In patients older than @ , the main goal of treatment in the last week was in the majority of cases palliative care ( @ % ) .


Patients between @ and @ more often received life-prolonging/curative treatment than older patients ( @ % vs. @ % ) .


Most patient and health care characteristics are similarly related to the main goal of treatment in both age groups .


The patient 's age was independently related to having comfort care as the main goal of treatment .


The main goal of treatment was also independently associated with the patient 's sex , cause and place of death and the time already in treatment .


Age is independently related to the main goal of treatment in the last week of life with people over @ being more likely to receive palliative care and less likely to receive curative/life-prolonging treatment compared with those aged @-@ .


This difference could be due to the patient 's wishes but could also be the result of the attitudes of care givers towards the treatment of older people .


To investigate baricitinib ( LY@ , formerly INCB@ ) , a novel , oral inhibitor of JAK@/JAK@ in patients with moderate to severe rheumatoid arthritis ( RA ) despite treatment with methotrexate .


In this phase IIb study , @ patients were randomised @:@:@:@:@ to receive once daily doses of placebo or @ , @ , @ or @mg baricitinib for @weeks .


Patients assigned to @ , @ and @ mg baricitinib continued blinded treatment for an additional @weeks .


Patients assigned to placebo or @ mg baricitinib were reassigned to @ mg twice daily or @ mg once daily baricitinib between weeks @-@ .


The primary endpoint was the proportion of patients in the combined @ and @ mg groups achieving an American College of Rheumatology @ % ( ACR@ ) response versus placebo at week @ .


Significantly more patients in the combined baricitinib @ and @ mg groups compared with placebo achieved an ACR@ response at week @ ( @ % vs @ % , p < @ ) .


At week @ , significant differences versus placebo were also observed in patients achieving ACR@ , ACR@ and remission as measured by Disease Activity Score for @-joint counts , Clinical Disease Activity Index and Simplified Disease Activity Index .


Patients receiving @ , @ , or @mg baricitinib maintained or improved in all measures through @weeks .


Similar proportions of patients experienced at least one adverse event in the placebo and baricitinib groups .


Serious infections developed in three patients receiving baricitinib .


No cases of tuberculosis , herpes zoster , opportunistic infections or deaths were reported .


Dose-dependent decreases in haemoglobin were observed with baricitinib .


Baricitinib improved the signs and symptoms of RA in methotrexate inadequate responders with active disease .


Baricitinib was well tolerated with no unexpected safety findings through week @ .


Modern immunosuppressant regimens have significantly decreased acute rejection rates , but may have increased the risk of graft loss driven by adverse drug reactions ( ADRs ) and medication errors ( MEs ) .


The objectives of this study were to determine the incidence and risk factors for MEs and ADRs and determine the association between transplant outcomes and these events .


This was a post hoc analysis of a prospective , randomized trial that included patients aged > @ years that received a solitary renal transplant at an academic medical center recruited between March @ and July @ .


Patients were divided into groups based on developing a clinical significant ME ( CSME ) , defined as a significant ME that contributed to a hospital admission .


The mean study follow-up was @ @ years .


There were a total of @ MEs and @ ADRs in the @ patients included in the analysis , with @ % of the cohort experiencing at least one ME and @ % experiencing an ADR ; @ patients ( @ % ) experienced a CSME .


Patients that experienced CSMEs had a trend toward more post-transplant readmissions ( median @ -LSB- interquartile range ( IQR ) , @-@ -RSB- versus @ -LSB- @-@ -RSB- ; P = @ ) , higher costs for readmissions ( median $ @,@ -LSB- IQR , $ @ - $ @,@ -RSB- versus $ @ -LSB- $ @ - $ @,@ -RSB- ; P < @ ) , and overall length of stay ( median @ days -LSB- IQR , @-@ @ -RSB- versus @ days -LSB- IQR , @-@ @ -RSB- ; P < @ ) after the CSME event .


CSME patients were also more likely to experience graft failure ( @ % versus @ % ; P = @ ) .


Significant MEs commonly occur in renal transplant recipients and are associated with an increased risk of deleterious clinical outcomes , including subsequent hospital days , costs , and graft loss .


In order to improve lung cancer survival in the UK , a greater proportion of resectable cancers must be diagnosed .


It is likely that resectability rates would be increased by more timely diagnosis .


Aside from screening , the only way of achieving this is to reduce the time to diagnosis in symptomatic cancers .


Currently , lung cancers are mainly diagnosed by general practitioners ( GPs ) using the National Institute for Health and Clinical Excellence ( NICE ) guidelines for urgent referral for chest X-ray , which recommend urgent imaging or referral for patients who have one of a number of chest symptoms for more than @ weeks .


We are proposing to expand this recommendation to include one of a number of chest symptoms of any duration in higher-risk patients .


We intend to conduct a trial of imaging in these higher-risk patients and compare it with NICE guidelines to see if imaging improves stage at diagnosis and resection rates .


This trial would have to be large ( and consequently resource-intensive ) because most of these patients will not have lung cancer , making optimal design crucial .


We are therefore conducting a pilot trial that will ascertain the feasibility of running a full trial and provide key information that will be required in order to design the full trial .


This trial will assess the feasibility and inform the design of a large , UK-wide , clinical trial of a change to the NICE guidelines for urgent referral for chest X-ray for suspected lung cancer .


It utilizes a combination of workshop , health economic , quality of life , qualitative , and quantitative methods in order to fully assess feasibility .


Sildenafil citrate is indicated for the treatment of erectile dysfunction .


An orally disintegrating tablet ( ODT ) of sildenafil citrate has been developed for the benefit of patients who have difficulty swallowing solid dosage forms .


The main goal of this study was to evaluate the bioequivalence of sildenafil ODT with and without water versus marketed sildenafil oral film-coated tablets .


A secondary objective was to evaluate the effects of a high-fat meal on the pharmacokinetics of sildenafil ODT .


The bioequivalence study of sildenafil ODT given with and without water versus marketed sildenafil citrate film-coated oral tablets was conducted in @ subjects .


In a food-effect study , the effect of a standard high-fat meal on the pharmacokinetics of sildenafil ODT was evaluated in @ subjects .


Both studies were randomized , open-label , crossover , single-dose ( @ mg ) studies in healthy men aged @ years .


Plasma samples were collected for @ hours postdose , and pharmacokinetics were determined by using noncompartmental analyses .


All subjects in both studies were Asian males between the ages of @ and @ years .


Sildenafil ODT without water was bioequivalent to the marketed sildenafil film-coated oral tablet as the @ % CI for the ratio of geometric means of Cmax , AUC@ - , and AUC@-last were contained within equivalence limits ( @ % -@ % ) .


When sildenafil ODTs were given with water , the @ % CIs for sildenafil AUC@ - and AUC@-last were contained within the range of @ % to @ % ; however , the @ % CI for sildenafil Cmax was not ( @-@ @ ) .


This difference in Cmax is unlikely to have any clinically meaningful impact .


High-fat meals reduced the rate but not the extent of absorption of sildenafil .


Mean Cmax was reduced by @ % , and median Tmax was delayed from @ hour ( fasting ) to @ hours ( high-fat meal ) .


However , AUC values were comparable between fed and fasted treatments .


Sildenafil ODT , given with or without water , provides equivalent systemic exposure compared with marketed sildenafil film-coated oral tablets , thus offering a convenient alternative method of administration .


Considering the results of the food-effect study , sildenafil ODT should be taken on an empty stomach .


ClinicalTrials.gov identifiers : NCT@ ( bioequivalence ) and NCT@ ( food effect ) .


Facial responses to pain are believed to be an act of communication and , as such , are likely to be affected by the relationship between sender and receiver .


To investigate this effect by examining the impact that variations in communicative relations ( from being alone to being with an intimate other ) have on the elements of the facial language used to communicate pain ( types of facial responses ) , and on the degree of facial expressiveness .


Facial responses of @ healthy participants to phasic heat pain were assessed in three different social situations : alone , but aware of video recording ; in the presence of an experimenter ; and in the presence of an intimate other .


Furthermore , pain catastrophizing and sex ( of participant and experimenter ) were considered as additional influences .


Whereas similar types of facial responses were elicited independent of the relationship between sender and observer , the degree of facial expressiveness varied significantly , with increased expressiveness occurring in the presence of the partner .


Interestingly , being with an experimenter decreased facial expressiveness only in women .


Pain catastrophizing and the sex of the experimenter exhibited no substantial influence on facial responses .


Variations in communicative relations had no effect on the elements of the facial pain language .


The degree of facial expressiveness , however , was adapted to the relationship between sender and observer .


Individuals suppressed their facial communication of pain toward unfamiliar persons , whereas they overtly displayed it in the presence of an intimate other .


Furthermore , when confronted with an unfamiliar person , different situational demands appeared to apply for both sexes .


To assess the incidence and progression of macular atrophy and other key anatomic outcomes over @ to @ years in an early cohort of ranibizumab-treated exudative age-related macular degeneration patients .


Follow-up analysis of long-term outcomes in a multicenter treatment cohort .


Fourteen study sites enrolled @ previous subjects from the ranibizumab treatment arms of the ANCHOR , MARINA , and HORIZON trials .


In a single update visit , clinical assessment and retinal imaging studies were performed , with comparison with each subject 's prior results from the previous trials .


Early Treatment Diabetic Retinopathy Study visual acuity was the primary outcome .


Secondary outcomes , including area of macular atrophy and selected anatomic factors , were analyzed for associations with long-term vision outcomes .


At a mean @ years after ANCHOR or MARINA enrollment , mean visual acuity was @ letters , study eyes having received a mean @ injections per year since the HORIZON study .


Macular atrophy was present in @ % of study eyes , the mean area increasing from @ @ mm ( @ ) at the ANCHOR or MARINA year @ exit to @ @ mm ( @ ) at the SEVEN-UP visit , a growth rate of @ mm ( @ ) / year .


Progression of macular atrophy was associated significantly with visual decline over this @-year period ( P < @ ) , and final macular atrophy lesion size was related significantly to final vision ( P < @ ) .


Other key anatomic outcomes ( macular thickening , thinning , or fluid and submacular fibrosis ) did not have significant effects on vision outcomes .


Seven years after initiation of intensive ranibizumab therapy for exudative age-related macular degeneration , macular atrophy progression and severity were the primary anatomic determinants of visual outcomes .


