitioners in primary health care ( PHC ) setting s in many countries have issued written prescriptions to patients to promote increased physical activity or exercise . The aim of this study is to describe and analyse a comprehensive physical activity referral ( PAR ) scheme implemented in a routine PHC setting in Östergötl and County . The study examines characteristics of the PARs recipients and referral practitioners , identifies reasons why practitioners opted to use PARs with their clients , and discusses prescribed activities and prescriptions in relation to PHC registries . Methods Prospect i ve prescription data were obtained for 90 % of the primary health care centres in Östergötl and County , Sweden , in 2004 and 2005 . The study population consisted of patients who were issued PARs after they were deemed likely to benefit from increased physical activity , as assessed by PHC staff . Results During the two-year period , a total of 6,300 patients received PARs . Two-thirds of the patients were female and half of the patients were 45–64 years . Half of the patients ( 50.8 % ) who received PARs were recommended a home-based activity , such as walking . One third ( 33 % ) of the patients issued PARs were totally inactive , reporting no days of physical activity that lasted for 30 minutes , and 29 % stated that they reached this level 1–2 days per week . The number of PARs prescribed per year in relation to the number of unique individuals that visited primary health care during one year was 1.4 % in 2004 and 1.2 % in 2005 . Two-thirds of the combined prescriptions were issued by physicians ( 38 % ) and nurses ( 31 % ) . Physiotherapists and behavioural scientists issued the highest relative number of prescriptions . The most common reasons for issuing PARs were musculoskeletal disorders ( 39.1 % ) and overweight ( 35.4 % ) , followed by high blood pressure ( 23.3 % ) and diabetes ( 23.2 % ) . Conclusion Östergötl and County 's PAR scheme reached a relatively high proportion of physically inactive people visiting local PHC centres for other health reasons . PAR-related statistics , including PAR-rates by individual PHC centres and PAR- rates per health professional category , show differences in prescribing activities , both by patient categories , and by prescribing professionals", "Background The National Institute for Health and Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials . Recent empirical evidence in health care and physical activity promotion context s provides a foundation for testing the feasibility and impact of a Self Determination Theory-based ( SDT ) exercise referral consultation . Methods An exploratory cluster r and omised controlled trial comparing st and ard provision exercise referral with an exercise referral intervention grounded in Self Determination Theory . Individuals ( N = 347 ) referred to an exercise referral scheme were recruited into the trial from 13 centres . Outcomes and processes of change measured at baseline , 3 and 6-months : Minutes of self-reported moderate or vigorous physical activity ( PA ) per week ( primary outcome ) , health status , positive and negative indicators of emotional well-being , anxiety , depression , quality of life ( QOL ) , vitality , and perceptions of autonomy support from the advisor , need satisfaction ( 3 and 6 months only ) , intentions to be active , and motivational regulations for exercise . Blood pressure and weight were assessed at baseline and 6 months . Results Perceptions of the autonomy support provided by the health and fitness advisor ( HFA ) did not differ by arm . Between group changes over the 6-months revealed significant differences for reported anxiety only . Within arm contrasts revealed significant improvements in anxiety and most of the Dartmouth CO-OP domains in the SDT arm at 6 months , which were not seen in the st and ard exercise referral group . A process model depicting hypothesized relationships between advisor autonomy support , need satisfaction and more autonomous motivation , enhanced well being and PA engagement at follow up was supported . Conclusions Significant gains in physical activity and improvements in quality of life and well-being outcomes emerged in both the st and ard provision exercise referral and the SDT-based intervention at programme end . At 6-months , observed between arm and within intervention arm differences for indicators of emotional health , and the results of the process model , were in line with SDT . The challenges in optimising recruitment and implementation of SDT-based training in the context of health and leisure services are discussed . Trial registration The trial is registered as Current Controlled trials IS RCT N07682833", "Background Although the benefits of physical activity ( PA ) on to prevent and manage non-communicable diseases are well known , strategies to help increase the levels of PA among different population s are limited . Exercise-referral schemes have emerged as one effective approach to promote PA ; however , there is uncertainty about the feasibility and effectiveness of these schemes in setting s outside high-income countries . This study will examine the effectiveness of a scheme to refer hypertensive patients identified in Primary Health Care facilities ( PHCU ) of the Mexican social security institution to a group PA program offered in the same institution . Methods and design We will describe the methods of a cluster r and omized trial study design ed to evaluate the effectiveness of an exercise referral scheme to increasing physical activity in hypertensive patients compared to a non-referral scheme . Four PHCU were selected for the study ; the PHCU will take part as the unit of r and omization and sedentary hypertensive patients as the unit of assessment . 2 PHCU of control group ( GC ) will provide information to hypertensive patients about physical activity benefits and ways to increase it safely . 2 PHCU of intervention group ( IG ) will refer patients to sports facilities at the same institution , to follow a group-based PA program developed to increase the PA levels with a design ed based on the Transtheoretical Model and Social Cognitive Theory . To evaluate the effects of the intervention as well as short-term maintenance of the intervention ’s effects , PA will be assessed at baseline , at 24 and 32 weeks of follow-up . The main outcome will be the difference before and after intervention in the percentage of participants meeting recommended levels of PA between and within intervention and control groups . PA will be measured through self-report and with objective measure by accelerometer . Discussion This study will allow us to evaluate a multidisciplinary effort to link the primary care and community-based areas of the same health care system . Our findings will provide important information about the feasibility and effectiveness of an exercise-referral scheme and will be useful for decision-making about the implementation of strategies for increasing PA among hypertensive and other clinical population s in Mexico and Latin America . Trial registration Clinical trials.gov Identifier : NCT01910935 . Date of registration : 07/05/2013", "Study objective : To compare health walks , a community based lay-led walking scheme versus advice only on physical activity and cardiovascular health status in middle aged adults . Design : R and omised controlled trial with one year follow up . Physical activity was measured by question naire . Other measures included attitudes to exercise , body mass index , cholesterol , aerobic capacity , and blood pressure . Setting : Primary care and community . Participants : 260 men and women aged 40–70 years , taking less than 120 minutes of moderate intensity activity per week . Main results : Seventy three per cent of people completed the trial . Of these , the proportion increasing their activity above 120 minutes of moderate intensity activity per week was 22.6 % in the advice only and 35.7 % in the health walks group at 12 months ( between group difference = 13 % ( 95 % CI 0.003 % to 25.9 % ) p=0.05 ) . Intention to treat analysis , using the last known value for missing cases , demonstrated smaller differences between the groups ( between group difference = 6 % ( 95 % CI −5 % to 16.4 % ) ) with the trend in favour of health walks . There were improvements in the total time spent and number of occasions of moderate intensity activity , and aerobic capacity , but no statistically significant differences between the groups . Other cardiovascular risk factors remained unchanged . Conclusions : There were no significant between group differences in self reported physical activity at 12 month follow up when the analysis was by intention to treat . In people who completed the trial , health walks was more effective than giving advice only in increasing moderate intensity activity above 120 minutes per week", "OBJECTIVES To evaluate and compare the effectiveness and cost-effectiveness of a leisure centre-based exercise programme , an instructor-led walking programme and advice-only in patients referred for exercise by their GPs . DESIGN A single-centre , parallel-group , r and omised controlled trial , consisting of three arms , with the primary comparison at 6 months . SETTING Assessment s were carried out at Copthall Leisure Centre in Barnet , an outer London borough , and exercise programmes conducted there and at three other leisure centres and a variety of locations suitable for supervised walking throughout the borough . PARTICIPANTS Participants were aged between 40 and 74 years , not currently physically active and with at least one cardiovascular risk factor . INTERVENTIONS The 943 patients who agreed to participate in the trial were assessed in cohorts and r and omised to one of the following three arms : a 10-week programme of supervised exercise classes , two to three times a week in a local leisure centre ; a 10-week instructor-led walking programme , two to three times a week ; an advice-only control group who received tailored advice and information on physical activity including information on local exercise facilities . After 6 months the control group were rer and omised to one of the other trial arms . Assessment s took place before r and omisation , at 10 weeks ( in a r and om 50 % sub sample of participants ) , 6 months and 1 year in the leisure centre and walking arms . The control participants were similarly assessed up to 6 months and then reassessed at the same intervals as those initially r and omised to the leisure centre and walking groups . MAIN OUTCOME MEASURES The primary outcome measures were changes in self-reported exercise behaviour , blood pressure , total cholesterol and lipid subfractions . Secondary outcomes included changes in anthropometry , cardiorespiratory fitness , flexibility , strength and power , self-reported lifestyle behaviour , general and psychological health status , quality of life and health service usage . The costs of providing and making use of the service were quantified for economic evaluation . RESULTS There was a net increase in the proportion of participants achieving at least 150 minutes per week of at least moderate activity in the sport/leisure and walking categories in all three study groups : at 6 months , the net increases were 13.8 % in the leisure centre group , 11.1 % in the walking group and 7.5 % in the advice-only group . There were significant reductions in systolic and diastolic blood pressure in all groups at each assessment point compared with baseline . There were also significant and sustained improvements in cardiorespiratory fitness and leg extensor power , and small reductions in total and low-density lipoprotein cholesterol in all groups , but there were no consistent differences between the groups for any parameter over time . All three groups showed improvement in anxiety and mental well-being scores 6 months after the beginning of the trial . Leisure centre and walking groups maintained this improvement at 1 year . There were no differences between groups . Costs to the participants amounted to pound 100 for the leisure centre scheme and pound 84 for the walking scheme , while provider costs were pound 186 and pound 92 , respectively . Changes in overall Short Form 36 scores were small and advice only appeared the most cost-effective intervention . CONCLUSIONS The results of this trial suggest that referral for tailored advice , supported by written material s , including details of locally available facilities , supplemented by detailed assessment s may be effective in increasing physical activity . The inclusion of supervised exercise classes or walks as a formal component of the scheme may not be more effective than the provision of information about their availability . On cost-effectiveness grounds , assessment and advice alone from an exercise specialist may be appropriate to initiate action in the first instance . Subsidised schemes may be best concentrated on patients at higher absolute risk , or with specific conditions for which particular programmes may be beneficial . Walking appears to be as effective as leisure centre classes and is cheaper . Efforts should be directed towards maintenance of increased activity , with proven measures such as telephone support . Further research should include an up date d meta- analysis of published exercise interventions using the st and ardised mean difference approach", "Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials . Recent empirical evidence in health care and physical activity promotion context s provides a foundation for testing the utility of a Self Determination Theory (SDT)-based exercise referral consultation . Methods / Design Design : An exploratory cluster r and omised controlled trial comparing st and ard provision exercise on prescription with a Self Determination Theory-based ( SDT ) exercise on prescription intervention . Participants : 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008 . The 13 exercise on prescription sites in Birmingham were r and omised to current practice ( n = 7 ) or to the SDT-based intervention ( n = 6 ) . Outcomes measured at 3 and 6-months : Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall ; physical health : blood pressure and weight ; health status measured using the Dartmouth CO-OP charts ; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score ; motivation and processes of change : perceptions of autonomy support from the advisor , satisfaction of the needs for competence , autonomy , and relatedness via physical activity , and motivational regulations for exercise . Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a st and ard programme and will test the underlying SDT-based process model ( perceived autonomy support , need satisfaction , motivation regulations , outcomes ) via structural equation modelling . Trial registration The trial is registered as Current Controlled trials IS RCT N07682833", "Abstract Background : It is well established in the literature that regular participation in physical activity is effective for chronic disease management and prevention . Remote monitoring technologies ( ie , mHealth ) hold promise for engaging patients in self-management of many chronic diseases . The purpose of this study was to test the effectiveness of an mHealth study with tailored physical activity prescription targeting changes in various intensities of physical activity ( eg , exercise , sedentary behavior , or both ) for improving physiological and behavioral markers of lifestyle-related disease risk . Methods : Forty-five older adults ( aged 55–75 years ; mean age 63 ± 5 years ) were r and omly assigned to receive a personal activity program targeting changes to either daily exercise , sedentary behavior , or both . All participants received an mHealth technology kit including smartphone , blood pressure monitor , glucometer , and pedometer . Participants engaged in physical activity programming at home during the 12-week intervention period and su bmi tted physical activity ( steps/day ) , blood pressure ( mm Hg ) , body weight ( kg ) , and blood glucose ( mmol/L ) measures remotely using study -provided devices . Results : There were no differences between groups at baseline ( P > 0.05 ) . The intervention had a significant effect ( F(10 488 ) = 2.947 , P = 0.001 , ηP2 = 0.057 ) , with similar changes across all groups for physical activity , body weight , and blood pressure ( P > 0.05 ) . Changes in blood glucose were significantly different between groups , with groups prescribed high-intensity activity ( ie , exercise ) demonstrating greater reductions in blood glucose than the group prescribed changes to sedentary behavior alone ( P < 0.05 ) . Conclusions : Findings demonstrate the utility of pairing mHealth technologies with activity prescription for prevention of lifestyle-related chronic diseases among an at-risk group of older men and women . Results support the novel approach of prescribing changes to sedentary behaviors ( alone , and in conjunction with exercise ) to reduce risk of developing lifestyle-related chronic conditions", "To assess the effectiveness of the ' Green Prescription ' ( GRx ) program in promoting self-reported health benefits in previously inactive individuals , between 2001 and 2002 , a retrospective survey was administered to 124 GRx patients throughout New Zeal and . Participants were a non-r and omized subset of a larger GRx population . Logistic regression was used to calculate odds ratios ( OR ) and 95 % confidence intervals ( CI ) for differences in health outcomes between participants who had increased physical activity levels compared to participants who had decreased or not altered activity levels since first being prescribed the GRx . Completed surveys were obtained from 124 of 263 eligible participants ; a response rate of 47 % . Fifty-six percent of participants reported increases in physical activity levels after the GRx program , with 70 % still undertaking some form of physical activity . Participants accumulated at least 30 minutes of physical activity per day on 3.4 + /- 2.5 days ( mean + /- SD ) per week . Participants who reported increased physical activity levels after the GRx reported substantially higher energy levels and improved breathing when compared to participants who reported less or about the same physical activity after the GRx intervention . Increased physical activity in GRx patients was associated with greater perceived health benefits . Effective and ongoing support networks were seen as important for behavior change", "Objective To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period . Design R and omised controlled trial . Setting 17 primary care practice s in Wellington , New Zeal and Participants 1089 women aged 40 - 74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months . Main outcome measure Physical activity assessed at baseline and 12 and 24 months . Secondary outcomes were quality of life ( SF-36 ) , weight , waist circumference , blood pressure , concentrations of fasting serum lipids , glycated haemoglobin ( HbA1c ) , glucose , insulin , and physical fitness . Results Mean age was 58.9 ( SD 7 ) years . Trial retention rates were 93 % and 89 % at 12 and 24 months , respectively . At baseline , 10 % of intervention participants and 11 % of control participants were achieving 150 minutes of at least moderate intensity physical activity a week . At 12 months rates increased to 43 % and 30 % and at 24 months to 39.3 % and 32.8 % ( P<0.001 ) , respectively . SF-36 physical functioning ( P=0.03 ) and mental health ( P<0.05 ) scores improved more in intervention compared with control participants , but role physical scores were significantly lower ( P<0.01 ) . There were no significant differences in clinical outcomes . More falls ( P<0.001 ) and injuries ( P=0.03 ) were recorded in the intervention group . Conclusions This programme of exercise on prescription increased physical activity and quality of life over two years , although falls and injuries also increased . This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ANZCTRN012605000490673", "Background The present study protocol describes the trial design of a primary care intervention cohort study , which examines whether an extended , multi-professional physical activity referral ( PAR ) intervention is more effective in enhancing and maintaining self-reported physical activity than physical activity prescription in usual care . The study targets patients with newly diagnosed hypertension and /or type 2 diabetes . Secondary outcomes include : need of pharmacological therapy ; blood pressure/plasma glucose ; physical fitness and anthropometric variables ; mental health ; health related quality of life ; and cost-effectiveness . Methods / Design The study is design ed as a long-term intervention . Three primary care centres are involved in the study , each constituting one of three treatment groups : 1 ) Intervention group ( IG ) : multi-professional team intervention with PAR , 2 ) Control group A ( CA ) : physical activity prescription in usual care and 3 ) Control group B : treatment as usual ( retrospective data collection ) . The intervention is based on self-determination theory and follows the principles of motivational interviewing . The primary outcome , physical activity , is measured with the International Physical Activity Question naire ( IPAQ ) and expressed as metabolic equivalent of task (MET)-minutes per week . Physical fitness is estimated with the 6-minute walk test in IG only . Variables such as health behaviours ; health-related quality of life ; motivation to change ; mental health ; demographics and socioeconomic characteristics are assessed with an electronic study question naire that su bmi ts all data to a patient data base , which automatically provides feed-back to the health-care providers on the patients ’ health status . Cost-effectiveness of the intervention is evaluated continuously and the intermediate outcomes of the intervention are extrapolated by economic modelling . Discussion sBy helping patients to overcome practical , social and cultural obstacles and increase their internal motivation for physical activity we aim to improve their physical health in a long-term perspective . The targeted patients belong to a patient category that is supposed to benefit from increased physical activity in terms of improved physiological values , mental status and quality of life , decreased risk of complications and maybe a decreased need of medication", "Abstract The aim of this study was to examine participant and scheme characteristics in relation to access , uptake , and participation in a physical activity referral scheme ( PARS ) using a prospect i ve population -based longitudinal design . Participants ( n = 3762 ) were recruited over a 3-year period . Logistic regression analyses identified the factors associated with the outcomes of referral uptake , participation , and completion ( ≥80 % attendance ) . Participant 's age , sex , referral reason , referring health professional , and type of leisure provider were the independent variables . Based on binary logistic regression analysis ( n = 2631 ) , only primary referral reason was associated with the PARS coordinator making contact with the participants . In addition to the influence of referral reason , females were also more likely ( odds ratio 1.250 , 95 % confidence interval 1.003 – 1.559 , P = 0.047 ) to agree to be assigned to a leisure provider . Referral reason and referring health professional were associated with taking up a referral opportunity . Older participants ( 1.016 , 1.010 – 1.023 , P < 0.001 ) and males were more likely to complete the referral . In conclusion , the PARS format may be less appropriate for those more constrained by time ( women , young adults ) and those with certain referral reasons ( overweight/obesity , mental health conditions ) . More appropriate targeting at the point of referral could improve participation rates by revealing or addressing barriers that might later result in dropout", "BACKGROUND Sedentary behaviour is a public health priority in many countries . Hundreds of community-based exercise referral schemes have been established in Europe and USA , to increase physical activity . Experimental evidence questions the effectiveness of these schemes . No previous evaluations have considered a population approach nor provide detailed information on the types of people accessing these schemes . This is of concern given increasing health inequalities in other areas of care . Our register-based study quantified the numbers and characteristics of patients referred and accessing a district-wide exercise referral scheme . The analysis considers the effectiveness of these schemes to a geographically defined population . METHODS Data were collected prospect ively from a patient register for referrals made to a district-wide exercise referral scheme in north-west Engl and . Analysis examined referral rates and the influence of practitioner and patient characteristics on access to the scheme . RESULTS Over 5 years , 6,610 adults were referred from 125 general practice s , with 60.8 per cent female and a mean age of 51.3 years ( SD 12.6 ) . This represents 4 per cent of the adult sedentary population in that district . The most common reason for referral was musculoskeletal or cardiovascular risk . Overall , 79 per cent attended at least the first appointment , with statistically significant predictors by age and reason for referral . Those referred for ' fitness ' or ' mental health ' were most likely to attend . Patients in the youngest and oldest age groups were least likely to attend . Patient 's sex and deprivation and the number of patients referred by each general practice did not influence attendance . CONCLUSIONS Primary -care patients seem to view the concept of exercise referral schemes positively but practitioners remain reluctant to refer many of their sedentary patients . There is doubt that exercise referral schemes like this will influence population levels of sedentary behaviour , when considered alongside their impact on physical activity in the longer term", "Aims : To estimate the willingness to pay for health improvements among participants in the programme ‘ ‘ Physical Activity on Prescription ’ ’ . The objective was also to examine predictors such as income , education level , health status , activity level and BMI , differences for long- and short-term health effects of physical activity and differences between a high- and low-intensity activity group . Methods : Willingness to pay ( WTP ) data were collected alongside a r and omized , controlled trial in Sweden 2007 , and 128 sedentary individuals , 20—80 years old ( intervention/high-intensity group n = 71 , control/low-intensity group n = 57 ) , with lifestyle-related health problems answered open-ended questions in this contingent valuation study . Results : The highest mean WTP ( 59/SEK 552 ) was stated for an immediate health improvement , but no significant differences compared with long-term health improvements . The high-intensity group showed higher WTP-values for all health improvements , but without significant differences compared with a low-intensity group . Regression analyses show strong associations between a higher level of education and the WTP for improved well-being and improved health , and also between income and the WTP for improved well-being . There are significant correlations between the WTP and the variables BMI , income and education level , as expected from economic theories . Conclusions : The willingness to pay for the health improvements of exercise is influenced by a higher education level , income and BMI . The highest WTP for a health outcome of physical activity is for an immediate health improvement . The results of this r and omized controlled trial in primary health care may be of interest to decision makers when evaluating different approaches to promoting physical activity among people who are sedentary", "There is convincing evidence about the benefits of exercise training in community dwelling frailer older people , but little evidence that this intervention can be delivered in general practice . In this prospect i ve cohort study in 14 general practice s in north London we assessed the feasibility and effectiveness of a tailored exercise referral programme for frail elderly patients delivered within a variety of inner city primary care setting s. One hundred and twenty-six women and 32 men aged 75 years and older , deemed borderline frail by their GPs , took part in a two-phase progressive exercise programme ( Stage 1 - - primary care setting ; Stage II -- leisure/community centre setting ) using the Timed Up And Go ( TUG ) test as the primary outcome measure . Baseline TUG measures confirmed that the participants were borderline frail and that GP selection was accurate . Of those referred by their GP or practice nurse 89 % took up the exercise programme ; 73 % completed Stage I and 63 % made the transition to the community Stage II programme . TUG improved in Stage I with a mean difference of 3.5 seconds ( P<0.001 ) . An individually tailored progressive exercise programme following GP referral , delivered in weekly group sessions by specialist exercise instructors within general practice s , was effective in achieving participation in exercise sessions and in improving TUG values in a significant number of frailer older citizens", "OBJECTIVES To determine whether a clinic-based physical activity promotion intervention can lead to more community-based exercise referrals by providers and higher exercise motivation in patients . DESIGN Cluster r and omized , controlled trial . SETTING Seattle Veterans Affairs General Internal Medicine Clinic . PARTICIPANTS Thirty-one physicians and nurse practitioners were r and omized to a physical activity counseling intervention or control condition ( counseling about tobacco cessation ) . Three hundred thirty-six patients aged 50 and older and visiting a study provider were enrolled . INTERVENTION Intervention providers were trained to offer referrals to community exercise programs for patients who reported before their clinic visit that they were \" contemplative \" about regular exercise . MEASUREMENTS Process measures of health behavior assessment and provider advice , exercise stage-of-change , proportion of participants reporting regular physical activity . RESULTS At baseline , 172 intervention patients and 164 controls were similar with respect to sex , age , comorbidity score , and exercise motivation level . Forty-five percent of all intervention patients and 35 % of controls reported receiving exercise advice ( P=.07 ) . Intervention patients who were contemplative about exercise were even more likely to receive exercise advice than contemplative controls ( 59 % vs 38 % ; P=.02 ) . After 4 months , 35 % of all intervention patients reported regular exercise , compared with 28 % of controls ( P=.06 ) . CONCLUSION Primary providers are more likely to offer exercise advice when informed whether patients are contemplative about exercise . Patients may be more likely to start regular exercise as a result of this advice", "Evidence supports the effectiveness of interventions delivered in primary care to promote physical activity ( PA ) . Specifically , approaches where physician counseling is coupled with other strategies ( eg , referrals to community re sources ) have been recognized as the most promising . The purpose of this study was to compare the effectiveness of a PA prescription plus referral intervention versus a prescription only intervention delivered in primary care . Ten family physicians and their female patients ( N = 35 , mean age = 36 years ) were r and omly assigned to 1 of 3 conditions : prescription plus ( n = 12 ) , prescription only ( n = 12 ) , and usual care ( n = 11 ) . The prescription plus group received a PA prescription plus a referral to a community program , the prescription only group received only the PA prescription , and the usual care group received usual health care . The Godin Leisure-Time Exercise Question naire was used to measure PA . A significant increase on the PA score ( P < .05 , partial η2 = .178 ) and on total weekly PA minutes ( P < .05 , partial η2 = .179 ) was observed in both prescription groups after the intervention . There were no significant group differences ( P > .05 ) . No PA changes were observed in the usual care group . Findings from this pilot study suggest that brief PA counseling and a prescription delivered in primary care can be effective for promoting PA among women . Referring patients did not seem to enhance the effect on PA", "The aim of this study was to compare short- ( 0 - 4 months ) and long-term ( 0 - 10 months ) effects of high-intensive Exercise on Prescription ( EoP ) intervention ( counseling and supervised exercise ) implemented in primary healthcare in a number of Danish counties with a low-intensive intervention ( counseling ) using maximal oxygen uptake ( VO(2max ) ) as the primary outcome . The study was conducted as a r and omized trial in 2005 - 2006 with a high and a low-intensive group . All the patients referred to the EoP scheme by their GP in the counties of Vejle and Ribe , Denmark , were eligible for the trial . The high-intensive EoP group received 4 months of group-based supervised training and attended five motivational counseling sessions . The low-intensive group only attended four motivational counseling sessions . Three hundred and twenty-seven patients entered the EoP scheme , and 52 ( 16 % ) volunteered for the r and omized trial . No short- or long-term differences were found between the high and the low-intensive groups for VO(2max ) ( short-term 95 % CI -1.1 ; 4.4 mL O(2)/(kg min ) , long-term 95 % CI -1.6 to 2.1 ) . The present study did not demonstrate any significant clinical outcome for the high-intensive EoP intervention as opposed to the low-intensive intervention", "Aim To assess the cost-effectiveness of exercise on prescription with ongoing support in general practice . Methods Prospect i ve cost-effectiveness study undertaken as part of the 2-year Women 's lifestyle study r and omised controlled trial involving 1089 ‘ less-active ’ women aged 40–74 . The ‘ enhanced Green Prescription ’ intervention included written exercise prescription and brief advice from a primary care nurse , face-to-face follow-up at 6 months , and 9 months of telephone support . The primary outcome was incremental cost of moving one ‘ less-active ’ person into the ‘ active ’ category over 24 months . Direct costs of programme delivery were recorded . Other ( indirect ) costs covered in the analyses included participant costs of exercise , costs of primary and secondary healthcare utilisation , allied health therapies and time off work ( lost productivity ) . Cost – effectiveness ratios were calculated with and without including indirect costs . Results Follow-up rates were 93 % at 12 months and 89 % at 24 months . Significant improvements in physical activity were found at 12 and 24 months ( p<0.01 ) . The exercise programme cost was New Zeal and dollars ( NZ$ ) 93.68 ( € 45.90 ) per participant . There was no significant difference in indirect costs over the course of the trial between the two groups ( rate ratios : 0.99 ( 95 % CI 0.81 to 1.2 ) at 12 months and 1.01 ( 95 % CI 0.83 to 1.23 ) at 24 months , p=0.9 ) . Cost – effectiveness ratios using programme costs were NZ$687 ( € 331 ) per person made ‘ active ’ and sustained at 12 months and NZ$1407 ( € 678 ) per person made ‘ active ’ and sustained at 24 months . Conclusions This nurse-delivered programme with ongoing support is very cost-effective and compares favourably with other primary care and community-based physical activity interventions internationally", "This study investigated the effectiveness of a 10-week primary care exercise referral intervention on the physical self-perceptions of 40 - 70 year olds . Participants ( N=142 ) were assessed , r and omized to an exercise or control group , and reassessed at 16 and 37 weeks . The Physical Self-Perception Profile ( PSPP ; K. R. Fox , 1990 ) , fitness , physical activity , body mass index , body fat ( skinfolds ) , and hip and waist circumference were assessed . A multivariate analysis of variance revealed significant Group X Time interactions , with the exercise group showing greater physical self-worth , physical condition , and physical health at 16 and 37 weeks . Changes in all PSPP scales at baseline and 37 weeks were related to changes in anthropometric measures and adherence to the 10-week exercise program but not to changes in submaximal fitness parameters", "Primary care is a promising venue to build patient motivation and confidence to increase physical activity ( PA ) . Physician PA counselling has demonstrated some success ; however , maintenance of behaviour change appears to require more intensive interventions . In reality , most physicians do not have the necessary training nor the time for this type of counselling . The purpose of this paper is to outline the rationale , methods , and interventions for the ongoing physical activity counselling ( PAC ) r and omized controlled trial ( RCT ) , which aims to assess the impact of integrating a PA counsellor into a primary care practice . This RCT has 2 arms : ( i ) brief PA counselling ( 2 - 4 min ) from a health care provider and ( ii ) brief PA counselling+intensive PA counselling from a PA counsellor ( 3 months ) . The impact of this intervention is being evaluated using the comprehensive RE- AIM framework . One hundred twenty insufficiently active adult patients , aged 18 to 69 y and recruited during regular primary care visits have been r and omized . Dependent measures include psychological mediators , PA participation , quality of life , and physical and metabolic outcomes . The PAC project represents an innovative , theoretically-based approach to promoting PA in primary care , focusing on psychological mediators of change . We anticipate that key lessons from this study will be useful for shaping future public health interventions , theories , and research", "Background The Wales National Exercise Referral Scheme ( NERS ) is a 16-week programme including motivational interviewing , goal setting and relapse prevention . Method A pragmatic r and omised controlled trial with nested economic evaluation of 2160 inactive participants with coronary heart disease risk ( CHD , 1559 , 72 % ) , mild to moderate depression , anxiety or stress ( 79 , 4 % ) or both ( 522 , 24 % ) r and omised to receive ( 1 ) NERS or ( 2 ) normal care and brief written information . Outcome measures at 12 months included the 7-day physical activity recall , the hospital anxiety and depression scale . Results Ordinal regression identified increased physical activity among those r and omised to NERS compared with those receiving normal care in all participants ( OR 1.19 , 95 % CI 0.99 to 1.43 ) , and among those referred for CHD only ( OR 1.29 , 95 % CI 1.04 to 1.60 ) . For those referred for mental health reason alone , or in combination with CHD , there were significantly lower levels of anxiety ( OR −1.56 , 95 % CI −2.75 to −0.38 ) and depression ( OR −1.39 , 95 % CI −2.60 to −0.18 ) , but no effect on physical activity . The base-case incremental cost-effectiveness ratio was £ 12 111 per quality adjusted life year , falling to £ 9741 if participants were to contribute £ 2 per session . Conclusions NERS was effective in increasing physical activity among those referred for CHD risk only . Among mental health referrals , NERS did not influence physical activity but was associated with reduced anxiety and depression . Effects were dependent on adherence . NERS is likely to be cost effective with respect to prevailing payer thresholds . Trial registration Current Controlled Trials IS RCT N47680448", "OBJECTIVE To assess the effectiveness of a primary care referral scheme on increasing physical activity at 1 year from referral . Design Two-group r and omized controlled trial recruiting primary care referrals to a borough-based exercise scheme . Setting A local authority borough in the north-west of Engl and . Participants 545 patients defined as sedentary by a primary care practitioner . Intervention Referral to a local-authority exercise referral scheme and written information compared with written information only . Main outcome measures Meeting physical activity target at 12 months following referral , with a secondary outcome measured at 6 months from referral . RESULTS At 12 months , a non-significant increase of 5 per cent was observed in the intervention compared with control group , for participation in at least 90 minutes of moderate/vigorous activity per week ( 25.8 versus 20.4 per cent , OR 1.45 , 0.84 to 2.50 , p = 0.18 ) . At 6 months , a 10 per cent treatment effect was observed which was significant ( 22.6 versus 13.6 per cent , OR 1.67 , 1.08 to 2.60 , p = 0.05 ) . The intervention increased satisfaction with information but this did not influence adherence with physical activity . CONCLUSION Community-based physical activity referral schemes have some impact on reducing sedentary behaviour in the short-term , but which is unlikely to be sustained and lead to benefits in terms of health", "Abstract A national objective as outlined in Healthy People 2000 is to increase to 50 % the proportion of primary care providers who routinely counsel clients about use of physical activity as a means to promote health . Results of this r and om national survey suggest that adult nurse practitioners are meeting the Healthy People 2000 objective by routinely counseling clients about physical activity", "Abstract Objectives . To analyse costs and consequences of changing physical activity behaviour due to the “ Physical Activity on Prescription ” ( PAP ) programme . Design . A r and omized controlled trial with a four-month intervention , with comparison between intervention and control group . Intervention . The PAP programme , with exercise twice a week , education , and motivational counselling . Subjects . 525 sedentary individuals , 20–80 years ( intervention group n = 268 , control group n = 257 ) , with lifestyle-related health problems . A total of 245 returned for the four-month assessment . Main outcome measure . Programme costs based on intention-to-treat estimations , direct and indirect costs of inactivity , and physical activity behaviour analysed with IPAQ ( International Physical Activity Question naire ) , self-reported physical activity , and measures of functional capacity . Results . The intention-to-treat programme costs for the four-month programme period was SEK ( Swedish Kronor ) 6475 ( € [ Euro ] 684 ) for the intervention group and SEK 3038 ( € 321 ) for the control group . Of this , healthcare providers ’ costs were 24 % in the intervention group , and 31 % in the control group . The physical activity behaviour was significantly improved in both groups , but no differences were found between the groups . Implication s. The largest share of the PAP programme costs was the participants ’ costs . Significant improvements were shown in physical activity behaviour in both groups , but no differences were found between the intervention and control groups . Due to many non-completers , the potential for improvements of the motivating assignment with sedentary individuals in primary healthcare is obvious . Long-term follow-up can determine the sustainability of the results , and can be used in a future cost-effectiveness analysis", "Purpose . We studied whether partial versus full subsidization and self versus other monitoring promote adherence to physician-prescribed exercise . Method . We r and omly assigned 132 participants to experimental conditions defined by two levels of subsidization and two types of monitoring . Physicians wrote prescriptions as referrals to an exercise facility . A computer recorded participants ' exercise for 12 weeks . A sponsoring medical organization paid half or all of the facility 's fees . Half of the participants kept records of workouts , and half reported workouts to research ers who telephoned them . Results . Fully subsidized patients averaged 21.41 workouts versus 16.67 workouts by partially subsidized patients ( p < .05 ) . Research er-monitored participants averaged 22.14 workouts versus 15.96 workouts by self-monitored participants ( p < .01 ) . Conclusions . Full subsidization and third-party monitoring increased exercise rates . These findings encourage use of both to enhance prescribed exercise rates and continued study of factors that contribute to the efficacy of prescribed exercise" ]

[ "24288164", "9516291" ]

[ "Employer attitudes towards the work inclusion of people with disability.", "Benefits and costs of supported employment from three perspectives" ]

[ "BACKGROUND This study examines the importance of work in life of people with disability and then focuses on employer attitudes towards these people . In the light of Stone and Colella 's model , the study examines the employer attitudes and the role of variables such as type of disability , employer experience in the hiring of persons with disabilities , the description of hypothetical hirees with disabilities , the ways in which employers evaluate work performance and social acceptability , and the work tasks that they consider appropriate for workers with disability . METHOD Eighty employers were r and omly assigned to st and ard condition ( c and i date s with disability were presented by referring to the disability they presented ) or positive condition ( c and i date s were presented with reference to their strengths ) . RESULTS It was found that the type of disability and its presentation influence employer attitudes . In addition , realistic and conventional tasks were considered appropriate for hirees with disabilities . CONCLUSIONS Implication s were discussed", "Administrators , consumers , and policy makers are increasingly interested in supported employment as a way of helping persons with severe mental illness get and keep competitive jobs . However , in an atmosphere of increased expectations for performance and declining public financing , administrators want to know the costs and benefits of different approaches before they reallocate scarce treatment or rehabilitative dollars . This article discusses the net benefits of two approaches to supported employment that were compared in a r and omized trial : Individual Placement and Support ( IPS ) and Group Skills Training ( GST ) . The authors analyze costs and benefits from societal , government , and consumer perspectives . Although a previous analysis showed that IPS participants were significantly more likely to find work , worked more hours , and had higher earnings , net benefits of the two programs were not significantly different . The authors also discuss some of the strengths and weaknesses of cost-benefit analysis in mental health care and suggest future directions for policy and research" ]

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[ "A comparison between chiropractic management and pain clinic management for chronic low-back pain in a national health service outpatient clinic.", "Multidisciplinary Group Rehabilitation Versus Individual Physiotherapy for Chronic Nonspecific Low Back Pain: A Randomized Trial", "United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care", "Preventing chronic back pain: evaluation of a theory-based cognitive-behavioural training programme for patients with subacute back pain.", "Evaluation of a Behavioral-medical Inpatient Rehabilitation Treatment Including Booster Sessions: A Randomized Controlled Study", "Chronic low-back pain: what does cognitive coping skills training add to operant behavioral treatment? Results of a randomized clinical trial.", "Randomized Clinical Trial of Lumbar Instrumented Fusion and Cognitive Intervention and Exercises in Patients with Chronic Low Back Pain and Disc Degeneration", "Effectiveness of back school for treatment of pain and functional disability in patients with chronic low back pain: a randomized controlled trial.", "Brief psychosocial education, not core stabilization, reduced incidence of low back pain: results from the Prevention of Low Back Pain in the Military (POLM) cluster randomized trial", "Sustainability of return to work in sick-listed employees with low-back pain. Two-year follow-up in a randomized clinical trial comparing multidisciplinary and brief intervention", "Can Chronic Disability Be Prevented?: A Randomized Trial of a Cognitive-Behavior Intervention and Two Forms of Information for Patients With Spinal Pain", "Mindfulness-based stress reduction for failed back surgery syndrome: a randomized controlled trial.", "The Impact of Physical Function and Pain on Work Status at 1-Year Follow-up in Patients With Back Pain", "Chronic low back pain: Physical training, graded activity with problem solving training, or both? The one-year post-treatment results of a randomized controlled trial", "Efficacy of classification-based cognitive functional therapy in patients with non-specific chronic low back pain: A randomized controlled trial", "Can It Be Predicted Which Patients With Chronic Low Back Pain Should Be Offered Tertiary Rehabilitation in a Functional Restoration Program?: A Search for Demographic, Socioeconomic, and Physical Predictors", "The Efficacy of a Short Education Program and a Short Physiotherapy Program for Treating Low Back Pain in Primary Care: A Cluster Randomized Trial", "Multidisciplinary Intensive Functional Restoration Versus Outpatient Active Physiotherapy in Chronic Low Back Pain: A Randomized Controlled Trial", "United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial: cost effectiveness of physical treatments for back pain in primary care", "Collaborative care for chronic pain in primary care: a cluster randomized trial.", "Psychosocial education improves low back pain beliefs: results from a cluster randomized clinical trial (NCT00373009) in a primary prevention setting", "Active rehabilitation for chronic low back pain: Cognitive-behavioral, physical, or both? First direct post-treatment results from a randomized controlled trial [ISRCTN22714229]", "Clinical effectiveness of an interdisciplinary pain management programme compared with standard inpatient rehabilitation in chronic pain: a naturalistic, prospective controlled cohort study.", "Management of low back pain in computer users: A multidisciplinary approach", "Function-centered rehabilitation increases work days in patients with nonacute nonspecific low back pain: 1-year results from a randomized controlled trial.", "Randomised controlled trial of integrated care to reduce disability from chronic low back pain in working and private life", "Cognitive Treatment of Illness Perceptions in Patients With Chronic Low Back Pain: A Randomized Controlled Trial", "Culturally sensitive group therapy for Turkish patients suffering from chronic pain: a randomised controlled intervention trial.", "A Participatory Return-to-Work Intervention for Temporary Agency Workers and Unemployed Workers Sick-Listed Due to Musculoskeletal Disorders: Results of a Randomized Controlled Trial", "Intensive group training protocol versus guideline physiotherapy for patients with chronic low back pain: a randomised controlled trial", "Does Early Intervention With a Light Mobilization Program Reduce Long-Term Sick Leave for Low Back Pain: A 3-Year Follow-up Study", "Prognosis and Course of Disability in Patients With Chronic Nonspecific Low Back Pain: A 5- and 12-Month Follow-up Cohort Study", "Exposure in vivo versus operant graded activity in chronic low back pain patients: Results of a randomized controlled trial", "The Effects of a Graded Activity Intervention for Low Back Pain in Occupational Health on Sick Leave, Functional Status and Pain: 12-Month Results of a Randomized Controlled Trial", "Participatory ergonomics to reduce exposure to psychosocial and physical risk factors for low back pain and neck pain: results of a cluster randomised controlled trial", "Three-year cost analysis of function-centred versus pain-centred inpatient rehabilitation in patients with chronic non-specific low back pain.", "Setting up a Pain Management Programme the Ayrshire Experience", "Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial", "Functional multidisciplinary rehabilitation versus outpatient physiotherapy for non specific low back pain: randomized controlled trial.", "Subacute and chronic, non-specific back and neck pain: cognitive-behavioural rehabilitation versus primary care. A randomized controlled trial", "The functional restoration approach to the treatment of chronic pain in patients with soft tissue and back injuries.", "Comparison of spinal fusion and nonoperative treatment in patients with chronic low back pain: long-term follow-up of three randomized controlled trials.", "Implementation of a multidisciplinary program for active duty personnel seeking care for low back pain in a U.S. Navy Medical Center: a feasibility study.", "The Effectiveness of High-Intensity Versus Low-Intensity Back Schools in an Occupational Setting: A Pragmatic Randomized Controlled Trial", "Effects of Functional Restoration Versus 3 Hours per Week Physical Therapy: A Randomized Controlled Study", "Surgical stabilisation of the spine compared with a programme of intensive rehabilitation for the management of patients with chronic low back pain: cost utility analysis based on a randomised controlled trial", "Management options of chronic low back pain. A randomized blinded clinical trial.", "One-Year Follow-Up in Employees Sick-Listed Because of Low Back Pain: Randomized Clinical Trial Comparing Multidisciplinary and Brief Intervention", "Subgroup analyses on return to work in sick-listed employees with low back pain in a randomised trial comparing brief and multidisciplinary intervention", "Exploring integrative medicine for back and neck pain - a pragmatic randomised clinical pilot trial", "Treatment of pregnancy-related pelvic girdle and/or low back pain after delivery design of a randomized clinical trial within a comprehensive prognostic cohort study [ISRCTN08477490]", "Daily functioning and self-management in patients with chronic low back pain after an intensive cognitive behavioral programme for pain management", "An educational approach based on a non-injury model compared with individual symptom-based physical training in chronic LBP. A pragmatic, randomised trial with a one-year follow-up", "Comparison of stratified primary care management for low back pain with current best practice (STarT Back): a randomised controlled trial", "High cost-benefit of early team-based biomedical and cognitive-behaviour intervention for long-term pain-related sickness absence.", "Predictive factors for successful clinical outcome 1 year after an intensive combined physical and psychological programme for chronic low back pain", "Long-Term Effect of a Combined Exercise and Motivational Program on the Level of Disability of Patients With Chronic Low Back Pain", "No difference in 9-year outcome in CLBP patients randomized to lumbar fusion versus cognitive intervention and exercises", "Cost-benefit and cost-effectiveness analysis of a disability prevention model for back pain management: a six year follow up study", "The comparative effectiveness of a multimodal program versus exercise alone for the secondary prevention of chronic low back pain and disability.", "Effect of integrated care for sick listed patients with chronic low back pain: economic evaluation alongside a randomised controlled trial", "The Effect of Back School Integrated with Core Strengthening in Patients with Chronic Low-Back Pain", "Change Factors Explaining Reductions of “Interference” in a Multidisciplinary and an Exercise Prevention Program for Low Back Pain", "The effectiveness of participatory ergonomics to prevent low-back and neck pain--results of a cluster randomized controlled trial.", "Early Intervention for the Management of Acute Low Back Pain: A Single-Blind Randomized Controlled Trial of Biopsychosocial Education, Manual Therapy, and Exercise", "Effectiveness and cost-effectiveness of adding a cognitive behavioral treatment to the rehabilitation of chronic low back pain.", "Patterns of sickness absence a decade after pain-related multidisciplinary rehabilitation", "Effect of a Long-lasting Multidisciplinary Program on Disability and Fear-Avoidance Behaviors in Patients With Chronic Low Back Pain: Results of a Randomized Controlled Trial", "Intensive Physical and Psychosocial Training Program for Patients with Chronic Low Back Pain; A Controlled Clinical Trial", "Reduction of pain catastrophizing mediates the outcome of both physical and cognitive-behavioral treatment in chronic low back pain.", "Health economic assessment of behavioural rehabilitation in chronic low back pain: a randomised clinical trial.", "Graded Activity for Low Back Pain in Occupational Health Care", "Functional Restoration versus Outpatient Physical Training in Chronic Low Back Pain: A Randomized Comparative Study", "[Reconditioning in groups: an effective programme for the rehabilitation of patients with low back pain?].", "No analgesic effect of ibuprofen or paracetamol vs placebo for hysterectomies.", "No difference in long-term trunk muscle strength, cross-sectional area, and density in patients with chronic low back pain 7 to 11 years after lumbar fusion versus cognitive intervention and exercises.", "Adding a physical exercise programme to brief intervention for low back pain patients did not increase return to work", "Psychological features and outcomes of the Back School treatment in patients with chronic non-specific low back pain. A randomized controlled study.", "Horticultural therapy for patients with chronic musculoskeletal pain: results of a pilot study.", "Comparison of a functional restoration program with active individual physical therapy for patients with chronic low back pain: a randomized controlled trial.", "Intermediate and Long-term Effects of a Standardized Back School for Inpatient Orthopedic Rehabilitation on Illness Knowledge and Self-management Behaviors: A Randomized Controlled Trial", "[Back school for patients with non-specific chronic low-back pain: benefits from the association of an exercise program with patient's education].", "Results of a Multidisciplinary Pain Management Program: A 6‐ and 12‐Month Follow‐up Study", "A Randomized Study of Back School in Women With Chronic Low Back Pain: Quality of Life at Three, Six, and Twelve Months Follow-up", "Intensive group training versus cognitive intervention in sub-acute low back pain: short-term results of a single-blind randomized controlled trial.", "Relative Cost-Effectiveness of Extensive and Light Multidisciplinary Treatment Programs Versus Treatment as Usual for Patients With Chronic Low Back Pain on Long-Term Sick Leave: Randomized Controlled Study", "Efficacy of perceptive rehabilitation in the treatment of chronic nonspecific low back pain through a new tool: a randomized clinical study", "Manipulative Therapy and Clinical Prediction Criteria in Treatment of Acute Nonspecific Low Back Pain", "Operant-behavioural and cognitive-behavioural treatment for chronic low back pain.", "Treatment of Chronic Low Back Pain: A Randomized, Clinical Trial Comparing Group-Based Multidisciplinary Biopsychosocial Rehabilitation and Intensive Individual Therapist-Assisted Back Muscle Strengthening Exercises", "Secondary Prevention of Work-Related Disability in Nonspecific Low Back Pain: Does Problem-Solving Therapy Help? A Randomized Clinical Trial", "Differences in outcome of a multidisciplinary treatment between subgroups of chronic low back pain patients defined using two multiaxial assessment instruments: the Multidimensional Pain Inventory and lumbar dynamometry", "A trial of an activating intervention for chronic back pain in primary care and physical therapy settings", "Treatment- and Cost-Effectiveness of Early Intervention for Acute Low-Back Pain Patients: A One-Year Prospective Study", "The effectiveness of graded activity for low back pain in occupational healthcare", "Cost-utility analysis of a three-month exercise programme vs usual care following multidisciplinary rehabilitation for chronic low back pain.", "Treatment outcome of chronic non-malignant pain patients managed in a Danish multidisciplinary pain centre compared to general practice: a randomised controlled trial", "Quality of life improved by multidisciplinary back school program in patıents with chronic non-specific low back pain: a single blind randomized controlled trial.", "A 3-year follow-up of a multidisciplinary rehabilitation programme for back and neck pain", "A prospective, randomized 5-year follow-up study of functional restoration in chronic low back pain patients", "The effectiveness of two active interventions compared to self-care advice in employees with non-acute low back symptoms: a randomised, controlled trial with a 4-year follow-up in the occupational health setting", "A controlled study on the outcome of inpatient and outpatient treatment of low back pain. Part I. Pain, disability, compliance, and reported treatment benefits three months after treatment.", "Comparison of short- and long-term outcomes for aggressive spine rehabilitation delivered two versus three times per week.", "Spouse-assisted training in pain coping skills and the outcome of multidisciplinary pain management for chronic low back pain treatment: a 1-year randomized controlled trial.", "[Assessment of the effectiveness of inpatient rehabilitation measures in patients with chronic low back pain: a prospective, randomized, controlled study].", "Efficiency and Costs of Medical Exercise Therapy, Conventional Physiotherapy, and Self‐Exercise in Patients With Chronic Low Back Pain: A Pragmatic, Randomized, Single‐Blinded, Controlled Trial With 1‐Year Follow‐Up", "Treatment of Chronic Low Back Pain: A Randomized Clinical Trial Comparing Multidisciplinary Group-based Rehabilitation Program and Oral Drug Treatment With Oral Drug Treatment Alone", "Early Intervention Options for Acute Low Back Pain Patients: A Randomized Clinical Trial with One-Year Follow-Up Outcomes", "Effects of Two Guideline Implementation Strategies on Patient Outcomes in Primary Care: A Cluster Randomized Controlled Trial", "Active treatment programs for patients with chronic low back pain: a prospective, randomized, observer-blinded study", "Treatment-based subgroups of low back pain: a guide to appraisal of research studies and a summary of current evidence.", "Predictors of functional outcome in patients with chronic low back pain undergoing back school, individual physiotherapy or spinal manipulation.", "Cost-Effectiveness of Two Self-Care Interventions to Reduce Disability Associated With Back Pain", "Incorporation of cognitive-behavioral treatment into the medical care of chronic low back patients: a controlled randomized study in German pain treatment centers.", "Behavioural rehabilitation of chronic low back pain: comparison of an operant treatment, an operant-cognitive treatment and an operant-respondent treatment.", "Comparison of three active therapies for chronic low back pain: results of a randomized clinical trial with one-year follow-up.", "\"Active back school\", prophylactic management for low back pain: three-year follow-up of a randomized, controlled trial.", "The Effects of Lifestyle Intervention for Hypertension on Low Back Pain: A Randomized Controlled Trial", "Two Psychological Interventions Are Effective in Severely Disabled, Chronic Back Pain Patients: A Randomised Controlled Trial", "Does Systematic Graded Exposure In Vivo Enhance Outcomes in Multidisciplinary Chronic Pain Management Groups?", "Group cognitive behavioural treatment for low-back pain in primary care: a randomised controlled trial and cost-effectiveness analysis", "Role of Physical Exercise in Low Back Pain Rehabilitation: A Randomized Controlled Trial of a Three-Month Exercise Program in Patients Who Have Completed Multidisciplinary Rehabilitation", "Comparative efficacy of two multimodal treatments on male and female sub-groups with low back pain (part II).", "Multidisciplinary intensive treatment for chronic low back pain: a randomized, prospective study.", "Cost-effectiveness of Combined Manipulation, Stabilizing Exercises, and Physician Consultation Compared to Physician Consultation Alone for Chronic Low Back Pain: A Prospective Randomized Trial With 2-Year Follow-up", "Surgery with disc prosthesis versus rehabilitation in patients with low back pain and degenerative disc: two year follow-up of randomised study", "Chronic Low Back Pain Rehabilitation Programs: A Study of the Optimum Duration of Treatment and a Comparison of Group and Individual Therapy", "TTM-based counselling in physiotherapy does not contribute to an increase of adherence to activity recommendations in older adults with chronic low back pain--a randomised controlled trial.", "The Effects of Cognitive-Behavioral and Physical Therapy Preventive Interventions on Pain-Related Sick Leave: A Randomized Controlled Trial", "Cost-Effectiveness and Cost-Benefit Analyses of a Multidisciplinary Intervention Compared With a Brief Intervention to Facilitate Return to Work in Sick-Listed Patients With Low Back Pain", "Multidisciplinary rehabilitation versus usual care for chronic low back pain in the community: effects on quality of life.", "A fitness programme for patients with chronic low back pain: 2-year follow-up of a randomised controlled trial", "Active back school: prophylactic management for low back pain. A randomized, controlled, 1-year follow-up study.", "Multidisciplinary Rehabilitation for Subacute Low Back Pain: Graded Activity or Workplace Intervention or Both?: A Randomized Controlled Trial", "Segmental mobility, disc height and patient-reported outcomes after surgery for degenerative disc disease: a prospective randomised trial comparing disc replacement and multidisciplinary rehabilitation.", "Improved Quality of Life, Working Ability, and Patient Satisfaction After a Pretreatment Multimodal Assessment Method in Patients With Mixed Chronic Muscular Pain: A Randomized-controlled Study", "The effectiveness of a functional training programme for patients with chronic low back pain – a pilot study", "Coordinated and Tailored Work Rehabilitation: A Randomized Controlled Trial with Economic Evaluation Undertaken with Workers on Sick Leave Due to Musculoskeletal Disorders", "Combined exercise and motivation program: effect on the compliance and level of disability of patients with chronic low back pain: a randomized controlled trial.", "Early Occupational Health Management of Patients with Back Pain: A Randomized Controlled Trial", "Coordination of Primary Health Care for Back Pain: A Randomized Controlled Trial", "More is not always better: Cost‐effectiveness analysis of combined, single behavioral and single physical rehabilitation programs for chronic low back pain", "Motivational enhancement therapy in addition to physical therapy improves motivational factors and treatment outcomes in people with low back pain: a randomized controlled trial.", "[Patients with chronic low back pain: the impact of psychosocial features].", "Individual work support for employed patients with low back pain: a randomized controlled pilot trial", "Cost effectiveness of two rehabilitation programmes for neck and back pain patients: A seven year follow-up", "A short goal-pursuit intervention to improve physical capacity: A randomized clinical trial in chronic back pain patients", "Work status and health-related quality of life following multimodal work hardening: a cluster randomised trial.", "[Intention-to-treat]." ]

