We sought the response of functional and fibrosis markers to therapy in a trial of aldosterone antagonism for treatment of DCM .


Biochemical , anthropometric , and echocardiographic data were measured in 225 subjects with T2DM .


Myocardial function was evaluated with standard echocardiography and myocardial deformation ; ischaemia was excluded by exercise echocardiography .


Calibrated integrated backscatter and post-contrast T1 mapping from cardiac magnetic resonance imaging were used to assess myocardial structure .


Amino-terminal propeptides of pro-collagen type I ( PINP ) and III ( PIIINP ) , the carboxy-terminal propeptide of pro-collagen type I ( PICP ) and transforming growth factor beta-1 were measured from peripheral blood or urine to assess myocardial collagen turnover .


Diastolic dysfunction was identified in 81 individuals , of whom 49 ( 25 male , age 60 10 years ) were randomized to spironolactone 25 mg/day or placebo therapy for 6 months .


Groups were well-matched at baseline .


Spironolactone therapy was associated with improvements in diastolic filling profile ( peak E wave velocity -4 15 vs. 9 10 ms , P = 0.001 ; E/A ratio -0.1 0.3 vs. 0.2 0.2 , P < 0.001 ) and cIB values ( -21.2 4.5 dB vs. -18.0 5.2 dB , P = 0.026 ; cIB -5.1 6.8 vs. -1.3 5.2 , P = 0.030 ) .


cIB was independently associated with spironolactone therapy ( = 0.320 , P = 0.026 ) but not blood pressure .


With intervention , pro-collagen biomarkers ( PINP P = 0.92 , PICP P = 0.25 , PIIINP P = 0.52 , and TGF-1 P = 0.71 ) and T1 values ( P = 0.54 ) remained similar between groups .


Spironolactone-induced changes in myocardial structure and diastolic properties in DCM are small , and are unassociated with changes in collagen biomarkers or T1 values .


The burden of acute gastroenteritis on children and their families continues to be enormous .


Probiotics , defined as viable microbial preparations that have a beneficial effect on the health of the host , represent a rapidly expanding field .


Although clinical trials in children with gastroenteritis have been performed , most have significant flaws , and guidelines do not consistently endorse their use .


PROGUT is a randomized , placebo-controlled , double-blind , five-center , Canadian , emergency department trial .


Children aged 3months to 48months who present between November 2013 and June 2017 with < 72hours of gastroenteritis symptoms will be assessed for eligibility .


A total of 886 children will be randomized ( 1:1 allocation via an internet based , third party , randomization service ) to receive 5days of a combination probiotic agent ( Lactobacillus rhamnosus and L. helveticus ) or placebo .


All participants , caregivers , and outcome assessors will be blinded to group assignment .


The study includes three key outcomes : 1 ) clinical - the development of moderate to severe disease following an emergency department ( ED ) evaluation that employs a validated clinical score ( Modified Vesikari Scale ) ; 2 ) safety - side effect ; and 3 ) mechanism - fecal secretory immunoglobulin A levels .


Definitive data are lacking to guide the clinical use of probiotics in children with acute gastroenteritis .


Hence , probiotics are rarely prescribed by North American physicians .


However , the following current trends obligate an urgent assessment : 1 ) probiotics are sold as food supplements , and manufacturers can encourage their use while their relevance has yet to be established ; 2 ) North American and European government agencies remain concerned about their value and safety ; 3 ) some institutions are now recommending the routine use of probiotics ; and 4 ) parents of affected children are often providing probiotics .


With probiotic consumption increasing in the absence of solid evidence , there is a need to conduct this definitive trial to overcome the limitations of prior work in this field .


ClinicalTrials.gov : NCT01853124 ; first registered 9 May 2013 .


During menopause , the decrease of estrogenic secretion induces the disruption of skin functioning , thus causing the decline in skin elasticity characteristic of skin aging .


The purpose of this study was to evaluate in postmenopausal women the effect of daily consumption and/or application of argan oil on skin elasticity .


Sixty postmenopausal women consumed butter during the stabilization period and were randomly divided into two groups for the intervention period : the treatment group of 30 participants received dietary argan oil , the control group of 30 participants received olive oil , and both groups applied cosmetic argan oil in the left volar forearm during a 60-day period .


