Cytology testing with and without methylation marker analysis was evaluated with regard to sensitivity , specificity , positive and negative predictive value , and referral rate .


Bi-marker CADM1/MAL-methylation positivity increased proportionally with severity of underlying lesions .


Overall , cytology and bi-marker CADM1/MAL-methylation analysis yielded similar performances with regard to CIN3 + detection , yet in combination a significantly higher sensitivity for CIN3 + ( 88.7 % ) was obtained at a specificity of 53.6 % and a colposcopy referral rate of 53.6 % .


The combined strategy detected all six cervical cancers , whereas triage by cytology alone failed to detect two of them .


Cytology and bi-marker CADM1/MAL-methylation analysis perform complementary for CIN2 + / CIN3 + detection when used as triage tool on cervical scrapes of HPV positive women .


This approach not only results in a higher CIN3 + sensitivity than cytology triage with an acceptable referral rate , but also seems to reduce the risk of missing cervical cancers and advanced high-grade lesions .


The analgesic efficacy of the transversus abdominis plane peripheral nerve block following abdominal tissue breast reconstruction has not been studied in a randomized controlled trial .


The authors conducted a double-blind , placebo-controlled , 1:1 allocation , two-arm parallel group , superiority design , randomized controlled trial in patients undergoing microsurgical abdominally based breast reconstruction .


Intraoperatively , epidural catheters were inserted under direct vision through the triangle of Petit on both sides of the abdomen into the transversus abdominis plane just before rectus fascial closure .


Patients received either bupivacaine ( study group ) or saline ( placebo group ) through the catheters for 2 postoperative days .


All patients received hydromorphone by means of a patient-controlled analgesic pump .


The primary outcome was the difference in the parenteral opioid consumption on each postoperative day between the groups .


The secondary outcome measures included the following : total in-hospital opioid ; antinausea medication ; pain , nausea , and sedation scores ; Quality of Recovery Score ; time to ambulation ; and hospital stay duration .


Between September of 2011 and June of 2013 , 93 patients were enrolled : 49 received bupivacaine and 44 received saline .


There were 11 postoperative complications ( 13 percent ) ; none were related to the catheter .


Primary outcomes were completed by 85 of 93 patients ( 91.3 percent ) ; the mean parenteral morphine consumption was significantly reduced on postoperative day 1 in the bupivacaine group ( 20.720.1 mg ) compared with 30.019.1 mg in the control group ( p = 0.02 ) .


There were no significant differences in secondary outcomes .


Following abdominally based breast reconstruction , transversus abdominis plane peripheral nerve block is safe and significantly reduces morphine consumption in the early postoperative period .


Therapeutic , II .


The aim of this study was to comparatively examine the convenience of use of the QUEST and GerdQ questionnaires as self-administered diagnostic instruments .


This was a two-way crossover study conducted from December 2011 to April 2012 .


The subjects were 70 third-year nursing students of Yokohama Soei University in Yokohama , Japan .


They were randomly assigned to fill in either of the study questionnaires first , and then the other on a later .


A significant difference was observed in the questionnaire completion time between the QUEST and GerdQ questionnaires ( 125.5 vs. 44 seconds , P < 0.0001 ) and also in the number of subjects asking questions while completing the questionnaires ( 26 vs. 1 subject , respectively : P < 0.0001 ) .


To detect GERD based on a QUEST score of 4 , ROC analysis revealed an area under the curve for the GerdQ score of 0.616 .


The optimal cutoff value of the GerdQ score was 6 , and the sensitivity and specificity calculated using this cutoff value were 0.842 and 0.312 , respectively .


This study revealed that Japanese subjects may find it easier to complete the GerdQ than the QUEST questionnaire .


Prevention of iron deficiency in infancy may promote neurodevelopment .


Delayed cord clamping ( DCC ) can prevent iron deficiency during the first 6 months of life .


However , no data are available on long-term effects on infant outcomes in relation to time for umbilical cord clamping .


To investigate effects of DCC , as compared with early cord clamping ( ECC ) , on infant iron status and neurodevelopment at age 12 months in a European setting .


Randomized clinical trial of 382 full-term infants born after a low-risk pregnancy at a Swedish county hospital .


Follow-up at 12 months included evaluation of iron status ( ferritin level , transferrin saturation , transferrin receptor level , reticulocyte hemoglobin level , and mean cell volume ) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire , second edition ( ASQ ) .


Infants were randomized to DCC ( 180 seconds after delivery ) or ECC ( 10 seconds after delivery ) .


The main outcome was iron status at age 12 months ; the secondary outcome was ASQ score .


In total , 347 of 382 infants ( 90.8 % ) were assessed .


The DCC and ECC groups did not differ in iron status ( mean ferritin level , 35.4 vs 33.6 ng/mL , respectively ; P = .40 ) or neurodevelopment ( mean ASQ total score , 229.6 vs 233.1 , respectively ; P = .42 ) at age 12 months .


Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood .


Predictors of ASQ score were infant sex and breastfeeding within 1 hour after birth .


For both outcomes , being a boy was associated with lower results .


Interaction analysis showed that DCC was associated with an ASQ score 5 points higher among boys ( mean [ SD ] score , 229 [ 43 ] for DCC vs 224 [ 39 ] for ECC ) but 12 points lower among girls ( mean [ SD ] score , 230 [ 39 ] for DCC vs 242 [ 36 ] for ECC ) , out of a maximum of 300 points ( P = .04 for the interaction term ) .


Delayed cord clamping did not affect iron status or neurodevelopment at age 12 months in a selected population of healthy term-born infants .


However , it may not be possible to demonstrate minor effects on neurodevelopment with the size of the study population and the chosen method for assessment .


The current data indicate that sex may influence the effects on infant development after DCC in different directions .


The magnitude and biological reason for this finding remain to be investigated .


TRIAL REGISTRATION clinicaltrials.gov Identifier : NCT01245296 .


Dacomitinib is an irreversible pan-HER tyrosine-kinase inhibitor with preclinical and clinical evidence of activity in non-small-cell lung cancer .


We designed BR .26 to assess whether dacomitinib improved overall survival in heavily pretreated patients with this disease .


In this double-blind , randomised , placebo-controlled , phase 3 trial , we enrolled adults ( aged 18 years ) with advanced or metastatic non-small-cell lung cancer from 75 centres in 12 countries .


Eligible patients had received up to three previous lines of chemotherapy and either gefitinib or erlotinib , and had assessable disease ( RECIST 1.1 ) and tumour tissue samples for translational studies .


Patients were stratified according to centre , performance status , tobacco use , best response to previous EGFR tyrosine-kinase inhibitor , weight loss within the previous 3 months , and ethnicity , and were then randomly allocated 2:1 to oral dacomitinib 45 mg once-daily or matched placebo centrally via a web-based system .


Treatment continued until disease progression or unacceptable toxicity .


The primary outcome was overall survival in the intention-to-treat population ; secondary outcomes included overall survival in predefined molecular subgroups , progression-free survival , the proportion of patients who achieved an objective response , safety , and quality of life .


This study is completed , although follow-up is ongoing for patients on treatment .


This study is registered with ClinicalTrials.gov , number NCT01000025 .


Between Dec 23 , 2009 , and June 11 , 2013 , we randomly assigned 480 patients to dacomitinib and 240 patients to placebo .


At the final analysis ( January , 2014 ) , median follow-up was 234 months ( IQR 156-296 ) for patients in the dacomitinib group and 244 months ( 115-389 ) for those in the placebo group .


Dacomitinib did not improve overall survival compared with placebo ( median 683 months [ 95 % CI 608-749 ] for dacomitinib vs 631 months [ 532-752 ] for placebo ; hazard ratio [ HR ] 100 [ 95 % CI 083-121 ] ; p = 0506 ) .


However , patients in the dacomitinib group had longer progression-free survival than those in the placebo group ( median 266 months [ 191-332 ] vs 138 months [ 099-174 ] , respectively ; HR 066 [ 95 % CI 055-079 ] ; p < 00001 ) , and a significantly greater proportion of patients in the dacomitinb group achieved an objective response than in the placebo group ( 34 [ 7 % ] of 480 patients vs three [ 1 % ] of 240 patients , respectively ; p = 0001 ) .


Compared with placebo , the effect of dacomitinib on overall survival seemed similar in patients with EGFR-mutation-positive tumours ( HR 098 , 95 % CI 067-144 ) and EGFR wild-type tumours ( 093 , 071-121 ; pinteraction = 069 ) .


However , we noted qualitative differences in the effect of dacomitinib on overall survival for patients with KRAS-mutation-positive tumours ( 210 , 105-422 ) and patients with KRAS wild-type tumours ( 079 , 061-103 ; pinteraction = 008 ) .


Compared with placebo , patients allocated dacomitinib had significantly longer time to deterioration of cough ( p < 00001 ) , dyspnoea ( p = 0049 ) , and pain ( p = 0041 ) .


185 ( 39 % ) of 477 patients who received dacomitinib and 86 ( 36 % ) of 239 patients who received placebo had serious adverse events .


The most common grade 3-4 adverse events were diarrhoea ( 59 [ 12 % ] patients on dacomitinib vs no controls ) , acneiform rash ( 48 [ 10 % ] vs one [ < 1 % ] ) , oral mucositis ( 16 [ 3 % ] vs none ) , and fatigue ( 13 [ 3 % ] vs four [ 2 % ] ) .


Dacomitinib did not increase overall survival and can not be recommended for treatment of patients with advanced non-small-cell lung cancer previously treated with chemotherapy and an EGFR tyrosine-kinase inhibitor .


Canadian Cancer Society Research Institute and Pfizer .


Treatment for CH-C contains interferon with substantial associated side effects and health-related quality of life ( HRQL ) impairment .


Currently , there is no published data assessing the impact of interferon-free regimens on HRQL .


The aim is to report the HRQL of patients who participated in clinical trials of sofosbuvir ( SOF ) for CH-C .


CH-C patients were treated with sofosbuvir ( SOF ) , pegylated interferon ( PegIFN ) , ribavirin ( RBV ) , or placebo in different combinations and duration ( POSITRON , FISSION , FUSION , and NEUTRINO phase III trials ) .


HRQL was assessed using SF-36 at baseline , during treatment , at the end of treatment , and at follow-up , and compared between treatment arms .


HRQL scores decreased over the course of treatment for all treatment arms in all studies ; however , patients returned to their baseline score by the end of follow-up .


Compared to placebo , SOF and RBV was not associated with HRQL impairment ( POSITRON ) .


Compared to SOF and RBV , HRQL was significantly more impaired in the PegIFN and RBV arm ( FISSION ) .


For those treated with SOF and RBV , there was no difference in HRQL between 12 weeks or 16 weeks of treatment ( FUSION ) .


Multivariate analysis demonstrated that depression , fatigue , and insomnia were important predictors of patients ' HRQL prior , during or after treatment .


Additionally , anemia and receiving interferon were predictors of HRQL impairment during treatment .


Achieving sustained virologic response after 12 weeks of follow-up ( SVR-12 ) with SOF and RBV was associated with improvement in HRQL scores from baseline .