[ "OBJECTIVES To compare outcomes in perception of pain and disability for a group of patients suffering with chronic low-back pain ( CLBP ) when managed in a hospital by either a regional pain clinic or a chiropractor . DESIGN The study was a pragmatic , r and omized , controlled trial . SETTING The trial was performed at a National Health Service ( NHS ) hospital outpatient clinic ( pain clinic ) in the United Kingdom . SUBJECTS AND INTERVENTIONS Patients with CLBP ( i.e. , symptom duration of > 12 weeks ) referred to a regional pain clinic ( outpatient hospital clinic ) were assessed and r and omized to either chiropractic or pain-clinic management for a period of 8 weeks . The study was pragmatic , allowing for normal treatment protocol s to be used . Treatment was administered in an NHS hospital setting . OUTCOME MEASURES The Rol and -Morris Disability Question naire ( RMDQ ) and Numerical Rating Scale were used to assess changes in perceived disability and pain . Mean values at weeks 0 , 2 , 4 , 6 , and 8 were calculated . The mean differences between week 0 and week 8 were compared across the two treatment groups using Student 's t-tests . Ninety-five percent ( 95 % ) confidence intervals ( CIs ) for the differences between groups were calculated . RESULTS R and omization placed 12 patients in the pain clinic and 18 in the chiropractic group , of which 11 and 16 , respectively , completed the trial . At 8 weeks , the mean improvement in RMDQ was 5.5 points greater for the chiropractic group ( decrease in disability by 5.9 ) than for the pain-clinic group ( 0.36 ) ( 95 % CI 2.0 points to 9.0 points ; p = 0.004 ) . Reduction in mean pain intensity at week 8 was 1.8 points greater for the chiropractic group than for the pain-clinic group ( p = 0.023 ) . CONCLUSIONS This study suggests that chiropractic management administered in an NHS setting may be effective for reducing levels of disability and perceived pain during the period of treatment for a sub population of patients with CLBP", "Study Design . A r and omized trial . Objective . To evaluate the effectiveness of a semi-intensive multidisciplinary rehabilitation for patients with chronic low back pain in an outpatient setting . Summary and Background Data . Systematic review s have shown that there is strong evidence that intensive multidisciplinary treatment ( > 100 hours ) , which includes functional restoration , improves function among chronic patients with low back pain , and moderate evidence that it reduces pain but contradictory evidence regarding improvement of working ability . However , there is paucity of data whether semi-intensive outpatient multidisciplinary rehabilitation in groups is more effective than individual physiotherapy . Material s and Methods . A total of 120 women employed as healthcare and social care professionals with nonspecific chronic low back pain were recruited from two occupational healthcare centers . The patients were r and omized into two intervention programs . Multidisciplinary rehabilitation ( n = 59 ) was conducted in groups and comprised of physical training , workplace interventions , back school , relaxation training , and cognitive-behavioral stress management methods for 70 hours . The individual physiotherapy ( n = 61 ) included physical exercise and passive treatment methods administered for 10 hours . Main outcome measures were : back pain and sciatic pain intensity , disability , sick leaves , healthcare consumption , symptoms of depression , and beliefs of working ability after 2 years . Results . There were no statistically significant differences between the two treatment groups in main outcome measures just after rehabilitation , at 6- , at 12- , or 24-month follow-up . In both intervention arms , however , the before- and -after comparison showed favorable effects , and the effects were still maintained at 2 years follow-up . Conclusions . The results of this study indicate that semilight outpatient multidisciplinary rehabilitation program for female chronic low back pain patients does not offer incremental benefits when compared with rehabilitation carried out by a physiotherapist having a cognitive-behavioral way of administering the treatment", "Abstract Objective To estimate the effect of adding exercise classes , spinal manipulation delivered in NHS or private premises , or manipulation followed by exercise to “ best care ” in general practice for patients consulting with back pain . Fig 1 Progress of the UK BEAM trial Design Pragmatic r and omised trial with factorial design . Setting 181 general practice s in Medical Research Council General Practice Research Framework ; 63 community setting s around 14 centres across the United Kingdom . Participants 1334 patients consulting their general practice s about low back pain . Main outcome measures Scores on the Rol and Morris disability question naire at three and 12 months , adjusted for centre and baseline scores . Results All groups improved over time . Exercise improved mean disability question naire scores at three months by 1.4 ( 95 % confidence interval 0.6 to 2.1 ) more than “ best care . ” For manipulation the additional improvement was 1.6 ( 0.8 to 2.3 ) at three months and 1.0 ( 0.2 to 1.8 ) at 12 months . For manipulation followed by exercise the additional improvement was 1.9 ( 1.2 to 2.6 ) at three months and 1.3 ( 0.5 to 2.1 ) at 12 months . No significant differences in outcome occurred between manipulation in NHS premises and in private premises . No serious adverse events occurred . Conclusions Relative to “ best care ” in general practice , manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months ; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months ; and exercise achieved a small benefit at three months but not 12 months", "OBJECTIVE For long-term treatment effects , patients with subacute back pain need to adhere to treatment recommendations beyond the prescribed exercise treatment . Adherence rates are as low as 30 % , so we developed a cognitive-behavioural training programme to enhance patients ' self-efficacy , maximise severity perceptions and reduce barrier perceptions . METHOD A 2 x 4 ( group x time ) repeated measurement design was applied . Forty-seven patients with non-specific , subacute back pain were r and omly assigned to a training group ( exercise treatment plus cognitive-behavioural training programme ) or a control group ( exercise treatment only ) . RESULTS Repeated measures ANOVA revealed significant main and interaction effects ; the training group reported enhanced self-efficacy and severity perceptions , reduced barrier perceptions , and self-reported that they exercised more often than the control group over time . However , no group differences regarding pain intensity emerged . CONCLUSION Our findings demonstrate that a short and inexpensive cognitive-behavioural training programme is an effective tool to enable back pain patients to follow treatment recommendations on a regular basis . PRACTICE IMPLICATION S The short and simple intervention can easily be conducted by personnel , other than psychologists , i.e. , physiotherapists", "Objectives The aim of this r and omized controlled study was to investigate whether additional psychologic interventions in the context of multidisciplinary inpatient pain treatment increases treatment efficacy compared with normal orthopedic rehabilitation . In addition , we aim ed to demonstrate the additional benefit of a subsequent maintenance program in further stabilizing treatment successes . Methods We r and omly assigned 363 chronic back pain patients to 1 of 3 treatment conditions : traditional orthopedic rehabilitation , multidisciplinary ( behavioral-medical ) rehabilitation alone , and multidisciplinary rehabilitation with subsequent booster sessions . Pain disability , depression , self-efficacy , health status , life satisfaction , and coping strategies were assessed at admission , discharge , and 12 months follow-up . The completion rate was 94 % . Results All 3 treatment conditions were effective in improving core outcome measures in chronic back pain patients in the short term . The results were almost maintained at follow-up ( small-to-medium within-group effect sizes ) . Significant advantages in favor of behavioral-medical interventions were found on almost all pain coping strategies and depression compared with traditional orthopedic rehabilitation . We found only slight advantages for the behavioral-medical treatment with subsequent booster sessions compared with the condition without a further maintenance program . Discussion The results concerning the efficacy of the multidisciplinary treatment are in accordance with former meta-analyses . Surprisingly , the findings suggest that the presented traditional orthopedic treatment was inherently very effective . The implication s of these findings are discussed with respect to the benefit of additional psychologic interventions and the benefit of aftercare approaches for chronic pain patients", "This study examined the supplemental value of a cognitive coping skills training when added to an operant-behavioral treatment for chronic low-back pain patients . The complete treatment package ( OPCO ) was compared with an operant program + group discussion ( OPDI ) and a waiting-list control ( WLC ) . After the WL period , the WLC patients received a less protocol ized operant program usually provided in Dutch rehabilitation centers ( OPUS ) . Regression analyses showed that , compared with WLC , both OPCO and OPDI led to less negative affect , higher activity tolerance , less pain behavior , and higher pain coping and pain control . At posttreatment , OPCO led to better pain coping and pain control than OPDI . Calculation of improvement rates revealed that OPCO and OPDI had significantly more improved patients than OPUS on all the dependent variables . The discussion includes findings regarding treatment credibility , compliance , and contamination bias", "Study Design . Single blind r and omized study . Objectives . To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration . Summary of Background Data . To the authors ’ best knowledge , only one r and omized study has evaluated the effectiveness of lumbar fusion . The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician . Patients and Methods . Sixty-four patients aged 25–60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4–L5 and /or L5–S1 at radiographic examination were r and omized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy , or cognitive intervention and exercises . The cognitive intervention consisted of a lecture to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The main outcome measure was the Oswestry Disability Index . Results . At the 1-year follow-up visit , 97 % of the patients , including 6 patients who had either not attended treatment or changed groups , were examined . The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery , compared with 42 to 30 after cognitive intervention and exercises . The mean difference between groups was 2.3 ( −6.7 to 11.4 ) ( P = 0.33 ) . Improvements inback pain , use of analgesics , emotional distress , life satisfaction , and return to work were not different . Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment , and lower limb pain was reduced more after surgery . The success rateaccording to an independent observer was 70 % after surgery and 76 % after cognitive intervention and exercises . The early complication rate in the surgical group was 18 % . Conclusion . The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration r and omized to cognitive intervention and exercises , or lumbar fusion", "OBJECTIVE To evaluate the effectiveness of the addition of back school to exercise and physical treatment modalities in relieving pain and improving the functional status of patients with chronic low back pain . DESIGN A r and omized controlled trial . PATIENTS A total of 146 patients with chronic low back pain were enrolled in the study . METHODS Subjects were divided into 2 groups : the back school group received exercise , physical treatment modalities and a back school programme ; and the control group received exercise and physical treatment modalities . Treatment efficacy was evaluated at the end of treatment and 3 months post-treatment , in terms of pain , measured with the Visual Analogue Scale , and functional status , measured with the Oswestry Low Back Pain Disability Question naire . RESULTS In both groups , Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire were significantly reduced after therapy ( p < 0.01 ) , but the difference between the scores at the end of treatment and 3 months post-treatment was not significant . There was a significant improvement in Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire in the back school group compared with the control group at the end of therapy and 3 months post-treatment ( p < 0.05 ) . CONCLUSION The addition of back school was more effective than exercise and physical treatment modalities alone in the treatment of patients with chronic low back pain", "Background Effective strategies for the primary prevention of low back pain ( LBP ) remain elusive with few large-scale clinical trials investigating exercise and education approaches . The purpose of this trial was to determine whether core stabilization alone or in combination with psychosocial education prevented incidence of low back pain in comparison to traditional lumbar exercise . Methods The Prevention of Low Back Pain in the Military study was a cluster r and omized clinical study with four intervention arms and a two-year follow-up . Participants were recruited from a military training setting from 2007 to 2008 . Soldiers in 20 consecutive companies were considered for eligibility ( n = 7,616 ) . Of those , 1,741 were ineligible and 1,550 were eligible but refused participation . For the 4,325 Soldiers enrolled with no previous history of LBP average age was 22.0 years ( SD = 4.2 ) and there were 3,082 males ( 71.3 % ) . Companies were r and omly assigned to receive traditional lumbar exercise , traditional lumbar exercise with psychosocial education , core stabilization exercise , or core stabilization with psychosocial education , The psychosocial education session occurred during one session and the exercise programs were done daily for 5 minutes over 12 weeks . The primary outcome for this trial was incidence of low back pain result ing in the seeking of health care . Results There were no adverse events reported . Evaluable patient analysis ( 4,147/4,325 provided data ) indicated no differences in low back incidence result ing in the seeking of health care between those receiving the traditional exercise and core stabilization exercise programs . However , brief psychosocial education prevented low back pain episodes regardless of the assigned exercise approach , result ing in a 3.3 % ( 95 % CI : 1.1 to 5.5 % ) decrease over two years ( numbers needed to treat ( NNT ) = 30.3 , 95 % CI = 18.2 to 90.9 ) . Conclusions Core stabilization has been advocated as preventative , but offered no such benefit when compared to traditional lumbar exercise in this trial . Instead , a brief psychosocial education program that reduced fear and threat of low back pain decreased incidence of low back pain result ing in the seeking of health care . Since this trial was conducted in a military setting , future studies are necessary to determine if these findings can be translated into civilian population s . Trial Registration NCT00373009 at Clinical Trials.gov - http:// clinical", "Background Sick-listed employees with low back pain had similar return to work ( RTW ) rates at one-year follow-up in a r and omized trial comparing two interventions , but the effects were modified by specific workplace related factors . The present study addressed the sustainability of the intervention effects by performing a two-year follow-up and by using different outcome measures . Methods A total of 351 employees sick-listed for 3–16 weeks due to LBP were recruited from their general practitioners and were r and omly allocated to a hospital-based brief or multidisciplinary intervention . Outcome measures were based on sick leave registered in a national data base of social and health-related benefits . RTW rates , RTW status , sick leave weeks and sick leave relapse were studied . Results During the two-year follow-up 80.0 % and 77.3 % had RTW for at least four weeks continuously , and the percentages with RTW at the 104th week were 61.1 % and 58.0 % in the brief and multidisciplinary intervention groups , respectively . At the 104th week 16.6 % and 18.8 % were on sick leave in the two groups , respectively , and about 12 % were employed in modified jobs or participated in job training . The number of weeks on sick leave in the first year was significantly lower in the brief intervention group ( median 14 weeks ) than in the multidisciplinary intervention group ( median 20 weeks ) , but during the second year the number of weeks on sick leave were not significantly different between intervention groups . Subgroups characterised by specific work related factors modified the effect of the intervention groups on RTW rates ( p = 0.017 ) . No difference in sick leave relapse was found between the intervention groups . Conclusion The effects of the brief and multidisciplinary interventions at the two-year follow-up were in general similar to the effects at one-year follow-up . Trial Registration Current Controlled Trials IS RCT", "Study Design . A r and omized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aim ed at preventing chronicity with two different forms of information . Objective . To develop a coping-oriented preventive intervention applicable in primary care , and to compare its impact with educational information . Summary of Background Data . Preventing long-term disability result ing from spinal pain has proved difficult . The information provided by health care professions and early interventions aim ed at preventing long-term disability may be important , but little scientific evidence exists concerning their use . Methods . A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research . The main focus was to prevent long-term disability by changing patients ’ behaviors and beliefs so they can cope better with their problems . Comparison groups received either a pamphlet shown earlier to have an effect , or a more extensive information package consisting of six installments . All the groups continued to receive treatment as usual in primary care . There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem . These patients were r and omized to the cognitive-behavioral intervention or one of the two information groups . Because the aim was to prevent long-term disability , the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use . Other variables were pain , function , fear-avoidance beliefs , and cognitions . Results . The comparison groups reported benefits . However , the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups ( relative risk , 9.3 ) . Participants in the cognitive-behavior group also reported a significant decrease in perceived risk . In addition , the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information , in which such use increased . All three groups tended to improve on the variables of pain , fear-avoidance , and cognitions . Conclusions . This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing . These findings underscore the significance of early interventions that specifically aim to prevent chronic problems . This approach might be applied to primary care setting", "CONTEXT Previous studies on the effect of mindfulness-based stress reduction ( MBSR ) therapy on chronic pain syndromes have been hampered by study design . OBJECTIVE To evaluate short-term efficacy of MBSR therapy for improving quality of life in adults with failed back surgery syndrome ( FBSS ) . DESIGN A single-center , prospect i ve , r and omized , single-blind , parallel-group clinical trial . PATIENTS AND SETTING Participants were recruited from a multidisciplinary spine and rehabilitation center in the greater Portl and , Maine , area . INTERVENTIONS AND MAIN OUTCOME MEASURES Patients were r and omly assigned at baseline to receive either MBSR therapy plus traditional therapy or traditional therapy alone for an 8-week period . Those receiving MBSR therapy completed weekly group sessions , and the control group continued with their traditional care as prescribed by their medical care providers . At study enrollment and at 12-week follow-up , all participants completed question naires on pain , quality of life , functionality , analgesic use , and sleep quality . Patients in the intervention group also completed question naires at 40-week follow-up . RESULTS The final analysis included 25 patients with FBSS ; 15 patients were in the MBSR intervention arm , and 10 in the control group . At 12-week follow-up , patients in the intervention arm had a mean 7.0-point increase ( on an 108-point [ corrected ] scale ) in pain acceptance and quality of life on the Chronic Pain Assessment Question naire , a mean 3.6-point [ corrected ] decrease ( on a 24-point scale ) in functional limitation on the Rol and -Morris Disability Question naire , a mean 6.9-point [ corrected ] reduction ( on a 30-point scale ) in pain level on the Summary Visual Analog Scale for Pain , a mean 1.5-point [ corrected ] reduction ( on a 4-point scale ) in frequency of use and potency of analgesics used for pain and recorded on logs , and a mean 2.0-point [ corrected ] increase ( on a 5-point scale ) in sleep quality on the abridged Pittsburgh Sleep Quality Inventory . These results were statistically and clinical ly significant compared to outcomes for the control group . CONCLUSION The results suggest that MBSR can be a useful clinical intervention for patients with FBSS", "Study Design . A r and omized , controlled trial . Objective . To examine the impact of physical function and pain on work status in patients who are long-term sick-listed because of back pain . Summary of Background Data . Sickness benefit is granted to a person who is incapable of working because of reduced functioning . Improved physical function and decrease of pain may be important in considering return to work . Methods . Physical performance ( five activities ) , disability , and pain ( self-reported question naires ) were assessed at baseline and at the 1-year follow-up evaluation in 117 patients r and omized to an intervention group ( n = 81 ) and a control group ( n = 36 ) . Results . At the 1-year follow-up evaluation , 50 % had returned to work . Statistically significant improvements were demonstrated from baseline to follow-up evaluation in returners to work : in the intervention group on all tests and in the control group on all except two performance tests . Improvement measures discriminated between returners and nonreturners to work in the intervention group on all physical tests and a pain test and in the control group on three physical tests and a pain test . In the intervention group , odds ratios for not having returned to work were high when test measures at follow-up indicated markedly impaired physical function and high pain ; in the control group , this appeared in high pain . Conclusions . Return to work was related to physical function and pain . More importance seemed to be attributed to physical performance in the intervention group than in the controls as a basis for returning patients to work", "& NA ; Several treatment principles for the reduction of chronic low back pain associated disability have been postulated . To examine whether a combination of a physical training and an operant‐behavioral grade d activity with problem solving training is more effective than either alone in the long‐term , a cluster r and omized controlled trial was conducted . In total 172 patients , 18–65 years of age , with chronic disabling non‐specific low back pain referred for rehabilitation treatment , were r and omized in clusters of four consecutive patients to 10 weeks of aerobic training and muscle strengthening of back extensors ( active physical treatment ; APT ) , 10 weeks of gradual assumption of patient relevant activities based on operant‐behavioral principles and problem solving training ( grade d activity plus problem solving training ; GAP ) , or APT combined with GAP ( combination treatment ; CT ) . The primary outcome was the Rol and Disability Question naire adjusted for centre of treatment , cluster , and baseline scores . Secondary outcomes were patients ’ main complaints , pain intensity , self‐perceived improvement , depression and six physical performance tasks . During the one‐year follow‐up , there were no significant differences between each single treatment and the combination treatment on the primary outcome , the Rol and Disability Question naire . Among multiple other comparisons , only one significant difference emerged , with GAP and APT showing higher self‐perceived improvement than CT . We conclude that the combination treatment integrating physical , grade d activity with problem solving training is not a better treatment option for patients with chronic low back pain", "Background : Non-specific chronic low back pain disorders have been proven resistant to change , and there is still a lack of clear evidence for one specific treatment intervention being superior to another . Methods : This r and omized controlled trial aim ed to investigate the efficacy of a behavioural approach to management , classification-based cognitive functional therapy , compared with traditional manual therapy and exercise . Linear mixed models were used to estimate the group differences in treatment effects . Primary outcomes at 12-month follow-up were Oswestry Disability Index and pain intensity , measured with numeric rating scale . Inclusion criteria were as follows : age between 18 and 65 years , diagnosed with non-specific chronic low back pain for > 3 months , localized pain from T12 to gluteal folds , provoked with postures , movement and activities . Oswestry Disability Index had to be > 14 % and pain intensity last 14 days > 2/10 . A total of 121 patients were r and omized to either classification-based cognitive functional therapy group n = 62 ) or manual therapy and exercise group ( n > = 59 ) . Results : The classification-based cognitive functional therapy group displayed significantly superior outcomes to the manual therapy and exercise group , both statistically ( p < 0.001 ) and clinical ly . For Oswestry Disability Index , the classification-based cognitive functional therapy group improved by 13.7 points , and the manual therapy and exercise group by 5.5 points . For pain intensity , the classification-based cognitive functional therapy improved by 3.2 points , and the manual therapy and exercise group by 1.5 points . Conclusions : The classification-based cognitive functional therapy produced superior outcomes for non-specific chronic low back pain compared with traditional manual therapy and exercise", "Study Design . A prospect i ve clinical trial was conducted that involved six groups of patients with chronic low back pain selected from a large cohort ( N = 816 ) . Objectives . To correlate pretreatment baseline variables with outcome parameters after treatment in a functional restoration program or in control programs , to identify possible factors predictive of the need for functional restoration . Summary of Background Data . Since the functional restoration program was first described , research has focused on identifying patients who will or will not benefit from such a program . The value of previous studies is limited , however , because predictive factors from a control group were not \" subtracted . \" Methods . Eight hundred sixteen patients with chronic low back disability were included . All had a structured medical examination , including various physical tests before participation in either a functional restoration program ( n = 621 ) or shorter \" control \" outpatient programs ( n = 144 ) . A smaller group of the cohort ( n = 51 ) had no treatment and served as a pure control group . Six groups were selected from the cohort : Three underwent an identical functional restoration program and three underwent different outpatient control programs . Several baseline demographic , physical , and socioeconomic variables were correlated to 1‐year outcome parameters . Results . Age , days of sick leave , connection to the work force , and back pain intensity , were significantly correlated to success 1 year after entry into the study in all groups , no matter what kind of treatment was administered . Back muscle endurance , sports activity , activity of daily living scores , and vibrations were of importance in some outcome parameters for success after functional restoration . Smoking was positively correlated to disability pension . Days of sick leave and , in functional restoration , ability to work were the only factors that were correlative with statistics for people who withdrew . Conclusions . Different factors can be identified as predictive of outcome in a functional restoration program , but most of these factors were also shown to predict success for shorter control outpatient programs or of no treatment", "Study Design . Cluster r and omized clinical trial . Objective . To assess the efficacy of a short education program and short physiotherapy program for treating low back pain ( LBP ) in primary care . Summary of Background Data . There is sparse evidence on the effectiveness of education and physiotherapy programs that are short enough to be feasible in primary care . Methods . Sixty-nine primary care physicians were r and omly assigned to 3 groups and recruited 348 patients consulting for LBP ; 265 ( 79.8 % ) were chronic . All patients received usual care , were given a booklet and received a consistent 15 minutes group talk on health education , which focused on healthy nutrition habits in the control group , and on active management for LBP in the “ education ” and “ education + physiotherapy ” groups . Additionally , in the “ education + physiotherapy ” group , patients were given a second booklet and a 15-minute group talk on postural hygiene , and 4 one-hour physiotherapy sessions of exercise and stretching which they were encouraged to keep practicing at home . The main outcome measure was improvement of LBP-related disability at 6 months . Patients ' assessment and data analyses were blinded . Results . During the 6-month follow-up period , improvement in the “ control ” group was negligible . Additional improvement in the “ education ” and “ education + physiotherapy ” groups was found for disability ( 2.0 and 2.2 Rol and Morris Question naire points , respectively ) , LBP ( 1.8 and 2.10 Visual Analogue Scale points ) , referred pain ( 1.3 and 1.6 Visual Analogue Scale points ) , catastrophizing ( 1.6 and 1.8 Coping Strategies Question naire points ) , physical quality of life ( 2.9 and 2.9 SF-12 points ) , and mental quality of life ( 3.7 and 5.1 SF-12 points ) . Conclusion . The addition of a short education program on active management to usual care in primary care leads to small but consistent improvements in disability , pain , and quality of life . The addition of a short physiotherapy program composed of education on postural hygiene and exercise intended to be continued at home , increases those improvements , although the magnitude of that increase is clinical ly irrelevant", "Study Design . R and omized parallel group comparative trial with a 1-year follow-up period . Objective . To compare in a population of patients with chronic low back pain , the effectiveness of a functional restoration program ( FRP ) , including intensive physical training and a multidisciplinary approach , with an outpatient active physiotherapy program at 1-year follow-up . Summary of Background Data . Controlled studies conducted in the United States and in Northern Europe showed a benefit of FRPs , especially on return to work . R and omized studies have compared these programs with st and ard care . A previously reported study presented the effectiveness at 6 months of both functional restoration and active physiotherapy , with a significantly greater reduction of sick-leave days for functional restoration . Methods . A total of 132 patients with low back pain were r and omized to either FRP ( 68 patients ) or active individual therapy ( 64 patients ) . One patient did not complete the FRP ; 19 patients were lost to follow-up ( 4 in the FRP group and 15 in the active individual treatment group ) . The number of sick-leave days in 2 years before the program was similar in both groups ( 180 ± 135.1 days in active individual treatment vs. 185 ± 149.8 days in FRP , P = 0.847 ) . Results . In both groups , at 1-year follow-up , intensity of pain , flexibility , trunk muscle endurance , Dallas daily activities and work and leisure scores , and number of sick-leave days were significantly improved compared with baseline . The number of sick-leave days was significantly lower in the FRP group . Conclusion . Both programs are efficient in reducing disability and sick-leave days . The FRP is significantly more effective in reducing sick-leave days . Further analysis is required to determine if this overweighs the difference in costs of both programs", "Abstract Objective To assess the cost effectiveness of adding spinal manipulation , exercise classes , or manipulation followed by exercise ( “ combined treatment ” ) to “ best care ” in general practice for patients consulting with low back pain . Design Stochastic cost utility analysis alongside pragmatic r and omised trial with factorial design . Setting 181 general practice s and 63 community setting s for physical treatments around 14 centres across the United Kingdom . Participants 1287 ( 96 % ) of 1334 trial participants . Main outcome measures Healthcare costs , quality adjusted life years ( QALYs ) , and cost per QALY over 12 months . Results Over one year , mean treatment costs relative to “ best care ” were £ 195 ( $ 360 ; € 279 ; 95 % credibility interval £ 85 to £ 308 ) for manipulation , £ 140 ( £ 3 to £ 278 ) for exercise , and £ 125 ( £ 21 to £ 228 ) for combined treatment . All three active treatments increased participants ' average QALYs compared with best care alone . Each extra QALY that combined treatment yielded relative to best care cost £ 3800 ; in economic terms it had an “ incremental cost effectiveness ratio ” of £ 3800 . Manipulation alone had a ratio of £ 8700 relative to combined treatment . If the NHS was prepared to pay at least £ 10 000 for each extra QALY ( lower than previous recommendations in the United Kingdom ) , manipulation alone would probably be the best strategy . If manipulation was not available , exercise would have an incremental cost effectiveness ratio of £ 8300 relative to best care . Conclusions Spinal manipulation is a cost effective addition to “ best care ” for back pain in general practice . Manipulation alone probably gives better value for money than manipulation followed by exercise", "CONTEXT Chronic pain is common in primary care patients and is associated with distress , disability , and increased health care use . OBJECTIVE To assess whether a collaborative intervention can improve chronic pain-related outcomes , including comorbid depression severity , in a Department of Veterans Affairs primary care setting . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized controlled trial of a collaborative care assistance with pain treatment intervention vs treatment as usual at 5 primary care clinics of 1 Department of Veterans Affairs Medical Center . Forty-two primary care clinicians were r and omized to the assistance with pain treatment intervention group or the treatment as usual group . The 401 patients had musculoskeletal pain diagnoses , moderate or greater pain intensity , and disability lasting 12 weeks or longer and were assigned to the same treatment groups as their clinicians . Recruitment occurred from January 2006 to January 2007 and follow-up concluded in January 2008 . INTERVENTION Assistance with pain treatment included a 2-session clinician education program , patient assessment , education and activation , symptom monitoring , feedback and recommendations to clinicians , and facilitation of specialty care . MAIN OUTCOME MEASURES Changes over 12 months in pain-related disability ( Rol and -Morris Disability Question naire , range of 0 - 24 ) , pain intensity ( Chronic Pain Grade [ CPG ] Pain Intensity subscale , range of 0 - 100 ) , and depression ( Patient Health Question naire 9 [ PHQ-9 ] , range of 0 - 27 ) , measured as beta coefficients ( difference in slopes in points per month ) . RESULTS Intervention patients had a mean ( SD ) of 10.6 ( 4.5 ) contacts with the assistance with pain treatment team . Compared with the patients receiving treatment as usual , intervention patients showed greater improvements in pain-related disability ( Rol and -Morris Disability Question naire beta , -0.101 [ 95 % confidence interval { CI } , -0.163 to -0.040 ] ; P = .004 and CPG Pain Intensity subscale beta , -0.270 [ 95 % CI , -0.480 to -0.061 ] ; P = .01 ) . Among patients with baseline depression ( PHQ-9 score > or = 10 ) , there was greater improvement in depression severity in patients receiving the intervention compared with patients receiving treatment as usual ( PHQ-9 beta , -0.177 [ 95 % CI , -0.295 to -0.060 ] ; P = .003 ) . The differences in scores between baseline and 12 months for the assistance with pain treatment intervention group and the treatment as usual group , respectively , were -1.4 vs -0.2 for the Rol and -Morris Disability Question naire , -4.7 vs -0.6 for the CPG Pain Intensity subscale , and -3.7 vs -1.2 for PHQ-9 . CONCLUSION The assistance with pain treatment collaborative intervention result ed in modest but statistically significant improvement in a variety of outcome measures . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00129480", "The general population has a pessimistic view of low back pain ( LBP ) , and evidence -based information has been used to positively influence LBP beliefs in previously reported mass media studies . However , there is a lack of r and omized trials investigating whether LBP beliefs can be modified in primary prevention setting s. This cluster r and omized clinical trial investigated the effect of an evidence -based psychosocial educational program ( PSEP ) on LBP beliefs for soldiers completing military training . A military setting was selected for this clinical trial , because LBP is a common cause of soldier disability . Companies of soldiers ( n = 3,792 ) were recruited , and cluster r and omized to receive a PSEP or no education ( control group , CG ) . The PSEP consisted of an interactive seminar , and soldiers were issued the Back Book for reference material . The primary outcome measure was the back beliefs question naire ( BBQ ) , which assesses inevitable consequences of and ability to cope with LBP . The BBQ was administered before r and omization and 12 weeks later . A linear mixed model was fitted for the BBQ at the 12-week follow-up , and a generalized linear mixed model was fitted for the dichotomous outcomes on BBQ change of greater than two points . Sensitivity analyses were performed to account for drop out . BBQ scores ( potential range : 9–45 ) improved significantly from baseline of 25.6 ± 5.7 ( mean ± SD ) to 26.9 ± 6.2 for those receiving the PSEP , while there was a significant decline from 26.1 ± 5.7 to 25.6 ± 6.0 for those in the CG . The adjusted mean BBQ score at follow-up for those receiving the PSEP was 1.49 points higher than those in the CG ( P < 0.0001 ) . The adjusted odds ratio of BBQ improvement of greater than two points for those receiving the PSEP was 1.51 ( 95 % CI = 1.22–1.86 ) times that of those in the CG . BBQ improvement was also mildly associated with race and college education . Sensitivity analyses suggested minimal influence of drop out . In conclusion , soldiers that received the PSEP had an improvement in their beliefs related to the inevitable consequences of and ability to cope with LBP . This is the first r and omized trial to show positive influence on LBP beliefs in a primary prevention setting , and these findings have potentially important public health implication s for prevention of LBP", "Background The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found", "OBJECTIVE To compare the effects of an interdisciplinary pain management programme with those of st and ard in-patient rehabilitation by comprehensive biopsychosocial self-- assessment . METHODS In this naturalistic prospect i ve controlled cohort study , 164 chronic pain patients who participated in the interdisciplinary pain programme and 143 who underwent st and ard rehabilitation were assessed using st and ardized instruments . Effect differences were compared bivariately and analysed by multivariate logistic regression to control for baseline differences in the outcome variables and confounders . RESULTS On entry into the clinic , the interdisciplinary pain programme patients were younger and showed significantly worse mental and psychosocial health than the st and ard rehabilitation patients . At discharge , the interdisciplinary pain programme patients reported greater improvement on pain ( multivariate p = 0.034 ) , social functioning ( bivariate p = 0.009 ) , and in trend in catastrophizing and ability to decrease pain . At the 6-month follow-up , the effects experienced by the st and ard rehabilitation group were higher on physical functioning , social functioning , anxiety , and life control ( multivariate p = 0.013 - 0.050 ) . CONCLUSION Intensive interdisciplinary rehabilitation with more behavioural therapies was accompanied by a greater improvement in patients who were severely affected by pain , compared with st and ard rehabilitation by the end of the stay , but not in the mid-term . Highly re source -consuming patients may benefit from subsequent , individually tailored outpatient care", "Background : Low back pain is a very common phenomenon in computer users . More than 80 % people using computers for more than 4 h complain of back pain . Objective : To compare the effectiveness of multidisciplinary treatment approach and conventional treatment approach amongst computer users . Material s and Methods : A prospect i ve interventional study was carried out at a private spine clinic amongst the computer users with the complaint of low back pain . The study participants were r and omly distributed in two groups . The first group comprised the study participants treated by conventional approach and the second group was treated by multidisciplinary approach . Primary outcomes analyzed were pain intensity , sick leave availed , and quality of life . Statistical analysis was done using proportions , unpaired “ t ” test , and Wilcoxon signed-rank test . Results : Totally 44 study participants were r and omly assigned to groups I and II , and each group had 22 study participants . Intensity of pain was reduced significantly in the group treated by multidisciplinary approach ( t = 5.718 ; P = 0.0001 ) . Similarly only 4 ( 19.19 % ) of the study participants of the group treated by multidisciplinary approach availed sick leave due to low back pain , while 14 ( 63.63 % ) study participants availed sick leave in the other group ( P = 0.02 ) . The quality of life amongst the study participants treated by multidisciplinary approach was significantly improved compared to the group treated by conventional approach ( t = 7.037 ; P = 0.0001 ) . Conclusion and Recommendation : The multidisciplinary treatment approach was better than the conventional treatment approach in low back pain cases when some factors like pain and quality of life were assessed . The multidisciplinary approach for treatment of low back pain should be promoted over conventional approach . Larger studies are required to confirm the findings in different setting", "OBJECTIVE To compare the effect of function-centered treatment ( FCT ) and pain-centered treatment ( PCT ) on the number of work days , permanent disability , and the unemployment rate . DESIGN R and omized controlled trial . SETTING Inpatient rehabilitation center . PARTICIPANTS Patients ( N=174 ; 79 % male ; mean age , 42 y ) with previous sick leave of 6 weeks or more . INTERVENTIONS FCT ( 4 h/d for 3 wk ) emphasized activity despite pain by using work simulation , strength , endurance , and cardiovascular training . PCT ( 2.5h/d for 3 wk ) emphasized pain reduction and included passive and active mobilization , stretching , strength training , and a 4-hour mini back school with education and exercise . Analysis was by intention to treat . MAIN OUTCOME MEASURES Work days , return to work , rate of patients receiving financial compensation for permanent disability , and unemployment rate . Effect sizes ( Cohen d ) were defined as small ( 0.2 - 0.5 ) , moderate ( 0.5 - 0.8 ) , and large ( > 0.8 ) . RESULTS After 1 year , the FCT group had significantly more work days ( mean , 118 ; median , 39.5 ; interquartile range [ IQR ] , 0 - 198 ) than the PCT group ( mean , 74 ; median , 0 ; IQR , 0 - 160 ; Mann-Whitney U test , P=.011 ) . The odds ratio of returning to work in the FCT group relative to the PCT group was 2.1 ( 95 % confidence interval , 1.1 - 3.9 ) . The differences in unemployment rates and in the numbers of patients receiving compensation for permanent disability were not significant . CONCLUSIONS FCT is more effective than PCT for increasing work days", "Objective To evaluate the effectiveness of an integrated care programme , combining a patient directed and a workplace directed intervention , for patients with chronic low back pain . Design Population based r and omised controlled trial . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) . Participants 134 adults aged 18 - 65 sick listed for at least 12 weeks owing to low back pain . Intervention Patients were r and omly assigned to usual care ( n=68 ) or integrated care ( n=66 ) . Integrated care consisted of a workplace intervention based on participatory ergonomics , involving a supervisor , and a grade d activity programme based on cognitive behavioural principles . Main outcome measures The primary outcome was the duration of time off work ( work disability ) due to low back pain until full sustainable return to work . Secondary outcome measures were intensity of pain and functional status . Results The median duration until sustainable return to work was 88 days in the integrated care group compared with 208 days in the usual care group ( P=0.003 ) . Integrated care was effective on return to work ( hazard ratio 1.9 , 95 % confidence interval 1.2 to 2.8 , P=0.004 ) . After 12 months , patients in the integrated care group improved significantly more on functional status compared with patients in the usual care group ( P=0.01 ) . Improvement of pain between the groups did not differ significantly . Conclusion The integrated care programme substantially reduced disability due to chronic low back pain in private and working life . Trial registration Current Controlled Trials IS RCT N28478651", "Background Illness perceptions have been shown to predict patient activities . Therefore , studies of the effectiveness of a targeted illness-perception intervention on chronic nonspecific low back pain ( CLBP ) are needed . Objective The purpose of this study was to compare the effectiveness of treatment of illness perceptions against a waiting list for patients with CLBP . Design This was a prospect ively registered r and omized controlled trial with an assessor blinded for group allocation . Setting The study was conducted in an outpatient rehabilitation clinic . Participants The participants were 156 patients ( 18–70 years of age ) with CLBP ( > 3 months ) . Intervention Patients were r and omly assigned to either a treatment group or to a waiting list ( control ) group . Trained physical therapists and occupational therapists delivered 10 to 14 one-hour treatment sessions according to the treatment protocol . Measurements The primary outcome measure was change in patient-relevant physical activities ( Patient-Specific Complaints question naire ) . The secondary outcome measures were changes in illness perceptions ( Illness Perceptions Question naire ) and generic physical activity level ( Quebec Back Pain Disability Scale ) . Measurements were taken at baseline ( 0 weeks ) and after treatment ( 18 weeks ) . Results A baseline-adjusted analysis of covariance showed that there were statistically significant differences between intervention and control groups at 18 weeks for the change in patient-relevant physical activities . This was a clinical ly relevant change ( 19.1 mm ) for the intervention group . Statistically significant differences were found for the majority of illness perception scales . There were no significant differences in generic physical activity levels . Limitations Longer-term effectiveness was not studied . Conclusions This first trial evaluating cognitive treatment of illness perceptions concerning CLBP showed statistically significant and clinical ly relevant improvements in patient-relevant physical activities at 18 weeks", "SUMMARY OF BACKGROUND DATA The incidence of chronic pain is higher among immigrants in Europe than among the native European population . Therapeutic interventions in this population are far less effective than in patients for whom these programmes were originally developed . OBJECTIVES In a r and omised trial , we investigated whether a cognitive behavioural treatment ( CBT ) programme supplemented with culturally sensitive aspects ( CsCBT ) improves pain intensity , pain disability and quality of life among immigrant patients , compared with a treatment of culturally sensitive exercise therapy ( CsET ) alone . Furthermore , we investigated whether healthcare costs would decrease . METHODS First-generation Turkish immigrants residing in Switzerl and ( 20 - 65 years of age ) who suffered from chronic pain were enrolled in the trial . Patients were r and omised to attend either CsCBT or CsET . The CsCBT intervention was based upon a manualised cognitive-behavioural group treatment programme for chronic pain patients and adapted to the needs of a Turkish immigrant population . The CsET intervention was based on principles of exercise therapy for treatment of nonspecific low back pain . RESULTS A total of 116 out patients were recruited between October 2004 and November 2006 . The intervention was completed by 89 patients ( 77 % ) . A total of 78 subjects ( 67 % ) completed follow-up , 12 months after the completion of the intervention programme . The intervention showed no effects in reducing pain , pain disability or quality of life . The analysis of healthcare utilisation yielded no intervention effect . CONCLUSIONS Cognitive behavioural intervention is feasible with immigrants with chronic disabling pain , but the evidence -based CBT programme , as well as exercise therapy supplemented with culturally sensitive aspects , showed no improvement", "Introduction Within the labour force workers without an employment contract represent a vulnerable group . In most cases , when sick-listed , these workers have no workplace/employer to return to . Therefore , the aim of this study was to evaluate the effectiveness on return-to-work of a participatory return-to-work program compared to usual care for unemployed workers and temporary agency workers , sick-listed due to musculoskeletal disorders . Methods The workers , sick-listed for 2–8 weeks due to musculoskeletal disorders , were r and omly allocated to the participatory return-to-work program ( n = 79 ) or to usual care ( n = 84 ) . The new program is a stepwise procedure aim ed at making a consensus-based return-to-work plan , with the possibility of a temporary ( therapeutic ) workplace . Outcomes were measured at baseline , 3 , 6 , 9 and 12 months . The primary outcome measure was time to sustainable first return-to-work . Secondary outcome measures were duration of sickness benefit , functional status , pain intensity , and perceived health . Results The median duration until sustainable first return-to-work was 161 days in the intervention group , compared to 299 days in the usual care group . The new return-to-work program result ed in a non-significant delay in RTW during the first 90 days , followed by a significant advantage in RTW rate after 90 days ( hazard ratio of 2.24 [ 95 % confidence interval 1.28–3.94 ] P = 0.005 ) . No significant differences were found for the measured secondary outcomes . Conclusions The newly developed participatory return-to-work program seems to be a promising intervention to facilitate work resumption and reduce work disability among temporary agency workers and unemployed workers , sick-listed due to musculoskeletal disorders", "Intensive group training using principles of grade d activity has been proven to be effective in occupational care for workers with chronic low back pain . Objective of the study was to compare the effects of an intensive group training protocol aim ed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain . The study was design ed as pragmatic r and omised controlled trial with a setup of 105 primary care physiotherapists in 49 practice s and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study . In the intensive group training protocol exercise therapy , back school and operant-conditioning behavioural principles are combined . Patients were treated during 10 individual sessions along 20 group sessions . Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain . Main outcome measures were functional disability ( Rol and Morris disability question naire ) , pain intensity , perceived recovery and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 and 52 weeks . Both an intention-to-treat analysis and a per- protocol analysis were performed . Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period , with one exception . After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group , but this difference was absent after 52 weeks . We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain", "Study Design . A r and omized clinical trial . Objectives . To evaluate long-term clinical and economical effects of a light mobilization program on the duration of sick leave for patients with subacute low back pain . Summary of Background Data . Twelve-month follow-up results from a previous study showed that early intervention with examination at a spine clinic , giving the patients information , reassurance , and encouragement to engage in physical activity as normal as possible had significant effect in reducing sick leave . At 12-month follow-up , 68.4 % in the intervention group were off sick leave , as compared with 56.4 % in the control group . Patients in this study were followed-up for a period of 3 years to investigate possible long-term effects . Material s and Methods . Four hundred fifty-seven patients placed on a sick list for 8 to 12 weeks for low back pain were r and omized into two groups : an intervention group ( n = 237 ) and a control group ( n = 220 ) . The intervention group was examined at a spine clinic and given information and advice to stay active . The control group was not examined at the clinic but was treated within the primary health care . Results . Over the 3 years of observation , the intervention group had significantly fewer days of sickness compensation ( average 125.7 d/person ) than the control group ( 169.6 d/person ) . This difference is mainly caused by a more rapid return to work during the first year . There was no significant difference for the second or third year . In particular , there is no increased risk for reoccurrence of illness from early return to work . At 6-month follow-up , patients in the intervention group were less likely to use bed rest and more likely to use stretching and walking to cope with their back pain compared with the control group . This effect diminished . At 12-month follow-up , the only significant difference between the groups was in the use of stretching . Economic returns of the intervention were calculated in terms of increases in the net present value of production for the society because of the reduction in number of days on sick leave . Net benefits accumulated over 3 years of treating the 237 patients in the intervention group amount to approximately $ 2,822 per person . Conclusions . For patients with subacute low back pain , a brief and simple early intervention with examination , information , reassurance , and encouragement to engage in physical activity as normal as possible had economic gains for the society . The effect occurred during the first year after intervention . There were no significant long-term effects of the intervention . The initial gain obtained during the first year does not lead to any increased costs or increased risks for reoccurrence of illness over the next 2 years", "Background Few data are available on the course of and predictors for disability in patients with chronic nonspecific low back pain ( CNSLBP ) . Objective The purpose of this study was to describe the course of disability and identify clinical ly important prognostic factors of low-back-pain – specific disability in patients with CNSLBP receiving multidisciplinary therapy . Design A prospect i ve cohort study was conducted . Methods A total of 1,760 patients with CNSLBP who received multidisciplinary therapy were evaluated for their course of disability and prognostic factors at baseline and at 2- , 5- , and 12-month follow-ups . Recovery was defined as 30 % reduction in low back pain – specific disability at follow-up compared with baseline and as absolute recovery if the score on the Quebec Back Pain Disability Scale ( QBPDS ) was ≤20 points at follow-up . Potential prognostic factors were identified using multivariable logistic regression analysis . Results Mean patient-reported disability scores on the QBPDS ranged from 51.7 ( SD=15.6 ) at baseline to 31.7 ( SD=15.2 ) , 31.1 ( SD=18.2 ) , and 29.1 ( SD=20.0 ) at 2 , 5 , and 12 months , respectively . The prognostic factors identified for recovery at 5 and 12 months were younger age and high scores on disability and on the 36-Item Short-Form Health Survey ( SF-36 ) ( Physical and Mental Component Summaries ) at baseline . In addition , at 5-month follow-up , a shorter duration of complaints was a positive predictor , and having no comorbidity and less pain at baseline were additional predictors at 12-month follow-up . Limitations Missing values at 5- and 12-month follow-ups were 11.1 % and 45.2 % , respectively . Conclusion After multidisciplinary treatment , the course of disability in patients with CNSLBP continued to decline over a 12-month period . At 5- and 12-month follow-ups , prognostic factors were identified for a clinical ly relevant decrease in disability scores on the QBPDS", "& NA ; Since pain‐related fear may contribute to the development and maintenance of chronic low back pain ( CLBP ) , an exposure in vivo treatment ( EXP ) was developed for CLBP patients . We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant grade d activity ( GA ) directly and 6 months post‐treatment in a multi‐centre r and omized controlled trial . In total , 85 patients suffering from disabling non‐specific CLBP reporting at least moderate pain‐related fear were r and omly allocated to EXP or GA . It was demonstrated that EXP , despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities , was equally effective as GA in improving functional disability and main complaints , although the group difference almost reached statistical significance favouring EXP . Both treatment conditions did not differ in pain intensity and daily activity levels either . Nor was EXP superior to GA in the subgroup of highly fearful patients . Irrespective of treatment , approximately half the patients reported clinical ly relevant improvements in main complaints and functional disability , although for the latter outcome the group difference was almost significant favouring EXP . Furthermore , the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities . In sum , this study demonstrates that up to 6 months after treatment EXP is an effective treatment , but not more effective than GA , in moderately to highly fearful CLBP patients , although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established . Possible explanations for these findings are discussed", "Introduction : Behaviorally oriented grade d activity interventions have been suggested for sick-listed workers with low back pain on return to work , but have not been extensively evaluated . Methods : One hundred and thirty-four workers were r and omly assigned to either a grade d activity intervention ( n = 67 ) or usual care ( n = 67 ) and followed-up for 12 months . Results : The grade d activity group returned back to work faster with a median of 54 days compared to 67 days in the usual care group . The grade d activity intervention was more effective after approximately 50 days post-r and omization ( HRR = 1.9 , CI = 1.2–3.1 , p = 0.01 ) . Differences between the groups in number of recurrent episodes , total number of days of sick leave due to low back pain , and total number of days of sick leave due to all diagnoses , were in favor of the grade d activity group , although not statistically significant . No effects of the grade d activity intervention were found for functional status or pain . Conclusion : Grade d activity intervention is a valuable strategy to enhance short-term return to work outcomes", "Objectives This study investigated the effectiveness of the Stay@Work participatory ergonomics programme to reduce workers′ exposure to psychosocial and physical risk factors . Methods 37 departments ( n=3047 workers ) from four Dutch companies participated in this cluster r and omised controlled trial ; 19 ( n=1472 workers ) were r and omised to an intervention group ( participatory ergonomics ) and 18 ( n=1575 workers ) to a control group ( no participatory ergonomics ) . During a 6 h meeting guided by an ergonomist , working groups devised ergonomic measures to reduce psychosocial and physical workload and implemented them within 3 months in their departments . Data on psychosocial and physical risk factors for low back pain and neck pain were collected at baseline and after 6 months . Psychosocial risk factors were measured using the Job Content Question naire and physical risk factors using the Dutch Musculoskeletal Question naire . Intervention effects were studied using multilevel analysis . Results Intervention group workers significantly increased on decision latitude ( 0.29 points ; 95 % CI 0.07 to 0.52 ) and decision authority ( 0.16 points ; 95 % CI 0.04 to 0.28 ) compared to control workers . However , exposure to awkward trunk working postures significantly increased in the intervention group ( OR 1.86 ; 95 % CI 1.15 to 3.01 ) compared to the control group . No significant differences between the intervention and control group were found for the remaining risk factors . After 6 months , loss to follow-up was 35 % in the intervention group and 29 % in the control group . Conclusion Participatory ergonomics was not effective in reducing exposure to psychosocial and physical risk factors for low back pain and neck pain among a large group of workers . Trial registration IS RCT N27472278", "OBJECTIVE To compare costs of function- and pain-centred inpatient treatment in patients with chronic low back pain over 3 years of follow-up . DESIGN Cost analysis of a r and omized controlled trial . PATIENTS A total of 174 patients with chronic low back pain were r and omized to function- or pain-centred inpatient treatment . METHODS Data on direct and indirect costs were gathered by question naires sent to patients , health insurance providers , employers , and the Swiss Disability Insurance Company . RESULTS There was a non-significant difference in total medical costs after 3 years ' follow-up . Total costs were 77,305 Euros in the function-centred inpatient treatment group and 83,085 Euros in the pain-centred inpatient treatment group . Likewise , indirect costs after 3 years from lost work days were non-significantly lower in the function-centred in-patient treatment group ( 6354 Euros ; 95 % confidence interval -20,892 , 8392 ) and direct medical costs were non-significantly higher in the function-centred inpatient treatment group ( 574 Euros ; 95 % confidence interval -862 , 2011 ) . CONCLUSION The total costs of function-centred and pain-centred inpatient treatment were similar over the whole 3-year follow-up", "A controlled trial of an outpatient cognitive behavioural pain management programme for sufferers of non-cancer chronic pain is described . A multidisciplinary team set up a programme of ten half day sessions for groups of ten to fourteen patients aim ing to improve activity levels and control over pain ; to reduce maladaptive pain behaviours and drug intake ; to mitigate negative mood ; to modify unhelpful beliefs and to maintain treatment gains by operant and cognitive methods . Self report question naires were employed before and six weeks , six months and one year after the programme . Fifty-eight patients entered the study group and 39 patients completed the programme and initial follow up with further attrition in long term follow up . There were no changes in the waiting list control group of twelve subjects but the study group made significant short and long term improvements in pain severity , activity levels , mood , coping and experienced fewer catastrophizing thoughts", "Abstract Objectives To assess the clinical effectiveness of surgical stabilisation ( spinal fusion ) compared with intensive rehabilitation for patients with chronic low back pain . Design Multicentre r and omised controlled trial . Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom . Participants 349 participants aged 18 - 55 with chronic low back pain of at least one year 's duration who were considered c and i date s for spinal fusion . Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy . Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after r and omisation . The SF-36 instrument was used as a secondary outcome measure . Results 176 participants were assigned to surgery and 173 to rehabilitation . 284 ( 81 % ) provided follow-up data at 24 months . The mean Oswestry disability index changed favourably from 46.5 ( SD 14.6 ) to 34.0 ( SD 21.1 ) in the surgery group and from 44.8 ( SD14.8 ) to 36.1 ( SD 20.6 ) in the rehabilitation group . The estimated mean difference between the groups was –4.1 ( 95 % confidence interval –8.1 to –0.1 , P = 0.045 ) in favour of surgery . No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures . Conclusions Both groups reported reductions in disability during two years of follow-up , possibly unrelated to the interventions . The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference , and the potential risk and additional cost of surgery also need to be considered . No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation", "INTRODUCTION In recent decades the treatment of non-specific low back pain has turned to active modalities , some of which were based on cognitive-behavioural principles . Non-r and omised studies clearly favour functional multidisciplinary rehabilitation over outpatient physiotherapy . However , systematic review s and meta- analysis provide contradictory evidence regarding the effects on return to work and functional status . The aim of the present r and omised study was to compare long-term functional and work status after 3-week functional multidisciplinary rehabilitation or 18 supervised outpatient physiotherapy sessions . METHODS 109 patients with non-specific low back pain were r and omised to either a 3-week functional multidisciplinary rehabilitation programme , including physical and ergonomic training , psychological pain management , back school and information , or 18 sessions of active outpatient physiotherapy over 9 weeks . Primary outcomes were functional disability ( Oswestry ) and work status . Secondary outcomes were lifting capacity ( Spinal Function Sort and PILE test ) , lumbar range-of-motion ( modified-modified Schöber and fingertip-to-floor tests ) , trunk muscle endurance ( Shirado and Biering-Sörensen tests ) and aerobic capacity ( modified Bruce test ) . RESULTS Oswestry disability index was improved to a significantly greater extent after functional multidisciplinary rehabilitation compared to outpatient physiotherapy at follow-up of 9 weeks ( P = 0.012 ) , 9 months ( P = 0.023 ) and 12 months ( P = 0.011 ) . Work status was significantly improved after functional multidisciplinary rehabilitation only ( P = 0.012 ) , result ing in a significant difference compared to outpatient physiotherapy at 12 months ' follow-up ( P = 0.012 ) . Secondary outcome results were more contrasted . CONCLUSIONS Functional multidisciplinary rehabilitation was better than outpatient physiotherapy in improving functional and work status . From an economic point of view , these results should be backed up by a cost-effectiveness study", "Background In the industrial world , non-specific back and neck pain ( BNP ) is the largest diagnostic group underlying sick-listing . For patients with subacute and chronic (= full-time sick-listed for 43 – 84 and 85 – 730 days , respectively ) BNP , cognitive-behavioural rehabilitation was compared with primary care . The specific aim was to answer the question : within an 18-month follow-up , will the outcomes differ in respect of sick-listing and number of health-care visits ? Methods After stratification by age ( ≤ 44/≥ 45 years ) and subacute/chronic BNP , 125 Swedish primary -care patients were r and omly allocated to cognitive-behavioural rehabilitation ( rehabilitation group ) or continued primary care ( primary -care group ) . Outcome measures were Return-to-work share ( percentage ) and Return-to-work chance ( hazard ratios ) over 18 months , Net days ( crude sick-listing days × degree ) , and the number of Visits ( to physicians , physiotherapists etc . ) over 18 months and the three component six-month periods . Descriptive statistics , Cox regression and mixed-linear models were used . Results All patients : Return-to-work share and Return-to-work chance were equivalent between the groups . Net days and Visits were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods ( p < .05 ) . Subacute patients : Return-to-work share was equivalent . Return-to-work chance was significantly greater for the rehabilitation group ( hazard ratio 3.5 [ 95%CI1.001 – 12.2 ] ) . Net days were equivalent over 18 months but decreased significantly more rapidly for the rehabilitation group over the six-month periods and there were 31 days fewer in the third period . Visits showed similar though non-significant differences and there were half as many in the third period . Chronic patients : Return-to-work share , Return-to-work chance and Net days were equivalent . Visits were equivalent over 18 months but tended to decrease more rapidly for the rehabilitation group and there were half as many in the third period ( non-significant ) . Conclusion The results were equivalent over 18 months . However , there were indications that cognitive-behavioural rehabilitation in the longer run might be superior to primary care . For subacute BNP , it might be superior in terms of sick-listing and health-care visits ; for chronic BNP , in terms of health-care visits only . More conclusive results concerning this possible long-term effect might require a longer follow-up . Trial registration NCT00488735", "A prospect i ve r and omized study of 542 injured workers with continuing pain compared 271 workers who were treated at either one of two clinics that provided functional restoration with a control group of 271 subjects . Chronic pain was caused by low back injury in 78 % of patients ; 79 % of those treated were at work 12 months after completion of treatment compared with 78 % of the control subjects . When the patients were divided into subsets , based on the accident date and followed monthly , the duration of absence from work , the compensation costs , the disability award costs , and the total costs were less for those treated than the control subjects , but these were not statistically significant . Using the difference in total costs as a measure of relative success , back injuries had better results than other injuries in this study", "BACKGROUND CONTEXT Chronic low back pain ( cLBP ) represents a major challenge to our health care systems . The relative efficacy of surgery over nonoperative treatment for the treatment of cLBP remains controversial , and little is known of the long-term comparative outcomes . PURPOSE To compare the clinical outcome at long-term follow-up ( LTFU ) of patients who were r and omized with either spinal fusion or multidisciplinary cognitive-behavioral and exercise rehabilitation for cLBP . STUDY DESIGN / SETTING Long-term clinical follow-up of three multicenter r and omized controlled trials ( RCTs ) of surgery ( instrumented or noninstrumented fusion , stabilization ) versus nonoperative treatment ( multidisciplinary cognitive-behavioral and exercise rehabilitation ) in Norway and the United Kingdom . PATIENT SAMPLE A total of 473 patients with cLBP of at least 1 year 's duration who were all considered c and i date s for spinal fusion . OUTCOME MEASURES The primary outcome was the Oswestry Disability Index ( ODIv2.1a for the United Kingdom and ODIv1 for Norway ) score measured at LTFU . Secondary outcomes included visual analog scale ( VAS ) pain intensity , pain frequency , pain medication use , work status , EuroQol VAS for health-related quality of life , satisfaction with care , and global treatment outcome at LTFU . METHODS Patients who consented to LTFU ( average 11.4 [ range 8 - 15 ] years after the initial treatment ) completed the outcome question naires . RESULTS Of 473 enrolled patients , 261 ( 55 % ) completed LTFU , 140/242 patients r and omized to receive surgery and 121/231 r and omized to receive multidisciplinary cognitive-behavioral and exercise rehabilitation . The intention-to-treat analysis showed no statistically or clinical ly significant differences between treatment groups for ODI scores at LTFU ( adjusted for baseline ODI , previous surgery , duration of LBP , sex , age , and smoking habit ) : the mean adjusted treatment effect of fusion was -0.7 points on the 0 - 100 ODI scale ( 95 % confidence interval [ CI ] , -5.5 to 4.2 ) . An as-treated analysis similarly demonstrated no advantage of surgery ( treatment effect , -0.8 points on the ODI ( 95 % CI , -5.9 to 4.3 ) . The results for the secondary outcomes were largely consistent with those of the ODI , showing no relevant group differences . CONCLUSIONS After an average of 11 years follow-up , there was no difference in patient self-rated outcomes between fusion and multidisciplinary cognitive-behavioral and exercise rehabilitation for cLBP . The results suggest that , given the increased risks of surgery and the lack of deterioration in nonoperative outcomes over time , the use of lumbar fusion in cLBP patients should not be favored in health care systems where multidisciplinary cognitive-behavioral and exercise rehabilitation programmes are available", "The aim of the pilot study was to evaluate a multidisciplinary program for nonspecific low back pain ( NSLBP ) at a major U.S. Navy base . In this single blinded r and omized clinical trial , subjects were drawn from a larger , prospect i ve cohort of active duty service members seeking care for NSLBP pain at a U.S. Navy Branch Medical Clinic . Outcome measures included return to work , self-reported pain , function , and psychological distress . Subjects were r and omly allocated to one of two study arms : a multidisciplinary reconditioning program or the current st and ard of care for low back pain . The intervention lasted 4 weeks with a 12-week follow-up . Thirty-three subjects were enrolled . Subjects allocated to multidisciplinary care reported significantly lower perceived disability ( p = 0.014 ) and less pain than those allocated to usual care at the end of the intervention period . All subjects returned to their usual duty following the conclusion of the intervention . The implementation of the intervention program was successful . Subjects in the multidisciplinary program showed a clinical ly significant improvement in the perception of disability compared to the usual care group . This is an important finding since perception of disability is associated with long-term functional outcome", "Study Design . R and omized controlled trial . Objectives . To compare high- and low-intensity back schools with usual care in occupational health care . Summary of Background Data . The content and intensity of back schools vary widely and the method ologic quality of r and omized controlled trials is generally weak . Until now , no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain . Methods . Workers ( n = 299 ) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and r and omly assigned to a high-intensity back school , a low-intensity back school , or care as usual . Outcome measures were days until return to work , total days of sick-leave , pain , functional status , kinesiophobia , and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up . Principal analyses were performed according to the intention-to-treat principle . Results . We r and omly allocated 299 workers . Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school , with hazard ratios of 1.4 ( P = 0.06 ) and 1.3 ( P = 0.09 ) , respectively . The comparison between high-intensity back school and usual care result ed in a hazard ratio of 1.0 ( P = 0.83 ) . The median number of sick-leave days was 68 , 75 , and 85 in the low-intensity back school , usual care , and high-intensity back school , respectively . Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school . No substantial differences on pain and perceived recovery were found between groups . Conclusions . The low-intensity back school was most effective in reducing work absence , functional disability , and kinesiophobia , and more workers in this group scored a higher perceived recovery during the 6-month follow-up", "Study Design . R and omized parallel-group comparative trial with a 6-month follow-up period . Objective . To compare , in chronic low back pain patients , the effectiveness of a functional restoration program , including intensive physical training , occupational therapy , and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks . Summary of Background Data . Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain , especially on return to work . R and omized Canadian and European trials had less favorable results . In France , there has been up to now no r and omized study . Controlled studies suggested a positive effect of functional restoration programs . Methods . Eighty-six patients with low back pain were r and omized to either the functional restoration ( 44 patients ) or the active individual therapy ( 42 patients ) program . One person in each group never started the program . Two patients did not complete the functional restoration program , and one was lost to follow-up at 6 months . The mean number of sick-leave days in the 2 previous years was 6 months . Results . After adjustment on the variable ≪ workplace enrolled in an ergonomic program ≫ , the mean number of sick-leave days was significantly lower in the functional restoration group . Physical criteria and treatment appreciation were also better . There was no significant difference in the intensity of pain , the quality of life and functional indexes , the psychological characteristics , the number of contacts with the medical system , and the drug intake . Conclusions . This study demonstrates the effectiveness of a functional restoration program on important outcome measures , such as sick leave , in a country that has a social system that protects people facing difficultiesat work", "Abstract Objective To determine whether , from a health provider and patient perspective , surgical stabilisation of the spine is cost effective when compared with an intensive programme of rehabilitation in patients with chronic low back pain . Design Economic evaluation alongside a pragmatic r and omised controlled trial . Setting Secondary care . Participants 349 patients r and omised to surgery ( n = 176 ) or to an intensive rehabilitation programme ( n = 173 ) from 15 centres across the United Kingdom between June 1996 and February 2002 . Main outcome measures Costs related to back pain and incurred by the NHS and patients up to 24 months after r and omisation . Return to paid employment and total hours worked . Patient utility as estimated by using the EuroQol EQ-5D question naire at several time points and used to calculate quality adjusted life years ( QALYs ) . Cost effectiveness was expressed as an incremental cost per QALY . Results At two years , 38 patients r and omised to rehabilitation had received rehabilitation and surgery whereas just seven surgery patients had received both treatments . The mean total cost per patient was estimated to be £ 7830 ( SD £ 5202 ) in the surgery group and £ 4526 ( SD £ 4155 ) in the intensive rehabilitation arm , a significant difference of £ 3304 ( 95 % confidence interval £ 2317 to £ 4291 ) . Mean QALYs over the trial period were 1.004 ( SD 0.405 ) in the surgery group and 0.936 ( SD 0.431 ) in the intensive rehabilitation group , giving a non-significant difference of 0.068 ( –0.020 to 0.156 ) . The incremental cost effectiveness ratio was estimated to be £ 48 588 per QALY gained ( –£279 883 to £ 372 406 ) . Conclusion Two year follow-up data show that surgical stabilisation of the spine may not be a cost effective use of scarce healthcare re sources . However , sensitivity analyses show that this could change — for example , if the proportion of rehabilitation patients requiring subsequent surgery continues to increase", "OBJECTIVE To compare efficacies of 2 active programs in the management of chronic low back pain ( CLBP ) . METHODS This prospect i ve , stratified , r and omized single-blinded controlled study was conducted in the Department of Rehabilitation Medicine , King Abdullah University Hospital , Irbid , Jordan , between February and December 2010 . A total of 100 patients were r and omized to either 6-weeks of multidisciplinary rehabilitation ( group A ) or therapist-assisted exercise ( group B ) . At baseline and 6 weeks , the visual analogue scale ( VAS ) pain score was estimated , as a primary outcome measure . McGill pain score , Oswestry Disability Index ( ODI ) , trunk forward flexion and extension , left and right lateral bending , were applied before and after treatment and were employed as secondary outcome measures . RESULTS All outcome measures significantly improved in group A after treatment , compared with group B. The VAS , McGill , ODI scores , left and right lateral bending decreased significantly , whereas forward and backward bending increased . A significant number of patients returned to work in group A at the end of 6 weeks , compared with group B. These effects were maintained over 12 and 24 weeks of follow-up . CONCLUSION Multidisciplinary rehabilitation improved functional indices and pain scale scores in group A compared with B. This would be an effective strategy in CLBP management", "Study Design . R and omized clinical trial comparing two interventions in employees sick-listed 3 to 16 weeks because of low back pain ( LBP ) . Objective . To compare 1-year return to work ( RTW ) , pain , disability and physical and mental health dimensions in subjects offered a hospital-based multidisciplinary intervention or a brief intervention . Summary of Background Data . Previous studies in sick-listed employees with LBP have indicated efficacy of both brief and more comprehensive multidisciplinary interventions . However , it remains unknown , which is the more effective , and which elements are instrumental in furthering RTW , and improving health . Methods . The brief intervention comprised clinical examination and advice offered by a rehabilitation physician and a physiotherapist . In the multidisciplinary intervention , this intervention was supplemented with the expertise of a team and the assignment of a case manager who drew up a rehabilitation plan in collaboration with the patient and the multidisciplinary team . One-year RTW was estimated by data from a comprehensive national data base of social transfer payments . Question naires were used to obtain baseline and 1-year data on Rol and Morris disability score , LBP Rating Scale , SF36 , and fear-avoidance . Results . A total of 351 patients were included and r and omized and 344 ( 98 % ) patients participated in all the consultations according to the study protocol . RTW was achieved by 125 ( 71.0 % ) participants in the multidisciplinary and 133 ( 76.0 % ) participants in the brief intervention group . The hazard ratio was 0.84 after adjustment for sex , age , smoking , compensation cl aims , disability score , and diagnosis ( 95 % confidence interval [ CI ] : 0.65–1.08,P = 0.18 ) . Multiple linear regression analysis displayed no differences in secondary outcomes , except for the mental health score ( SF36 ) , which was a little higher in the multidisciplinary intervention group than in the brief intervention group . Conclusion . Hospital-based multidisciplinary intervention may be no better than brief intervention to increase RTW and improve health in sick-listed employees with low back pain", "Background Multidisciplinary intervention is recommended for rehabilitation of employees sick-listed for 4 - 12 weeks due to low back pain ( LBP ) . However , comparison of a brief and a multidisciplinary intervention in a r and omised comparative trial of sick-listed employees showed similar return to work ( RTW ) rates in the two groups . The aim of the present study was to identify subgroups , primarily defined by work-related baseline factors that would benefit more from the multidisciplinary intervention than from the brief intervention . Methods A total of 351 employees sick-listed for 3 - 16 weeks due to LBP were recruited from their general practitioners . They received a brief or a multidisciplinary intervention . Both interventions comprised clinical examination and advice by a rehabilitation doctor and a physiotherapist . The multidisciplinary intervention also comprised assignment of a case manager , who made a rehabilitation plan in collaboration with the patient and a multidisciplinary team . Using data from a national data base , we defined RTW as no sickness compensation benefit disbursement for four consecutive weeks within the first year after the intervention . At the first interview in the clinic , it was ensured that sick leave was primarily due to low back problems . Question naires were used to obtain data on health , disability , demographic and workplace-related factors . Cox hazard regression analyses were used with RTW as outcome measure and hazard rate ratios ( HRR = HRmultidisciplinary/HRbrief ) were adjusted for demographic and health-related variables . An interaction term consisting of a baseline variable*intervention group was added to the multivariable regression model to analyse whether the effects of the interventions were moderated by the baseline factor . Subsequently , a new study was performed that included 120 patients who followed the same protocol . This group was analyzed in the same way to verify the findings from the original study group . Results The multidisciplinary intervention group ensured a quicker RTW than the brief intervention group in a subgroup with low job satisfaction , notably when cl aim ants were excluded . The opposite effect was seen in the subgroup with high job satisfaction . When cl aim ants were excluded , the effect was also in favour of the multidisciplinary intervention in subgroups characterised by no influence on work planning and groups at risk of losing their job . Inversely , the effect was in favour of the brief intervention in the subgroups who were able to influence the planning of their work and who had no risk of losing their job due to current sick leave . Interaction analysis of the data in the new study displayed similar or even more pronounced differences between subgroups in relation to intervention type . Conclusions Multidisciplinary intervention seemed more effective than brief intervention in subgroups of patients with low job satisfaction , no influence on work planning and feeling at risk of losing their jobs due to their sick leave as compared with subgroups not fulfilling these criteria", "Background A model for integrative medicine ( IM ) adapted to Swedish primary care was previously developed . The aim of this study was to explore the feasibility of a pragmatic r and omised clinical trial to investigate the effectiveness of the IM model versus conventional primary care in the management of patients with non-specific back/neck pain . Specific objectives included the exploration of recruitment and retention rates , patient and care characteristics , clinical differences and effect sizes between groups , selected outcome measures and power calculations to inform the basis of a full-scale trial . Methods Eighty patients with back/neck pain of at least two weeks duration were r and omised to the two types of care . Outcome measures were st and ardised health related quality of life ( the eight domains of SF-36 ) complemented by a set of exploratory \" IM tailored \" outcomes targeting self-rated disability , stress and well-being ( 0 - 10 scales ) ; days in pain ( 0 - 14 ) ; and the use of analgesics and health care over the last two weeks ( yes/no ) . Data on clinical management were derived from medical records . Outcome changes from baseline to follow-up after 16 weeks were used to explore the differences between the groups . Results Seventy-five percent ( 80/107 ) of screened patients in general practice were eligible and feasible to enrol into the trial . Eighty-two percent ( 36/44 ) of the integrative and 75 % ( 27/36 ) of the conventional care group completed follow-up after 16 weeks . Most patients had back/neck pain of at least three months duration . Conventional care typically comprised advice and prescription of analgesics , occasionally complemented with sick leave or a written referral to physiotherapy . IM care generally integrated seven treatment sessions from two different types of complementary therapies with conventional care over ten weeks . The study was underpowered to detect any statistically significant differences between the groups . One SF-36 domain showed a clinical ly relevant difference between groups that was also supported by a small distribution based effect size , i.e. vitality ( -7.3 points , Cohen 's d -0.34 ) which was in favour of IM . There was a clinical trend between groups showing that IM contributed to less use of prescription and non-prescription analgesics ( -11.7 and - 9.7 percent units respectively ) compared to conventional care . Exploring clinical ly relevant differences and the SF-36 as the basis for a main outcome measure showed that the sample sizes needed per arm to adequately power a full-scale trial depended on the target domain , i.e. ranging from 60 ( vitality ) to 339 ( role emotion ) . Conclusion This pilot study investigated the implementation of IM in the primary care management of non-specific back and neck pain . Recruiting patients and implementing IM in routine clinical practice was feasible . The results warrant further exploration into different perspectives and relevant combinations of outcome measures including the use of health re sources , drugs and cost-effectiveness to help underst and the relevance of IM in primary care . Future research should prioritise larger scale studies considering variability , pain duration and small to moderate treatment effects . Trial registration Clinical trials", "Background Pregnancy-related pelvic girdle and /or low back pain is a controversial syndrome because insight in etiology and prognosis is lacking . The controversy relates to factors eliciting pain and some prognostic factors such as the interpretation of pain at the symphysis . Recent research about treatment strategies also reflects those various opinions , in fact suggesting there is professional uncertainty about the optimal approach . Currently , physiotherapists often prescribe a pain-contingent treatment regime of relative rest and avoiding several day-to-day activities . Additionally , treatment more often includes an exercise program to guide rectification of the muscle imbalance and alignment of the pelvic girdle . Effectiveness of those interventions is not proven and the majority of the studies are method ologically flawed . Investigators draw particular attention to biomedical factors but there is growing evidence that important prognostic issues such as biopsychosocial factors appear to be even more important as point of action in a treatment program . Methods / design This pragmatic r and omized controlled trial is design ed to evaluate the effectiveness of a tailor-made treatment program with respect to biopsychosocial factors in primary care . The effect of the experimental intervention and usual care are evaluated as they are applied in primary health care . The trial is embedded in a cohort study that is design ed as a longitudinal , prospect i ve study , which studies prevalence , etiology , severity and prognosis during pregnancy until one year after delivery . The present paper focuses on choices regarding recruitment procedures , in-/exclusion criteria and the development of a well-timed intervention . Discussion This section briefly discusses the actions taken to minimize bias in the design , the proper time-window for the experimental intervention and the contrast between the experimental intervention and usual care", "Chronic low back pain ( CLBP ) is associated with persistent or recurrent disability which results in high costs for society . Cognitive behavioral treatments produce clinical ly relevant benefits for patients with CLBP . Nevertheless , no clear evidence for the most appropriate intervention is yet available . The purpose of this study is to evaluate the mid-term effects of treatment in a cohort of patients with CLBP participating in an intensive pain management programme . The programme provided by RealHealth-Netherl and s is based on cognitive behavioral principles and executed in collaboration with orthopedic surgeons . Main outcome parameters were daily functioning ( Rol and and Morris Disability Question naire and Oswestry Disability Question naire ) , self-efficacy ( Pain Self-Efficacy Question naire ) and quality of life ( Short Form 36 Physical Component Score ) . All parameters were measured at baseline , last day of residential programme and at 1 and 12 months follow-up . Repeated measures analysis was applied to examine changes over time . Clinical relevance was examined using minimal clinical important differences ( MCID ) estimates for main outcomes . To compare results with literature effect sizes ( Cohen ’s d ) and St and ardized Morbidity Ratios ( SMR ) were determined . 