Assessments of skin elasticity parameters , ie , the three R-parameters ( R2 or gross-elasticity of the skin , R5 or net elasticity of the skin , and R7 or biological elasticity ) , and the resonance running time ( RRT ) at both volar forearms of the two groups were performed during three visits : before starting oils consumption and application , after 30 days of oils consumption and application , and after 60 days of oils consumption and application .


The consumption of argan oil led to a significant increase of gross-elasticity of the skin ( R2 ) ( P < 0.001 ) , net elasticity of the skin ( R5 ) ( P < 0.001 ) , biological elasticity ( R7 ) ( P < 0.001 ) , and a significant decrease of RRT ( P = 0.002 ) .


The application of argan oil led to a significant increase of gross-elasticity of the skin ( R2 ) ( P < 0.001 ) , net elasticity of the skin ( R5 ) ( P < 0.001 ) , biological elasticity ( R7 ) ( P = 0.001 ) , and a significant decrease of RRT ( P < 0.001 ) .


Our findings suggest that the daily consumption and/or topical application of argan oil have an anti-aging effect on the skin demonstrated by the improvement of skin elasticity , characterized by an increase of R-parameters ( R2 , R5 , and R7 ) and a decrease of RRT .


The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence .


The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence , potentially by bolstering T-cell mediated responses .


This observer-blind study , conducted in the United States ( US ) and Spain during the 2008-2009 influenza season , evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine ( TIV ) in 65 year-old adults.Medically-stable adults aged 65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV ( TIV/AS03 ) or TIV .


Healthy adults aged 18-40 years received only TIV .


Blood samples were collected on Day 0 , Day 21 , Day 42 and Day 180 .


Influenza-specific CD4 + T cells , defined by the induction of the immune markers CD40L , IL-2 , IFN - , or TNF - , were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells .


A total of 192 adults were vaccinated : sixty nine and seventy three 65 year olds received TIV/AS03 and TIV , respectively ; and fifty 18 - 40 year olds received TIV .


In the 65 year-old group on Day 21 , the frequency of CD4 + T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV ( p < 0.001 ) .


On Days 42 and 180 , the adjusted-geometric mean specific CD4 + T-cell frequencies were also higher in the TIV/AS03 recipients than in the TIV recipients ( p < 0.001 ) .


Furthermore , the adjusted-geometric mean specific CD4 + T-cell frequencies were higher in the 65 year-old recipients of TIV/AS03 than in the18 - 40 year old recipients of TIV on Days 21 ( p = 0.006 ) and 42 ( p = 0.011 ) .


This positive effect of AS03 Adjuvant System on the CD4 + T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population .


( Clinicaltrials.gov . )


NCT00765076 .


The purpose of the study was to rigorously test Illness Management and Recovery ( IMR ) against an active control group in a sample that included veterans .


A total of 118 participants with schizophrenia spectrum disorders , 56 of whom were veterans , were recruited from a Department of Veterans Affairs medical center and a community mental health center in the same city and were randomly assigned to an IMR group ( N = 60 ) or a weekly problem-solving group intervention ( N = 58 ) .


Groups met weekly for nine months .


Blinded assessments were conducted at baseline , nine months , and 18 months on measures of symptoms , functioning , illness self-management , medication adherence , subjective recovery experiences , and service utilization .


No significant differences were found between IMR and problem-solving groups .


Participants in both groups improved significantly over time in symptom severity , illness management , and quality of life and had fewer emergency department visits .


Participation rates in both interventions were low .


Only 28 % of consumers assigned to IMR and 17 % of those assigned to the problem-solving group participated in more than half the scheduled groups , and 23 % and 34 % , respectively , attended no sessions .


This is the first randomized controlled trial of IMR to report negative findings .


Given the inclusion of an active control group and the low participation rates , further research is needed to understand factors affecting IMR effectiveness .


Increased attention may need to be paid to facilitate more active participation in IMR , such as individual follow-up with consumers and the integration of IMR with ongoing treatment .


To analyze the clinical evaluation of Parkinson 's disease ( PD ) patients receiving integrated Chinese and Western medicine therapy .


One hundred and twenty patients were enrolled and randomly allocated to a control group or treatment group .