Poisoning with organophosphorus ( OP ) compounds constitutes a global public health problem .


Standard treatment of OP poisoning involves use of atropine and pralidoxime .


While efficacy of atropine is well-established , clinical experience with pralidoxime in management of OP poisoning is controversial .


To explore the efficacy of add-on pralidoxime with atropine over atropine alone in the management of OP poisoning .


An open-label , parallel-group , randomized clinical trial was conducted in a tertiary care district hospital in West Bengal .


Patients presenting with features of OP poisoning were randomly allocated to receive atropine or atropine-plus-pralidoxime .


Efficacy was assessed by analyzing mortality , requirement for ventilator support and the duration of stay in hospital .


Chi-square test was done to compare the efficacy parameters between the two groups .


A two-tailed P-value < @ was considered as statistically significant .


During the study period , @ patients were screened following which @ patients were randomized to either of the treatment arms .


Add-on pralidoxime therapy did not offer any appreciable benefit over atropine alone in terms of reducing mortality ( @ % ( @/@ ) versus @ % ( @/@ ) ) and ventilator requirement ( @ % ( @/@ ) versus @ % ( @/@ ) ) .


However , patients randomized in the add-on pralidoxime arm experienced longer duration of hospital stay ( @ @ days ) than those receiving atropine-alone therapy ( @ @ days ) ( P < @ ) .


The present study suggested that add-on pralidoxime with atropine therapy did not offer any appreciable benefit over atropine alone in management of OP poisoning .


However , further trials are needed to explore different dosing regimens of pralidoxime in order to determine its efficacy in OP poisoning .


Inflammatory markers show significant associations with cardiovascular events and all-cause mortality after kidney transplantation .


Neopterin , reflecting interferon -- release , may better reflect the proinflammatory state of recipients than less specific markers .


Kidney transplant recipients in the Assessment of LEscol in Renal Transplant ( ALERT ) trial were examined and investigated for an association between serum neopterin and subsequent clinical events : graft loss , major cardiovascular events ( MACE ) and all-cause mortality .


After adjustment for established and emerging risk factors neopterin expressed as neopterin-to-creatinine ratio was significantly associated with MACE ( p = @ ) and all-cause mortality ( p = @ ) .


Endpoints were more frequent with increasing quartiles of neopterin-to-creatinine ratio .


The incidence rates of MACE and all-cause mortality were significantly increased in the upper quartiles compared with the first .


This long-term prospective analysis in stable kidney allograft recipients suggests that neopterin is associated with long-term risk of cardiovascular events and all-cause mortality , but not renal outcomes .


Acute pain can lead to immune dysfunction , which can be partly ameliorated by successful pain management .


Opioids , which are widely used for analgesia , can result in the deterioration of immune function .


This study aimed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery .


@ patients undergoing gastric cancer surgery were equally randomized into two groups .


They received post-operative patient-controlled intravenous ( IV ) analgesia using morphine either with or without flurbiprofen .


Visual analogue scale ( VAS ) scores , Bruggemann comfort scale ( BCS ) scores , morphine consumption , time of first flatus , incidence of nausea/vomiting , and T-lymphocyte subsets ( CD@ , CD@ , and CD@ ) and natural killer cells ( CD@CD@CD@ ) were evaluated .


No significant difference was observed in the VAS scores , BCS scores , and nausea/vomiting incidence between groups .


Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone .


The expression of CD@ , CD@ , CD@/CD@ , and CD@CD@CD@ decreased at @ hours after incision and , except for CD@CD@CD@ , returned to baseline at @ hours after surgery .


Moreover , the expression of CD@CD@CD@ at @ hours after incision and the expression of CD@ , CD@ , CD@/CD@ , and CD@CD@CD@ at @ hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone .


The combination of morphine and flurbiprofen ameliorates the immune depression in Tlymphocyte subsets and natural killer cells and provides a similar analgesic efficacy to morphine alone in patients undergoing gastric cancer surgery .


Vitamin C has important physical and mental health benefits and plasma concentrations reflect recent intakes .


Inflammation associated with any acute illness can lead to poor appetite and low food intake in older people .


The aims of this report were to assess the prevalence and clinical significance of vitamin C deficiency among hospitalized acutely-ill older patients .


Three hundred and twenty two patients ( @ -LSB- @ % -RSB- female ) , aged @ yrs .


and over who took part in a randomized , double blind , placebo-controlled trial had their nutritional status assessed from anthropometric , hematological and biochemical data at baseline , and after @ weeks and @ months .


Vitamin C was measured using a fluorimetric technique and logistic regression analysis was performed to determine the influence of a number of clinical indicators , including tissue inflammation measured using C-reactive protein on vitamin C concentrations .


Clinical outcome measures including symptoms of depression were also compared between patients with vitamin C deficiency and those with normal levels .


At baseline , @ ( @ % ) patients had a vitamin C concentration below @ mol/L indicating biochemical depletion .


The figures at @ weeks and @ months were @ ( @ % ) and @ ( @ % ) patients , respectively .


Older age , male gender , smoking , increased dependency and tissue inflammation were associated with lower vitamin C concentrations .


Patients with vitamin C biochemical depletion had significantly increased symptoms of depression compared with those with higher concentrations at baseline ( p = @ ) and at @ weeks ( p = @ ) .


A high proportion of older patients had sub-optimal vitamin C status and this was associated with increased symptoms of depression .


There is a paucity of research on prehypertension and incident hypertension among postmenopausal Hispanic women .


The overall objective is to determine the multiple risk factors associated with the prevalence of hypertension status at baseline and incident hypertension at year @ in postmenopausal Hispanic women .


For the analyses in this paper , we included a total of @,@ Hispanic women who participated in the Women 's Health Initiative ( WHI ) , a randomized clinical trial and observational study , at baseline ( @-@ ) and at third-year follow-up and for whom blood pressure was measured at year @ ( n = @,@ ) .


Multivariable logistic regression models were used to estimate odds ratios ( ORs ) and @ % confidence intervals ( CIs ) of hypertension status , defined as systolic blood pressure @ mm Hg and/or diastolic blood pressure @ mm Hg , to assess the odds of incident hypertension at year @ of follow-up in association with the factors included in the baseline models .


At year @ of follow-up , @ % of Hispanic women who were normotensive at baseline had progressed to prehypertension , and @ % had become hypertensive .


Among the prehypertensive participants at baseline , @ % had progressed to hypertension .


Compared with normotensive Hispanic women , hypertensive participants had a higher number of cardiovascular risk factors : body mass index @ kg/m ( @ ) ( OR = @ ; @ % CI = @-@ @ ) , a family history of diabetes , stroke , and/or myocardial infarction ( OR = @ ; @ % CI @-@ @ ) , treated hypercholesterolemia ( OR = @ ; @ % CI = @-@ @ ) , treated diabetes ( OR = @ ; @ % CI = @-@ @ ) , and a history of cardiovascular disease ( OR = @ ; @ % CI = @-@ @ ) .


Hispanic women seem to experience an increased risk of incident hypertension in later adulthood .


On a practical level , recommendations for preventive care and population-wide adoption of health behaviors , such as community-focused campaigns to engage in physical activity , may contribute to reductions in hypertension risk factors .


Since the @s , MORA bioresonance therapy has globally been applied in the context of complementary medicine for various indications .


In this regard , practitioners also report successful application in smoking cessation .


The present study aims to verify these reports in a controlled study setting .


In order to achieve the aforementioned objective , we subjected the bioresonance method to a prospective , placebo-controlled , double-blind , parallel-group study involving @ smokers .


In both study groups ( placebo n = @ ; active bioresonance group ; n = @ ) the course of treatment and study conditions were standardized .


@ week ( @ % vs. @ % ) , @ weeks ( @ % vs. @ % ) , @ month ( @ % vs. @ % ) , and @ year ( @ % vs. @ % ) after treatment , the success rate in the verum group differed significantly from the results in the placebo group .


Also , the subjective health condition after treatment and subjective assessment of efficacy , polled after @ week , were significantly more positive among participants in the active bioresonance therapy group than among those in the placebo group .


Adverse side effects were not observed .


According to the findings attained by this pilot study , bioresonance therapy is clinically effective in smoking cessation and does not show any adverse side effects .


Graves ' orbitopathy ( GO ) is a potentially sight-threatening disease for which available medical therapy is not uniformly successful .


Multiple case series suggest that rituximab ( RTX ) may be effective therapy for GO patients .


To determine the efficacy of RTX in GO .


It is a prospective , randomized , double-masked , placebo-controlled trial .


The study was conducted at a large academic private practice .


Twenty five patients with active moderate to severe GO were enrolled , and @ completed the study to the primary endpoint .


Two RTX infusions ( @ mg each ) or two saline infusions were given @ weeks apart .


The primary endpoint was a reduction in clinical activity score ( CAS ) assessed as a continuum and separately as improvement by @ points at @ weeks .


Secondary endpoints included success and failure rates , proportions showing clinically significant improvement in proptosis , lid fissure width , diplopia score , lagophthalmos and disease severity , and changes in those parameters , orbital fat / muscle volume and quality-of-life .


The treatment groups were similar in all parameters at baseline .


The last observation was carried forward if the patient discontinued prematurely .


No differences were found in the proportions of patients showing CAS improvement at @ weeks ( @ % placebo ; @ % RTX , P = @ ) or in CAS decrease from baseline to @ or @ weeks -LSB- mean @ points ( @ SD ) placebo ; @ ( @ SD ) RTX at @ weeks , P = @ -RSB- .


Similarly , there were no differences between groups in any of the secondary endpoints at either @ or @ weeks .


There were four adverse events ( AE ) in @/@ placebo patients and @ AE in @/@ RTX-treated patients ; @/@ moderate or severe AE occurred in the RTX group .


RTX offered no additional benefit over placebo to our patients with active and moderate to severe GO and carried with it non-negligible adverse effects .


Borderline personality disorder ( BPD ) is a severe and highly prevalent mental disorder .


Schema therapy ( ST ) has been found effective in the treatment of BPD and is commonly delivered through an individual format .


A group format ( group schema therapy , GST ) has also been developed .


GST has been found to speed up and amplify the treatment effects found for individual ST. Delivery in a group format may lead to improved cost-effectiveness .