107 patients with CLBP participated in this programme . Mean scores on outcome measures showed a similar pattern : improvement after residential programme and maintenance of results over time . Effect sizes were 0.9 for functioning , 0.8 for self-efficacy and 1.3 for physical functioning related quality of life . Clinical relevancy : 79 % reached MCID on functioning , 53 % on self-efficacy and 80 % on quality of life . Study results on functioning were found to be 36 % better and 2 % worse when related to previous research on , respectively , rehabilitation programmes and spinal surgery for similar conditions ( SMR 136 and 98 % , respectively ) . The participants of this evidence -based programme learned to manage CLBP , improved in daily functioning and quality of life . The study results are meaningful and comparable with results of spinal surgery and even better than results from less intensive rehabilitation programmes", "Background In the treatment of chronic back pain , cognitive methods are attracting increased attention due to evidence of effectiveness similar to that of traditional therapies . The purpose of this study was to compare the effectiveness of performing a cognitive intervention based on a non-injury model with that of a symptom-based physical training method on the outcomes of low back pain ( LBP ) , activity limitation , LBP attitudes ( fear-avoidance beliefs and back beliefs ) , physical activity levels , sick leave , and quality of life , in chronic LBP patients . Methods The study was a pragmatic , single-blind , r and omised , parallel-group trial . Patients with chronic/recurrent LBP were r and omised to one of the following treatments : 1 . Educational programme : the emphasis was on creating confidence that the back is strong , that loads normally do not cause any damage despite occasional temporary pain , that reducing the focus on the pain might facilitate more natural and less painful movements , and that it is beneficial to stay physically active . 2 . Individual symptom-based physical training programme : directional-preference exercises for those central ising their pain with repetitive movements ; ' stabilising exercises ' for those deemed ' unstable ' based on specific tests ; or intensive dynamic exercises for the remaining patients . Follow-up question naires ( examiner-blinded ) were completed at 2 , 6 and 12 months . The main statistical test was an ANCOVA adjusted for baseline values . Results A total of 207 patients participated with the median age of 39 years ( IQR 33 - 47 ) ; 52 % were female , 105 were r and omised to the educational programme and 102 to the physical training programme . The two groups were comparable at baseline . For the primary outcome measures , there was a non-significant trend towards activity limitation being reduced mostly in the educational programme group , although of doubtful clinical relevance . Regarding secondary outcomes , improvement in fear-avoidance beliefs was also better in the educational programme group . All other variables were about equally influenced by the two treatments . The median number of treatment sessions was 3 for the educational programme group and 6 for the physical training programme group . Conclusions An educational approach to treatment for chronic LBP result ed in at least as good outcomes as a symptom-based physical training method , despite fewer treatment sessions . Trial registration Clinical trials.gov : #", "Summary Background Back pain remains a challenge for primary care internationally . One model that has not been tested is stratification of the management according to the patient 's prognosis ( low , medium , or high risk ) . We compared the clinical effectiveness and cost-effectiveness of stratified primary care ( intervention ) with non-stratified current best practice ( control ) . Methods 1573 adults ( aged ≥18 years ) with back pain ( with or without radiculopathy ) consultations at ten general practice s in Engl and responded to invitations to attend an assessment clinic . Eligible participants were r and omly assigned by use of computer-generated stratified blocks with a 2:1 ratio to intervention or control group . Primary outcome was the effect of treatment on the Rol and Morris Disability Question naire ( RMDQ ) score at 12 months . In the economic evaluation , we focused on estimating incremental quality -adjusted life years ( QALYs ) and health-care costs related to back pain . Analysis was by intention to treat . This study is registered , number IS RCT N37113406 . Findings 851 patients were assigned to the intervention ( n=568 ) and control groups ( n=283 ) . Overall , adjusted mean changes in RMDQ scores were significantly higher in the intervention group than in the control group at 4 months ( 4·7 [ SD 5·9 ] vs 3·0 [ 5·9 ] , between-group difference 1·81 [ 95 % CI 1·06–2·57 ] ) and at 12 months ( 4·3 [ 6·4 ] vs 3·3 [ 6·2 ] , 1·06 [ 0·25–1·86 ] ) , equating to effect sizes of 0·32 ( 0·19–0·45 ) and 0·19 ( 0·04–0·33 ) , respectively . At 12 months , stratified care was associated with a mean increase in generic health benefit ( 0·039 additional QALYs ) and cost savings ( £ 240·01 vs £ 274·40 ) compared with the control group . Interpretation The results show that a stratified approach , by use of prognostic screening with matched pathways , will have important implication s for the future management of back pain in primary care . Funding Arthritis Research UK", "OBJECTIVE To report the results from a prospect i ve , cognitive-behavioural team-based , individually geared , low-intensity , rehabilitation programme , r and omly assigned to care-seekers in primary care physiotherapy with new pain-related sick leave , and to examine a possible reduction in social security expenditure . METHODS A total of 194 care-seekers were included in a stepwise procedure from November 2000 to February 2002 . Control group n = 381 . RESULTS The median number of days of sick leave in the intervention group was 22 during the first 6-month period . After 180 days 5.2 % were still on sick leave and after 360 days 4.2 % . The comparable figures in the control group were 30 days , 9.7 % and 7.2 % , respectively . Reductions in social security expenditure were statistically significant from the fourth month . As predicted , clinical ly relevant subgroups contributed differently to this reduction , both early and later on . The overall problem for one-third of the subgroups was insufficient co-ordination from the employer and the social security executive . CONCLUSION It was possible to reduce the social security expenditure in this setting . The intervention costs were balanced out during the first year . A large potential for further cost reductions was identified in increased implementation of workplace-based return-to-work interventions", "Purpose The aim of this longitudinal study is to determine the factors which predict a successful 1-year outcome from an intensive combined physical and psychological ( CPP ) programme in chronic low back pain ( CLBP ) patients . Methods A prospect i ve cohort of 524 selected consecutive CLBP patients was followed . Potential predictive factors included demographic characteristics , disability , pain and cognitive behavioural factors as measured at pre-treatment assessment . The primary outcome measure was the oswestry disability index ( ODI ) . A successful 1-year follow-up outcome was defined as a functional status equivalent to ‘ normal ’ and healthy population s ( ODI ≤22 ) . The 2-week residential programme fulfills the recommendations in international guidelines . For statistical analysis we divided the data base into two equal sample s. A r and om sample was used to develop a prediction model with multivariate logistic regression . The remaining cases were used to vali date this model . Results The final predictive model suggested being ‘ in employment ’ at pre-treatment [ OR 3.61 ( 95 % CI 1.80–7.26 ) ] and an initial ‘ disability score ’ [ OR 0.94 ( 95 % CI 0.92–0.97 ) ] as significant predictive factors for a successful 1-year outcome ( R2 = 22 % ; 67 % correctly classified ) . There was no predictive value from measures of psychological distress . Conclusion CLBP patients who are in work and mild to moderately disabled at the start of a CPP programme are most likely to benefit from it and to have a successful treatment outcome . In these patients , the disability score falls to values seen in healthy population s. This small set of factors is easily identified , allowing selection for programme entry and triage to alternative treatment regimes", "Study Design . A prospect i ve clinical r and omized controlled trial . Objectives . To determine the long-term effect of a combined exercise and motivational program on the level of disability of patients with chronic and recurrent low back pain ( LBP ) . Summary of Background Data . There is agreement on the importance of exercise during the course of chronic LBP . However , it is well known that long-term adherence with exercises is particularly low . Methods . A total of 93 patients with LBP were r and omly assigned to the control group ( st and ard exercise program ) or the motivational group ( combined exercise and motivational program ) . Follow-up assessment s were performed at 3.5 weeks , 4 months , 12 months , and 5 years . Main outcome measures were disability scores , pain intensity , and working ability . In addition to classic statistics , the sophisticated linear partial credit model was used to test the effects of treatment on disability scores . Results . In both groups , significant improvements in the disability scores were found at all points of follow-up assessment , however , the cumulative effect of the treatment in the motivational group was more than twice as much as in the control group . This result is in accordance with the increasing divergence in pain intensity between groups between 12 months and 5 years after intervention . A significant , positive long-term effect at the 5-year re assessment in working ability was only seen in the motivational group . All statistically significant results were confirmed by intention-to-treat analyses . Conclusions . Regarding long-term efficacy , the combined exercise and motivation program was superior to the st and ard exercise program . Five years after the supervised combined exercise and motivational program , patients had significant improvements in disability , pain intensity , and working ability", "Purpose To compare the 9-year outcome in patients with chronic low back pain treated by instrumented lumbar fusion versus cognitive intervention and exercises . Methods The main outcome measure was the Oswestry Disability Index ( ODI ) . Secondary outcome measures included pain , fear-avoidance beliefs , trunk muscle strength , medication , and return to work . Results One-third of the patients r and omized to cognitive intervention and exercises had crossed over and been operated and one-third of the patients allocated to lumbar fusion had been re-operated . The intention-to-treat analysis detected no differences between the two groups . The mean adjusted treatment effect for ODI was 1.9 ( 95 % CI −7.8 to 11.6 ) . Analysed according to the treatment received , more operated patients used pain medication and were out of work . Conclusions The outcome at 9 years was not different between instrumented lumbar fusion and cognitive intervention and exercises", "Aims : To test the long term cost-benefit and cost-effectiveness of the Sherbrooke model of management of subacute occupational back pain , combining an occupational and a clinical rehabilitation intervention . Methods : A r and omised trial design with four arms was used : st and ard care , occupational arm , clinical arm , and Sherbrooke model arm ( combined occupational and clinical interventions ) . From the Quebec WCB perspective , a cost-benefit ( amount of consequence of disease costs saved ) and cost-effectiveness analysis ( amount of dollars spent for each saved day on full benefits ) were calculated for each experimental arm of the study , compared to st and ard care . Results : At the mean follow up of 6.4 years , all experimental study arms showed a trend towards cost benefit and cost effectiveness . These results were owing to a small number of very costly cases . The largest number of days saved from benefits was in the Sherbrooke model arm . Conclusions : A fully integrated disability prevention model for occupational back pain appeared to be cost beneficial for the workers ’ compensation board and to save more days on benefits than usual care or partial interventions . A limited number of cases were responsible for most of the long term disability costs , in accordance with occupational back pain epidemiology . However , further studies with larger sample s will be necessary to confirm these results", "OBJECTIVE The objective of this study was to examine whether a multimodal , secondary prevention program ( MP ) is superior to a general physical exercise program ( EP ) in influencing the process leading to chronic low back pain ( LBP ) in nurses with a history of back pain . DESIGN The study was conducted as a r and omized controlled parallel-group trial . SETTING The interventions were performed in a single center at the Department of Physical and Rehabilitation Medicine at the University of Munich in Germany . PARTICIPANTS A total of 235 nurses from 14 nearby hospitals and nursing homes who experienced at least one episode of back pain during the previous 2 years were invited into the study . Of these , 183 nurses were enrolled and 169 ( 83 in the MP and 86 in the EP ) qualified for the intent-to-treat analysis . INTERVENTIONS The EP consisted of 11 group sessions , each lasting 1 hour . After introductory sessions , subsequent sessions included general physical strengthening and stretching exercises as well as instructions for a home-training program . The MP consisted of 17 group sessions of 1.75 hours and one individual session of 45 minutes . In addition to the full EP , the MP included 5 psychological units , 7 segmental stabilization exercises units , and 8 ergonomic and workplace-specific units . MAIN OUTCOME MEASUREMENTS The primary study end-point variable was pain interference , and the secondary study end-point variables were pain intensity and functioning as measured with the West Haven-Yale Multidimensional Pain Inventory and the Short Form-36 , respectively . These study end-point variables were defined a priori . RESULTS There was no statistically significant difference between the 2 groups . Small-to-moderate effects were observed in both intervention programs across all study end-point variables . For pain interference , the effect size at 12 months after intervention was 0.58 in the MP and 0.47 in the EP . CONCLUSIONS A multimodal program is not superior to a general exercise program in influencing the process leading to chronic LBP in a population of nurses with a history of pain . The most likely explanation is a common psychological mechanism leading to improved pain interference that is irrespective of the program used . Considering the lower re sources of the general exercise program , the expense for a multimodal program is not justified for the secondary prevention of LBP and disability", "Objective To evaluate the cost effectiveness , cost utility , and cost-benefit of an integrated care programme compared with usual care for sick listed patients with chronic low back pain . Design Economic evaluation alongside a r and omised controlled trial with 12 months ’ follow-up . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) in the Netherl and s , 2005 - 9 . Participants 134 adults aged 18 - 65 sick listed because of chronic low back pain : 66 were r and omised to integrated care and 68 to usual care . Interventions Integrated care consisted of a workplace intervention based on participatory ergonomics , with involvement of a supervisor , and a grade d activity programme based on cognitive behavioural principles . Usual care was provided by general practitioners and occupational physicians according to Dutch guidelines . Main outcome measures The primary outcome was duration until sustainable return to work . The secondary outcome was quality adjusted life years ( QALYs ) , measured using EuroQol . Results Total costs in the integrated care group ( £ 13 165 , SD £ 13 600 ) were significantly lower than in the usual care group ( £ 18 475 , SD £ 13 616 ) . Cost effectiveness planes and acceptability curves showed that integrated care was cost effective compared with usual care for return to work and QALYs gained . The cost-benefit analyses showed that every £ 1 invested in integrated care would return an estimated £ 26 . The net societal benefit of integrated care compared with usual care was £ 5744 . Conclusions Implementation of an integrated care programme for patients sick listed with chronic low back pain has a large potential to significantly reduce societal costs , increase effectiveness of care , improve quality of life , and improve function on a broad scale . Integrated care therefore has large gains for patients and society as well as for employers", "Yang EJ , Park W-B , Shin H-I , Lim J-Y : The Effect of Back School Integrated with Core Strengthening in Patients with Chronic Low-Back Pain . Objective : To assess the effect of back school integrated with core-strengthening exercises on back-specific disability and pain-coping strategies and to examine how reactions to pain affect the outcomes of back school in patients with chronic low back pain . Design : A single-center prospect i ve trial was conducted with 142 participants with chronic low-back pain ( 38 men and 104 women ) who completed a back school program at the spine center of a university hospital . The subjects participated in a 4-wk program integrated with core-strengthening exercises . Back-specific disabilities were measured as a primary outcome before and after the program . Secondary outcomes were pain , Chronic Pain Coping Inventory , general health status assessed by the SF-36 , and quantitative functional evaluations of factors , such as trunk muscle strength , endurance , and the back performance scale . A subgroup of 28 subjects ( 12 men and 16 women ) of the total sample of 142 subjects was used to analyze the longitudinal association between coping strategies and the primary outcome in a long-term follow-up study . These participants were divided into three groups ( much improved , slightly improved , and unimproved ) based on changes in back-specific disability scores . Results : Participants improved significantly in terms of back-specific disability , pain , general health , and quantitative functional tests according to the short-term evaluation . They used more relaxation and exercise/stretching techniques as coping strategies . Of the groups participating in the longer-term follow-up ( T3 ) , the much-improved group showed significant improvement between T1 ( before back school ) and T2 ( after back school ) in scores for relaxation ( 1.6 ± 1.0 vs. 2.6 ± 1.1 ) , task persistence ( 2.9 ± 1.2 vs. 3.7 ± 1.2 ) , and exercise ( 3.3 ± 1.1 vs. 5.2 ± 1.9 ) , but the coping strategies of those in the slightly improved and unimproved groups did not change significantly at T2 . Conclusions : Our back school program may help patients with chronic low back pain reduce back-specific disability and pain and develop wellness-focused coping strategies such as exercise and stretching", "Objectives To identify relevant changes in process variables that are associated with outcome following an exercise and a multidisciplinary secondary prevention program for low back pain . Methods Data from a r and omized controlled clinical trial to examine the effectiveness of an exercise and a multidisciplinary prevention program were analyzed using multiple regression analyses . The specific goal was to examine the amount of variance in changes in “ interference ” postintervention that could be explained by prechanges to postchanges in physical and psychologic parameters , and to determine if there are interactions between physical/psychologic parameters and the program type . Results One hundred sixty-two ( 89 % ) participants were included in the regression analyses . Reductions of interference at postmeasurement were explained best by reductions of pain intensity and catastrophizing in the multidisciplinary and the exercise prevention program . No significant interaction between the changes in process variables and the program type was found . The final model could explain 68.7 % of variance . Conclusions Owing to method ologic limitations , strong conclusions can not be drawn from this study . The findings suggest that treatment success in exercise and multidisciplinary interventions might be influenced by the same change factors , namely changes in pain and psychologic factors . The results raise the question of whether the mechanism through which exercise works , is improve in physical variables , or rather a change in psychologic attributes , in that people correct their irrational cognitions by making experiences that differ from their expectations . If these findings can be confirmed in longitudinal studies with more measurement points , they would have implication s for treatment refinement", "OBJECTIVE The aim of this r and omized controlled trial ( RCT ) was to investigate the effectiveness of the Stay@Work participatory ergonomics ( PE ) program to prevent low-back and neck pain . METHODS A total of 37 departments were r and omly allocated to either the intervention ( PE ) or control group ( no PE ) . During a six-hour meeting , working groups followed the PE steps and composed and prioritized ergonomic measures aim ed at preventing low-back and neck pain . Subsequently , working groups were requested to implement the ergonomic measures in the departments . The primary outcomes were low-back and neck pain prevalence and secondary outcomes were pain intensity and duration . Data were collected by question naires at baseline , and after 3- , 6- , 9- , and 12-months follow-up . Additionally , the course of low-back and neck pain ( transitions from no symptoms to symptoms and from symptoms to no symptoms ) was modeled . RESULTS The r and omization procedure result ed in 19 intervention departments ( N=1472 workers ) and 18 control departments ( N=1575 workers ) . After 12 months , the intervention was not more effective than the control group in reducing the prevalence of low-back and neck pain or reducing pain intensity and duration . PE did not increase the probability of preventing low-back pain [ odds ratio ( OR ) 1.23 , 95 % confidence interval ( 95 % CI ) 0.97 - 1.57 ) or neck pain ( OR 1.01 , 95 % CI 0.74 - 1.40 ) . However , PE increased the probability of recovering from low-back pain ( OR 1.41 , 95 % CI 1.01 - 1.96 ) , but not from neck pain ( OR 0.95 , 95 % CI 0.72 - 1.26 ) . CONCLUSION PE neither reduced low-back and neck pain prevalence nor pain intensity and duration nor was it effective in the prevention of low-back and neck pain or the recovery from neck pain . However , PE was more effective in the recovery from low-back pain", "Study Design . A single blind r and omized controlled trial comparing two models of care for patients with acute simple low back pain . Objectives . To compare two research -based models of care for acute low back pain and investigate the effect of the timing of physical intervention . Summary of Background Data . National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain . The guidelines suggest two different models of care . Direct comparisons between these models are lacking in the literature . The present study aims to compare these approaches to the management of acute low back pain . Methods . Among 804 referred patients , 102 subjects met the specific admission criteria and were r and omly assigned to an “ assess/advise/treat ” group or an “ assess/advise/wait ” group . The intervention consisted of biopsychosocial education , manual therapy , and exercise . Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active . Assessment of long-term outcome enables comparison to be made between early and late intervention . Study outcomes of reported pain ( Visual Analogue Scale ) , functional disability ( the Rol and and Morris Disability Question naire ) , mood ( Modified Zung Self Rated Depression Score , Modified Somatic Perception Question naire , State-Trait Anxiety Inventory ) , general health ( Euroqol ) , and quality of life ( Short Form 36 ) were assessed at baseline , 6 weeks , 3 months , and 6 months . Results . At 6 weeks , the assess/advise/treat group demonstrated greater improvements in disability , mood , general health , and quality of life than patients in the assess/advise/wait group ( P < 0.05 ) . Disability and pain were not significantly different between the groups at long-term follow up ( P > 0.05 ) . However , mood , general health , and quality of life remained significantly better in the assess/advise/treat group ( P < 0.05 ) . Conclusions . At short-term , intervention is more effective than advice on staying active , leading to more rapid improvement in function , mood , quality of life , and general health . The timing of intervention affects the development of psychosocial features . If treatment is provided later , the same psychosocial benefits are not achieved . Therefore , an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care", "OBJECTIVE To investigate return to work and cost-effectiveness of the addition of cognitive-behavioral treatment to st and ard therapy compared to st and ard 3-week inpatient rehabilitation for patients with chronic low back pain . METHODS A prospect i ve economic evaluation alongside a r and omized controlled trial was performed . Outcomes included days off work due to spinal complaints , health-related quality of life , and direct and indirect disease-related costs . RESULTS A total of 409 patients with chronic low back pain , who were admitted to a 3-week inpatient rehabilitation , were r and omly assigned to usual care or usual care plus cognitive behavioral treatment . Average incremental costs for psychological treatment during rehabilitation were Euros 127 ( 95 % CI 125.6 , 130.9 ; p < 0.001 ) . Six months after rehabilitation , patients in the intervention group were absent from work an average of 5.4 ( 95 % CI -1.4 , 12.1 ; p = 0.12 ) days less than patients receiving usual treatment . Between groups , there were no significant differences in quality -adjusted life-years gained or in direct medical or nonmedical costs . The cognitive behavioral treatment showed lower indirect costs : Euros 751 ( 95 % CI -145 , 1641 ; p = 0.097 ) . CONCLUSION Adding a cognitive behavioral component to st and ard therapy may reduce work days lost and thus decrease indirect costs . From a societal perspective , the cost of the psychological treatment was compensated by lower indirect costs", "& NA ; Multidisciplinary programmes using a vocational approach can enhance work return in chronic pain patients , but little is known about the long‐term effects of rehabilitation . The current study examined the patterns of sickness absence 10 years after participation in 3 treatment groups ( physiotherapy , cognitive behavioural therapy , and vocational multidisciplinary rehabilitation ) in comparison to a control group receiving treatment‐as‐usual . Cost‐effectiveness was also assessed . Two hundred fourteen patients participated in a r and omized controlled trial and were followed‐up via register data 10 years after the interventions . On average , persons in multidisciplinary rehabilitation had 42.98 fewer days on sickness absence per year compared to those treated‐as‐usual ( 95 % confidence interval −82.45 to −3.52 , P = 0.03 ) . The corresponding reduction of sickness absence after physiotherapy and cognitive behavioural therapy was not significantly different from the control group . The effect of rehabilitation seems to be more pronounced for disability pension than for sick leave . The economic analyses showed substantial cost savings for individuals in the multidisciplinary group compared to the control group . Intensive multidisciplinary rehabilitation for persistent back and neck pain reduces sickness absence 10 years after intervention and shows greater cost reductions than physiotherapy and cognitive behavioural therapy alone", "Objective : To evaluate the effect on disability , kinesiophobia , pain , and the quality of life of a long-lasting multidisciplinary program based on cognitive-behavioral therapy and targeted against fear-avoidance beliefs in patients with chronic low back pain . Methods : Study design : parallel-group , r and omized , superiority controlled study . Ninety patients were r and omly assigned to a multidisciplinary program consisting of cognitive-behavior therapy and exercise training ( experimental group , 45 patients ) or exercise training alone ( control group , 45 patients ) . Before treatment ( T1 ) , 5 weeks later ( instructive phase , T2 ) , and 12 ( posttreatment analysis , T3 ) and 24 months after the end of the instructive phase ( 1-year follow-up , T4 ) , all of the patients completed a booklet containing the Rol and -Morris Disability Question naire Scale ( primary outcome ) , the Tampa Scale for Kinesiophobia , a pain numerical rating scale , and the Short-Form Health Survey . A linear mixed model for repeated measures was used to analyze each outcome measure , and the reliable change index/ clinical ly significant change method was used to assess the clinical significance of the changes . Results : The linear mixed model analysis showed a remarkable group , time , and interaction effect for group * time in all of the primary and secondary outcomes ( P always < 0.001 ) . The majority of the patients in the experimental group achieved a reliable and clinical ly significant improvement , whereas the majority of those in the control group experienced no change . Conclusions : The long-lasting multidisciplinary program was superior to the exercise program in reducing disability , fear-avoidance beliefs and pain , and enhancing the quality of life of patients with chronic low back pain . The effects were clinical ly tangible and lasted for at least 1 year after the intervention ended", "Study Design The authors conducted a controlled clinical trial with 1-year follow-up to define the effectiveness of an intensive physical and psychosocial training program on patients with low back pain . Summary of Background Data The intervention group included 152 patients ( mean age 40.5 yr , Million index 45.1/100 ) , and the reference group included 141 patients ( mean age 40.4 yr , Million index 44.5/100 ) . Methods The progressive intervention program consisted of intensive physical training and psychosocial activation . The outcomes were physical and psychosocial measures , the pain and disability index ( Million ) , sick leaves , and occupational h and icap . Results The intervention was more efficient with respect to physical measures and pain and disability index . There were only mild or no differences in changes between the study groups in psychology variables , sick leaves , or retirement . Conclusions The intervention program could improve physical disability , but to improve occupational h and icap , activities of the whole society ( social legislation , labor market policy ) are needed", "UNLABELLED The aim of this study was to examine whether treatments based on different theories change pain catastrophizing and internal control of pain , and whether changes in these factors mediate treatment outcome . Participants were 211 patients with nonspecific chronic low back pain ( CLBP ) participating in a r and omized controlled trial , attending active physical treatment ( APT , n = 52 ) , cognitive-behavioral treatment ( CBT , n = 55 ) , treatment combining the APT and CBT ( CT , n = 55 ) , or waiting list ( WL , n = 49 ) . Pain catastrophizing decreased in all 3 active treatment groups and not in the WL . There was no difference in the change in internal control across all 4 groups . In all the active treatment groups , patients improved regarding perceived disability , main complaints , and current pain at post-treatment , and no changes were observed in the WL group . Depression only changed significantly in the APT group . Change in pain catastrophizing mediated the reduction of disability , main complaints , and pain intensity . In the APT condition , pain catastrophizing also mediated the reduction of depression . Not only cognitive-behavioral treatments but also a physical treatment produced changes in pain catastrophizing that seemed to mediate the outcome of the treatment significantly . The implication s and limitations of these results are discussed . PERSPECTIVE This article shows that treatment elements that do not deliberately target cognitive factors can reduce pain catastrophizing . Reduction in pain catastrophizing seemed to mediate the improvement of functioning in patients with chronic low back pain . The results might contribute to the development of more effective interventions", "The aim of this cost-effectiveness study was to compare a combined operant programme plus cognitive/relaxation programme with an operant programme plus attention-control and to compare both programmes with a waiting-list control group and with operant rehabilitation provided , as usual , by the same rehabilitation centre . One hundred and forty eight patients with chronic low back pain were r and omly assigned to the different conditions . The economic endpoints were the costs of the programme and other health care utilisation , costs for the patient , and indirect costs associated with production losses due to low back pain . The effects were measured in terms of global assessment of change and utilities , using rating scale and st and ard gamble methods . The 3-year study determined that adding a cognitive component to an operant treatment did not lead to significant differences in costs and improvement in quality of life when compared with the operant treatment alone . Compared with the common individual rehabilitation therapy it can be concluded that the same effects can be reached at the same or lower costs with a shorter , more intense st and ardised group programme . The operant treatment alone is more effective than providing no treatment in the waiting-list control group", "Context Low back pain causes frequent disability and lost productive time . Contribution This r and omized trial compared a behavioral-oriented grade d activity program with usual care in 134 Dutch airline company workers who had missed work because of persistent low back pain . Grade d activity consisted of biweekly 1-hour exercise sessions with physiotherapists who emphasized operant-conditioning principles . Over 6 months of follow-up , participants in the grade d activity program missed 58 days of work , while participants receiving usual care missed 87 days . Implication s A behavioral-oriented grade d activity program returned participants with low back pain to work more often than did usual care . The Editors Nonspecific low back pain is an uncomfortable medical condition that causes frequent disability and absence from work . Most episodes of low back pain resolve fairly quickly and cause only short periods of absence from work . However , some workers with low back pain miss work for several days to weeks and are at risk for more permanent disability ( 1 ) . To reduce the individual and socioeconomic burden related to this absenteeism , we need effective intervention strategies in occupational health care setting s that promote safe and rapid return to work . One promising and often-advocated intervention strategy for workers with prolonged nonspecific low back pain is active rehabilitation that is directed toward return to normal activity and work ( 2 ) . Examples are grade d activity interventions that include physical exercise , application of operant-conditioning behavioral principals , and promotion of improved functioning and safe return to work even if pain persists ( 3 - 6 ) . In a r and omized , controlled trial , Lindstrm and colleagues ( 3 , 4 ) found that a grade d activity intervention reduced absence from work more than did traditional care in Swedish workers employed in the automobile industry . We investigate , in a second r and omized , controlled trial , whether absence from work because of low back pain is reduced more with grade d activity intervention than with traditional care in an occupational health care setting in the Netherl and s. Methods Study Design and Sample The study was a single-blind , r and omized , controlled trial in an occupational health services center ( KLM Health , Safety and Environment ) at Schiphol Airport , Amsterdam , the Netherl and s. The center provides occupational health services for all employees of a major Dutch airline ( KLM Royal Dutch Airlines ) . The source sample ( n = 20 000 ) consisted of workers who were employed in the following organizational units of the airline : baggage and aircraft turnaround services , passenger services , engineering and maintenance , cargo , and cabin and cockpit . Workers who were listed as absent from work because of low back pain were invited for a consultation with the occupational physician . Those who were thought to be eligible for inclusion were referred to the research assistant , who judged whether they met the inclusion criteria : full or partial absence from work because of nonspecific low back pain and low back pain symptoms with a minimum duration of 4 weeks in succession . The exclusion criteria were low back pain with radiation below the knee with signs of nerve-root compression ( 7 ) ; cardiovascular contraindications for physical activity , as checked according to the Physical Activities Readiness Question naire ( 8 , 9 ) ; any conflict between worker and employer with legal involvement ; or pregnancy . Workers who met the inclusion criteria were informed of the purpose and procedures of the study and were enrolled after giving informed consent . The Medical Ethical Committee of the VU University Medical Center , Amsterdam , the Netherl and s , approved the study . Treatment Allocation The participants were assigned to grade d activity or usual care on the basis of block r and omization , after prestratification for the organizational unit in the workplace from which they were recruited ( the 5 organizational units listed earlier ) and for the severity of pain symptoms ( scored on a scale of 0 to 10 ; severity scores were < 6 or 6 points ) . This result ed in a total of 10 strata . R and omized , permuted blocks of 4 allocations were generated for each stratum through a computer-generated r and om-sequence table . Opaque , sequentially numbered , sealed envelopes were prepared for each stratum by a research er who was not involved in enrolling the participants or assigning them to their groups . The envelopes contained a sheet of paper that indicated 1 of the 2 interventions . Participants learned their group assignments after a research assistant completed the baseline measurements and delivered the sealed envelopes . Blinding The research assistants who collected the data were blinded to the treatment allocation . All participants were repeatedly asked not to reveal any information about their treatment allocation . The participants and treatment providers were not blinded to treatment allocation . Interventions In the Dutch occupational health care system , occupational physicians guide disabled workers who are absent from work through their disability period . These occupational physicians are employed by occupational health services that are paid for by the companies . The occupational physicians adhere to back pain management strategies that consist of advising workers on ergonomics , prevention , and return-to-work schedules and advising and communicating with other stakeholders ( such as health care providers and representatives of the workplace ) . Disabled workers who participated in the present study were assigned to either grade d activity or usual care within the context of the Dutch occupational health care setting . Grade d Activity The intervention group received the usual guidance from the occupational physician about work-related problems and barriers to return to work as well as the grade d activity intervention supervised by a physiotherapist . Three physiotherapists who worked in a private practice at Schiphol Airport provided the treatment according to the grade d activity protocol . Two of those physiotherapists were also trained as manual therapists , and 1 was also a human movement scientist . Before the study , the physiotherapists had been specifically trained to treat patients with low back pain according to behavioral principles . A research physiotherapist who was experienced in treating patients with chronic pain in rehabilitation centers instructed the physiotherapists in three 2-hour sessions and practice d patienttherapist interactions with them through role-play . Before the study , the physiotherapists treated several patients according to the grade d activity protocol to gain more experience . The physiotherapists made audiotapes of the intervention sessions before and during the study period . The contents of these audiotapes were assessed and discussed with the research physiotherapist in 3 additional meetings . Furthermore , the physiotherapists summarized the treatment after each session , and research ers used these summaries to review the sessions . The same physiotherapist treated participants each time , except for temporary st and -in sessions that were supervised by colleagues because of holidays or other reasons . Specific therapists were not systematic ally selected to treat specific participants ; selection was based on pragmatic reasons , such as the time available in the work schedules of the physiotherapists or the days of treatment preferred by the participants . Table 1 presents the concept and content of the grade d activity intervention . The intervention consisted of 1-hour exercise sessions that participants attended twice per week until they returned completely to regular work or until the maximum therapy duration of 3 months was reached . At the start of the intervention , the physiotherapist inquired about the participant 's medical history and completed a brief physical examination consisting of flexion , extension , and lateroflexion of the lumbar spine and a brief screening for nerve-root pain ( 10 ) . The purpose of the physical examination was to confirm the diagnosis of benign , nonspecific low back pain and to reduce participants ' fears about any presumed underlying disease . The participants were reassured that despite the annoying pain , nothing was seriously wrong with their backs . Subsequently , the physiotherapist and participant decided on a set of general exercises and individually tailored exercises . Both types of exercises had to be performed during each session . The general exercises were aerobic exercises , such as cycling or rowing , and strengthening exercises for large muscle groups , and most were carried out in a gym while using exercise equipment . The strengthening exercises were a floor abdominal sit-up exercise , a dynamic back extension exercise , a leg-press exercise , a latissimus pull-down exercise , and st and ing up from a low chair . Participants in the grade d activity group had to perform not only these general exercises but also individually tailored exercises , which imitated physical tasks at work or difficult and painful activities of daily living . For example , a participant who reported back problems while lifting and moving suitcases from a luggage wagon into an airplane might be given an exercise to practice lifting and moving a suitcase with a certain number of repetitions . During the first 3 sessions , the maximal performance ( for example , the maximum number of repetitions ) was assessed for each exercise separately , and the average score for each exercise over the 3 sessions was used as a baseline value for specifying a gradually progressive exercise scheme . Subsequently , the participant was asked to propose a date for full return to regular work , which would consequently be the end point of the physical exercise program . Before returning to full regular work , participants could return to work with modified hours and duties . Advised by the physiotherapist , the participant", "Study Design . A r and omized parallel-group comparative trial with a 1-year follow-up period was performed . Objective . To compare the effect of a comprehensive functional restoration program involving intensive physical training , ergonomic training , and behavioral support ( 39 hours per week for 3 weeks ) with the effect of outpatient intensive physical training ( 1.5 hours three times per week for 8 weeks ) . Summary of Background Data . Nonr and omized studies conducted in the United States favor functional restoration for patients with chronic low back pain . Two previously reported r and omized studies from the authors ’ Back Center in Copenhagen concur with this recommendation , although the positive effects in one of the studies had faded out after 2 years . R and omized functional restoration studies in Canada and Finl and have failed to demonstrate any substantive effect . Methods . Initially , 138 patients with chronic low back pain were included in the current study . They then were r and omized to either functional restoration ( n = 64 ) or outpatient intensive physical training ( n = 74 ) . Of the initial 138 patients , 11 never started ( 5 and 6 , respectively ) ; 21 dropped out during treatment ( 8 and 13 ) ; and 7 of the graduates did not take part in the 1-year follow-up evaluation ( 3 and 4 ) . The conclusions were drawn from the 99 patients ( 48 and 51 , respectively ) who graduated and participated in a 1-year follow-up evaluation . The median age of the patients was 42 years ( range , 21–55 years ) The female-to-male ratio was 68 to 31 , and the median sick leave days during the preceding 3 years was 180 ( range , 0–1080 days ) . The average back pain was rated 5.5 on a scale of 0 ( no pain ) to 10 ( maximal pain ) . For these variables , there were no important differences between the groups . However , the functional restoration group tended to be more capable of work at baseline ( 58%vs 42%;P = 0.09 ) . Results . At the 1-year follow-up evaluation , overall assessment favored functional restoration . Otherwise , no significant differences were observed regarding work capability , sick leave for those at work , health care contacts , back pain , leg pain , or self-reported activities of daily living . Conclusions . Only in terms of overall assessment , the functional restoration program was superior to a comparatively short time-consuming outpatient physical training program . Discussion . It may be that lower economic benefits during sick leave in the United States lead to favorable results from functional restoration programs , whereas greater benefits in Canada , Finl and , and Denmark result in different conclusions . Finally , it may be that the difference in results across studies points simply to whether the studies were r and omized", "The article reports on a study in which elements of a group-oriented reconditioning programme for patients with low back pain were incorporated into the routine of an in-patient orthopaedic rehabilitation clinic . The specific elements of the new programme consisted of stable group structures during the whole stay of 3 to 4 weeks , and of 3 to 7 hrs . walks in hilly ground three times a week . The effects of this programme were tested against a st and ard programme with a mix of passive and active elements using a controlled study design . 92 persons participated in an experimental group and 81 persons in a control group with no significant differences found between the two groups at admission . Effects were measured by means of a physicians ' question naire and a multidimensional patients ' question naire ( IRES ) answered at admission , at discharge , and at six- and twelve-month follow-up . The results of a two-factorial analysis of variance with repeated measures showed that the interaction between group and time on the summary score of the IRES was not significant , although the experimental group showed somewhat better effects at all times of measurement . The discussion focuses on the reasons for this result , among which the unexpectedly good effects in the control group are named , as well as certain difficulties with the implementation of a strongly activity-oriented programme into the course of a \" normal \" rehabilitation clinic", "The aim of the present study was to evaluate the postoperative opioid-sparing effect of a pre-operative nonsteroidal anti-inflammatory drug ( NSAID ) ( ibuprofen ) vs paracetamol in a prospect i ve , double-blind , placebo-controlled study . It was also investigated whether the use of ibuprofen or paracetamol would influence the amount of surgical bleeding . Sixty-six women scheduled for elective open hysterectomy were r and omized into one of three groups . All patients received premedication ( diazepam 10 mg ) and test drugs orally 1 h before the start of anaesthesia : Group 1 ( n=23 ) received 800 mg ibuprofen ; Group 2 ( n=22 ) received 1000 mg paracetamol ; and Group 3 ( n=21 ) received placebo . General anaesthesia was given with thiopentone-fentanyl-atracurium induction , and maintained with nitrous oxide-isoflurane . Postoperatively , the patients were evaluated hourly during the recovery period , and 1 and 4 days after the procedure . Postoperative pain was measured by visual analogue scale ( VAS ) , verbal pain score and the need of st and ardized opioid rescue medication . Intra-operative bleeding was measured , as well as reduction in blood haemoglobin content 24 h and 4 days after the procedure . No differences were found between the groups in postoperative pain measured by any variable or opioid consumption at any time . The amount of surgical bleeding was equal in the three groups . Ibuprofen or paracetamol given pre-operatively to hysterectomy patients do not have a postoperative analgesic or opioid-sparing effect . Perioperative surgical bleeding is not influenced by these drugs", "BACKGROUND CONTEXT Reduced muscle strength and density observed at 1 year after lumbar fusion may deteriorate more in the long term . PURPOSE To compare the long-term effect of lumbar fusion and cognitive intervention and exercises on muscle strength , cross-sectional area , density , and self-rated function in patients with chronic low back pain ( CLBP ) and disc degeneration . STUDY DESIGN R and omized controlled study with a follow-up examination at 8.5 years ( range , 7 - 11 years ) . PATIENTS AND METHODS Patients with CLBP and disc degeneration r and omized to either instrumented posterolateral fusion of one or both of the two lower lumbar levels or a 3-week cognitive intervention and exercise program were included . Isokinetic muscle strength was measured by a Cybex 6000 ( Cybex-Lumex , Inc. , Ronkonkoma , NY , USA ) . All patients had previous experience with the test procedure . The back extension ( E ) flexion ( F ) muscles were tested , and the E/F ratios were calculated . Cross-sectional area and density of the back muscles were measured at the L3-L4 segment by computed tomography . Patients rated their function by the General Function Score . OUTCOME MEASURES Trunk muscle strength , cross-sectional area , density , and self-rated function . RESULTS Fifty-five patients ( 90 % ) were included at long-term follow-up . There were no significant differences in cross-sectional area , density , muscle strength , or self-rated function between the two groups . The cognitive intervention and exercise group increased trunk muscle extension significantly ( p<.05 ) , and both groups performed significantly better on trunk muscle flexion tests ( p<.01 ) at long-term follow-up . On average , self-rated function improved by 56 % , cross-sectional area was reduced by 8.5 % , and muscle density was reduced by 27 % . CONCLUSION Although this study did not assess the morphology of muscles likely damaged by surgery , trunk muscle strength and cross-sectional area above the surgical levels are not different between those who had lumbar fusion or cognitive intervention and exercises at 7- to 11-year follow-up", "Aims : To investigate if a st and ardised physical exercise programme given in addition to a brief intervention at a spine clinic had an effect on return to work . Methods : A total of 246 patients sick-listed 8—12 weeks for non-specific low back pain were offered a brief intervention programme at the spine clinic with examination , information , reassurance , and encouragement to engage in physical activity as normal as possible , before they were r and omised into an intervention group ( n = 124 ) and a control group ( n = 122 ) . Patients in the intervention group participated in a physical exercise programme at the spine clinic . Results : During the 2-year follow-up , there were no significant differences between the groups on sick leave , pain , use of analgesics , psychological distress , coping strategies , fear-avoidance beliefs , self-reported disability , or walking distances . However , both groups increased return to work , reported less pain and better function , and reduced fear-avoidance beliefs for physical activity during the follow-up period . Fear-avoidance beliefs for work were not changed . Conclusions : A physical exercise programme for low back pain patients given after a brief intervention at a spine clinic did not have any additional effect on sick leave or fear-avoidance beliefs . Both groups reported less pain , better physical function , and increased return to work during follow-up . The treatment at the spine clinic did not contain a vocational rehabilitation programme directed towards individual work-related problems , which might explain no change in fear-avoidance beliefs for work", "BACKGROUND Low back pain is a worldwide health problem , affecting up to 80 % of adult population . Psychological factors are involved in its development and maintenance . Many clinical trials have evaluated the efficacy of different interventions for chronic non-specific low back pain . In this field , Back School program has been demonstrated effective for people with chronic non-specific low back . AIM To evaluate the relationship between the effects of the Back School treatment and psychological features measured by MMPI-II of patients with chronic non-specific low back pain . DESIGN A r and omised controlled trial with three and six-month follow-up . SETTING Ambulatory rehabilitative university centre . POPULATION Fifty patients with chronic non-specific low back pain out of 77 screened patients . METHODS Patients were r and omly placed in a 3:2 form and were allocated into two groups ( Treatment versus Control ) . The Treatment Group participated to an intensive multidisciplinary Back School program ( BSG , N.=29 ) , while the Control Group received medical assistance ( CG , N.=21 ) . Medication was the same in both groups . Then , patients were subgrouped in those with at least an elevation in one scale of MMPI-II , and those without it . The Short Form 36 Health Status Survey for the assessment of quality of life ( primary outcome measure ) , pain Visual Analogue Scale , Waddel Index and Oswestry Disability Index were collected at baseline , at the end of treatment , and at the three and six-month follow-up . RESULTS Only the two treated subgroups showed a significant improvements in terms of quality of life , disability and pain . Among treated subjects , only those with at least one scale elevation in MMPI-II showed also a significant improvement in terms of Short Form 36 mental composite score and relevant subscores . CONCLUSION These results suggest that Back School program has positive effects , even in terms of mental components of quality of life in patients with scale elevations of MMPI-II . Probably these findings are due to its educational and cognitive-behavioural characteristics . CLINICAL REHABILITATION IMPACT Because of its educational purpose s , the Back School treatment can have positive effects also on the mental status of patients with low back pain when it affects their psychological features", "CONTEXT Therapists can use horticultural therapy as an adjuvant therapy in a non threatening context , with the intent of bringing about positive effects in physical health , mental health , and social interaction . Very few experimental studies exist that test its clinical effectiveness . OBJECTIVE To determine whether the addition of horticultural therapy to a pain-management program improved physical function , mental health , and ability to cope with pain . DESIGN The research team design ed a prospect i ve , nonr and omized , controlled cohort study , enrolling all patients consecutively referred to the Zurzach Interdisciplinary Pain Program ( ZISP ) who met the study s criteria . The team divided them into two cohorts based on when medical professionals referred them : before ( control group ) or after ( intervention group ) introduction of a horticultural therapy program . SETTING The setting was the rehabilitation clinic ( RehaClinic ) in Bad Zurzach , Switzerl and . PARTICIPANTS Seventy-nine patients with chronic musculoskeletal pain ( fibromyalgia or chronic , nonspecific back pain ) participated in the study . INTERVENTIONS The research team compared a 4-week , inpatient , interdisciplinary pain-management program with horticultural therapy ( intervention , n = 37 ) with a pain-management program without horticultural therapy ( control , n = 42 ) . The horticultural therapy program consisted of seven sessions of group therapy , each of 1-hour duration . OUTCOME MEASURES The research team assessed the outcome using the Medical Outcome Study Short Form-36 ( SF-36 ) , the West Haven-Yale Multidimensional Pain Inventory ( MPI ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Coping Strategies Question naire ( CSQ ) , and two functional performance tests . The team tested participants on entry to and discharge from the 4-week pain-management program . RESULTS Between-group differences in sociodemographic and outcome variables were not significant on participants entry to the pain-management program . On discharge , the research team measured small to moderate outcome effects ( effect size [ ES ] up to 0.71 ) within both groups . The study found significantly larger improvements for the horticultural therapy group vs the control group in SF-36 role physical ( ES = 0.71 vs 0.22 ; P = .018 ) ; SF-36 mental health ( ES = 0.46 vs 0.16 ; P = .027 ) ; HADS anxiety ( ES = 0.26 vs 0.03 ; P = .043 ) ; and CSQ pain behavior ( ES = 0.30 vs -0.05 ; P = .032 ) . CONCLUSION The addition of horticultural therapy to a pain management program improved participants ' physical and mental health and their coping ability with respect to chronic musculoskeletal pain", "OBJECTIVE To compare the short-term outcomes of active individual therapy ( AIT ) with those of a functional restoration program ( FRP ) . DESIGN Prospect i ve r and omized controlled study . SETTING Two rehabilitation centers and private ambulatory physiotherapy facilities . PARTICIPANTS One hundred thirty-two adults with chronic low back pain . Fifty-one percent of patients on sick leave or out of work ( mean duration , 180d in the 2y before treatment ) . INTERVENTIONS For 5 weeks , FRP ( at 25h/wk ) or AIT ( at 3h/wk ) . MAIN OUTCOME MEASURES Trunk flexibility , back flexor , and extensor endurance ( Ito and Sorensen tests ) , general endurance , pain intensity , Dallas Pain Question naire ( DPQ ) scores , daily activities , anxiety depression , social interest , and work and leisure activities , and self-reported improvement ( work ability , resumption of sport and leisure activities ) . RESULTS All outcome measures improved after treatment except endurance in AIT . There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores . Better results were observed in FRP for all other outcome measures . There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction ; a significant effect of treatment and initial value on the gains of Ito , endurance , and DPQ social interest and anxiety depression scores , with no treatment or initial value interaction ; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores . CONCLUSIONS Low-cost ambulatory AIT is effective . The main advantage of FRP is improved endurance . We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities", "Objectives A back school is a m and atory part of the multimodal rehabilitation program for patients with chronic low back pain in Germany . However , no st and ardized and evaluated back school program has been available for routine use . In this study , we report the evaluation of a new back school that was developed based on theories of health behavior , treatment evidence , practice guidelines , and quality criteria for patient education . Methods R and omized controlled trial of patients with low back pain ( n=360 ) in inpatient orthopedic rehabilitation clinic in Germany . Intervention patients received the new back school , whereas control patients a traditional back school ( usual care ) . Illness knowledge ( primary outcome ) and secondary behavioral and health outcomes were assessed at admission , discharge , and 6 and 12 months follow-up . Results Results showed a significant medium between-group treatment effect in patients ' knowledge about back pain at discharge ( & eegr;2=0.081 ) , after 6 ( & eegr;2=0.056 ) , and 12 months ( & eegr;2=0.026 ) . Furthermore , small-to-medium effects were observed among the secondary self-management behaviors , such as physical activity , back exercises , back posture habits , and coping with pain , after 6 and 12 months . Discussion The superior effectiveness of the back school based on a biopsychosocial approach was demonstrated with regard to illness knowledge and self-management behaviors up to 1 year . Thus , the program may be recommended for dissemination within medical rehabilitation", "OBJECTIVE < < Back School > > has been used as a way of preventing and treating back pain since 1969 , but reports in the literature on its effectiveness remain controversial . The purpose of this trial was to evaluate efficacy of a back school program for non- -specific chronic low-back pain . PATIENTS AND METHODS Seventy patients were r and omized into two groups : experimental group ( 34 patients ) and control group ( 36 patients ) . Experimental group patients participated in a theoretical and practical back school program , which was composed of 4 weekly classes of 60 minutes . Control group patients were allocated at a waiting list . Three evaluations took place ( baseline , after 4 and 16 weeks ) . The following variables were analyzed : pain intensity ( visual numeric analogue scale ) , functional disability ( Rol and -Morris Disability Question naire ) and spinal mobility ( Schöber index ) . Statistical analysis for intra-group and inter-group used significance level of p < 0.05 . RESULTS 57 patients were analyzed ( 29 in experimental group and 28 in control group ) . A statistically significant improvement was observed only in the experimental group , regarding pain intensity , functional disability and spine mobility . Such improvements have persisted after 16 weeks in pain intensity and functional disability variables . In the inter-group analysis we observed a statistically significant difference in the second and third evaluations concerning the functional disability variables and spinal mobility . CONCLUSION The Back School program proposed in this study seems to be effective for non-specific chronic low back pain", "& NA ; The aim of this study was to evaluate an 8‐week multidisciplinary pain management program offered to patients suffering from chronic pain . The study initially included 88 participants , and 61 of the sample completed a follow‐up program conducted at 6 and 12 months after the initial programs . The pain mangement program was based on a cognitive behavioral approach with active patient participation in learning new coping skills . The intervention consisted of supervised dialog , physical activity and education . The main goals were change of focus from pain and disability to re sources and functional coping strategies . It was hypothesized that the positive changes gained at posttest registration after an 8‐week program on coping , health‐related quality of life , and pain intensity would be maintained during follow‐up sessions . The results indicated that these hypotheses were mainly supported and further pain reduction , decreased emotion‐focused coping , better social functioning , and overall physical and mental health gains were observed . The participants who did not complete the follow‐up program did not differ from the patients who completed the program on background variables investigated . The study also supported the cl aim that professional nurses are competent to lead such programs and to evaluate treatment results . Clinical and research implication s are discussed", "Study Design . A r and omized controlled trial . Objective . To examine the effects of the back school program on quality of life in women with chronic low back pain . Summary of Background Data . There is a controversial debate whether back school program might improve quality of life in back pain patients . This study aim ed to address this issue . Methods . One hundred and two eligible women were r and omly allocated into 2 groups . The 2 groups including back school group who received the back school program plus medication ( n = 50 ) and clinic group who received just medication ( n = 52 ) were compared at 4 points in time . Data were collected at baseline and at 3 , 6 , and 12 months follow-up using the SF-36 question naire . Repeated measures analysis was performed to compare quality of life scores in 2 groups . Results . Quality of life scores were significantly different between 2 groups throughout the study ( P < 0.0001 ) indicating a better quality of life among intervention group . Conclusion . The back school program might improve the quality of life score in women with chronic low back pain", "OBJECTIVE To evaluate the short-term effect of physical exercise and a cognitive intervention in low back pain . DESIGN R and omized controlled trial . SUBJECTS Ninety-three patients sick-listed for 8 - 12 weeks for sub-acute low back pain were r and omized to an exercise regime ( n = 30 ) , a cognitive intervention ( n = 34 ) or a control group ( n = 29 ) . METHODS Primary outcome measures were pain , disability , sick-listing and satisfaction with care . Secondary outcome measures were self-efficacy for pain and for function , fear-avoidance beliefs , emotional distress , generic health status and life satisfaction . RESULTS Eighteen percent of subjects dropped out . Drop-out was most frequent in the exercise group . At 18 weeks after inclusion fear-avoidance beliefs were reduced in both intervention groups . The cognitive group demonstrated significant improvement in disability , self-efficacy for pain , emotional distress , general health and life satisfaction . Patients in the exercise group were significantly more satisfied with the treatment , and patients following the exercise protocol reduced pain significantly . No effect on sick-listing was seen . CONCLUSION Cognitive intervention improved disability and may be feasible for most patients sick-listed in the sub-acute phase . Physical exercise reduced patients ' symptoms , but requires high motivation by patients . Despite positive effects in intervention groups on variables considered as negative prognostic factors for long-term disability and sickness absence , interventions had no effect on sick-listing", "Study Design . A subgroup of 195 patients with chronic low back pain , being part of a larger study of other musculoskeletal patients , were included in a r and omized controlled prospect i ve clinical study . Objectives . To evaluate the outcome in terms of return to work and cost-effectiveness of a light multidisciplinary treatment program with an extensive multidisciplinary program and treatment as usual initiated by their general practitioner . Summary of Background Data . Light multidisciplinary programs seem to reduce sick leave in patients with subacute low back pain . There are few , if any , previous studies of the effectiveness of light versus extensive multidisciplinary treatment on return to work in patients with chronic low back pain . Methods . Patients with chronic low back pain ( n = 195 ) , on an average sick-listed for 3 months , were included . The patients were r and omized to a light multidisciplinary treatment program , an extensive multidisciplinary program , or treatment as usual by their primary physician . Full return to work was used as outcome response , and follow-up was 26 months after the end of treatment . Cost – benefit was calculated for the treatment programs . Results . In men significantly better results for full return to work were found for the light multidisciplinary treatment compared with treatment as usual , but no differences were found between extensive multidisciplinary treatment and treatment as usual . No significant differences between any of the two multidisciplinary treatment programs and the controls were found for women . Productivity gains for the society from light multidisciplinary treatment versus “ treatment as usual ” of 57 male patients with low back pain would during the first 2 years accumulate to U.S. $ 852.000 . Conclusions . The light multidisciplinary treatment model is a cost-effective treatment for men with chronic low back pain", "Objective : To evaluate the efficacy of a perceptive rehabilitative approach , based on a new device , with regard to pain and disability in patients with chronic nonspecific low back pain . Design : Single blind , r and omized , controlled trial . Setting : An outpatient academic hospital . Patients : Seventy-five patients with chronic low back pain . Interventions : Patients were r and omized into three groups . Twenty-five subjects received 10 sessions in one month , based on specific perceptive exercises that were performed on a suitably developed device . Twenty-five patients entered a Back School programme . Twenty-five patients comprised a control group that received the same medical and pharmacological assistance as the other groups . Main outcome measures : Pain was assessed using the Visual Analogue Scale and McGill Pain Question naire . Disability was evaluated using the Oswestry Disability Index and Waddell Disability Index . All measurements were recorded before treatment , at the end of the study , and at 12 and 24 weeks . Results : General pain relief was recorded in all the groups , which was elicited more quickly in the perceptive treatment group ; significant differences in pain scores were observed at the end of treatment ( P < 0.001 for visual analogue scale and P = 0.001 for Question naire ) versus the other groups . Disability scores in the perceptive group did not differ significantly from those in the other group , whereas these scores significantly differed between Back School and control groups at the follow-ups ( P < 0.01 for both scales ) . Conclusion : Perceptive rehabilitation has immediate positive effects on pain . Back School reduces disabilities at follow-up", "Manipulative therapy as part of a multidimensional approach may be more effective than st and ard physical therapy in treating Acute Nonspecific Low Back Pain . 64 participants , 29 women and 35 men , with Acute Nonspecific Low Back Pain and a mean age of 40 yr . ( SD = 9.6 ) were r and omly assigned to two groups : an experimental group ( manipulative therapy plus physical therapy ) and a control group ( only physical therapy ) . A multicentre , nonblinded , r and omised clinical trial was conducted . Pain relief was the main performance criteria measured together with secondary criteria which included functional status and mobility of the lower back . Fritz , Childs , and Flynn 's clinical prediction rule — a duration of symptoms less than 16 days , no pain distal of the knee — was used to analyse the results . In combination with an age > 35 years , results showed a statistical significant effect for disability , but no statistically significant benefit of additional manipulative therapy over physical therapy found for pain and mobility within 4 treatments . Controlled for the applied clinical prediction rule , there were statistically significant interaction effects with low effect size for disability and sex , but no significant effects were found for pain of mobility", "Fifty-eight out patients with chronic low back pain were r and omly allocated to one of six experimental conditions . Four conditions were design ated as treatment conditions and two as control conditions . The four treatment groups consisted of : cognitive treatment ( either with or without relaxation training ) and behavioural treatment ( either with or without relaxation training ) . The cognitive and behavioural groups also received physiotherapy . The two control conditions consisted of : attention ( physiotherapy plus discussion sessions ) and no-attention ( physiotherapy-only ) conditions . All conditions , including the two controls , received the same physiotherapy back-education and exercise program . For the sample as a whole , improvements were obtained on measures of affective distress , functional impairment , medication use , pain-related dysfunctional cognitions and use of active coping strategies . These improvements were generally maintained at 6- and 12-month follow-ups . The combined psychological/physiotherapy treatment conditions improved significantly more than the physiotherapy-only conditions from pre to posttreatment on measures of pain intensity , self-rated functional impairment and pain-related dysfunctional cognitions . However , these differences were only weakly maintained at 6- and 12-month follow-ups . The behavioural conditions improved significantly more than the cognitive conditions from pre to posttreatment on the self-rated measure of functional impairment , but this difference was not maintained at 6- and 12-month follow-ups . Progressive relaxation training was found to make little contribution to either cognitive or behavioural treatments", "Study Design . A stratified r and omized single-blinded clinical trial . Objective . To compare the efficacies of 2 active therapies for chronic low back pain ( CLBP ) . Summary of Background Data . Both a multidisciplinary biopsychosocial rehabilitation program and an intensive individual therapist-assisted back muscle strengthening exercise program used in Denmark have been reported to be effective for the treatment of CLBP . Methods . A total of 286 patients with CLBP were r and omized to either a group-based 12-week program comprising 73 hours of therapist exposure ( approximately 12 h/patient ) : 35 hours of hard physical exercise , 22 hours of light exercise/occupational therapy , and 16 hours of education ( group A ) or a 12-week program comprising 1 hour of personal training twice a week , i.e. , therapist exposure 24 h/patient ( group B ) . At baseline and at 3 , 6 , 12 , and 24 months , patients filled out question naires on pain ( visual analogue scale [VAS]-pain average , which was the primary outcome measure ) , Rol and -Morris disability question naire , global perceived outcome , and 36-Item Short-Form General Health Survey . Data were analyzed using the intention-to-treat principle . Results . Of the 286 patients , 14 patients did not start treatment . Of the remaining patients , 25 ( 9 % ) dropped out of therapy . The 2 groups were comparable regarding baseline characteristic . After treatment , significant improvements were observed with regard to pain , disability , and most of the quality of life dimensions . These effects were sustained over the 24-month follow-up period . There were some statistically significant differences between the 2 groups relating to secondary end points , Rol and -Morris disability question naire , and in the MOS 36-Item Short-Form Health Survey the “ physical functioning ” dimension and the “ physical component summary . ” Conclusion . Both groups showed long-term improvements in pain and disability scores , with only minor statistically significant differences between the 2 groups . The minor outcome difference in favor of the group-based multidisciplinary rehabilitation program is hardly of clinical interest for individual patients", "Objectives Given the individual and economic burden of chronic work disability in low back pain patients , there is a need for effective preventive interventions . The aim of the present study was to investigate whether problem-solving therapy had a supplemental value when added to behavioral grade d activity , regarding days of sick leave and work status . Design R and omized controlled trial . Patients and Setting Employees who were recently on sick leave as a result of nonspecific low back pain were referred to the rehabilitation center by general practitioner , occupational physician , or rehabilitation physician . Forty-five employees had been r and omly assigned to the experimental treatment condition that included behavioral grade d activity and problem-solving therapy ( GAPS ) , and 39 employees had been r and omly assigned to behavioral grade d activity and group education ( GAGE ) . Outcome Measures Days of sick leave and work status . Data were retrieved from occupational health services . Results Data analyses showed that employees in the GAPS group had significantly fewer days of sick leave in the second half-year after the intervention . Moreover , work status was more favorable for employees in this condition , in that more employees had a 100 % return-to-work and fewer patients ended up receiving disability pensions one year after the intervention . Sensitivity analyses confirmed these results . Conclusions The addition of problem-solving therapy to behavioral grade d activity had supplemental value in employees with nonspecific low back pain", "Objective : To investigate the effects of a multidisciplinary back school programme ( Roessingh Back Rehabilitation Programme , RRP ) compared with usual care , as well as differences in treatment outcome between subgroups defined using two multiaxial assessment instruments : the Multidimensional Pain Inventory ( MPI-DLV ) and lumbar dynamometry . Design : R and omized controlled trial . Setting : Rehabilitation . Subjects : One hundred and sixty-three patients with chronic , aspecific low back pain . Intervention : All subjects were r and omly assigned either to a multidisciplinary , physically oriented group treatment or to their usual care . Main outcome measures : The Rol and Disability Question naire and health-related quality of life ( EuroQol , EQ5-D ) were measured as primary outcomes before r and omization and after eight weeks and six months follow-up . Result : Only 30 - 50 % of the patients in the RRP group showed improvement and this number is not significantly different from the control group . Subgroup analyses give some first indications that multiaxial measurement instruments can be used to identify subgroups with differences in treatment effects . Conclusion : The overall effect of a multidisciplinary treatment is disappointing , however multiaxial assessment before admission might be valuable in clinical practice , result ing in more effective treatments for patients with chronic low back pain", "In primary care and physical therapy setting s , we evaluated an intervention for chronic back pain patients which incorporated fear reducing and activating techniques . Primary care patients seen for back pain in primary care were screened to identify persons with significant activity limitations 8–10 weeks after their visit . Eligible and willing patients were r and omized ( N=240 ) . A brief , individualized program to reduce fear and increase activity levels was delivered by a psychologist and physical therapists . Over a 2 year follow‐up period , intervention patients reported greater reductions in pain‐related fear ( P<0.01 ) , average pain ( P<0.01 ) and activity limitations due to back pain ( P<0.01 ) relative to control patients . The percent with greater than a one‐third reduction in Rol and Disability Question naire scores at 6 months was 42 % among Intervention patients and 24 % among control patients ( P<0.01 ) . Over the 2 year follow‐up , fewer intervention patients reported 30 or more days unable to carry out usual activities in the prior 3 months ( P<0.01 ) . The adjusted mean difference in activity limitation days was 4.5 days at 6 months , 2.8 days at 12 months , and 6.9 days at 24 months . No differences were observed in the percent unemployed or the percent receiving worker 's compensation or disability benefits , but these outcomes were relatively uncommon . We conclude that an intervention integrating fear reducing and activating interventions into care for chronic back pain patients produced sustained reductions in patient fears , common activity limitations related to back pain , and days missed from usual activities due to back pain", "In an attempt to prevent acute low-back pain from becoming a chronic disability problem , an earlier study developed a statistical algorithm which accurately identified those acute low-back pain patients who were at high risk for developing such chronicity . The major goal of the present study was to evaluate the clinical effectiveness of employing an early intervention program with these high-risk patients in order to prevent the development of chronic disability at a 1-year follow-up . Approximately 700 acute low-back pain patients were screened for their high-risk versus low-risk status . On the basis of this screening , high-risk patients were then r and omly assigned to one of two groups : a functional restoration early intervention group ( n = 22 ) , or a nonintervention group ( n = 48 ) . A group of low-risk subjects ( n = 54 ) who did not receive any early intervention was also evaluated . All these subjects were prospect ively tracked at 3-month intervals starting from the date of their initial evaluation , culminating in a 12-month follow-up . During these follow-up evaluations , pain disability and socioeconomic outcomes ( such as return-to-work and healthcare utilization ) were assessed . Results clearly indicated that the high-risk subjects who received early intervention displayed statistically significant fewer indices of chronic pain disability on a wide range of work , healthcare utilization , medication use , and self-report pain variables , relative to the high-risk subjects who do not receive such early intervention . In addition , the high-risk nonintervention group displayed significantly more symptoms of chronic pain disability on these variables relative to the initially low-risk subjects . Cost-comparison savings data were also evaluated . These data revealed that there were greater cost savings associated with the early intervention group versus the no early intervention group . The overall results of this study clearly demonstrate the treatment- and cost-effectiveness of an early intervention program for acute low-back pain patients", "Background : Low back pain is a common medical and social problem associated with disability and absence from work . Knowledge on effective return to work ( RTW ) interventions is scarce . Objective : To determine the effectiveness of grade d activity as part of a multistage RTW programme . Design : R and omised controlled trial . Setting : Occupational healthcare . Subjects : 112 workers absent from work for more than eight weeks due to low back pain were r and omised to either grade d activity ( n = 55 ) or usual care ( n = 57 ) . Intervention : Grade d activity , a physical exercise programme aim ed at RTW based on operant-conditioning behavioural principles . Main outcome measures : The number of days off work until first RTW for more then 28 days , total number of days on sick leave during follow up , functional status , and severity of pain . Follow up was 26 weeks . Results : Grade d activity prolonged RTW . Median time until RTW was equal to the total number of days on sick leave and was 139 ( IQR = 69 ) days in the grade d activity group and 111 ( IQR = 76 ) days in the usual care group ( hazard ratio = 0.52 , 95 % CI 0.32 to 0.86 ) . An interaction between a prior workplace intervention and grade d activity , together with a delay in the start of the grade d activity intervention , explained most of the delay in RTW ( hazard ratio = 0.86 , 95 % CI 0.40 to 1.84 without prior intervention and 0.39 , 95 % CI 0.19 to 0.81 with prior intervention ) . Grade d activity did not improve pain or functional status clinical ly significantly . Conclusions : Grade d activity was not effective for any of the outcome measures . Different interventions combined can lead to a delay in RTW . Delay in referral to grade d activity delays RTW . In implementing grade d activity special attention should be paid to the structure and process of care", "OBJECTIVE To assess the cost-utility of an exercise programme vs usual care after functional multidisciplinary rehabilitation in patients with chronic low back pain . DESIGN Cost-utility analysis alongside a r and omized controlled trial . SUBJECTS/ PATIENTS A total of 105 patients with chronic low back pain . METHODS Chronic low back pain patients completing a 3-week functional multidisciplinary rehabilitation were r and omized to either a 3-month exercise programme ( n = 56 ) or usual care ( n = 49 ) . The exercise programme consisted of 24 training sessions during 12 weeks . At the end of functional multidisciplinary rehabilitation and at 1-year follow-up quality of life was measured with the SF-36 question naire , converted into utilities and transformed into quality --adjusted life years . Direct and indirect monthly costs were measured using cost diaries . The incremental cost-effectiveness ratio was calculated as the incremental cost of the exercise programme divided by the difference in quality -adjusted life years between both groups . RESULTS Quality of life improved significantly at 1-year follow-up in both groups . Similarly , both groups significantly reduced total monthly costs over time . No significant difference was observed between groups . The incremental cost-effectiveness ratio was 79,270 euros . CONCLUSION Adding an exercise programme after functional multidisciplinary rehabilitation compared with usual care does not offer significant long-term benefits in quality of life and direct and indirect costs", "Abstract This r and omised controlled study investigated the effect of outpatient multidisciplinary pain centre treatment ( MPT ) compared with treatment by a general practitioner after initial supervision by a pain specialist ( GP‐group ) and with a group of patients waiting for 6 months before treatment was initiated ( WL‐group ) . One‐hundred‐ and ‐eighty‐nine chronic non‐malignant pain patients were studied . At referral , and after 3 and 6 months patients filled in question naires evaluating pain intensity , health related quality of life ( HRQL ) and use of analgesics . HRQL was evaluated using the Medical Outcome Study ‐Short Form ( SF‐36 ) , the Hospital Anxiety and Depression scale ( HAD ) and the Psychological General Well‐being Scale ( PGWB ) . After 6 months patients allocated to MPT ( n=63 ) reported statistically significant reduction in pain intensity ( VAS‐score , P<0.001 ) , improvement in psychological well‐being ( PGWB , P<0.001 ) , quality of sleep ( P<0.05 ) and physical functioning ( SF‐36‐Phycical Functioning , P<0.05 ) . No improvements were seen in the GP‐group ( n=63 ) . In the WL‐group ( n=63 ) a statistically significant deterioration was observed in PGWB‐scores , HAD‐scores and in 6 of 8 SF‐36‐subscores ( P ≤ 0.05 ) . A reduction in use of opioids administered on dem and was obtained in the group receiving MPT ( P<0.001 ) . In the MPT‐ and GP‐groups a decrease in the use of short acting opioids was observed ( P<0.01 ) . No change in use of analgesics was seen in the WL‐group . The study showed that ( i ) in the MPT‐group there was a significant reduction in pain intensity and improvement of HRQL compared to the WL‐group , and ( ii ) the mere establishment of a pain diagnosis and a pain management plan by a pain specialist was not sufficient to enable the referring GP to manage severely chronic pain patients", "STUDY DESIGN A three and six months follow-up in a r and omized controlled trial . BACKGROUND Back School has become a widespread exercise program for low back pain ( LBP ) , since its introduction in 1969 . Back School could improve quality of life ( QoL ) , but there are controversial data regarding its effectiveness . AIM To evaluate the effects of the Back School program on quality of life ( primary outcome ) , disability and pain perceptions ( secondary outcomes ) in patients with chronic and non-specific low back pain . SETTING Rehabilitative specialized centre . POPULATION Seventy four patients with chronic non-specific LBP . METHODS Patients were r and omly placed in a 3:2 form and were allocated into 2 groups ( treated-control ) . Treatment group participated in a intensive multidisciplinary Back School program including brief education and active back exercises ( BSG , N.