Patients in the two groups received placebo and Bushen Huoxue Granule ( , BHG ) , respectively .


Both groups received baseline levodopa and benserazide ( Madopar ) .


The effects of treatment were assessed monthly during the 9-month treatment .


Means of evaluation included Unified PD Rating Scale ( UPDRS ) scores ( II and III ) , sleep scale score , 10 m turn back test ( getting up time , 10 m2 times , and turning time ) , timing motor test ( TMT ) - left and TMT-right , which were treated as the dependent variables ; and age , sex , duration of PD , Hoehn and Yahr ( H-Y ) stage and Madopar dosage of admitted PD patients were as the independent variables .


Multiple linear regression was used to analyze these factors .


H-Y stage significantly affected UPDRS II score , UPDRS III score , and getting up time ( P < 0.01 ) .


Madopar dosage and H-Y stage significantly affected the 10 m2 times ( P < 0.05 or < 0.01 ) .


Madopar dosage significantly affected the sleep scale score ( P < 0.05 ) .


There were also significant correlations between age and TMT-left or TMT-right ( P < 0.01 ) , and duration of PD and TMT-right ( P < 0.05 ) .


The six assessed means of clinical evaluation ( including UPDRS II and UPDRS III scores , sleep scale score , getting up time , 10 m2 times , and turning time ) are sensitive indexes in all PD patients .


H-Y stage and Madopar dosage are the major factors influencing means of clinical assessment of PD treatment .


Women are more likely than men to experience adverse cardiac events after ST-elevation myocardial ( STEMI ) .


Whether differences in infarct size or reperfusion contribute to sex differences in outcomes is unknown .


We compared baseline and procedural characteristics , angiographic and electrocardiographic indices of reperfusion , microvascular obstruction , infarct size , and clinical outcomes in 118 women and 334 men with anterior STEMI enrolled in the INFUSE-AMI randomized trial of intralesion abciximab and aspiration thrombectomy ( NCT00976521 ) .


Infarct size was assessed by cardiac magnetic resonance imaging at 30 days , and clinical end points were adjudicated by an independent committee .


Women were older , were more commonly affected by hypertension and renal impairment , and had a 50.5-minute longer delay to reperfusion .


There were no differences in infarct size , microvascular obstruction , or reperfusion success .


At 30 days , major adverse cardiac events ( MACE ) , defined as death , reinfarction , new-onset severe heart failure , or rehospitalization for heart failure , were more common in women ( 11.1 % vs 5.4 % , hazard ratio 2.09 , 95 % CI 1.03-4 .27 , P = .04 ) .


After multivariable adjustment , age , but not sex or time to reperfusion , was an independent predictor of MACE .


In the INFUSE-AMI randomized trial , women with anterior STEMI experienced a higher rate of MACE , attributable to older age .


Despite longer delay from symptom onset to reperfusion therapy , there was no difference between women and men in infarct size or reperfusion success .


To compare the efficacy of vaginal misoprostol with buccal misoprostol for second-trimester termination of pregnancies .


In a randomized trial , we compared 400 micrograms vaginal and buccal misoprostol every 3 hours for up to six doses for induction of labor at 13-24 weeks of gestation with a live fetus and intact membranes .


Women who had a uterine scar were excluded from the study .


The primary outcome of the study was induction-to-abortion interval .


Based on a two-tailed of 0.05 , we planned to include 65 patients per group to detect a 50 % difference in the primary outcome with a power of 80 % .


From January 2014 to December 2014 , 172 women were screened and 130 were randomized : 65 vaginal and 65 buccal misoprostol .


Characteristics of patients were similar between groups .


Patients administered vaginal misoprostol compared with buccal misoprostol had a shorter induction-to-abortion interval ( 2517 hours compared with 4029 hours , P = .001 ) and a higher abortion rate within both 24 hours ( 41 [ 63 % ] compared with 27 [ 42 % ] P = .014 ) and 48 hours ( 59 [ 91 % ] compared with 44 [ 68 % ] , P = .001 ) .


Complete abortion rates were similar in both groups ( vaginal 51 [ 78 % ] compared with buccal 54 [ 83 % ] ) .


The incidence of side effects was similar for both groups .


The perceived pain was higher in the buccal group , but the small difference did not appear to be clinically meaningful .