Treatment-related HRQL impairment during SOF and RBV regimen is mild , and does not increase with longer treatment duration .


Achieving SVR-12 with SOF and RBV is associated with an improvement in HRQL .


Fetal Alcohol Spectrum Disorders ( FASDs ) are the leading known preventable birth defects in North America .


Knowledge surveys about FASD have been conducted with various health and allied healthcare providers and have proven useful in identifying gaps in knowledge and differences among provider groups to support prevention efforts .


To date , no research has been conducted exploring FASD knowledge among college students .


This study explored FASD knowledge in a sample of college students , a group at particularly high risk for alcohol-exposed pregnancies .


Findings are compared to professionals in several healthcare and affiliated professional groups who were previously surveyed with the same FASD-related items .


Surveys from 1,035 college students at a northwestern university were analyzed .


Included with the ACHA-National College Health Assessment II were questions regarding FASD .


College students ' knowledge was compared with that of professionals in key healthcare and affiliated positions to define their relative awareness of FASD risk .


Overall , findings revealed adequate FASD knowledge among college students .


Although minor differences emerged when comparing students and professionals ' responses , most respondent groups answered with an 85 % accuracy rate or higher .


College students demonstrated adequate knowledgeable about FASD .


Future research must explore whether such knowledge translates into lower risk behavior and consequent reduction in alcohol-exposed pregnancies .


High - and low-frequency repetitive transcranial magnetic stimulation ( HF-rTMS and LF-rTMS ) has been shown to be beneficial for upper limb hemiparesis in patients with acute stroke .


However , no study has examined the usefulness of bilateral application of HF - and LF-rTMS ( BL-rTMS ) .


Fifty-eight hemiparetic patients with acute stroke were randomly assigned into two groups : HF-rTMS group and BL-rTMS group .


All patients were scheduled to receive five sessions of either HF-rTMS over the lesional hemisphere or BL-rTMS over both hemispheres for 5 days .


Motor function of the affected upper limb was evaluated using the Brunnstrom Recovery Stage ( BRS ) for upper-limb and hand-fingers , grip strength and tapping frequency , before the first session and after the last session of rTMS .


Improvement of BRS for the upper limb and hand/finger was significantly greater in the BL-rTMS group than the HF-rTMS group ( p < 0.01 ) .


Improvement in grip strength and tapping frequency was also greater in the BL-rTMS group , although the differences were not statistically significant .


The proposed BL-rTMS is safe and feasible and showed a greater improvement of BRS of the affected upper limb compared to HF-rTMS .


This novel rTMS approach may be a useful intervention for hemiparetic patients with acute stroke .


The evaluation of intestinal trophism , mainly the mucosal layer , is an important issue in various conditions associated with injury , atrophy , recovery , and healing of the gut .


The aim of the present study was to evaluate the kinetics of the proliferation and apoptosis of enterocytes by immunohistochemistry and to assess the complexity of intestinal mucosa by fractal dimension ( FD ) analysis in Solea solea fed different experimental diets .


Histomorphological evaluation of all intestinal segments did not show signs of degeneration or inflammation .


Cell proliferation index and FD were significantly reduced with a diet high in mussel meal ( MM ; p = 0.0034 and p = 0.01063 , respectively ) , while apoptotic index did not show any significant difference for the same comparison ( p = 0.3859 ) .


Linear regression analysis between apoptotic index ( independent variable ) and FD ( dependent variable ) showed a statistically significant inverse relationship ( p = 0.002528 ) .


Linear regression analysis between cell proliferation index ( independent variable ) and FD ( dependent variable ) did not show any significant correlation ( p = 0.131582 ) .


The results demonstrated that diets containing increasing levels of mussel meal in substitution of fishmeal did not incite a hyperplastic response of the intestinal mucosa .


The mussel meal , which is derived from molluscs , could mimic the characteristics of the sole 's natural prey , being readily digestible , even without increasing the absorptive surface of intestinal mucosa .


Interestingly , from this study emerged that FD could be used as a numeric indicator complementary to in situ quantification methods to measure intestinal trophism , in conjunction with functional parameters .


It is unclear whether d-cycloserine ( DCS ) , a partial N-methyl-d-aspartate agonist that enhances fear extinction , can augment the effects of exposure-based cognitive behavioral therapy ( CBT ) for obsessive-compulsive disorder ( OCD ) .


To examine whether DCS augments the effects of CBT for OCD and to explore ( post hoc ) whether concomitant antidepressant medication moderates the effects of DCS .


A 12-week , double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4 , 2012 , and September 26 , 2013 .


Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) score of 16 or higher .


Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial .


The main analysis was by intention-to-treat population .


All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo , administered 1 hour before each of 5 exposure and response prevention tasks .


Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up .


Remission was defined as a score of 12 or lower on the Y-BOCS .


In the primary intention-to-treat analyses , DCS did not augment the effects of CBT compared with placebo ( mean [ SD ] clinician-rated Y-BOCS score , DCS : 13.86 [ 6.50 ] at week 12 and 12.35 [ 7.75 ] at 3-month follow-up ; placebo : 11.77 [ 5.95 ] at week 12 and 12.37 [ 6.68 ] at 3-month follow-up ) but showed a significant interaction with antidepressants ( clinician-rated Y-BOCS , B = -1.08 ; Z = -2.79 ; P = .005 ) .


Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group , at both posttreatment and follow-up ( clinician-rated Y-BOCS : t62 = -3.00 ; P = .004 ; and t61 = -3.49 ; P < .001 , respectively ) .


In the DCS group , a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up ( 60 % [ 95 % CI , 45 % -74 % ] ) than antidepressant-medicated patients ( 24 % [ 95 % CI , 9 % -48 % ] ) ( P = .008 ) .


Antidepressants had no effect in the placebo group ( 50 % [ 95 % CI , 36 % -64 % ] remission rate in both groups ) .


The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction .


Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD .


clinicaltrials.gov Identifier : NCT01649895 .


Acute heart failure ( AHF ) is characterized by inadequate cardiac output ( CO ) , congestive symptoms , poor peripheral perfusion and end-organ dysfunction .


Treatment often includes a combination of diuretics , oxygen , positive pressure ventilation , inotropes and vasodilators or vasopressors .


Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress .


We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF .


We conducted a prospective , randomised , controlled , open-label , pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF : ( 1 ) left ventricular ejection fraction < 40 % , ( 2 ) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and ( 3 ) currently receiving vasopressor and/or inotropic support .


Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours .


The control group received only a 3 ml/kg bolus of Hartmann 's solution without continuous infusion .


The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation .


Secondary outcomes included a measure of right ventricular systolic function ( tricuspid annular plane systolic excursion ( TAPSE ) ) , acid-base balance , electrolyte and organ function parameters , along with length of stay and mortality .


The infusion of half-molar sodium lactate increased ( meanSD ) CO from 4.051.37 L/min to 5.491.9 L/min ( P < 0.01 ) and TAPSE from 14.75.5 mm to 18.37 mm ( P = 0.02 ) .


Plasma sodium and pH increased ( 1364 to 1466 and 7.400.06 to 7.530.03 , respectively ; both P < 0.01 ) , but potassium , chloride and phosphate levels decreased .


There were no significant differences in the need for vasoactive therapy , respiratory support , renal or liver function tests , duration of ICU and hospital stay or 28 - and 90-day mortality .


Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function .


Clinicaltrials.gov NCT01981655 .


Registered 13 August 2013 .


Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding , but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown .


FXI-ASO ( ISIS 416858 ) is a second-generation antisense oligonucleotide that specifically reduces factor XI levels .


We compared the efficacy and safety of FXI-ASO with those of enoxaparin in patients undergoing total knee arthroplasty .


In this open-label , parallel-group study , we randomly assigned 300 patients who were undergoing elective primary unilateral total knee arthroplasty to receive one of two doses of FXI-ASO ( 200 mg or 300 mg ) or 40 mg of enoxaparin once daily .


The primary efficacy outcome was the incidence of venous thromboembolism ( assessed by mandatory bilateral venography or report of symptomatic events ) .


The principal safety outcome was major or clinically relevant nonmajor bleeding .


Around the time of surgery , the mean ( SE ) factor XI levels were 0.380.01 units per milliliter in the 200-mg FXI-ASO group , 0.200.01 units per milliliter in the 300-mg FXI-ASO group , and 0.930.02 units per milliliter in the enoxaparin group .


The primary efficacy outcome occurred in 36 of 134 patients ( 27 % ) who received the 200-mg dose of FXI-ASO and in 3 of 71 patients ( 4 % ) who received the 300-mg dose of FXI-ASO , as compared with 21 of 69 patients ( 30 % ) who received enoxaparin .


The 200-mg regimen was noninferior , and the 300-mg regimen was superior , to enoxaparin ( P < 0.001 ) .


Bleeding occurred in 3 % , 3 % , and 8 % of the patients in the three study groups , respectively .


This study showed that factor XI contributes to postoperative venous thromboembolism ; reducing factor XI levels in patients undergoing elective primary unilateral total knee arthroplasty was an effective method for its prevention and appeared to be safe with respect to the risk of bleeding .


( Funded by Isis Pharmaceuticals ; FXI-ASO TKA ClinicalTrials.gov number , NCT01713361 . )


Inhalation of capsaicin , the extract of hot chili peppers , induces coughing in both animals and human subjects through activation of transient receptor potential vanilloid 1 ( TRPV1 ) on airway sensory nerves .


Therefore the TRPV1 receptor is an attractive target for the development of antitussive agents .


We sought to assess the antitussive effect of TRPV1 antagonism in patients with refractory chronic cough .


Twenty-one subjects with refractory chronic cough ( > 8 weeks ) attending a specialist clinic were recruited to a randomized , double-blind , placebo-controlled crossover trial assessing a TRPV1 antagonist ( SB-705498 ) .


Cough reflex sensitivity to capsaicin ( concentration of capsaicin inducing at least 5 coughs ) and 24-hour cough frequency were coprimary end points assessed after a single dose of SB-705498 ( 600 mg ) and matched placebo .


Cough severity and urge to cough were reported on visual analog scales , and cough-specific quality of life data were also collected .


Treatment with SB-705498 produced a significant improvement in cough reflex sensitivity to capsaicin at 2 hours and a borderline significant improvement at 24 hours compared with placebo ( adjusted mean difference of +1.3 doubling doses at 2 hours [ 95 % CI , +0.3 to +2.2 ; P = .0049 ] and +0.7 doubling doses at 24 hours [ 95 % CI , +0.0 to +1.5 ; P = .0259 ] ) .


However , 24-hour objective cough frequency was not improved compared with placebo .


Patient-reported cough severity , urge to cough , and cough-specific quality of life similarly suggested no effect of SB-705498 .


This study raises important questions about both the role of TRVP1-mediated mechanisms in patients with refractory chronic cough and also the predictive value of capsaicin challenge testing in the assessment of novel antitussive agents .