=41 ) , while the control group received medical assistance ( CG , N.=29 ) . Medication was the same in both groups . The Short Form 36 Health Status Survey , Waddel Index , Oswestry Disability Index and Visual Analogue Scale were collected at baseline , at the end of treatment , and at the three and six month follow-up . RESULTS Quality of life significantly improved along time more in BSG , both in Physical and Mental Composite Score ( repeated measure Anova : interaction time per group : P<0.001 and P=0.002 , respectively ) . We also observed a significant improvement in disability scores along time ( P<0.001 ) in BSG with significant differences between groups at three and at six months for Waddell Index ( P=0.006 and P=0.009 respectively ) and for Oswestry Disability Index ( P=0.018 and 0.011 respectively ) . Moreover , pain perception score VAS showed a reduction in both groups , but it was significantly lower in BSG at end of treatment and both follow-ups ( P<0.001 ) . CONCLUSION Our Back School program can be considered an effective treatment in people with chronıc non-specıfıc LBP", "& NA ; The aim of the present study was to evaluate the long‐term outcome of a behavioural medicine rehabilitation programme and the outcome of its two main components , compared to a ‘ treatment‐as‐usual ’ control group . The study employed a 4 × 5 repeated‐ measures design with four groups and five assessment periods during a 3‐year follow‐up . The group studied consisted of blue‐collar and service/care workers on sick leave , identified in a nationwide health insurance scheme in Sweden . After inclusion , the subjects were r and omised to one of the four conditions : behaviour‐oriented physiotherapy ( PT ) , cognitive behavioural therapy ( CBT ) , behavioural medicine rehabilitation consisting of PT+CBT ( BM ) and a ‘ treatment‐as‐usual ’ control group ( CG ) . Outcome variables were sick leave , early retirement and health‐related quality of life . A cost‐effectiveness analysis , comparing the programmes , was made . The results showed , consistently , the full‐time behavioural medicine programme being superior to the three other conditions . The strongest effect was found on females . Regarding sick leave , the mean difference in the per‐ protocol analysis between the BM programme and the control group was 201 days , thus reducing sick leave by about two‐thirds of a working year . Rehabilitating women has a substantial impact on costs for production losses , whereas rehabilitating men seem to be effortless with no significant effect on either health or costs . In conclusion , a full‐time behavioural medicine programme is a cost‐effective method for improving health and increasing return to work in women working in blue‐collar or service/care occupations and suffering from back/neck pain", "Abstract A functional restoration ( FR ) program , dealing with a combination of intensive physical and ergonomic training , psychological pain management , and patient education , was tested in two r and omized , parallel group studies . In one of these patients following the FR program were compared with a non-treated control group ( project A ) , and in the other with patients on two less intensive treatment programs ( project B ) . A total of 238 chronic low back pain patients participated in the two studies , 106 entering project A and 132 project B. Patients from the two projects were comparable except that the patients in project A were recruited from all over the country , whereas patients in project B all were living in and around Copenhagen . Thirteen patients never started any treatment , and 20 patients ( 9 % ) dropped out during the treatment period . Of the 207 who completed treatment , 89 % returned a mailed question naire 5 years later . This was the case for 55 % of the drop-outs . The questions referred to work situation , pain level , activities of daily living , days of sick leave , contact with health care professionals , physical activity , use of medication , and a subjective overall assessment . The results show that in project A the treated group reported significantly fewer contacts with the health care system and significantly fewer days of sick leave over the 5-year follow-up period compared to the control group . In all other parameters , including work ability , there was no statistically significant difference between the two groups . In project B , patients treated in the FR program did significantly better in most measured parameters , except in leg pain , use of pain medication and sport activity , where no significant differences were found between groups . The overall result shows a positive long-term effect of the FR program , but it also shows the necessity of testing a given treatment in different projects and design s , among other things due to statistical variations", "Objective Evaluate the effectiveness of two active interventions , aim ed at secondary prevention of low back pain ( LBP ) , in occupational health . Methods We performed a survey of LBP ( n=2480 ; response rate 71 % ) and r and omized 143 employees ( 66 % males , 45 years ) with LBP over 34 mm on VAS into Rehabilitation ( n=43 ) , Exercise ( n=43 ) or self-care ( n=40 ) groups . Primary outcomes were LBP , physical impairment ( PI ) and health-related quality of life ( HRQoL ) for two years and sickness absence ( SA ) days during four years ( LBP specific , total ) . Results Compared to self-care , exercise reduced LBP at 12 months ( mean difference ( MD ) −12 mm ; 95 % CI −21 to −2 ) and improved HRQoL at 12 and 24 months ( 0.03 ; 0.00 to 0.05 ) , but did not reduce PI . The MDs of SA days in four years were −17 ( −70 to 35 , total ) and −15 ( −47 to 13 , LBP specific ) . Exercise reduced the probability of LBP specific SA during the third and fourth year . Compared to self-care , Rehabilitation reduced LBP at 3 months ( −10 mm ; −19 to −1 ) and 6 months ( −10 mm ; −20 to − 1 ) , but was not effective in HRQoL or PI . The MDs of SA days in four years were −41 ( −93 to 8 ; total ) and 5 ( −30 to 47 ; LBP specific ) . Rehabilitation reduced the probability of total SA during first and second year and amount of total SA days in the fourth year . Conclusions Among employees with relatively mild LBP , both interventions reduced pain , but the effects on SA and PI were minor . Exercise improved HRQoL. The effect sizes were rather small . Trial registration Number Clinical Trials.gov NCT00908102", "Outcome of inpatient and outpatient treatment of low back pain was studied in 459 patients ( aged 35 - 54 years , 63 % men ) ; 156 in patients , 150 out patients and 153 controls . Changes in low back pain and in disability caused by it , and adherence and accomplishment of back exercises were used as short-term outcome criteria . The overall results showed a significant decrease in pain and disability and better compliance in the two treated groups when compared to the controls . There was also a significant difference in treatment gains between the in patients and out patients ; i.e. the decrease in pain was greater and the frequency of back exercises higher in the in patients . The in patients also estimated their treatment benefits more positively than the out patients", "BACKGROUND CONTEXT Rehabilitation services using intensive exercise for the treatment of chronic spinal pain have traditionally been scheduled at a frequency of three times per week . PURPOSE In an attempt to reduce the cost of rehabilitation services , this study was design ed to determine whether treatment offered two times per week could produce similar outcomes when compared with an established three times per week spine therapy program . STUDY DESIGN Prospect i ve cohort study . PATIENT SAMPLE Seventy-seven consecutive patients with chronic spinal pain were treated with aggressive spine rehabilitation either two or three times per week . OUTCOME MEASURES Flexibility , trunk strength and lifting capacity were quantified before and after treatment . Pain visual analog scores and Oswestry disability scores were measured before and after treatment , as well as 12 months after treatment . METHODS A two times per week physical therapy program was developed to be identical in its treatment method to an established three times per week , group-oriented physical therapy program used for the treatment of chronic spinal pain . Patients with spinal pain who continued to work despite chronic pain complaints were allowed to choose between the two therapy programs based on availability of treatment slots and convenience . Treatment consisted of non-pain contingent quota-based exercises targeting identified physical impairments . Treatment sessions lasted for 2 hours and consisted of 30 minutes of stretching , 30 minutes of low-impact step aerobics class and 1 hour of exercise on strength and endurance equipment . Therapy occurred in groups consisting of a maximum of eight patients who were closely supervised by two therapists . Targeted treatment time was 6 weeks . At 12 months after treatment , subjects were surveyed by mailed question naires . RESULTS Seventy-seven patients with chronic spinal pain with a mean duration of symptoms of 32 months underwent treatment . Twenty-four subjects opted for the twice per week and 53 opted for the three times per week treatment . Seventy-one percent of subjects responded to the 12-month follow-up question naire . Physical and self-reported measures improved with both treatment frequencies . There were no differences in outcomes between treatment frequencies for measured flexibility , trunk strength , lifting capacity , pain intensity scores or Oswestry scores at the completion of treatment . At 12-month follow-up , no differences were noted between treatment frequencies for pain scores , Oswestry scores , patients ' perceptions of adequacy of treatment , posttreatment exercise compliance or use of other treatments for their spinal problem . Total therapy visits were less in the two than three times per week groups ( 12 vs 15 visits ) . CONCLUSION Similar outcomes were obtained from aggressive spine rehabilitation occurring two versus three times per week in patients presenting with moderate levels of chronic spinal pain . Reduction in physical therapy services and therefore cost did not adversely affect clinical outcomes in the treatment of this patient population", "This study examined the comparative efficacy of three interventions : a spouse-assisted coping skills training protocol for patients undergoing a multidisciplinary pain management programme ( SA-MPMP ) , conventional patient-oriented multidisciplinary pain management programme ( P-MPMP ) and st and ard medical care ( SMC ) . Thirty-six chronic low back pain ( CLBP ) patients and their spouses were r and omly assigned to one of the three conditions . The SA-MPMP condition consisted of seven , weekly , 2-h , group sessions of training in dyadic pain coping and couple skills , delivered by a clinical psychologist with support of a multidisciplinary team of specialists , to patients together with their spouses . P-MPMP consisted of the SA-MPMP training delivered to the patient only ( i.e. , no spouse participation and assistance ) . The SMC condition entailed continuation of routine treatment , entailing medical care only . Data analysis revealed that , at the 12-month follow-up time point , patients receiving SA-MPMP had significant improvements in kinesiophobia and rumination about pain compared to those receiving P-MPMP and SMC . In patients suffering from CLBP , an intervention that combines spouse-assisted coping skills training with a multidisciplinary pain management programme can improve fear of movement and rumination about low back pain", "Chronic low-back pain is a frequent symptom causing considerable socioeconomic costs in many countries . Outpatient treatment of low-back pain often remains unsatisfactory . In our prospect i ve study , one hundred patients on the five months waiting list were allocated r and omly to attending the hospital either four months or six months later , the latter serving as a control group for those undergoing treatment . Health status was assessed using a multidimensional question naire , which had proven a reliable , valid and sensitive instrument in former studies . After four to six weeks of multidisciplinary inpatient treatment , a significant decrease in pain , anxiety and depression was found , whereas no improvement was observed in the control group . Multidisciplinary inpatient treatment therefore at least has short-term positive effects on patients ' health status", "Study Design . A multicenter , r and omized , single‐blinded controlled trial with 1‐year follow‐up . Objectives . To evaluate the efficiency of progressively grade d medical exercise therapy , conventional physiotherapy , and self‐exercise by walking in patients with chronic low back pain . Summary and Background Data . Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms , improve function , and decrease sickness absence , but this opinion is controversial . Methods . Patients with chronic low back pain or radicular pain sick‐listed for more than 8 weeks and less than 52 weeks ( Sickness Certificate II ) were included . The treatment lasted 3 months ( 36 treatments ) . Pain intensity , functional ability , patient satisfaction , return to work , number of days on sick leave , and costs were recorded . Results . Of the 208 patients included in this study , 71 were r and omly assigned to medical exercise therapy , 67 to conventional physiotherapy , and 70 to self‐exercise . Thirty‐three ( 15.8 % ) patients dropped out during the treatment period . No difference was observed between the medical exercise therapy and conventional physiotherapy groups , but both were significantly better than self‐exercise group . Patient satisfaction was highest for medical exercise therapy . Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started , with 123 patients were back to work . In terms of costs for days on sick leave , the medical exercise therapy group saved 906,732 Norwegian Kroner ( NOK ) ( $ 122,531.00 ) , and the conventional physiotherapy group saved NOK 1,882,560 ( $ 254,200.00 ) , compared with the self‐exercise group . Conclusions . The efficiency of medical exercise therapy and conventional physiotherapy is shown . Leaving patients with chronic low back pain untampered poses a risk of worsening the disability , result ing in longer periods of sick leave", "Objective This r and omized clinical trial examined the efficacies of a group-based multidisciplinary rehabilitation program and oral drug treatment versus oral drug treatment alone in Iran . Methods A total of 197 patients with chronic low back pain were r and omized to either intervention group ( n=97 ) receiving a group-based , 5-session multidisciplinary rehabilitation program plus oral medication or to control group ( n=100 ) receiving just oral medication . At baseline and at 3 and 6-month follow-ups , patients filled out question naires on health-related quality of life ( 36-item Short-form General Health Survey ) and disability Question naires ( Quebec Disability Scale and Ronald-Morris Disability ) . Repeated measure analysis of variance was used to compare 2 groups during time . Results The 2 groups were comparable regarding all baseline characteristics ( P>0.05 ) . There were significant differences within each group by time in terms of all subscales of 36-item Short-form ( P<0.01 ) except for mental health ( P=0.7 ) . Furthermore , there were significant deferences between groups in terms of all domains of SF-36 scale except for general health ( P=0.06 ) , social function ( P=0.08 ) and role emotional ( P=0.7 ) . Furthermore , according to the scores of Ronald-Morris Disability Question naire and Quebec Disability Scale , the disability of patients in the intervention group was improved over time significantly ( P=0.01 and P<0.0001 , respectively ) . Discussion The findings revealed that the group-based multidisciplinary program could improve most domains of quality of life in chronic low back pain patients in the 6-month period . However , there were no significant differences between two groups in sub scales such as general health , social function and role emotional", "Introduction In an earlier study , Gatchel et al. ( J Occup Rehabil 13:1–9 , 2003 ) demonstrated that participants at high risk for developing chronic low back pain disability ( CLBPD ) , who received a biopsychosocial early intervention treatment program , displayed significantly more symptom improvement , as well as cost savings , relative to participants receiving st and ard care . The purpose of the present study was to exp and on these results by examining whether the addition of a work-transition component would further strengthen the effectiveness of this early intervention treatment . Methods Using an existing algorithm , participants were identified as being high-risk ( HR ) or low-risk ( LR ) for developing CLBPD . HR participants were then r and omly assigned to one of three groups : early intervention ( EI ) ; early intervention with work transition ( EI/WT ) ; or st and ard care ( SC ) . Participants provided information regarding pain , disability , work status , and psychosocial functioning at baseline , periodically during treatment , and again 1 year following completion of treatment . Results At 1-year follow-up , no significant differences were found between the EI and EI/WT groups in terms of occupational status , self-reports of pain and disability , coping ability or psychosocial functioning . However , significant differences in all these outcomes were found comparing these groups to st and ard care . Conclusion The addition of a work transition component to an early intervention program for the treatment of ALBP did not significantly contribute to improved work outcomes . However , results further support the effectiveness of early intervention for high-risk ALBP patients", "Study Design . Cluster r and omized controlled trial . Objective . To improve quality of care for patients with low back pain ( LBP ) a multifaceted general practitioner education alone and in combination with motivational counseling by practice nurses has been implemented in German general practice s. We studied effects on functional capacity ( main outcome ) , days in pain , physical activity , quality of life , or days of sick leave ( secondary outcomes ) compared with no intervention . Summary of Background Data . International research has lead to the development of the German LBP guideline for general practitioners . However , there is still doubt about the most effective implementation strategy . Although effects on process of care have been observed frequently , changes in patient outcomes are rarely seen . Methods . We recruited 1378 patients with LBP in 118 general practice s , which were r and omized to 1 of 3 study arms : a multifaceted guideline implementation ( GI ) , GI plus training of practice nurses in motivational counseling ( MC ) , and the postal dissemination of the guideline ( controls , C ) . Data were collected ( question naires and patient interviews ) at baseline and after 6 and 12 months . Multilevel mixed effects modeling was used to adjust for clustering of data and potential confounders . Results . After 6 months , functional capacity was higher in the intervention groups with a cluster adjusted mean difference of 3.650 between the MC group and controls ( 95 % CI = 0.320–6.979 , P = 0.032 ) and 2.652 between the GI group and controls ( 95 % CI = −0.704 to 6.007 , P = 0.120 ) . Intervention effects were more pronounced regarding days in pain per year with an average reduction of 16 ( GI ) to 17 days ( MC ) after 6 months ( 12 and 9 days after 12 months ) compared with controls . Conclusion . Active implementation of the German LBP guideline results in slightly better outcomes during 6 months follow-up than its postal dissemination . Results are more distinct when practice nurses are trained in motivational counseling", "Summary Several new studies have indicated that an active approach to patients with chronic disabling low back pain ( LBP ) seems effective . Some of these studies emphasize the importance of dealing with the patient 's total situation in comprehensive multidisciplinary programs — the bio-psycho-social model . However , these programs are expensive . The aim of this study was to evaluate the rehabilitation outcome from three different active programs in terms of : ( 1 ) return-to-work rate , ( 2 ) days of sick leave , ( 3 ) health-care contacts , ( 4 ) pain and disability scores , and ( 5 ) staying physically active . The subjects included 132 patients r and omized to the study , of whom 123 started one of the treatment programs . They had all had at least 6 months of chronic LBP . The patients were r and omized into one of three programs : group 1 — a full-time , intensive 3-week multidisciplinary program , including active physical and ergonomic training and psychological pain management , followed by 1 day weekly for the subsequent 3 weeks ; group 2 — active physical training , twice a week for 6 weeks , for a total of 24h ; group 3 — psychological pain management combined with active physical training , twice a week for 6 weeks , also for a total of 24h . The results presented here are based on data collected 4 months following treatment , which shows an 86 % response rate . The initial examination and the follow-up evaluation were performed by a blinded observer . The results show that 4 months after treatment , the intensive multidisciplinary program is superior to the less intensive programs in terms of return-to-work rate , health-care contacts , pain and disability scores , and staying physically active . In conclusion , it seems that although the multidisciplinary program is initially expensive compared to the less intensive programs , the savings in sick pay , early retirement pensions , and health care contacts make it economically worthwhile . Long-term follow-up will show whether this effect continues", "There has been a recent increase in research evaluating treatment-based subgroups of non-specific low back pain . The aim of these sub-classification schemes is to identify subgroups of patients who will respond preferentially to one treatment as opposed to another . Our article provides accessible guidance on to how to interpret this research and determine its implication s for clinical practice . We propose that studies evaluating treatment-based subgroups can be interpreted in the context of a three-stage process : ( 1 ) hypothesis generation-proposal of clinical features to define subgroups ; ( 2 ) hypothesis testing-a r and omised controlled trial ( RCT ) to test that subgroup membership modifies the effect of a treatment ; and ( 3 ) replication-another RCT to confirm the results of stage 2 and ensure that findings hold beyond the specific original conditions . At this point , the bulk of research evidence in defining subgroups of patients with low back pain is in the hypothesis generation stage ; no classification system is supported by sufficient evidence to recommend implementation into clinical practice", "BACKGROUND Recent studies on chronic low back pain ( cLBP ) rehabilitation suggest that predictors of treatment outcome may be differ according to the considered conservative treatment . AIM To identify predictors of response to back school ( BS ) , individual physiotherapy ( IP ) or spinal manipulation ( SM ) for cLBP . POPULATION out patients with cLBP . SETTING Outpatient rehabilitation department . DESIGN Retrospective analysis from a r and omized trial . METHODS Two hundred and ten patients with cLBP were r and omly assigned to either BS , IP or SM ; the Rol and Morris Disability Question naire ( RM ) was assessed before and after treatment : those who decreased their RM score < 2.5 were considered non-responders . Baseline potential predictors of outcome included demographics , general and cLBP history , life satisfaction . RESULTS Of the 205 patients who completed treatment ( 140/205 women , age 58 + 14 years ) , non-responders were 72 ( 34.2 % ) . SM showed the highest functional improvement and the lowest non-response rate . In a multivariable logistic regression , lower baseline RM score ( OR 0.82 , 95 % CI 0.76 - 0.89 , P<0.001 ) and received treatment ( OR 0.32 , 95 % CI 0.21 - 0.50 , P<0.001 ) were independent predictors of non-response . Being in the lowest tertile of baseline RM score ( < 6 ) predicted non response to treatment for BS and IP , but not for SM ( same risk for all tertiles ) . CONCLUSIONS In our patients with cLBP lower baseline pain-related disability predicted non-response to physiotherapy , but not to spinal manipulation . CLINICAL REHABILITATION IMPACT Our results suggest that , independent form other characteristics , patients with cLBP and low pain-related disability should first consider spinal manipulation as a conservative treatment", "Study Design . Two r and omized , controlled trials . Objective . To evaluate the incremental cost-effectiveness of psychologist-led and lay-led interventions in reducing disability in 2 cohorts of primary care patients with back pain . Summary of Background Data . Although activating self-care interventions have been advanced as effective tools to reduce back pain-related activity limitations , few studies have evaluated the added costs of these programs relative to their added benefits . Methods . We estimated the incremental benefits and incremental costs associated with 2 self-care interventions for primary care patients with back pain . Effectiveness was measured as the number of low-impact back pain days ( i.e. , days when patients were satisfied with their level of back pain ) over a 1-year follow-up . Costs of back-pain related services were estimated from health plan cost data . Incremental cost-effectiveness ratios were calculated for each intervention to determine the costs associated with an additional low-impact back pain day . Results . Patients assigned to the lay and psychologist interventions had a mean of 14.3 ( 95 % confidence interval [ CI ] −2.7 to 30.9 ) and 26.2 ( 95 % CI 9.1–44.4 ) additional low-impact back pain days , respectively , compared with patients receiving usual care . The incremental per-person costs of the lay-led and psychologist-led interventions were $ 139 ( 95 % CI −$62.13 to $ 321.76 ) and $ 161 ( 95 % CI $ 51.18 to $ 275.93 ) , respectively . The mean cost of an additional low-impact back pain day was $ 9.70 for the lay-led intervention and $ 6.13 for the psychologist-led intervention . Conclusions . Both the lay and psychologist interventions were associated with modest improvements in outcomes but with somewhat higher costs compared to usual care", "Cognitive behavioral treatment has been incorporated into st and ard medical treatment procedures in German pain centers . Acceptance of the treatment by patients and outcome in terms of pain , coping , and disability was investigated . Components of the psychological treatment are education , relaxation and imagery , modifying thoughts and feelings , enhancement of pleasant activities , and training of good postural habits . The program was conducted in a group setting in accordance with a treatment manual and consists of 12 weekly 2.5-h sessions . A two-factor experiment with repeated measures on one factor was applied . Ninety-four consecutive patients with low-back pain were r and omly assigned to an experimental group having a combined medical and cognitive-behavioral treatment , or to a control group with medical treatment only . Assessment s were taken pre-treatment , post-treatment , and --in the treated group only -- at a 6-months follow-up . At each assessment , patients kept a pain diary over a period of 4 weeks , and filled in self-report question naires . The sample consisted of 36 experimental and 40 control subjects at post-treatment . Experimental subjects reported less pain , better control over pain , more pleasurable activities and feelings , less avoidance and less catastrophizing . In addition , disability was reduced in terms of social roles , physical functions and mental performance . The results were maintained at follow-up . Patients who only received medical treatment showed little improvement . Data indicate that the program meets the needs of the patients and should be continued", "Seventy-one chronic low back pain patients were assigned to one of three behavioural rehabilitation treatments or a waiting-list condition . The first intervention consisted of an operant treatment , aim ed at increasing health behaviours and activity levels and at reducing pain and illness behaviours . In the second intervention , a cognitive treatment , aim ed at the reinterpretation of catastrophizing pain cognitions and at enhancing self-control , was combined with an operant treatment . The third intervention consisted of the combination of the operant approach and a respondent treatment . During the respondent treatment , patients were taught to decrease muscle tension levels , using the ' applied relaxation ' technique supported by EMG-biofeedback and grade d exposure to tension-eliciting situations . A repeated measurements design included observer rating of pain behaviours , observer ratings of mood , self-reported depression , residual health behaviours , pain cognitions and experienced pain intensity . Follow-up assessment occurred at six months and one year after termination of treatment . Results suggest that , for the sample as a whole , improvements are found on measures of pain behaviours , health behaviours , pain cognitions and affective distress and that these improvements are maintained at six months and one year follow-up . During the treatment the three treatment groups improved significantly more than the waiting-list control group on most of the measures . Further , the results of this study provide evidence that the operant-cognitive and operant-respondent conditions are more efficacious in decreasing pain behaviours and in increasing health behaviours and efficacy expectations than operant treatment alone . This differential effect among the conditions is maintained at follow-up . Patients who received the OC and OR treatments catastrophize less than OP patients , and OC patients showed better scores on outcome -efficacy than OR patients . In general , the results suggest that behavioural rehabilitation programmes for chronic low back pain are effective and that the effects of an operant treatment are magnified when self-control techniques are added", "OBJECTIVES To examine the relative efficacy of three active therapies for patients with chronic low back pain . METHODS One hundred and forty-eight subjects with chronic low back pain were r and omized to receive , twice weekly for 3 months , ( i ) active physiotherapy , ( ii ) muscle reconditioning on training devices , or ( ii ) low-impact aerobics . Question naires were administered to assess pain intensity , pain frequency and disability before and after therapy and at 6 and 12 months of follow-up . RESULTS One hundred and thirty-two of the 148 patients ( 89 % ) completed the therapy programmes and 127 of the 148 ( 86 % ) returned a question naire at all four time-points . The three treatments were equally efficacious in significantly reducing pain intensity and frequency for up to 1 yr after therapy . However , the groups differed with respect to the temporal changes in self-rated disability over the study period ( P=0.03 ) : all groups showed a similar reduction after therapy , but for the physiotherapy group disability increased again during the first 6 months of follow-up whilst the other two groups showed a further decline . In all groups the values then remained stable up to the 12-month follow-up . The larger group size and minimal infrastructure required for low-impact aerobics rendered it considerably less expensive to administer than the other two programmes . CONCLUSIONS The introduction of low-impact aerobic exercise programmes for patients with chronic low back pain may reduce the enormous costs associated with its treatment", "The purpose of the present study was to investigate the long-term effect of the Active Back School programme on minimizing recurrences of episodes of low back pain . Forty-three subjects were r and omly allocated to the Active Back School group and 38 to the control group . There were no significant differences between the groups with regard to baseline characteristics . The Active Back School programme comprised 20 lessons each divided into a 20-min theoretical and a 40-min exercise part during a 13-week period . Nine participants ( 11 % ) dropped out during the study period . Recurrence of new low back pain episodes was significantly less ( p = 0.04 ) , and the time from inclusion to the first new low back pain episode was significantly on the side of the Active Back School group ( p < 0.01 ) . The duration of sick leave was found to be significantly shorter ( p < 0.01 ) in the Active Back School group compared to the control group . The Active Back School reduced the recurrence and severity of new low back pain episodes at 36 months ' follow-up", "Study Design . R and omized controlled trial . Objective . To assess the effects of a lifestyle intervention for hypertension on low back pain . Summary of Background Data . According to prospect i ve etiologic studies , a causal association exists between certain lifestyle factors and low back pain . These factors are similar to those that elevate the risk for hypertension . Nevertheless , no r and omized controlled trial has assessed effectiveness of lifestyle intervention for the treatment of hypertension on the prevalence of low back pain . Methods . A total of 731 hypertensive employees from 45 worksites were assigned to multidisciplinary lifestyle interventions for hypertension in a rehabilitation center or to routine care in occupational or primary healthcare services during 12 months . Question naire data on low back pain were used to assess the effects of the intervention on the extent of low back pain and disability . Results . The changes in prevalence and duration of low back pain , and related disability did not differ between the 2 groups , although there were favorable changes in some risk factors , such as body weight and physical inactivity . Subgroup analyses among patients with moderately heavy or heavy work showed that the prevalence of low back pain during the previous 12 months decreased more in the intervention than in the control group . Conclusion . Multidisciplinary lifestyle intervention aim ed to reduce hypertension is not effective at reducing prevalence of low back pain or disability . However , in thesubgroup of persons doing moderate or heavy work , the intervention seemed to reduce prevalence of low back pain during the 1-year follow-up", "Background Many pain patients appreciate biofeedback interventions because of the integration of psychological and physiological aspects . Therefore we wanted to investigate in a sample of chronic back pain patients whether biofeedback ingredients lead to improved outcome of psychological interventions . Method One hundred and twenty-eight chronic back pain patients were r and omly assigned to cognitive-behavioural therapy ( CBT ) , cognitive-behavioural therapy including biofeedback tools ( CBT-B ) or waitlist control ( WLC ) . The sample was recruited from a highly disabled group including many patients with low education status and former back surgeries . Measures on pain , physical functioning , emotional functioning , coping strategies and health care utilisation were taken at pretreatment , posttreatment and 6 months of follow-up . Results The results indicated significant improvements on most outcome measures for CBT-B and CBT in comparison to WLC . CBT-B and CBT were equally effective ( e.g. ITT effect sizes for pain intensity : CBT-B , 0.66 ( 95 % CI 0.39–0.95 ) ; CBT , 0.60 ( 95 % CI 0.33–0.87 ) ) . Conclusion In conclusion , biofeedback ingredients did not lead to improved outcome of a psychological intervention . Cognitive-behavioural treatment as a “ package ” of respondent , operant and cognitive interventions was effective for ameliorating pain-related symptoms for chronic back pain patients treated in an outpatient setting . The high treatment acceptability associated with biofeedback ingredients can also be achieved with pure psychological interventions", "Objectives Grade d exposure in vivo ( GEXP ) treatment has been successfully used to reduce levels of pain-related fear and disability in some chronic pain patients , but its effectiveness has not been evaluated in general clinical setting s using group- design studies . The purpose of this study was to determine if the systematic incorporation of GEXP into a multidisciplinary chronic pain management group ( PMG ) treatment program would result in better treatment outcomes than usual PMG treatment . Methods One hundred forty-three chronic pain patients who were assessed as suitable for an outpatient multidisciplinary chronic PMG program were r and omly allocated to 3 experimental conditions ; usual PMG , PMG incorporating systematic grade d exposure , and wait-list control . Results The clinical outcomes of the 2 treatment conditions were not significantly different , suggesting that the systematic incorporation of GEXP into a multidisciplinary PMG program did not result in better treatment outcomes than usual PMG treatment . Both group treatment programs were associated with significant treatment effects when compared with the wait-list control on measures of pain intensity , fear of movement/(re)injury , pain self-efficacy , activity level , and depression . No treatment effects were found on self-report measures of pain disability or anxiety . Discussion The addition of systematic grade d exposure into a multidisciplinary chronic pain management program did not result in better clinical outcomes than the usual group treatment program . The validity of GEXP to the broader population of chronic pain patients warrants further investigation", "BACKGROUND Low-back pain is a common and costly problem . We estimated the effectiveness of a group cognitive behavioural intervention in addition to best practice advice in people with low-back pain in primary care . METHODS In this pragmatic , multicentre , r and omised controlled trial with parallel cost-effectiveness analysis undertaken in Engl and , 701 adults with troublesome subacute or chronic low-back pain were recruited from 56 general practice s and received an active management advisory consultation . Participants were r and omly assigned by computer-generated block r and omisation to receive an additional assessment and up to six sessions of a group cognitive behavioural intervention ( n=468 ) or no further intervention ( control ; n=233 ) . Primary outcomes were the change from baseline in Rol and Morris disability question naire and modified Von Korff scores at 12 months . Assessment of outcomes was blinded and followed the intention-to-treat principle , including all r and omised participants who provided follow-up data . This study is registered , number IS RCT N54717854 . FINDINGS 399 ( 85 % ) participants in the cognitive behavioural intervention group and 199 ( 85 % ) participants in the control group were included in the primary analysis at 12 months . The most frequent reason for participant withdrawal was unwillingness to complete question naires . At 12 months , mean change from baseline in the Rol and Morris question naire score was 1.1 points ( 95 % CI 0.39 - 1.72 ) in the control group and 2.4 points ( 1.89 - 2.84 ) in the cognitive behavioural intervention group ( difference between groups 1.3 points , 0.56 - 2.06 ; p=0.0008 ) . The modified Von Korff disability score changed by 5.4 % ( 1.99 - 8.90 ) and 13.8 % ( 11.39 - 16.28 ) , respectively ( difference between groups 8.4 % , 4.47 - 12.32 ; p<0.0001 ) . The modified Von Korff pain score changed by 6.4 % ( 3.14 - 9.66 ) and 13.4 % ( 10.77 - 15.96 ) , respectively ( difference between groups 7.0 % , 3.12 - 10.81 ; p<0.0001 ) . The additional quality -adjusted life-year ( QALY ) gained from cognitive behavioural intervention was 0.099 ; the incremental cost per QALY was 1786 pound sterling , and the probability of cost-effectiveness was greater than 90 % at a threshold of 3000 pound sterling per QALY . There were no serious adverse events attributable to either treatment . INTERPRETATION Over 1 year , the cognitive behavioural intervention had a sustained effect on troublesome subacute and chronic low-back pain at a low cost to the health-care provider . FUNDING National Institute for Health Research Health Technology Assessment Programme", "Study Design . R and omized controlled trial with 1-year follow-up . Objective . To analyze the effects of an exercise program or routine follow-up on patients with chronic low back pain who have completed functional multidisciplinary rehabilitation . The short- and long-term outcome in terms of symptoms and physical and social functioning was compared . Summary of Background Data . Systematic review s have shown that functional multidisciplinary rehabilitation improves physical function and reduces pain in patients with chronic low back pain . However , long-term maintenance of these improvements is inconsistent and the role of exercise in achieving this goal is unclear . Methods . One hundred five chronic patients with low back pain who had completed a 3-week functional multidisciplinary rehabilitation program were r and omized to either a 3-month exercise program ( n = 56 ) or routine follow-up ( n = 49 ) . The exercise program consisted of 24 training sessions during 12 weeks . Patients underwent evaluations of trunk muscle endurance , cardiovascular endurance , lumbar spine mobility ( flexion and extension range-of-motion , fingertip-to-floor distance ) , pain and perceived functional ability at the beginning and the end of functional multidisciplinary rehabilitation , at the end of the exercise program ( 3 months ) and at 1-year follow-up . Disability was also assessed at the same time points except at the beginning of functional multidisciplinary rehabilitation . Results . At the end of the functional multidisciplinary rehabilitation , both groups improved significantly in all physical parameters except flexion and extension range-of-motion . At the 3 month and 1 year follow-up , both groups maintained improvements in all parameters except for cardiovascular endurance . Only the exercise program group improved in disability score and trunk muscle endurance . No differences between groups were found . Conclusion . A favorable long-term outcome was observed after functional multidisciplinary rehabilitation in both patient groups . Patients who participated in an exercise program obtained some additional benefits . The relevance of these benefits to overall health status need to be further investigated", "OBJECTIVE This study determines the efficacy of two such multimodal treatments in the management of lumbar pain syndrome in males and females . METHOD Total subjects of 141 male or female were r and omized to treat either with conventional treatment or by DMST ( dynamic muscular stabilization techniques ) . After stratification on the basis of gender ( 51 male and 21 female ) were found in DMST group whereas ( 40 male and 29 female ) were found in conventional group . The primary outcome measures were pain severity , physical strength ( BPC and APC ) , functional ability ( Walking , Stairs climbing and St and -ups ) and QOL . All patients were assessed at baseline ( day 0 ) , 10 days , 20 days , 90 days and at the end treatment or follow up ( day 180 ) . RESULT In this study the improvement of pain , BPC , APC , Walking , Stair climbing and st and -ups in females and males were 22.5 % and 29.0 % , 60.9 % and 53.7 % , 42.0 % and 51.9 % , 49.8 % and 49.3 % , 54.2 % and 48.7 % , 52.3 % and 39.7 % , higher respectively in DMST as compared to CONV whereas QOL in females of DMST improved by 53.6 % more than the females of CONV while males of DMST improved by 57.9 % more than the males of CONV . CONCLUSION DMST as well as CONV treatments are more effective in males than the females . Study also concluded that subgroup \" female \" may need more clinical attention during the management of LBP", "BACKGROUND Americans with low back pain have been helped to return to work by multidisciplinary intensive treatment programs . Whether this treatment method will succeed in countries with a more generous social welfare system , where the incentive to return to work might be less , is not proven . OBJECTIVES To evaluate a Danish program of functional restoration combined with behavioral support . METHODS Patients who had experienced at least 6 months of disabling low back pain were r and omly assigned to either a 3-week intensive treatment program ( n = 55 ) or an untreated control group ( n = 51 ) . RESULTS Of the 106 patients r and omized , 94 ( 89 % ) returned for a 4-month follow-up visit . At that time , 29 ( 64 % ) of the 45 treated patients were able to work , compared with 14 of 49 ( 29 % ) in the control group . The treated patients had used fewer days of sick leave ( P < .02 ) , had contacted health care . professionals fewer times ( P < .001 ) , and had lower pain and disability scores . CONCLUSIONS Although such programs are expensive , they can reduce pension expenditures , sick leave days , health care contacts , and pain", "Study Design . A prospect i ve , r and omized controlled trial . Objective . To examine long-term effects and costs of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain ( cLBP ) . Summary of Background Data . An obvious gap exists in knowledge concerning long-term efficacy and cost-effectiveness of manipulative treatment methods . Methods . Of 204 patients with cLBP whose Oswestry Disability Index ( ODI ) was at least 16 % , 102 were r and omized into a combined manipulative treatment , exercise , and physician consultation group ( i.e. , a combination group ) , and 102 to a consultation alone group . All patients were clinical ly examined , informed about their back pain , and encouraged to stay active and exercise according to specific instructions based on clinical evaluation . Treatment included 4 sessions of manual therapy and stabilizing exercises aim ed at correcting the lumbopelvic rhythm . Question naires inquired about pain ( visual analog scale [ VAS ] ) , disability ( ODI ) , health-related quality of life ( 15D Quality of Life Instrument ) , satisfaction with care , and costs . Results . Significant improvement occurred in both groups on every self-rated outcome measurement . Within 2 years , the combination group showed only a slightly more significant reduction in VAS ( P = 0.01 , analysis of variance ) but clearly higher patient satisfaction ( P = 0.001 , Pearson & khgr;2 ) as compared to the consultation group . Incremental analysis showed that for combined group compared to consultation group , a one-point change in VAS scale cost $ 512 . Conclusions . Physician consultation alone was more cost-effective for both health care use and work absenteeism , and led to equal improvement in disability and health-related quality of life . It seems obvious that encouraging information and advice are major elements for the treatment of patients with cLBP", "Objective To compare the efficacy of surgery with disc prosthesis versus non-surgical treatment for patients with chronic low back pain . Design A prospect i ve r and omised multicentre study . Setting Five university hospitals in Norway . Participants 173 patients with a history of low back pain for at least one year , Oswestry disability index of at least 30 points , and degenerative changes in one or two lower lumbar spine levels ( 86 patients r and omised to surgery ) . Patients were treated from April 2004 to September 2007 . Interventions Surgery with disc prosthesis or outpatient multidisciplinary rehabilitation for 12 - 15 days . Main outcome measures The primary outcome measure was the score on the Oswestry disability index after two years . Secondary outcome measures were low back pain , satisfaction with life ( SF-36 and EuroQol EQ-5D ) , Hopkins symptom check list ( HSCL-25 ) , fear avoidance beliefs ( FABQ ) , self efficacy beliefs for pain , work status , and patients ’ satisfaction and drug use . A blinded independent observer evaluated scores on the back performance scale and Prolo scale at two year follow-up . Results The study was powered to detect a difference of 10 points on the Oswestry disability index between the groups at two years . At two years there was a mean difference of −8.4 points ( 95 % confidence interval −13.2 to −3.6 ) in favour of surgery . In the analysis of prespecified secondary outcomes , there were significant differences in favour of surgery for low back pain ( mean difference −12.2 , −21.3 to −3.1 ) , patients ’ satisfaction ( 63 % ( n=46 ) v 39 % ( n=26 ) ) , SF-36 physical component score ( mean difference 5.8 , 2.5 to 9.1 ) , self efficacy for pain ( mean difference 1.0 , 0.2 to 1.9 ) , and the Prolo scale ( mean difference 0.9 , 0.1 to 1.6 ) . There were no significant differences in return to work , SF-36 mental component score , EQ-5D , fear avoidance beliefs , Hopkins symptom check list , drug use , and the back performance scale . One serious complication of leg amputation occurred during surgical revision of a polyethylene dislodgement . The drop-out rate was 20 % ( 34 ) and the crossover rate was 6 % ( 5 ) . Conclusions Surgical intervention with disc prosthesis for chronic low back pain result ed in a significantly greater improvement in the Oswestry score compared with rehabilitation , but this improvement did not clearly exceed the prespecified minimally important clinical difference between groups of 10 points , and the data are consistent with a wide range of differences between the groups , including values well below 10 points . The potential risks of surgery and the substantial amount of improvement experienced by a sizeable proportion of the rehabilitation group also have to be incorporated into overall decision making . Trial registration NCT 00394732", "Study design . Eighty‐four patients with chronic low back pain were treated using cognitive behavioral principles on a pain management program . Outcome data were collected at four points : 10 weeks before treatment , immediately before and immediately after treatment , and 6 months after treatment . In part 1 of the study , patients were assigned r and omly to group or individual treatment context s. In part 2 of the study , patients were assigned r and omly to programs of 15 , 30 , or 60 hours duration . Objectives . To identify the differences in outcome between programs that treated patients as part of a group and those that treated patients individually and the effects of duration of treatment on outcome . Summary of Background Data . Cognitive behavioral programs have been shown to be an effective means of managing chronic low back pain . The literature is concerned with group programs , however , the duration of which vary widely . Method . Psychological and functional variables were measured before and after treatment and at the 6‐month follow‐up visit . Changes in these variables were measured , and comparisons were made between group and individual programs and between 15‐ , 30‐ , and 60‐hour programs . Results . Data analysis showed a significant , beneficial effect of intervention in terms of the majority of variables ; however , these changes were generally independent of whether patients were treated as part of a group or individually and whether patients completed a 15‐ , 30‐ , or 60‐hour program . Conclusions . Cognitive behavioral rehabilitation programs have been demonstrated to be an effective means of reducing psychological distress , of changing cognition , and of improving the function of patients with chronic low back pain ; however , the length of program and whether patients were treated individually or as part of a group did not affect outcome . This finding has clinical and economic implication", "AIMS The present study examines the outcome of counselling in physiotherapy based on the Transtheoretical Model ( TTM ) in a sample of elderly individuals with chronic low back pain . METHODS In a prospect i ve r and omised trial with concealed assignment , elderly individuals with chronic low back pain were allocated to two treatment conditions . Both contained 10 sessions of physiotherapy , each of 20min duration . In addition , the experimental group ( EG ) received 10min counselling prior to every session based on the TTM , also provided by the physiotherapist , and the control group ( CG ) underwent a placebo ultrasound treatment with an inactivated device to control for the additional attention given to the EG . Assessment s took place prior to the treatment ( t1 ) , immediately after termination of the treatment ( t2 ) , and at a 6-months follow-up . Outcome measures were physical activity calculated from one-week activity diaries , self-reported functional capacity , and range of motion measured by ultrasound topometry . RESULTS A total of 170 individuals ( 64 % female ) with a mean age of 70.3 years ( SD=4.4 , range 65 - 84 ) participated in the study . The retention rate was 90 % . At t3 , both EG and CG showed increased physical activity and functional capacity , but no change in range of motion . Effect sizes were large . Contrary to our hypothesis , however , motivational training did not result in a better outcome compared with placebo treatment . CONCLUSION The study does not provide evidence that a short TTM-based motivation programme is superior to placebo treatment regarding adherence to activity recommendations", "Objective : Recent recommendations suggest that reassuring patients with an acute bout of low back pain and encouraging a return to normal activities may be helpful in preventing the development of chronic disability . There is also a question as to whether psychologic or physical therapy interventions actually add anything to such reassurance and advice in terms of preventing chronicity . This study aim ed to ascertain the preventive effects on future sick leave and health-care utilization of adding on a cognitive-behavioral group intervention or a cognitive-behavioral group intervention and preventive physical therapy ( focused on activity and exercise ) relative to a minimal treatment group ( examination , reassurance , and activity advice ) . Subjects : A total of 185 patients seeking care for nonspecific back or neck pain who were employed and at risk for developing long-term disability volunteered to participate in the study . Of these 185 , 158 ( 85 % ) completed the pre- and 1-year follow-up assessment s. Results : Significant differences were observed on the key outcome variables of future health-care utilization and work absenteeism . For health-care utilization , the cognitive-behavioral intervention group and preventive physical therapy group had significantly fewer healthcare visits than did the Minimal Treatment Group . For work absenteeism , the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group had fewer days during the 12-month follow-up than did the Minimal Treatment Group . The risk for developing long-term sick disability leave was more than five-fold higher in the Minimal Group as compared with the other 2 groups . However , there was no difference between the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group on sick leave . Conclusion : Taken as a whole , this study shows that adding cognitive-behavioral intervention and cognitive-behavioral intervention and preventive physical therapy can enhance the prevention of long-term disability . There was no substantial difference in the results between the cognitive-behavioral intervention group and cognitive-behavioral intervention and preventive physical therapy group", "Study Design . R and omized clinical trial of 2 interventions in 351 employees sick listed due to low back pain ( LBP ) and a subsequent validation study ( n = 120 ) to vali date results from subgroup analyses in the original study . Objective . To compose health economic analyses ( cost-effectiveness- and cost-benefit analyses ) of multidisciplinary versus brief intervention by calculating health care sector costs and sick leave benefits . Summary of Background Data . Both brief and multidisciplinary interventions have been reported to be superior relative to usual care when comparing intervention costs with saved costs for sick leave benefits . We reported similar return to work rates in a brief and a multidisciplinary intervention group , but different return to work rates in subgroups . Methods . The brief intervention comprised clinical examination and reassuring advice . The multidisciplinary intervention was conducted by a case manager and a team of specialists . The costs of medicine , health care services , and sick leave benefits were calculated on the basis of registers . Results . The mean intervention cost per patient was & OV0556;1377 higher in the multidisciplinary intervention ( n = 176 ) than in the brief intervention group ( n = 175 ) , and sick leave was not averted . However , sick leave was averted in a subgroup receiving the multidisciplinary intervention and the mean incremental intervention cost for 1 saved sick leave week in this subgroup ( n = 60 ) of patients , who thought they were at risk of losing their job or had little influence on their work situation was & OV0556;217 . The latter finding was verified in the validation study ( n = 28 ) . Conclusion . The brief intervention result ed in fewer sick leave weeks and was less expensive than the multidisciplinary intervention . The multidisciplinary intervention only outperformed the brief intervention in terms of costs in a subgroup of sick-listed employees who thought they were at risk of losing their job or had little influence on their work situation . Level of Evidence :", "BACKGROUND CONTEXT Multidisciplinary biopsychosocial rehabilitation has been shown in controlled studies to improve pain and function in patients with chronic back pain . However , specialized back pain rehabilitation centers are rare and only a few patients can participate on this therapy . Implementation of multidisciplinary rehabilitation services in community medicine may enhance both early availability and treatment capacity for comprehensive back pain rehabilitation . PURPOSE To compare the outcome of a multidisciplinary rehabilitation program ( MRP ) that was organized by cooperation of local health-care providers in the community with that of the usual care by independent physicians for patients with chronic low back pain . STUDY DESIGN A comparison between the outcomes ( follow-up time of 6 months ) of treatment for chronic back pain in the community in a prospect i ve intervention group versus a prospect i ve observational usual care group . PATIENT SAMPLE All patients were recruited from independent physicians in the community of a selected region who participated voluntarily in the study . Patients were included in the study if they were seeking treatment of pain in the back with possible irradiation into the legs , the pain persisted for at least 3 months without decreasing intensity and there was no indication for surgical intervention . OUTCOME MEASURES Outcome was assessed from patients ' responses in self-report question naires at baseline and after an interval of 6 months . For outcome , we evaluated the health-related quality of life ( German version of Short Form [ SF ] 36 ) , the average pain severity ( Numeric Rating Scale ) , the pain-related interference of function ( German version of Brief Pain Inventory ) , depression ( Allgemeine Depressionsskele ) , time off from work within 3 months before entering and leaving the study and the self- appraisal of improvement . METHODS In a baseline group , the independent physicians treated the patients with usual care . In the intervention group , the patients were referred by the independent physicians to the study coordinator in the outpatient facilities of the Departments of Neurology or Orthopedics for inclusion in the MRP . The MRP was organized by cooperation of local health-care providers in the community with different specialties ( sport teachers , clinical psychologist , physiotherapist and physician ) who were experienced in the management of back pain . The MRP ( 4 hours per day , 3 days per week , 20 days ) included 1.5 hours restorative exercise therapy , 0.5 hours physiotherapy , 1 hour cognitive-behavioral therapy , 0.5 hours progressive muscle relaxation and 0.5 hours education . RESULTS Complete data sets were obtained from 157 patients in the usual care group ( documented by 35 independent physicians ) and 51 patients in the MRP group . Patients of the MRP group improved in the physical and mental health domains of the SF-36 more than patients treated by usual care ( p<.05 ) . Furthermore , days off work were more ( p<.05 ) reduced by the MRP ( 16+/-35 days ) than by usual care ( -2+/-39 days ) . Finally , overall appraisal of successful outcome was better ( p<.01 ) after MRP ( 54 % of patients ) as compared with usual care ( 24 % of patients ) . However , the pain intensity ( NRS ) , the pain-related interference with function ( Brief Pain Inventory ; BPI ) and the depression scores ( ADS ) did not differ significantly between both groups . CONCLUSIONS MRP is promising to improve health-related quality of life for patients with chronic back pain in the community . Before implementation of MRP in the repertoire of community medicine , superiority of MRP over usual care should be confirmed by a r and omized controlled trial", "& NA ; The aim of this study was to assess the long‐term effect of a supervised fitness programme on patients with chronic low back pain . The design of the study was a single blind r and omised controlled trial with follow‐up , by postal question naire , 2 years after intervention . The Oswestry Low Back Pain Disability Index was used as the outcome measure to assess daily activity affected by back pain . Eighty‐one patients with chronic low back pain , who were referred to the physiotherapy department of a National Health Service orthopaedic hospital , were r and omised to either a supervised fitness programme or a control group . Patients in the intervention group and control group were taught specific exercises to be continued at home and referred to a backschool for back care education . In addition , the intervention group attended eight sessions of a supervised fitness programme . Sixty‐two patients ( 76 % ) with a mean age of 37 years , returned the Oswestry Low Back Pain Disability Index question naire . Of these , 29 were in the intervention group and 31 in the control group . Patients in the intervention group demonstrated a mean reduction of 7.7 % in the Oswestry Low Back Pain Disability Index score ( 95 % confidence interval of mean paired difference 3.9 , 11.6 P<0.001 ) , compared with only 2.4 % in the control group ( 95 % confidence interval of mean paired difference −2.0 , 6.9 P>0.05 ) . Between group comparisons demonstrated a statistically significant difference in disability scores between the treatment and control group ( mean difference 5.8 , 95 % confidence interval 0.3 , 11.4 P<0.04 ) . This study supports the current trend towards a more active treatment approach to low back pain . We have demonstrated clinical effectiveness of a fitness programme 2 years after treatment but this needs to be replicated in a larger study which should include a cost effectiveness analysis , further analysis of objective functional status and a placebo intervention group", "STUDY DESIGN A r and omized , controlled , single-center trial with a stratified group design . OBJECTIVE To investigate the secondary prophylactic effect of the Active Back School program on minimizing recurrences of low back pain episodes . SUMMARY OF BACKGROUND DATA The results of back school interventions are controversial . Previous work often used short intervention periods and low doses of practical training . However , studies with the highest method ologic scores have shown the best results , especially when conducted in occupational setting s and coupled with a comprehensive rehabilitation program . METHODS By block r and omization , 19 men and 24 women were allocated to Active Back School , with 18 men and 20 women as control subjects . The Slumps test and number of low back pain episodes during the previous 36 months were used as stratification factors . There were no significant differences between the groups with regard to demographic factors and initially observed variables . Active Back School consisted of 20 lessons over a 13-week period . Each lesson was divided into a 20-minute theoretical part and a 40-minute exercise part . All participants were examined on enrollment , then 5 and 12 months after initiation of the program . Outcome measures were recurrence of low back pain episodes and number of days of sick leave . RESULTS The recurrence of new low back pain episodes was significantly lower ( P < 0.05 ) and the time from inclusion to the first new episode significantly longer ( P < 0.01 ) in the Active Back School group than in the control group . In the Active Back School group , seven participants took sick leave because of low back pain episodes during the first 12 months of follow-up compared with 11 among the control subjects . The number of sick leave days was significantly lower ( P < 0.05 ) in the Active Back School group than in the control group . CONCLUSION Active Back School reduced the recurrence and severity of new low back pain episodes according to results of follow-up examinations performed 5 and 12 months after enrollment", "Study design . Population -based r and omized controlled trial . Objective . To assess the effectiveness of workplace intervention and grade d activity , separately and combined , for multidisciplinary rehabilitation of low back pain ( LBP ) . Summary of Background Data . Effective components for multidisciplinary rehabilitation of LBP are not yet established . Methods . Participants sick-listed 2 to 6 weeks due to nonspecific LBP were r and omized to workplace intervention ( n = 96 ) or usual care ( n = 100 ) . Workplace intervention consisted of workplace assessment , work modifications , and case management involving all stakeholders . Participants still sick-listed at 8 weeks were r and omized for grade d activity ( n = 55 ) or usual care ( n = 57 ) . Grade d activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles . Outcomes were lasting return to work , pain intensity and functional status , assessed at baseline , and at 12 , 26 , and 52 weeks after the start of sick leave . Results . Time until return to work for workers with workplace intervention was 77 versus 104 days ( median ) for workers without this intervention ( P = 0.02 ) . Workplace intervention was effective on return to work ( hazard ratio = 1.7 ; 95 % CI , 1.2–2.3 ; P = 0.002 ) . Grade d activity had a negative effect on return to work ( hazard ratio = 0.4 ; 95 % CI , 0.3–0.6 ; P < 0.001 ) and functional status . Combined intervention had no effect . Conclusion . Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP . Grade d activity or combined intervention is not advised", "This prospect i ve multicentre study was undertaken to determine segmental movement , disc height and sagittal alignment after total disc replacement ( TDR ) in the lumbosacral spine and to assess the correlation of biomechanical properties to clinical outcomes .A total of 173 patients with degenerative disc disease and low back pain for more than one year were r and omised to receive either TDR or multidisciplinary rehabilitation ( MDR ) . Segmental movement in the sagittal plane and disc height were measured using distortion compensated roentgen analysis ( DCRA ) comparing radiographs in active flexion and extension . Correlation analysis between the range of movement or disc height and patient-reported outcomes was performed in both groups . After two years , no significant change in movement in the sagittal plane was found in segments with TDR or between the two treatment groups . It remained the same or increased slightly in untreated segments in the TDR group and in this group there was a significant increase in disc height in the operated segments . There was no correlation between segmental movement or disc height and patient-reported outcomes in either group . In this study , insertion of an intervertebral disc prosthesis TDR did not increase movement in the sagittal plane and segmental movement did not correlate with patient-reported outcomes . This suggests that in the lumbar spine the movement preserving properties of TDR are not major determinants of clinical outcomes", "Objective : To investigate whether a pretreatment multimodal ( MM ) assessment of patients with chronic muscular pain has an impact on treatment outcome . Methods : The present r and omized-controlled study evaluated an MM assessment compared with routine multidisciplinary assessment given to a control group . The study population consisted of primary care patients with mixed chronic muscular pain . Variables assessed were : pain intensity , depression , life stress , quality of life ( QOL ) , disability , working ability , and treatment satisfaction . Follow-up was performed at 15 months and 182 patients of 220 ( 83 % ) completed the study . Results : Univariate and multivariate logistic regression showed from baseline to 15 months a significant improvement in QOL as measured by Short-Form 36 in the MM group compared with the control group on the domains of physical function ( odds ratio 2.40 ; 95 % confidence interval 1.32 - 4.37 ) , role physical ( 2.37 ; 1.10 - 5.09 ) , and role emotional ( 2.05 ; 1.05 - 3.96 ) . Working ability improved more significantly in the MM group ( 46 % vs. 35 % ) and impairment was less ( 1 % vs. 15 % ) compared with the control group ( P=0.016 ) . Satisfaction with the assessment was , on average , higher ( P<0.001 ) in the MM group than in the control group . Discussion : Patients who underwent an MM assessment before treatment in comparison with patients receiving routine multidisciplinary assessment improved QOL , working ability , and were also significantly more satisfied . This result indicates that MM pretreatment assessment could be advantageous in the selection of patients for suitable rehabilitation treatment in a primary care setting , and also be used to prepare patients for future rehabilitation", "Introduction . To investigate the effect of an individualised functional training programme for patients with low back pain ( LBP ) . Methods . A r and omised , controlled trial with single-blind design was conducted . Patients with non-specific LBP for at least 3 months were recruited and r and omised into training and control groups . Both groups maintained their current treatment , and the training group participated in an additional programme for 100 h. Measures were performed initially and after completing the programme , and included rating determining impairment associated with pain , Oswestry disability index ( ODI ) and functional capacity evaluation ( FCE ) . Results . Thirteen in the training group completed the training and measurements , and 12 in the control group completed their measurements . Twelve items in FCE had significant improvement in training group , but only one in control group . Severity of pain ( 11.8 ± 3.6–5.6 ± 3.6 ) , activity limitation from pain ( 3.2 ± 1.5–1.5 ± 1.1 ) and emotional disturbance by pain ( 4.3 ± 1.7–2.2 ± 1.4 ) significantly decreased in the training group , no significant change in the control group . The ODI demonstrated a significant reduction ( p = 0.044 ) in the training group ( 22 ± 9–16 ± 9 ) , but not in the control group . Conclusion . An individualised functional training programme benefits chronic LBP patients", "Introduction In Denmark , the magnitude and impact of work disability on the individual worker and society has prompted the development of a new “ coordinated and tailored work rehabilitation ” ( CTWR ) approach . The aim of this study was to compare the effects of CTWR with conventional case management ( CCM ) on return-to-work of workers on sick leave due to musculoskeletal disorders ( MSDs ) . Methods The study was a r and omized controlled trial with economic evaluation undertaken with workers on sick leave for 4–12 weeks due to MSDs . CTWR consists of a work disability screening by an interdisciplinary team followed by the collaborative development of a RTW plan . The primary outcome variable was registered cumulative sickness absence hours during 12 months follow-up . Secondary outcomes were work status as well as pain intensity and functional disability , measured at baseline , 3 and 12 months follow-up . The economic evaluation ( intervention costs , productivity loss , and health care utilization costs ) was based on administrative data derived from national registries . Results For the time intervals 0–6 months , 6–12 months , and the entire follow-up period , the number of sickness absence hours was significantly lower in the CTWR group as compared to the control group . The total costs saved in CTWR participants compared to controls were estimated at US $ 1,366 per person at 6 months follow-up and US $ 10,666 per person at 12 months follow-up . Conclusions Workers on sick leave for 4–12 weeks due to MSD who underwent “ CTWR ” by an interdisciplinary team had fewer sickness absence hours than controls . The economic evaluation showed that — in terms of productivity loss — CTWR seems to be cost saving for the society", "OBJECTIVE To assess the effect of a combined exercise and motivation program on the compliance and level of disability of patients with chronic and recurrent low back pain . DESIGN A double-blind prospect i ve r and omized controlled trial . SETTING Physical therapy outpatient department , tertiary care . PATIENTS Ninety-three low back pain patients were r and omly assigned to either a st and ard exercise program ( n = 49 ) or a combined exercise and motivation program ( n = 44 ) . INTERVENTIONS Patients were prescribed 10 physical therapy sessions and were advised to continue exercising after treatment termination . The motivation program consisted of five compliance-enhancing interventions . Follow-up assessment s were performed at 3 1/2 weeks , 4 months , and 12 months . MAIN OUTCOME MEASURES Disability ( low back outcome score ) , pain intensity , physical impairment ( modified Waddell score , fingertip-to-floor distance , abdominal muscle strength ) , working ability , motivation , and compliance . RESULTS The patients in the motivation group were significantly more likely to attend their exercise therapy appointments ( p = .0005 ) . Four and 12 months after study entry there was a significant difference in favor of the motivation group with regard to the disability score ( p = .004 ) and pain intensity ( p < or = .026 ) . At 4 months , there was a significant advantage for the motivation group in the fingertip-to-floor distance ( p = .01 ) and in abdominal muscle strength ( p = .018 ) . No significant differences were found in motivation scores , self-reported compliance with long-term exercise , and modified Waddell score . In terms of working ability , there was a trend favoring the combined exercise and motivation program . CONCLUSION The combined exercise and motivation program increased the rate of attendance at scheduled physical therapy sessions , ie , short-term compliance , and reduced disability and pain levels by the 12-month follow-up . However , there was no difference between the motivation and control groups with regard to long-term exercise compliance", "Study Design . A r and omized controlled trial in occupational health practice was conducted . Objective . To study the efficacy of early management of workers with low back pain by occupational physicians , as compared with management by the supervisor only . Summary of Background data . Health care and university workers with back pain and on sick leave for less than 1 month were included in the study . Methods . Patients with low back pain for at least 10 days on sick leave were r and omly assigned to early management by the occupational physician ( n = 61 ) or to a reference group with management by the worker ’s supervisor during the first 3 months of sick leave ( n = 59 ) . The patients were observed for 1 year and compared in terms of time until return to work , pain intensity , functional disability , and general health perception . The occupational physicians were provided with management guidelines . Results . No significant differences were found after 3 and 12 months of follow-up evaluation in terms of time until return to work ( hazard ratio , 1.3 ; 95 % CI , 0.90–1.90 ) or in terms of other health outcomes . Recurrences , however , occurred more frequently in the intervention group , but the total duration of sick leave in 1 year did not differ between the groups . Conclusions . The findings do not show a significant positive effect of an early intervention by occupational physicians on workers with low back pain . This might reflect the early phase of disability or the low intensity of the intervention result ing from overestimation of the physicians ’ compliance with the guidelines", "Study Design . A r and omized controlled trial comparing usual care with a program for the coordination of primary health care ( CORE ) for the treatment of subacute low-back pain patients . Objectives . To measure the effectiveness of the CORE program as a mean for implementing clinical practice guidelines for low-back pain in an urban community . Summary of Background Data . Clinical practice guidelines have been developed for primary care physicians and patients on the clinical management of low-back pain . The implementation of the guidelines in a large community is difficult with the multiplicity of medical and nonmedical back care providers and products . The CORE program was design ed to make the guidelines fit in this complex environment . Methods . One hundred ten workers compensated for low-back pain for 4 to 8 weeks in metropolitan Montreal were r and omized in two groups : usual care ( N=56 ) and the CORE program ( N=54 ) . Coordination of primary health care was performed by two primary care physicians and a nurse in liaison with the treating physicians , and included a complete examination , recommendations for the clinical management , and support to carry out the recommendations . All workers were followed for 6 months . Back pain and functional status were assessed at baseline , 3 months , and 6 months . Results . In the 6-month follow-up , the CORE group returned to work 6.6 days ( st and ard error = 8.9 ) quicker than the control group , a difference that was not statistically significant . However , the CORE group showed a sustained improvement in pain and functional status with two-fold differences at the end of the 6 months of follow-up . This represented nine points on the Oswestry scale ( P = 0.02 ) and 12 points on the Quebec Back Pain Disability Scale ( P = 0.01 ) . The CORE group also used three times less specialized imaging tests of the spine at 3 months ( P < 0.01 ) and exercised twice as much at 6 months ( P < 0.05 ) than the controls . Conclusions . The therapeutic results for workers with low-back pain could be improved by implementing the clinical practice guidelines with primary care physicians in a large community , without delaying the return to work . The CORE intervention for back pain patients ishighly relevant to primary care practice . It is simple in its application , flexible to accommo date physicians ’ and patients ’ preferences in health care , and it is effective on patients ’ clinical outcome", "Several treatment principles for the reduction of chronic low back pain associated disability have been postulated . To examine whether a combination of a physical training and operant‐behavioral grade d activity with problem solving training is cost‐effective compared to either alone one year post‐treatment , a full economic analysis alongside a r and omized controlled trial was conducted . In total 172 patients with chronic disabling non‐specific low back pain referred for rehabilitation treatment , were r and omized to 10 weeks of aerobic training and muscle strengthening of back extensors ( active physical treatment ; APT ) , 10 weeks of gradual assumption of patient relevant activities based on operant‐behavioral principles and problem solving training ( grade d activity plus problem solving training ; GAP ) , or APT combined with GAP ( combination treatment ; CT ) . Total costs , existing of direct health and non‐health costs and indirect costs due to absence of paid work were calculated by using cost diaries and treatment attendance lists . The Rol and Disability Question naire was used to calculate the cost‐effectiveness to reduce disability and the gain in quality adjusted life year ( QALY ) by using the EuroQol‐5D . APT , followed by CT showed , although not significant , higher total costs than GAP . Reduction of disability and gain in QALY did not differ significantly between CT and the single treatment modalities . Based on the incremental cost effectiveness ratios ( ICERs ) and cost‐effectiveness acceptability curves CT is not cost‐effective at all . However , GAP is cost‐effective regarding the reduction of disability and gain in QALY , and to a lesser degree APT is more cost‐effective than CT in reducing disability", "OBJECTIVES To examine whether the addition of motivational enhancement treatment ( MET ) to conventional physical therapy ( PT ) produces better outcomes than PT alone in people with chronic low back pain ( LBP ) . DESIGN A double-blinded , prospect i ve , r and omized , controlled trial . SETTING PT outpatient department . PARTICIPANTS Participants ( N=76 ) with chronic LBP were r and omly assigned to receive 10 sessions of either MET plus PT or PT alone . INTERVENTION MET included motivational interviewing strategies and motivation-enhancing factors . The PT program consisted of interferential therapy and back exercises . MAIN OUTCOME MEASURES Motivational-enhancing factors , pain intensity , physical functions , and exercise compliance . RESULTS The MET-plus-PT group produced significantly greater improvements than the PT group in 3 motivation-enhancing factors ; proxy efficacy ( P<.001 ) , working alliance ( P<.001 ) , and treatment expectancy ( P=.011 ) . Furthermore , they performed significantly better in lifting capacity ( P=.015 ) , 36-Item Short Form Health Survey General Health subscale ( P=.015 ) , and exercise compliance ( P=.002 ) than the PT group . A trend of a greater decrease in visual analog scale and Rol and -Morris Disability Question naire scores also was found in the MET-plus-PT group than the PT group . CONCLUSION The addition of MET to PT treatment can effectively enhance motivation and exercise compliance and show better improvement in physical function in patients with chronic LBP compared with PT alone", "BACKGROUND Chronic low back pain ( CLBP ) is often associated with clinical and sub clinical levels of psychological problems . A higher stage of chronicity is associated with an increase in co-existing psychological disorders . Previous programmes of inpatient orthopaedic rehabilitation reveal little evidence of sustained rehabilitation effects , a finding which may be attributable to the absence of specific psychological treatment during the programme . PURPOSE Does cognitive-behavioural depression management training in patients with CLBP and depressive symptoms improve the inpatient orthopaedic rehabilitation success depending on the stage of chronicity ? METHOD Effects of the new programme on psychological well-being ( ADS depressive symptoms , HADS anxiety , SCL somatization and mental health of the SF-12 ) were investigated in n=75 patients with first and second stage of chronicity immediately after , six months after and 24 months after rehabilitation and were compared to st and ard rehabilitation without management of depressive symptoms . RESULTS All patients benefited from both treatments immediately after rehabilitation . However , six months after rehabilitation only patients of the intervention group showed significant beneficial effects with regard to depressive symptoms and mental health . The lowered depressive symptoms remained stable up to the 24-month follow-up assessment . Anxiety in the second stage of chronicity was reduced up to the 6-month follow-up and in the first stage up to the 24-month follow-up . CONCLUSIONS The new programme with a cognitive-behavioural depression management training revealed beneficial effects on mental health in the mid-term and on depressive symptoms in the long-term . However , the effects need to be further improved by after-care programmes", "Objective : To investigate the feasibility and effectiveness of individual work support for employed patients with low back pain . Design : Pilot r and omized controlled trial of a 16-week vocational intervention with six-month follow-up . Setting : Community/outpatient . Participants : Fifty-one employed participants concerned about their ability to work due to low back pain . Outcome data was obtained for 38 participants at six-month follow-up . Interventions : The intervention group received up to eight individually targeted vocational sessions in conjunction with group rehabilitation for low back pain . The control group received group rehabilitation . Outcome measures : The feasibility of the intervention was assessed by the recruitment rate , drop-out and loss to follow-up of the participants and the content and delivery of the intervention as recorded by the research er . The primary outcome measure was perceived work ability . Results : Seventy-three participants were referred to the study over six months . Eighty-seven individual work support sessions were delivered . Thirty-one participants ( 61 % of those retained in the study ) attended more than half of the group rehabilitation sessions . The intervention was influenced by the uptake of group rehabilitation , the willingness of the participants to involve their workplace and of their workplace to involve the research therapist . The effect of the intervention on work ability was equivocal . Conclusions : Although it was possible to recruit participants and to deliver the intervention , considerable method ological problems were identified . However , even if these were addressed , the impact of such interventions is likely to be limited unless there is an integrated approach between healthcare , employers and employees . Further research is required to evaluate work-focused interventions with this client group", "ABSTRACT The cost effectiveness of work‐oriented rehabilitation for persons on long‐term sick leave needs to be assessed . This prospect i ve observational study presents a follow‐up seven years after rehabilitation using two different evidence ‐based work‐oriented regimens . Individuals on sick leave for neck and back pain were referred to two rehabilitation programmes in Sweden . The first programme was a relatively low‐intensity programme based on orthopaedic manual therapy and exercise programme ( OMTP ) . The second programme was a full‐time multidisciplinary programme ( MDP ) . The primary outcome was sickness absence seven years after intervention . Cost effectiveness was calculated on the basis of loss of production due to sickness absence . The results show that participants referred to MDP and with less than 60 sick days before rehabilitation have reduced sickness absence after intervention as compared to matched controls . This corresponds to a cost reduction of about 94,494 EUR per referred individual . Further , the results indicate that participants of the OMTP who have more than 60 sick days before rehabilitation have a statistically significant increased risk of disability pension . This means increased cost in terms of loss of production of 44,593 EUR per referred individual . The results of this study show that MPD but not OMTP achieves the goal of working life‐oriented rehabilitation . A direct comparison between the rehabilitation programmes strengthened the assumption that long‐term sickness absence prior to rehabilitation is associated with more days on sick leave after rehabilitation . This analysis also indicated the importance of participants ’ pain self‐efficacy beliefs and recovery beliefs on rehabilitation outcome", "& NA ; The present study tested a short intervention using goal ‐pursuit strategies to increase physical capacity in pain patients . Sixty chronic back pain patients were r and omly assigned to intervention or control conditions . Both groups followed a 3‐week conventional back pain program at an outpatient back pain center . Instead of routine treatment , the intervention group received a one‐hour intervention consisting of a combination of ( a ) a goal ‐ setting strategy ( i.e. , mental contrasting , MC ) aim ed at commitment to improved physical capacity , ( b ) a short cognitive behavioral therapy‐oriented problem‐solving approach ( CBT ) to help patients overcome the obstacles associated with improving physical capacity , and ( c ) a goal ‐pursuit strategy , i.e. , implementation intentions ( II ) aim ed at performing physical exercise regularly . At two follow‐ups ( 3 weeks after discharge and 3 months after returning home ) the MCII‐CBT group had increased its physical capacity significantly more than the control group as measured by both behavioral measures ( ergometer , lifting ) and subjective ratings . Findings are discussed with relation to the use of the intervention as a specific treatment to increase chronic pain patients ’ motivation to be physically active", "BACKGROUND Systematic review s have confirmed the effectiveness of work-related rehabilitation with significant cognitive-behavioural components for patients with musculoskeletal disorders ( MSDs ) . In Germany , however , work-related rehabilitation focuses mainly on functional capacity training and less on psychosocial work dem and s. OBJECTIVE To evaluate the efficacy of multimodal work hardening ( MWH ) with a cognitive-behavioural approach . METHODS Patients with MSDs result ing in severe restriction of work ability were r and omly assigned to treatment by either MWH or conventional musculoskeletal rehabilitation ( controls ) . The primary outcome was work status . The work status at 6 months of follow-up was defined as positive if the patient was working and had ≤ 6 weeks of sick leave , and that at 12 months was defined as positive if the patient was working and had ≤12 weeks of sick leave . Follow-up data were collected by postal question naires . RESULTS 236 patients consented to participate . Follow-up data were obtained from 169 ( 71.6 % ) participants at 6 months and 146 ( 61.9 % ) participants at 12 months . At 6 months , participants in the MWH group had a 2.4 times higher chance of a positive work status than the controls ( OR=2.363 ; 95 % CI : 1.266 to 4.410 ; p=0.007 ) . At 12 months , the chances of a positive work status were still higher , but this difference was not statistically significant ( OR=1.914 ; 95 % CI : 0.849 to 4.317 ; p=0.118 ) . Significance of the interaction term of treatment and time indicated more favourable outcomes for depression and anxiety , mental and physical health-related quality of life , and pain management in the MWH group . CONCLUSIONS MWH improves health-related quality of life and is able to enhance the mid-term chances of work-life participation", "What is meant by intention-to-treat ? Why should data be analyzed in controlled trials in a way that all participants are included in the group to which they were r and omly assigned , regardless of whether they completed the intervention given to the group ? In this Tutorial , the logic of the intention-to-treat principle is outlined . It is shown that study results may be biased by excluding patients post hoc thus producing spurious effects that do not exist in the population under study . The intention-to-treat strategy avoids this bias" ]