An important question is how GST compares to treatment as usual ( TAU ) and what format for delivery of schema therapy ( format A ; intensive group therapy only , or format B ; a combination of group and individual therapy ) produces the best outcomes .


An international , multicentre randomized controlled trial ( RCT ) will be conducted with a minimum of fourteen participating centres .


Each centre will recruit multiple cohorts of at least sixteen patients .


GST formats as well as the orders in which they are delivered to successive cohorts will be balanced .


Within countries that contribute an uneven number of sites , the orders of GST formats will be balanced within a difference of one .


The RCT is designed to include a minimum of @ patients with BPD .


The primary clinical outcome measure will be BPD severity .


Secondary clinical outcome measures will include measures of BPD and general psychiatric symptoms , schemas and schema modes , social functioning and quality of life .


Furthermore , an economic evaluation that consists of cost-effectiveness and cost-utility analyses will be performed using a societal perspective .


Lastly , additional investigations will be carried out that include an assessment of the integrity of GST , a qualitative study on patients ' and therapists ' experiences with GST , and studies on variables that might influence the effectiveness of GST .


This trial will compare GST to TAU for patients with BPD as well as two different formats for the delivery of GST .


By combining an evaluation of clinical effectiveness , an economic evaluation and additional investigations , it will contribute to an evidence-based understanding of which treatment should be offered to patients with BPD from clinical , economic , and stakeholders ' perspectives .


Nonsteroidal anti-inflammatory drugs relieve osteoarthritis ( OA ) symptoms but cause adverse effects .


D-@ , a mixture of beeswax alcohols , is effective against experimental OA .


A pilot study found that D-@ ( @ mg/day ) for @ weeks improves OA symptoms .


The aim of this study was to investigate the effects of D-@ ( @ to @ mg/day ) administered for @ weeks on OA symptoms .


Patients with OA symptoms were double-blindly randomized to D-@ ( @ mg ) or placebo for @ weeks .


Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index ( WOMAC ) and the visual analog scale ( VAS ) scores .


Patients without symptom improvement at week @ were titrated to two daily tablets .


The primary outcome was the total WOMAC score .


WOMAC pain , joint stiffness and physical function scores , VAS score , and use of rescue medications were secondary outcomes .


All randomized patients ( n = @ ) completed the study , and @ experienced dose titration ( two in the D-@ and @ in the placebo groups ) .


At study completion , D-@ reduced total WOMAC ( @ % ) , pain ( @ % ) , joint stiffness ( @ % ) , and physical function ( @ % ) WOMAC scores , and the VAS score ( @ % ) versus placebo .


These reductions were significant beginning in the second week , and became enhanced during the trial .


The use of rescue medication by the D-@ ( @/@ ) group was lower than that in the placebo ( @/@ ) group .


The treatment was well tolerated .


Seven patients ( two in the D-@ and five in the placebo group ) reported adverse events .


These results indicate that D-@ ( @ to @ mg/day ) for @ weeks ameliorated arthritic symptoms and was well tolerated .


To present the short-term follow-up findings of the Steps to Health study , a randomized trial to evaluate the effectiveness of two employee weight management programs offered within Duke University and the Health System .


A total of @ obese ( body mass index , @ kg/m@ ) employees were randomized @:@ between January @ and June @ to the education-based Weight Management ( WM ) or the WM + arm , which focused on behavior modification .


Employees were contacted to complete a follow-up visit approximately @ months after baseline .


There were no clinically , or statistically , meaningful differences between arms , but there were modest reductions in body mass index , and positive , meaningful changes in diet and physical activity for both arms .


The modest positive effects observed in this study may suggest that to achieve weight loss through the workplace more intensive interventions may be required .


Treatment of neonates and infants with adrenal insufficiency is unsatisfactory because unlicensed hydrocortisone formulations are used .


The objectives were to survey current hydrocortisone prescribing practice and develop a novel hydrocortisone formulation , Infacort .


The use of hydrocortisone by European pediatric endocrinologists was surveyed .


Based on this , an oral hydrocortisone granule formulation , Infacort , with taste masking was developed and evaluated in vitro and then in vivo in a phase I pharmacokinetic study .


The survey showed that pediatricians use a variety of unlicensed compounded adult medications at doses of between @ and @ mg .


Infacort was formulated with a taste-masking layer stable for at least @ minutes in aqueous media and was produced in unit doses of @ , @ , @ , and @ mg .


Infacort @ mg is the bioequivalent of a @-mg hydrocortisone tablet ( mean area under the curve from zero to infinity -LSB- AUC ( @-inf ) -RSB- ratio , @ % ; @ % confidence interval , @-@ % ) .


Mean cortisol maximum concentration ( C ( max ) ) and AUC ( @-inf ) values after administration of Infacort were linear with dose and dose proportional when adjusted for saturable plasma protein binding .


Subjects rated Infacort as `` not good or bad '' for smell ( @ % ) , feel in the mouth ( @ % ) , and taste ( @ % ) .


No serious adverse events were reported .


This phase @ study demonstrates that Infacort is safe , well tolerated , of neutral taste , bioequivalent to hydrocortisone licensed for adults , and shows dose proportionality with respect to cortisol exposure .


Infacort is expected to facilitate optimization of hydrocortisone dosing in neonates and children with adrenal insufficiency ; however , clinical studies will be required to demonstrate efficacy in this patient age group .


Late-onset infections commonly occur in extremely preterm infants and are associated with high rates of mortality and neurodevelopmental impairment .


Hand hygiene alone does not always achieve the desired clean hands , as microorganisms are still present more than @ % of the time .


We hypothesize that glove use after hand hygiene may further decrease these infections .


To determine if nonsterile glove use after hand hygiene before all patient and intravenous catheter contact , compared with hand hygiene alone , prevents late-onset infections in preterm infants .


A prospective , single-center , clinical , randomized trial was conducted in infants admitted to the neonatal intensive care unit who weighed less than @ g and/or had a gestational age of less than @ weeks and were less than @ days old .


There were @ eligible infants , of which @ were enrolled during a @-month period from December @ , @ , to June @ , @ .


Infants were randomly assigned to receive care with nonsterile gloves after hand hygiene ( group A ) or care after hand hygiene alone ( group B ) before all patient and intravenous line ( central and peripheral ) contact .


Study intervention was continued while patients had central or peripheral venous access .


One or more episodes of late-onset ( > @ hours of age ) infection in the bloodstream , urinary tract , or cerebrospinal fluid or necrotizing enterocolitis .


The @ groups were similar in baseline demographic characteristics .


Late-onset invasive infection or necrotizing enterocolitis occurred in @ % of infants ( @ of @ ) in group A compared with @ % of infants ( @ of @ ) in group B ( difference , -@ % ; @ % CI , -@ % to @ % ; P = @ ) .


In group A compared with group B , there were @ % fewer gram-positive bloodstream infections ( @ % -LSB- @ of @ -RSB- vs @ % -LSB- @ of @ -RSB- ; difference , -@ % ; @ % CI , -@ % to -@ % ; P = @ ) and @ % fewer central line-associated bloodstream infections ( @ vs @ per @ central line days ; ratio , @ ; @ % CI , @ to @ ; P = @ ) .


Glove use after hand hygiene prior to patient and line contact is associated with fewer gram-positive bloodstream infections and possible central line-associated bloodstream infections in preterm infants .


This readily implementable infection control measure may result in decreased infections in high-risk preterm infants .


Retrospective analysis of prospectively collected follow-up data for @ years .


To determine the natural history of subsequent morphometric fracture rates at adjacent levels ( one level above or below a previous known baseline fracture ) in a large patient database .


The long-term risk and risk factors for adjacent-level vertebral fractures in patients with osteoporosis are unknown .


The fracture intervention trial is a large randomized , placebo-controlled trial of alendronate treatment for osteoporosis .


Data from both bisphosphonate-treated and bisphosphonate-naive patients ( N = @ , vertebral fracture arm ) was analyzed to detect incident morphometric fracture rates .


During a mean follow-up of @ years , @ % of patients in the alendronate group and @ % in the placebo group experienced adjacent-level vertebral fractures .


The annual rate of adjacent-level vertebral fractures was @ % in the alendronate group , and @ % in the placebo group ( overall , @ % per year in both groups combined ) .


As expected , the thoracolumbar region ( defined as T@ , T@ , and L@ ) seemed to be the most prone to new adjacent-level fractures .


Among females with baseline prevalent fractures at the thoracolumbar junction , who subsequently experienced at least one new fracture anywhere along the spine ( N = @ ) , @ % had a new adjacent-level fracture in this region .


Older age at randomization , lower bone mineral density , inactivity , and placebo therapy were significantly associated with the development of adjacent-level fractures in univariate analysis ( P @ ) .


Multivariate analysis indicated decreased odds of adjacent-level fractures with bisphosphonate therapy and higher bone mineral density , and increased odds with older age at randomization ( P @ ) .


New vertebral fractures adjacent to prevalent fractures occurred relatively infrequently in this treatment trial of alendronate in females with osteoporosis , and were more common with older age at randomization , lower bone mineral density and placebo treatment .


Observational studies suggest that vitamin D may lower the risk of type @ diabetes .


However , data from long-term trials are lacking .


The Vitamin D and Type @ Diabetes ( D@d ) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type @ diabetes .


D@d was designed with support from a U@ planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) .


The final protocol was approved by the D@d Research Group , the data and safety monitoring board , and NIDDK .


Key eligibility criteria are age @ years , BMI of @ ( @ for Asian Americans ) to @ kg/m ( @ ) , increased risk for diabetes ( defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association -LSB- fasting glucose @-@ mg/dL ( @-@ @ mmol/L ) , @-h postload glucose after @-g glucose load @-@ mg/dL ( @-@ @ mmol/L ) , hemoglobin Ac @-@ @ % ( @-@ mmol/mol ) -RSB- ) , and no hyperparathyroidism , nephrolithiasis , or hypercalcemia .


D@d participants are randomized to once-daily vitamin D ( cholecalciferol @,@ IU ) or placebo and followed for an average of @ years .


The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D@d .


Recruitment was initiated at the end of @ .


D@d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type @ diabetes .


Increasing numbers of patients are surviving critical illness , but survival may be associated with a constellation of physical and psychological sequelae that can cause ongoing disability and reduced health-related quality of life .