To develop an optimal model and age-specific centiles for the decline in antimllerian hormone ( AMH ) as measured by the new Beckman Coulter AMH Generation II ( Gen II ) assay and compare this to the previous nomogram derived for the Diagnostics Systems Laboratory ( DSL ) assay .


Multicenter retrospective population study , with validation of linear , biphasic linear , differential , power , and quadratic equations .


Two clinical pathology laboratories .


A new cohort of 10,984 women aged 25 to 45 years old attending infertility clinics , randomly divided into a training cohort of 5,492 women and a validation cohort of 5,492 women , and an existing cohort of 9,601 women , who had contributed to the development and validation of a nomogram for AMH measured by the DSL assay .


Serum measurement of AMH as determined by the Beckman Coulter AMH Generation II assay in 10,984 women .


Optimal model for the decline in AMH as measured by the AMH Gen II assay with age , with age-specific 5th , 10th , 25th , 50th , 75th , 90th , and 95th percentiles .


A quadratic model defined as ( 2.431 + 0.089 * Age + -0.003 * Age ( 2 ) ) fitted the decline in AMH with age .


The anticipated 40 % increase in age-specific population values relative to the previously validated DSL assay nomogram was not observed .


Age-specific reference ranges for the AMH gen II assay suggest a systematic shift in assay calibration since initial evaluation and commercial release of the AMH Gen II assay .


Mild cognitive impairment ( MCI ) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging , but less severe than dementia .


Reduced working memory ( WM ) is regarded as one of the core symptoms of an MCI condition .


Recent studies have indicated that WM can be improved through computer-based training .


The objective of this study is to evaluate if WM training is effective in improving cognitive function in elderly patients with MCI , and if cognitive training induces structural changes in the white and gray matter of the brain , as assessed by structural MRI .


The proposed study is a blinded , randomized , controlled trail that will include 90 elderly patients diagnosed with MCI at a hospital-based memory clinic .


The participants will be randomized to either a training program or a placebo version of the program .


The intervention is computerized WM training performed for 45minutes of 25 sessions over 5weeks .


The placebo version is identical in duration but is non-adaptive in the difficulty level of the tasks .


Neuropsychological assessment and structural MRI will be performed before and 1 month after training , and at a 5-month folllow-up .


If computer-based training results in positive changes to memory functions in patients with MCI this may represent a new , cost-effective treatment for MCI .


Secondly , evaluation of any training-induced structural changes to gray or white matter will improve the current understanding of the mechanisms behind effective cognitive interventions in patients with MCI .


ClinicalTrials.gov NCT01991405 .


November 18 , 2013 .


We compared mindfulness-based cognitive therapy ( MBCT ) with both cognitive psychological education ( CPE ) and treatment as usual ( TAU ) in preventing relapse to major depressive disorder ( MDD ) in people currently in remission following at least 3 previous episodes .


A randomized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU , CPE plus TAU , and TAU alone , and data were analyzed for the 255 ( 93 % ; MBCT = 99 , CPE = 103 , TAU = 53 ) retained to follow-up .


MBCT was delivered in accordance with its published manual , modified to address suicidal cognitions ; CPE was modeled on MBCT , but without training in meditation .


Both treatments were delivered through 8 weekly classes .


Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up , hazard ratio for MBCT vs. CPE = 0.88 , 95 % CI [ 0.58 , 1.35 ] ; for MBCT vs. TAU = 0.69 , 95 % CI [ 0.42 , 1.12 ] .


However , severity of childhood trauma affected relapse , hazard ratio for increase of 1 standard deviation = 1.26 ( 95 % CI [ 1.05 , 1.50 ] ) , and significantly interacted with allocated treatment .


Among participants above median severity , the hazard ratio was 0.61 , 95 % CI [ 0.34 , 1.09 ] , for MBCT vs. CPE , and 0.43 , 95 % CI [ 0.22 , 0.87 ] , for MBCT vs. TAU .


For those below median severity , there were no such differences between treatment groups .


MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma , but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression .


The aim of this study was to evaluate the patient 's perceived pain response to injection and anesthetic deposition for the greater palatine nerve block .


Heft-Parker Visual Analog Scale ( VAS ) pain scale measurements were used to compare the following techniques for the injection : ( 1 ) control ( no concurrent stimulation ) , ( 2 ) pressure , ( 3 ) pressure and topical anesthetic ( 20 % benzocaine ) , and ( 4 ) pressure and cold ( TFE ) .


Forty-two volunteers , 21 male and 21 female , participated in the study .


A bilateral model was used on each patient to give an injection on each side of the palate with two different techniques followed by the next appointment ( > or = two weeks later ) , when the two other injection techniques were used .


Following injection given in the supine position , the patients were returned to an upright position and asked to rate their pain on a VAS .


Pain upon needle insertion appears less than that of anesthetic deposition .


There was no statistically significant difference in perceived pain response among the four techniques , the visit , the order , the side , or patient gender at either time point .


Following the application of Endo Ice , 81 % of participants reported a sore on their palate occurring two to 48 hours after cold application and persisting for one to 10 days .


The pain score for this injection had a mean value of 30 % ( 51.4 / 170 ) .


This prospective , single-blind study evaluating three injection techniques to reduce posterior palatal injection pain to a control injection method showed no significant reduction in pain with any of the three techniques .


Furthermore , 1,1,1,2-tetrafluoroethane placed with pressure for 10 seconds appeared injurious to the oral mucosa .


Continuous glucose monitoring ( CGM ) has been shown to improve glucose control in adults with type 1 diabetes .


Effectiveness of CGM is directly linked with CGM adherence , which can be challenging to maintain in children and adolescents .


We hypothesize that initiating CGM at the same time as starting insulin pump therapy in pump nave children and adolescents with type 1 diabetes will result in greater CGM adherence and effectiveness compared to delaying CGM introduction by 6 months , and that this is related to greater readiness for making behaviour change at the time of pump initiation .


The CGM TIME Trial is a multicenter randomized controlled trial .


Eligible children and adolescents ( 5-18 years ) with established type 1 diabetes were randomized to simultaneous initiation of pump ( Medtronic Veo ) and CGM ( Enlite ) or to standard pump therapy with delayed CGM introduction .


Primary outcomes are CGM adherence and hemoglobin A1C at 6 and 12 months post pump initiation .


Secondary outcomes include glycemic variability , stage of readiness , and other patient-reported outcomes with follow-up to 24 months .


144 ( 95 % ) of the 152 eligible patients were enrolled and randomized .


Allowing for 10 % withdrawals , this will provide 93 % power to detect a between group difference in CGM adherence and 86 % power to detect a between group difference in hemoglobin A1C .


Baseline characteristics were similar between the treatment groups .


Analysis of 12 month primary outcomes will begin in September 2014 .


The CGM TIME Trial is the first study to examine the relationship between timing of CGM initiation , readiness for behaviour change , and subsequent CGM adherence in pump nave children and adolescents .


Its findings will advance our understanding of when and how to initiate CGM in children and adolescents with type 1 diabetes .


ClinicalTrial.gov NCT01295788 .


Registered 14 February 2011 .


Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events .


This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular ( LV ) function in patients with ST-elevated myocardial infarction ( STEMI ) .


Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group ( rosuvastatin ; 5 mg/day , n = 38 ) and hydrophobic statin group ( atorvastatin ; 10 mg/day , n = 37 ) for 6 months .


LV ejection fraction ( LVEF ) , and B-type natriuretic peptide ( BNP ) and co-enzyme Q10 ( CoQ10 ) levels were measured at baseline and the end of treatment .


The myocardial salvage index was assessed by single photon emission computed tomography with ( 123 - ) I -- methyl-iodophenylpentadecanoic acid ( ischemic area-at-risk at onset of STEMI : AAR ) and ( 201 - ) thallium scintigraphy ( area-at-infarction at 6 months : AAI ) [ myocardial salvage index = ( AAR-AAI ) 100/AAR ( % ) ] .


Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups .


After 6 months , rosuvastatin ( -37.6 % 17.2 % ) and atorvastatin ( -32.4 % 22.4 % ) equally reduced low-density lipoprotein-cholesterol ( LDL-C ) levels ( p = 0.28 ) .


However , rosuvastatin ( +3.1 % 5.9 % , p < 0.05 ) , but not atorvastatin ( +1.6 % 5.7 % , p = 0.15 ) , improved LVEF .


Rosuvastatin reduced BNP levels compared with atorvastatin ( -53.3 % 48.8 % versus -13.8 % 82.9 % , p < 0.05 ) .


The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group ( 78.6 % 29.1 % versus 52.5 % 38.0 % , p < 0.05 ) .


CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group ( +23.5 % , p < 0.01 ) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index ( r = 0.56 , p < 0.01 ) .


Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients , including long-term cardiac function , associated with increasing CoQ10/LDL-C .


URL http://www.umin.ac.jp/ctr/index.htm Unique Identifier : UMIN000003893 .


Laparoscopic common bile duct exploration ( LCBDE ) is now one of the main methods for treating choledocholithiasis accompanied with cholelithiasis .


The objective of our study was to assess the safety and effectiveness of laparoscopic primary closure for the treatment of common bile duct ( CBD ) stones compared with T-tube drainage .


Patients who underwent CBD stones were studied prospectively from 2002-2012 in a single center .


A total of 194 patients were randomly assigned to group A ( LCBDE with primary closure ) with 101 cases and group B ( LCBDE with T-tube drainage ) with 93 cases .


Intraoperative cholangiography and choledochoscopy were performed in all patients .


Patient demographics , intraoperative findings , postoperative stay , complications , and hospital expenses were recorded and analyzed .


There was no mortality in the two groups .


Four patients ( 3.96 % ) of group A were converted to open surgery , and three patients ( 3.23 % ) in group B.


The mean operating time was much shorter in group A than in group B ( 102.6 15.2 min versus 128.6 20.4 min , P < 0.05 ) .


The length of postoperative hospital stay was longer in group B ( 4.9 3.2 d ) than in group A ( 3.2 2.1 d ) .


The hospital expenses were significantly lower in group A. Three patients experienced postoperative complications , which were related to the usage of the T-tube in group B.


The incidences of overall postoperative complications were insignificantly lower in group A.


Laparoscopic primary closure of CBD is safe and effective for the management of CBD stones , and can be performed routinely as an alternative to T-tube drainage .


A recently discovered myokine , irisin , may have an important role in energy metabolism .


This study aimed to evaluate the relationship between this hormone and the lipid profile of patients with metabolic syndrome ( MetS ) following a hypocaloric diet .


Ninety-three Caucasian adults ( 52 men/41 women ) diagnosed with MetS followed an 8-week-long energy-restricted programme ( -30 % of the energy requirements ) .


Anthropometric measurements , biochemical markers and plasma irisin levels were analysed before and after the nutritional intervention .


Global plasma irisin levels were significantly reduced at the end of the study ( -72.0 100.9 ng/ml , P < 0.001 ) accompanying the weight loss ( -6.9 % ) .