[ "22892463", "19641152", "3538059", "22251037", "16040729", "22621162", "28989974", "26037274", "11808764" ]

[ "Randomized clinical trial on effectiveness of silver diamine fluoride and glass ionomer in arresting dentine caries in preschool children.", "Efficacy of Silver Diamine Fluoride for Arresting Caries Treatment", "Short term serum pharmacokinetics of diammine silver fluoride after oral application", "Paradigm shift in the effective treatment of caries in schoolchildren at risk.", "Efficacy of Silver Diamine Fluoride for Caries Reduction in Primary Teeth and First Permanent Molars of Schoolchildren: 36-month Clinical Trial", "Effect of silver diamine fluoride on microtensile bond strength to dentin.", "Arresting Dentine Caries with Different Concentration and Periodicity of Silver Diamine Fluoride", "A randomized clinical trial on arresting dentine caries in preschool children by topical fluorides--18 month results.", "A Community-based Caries Control Program for Pre-school Children Using Topical Fluorides: 18-month Results" ]

[ "OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p<0.001 ) , and those in buccal/lingual smooth surfaces ( OR=15.6 , p=0.004 ) . CONCLUSION Annual application of either SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome", "Arresting Caries Treatment ( ACT ) has been proposed to manage untreated dental caries in children . This prospect i ve r and omized clinical trial investigated the caries-arresting effectiveness of a single spot application of : ( 1 ) 38 % silver diamine fluoride ( SDF ) with tannic acid as a reducing agent ; ( 2 ) 38 % SDF alone ; ( 3 ) 12 % SDF alone ; and ( 4 ) no SDF application in primary teeth of 976 Nepalese schoolchildren . The a priori null hypothesis was that the different treatments have no effect in arresting active cavitated caries . Only the single application of 38 % SDF with or without tannic acid was effective in arresting caries after 6 months ( 4.5 and 4.2 mean number of arrested surfaces ; p < 0.001 ) , after 1 year ( 4.1 and 3.4 ; p < 0.001 ) , and after 2 years ( 2.2 and 2.1 ; p < 0.01 ) . Tannic acid conferred no additional benefit . ACT with 38 % SDF provides an alternative when restorative treatment for primary teeth is not an option", "Background There is growing interest in the use of diammine silver fluoride ( DSF ) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world . While DSF has been available in various formulations for many years , most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized . Methods This preliminary study determined the applied doses ( 3 teeth treated ) , maximum serum concentrations , and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode , and silver was determined using inductively coupled plasma-mass spectrometry . The mean amount of DSF solution applied to the 3 teeth was 7.57 mg ( 6.04 μL ) . Results Over the 4 hour observation period , the mean maximum serum concentrations were 1.86 μmol/L for fluoride and 206 nmol/L for silver . These maximums were reached 3.0 h and 2.5 h for fluoride and silver , respectively . Conclusions Fluoride exposure was below the U.S. Environmental Protection Agency ( EPA ) oral reference dose . Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime , but for occasional use was well below concentrations associated with toxicity . This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults . Clinical trials registration NCT01664871", "BACKGROUND Silver diamine fluoride ( SDF ) is an effective agent for the arrest of caries in children , is easy to apply and can be used outside the clinical environment . Interim restorative treatment ( IRT ) using glass ionomer cement has also been cl aim ed to be a simple and effective method to arrest caries in deciduous teeth . OBJECTIVE To examine whether , for underprivileged schoolchildren with cavities , treatment with 30 % SDF gives better results than IRT for carries arrest . METHOD This r and omised controlled study compares the effect of IRT ( FUJI IX ) with 30 % SDF in 91 children aged 5 - 6 years . RESULTS After 1 year , treatment with SDF was more effective [ relative risk ( RR ) = 66.9 % ] than IRT ( RR = 38.6 % ) for the arrest of caries ; this was statistically significant ( P < 0.05 ) . CONCLUSION The SDF technique showed better results than IRT for the arrest of cavities in deciduous teeth , indicating that its use for underprivileged communities may justify a paradigm shift in paediatric dentistry", "We hypothesized that the six-monthly application of silver diamine fluoride ( SDF ) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars . A prospect i ve controlled clinical trial was conducted on the efficacy of a 38 % SDF solution for caries reduction . Four hundred and twenty-five six-year-old children were divided into two groups : One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos . The second group served as controls . The 36-month follow-up was completed by 373 children . The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls . The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls . The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren", "The aim of this in vitro study was to investigate the effect of the cariostatic and preventive agent silver diamine fluoride ( SDF ) on the microtensile bond strength of resin composite to dentin . Forty-two caries-free , extracted molars were flattened occlusally and apically using a diamond saw , and the exposed occlusal dentin was polished with a series of silicon carbide papers , all under water irrigation . The teeth were then r and omly divided into six groups of seven teeth each that were treated as follows : 1 ) Peak SE self-etch bonding agent ; 2 ) 12 % SDF + Peak SE ; 3 ) 38 % SDF + Peak SE ; 4 ) Peak LC etch- and -rinse bonding agent ; 5 ) 12 % SDF + Peak LC ; and 6 ) 38 % SDF + Peak LC . Four-millimeter buildups of Amelogen Plus were incrementally placed on all teeth ; after a 24-hour storage period in distilled water , the specimens were sectioned perpendicular to the adhesive interface to produce beams of cross-sectional surface area measuring approximately 1 mm(2 ) . The beams were placed on a microtensile testing machine , which utilized a single-speed pump motor and force gauge at 20 kgf × 0.01 second to record maximum tensile force before failure occurred . Two-way analysis of variance and post hoc Tukey tests were performed to compare the effects of the SDF on microtensile bond strength , with statistical significance set at α = 0.05 . None of the experimental groups treated with different concentrations of SDF showed a significant difference in bond strength compared to the control groups , and there was no significant difference in bond strength between self-etch and etch- and -rinse groups . However , the effect of SDF on self-etch bonded teeth compared to etch- and -rinse bonded teeth was statistically significant ( p=0.0363 ) , specifically at the 12 % concentration . SDF does not adversely affect the bond strength of resin composite to noncarious dentin", "Different regimens of silver diamine fluoride ( SDF ) have been used to manage early childhood caries . So far , there is limited information regarding the concentrations and frequency of applications for effective caries control in primary teeth . This study aim ed to compare the efficacy of 2 commercially available SDF solutions at preprepared concentrations of 38 % and 12 % when applied annually or biannually over 18 mo in arresting dentine caries in primary teeth . This r and omized double-blinded clinical trial recruited kindergarten children aged 3 to 4 y who had at least 1 tooth with dentine caries . The children were r and omly allocated to receive 4 treatment protocol s : group 1 , annual application of 12 % SDF ; group 2 , biannual application of 12 % SDF ; group 3 , annual application of 38 % SDF ; and group 4 , biannual application of 38 % SDF . Clinical examinations at 6-mo intervals were conducted to assess whether active carious lesions became arrested . Information on the children ’s background and oral hygiene habits was collected through a parental question naire at baseline and follow-up examinations . A total of 888 children with 4,220 dentine carious tooth surfaces received treatment at baseline . After 18 mo , 831 children ( 94 % ) were examined . The caries arrest rates were 50 % , 55 % , 64 % , and 74 % for groups 1 , 2 , 3 , and 4 , respectively ( P < 0.001 ) . Lesions treated with SDF biannual application had a higher chance of becoming arrested compared with those receiving SDF annual application ( odds ratio , 1.33 ; 95 % confidence interval , 1.04–1.71 ; P = 0.025 ) . The interaction between concentration and lesion site was statistically significant ( P < 0.001 ) . Compared with 12 % SDF , the use of 38 % SDF increased a chance of becoming arrested ( P < 0.05 ) , except lesions on occlusal surfaces . Based on the 18-mo results , SDF is more effective in arresting dentin caries in the primary teeth of preschool children at 38 % concentration than 12 % concentration and when applied biannually rather than annually . Knowledge Transfer Statement : The results of this study can be used by clinicians and dental public health professionals when deciding which concentrations and frequency of application of silver diamine fluoride solution should be adopted for arresting dentine caries . With consideration of caries arrest treatment with silver diamine fluoride , which is painless , simple , and low cost , this information could lead to more appropriate therapeutic decisions for caries control in young children or those who lack access to affordable conventional dental care", "OBJECTIVES This study aim ed to compare the effectiveness of three topical fluoride application protocol s in arresting dentine caries in primary teeth of preschool children in a fluori date d area . METHODS Children aged 3 - 4 years who had at least one active dentine caries lesion were r and omly allocated into three intervention groups : Group 1-application of 30 % silver diammine fluoride ( SDF ) solution every 12 months ; Group 2-three applications of 30 % SDF solution at weekly interval at baseline ; and Group 3-three applications of 5 % sodium fluoride ( NaF ) varnish at weekly interval at baseline . A masked examiner carried out follow-up examinations every 6 months to assess whether the treated lesions had become arrested . RESULTS A total of 304 children with 1670 tooth surfaces with dentine caries received treatment at baseline . After 18 months , 275 children ( 91 % ) remained in the study . The caries arrest rates at tooth surface level were 40 % , 35 % and 27 % for Groups 1 , 2 and 3 , respectively ( p<0.001 ) . Result of the multi-level survival analysis showed that the two SDF application protocol s could shorten the time to arrest of dentine caries compared with the NaF application protocol . Presence of plaque on lesion surface , tooth type and tooth surface all had significant effects on caries arrest rates . CONCLUSIONS Annual or three consecutive weekly applications of SDF solution is more effective in arresting dentine caries in primary teeth than three consecutive weekly applications of NaF varnish . CLINICAL SIGNIFICANCE In a water fluori date d area , application of SDF solution , either three weekly applications at baseline or annually , can arrest active dentine caries lesions in primary teeth faster than three weekly applications of NaF varnish at baseline", "Dental caries in Chinese pre-school children is common , and restorative treatment is not readily available . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . We divided 375 children ( aged 3 - 5 yrs ) with carious upper anterior teeth into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . NaF varnish ( 22,600 ppm F ) was applied every three months onto the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . We followed 341 children for 18 months . The mean numbers of new caries surfaces in the five groups were 0.4 , 0.4 , 0.8 , 0.6 , and 1.2 , respectively ( p = 0.001 ) . The respective mean numbers of arrested carious tooth surfaces were 2.8 , 3.0 , 1.7 , 1.5 , and 1.0 ( p < 0.001 )" ]

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[ "Contingency management and motivational enhancement: a randomized clinical trial for college student smokers.", "Reinforcing breath carbon monoxide reductions in chronic obstructive pulmonary disease.", "Influence of the duration of abstinence on the relative reinforcing effects of cigarette smoking", "Interventions to increase use of nicotine gum: a randomized, controlled, single-blind trial.", "Implementing a Year-Long, Worksite-Based Incentive Program for Smoking Cessation", "The Impact of Including Incentives and Competition in a Workplace Smoking Cessation Program on Quit Rates", "Biochemical validation of smoking status: pros, cons, and data from four low-intensity intervention trials.", "Contingent reinforcement for reduced breath carbon monoxide levels: target-specific effects on cigarette smoking.", "Contingent reinforcement for carbon monoxide reduction: within-subject effects of pay amount.", "A randomized, controlled trial of financial incentives for smoking cessation.", "Effects of voucher-based incentives on abstinence from cigarette smoking and fetal growth among pregnant women.", "Smoking cessation in methadone maintenance.", "A deposit contract method to deliver abstinence reinforcement for cigarette smoking.", "Behavioral anti-smoking trial in chronic obstructive pulmonary disease patients", "Effectiveness of a low-intensity intra-worksite intervention on smoking cessation in Japanese employees: a three-year intervention trial.", "Evaluation of intrinsic and extrinsic motivation interventions with a self-help smoking cessation program.", "Nicotine gum and self-help behavioral treatment for smoking relapse prevention: results from a trial using population-based recruitment.", "Employee and organizational factors associated with participation in an incentive-based worksite smoking cessation program", "Social Support in a Worksite Smoking Intervention", "Contingency management for smoking cessation in adolescent smokers.", "An Empirical Evaluation of the Effectiveness of Tangible Incentives in Increasing Participation and Behavior Change in a Worksite Health Promotion Program", "Changes in the relative reinforcing effects of cigarette smoking as a function of initial abstinence", "The effects of contingent payment and frequent workplace monitoring on smoking abstinence.", "Worksite Health Promotion: Feasibility Testing of Repeated Weight Control and Smoking Cessation Classes", "The effectiveness of a worksite self-help smoking cessation program: A randomized trail", "Nicotine fading, behavioral contracting, and extended treatment: effects on smoking cessation.", "A follow-up of a media-based, worksite smoking cessation program", "The Effects of Reduced Cigarette Smoking on Discounting Future Rewards: An Initial Evaluation", "A pilot study on voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum.", "The use of contingency management to reduce cigarette smoking among college students.", "Mood disturbance fails to resolve across 31 days of cigarette abstinence in women.", "Results of a year-long incentives-based worksite smoking-cessation program.", "Prolonging the effects of deposit contracts with smokers.", "Shaping smoking cessation using percentile schedules.", "A Comparison of Smoking Cessation Treatments for Persons with Schizophrenia and Other Serious Mental Illnesses", "Randomised controlled trial using social support and financial incentives for high risk pregnant smokers: Significant Other Supporter (SOS) program", "The SUCCESS project: the effect of program format and incentives on participation and cessation in worksite smoking cessation programs.", "The Healthy Worker Project: a work-site intervention for weight control and smoking cessation.", "A worksite smoking intervention: a 2 year assessment of groups, incentives and self-help.", "Work-site cardiovascular risk reduction: a randomized trial of health risk assessment, education, counseling, and incentives.", "Effectiveness of payment for reduced carbon monoxide levels and noncontingent payments on smoking behaviors in cocaine-abusing outpatients wearing nicotine or placebo patches.", "The effects of a deposit contract as a component in a behavioural programme for stopping smoking.", "Voucher-based contingent reinforcement of smoking abstinence among methadone-maintained patients: a pilot study.", "Deposit contracts with smokers: varying frequency and amount of repayments.", "Smokers with multiple behavioral risk factors: how are they different?", "[\"Be smart--don't start\". Results of a non-smoking competition in Germany 1997-2007].", "[Are competitions an appropriate instrument for youth smoking cessation? A 1-year follow-up of the Germany-wide \"Smoke-free 2004\" campaign].", "Intraclass Correlation for Measures from a Worksite Health Promotion Study: Estimates, Correlates, and Applications" ]

[ "INTRODUCTION The efficacy of contingency-management ( CM ) and motivational enhancement therapy ( MET ) for college student smoking cessation was examined . METHODS Nontreatment-seeking daily smokers ( N = 110 ) were r and omly assigned to 3 weeks of CM versus noncontingent reinforcement ( NR ) and to three individual sessions of MET versus a relaxation control in a 2 x 2 experimental design . Expired carbon monoxide ( CO ) sample s were collected twice daily for 3 weeks . Participants earned 5 US dollars for providing each sample ; additionally , those r and omized to CM earned escalating monetary rewards based on CO reductions ( Week 1 ) and smoking abstinence ( Weeks 2 - 3 ) . RESULTS Compared with NR , CM result ed in significantly lower CO levels and greater total and consecutive abstinence during the intervention . Those in the CM and MET groups reported greater interest in quitting smoking posttreatment , but rates of confirmed abstinence at follow-up were very low ( 4 % at 6-month follow-up ) and did not differ by group . DISCUSSION Findings support the short-term efficacy of CM for reducing smoking among college students . Future research should explore enhancements to CM in this population , including a longer intervention period and the recruitment of smokers who are motivated to quit", "Chronic Obstructive Pulmonary Disease ( COPD ) usually results from tobacco smoking . Smoking cessation slows COPD 's progression , but few have studied anti-smoking treatments in COPD . In 3-month trials we paid lottery tickets during daily home visits to still-smoking COPD patients for reductions in breath carbon monoxide ( CO ) , a measure of smoke intake . In our first protocol experimental patients received 0 - 3 tickets per day , depending upon the extent of CO reduction below pre-treatment baselines ; yoked controls received the same number of tickets , but not contingent on CO . The protocol produced no change . In a second study patients were assigned a post-baseline quit- date , received nicotine gum , and were paid up to 5 tickets per night , but only for CO less than 10 parts per million ( ppm ) . CO fell sharply as the intervention began , but gradually rose again . A third protocol added special reinforcement schedules for those who did not quit or relapsed ( up to 20 tickets per night for CO less than 10 ppm ) . Daily CO concentrations fell from 27.1 parts per million ( baseline mean ) to 12.7 ( intervention mean ) , but rapid increases followed the intervention . Few patients stopped smoking , but CO and cigarettes used per day significantly fell during Studies 2 and 3 . Post-hoc analysis suggested only a small effect from gum", "Rationale Sustaining smoking abstinence during the initial weeks of a cessation effort is highly correlated with long-term smoking abstinence . However , experimental research is needed to establish a direct causal relationship between achieving early abstinence and lowered relapse risk . Objective In the present study , we tested whether a period of sustained abstinence directly decreases the relative reinforcing effects of cigarette smoking . Methods Participants were 63 adult smokers who were r and omized into one of three conditions : 14-day ( 14C ) , 7-day ( 7C ) , and 1-day ( 1C ) contingent payment for smoking abstinence . Smoking status was assessed three times per day for 14 consecutive days using breath carbon monoxide monitoring and an abstinence criterion of ≤4 ppm . In the 14C condition , monetary payment was contingent on abstinence for all 14 days ; in the 7C condition , payment was noncontingent for days 1–7 and contingent for days 8–14 ; in the 1C condition , payment was noncontingent for days 1–13 and contingent for day 14 . On day 14 , all participants completed a 3-h preference session under controlled laboratory conditions wherein they could make a maximum of 20 exclusive choices between options to smoke ( two puffs/choice ) or earn money ( $ 0.25/choice ) . Preference was deemed an index of the relative reinforcing effects of smoking and money . Results A significantly lower proportion of participants in the 14C condition ever chose the smoking option ( 19 % ) compared to those in the 7C ( 57 % ) or 1C ( 62 % ) conditions . Conclusions These results provide experimental evidence that sustained abstinence can decrease the relative reinforcing effects of smoking , an effect that may be related to the commonly observed decrease in relapse risk among those who are able to sustain smoking abstinence during the initial weeks of a cessation effort", "Medication noncompliance with smoking cessation pharmacotherapies is a significant problem in both research and clinical setting s. This r and omized , controlled , single-blind study compared three single-session psychological interventions to increase use of nicotine gum during a 15-day treatment period . A total of 97 adult smokers were r and omized to receive st and ard treatment ( ST , n = 31 ) , brief feedback ( BF , n = 32 ) plus ST , or contingency management ( CM ; i.e. , payment for chewing at least 12 pieces/day on 10 of 15 intervention days , n = 34 ) plus ST and BF . Only the CM condition led to significantly greater average daily gum use ( pieces/day : ST , 6.17 ; BF , 7.81 ; CM , 10.17 [ p values < .05 ] ) and higher rates of compliance ( ST , 13.6 % ; BF , 25.2 % ; CM , 65.6 % [ p values < .001 ] ) . No differences were observed in smoking abstinence , nicotine withdrawal , or urinary cotinine as a function of treatment . Implication s of the present findings are discussed , including application to clinical trials and extension to real-world use of nicotine gum", "Background . There have been few reports of the process of implementing ongoing worksite health promotion programs . This article describes the implementation of a year-long smoking cessation program in nine worksites employing a total of approximately 700 smokers . Methods . Issues discussed include : forming a partnership with organizations , design of the multicomponent incentive intervention , program promotion , maintaining participation , and the need to modify program components over time . Results . The program produced high participation rates ( 29 % of smokers joined the program ) and moderate cessation rates among participants ( during the last half of the program , monthly cessation rates averaged 20 % ) . There was marked variability across worksites on both participation and cessation , and qualitative features of organizations associated with outcome are discussed . Discussion . The importance of working with employee steering committees to tailor health promotion programs to fit the organization is discussed . The article concludes with recommendations for implementation of similar programs", "Purpose . To determine the effectiveness of a multicomponent smoking cessation program supplemented by incentives and team competition . Design . A quasi-experimental design was employed to compare the effectiveness of three different smoking cessation programs , each assigned to separate worksites . Setting . The study was conducted from 1990 to 1991 at three aerospace industry worksites in California . Subjects . All employees who were current , regular tobacco users were eligible to participate in the program offered at their site . Intervention . The multicomponent program included a self-help package , telephone counseling , and other elements . The incentive-competition program included the multicomponent program plus cash incentives and team competition for the first 5 months of the program . The traditional program offered a st and ard smoking cessation program . Measures . Self-reported question naires and carbon monoxide tests of tobacco use or abstinence were used over a 12-month period . Results . The incentive-competition program had an abstinence rate of 41 % at 6 months ( n = 68 ) , which was significantly better than the multicomponent program ( 23 % , n = 81 ) or the traditional program ( 8 % , n = 36 ) . At 12 months , the quit rates for the incentive and multicomponent programs were statistically indistinguishable ( 37 % vs. 30 % ) , but remained higher than the traditional program ( 11 % ) . Chi-square tests , t-tests , and logistic regression were used to compare smoking abstinence across the three programs . Conclusions . Offering a multicomponent program with telephone counseling may be just as effective for long-term smoking cessation as such a program plus incentives and competition , and more effective than a traditional program", "Biochemical validation of smoking status has long been considered essential , but recent reports have question ed its utility in certain kinds of field trials . We describe efforts to biochemically vali date self-reports of smoking cessation from participants in four large-scale r and omized trials in outpatient clinics , hospitals , worksites , and dental clinics . These studies included over 5,000 adults smokers who participated in the population -based low-intensity intervention evaluations . At a 1-year follow-up , 798 subjects reported no tobacco use . We attempted to verify these reports using saliva continine/carbon monoxide validation procedures . Overall , there was a moderately high nonparticipation rate ( 27 % ) , a low disconfirmation rate ( 4 % ) , and a high self-reported relapse rate ( 12 % ) in the interval between survey and biochemical validation . There were no differences between intervention and control conditions on any of the above variables . Longer duration s of self-reported abstinence were strongly related to increased probability of biochemical confirmation . Differences in results across projects were related to how biochemical validation was conducted . These results , as well as statistical power considerations , raise questions about whether biochemical validation procedures are practical , informative , or cost-effective in such population -based , low-intensity intervention research", "This study determined the effects on smoking behavior of providing contingent reinforcement for nonsmoking versus reduced smoking afternoon breath carbon monoxide ( CO ) target levels . Twenty-eight hired chronic smoker volunteers were r and omly assigned to one of three experimental conditions during a 10-day intervention : ( a ) 8 ppm target CO , $ 5 per day incentive ( n = 11 ) ; ( b ) 16 ppm target CO , $ 4 per day incentive ( n = 8) ; or ( c ) 8 ppm target CO , no incentive ( n = 9 ) . Both payment groups showed significantly lower CO levels and greater amounts of daytime smoking reduction than the no-pay group . A specific effect of CO target was also seen ; 45 % of subjects in the 8 ppm group compared with 0 % of subjects in the 16 ppm target and no-pay groups produced average afternoon CO levels of 8.5 ppm or lower during the intervention . Average levels of CO and smoking reduction did not differ for the two paid groups , however , because some subjects in the 8 ppm group failed to reduce CO sufficiently to contact the reinforcer . Contingent reinforcement based on expired air CO levels can exercise powerful and precise ( target-specific ) control over smoking behavior , but there may be individual differences in ability to meet reinforcement contingencies if difficult targets are introduced abruptly", "The relationship between reinforcer amount and daytime smoking reduction in smokers offered money for reduced afternoon breath carbon monoxide ( CO ) levels was examined . Twenty-three hired regular smokers with average baseline CO levels of about 30 ppm were exposed in r and om order to five sliding scale payment schedules that changed daily or weekly . Money was available for afternoon CO readings between 0 and 21 ppm with pay amount inversely related to the absolute CO reading obtained . Maximum pay amount for readings below 7 ppm varied among $ 0 , $ 1.50 , $ 3 , $ 6 , and $ 12 per day . Contingent reinforcement promoted CO and daytime cigarette reduction within individuals with the amount of behavior change related to the amount of payment available . Average CO levels decreased from 30 to 15 ppm as a function of pay amount whereas self-reported daytime cigarettes decreased from 12 to 5 per day . Average minutes of cigarette abstinence prior to the afternoon study contact increased from 62 to 319 minutes as a function of pay amount , whereas the percentage of available money earned increased from 22 % to 48 % . Nontargeted evening cigarette use also decreased during periods of daytime smoking reduction . The orderly effects of this contingent reinforcement intervention on daytime smoking of regular smoker volunteers suggest that this is a sensitive model for continued evaluation of factors that influence smoking reduction and cessation", "BACKGROUND Smoking is the leading preventable cause of premature death in the United States . Previous studies of financial incentives for smoking cessation in work setting s have not shown that such incentives have significant effects on cessation rates , but these studies have had limited power , and the incentives used may have been insufficient . METHODS We r and omly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs ( 442 employees ) or to receive information about programs plus financial incentives ( 436 employees ) . The financial incentives were $ 100 for completion of a smoking-cessation program , $ 250 for cessation of smoking within 6 months after study enrollment , as confirmed by a biochemical test , and $ 400 for abstinence for an additional 6 months after the initial cessation , as confirmed by a biochemical test . Individual participants were stratified according to work site , heavy or nonheavy smoking , and income . The primary end point was smoking cessation 9 or 12 months after enrollment , depending on whether initial cessation was reported at 3 or 6 months . Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs . RESULTS The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment ( 14.7 % vs. 5.0 % , P<0.001 ) and 15 or 18 months after enrollment ( 9.4 % vs. 3.6 % , P<0.001 ) . Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program ( 15.4 % vs. 5.4 % , P<0.001 ) , completion of a smoking-cessation program ( 10.8 % vs. 2.5 % , P<0.001 ) , and smoking cessation within the first 6 months after enrollment ( 20.9 % vs. 11.8 % , P<0.001 ) . CONCLUSIONS In this study of employees of one large company , financial incentives for smoking cessation significantly increased the rates of smoking cessation . ( Clinical Trials.gov number , NCT00128375 .", "AIMS This study examined whether voucher-based reinforcement therapy ( VBRT ) contingent upon smoking abstinence during pregnancy is an effective method for decreasing maternal smoking during pregnancy and improving fetal growth . DESIGN , SETTING AND PARTICIPANTS A two-condition , parallel-groups , r and omized controlled trial was conducted in a university-based research clinic . A total of 82 smokers entering prenatal care participated in the trial . INTERVENTION Participants were assigned r and omly to either contingent or non-contingent voucher conditions . Vouchers exchangeable for retail items were available during pregnancy and for 12 weeks postpartum . In the contingent condition , vouchers were earned for biochemically verified smoking abstinence ; in the non-contingent condition , vouchers were earned independent of smoking status . MEASUREMENTS Smoking outcomes were evaluated using urine-toxicology testing and self-report . Fetal growth outcomes were evaluated using serial ultrasound examinations performed during the third trimester . FINDINGS Contingent vouchers significantly increased point-prevalence abstinence at the end-of-pregnancy ( 41 % versus 10 % ) and at the 12-week postpartum assessment ( 24 % versus 3 % ) . Serial ultrasound examinations indicated significantly greater growth in terms of estimated fetal weight , femur length and abdominal circumference in the contingent compared to the non-contingent conditions . CONCLUSIONS These results provide further evidence that VBRT has a substantive contribution to make to efforts to decrease maternal smoking during pregnancy and provide new evidence of positive effects on fetal health", "AIMS To evaluate relapse prevention ( relapse prevention ) and contingency management ( contingency management ) for optimizing smoking cessation outcomes using nicotine replacement therapy for methadone-maintained tobacco smokers . DESIGN Experimental , 2 ( relapse prevention)x2 ( contingency management ) repeated measures design using a platform of nicotine replacement therapy featuring a 2-week baseline period , followed by r and omization to 12 weeks of treatment , and 6- and 12-month follow-up visits . SETTING Three narcotic treatment centers in Los Angeles . PARTICIPANTS One hundred and seventy-five participants who met all inclusion and no exclusion criteria . INTERVENTION Participants received 12 weeks of nicotine replacement therapy and assignment to one of four conditions : patch-only , relapse prevention + patch , contingency management + patch and relapse prevention + contingency management + patch . MEASUREMENTS Thrice weekly sample s of breath ( analyzed for carbon monoxide ) and urine ( analyzed for metabolites of opiates and cocaine ) and weekly self-reported numbers of cigarettes smoked . FINDINGS Participants ( 73.1 % ) completed 12 weeks of treatment . During treatment , those assigned to receive contingency management showed statistically higher rates of smoking abstinence than those not assigned to receive contingencies ( F3,4680=6.3 , P=0.0003 ) , with no similar effect observed for relapse prevention . At follow-up evaluations , there were no significant differences between conditions . Participants provided more opiate and cocaine-free urines during weeks when they met criteria for smoking abstinence than during weeks when they did not meet these criteria ( F1,2054=14.38 , P=0.0002 ; F1,2419=16.52 , P<0.0001 ) . CONCLUSIONS Contingency management optimized outcomes using nicotine replacement therapy for reducing cigarette smoking during treatment for opiate dependence , although long-term effects are not generally maintained . Findings document strong associations between reductions in cigarette smoking and reductions in illicit substance use during treatment", "Eight smokers were r and omly assigned to a deposit contract ( $ 50.00 ) or to a no-deposit group . Using a reversal design , participants could recoup their deposit ( deposit group ) or earn vouchers ( no-deposit group ) for smoking reductions and abstinence ( breath carbon monoxide [ CO ] < or = 4 parts per million ) during treatment phases . Treatment was delivered via a novel Internet-based method to monitor smoking status . Although equivalent decreases in breath CO and abstinence were observed during treatment in both groups , $ 178.50 in vouchers were distributed to participants in the no-deposit group , whereas a small surplus remained in the deposit group . A deposit contract method may represent a cost-effective model to deliver abstinence reinforcement for cigarette smoking", "Smoking causes chronic obstructive pulmonary disease ( COPD ) , but few controlled studies have tested anti-smoking treatments in COPD . With procedures likely to attract unmotivated persons we recruited 49 quite-ill , smoking COPD patients . During one or two daily home visits for 85 days , breath carbon monoxide ( CO ) and self-reports of daily smoking were obtained . Patients , given quit date s and nicotine gum ( 2-mg pieces , up to 30 per day ) , were assigned r and omly to three groups : Experimentals were reinforced with lottery tickets for CO < 10 ppm . Cigarette Self Report ( CSR ) patients were reinforced for reporting no smoking that day . Controls received non-contingent payments . Each group 's mean CO level fell at the quit date . Thereafter , reinforced patients maintained significantly lower CO levels than Controls . Although many more 24-h abstentions occurred in the intervention period than in baseline , few patients sustained abstinence ; the groups did not differ in that regard . Outcome was predicted by decisions to throw away cigarettes when intervention began , but not by motivation scales nor Fagerstrom dependence scores . Pay schedules apparently exaggerated self-reports of reduced smoking . Although results are statistically significant , there is still no proven , practical treatment for smoking in advanced COPD", "To test the effectiveness of a low-intensity intervention program for smoking cessation targeting the worksite environment in employees who had a low readiness to quit , we conducted an intervention trial at six intervention and six control worksites in Japan . A total of 2,307 smokers at baseline who remained at their worksite throughout the three-year study period were analyzed ( 1,017 in intervention and 1,290 in control groups ) . The multi-component program at the worksites consisted of ( 1 ) presenting information on the harms of tobacco smoking and the benefits of cessation by posters , websites , and newsletters ; ( 2 ) smoking cessation campaigns for smokers ; ( 3 ) advice on design ation of smoking areas ; and ( 4 ) periodic site-visits of the design ated smoking areas by an expert research er . At baseline , the intervention and control groups each had high prevalence of immotive or precontemplation , that reflected low readiness to quit ( 71.5 % and 73.2 % , respectively ) . The smoking cessation rate , as not having smoked for the preceding six months or longer , assessed at 36 months after the baseline survey by a self-administered question naire was significantly higher in the intervention group than the control group ( 12.1 % , vs. 9.4 % , p=0.021 ) . The intervention program still had a significant effect on the smoking cessation rate after multiple logistic regression analysis adjusted for sex , age , type of occupation , age of starting smoking , quit attempts in the past , number of cigarettes per day , and readiness to quit ( odds ratio : 1.38 , 95 % confidence interval : 1.05 - 1.81 , p=0.02 ) . The cost per additional quitter due to the intervention was calculated to be Yen 70,080 . These findings indicate that this program is effective and can be implemented in similar workplaces where the prevalence of smoking is high and smokers ' readiness to cease smoking is low", "Personalized feedback and a financial incentive , developed from an intrinsic/extrinsic motivation framework , were evaluated as adjuncts to self-help material s for smoking cessation . Ss ( N = 1,217 ) were r and omized to 4 treatment groups and were followed up at 3 and 12 months . Consistent with hypotheses derived from the motivation framework , the financial incentive increased the use of self-help material s , did not increase cessation rates among program users , and was associated with higher relapse rates among those who did manage to quit . The personalized feedback increased both smoking cessation and use of the material s 3 months after distribution of the material s. Continuous abstinence ( abstinence at 3 and 12 months ) in the group that received the personalized feedback alone was twice the rate of the other groups", "Smokers aged 18 to 65 years ( N = 1,044 ) who were able to quit for 24 hr were r and omized using a 2 x 2 factorial design to compare nicotine gum to no gum use and self-help material s to no use of material s. All participants were offered a $ 100 incentive to quit and stay quit for 6 months . Six-month abstinence was 27 % in the gum groups , compared with 19 % in the no-gum group ( p = .002 ) . Compared with the no-gum group , relapse occurred at a significantly lower rate in the gum group for the entire 12 months of follow-up ( odds of relapse in the gum group was 0.72 , 95 % confidence interval , 0.62 to 0.83 ) . There was no significant main effect for the self-help material s , no interaction between gum and material s , and no evidence that the effectiveness of gum differed between the sexes or between heavy and light smokers . Nicotine gum is an effective adjunct to minimal-contact smoking cessation material s plus monetary incentive in a population -based sample of smokers", "This study investigated employee and worksite characteristics prospect ively predictive of participation among 474 smokers in nine different worksites taking part in a year-long incentive-based smoking cessation program . Several different ways of defining participation ( e.g. , joining versus level of attendance , first 6 months versus entire program ) were studied . A consistent pattern of results was observed across two of the participation indices , joining the program and participating in one or more monthly follow-up meetings . Both worksite ( number of employees , previous health promotion history , degree of support from management ) and employee ( gender , motivation , previous quit attempts ) variables were predictive of participation . Logistic regression analyses revealed that each set of variables , worksite and employee characteristics , was significantly related to participation after controlling for the effects of the other set . We were less able to predict level of attendance among participants who joined the program . Implication s of these findings for future studies of participation in health promotion programs are discussed", "To better underst and how social support operates in smoking cessation , three models of support were tested : main effect , stress-buffering , and indirect . Employees from 61 worksites received ( a ) self-help manuals ( SH ) ; ( b ) self-help manuals and incentives ( I ) ; or ( c ) self-help manuals , incentives , and social support groups ( G ) . At 24 months , results suggest that the main effect model of social support was operating in this study . That is , social support had a direct influence on smoking cessation . The group intervention significantly enhanced positive partner support across all time points , and partner support facilitated quitting smoking . Higher levels of appraisal support also significantly predicted successful quitting . The beneficial effects of social support were sustained throughout the process of quitting and long-term maintenance", "This pilot study evaluated the use of contingency management ( CM ) procedures in combination with cognitive-behavioral therapy ( CBT ) for smoking cessation in adolescents . Twenty-eight treatment-seeking adolescent smokers participated in a 1-month , school-based smoking cessation program and were r and omly assigned to receive either CM with weekly CBT or CBT alone . In the CM+CBT group , biochemical verification of abstinence was obtained twice daily during the first 2 weeks , followed by daily appointments during the 3rd week and once every other day during the 4th week . Participants were monetarily reinforced for abstinence on an escalating magnitude schedule with a reset contingency . At the end of 1 week and 1 month of treatment , abstinence verified using quantitative urine cotinine levels was higher in participants in the CM+CBT group ( 1 week : 76.7 % ; 1 month : 53.0 % ) when compared with the CBT-alone group ( 1 week : 7.2 % ; 4 weeks : 0 % ) . These preliminary results provide a strong initial signal supporting the utility of CM techniques for smoking cessation in adolescents and demonstrate the feasibility of implementing such a program in a school setting", "The first is that they have value in enhancing the program ’s salience . For participants they serve as a reminder of their commitment and goals . For non participants they may function as a means of making them more aware of the program and thus enhancing the likelihood that they will participate in future program offerings . A second reason for using tangible incentives is for their direct motivational value . To the extent that they are delivered contingent on level of participation or accomplishment , employees may participate at a higher level and change their behavior more in order to earn these rewards . A number of worksite health promotion programs have employed tangible incentives . 4 - 1 ° In the well-known Live for Life program developed by Johnson and Johnson , for example , employees are offered annual risk factor screening as well as a variety of educational classes on diet , exercise , smoking cessation , and stress management . Participants in these classes receive a variety of tangible items , including T-shirts , pens , and caps . This program is reported to have had positive effects on smoking , l~ exercise ] 2 and absenteeism ? \"", "Rationale Experimental research is needed in investigating how early smoking abstinence affects relapse risk . Objective The present study assessed the feasibility of promoting smoking abstinence using once- rather than thrice-daily abstinence monitoring and the relationship between different duration s of initial abstinence and changes in smoking preference . Methods Participants were 34 adult smokers r and omized into one of two conditions : 14-day ( 14C ) and 1-day ( 1C ) contingent payment for smoking abstinence . Smoking status and participant ratings were assessed daily ; a delay discounting task involving hypothetical money and an inter-temporal choice task involving hypothetical money and cigarettes were administered at baseline and days 7 and 14 ; a direct test of preference for smoking versus money was assessed on day 14 . Results Once-daily monitoring gained robust experimental control over smoking abstinence . No differences in delay discounting for hypothetical money were observed between the two conditions . Compared to the 1C condition , participants in the 14C condition ( 1 ) showed significant increases in the mean percent of delayed hypothetical money over cigarettes choices in the inter-temporal choice task , ( 2 ) were significantly less likely to ever choose the smoking option in the direct test of preference for smoking versus money , and ( 3 ) reported greater ease of abstaining from smoking and lower nicotine withdrawal and craving . Conclusions These results offer a more efficient procedure for experimentally promoting smoking abstinence , while providing further evidence that an initial period of sustained abstinence produces a profile of changes consistent with an overall lowering of relapse risk", "This study examined the relative contribution of contingent payment and worksite CO monitoring to the long-term maintenance of smoking abstinence . Forty-seven hospital employees who had abstained from smoking for five days ( confirmed by CO analysis ) were r and omly assigned to one of three follow-up groups : ( a ) contingent payment/frequent monitoring ( n = 17 ) ; ( b ) noncontingent payment/frequent monitoring ( n = 16 ) ; or ( c ) non-contingent payment/infrequent monitoring ( n = 14 ) . Contingent payment combined with frequent CO monitoring delayed but did not ultimately prevent subjects relapse to smoking by the end of the six month follow-up . Contingent subjects maintained CO values less than or equal to 11 ppm significantly longer than did either the Non-contingent or the Control subjects ( p = .03 ) . CO monitoring alone had no effect on abstinence outcomes ; both Noncontingent and Control subjects showed high rates of early relapse", "This paper describes a study examining the feasibility of a worksite health promotion program that was repeated twice in one year . Weight control and smoking cessation classes , which included a supporting incentive component , were made available at a worksite of 485 white-collar employees continuously throughout one year . Identical education programs were offered twice at six-month intervals . Results suggest that this model of program implementation is attractive to employees . Total participation over 12 months included an estimated 53 % of overweight employees in the weight program and 23 % of smokers in the smoking cessation program . The two series of classes , run back to back , generated similar participation . Thirty-nine percent of weight control participants and six percent of smoking cessation participants who enrolled in the first program also enrolled in the second . Weight losses and smoking cessation rates were comparable for the two cycles , with a mean weight loss of about seven pounds and a smoking cessation rate at six months of about 33 % . Surveys of a r and om sample of employees at baseline and again at 12 months showed a 28 % reduction in the prevalence of cigarette smoking , but no change in average weight or the prevalence of overweight . This study suggests that health promotion programs at worksites which offer repeated opportunities for employee participation are promising and deserve further study", "A 2 × 2 r and omized , factorial pretest/posttest group design was used to evaluate the effectiveness of self-help smoking cessation methods at the worksite . The study investigated the effect of a multicomponent health education and skill intervention versus the effect of a monetary incentive to the employee for quitting . All employees received , in addition , a st and ardized self-help smoking cessation manual and maintenance manual . Following agreement to participate and a baseline smoking history , all participants were followed for 6 weeks , 6 months , and 12 months . Saliva was obtained for thiocyanate ( SCN ) analysis of smoking status . Of the estimated 2000 smokers at the site , 387 smokers were recruited . Employees were r and omly assigned to one of four groups . Results of this r and om trial indicate that those employees receiving a multicomponent program were most successful in quitting and remaining abstinent . The monetary incentive appears to have no effect on quit rate", "Twenty-eight subjects were r and omly allocated to either a nicotine fading or a maintenance condition . The maintenance condition utilized behavioral contracting and extended treatment in addition to the nicotine fading to improve treatment outcome and avoid relapse . The maintenance condition achieved superior outcome on smoking measures at post-treatment and follow-up periods for self-reported smoking levels . Carbon monoxide levels were significantly lower for the maintenance condition at post-treatment , three month and six month follow-up . Saliva thiocyanate levels were significantly lower for the maintenance condition at the three month follow-up . Changes in health functioning indicated significantly lower diastolic and systolic blood pressure at six month follow-up for the maintenance condition . Additional research on nicotine regulation during nicotine fading and thiocyanate levels during experimental smoking would be useful . The use of behavioral contracting to enhance maintenance without therapeutic support warrants further research as well", "Described an examination of data collected 2 years following the onset of a media-based , worksite smoking cessation intervention . Thirty-eight companies in Chicago were r and omly assigned to one of two experimental conditions . In the inital 3-week phase , all participants in both conditions received self-help manuals and were instructed to watch a 20-day televised series design ed to accompany the manual . In addition , participants in the group ( G ) condition received six sessions emphasizing quitting techniques and social support . In the second phase , which continued for 12 months , employees in G participated in monthly peer-led support groups and received incentives , while participants in the nongroup ( NG ) condition received no further treatment . Twenty-four months after pretest , 30 % of employees in G were abstinent compared to only 19.5 % in NG . This study is one of the few experimentally controlled worksite smoking cessation interventions to demonstrate significant program differences 2 years following the initial intervention", "To determine whether reduction of smoking via contingency management in depen-dent smokers would decrease the discounting of delayed reinforcers compared with smokers who did not reduce their smoking , moderate to heavy cigarette smokers were r and omly assigned to one of two conditions : a contingency management condi-tion and a control condition . In three phases ( baseline discounting determination for hypothetical money and cigarettes , implementation of a contingency management or control condition , and postintervention discounting determination ) , the procedure to reinforce reduction in cigarette smoking produced CO decreases in all subjects exposed to that procedure . Discounting decreased significantly for both cigarettes and money among the group for whom smoking reductions were reinforced , whereas the control group showed no significant change for either commodity . Reductions in smoking can lead to reductions in discounting , and increased discounting in current smokers may be a reversible effect of nicotine dependence", "We report results from a pilot study examining the use of vouchers redeemable for retail items as incentives for smoking cessation during pregnancy and postpartum . Of 100 study -eligible women who were still smoking upon entering prenatal care , 58 were recruited from university-based and community obstetric practice s to participate in a smoking cessation study . Participants were assigned to either contingent or noncontingent voucher conditions . Vouchers were available during pregnancy and for 12 weeks postpartum . In the contingent condition , vouchers were earned for biochemically verified smoking abstinence . In the noncontingent condition , vouchers were earned independent of smoking status . Abstinence monitoring and associated voucher delivery was conducted daily during the initial 5 days of the cessation effort , gradually decreased to every other week antepartum , increased to once weekly during the initial 4 weeks postpartum , and then decreased again to every other week for the remaining 8 weeks of the postpartum intervention period . Contingent vouchers increased 7-day point-prevalence abstinence at the end-of-pregnancy ( 37 % vs. 9 % ) and 12-week postpartum ( 33 % vs. 0 % ) assessment s. That effect was sustained through the 24-week postpartum assessment ( 27 % vs. 0 % ) , which was 12 weeks after discontinuation of the voucher program . Total mean voucher earnings across antepartum and postpartum were 397 US dollars ( SD=414 US dollars ) and 313 US dollars ( SD=142 dollars ) in the contingent and noncontingent conditions , respectively . The magnitude of these treatment effects exceed levels typically observed with pregnant and recently postpartum smokers , and the maintenance of effects through 24 weeks postpartum extends the duration beyond those reported previously", "The current study tested the feasibility of using contingency management to reduce cigarette smoking among college students . Eighty-eight undergraduate smokers were enrolled in a 3-week ABA study . During the baseline weeks , participants earned noncontingent monetary payments for attending data collection sessions . During the intervention week , participants earned monetary payments contingent on demonstrating recent abstinence . Participants were r and omly assigned to either a low- or a high-reinforcer magnitude condition that controlled the amount of money that could be earned during the intervention week . Cigarette smoking was significantly reduced during the intervention week relative to the baseline weeks , and greater reductions were achieved under the high-reinforcer magnitude condition . These results suggest that cigarette smoking among college students is responsive to contingency management procedures", "Smoking abstinence responses were characterized in 96 female smokers . Participants completed subjective state measures twice per week for 5 weeks and were then r and omly assigned to a group required to abstain for 31 days or a control group that continued to smoke . Financial incentives for biochemically verified abstinence result ed in an 81 % completion rate . Abstinence-related increases in depression , tension , anger , irritability , and appetite showed little tendency to return to prequit levels and remained significantly elevated above smoke-group levels . In contrast to psychological components of anxiety , physical components decreased to smoke group levels by the 2nd week of abstinence . Trait depression and neuroticism predicted larger increased abstinence-associated negative affect . The Big Five personality dimensions predicted variance not associated with depressive traits", "This study evaluated the impact of a year-long incentives-based worksite smoking-cessation program . Nineteen moderate-sized worksites , employing a total of approximately 1100 smokers , were r and omized to Incentive or No Incentive conditions . All identified smokers in the worksite were considered as subjects , whether or not they participated in the intervention . Analyses were conducted at both the worksite and individual level , and using both self-reported and biochemically vali date d cessation as endpoints . The incentive program did not significantly improve cessation rates at either the 1-year or 2-year follow-up assessment s. We conclude that more broadly focused interventions that also address worksite smoking policies , skills training , and cessation re sources , or programs that target additional risk factors are needed to substantially enhance quit rates", "Abstract Three group-comparison studies are reported which investigate possible ways of prolonging the effectiveness and increasing the acceptability of deposit contracts with smokers . In Experiment 1 deposits held for a total of 4 months were compared with those lasting 2 months . In Experiment 2 a ‘ reinforcement thinning ’ procedure in which the intervals between deposit repayments are progressively increased was compared with contracts involving equal intervals between repayments . In Experiment 3 the effects on compliance , drop-out rates and treatment outcome of a cumulative-deposit procedure were studied . Subjects in this condition were asked to supply a deposit in 4 weekly instalments rather than as a lump sum . The results of Experiments 1 and 2 were disappointing . There were no significant differences between treatments , although there was a trend in favour of ‘ thinning ’ deposits . Experiment 3 , however , showed that the cumulative-deposit procedure was effective in influencing more subjects to provide deposits . Neither drop-out rate nor treatment outcome was adversely affected . It is difficult for a straightforward reinforcement model to account for these results . Other models are discussed , and ways of testing them suggested . A larger study is still needed to determine whether certain deposit-contract procedures can add to the long-term effectiveness of behavioural-package programmes for stopping smoking", "Behavioral interventions that provide incentives contingent upon abstinence are effective addiction treatments . Nevertheless , these treatments often fail for individuals whose recent behaviors are very different from those reinforced . These hard-to-treat individuals may require shaping to achieve abstinence . We used percentile schedules to shape smokers ' delivery of breath sample s indicative of recent smoking abstinence ( breath carbon monoxide ( BCO ) < 4 ppm ) . Percentile schedules deliver incentives to current behaviors proximal to the target . Participants ( N = 102 ) were assigned to treatments delivering incentives for breath COs at or below the 10th , 30th , 50th , or 70th percentile of recent breath COs . Each condition effectively ensured contact with available contingencies , and result ed in BCO < 4 ppm in > 90 % of the 30th , 50th and 70th percentile groups versus 63 % in the 10th percentile . The 30th , 50th and 70th percentiles were especially effective in a sub- sample of hard-to-treat participants who did not deliver a breath CO < 4 ppm during an initial abstinence test or during a nine-visit baseline period , suggesting the value of shaping for this important sub- sample", "Abstract Adults with any DSM-IV diagnosed mental illness smoke nearly half of the cigarettes consumed in the U.S. ( Lasser et al. 2000 ) . This study compared two smoking cessation interventions for persons with schizophrenia or other serious mental illness because national data suggests that : ( 1 ) they smoke at two to three times the rate of the general population ; ( 2 ) cessation interventions for this population are understudied ; ( 3 ) most cessation studies exclude persons with serious mental illness ; and ( 4 ) cessation results in public health care savings and disposable income savings for clients . This study included a large number of persons with serious mental illness ( N = 181 ) who were r and omly assigned to one of three groups : contingent reinforcement ( CR ) , CR plus nicotine patch ( 21 mg , CR+NRT ) for 16 weeks , and a minimal intervention , self-quit control group . These participants were followed for 36 weeks . CR was accomplished with escalating financial compensation for achieving and maintaining abstinence as verified by expired carbon monoxide ( CO ) . Quit rates , as measured by expired CO , were higher and discordant with saliva cotinine quit rates . Cotinine showed lower quit rates and small differences between intervention and control partici pants at weeks 20 and 36 . There was , however , evidence of reduced smoking and importantly , no evidence of psychiatric exacerbation", "Smoking cessation interventions have posed significant challenges for health professionals , particularly when directed at high risk , low income , pregnant smokers . Typical quit rates for pregnant women who receive publicly financed obstetrical care have rarely exceeded 12–16%.1 As many as 70 % of women who quit smoking during pregnancy relapse within one year of delivery.2 Two areas that have received particular attention as possible adjuncts to behaviour change are the use of reinforcements and social supports . Reinforcement in the form of incentives/rewards for positive behaviours has been controversial as an intervention strategy . Some argue that the “ overjustification effect ” of external rewards may cause subjects to lose internal motivation to modify behaviour over the long term.3 However , results of several studies , including two meta-analyses on reinforcement , provide compelling evidence that positive reinforcement provides positive behavioural changes.4 - 8 A second area of study that has been explored in the behaviour change research is the role of social support in motivating and sustaining selected behaviour change . Recent studies have empirically linked tobacco quit rates with daily interaction with a supportive “ other , ” preferably one who did not smoke.9 10 The primary objective of our intervention was to determine whether the combination of bolstered social support and financial incentives had an effect in significantly reducing smoking behaviour among low income , high risk , pregnant and postpartum women who participate in Oregon 's Women , Infants , and Children ( WIC ) program . The Significant Other Supporter ( SOS ) program was a r and omised , experimentally design ed smoking cessation study implemented in four Oregon WIC program sites . Criteria for entry into the study included the following : age 15 years or older ; self reported smoker ( “ even a puff in the last seven days ” ) ; English speaker/reader ; WIC eligible ; and 28 weeks gestation or less . Eligible subjects were r and omised into one of two groups , and were", "OBJECTIVES This study examined the effect of program format and incentives on participation and cessation in worksite smoking cessation programs . METHODS Twenty-four worksites were r and omized to 6 conditions that differed in cessation program format and the use of incentives . Programs were offered for 18 months in each worksite . A total of 2402 cigarette smokers identified at baseline were surveyed 12 and 24 months later to assess participation in programs and cessation . RESULTS A total of 407 ( 16.9 % ) of the smoker cohort registered for programs ; on the 12- and 24-month surveys , 15.4 % and 19.4 % of the cohort , respectively , reported that they had not smoked in the previous 7 days . Registration for programs in incentive sites was almost double that of no-incentive sites ( 22.4 % vs 11.9 % ) , but increased registration did not translate into significantly greater cessation rates . Program type did not affect registration or cessation rates . CONCLUSIONS Although incentives increase rates of registration in worksite smoking cessation programs , they do not appear to increase cessation rates . Phone counseling seems to be at least as effective as group programs for promoting smoking cessation in worksites", "OBJECTIVES A r and omized trial was conducted to evaluate the effectiveness of a work-site health promotion program in reducing obesity and the prevalence of cigarette smoking . METHODS Thirty-two work sites were r and omized to treatment or no treatment for 2 years . Treatment consisted of health education classes combined with a payroll-based incentive system . Evaluation was based on cohort and cross-sectional surveys . RESULTS Of 10,000 total employees in treatment work sites , 2041 and 270 participated in weight control and smoking cessation programs , respectively . Weight losses averaged 4.8 lbs , and 43 % of smoking participants quit . Net 2-year reductions in smoking prevalence in treatment vs control work sites were 4.0 % and 2.1 % in cross-sectional and cohort surveys , respectively . No treatment effect was found for weight . Treatment effects for smoking prevalence and weight were both positively correlated with participation rates in the intervention programs ( r = .45 for smoking and r = .55 for weight ) . CONCLUSIONS This work-site health promotion program was effective in reducing smoking prevalence at a cost that is believed to make the investment worthwhile", "Sixty-three companies in the Chicago area were recruited to participate in a worksite smoking cessation program . Participants in each worksite received a television program and newspaper supplement ( part of a community-wide media campaign ) , and one of three conditions : ( 1 ) self-help manuals alone ( M ) , ( 2 ) self-help manuals and incentives for 6 months ( IM ) or ( 3 ) maintenance manuals , incentives and cognitive-behavioral support groups for 6 months ( GIM ) . Results at the 2 year assessment are examined using a r and om-effects regression model . In addition , various definitions of quit-rate commonly used in smoking cessation research are explored and the advantages of using a public health approach in the worksite are examined", "OBJECTIVES This study reports an efficacy trial of four work-site health promotion programs . It was predicted that strategies making use of behavioral counseling would produce a greater reduction in cardiovascular disease risk factors than screening and educational strategies . METHODS Twenty-eight work sites were r and omly allocated to a health risk assessment , risk factor education , behavioral counseling , or behavioral counseling plus incentives intervention . Participants were assessed before the intervention and at 3 , 6 , and 12 months . RESULTS Compared with the average of the health risk assessment and risk factor education conditions , there were significantly higher vali date d continuous smoking cessation rates and smaller increases in body mass index and estimated percentage of body fat in the two behavioral counseling conditions . The behavioral counseling condition was associated with a greater reduction in mean blood pressure than was the behavioral counseling plus incentives condition . On average among all groups , there was a short-term increase in aerobic capacity followed by a return to baseline levels . CONCLUSIONS Work-site interventions that use behavioral approaches can produce lasting changes in some cardiovascular risk factors and , if implemented routinely , can have a significant public health impact", "In a 2-week intervention to reduce cigarette smoking among out patients in treatment for cocaine addiction , 20 subjects were r and omly assigned to a contingent group , receiving monetary vouchers for breath sample s with carbon monoxide ( CO ) levels of 8 ppm or less , or to a noncontingent group , receiving vouchers regardless of CO level . Subjects wore either nicotine or placebo patches in a r and omized crossover design . Contingent subjects had significantly lower CO levels and met the 8 ppm target significantly more often than did noncontingent subjects ; however , number of cigarettes reported smoked did not differ between groups . Use of nicotine patches result ed in CO levels significantly lower than did use of placebo patches , but levels still exceeded 8 ppm regardless of type of patch . Because contingent reward helped cocaine-dependent smokers achieve nonsmoking CO targets , behavioral antismoking interventions merit continued study in similar population", "Abstract A contract procedure is described in which a money deposit provided by cigarette smokers at the time of stopping smoking is returned at set intervals contingent on their having not smoked . Outcome results up to 6 months after the stop smoking date are presented for 33 smokers who used this procedure as a component in a behavioural programme , and for 27 smokers who received the same treatment package but without the deposit component . The results for both groups are encouraging , and in the short term the deposit group did significantly better than the no-deposit group . Reasons for the failure of this difference to be maintained are discussed , and it is suggested that long term results would be improved by holding deposits over a longer interval . Other evidence is presented to show that the deposit procedure had a specific effect on smoking rather than a more general effect on attendance rates . Deposit contracts also appear acceptable to smokers . Urinary nicotine analysis appeared effective in deterring as well as detecting faking", "This study evaluated the efficacy of a contingency management ( CM ) intervention to promote smoking cessation in methadone-maintained patients . Twenty participants , r and omized into contingent ( n=10 ) or noncontingent ( n=10 ) experimental conditions , completed the 14-day study . Abstinence was determined using breath carbon monoxide and urine cotinine levels . Contingent participants received voucher-based incentives for biochemical evidence of smoking abstinence . Noncontingent participants earned vouchers independent of smoking status . Contingent participants achieved significantly more smoking abstinence and longer duration s of continuous smoking abstinence than did noncontingent participants . These results support the potential efficacy of using voucher-based CM to promote smoking cessation among methadone-maintained patients", "Abstract Predictions concerning the effects of variations in the parameters of deposit contracts with smokers were derived from the operant conditioning literature . The predictions were tested by group comparison studies involving 83 subjects in 12 treatment groups , using three deposit procedures . As predicted , increasing the amount of money returned in each deposit repayment improved short term abstinence rates . Increasing repayment frequency had a similar but not quite significant effect . The predicted relationship between frequency and amount of repayments , with variations in frequency having more effect , was not found . There were no long term differences between groups . The usefulness of the operant framework was therefore partially demonstrated . Some clinical implication s of the findings are discussed", "OBJECTIVE The first aim of the present investigation was to examine cross-sectional differences between smokers who engage in additional health risk behaviors ( i.e. , high-fat diets and low physical activity levels ) and those who do not that could affect readiness for smoking cessation treatment and treatment prognosis . The second aim was to examine prospect i ve associations between risk factor status and smoking outcomes ( i.e. , cessation and quit attempts ) . DESIGN Data were derived from baseline and 1-year follow-up surveys for the SUCCESS project , a r and omized trial of worksite smoking interventions conducted in 24 worksites in Minneapolis/St . Paul , Minnesota . Included in the analyses were 2,149 study participants who reported smoking at baseline . METHODS Current smokers were categorized into one of three \" risk groups \" : the \" 1 additional risk factor \" group ( i.e. , either low physical activity level or high dietary fat intake ) , the \" 2 additional risk factor \" group ( i.e. , both low physical activity and high dietary fat intake ) , and the \" smoker only \" group ( i.e. , neither low physical activity nor high dietary fat intake ) . Mixed model regression analyses examined cross-sectional associations between risk group status and baseline demographic variables , smoking dependency , social environments for smoking , and health problems . Prospect i ve associations between baseline risk group status and 1-year follow-up cessation attempts and quits were also examined . RESULTS At baseline , risk factor status was associated with smoking dependency for both men and women . Women smokers with at least one additional risk factor reported a greater number of cigarettes smoked per day , higher Fagerstrom Nicotine Dependence scores , and lower self-efficacy for refraining from smoking in a variety of situations compared with smokers with no additional risk factors . Men smokers with at least one additional risk factor reported higher Fagerstrom Nicotine Dependence scores compared with smokers with no additional risk factors . Women smokers with at least one additional risk factor were more likely to report being encouraged to quit by co-workers compared with smokers with no other risk factors . No relationship between risk factor status and social pressure to quit was observed among men . Prospect i ve analyses indicated that baseline risk factor status was marginally related to smoking outcome at 1-year follow-up ; however , these relationships were attenuated considerably when controlling for smoking dependence . Relationships between risk factor status and smoking outcomes were stronger for men . CONCLUSION Results indicated that the presence of multiple health risk behaviors was related to more serious problems with smoking . However , the presence of additional risk factors did not strongly affect prognosis for smoking cessation", "PURPOSE The purpose of this article is to describe the diffusion and evaluation of the smoking prevention programme \" Be Smart -- Don't Start \" , the German \" Smoke Free Class Competition \" . METHOD The diffusion is described by means of numbers of participating classes and a representative population -based interview of 3,600 12 - 19-year-olds , which was conducted in 2005 . Two controlled and two r and omised controlled studies carried out in three countries ( Germany , Finl and and the Netherl and s ) with a total number of 12,812 adolescents ( N of the intervention group : 8,086 ; N of the control group : 4,726 ) have been realised to evaluate the intervention . RESULTS In 2005 20 % of all 12 - 15 year-olds and 9 % of all 16 - 19-year-olds living in Germany had participated in the programme . From baseline to follow-up test 12 - 24 months later smoking increased by 21.78 per cent points in the control group , compared to an increase of 16.02 per cent points in the intervention group . At follow-up 27.57 % of the pupils from the intervention group , and 35.91 % of the pupils from the control group are actual smokers ( odds ratio=0.65 , 95 % confidence interval : 0.57 - 0.74 ) . CONCLUSIONS Participating rate in the competition is high . The results indicate that the competition might have a short-term effect and be able to delay the onset of smoking", "BACKGROUND In 2004 , the German Cancer Research Center ( \" Deutsches Krebsforschungszentrum \" [ DKFZ ] ) , collaborating with the Federal Center for Health Education ( \" \" Bundeszentrale für gesundheitliche Aufklärung \" [ BZgA ] ) and supported by the World Health Organization ( WHO ) , carried out a population -related smoking cessation campaign entitled \" Rauchfrei 2004 \" ( \" Smoke-free 2004 \" ) . Using mass-media communication , the campaign was intended to motivate as many smokers as possible to quit smoking for at least 4 weeks , so as to achieve , ideally , complete cessation of tobacco consumption . This prevention campaign explicitly included juvenile smokers . METHODS Within a 1-year follow-up survey , a 1/3 r and om sample was taken from a total of 4,358 juvenile participants whose smoking status by the end of the competition and 1 year later was evaluated according to international st and ards . RESULTS 42 % of juvenile participants named monetary reasons , 33 % health-related reasons as their chief motivation for participating in the competition . 61 % of young adults question ed stated that they were abstinent at the end of the competition , i.e. , at least for 4 weeks . 1 year later , 19 % of juvenile participants stated to be nonsmokers . 12 % of them stated to have been continuously abstinent for 12 months after the start of the competition . CONCLUSION This publication is the first scientific evaluation of juvenile participation in a competition-based smoking cessation campaign . Although some method ological restrictions need to be taken into account , abstinence rates determined according to internationally applied WHO evaluation guidelines are significantly higher than the secular trend . Thus , the prevention approach presented here appears to be similarly effective as alternative intervention programs that tend to be more expensive", "Objectives . Investigators planning studies employing group-r and omized design s need good estimates of the extra variation introduced as a result of correlated observations within units of assignment . We report intraclass correlation coefficients ( ICCs ) for a wide range of outcomes commonly employed in worksite studies and demonstrate analysis methods that can limit their deleterious impact . Methods . A sample of 11 , 711 employees of 24 firms recruited from the Minneapolis/St . Paul metropolitan area completed a mailed survey in the SUCCESS study , reporting on a broad array of outcomes . Applying mixed-model regression , we provide both crude and adjusted estimates of ICCs for 27 outcomes . Results . The crude ICCs were generally small , with a mean of .0163 and values ranging from 0 to .0650 . Adjustment for demographics reduced the ICCs for 25 of the 27 outcomes , and adjustment for additional individual-level covariates further reduced the ICCs for 23 of the 27 outcomes . Conclusions . Our results suggest that worksite-level ICCs for a variety of outcomes are generally small and can generally be reduced by adjustment for individual-level characteristics . Incorporating this information in planning worksite studies can improve sample size calculations to avoid underpowered studies" ]

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[ "Association between sauna bathing and fatal cardiovascular and all-cause mortality events.", "Sauna-induced acceleration in insulin absorption from subcutaneous injection site.", "Repeated sauna therapy reduces urinary 8-epi-prostaglandin F(2alpha).", "Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans.", "Sauna bathing is inversely associated with dementia and Alzheimer's disease in middle-aged Finnish men", "Sauna Bathing and Incident Hypertension: A Prospective Cohort Study", "The effect of ambient temperature on glucose tolerance and its implications for the tropics.", "Effect of hand heating by a warm air box on O2 consumption of the contralateral arm.", "The effects of repeated thermal therapy on quality of life in patients with type II diabetes mellitus.", "Changes in forearm blood flow at elevated ambient temperature and their role in the apparent impairment of glucose tolerance.", "Enhanced neuroendocrine response to insulin tolerance test performed under increased ambient temperature", "Repeated sauna treatment improves vascular endothelial and cardiac function in patients with chronic heart failure.", "Heat stress and cardiovascular, hormonal, and heat shock proteins in humans.", "Impaired glucose tolerance after brief heat exposure: a randomized crossover study in healthy young men.", "Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study", "Sauna bathing reduces the risk of stroke in Finnish men and women", "Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.", "An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults.", "Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure" ]