Vaginal compared with buccal misoprostol administration has a shorter induction-to-abortion interval for second-trimester termination of viable pregnancies .


However , both administration routes are equally effective for induction of termination .


ClinicalTrials.gov , www.clinicaltrials.gov , NCT02048098 .


I.


Heart failure activates neurohormones , and elevated levels of brain natriuretic peptide ( BNP ) are associated with adverse outcomes .


The SENIORS trial showed that nebivolol , a highly selective beta-1 antagonist with vasodilating properties , reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure .


We explored the effects of nebivolol on a range of neurohormones , cytokines and markers of nitric oxide activity in heart failure .


In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide ( NT-BNP ) , pro atrial natriuretic peptide ( Pro-ANP ) , endothelin-1 ( ET-1 ) , peripheral norepinephrine ( PNE ) , soluble Fas ( sFas ) , soluble Fas-ligand ( sFas-L ) , tumour necrosis factor-alpha ( TNF - ) , serum uric acid ( SUA ) , symmetrical dimethyl arginine ( SDMA ) , arginine , citrulline and asymmetrical dimethyl arginine ( ADMA ) at baseline ( before study drug ) , at 6 months and 12 months in a prespecified substudy .


One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample .


There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months .


NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo ( P = 0.08 ) and sFas showed a numerical increase in patients on placebo ( P = 0.08 ) .


Mean baseline LVEF was 35 % in both groups and at 12 months was 43 % on nebivolol group and 34 % on placebo group ( P = 0.01 ) .


There were trends but no clear changes associated with nebivolol in neurohormones , cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure .


Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure .


Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct ( stroke or silent cerebral infarct ) .


We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care .


In this randomized , single-blind clinical trial , we randomly assigned children with sickle cell anemia to receive regular blood transfusions ( transfusion group ) or standard care ( observation group ) .


Participants were between 5 and 15 years of age , with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions .


The primary end point was the recurrence of an infarct , defined as a stroke or a new or enlarged silent cerebral infarct .


A total of 196 children ( mean age , 10 years ) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years .


In the transfusion group , 6 of 99 children ( 6 % ) had an end-point event ( 1 had a stroke , and 5 had new or enlarged silent cerebral infarcts ) .


In the observation group , 14 of 97 children ( 14 % ) had an end-point event ( 7 had strokes , and 7 had new or enlarged silent cerebral infarcts ) .


The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events , respectively , per 100 years at risk , corresponding to an incidence rate ratio of 0.41 ( 95 % confidence interval , 0.12 to 0.99 ; P = 0.04 ) .


Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia .


( Funded by the National Institute of Neurological Disorders and Stroke and others ; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number , NCT00072761 , and Current Controlled Trials number , ISRCTN52713285 . )


The TARGIT ( TARGeted Intraoperative Radiotherapy ) trial was designed to compare local recurrence and complication rates in breast cancer patients , prospectively randomised to either EBRT ( external beam whole breast radiotherapy ) or a single dose of IORT ( intraoperative radiotherapy ) .


The aim of our study was to compare follow-up mammographic findings , ultrasound and biopsy rates in each group .


Follow-up imaging and breast biopsies of women from one centre participating in the TARGIT-A trial were independently reviewed by two radiologists blinded to the radiotherapy treatment received .


The cohort consisted of 141 patients ( EBRT n = 80/IORT n = 61 ) .


There was no significant difference in the patient or disease characteristics of the two groups .


The number of follow-up mammograms and length of follow-up was similar ( EBRT/IORT n = 2.0 / 2.4 ; 4.3 yr/5 .1 yr ; p = 0.386 ( 2 ) test ) .


There were no significant differences in mammographic scar or calcification appearances of the post-operative site .


Generalised increase in breast density and skin thickening were more common in the EBRT compared to the IORT group ( p = 0.002 ; p = 0.030 , ( 2 ) test respectively ) .


A trend towards additional ultrasound at follow-up was observed in the IORT group ( 15 of 61 [ 24.6 % ] versus 11 of 80 [ 13.8 % ] ) , however this was not statistically significant ( p = 0.100 ( 2 ) test ) .


No disease recurrence was demonstrated on any of the breast biopsies taken .


Only one biopsy was reported as fat necrosis in the IORT group .