Limited evidence currently exists to guide the optimum structure , timing , and content of rehabilitation programmes .


There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period .


This paper describes the construct development for a complex rehabilitation intervention intended to promote physical recovery following critical illness .


The intervention is currently being evaluated in a randomised trial ( ISRCTN@ ; funder Chief Scientists Office , Scotland ) .


The intervention was developed using the Medical Research Council ( MRC ) framework for developing complex healthcare interventions .


We ensured representation from a wide variety of stakeholders including content experts from multiple specialties , methodologists , and patient representation .


The intervention construct was initially based on literature review , local observational and audit work , qualitative studies with ICU survivors , and brainstorming activities .


Iterative refinement was aided by the publication of a National Institute for Health and Care Excellence guideline ( No. @ ) , publicly available patient stories ( Healthtalkonline ) , a stakeholder event in collaboration with the James Lind Alliance , and local piloting .


Modelling and further work involved a feasibility trial and development of a novel generic rehabilitation assistant ( GRA ) role .


Several rounds of external peer review during successive funding applications also contributed to development .


The final construct for the complex intervention involved a dedicated GRA trained to pre-defined competencies across multiple rehabilitation domains ( physiotherapy , dietetics , occupational therapy , and speech/language therapy ) , with specific training in post-critical illness issues .


The intervention was from ICU discharge to @ months post-discharge , including inpatient and post-hospital discharge elements .


Clear strategies to provide information to patients/families were included .


A detailed taxonomy was developed to define and describe the processes undertaken , and capture them during the trial .


The detailed process measure description , together with a range of patient , health service , and economic outcomes were successfully mapped on to the modified CONSORT recommendations for reporting non-pharmacologic trial interventions .


The MRC complex intervention framework was an effective guide to developing a novel post-ICU rehabilitation intervention .


Combining a clearly defined new healthcare role with a detailed taxonomy of process and activity enabled the intervention to be clearly described for the purpose of trial delivery and reporting .


These data will be useful when interpreting the results of the randomised trial , will increase internal and external trial validity , and help others implement the intervention if the intervention proves clinically and cost effective .


Foot musculoskeletal deficits are seldom addressed by preventive medicine despite their high prevalence in patients with diabetic polyneuropathy .


To investigate the effects of strengthening , stretching , and functional training on foot rollover process during gait .


A two-arm parallel-group randomized controlled trial with a blinded assessor was designed .


Fifty-five patients diagnosed with diabetic polyneuropathy , @ to @ years-old were recruited .


Exercises for foot-ankle and gait training were administered twice a week , for @ weeks , to @ patients assigned to the intervention group , while @ patients assigned to control group received recommended standard medical care : pharmacological treatment for diabetes and foot care instructions .


Both groups were assessed after @ weeks , and the intervention group at follow-up ( @ weeks ) .


Primary outcomes involved foot rollover changes during gait , including peak pressure ( PP ) .


Secondary outcomes involved time-to-peak pressure ( TPP ) and pressure-time integral ( PTI ) in six foot-areas , mean center of pressure ( COP ) velocity , ankle kinematics and kinetics in the sagittal plane , intrinsic and extrinsic muscle function , and functional tests of foot and ankle .


Even though the intervention group primary outcome ( PP ) showed a not statistically significant change under the six foot areas , intention-to-treat comparisons yielded softening of heel strike ( delayed heel TPP , p = @ ) , better eccentric control of forefoot contact ( decrease in ankle extensor moment , p < @ ; increase in function of ankle dorsiflexion , p < @ ) , earlier lateral forefoot contact with respect to medial forefoot ( TPP anticipation , p < @ ) , and increased participation of hallux ( increased PP and PTI , p = @ ) and toes ( increase in PTI , medium effect size ) .


A slower COP mean velocity ( p = @ ) , and an increase in overall foot and ankle function ( p < @ ) were also observed .


In most cases , the values returned to baseline after the follow-up ( p < @ ) .


Intervention discreetly changed foot rollover towards a more physiological process , supported by improved plantar pressure distribution and better functional condition of the foot ankle complex .


Continuous monitoring of the foot status and patient education are necessary , and can contribute to preserving the integrity of foot muscles and joints impaired by polyneuropathy .


In the Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease , all patients were at high cardiovascular risk , and a substantial proportion were hypertensive .


We performed a post-hoc analysis to explore the hypothesis that telmisartan has a differential action in hypertensive vs. nonhypertensive patients .


The primary four-fold endpoint ( composite of cardiovascular death , myocardial infarction ( MI ) , stroke , or hospitalization for heart failure ) , the secondary three-fold endpoint ( cardiovascular death , MI , and stroke ) , the individual components , new onset of left ventricular hypertrophy ( LVH ) , and new onset of albuminuria were analyzed .


There was no evidence for a significantly differential treatment effect of telmisartan in hypertensive and nonhypertensive patients for any endpoints , although the occurrence of the secondary three-fold endpoint was significantly lower in the telmisartan group ( @ % ) compared with placebo ( @ % , P < @ ) only in hypertensive patients .


Moreover , data from this post-hoc analysis suggest that MI may be less frequent in hypertensive patients treated with telmisartan ( @ vs. @ % ; P < @ ) .


Telmisartan may also reduce new onset of LVH ( nonhypertensive patients P < @ ; hypertensive patients P < @ ) in both subgroups , and new onset of microalbuminuria and macroalbuminuria in hypertensive patients ( P < @ and P < @ , respectively ) .


The effect of telmisartan in hypertensive and nonhypertensive patients at high cardiovascular risk was not different .


This post-hoc analysis suggests that MI may be further reduced by telmisartan in hypertensive patients .


Further investigations are needed to study the hypotheses raised by this explanatory analysis .


It is now recognized that preterm infants @weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure .


However , this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency , with the result that intubation and delayed surfactant therapy are then required .


Infants following this path are known to have a higher risk of adverse outcomes , including death , bronchopulmonary dysplasia and other morbidities .


In an effort to circumvent this problem , techniques of minimally-invasive surfactant therapy have been developed , in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure .


A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea ( the `` Hobart method '' ) has been shown to be feasible and potentially effective , and now requires evaluation in a randomised controlled trial .


This is a multicentre , randomised , masked , controlled trial in preterm infants @-@ weeks gestation .


Infants are eligible if managed on continuous positive airway pressure without prior intubation , and requiring FiO@ @ at an age @hours .


Randomisation will be to receive exogenous surfactant ( @mg/kg poractant alfa ) via the Hobart method , or sham treatment .


Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached ( FiO@ @ , unremitting apnoea or persistent acidosis ) .


Primary outcome is the composite of death or physiological bronchopulmonary dysplasia , with secondary outcomes including incidence of death ; major neonatal morbidities ; durations of all modes of respiratory support and hospitalisation ; safety of the Hobart method ; and outcome at @years .


A total of @ infants will be enrolled .


The trial will be conducted in > @ centres worldwide , and is expected to be completed by end-@ .


Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants .


The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at @-@ weeks gestation .


Patients with excessive daytime sleepiness ( EDS ) are at high risk for driving accidents , and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients .


No study has up to now investigated the effect of modafinil ( a reference drug to treat EDS in patients with hypersomnia ) on on-road driving performance of patients suffering from central hypersomnia .


The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance .


Randomized , crossover , double-blind placebo-controlled trial conducted among @ patients with narcolepsy and @ patients with idiopathic hypersomnia .


Patients were randomly assigned to receive modafinil ( @ mg ) or placebo for @ days prior to the driving test .


Each condition was separated by at least @ weeks of washout .


Mean number of Inappropriate Line Crossings , Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed .


Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo ( F ( @,@ ) = @ , P < @ and F ( @,@ ) = @ , P = @ tendency ) .


Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings ( r = -@ , P < @ ) .


Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia .


The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population .


Healthy gut microflora is essential for oral tolerance and immunity .


A promising approach to preventing allergic diseases in genetically at-risk infants is to introduce administration of probiotics early in life when their immune system is still relatively immature .


In this follow-up study , we aim to determine if early-life supplementation with strains of probiotics has any long-term effect on allergic outcomes .


We analyzed the charts and electronic databases of the PROMPT ( Probiotics in Milk for the Prevention of Atopy Trial ) study cohort .


This cohort consisted of @ infants at risk for allergy who were administered cow 's milk supplemented with or without probiotics from the first day of life to the age of @ months .


The cohort was then followed up until the children were @ years old and clinical outcomes were assessed .


Of the @ children recruited into the study , @ ( @ % ) completed the follow-up .


At the age of @ years , there were no significant differences between the groups in the proportion of children who had developed any asthma , allergic rhinitis , eczema , food allergy and sensitization to inhalant allergens .


Similar growth rates were observed in both groups .


The supplementation of probiotics in early childhood did not play a role in the prevention of allergic diseases .


Clinical/Key Message : Early-life supplementation with probiotics did not change allergic outcomes at @ years of age .


To investigate the efficacy of erlotinib versus docetaxel in previously treated patients with advanced non-small-cell lung cancer ( NSCLC ) in an epidermal growth factor receptor ( EGFR ) - unselected patient population .


The primary end point was progression-free survival ( PFS ) .


Secondary end points included overall survival ( OS ) , response rate , safety , and analyses on EGFR wild-type tumors .


Patients with stage IIIB or IV NSCLC , previous treatment with one or two chemotherapy regimens , evaluable or measurable disease , and performance status of @ to @ were eligible .


From August @ to July @ , @ and @ patients were randomly assigned to erlotinib ( @ mg daily ) and docetaxel ( @ mg/m ( @ ) every @ weeks ) , respectively .


EGFR wild-type NSCLC was present in @ and @ patients in the erlotinib and docetaxel groups , respectively .


Median PFS for erlotinib versus docetaxel was @ v @ months ( hazard ratio -LSB- HR -RSB- , @ ; @ % CI , @ to @ ; P = @ ) , and median OS was @ v @ months ( HR , @ ; @ % CI , @ to @ ; P = @ ) , respectively .


In a subset analysis of EGFR wild-type tumors , PFS for erlotinib versus docetaxel was @ v @ months ( HR , @ ; @ % CI , @ to @ ; P = @ ) , and OS was @ v @ months ( HR , @ ; @ % CI , @ to @ ; P = @ ) , respectively .