[ "IMPORTANCE Sauna bathing is a health habit associated with better hemodynamic function ; however , the association of sauna bathing with cardiovascular and all-cause mortality is not known . OBJECTIVE To investigate the association of frequency and duration of sauna bathing with the risk of sudden cardiac death ( SCD ) , fatal coronary heart disease ( CHD ) , fatal cardiovascular disease ( CVD ) , and all-cause mortality . DESIGN , SETTING , AND PARTICIPANTS We performed a prospect i ve cohort study ( Finnish Kuopio Ischemic Heart Disease Risk Factor Study ) of a population -based sample of 2315 middle-aged ( age range , 42 - 60 years ) men from Eastern Finl and . Baseline examinations were conducted from March 1 , 1984 , through December 31 , 1989 . EXPOSURES Frequency and duration of sauna bathing assessed at baseline . RESULTS During a median follow-up of 20.7 years ( interquartile range , 18.1 - 22.6 years ) , 190 SCDs , 281 fatal CHDs , 407 fatal CVDs , and 929 all-cause mortality events occurred . A total of 601 , 1513 , and 201 participants reported having a sauna bathing session 1 time per week , 2 to 3 times per week , and 4 to 7 times per week , respectively . The numbers ( percentages ) of SCDs were 61 ( 10.1 % ) , 119 ( 7.8 % ) , and 10 ( 5.0 % ) in the 3 groups of the frequency of sauna bathing . The respective numbers were 89 ( 14.9 % ) , 175 ( 11.5 % ) , and 17 ( 8.5 % ) for fatal CHDs ; 134 ( 22.3 % ) , 249 ( 16.4 % ) , and 24 ( 12.0 % ) for fatal CVDs ; and 295 ( 49.1 % ) , 572 ( 37.8 % ) , and 62 ( 30.8 % ) for all-cause mortality events . After adjustment for CVD risk factors , compared with men with 1 sauna bathing session per week , the hazard ratio of SCD was 0.78 ( 95 % CI , 0.57 - 1.07 ) for 2 to 3 sauna bathing sessions per week and 0.37 ( 95 % CI , 0.18 - 0.75 ) for 4 to 7 sauna bathing sessions per week ( P for trend = .005 ) . Similar associations were found with CHD , CVD , and all-cause mortality ( P for trend ≤.005 ) . Compared with men having a sauna bathing session of less than 11 minutes , the adjusted hazard ratio for SCD was 0.93 ( 95 % CI , 0.67 - 1.28 ) for sauna bathing sessions of 11 to 19 minutes and 0.48 ( 95 % CI , 0.31 - 0.75 ) for sessions lasting more than 19 minutes ( P for trend = .002 ) ; significant inverse associations were also observed for fatal CHDs and fatal CVDs ( P for trend ≤.03 ) but not for all-cause mortality events . CONCLUSIONS AND RELEVANCE Increased frequency of sauna bathing is associated with a reduced risk of SCD , CHD , CVD , and all-cause mortality . Further studies are warranted to establish the potential mechanism that links sauna bathing and cardiovascular health", "The effect of the Finnish sauna on insulin absorption from a subcutaneous injection site was examined in eight insulin-dependent diabetic patients by measuring externally the disappearance rate of 125I-labelled rapid-acting insulin . The sauna ( twice for 25 minutes at 85 degrees C ) accelerated insulin absorption by 110 % as compared with room temperature ( p < 0.01 ) . After the sauna blood glucose concentrations were 3.0 - 3.3 mmol/1 ( 54.1 - 59.5 mg/100 ml ) lower than on the control day ( p < 0.05 ) . The fall in blood glucose values was proportional to the increased rate of insulin absorption ( r = 0.30 ; p < 0.01 ) . The hypoglycaemic effect of a sauna in insulin-treated diabetics is clearly at least partly due to enhanced insulin absorption from the injection site . Such an effect might be prevented by taking a snack or reducing the insulin dose", "We have reported that repeated sauna therapy improves impaired vascular endothelial function in a patient with coronary risk factors . We hypothesized that sauna therapy decreases urinary 8-epi-prostagl and in F(2alpha ) ( PGF(2alpha ) ) levels as a marker of oxidative stress and conducted a r and omized , controlled study . Twenty-eight patients with at least one coronary risk factor were divided into a sauna group ( n = 14 ) and non-sauna group ( n = 14 ) . Sauna therapy was performed with a 60 degrees C far infrared-ray dry sauna for 15 minutes and then bed rest with a blanket for 30 minutes once a day for two weeks . Systolic blood pressure and increased urinary 8-epi-PGF(2alpha ) levels in the sauna group were significantly lower than those in the non-sauna group at two weeks after admission ( 110 + /- 15 mmHg vs 122 + /- 13 mmHg , P < 0.05 , 230 + /- 67 pg/mg x creatinine vs 380 + /- 101 pg/mg x creatinine , P < 0.0001 , respectively ) . These results suggest that repeated sauna therapy may protect against oxidative stress , which leads to the prevention of atherosclerosis", "KEY POINTS A recent 30 year prospect i ve study showed that lifelong sauna use reduces cardiovascular-related and all-cause mortality ; however , the specific cardiovascular adaptations that cause this chronic protection are currently unknown . We investigated the effects of 8 weeks of repeated hot water immersion ( ' heat therapy ' ) on various biomarkers of cardiovascular health in young , sedentary humans . We showed that , relative to a sham group which participated in thermoneutral water immersion , heat therapy increased flow-mediated dilatation , reduced arterial stiffness , reduced mean arterial and diastolic blood pressure , and reduced carotid intima media thickness , with changes all on par or greater than what is typically observed in sedentary subjects with exercise training . Our results show for the first time that heat therapy has widespread and robust effects on vascular function , and as such , could be a viable treatment option for improving cardiovascular health in a variety of patient population s , particularly those with limited exercise tolerance and /or capabilities . ABSTRACT The majority of cardiovascular diseases are characterized by disorders of the arteries , predominantly caused by endothelial dysfunction and arterial stiffening . Intermittent hot water immersion ( ' heat therapy ' ) results in elevations in core temperature and changes in cardiovascular haemodynamics , such as cardiac output and vascular shear stress , that are similar to exercise , and thus may provide an alternative means of improving health which could be utilized by patients with low exercise tolerance and /or capabilities . We sought to comprehensively assess the effects of 8 weeks of heat therapy on biomarkers of vascular function in young , sedentary subjects . Twenty young , sedentary subjects were assigned to participate in 8 weeks ( 4 - 5 times per week ) of heat therapy ( n = 10 ; immersion in a 40.5 ° C bath sufficient to maintain rectal temperature ≥ 38.5 ° C for 60 min per session ) or thermoneutral water immersion ( n = 10 ; sham ) . Eight weeks of heat therapy increased flow-mediated dilatation from 5.6 ± 0.3 to 10.9 ± 1.0 % ( P < 0.01 ) and superficial femoral dynamic arterial compliance from 0.06 ± 0.01 to 0.09 ±0.01 mm(2 ) mmHg(-1 ) ( P = 0.03 ) , and reduced ( i.e. improved ) aortic pulse wave velocity from 7.1 ± 0.3 to 6.1 ± 0.3 m s(-1 ) ( P = 0.03 ) , carotid intima media thickness from 0.43 ± 0.01 to 0.37 ± 0.01 mm ( P < 0.001 ) , and mean arterial blood pressure from 83 ± 1 to 78 ± 2 mmHg ( P = 0.02 ) . No changes were observed in the sham group or for carotid arterial compliance , superficial femoral intima media thickness or endothelium-independent dilatation . Heat therapy improved endothelium-dependent dilatation , arterial stiffness , intima media thickness and blood pressure , indicating improved cardiovascular health . These data suggest heat therapy may provide a simple and effective tool for improving cardiovascular health in various population", "Background there are no previous studies linking repeated heat exposure of sauna and the risk of memory diseases . We aim ed to investigate whether frequency of sauna bathing is associated with risk of dementia and Alzheimer 's disease . Setting prospect i ve population -based study . Methods the frequency of sauna bathing was assessed at baseline in the Kuopio Ischaemic Heart Disease population -based prospect i ve cohort study of 2,315 apparently healthy men aged 42 - 60 years at baseline , with baseline examinations conducted between 1984 and 1989 . Hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) for dementia and Alzheimer 's disease were ascertained using Cox-regression modelling with adjustment for potential confounders . Results during a median follow-up of 20.7 ( interquartile range 18.1 - 22.6 ) years , a total of 204 and 123 diagnosed cases of dementia and Alzheimer 's disease were respectively recorded . In analysis adjusted for age , alcohol consumption , body mass index , systolic blood pressure , smoking status , Type 2 diabetes , previous myocardial infa rct ion , resting heart rate and serum low-density lipoprotein cholesterol , compared with men with only 1 sauna bathing session per week , the HR for dementia was 0.78 ( 95 % CI : 0.57 - 1.06 ) for 2 - 3 sauna bathing sessions per week and 0.34 ( 95 % CI : 0.16 - 0.71 ) for 4 - 7 sauna bathing sessions per week . The corresponding HRs for Alzheimer 's disease were 0.80 ( 95 % CI : 0.53 - 1.20 ) and 0.35 ( 95 % CI : 0.14 - 0.90 ) . Conclusion in this male population , moderate to high frequency of sauna bathing was associated with lowered risks of dementia and Alzheimer 's disease . Further studies are warranted to establish the potential mechanisms linking sauna bathing and memory diseases", "BACKGROUND Sauna bathing is associated with reduced cardiovascular risk , but the mechanisms underlying this beneficial effect are not entirely understood . We aim ed to assess the relationship between sauna bathing and risk of incident hypertension . METHODS Frequency of sauna bathing was ascertained using question naires in the Kuopio Ischemic Heart Disease Study , a prospect i ve cohort study conducted in Eastern Finl and that comprised a population -based sample of 1,621 men aged 42 to 60 years without hypertension at baseline . The incidence of hypertension was defined as a physician diagnosis of hypertension , systolic blood pressure ( SBP ) > 140 mm Hg , diastolic blood pressure > 90 mm Hg , or use of antihypertensive medication . RESULTS During a median follow-up of 24.7 years , 251 incident cases ( 15.5 % ) were recorded . In Cox regression analysis adjusted for baseline age , smoking , body mass index , and SBP ; compared to participants reporting 1 sauna session per week , the hazard ratio for incident hypertension in participants reporting 2 to 3 sessions and 4 to 7 sessions was 0.76 ( 95 % confidence interval : 0.57 - 1.02 ) and 0.54 ( 0.32 - 0.91 ) , respectively . The corresponding hazard ratios were similar after further adjustment for glucose , creatinine , alcohol consumption , heart rate , family history of hypertension , socioeconomic status , and cardiorespiratory fitness : 0.83 ( 95 % confidence interval : 0.59 - 1.18 ) and 0.53 ( 0.28 - 0.98 ) , respectively . CONCLUSIONS Regular sauna bathing is associated with reduced risk of hypertension , which may be a mechanism underlying the decreased cardiovascular risk associated with sauna use . Further epidemiological and experimental studies could help eluci date the effects of sauna bathing on cardiovascular function", "There have been a few reports in Caucasians that glucose tolerance is worse at higher environmental temperatures . In investigating these observations in a tropical African population , we performed st and ard oral glucose tolerance tests in the morning after overnight fasting in 16 diabetic ( with varying glycaemic control ) and 16 nondiabetic subjects , both groups with differing body weights . Each volunteer ingested 75 g glucose at two different ambient temperatures of 22 - 23 degrees C and 32 - 33 degrees C in r and om order . These room temperatures are typically observed during hot and humid seasons in sub-Saharan Africa . Our results confirm that glucose tolerance was worse at the higher room temperature ( p less than 0.01 ) . The post-oral glucose 2 h values at the lower room temperature were lower by about 5 mmol/l in the diabetics and 0.5 mmol/l in the non-diabetics ( both p less than 0.02 ) . Similarly , the total and incremental areas under the 2 h glucose/time curves were greater at the higher room temperature . These results were not influenced by obesity . We conclude that glucose tolerance in tropical Africans is dependent on environmental temperature . An ambient temperature for the performance of diagnostic oral glucose tolerance test should therefore be specified , especially when evaluating differences in diabetes prevalence rates in population s resident in different climatic regions", "Arterialization of venous blood is often used in study ing forearm metabolism . Astrup et al. [ Am . J. Physiol . 255 ( Endocrinol . Metab . 18 ) : E572-E578 , 1988 ] showed that heating of the h and by a warming blanket caused a redistribution of blood flow in the contralateral arm and thus introduced errors in forearm skeletal muscle flux calculations . The present study was undertaken to investigate how h and heating by a warm air box ( 60 degrees C ) would affect metabolism and blood flow in the contralateral arm before and during 3 h after a glucose load . Eleven healthy volunteers ( 5 males , 6 females ) underwent an oral glucose tolerance test ( 70 g ) on two different occasions , one test with and one without heating of the contralateral h and , in r and om order . Heating the h and for 30 min before glucose intake did not affect skin temperature , rectal temperature , deep venous oxygen saturation , forearm blood flow , or oxygen consumption of forearm skeletal muscle . Although , after the glucose load , heating significantly increased forearm blood flow ( P less than 0.05 ) , the integrated response after glucose was not significantly different between control and heating experiments [ 67 + /- 43 and 117 + /- 41 ( SE ) ml/100 ml tissue ] . With both conditions , there was an increase in skin temperature ( P less than 0.001 , integrated response control : 369 + /- 79 and heating : 416 + /- 203 degrees C ) and oxygen consumption of forearm muscle ( control : 290 + /- 73 , P less than 0.05 and heating : 390 + /- 130 mumol/100 ml , P less than 0.05 ) after glucose intake . These responses did not significantly differ between the conditions . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVES Decreased quality of life in diabetes is associated with poor health outcomes . Far-infrared sauna treatments improve the quality of life for those with chronic pain , chronic fatigue syndrome , depression , and congestive heart failure . The objective of this study is to determine whether far-infrared saunas have a beneficial effect on quality of life in those with type II diabetes . DESIGN This was a sequential , longitudinal , interrupted time series design study . SETTING /LOCATION The setting was Fraser Lake BC , a rural village in central British Columbia , Canada . SUBJECTS All patients of the Fraser Lake Community Health Center with type II diabetes were invited to participate in this study . INTERVENTIONS The study consisted of 20-minute , 3 times weekly infrared sauna sessions , over a period of 3 months . OUTCOME MEASURES To assess quality of life , subjects completed the 36-item Short-form Health Survey Version 2 ( SF-36v2 ) question naire as well as \" Zero-to-Ten \" Visual Analogue Scales . Baseline study parameters were measured within 1 week prior to commencing sauna sessions . Postintervention measurements were collected between 1 and 3 days after the last sauna session . RESULTS Physical health , general health , and social functioning indices of the SF-36v2 improved . Visual Analogue Scales for stress and fatigue improved . CONCLUSIONS Far-infrared sauna use maybe associated with improved quality of life in people with type II diabetes mellitus . Uptake of infrared saunas use is greater than the uptake of other lifestyle interventions", "1 . Antecubital venous plasma glucose and insulin concentrations after ingestion of 75 g of glucose were higher in six normal subjects when studied at an ambient temperature of 33 degrees C at an ambient temperature of 23 degrees C ; the mean area under the glucose-time curve increased from 833 at 23 degrees C to 990 mmol min-1 at 33 degrees C , that for insulin from 5300 to 7900 m-units min 1 - 1 . 2 . Core temperature was elevated by 0.5 degree C at 33 degrees C ambient , although there was no marked stress response as judged by plasma levels of catecholamines , cortisol and growth hormone ; at 2 h after glucose ingestion , mean noradrenaline levels were lower at 33 degrees C than at 23 degrees C ( 1.1 at 33 degrees C vs 1.8 nmol/l at 23 degrees C ) , adrenaline slightly higher ( 0.18 at 33 degrees C vs 0.09 nmol/l at 23 degrees C ) , cortisol and growth hormone unchanged . 3 . Forearm blood flow was markedly elevated at 33 degrees C ambient ( mean total flow 9.1 at 33 degrees C vs 1.8 ml min-1 100 ml-1 at 23 degrees C ) , as were antecubital venous partial pressure of oxygen ( mean 10.1 at 33 degrees C vs 5.6 kPa at 23 degrees C ) and oxygen saturation ( mean 92 % at 33 degrees C vs 70 % at 23 degrees C ) . There was a positive correlation between oxygen saturation and area under the glucose tolerance curve . 4 . In separate experiments , arterialized glucose concentrations were measured after glucose ingestion at 23 degrees C ambient . ( ABSTRACT TRUNCATED AT 250 WORDS", "The hypothesis that an increase in ambient temperature modulates neuroendocrine response in clinical ly used provocative pituitary function tests was verified . Healthy male volunteers were subjected to insulin tolerance tests in two r and omized trials . In the first trial hypoglycemia was induced by a bolus injection of insulin ( 0.1 U per kg of BW , iv ) at room temperature . In the second trial , the subjects were exposed to increased ambient temperature for 45 min before insulin injection and for 45 min thereafter . The environmental temperature was selected to increase body temperature less than 1C . Under conditions of increased temperature basal hormone levels as measured in antecubital venous blood sample s failed to be modified and the hypoglycemia was less severe . Nevertheless , the responses of most ( β-endorphin , ACTH , prolactin , catecholamines ) , but not all ( growth hormone , Cortisol ) , hormones to hypoglycemia were exaggerated . The remarkable increase in ACTH and β-endorphin release was not accompanied by concomitant increase of plasma Cortisol response . The sympathetic-adrenomedullary system was significantly activated , which was manifested particularly by enhanced norepinephrine release . Growth hormone response to hypoglycemia was not modified , while that of prolactin was enhanced . Thus during evaluation of neuroendocrine function under clinical conditions , changes in ambient and body temperature should not be underestimated", "OBJECTIVES The purpose of this study was to determine the mechanism by which 60 degrees C sauna treatment improves cardiac function in patients with chronic heart failure ( CHF ) . BACKGROUND We have previously reported that repeated 60 degrees C sauna treatment improves hemodynamic data and clinical symptoms in patients with CHF . We hypothesized that the sauna restores endothelial function and then improves cardiac function . METHODS Twenty patients ( 62 plus minus 15 years ) in New York Heart Association ( NYHA ) functional class II or III CHF were treated in a dry sauna at 60 degrees C for 15 min and then kept on bed rest with a blanket for 30 min , daily for two weeks . Ten patients with CHF , matched for age , gender and NYHA functional class , were placed on a bed in a temperature-controlled ( 24 degrees C ) room for 45 min as the nontreated group . Using high-resolution ultrasound , we measured the diameter of the brachial artery at rest and during reactive hyperemia ( percent flow-mediated dilation , % FMD : endothelium-dependent dilation ) , as well as after sublingual administration of nitroglycerin ( % NTG : endothelium-independent dilation ) . Cardiac function was evaluated by measuring the concentrations of plasma brain natriuretic peptide ( BNP ) . RESULTS Clinical symptoms were improved in 17 of 20 patients after two weeks of sauna therapy . The % FMD after two-week sauna treatment significantly increased from the baseline value , whereas the % NTG-induced dilation did not . Concentrations of BNP after the two-week sauna treatment decreased significantly . In addition , there was a significant correlation between the change in % FMD and the percent improvement in BNP concentrations in the sauna-treated group . In contrast , none of the variables changed at the two-week interval in the nontreated group . CONCLUSIONS Repeated sauna treatment improves vascular endothelial function , result ing in an improvement in cardiac function and clinical symptoms", "CONTEXT Conditions such as osteoarthritis , obesity , and spinal cord injury limit the ability of patients to exercise , preventing them from experiencing many well-documented physiologic stressors . Recent evidence indicates that some of these stressors might derive from exercise-induced body temperature increases . OBJECTIVE To determine whether whole-body heat stress without exercise triggers cardiovascular , hormonal , and extracellular protein responses of exercise . DESIGN R and omized controlled trial . SETTING University research laboratory . PATIENTS OR OTHER PARTICIPANTS Twenty-five young , healthy adults ( 13 men , 12 women ; age = 22.1 ± 2.4 years , height = 175.2 ± 11.6 cm , mass = 69.4 ± 14.8 kg , body mass index = 22.6 ± 4.0 ) volunteered . INTERVENTION(S ) Participants sat in a heat stress chamber with heat ( 73 ° C ) and without heat ( 26 ° C ) stress for 30 minutes on separate days . We obtained blood sample s from a subset of 13 participants ( 7 men , 6 women ) before and after exposure to heat stress . MAIN OUTCOME MEASURE(S ) Extracellular heat shock protein ( HSP72 ) and catecholamine plasma concentration , heart rate , blood pressure , and heat perception . RESULTS After 30 minutes of heat stress , body temperature measured via rectal sensor increased by 0.8 ° C . Heart rate increased linearly to 131.4 ± 22.4 beats per minute ( F₆,₂₄ = 186 , P < .001 ) and systolic and diastolic blood pressure decreased by 16 mm Hg ( F₆,₂₄ = 10.1 , P < .001 ) and 5 mm Hg ( F₆,₂₄ = 5.4 , P < .001 ) , respectively . Norepinephrine ( F₁,₁₂ = 12.1 , P = .004 ) and prolactin ( F₁,₁₂ = 30.2 , P < .001 ) increased in the plasma ( 58 % and 285 % , respectively ) ( P < .05 ) . The HSP72 ( F₁,₁₂ = 44.7 , P < .001 ) level increased with heat stress by 48.7 % ± 53.9 % . No cardiovascular or blood variables showed changes during the control trials ( quiet sitting in the heat chamber with no heat stress ) , result ing in differences between heat and control trials . CONCLUSIONS We found that whole-body heat stress triggers some of the physiologic responses observed with exercise . Future studies are necessary to investigate whether carefully prescribed heat stress constitutes a method to augment or supplement exercise", "A high dem and on thermoregulatory processes may challenge homoeostasis , particularly regarding glucose regulation . This has been understudied , although it might concern millions of humans . The objective of this project was to examine the isolated and combined effects of experimental short-term mild heat exposure and metabolic level on glucoregulation . Two experimental r and omized crossover studies were conducted . Ten healthy young men participated in study A , which comprises four sessions in a fasting state at two metabolic levels [ rest and exercise at 60 % of maximal oxygen uptake ( O2 ) for 40 min ] in two environmental temperatures ( warm : 31 ° C and control : 22 ° C ) . Each session ended with an ad libitum meal , result ing in similar energy intake across sessions . In study B , 12 healthy young men underwent two 3 h oral glucose tolerance tests ( OGTTs ) in warm and control environmental temperatures . Venous blood was sample d at several time points . In study A , repeated measure ANOVAs revealed higher postpr and ial serum glucose and insulin levels with heat exposure . Glycaemia following the OGTT was higher in the warm temperature compared with control . The kinetics of the serum glucose response to the glucose load was also affected by the environmental temperature ( temperature-by-time interaction , P=0.030 ) , with differences between the warm and control conditions observed up to 90 min after the glucose load ( all P<0.033 ) . These studies provide evidence that heat exposure alters short-term glucoregulation . The implication of this environmental factor in the physiopathology of Type 2 diabetes has yet to be investigated", "Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % )", "Objective To assess the association between frequency of sauna bathing and risk of future stroke . Methods Baseline habits of sauna bathing were assessed in 1,628 adult men and women aged 53–74 years ( mean age , 62.7 years ) without a known history of stroke in the Finnish Kuopio Ischemic Heart Disease prospect i ve cohort study . Three sauna bathing frequency groups were defined : 1 , 2–3 , and 4–7 sessions per week . Hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) were estimated for incident stroke . Results During a median follow-up of 14.9 years , 155 incident stroke events were recorded . Compared with participants who had one sauna bathing session per week , the age- and sex-adjusted HR ( 95 % CI ) for stroke was 0.39 ( 0.18–0.83 ) for participants who had 4–7 sauna sessions per week . After further adjustment for established cardiovascular risk factors and other potential confounders , the corresponding HR ( 95 % CI ) was 0.39 ( 0.18–0.84 ) and this remained persistent on additional adjustment for physical activity and socioeconomic status at 0.38 ( 0.18–0.81 ) . The association between frequency of sauna bathing and risk of stroke was not modified by age , sex , or other clinical characteristics ( p for interaction > 0.10 for all subgroups ) . The association was similar for ischemic stroke but modest for hemorrhagic stroke , which could be attributed to the low event rate ( n = 34 ) . Conclusions This long-term follow-up study shows that middle-aged to elderly men and women who take frequent sauna baths have a substantially reduced risk of new-onset stroke", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control . Therefore , the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose , insulin , and leptin responses to an oral glucose challenge ( OGTT ) in obese type 2 diabetics and healthy humans . Nine obese ( 45±7.1 % fat mass ) type 2 diabetics ( T2DM : 50.1±12y , 7.5±1.8 % HbA1c ) absent of insulin therapy and nine similar aged ( 41.1±13.7y ) healthy non-obese controls ( HC : 33.4±7.8 % fat mass , P<0.01 ; 5.3±0.4 % HbA1c , P<0.01 ) participated . Using a r and omized design , subjects underwent either a whole body passive hyperthermia treatment via head-out hot water immersion ( 1h resting in 39.4±0.4 ° C water ) that increased internal temperature above baseline by ∆1.6±0.4 ° C or a control resting condition . Twenty-four hours post treatments , a 75 g OGTT was administered to evaluate changes in plasma glucose , insulin , C-peptide , and leptin concentrations . Hyperthermia itself did not alter area under the curve for plasma glucose , insulin , or C-peptide during the OGTT in either group . Fasting absolute and normalized ( kg·fat mass ) plasma leptin was significantly increased ( P<0.01 ) only after the hyperthermic exposure by 17 % in T2DM and 24 % in HC groups ( P<0.001 ) when compared to the control condition . These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals", "Extracellular heat shock protein 72 ( eHsp72 ) concentration increases during exercise-heat stress when conditions elicit physiological strain . Differences in severity of environmental and exercise stimuli have elicited varied response to stress . The present study aim ed to quantify the extent of increased eHsp72 with increased exogenous heat stress , and determine related endogenous markers of strain in an exercise-heat model . Ten males cycled for 90 min at 50 % V⋅O2peak$$ \\overset{\\cdot } { \\mathrm{V}}{\\mathrm{O}}_{2\\mathrm{peak } } $ $ in three conditions ( TEMP , 20 ° C/63 % RH ; HOT , 30.2 ° C/51%RH ; VHOT , 40.0 ° C/37%RH ) . Plasma was analysed for eHsp72 pre , immediately post and 24-h post each trial utilising a commercially available ELISA . Increased eHsp72 concentration was observed post VHOT trial ( + 172.4 % ) ( p < 0.05 ) , but not TEMP ( −1.9 % ) or HOT ( + 25.7 % ) conditions . eHsp72 returned to baseline values within 24 h in all conditions . Changes were observed in rectal temperature ( Trec ) , rate of Trec increase , area under the curve for Trec of 38.5 and 39.0 ° C , duration Trec ≥ 38.5 and ≥39.0 ° C , and change in muscle temperature , between VHOT , and TEMP and HOT , but not between TEMP and HOT . Each condition also elicited significantly increasing physiological strain , described by sweat rate , heart rate , physiological strain index , rating of perceived exertion and thermal sensation . Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration . Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large , rapid changes in core temperature" ]

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[ "An assessment of the use of prophylactic antibiotics in third molar surgery.", "Effect of azidocillin, erythromycin, clindamycin and doxycycline on postoperative complications after surgical removal of impacted mandibular third molars.", "Evaluation of antibiotic prophylaxis in reducing postoperative infection after mandibular third molar extraction in young patients.", "Role of antimicrobials in third molar surgery: prospective, double blind,randomized, placebo-controlled clinical study.", "The impact of intravenous antibiotics on health-related quality of life outcomes and clinical recovery after third molar surgery.", "Metronidazole (Flagyl) and Arnica Montana in the prevention of post-surgical complications, a comparative placebo controlled clinical trial.", "The prevention of 'dry socket' with topical metronidazole in general dental practice", "Relationships between patient characteristics and reasons for tooth extraction in Japan.", "Prophylaxis versus pre-emptive treatment for infective and inflammatory complications of surgical third molar removal: a randomized, double-blind, placebo-controlled, clinical trial with sustained release amoxicillin/clavulanic acid (1000/62.5 mg).", "Does metronidazole prevent alveolitis sicca dolorosa? A double-blind, placebo-controlled clinical study.", "The effect of Nivemycin on pain and swelling following lower third molar removal.", "Postoperative prophylactic antibiotic treatment in third molar surgery--a necessity?", "Randomized Study of Surgical Prophylaxis in Immunocompromised Hosts", "Impact of topical minocycline with third molar surgery on clinical recovery and health-related quality of life outcomes.", "Bilateral surgical removal of impacted lower third molar teeth as a model for drug evaluation: A test with ibuprofen", "Antibiotic Prophylaxis in Third Molar Surgery", "Prophylactic use of phenoxymethylpenicillin and tinidazole in mandibular third molar surgery, a comparative placebo controlled clinical trial.", "Metronidazole for the prevention of dry socket after removal of partially impacted mandibular third molar: a randomised controlled trial.", "Trends in reasons for tooth extractions in Norway from 1968 to 1998", "Antibiotic prophylaxis in third molar surgery: A randomized double-blind placebo-controlled clinical trial using split-mouth technique.", "A comparison of the effect of phenoxymethylpenicillin and azidocillin on postoperative complications after surgical removal of impacted mandibular third molars.", "Assessing postoperative discomfort after third molar surgery: a prospective study.", "A double-blind study on the effectiveness of tetracycline in reducing the incidence of fibrinolytic alveolitis.", "Third Molar Surgery: The Effect of Primary Closure, Wound Dressing and Metronidazole on Postoperative Recovery", "Effects of 0.2% chlorhexidine gluconate and amoxicillin plus clavulanic acid on the prevention of alveolar osteitis following mandibular third molar extractions.", "A comparative study of the effectiveness of metronidazole and penicillin V in eliminating anaerobes from postextraction bacteremias.", "Single-dose and multi-dose clindamycin therapy fails to demonstrate efficacy in preventing infectious and inflammatory complications in third molar surgery.", "Efficacy and safety comparison of two amoxicillin administration schedules after third molar removal. A randomized, double-blind and controlled clinical trial.", "Patients' perception of recovery after third molar surgery following postoperative treatment with moxifloxacin versus amoxicillin and clavulanic acid: a randomized, double-blind, controlled study.", "Value of penicillin in the prevention of pain, swelling and trismus following the removal of ectopic mandibular third molars.", "Efficacy of amoxicillin/clavulanic acid in preventing infectious and inflammatory complications following impacted mandibular third molar extraction.", "Postoperative complications after surgical removal of mandibular third molars. Effects of penicillin V and chlorhexidine.", "Routine antibiotic prophylaxis is not necessary during operations to remove third molars.", "Incidence of dry socket, alveolar infection, and postoperative pain following the extraction of erupted teeth.", "A controlled clinical trial of prophylactic tinidazole for chemoprophylaxis in third molar surgery", "Reasons for extraction in a group of Libyan patients.", "Extraction of teeth over 5 years in regularly attending adults.", "Tinidazole or pivampicillin in third molar surgery.", "Antibiotic therapy in impacted third molar surgery.", "Metronidazole in the prevention of 'dry socket'.", "Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction.", "Efficacy of amoxicillin treatment in preventing postoperative complications in patients undergoing third molar surgery: a prospective, randomized, double-blind controlled study." ]

[ "Abstract The use of systemic prophylactic antibiotics in third molar surgery is still a controversial issue . A double-blind study has been conducted with 75 selected patients r and omized into two groups . After exclusions , 68 patients requiring removal of 133 bone impacted m and ibular third molars remained . Surgery was carried out under general anesthesia and a St and ard operative technique used . Postoperative raorbidity was assessed by recording trismus , swelling , pain , and the incidence of infection . In the group given an antibiotic 15.1 % of patients and 7.8 % of sockets became infected ; in the control group the incidence was 14.3 % and 8.7 % , respectively . Difficult extraction s were more likely to give rise to postoperative infection , but neither the state of eruption nor the occurrence of previous pericoronitis appeared to predispose to dry socket . Trismus and swelling were associated with increased difficulty of extraction , but increased pain did not usually occur unless a socket became infected , Differences of overall morbidity between the groups were slight and not statistically significant . The main conclusion from the study is that the use of prophylactic antibiotics in third molar surgery is unnecessary unless specific systemic factors are present", "Treatment of osteitis after surgical removal of the third molar of the m and ible is still a clinical problem . A total of 140 patients undergoing operations for removal of an impacted third molar of the m and ible , were included in a double-blind study . Placebo or antibiotics - azidocillin , erythromycin , clindamycin and doxycycline - were given to the patients preoperatively and for the following 7 days . The concentrations in serum , alveolar serum and m and ibular bone were measured and the postoperative courses - pain , trismus , swelling and wound-healing - were recorded . No correlation was obtained between the antibiotic concentration and the postoperative complaints , except in the azidocillin group on day 2 , in which fewer complaints were noticed in patients with high concentrations of the drug at the time of operations . The 80 patients in the antibiotic groups responded significantly better with respect to wound-healing than the 60 patients in the placebo groups . Only 15 operations lasted more than 15 min and the three of them which subsequently result ed in alveolitis were in the placebo groups . Antibiotics significantly reduced pain on day 7 postoperatively . In general , no statistically significant differences in trismus and swelling could be demonstrated between the patient groups . However , there was a significant difference between the placebo and doxycycline groups with respect to swelling ( day 2 postoperative , P < 0.01 ; day 5 postoperative , P < 0.05 ) . Thus systemically administered antibiotics offered only slight advantages in routine operations of impacted third m and ibular molars , but could decrease the rate of infections after traumatic operations", "PURPOSE This study evaluated the influence of antibiotic prophylaxis on postoperative complications after inferior third molar removal in young patients . PATIENTS AND METHODS We extracted 59 m and ibular third molars from 59 patients with a mean age of 15 years ( range , 12 - 19 years ) . The patients were included in the study when radiographs at the time of surgery showed that only the crown of the tooth germ was formed . Patients were r and omized into 2 groups , the test group and the control group . The test group received 2-g amoxicillin tablets 1 hour before surgery , and the control group received no antibiotic therapy . The test group included 32 patients , 20 of whom were female and 12 were male ; the mean age was 15 years . The control group included 27 patients , 12 of whom were female and 15 were male ; the mean age was 15 years . Postoperative complications such as pain , swelling , wound infection , and fever were recorded by use of a question naire completed by the patient for the week after the extraction . Suture removal and question naire evaluation were performed by a surgeon who did not know the preoperative regimen . RESULTS The mean operating time was 34 minutes in the control group and 31 minutes in the test group . This difference was not significant . In the test group there was a statistically significant reduction of postoperative pain in the 7 days after the extraction , and the patients had a consistent minor consumption of analgesics . Swelling was always present in the control and test groups in the postoperative week , but in the test group it was a minor sequela and was absent in 2 patients . Wound infection was a sequela reported in 4 patients in the control group and in 1 patient in the test group ; this difference was statistically significant ( P < .01 ) . Fever was present in 2 patients in the control group and in 1 patient in the test group ; this difference was not statistically significant . CONCLUSIONS A statistically significant difference was found between patients receiving preoperative amoxicillin and the control group in the incidence of postoperative pain , fever , and wound infection . Another important finding was the statistically minor consumption of analgesics in the test group in the postoperative week", "AIM To test the efficacy of two dosing regimens of antimicrobial prophylaxis during the removal of impacted lower third molars . DESIGN Double blind , prospect i ve , placebo-controlled trial . SETTING Teaching hospital , India . SUBJECTS 151 patients aged 19 - 36 having impacted lower third molars removed . METHODS R and om allocation into three groups : placebo ( n= 34 ) , metronidazole 1 g orally , 1 hour preoperatively ( n= 44 ) , or metronidazole 400 mg orally eight hourly for 5 days postoperatively ( n= 47 ) . Patients were recalled on the sixth postoperative day for assessment of pain scores on the second and sixth days , swelling , differences in mouth opening between preoperative and the sixth postoperative day , and the state of the wound . RESULTS There were no significant differences in the outcome between the three groups ( P= 0.09 ) . CONCLUSION Antimicrobial prophylaxis does not seem to reduce morbidity after removal of lower third molars", "PURPOSE We sought to compare recovery for clinical and health-related quality of life ( HRQOL ) outcomes after third molar surgery in patients treated with or without intravenous antibiotics at surgery . PATIENTS AND METHODS Fifty-six patients at least 18 years of age and with all 4 third molars below the occlusal plane , treated at 3 clinical centers , were given intravenous antibiotics just before third molar surgery . Clinical and HRQOL outcomes of these patients were compared with those of a nonconcurrent control group ( n = 60 patients ) who did not receive antibiotics . The control group was selected using the same criteria and treated under the same surgical protocol as the antibiotic group . Differences between the groups were assessed with Cochran-Mantel-Haenszel row mean score statistics . RESULTS The incidence of delayed clinical recovery defined as a postsurgery visit with treatment was higher in the control group compared with the antibiotic group . In the antibiotic group , 4 % had 1 postsurgery visit with treatment ; no patient had 2 visits . In the control group without antibiotics , 28 % had at least 1 postsurgery visit with treatment ( P < .0001 ) and 13 % had at least 2 postsurgery visits with treatment . No statistically significant differences in HRQOL outcomes were found between the 2 groups . CONCLUSIONS Administration of intravenous antibiotics before third molar surgery may improve clinical recovery in healthy adult patients with all 4 third molars below the occlusal plane , a presenting characteristic that has been suggested as a risk factor for delayed recovery . The findings from this exploratory trial indicate that evaluation of the effectiveness of systemic antibiotic administration with third molar surgery in a r and omized , multi-intervention , explanatory clinical trial is warranted", "A double blind trial , was design ed , in which 118 patients undergoing the removal of impacted wisdom teeth were r and omly divided into the following groups ; 41 patients received Metronidazole , 39 patients received Arnica Montana , 38 patients received the placebo . Metronidazole was more effective in pain control than Arnica ( p less than 0.001 ) and placebo ( p less than 0.01 ) . It prevented swelling better than Arnica ( p less than 0.01 ) and placebo ( p less than 0.05 ) and was more effective in promoting healing than Arnica ( p less than 0.01 ) and placebo ( p greater than 0.02 ) . Arnica Montana appeared to give rise to greater pain than placebo ( p less than 0.05 ) and caused more swelling than the placebo ( p less than 0.01 )", "Objective The purpose of the study was to determine if the intra-alveolar application of topical metronidazole gel could reduce the incidence of alveolar osteitis ( dry socket ) following routine tooth extraction in molar and premolar extraction sites . Design This was a multicentre , double blind , r and omised , placebo-controlled clinical trial . A total of 302 patients took part , of which 23 returned with alveolar osteitis . Of these , eight had received the metronidazole gel and 15 the placebo . Setting The study was carried out in three general dental practice s by general dental practitioners working in Engl and over the period 2000 - 2003.Main outcome measures Following extraction of either a molar or premolar tooth , either a 25 % metronidazole gel or KY Jelly was syringed gently into the socket . A painful post operative complication was recorded if either a dry socket was present or the patient returned with pain . Results and conclusions The difference in the incidence of alveolar osteitis between the placebo and the active gel groups was not significant and it was concluded that 25 % topical metronidazole gel was not effective in reducing the incidence of alveolar osteitis . It was found that the incidence of alveolar osteitis reduced with increasing age and was more likely to occur in a patient with a previous history of the condition", "OBJECTIVES The purpose of this study was to examine the relationships between patient characteristics and reasons for extraction of permanent teeth . METHODS 5131 dentists were selected from the list of the membership directory of the Japan Dental Association by systematic r and om selection . The dentists were asked to record the reason for each extraction of permanent teeth during a period from February 1 to 7 , 2005 . Reasons for tooth extraction were assigned to five groups : caries , fracture of teeth weakened by caries or endodontics , periodontal diseases , orthodontics and other reasons . We used cross tabulation and multiple logistic regression analysis to estimate the relationships between patient characteristics and reasons for tooth extraction . RESULTS 2001 dentists ( response rate of 39.0 % ) returned the forms , and complete information on 7333 patients was obtained . A total of 3,196 ( 43.6 % ) patients underwent tooth extraction due to caries and its sequela , and 2721 ( 37.1 % ) patients underwent tooth extraction due to periodontal disease . Multiple logistic regression analysis showed that denture wearers were more likely to undergo tooth extraction due to periodontal disease in all age groups ( p < 0.05 ) . Males tended to undergo tooth extraction due to periodontal disease than did females in all age groups ( p < 0.05 ) except for age group 30 - 49 . Subjects with 19 or less teeth were more likely to undergo tooth extraction due to periodontal disease in the age groups 30 - 49 ( p < 0.001 ) and 50 - 69 ( p < 0.001 ) . In the age group of 50 years or older , female ( p<0.01 ) and the possession of 20 or more natural teeth ( p < 0.05 ) were related to caries extraction . However , there was no clear relationship between caries extraction and patient characteristics under 50 years old . CONCLUSION There was a significant relationship between denture wearing and periodontal extraction . In the middle aged population , patients with 19 or less teeth lost their teeth mainly due to periodontal disease", "The most common complications after surgical extraction of the third m and ibular molar are trismus , oedema or swelling , local pain , dysphagia and infection . The aim of this comparative , double-blind , r and omized clinical trial was to evaluate the efficacy of two sustained release amoxicillin/clavulanate regimens in the reduction of infection after third molar extractive surgery . A total of 225 patients were r and omized into three equal groups : placebo , prophylaxis with single pre-surgical dose of two tablets amoxicillin/clavulanate 1000/62.5 mg , and pre-emptive post-surgery therapy with two tablets amoxicillin/clavulanate 1000/62.5 mg BID for 5 days . A higher rate of infection ( P=0.006 ) was found among patients receiving placebo ( 16 % ) than those receiving single-dose prophylaxis ( 5.3 % ) or 5-day pre-emptive therapy ( 2.7 % ) . A relationship between both the duration ( 13.8 % for long versus 7.4 % for medium versus 1.6 % for short ) and difficulty ( 12.7 % with ostectomy versus 3.5 % without ostectomy ; P=0.011 ) of surgical procedure and incidence of subsequent infection was also observed . Both prophylactic and therapeutic regimens versus placebo achieved greater reduction of pain after surgery on day 3 ( P=0.001 ) . Logistic regression analysis revealed a risk of infection of 24 % , 9 % and 4 % for ostectomy with placebo , prophylaxis and pre-emptive treatment , respectively , whereas it was 7 % , 2 % and 1 % if ostectomy was not performed . Pre-emptive therapy with the oral sustained release amoxicillin/clavulanate formulation reduced the rate of subsequent infection in patients undergoing ostectomy . Prophylaxis was beneficial in simpler procedures and may be indicated in cases where ostectomy is not performed", "The effect of a single preoperative dose of metronidazole in the prevention of alveolitis sicca dolorosa ( ASD ) after surgical removal of one impacted , non-infected m and ibular third molar was investigated . A patient sample of 270 were given either 1000 mg of metronidazole or placebo at least 30 min before surgery . The preoperative recordings included gender , age , tooth to be removed , experience of surgeon , time of test medication , and duration of surgery . No difference was found between the metronidazole and placebo groups in the occurrence of ASD . The duration of surgery and the experience of the operating surgeons had no effect on the occurrence of ASD . The present study failed to demonstrate any preventive effect of a single dose of metronidazole on the development of ASD", "Summary A double-blind placebo controlled study has shown that Nivemycin is not of value in the prevention of pain and swelling following the removal of ectopic lower third molars", "PURPOSE We evaluated the need for prophylactic postoperative oral antibiotic treatment in the removal of asymptomatic third molars . MATERIAL S AND METHODS In a prospect i ve study of more than 30 months , a total of 528 impacted lower third molars were surgically removed in 288 patients . All patients were referred to our department by a dentist or a general practitioner . No patient showed any sign of pain , inflammation , or swelling at the time of removal . Three groups were established . In the first group , antibiotic treatment with amoxicillin/clavulanic acid as an oral medication was carried out for 5 days postoperatively . In the second group , we used clindamycin . In the third group , the patients received no antibiotic treatment . Clinical and radiologic factors were recorded for each case , and the rationale for assigning the patients to the groups was strictly r and om . The surgical technique was the same in all cases , and the follow-up period was 4 weeks . Parameters that were evaluated were pain , differences in mouth opening , infection , the occurrence of dry socket , and adverse postoperative side effects . RESULTS We could not find any significant difference between the 3 groups regarding the evaluated parameters , but in 69.6 % of the patients with dry socket , the teeth were partially erupted , which showed a significant difference . CONCLUSIONS The results of our study show that specific postoperative oral prophylactic antibiotic treatment after the removal of lower third molars does not contribute to a better wound healing , less pain , or increased mouth opening and could not prevent the cases of inflammatory problems after surgery , respectively , and therefore is not recommended for routine use", "Although prophylaxis is current practice , there are no r and omized controlled studies evaluating preoperative antimicrobial prophylaxis in dental procedures in patients immunocompromised by chemotherapy or organ transplants . To evaluate prophylaxis in dental-invasive procedures in patients with cancer or solid organ transplants , 414 patients were r and omized to receive one oral 500-mg dose 2 hours before the procedure ( 1-dose group ) or a 500-mg dose 2 hours before the procedure and an additional dose 8 hours later ( 2-dose group ) . Procedures were exodontia or periodontal scaling/root planing . Follow-up was 4 weeks . No deaths or surgical site infections occurred . Six patients ( 1.4 % ) presented with use of pain medication > 3 days or hospitalization during follow-up : 4 of 207 ( 2 % ) in the 1-dose group and 2 of 207 ( 1 % ) in the 2-dose group ( relative risk , 2.02 ; 95 % confidence interval , 0.37 - 11.15 ) . In conclusion , no statistically significant difference occurred in outcome using 1 or 2 doses of prophylactic amoxicillin for invasive dental procedures in immunocompromised patients", "PURPOSE Compare recovery for clinical and health-related quality of life ( HRQOL ) outcomes after third molar surgery in patients treated with or without topical minocycline at surgery . PATIENTS AND METHODS Sixty-three patients at least 18 years of age with all 4 third molars below the occlusal plane were treated with topical minocycline during third molar surgery . Topical minocycline ( 1.0 mg in bioresorbable polyglycolide-co-dl-lactide [ PGLA ] sustained-release microspheres ) was placed sequentially in bony defects after removal of lower third molars . Clinical and health-related quality of life ( HRQOL ) outcomes of these patients postsurgery were compared with those of a nonconcurrent control group ( n = 60 patients ) who did not receive antibiotics . The control group was selected using the same criteria and treated under the same surgical protocol as the antibiotic group . Differences between the groups were assessed with Cochran-Mantel-Haenszel row mean score statistics . RESULTS The 63 patients in the minocycline group were treated at 4 clinical centers . The incidence of delayed clinical recovery , defined as a postsurgery visit with treatment , was significantly lower in the minocycline group compared with the control group . In the minocycline group , 10 % had 1 postsurgery visit with treatment ; no patient had 2 visits . In the control group without antibiotics , 28 % had at least 1 postsurgery visit with treatment ( P = .01 ) and 13 % had at least 2 postsurgery visits with treatment . Recovery time to \" no \" or \" little trouble \" with chewing and mouth opening was significantly improved in the minocycline group ( P < .05 ) . CONCLUSIONS Administration of topical minocycline with third molar surgery may improve clinical and HRQOL recovery in healthy adult patients with all 4 third molars below the occlusal plane , a presenting characteristic that has been suggested as a risk factor for delayed recovery", "Summary It was considered that double-blind crossover studies of therapeutic efficacy after acute injury could well be done in patients who required surgical removal of impacted wisdom teeth from both sides of the lower jaw . In the present trial 24 healthy patients received either placebo or ibuprofen ( Brufen ® : 400 mg three times daily ) , a non-steroidal anti-inflammatory agent , for 5 days commencing the day before surgery . Treatments were given on the two occasions when impacted wisdom teeth were to be removed from one side or other of the lower jaw . A number of objective and subjective parameters were recorded for paired comparison of the post-operative courses , including swelling , trismus and pain . A mechanical device which allows simple and accurate measurement of cheek swelling is described . On the 1st , 3rd and 5th post-operative days in the ibuprofen group the measured swelling averaged 93 , 89 and 82 % , respectively , of that in the placebo group ; the corresponding α-values were 0.35 , 0.06 and 0.07 . Patients with less swelling after ibuprofen were not always those with a high serum concentration of the drug . Ibuprofen significantly reduced pain on the day of the operation . This may at least partly account for less trismus and the preference of the patients for their post-operative courses with ibuprofen . Examination of various haematological parameters did not reveal any significant difference between the two operations . Subjective scores indicated that neither wound-healing nor bleeding was affected by ibuprofen , nor were any side effects detected", "Aims and Objectives : To evaluate the role of prophylactic antibiotics , if any , in the removal of m and ibular impacted third molars . Patients and Methods : A total of 89 patients were r and omly allocated in 3 groups ( group 1 , placebo ; group 2 , amoxicillin 1 g orally 1 h before surgery ; and group 3 , metronidazole 800 mg orally 1 h before surgery ) . Results : Of the 89 patients , 5 had surgical wound infection ( 3 [ 10.33 % ] in group 1 , 2 [ 6.45 % ] in group 2 , and none [ 0 % ] in group 3 ) , leading to an overall infection rate of 5.61 % . There was no statistically significant difference found in surgical wound infection between the groups . Conclusions : Our study failed to show any advantage in the routine use of prophylactic antibiotics because we found no statistically significant difference between the groups", "A clinical double-blind placebo controlled trial was carried out in 136 patients to test the value of the prophylactic use of phenoxymethylpenicillin and tinidazole in m and ibular third molar surgery . The three patient groups were uniform with regard to the background data such as age and weight of the patients and the clinical status of the operated tooth , as well as to the observations made at surgery . No statistically significant differences were found between the study groups in the parameters used for evaluation . The results indicate that neither penicillin nor tinidazole have more effect on postoperative complications following operative extraction of wisdom teeth , than placebo tablets", "We r and omised 119 patients who had been referred for removal of partially impacted m and ibular third molars to be given either metronidazole 1600 mg or placebo as a single dose 45 min before operation . Ten of the fifty-nine patients who were given metronidazole and 13 of the 60 given placebo developed dry sockets . Two variables were significantly associated with the development of a dry socket : pericoronitis and oral contraceptives", "The aims of this study were ( i ) to determine the reasons for extraction of permanent teeth in Norway in 1998 and ( ii ) to describe changes in reasons for extraction in time-trend and quasi-longitudinal perspectives over 30 years based on three cross-sectional studies . The 1998 data were obtained from question naires distributed to a national r and om sample of 1,500 dentists , of whom 1,008 responded ( 67 % ) . A total of 1,495 teeth were extracted for 1,164 patients ( age 10±92 years ) during a period of 2 weeks . Caries accounted for 40 % of the extraction s and periodontal diseases for 24 % . Caries was the primary reason in patients 10±45 years old , while periodontal diseases dominated among adults > 45 years old . In a time-trend perspective , among patients ≤21 years , a significant decrease in the proportion of extraction s because of caries was observed between 1968 and 1988 , while non-significant changes were found between 1988 and 1998 . Extraction s because of periodontal disease accounted for about 26 % in all surveys . Followed longitudinally , the three cohorts born 1923±32 , 1933±42 , 1943±52 showed a decrease in the proportion of extraction s due to caries , and an increase in the proportion of periodontal extraction s during the period , more so between 1968 and 1988 than between 1988 and 1998 . The three cohorts showed a variable trend of change , which may indicate that period and age effects do not necessarily operate in the same direction", "The use of prophylactic antibiotics to reduce postoperative complications in third molar surgery remains controversial . The study was a prospect i ve , r and omized , double blind , placebo-controlled clinical trial . 100 patients were r and omly assigned to two groups . Each patient acted as their own control using the split-mouth technique . Two unilateral impacted third molars were removed under antibiotic cover and the other two were removed without antibiotic cover . The first group received antibiotics on the first surgical visit . On the second surgical visit ( after 3 weeks ) , placebo capsules were given or vice versa . The second group received antibiotics with continued therapy for 2 days on the first surgical visit and on the second surgical visit ( after 3 weeks ) placebo capsules were given or vice versa . Pain , swelling , infection , trismus and temperature were recorded on days 3 , 7 and 14 after surgery . Of 380 impactions , 6 sockets ( 2 % ) became infected . There was no statistically significant difference in the infection rate , pain , swelling , trismus , and temperature between the two groups ( p>0.05 ) . Results of the study showed that prophylactic antibiotics did not have a statistically significant effect on postoperative infections in third molar surgery and should not be routinely administered when third molars are removed in non-immunocompromised patients", "Postoperative complications after surgical removal of m and ibular third molars are still a clinical problem . Sixty patients undergoing operations for removal of an impacted third m and ibular molar , were included in a double blind study . Phenoxymethylpenicillin 800 mg , azidocillin 750 mg , or placebo were given to the patients pre-operatively and then twice per day for the following seven days . The concentrations of phenoxymethylpenicillin and azidocillin in serum and alveolar serum were measured and the postoperative courses - pain , trismus , swelling and wound-healing - were recorded . The 40 patients in the antibiotic groups responded significantly better with respect to wound-healing than the 20 patients in the placebo group , and there were no differences between phenoxymethylpenicillin and azidocillin . Antibiotics significantly reduced pain on day 7 postoperatively . There were no differences between antibiotic groups and placebo with respect to trismus and swelling . When the dental alveolar serum concentrations of phenoxymethylpenicillin 3.0 microgram/ml and azidocillin 7.9 microgram/ml were related to their range of inhibitory concentrations for microorganisms isolated from orofacial infections , it was noticed that the two drugs achieved levels sufficient to inhibit most strains . The effect of phenoxymethylpenicillin and azidocillin on postoperative infections can be of value after traumatic oral surgery or after operations on patients especially susceptible to infections", "PURPOSE The purpose of this study was to identify the risk factors for severe discomfort after m and ibular third molar surgery and to assess the validity of the Postoperative Symptom Severity ( PoSSe ) scale . PATIENTS AND METHODS In a 2-year prospect i ve study , a total of 255 unilateral impacted m and ibular third molar teeth were surgically removed under local anesthesia by 3 surgeons . St and ardized surgical and analgesic protocol s were followed . At the review appointment , 1 week after surgery , all patients returned a completed follow-up question naire ( PoSSe scale ) and were evaluated clinical ly for postoperative pain ( number of painkillers taken ) and trismus ( differences in mouth opening ) . Sixteen predictive variables were evaluated using stepwise logistic regression analysis to identify the risk factors associated with severe discomfort . RESULTS Severe postoperative discomfort was predicted by these independent variables : gender , tobacco use , ramus relationship/space available , and antibiotic prophylaxis . Oral contraceptive use and operation time were not identified as risk factors . The patients ' perceptions of the severity of symptoms ( PoSSe scale score ) was strongly correlated with clinical assessment of trismus ( r = 0.54 ) and pain ( r = 0.42 ) . CONCLUSION The PoSSe scale result ed in a valid and responsive measure of the severity of symptoms after surgical extraction of lower third molars and reflected the clinical severity of the postoperative discomfort . From a patient 's perspective , operative factors had little bearing on the quality of life after removal of m and ibular third molars", "This study presents the results of a double-blind study evaluating the effectiveness of topical tetracycline used as a suspension in a square of gelatin sponge and placed in the sockets of extracted m and ibular third molars for the prevention of dry socket . An assessment of the relationship between the amount of bone relief ( trauma ) incidental to the surgery and the occurrence of dry socket also is made . Dry socket occurred in 20.4 % of the placebo-treated sockets , whereas the incidence in the tetracycline-treated sockets was 3.9 % . No correlation was observed between the amount of bone relief attendant to the surgery and the incidence of dry socket . It is concluded that tetracycline is an effective prophylaxis for fibrinolytic alveolitis", "One hundred and forty eight patients with bilateral symmetrically impacted lower third molars entered a clinical crossover trial to compare the effects on postoperative recovery of a Bismuth Iodoform Paraffin Paste ( BIPP ) socket dressing , primary closure using a resorbable suture ( Softgut ) and to ascertain if prophylactic metronidazole influenced the outcome . The results reaffirm the surgical principle that contaminated surgical wounds such as third molar sockets are best kept open with a dressing . Attempts at primary closure should be resisted if there is no intention to prescribe antibiotic cover . However , if a suitable antibiotic is taken then primary closure using a resorbable suture can be carried out with confidence . This may reduce the need for outpatient follow up", "OBJECTIVE The purpose of this study was to evaluate the use of a 0.2 % chlorhexidine gluconate and amoxicillin plus clavulanic acid combination as a prophylactic therapy for the prevention of alveolar osteitis after m and ibular third molar extraction s and to investigate adverse reactions to chlorhexidine . STUDY DESIGN This r and omized , placebo-controlled , parallel group study was conducted in a group of 177 subjects , from which 3 groups were formed . The first group ( n = 62 ) received 0.2 % chlorhexidine gluconate , the second group ( n = 56 ) received a 0.2 % chlorhexidine gluconate and amoxicillin plus clavulanic acid combination , and the third group ( n = 59 ) received 0.09 % sterile saline solution . All patients were recalled for the diagnosis of alveolar osteitis on the third and seventh postoperative days . RESULTS When patients in the antibiotic group were compared with those in the other 2 groups , a significant reduction in alveolar osteitis was noted ( P < .05 ) . An alteration in taste , the bad taste of the solution , and staining of dentures and oral tissues were the major complaints about chlorhexidine . CONCLUSION It would be more beneficial to use chlorhexidine solution with a beta-lactamase inhibitor-containing antibiotic to enhance its effectiveness for the prevention of alveolar osteitis", "Recent reports have indicated the serious nature of anaerobic endocarditis and septicemia . As anaerobes can be isolated from post extraction bacteremias , this study was undertaken to evaluate the effectiveness of metronidazole and penicillin V in eliminating anaerobes from post extraction bacteremias . Twenty-five patients were r and omly assigned to each of three groups -- a placebo group , a metronidazole group , and a penicillin V group -- for a total of seventy-five patients . Although penicillin V reduced the occurrence of anaerobes to a greater degree than did metronidazole , it was noted that gram-negative anaerobes were still detected in the blood of four patients in the penicillin V group . In the metronidazole group no gram-negative anaerobes were cultured . Because of the marked effectiveness of metronidazole against gram-negative anaerobes , the use of penicillin V and metronidazole in combination might be effective in the prevention of the sequelae of post extraction bacteremias . However , further studies , using a larger sample size , to investigate specifically gram-negative anaerobes are required", "The goal of this study was to evaluate the efficacy of single- and multi-dose ( 5-day ) clindamycin therapy for the prevention of inflammatory complications in patients undergoing lower third molar surgical extraction with bone removal . Patients who qualified for the prospect i ve , r and omized , double-masked , placebo-controlled trial were r and omly divided into three groups : ( 1 ) single dose of oral clindamycin administered preoperatively ( single-dose group ) ; ( 2 ) clindamycin administered preoperatively with continued therapy for 5 days ( 5-day group ) ; and ( 3 ) a placebo group . The following parameters were evaluated on the first , second and seventh days postsurgery : trismus , facial swelling , body temperature , lymphadenopathy , alveolar osteitis and subjective pain sensations . There were 86 patients ( 31 in the single-dose group , 28 in the 5-day group and 27 in the placebo group ) enrolled in the study . There were no statistically significant differences in postoperative inflammatory complications in patients during the first and second days postsurgery . A statistically significant variation in body temperature was reported on the seventh day . Analysis of the postoperative analgesic intake did not show statistically significant differences between examined groups . Clindamycin applied in a single preoperative dose of 600 mg with or without subsequent 5-day therapy does not demonstrate efficacy in prophylaxis for postoperative inflammatory complications after third molar surgery", "OBJECTIVE The aim of this comparative double-blind , prospect i ve , r and omized , clinical trial was to evaluate two amoxicillin administration patterns . The first was a short prophylactic therapy and the second a long postoperative regimen . STUDY DESIGN The study population consisted of 160 patients who underwent m and ibular third molar extraction . Patients were r and omized into two equal groups . In group 1 , 2 grams of amoxicillin were administered 1 hour before the procedure and 1 gram 6 hours after surgery . In group 2 , patients received 1 gram of amoxicillin 6 hours after surgery followed by 1 gram every 8 hour for 4 days . All patients received the same number of tablets thanks to the use of placebo pills . A total of 25 variables were evaluated , such as alveolitis , surgical infection , number of analgesic needed , subjective pain scale , post-surgical inflammation , consistency of the diet , axillary temperature and millimeters of mouth opening loss after the surgery . RESULTS No statistically significant post-operative differences were found within the recorded parameters between the groups . CONCLUSIONS Postoperative 4-days amoxicillin therapy is not justified", "PURPOSE To analyze the impact of the postoperative administration of moxifloxacin ( MXF ) on oral function and quality of life after third molar ( TM ) surgery . MATERIAL S AND METHODS A single-center , prospect i ve , r and omized , double-blind , controlled clinical trial was design ed . The study population consisted of 100 patients who underwent impacted TM extraction s. Patients were distributed into 2 groups of 50 individuals each . Postoperatively , one group was administered MXF ( 400 mg/24 hours for 5 days ) ; the positive control group received amoxicillin and clavulanic acid ( AMX-CLV ) ( 500/125 mg/8 hours for 5 days ) . Follow-up was performed for 7 postoperative days , during which the patient recorded information on pain , the use of rescue analgesia , undesirable effects of the medication , difficulty in speaking , difficulty in chewing , diet consistency , difficulty performing oral hygiene , asthenia , time in bed , going out of the house , and returning to work . RESULTS The administration of MFX was significantly associated with headache , and AMX-CLV was significantly associated with diarrhea . Greater difficulty in chewing and performing oral hygiene was observed in the AMX-CLV group compared with the MXF group . The percentage of patients who tolerated a diet of normal consistency was significantly higher in the MXF group compared with the AMX-CLV group . During the first 4 days of follow-up , the percentage of patients who returned to work was significantly higher in the MXF group than in the AMX-CLV group . CONCLUSIONS Moxifloxacin shortens the period of postoperative recovery in terms of oral function and return to work . Therefore , MXF could be a useful option in TM surgery when antibiotics are indicated , particularly if patients are allergic to beta-lactams , their oral flora is resistant to macrolides , or they are intolerant of either of these antibiotics", "A double-blind r and omised placebo-controlled study of the value of systemic penicillin in preventing pain , swelling and trismus following the removal of impacted m and ibular third molars and indicates that penicillin may be used justifiably in the more difficult cases", "OBJECTIVE To find out whether the frequency of postoperative infectious and inflammatory complications ( IC ) in subjects treated with placebo ( Pl ) is greater than those treated with antibiotic ( Ab ) after extraction of an impacted m and ibular third molar ( M3 ) . Our hypothesis is there are more IC in Pl than in Ab , with a maximum ratio difference of 0.067 . STUDY DESIGN A double-blind placebo-controlled r and omized clinical trial . The sample was derived from the population of subjects attending Cruces Hospital for evaluation and extraction of 1 M3 under local anesthesia . Patients were treated with postoperative placebo or amoxicillin/clavulanic acid 500/125 mg 3 times a day during 4 days . The outcome variable was infectious and inflammatory complications . Sex , age , smoking , molar depth , angulation , need for sectioning , ostectomy , and operation time were recorded . Analysis was by intention to treat , risk measures , and logistic regression . RESULTS In 490 subjects ( 259 Ab and 231 Pl ) , the frequency of IC was 1.9 % in the Ab and 12.9 % in the Pl group ( OR 7.6 , 95%CI 2.9 - 19.9 ; P < .001 ) . The number needed to treat was 10 ( 7 - 16 ) . Unadjusted relative risk was 0.15 ( 0.06 - 0.38 ) ( P < .001 ) . Absolute reduction risk was 0.11(0.066 - 0.155 ) ] . Therefore , the hypothesis can not be rejected . Multivariate analysis shows treatment with antibiotic ( OR = 8.66 ( 3.17 - 23.67 ) ; P < .001 ) and age ( OR = 1.08 ( 1.00 - 1.16 ) ; P = .029 ) are the only variables to be included in the logistic regression model . CONCLUSION Amoxicillin/clavulanic acid is efficacious in reducing the incidence of IC following third molar extraction but should not be prescribed in all cases", "A r and om material of 112 patients , was investigated after surgical removal of impacted lower third molars . 2 experimental groups and 1 control group were studied . Prophylactic medication with penicillin V combined with preoperative rinsing using 0.2 % chlorhexidine gluconate ( Hibitane ) was found to reduce postoperative symptoms , when compared with preoperative rinsing alone . In both cases , patients were compared with the control group", "The purpose of this study was to evaluate the efficacy of antibiotic prophylaxis during removal of impacted third molars . We studied 150 patients with impacted m and ibular or maxillary third molars who were divided r and omly into three groups . The first was given amoxicillin 2 g combined with clavulanic acid , orally daily for 5 days postoperatively ; starting at the end of the operation . The second group was given the same drugs but the regimen started 5 days before the operation . The third was given no antibiotics . Pain , infection , swelling , alveolar osteitis , and interincisal mouth opening ( mm ) were evaluated . There were no significant differences among the groups in the incidence of these complications . We can not recommend routine oral antibiotic prophylaxis in third molar surgery", "AIM The aim of this study was to determine the incidence of dry socket , alveolar infection , and postoperative pain following the routine extraction of erupted teeth . METHODS AND MATERIAL S Using a question naire , this prospect i ve cross-sectional study evaluated 357 consecutive surgeries in which 473 erupted teeth were extracted by dental students under rigorous control of microbiologic contaminants during a 22-month period . The subject sample consisted of 210 ( 58.8 % ) male patients ranging in age from 11 to 79 years ( mean 41 + /- 16.3 ) . The most prevalent self-reported ethnicity was Caucasian ( 78.2 % ) . The question naire consisted of 60 questions directed to the patient and to the dental student who performed the surgical procedure . The question naires were completed before and within seven days after the surgery to obtain outcomes data . Forty-five question naires were excluded due to lack of information , inconsistencies , or lack of contact with the patient ; however , none had indications of alveolar infection or dry socket . The data were analyzed using descriptive statistics , chi-square tests ( x(2 ) ) , and an odds ratio ( OR ) as appropriate at the critical level of significance , set at p<0.05 ( x(2 ) ) or p<0.01 ( x(2 ) , with the Monte Carlo simulation ) . RESULTS The observed incidence was 0.6 % ( two cases each ) for both alveolar infection and dry socket . Higher pain levels and pain persisting longer than two days were observed with more traumatic surgeries , or associated with postoperative complications . Smoking was found to be statistically associated with the development of postoperative complications . CONCLUSION The incidence of alveolar infection , dry socket , and severe pain were very low for the routine extraction of erupted teeth . Severe pain that persists for more than two days can represent a sign of a postoperative complication such as dry socket . CLINICAL SIGNIFICANCE Dental extraction is part of the dentists ' daily work and intercurrences like dry socket , infection , and pain can occur . This manuscript reports the incidence of these occurrences and search for its predisposing factors", "A controlled clinical trial of prophylactic tinidazole for chemoprophylaxis in third molar", "AIMS AND OBJECTIVES To investigate the pattern and causes of tooth loss in patients among eastern part of Libya . MATERIAL S AND METHODS This study carried out at Faculty of Dentistry , Garyounis University , Benghazi , Libya . The out patients undergoing extraction s at the Oral Surgery Department were r and omly selected for this study between Jan 2007 and March 2008 where a total of 9,570 extraction s were performed on 8,514 patients . The incidence and reasons for tooth extraction , their distribution according to age and sex were studied . RESULTS Males had more teeth extracted than females . Forty patients had one or more systemic illnesses , 34 were on regular medication . The study revealed two major causes of tooth loss : dental caries ( 55.90 % ) and periodontal diseases ( 34.42 % ) . Other important causes were trauma ( 3.76 % ) , impaction ( 1.83 % ) , prosthodontic reasons ( 2.19 % ) , and orthodontic reasons ( 1.30 % ) and others which included extraction where the tooth was associated with a tumour , cyst or supernumerary tooth ( 1.61 % ) . Dental caries was the main causes of tooth loss during the 2nd , 3rd and 4th decades . While periodontal diseases were the prevalent aetiological factor during the 4th , 5th , 6th and 7th decades of life . The posterior teeth most frequently extracted due to dental caries were lower first molars ( 43.92 % ) . Whereas anterior teeth were more frequently extracted due to periodontal diseases ( 28 % ) with the remaining posterior teeth also being extracted ( 7 % )", "OBJECTIVES This prospect i ve study was conducted to describe the incidence of tooth extraction in a group of regularly attending adults and to assess factors that are predictive of tooth loss . METHODS Baseline and annual incremental clinical data were obtained from 23 general dental practitioners on a group of their regularly attending , dentate adult patients over a 5-year period . The patients completed a postal question naire with questions relating to dental health behaviours , attitudes and knowledge , and social factors . RESULTS Complete clinical data were obtained from 2799 patients . Four hundred and seventy ( 17 % ) patients underwent extraction s , 72 % of which were posterior teeth . The majority of extraction s were for reasons other than caries ( 79 % ) . Bivariate analyses revealed many significant differences between patients who underwent extraction s and those who did not , with respect to the clinical , social , behavioural and attitudinal variables . The logistic regression model for tooth loss included three clinical variables , number of teeth , crowns and sites with recession . Other variables in the final model included the dentist 's and patient 's prediction of treatment need , having sensitive teeth , having a sweet tooth , living alone and smoking . The sensitivity for the model was 0.57 with specificity 0.72 . CONCLUSIONS This study is unique in its examination of patients and has highlighted that both clinical and other factors are important in predicting who will undergo extraction s. Future investigations should assess the consequence of having extraction s in terms of health benefit or detriment", "There is an increasing body of evidence implicating oral anaerobic bacteria in the aetiology of post-surgical dentoalveolar infections . This information has lead to several studies demonstrating the usefulness of specific anaerobicidal drugs in the prevention and treatment of dento-alveolar infection . One such study utilised a single 2 g preoperative oral dose of tinidazole which was found to be significantly better than placebo in preventing infective sequelae after removal of impacted m and ibular third molars . The present study was design ed to compare a high-dose short-term broad spectrum penicillin , ( pivampicillin ) , with the previously described regimen , using tinidazole in order to discern the existence or otherwise of any practical difference between an anaerobicidal and a broad spectrum antibiotic when local infection was considered", "The use of routine antibiotic therapy in patients undergoing surgical third molar extraction is controversial . The efficacy of antibiotic therapy in preventing postoperative complications following surgical third molar extraction s was evaluated in 141 patients . In the test group ( 66 patients ) , the protocol utilized a regimen of 2 g of amoxicillin orally daily for 5 d postoperatively , starting at the completion of surgery . In the control group ( 75 patients ) , no antibiotic therapy was given . No significant difference was found between the test group and the control group in the incidence of postoperative sequelae , i.e. fever , pain , swelling and alveolar osteitis . A statistically significant association between smoking , habitual drinking and increased postoperative pain and fever was found . Patient age > or = 18 yr was positively correlated with an increased incidence of alveolar osteitis . Swelling was found to be gender-related , in that female patients experienced more swelling than male patients . No correlation was found between the time required for surgery or difficulty of extraction and post-operative pain . In conclusion , no difference was found between patients receiving postoperative amoxicillin and the control group in the incidence of postoperative sequelae", "Prophylactic metronidazole was found to be an effective means of preventing ' dry socket ' after routine dental extraction s. The oral anaerobic bacterial may be implicated therefore in the development of the disorder . It has been confirmed in this study that ' dry socket ' occurs following three per cent of routine dental extraction s and almost exclusively in the m and ible . The causes of the condition are probably numerous and may even vary from patient to patient , but the control of infection by anerobic organisms may be important in its prevention or early resolution . The prophylactic administration of metronidazole ( Flagyl ) has been shown to be a simple and effective method of prevention which would suggest the implication of anaerobic organisms in ' dry socket ' . The drug appears to be free from side effects when a dosage of 200 mgs eight hourly for three days is given", "Combined treatments with non-steroidal anti-inflammatory drugs and antibiotics may offer significant benefits in the prevention of pain and infections associated with oral surgery . In this study , piroxicam and azithromycin were administered to patients undergoing dental extraction to examine the efficacy of piroxicam in the prevention of post-operative pain and inflammatory complications , either in the absence or in the presence of a concomitant antibiotic treatment . Thirty patients were r and omly assigned to three groups and treated for 3 days , before impacted lower third molar removal , as follows : ( 1 ) sublingual piroxicam-FDDF ( fast dissolving dosage formulation ) 20 mg/day ; ( 2 ) oral azithromycin 500 mg/day ; ( 3 ) piroxicam-FDDF 20 mg/day plus azithromycin 500 mg/day . Oral acetaminophen ( 500 mg tablets ) was allowed as rescue analgesic medication . Pain intensity was evaluated on a 100-mm visual-analogue scale after dental extraction ( day 1 ) , and at days 2 , 3 , 7 after surgery . Edema and trismus were estimated at days 2 and 7 . At days 1 and 2 , pain intensity was significantly lower in patients treated with piroxicam-FDDF , either alone ( p < 0.05 ) or in combination with azithromycin ( p < 0.05 ) , than in patients administered with azithromycin alone . A higher acetaminophen consumption was also recorded in the latter group ( p < 0.01 ) . Pain intensity values did not differ among treatment groups at days 3 and 7 . At day 2 , the facial edema was significantly less intense in patients exposed to piroxicam-FDDF alone , as compared to patients treated with azithromycin , either alone ( p < 0.05 ) or in combination with piroxicam-FDDF ( p < 0.05 ) . No significant differences were detected when comparing groups for trismus at days 2 and 7 . The present results indicate that , when given alone in the pre-operative period , piroxicam-FDDF effectively counteracts post-surgical pain and inflammatory reactions in oral tissues . Upon combined treatment with piroxicam-FDDF and azithromycin , the macrolide antibiotic may reduce the influence of piroxicam on post-operative inflammation , without affecting its beneficial effect on surgical pain", "PURPOSE The aim of the present study was to evaluate and compare the occurrence of postoperative complications in patients receiving either pre- or postoperative amoxicillin versus placebo after third molar surgery . PATIENTS AND METHODS A r and omized , double-blind , placebo-controlled clinical trial was performed in 123 patients undergoing third molar surgery . The patients were r and omized to 3 groups , according to the treatment regimen : preoperative amoxicillin , postoperative amoxicillin , and placebo . Both surgeon and patients were unaware of the treatment assignment . The clinical outcomes , including pain , wound infection , trismus , temperature , intra- and extraoral swelling , dysphagia , side effects , and postoperative complications , were assessed . RESULTS Statistically significant differences were found in the incidence of pain , wound infection , temperature , trismus , and dysphagia between the groups receiving amoxicillin versus placebo . Suture dehiscence and infection of 5 sockets were only found in the placebo group . No cases of alveolitis were observed in the 3 groups studied . No significant differences in swelling were found among the different groups . No statistically significant differences in side effects were found between the groups . The efficacy was greatest in the group receiving postoperative amoxicillin compared with the group receiving a prophylactic preoperative dose . CONCLUSION Amoxicillin administered pre- or postoperatively demonstrated greater efficacy than placebo in preventing postoperative complications in patients undergoing third molar surgery . The best results were obtained using the postoperative protocol" ]