The depletion of irisin significantly correlated with changes in some atherogenic-related variables : total cholesterol ( B = 0.106 , P = 0.018 ) , total cholesterol/high-density lipoprotein cholesterol ratio ( B = 0.002 , P = 0.036 ) , low-density lipoprotein cholesterol ( B = 0.085 , P = 0.037 ) and apolipoprotein B ( B = 0.052 , P = 0.002 ) , independently of changes in body weight .


An association between the reduction in plasma irisin levels and the depletion of important lipid metabolism biomarkers was observed in patients with MetS undergoing an energy-restricted programme .


The 23-valent pneumococcal polysaccharide vaccine is recommended for elders , especially those with chronic conditions .


The aim of this study was to determine if an additional multi-component health education intervention increases the uptake rate of the pneumococcal vaccination among older patients with chronic diseases .


A cluster randomized controlled trial was conducted from 3 December 2007 to 7 March 2008 .


The clusters were the individual weeks within five Hong Kong outpatient clinics over a 10-week period .


A sample of 2517 patients aged 65 or above with chronic diseases was recruited .


Intervention group received a 3-min brief telephone education intervention before and a 3-min face-to-face intervention during scheduled medical appointments at the respective clinics .


All subjects received standard care including health education leaflets and/or a video show at the clinics .


Pneumococcal vaccination rate and awareness of the vaccination at 3-month follow up were measured .


The vaccination rate was higher in the intervention group compared to the control group ( 57 % vs 48 % ; relative risk = 1.20 , 95 % CI = 1.06-1 .37 ) , but the two groups did not differ significantly in their awareness of the vaccination at 3-month follow up ( 65 % vs 59 % , relative risk = 0.86 , 95 % CI = 0.69-1 .07 ) .


A nurse-delivered brief health education intervention was effective in increasing uptake of pneumococcal vaccination among older patients with chronic diseases .


In assessing quality of care in developing countries , retrospectively collected data are usually used given their availability .


Retrospective data however suffer from such biases as recall bias and non-response bias .


Comparing results obtained using prospectively and retrospectively collected data will help validate the use of the easily available retrospective data in assessing quality of care in past and future studies .


Prospective and retrospective datasets were obtained from a cluster randomized trial of a multifaceted intervention aimed at improving paediatric inpatient care conducted in eight rural Kenyan district hospitals by improving management of children admitted with pneumonia , malaria and diarrhea and/or dehydration .


Four hospitals received a full intervention and four a partial intervention .


Data were collected through 3 two weeks surveys conducted at baseline , after 6 and 18 months .


Retrospective data was sampled from paediatric medical records of patients discharged in the preceding six months of the survey while prospective data was collected from patients discharged during the two week period of each survey .


Risk Differences during post-intervention period of 16 quality of care indicators were analyzed separately for prospective and retrospective datasets and later plotted side by side for comparison .


For the prospective data there was strong evidence of an intervention effect for 8 of the indicators and weaker evidence of an effect for one indicator , with magnitude of effect sizes varying from 23 % to 60 % difference .


For the retrospective data , 10 process ( these include the 8 indicators found to be statistically significant in prospective data analysis ) indicators had statistically significant differences with magnitude of effects varying from 10 % to 42 % .


The bar-graph comparing results from the prospective and retrospective datasets showed similarity in terms of magnitude of effects and statistical significance for all except two indicators .


Multifaceted interventions can help improve adoption of clinical guidelines and hence improve the quality of care .


The similar inference reached after analyses based on prospective assessment of case management is a useful finding as it supports the utility of work based on examination of retrospectively assembled case records allowing longer time periods to be studied while constraining costs .


Current Controlled Trials ISRCTN42996612 .


Trial registration date : 20/11/2008 .


Poor patient understanding of their diagnosis and treatment plan can adversely impact clinical outcome following hospital discharge .


Discharge summaries are primarily written for the doctor rather than the patient .


We determined patient understanding of the reasons for hospitalisation , in-hospital tests , treatments and post-discharge recommendations , and whether a brief patient-directed discharge letter ( PADDLE ) delivered during a brief discussion prior to discharge would improve understanding .


A prospective randomised controlled trial was conducted , including 67 hospitalised patients .


After a baseline questionnaire , patients were randomised to receive the PADDLE letter or usual care .


Those receiving the letter had an immediate follow-up questionnaire .


Patient understanding was compared with a summary letter written by the treating clinician , using a 5-point Likert scale ranging from none to full understanding .


A questionnaire was administered at 3 and 6 months .


At baseline , patients had almost full understanding ( median score 4 ) of reasons for hospitalisation and treatments .


However , despite high self-appraisal , patients objectively had very little understanding of tests performed and post-discharge recommendations ( median 2 ) .


Those receiving the letter had an immediate increase to almost full understanding ( median 4 ) of tests performed ( P < 0.001 ) and to full understanding ( median 5 ) of post-discharge recommendations .


This increase did not persist at 3 or 6 months .


A simple patient-directed letter delivered during a brief discussion improves patient understanding of their hospitalisation and post-discharge recommendations , which is otherwise limited .


Further evaluation of this brief and well-received intervention is indicated , with the goal of improving patient understanding , satisfaction and clinical outcomes .


Patient reported outcome measures ( PROMs ) are used to evaluate lifestyle interventions but little is known about differences between patients returning valid and invalid responses , or of potential for bias in evaluations .


We aimed to examine the characteristics of patients who returned valid responses to lifestyle questionnaires compared to those whose responses were invalid for evaluating lifestyle change .


We conducted a secondary data analysis from the SPHERE Study , a trial of an intervention to improve outcomes for patients with coronary heart disease in primary care .


Postal questionnaires were used to assess physical activity ( Godin ) and diet ( DINE ) among study participants at baseline and 18 month follow-up .


Three binary response variables were generated for analysis : ( 1 ) valid Godin score ; ( 2 ) valid DINE Fibre score ; and ( 3 ) valid DINE Total Fat score .


Multivariate analysis comprised generalised estimating equation regression to examine the association of patients ' characteristics with their return of valid responses at both timepoints .


Overall , 92.1 % of participants ( 832/903 ) returned questionnaires at both baseline and 18 months .


Relatively fewer valid Godin scores were returned by those who left school aged < 15 years ( 36.5 % ) than aged 18 and over ( 50.5 % ) , manual workers ( 39.5 % ) than non-manual ( 49.5 % ) and those with an elevated cholesterol ( > 5 mmol ) ( 34.7 % ) than those with a lower cholesterol ( 44.4 % ) but multivariate analysis identified that only school leaving age ( p = 0.047 ) was of statistical significance.Relatively fewer valid DINE scores were returned by manual than non-manual workers ( fibre : 80.8 % v 86.8 % ; fat : 71.2 % v 80.0 % ) , smokers ( fibre : 72.6 % v 84.7 % ; fat : 67.5 % v 76.9 % ) , patients with diabetes ( fibre : 75.9 % v 82.9 % ; fat : 66.9 % v 75.8 % ) and those with cholesterol > 5 mmol ( fat : 68.2 % v 76.2 % ) but multivariate analysis showed statistical significance only for smoking ( fibre : p = 0.013 ; fat : p = 0.045 ) , diabetes ( fibre : p = 0.039 ; fat : p = 0.047 ) , and cholesterol ( fat : p = 0.039 ) .


Our findings illustrate the importance of detailed reporting of research methods , with clear information about response rates , respondents and valid outcome data .


Outcome measures which are relevant to a study population should be chosen carefully .


The impact of methods of outcome measurement and valid response rates in evaluating healthcare requires further study .


Previous studies have shown that a calcium ( Ca ) pre-rinse given before a 228 ppm fluoride ( F ) rinse greatly increased salivary fluoride .


Objectives .


The aim of this randomized controlled trial is to examine if Ca pre-rinse could increase the fluoride concentration in the overnight unstimulated saliva after a 905 ppm F-rinse .


Pre-rinses containing 150 mM , 75 mM or 0 mM Ca-lactate prepared by a validated pharmaceutical cGPM procedure were tested by nine subjects in a randomized order immediately followed by a 905 ppm F-rinse .


The fluoride concentration was measured in unstimulated saliva collected 10 h later .


The Ca pre-treatment significantly increased F level in overnight saliva following the 905 ppm fluoride rinse by 1.7 relative to the 905 ppm F-rinse alone ; however , a significant effect was only observed with the highest ( 150 mM ) Ca concentration as pre-rinse .


Clinical relevance .


High concentration F rinses ( 905 ppm ) are commonly recommended for patients at high-risk of caries .


A pre-treatment with high levels of Ca may further improve the cariostatic effect of this ion .


Social media sites , such as Facebook , merge two factors that influence risk for eating disorders : media and peers .


Previous work has identified cross-sectional and temporal associations between Facebook use and disordered eating .


This study sought to replicate and extend these findings using an experimental design .


In Study 1 , 960 women completed self-report surveys regarding Facebook use and disordered eating .


In Study 2 , 84 women were randomly assigned to use Facebook or to use an alternate internet site for 20 min .


More frequent Facebook use was associated with greater disordered eating in a cross-sectional survey .


Facebook use was associated with the maintenance of weight/shape concerns and state anxiety compared to an alternate internet activity .


Facebook use may contribute to disordered eating by maintaining risk for eating pathology .


As such , targeting Facebook use may be helpful in intervention and prevention programs .


Oritavancin is a lipoglycopeptide antibiotic with rapid bactericidal activity against gram-positive bacteria .


Its concentration-dependent activity and long half-life allow for single-dose treatment .


In a randomized , double-blind trial , adults with acute bacterial skin and skin structure infections ( ABSSSIs ) received either a single intravenous 1200-mg dose of oritavancin or 7-10 days of twice-daily vancomycin .


Three efficacy endpoints were tested for noninferiority : ( 1 ) primary composite endpoint at 48-72 hours ( cessation of spreading or reduction in lesion size , absence of fever , and no rescue antibiotic ) ; ( 2 ) investigator-assessed clinical cure 7-14 days after end of treatment ; and ( 3 ) 20 % reduction in lesion area at 48-72 hours .


A total of 503 and 502 patients comprised the modified intent-to-treat population for oritavancin and vancomycin , respectively .


All 3 efficacy endpoints met the 10 % noninferiority margin : the primary composite endpoint ( 80.1 % vs 82.9 % ; 95 % confidence interval [ CI ] , -7.5 to 2.0 ) , investigator-assessed clinical cure ( 82.7 % vs 80.5 % ; 95 % CI , -2.6 to 7.0 ) , and proportion of patients attaining 20 % reduction in lesion area ( 85.9 % vs 85.3 % ; 95 % CI , -3.7 to 5.0 ) for oritavancin vs vancomycin , respectively .


Efficacy outcomes by pathogen , including methicillin-resistant Staphylococcus aureus and the frequency of adverse events , were similar between treatment groups .


A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens , and was well tolerated .


Oritavancin provides a single-dose alternative to multidose therapies for the treatment of ABSSSIs .


Clinical Trials Registration .


NCT01252732 .


To test a combination of dexamethasone intravitreal implant with macular grid laser for macular edema in patients with branch retinal vein occlusion ( BRVO ) .