Erlotinib failed to show an improvement in PFS or OS compared with docetaxel in an EGFR-unselected patient population .


The OPUS study demonstrated that addition of cetuximab to @-fluorouracil , folinic acid and oxaliplatin ( FOLFOX@ ) significantly improved objective response and progression-free survival ( PFS ) in the first-line treatment of patients with KRAS exon @ wild-type metastatic colorectal cancer ( mCRC ) .


In patients with KRAS exon @ mutations , a detrimental effect was seen upon addition of cetuximab to FOLFOX@ .


The current study reports outcomes in subgroups defined by extended RAS testing .


Samples from OPUS study KRAS exon @ wild-type tumours were reanalysed for other RAS mutations in four additional KRAS codons ( exons @-@ ) and six NRAS codons ( exons @-@ ) using BEAMing .


A cutoff of @ % mutant/wild-type sequences was selected to define RAS status ; we also report an analysis using a cutoff based on the technical lower limit for mutation identification ( @ % ) .


Other RAS mutations were detected in @/@ ( @ % ) evaluable patients .


In the extended analysis of RAS wild-type tumours ( n = @ ) , objective response was significantly improved by addition of cetuximab to FOLFOX@ ( @ % versus @ % ; odds ratio @ -LSB- @ % confidence interval @-@ @ -RSB- ; P = @ ) ; although limited by population size , there also appeared to be trends favouring the cetuximab arm in terms of PFS and overall survival in the RAS wild-type group compared with the RAS evaluable group .


There was no evidence that patients with other RAS mutations benefited from cetuximab , but small numbers precluded precise estimations of treatment effects .


In the combined population of patients with any RAS mutation ( KRAS exon @ or other RAS ) , a clear detrimental effect was associated with addition of cetuximab to FOLFOX@ .


Patients with RAS-mutant mCRC , as defined by mutations in KRAS and NRAS exons @-@ , derive no benefit and may be harmed by the addition of cetuximab to FOLFOX@ .


Restricting cetuximab administration to patients with RAS wild-type tumours will further tailor therapy to maximise benefit .


Refractory chronic low back pain ( CLBP ) often leads to treatment with long-term opioids .


Our goal was to describe the pharmaco-toxicological profile of opioid-treated CLBP patients and identify potential areas for care optimization .


Cross-sectional analysis .


Outpatient primary care .


CLBP patients prescribed @ mg/d of morphine-equivalent dose ( MED ) for @ months .


Self-reported clinical , medication ( verified ) and substance use , and urine drug testing ( UDT ) data were collected .


Participants ( N = @ ) were @ @ years old , @ percent female with CLBP for @ @ years , treated with opioids for @ @ years , with severe disability ( Oswestry Disability Index score : @ @ ) , and average pain score of @ @ ( @-@ rating scale ) .


Participants reported using tobacco ( N = @ ) , alcohol ( N = @ ) and illicit drugs or unprescribed medications ( N = @ ) .


On average , participants took @ @ daily medications , including @ @ pain-modulating and @ @ sedating medications .


Among prescribed opioids , @ percent were long-acting and @ percent were short-acting , with a total of @ @ mg/d of MED .


Sixteen participants were prescribed benzodiazepines and/or zolpidem / zaleplon .


Fifteen participants had UDT positive for illicit drugs or unprescribed medications ; in addition , eight tested positive for alcohol and @ for cotinine .


Compared to those with negative UDTs , those with positive UDTs ( N = @ ) received lower daily `` total '' and `` extended release '' opioid doses , and were more likely to test positive for cotinine ( p < @ ) .


Study findings corroborate existing evidence for high medication burden and high likelihood of substance misuse among opioid-treated CLBP patients .


Further research is needed to help understand causality and ways to optimize care and clinical outcomes .


Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder .


This exploratory study examines differences in lithium response and treatment outcomes in Hispanics , African Americans , and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study ( LiTMUS ) .


LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment ( OPT ; personalized , evidence-based pharmacotherapy ) vs. OPT alone in outpatients with bipolar disorder .


Of @ participants , @ African Americans , @ Hispanics , and @ non-Hispanic whites were examined .


We predicted minority groups would have more negative medication attitudes and higher attrition rates , but better clinical outcomes .


African Americans in the lithium group improved more on depression and life functioning compared to whites over the @ month study .


African Americans in the OPT only group had marginal improvement on depression symptoms .


For Hispanics , satisfaction with life did not significantly improve in the OPT only group , in contrast to whites and African Americans who improved over time on all measures .


Attitudes toward medications did not differ across ethnic/racial groups .


African Americans show some greater improvements with lithium than non-Hispanic whites , and Hispanics showed more consistent improvements in the lithium group .


The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics .


Given that the control group ( regardless of ethnicity/race ) had significant improvements , optimized treatment may be beneficial for any ethnic group .


Approximately @ in @ pregnant women in the United Kingdom are obese .


In addition to being associated generally with poor health , obesity is known to be a contributing factor to pregnancy and birth complications and the retention of gestational weight can lead to long term obesity.This paper describes the protocol for a cluster randomised trial to evaluate whether a weight management intervention for obese pregnant women is effective in reducing women 's Body Mass Index at @ months following birth .


The study is a cluster randomised controlled trial involving @ maternity units across England and Wales .


The units will be randomised , @ to the intervention group and @ to the control group .


@ pregnant women aged @ years or over , with a Body Mass Index of + / = @ ( kg/m@ ) and between @ and @ weeks gestation will be recruited .


Women allocated to the control group will receive usual care and two leaflets giving advice on diet and physical activity .


In addition to their usual care and the leaflets , women allocated to the intervention group will be offered to attend a weekly @ hour weight management group , which combines expertise from Slimming World with clinical advice and supervision from National Health Service midwives , until @ weeks postpartum.Participants will be followed up at @ weeks gestation and at @ weeks , @ months and @ months postpartum .


Body Mass Index at @ months postpartum is the primary outcome .


Secondary outcomes include pregnancy weight gain , quality of life , mental health , waist-hip ratio , child weight centile , admission to neonatal unit , diet , physical activity levels , pregnancy and birth complications , social support , self-regulation and self-efficacy .


A cost effectiveness analysis and process evaluation will also be conducted .


This study will evaluate the effectiveness of a theory-based intervention developed for obese pregnant women .


If successful the intervention will equip women with the necessary knowledge and skills to enable them to make healthier choices for themselves and their unborn child .


Effective medicines have not been introduced for insulin resistance-related fatty liver .


The efficacy and safety of treatment between a combination of metformin and carnitine-orotate complex and metformin alone in a @-week , double-blind , randomized , placebo-controlled study on drug-nave patients with impaired glucose metabolism and fatty liver were compared .


Fifty-two patients with fasting glucose @-@mg / dL or glycosylated hemoglobin ( HbA@c ) @ % and alanine aminotransferase ( ALT ) @-@ IU/L were randomized to receive metformin ( @mg t.i.d. ) , or metformin ( @mg t.i.d. ) and carnitine-orotate complex ( @mg t.i.d. ) for @ weeks ( n = @ per group ) .


The primary end-point was a change from baseline ALT level .


Secondary end-points were changes in fasting glucose , HbA@c , aspartate aminotransferase levels , mitochondrial DNA ( mtDNA ) copy number in the peripheral blood , and urinary output of @-hydroxy-@ ' - deoxyguanosine , a marker of oxidative stress .


The combined treatment reduced ALT level significantly more than metformin alone ( -@ IU/Lvs -@ IU/L , P = @ ) .


The HbA@c levels also decreased significantly in both groups but there was no significant difference between them ( -@ % @ % vs -@ % @ % ) .


Treatment with the complex decreased the urinary @-hydroxy-@ ' - deoxyguanosine level and increased mtDNA copy number significantly compared with metformin alone ( both P < @ ) .


No severe adverse events were observed .


A @-week treatment with metformin and carnitine-orotate complex significantly improved liver function enzyme levels .


This was associated with changes in oxidative stress and mtDNA copy number compared with metformin alone in patients with impaired glucose metabolism and fatty liver ( clinical trial number : KCT@ ) .


There are limited therapeutic options to slow the progression of autosomal dominant polycystic kidney disease ( ADPKD ) .


Recent clinical studies indicate that somatostatin analogues are promising for treating polycystic liver disease and potentially also for the kidney phenotype .


We report on the design of the DIPAK @ ( Developing Interventions to Halt Progression of ADPKD @ ) Study , which will examine the efficacy of the somatostatin analogue lanreotide on preservation of kidney function in ADPKD .


The DIPAK @ Study is an investigator-driven , randomized , multicenter , controlled , clinical trial .


We plan to enroll @ individuals with ADPKD and estimated glomerular filtration rate ( eGFR ) of @-@ mL/min/@ @ m ( @ ) who are aged @-@ years .


Patients will be randomly assigned ( @:@ ) to standard care or lanreotide , @ mg , subcutaneously every @ days for @ weeks , in addition to standard care .


Main study outcome is the slope through serial eGFR measurements starting at week @ until end of treatment for lanreotide versus standard care .


Secondary outcome parameters include change in eGFR from pretreatment versus @ weeks after treatment cessation , change in kidney volume , change in liver volume , and change in quality of life .


Blood and urine will be collected and questionnaires will be filled in following a fixed scheme .


Magnetic resonance imaging will be performed for assessment of kidney and liver volume .


Assuming an average change in eGFR of @ @ ( SD ) mL/min/@ @ m ( @ ) per year in untreated patients , @ patients are needed in each group to detect a @ % reduction in the rate of kidney function loss between treatment groups with @ % power , @-sided = @ , and @ % protocol violators and/or dropouts .


The design is an open randomized controlled trial and measurement of our primary end point does not begin at randomization .


The DIPAK @ Study will show whether subcutaneous administration of lanreotide every @ weeks attenuates disease progression in patients with ADPKD .


Exercise is important for fitness and recovery of older adults after hospitalization for treatment of cardiovascular disease .


Home-based , nurse-led exercise programs may be beneficial .


The aim of this study was to test the effects of a low-intensity , home-based exercise protocol led by an advanced practice nurse on health-related quality of life ( HRQOL ) , physical fitness , and left ventricular ejection fraction ( LVEF ) in older adults after hospital discharge with a cardiovascular disease diagnosis .