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[ "Sonography of pregnancies with first-trimester bleeding and a viable embryo: a study of prognostic indicators by logistic regression analysis.", "Double-blind controlled trial of progesterone substitution in threatened abortion.", "[The treatment of threatened abortion (author's transl)].", "Progesterone and threatened abortion: a randomized clinical trial on endocervical cytokine concentrations.", "A randomised trial of progesterone prophylaxis after midtrimester amniocentesis.", "A randomized study comparing the efficacy of reducing the spontaneous abortion rate following lymphocyte immunotherapy and progesterone treatment versus progesterone alone in primary habitual aborters.", "Therapeutic value of indomethacin in threatened abortion.", "Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial.", "Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.", "[A randomized prospective study comparing supplementation of the luteal phase and early pregnancy by natural progesterone administered by intramuscular or vaginal route].", "Endocrine effects of 17 alpha‐hydroxyprogesterone caproate during early pregnancy: a double‐blind clinical trial", "A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation.", "Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone.", "Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice", "Fetal loss following ultrasound diagnosis of a live fetus at 6-10 weeks of gestation.", "A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage.", "Dydrogesterone support in threatened miscarriage.", "[Is hormonal therapy still justified in imminent abortion? (author's transl)].", "Randomised trial comparing expectant with medical management for first trimester miscarriages", "Dydrogesterone in threatened miscarriage: a Malaysian experience.", "A DOUBLE‐BLIND STUDY OF PROGESTOGEN TREATMENT IN SPONTANEOUS ABORTION", "Dydrogesterone in threatened abortion: Pregnancy outcome", "Effect of medroxyprogesterone acetate upon the duration and characteristics of human gestation and labor.", "Dydrogesterone in the reduction of recurrent spontaneous abortion", "Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy." ]

[ "The objective of our study was to investigate the relationship between sonographic findings and the occurrence of abortion in pregnancies complicated by first-trimester bleeding in which fetal cardiac activity was documented upon admission . A prospect i ve study of transvaginal sonography was performed in 270 pregnant patients with bleeding between 5 and 12 weeks ' gestation . The study group included 149 cases in which a singleton fetus with cardiac activity was initially documented . The outcome variable was pregnancy loss prior to 20 weeks . The influence of sonographic findings on admission was studied by univariate analysis and logistic regression . The prevalence of abortion was 23/149 ( 15 % ) . A significant relationship ( p < 0.05 ) was found between the occurrence of abortion and the following : fetal bradycardia ( heart rate less than -1.2 SD from the mean ) , a discrepancy between the diameter of the gestational sac and crown-rump length less than -0.5 SD from the mean , and a discrepancy between menstrual and sonographic age of more than 1 week . According to the logistic regression equation that was obtained , the probability of abortion in first-trimester bleeding with documented fetal cardiac activity upon admission varied between a minimum of 6 % when none of the above risk factors were present and a maximum of 84 % when all were present . The presence of any of the above factors identified 84 % of all subsequent abortions", "Between 1983 and 1984 a double-blind r and omized study with progesterone substitution in threatened abortion was carried out . Fifty-six patients with vaginal bleeding during the first trimester of pregnancy , the internal cervical os being closed , were referred to the hospital . Twenty-five women ( 5th and 6th week of gestation ) with positive serum concentrations of beta-hCG were admitted to the study without regard to sonogram results . In other 25 women ( 7th-10th week of pregnancy ) and 6 women ( greater than or equal to 11th week of pregnancy ) fetal heart action and movement could be demonstrated by ultrasound . The patients were prescribed bed rest and vaginal suppositories twice daily , containing either 25 mg progesterone or only polyethylene glycol . The code was not broken until after completion of the study . Serial serum determinations of beta-hCG , estradiol-17 beta ( E2 ) , progesterone , and ultrasound were performed . Four patients had to be omitted from final analysis ( two tubal pregnancies , one intrauterine infection , one sectio parva ) . Three of 26 patients progesterone ( 11 % ) and five of 26 patients with placebo ( 19 % ) had an abortion , which represented no significant difference . Frequency of abortion was increased in women more than 30 years old , in women with previous abortions and after ovulation induction . Progesterone treatment result ed in a significant elevation of serum progesterone concentrations ( p less than 0.01 ) , while beta-hCG and E2 were unchanged . The results of this study confirm that pregnancy outcome is favorable in women with bleeding and normal hormone concentrations without hormonal treatment and unfavorable in women with reduced beta-hCG and E2-concentrations . ( ABSTRACT TRUNCATED AT 250 WORDS", "In a prospect i ve study 265 patients with threatened abortions were divided into 2 groups . One group of 134 patients received treatment with Oestradiol benzoat and hydroxyprogesterone capronat . The other group of 131 patients received no hormonal treatment . Of the group treated with hormones 40.7 % of the women had an abortion . Of the group treated with placebos 39.7 % of the patients had an abortion . There was therefore no difference in the success rate of the treatment of threatened abortion irrespective of the administration of hormones or placebos . The value of hormonal therapy in the treatment of threatened abortion is therefore question able", "The purpose of this study was to investigate the effect of vaginal progesterone on endocervical cytokine concentration in women at risk of threatened abortion . One hundred and sixty pregnant women with clinical symptoms of threatened abortion before the 20th week of pregnancy were r and omly assigned to receive vaginal progesterone or placebo . Cervical fluids were collected and endocervical concentrations of different cytokines ( IFNγ , TNFα , IL-8 , IL-10 and IL-12 ) were analyzed before and one week after progesterone or placebo treatment . A significant decrease in IFNγ and increase in IL-10 in endocervical fluid was seen when the values were compared before and after progesterone treatment . However , there were no significant differences in pregnancy outcomes between the placebo and progesterone groups . We conclude that despite the failure of vaginal progesterone treatment to improve pregnancy outcomes , progesterone can induce a shift in the concentration of cytokines in endocervical secretions", "BACKGROUND Midtrimester amniocentesis to investigate fetal karyotype carries a small risk of fetal loss . AIM To test the hypothesis that progesterone prophylaxis may reduce this . STUDY DESIGN A r and omised controlled trial comparing a short prophylactic treatment with progesterone after amniocentesis with untreated controls . RESULTS There were no differences in frequency of miscarriage , preterm delivery or neonatal outcome . CONCLUSION Prophylactic progesterone treatment after amniocentesis does not improve obstetric outcome", "Presented herein is a r and omized prospect i ve study performed to evaluate the efficacy of the addition of lymphocyte immunotherapy ( LI ) to progesterone ( P ) therapy ( LI/P ) for the prevention of spontaneous abortion ( SAB ) in primary aborters with a history of three SABs . The incidence of intrauterine pregnancies in four cycles was 23 of 35 ( 65.7 % ) patients for LI/P vs. 14 of 31 ( 45.1 % ) patients treated with progesterone alone . SABs occurred in 6 of 23 ( 26.0 % ) LI/P-treated patients compared to 8 of 14 ( 57.1 % ) given progesterone alone . The mean number of previous abortions in both groups was 3.9 . The mean age of the LI/P group was 34.1 vs. 33.6 years for the group treated with progesterone alone . These data could be interpreted to show that progesterone therapy and LI independently inhibit SAB or that LI/P acts synergistically to inhibit immune destruction . LI/P therapy was found to be more effective than progesterone therapy alone", "One hundred cases of threatened abortion were r and omly allocated to four lines of treatment namely , long acting progesterone , antispasmodic , indomethacin and placebo . The lowest success rate was encountered in the indomethacin treated group ; symptoms of intolerance were common and three cases out of sixteen turned into missed abortion . Indomethacin does not offer any advantage over other lines of treatment in threatened abortion", "BACKGROUND The aim was to study whether prolongation of luteal support during early pregnancy influences the delivery rate after IVF . METHODS Dual centre study including 303 women who achieved pregnancy after IVF or ICSI was used . All were treated with the long protocol using GnRH agonists and given luteal support with 200 mg vaginal progesterone three times daily during 14 days from the day of transfer until the day of a positive HCG test . The study group ( n = 150 ) withdrew vaginal progesterone from the day of positive HCG . The control group ( n = 153 ) continued administration of vaginal progesterone during the next 3 weeks of pregnancy . RESULTS The number of miscarriages prior to and after week 7 of gestation was seven ( 4.6 % ) and 15 ( 10.0 % ) in the study group and five ( 3.3 % ) and 13 ( 8.5 % ) in the control group respectively . The number of deliveries was 118 ( 78.7 % ) in the study group and 126 ( 82.4 % ) in the control group . The differences were not significant . CONCLUSIONS Prolongation of progesterone supplementation in early pregnancy has no influence on the miscarriage rate , and thus no effect on the delivery rate . Progesterone supplementation can safely be withdrawn at the time of a positive HCG test", "BACKGROUND Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies . The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate ( 17P ) may reduce the risk of preterm delivery . METHODS We conducted a double-blind , placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery . Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and r and omly assigned by a central data center , in a 2:1 ratio , to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo ; injections were continued until delivery or to 36 weeks of gestation . The primary outcome was preterm delivery before 37 weeks of gestation . Analysis was performed according to the intention-to-treat principle . RESULTS Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar . Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation ( incidence , 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group ; relative risk , 0.66 [ 95 percent confidence interval , 0.54 to 0.81 ] ) , delivery at less than 35 weeks of gestation ( incidence , 20.6 percent vs. 30.7 percent ; relative risk , 0.67 [ 95 percent confidence interval , 0.48 to 0.93 ] ) , and delivery at less than 32 weeks of gestation ( 11.4 percent vs. 19.6 percent ; relative risk , 0.58 [ 95 percent confidence interval , 0.37 to 0.91 ] ) . Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis , intraventricular hemorrhage , and need for supplemental oxygen . CONCLUSIONS Weekly injections of 17P result ed in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants", "Deficiency in the luteal phase has been shown during stimulated cycles using a protocol involving a GnRH agonist . The authors undertook a r and omised prospect i ve trial of supplementation by progesterone of the luteal phase and of early pregnancy in two hundred and seventy two patients requiring fertilisation in vitro ( FIV ) , gamete inter-fallopian transfer ( GIFT ) or zygote inter-fallopian transfer ( ZIFT ) . Either progesterone in solution in oil ( 50 mg/day ) administered by intramuscular injection or micronized progesterone administered intra-vaginally ( 600 mg/d ) were used as support for the luteal phase . Administration of progesterone in association with estradiol valerate was started on the day prior to oocyte puncture and was continued until the 12th week of pregnancy . The implantation rate was very close to the threshold of significance ( P = 0.07 ) in favour of the patients given vaginal progesterone . There was a higher rate of clinical pregnancies ( 33.6 versus 26.7 p. cent ) in the latter group , though this was not significant . While plasma progesterone ( Pg ) levels were lower in patients using vaginal progesterone , the abortion rate during the first three months was lower in this group ( P < 0.05 ) . Micronized progesterone administered vaginally was well tolerated by all patients . During stimulated cycles , notably by GnRHa , it thus proved to be more effective than Pg administered by intramuscular injection with regard to implantation and abortion rates", "Summary . The clinical and endocrine effects of progestogen therapy in early pregnancy were investigated using a double‐blind r and omized trial in 64 patients who had a viable fetus at 6 weeks gestation and had an increased risk of miscarriage . The patients were r and omly allocated to receive either 17 alpha‐hydroxyprogesterone caproate or a placebo between 7 and 12 weeks gestation . Four fetal ultrasonographic variables and 17 maternal endocrine variables were studied in each woman . Only four maternal serum variables ( 17 alpha‐hydroxyprogesterone , prolactin , thyroxin and thyroxin binding globulin ) rose significantly . The serum progesterone levels in the hormone supplemented group were on average 20 % higher than in the placebo group but the difference was not statistically significant . However , the relation between the progesterone levels and the fetal outcome was not clear . Therefore it is not advisable to prescribe 17‐OHP‐C during early pregnancy to prevent a miscarriage", "BACKGROUND A combination of mifepristone and misoprostol provides an effective method of medical abortion for early pregnancy . This is the first r and omized trial comparing the use of sublingual misoprostol with vaginal misoprostol in combination with mifepristone for termination of early pregnancies up to 63 days . METHODS A total of 224 women who requested legal termination of pregnancy up to 63 days were r and omized by computer- generated list into two groups and given 200 mg of oral mifepristone followed 48 h later by either 800 micro g of sublingual ( n = 112 ) or vaginal ( n = 112 ) misoprostol . RESULTS Complete abortion occurred in 98.2 % ( 95 % CI : 93 - 99 ) of women in the sublingual group and 93.8 % ( 95 % CI : 88 - 97 ) in the vaginal group . There were three ongoing pregnancies in the vaginal group but none in the sublingual group . The median duration of vaginal bleeding was 17 days . There was no serious complication . Fever , chills and gastrointestinal side-effects ( nausea , vomiting and diarrhoea ) were significantly more common in the sublingual group . CONCLUSIONS The combination of mifepristone and misoprostol is effective for medical abortion up to 63 days . Both the sublingual and vaginal are effective routes of administration . Further r and omized trials are required to find out the optimal dose of sublingual misoprostol that can give the highest complete abortion rate and lowest incidence of side-effects", "OBJECTIVE To compare the influence of vaginal micronized progesterone and oral dydrogesterone supplementation on uteroplacental circulation in early pregnancy that is complicated by threatened abortion . DESIGN R and omized , parallel group , double-blind , double dummy-controlled study . SETTING Tertiary care university hospital . PATIENT(S ) Fifty-three patients with threatened abortion and a living embryo . INTERVENTION(S ) Three hundred milligrams of micronized vaginal progesterone or 30 mg of oral dydrogesterone daily supplementation for 6 weeks , serial transvaginal Doppler ultrasound measurement of pulsatility index , resistance index , and systolic/diastolic ratio of the spiral arteries , the uterine arteries , and the intrachorionic area . MAIN OUTCOME MEASURE(S ) Uteroplacental blood flow . RESULT ( S ) The study demonstrated that vaginal progesterone administration , but not oral dydrogesterone treatment , results in the decrease in the spiral artery pulsatility and resistance index and systolic/diastolic ratio . Insignificant decrease in pulsatility index and resistance index of the uterine artery was observed at > 9 weeks and was not associated with treatment regimen . Dydrogesterone treatment was only accompanied by the decrease in the uterine artery systolic/diastolic ratio . CONCLUSION ( S ) Vaginal progesterone and oral dydrogesterone supplementation have a different influence on the uteroplacental circulation in early pregnancy that is complicated by threatened abortion", "Abstract Objective : To estimate the miscarriage rate in a cohort of pregnant women and the final outcome of pregnancy . Design : Two year prospect i ve community study . Setting : Women registered with four semirural practice s at one health centre . Subjects : 626 pregnant women from a population 21 448 , 5140 of whom were women aged 15 - 44 years . Main outcome measures : Vaginal bleeding and outcome of pregnancy . Results : 76 of the 89 women with an unwanted pregnancy requested a termination . In the 550 ongoing pregnancies bleeding occurred before the 20th week in 117 ( 21 % ) , and 67 ( 12 % ) ended in miscarriage . The risk of miscarriage was not significantly increased after a miscarriage in the previous pregnancy ( 11 ( 15 % ) women had miscarriage v 55 ( 12 % ) women who had not had miscarriage ) who had previously had a live birth ) . Of the 117 women with bleeding , 64 were not admitted to hospital by the general practitioner ; 42 of these women had an ultrasound examination at the health centre and 19 subsequently miscarried at home . In hospital 41 of 46 women who miscarried had evacuation of the uterus . Conclusions : Bleeding occurred in one fifth of recognised pregnancies before the 20th week and over half of these miscarried . Treatment of women with miscarriage at home means current statistics on miscarriage in Britain are missing many cases . Key messages No national statistics for Britain are published on miscarriages Extrapolations from this survey indicate that in 1993 there may have been 70 000 - 90 000 miscarriages in Engl and and Wales Bleeding in early pregnancy is followed by a live birth in about half the affected pregnancies At least a quarter of all miscarriages were treated at home by general practitioners and would therefore not be recorded in any published statistics Women who had had a miscarriage did not have a significantly higher chance of a second consecutive", "OBJECTIVE To examine prospect ively the value of demographic characteristics and ultrasound findings in the prediction of subsequent fetal loss in pregnancies with live fetuses at 6 - 10 weeks of gestation . METHODS Transvaginal ultrasound examination was performed in 866 pregnancies at 6 - 10 weeks of gestation . The relation of demographic data and ultrasound findings at the time of the initial assessment to subsequent fetal loss was examined . RESULTS In the 668 singleton pregnancies with live fetuses and complete follow-up there were 50 ( 7.5 % ) fetal losses . The incidence of fetal loss increased significantly with maternal age and decreased with gestation . In the pregnancies result ing in fetal loss , compared to those with live births , the incidence of vaginal bleeding and cigarette smoking was higher , the fetal heart rate was significantly lower and the gestation sac diameter was smaller but the yolk sac diameter was not significantly different . CONCLUSION In pregnancies with a live fetus at 6 - 10 weeks ' gestation the rate of subsequent fetal loss is related to maternal age , gestation , cigarette smoking , history of vaginal bleeding and the ultrasound findings of small gestation sac diameter and fetal bradycardia , relative to crown-rump length", "Recurrent miscarriage is a difficult clinical problem occurring in approximately 1 - 2 % of fertile women . Following investigation , most cases fail to reveal an identifiable cause and are therefore classified as idiopathic . The aim of this study was to identify important gestational milestones for pregnancy success prediction in women following idiopathic recurrent miscarriage . A total of 325 consecutive patients with idiopathic recurrent miscarriage was involved in a prospect i ve longitudinal observational study . Patients were identified from a miscarriage data base of 716 patients . Preconceptual presentation and investigation excluded patients from the study sample with known associations of recurrent pregnancy loss , such as antiphosholipid syndrome , oligomenorrhoea , mid-trimester loss and other rare causes , e.g. abnormal parental karyotype . Following early presentation in a subsequent pregnancy , all patients followed a st and ard clinic protocol including fetal viability ultrasonography on a fortnightly basis throughout the first trimester . Kaplan-Meier curves were constructed for pregnancy outcome . Out of 325 idiopathic cases , 70 % ( n = 226 ) conceived , with a 75 % success rate . Of 55 miscarriages , longitudinal assessment showed that six losses occurred following detection of fetal cardiac activity ( 3 % ) . Data from this large study group have enabled accurate prediction of future pregnancy success and have established important gestational milestones for women with idiopathic recurrent miscarriage", "INTRODUCTION The aim of this study was to determine whether dydrogesterone helps to preserve pregnancy in women with threatened miscarriage . METHODS 146 women who presented with mild or moderate vaginal bleeding during the first trimester of pregnancy were r and omised to receive oral dydrogesterone ( 10 mg b.i.d . ) ( n=86 ) or no treatment ( n=60 ) . Dydrogesterone was continued until 1 week after the bleeding had stopped . All women received st and ard supportive care . RESULTS The incidence of miscarriage was significantly lower in the dydrogesterone group than in the untreated group ( 17.5 % vs. 25 % ; p<0.05 ) . There were no statistically significant differences between the groups with respect to pregnancy complications or congenital abnormalities . CONCLUSION Dydrogesterone appears to have beneficial effects in women with threatened miscarriage", "In a prospect i ve study , 300 women were treated during 1976 to 1978 alternatingly with hormones or placebo , the comparability of both groups being established in respect of certain influencing factors . No statistically confirmed difference was found in the total success rates of both types of treatment . The age of the pregnant women , and any previous abortions , did not represent any risk factor for imminent abortion . A better success rate was obtained with gestagen therapy , depending on the gestation period . (= 9th week of pregnancy )", "Objective To compare the efficacy of antiprogesterone ( mifepristone ) in combination with a synthetic prostagl and in E , analogue ( misoprostol ) for outpatient treatment of miscarriages", "INTRODUCTION Threatened miscarriage is a common problem during pregnancy . METHODS The aim of this prospect i ve , open , r and omised study was to determine whether dydrogesterone was more effective than conservative management alone in preventing miscarriage in women with vaginal bleeding up to week 16 of pregnancy . Women were excluded if they had a history of recurrent miscarriage . A total of 191 women were r and omised to dydrogesterone ( 40 mg stat followed by 10 mg twice daily ) or conservative management ( control group ) . The treatment was considered successful if the pregnancy continued beyond 20 weeks of gestation . RESULTS The success rate in the dydrogesterone group was statistically significantly higher than that in the control group ( 87.5 % vs. 71.6 % ; p<0.05 ) . Miscarriage occurred in 12.5 % of women in the dydrogesterone group compared with 28.4 % in the control group ( p<0.05 ) . There were no differences between the groups with regard to the incidence of Caesarean section , placenta praevia , antepartum haemorrhage , preterm labour ( weeks 28 - 36 ) , pregnancy-induced hypertension or low birth weight ( < 2500 g ) babies . There were no intrauterine deaths or congenital abnormalities in either group . CONCLUSION Compared with conservative management , dydrogesterone had beneficial effects on maintaining pregnancy in women with threatened miscarriage", "THE authors have planned a statistically controlled double-blind experiment which would compare the action of 17aOH-progesterone caproate , retroprogesterone and a placebo . A preliminary report on the first 35 cases of the study is presented , the small number of cases so far available being due to the severity of the selection criteria , which were : ( 1 ) Spontaneous threatened abortion before the 20th week , exhibiting painful uterine contractions with or without bleeding . ( 2 ) Pregnancy confirmed by qualitative immunological and biological tests on the urine . ( 3 ) No previous treatment at all with steroids or antispasmodic drugs . ( 4 ) Desire by the patient to maintain pregnancy and accept the necessary measures of investigation and treatment . ( 5 ) No clinical or haematological sign of infection . Identical packages were prepared containing the whole set of tablets and vials necessary for one “ treatment ” . They were numbered following a code which correspond to the experimental design and was unknown to the investigator . All the patients were examined and supervised by the same investigator working with a smalI team of two nurses . In order to estimate the severity of the threat several criteria were used , including clinical data , the steroid excretion and the study of vaginal smears . No valid conclusion can yet be derived from this study but it is apparent that no dramatic difference appears between the placebo “ treatment ” and the two others . On the contrary the greater rate of salvage was obtained with the placebo “ treatment ” . As this could be due to the differences in the severity of the threatened abortion , the cases were brought together according to the grading of severity and the time of termination of pregnancy . The apparent beneficial effect of the placebo was found to be due to the chance that the patients so treated exhibited lower grade s of severity , especially when the steroid excretion and vaginal smear gradings were considered . It is clear that the final issue depends more on the severity grading than on the treatment , and that the patients in this series who succeeded in their pregnancies would have done so with or without progesterone treatment", "OBJECTIVE To determine whether therapy with dydrogesterone in threatened abortion during the first trimester of pregnancy will improve pregnancy outcome . DESIGN Prospect i ve open study . SUBJECTS Pregnant women presenting to the obstetric and gynaecology clinic admitting center with vaginal bleeding before 13 weeks gestation were evaluated for entry into the study . Women were excluded if they had a history of recurrent miscarriage . METHOD Eligible subjects were r and omized to receive either dydrogesterone 40 mg stat dose followed by 10 mg twice a day for one week or conservative therapy . RESULTS One hundred and 54 women were recruited . There was no statistically significant differences between the two groups with regard to pre-treatment status . The continuing pregnancy success rate was significantly ( p=0.037 ) higher in women treated with dydrogesterone ( 95.9 % ) compared with women who received conservative treatment ( 86.3 % ) . The odds ratio of the success rate between dydrogesterone treatment and non-treatment was 3.773 ( 95 % confidence interval : 1.009 - 14.108 ) . CONCLUSION Corpus luteal support with dydrogesterone has been shown to reduce the incidence of pregnancy loss in threatened abortion during the first trimester in women without a history of recurrent abortion", "The effect of medroxyprogesterone acetate upon the duration and char acteristics of human gestation and labor was studied . 200 pregnant women ( 36 - 38 weeks gestation ) were r and omly assigned to a group receiving 20 mg 4 times/day or to a group receiving only the tablet base . This double-blind study failed to reveal any effect upon the duration of pregnancy or the characteristics of pregnancy labor or fetal conditions", "One hundred and eighty women with a history of recurrent , unexplained spontaneous abortion ( mean 3.5 abortions ) were r and omised to receive oral dydrogesterone ( 10 mg b.i.d . ) , intramuscular human chorionic gonadotrophin ( hCG ; 5000 IU every 4 days ) or no additional treatment ( controls ) . Treatment was started as soon as possible after confirmation of pregnancy and continued until the 12th gestational week . All women received st and ard supportive care . Abortions were significantly ( p < or = 0.05 ) less common in the dydrogesterone group ( 13.4 % ) than in the control group ( 29 % ) ; there were no statistically significant differences between the hCG group and the control group . There were no differences between the groups with respect to pregnancy complications or congenital abnormalities . In conclusion , hormonal support with dydrogesterone can increase the chances of a successful pregnancy in women with a history of recurrent spontaneous abortion", "Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospect i ve , r and omized , double-blind study in one medical center carried out with a parallel trial . The primary objective was to establish the effects of vaginal progesterone ( Crinone 8 % ) in reducing both pain and uterine contractions ( UCs ) . The gel with or without ( placebo ) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days . The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation , while the UCs were evaluated by ultrasound . The secondary objective of the study was to evaluate the outcome of the pregnancies . The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration ( P < 0.005 ) . The evaluation of the ongoing pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried ( P < 0.05 ) . In conclusion , patients with threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain . The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase" ]

[ "3773634", "2000864", "3934788", "11488322", "3898411", "25059421", "26386702", "4420253", "4853970", "4642399", "17297523", "15497198", "28005003", "4687694" ]

[ "Representativeness and optimal use of body mass index (BMI) in the UK Clinical Practice Research Datalink (CPRD)", "Cost-effectiveness of a nurse-led telemonitoring intervention based on peak expiratory flow measurements in asthmatics: results of a randomised controlled trial", "Pragmatic randomised trials using routine electronic health records: putting them to the test", "Respiratory illness and healthcare utilization in children: the primary and secondary care interface.", "Completeness and diagnostic validity of recording acute myocardial infarction events in primary care, hospital care, disease registry, and national mortality records: cohort study", "Identifying patient-level health and social care costs for older adults discharged from acute medical units in England.", "Validation of the Hospital Episode Statistics Outpatient Dataset in England", "Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre Randomised Controlled Trial (AMIGOS)", "Validating the use of Hospital Episode Statistics data and comparison of costing methodologies for economic evaluation: an end-of-life case study from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)", "Preventing and Lessening Exacerbations of Asthma in School-aged children Associated with a New Term (PLEASANT): Recruiting Primary Care Research Sites–the PLEASANT experience", "The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK.", "Estimating mean QALYs in trial-based cost-effectiveness analysis: the importance of controlling for baseline utility.", "PLEASANT: Preventing and Lessening Exacerbations of Asthma in School-age children Associated with a New Term - a cluster randomised controlled trial and economic evaluation.", "Economic Evaluation of a General Hospital Unit for Older People with Delirium and Dementia (TEAM Randomised Controlled Trial)" ]

[ "Objectives To assess the completeness and representativeness of body mass index ( BMI ) data in the Clinical Practice Research Data link ( CPRD ) , and determine an optimal strategy for their use . Design Descriptive study . Setting Electronic healthcare records from primary care . Participants A million patient r and om sample from the UK CPRD primary care data base , aged ≥16 years . Primary and secondary outcome measures BMI completeness in CPRD was evaluated by age , sex and calendar period . CPRD-based summary BMI statistics for each calendar year ( 2003–2010 ) were age-st and ardised and sex-st and ardised and compared with equivalent statistics from the Health Survey for Engl and ( HSE ) . Results BMI completeness increased over calendar time from 37 % in 1990–1994 to 77 % in 2005–2011 , was higher among females and increased with age . When BMI at specific time points was assigned based on the most recent record , calendar – year-specific mean BMI statistics underestimated equivalent HSE statistics by 0.75–1.1 kg/m2 . Restriction to those with a recent ( ≤3 years ) BMI result ed in mean BMI estimates closer to HSE ( ≤0.28 kg/m2 underestimation ) , but excluded up to 47 % of patients . An alternative strategy of imputing up-to- date BMI based on modelled changes in BMI over time since the last available record also led to mean BMI estimates that were close to HSE ( ≤0.37 kg/m2 underestimation ) . Conclusions Completeness of BMI in CPRD increased over time and varied by age and sex . At a given point in time , a large proportion of the most recent BMI s are unlikely to reflect current BMI ; consequent BMI misclassification might be reduced by employing model-based imputation of current BMI", "Background Asthma is a chronic lung disease in which recurrent asthma symptoms create a substantial burden to individuals and their families . At the same time the economic burden associated with asthma is considerable . Methods The cost-effectiveness study was part of a single centre prospect i ve r and omised controlled trial comparing a nurse-led telemonitoring programme to usual care in a population of asthmatic out patients . The study included 109 asthmatic out patients ( 56 children ; 53 adults ) . The duration of follow-up was 12 months , and measurements were performed at baseline , 4 , 8 , and 12 months . Patients were asked to transfer their monitor data at least twice daily and by judging the received data and following a stepwise intervention protocol a nurse was able to act as the main caregiver in the intervention group . In both groups the EQ-5D and the SF-6D were used to obtain estimates of health state utilities . One year health care costs , patient and family costs , and productivity losses were calculated . The mean incremental costs were weighted against the mean incremental effect in terms of QALY . Results The study population generally represented mild to moderate asthmatics . No significant differences were found between the groups with regard to the generic quality of life . Overall , the mean health care costs per patient were higher in the intervention group than in the control group . The intervention costs mainly caused the cost difference between the groups . The intervention costs the society € 31,035/QALY gained with regard to adults and with regard to children € 59,071/QALY gained . Conclusion If the outcome is measured by generic quality of life the nurse-led telemonitoring programme is of limited cost-effectiveness in the study population . From the societal perspective the probability of the programme being cost-effective compared to regular care was 85 % at a ceiling ratio of € 80,000/QALY gained among the adults and 68 % among the children . A decrease in the price of the asthma monitor will substantial increase the probability of the programme to be cost-effective . Trial registration Number :", "What to prescribe for a patient in general practice when the choice of treatments has a limited evidence base ? Tjeerd-Pieter van Staa and colleagues argue that using electronic health records to enter patients into r and omised trials of treatments in real time could provide the", "The aim of the present study was to quantify the healthcare utilization of a child population according to level of respiratory illness . A stratified r and om sample of 713 children was selected from respondents to a postal respiratory question naire , carried out in two general practice population s in 1993 . Children were stratified into four groups according to the number of positive responses to five key questions . These groups were used as indicators of likelihood of asthma diagnosis . A search was made of these childrens ' practice records covering a 2-yr period , to include both primary and secondary healthcare . There was a significant increase across positive response groups in the proportion of children having primary and secondary care based consultations , particularly for respiratory conditions ( p = 0.001 ) . There was also a significant increase in prescribing . Of those children considered to be \" likely asthmatics \" from their question naire responses , 8.1 % ( n = 31 ) did not receive any primary or secondary care for a respiratory problem over the 2-yr period . As the likelihood of respiratory illness increased in this population , more dem and was made upon re sources for the treatment of respiratory illness . Quantification of this dem and enables evidence based re source allocation decisions to be made . This method of quantification could be applied in other population", "Objective To determine the completeness and diagnostic validity of myocardial infa rct ion recording across four national health record sources in primary care , hospital care , a disease registry , and mortality register . Design Cohort study . Participants 21 482 patients with acute myocardial infa rct ion in Engl and between January 2003 and March 2009 , identified in four prospect ively collected , linked electronic health record sources : Clinical Practice Research Data link ( primary care data ) , Hospital Episode Statistics ( hospital admissions ) , the disease registry MINAP ( Myocardial Ischaemia National Audit Project ) , and the Office for National Statistics mortality register ( cause specific mortality data ) . Setting One country ( Engl and ) with one health system ( the National Health Service ) . Main outcome measures Recording of acute myocardial infa rct ion , incidence , all cause mortality within one year of acute myocardial infa rct ion , and diagnostic validity of acute myocardial infa rct ion compared with electrocardiographic and troponin findings in the disease registry ( gold st and ard ) . Results Risk factors and non-cardiovascular coexisting conditions were similar across patients identified in primary care , hospital admission , and registry sources . Immediate all cause mortality was highest among patients with acute myocardial infa rct ion recorded in primary care , which ( unlike hospital admission and disease registry sources ) included patients who did not reach hospital , but at one year mortality rates in cohorts from each source were similar . 5561 ( 31.0 % ) patients with non-fatal acute myocardial infa rct ion were recorded in all three sources and 11 482 ( 63.9 % ) in at least two sources . The crude incidence of acute myocardial infa rct ion was underestimated by 25 - 50 % using one source compared with using all three sources . Compared with acute myocardial infa rct ion defined in the disease registry , the positive predictive value of acute myocardial infa rct ion recorded in primary care was 92.2 % ( 95 % confidence interval 91.6 % to 92.8 % ) and in hospital admissions was 91.5 % ( 90.8 % to 92.1 % ) . Conclusion Each data source missed a substantial proportion ( 25 - 50 % ) of myocardial infa rct ion events . Failure to use linked electronic health records from primary care , hospital care , disease registry , and death certificates may lead to biased estimates of the incidence and outcome of myocardial infa rct ion . Trial registration NCT01569139 clinical trials.gov", "BACKGROUND acute medical units allow for those who need admission to be correctly identified , and for those who could be managed in ambulatory setting s to be discharged . However , re-admission rates for older people following discharge from acute medical units are high and may be associated with substantial health and social care costs . OBJECTIVE identifying patient-level health and social care costs for older people discharged from acute medical units in Engl and . DESIGN a prospect i ve cohort study of health and social care re source use . SETTING an acute medical unit in Nottingham , Engl and . PARTICIPANTS four hundred and fifty-six people aged over 70 who were discharged from an acute medical unit within 72 h of admission . METHODS hospitalisation and social care data were collected for 3 months post-recruitment . In Nottingham , further approvals were gained to obtain data from general practice s , ambulance services , intermediate care and mental healthcare . Re source use was combined with national unit costs . RESULTS costs from all sectors were available for 250 participants . The mean ( 95 % CI , median , range ) total cost was £ 1926 ( 1579 - 2383 , 659 , 0 - 23,612 ) . Contribution was : secondary care ( 76.1 % ) , primary care ( 10.9 % ) , ambulance service ( 0.7 % ) , intermediate care ( 0.2 % ) , mental healthcare ( 2.1 % ) and social care ( 10.0 % ) . The costliest 10 % of participants accounted for 50 % of the cost . CONCLUSIONS this study highlights the costs accrued by older people discharged from acute medical units ( AMUs ) : they are mainly ( 76 % ) in secondary care and half of all costs were incurred by a minority of participants ( 10 % )", "Objectives The Hospital Episode Statistics ( HES ) data set is a source of administrative ‘ big data ’ with potential for costing purpose s in economic evaluations alongside clinical trials . This study assesses the validity of coverage in the HES outpatient data set . Methods Men who died of , or with , prostate cancer were selected from a prostate-cancer screening trial ( CAP , Cluster r and omised triAl of PSA testing for Prostate cancer ) . Details of visits that took place after 1/4/2003 to hospital outpatient departments for conditions related to prostate cancer were extracted from medical records ( MR ) ; these appointments were sought in the HES outpatient data set based on date . The matching procedure was repeated for periods before and after 1/4/2008 , when the HES outpatient data set was accredited as a national statistic . Results 4922 outpatient appointments were extracted from MR for 370 men . 4088 appointments recorded in MR were identified in the HES outpatient data set ( 83.1 % ; 95 % confidence interval [ CI ] 82.0–84.1 ) . For appointments occurring prior to 1/4/2008 , 2195/2755 ( 79.7 % ; 95 % CI 78.2–81.2 ) matches were observed , while 1893/2167 ( 87.4 % ; 95 % CI 86.0–88.9 ) appointments occurring after 1/4/2008 were identified ( p for difference < 0.001 ) . 215/370 men ( 58.1 % ) had at least one appointment in the MR review that was unmatched in HES , 155 men ( 41.9 % ) had all their appointments identified , and 20 men ( 5.4 % ) had no appointments identified in HES . Conclusions The HES outpatient data set appears reasonably valid for research , particularly following accreditation . The data set may be a suitable alternative to collecting MR data from hospital notes within a trial , although caution should be exercised with data collected prior to accreditation", "Background Poor outcomes and high re source -use are observed for frail older people discharged from acute medical units . A specialist geriatric medical intervention , to facilitate Comprehensive Geriatric Assessment , was developed to reduce the incidence of adverse outcomes and associated high re source -use in this group in the post-discharge period . Objective To examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit , compared with st and ard care . Methods Economic evaluation was conducted alongside a two-centre r and omised controlled trial ( AMIGOS ) . 433 patients ( aged 70 or over ) at risk of future health problems , discharged from acute medical units within 72 hours of attending hospital , were recruited in two general hospitals in Nottingham and Leicester , UK . Participants were r and omised to the intervention , comprising geriatrician assessment in acute units and further specialist management , or to control where patients received no additional intervention over and above st and ard care . Primary outcome was incremental cost per quality adjusted life year ( QALY ) gained . Results We undertook cost-effectiveness analysis for 417 patients ( intervention : 205 ) . The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 ( 95 % confidence interval [ CI ] : -0.009 , 0.007 ) . Total adjusted secondary and social care costs , including direct costs of the intervention , at 3 months were £ 4412 ( € 5624 , $ 6878 ) and £ 4110 ( € 5239 , $ 6408 ) for the intervention and st and ard care groups , the incremental cost was £ 302 ( 95 % CI : 193 , 410 ) [ € 385 , $ 471 ] . The intervention was dominated by st and ard care with probability of 62 % , and with 0 % probability of cost-effectiveness ( at £ 20,000/QALY threshold ) . Conclusions The specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective . Further research on design ing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed . Trial Registration IS RCT N registry IS RCT N21800480 http://www.is rct n.com/IS RCT", "Objectives To evaluate the accuracy of routine data for costing inpatient re source use in a large clinical trial and to investigate costing method ologies . Design Final-year inpatient cost profiles were derived using ( 1 ) data extracted from medical records mapped to the National Health Service ( NHS ) reference costs via service codes and ( 2 ) Hospital Episode Statistics ( HES ) data using NHS reference costs . Trust finance departments were consulted to obtain costs for comparison purpose s. Setting 7 UK secondary care centres . Population A sub sample of 292 men identified as having died at least a year after being diagnosed with prostate cancer in Cluster r and omised triAl of PSA testing for Prostate cancer ( CAP ) , a long-running trial to evaluate the effectiveness and cost-effectiveness of prostate-specific antigen ( PSA ) testing . Results Both inpatient cost profiles showed a rise in costs in the months leading up to death , and were broadly similar . The difference in mean inpatient costs was £ 899 , with HES data yielding ∼8 % lower costs than medical record data ( differences compatible with chance , p=0.3 ) . Events were missing from both data sets . 11 men ( 3.8 % ) had events identified in HES that were all missing from medical record review , while 7 men ( 2.4 % ) had events identified in medical record review that were all missing from HES . The response from finance departments to requests for cost data was poor : only 3 of 7 departments returned adequate data sets within 6 months . Conclusions Using HES routine data coupled with NHS reference costs result ed in mean annual inpatient costs that were very similar to those derived via medical record review ; therefore , routinely available data can be used as the primary method of costing re source use in large clinical trials . Neither HES nor medical record review represent gold st and ards of data collection . Requesting cost data from finance departments is impractical for large clinical trials . Trial registration number IS RCT N92187251 ; Pre- results", "Background : Recruitment of general practice s and their patients into research studies is frequently reported as a challenge . The Preventing and Lessening Exacerbations of Asthma in School-aged children Associated with a New Term ( PLEASANT ) trial recruited 142 general practice s , across Engl and and Wales and delivered the study intervention to time and target . Aims : To describe the process of recruitment used within the cluster r and omised PLEASANT trial and present results on factors that influenced recruitment . Methods : Data were collected on the number of and types of contact used to gain expression of interest and subsequent r and omisation into the PLEASANT trial . Practice size and previous research experience were also collected . Results : The mean number of contacts required to gain expression of interest were m=3.01 ( s.d . 1.6 ) and total number of contacts from initial invitation to r and omisation m=6.8 ( s.d . 3.5 ) . Previous r and omised controlled trial involvement ( hazard ratio (HR)=1.81 ( confidence interval ( CI ) 95 % , 1.55–2.11 ) P<0.001 ) and number of studies a practice had previously engaged in ( odds ratio ( OR ) 1.91 ( CI 95 % , ( 1.52–2.42 ) ) P<0.001 ) , significantly influenced whether a practice would participate in PLEASANT . Practice size was not a significant deciding factor ( OR=1.04 ( 95 % CI 0.99–1.08 ) P=0.137 ) . Conclusions : Recruitment to time and target can be achieved in general practice . The amount of re source required for site recruitment should not , however , be underestimated and multiple strategies for contacting practice s should be considered . General practitioners with more research experience are more likely to participate in studies", "INTRODUCTION The objective of this study was to report the impact of exacerbations on health-related quality of life ( HRQL ) and health utility in patients with moderate to severe asthma ( BTS levels 4 & 5 ) in the UK . MATERIAL S AND METHODS Prospect i ve data regarding HRQL were collected ( n=112 ) using the EQ-5D , mini Asthma Quality of Life Question naire ( mAQLQ ) , and Asthma Symptom Utility ( ASUI ) measures . RESULTS The mAQLQ , EQ-5D and ASUI were all significantly worse for patients suffering exacerbations ( p<0.001 ) compared to those without . There was also evidence of a further HRQL decrement in those patients who had been admitted to hospital as a result of an exacerbation during the four-week study . CONCLUSIONS This study documents the impact of asthma exacerbations on HRQL in patients with moderate to severe asthma . There was some evidence of floor effects on the mAQLQ and ASUI in their ability to capture the impact of exacerbations . These study data are suitable for use in economic evaluations", "In trial-based cost-effectiveness analysis baseline mean utility values are invariably imbalanced between treatment arms . A patient 's baseline utility is likely to be highly correlated with their quality -adjusted life-years ( QALYs ) over the follow-up period , not least because it typically contributes to the QALY calculation . Therefore , imbalance in baseline utility needs to be accounted for in the estimation of mean differential QALYs , and failure to control for this imbalance can result in a misleading incremental cost-effectiveness ratio . This paper discusses the approaches that have been used in the cost-effectiveness literature to estimate absolute and differential mean QALYs alongside r and omised trials , and illustrates the implication s of baseline mean utility imbalance for QALY calculation . Using data from a recently conducted trial-based cost-effectiveness study and a micro-simulation exercise , the relative performance of alternative estimators is compared , showing that widely used methods to calculate differential QALYs provide incorrect results in the presence of baseline mean utility imbalance regardless of whether these differences are formally statistically significant . It is demonstrated that multiple regression methods can be usefully applied to generate appropriate estimates of differential mean QALYs and an associated measure of sampling variability , while controlling for differences in baseline mean utility between treatment arms in the trial", "BACKGROUND Asthma episodes and deaths are known to be seasonal . A number of reports have shown peaks in asthma episodes in school-aged children associated with the return to school following the summer vacation . A fall in prescription collection in the month of August has been observed , and was associated with an increase in the number of unscheduled contacts after the return to school in September . OBJECTIVE The primary objective of the study was to assess whether or not a NHS-delivered public health intervention reduces the September peak in unscheduled medical contacts . DESIGN Cluster r and omised trial , with the unit of r and omisation being 142 NHS general practice s , and trial-based economic evaluation . SETTING Primary care . INTERVENTION A letter sent ( n = 70 practice s ) in July from their general practitioner ( GP ) to parents/carers of school-aged children with asthma to remind them of the importance of taking their medication , and to ensure that they have sufficient medication prior to the start of the new school year in September . The control group received usual care . MAIN OUTCOME MEASURES The primary outcome measure was the proportion of children aged 5 - 16 years who had an unscheduled medical contact in September 2013 . Supporting end points included the proportion of children who collected prescriptions in August 2013 and unscheduled contacts through the following 12 months . Economic end points were quality -adjusted life-years ( QALYs ) gained and costs from an NHS and Personal Social Services perspective . RESULTS There is no evidence of effect in terms of unscheduled contacts in September . Among children aged 5 - 16 years , the odds ratio ( OR ) was 1.09 [ 95 % confidence interval ( CI ) 0.96 to 1.25 ] against the intervention . The intervention did increase the proportion of children collecting a prescription in August ( OR 1.43 , 95 % CI 1.24 to 1.64 ) as well as scheduled contacts in the same month ( OR 1.13 , 95 % CI 0.84 to 1.52 ) . For the wider time intervals ( September-December 2013 and September-August 2014 ) , there is weak evidence of the intervention reducing unscheduled contacts . The intervention did not reduce unscheduled care in September , although it succeeded in increasing the proportion of children collecting prescriptions in August as well as having scheduled contacts in the same month . These unscheduled contacts in September could be a result of the intervention , as GPs may have wanted to see patients before issuing a prescription . The economic analysis estimated a high probability that the intervention was cost-saving , for baseline-adjusted costs , across both base-case and sensitivity analyses . There was no increase in QALYs . LIMITATION The use of routine data led to uncertainty in the coding of medical contacts . The uncertainty was mitigated by advice from a GP adjudication panel . CONCLUSIONS The intervention did not reduce unscheduled care in September , although it succeeded in increasing the proportion of children both collecting prescriptions and having scheduled contacts in August . After September there is weak evidence in favour of the intervention . The intervention had a favourable impact on costs but did not demonstrate any impact on QALYs . The results of the trial indicate that further work is required on assessing and underst and ing adherence , both in terms of using routine data to make quantitative assessment s , and through additional qualitative interviews with key stakeholders such as practice nurses , GPs and a wider group of children with asthma . TRIAL REGISTRATION Current Controlled Trials IS RCT N03000938 . FUNDING DETAILS This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 93 . See the HTA programme website for further project information", "Background One in three hospital acute medical admissions is of an older person with cognitive impairment . Their outcomes are poor and the quality of their care in hospital has been criticised . A specialist unit to care for older people with delirium and dementia ( the Medical and Mental Health Unit , MMHU ) was developed and then tested in a r and omised controlled trial where it delivered significantly higher quality of , and satisfaction with , care , but no significant benefits in terms of health status outcomes at three months . Objective To examine the cost-effectiveness of the MMHU for older people with delirium and dementia in general hospitals , compared with st and ard care . Methods Six hundred participants aged over 65 admitted for acute medical care , identified on admission as cognitively impaired , were r and omised to the MMHU or to st and ard care on acute geriatric or general medical wards . Cost per quality adjusted life year ( QALY ) gained , at 3-month follow-up , was assessed in trial-based economic evaluation ( 599/600 participants , intervention : 309 ) . Multiple imputation and complete-case sample analyses were employed to deal with missing QALY data ( 55 % ) . Results The total adjusted health and social care costs , including direct costs of the intervention , at 3 months was £ 7714 and £ 7862 for MMHU and st and ard care groups , respectively ( difference -£149 ( 95 % confidence interval [ CI ] : -298 , 4 ) ) . The difference in QALYs gained was 0.001 ( 95 % CI : -0.006 , 0.008 ) . The probability that the intervention was dominant was 58 % , and the probability that it was cost-saving with QALY loss was 39 % . At £ 20,000/QALY threshold , the probability of cost-effectiveness was 94 % , falling to 59 % when cost-saving QALY loss cases were excluded . Conclusions The MMHU was strongly cost-effective using usual criteria , although considerably less so when the less acceptable situation with QALY loss and cost savings were excluded . Nevertheless , this model of care is worthy of further evaluation . Trial Registration Clinical Trials.gov" ]

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[ "A preliminary study of factors influencing perception of menstrual blood loss volume.", "Management of menorrhagia in primary care-impact on referral and hysterectomy: data from the Somerset Morbidity Project.", "[Treatment of menorrhagia with tranexamic acid. A clinical trial of an underestimated problem in general practice].", "A DOUBLE-BLIND TRIAL OF ETHAMSYLATE IN THE TREATMENT OF PRIMARY AND INTRAUTERINE-DEVICE MENORRHAGIA", "Randomised controlled trial of educational package on management of menorrhagia in primary care: the Anglia menorrhagia education study", "Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid", "Reduction of menstrual blood loss in women suffering from idiopathic menorrhagia with a novel antifibrinolytic drug (Kabi 2161)", "Treatment of Menorrhagia with Tranexamic Acid. A Double-blind Trial", "Comparative study of tranexamic acid and norethisterone in the treatment of ovulatory menorrhagia", "[Treatment by tranexamic acid in menorrhagia in women using intrauterine devices].", "Effect of ethamsylate and aminocaproic acid on menstrual blood loss in women using intrauterine devices.", "Treatment of Menorrhagia with Epsilon Aminocaproic Acid", "Comparison between antifibrinolytic and antiprostaglandin treatment in the reduction of increased menstrual blood loss in women with intrauterine contraceptive devices", "Effect of tranexamic acid (AMCA) in menorrhagia with intrauterine contraceptive devices.", "An Objective Evaluation of Flurbiprofen and Tranexamic Acid in the Treatment of Idiopathic Menorrhagia", "A comparative study of ethamsylate and mefenamic acid in dysfunctional uterine bleeding" ]

[ "Sixty-nine women with a convincing complaint of menorrhagia took part in a double-blind treatment trial . Menstrual blood loss was measured and the subject 's own perception was carefully recorded . Only 38 % had objective menorrhagia with a measured loss greater than 80 ml although 59 % would qualify with an upper limit of normal of 60 ml . Overall the measured loss in the \" heaviest \" periods ( 69.6 + /- 7.3 ml ; mean + /- SEM ) were significantly greater than that of the \" lightest \" periods ( 42.7 + /- 4.7 ml ; p less than 0.001 ) , but there were many major errors in perception by individuals . Perceived daily blood loss volume on a 4-point rating scale gave the following group means and ranges : spotting , 2.5 ml ( 0.1 to 15.5 ) ; light , 5.7 ml ( 0.1 to 63.1 ) ; moderate , 16.1 ml ( 0.5 to 108.6 ) ; very heavy , 22.0 ml ( 1.4 to 215.8 ) ; very wide individual ranges of assessment are illustrated . As a whole the group was also able to distinguish between a day-to-day volume increase or decrease , but again there were many major errors . Some subjects who experienced a reduction in measured blood loss from one day to the next actually perceived this as a large increase . Menstrual pain and duration of bleeding were not found to influence perception of blood loss volume , whereas younger subjects ( 26 and under ) were significantly more likely than older women ( 37 and over ) to regard a moderate loss as very heavy . There was no significant correlation between the number of pads/tampons used and the measured menstrual loss , and some individuals showed extreme variations between blood loss and pad usage . This study suggests that the only reliable assessment of menstrual blood loss volume and changes in volume in women complaining of menorrhagia is obtained by objective measurement of blood loss by a technique such as alkaline hematin extraction", "OBJECTIVE To investigate the management of menorrhagia in primary care and its impact on referral and hysterectomy rates . DESIGN Prospect i ve observational study . SETTING 11 general practice s from the Somerset Morbidity Project . SUBJECTS 885 women consulting their general practitioner with menorrhagia over four years . MAIN OUTCOME MEASURES Proportions of these women investigated and treated with drugs in primary care , referred to a gynaecologist and undergoing operative procedures . The relation between investigation and prescribing in primary care and referral to and surgery in secondary care . RESULTS Less than half of women had a vaginal examination ( 42 % , 95 % CI 39 % to 45 % ) , or a full blood count ( 39 % , 95 % CI 36 % to 43 % ) . Almost a quarter of women , 23 % ( 95 % CI 20 % to 26 % ) , received no drugs and 37 % ( 95 % CI 34 % to 40 % ) received norethisterone . Over a third , 38 % ( 95 % CI 34 % to 40 % ) , of women were referred , and once referred 43 % ( 95 % CI 38 % to 48 % ) of women were operated on . Women referred to a gynaecologist were significantly more likely to have received tranexamic acid and /or mefenamic acid in primary care ( chi(2)=16.4 , df=1 , p<0.001 ) . There were substantial between practice variations in management , for example in prescribing of tranexamic acid and /or mefenamic acid ( range 16 % to 72 % ) and referral to gynaecology ( range 24 % to 52 % ) . There was a significant association between high referral and high operative rates ( Spearman 's correlation coefficient=0.86 , p=0.001 ) . CONCLUSIONS Substantial differences in management exist between practice s when investigating and prescribing for menorrhagia in primary care . Rates of prescribing of effective medical treatment remain low . The decision to refer a woman impacts markedly on her chances of subsequently being operated on . Effective management in primary care may not reduce referral or hysterectomy rates", "44 women with heavy menstrual bleeding participated in a six months r and omised , double blind , cross over clinical trial . The objective was to use simple methods to study whether treatment of menorrhagia with tranexamic acid has an effect that can be detected by the women themselves . The effect was evaluated by means of diaries and a visual analog scale . The bleeding during each period of treatment was compared with the bleeding during untreated periods . Bleeding during the different periods of treatment was also compared directly . The results indicate that tranexamic acid was more effective than placebo . This difference was not disclosed , however , in the laboratory data . After the study , 75 % of the women wished to continue treatment with tranexamic acid", "22 patients complaining of primary menorrhagia or menorrhagia associated with an intrauterine device ( I.U.C.D. ) were studied in a double blind trial with crossover of ethamsylate and placebo . Acutal menstrual blood-losses were calculated from the iron content of used sanitary material during one pre-trail menstrual period and four trial menstrual periods , during which patients received ethamsylate ( \" Dicynene \" ) treatment during two menstrual cycles and placebo during two cycles . During ethamsylate treatment the mean menstrual blood-loss was reduced by 50 % in patients with primary menorrhagia and by 19 % in patients with an I.U.C.D. This difference between the two groups is probably accounted for by the differing values of initial blood-loss which was significantly higher in the group with primary menorrhagia . Tampon usage and the duration of bleeding were not significantly altered by ethamsylate treatment . Reported side-effects , which were not serious , were equally common during ethamsylate and placebo treatment", "Abstract Objective : To determine whether an educational package could influence the management of menorrhagia , increase the appropriateness of choice of non-hormonal treatment , and reduce referral rates from primary to secondary care . Design : R and omised controlled trial . Setting : General practice s in East Anglia . Subjects : 100 practice s ( 348 doctors ) in primary care were recruited and r and omised to intervention ( 54 ) and control ( 46 ) . Interventions : An educational package based on principles of “ academic detailing ” with independent academics was given in small practice based interactive groups with a visual presentation , a printed evidence based summary , a graphic management flow chart , and a follow up meeting at 6 months . Outcome measures : All practice s recorded consultation details , treatments offered , and outcomes for women with regular heavy menstrual loss ( menorrhagia ) over 1 year . Results : 1001 consultation data sheets for menorrhagia were returned . There were significantly fewer referrals ( 20 % v 29 % ; odds ratio 0.64 ; 95 % confidence interval 0.41 to 0.99 ) and a significantly higher use of tranexamic acid ( odds ratio 2.38 ; 1.61 to 3.49 ) in the intervention group but no overall difference in norethisterone treatment compared with controls . There were more referrals when tranexamic acid was given with norethisterone than when it was given alone . Those practice s reporting fewer than 10 cases showed the highest increase in prescribing of tranexamic acid . Conclusions : The educational package positively influenced referral for menorrhagia and treatment with appropriate non-hormonal drugs", "Abstract Objective : To compare the efficacy and acceptability of ethamsylate , mefenamic acid , and tranexamic acid for treating menorrhagia . Design : R and omised controlled trial . Setting : A university department of obstetrics and gynaecology . Subjects : 76 women with dysfunctional uterine bleeding . Interventions : Treatment for five days from day 1 of menses during three consecutive menstrual periods . 27 patients were r and omised to take ethamsylate 500 mg six hourly , 23 patients to take mefenamic acid 500 mg eight hourly , and 26 patients to take tranexamic acid 1 g six hourly . Main outcome measures : Menstrual loss measured by the alkaline haematin method in three control menstrual periods and three menstrual periods during treatment ; duration of bleeding ; patient 's estimation of blood loss ; sanitary towel usage ; the occurrence of dysmenorrhoea ; and unwanted events . Results : Ethamsylate did not reduce mean menstrual blood loss whereas mefenamic acid reduced blood loss by 20 % ( mean blood loss 186 ml before treatment , 148 ml during treatment ) and tranexamic acid reduced blood loss by 54 % ( mean blood loss 164 ml before treatment , 75 ml during treatment ) . Sanitary towel usage was significantly reduced in patients treated with mefenamic acid and tranexamic acid . Conclusions : Tranexamic acid given during menstruation is a safe and highly effective treatment for excessive bleeding . Patients with dysfunctional uterine bleeding should be offered medical treatment with tranexamic acid before a decision is made about surgery . Key messages In any year around 5 % of women aged 30 - 49 years visit their general practitioners with menor-rhagia Every year in the United Kingdom around 45 000 hysterectomies and a further 10 000 endometrial ablations are performed for menorrhagia The commonest drug prescribed in the British Isles for menorrhagia ( norethisterone ) has little or no effect in reducing menstrual bleeding Tranexamic acid ( an antifibrinolytic ) 1 g six to eight hourly reduces menstrual blood loss by over half and should be offered to women with dysfunctional bleeding before a decision is made about", "Objective To compare the effect of Kabi 2161 ( a prodrug of tranexamic acid ) and placebo on the reduction of menstrual blood loss in women suffering from idiopathic menorrhagia and to evaluate tolerance and effectiveness in a two‐dose regimen", "In a double-blind trial tranexamic acid ( Cyclokapron ) 1 g. four times a day for the first four days of menstruation , significantly decreased menstrual blood loss in women with menorrhagia for which no organic cause had been found . No difference in side-effects was noted between the active and placebo treatment", "Objective To compare the efficacy and safety of tranexamic acid and norethisterone in the treatment of ovulatory menorrhagia", "A double-blind study of 65 women , aged 15 - 44 , was performed to determine if IUD use caused menorrhagia , and if so , if the menorrhagia could be prevented with Cyclocaprone . IUDs were inserted and the women were given pills to take during their menstrual periods . The pills were given at r and om ; 34 received Cyclocaprone and 31 received placebos . The volume of menstrual bleeding was measured during 1 menstrual period before the experiment , which served as a control , and for up to 4 menstrual periods after the insertion of the IUD and administration of the pills . The average volume of blood loss during the control period was about 35.75 ml ; during the following menstrual periods this increased 11.5 % among the women who had received Cyclocaprone and 82.7 % among those who had received placebos . The difference between the 2 groups was statistically significant ( p less than .001 ) . The majority of the women subjectively reported an increase in menstrual bleeding . The cyclocaprone users may have experienced an abnormally heavy bleeding during the menstrual period which caused them to report an increase in menstrual bleeding . In 13 of the menstrual cycles , blood loss exceeded 100 ml ; all of these cases were among women who had received placebos . The greatest increase in blood loss occurred in the menstrual cycle after the insertion of the IUD ; blood loss decreased in each subsequent menstrual period . 3 women who had received placebos had a hemoglobin concentration of less than 10.5 gm% . There were 5 cases of side effects among the women using Cyclocaprone and 2 among the women taking placebos . The results suggest that the IUD causes an activation of plasminogen in the endometrium early in the menstrual cycle ; cyclocaprone prevents this activation and the result ing menorrhagia", "abnormality in the giant platelet syndrome of Bernard-Soulierl 8 and also in von Willebr and 's disease , in which the abnormality is probably secondary to a deficiency or defect of a plasma protein related to factor VIIII-the factor VII I-related protein . ' 9 In our patient the defective ristocetin platelet aggregation seemed to be due to a plasma defect rather than to a primary platelet abnormality because aggregation was corrected partially or completely by the addition of normal plasma , cryoprecipitate , or a plasma fraction rich in factor VIII-related in protein . On the other h and the level of factor VIII-related protein in the infant 's plasma was normal , which suggested that either there was a functional abnormality of this protein or the patient lacked another substance necessary for ristocetin platelet aggregation . This did not seem to be fibrinogen , which , it has been suggested , is a co-factor for ristocetin aggregation,20 because the thrombin clotting times and fibrinogen levels were normal . The small volumes of blood obtainable from the infant precluded more detailed in-vitro studies , and it is possible that the vitamin E deficiency was directly responsible for the defective platelet ristocetin aggregation or that the deficiency result ed in the synthesis of an abnormal factor VIII-related protein . The normal bleeding time , the lack of family history , and the results of treatment , however , did not suggest that the infant was suffering from von Willebr and 's disease . The role of iron or folate deficiency in the pathogenesis of the patient 's haematological status is difficult to assess . It has been suggested that folate deficiency may aggravate haemolysis in vitamin E deficiency,2 ' but though the patient 's folate status was not certain his marrow was normoblastic , a finding which suggested that he did not have severe folate deficiency . Iron treatment is also thought to aggravate vitamin E deficiency and enhance lipid peroxidation and haemolysis,22 23 but the child was not on iron treatment when his peroxide lysis tests gave persistently abnormal results . This persisting abnormality , however , was not really surprising because the serum vitamin E levels were not fully corrected with treatment . Though a relation between vitamin E deficiency and the abnormal platelet function was not definitely proved the response of the platelets to vitamin E treatment was striking . This finding suggests a possible relation between vitamin E and ristocetin-induced platelet aggregation which warrants further studies in patients in severe tocopherol-deficient states", "A series consisting of 37 women ( 17 - 50 years of age ) referred because of suspected menorrhagia was used to investigate the therapeutic value of epsilon amino caproic acid ( EACA ) in control of this menstruation disorder . The study was double-blind . A statistically significant difference in blood loss ( P > .001 ) per menstruation was found between EACA users ( 52 ml ) and placebo users ( 127 ml ) . 26/37 patients who had lost more than 60 ml of blood when given the placebo were treated . Their mean blood loss when treated with EACA was 61 + or -10 ml vs. 164 + or -29 ml when treated by placebo . This 60 % reduction of blood loss was statistically significant ( P > .001 ) . 11 women did not fulfill the criteria for menorrhagia . When treated with EACA their average blood loss was 31 + or -6 ml vs. 39 + or -5 ml with placebo . This 20 % reduction was not statistically significant ( P=.4-.3 ) . For 2 patients the reduction was less than 50 % and in 6 patients treated with EACA no decrease in blood loss occurred . Loss of blood mainly occurred during the 1st 3 days of menstruation and this period is where the decrease occurred with EACA administration . In 13 cases there were no side effects in connection with either EACA or the placebo . 13 patients had side effects only when given EACA . The symptoms were stated to be mainly nausea or orthostatism . 4 patients had side effects only when they received the placebo medication and 7 displayed side effects with both EACA and placebo . The EACA doses were 6 measuring spoons daily orally for the 1st 3 days of the period and then 432 and 1 measuring spoon respectively for the following 4 days", "Summary . The effects of a fibrinolysis inhibitor ( tranexamic acid , TA ) and prostagl and in synthesis inhibitor ( diclofenac sodium , DS ) were compared in the reduction of excessive menstrual blood loss in 19 women with an intrauterine contraceptive device ( IUCD ) . These women ( mean blood loss before treatment to 135.1±18.9 SE ml , range 70–294 ml ) were treated in r and om order with TA ( 1.5 g three times daily for 5 days starting on the first day of menstruation for two periods ) , and with DS ( 50 mg three times on the first day followed by 25 mg three times daily for 4 days , for two periods ) , or with placebo ( one period ) in a double‐blind trial . The placebo treatment did not change menstrual blood loss ( 128.3±15.6 ml ) . The TA treatment decreased blood loss to 59.4±7.7 ml ( P<0.001 ) and the DS treatment to 102.1±13.6 ml ( P<0.01 ) . Neither treatment abolished pelvic discomfort during menstruation or shortened its duration . Various side‐effects were noted by 12 women during 19 TA treatments and by five women during six DS treatments . Thus , while TA is generally far more effective , DS gave pronounced decreases in menstrual bleeding in some women and had less frequent side‐effects", "The effect of tranexamic acid on the increase in menstrual blood loss after the insertion of an IUD was studied in 65 women in a double blind study . 253 cycles 65 prior to IUD insertion 97 with tranexamic acid treatment and 91 with placebo treatment were studied . In the placebo group menstrual blood loss increased 82.7 % over the mean control menstruation . In the tranexamic acid cycles menstrual blood loss increased 11.5 % . There was no difference in duration of bleeding between the groups", "The effect of flurbiprofen ( 100 mg × 2 for 5 days ) was compared with tranexamic acid ( 1.5 g × 3 for 3 days , 1 g × 2 days 4 and 5 ) in the treatment of 15 women with idiopathic menorrhagia . The mean blood loss during two medication‐free periods was 295 ± 52 ml . A significant ( p < 0.01 ) reduction in menstrual blood loss was recorded during treatment with both flurbiprofen and tranexamic acid . The menstrual blood loss was significantly ( p < 0.01 ) lower during treatment with tranexamic acid ( 155 ± 33 ml ) than with flurbiprofen ( 223 ± 44 ml ) . Various side effects were recorded by 7 of 15 women during treatment with tranexamic acid and by 4 women of 15 during treatment with flurbiprofen . Many women with menorrhagia suffer simultaneously from dysmenorrhea . Thus although tranexamic acid was generally more effective in reducing menstrual blood loss , flurbiprofen provides an important therapeutic alternative to antifibrinolytic agents , especially in patients with concomitant dysmenorrhea", "Summary . The effects of ethamsylate and mefenamic acid on menstrual blood loss were compared in a double‐blind trial in 34 women with men‐orrhagia . Both drugs produced statistically significant reductions in blood loss during the 3 months of treatment ; the overall reduction was 20 % in the ethamsylate group and 24 % in the mefenamic acid group . Compared with pretreatment values , blood loss was significantly less in each of the 3 treatment months in the mefenamic acid group , but only in the second and third months of treatment in the ethamsylate group . However , more women had a clinical ly useful reduction in blood loss ( > 40 % ) in the ethamsylate group . The onset of effect of mefenamic acid was rapid but ethamsylate showed a comparatively greater effect as the trial progressed . Cessation of treatment was followed by an increase in blood loss , more pronounced in mefenamic acid group who reverted to pre‐treatment levels . A greater number of side‐effects were reported with mefenamic acid" ]

[ "3112215", "11602545", "9529264", "9247512", "16267070", "14510659", "18157961", "11099991" ]