Prospective interventional , randomized , multicenter study .


Patients with macular edema secondary to BRVO underwent an Ozurdex intravitreal implant at baseline .


After 1 month , patients were randomly assigned to 2 study groups .


Patients in Group 1 were followed up monthly and retreated with Ozurdex implant whenever there was a recurrence of macular edema or a decrease in best-corrected visual acuity ( BCVA ) .


In Group 2 patients macular grid laser was performed between weeks 6 and 8 .


After that , patients were followed up and retreated as for Group 1 .


In Group 1 at 4 months , mean BCVA was 0.49 0.35 logMAR and central retinal thickness ( CRT ) was 391 172 m ; both improved significantly at 6 months , to 0.32 0.29 logMAR and 322 160 m , respectively .


In Group 2 , CRT was reduced significantly to 291 76 m at 4 months , and BCVA improved to 0.25 0.20 logMAR .


At the final visit , BCVA was 0.18 0.14 logMAR and mean CRT was 271 44 m.


The number of Ozurdex implants at 4 months was 12 of 25 ( 48 % ) in Group 1 patients vs 3 of 25 ( 12 % ) in Group 2 patients ( P = .012 ) .


At 6 months 3 of 25 patients ( 12 % ) in Group 1 vs 0 of 25 ( 0 % ) in Group 2 ( P = .23 ) were retreated .


The combination of Ozurdex implant and macular grid laser is synergistic in increasing BCVA and lengthening the time between injections .


Pulmonary arterial hypertension ( PAH ) is a progressive disease with high rates of morbidity and mortality .


Current therapies improve symptoms , functional capacity , and , in select cases , survival .


Little is known about patient factors that may predict the likelihood of patient-important , clinically relevant responses to therapy such as the 6-min walk distance ( 6MWD ) and health-related quality of life ( HRQoL ) .


Data from the randomized clinical trial of tadalafil in PAH were used .


Adjusted logistic regression models were created to examine the relationship between baseline characteristics and odds of achieving the minimal important difference ( MID ) in three parameters , defined as either a > 33-m increase in 6MWD , a > 5-unit increase in physical component summary score of the Medical Outcomes Study Short Form-36 ( SF-36 ) , or a > 5-unit increase in mental component summary score of the SF-36 .


The study included 405 subjects .


Younger age , male sex , lower baseline 6MWD , and disease etiology were associated with greater odds of achieving the MID for the 6-min walk test .


Active treatment , younger age , and male sex were associated with greater odds of achieving the MID for the physical component summary score .


Male sex was associated with greater odds of achieving the MID for the mental component summary score .


Age , sex , baseline functional capacity , and disease etiology are variably associated with the likelihood of achieving clinically relevant responses in patient-important outcomes to PAH-specific therapy such as 6MWD and HRQoL .


The increased likelihood of response in men compared with women is a novel finding and may reflect pathophysiologic differences between sexes .


Vascular calcification is a potent predictor of plaque instability and cardiac events .


Osteoprotegerin ( OPG ) , well-known vascular calcification mediator , is a signaling molecule involved in bone remodeling , which has been implicated in the regulation of vascular calcification and atherogenesis .


The purpose of this study was to compare the combination treatments of olmesartan/azelnidipine and olmesartan/diuretics on serum bone-related markers in patients with essential hypertension .


A total of 48 patients with hypertension treated with 20 mg olmesartan were randomized to receive combination treatment with 16 mg azelnidipine ( O/A group ) or diuretics ( 1 mg indapamide ; O/D group ) for 12 months .


Osteoprotegerin , matrix metalloproteinase 2 ( MMP-2 ) , and high-sensitive CRP ( hs-CRP ) were measured after 3 and 12 months of treatment .


Cardio-ankle vascular index ( CAVI ) was measured as the arterial stiffness using a VaSera CAVI instrument at the same time points .


In both groups , the systolic and diastolic blood pressure reduction is similar .


Serum OPG , MMP-2 , and hs-CRP were significantly decreased at 12 months in the O/A group ( P < .05 ) , while there were no significant reductions in the O/D group .


CAVI was significantly improved at 12 months in both the treatment groups .


The improvement in CAVI was significantly greater in the O/A group than in the O/D group .


Azelnidipine , but not indapamide , combined with olmesartan , improved arterial stiffness and were associated with significant decrease in OPG , MMP-2 , and hs-CRP concentrations .


These results suggest that the beneficial effects of the combination treatments of olmesartan/azelnidipine on arterial stiffness are mediated by alteration in bone-remodeling and inflammatory markers .


Excessive alcohol use is a prevalent and worldwide problem .


Excessive drinking causes a significant burden of disease and is associated with both morbidity and excess mortality .


Prototype alteration and provision of a cue reminder could be useful strategies to enhance the effectiveness of online tailored interventions for excessive drinking .


Through a Web-based randomized controlled trial , 2 strategies ( ie , prototype alteration and cue reminders ) within an existing online personalized feedback intervention ( Drinktest ) aimed to reduce adults ' excessive drinking .


It was expected that both strategies would add to Drinktest and would result in reductions in alcohol consumption by intrinsic motivation and the seizure of opportunities to act .


Participants were recruited online and through printed materials .


Excessive drinking adults ( N = 2634 ) were randomly assigned to 4 conditions : original Drinktest , Drinktest plus prototype alteration , Drinktest plus cue reminder , and Drinktest plus prototype alteration and cue reminder .


Evaluation took place at 1-month posttest and 6-month follow-up .


Differences in drinking behavior , intentions , and behavioral willingness ( ie , primary outcomes ) were assessed by means of longitudinal multilevel analyses using a last observation carried forward method .


Measures were based on self-reports .


All conditions showed reductions in drinking behavior and willingness to drink , and increased intentions to reduce drinking .


Prototype alteration ( B = -0.15 , P < .05 ) and cue reminder usage ( B = -0.15 , P < .05 ) were both more effective in reducing alcohol consumption than when these strategies were not provided .


Combining the strategies did not produce a synergistic effect .


No differences across conditions were found regarding intentions or willingness .


Although individuals ' awareness of their cue was reasonable , their reported alcohol consumption was nevertheless reduced .


Individuals appeared to distance their self-image from heavier drinking prototypes .


Thus , prototype alteration and cue reminder usage may be feasible and simple intervention strategies to promote reductions in alcohol consumption among adults , with an effect up to 6 months .


Nederlands Trial Register ( NTR ) : 4169 ; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4169 ( Archived by WebCite at http://www.webcitation.org/6VD2jnxmB ) .


Evidence suggests depression increases hospital readmission risk .


Determine whether depressive symptoms are associated with unplanned readmission within 30 days of discharge of general medical patients .


Secondary analysis of the Project Re-Engineered Discharge ( RED ) randomized controlled trials .


Urban academic safety-net hospital .


A total of 1418 hospitalized adult English-speaking patients .


The 9-Item Patient Health Questionnaire ( PHQ-9 ) was used to screen patients for depressive symptoms .


Hospital readmission within 30 days of discharge .


Poisson regression was used to control for confounding variables .


There were 225 ( 16 % ) patients who screened positive for mild depressive symptoms ( 5 PHQ-9 9 ) and 336 ( 24 % ) for moderate or severe depressive symptoms ( PHQ-9 10 ) .


After controlling for confounders , a higher rate of readmission was observed in subjects with mild depressive symptoms compared to subjects with PHQ-9 < 5 , incidence rate ratio ( IRR ) 1.49 ( 95 % confidence interval [ CI ] : 1.11-2 .00 ) .


The adjusted IRR of readmission for those with moderate-to-severe symptoms was 1.96 ( 95 % CI : 1.51-2 .49 ) compared to those with no depression .


Screening positive for mild and moderate-to-severe depressive symptoms during a hospitalization on a general medical service is associated with an increased dose-dependent readmission rate within 30 days of discharge in an urban , academic , safety-net hospital .


Further research is needed to determine whether treatments targeting the reduction of depressive symptoms reduce the risk of readmission .


Gaucher disease type 1 is characterized by hepatosplenomegaly , anemia , thrombocytopenia , and skeletal disease .


A safe , effective oral therapy is needed .


To determine whether eliglustat , a novel oral substrate reduction therapy , safely reverses clinical manifestations in untreated adults with Gaucher disease type 1 .


Phase 3 , randomized , double-blind , placebo-controlled trial conducted at 18 sites in 12 countries from November 2009 to July 2012 among eligible patients with splenomegaly plus thrombocytopenia and/or anemia .


Of 72 patients screened , 40 were enrolled .


Patients were stratified by spleen volume and randomized 1:1 to receive eliglustat ( 50 or 100 mg twice daily ; n = 20 ) or placebo ( n = 20 ) for 9 months .


The primary efficacy end point was percentage change in spleen volume in multiples of normal from baseline to 9 months ; secondary efficacy end points were change in hemoglobin level and percentage changes in liver volume and platelet count .


All patients had baseline splenomegaly and thrombocytopenia ( mostly moderate or severe ) , most had mild or moderate hepatomegaly , and 20 % had mild anemia .


Least-square mean spleen volume decreased by 27.77 % ( 95 % CI , -32.57 % to -22.97 % ) in the eliglustat group ( from 13.89 to 10.17 multiples of normal ) vs an increase of 2.26 % ( 95 % CI , -2.54 % to 7.06 % ) in the placebo group ( from 12.50 to 12.84 multiples of normal ) for an absolute treatment difference of -30.03 % ( 95 % CI , -36.82 % to -23.24 % ; P < .001 ) .


For the secondary end points , the least-square mean absolute differences between groups all favored eliglustat , with a 1.22-g / dL increase in hemoglobin level ( 95 % CI , 0.57-1 .88 g/dL ; P < .001 ) , 6.64 % decrease in liver volume ( 95 % CI , -11.37 % to -1.91 % ; P = .007 ) , and 41.06 % increase in platelet count ( 95 % CI , 23.95 % -58.17 % ; P < .001 ) .


No serious adverse events occurred .


One patient in the eliglustat group withdrew ( non-treatment related ) ; 39 of the 40 patients transitioned to an open-label extension study .


Among previously untreated adults with Gaucher disease type 1 , treatment with eliglustat compared with placebo for 9 months resulted in significant improvements in spleen volume , hemoglobin level , liver volume , and platelet count .


The clinical significance of these findings is uncertain , and more definitive conclusions about clinical efficacy and utility will require comparison with the standard treatment of enzyme replacement therapy as well as longer-term follow-up .


clinicaltrials.gov Identifier : NCT00891202 .


To investigate urine excretion of nephrin in patients with proteinuric nephropathies associated with rheumatoid arthritis ( RA ) .


We enrolled in the study 42 patients with seropositive RA and proteinuria , the control group ( 20 persons ) was formed from healthy blood donors , the comparison group ( 23 persons ) was formed from RA patients without proteinuria .


Kidney biopsy was performed in 26 patients ( glomerulonephritis was diagnosed in 14 patients , - amyloidosis in 7 patients and tubulointerstitial nephritis in 5 patients ) .