Mammographic changes were more common following EBRT , although more additional follow-up ultrasounds were performed in the IORT group .


IORT is not detrimental to subsequent radiological follow up .


home-based telecare ( TC ) is utilised to manage risks of independent living and provide prompt emergency responses .


This study examined the effect of TC on health-related quality of life ( HRQoL ) , anxiety and depressive symptoms over 12 months in patients receiving social care .


a study of participant-reported outcomes [ the Whole Systems Demonstrator ( WSD ) Telecare Questionnaire Study ; baseline n = 1,189 ] was nested in a pragmatic cluster-randomised trial of TC ( the WSD Telecare trial ) , held across three English Local Authorities .


General practice ( GP ) was the unit of randomisation and TC was compared with usual care ( UC ) .


participant-reported outcome measures were collected at baseline , short-term ( 4 months ) and long-term ( 12 months ) follow-up , assessing generic HRQoL , anxiety and depressive symptoms .


Primary intention-to-treat analyses tested treatment effectiveness and were conducted using multilevel models to control for GP clustering and covariates for participants who completed questionnaire measures at baseline assessment plus at least one other assessment ( n = 873 ) .


analyses found significant differences between TC and UC on Short Form-12 mental component scores ( P < 0.05 ) , with parameter estimates indicating being a member of the TC trial-arm increases mental component scores ( UC-adjusted mean = 40.52 ; TC-adjusted mean = 43.69 ) .


Additional significant analyses revealed , time effects on EQ5D ( decreasing over time ) and depressive symptoms ( increasing over time ) .


TC potentially contributes to the amelioration in the decline in users ' mental HRQoL over a 12-month period .


TC may not transform the lives of its users , but it may afford small relative benefits on some psychological and HRQOL outcomes relative to users who only receive UC .


International Standard Randomised Controlled Trial Number Register : ISRCTN 43002091 .


Choice of calcineurin inhibitor may influence response to antiviral therapy in liver transplant patients with hepatitis C virus ( HCV ) infection .


In a randomized , multicenter , 80-week trial , liver transplant recipients ( > 6 months and 10 years post-transplant ) with recurrent HCV infection received cyclosporine ( n = 50 ) or tacrolimus ( n = 42 ) with a 48-week course of pegylated interferon ( peg-IFN2a ) and ribavirin .


Twenty-three patients in each group completed the trial on study medication .


The primary endpoint was sustained virological response ( SVR ) 24 weeks after the end of antiviral therapy , for which 43 patients were eligible for analysis .


The rate of SVR was 60.0 % ( 12/20 ) with cyclosporine and 43.5 % ( 10/23 ) with tacrolimus ( adjusted odds ratio 1.85 ; 95 % CI 0.53-6 .43 ; p = 0.331 ) .


There were no significant intergroup differences for rapid or early virological response , relapse , HCV RNA viral load , or fibrosis progression .


One cyclosporine-treated patient experienced acute rejection .


One patient died in each group .


Adverse events , treatment-related adverse events , and serious adverse events were similar between groups .


Since fewer patients were recruited than planned ( 92 versus 355 ) , the study was underpowered and robust conclusions can not be drawn regarding the effect of cyclosporine and tacrolimus on virological responses to antiviral treatment for recurrent HCV after liver transplantation .


However , as reported in other trials , SVR was higher in cyclosporine-treated patients .


Overweight and obesity are major health problems worldwide .


This protocol describes the HEALTHI ( Healthy Eating and Active LifesTyle Health Intervention ) Program , a 12-week randomised-controlled weight-loss intervention that adopts two theory-based intervention techniques , mental imagery and implementation intentions , a behaviour-change technique based on planning that have been shown to be effective in promoting health-behaviour change in previous research .


The effectiveness of goal-reminder text messages to augment intervention effects will also be tested .


The trial will determine the effects of a brief , low cost , theory-based weight-loss intervention to improve dietary intake and physical activity behaviour and facilitate weight-loss in overweight and obese individuals .


Overweight or obese participants will be randomly allocated to one of three conditions : ( 1 ) a psycho-education plus an implementation intentions and mental imagery condition ; ( 2 ) a psycho-education plus an implementation intentions and mental imagery condition with text messages ; or ( 3 ) a psycho-education control condition .