[ "Incidence of Atrial Fibrillation in Patients with either Heart Failure or Acute Myocardial Infarction and Left Ventricular Dysfunction: A Cohort Study", "Incidence and prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data", "Significance of paroxysmal atrial fibrillation complicating acute myocardial infarction in the thrombolytic era. SPRINT and Thrombolytic Survey Groups.", "Atrial fibrillation in the setting of acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.", "Increased risk of sudden and non-sudden cardiovascular death in patients with atrial fibrillation/flutter following acute myocardial infarction.", "Predictive Value of P‐Wave Signal‐Averaged Electrocardiogram for Atrial Fibrillation in Acute Myocardial Infarction", "Relation of recurrence of atrial fibrillation after non-ST-elevation acute myocardial infarction to left atrial abnormality.", "New atrial fibrillation after acute myocardial infarction independently predicts death: the GUSTO-III experience." ]

[ "Background We examined the incidence of new-onset atrial fibrillation in patients with left ventricular dysfunction . Patients either had a recent myocardial infa rct ion ( with or without clinical heart failure ) or symptomatic heart failure ( without a recent MI ) . Patients were with and without treatment with the class III antiarrhythmic drug dofetilide over 36 months . Methods The Danish Investigations of Arrhythmia and Mortality ON Dofetilide ( DIAMOND ) studies included 2627 patients without atrial fibrillation at baseline , who were r and omised to treatment with either dofetilide or placebo . Results The competing risk analyses estimated the cumulative incidences of atrial fibrillation during the 42 months of follow-up to be 9.6 % in the placebo-treated heart failure-group , and 2.9 % in the placebo-treated myocardial infa rct ion-group . Cox proportional hazard regression found a 42 % significant reduction in the incidence of new-onset AF when assigned to dofetilide compared to placebo ( hazard ratio 0.58 , 95 % confidence interval 0.40 - 0.82 ) and there was no interaction with study ( p = 0.89).In the heart failure-group , the incidence of atrial fibrillation was significantly reduced to 5.6 % in the dofetilide-treated patients ( hazard ratio 0.57 , 95 % confidence interval 0.38 - 0.86).In the myocardial infa rct ion-group the incidence of atrial fibrillation was reduced to 1.7 % with the administration of dofetilide . This reduction was however not significant ( hazard ratio 0.61 , 95 % confidence interval 0.30 - 1.24 ) . Conclusion In patients with left ventricular dysfunction the incidence of AF in 42 months was 9.6 % in patients with heart failure and 2.9 % in patients with a recent MI . Dofetilide significantly reduced the risk of developing atrial fibrillation compared to placebo in the entire study group and in the subgroup of patients with heart failure . The reduction in the subgroup with recent MI was not statistically significant , but the hazard ratio was similar to the hazard ratio for the heart failure patients , and there was no difference between the effect in the two studies ( p = 0.89 for interaction )", "BACKGROUND Atrial fibrillation is the most common supraventricular arrhythmia in patients with acute myocardial infa rct ion . Recent advances in pharmacological treatment of myocardial infa rct ion may have changed the impact of this arrhythmia . OBJECTIVE To assess the incidence and prognosis of atrial fibrillation complicating myocardial infa rct ion in a large population of patients receiving optimal treatment , including angiotensin converting enzyme ( ACE ) inhibitors . METHODS Data were derived from the GISSI-3 trial , which included 17 944 patients within the first 24 hours after acute myocardial infa rct ion . Atrial fibrillation was recorded during the hospital stay , and follow up visits were planned at six weeks and six months . Survival of the patients at four years was assessed through census offices . RESULTS The incidence of in-hospital atrial fibrillation or flutter was 7.8 % . Atrial fibrillation was associated with indicators of a worse prognosis ( age > 70 years , female sex , higher Killip class , previous myocardial infa rct ion , treated hypertension , high systolic blood pressure at entry , insulin dependent diabetes , signs or symptoms of heart failure ) and with some adverse clinical events ( reinfa rct ion , sustained ventricular tachycardia , ventricular fibrillation ) . After adjustment for other prognostic factors , atrial fibrillation remained an independent predictor of increased in-hospital mortality : 12.6%v 5 % , adjusted relative risk ( RR ) 1.98 , 95 % confidence interval ( CI ) 1.67 to 2.34 . Data on long term mortality ( four years after acute myocardial infa rct ion ) confirmed the persistent negative influence of atrial fibrillation ( RR 1.78 , 95 % CI 1.60 to 1.99 ) . CONCLUSIONS Atrial fibrillation is an indicator of worse prognosis after acute myocardial infa rct ion , both in the short term and in the long term , even in an unselected population", "BACKGROUND Paroxysmal atrial fibrillation ( PAF ) is considered a frequent complication of acute myocardial infa rct ion ( AMI ) , associated with increased in-hospital and long-term mortality rates . This notion is based on data collected before thrombolysis and additional modern methods of treatment became widely available , and no information is available on the significance of PAF in the general population with AMI in the thrombolytic era . The aim of the present study was to define the incidence , associated clinical parameters , and short- and long-term prognostic significance of PAF in patients with AMI in the thrombolytic era . METHODS AND RESULTS A prospect i ve , nationwide survey was conducted of 2866 consecutive patients admitted with AMI in all 25 coronary care units in Israel during January/February 1992 , 1994 , and 1996 ( thrombolytic era [ TE ] ) . The data were compared with a previous Israeli study of 5803 patients with AMI hospitalized in 1981 through 1983 ( prethrombolytic era [ PTE ] ) . Patients in the TE with PAF were older and had a worse risk profile than those without PAF . PAF in the TE was independently associated with increased 30-day ( odds ratio , 1.32 ; 95 % confidence interval , 0.92 to 1.87 ) and 1-year ( relative risk , 1.33 ; 95 % confidence interval , 1.05 to 1.68 ) mortality rates . The incidence of PAF ( 8.9 % and 9.9 % ) and the 30-day ( 25.1 % and 27.6 % ) and 1-year ( 38.4 % and 42.5 % ) mortality rates of patients with PAF were similar in the TE and PTE , although PAF in the TE occurred in older and sicker patients than those in the PTE . After adjustment for conventional risk factors , PAF was associated with significantly lower 30-day ( odds ratio , 0.64 ; 95 % confidence interval , 0.44 to 0.94 ) and 1-year ( relative risk , 0.69 ; 95 % confidence interval , 0.54 to 0.88 ) mortality rates compared with the PTE . CONCLUSIONS Patients with AMI who develop PAF in the TE have significantly worse short- and long-term prognoses than patients without PAF , mostly due to their worse risk profile . After adjustment for confounding factors , patients with PAF in the TE have a better overall outcome than counterparts in the PTE , probably reflecting the better management of patients with AMI in the TE", "OBJECTIVES We examined the clinical predictors and angiographic and clinical outcomes associated with atrial fibrillation in the setting of acute myocardial infa rct ion ( MI ) . BACKGROUND This condition has been studied primarily in prethrombolytic era small trials . METHODS We compared baseline clinical characteristics , short-term clinical and angiographic outcomes and 1-year mortality of patients enrolled in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries ( GUSTO-I ) trial with atrial fibrillation on admission electrocardiography ( n = 1,026 [ 2.5 % ] ) or after enrollment ( n = 3,254 [ 7.9 % ] ) and those without atrial fibrillation ( n = 36,611 [ 89.6 % ] ) . Univariable and multivariable analyses were used to assess relations between baseline factors and the development of atrial fibrillation . RESULTS Patients with any atrial fibrillation more often had three-vessel coronary artery disease and initial Thrombolysis in Myocardial Infa rct ion ( TIMI ) grade < 3 flow than those without the arrhythmia . In-hospital stroke was increased in patients with atrial fibrillation ( 3.1 % vs. 1.3 % , p = 0.0001 ) , mainly ischemic stroke ( 1.8 % vs. 0.5 % , p = 0.0001 ) . Significant multivariable predictors of later atrial fibrillation included advanced age , higher peak creatine kinase levels , worse Killip class and increased heart rate . The unadjusted mortality rate was significantly higher at 30 days ( 14.3 % vs. 6.2 % , p = 0.0001 ) and at 1 year ( 21.5 % vs. 8.6 % , p < 0.0001 ) in patients with atrial fibrillation . The adjusted 30-day mortality rate remained significantly higher with any ( odds ratio [ OR ] 1.3 , 95 % confidence interval [ CI ] 1.2 to 1.4 ) or later ( OR 1.4 , 95 % CI 1.3 to 1.5 ) atrial fibrillation but not with baseline atrial fibrillation ( OR 1.1 , 95 % CI 0.88 to 1.3 ) . CONCLUSIONS Atrial fibrillation in the setting of acute MI independently predicts stroke and 30-day mortality . More aggressive treatment strategies in this subgroup may be warranted and deserve further study", "AIMS Atrial fibrillation ( AF ) is a common complication in patients with acute myocardial infa rct ion and is associated with an increase in the risk of death . The excess mortality associated with AF complicating acute myocardial infa rct ion has not been studied in detail . Observations indicate that AF facilitates induction of ventricular arrhythmias , which may increase the risk of sudden cardiovascular death ( SCD ) . A close examination of the mode of death could potentially provide useful knowledge to guide further investigations and treatments . METHODS AND RESULTS We analysed the relation between AF/atrial flutter ( AFL ) and modes of death in 5983 consecutive patients discharged alive after an acute myocardial infa rct ion screened in the TR And olapril Cardiac Evaluation registry . This cohort of patients with an enzyme-verified acute myocardial infa rct ion was admitted to 27 centres in 1990 - 92 . Survival status was obtained 2 years after screening of the last patient . An independent endpoint committee assessed the modes of death . Left ventricular ejection fraction was determined in all the screened patients and information about presence or absence of AF/AFL was prospect ively collected . Sustained or paroxysmal AF/AFL was observed in 1149 patients ( 19 % ) during hospitalization . During follow-up , 1659 patients ( 34 % ) died : 482 ( 50 % ) patients with AF/AFL and 1177 ( 30 % ) patients without AF/AFL , P<0.001 . SCD occurred in 536 , non-SCD occurred in 725 , and 398 died of non-cardiovascular causes ( includes 142 unclassifiable cases ) . The adjusted risk ratio of AF/AFL for total mortality was 1.33 ( 95 % CI : 1.19 - 1.49 ; P<0.0001 ) and the risk ratio for SCD was 1.31 ( 95 % CI : 1.07 - 1.60 ; P<0.009 ) . The adjusted risk ratio of AF/AFL for non-SCD was 1.43 ( 95 % CI : 1.21 - 1.70 ; P<0.0001 ) . CONCLUSION The excess mortality observed in patients with AF/AFL following acute myocardial infa rct ion is due to a significant increase in both SCD and non-SCD", "Background : Atrial fibrillation ( AF ) is a common complication of acute myocardial infa rct ion ( AMI ) with a reported incidence of 7–18 % . Recently , P‐wave signal‐averaged electrocardiogram ( P‐SAECG ) has been used to assess the risk of paroxysmal AF attacks in some diseases . The aim of this study was to determine prospect ively whether patients with AMI at risk for paroxysmal AF would be identified by P‐SAECG and other clinical variables", "Atrial fibrillation ( AF ) is common during the course of acute myocardial infa rct ion and is associated with left atrial ( LA ) dilatation . However , the role of LA depolarization abnormality on the electrocardiogram ( ECG ) in the setting of LA dilatation was not studied in this context . Patients admitted with non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) who developed new-onset AF ( International Classification of Diseases , Ninth Revision code 427.31 ) were prospect ively identified . Baseline ECGs and echocardiograms before the admission event were review ed . Follow-up was directed toward pertinent cardiovascular events , atrial tachyarrhythmias , and death as end points . Of 101 patients with NSTEMI who had new-onset AF , 88 had current echocardiograms and 69 had LA dilatation ( 78 % ) . Total follow-up was 24 months ( mean 21.4 ) . Prolonged P-wave duration ( > or = 110 ms ) and decreased left ventricular fractional shortening were most significant in those with LA dilatation and were independently associated with AF . In those with LA dilatation , the prevalence of such abnormal atrial depolarization on ECGs was 56 % . AF ( 43 % vs 15 % ; p = 0.03 ) and heart failure ( 63 % vs 35 % ; p = 0.03 ) occurred more often in this subset , but there was no difference in mortality . However , the overall prevalence of late cardiovascular complications in this subset was higher ( 71 % vs 45 % ; p = 0.02 ) compared with that of immediate complications ( 20 % vs 26 % ; p = 0.60 ) . In conclusion , there is higher recurrence of AF in patients with NSTEMI who have a combination of electrocardiographic and echocardiographic LA abnormalities compared with those without", "BACKGROUND Atrial fibrillation ( AF ) or flutter occurring after myocardial infa rct ion may occur alone or in association with other complications . Whether the arrhythmia portends a poor prognosis independent of other complications with contemporary therapy is unknown . METHODS AND RESULTS As part of the Global Use of Strategies To Open occluded coronary arteries ( GUSTO-III ) trial , we evaluated whether postinfa rct ion complications were associated with the subsequent development of AF and whether AF independently predicted death over periods of 30 days and 1 year . Information including exact timing was collected on deaths and major in-hospital postinfa rct ion complications up to 30 days . Of the 13,858 patients with sinus rhythm at enrollment , 906 later had AF or flutter and 12 , 952 did not . We compared outcomes between these 2 groups , adjusting for differences in baseline characteristics and prefibrillation complications . Worsening heart failure , hypotension , third-degree heart block , and ventricular fibrillation were independent predictors of new-onset AF . The unadjusted odds ratio ( OR ) for death among patients with versus those without AF was 2.74 ( 95 % confidence interval [ 95 % CI ] , 2.56 - 3.34 ) . After adjusting for baseline differences , the OR was reduced to 1.63 ( 95 % CI , 1.31 - 2.02 ) . Adjustment for other in-hospital complications before the onset of AF further reduced the OR to 1.49 ( 95 % CI , 1.17 - 1.89 ) . CONCLUSIONS Atrial fibrillation or flutter occurs secondary to other postinfa rct ion complications but independently portends a worse prognosis . Prevention and management may improve outcome" ]

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[ "Treatment strategies in patients with major depression not responding to first-line sertraline treatment", "Assessing Response Profiles from Incomplete Longitudinal Clinical Trial Data Under Regulatory Considerations", "Assessing effectiveness of treatment of depression in primary care. Partially randomised preference trial.", "Effectiveness of St John's wort in major depression: a randomized controlled trial.", "Cross-sectional and prospective study of exercise and depressed mood in the elderly : the Rancho Bernardo study.", "Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.", "Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients.", "Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression", "Light therapy for seasonal affective disorder. A review of efficacy.", "Effects of Adding Cognitive Therapy to Fluoxetine Dose Increase on Risk of Relapse and Residual Depressive Symptoms in Continuation Treatment of Major Depressive Disorder", "Preventing recurrent depression using cognitive therapy with and without a continuation phase: a randomized clinical trial.", "Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy, and usual general practitioner care for patients with depression. I: Clinical effectiveness", "Psychodynamic psychotherapy and clomipramine in the treatment of major depression.", "Compliance with antidepressants in a primary care setting, 1: Beyond lack of efficacy and adverse events.", "Exercise and depressive symptoms: a comparison of aerobic and resistance exercise effects on emotional and physical function in older persons with high and low depressive symptomatology.", "Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms", "Cost-Effectiveness of a Program to Prevent Depression Relapse in Primary Care", "A novel augmentation strategy for treating resistant major depression.", "Combining psychotherapy and antidepressants in the treatment of depression.", "Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects.", "Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder: randomised controlled trial.", "Effectiveness of antidepressant pharmacotherapy: the impact of medication compliance and patient education.", "Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder.", "Sertraline versus imipramine to prevent relapse in chronic depression.", "ACCOUNTING FOR DROPOUT BIAS USING MIXED-EFFECTS MODELS", "The efficacy of exercise as a long-term antidepressant in elderly subjects: a randomized, controlled trial.", "Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care.", "A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs.", "Double-Blind Study of High-Dose Fluoxetine Versus Lithium or Desipramine Augmentation of Fluoxetine in Partial Responders and Nonresponders to Fluoxetine", "A randomized trial of a specific adherence enhancement program in sertraline-treated adults with major depressive disorder in a primary care setting" ]

[ "Abstract . Rationale : A large proportion of patients with major depression do not respond sufficiently to any first-line treatment . Objectives : The aim of this study was to compare a strategy of sertraline dose increase with a strategy of adding mianserin in patients with major depression insufficiently responding to 6 weeks of open treatment with sertraline , controlling for the effect of an extended duration of treatment . Methods : One thous and six hundred and twenty-nine patients , 18–65 years of age , with major depression scoring at least 18 on the 17-item Hamilton depression scale ( HDS ) were treated openly with 50 mg/day sertraline , and patients who after 4 weeks had not responded ( achieving at least a 50 % reduction in score on the HDS ) were treated with 100 mg/day sertraline for an additional 2-week period . The patients who had still not responded were then r and omised to double-blind treatment for an additional 5 weeks with either 100 mg/day sertraline plus placebo , 200 mg/day sertraline plus placebo or 100 mg/day sertraline plus 30 mg/day mianserin . Results : After 6 weeks of open treatment , 60 % had responded and 22 % had dropped out , leaving 295 non-responding patients ( 18 % ) for r and omisation . In the intention-to-treat- analysis , continuing the treatment with 100 mg/day sertraline result ed in response in 70 % of the non-responders , similar to the response rate ( 67 % ) obtained in the patients who had mianserin added . However , increasing the sertraline dose to 200 mg/day result ed in a lower response rate at 56 % ( P<0.05 ) . Similar results were seen in the completers . A substantial increase in the accumulated response rate from week 6 to week 8 was seen . There was no influence of baseline variables , including the presence of melancholic features on the overall post-r and omisation response rate . Conclusion : After 6 weeks of insufficient antidepressant treatment with 50–100 mg/day sertraline , a continued treatment with 100 mg/day sertraline can be considered until at least week 8 before considering changing strategy , unless the condition deteriorates", "Treatment effects are often evaluated by comparing change over time in outcome measures . However , valid analyses of longitudinal data can be problematic , particularly when some data are missing for reasons related to the outcome . In choosing the primary analysis for confirmatory clinical trials , regulatory agencies have for decades favored the last observation carried forward ( LOCF ) approach for imputing missing values . Many advances in statistical methodology , and also in our ability to implement those methods , have been made in recent years . The characteristics of data from acute phase clinical trials can be exploited to develop an appropriate analysis for assessing response profiles in a regulatory setting . These data characteristics and regulatory considerations will be review ed . Approaches for h and ling missing data are compared along with options for modeling time effects and correlations between repeated measurements . Theory and empirical evidence are utilized to support the proposal that likelihood-based mixed-effects model repeated measures ( MMRM ) approaches , based on the missing at r and om assumption , provide superior control of Type I and Type II errors when compared with the traditional LOCF approach , which is based on the more restrictive missing completely at r and om assumption . It is further reasoned that in acute phase clinical trials , unstructured modeling of time trends and within-subject error correlations may be preferred", "BACKGROUND There is a mismatch between the wish of a patient with depression to have counselling and the prescription of antidepressants by the doctor . AIMS To determine whether counselling is as effective as antidepressants for depression in primary care and whether allowing patients to choose their treatment affects their response . METHOD A partially r and omised preference trial , with patients r and omised to either antidepressants or counselling or given their choice of either treatment . The treatment and follow-up were identical in the r and omised and patient preference arms . RESULTS There were 103 r and omised and 220 preference patients in the trial . We found : no differences in the baseline characteristics of the r and omised and preference groups ; that the two treatments were equally effective at 8 weeks , both for the r and omised group and when the r and omised and patient preference groups for a particular treatment were combined ; and that expressing a preference for either treatment conferred no additional benefit on outcome . CONCLUSIONS These data challenge several assumptions about the most appropriate treatment for depression in a primary care setting", "CONTEXT Extracts of St John 's wort are widely used to treat depression . Although more than 2 dozen clinical trials have been conducted with St John 's wort , most have significant flaws in design and do not enable meaningful interpretation . OBJECTIVE To compare the efficacy and safety of a st and ardized extract of St John 's wort with placebo in out patients with major depression . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States . PARTICIPANTS Two hundred adult out patients ( mean age , 42.4 years ; 67.0 % female ; 85.9 % white ) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression ( HAM-D ) score of at least 20 . INTERVENTION Participants completed a 1-week , single-blind run-in of placebo , then were r and omly assigned to receive either St John 's wort extract ( n = 98 ; 900 mg/d for 4 weeks , increased to 1200 mg/d in the absence of an adequate response thereafter ) or placebo ( n = 102 ) for 8 weeks . MAIN OUTCOME MEASURES The primary outcome measure was rate of change on the HAM-D over the treatment period . Secondary measures included the Beck Depression Inventory ( BDI ) , Hamilton Rating Scale for Anxiety ( HAM-A ) , the Global Assessment of Function ( GAF ) scale , and the Clinical Global Impression-Severity and -Improvement scales ( CGI-S and CGI-I ) . RESULTS The r and om coefficient analyses for the HAM-D , HAM-A , CGI-S , and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction ( for HAM-D scores , P<.001 , P = .16 , and P = .58 , respectively ) . Analysis of covariance showed nonsignificant effects for BDI and GAF scores . The proportion of participants achieving an a priori definition of response did not differ between groups . The number reaching remission of illness was significantly higher with St John 's wort than with placebo ( P = .02 ) , but the rates were very low in the full intention-to-treat analysis ( 14/98 [ 14.3 % ] vs 5/102 [ 4.9 % ] , respectively ) . St John 's wort was safe and well tolerated . Headache was the only adverse event that occurred with greater frequency with St John 's wort than placebo ( 39/95 [ 41 % ] vs 25/100 [ 25 % ] , respectively ) . CONCLUSION In this study , St John 's wort was not effective for treatment of major depression", "This study examined cross-sectional and prospect i ve associations of exercise with depressed mood in a community-based sample of older men and women ( aged 50 - -89 years in 1984 - -1987 ) in southern California . Regular strenuous exercise and exercise > or =3 times per week were reported ; depressed mood was assessed by using the Beck Depression Inventory ( BDI ) . After exclusion of persons with categorical depression and those rating themselves largely or extremely physically limited during the previous month , data on 932 men and 1,097 women were available for cross-sectional analysis . Exercise and depressed mood were reassessed for 404 men and 540 women in 1992 - -1995 ; these data were the focus of prospect i ve analyses . In 1984 - -1987 , exercise rates were high ( > 80 % ) , and average BDI scores were low . Cross-sectional analyses indicated that before and after adjustment for covariates , exercise was significantly associated with less depressed mood . However , prospect i ve analyses of the 944 persons who attended both clinic visits indicated no association between baseline exercise and either follow-up BDI score ( p > 0.10 ) or change in BDI score between baseline and follow-up ( p > 0.10 ) . Results confirm that exercisers have less depressed mood . However , exercise does not protect against future depressed mood for those not clinical ly depressed at baseline", "CONTEXT Extracts of Hypericum perforatum ( St John 's wort ) are widely used for the treatment of depression of varying severity . Their efficacy in major depressive disorder , however , has not been conclusively demonstrated . OBJECTIVE To test the efficacy and safety of a well-characterized H perforatum extract ( LI-160 ) in major depressive disorder . DESIGN AND SETTING Double-blind , r and omized , placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States . PARTICIPANTS Adult out patients ( n = 340 ) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale ( HAM-D ) of at least 20 . INTERVENTIONS Patients were r and omly assigned to receive H perforatum , placebo , or sertraline ( as an active comparator ) for 8 weeks . Based on clinical response , the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg . Responders at week 8 could continue blinded treatment for another 18 weeks . MAIN OUTCOME MEASURES Change in the HAM-D total score from baseline to 8 weeks ; rates of full response , determined by the HAM-D and Clinical Global Impressions ( CGI ) scores . RESULTS On the 2 primary outcome measures , neither sertraline nor H perforatum was significantly different from placebo . The r and om regression parameter estimate for mean ( SE ) change in HAM-D total score from baseline to week 8 ( with a greater decline indicating more improvement ) was -9.20 ( 0.67 ) ( 95 % confidence interval [ CI ] , -10.51 to -7.89 ) for placebo vs -8.68 ( 0.68 ) ( 95 % CI , -10.01 to -7.35 ) for H perforatum ( P = .59 ) and -10.53 ( 0.72 ) ( 95 % CI , -11.94 to -9.12 ) for sertraline ( P = .18 ) . Full response occurred in 31.9 % of the placebo-treated patients vs 23.9 % of the H perforatum-treated patients ( P = .21 ) and 24.8 % of sertraline-treated patients ( P = .26 ) . Sertraline was better than placebo on the CGI improvement scale ( P = .02 ) , which was a secondary measure in this study . Adverse-effect profiles for H perforatum and sertraline differed relative to placebo . CONCLUSION This study fails to support the efficacy of H perforatum in moderately severe major depression . The result may be due to low assay sensitivity of the trial , but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy", "BACKGROUND The necessity of antidepressant continuation-phase therapy following acute-phase response has result ed in the need to characterize the longer-term efficacy and safety of all new medications . Previous studies using \" extension \" protocol s suggest that mirtazapine has sustained antidepressant effects . The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy , using a more rigorous , r and omized , placebo-controlled discontinuation design . METHOD An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine ( flexibly titrated , 15 - 45 mg/day ) . Thereafter , 156 fully remitted patients ( according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores ) were r and omly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo . RESULTS Mirtazapine therapy reduced the rate of depressive relapse by more than half , with 43.8 % of patients relapsing on treatment with placebo as compared with 19.7 % of the mirtazapine-treated patients . The discontinuation rate due to adverse events was 11.8 % for active mirtazapine therapy versus 2.5 % for placebo . Although weight gain was significantly greater in the group receiving active medication during the double-blind phase ( p = .001 ) , patients taking mirtazapine gained only 1.4 kg ( 3.1 lb ) across the 40 weeks of continuation therapy , and there was no difference in the rates of weight gain as a newonset adverse event . CONCLUSION Continuation-phase therapy with mirtazapine is effective and well tolerated", "BACKGROUND This was the first controlled continuation phase study ( up to 1-year total treatment ) to evaluate the safety and efficacy of bupropion SR for decreasing the risk for relapse of depression in patients who responded to bupropion SR . METHODS Patients with recurrent major depression were treated with bupropion SR 300 mg/day during an 8-week open-label phase . Responders ( based on Clinical Global Impressions Scale for Improvement of Illness scores ) entered a r and omized , double-blind phase where they received bupropion SR 300 mg/day or placebo for up to 44 weeks . After r and omization , relapse was defined as the point at which the investigator intervened by withdrawing the patient from the study to treat depression . RESULTS Four hundred twenty-three patients were r and omized . A statistically significant difference in favor of bupropion SR over placebo was seen in the time to treatment intervention for depression when survival curves were compared ( log-rank test , p = .003 ) . Statistically significant separation between bupropion SR and placebo began at double-blind week 12 ( p < .05 ) . Adverse events in bupropion SR-treated patients accounted for 9 % and 4 % of discontinuations from the open-label and double-blind phases , respectively . CONCLUSIONS Bupropion SR was shown to be effective and well tolerated in decreasing the risk for relapse of depression for up to 44 weeks", "Bright artificial light has been found effective in reducing winter depressive symptoms of Seasonal Affective Disorder , although conclusions about the true magnitude of treatment effect and importance of time of day of light exposure have been limited by method ologic problems . Individual subjects ' data from 14 research centers study ing 332 patients over 5 years were analyzed with a pooled clustering technique . Overall , 2500-lux intensity light exposure for at least 2 hours daily for 1 week result ed in significantly more remissions -- Hamilton Depression Rating Scale ( HAM-D ) score reduction of 50 % or more to a level under 8 - -when administered in the early morning ( 53 % ) than in the evening ( 38 % ) or at midday ( 32 % ) . All three times were significantly more effective than dim light controls ( 11 % ) . Dual daily exposures ( morning-plus-evening light ) provided no benefit over morning light alone . In morning-evening crossovers , remission rates were 62 % under morning light alone , compared with 28 % under evening light alone , with a differential morning-evening response present in 59 % of morning responders compared with 10 % of evening responders ( p less than 0.001 ) . Remission rates with morning light were highest given low severity at baseline ( HAM-D score of 10 - 16 : 67 % remission ) , as compared with moderate-to-severe cases ( HAM-D score above 16 : approximately 40 % remission ) where no morning-evening differences were found . Firmer conclusions await treatment studies with larger sample sizes and full assessment of atypical vegetative symptoms seen in winter depression but underrepresented in the Hamilton scale . Longer treatment course and greater light intensity may help clarify clinical response despite the impossibility of achieving a conventional blind placebo control", "Patients with major depressive disorder remain at risk for relapse following remission and often continue to experience subthreshold symptoms . This study compared the rate of relapse of major depressive disorder and the prevalence of residual depressive symptoms during the continuation phase for patients treated with fluoxetine dose increase alone or in combination with cognitive therapy . A total of 132 out patients with major depressive disorder who achieved remission with 8 weeks of treatment with fluoxetine 20 mg had the dose increased to 40 mg . They were r and omized to receive cognitive therapy or medication management alone and were followed for up to 28 weeks for depressive relapse and change in depressive symptoms . A total of 47 ( 35.6 % ) out of 132 patients did not complete the 28-week continuation phase . Rates of discontinuation or relapse did not differ significantly between the groups . Change in residual symptoms or wellbeing as measured by Hamilton Depression Scale score or Symptom Question naire self-report also did not differ between groups . In this sample of out patients in continuation phase treatment for major depressive disorder , the combination of cognitive therapy and fluoxetine 40 mg failed to yield any significant benefit in symptoms or relapse rates over fluoxetine 40 mg alone during 28 weeks of follow-up", "BACKGROUND Cognitive therapy ( CT ) may reduce depressive relapse and recurrence when patients learn and use the associated skills . Reported relapse and recurrence rates after CT discontinuation vary widely . The factors that determine when CT is preventive remain unidentified . We developed continuation-phase CT ( C-CT ) to teach responders skills to prevent relapse . This is the first r and omized trial comparing CT with and without a continuation phase in responders to CT who were vulnerable , given their history of recurrent unipolar depression . METHODS Patients aged 18 to 65 years ( n = 156 ) with recurrent DSM-IV major depressive disorder ( MDD ) entered 20 sessions of acute-phase CT ( A-CT ) . Unmedicated responders ( ie , no MDD and 17-item Hamilton Rating Scale for Depression score < or = 9 ; n = 84 ) were r and omized to either 8 months ( 10 sessions ) of C-CT or control ( evaluation without CT ) . Follow-up lasted an additional 16 months . A clinician blind to assignment evaluated relapse and recurrence ( ie , DSM-IV MDD ) . RESULTS Over an 8-month period , C-CT significantly reduced relapse estimates more than control ( 10 % vs 31 % ) . Over 24 months , including the CT-free follow-up , age of onset and quality of remission during the late phase of A-CT each interacted with condition assignment to influence durability of effects . In patients with early-onset MDD , C-CT significantly reduced relapse and recurrence estimates ( 16 % vs 67 % in control ) . When patients had unstable remission during late A-CT , C-CT significantly reduced relapse and recurrence estimates to 37 % ( vs 62 % in control ) . CONCLUSIONS Findings suggest that 8 months of C-CT significantly reduces relapse and recurrence in the highest-risk patients with recurrent MDD . Risk factors influenced the necessity for C-CT", "Abstract Objective : To compare the clinical effectiveness of general practitioner care and two general practice based psychological therapies for depressed patients . Design : Prospect i ve , controlled trial with r and omised and patient preference allocation arms . Setting : General practice s in London and greater Manchester . Participants : 464 of 627 patients presenting with depression or mixed anxiety and depression were suitable for inclusion . Interventions : Usual general practitioner care or up to 12 sessions of non-directive counselling or cognitive-behaviour therapy provided by therapists . Main outcome measures : Beck depression inventory scores , other psychiatric symptoms , social functioning , and satisfaction with treatment measured at baseline and at 4 and 12 months . Results : 197 patients were r and omly assigned to treatment , 137 chose their treatment , and 130 were r and omised only between the two psychological therapies . All groups improved significantly over time . At four months , patients r and omised to non-directive counselling or cognitive-behaviour therapy improved more in terms of the Beck depression inventory ( mean ( SD ) scores 12.9 ( 9.3 ) and 14.3 ( 10.8 ) respectively ) than those r and omised to usual general practitioner care ( 18.3 ( 12.4 ) ) . However , there was no significant difference between the two therapies . There were no significant differences between the three treatment groups at 12 months ( Beck depression scores 11.8 ( 9.6 ) , 11.4 ( 10.8 ) , and 12.1 ( 10.3 ) for non-directive counselling , cognitive-behaviour therapy , and general practitioner care ) . Conclusions : Psychological therapy was a more effective treatment for depression than usual general practitioner care in the short term , but after one year there was no difference in outcome", "OBJECTIVE The authors compared a combination of clomipramine and psychodynamic psychotherapy with clomipramine alone in a r and omized controlled trial among patients with major depression . METHODS Seventy-four patients between the ages of 20 and 65 years who were assigned to ten weeks of acute outpatient treatment for major depression were studied . Bipolar disorder , psychotic symptoms , severe substance dependence , organic disorder , past intolerance to clomipramine , and mental retardation were exclusion criteria . RESULTS Marked improvement was noted in both treatment groups . Combined treatment was associated with less treatment failure and better work adjustment at ten weeks and with better global functioning and lower hospitalization rates at discharge . A cost savings of 2,311 dollars per patient in the combined treatment group , associated with lower rates of hospitalization and fewer lost work days , exceeded the expenditures related to providing psychotherapy . CONCLUSIONS Provision of supplemental psychodynamic psychotherapy to patients with major depression who are receiving antidepressant medication is cost-effective", "BACKGROUND Treatment guidelines recommend antidepressant treatment be continued for at least 6 months to ensure maximal improvement and to prevent relapse . Naturalistic studies show that the average length of treatment is shorter than 6 months and that dropout rates are high . Factors leading patients to discontinuation of therapy are not well understood . This study investigates when and why patients stop treatment and whether they inform their doctors . METHOD Patients ( N = 272 ) receiving antidepressant therapy due to an episode of major depressive disorder ( DSM-IV ) were asked to complete an antidepressant compliance question naire . Patients were then telephoned monthly while they continued on antidepressant therapy , up to 6 months . During each call , patients were asked st and ard questions . RESULTS By endpoint , 53 % of patients had discontinued antidepressant treatment . The most common reason given was \" feeling better . \" However , different dropout reasons were prevalent at different times after initiation of therapy . Overall , 24 % of the patients did not inform their physician about stopping the antidepressant medication . The likelihood of patients ' informing their physicians differed according to the patients ' reasons for discontinuation and according to the patients ' perceptions of their relationship with their physicians . CONCLUSION These results provide new guidelines for improving compliance . Strategy should be adapted to the stage of treatment , as patients ' reasons for discontinuation vary as treatment progresses . The attitude of the physician and the information provided by the physician significantly influence whether patients inform the physician when they discontinue antidepressant therapy", "This study examines and compares the effect of aerobic and resistance exercise on emotional and physical function among older persons with initially high or low depressive symptomatology . Data are from the Fitness , Arthritis and Seniors Trial , a trial among 439 persons 60 years or older with knee osteoarthritis r and omized to health education ( control ) , resistance exercise , or aerobic exercise groups . Depressive symptoms ( assessed by the Center for Epidemiologic Studies --Depression scale ) and physical function ( disability , walking speed , and pain ) were assessed at baseline and after 3 , 9 , and 18 months . Compared with results for the control group , aerobic exercise significantly lowered depressive symptoms over time . No such effect was observed for resistance exercise . The reduction in depressive symptoms with aerobic exercise was found both among the 98 participants with initially high depressive symptomatology and among the 340 participants with initially low depressive symptomatology and was the strongest for the most compliant persons . Aerobic and resistance exercise significantly reduced disability and pain and increased walking speed both , and to an equal extent , in persons with high depressive symptomatology and persons with low depressive symptomatology", "Abstract Objectives : To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice . To determine whether the outcomes were similar for patients with r and omly allocated treatment and those expressing a treatment preference . Design : R and omised controlled trial , with patient preference arms . Follow up at 8 weeks and 12 months and abstract ion of GP case notes . Setting : 31 general practice s in Trent region . Participants : Patients aged 18–70 who met research diagnostic criteria for major depression ; 103 patients were r and omised and 220 patients were recruited to the preference arms . Main outcome measures : Difference in mean Beck depression inventory score ; time to remission ; global outcome assessed by a psychiatrist using all data sources ; and research diagnostic criteria . Results : At 12 months there was no difference between the mean Beck scores in the r and omised arms . Combining the r and omised and patient preference groups , the difference in Beck scores was 0.4 ( 95 % confidence interval −2.7 to 3.5 ) . Patients choosing counselling did better than those r and omised to it ( mean difference in Beck score 4.6 , 0.0 to 9.2 ) . There was no difference in the psychiatrist 's overall assessment of outcome between any of the groups . 221/265 ( 83 % ) of participants with a known outcome had a remission . Median time to remission was shorter in the group r and omised to antidepressants than the other three groups ( 2 months v 3 months ) . 33/221 ( 15 % ) patients had a relapse . Conclusions : Generic counselling seems to be as effective as antidepressant treatment for mild to moderate depressive illness , although patients receiving antidepressants may recover more quickly . General practitioners should allow patients to have their preferred treatment . What is already known on this topic Antidepressants and specific psychological interventions are effective in major depression . Generic counselling has not previously been compared with antidepressants in primary care What this study adds 12 months after starting treatment , generic counselling is as effective as antidepressants Patients treated with antidepressants may recover more quickly Given a choice , more patients opt for counselling Patients who choose counselling may benefit more than those with no strong", "Objective . Evaluate the incremental cost-effectiveness of a depression relapse prevention program in primary care Material s and Methods . Primary care patients initiating antidepressant treatment completed a st and ardized telephone assessment 6–8 weeks later . Those recovered from the current episode but at high risk for relapse ( based on history of recurrent depression or dysthymia ) were offered r and omization to usual care or a relapse prevention intervention . The intervention included systematic patient education , two psychoeducational visits with a depression prevention specialist , shared decision-making regarding maintenance pharmacotherapy , and telephone and mail monitoring of medication adherence and depressive symptoms . Outcomes in both groups were assessed via blinded telephone assessment s at 3 , 6 , 9 , and 12 months and health plan cl aims and accounting data . Results . Intervention patients experienced 13.9 additional depression-free days during a 12-month period ( 95 % CI , −1.5 to 29.3 ) . Incremental costs of the intervention were $ 273 ( 95 % CI , $ 102 to $ 418 ) for depression treatment costs only and $ 160 ( 95 % CI , −$173 to $ 512 ) for total outpatient costs . Incremental cost-effectiveness ratio was $ 24 per depression-free day ( 95 % CI , −$59 to $ 496 ) for depression treatment costs only and $ 14 per depression-free day ( 95 % CI , −$35 to $ 248 ) for total outpatient costs . Conclusions . A program to prevent depression relapse in primary care yields modest increases in days free of depression and modest increases in treatment costs . These modest differences reflect high rates of treatment in usual care . Along with other recent studies , these findings suggest that improved care of depression in primary care is a prudent investment of health care re sources", "OBJECTIVE Treatment-resistant depression is a significant public health concern ; drug switching or augmentation often produce limited results . The authors hypothesized that fluoxetine could be augmented with olanzapine to successfully treat resistant depression . METHOD An 8-week double-blind study was conducted with 28 patients who were diagnosed with recurrent , nonbipolar , treatment-resistant depression without psychotic features . Subjects were r and omly assigned to one of three groups : olanzapine plus placebo , fluoxetine plus placebo , or olanzapine plus fluoxetine . RESULTS Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression . The benefits of olanzapine monotherapy were modest . Olanzapine plus fluoxetine produced significantly greater improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week . There were no significant differences between treatment groups on extrapyramidal measures nor significant adverse drug interactions . CONCLUSIONS Olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared to either agent alone", "OBJECTIVE To compare the efficacy of antidepressants with that of antidepressants plus psychotherapy ( \" combined therapy \" ) in the treatment of depression . METHODS 6 month r and omised clinical trial of antidepressants ( N=84 ) and combined therapy ( N=83 ) in ambulatory patients with Major Depression and a 17-item HDRS baseline score of at least 14 points . The antidepressant protocol provides for three successive steps in case of intolerance or inefficacy : fluoxetine , amitriptyline and moclobemide . The combined therapy condition consists , in addition to pharmacotherapy , of 16 sessions of Short Psychodynamic Supportive Psychotherapy . Efficacy is assessed using the 17-item HDRS , the CGI of Severity and of Improvement , the depression subscale of the SCL-90 , and the Quality of Life Depression Scale . The data analysis is conducted on three sample s : the intention-to-treat sample , the per protocol sample and the observed cases sample . RESULTS After r and omisation , 32 % of the patients refused the proposed pharmacotherapy while 13 % refused the proposed combined therapy . In 24 weeks , 40 % of the patients who started with the pharmacotherapy stopped medication ; 22 % of those receiving the combined therapy did so . The difference in success rates is statistically significant , favouring combined therapy , in 23 % , 31 % and 62 % of the patients after 8 , 16 and 24 weeks of treatment , respectively . At week 24 , the mean success rate is 40.7 % in the pharmacotherapy group and 59.2 % in the combined therapy group . CONCLUSION Patients found combined treatment significantly more acceptable , they were significantly less likely to drop out of combined therapy and , ultimately , significantly more likely to recover . Combined therapy is preferable to pharmacotherapy in the treatment of ambulatory patients with major depression", "BACKGROUND This study was design ed to evaluate the effect of combining bupropion sustained release ( SR ) with venlafaxine , paroxetine , or fluoxetine in patients who reported unacceptable sexual dysfunction when treated with monotherapy with the latter 3 agents . METHOD Following a minimum of 6 weeks of antidepressant treatment with a selective serotonin reuptake inhibitor ( SSRI ) or venlafaxine ( a serotonin-norepinephrine reuptake inhibitor ) , eligible subjects received a further 8 weeks of monitored combination therapy with bupropion SR at a dose of 150 mg/day with no alterations to index antidepressant dosing . RESULTS There was a clinical ly significant benefit in 14 ( 78 % ) of 18 partial responders or nonresponders , and 33 % ( N = 6 ) achieved a full response ( chi2= 8.06 , df = 2 , p = .017 ) . Sexual dysfunction , particularly a decrease in orgasmic delay , was also significantly improved with combination therapy ( men : paired t = -2.1 , df = 6 , p = .08 ; women : paired t = -3.0 , df = 7 , p = .02 ) . Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels ( F = 6.89 , df = 4,24 ; p = .001 ) accompanied by a decrease in O-desmethylvenlafaxine ( F = 14.26 ; df = 4,24 ; p < .0005 ) during combined treatment with bupropion SR . There were no statistically significant changes in plasma levels of SSRIs ( paroxetine and fluoxetine ) during the trial . CONCLUSION Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs . Further investigation of combination treatments under r and omized , double-blind conditions is recommended", "BACKGROUND Depression is common in later life . AIMS To determine whether exercise is effective as an adjunct to antidepressant therapy in reducing depressive symptoms in older people . METHOD Patients were r and omised to attend either exercise classes or health education talks for 10 weeks . Assessment s were made \" blind \" at baseline , and at 10 and 34 weeks . The primary outcome was seen with the 17-item Hamilton Rating Scale for Depression ( HRSD ) . Secondary outcomes were seen with the Geriatric Depression Scale , Clinical Global Impression and Patient Global Impression . RESULTS At 10 weeks a significantly higher proportion of the exercise group ( 55 % v. 33 % ) experienced a greater than 30 % decline in depression according to HRSD ( OR=2.51 , P=0.05 , 95 % CI 1.00 - 6.38 ) . CONCLUSIONS Because exercise was associated with a modest improvement in depressive symptoms at 10 weeks , older people with poorly responsive depressive disorder should be encouraged to attend group exercise activities", "This study was design ed to investigate the impact of a time-phased patient education program ( RHYTHMS ) on medication compliance and treatment outcomes of primary care patients diagnosed with major depression and started on antidepressant pharmacotherapy . Two hundred forty-six depressed patients , diagnosed and treated at one of three outpatient clinics affiliated with the Kaiser-Permanente Northwest Region ( KPNW ) healthcare system , were r and omly assigned to either receive or not receive ( usual care ) the educational material s by mail . Depression severity and functional impairment affecting patients ' quality of life were assessed at baseline and 4 , 12 , and 30 weeks later . Self-reported impressions of improvement and patient satisfaction with treatment were also assessed at follow-up . Clinical assessment data were obtained using an interactive voice response ( IVR ) system . Study subjects were compensated $ 5 , $ 10 , $ 15 , and $ 25 for completing each assessment ( Baseline to Week 30 , respectively ) . Upon study completion , prescription fill data of the subjects were extracted from the KPNW Pharmacy System for analysis of medication compliance . Most of the study subjects ( 63.5 % ) responded to the pharmacotherapy treatment by study end-point . Few statistically significant differences in either treatment outcomes or duration of medication compliance were found between the treatment groups , and significant differences found were of fairly small magnitude . Patients not receiving the educational material s initially exhibited a more positive response to treatment ( Week 4 ) , but this difference did not persist at later follow-ups and was associated with significantly higher relapse rates . A strong time-dose relationship was evident between the duration of the initial treatment episode and treatment outcomes at follow-up , but r and omized treatment assignment did not influence the duration of initial medication compliance . Educational programs design ed to encourage depressed patients to obtain adequate pharmacotherapy likely provide medical benefits . Such benefits appear to be relatively subtle and method ological differences between studies contribute to inconsistent conclusions concerning observed benefits . The intent of providing time-phased educational material s to patients is to maximize the relevance of such information by synchronizing it with typical recovery processes and issues . This study suggests that additional efforts at engaging patients earlier after the initiation of treatment might be of most benefit", "OBJECTIVE Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder . The authors studied a specific omega-3 fatty acid , the ethyl ester of eicosapentaenoic acid ( E-EPA ) , as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy . METHOD Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week , parallel-group , double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy . Seventeen of the patients were women , and three were men . RESULTS Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment . CONCLUSIONS It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own", "BACKGROUND Chronic depressions are common , disabling and under-treated , and long-term treatment is little studied . We report the continuation phase results from a long-term treatment study . METHODS After 12 weeks of acute phase treatment in a double-blind , r and omized , parallel-group , multi-center trial of sertraline or imipramine , patients with chronic depression ( > or = 2 years in major depression , or major depression superimposed on dysthymia ) continued study drug for 16 weeks . Initially , 635 patients were r and omized to sertraline or imipramine in a 2:1 ratio . Nonresponders after 12 weeks entered a 12-week double-blind crossover trial of the alternate medication . Entry into continuation treatment required at least a satisfactory response ( partial remission ) to initial or crossover treatment . RESULTS Of 239 acute or crossover responders to sertraline , 60 % entered continuation in full remission and 40 % with a partial remission . These proportions were identical for imipramine patients ( n = 147 ) . For both drug groups , over two-thirds of those entering in full remission retained it . For those entering in partial remission , over 40 % achieved full remission . Patients requiring crossover treatment were less likely to maintain or improve their response during continuation treatment . The two drugs did not differ significantly in response distribution , drop out rates or discontinuation due to side effects during continuation treatment . LIMITATIONS The absence of a placebo group constrains interpretation of our results , but chronic depressions have low placebo response rates . CONCLUSIONS Most chronic depression patients who remit with 12 weeks of sertraline or imipramine treatment maintain remission during 16 weeks of continuation treatment . Most patients with a satisfactory therapeutic response ( partial remission ) after 12 weeks of treatment maintain it or further improve . Patients treated with imipramine experienced more side effects , but both drugs were well tolerated", "Treatment effects are often evaluated by comparing change over time in outcome measures . However , valid analyses of longitudinal data can be problematic when subjects discontinue ( dropout ) prior to completing the study . This study assessed the merits of likelihood-based repeated measures analyses ( MMRM ) compared with fixed-effects analysis of variance where missing values were imputed using the last observation carried forward approach ( LOCF ) in accounting for dropout bias . Comparisons were made in simulated data and in data from a r and omized clinical trial . Subject dropout was introduced in the simulated data to generate ignorable and nonignorable missingness . Estimates of treatment group differences in mean change from baseline to endpoint from MMRM were , on average , markedly closer to the true value than estimates from LOCF in every scenario simulated . St and ard errors and confidence intervals from MMRM accurately reflected the uncertainty of the estimates , whereas st and ard errors and confidence intervals from LOCF underestimated uncertainty", "BACKGROUND Pharmacological treatment of depression in geriatric patients is often difficult . Although unsupervised exercise has been shown to benefit younger depressed patients , there is no evidence that unsupervised exercise can be used as a maintenance treatment for depression in elderly patients . Our aim was to test the feasibility and efficacy of unsupervised exercise as a long-term treatment for clinical depression in elderly patients . METHODS We studied 32 subjects ( 71.3 + /- 1.2 years of age , mean + /- SE ) in a 20-week , r and omized , controlled trial , with follow-up at 26 months . Subjects were community-dwelling patients with major or minor depression or dysthymia . Exercisers engaged in 10 weeks of supervised weight-lifting exercise followed by 10 weeks of unsupervised exercise . Controls attended lectures for 10 weeks . No contact was made with either group after 20 weeks until final follow-up . Blinded assessment was made with the Beck Depression Inventory ( BDI ) , the Philadelphia Geriatric Morale Scale , and Ewart 's Self Efficacy Scale at 20 weeks and with the BDI and physical activity question naire at 26 months . RESULTS Patients r and omized to the exercise condition completed 18 + /- 2 sessions of unsupervised exercise during Weeks 10 to 20 . The BDI was significantly reduced at both 20 weeks and 26 months of follow-up in exercisers compared with controls ( p < .05-.001 ) . At the 26-month follow-up , 33 % of the exercisers were still regularly weight lifting , versus 0 % of controls ( p < .05 ) . CONCLUSIONS Unsupervised weight-lifting exercise maintains its antidepressant effectiveness at 20 weeks in depressed elderly patients . Long-term changes in exercise behavior are possible in some patients even without supervision", "OBJECTIVES The aim of this study was to determine both the clinical and cost-effectiveness of usual general practitioner ( GP ) care compared with two types of brief psychological therapy ( non-directive counselling and cognitive-behaviour therapy ) in the management of depression as well as mixed anxiety and depression in the primary care setting . DESIGN The design was principally a pragmatic r and omised controlled trial , but was accompanied by two additional allocation methods allowing patient preference : the option of a specific choice of treatment ( preference allocation ) and the option to be r and omised between the psychological therapies only . Of the 464 patients allocated to the three treatments , 197 were r and omised between the three treatments , 137 chose a specific treatment , and 130 were r and omised between the psychological therapies only . The patients underwent follow-up assessment s at 4 and 12 months . SETTING The study was conducted in 24 general practice s in Greater Manchester and London . SUBJECTS A total of 464 eligible patients , aged 18 years and over , were referred by 73 GPs and allocated to one of the psychological therapies or usual GP care for depressive symptoms . INTERVENTIONS The interventions consisted of brief psychological therapy ( 12 sessions maximum ) or usual GP care . Non-directive counselling was provided by counsellors who were qualified for accreditation by the British Association for Counselling . Cognitive-behaviour therapy was provided by clinical psychologists who were qualified for accreditation by the British Association for Behavioural and Cognitive Psychotherapies . Usual GP care included discussion s with patients and the prescription of medication , but GPs were asked to refrain from referring patients for psychological intervention for at least 4 months . Most therapy sessions took place on a weekly basis in the general practice s. By the 12-month follow-up , GP care in some cases did include referral to mental healthcare specialists . MAIN OUTCOME MEASURES The clinical outcomes included depressive symptoms , general psychiatric symptoms , social function and patient satisfaction . The economic outcomes included direct and indirect costs and quality of life . Assessment s were carried out at baseline during face-to-face interviews as well as at 4 and 12 months in person or by post . RESULTS At 4 months , both psychological therapies had reduced depressive symptoms to a significantly greater extent than usual GP care . Patients in the psychological therapy groups exhibited mean scores on the Beck Depression Inventory that were 4 - 5 points lower than the mean score of patients in the usual GP care group , a difference that was also clinical ly significant . These differences did not generalize to other measures of outcome . There was no significant difference in outcome between the two psychological therapies when they were compared directly using all 260 patients r and omised to a psychological therapy by either r and omised allocation method . At 12 months , the patients in all three groups had improved to the same extent . The lack of a significant difference between the treatment groups at this point result ed from greater improvement of the patients in the GP care group between the 4- and 12-month follow-ups . At 4 months , patients in both psychological therapy groups were more satisfied with their treatment than those in the usual GP care group . However , by 12 months , patients who had received non-directive counselling were more satisfied than those in either of the other two groups . There were few differences in the baseline characteristics of patients who were r and omised or expressed a treatment preference , and no differences in outcome between these patients . Similar outcomes were found for patients who chose either psychological therapy . Again , there were no significant differences between the two groups at 4 or 12 months . Patients who chose counselling were more satisfied with treatment than those who chose", "BACKGROUND In depressed patients , low blood levels of eicosapentaenoic acid are seen . We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients . METHODS We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a st and ard antidepressant . Patients were r and omized on a double-blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1 , 2 , or 4 g/d for 12 weeks in addition to unchanged background medication . Patients underwent assessment using the 17-item Hamilton Depression Rating Scale , the Montgomery-Asberg Depression Rating Scale , and the Beck Depression Inventory . RESULTS Forty-six ( 88 % ) of 52 patients receiving ethyl-eicosapentaenoate and 14 ( 78 % ) of 18 patients receiving placebo completed the 12-week study with no serious adverse events . The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales . In the intention-to-treat group , 5 ( 29 % ) of 17 patients receiving placebo and 9 ( 53 % ) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50 % reduction on the Hamilton Depression Rating Scale score . In the per- protocol group , the corresponding figures were 3 ( 25 % ) of 12 patients for placebo and 9 ( 69 % ) of 13 patients for the 1-g/d group . The 2-g/d group showed little evidence of efficacy , whereas the 4-g/d group showed nonsignificant trends toward improvement . All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo , with strong beneficial effects on items rating depression , anxiety , sleep , lassitude , libido , and suicidality . CONCLUSION Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating depression in patients who remained depressed despite adequate st and ard therapy", "In a previous study , of 41 depressed patients who had not responded to fluoxetine 20 mg/day , 53 % were treated with high-dose fluoxetine ( 40–60 mg/ day ) and responded ( i.e. , their 17-item Hamilton Rating Scale for Depression [ HAM-D-17 ] score was < 7 ) versus 29 % and 25 % of patients treated with fluoxetine plus lithium ( 300–600 mg/day ) or fluoxetine plus desipramine ( 25–50 mg/day ) , respectively . We wanted to assess whether these findings could be replicated in a larger sample of depressed out patients . We identified 101 out patients with major depressive disorder ( 52 men and 49 women ; mean age , 41.6 + 10.6 years ) who were either partial responders ( n = 49 ) or nonresponders ( n = 52 ) to 8 weeks of treatment with fluoxetine 20 mg/ day . These patients were r and omized to 4 weeks of double-blind treatment with high-dose fluoxetine ( 40–60 mg/day ) , fluoxetine plus lithium ( 300–600 mg/day ) , or fluoxetine plus desipramine ( 25–50 mg/day ) . In the overall group of patients ( N = 101 ) , there was no significant difference in response rates across the three treatment groups ( high-dose fluoxetine , 42.4 % ; fluoxetine plus desipramine , 29.4 % ; fluoxetine plus lithium , 23.5 % ) . Dropout rates were also comparable , ranging from 9.1 % ( high-dose fluoxetine ) to 14.7 % ( fluoxetine plus desipramine and fluoxetine plus lithium ) . There were also no significant differences in response rates across the three treatment groups among partial responders ( high-dose fluoxetine , 50.0 % ; fluoxetine plus desipramine , 33.3 % ; fluoxetine plus lithium , 33.3 % ) and nonresponders ( high-dose fluoxetine , 35.3 % ; fluoxetine plus desipramine , 26.3 % ; fluoxetine plus lithium , 12.5 % ) . At the end of the study , the mean lithium level was 0.37 + 0.15 mEq/L ( n = 27 ; range , 0.1–0.8 mEq/L ) among lithium-treated patients , and the mean desipramine level was 104.7 + 58.8 ng/mL ( n = 22 ; range , 25–257 ng/mL ) . There were no significant relationships between lithium or desipramine blood levels and degree of improvement ( as measured by the change in HAM-D-17 score ) . We found no significant differences in efficacy among these three treatment strategies among patients who had failed to respond adequately to 8 weeks of treatment with fluoxetine 20 mg/day , although the high-fluoxetine group was associated with nonsignificantly higher response rates in both partial responders and nonresponders", "Adherence to drug therapy is a limitation in treatment success for major depressive disorder ( MDD ) . The influence of RHYTHMS , an information and ongoing interactive program design ed by Pfizer Pharmaceuticals , to address patient adherence to sertraline therapy was evaluated in a primary care setting using a r and omized , double-blind , parallel group controlled trial over 29 weeks . Remission was the primary outcome evaluated . At study completion , no statistically significance between group differences was noted for remission rates , treatment adherence or mean Hamilton Depression Rating Scale ( HDRS ) score . However , the RHYTHMS group reported significantly greater satisfaction with knowledge received about depression and its treatment and demonstrated significantly greater satisfaction with treatment received . We conclude that the application of RHYTHMS in a primary care setting has a substantial role in improving satisfaction with sertraline treatment by patients with MDD" ]

[ "19939861", "2387789", "18352997", "17938389" ]

[ "Depression, anxiety and obsessive-compulsive symptoms and quality of life in children with attention-deficit hyperactivity disorder (ADHD) during three-month methylphenidate treatment", "The adolescent outcome of hyperactive children diagnosed by research criteria: I. An 8-year prospective follow-up study.", "Effects of methylphenidate on quality of life in children with both developmental coordination disorder and ADHD.", "Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and Elaboration" ]

[ "The current study was design ed to investigate the changes that occur in depression , anxiety , obsessive — compulsive symptoms and health-related quality of life during methylpheni date ( MPH ) treatment in children with attention-deficit hyperactivity disorder ( ADHD ) . Forty-five treatment naive children with ADHD , aged 8—14 , were assessed based on self , parent and teacher reports at the baseline and at the end of the first and third month of MPH treatment regarding changes in inattention , hyperactivity , impulsivity , depression , anxiety and obsessive — compulsive symptoms . Changes in the quality of life were also noted . Repeated measures of analysis of variance ( ANOVA ) tests with Bonferroni corrections were conducted in order to evaluate the data . Symptoms of inattention , hyperactivity and impulsivity were significantly reduced ( p < 0.017 ) following a three-month MPH treatment . There were significant decreases in depression ( p = 0.004 ) , trait anxiety ( p = 0.000 ) and checking compulsion symptom scores ( p = 0.001 ) . Moreover , parents reported significant improvements in psychosocial ( p = 0.001 ) and total scores ( p = 0.009 ) of quality of life , despite no change in physical health scores ( p > 0.05 ) . Children ’s ratings of quality of life measures showed no significant changes in physical health and psychosocial scores ( p > 0.05 ) , while total scores significantly improved ( p = 0.001 ) after the treatment . Over a three-month MPH treatment , depression , trait anxiety and checking compulsion symptoms decreased and quality of life seemed to improve along with those of inattention , hyperactivity and impulsivity", "The psychiatric outcome is reported for a large sample of hyperactive children ( N = 123 ) , meeting research diagnostic criteria , and normal control children ( N = 66 ) followed prospect ively over an 8-year period into adolescence . Over 80 % of the hyperactives were attention deficit hyperactivity disorder ( ADHD ) and 60 % had either oppositional defiant disorder and /or conduct disorder at outcome . Rates of antisocial acts were considerably higher among hyperactives than normals , as were cigarette and marijuana use and negative academic outcomes . The presence of conduct disorder accounted for much though not all of these outcomes . Family status of hyperactives was much less stable over time than in the normal subjects . The use of research criteria for diagnosing children as hyperactive identifies a pattern of behavioral symptoms that is highly stable over time and associated with considerably greater risk for family disturbance and negative academic and social outcomes in adolescence than has been previously reported", "Measurement of health-related quality of life ( HRQOL ) in attention-deficit-hyperactivity disorder ( ADHD ) gives a more complete picture of day-to-day functioning and treatment effects than behavioural rating alone . The aim of this pilot study was to investigate the impact of the combined diagnoses of developmental coordination disorder ( DCD ) and ADHD on HRQOL , and the effectiveness of methylpheni date ( MPH ) on HRQOL . HRQOL was established using the Dutch-Child-AZL-TNO- Quality -of-Life ( DUX-25 ) and the TNO-AZL-Child- Quality -of-Life ( TACQOL ) question naires , completed by children and parents . HRQOL of these children was compared with that of 23 age- and sex-matched healthy controls . Twenty-three children ( 21 males , two females ; mean age 8 y 6 mo , [ SD 3 mo ] range 7 y-10 y 8 mo ) with ADHD/DCD entered a 4-week , open-label MPH study , after MPH-sensitivity was established , in a double-blind , placebo-controlled trial . In these children 's self- and proxy reports , impact of both DCD and ADHD was reflected in lower general well-being ( self and proxy report p=0.001 ) due to lower functioning in motor ( selfp=0.026 ; proxy 0.001 ) , autonomic ( self p<0.001 ; proxy p=0.047 ) , cognitive ( self p=0.001 ; proxy p=0.01 ) , and social ( self and proxy p<0.001 ) domains . HRQOL scores improved in 18 children receiving MPH ( p=0.001 ) versus controls . The ADHD /DCD group also demonstrated a significant improvement in ADHD symptoms ( p<0.001 ) and motor functioning ( p<0.001 ) . Additional motor therapy will still be needed in about half of the children with ADHD/DCD receiving MPH , within multimodal treatment including educational and psychosocial assistance", "Editor 's Note : In order to encourage dissemination of the STROBE Statement , this article is being published simultaneously in Annals of Internal Medicine , Epidemiology , and PLoS Medicine . It is freely accessible on the Annals of Internal Medicine Web site ( www.annals.org ) and will also be published on the Web sites of Epidemiology and PLoS Medicine . The authors jointly hold the copyright of this article . For details on further use , see the STROBE Web site ( www.strobe-statement.org ) . Rational health care practice s require knowledge about the etiology and pathogenesis , diagnosis , prognosis , and treatment of diseases . R and omized trials provide valuable evidence about treatments and other interventions . However , much of clinical or public health knowledge comes from observational research ( 1 ) . About 9 of 10 research papers published in clinical specialty journals describe observational research ( 2 , 3 ) . The STROBE Statement Reporting of observational research is often not detailed and clear enough to assess the strengths and weaknesses of the investigation ( 4 , 5 ) . To improve the reporting of observational research , we developed a checklist of items that should be addressed : the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement ( Appendix Table ) . Items relate to the title , abstract , introduction , methods , results , and discussion sections of articles . The STROBE Statement has recently been published in several journals ( 6 ) . Our aim is to ensure clear presentation of what was planned , done , and found in an observational study . We stress that the recommendations are not prescriptions for setting up or conducting studies , nor do they dictate methodology or m and ate a uniform presentation . Appendix Table . The Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) Statement : Checklist of Items That Should Be Addressed in Reports of Observational Studies STROBE provides general reporting recommendations for descriptive observational studies and studies that investigate associations between exposures and health outcomes . STROBE addresses the 3 main types of observational studies : cohort , casecontrol , and cross-sectional studies . Authors use diverse terminology to describe these study design s. For instance , follow-up study and longitudinal study are used as synonyms for cohort study , and prevalence study as a synonym for cross-sectional study . We chose the present terminology because it is in common use . Unfortunately , terminology is often used incorrectly ( 7 ) or imprecisely ( 8) . In Box 1 , we describe the hallmarks of the 3 study design s. Box 1 . Main Study Design s Covered by STROBE The Scope of Observational Research Observational studies serve a wide range of purpose s , from reporting a first hint of a potential cause of a disease to verifying the magnitude of previously reported associations . Ideas for studies may arise from clinical observations or from biological insight . Ideas may also arise from informal looks at data that lead to further explorations . Like a clinician who has seen thous and s of patients and notes 1 that strikes her attention , the research er may note something special in the data . Adjusting for multiple looks at the data may not be possible or desirable ( 9 ) , but further studies to confirm or refute initial observations are often needed ( 10 ) . Existing data may be used to examine new ideas about potential causal factors , and may be sufficient for rejection or confirmation . In other instances , studies follow that are specifically design ed to overcome potential problems with previous reports . The latter studies will gather new data and will be planned for that purpose , in contrast to analyses of existing data . This leads to diverse viewpoints , for example , on the merits of looking at subgroups or the importance of a predetermined sample size . STROBE tries to accommo date these diverse uses of observational research from discovery to refutation or confirmation . Where necessary , we will indicate in what circumstances specific recommendations apply . How to Use this Paper This paper is linked to the shorter STROBE paper that introduced the items of the checklist in several journals ( 6 ) , and forms an integral part of the STROBE Statement . Our intention is to explain how to report research well , not how research should be done . We offer a detailed explanation for each checklist item . Each explanation is preceded by an example of what we consider transparent reporting . This does not mean that the study from which the example was taken was uniformly well reported or well done ; nor does it mean that its findings were reliable , in the sense that they were later confirmed by others : It only means that this particular item was well reported in that study . In addition to explanations and examples , we included boxes with supplementary information . These are intended for readers who want to refresh their memories about some theoretical points or be quickly informed about technical background details . A full underst and ing of these points may require study ing the textbooks or method ological papers that are cited . STROBE recommendations do not specifically address topics , such as genetic linkage studies , infectious disease modeling , or case reports and case series ( 11 , 12 ) . As many of the key elements in STROBE apply to these design s , authors who report such studies may nevertheless find our recommendations useful . For authors of observational studies that specifically address diagnostic tests , tumor markers , and genetic associations , STARD ( 13 ) , REMARK ( 14 ) , and STREGA ( 15 ) recommendations may be particularly useful . The Items in the STROBE Checklist We now discuss and explain the 22 items in the STROBE checklist ( Appendix Table ) and give published examples for each item . Some examples have been edited by removing citations or spelling out abbreviations . Eighteen items apply to all 3 study design s , whereas 4 are design -specific . Starred items ( for example , item 8) indicate that the information should be given separately for cases and controls in casecontrol studies , or exposed and unexposed groups in cohort and cross-sectional studies . We advise authors to address all items somewhere in their paper , but we do not prescribe a precise location or order . For instance , we discuss the reporting of results under a number of separate items , while recognizing that authors might address several items within a single section of text or in a table . Title and Abstract 1(a ) Indicate the study 's design with a commonly used term in the title or the abstract . Example Leukaemia incidence among workers in the shoe and boot manufacturing industry : a casecontrol study ( 18 ) . Explanation Readers should be able to easily identify the design that was used from the title or abstract . An explicit , commonly used term for the study design also helps ensure correct indexing of articles in electronic data bases ( 19 , 20 ) . 1(b ) Provide in the abstract an informative and balanced summary of what was done and what was found . Example Background : The expected survival of HIV-infected patients is of major public health interest . Objective : To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population . Design : Population -based cohort study . Setting : All HIV-infected persons receiving care in Denmark from 1995 to 2005 . Patients : Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex , date of birth , and municipality of residence . Measurements : The authors computed KaplanMeier life tables with age as the time scale to estimate survival from age 25 years . Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient 's HIV diagnosis until death , emigration , or 1 May 2005 . Results : 3990 HIV-infected patients and 379 872 persons from the general population were included in the study , yielding 22 744 ( median , 5.8 y/person ) and 2 689 287 ( median , 8.4 y/person ) person-years of observation . Three percent of participants were lost to follow-up . From age 25 years , the median survival was 19.9 years ( 95 % CI , 18.5 to 21.3 ) among patients with HIV infection and 51.1 years ( CI , 50.9 to 51.5 ) among the general population . For HIV-infected patients , survival increased to 32.5 years ( CI , 29.4 to 34.7 ) during the 2000 to 2005 period . In the subgroup that excluded persons with known hepatitis C coinfection ( 16 % ) , median survival was 38.9 years ( CI , 35.4 to 40.1 ) during this same period . The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age , whereas the excess mortality rate increased with increasing age . Limitations : The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years . Conclusions : The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era . However , an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population ( 21 ) . Explanation The abstract provides key information that enables readers to underst and a study and decide whether to read the article . Typical components include a statement of the research question , a short description of methods and results , and a conclusion ( 22 ) . Abstract s should summarize key details of studies and should only present information that is provided in the article . We advise presenting key results in a numerical form that includes numbers of participants , estimates of associations , and appropriate measures of variability and uncertainty ( for example , odds ratios with confidence intervals ) . We regard it insufficient to state only that an exposure is or is not significantly associated with an" ]