Urine nephrin concentration in patients with RA and proteinuria was 6.2 ( 3.0 ; 8.8 ) ng/ml and significantly differed in its levels both in controls - 3.6 ( 2.4 ; 5.3 ) ng/ml ( p = 0.03 ) and RA patients without proteinuria - 3.2 ( 2.1 ; 5.1 ) ng / ml ( p = 0.015 ) group .


In RA patients with proteinuria , we found a positive correlation between urine nephrin and protein concentrations ( r = 0.4 ; p = 0.04 ) .


Urine nephrin levels in patients of the glomerulonephritis - 7.3 ( 5.9 ; 9.2 ) and amyloidosis groups - 6.9 ( 3.9 ; 9.8 ) ng/ml were higher than in the controls ( p = 0.001 ; p = 0.04 ) and in the group of patients without proteinuria ( p = 0.005 ; p = 0.03 ) .


In the patients with tubulointerstitial nephritis urine nephrin concentration did not differ significantly with the values in both the control and the RA patients without proteinuria groups .


According to our data , proteinuria in the overall cohort of patients with seropositive RA is associated with increased levels of urine nephrin excretion , the highest levels of nephrin excretion were registered in patients with glomerulonephritis and amyloidosis .


Depression is one the most common mental disorders that can be seen all over the world .


In traditional Persian medicine , some medicinal herbs are recommended for depression treatment .


This study aimed to evaluate the effects of Cuscuta planiflora Ten .


and Nepeta menthoides Boiss .


& Buhse in patients with major depression .


This study is a randomized triple-blind controlled clinical trial conducted in the year 2010 in Shiraz University of Medical Sciences on patients with major depression .


Pharmaceutical capsules of Cuscuta planiflora ( 500 mg ) and Nepeta menthoides ( 400 mg ) were prepared by a pharmacist .


Patients were randomly assigned to 3 groups : group A ( treated with Nepeta menthoides capsules and conventional drugs ) , group B ( treated with Cuscuta planiflora capsules and conventional drugs ) , and group C ( treated only with conventional drugs ) .


The study period was 8 weeks and depression was measured before and after the study by Beck Depression Inventory and Hamilton Depression Inventory .


The data were analyzed by SPSS version 20 and the P < .05 was considered statistically significant .


A total of 43 subjects participated in this study , of whom 81.4 % were females ( n = 35 ) and 18.6 % were males ( n = 8 ) .


The mean standard deviation of age of the participants was 38 10.9 years .


The majority of patients ( 65.1 % , n = 28 ) were married .


There were 15 patients ( 34.9 % ) in group A , 13 ( 30.29 % ) in group B , and 15 ( 34.9 % ) in group C.


There was a significant decrease in mean scores of Beck and Hamilton depression inventories in the 3 groups after treatment ( P < .01 ) ; moreover , there was more decrease in scores of the Beck and Hamilton depression inventories in groups A and B compared with group C after treatment ( P < .01 ) .


Despite the paucity of the population under study , the findings showed that Cuscuta planiflora and Nepeta menthoides capsules could be effective , affordable herbal medicines with improved cost-benefit in treatment of major depression and it is worth designing further and more extensive studies to get to a more accurate conclusion .


To evaluate the effect of side-cut angle profile on corneal biomechanical properties after femtosecond laser in situ keratomileusis ( FS-LASIK ) .


Ninety-six myopic eyes of 48 patients underwent FS-LASIK .


One eye of each patient was randomized to flap creation with a side-cut angle of 115 .


The fellow eye flap side-cut angle was adjusted to 70 .


Mean absolute error of flap diameter and mean change in Goldmann-correlated intra-ocular pressure ( IOPg ) , corneal-compensated IOP ( IOPcc ) , corneal hysteresis ( CH ) , corneal resistance factor ( CRF ) , p1 area , p2 area , p1 area 1 and p2 area 1 were compared between both groups .


Overall , the mean IOPg and CRF showed significant reduction at the end of 1 and 3months , as well as between 1 and 3months postoperatively ( p0 .03 ) .


The mean IOPcc and CH showed significant reduction ( p < 0.001 ) at the end of 3months postoperatively .


The parameters p1 area , p2 area , p1 area 1 and p2 area 1 changed significantly at the end of 1 and 3months postoperatively ( p < 0.001 ) .


There was no significant difference between both groups with regards to the mean change of IOPg , IOPcc , CH , CRF , p1 area , and p1 area 1 .


In 115 group , the mean absolute error in flap diameter was greater compared with 70 group ( p = 0.014 ) .


The stability of IOP and corneal biomechanical properties were not enhanced in FS-LASIK flaps with an inverted side-cut angle .


The size of corneal flap created with 70 side-cut angle was more accurate compared with 115 side-cut angle .


To study post-operative pain and blood loss after intraoperative periarticular injection with the multimodal drugs diclofenac , adrenaline , marcaine ( bupivacaine ) and morphine in total knee arthroplasty .


A prospective randomized controlled trial of knee osteoarthritis patients age more than 55 years undergoing total knee arthroplasty at Maharat Nakhon Ratchasima hospital from January 2011 through June 2012 was performed .


A group receiving intra-operative periarticular injections was compared to a control group receiving no injections .


Half of a group of forty-two patients , 2 males and 40 females , average age 67.9 years ( range 57-84 years ) , were randomly assigned to receive the periarticular injection ( the injection group ) , the others to the control group .


Pain was measured by two methods : visual analog score at 6 , 12 , 24 and 48 hours post-operation and by patient controlled analgesia ( PCA ) measuring the daily amount of intravenous morphine used .


The amount of blood loss post operation ( in the redivac drain ) , degree of knee flexion , time to onset of assisted ambulation , length of hospital stay and any complications were also analyzed .


The mean VAS at 6 and 12 hours post operation of the injection group were 2.67 and 2.48 , whereas the values for the control group were 6.10 and 4.95 , respectively ( p < 0.05 ) .


Mean quantities of morphine used by PCA by the injection group during the first day was 9.43 mg , significantly lower than the 18.81 mg used by the control group .


Average blood loss of the injection group at 263.8 ml was also significantly below the 362.1 ml of the control group ( p < 0.05 ) .


The degree of knee flexion , time to onset of assist ambulation , length of hospital stay and complications , however were not significantly different between the groups .


Multimodal drugs , periarticular injections consisting of diclofenac , adrenaline , Marcaine plus a patient controled anesthetic machine ( PCA ) with morphine can significantly reduce post-operative pain and blood loss in total knee arthroplasty without significant adverse effects .


Most primary care clinicians lack the skills and resources to offer effective lifestyle and medication ( L&M ) counseling to reduce coronary heart disease ( CHD ) risk .


Thus , effective and feasible CHD prevention programs are needed for typical practice settings .


To assess the effectiveness , acceptability , and cost-effectiveness of a combined L&M intervention to reduce CHD risk offered in counselor-delivered and web-based formats .


A comparative effectiveness trial in 5 diverse family medicine practices in North Carolina .


Participants were established patients , aged 35 to 79 years , with no known cardiovascular disease , and at moderate to high risk for CHD ( 10-year Framingham Risk Score [ FRS ] , 10 % ) .


Participants were randomized to counselor-delivered or web-based format , each including 4 intensive and 3 maintenance sessions .


After randomization , both formats used a web-based decision aid showing potential CHD risk reduction associated with L&M risk-reducing strategies .


Participants chose the risk-reducing strategies they wished to follow .


The primary outcome was within-group change in FRS at 4-month follow-up .


Other measures included standardized assessments of blood pressure , blood lipid levels , lifestyle behaviors , and medication adherence .


Acceptability and cost-effectiveness were also assessed .


Outcomes were assessed at 4 and 12 months .


Of 2274 screened patients , 385 were randomized ( 192 counselor ; 193 web ) : mean age , 62 years ; 24 % African American ; and mean FRS , 16.9 % .


Follow-up at 4 and 12 months included 91 % and 87 % of the randomized participants , respectively .


There was a sustained reduction in FRS at both 4 months ( primary outcome ) and 12 months for both counselor-based ( -2.3 % [ 95 % CI , -3.0 % to -1.6 % ] and -1.9 % [ 95 % CI , -2.8 % to -1.1 % ] , respectively ) and web-based groups ( -1.5 % [ 95 % CI , -2.2 % to -0.9 % ] and -1.7 % [ 95 % CI , -2.6 % to -0.8 % ] respectively ) .


At 4 months , the adjusted difference in FRS between groups was -1.0 % ( 95 % CI , -1.8 % to -0.1 % ) ( P = .03 ) , and at 12 months , it was -0.6 % ( 95 % CI , -1.7 % to 0.5 % ) ( P = .30 ) .


The 12-month costs from the payer perspective were $ 207 and $ 110 per person for the counselor - and web-based interventions , respectively .


Both intervention formats reduced CHD risk through 12-month follow-up .


The web format was less expensive .


clinicaltrials.gov Identifier : NCT01245686 .


This randomized , double-blind 8 week study compared the efficacy and tolerability of fixed-dose treatment with vortioxetine ( 10mg/day ) and venlafaxine extended release ( XR ) ( 150mg/day ) in major depressive disorder ( MDD ) patients .


Patients aged 18-65 years with a primary diagnosis of recurrent MDD , a Montgomery-sberg Depression Rating Scale ( MADRS ) total score 26 and a Clinical Global Impression-Severity ( CGI-S ) score 4 were randomized ( 1:1 ) to treatment with either vortioxetine or venlafaxine XR .


The primary endpoint was change from baseline to Week 8 in MADRS total score ( analysis of covariance [ ANCOVA ] , full-analysis set [ FAS ] , last observation carried forward [ LOCF ] ) , using a non-inferiority margin of +2.5 points .


Pre-specified secondary endpoints included MADRS response and remission rates , anxiety symptoms ( HAM-A ) , CGI , overall functioning ( SDS ) , and health-related quality of life ( Q-LES-Q ) .


This study ( SOLUTION ) has the www.ClinicalTrials.gov identifier : NCT01571453 .


On the primary efficacy endpoint at Week 8 , non-inferiority was established with a difference of -1.2 MADRS points in favor of vortioxetine ( 95 % CI : -3.0 to 0.6 ) .


The MADRS total score decreased ( improved ) from 32.34.6 at baseline to 13.69.6 ( vortioxetine : n = 209 ) and from 32.34.5 to 14.810.4 ( venlafaxine XR : n = 215 ) ( FAS , LOCF ) .


At Week 8 , the HAM-A and SDS total scores , CGI and Q-LES-Q scores , and response and remission rates demonstrated similar improvement for vortioxetine and venlafaxine XR , with remission rates ( MADRS 10 ) of 43.1 % ( vortioxetine ) versus 41.4 % ( venlafaxine XR ) ( LOCF ) .


Fewer vortioxetine than venlafaxine XR patients withdrew for any reason ( 18.0 % versus 27.4 % ) or for adverse events ( 6.6 % versus 13.7 % ) .


The most frequent adverse events ( 5 % ) for both treatments were nausea , dizziness , headache , and dry mouth .