The intervention will be delivered via video presentation to increase the intervention 's applicability in multiple contexts and keep costs low .


We hypothesise that the intervention conditions will lead to statistically-significant changes in the primary and secondary outcome variables measured at 6 and 12 weeks post-intervention relative to the psycho-education control condition after controlling for baseline values .


The primary outcome variable will be body weight and secondary outcome variables will be biomedical ( body mass , body fat percentage , muscle mass , waist-hip circumference ratio , systolic and diastolic blood pressure , low-density lipoprotein , high-density lipoprotein , total cholesterol , triglycerides , blood glucose and insulin levels ) , psychological ( quality of life , motivation , risk perception , outcome expectancy , intention , action self-efficacy , maintenance self-efficacy , goal setting and planning ) , and behavioural ( self-reported diet intake , and physical activity involvement ) measures .


We also expect the intervention condition augmented with text messages to lead to statistically significant differences in the primary and secondary outcome variables at the follow up periods after controlling for baseline values .


The planned trial will test the effectiveness of the theory-based HEALTHI program intervention to reduce weight and salient psychological , biomedical , and behavioural outcomes in overweight and obese adults .


The study has been designed to maximise applicability to real world settings and could be integrated into existing weight management practices .


ACTRN : ACTRN12613001274763 .


Registration date 19/11/2013 .


To characterize the safety and efficacy of deep sedation ( DS ) as compared to general anaesthesia ( GA ) in percutaneous mitral valve repair ( PMVR ) using the MitraClip system .


PMVR with the MitraClip system has emerged as a therapeutic alternative to surgical valve repair in high-risk patients .


The PMVR procedure is typically performed under GA. .


Due to their high surgical risk , avoidance of GA in many of those patients would be desirable .


In an open-label observational study 21 patients with severe mitral regurgitation were randomized to either GA or DS using propofol .


Primary endpoints of this comparison were related to safety with rate of conversion from DS to GA , bleeding , aspiration , and pneumonia .


Secondary endpoints were related to efficacy with procedural , in-hospital , and mid-term outcome at 1 month .


All clips have been implanted successfully in both groups .


No conversion from DS to GA was necessary .


Four patients undergoing GA suffered from upper respiratory tract infections and two from peripheral vascular complications during placement of central venous catheter for GA. .


Short - and mid-term efficacy were comparable in both groups with a reduced hospital stay in the DS group .


PVMR in high-risk patients performed under DS is as safe and effective as with GA , preventing complications related to GA and shortening hospital stay .


The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer .


Preliminary findings reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival .


Based on the sample size calculation , we planned to analyse overall survival when 190 deaths occurred ; this target has now been reached , after a median 10 years of follow-up .


RT01 was a phase 3 , open-label , international , randomised controlled trial enrolling men with histologically confirmed T1b-T3a , N0 , M0 prostate cancer with prostate specific antigen of less than 50 ng/mL .


Patients were randomly assigned centrally in a 1:1 ratio , using a computer-based minimisation algorithm stratifying by risk of seminal vesicle invasion and centre to either the control group ( 64 Gy in 32 fractions , the standard dose at the time the trial was designed ) or the escalated-dose group ( 74 Gy in 37 fractions ) .


Neither patients nor investigators were masked to assignment .


All patients received neoadjuvant androgen deprivation therapy for 3-6 months before the start of conformal radiotherapy , which continued until the end of conformal radiotherapy .


The coprimary outcome measures were biochemical progression-free survival and overall survival .


All analyses were done on an intention-to-treat basis .


Treatment-related side-effects have been reported previously .


This trial is registered , number ISRCTN47772397 .


Between Jan 7 , 1998 , and Dec 20 , 2001 , 862 men were registered and 843 subsequently randomly assigned : 422 to the escalated-dose group and 421 to the control group .


As of Aug 2 , 2011 , 236 deaths had occurred : 118 in each group .


Median follow-up was 100 years ( IQR 91-108 ) .


Overall survival at 10 years was 71 % ( 95 % CI 66-75 ) in each group ( hazard ratio [ HR ] 099 , 95 % CI 077-128 ; p = 096 ) .


Biochemical progression or progressive disease occurred in 391 patients ( 221 [ 57 % ] in the control group and 170 [ 43 % ] in the escalated-dose group ) .