The study was randomized and single blinded .


Seventy-seven older adults ( @ years old , mean = @ years old ) were included ; @ subjects in the intervention and @ in the control group completed the study .


The low-intensity , home-based exercise protocol is composed of @-type joint exercises and walking for @ weeks .


The main outcome measures were assessments on the Medical Outcomes Study Short-Form-@ , the Senior Fitness Test , and LVEF at baseline and @ weeks after hospital discharge .


After @ weeks , the intervention group showed significant improvements in HRQOL ( physical functioning , role-physical , bodily pain , and vitality ; p < @ ) as well as on the Senior Fitness Test ( chair stands , arm curls , Timed Up and Go , and @-minute walk distance ; p < @ ) ; there was no significant improvement in LVEF ( p = @ ) .


The low-intensity , home-based exercise led by an advanced practice nurse was effective in improving HRQOL and physical fitness .


Adherence was high , and there were no adverse events related to exercise .


Tobacco use is responsible for the death of about @ in @ individuals worldwide .


Mindfulness training has shown preliminary efficacy as a behavioral treatment for smoking cessation .


Recent advances in mobile health suggest advantages to smartphone-based smoking cessation treatment including smartphone-based mindfulness training .


This study evaluates the efficacy of a smartphone app-based mindfulness training program for improving smoking cessation rates at @-months follow-up .


A two-group parallel-randomized clinical trial with allocation concealment will be conducted .


Group assignment will be concealed from study researchers through to follow-up .


The study will be conducted by smartphone and online .


Daily smokers who are interested in quitting smoking and own a smartphone ( n = @ ) will be recruited through study advertisements posted online .


After completion of a baseline survey , participants will be allocated randomly to the control or intervention group .


Participants in both groups will receive a @-day smartphone-based treatment program for smoking .


Participants in the intervention group will receive mobile mindfulness training plus experience sampling .


Participants in the control group will receive experience sampling-only .


The primary outcome measure will be one-week point prevalence abstinence from smoking ( at @-months follow-up ) assessed using carbon monoxide breath monitoring , which will be validated through smartphone-based video chat .


This is the first intervention study to evaluate smartphone-based delivery of mindfulness training for smoking cessation .


Such an intervention may provide treatment in-hand , in real-world contexts , to help individuals quit smoking .


Triptans are a family of selective serotonin ( @-HT@B / @D ) receptor agonists that are widely used to treat acute migraine attacks .


Their efficacy is limited by side effects and the gastrointestinal manifestations of migraine .


To compare the efficacy of a single intravenous administration of propacetamol , a prodrug of paracetamol ( acetaminophen ) with a single dose of oral rizatriptan in treating acute migraine attacks .


Patients were selected from those who presented to the emergency room with a diagnosed migraine attack and who had not previously taken any analgesics .


They were randomized into @ groups : treatment with a single @g IV dose of propacetamol or with a single oral dose of @mg rizatriptan .


Their Visual Analogue Scale ( VAS ) pain scores were assessed before and at @ , @ , and @min after treatment .


The patients who received the propacetamol had significantly improved VAS scores at @min compared to the rizatriptan group .


There were no significant differences in VAS scores at @ or @min post-treatment .


Propacetamol is either equivalent or superior in efficacy to rizatriptan for treating acute migraine attacks , while having the advantage of parenteral administration in patients whose migraines are accompanied by nausea and vomiting .


Onychomycosis , a fungal nail infection , can impact quality of life .


We sought to evaluate the efficacy and safety of tavaborole topical solution , @ % for treatment of toenail onychomycosis .


In @ phase-III trials , adults with distal subungual onychomycosis affecting @ % to @ % of a target great toenail were randomized @:@ to tavaborole or vehicle once daily for @ weeks .


The primary end point was complete cure of the target great toenail ( completely clear nail with negative mycology ) at week @ .


Secondary end points included completely or almost clear nail , negative mycology , completely or almost clear nail plus negative mycology , and safety .


Rates of negative mycology ( @ % -@ % vs @ % -@ % ) and complete cure ( @ % and @ % vs @ % and @ % ) significantly favored tavaborole versus vehicle ( P @ ) .


Completely or almost clear nail rates also significantly favored tavaborole versus vehicle ( @ % -@ % vs @ % -@ % ; P < @ ) .


Rates of completely or almost clear nail plus negative mycology ( @ % -@ % vs @ % -@ % ) were significantly greater for tavaborole versus vehicle ( P < @ ) .


Application-site reactions with tavaborole included exfoliation ( @ % ) , erythema ( @ % ) , and dermatitis ( @ % ) .


Duration of follow-up is a limitation .


Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis .


Atrial fibrillation ( AF ) is frequently comorbid in patients receiving cardiac resynchronization therapy ( CRT ) , and suppression is typically difficult .


Herein , we sought to understand the benefit of atrial rhythm control in the setting of ventricular rate and regularity control induced by atrioventricular node ( AVN ) ablation .


Fifty-two patients with heart failure , persistent AF , left ventricular ( LV ) ejection fraction < @ % , and left bundle branch block underwent cardiac resynchronization therapy ( CRT ) + AVN ablation , and were randomized to one of the following groups : ( @ ) Atrial Rhythm Control ( ARC ) ; ( @ ) AF .


Patients were subsequently followed for up to @ year .


Similar numbers of patients in each group were lost to follow-up or have withdrawn ( ARC two ; AF three ) .


Rhythm control in four patients in the ARC group was inadequate .


Among the remaining patients , the incidence of death ( ARC = @ , AF = @ ) or left ventricular assist device + / - transplantation ( ARC = @ , AF = @ ) were similar .


Among the remaining patients ( ARC @ , AF @ ) , at @ year , there were no significant differences in CRT response rate , Minnesota Living with Heart Failure survey score , @-minute hall walk distance , ventricular tachyarrhythmia occurrence , or LV dimensions .


A significantly higher hospital encounter rate among ARC patients was attributable to efforts to maintain uniform atrial rhythm .


In this pilot study , no incremental benefit for ARC was apparent .


A larger study will be necessary to adequately examine these issues .


Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system ( RAAS ) blockade efficacy in non-diabetic nephropathy .


We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide , separately and in combination , added to RAAS blockade on residual albuminuria in patients with type @ diabetic nephropathy .


In this multicentre , double-blind , placebo-controlled , crossover randomised trial , we included patients with type @ diabetic nephropathy .


Main entry criteria were microalbuminaria or macroalbuminuria , and creatinine clearance of @ mL/min or higher with less than @ mL/min decline in the previous year .


We tested the separate and combined effects of sodium restriction ( dietary counselling in the outpatient setting ) and hydrochlorothiazide ( @ mg daily ) , added to standardised maximal angiotensin-converting enzyme ( ACE ) inhibition ( lisinopril @ mg daily ) , on albuminuria ( primary endpoint ) .


Patients were given hydrochlorothiazide ( @ mg per day ) or placebo during four treatment periods of @ weeks .


Both treatments were combined with regular sodium diet or sodium restriction ( target sodium intake @ mmol Na ( + ) per day ) .


The @-week treatment periods were done consecutively in a random order .


Patients were randomised in blocks of two patients .


The trial was analysed by intention to treat .


The trial is registered with TrialRegister.nl , number @ .


Of @ eligible patients , @ were included in the study .


Both sodium restriction and hydrochlorothiazide significantly reduced albuminuria , irrespective of treatment sequence .


Residual geometric mean albuminuria with baseline treatment was @ mg per day ( @ % CI @-@ ) ; it was significantly reduced by sodium restriction ( @ mg per day -LSB- @-@ -RSB- , p = @ ) , by hydrochlorothiazide ( @ mg per day -LSB- @-@ -RSB- , p = @ ) , and to the greatest extent by their combination ( @ mg per day -LSB- @-@ -RSB- , p < @ ) .


Orthostatic complaints were present in two patients ( @ % ) during baseline treatment , five ( @ % ) during addition of sodium restriction , five ( @ % ) during hydrochlorothiazide treatment , and @ ( @ % ) during combination treatment .


No serious adverse events occurred .


We conclude that sodium restriction is an effective non-pharmacological intervention to increase RAAS blockade efficacy in type @ diabetic nephropathy .


Many patients have symptoms suggestive of coronary artery disease ( CAD ) and are often evaluated with the use of diagnostic testing , although there are limited data from randomized trials to guide care .


We randomly assigned @,@ symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography ( CTA ) or to functional testing ( exercise electrocardiography , nuclear stress testing , or stress echocardiography ) .


The composite primary end point was death , myocardial infarction , hospitalization for unstable angina , or major procedural complication .


Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure .


The mean age of the patients was @ years , @ % were women , and @ % had chest pain or dyspnea on exertion .


The mean pretest likelihood of obstructive CAD was @ % .


Over a median follow-up period of @ months , a primary end-point event occurred in @ of @ patients in the CTA group ( @ % ) and in @ of @ ( @ % ) in the functional-testing group ( adjusted hazard ratio , @ ; @ % confidence interval , @ to @ ; P = @ ) .


CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing ( @ % vs. @ % , P = @ ) , although more patients in the CTA group underwent catheterization within @ days after randomization ( @ % vs. @ % ) .


The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group ( @ mSv vs. @ mSv ) , but @ % of the patients in the functional-testing group had no exposure , so the overall exposure was higher in the CTA group ( mean , @ mSv vs. @ mSv ; P < @ ) .


In symptomatic patients with suspected CAD who required noninvasive testing , a strategy of initial CTA , as compared with functional testing , did not improve clinical outcomes over a median follow-up of @ years .


( Funded by the National Heart , Lung , and Blood Institute ; PROMISE ClinicalTrials.gov number , NCT@ . )


Electroencephalographic-based monitoring systems such as the bispectral index ( BIS ) may reduce anaesthetic overdose rates .


We hypothesised that goal-directed sevoflurane administration ( guided by BIS monitoring ) could reduce the sevoflurane plasma concentration ( SPC ) and intraoperative vasopressor doses during on-pump cardiac surgery .


A prospective , controlled , sequential two-arm clinical study .


German university medical centre with more than @ cardiac surgery interventions per year .


Sixty elective on-pump cardiac surgery patients .