In addition , accidental overdose , decreased appetite , constipation and insomnia were reported by ( 5 % ) of patients treated with venlafaxine XR .


The inclusion and exclusion criteria may limit the generalizability of the study .


Since patients with a history of lack of response to venlafaxine XR were excluded from this study , there is a selection bias in favor of venlafaxine XR .


Vortioxetine was at least as efficacious as venlafaxine XR and was safe and better tolerated than venlafaxine XR .


Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer , but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant ( MDR ) bacteria .


In this multicenter , open-label , randomized , superiority trial , adult , febrile , high-risk neutropenic patients ( FhrNPs ) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam ( 4.5 g intravenously every 8 hours ) with or without tigecycline ( 50 mg intravenously every 12 hours ; loading dose 100 mg ) .


The primary end point was resolution of febrile episode without modifications of the initial allocated treatment .


Three hundred ninety FhrNPs were enrolled ( combination/monotherapy , 187/203 ) and were included in the intention-to-treat analysis ( ITTA ) .


The ITTA revealed a successful outcome in 67.9 % v 44.3 % of patients who had received combination therapy and monotherapy , respectively ( 127/187 v 90/203 ; absolute difference in risk ( adr ) , 23.6 % ; 95 % CI , 14 % to 33 % ; P < .001 ) .


The combination regimen proved better than monotherapy in bacteremias ( adr , 32.8 % ; 95 % CI , 19 % to 46 % ; P < .001 ) and in clinically documented infections ( adr , 36 % ; 95 % CI , 9 % to 64 % ; P < .01 ) .


Mortality and number of adverse effects were limited and similar in the two groups .


The combination of piperacillin/tazobactam and tigecycline is safe , well tolerated , and more effective than piperacillin/tazobactam alone in febrile , high-risk , neutropenic hematologic patients with cancer .


In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms , this combination could be considered as one of the first-line empiric antibiotic therapies .


To compare pregabalin versus placebo and pramipexole for reducing restless legs syndrome ( RLS ) - related sleep disturbance .


Randomized , double-blinded , crossover trial .


Twenty-three US sleep centers .


Eighty-five individuals with moderate to severe idiopathic RLS and associated sleep disturbance .


Participants were randomized across 6 treatment sequences comprising three 4-week periods on pregabalin 300 mg/day ( n = 75 ) , pramipexole 0.5 mg/day ( n = 76 ) , or placebo ( n = 73 ) .


Polysomnography was conducted over 2 nights at the end of each period .


Primary ( wake after sleep onset [ WASO ] , pregabalin vs placebo ) and key secondary endpoints were analyzed for statistical significance , with descriptive statistics for other endpoints .


Pregabalin improved sleep maintenance , demonstrated by reductions in WASO ( -27.1 min vs placebo [ P < 0.0001 ] ; -26.9 vs pramipexole ) and number of awakenings after sleep onset ( -2.7 vs placebo ; -7.9 vs pramipexole [ P < 0.0001 ] ) by polysomnography , and an increase in subjective total sleep time ( 30.8 min vs placebo [ P < 0.0001 ] ; 26.8 vs pramipexole ) .


Pregabalin also increased slow wave sleep duration ( 20.9 min vs placebo ; 32.1 vs pramipexole [ P < 0.0001 ] ) .


Reduction in periodic limb movement arousal index ( PLMAI ) with pregabalin was similar to pramipexole and greater than placebo ( -3.7 PLMA/h [ P < 0.0001 ] ) , although reduction in total PLM in sleep was less than for pramipexole .


This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole .


Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole .


ClinicalTrials.gov identifier , NCT00991276 ; http://clinicaltrials.gov/show/NCT00991276 .


Limited data exist on radial access in carotid artery stenting .


This multicentre prospective randomised study was performed to compare the outcome and complication rates of transradial and transfemoral carotid artery stenting .


The clinical and angiographic data of 260 consecutive patients with high risk for carotid endarterectomy , treated between 2010 and 2012 by carotid stenting with cerebral protection , were evaluated .


Patients were randomised to transradial ( n = 130 ) or transfemoral ( n = 130 ) groups and several parameters were evaluated .


Primary combined endpoint : major adverse cardiac and cerebral events , rate of access-site complications .


Secondary endpoints : angiographic outcome of the procedure , fluoroscopy time and X-ray dose , procedural time , crossover rate to another puncture site and hospitalisation in days .


Procedural success was achieved in all 260 patients ( 100 % ) , the crossover rate was 10 % in the TR and 1.5 % in the TF group ( p < 0.05 ) .


A major access-site complication was encountered in one patient ( 0.9 % ) in the TR group and in one patient ( 0.8 % ) in the TF group ( p = ns ) .


The incidence of major adverse cardiac and cerebral events was 0.9 % in the TR and 0.8 % in the TF group ( p = ns ) .


Procedure time ( 1,620 [ 1,230-2 ,100 ] vs. 1,500 [ 1,080-2 ,100 ] sec , p = ns ) and fluoroscopy time ( 540 [ 411-735 ] vs. 501 [ 378-702 ] sec , p = ns ) were not significantly different , but the radiation dose was significantly higher in the TR group ( 195 [ 129-274 ] vs. 148 [ 102-237 ] Gy * cm2 , p < 0.05 ) by per-protocol analysis .


Hospitalisation days were significantly lower in the TR group ( 1.170.40 vs. 1.250.45 , p < 0.05 ) .


By intention-to-treat analysis there was a significantly higher radiation dose in the TR group ( 195 [ 130-288 ] vs. 150 [ 104-241 ] , p < 0.05 ) , but no difference in major events ( 0.9 vs. 0.8 , p = ns ) and length of hospitalisation in days ( 1.42.6 vs. 1.250.45 , p = ns ) .


The transradial approach for carotid artery stenting is safe and efficacious ; however , the crossover rate is higher with transradial access .


There are no differences in the total procedure duration and fluoroscopy time between the two approaches but the radiation dose is significantly higher in the radial group , and the hospitalisation is shorter with the use of transradial access by per-protocol analysis .


By evaluating the patient data according to intention-to-treat analysis we found no difference in major adverse events and hospitalisation .


In both groups , vascular complications rarely occurred .


Here , we evaluated the safety and immunogenicity of hepatitis B virus ( HBV ) DNA vaccine , HB-110 , in mice and Korean patients with chronic hepatitis B ( CHB ) undergoing adefovir dipivoxil ( ADV ) treatment .


For animal study , mice ( BALB/c or HBV transgenic ) were immunized with mHB-110 , and T-cell and antibody responses were evaluated .


For clinical study , 27 patients randomly received either ADV alone or ADV in combination with HB-110 .


Liver function tests , serum HBV DNA levels and the presence of HBeAg/anti-HBe were analysed .


T-cell responses were estimated by ELISPOT and FACS analysis .


mHB-110 induced higher T-cell and antibody responses than mHB-100 in mice .


No adverse effects were observed by HB-110 cotreated with ADV. HBV-specific T-cell responses were induced in a portion of patients in medium to high dose of HB-110 .


Interestingly , HB-110 exhibited positive effects on ALT normalization and maintenance of HBeAg seroconversion .


One patient , who received high dose of HB-110 exhibited HBeAg seroconversion during vaccination , which correlated with vaccine-induced T-cell responses without ALT elevation .


HB-110 was safe and tolerable in CHB patients .


In contrast to results in animal models , HB-110 in Korean patients exhibited weaker capability of inducing HBV-specific T-cell responses and HBeAg seroconversion than HB-100 in Caucasian patients .


As Asian patients , who are generally infected via vertical transmission , appeared to have higher level of immune tolerance than Caucasian , novel approaches for breaking immune tolerance rather than enhancing immunogenicity may be more urgently demanded to develop effective therapeutic HBV DNA vaccines .


We assessed the efficacy , safety , and tolerability of ponesimod , an oral , selective , reversible modulator of sphingosine 1-phosphate receptor 1 , in patients with moderate to severe chronic plaque psoriasis .


Between Sept 22 , 2010 , and Oct 24 , 2012 , patients with psoriasis area and severity index ( PASI ) scores higher than 10 were enrolled into this multicentre double-blind , phase 2 study .


They received 20 mg or 40 mg ponesimod or placebo once daily for 16 weeks .


Those with at least 50 % reduction in PASI score at 16 weeks and who were receiving ponesimod were rerandomised to receive maintenance ponesimod therapy or placebo until week 28 .


The primary endpoint was reduction in PASI score from baseline of at least 75 % ( PASI75 ) at week 16 .


This study is registered with ClinicalTrials.gov , number NCT01208090 .


Of 326 patients initially randomised ( 20 mg ponesimod n = 126 , 40 mg ponesimod n = 133 , and placebo n = 67 ) PASI75 was achieved at week 16 in 58 ( 460 % ) , 64 ( 481 % ) , and nine ( 134 % ) , respectively .


The treatment effect was significant for the two ponesimod doses ( both p < 00001 ) .


Of 219 patients who entered the maintenance period , PASI75 was achieved by week 28 in 35 ( 714 % ) of 49 who continued on 20 mg ponesimod and 41 ( 774 % ) of 53 on 40 mg ponesimod , and in 19 ( 422 % ) of 45 who swapped from 20 mg to placebo and 19 ( 404 % ) of 47 from 40 mg to placebo .


Ponesimod was associated with dyspnoea , raised liver enzyme concentrations , and dizziness .


Significant clinical benefit was seen at week 16 that increased with maintenance therapy .


Actelion Pharmaceuticals .


We have previously reported excellent cecal intubation rates using a short double-balloon endoscope in patients with a history of incomplete colonoscopy .


However , data on the endoscopic treatment of colorectal tumors using a double-balloon endoscope are limited .


The aim of the present study was to evaluate the efficacy and safety of endoscopic intervention of colorectal tumors using a short double-balloon endoscope .


We analyzed data from a multicenter , prospective study on 110 patients ( 62 men , median age 66.5 years ) who underwent total colonoscopy after incomplete colonoscopy to assess the characteristics of colorectal tumors , endoscopic interventions , and complications .


In all , 113 colorectal tumors were detected in 55 patients ; 109 of the tumors were adenomas ( 24 advanced adenomas ) and two each were intramucosal and advanced cancers .


Locations of the lesions were eight in the cecum , 30 in the ascending colon , 18 in the transverse colon , 12 in the descending colon , 34 in the sigmoid colon , five in the rectosigmoid and six in the rectum .


Average tumor diameter was 6.86.3 mm .


Fifty-nine polypectomies , 22 endoscopic mucosal resections , four hot biopsies , and six cold biopsies were done .


All endoscopic interventions were successfully completed and no complications were noted .


Two advanced cancers were located in the ascending colon and only a double-balloon endoscope could reach them to take a biopsy sample .


Double-balloon endoscopy is effective and safe for endoscopic intervention of colorectal tumors , irrespective of the location , in patients after incomplete colonoscopy .