In group Sevo@ @ % ( n = @ ) , the sedation depth was maintained with a sustained inspired concentration of sevoflurane @ % before and during cardiopulmonary bypass ( CPB ) .


In group SevoBIS ( n = @ ) , the inspired sevoflurane concentration was titrated to maintain a BIS target between @ and @ .


SPC during CPB and the intraoperative administration of noradrenaline .


Additional analyses were performed on intraoperative awareness , postoperative blood lactate concentration , duration of mechanical ventilation , intensive care unit length of stay and kidney injury .


Mean inspired sevoflurane concentration was @ % in group SevoBIS , representing a @ % reduction ( P < @ ) compared with group Sevo@ @ % .


The mean SPC was @ gml ( -@ ) -LSB- @ % confidence interval ( CI ) @ to @ -RSB- in group Sevo@ @ % and @ gml ( -@ ) ( @ % CI @ to @ ) in group SevoBIS , representing a @ % reduction ( P < @ ) .


During CPB , the mean cumulative dose of noradrenaline administered was @ gkg ( -@ ) ( @ % CI @ to @ ) in group Sevo@ @ % and @ gkg ( -@ ) ( @ % CI @ to @ ) in group SevoBIS ( P < @ ) .


Pearson 's correlation coefficient ( between the cumulative applied dosage of sevoflurane calculated from the area under the curve of the SPC over time and the administered cumulative noradrenaline dose ) was @ ( P < @ ) .


No intraoperative awareness signs were detected .


BIS-guided titration of sevoflurane reduces the SPC and decreases noradrenaline administration compared with routine care during on-pump cardiac surgery .


Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects .


To report the @-month extension of a phase II trial evaluating the efficacy , safety and tolerability of atorvastatin @ mg/d added to interferon beta-@b ( IFNB-@b ) in relapsing-remitting multiple sclerosis ( RRMS ) .


In the randomized , multicenter , parallel-group , rater-blinded core study , @ RRMS patients started IFNB-@b .


At month three they were randomized @ to receive atorvastatin @ mg/d or not in addition to IFNB-@b until month @ .


In the subsequent extension study , patients continued with unchanged medication for another @ months .


Data at study end were compared to data at month three of the core study .


@ of @ patients that finished the core study entered the extension study .


@ patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study .


The primary end point , the proportion of patients with new lesions on T@-weighted images was equal in both groups ( odds ratio @ ; @ % CI @-@ @ ; p = @ ) .


All secondary endpoints including number of new lesions and total lesion volume on T@-weighted images , total number of Gd-enhancing lesions on T@-weighted images , volume of grey and white matter , EDSS , MSFC , relapse rate , number of relapse-free patients and neutralizing antibodies did not show significant differences either .


The combination therapy was well tolerated .


Atorvastatin @ mg/day in addition to IFNB-@b did not have any beneficial effects on RRMS compared to IFNB-@b monotherapy over a period of @ months .


Convergent biological , epidemiological , and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease ( PD ) .


To determine the safety , tolerability , and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial .


The Safety of Urate Elevation in PD ( SURE-PD ) study , a randomized , double-blind , placebo-controlled , dose-ranging trial of inosine , enrolled participants from @ to @ and followed them for up to @ months at outpatient visits to @ credentialed clinical study sites of the Parkinson Study Group across the United States .


Seventy-five consenting adults ( mean age , @ years ; @ % women ) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than @ mg/dL ( the approximate population median ) were enrolled .


Participants were randomized to @ of @ treatment arms : placebo or inosine titrated to produce mild ( @-@ @ mg/dL ) or moderate ( @-@ @ mg/dL ) serum urate elevation using @-mg capsules taken orally up to @ capsules @ times per day .


They were followed for up to @ months ( median , @ months ) while receiving the study drug plus @ washout month .


The prespecified primary outcomes were absence of unacceptable serious adverse events ( safety ) , continued treatment without adverse event requiring dose reduction ( tolerability ) , and elevation of urate assessed serially in serum and once ( at @ months ) in cerebrospinal fluid .


RESULTS Serious adverse events ( @ ) , including infrequent cardiovascular events , occurred at the same or lower rates in the inosine groups relative to placebo .


No participant developed gout and @ receiving inosine developed symptomatic urolithiasis .


Treatment was tolerated by @ % of participants at @ months , and no participant withdrew because of an adverse event .


Serum urate rose by @ and @ mg/dL in the @ inosine groups ( P < @ for each ) vs placebo , and cerebrospinal fluid urate level was greater in both inosine groups ( P = @ and < @ , respectively ) .


Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability .


Inosine was generally safe , tolerable , and effective in raising serum and cerebrospinal fluid urate levels in early PD .


The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD .


Endoscopic injection of a bulking agent is becoming a first-line treatment for low grade vesicoureteral reflux .


We prospectively compared the efficacy of @ such products commercially available in Canada .


A total of @ patients with documented grade I to V vesicoureteral reflux were prospectively enrolled in a comparative study between April @ and February @ to be randomly treated endoscopically with either polydimethylsiloxane ( Macroplastique ) or dextranomer/hyaluronic acid copolymer ( Deflux ) .


Of the ureters @ were treated with polydimethylsiloxane and @ with dextranomer/hyaluronic acid copolymer .


Patients were followed with voiding cystourethrography at @ months and renal ultrasonography at @ months and at @ year .


Median followup was @ years .


The primary outcome was surgical success ( resolution vs nonresolution ) , and secondary outcomes included occurrence of adverse events .


Vesicoureteral reflux was fully corrected in @ of @ ureters ( @ % ) treated with polydimethylsiloxane , compared to @ of @ ( @ % ) treated with dextranomer/hyaluronic acid copolymer ( p < @ ) .


Obstruction was found in @ureters .


Univariate and multivariate analyses did not allow identification of any characteristics that could explain the significant difference in the success rates except for the type of product used .


We present the largest known prospective evaluation comparing @bulking agents for the treatment of vesicoureteral reflux .


Endoscopic injection of polydimethylsiloxane resulted in a better success rate than dextranomer/hyaluronic acid copolymer .


The rate of resolution obtained with the latter is lower than those previously published due to the inclusion of high grade reflux .


Economic evaluation is important for making decisions about resource allocation .


Few cost-utility or cost-effectiveness studies on breast hypertrophy have been reported in the medical literature .


The authors sought to determine the cost-utility of reduction mammaplasty in the Brazilian national health care system .


This randomized controlled study was conducted in a university-affiliated hospital .


Sixty patients with breast hypertrophy were enrolled prospectively and were assigned randomly to either the control group ( n = @ patients who received follow-up for @ months ) or the treatment group ( n = @ patients who underwent reduction mammaplasty ) .


Direct costs were recorded , and the Medical Outcomes Study @-Item Short-Form Health Survey ( SF-@ ) was administered to both groups at the beginning of the study ( preoperatively for the treatment group ) and @ and @ months postoperatively .


Utility was determined with Instrument @D of the Brazilian version of the Short-Form Health Survey ( SF-@D ) , from the SF-@ data .


At the @-month follow-up , the treatment group showed an improvement in utility , with an average direct cost of approximately @ .


Reduction mammaplasty performed in the Brazilian national health care system provides a cost-utility ratio equivalent to approximately @ per @ quality-adjusted life year .


We aimed to compare the effectiveness of esmolol @ mg/kg and lidocaine @ mg/kg for injection pain and for the prevention of rocuronium-induced withdrawal response .


We enrolled a total of @ patients in the study .


Patients were randomly assigned to receive either @ mL of @ % NaCl ( Group P ) , esmolol @ mg/kg ( Group E ) , or lidocaine @ mg/kg ( Group L ) .


A subparalyzing dose of rocuronium @ mg / kg was administered to all patients and its effects were recorded .


Anesthesia was induced with intravenous propofol and intravenous rocuronium @ mg/kg in all groups .


The withdrawal movements of the patient groups were subsequently graded .


There was a statistically significant difference in overall incidence of pain in group E and L compared to the placebo group after administrating the subparalyzed dose ( no pain response : Group E = @ % , Group L = @ % , Group P = @ % ) ( P < @ ) .


After intravenous administration of an intubating dose of rocuronium , the esmolol group had a significantly lower incidence of withdrawal movement than the other groups ( no response : Group E = @ % , Group L = @ % , Group P = @ % ) ( P < @ ) .


We found that esmolol significantly attenuates rocuronium-induced withdrawal movement and also reduces pain when used at subparalyzing doses .


Necitumumab is a second-generation recombinant human immunoglobulin G@ EGFR monoclonal antibody that competitively inhibits ligand binding .


We aimed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated , stage IV , non-squamous non-small-cell lung cancer ( NSCLC ) .


We did this randomised , open-label , controlled phase @ study at @ sites in @ countries .


Patients aged @ years or older , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of @-@ and adequate organ function , were randomly assigned @:@ to treatment with a block randomisation scheme ( block size of four ) via a telephone-based interactive voice-response system or interactive web-response system .


Patients received either cisplatin @ mg/m ( @ ) and pemetrexed @ mg/m ( @ ) on day @ of a @-week cycle for a maximum of six cycles alone , or with necitumumab @ mg on days @ and @ .


Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects .


Randomisation was stratified by smoking history , ECOG performance status , disease histology , and geographical region .


Patients and study investigators were not masked to group assignment .


The primary endpoint was overall survival .


Efficacy analyses were by intention to treat .


This trial is registered with ClinicalTrials.gov , number NCT@ .


Between Nov @ , @ , and Feb @ , @ , we randomly assigned @ patients to receive either necitumumab plus pemetrexed and cisplatin ( n = @ ) or pemetrexed and cisplatin alone ( n = @ ) .


Enrolment was stopped on Feb @ , @ , after a recommendation from the independent data monitoring committee .


There was no significant difference in overall survival between treatment groups , with a median overall survival of @ months ( @ % CI @-@ ) in the necitumumab plus pemetrexed and cisplatin group versus @ months ( @-@ ) in the pemetrexed and cisplatin group ( hazard ratio @ -LSB- @ % CI @-@ -RSB- ; p = @ ) .


The incidence of grade @ or worse adverse events , including deaths , was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ; in particular , deaths regarded as related to study drug were reported in @ ( @ % ) of @ patients in the necitumumab group versus nine ( @ % ) of @ patients in the pemetrexed and cisplatin group .


Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ( @ -LSB- @ % -RSB- of @ vs @ -LSB- @ % -RSB- of @ patients ) .


Patients in the necitumumab plus pemetrexed and cisplatin group had more grade @-@ rash ( @ -LSB- @ % -RSB- of @ vs one -LSB- < @ % -RSB- of @ patients in the pemetrexed and cisplatin alone group ) , hypomagnesaemia ( @ -LSB- @ % -RSB- vs seven -LSB- @ % -RSB- patients ) , and grade @ or higher venous thromboembolic events ( @ -LSB- @ % -RSB- vs @ -LSB- @ % -RSB- patients ) than did those in the pemetrexed and cisplatin alone group .


Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC .


Unless future studies identify potentially useful predictive biomarkers , necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin .


Current guidelines recommend intensive low-density lipoprotein ( LDL ) cholesterol lowering with statins , with a target of @ mg/dL ( @ mmol/L ) LDL cholesterol for those with a very high risk of coronary artery events .


However , there is no multicenter study assessing the effect of intensive lipid-lowering therapy with statins on acute coronary syndrome ( ACS ) in a Chinese population with low baseline LDL cholesterol levels .


Patients ( n = @ ) with ACS were treated with a moderate dose of statin ( atorvastatin @ mg/d , or equivalent dose of other statins , n = @ ) or with an intensive dose of statin ( atorvastatin , @ or @ mg/d , or equivalent dose of other statins , n = @ ) for @ years .


The primary end points were cardiac death , non-fatal acute myocardial infarction ( MI ) , revascularization , ischemic stroke and documented unstable angina or severe heart failure requiring emergency hospitalization .


Baseline lipid levels were nearly identical in both groups with a mean LDL cholesterol level of @ mmol/L ( @ mg/dL ) .


At @ months , LDL cholesterol levels declined @ % in the moderate dose statin group and @ % in the intensive statin group , respectively ( P < @ ) .


In a @-year follow-up , a primary end point event occurred in @ patients in the moderate dose statin group and in @ patients in the intensive statin group .


There was no significant between-group difference in the primary outcome ( hazard ratio , @ ; @ % confidence interval -LSB- CI -RSB- , @-@ @ ; P = @ ) .


For ACS patients with a relatively low baseline LDL cholesterol level who received optimized current medication and interventional therapy , the incremental LDL cholesterol reduction of @ % achieved by double-dose statin did not bring significant clinical effectiveness .


Response to cardiac resynchronization therapy is variable .


The aim of this study was to test the hypothesis that left ventricular ( LV ) lead position in proximity to myocardial scar is associated with less favorable outcomes .


A total of @ patients were included in this substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial using echocardiographic radial strain for basal and middle LV segments and transverse strain for apical segments to estimate scar .


Sixty-four patients with high-dose rest ( @m ) Tc sestamibi single-photon emission computed tomographic imaging were used for validation in @ LV free-wall segments .


The relationship of LV lead position to segments estimated as scar was defined as concordant , adjacent , or remote .


The prespecified primary end point was heart failure hospitalization or death over @ years .


Wall thickening < @ % by radial strain in LV free wall segments was associated with absent ( @m ) Tc sestamibi uptake indicative of scar with @ % sensitivity and @ % specificity and strain < @ % was accordingly used as the surrogate for scar .


Event-free survival was most favorable in patients with nonischemic disease ( @ % ) , similarly favorable in patients with ischemic disease and LV leads remote from scar ( @ % ) , but significantly worse in patients with ischemic disease and LV leads adjacent to ( @ % ) or within scar ( @ % ) ( P = @ ) .


Preserved wall thickening at the LV lead site was independently associated with favorable outcome and additive to pacing at the site of latest mechanical activation ( P = @ ) and remained significant after adjusting for scar burden .


Echocardiographic speckle-tracking strain has the potential to estimate free wall scar in patients with ischemic cardiomyopathy and influence LV lead positioning away from scar to improve clinical outcomes after cardiac resynchronization therapy .


Tripterygium wilfordii Hook .


f. ( TwHF ) has been used for many years to induce the remission of Crohn 's disease in China .


To compare TwHF versus azathioprine for the prevention of postoperative recurrence in Crohn 's disease .


@ Crohn 's disease patients who had undergone resection were treated with TwHF @ mg/kg/day or azathioprine @ mg/kg/day .


The primary endpoint was clinical recurrence , and the secondary endpoint was endoscopic recurrence .


@ patients completed the trial .


Clinical recurrence was observed in @/@ patients in the TwHF group and @/@ patients in the azathioprine group at week @ ( P = @ ) .


At week @ , @/@ azathioprine patients and @/@ TwHF patients had clinical recurrence ( P = @ ) .


During the first @ weeks , @ % of the patients in the TwHF group versus @ % in the azathioprine group experienced endoscopic recurrence ( P = @ ) .


However , at week @ , @ % of patients in the TwHF group and @ % in the azathioprine group had endoscopic recurrence ( P = @ ) .


TwHF was less effective in maintaining endoscopic remission at week @ , even though TwHF was comparable to azathioprine for preventing postoperative clinical recurrence .


To test the efficacy of meaning-centered group psychotherapy ( MCGP ) to reduce psychological distress and improve spiritual well-being in patients with advanced or terminal cancer .


Patients with advanced cancer ( N = @ ) were randomly assigned to manualized eight-session interventions of either MCGP or supportive group psychotherapy ( SGP ) .


Patients were assessed before and after completing the treatment and @ months after treatment .


The primary outcome measures were spiritual well-being and overall quality of life , with secondary outcome measures assessing depression , hopelessness , desire for hastened death , anxiety , and physical symptom distress .


Hierarchical linear models that included a priori covariates and only participants who attended three sessions indicated a significant group time interaction for most outcome variables .


Specifically , patients receiving MCGP showed significantly greater improvement in spiritual well-being and quality of life and significantly greater reductions in depression , hopelessness , desire for hastened death , and physical symptom distress compared with those receiving SGP .


No group differences were observed for changes in anxiety .


Analyses that included all patients , regardless of whether they attended any treatment sessions ( ie , intent-to-treat analyses ) , and no covariates still showed significant treatment effects ( ie , greater benefit for patients receiving MCGP v SGP ) for quality of life , depression , and hopelessness but not for other outcome variables .


This large randomized controlled study provides strong support for the efficacy of MCGP as a treatment for psychological and existential or spiritual distress in patients with advanced cancer .


We investigated the contribution of electrocortical stimulation ( ECS ) , induced high gamma electrocorticography ( hgECoG ) and functional magnetic resonance imaging ( fMRI ) for the localization of somatosensory and language cortex .


@ Epileptic patients with subdural electrodes underwent a protocol of somatosensory stimulation and/or an auditory semantic decision task .


@ Patients did the same protocol with fMRI prior to implantation .


ECS resulted in the identification of thumb somatosensory cortex in @/@ patients .


Taking ECS as a gold standard , hgECoG and fMRI identified @ / @ % of true positive and @/@ % of false positive contacts , respectively .


The hgECoG false positive sites were all found in the hand area of the post-central gyrus .


ECS localized language-related sites in @/@ patients with hgECoG and fMRI showing @/@ % of true positive and @/@ % of false positive contacts , respectively .


All but one of the hgECoG/fMRI false positive contacts were located in plausible language areas .


Four patients showed post-surgical impairments : the resection included the sites positively indicated by ECS , hgECoG and fMRI in @ patients and a positive hgECoG site in one patient .


HgECoG and fMRI provide additional localization information in patients who can not sufficiently collaborate during ECS .


HgECoG and fMRI make the cortical mapping procedure more flexible not only by identifying priority cortical sites for ECS or when ECS is not feasible , but also when ECS does not provide any result .


Tissue factor ( TF ) expression is increased in inflammatory atherosclerotic plaques and has been related to their thrombogenicity .


Blood-borne TF has been also demonstrated to contribute to thrombogenesis .


However , few studies have evaluated the association of circulating levels of TF with stroke .


We investigated the association of baseline circulating levels of TF with stroke events occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort .


Using a nested case-cohort design , a center-stratified random sample of @ subjects ( @ % women ; age range , @-@ years ) was selected as subcohort and compared with @ strokes in a mean follow-up of @ years .


Blood samples were collected at baseline in citrate , plasma was stored in liquid nitrogen and TF was measured by ELISA ( IMUBIND , TF ELISA , Instrumentation Laboratory , Milan , Italy ) .


The odd ratios and @ % confidence intervals , adjusted by relevant confounders ( covariates of TF ) and stratified by center , were estimated by a Cox regression model using Prentice method .


Individuals in the highest compared with the lowest quartile of TF plasma levels had significantly increased risk of stroke ( odds ratioIVvsI quartile , @ ; @ % confidence interval , @-@ @ ) .


The association was independent from several potential confounders ( odds ratioIVvsI quartile , @ ; @ % confidence interval , @-@ @ ) .


No differences were observed between men and women .


The increase in risk was restricted to ischemic strokes ( odds ratioIVvsI quartile , @ ; @ % confidence interval , @-@ @ ; fully adjusted model ) , whereas high levels of TF were not associated with the risk of hemorrhagic stroke ( odds ratioIVvsI quartile , @ ; @ % confidence interval , @-@ @ ; fully adjusted model ) .


Our data provide evidence that elevated levels of circulating TF are potential risk factors for ischemic strokes .


Recently , the usefulness of neuromuscular electrical stimulation and repetitive transcranial magnetic stimulation for poststroke dysphagia has been reported .


However , there is no report that describes the effectiveness of functional magnetic stimulation ( FMS ) for dysphagia .


The purpose of this study is to clarify the effectiveness of FMS for poststroke dysphagia .


Twenty poststroke dysphagic patients ( age at treatment : @-@ years ; interval between onset of stroke and treatment : @ to @ months ) were randomly assigned to a real group or a sham group .


In the real group , FMS of @ Hz was applied for suprahyoid muscles in a @-sec train using a parabolic coil for @ min ( total @ pulses ) .


In the sham group , sham stimulation was applied for @ min at the same site .


Swallowing function was evaluated by the timed water swallow test , interswallow interval ( ISI ) , swallowing volume velocity ( speed ) , and volume per swallow ( capacity ) were measured before and after stimulation .