The commonality between chronic conditions that are treated with low-dose ketamine , such as specific chronic pain conditions , depression , and post-traumatic stress disorder , can be found in relation to the stress system , particularly the hypothalamus-pituitary-adrenal axis .


In this study we assess the effect of ketamine on the stress system by measuring plasma and saliva cortisol production during and following exposure to low-dose ketamine .


In a double-blind , randomized , placebo-controlled study , the influence of subanaesthetic ketamine ( 0.29 mg kg ( -1 ) h ( -1 ) for 1 h , followed by 0.57 mg kg ( -1 ) h ( -1 ) for another hour ) was studied with repeated plasma and saliva cortisol samples in 12 healthy male volunteers .


A pharmacokinetic-pharmacodynamic model was used to describe the circadian rhythm-dependent ketamine-induced production of cortisol .


The endogenous mean baseline cortisol production was 7.9 ( SE 1.5 ) nM min ( -1 ) .


Consistent with the circadian rhythm , cortisol production decayed by 1.25 nM min ( -1 ) h ( -1 ) .


Ketamine doubled the cortisol production at a concentration of 165 ( SE 35 ) ng ml ( -1 ) .


The salivary cortisol concentration closely mirrored the plasma concentration and was exponentially related to the plasma concentration with , at 100 ng ml ( -1 ) ketamine , a saliva : plasma ratio of 0.036 ( se 0.006 ) .


Ketamine has an appreciable effect on cortisol production .


This may impact on critical physiological and psychological functions .


This study was registered in the Dutch Trial Register under number NTR2717 at www.trialregister.nl .


The purpose of this randomized controlled study was to compare knee stability , kneeling pain , harvest site pain , sensitivity loss , and subjective clinical outcome after primary anterior cruciate ligament ( ACL ) reconstruction with either bone-patellar tendon-bone ( BPTB ) or quadriceps tendon-bone ( QTB ) autografts in a noninferiority study design .


From 2005 to 2009 , a total of 51 patients were included in the present study .


Inclusion criteria were isolated ACL injuries in adults .


Twenty-five patients were randomized to BPTB grafts and 26 to QTB grafts .


An independent examiner performed follow-up evaluations 1 and 2 years postoperatively .


Anteroposterior knee laxity was measured with a KT-1000 arthrometer ( MEDmetric , San Diego , CA ) .


Anterior knee pain was assessed clinically and by knee-walking ability .


Knee Injury and Osteoarthritis Outcome Score ( KOOS ) and subjective International Knee Documentation Committee ( IKDC ) score were used for patient-evaluated outcome .


Anterior knee laxity was equal between the 2 groups with KT-1000 values of 1.1 1.4 mm and 0.8 1.7 mm standard deviation ( SD ) at follow-up in QTB and BPTB groups , respectively ( P = .65 ) , whereas positive pivot shift test results were seen less frequently ( 14 % compared with 38 % , respectively ; P = .03 ) .


Anterior kneeling pain , evaluated by the knee walking ability test , was significantly less in the QTB group , with only 7 % of patients grading knee walking as difficult or impossible compared with 34 % in the BPTB group .


At 1 and 2 years ' follow-up , there was no difference between the 2 groups in subjective patient-evaluated outcome .


The IKDC score was 75 13 patients and 76 16 SD at 1-year follow-up in QTB and BPTB groups , respectively ( P = .78 ) .


At 2 years , 12 patients were lost to follow-up , resulting in 18 in the BPTB group and 21 in the QTB group .


The use of the QTB graft results in less kneeling pain , graft site pain , and sensitivity loss than seen with BPTB grafts ; however , similar anterior knee stability and subjective outcomes are seen .


The results of this study show that QTB is a viable option for ACL reconstruction .


Level II , randomized controlled clinical trial .


This study was aimed to investigate the effects of raloxifene on intact parathyroid hormone ( PTH ) level and bone mineral density ( BMD ) for 8 months in women on hemodialysis and women with chronic kidney disease stage 5 not dependent on dialysis to determine its effect on secondary hyperparathyroidism and osteoporosis .


Fifty-one women on hemodialysis and 9 with chronic kidney disease stage 5 were randomly assigned to receive oral raloxifene , 60 mg/d , or placebo for 8 months .


Baseline blood determinations and BMD were done and repeated after 8 months .


Serum levels of total calcium , phosphorus , alkaline phosphatase , and intact PTH were measured .


Serum levels of intact PTH significantly decreased in both groups , and there was no difference between the two groups after 8 months ( P = .37 ) .


Serum phosphorus levels also decreased by 1.8 % in the two groups .


After 8 months of treatment , the BMD of the lumbar spine and femural neck decreased by 1.9 % in the control group , while an increase in BMD was observed in the raloxifene group , with an average increase in both BMDs of the lumbar spine and the femural neck by 2 % ( significant in the lumbar spine ; P = .01 ) .


Raloxifene has proven to be an effective medication in terms of improving BMD , with no adverse effects .


However , it had no effect on controlling hyperparathyroidism in our patients .


Long-term studies should be done to investigate the effects of raloxifene in chronic kidney disease and dialysis patients .


To determine whether the addition of 8 mg dexamethasone to axillary brachial plexus block would prolong the duration of sensory and motor block in patients undergoing hand and forearm surgery .


The prospective , randomised , double-blinded study was conducted at the Eskisehir Osmangazi University Medical School , Turkey , from October 2008 to December 2009 .


It comprised 45 American Society of Anaesthesiologists grade I and II patients under elective surgery of the hand and forearm .


The patients were randomly divided into 3 groups : 5 mg/kg of 2 % prilocaine was applied to Group 1 ; 5 mg/kg of 2 % prilocaine +8 mg of dexamethasone ( 2 ml ) was applied to Group 2 ; and 1.5 mg/kg 0.5 % levobupivacaine was applied to Group 3 .


Sensory and motor block onset time as well as the duration of motor and sensory block of those were monitored and recorded .


SPSS 15 was used for statistical analysis .


Of the 45 patients , 27 ( 60 % ) were men and 18 ( 40 % ) were women .


There was no significant difference among the groups in terms of demographic data .


Based on the duration of motor and sensory block , similar periods of time in Group 1 and Group 2 were noted , whereas this period was statistically different and significantly longer in Group 3 ( p < or = 0.001 ) .


There were no complications encountered .


The addition of dexamethasone to prilocaine prolonged the duration of sensory and motor block .


It could be used as an effective adjuvant agent .


Levobupivacain could be a more appropriate local anaesthetic in postoperative analgesia and prolonged surgical procedures .


To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide ( tNOx ) availability and iNOS/nNOS expression , oxidative stress ( OS ) and inflammation in obese humans with or without type 2 diabetes mellitus ( T2DM ) .


Twenty-five sedentary , obese ( BMI > 30 kg/m2 ) males ( 52.8 7.2 years ) ; 12 controls versus 13 T2DM were randomly allocated to four groups that exercised for 30 min , three times per week either at low ( Fat-Max ; 30-40 % VO ( 2max ) ) or moderate ( T ( vent ) ; 55-65 % VO ( 2max ) ) intensity .


Before and after training , blood and muscle samples ( v. lateralis ) were collected .


Baseline erythrocyte glutathione was lower ( 21.8 2.8 vs. 32.7 4.4 nmol/ml ) and plasma protein oxidative damage and IL-6 were higher in T2DM ( 141.7 52.1 vs. 75.5 41.6 nmol/ml ) .


Plasma catalase increased in T2DM after T ( vent ) training ( from 0.98 0.22 to 1.96 0.3 nmol/min/ml ) .


T2DM groups demonstrated evidence of oxidative damage in response to training ( elevated protein carbonyls ) .


Baseline serum tNOx were higher in controls than T2DM ( 18.68 2.78 vs. 12.34 3.56 mol/l ) .


Training at T ( vent ) increased muscle nNOS and tNOx in the control group only .


Pre-training muscle nNOS was higher in controls than in T2DMs , while the opposite was found for iNOS .


No differences were found after training for plasma inflammatory markers .


Exercise training did not change body composition or aerobic fitness , but improved OS markers , especially when performed at T ( vent ) .


Non-diabetics responded to T ( vent ) training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM , perhaps due to higher insulin resistance ( unchanged after intervention ) .


To verify the efficacy of Jianpi-xingniao needling therapy on prevention and treatment of motion sickness .


Sixty volunteers of motion sickness were randomized into an acupuncture group and a delayed acupuncture group , 30 cases in each one .


In the acupuncture group , acupuncture was given at Baihui ( GV 20 ) , Sishencong ( EX-HN 1 ) , Neiguan ( PC 6 ) , Zusanli ( ST 36 ) and Hegu ( LI 4 ) .


The needles were retained for 20 min .


The treatment was given twice a week and 10 treatments were required .


In the delayed acupuncture group , acupuncture was postponed , meaning no acupuncture during observation stage .


Graybel scale was adopted to observe the score of symptoms and physical signs of the subjects of motion sickness before and after intervention .


The efficacy was compared between the two groups .


Twenty-five cases in the acupuncture group and 22 cases in the delayed acupuncture group were included in the statistical analysis .


The score of symptoms and physical signs of motion sickness was reduced significantly after treatment in the acupuncture group as compared with that before treatment ( 10.12 + / - 3.37 vs 0.92 + / - 0.40 , P < 0.05 ) .


The score in the acupuncture group was lower apparently than that in the delayed acupuncture group ( 0.92 + / - 0.40 vs 9.86 + / - 2.53 , P < 0.05 ) .


The difference was not significant before and after treatment in the self-comparison of the delayed acupuncture group ( P > 0.05 ) .


The total effective rate was 96.0 % ( 24/25 ) in the acupuncture group , which was significantly better than 0.0 % ( 0/22 ) in the delayed acupuncture group ( P < 0.01 ) .


Jianpixingniao needling therapy relieves the symptoms of motion sickness in the patients and achieves a better clinical efficacy .


Rapid HIV testing in high-risk populations can increase the number of persons who learn their HIV status and avoid spending clinic resources to locate persons identified as HIV infected .


We determined the cost to sexually transmitted disease ( STD ) clinics of point-of-care rapid HIV testing using data from 7 public clinics that participated in a randomized trial of rapid testing with and without brief patient-centered risk reduction counseling in 2010 .


Costs included counselor and trainer time , supplies , and clinic overhead .


We applied national labor rates and test costs .


We calculated median clinic start-up costs and mean cost per patient tested , and projected incremental annual costs of implementing universal rapid HIV testing compared with current testing practices .


Criteria for offering rapid HIV testing and methods for delivering nonrapid test results varied among clinics before the trial .


Rapid HIV testing cost an average of US $ 22/patient without brief risk reduction counseling and US $ 46/patient with counseling in these 7 clinics .


Median start-up costs per clinic were US $ 1100 and US $ 16,100 without and with counseling , respectively .


Estimated incremental annual costs per clinic of implementing universal rapid HIV testing varied by whether or not brief counseling is conducted and by current clinic testing practices , ranging from a savings of US $ 19,500 to a cost of US $ 40,700 without counseling and a cost of US $ 98,000 to US $ 153,900 with counseling .