At 10 years , biochemical progression-free survival was 43 % ( 95 % CI 38-48 ) in the control group and 55 % ( 50-61 ) in the escalated-dose group ( HR 069 , 95 % CI 056-084 ; p = 00003 ) .


At a median follow-up of 10 years , escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival , but this advantage did not translate into an improvement in overall survival .


These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-effects .


UK Medical Research Council .


Pulmonary vein isolation ( PVI ) is an accepted treatment to relieve symptoms in patients with atrial fibrillation ( AF ) .


We studied 3 year outcome after PVI guided by duty-cycled multi-electrode radiofrequency ( RF ) ablation ( pulmonary vein ablation catheter , PVAC ) and provided comparative data to outcome after conventional PVI ( CPVI ) using mapping with irrigated , point-per-point RF ablation .


One hundred and sixty-one consecutive patients with symptomatic paroxysmal or persistent AF and minimal heart disease underwent PVI ( PVAC , n = 79 vs. CPVI , n = 82 ) .


Follow-up ( with symptom-guided rhythm monitoring ) was truncated at 3 years in all patients .


Success was defined as freedom of documented arrhythmia after a single procedure and without antiarrhythmic drug treatment ( ADT ) .


Baseline characteristics did not differ between both groups .


At 3 years follow-up , single-procedure success without ADT was comparable between PVAC and CPVI ( 65 % vs. 55 % , P = NS ) .


The majority of recurrences occurred during the first year ( PVAC 79 % vs. CPVI 70 % , P = NS ) .


The annual rate of very late recurrence ( i.e. beyond 1 year ) was similar in both groups ( 10.5 % vs. 15 % , P = NS ) .


At 3 years follow-up , outcome after PVAC-guided PVI is comparable to conventional isolation by irrigated point-by-point RF ablation .


In both strategies , the majority of recurrences occurred in the first year of ablation .


The aim of this study was to determine the negative and positive agreement of a point-of-care matrix metalloproteinase-9 test in confirming the diagnosis of dry eye and to evaluate the ease of use by untrained ophthalmic technicians .


The study was a prospective , sequential , masked , clinical trial with 4 clinical trial sites .


The InflammaDry test was compared with the clinical assessment of tear break-up time , Schirmer tear testing , and corneal staining for the confirmation of dry eye , both with and without the inclusion of the Ocular Surface Disease Index ( OSDI ) , as a confirmatory test .


The study enrolled 237 patients .


If the OSDI is included in the definition for mild dry eye , the InflammaDry test was shown to have a total positive agreement of 81 % ( 127/157 ) and a negative agreement of 98 % ( 78/80 ) .


The removal of the OSDI shifted the categorization of 11 patients previously considered positive for dry eye to become categorized as negative for dry eye .


If the OSDI is excluded from the definition of dry eye , the InflammaDry test demonstrates a positive agreement of 86 % ( 126/146 ) and a negative agreement of 97 % ( 88/91 ) against the clinical assessment .


The InflammaDry test demonstrates a high positive and negative agreement for confirming suspected dry eye disease .


In addition , the test was safely and effectively performed by untrained operators .


These findings support the intended use of the InflammaDry test as an aid in the diagnosis of dry eye .


Arterial puncture can be a painful procedure for many patients .


This study investigates whether precooling of a puncture site with ice can reduce the pain associated with arterial puncture .


This was a stratified randomized controlled trial of a convenience sample of out-patients with a physician order for an arterial blood gas ( ABG ) test .


The intervention group had a plastic bag of ice applied to their wrists for 3 min before drawing an ABG sample from the radial artery .


The control group had an ABG sample drawn from the radial artery without the application of ice .


Pain from the arterial puncture was measured with a 100-mm visual analog scale .


Subjects pretreated with ice reported less pain from arterial puncture compared with subjects in the control group ( mean visual analog scale 13.8 16.9 vs 25 23 mm , P = .01 ; median visual analog scale 7 mm , interquartile range ( IQR ) 1.5-19 vs 20 mm , IQR 4.5-38 .5 mm , P = .01 ) .


Stratified analysis showed that visual analog scale pain scores were lower in the naive group when ice was applied ( naive ice vs naive control : mean visual analog scale 11 14.3 vs 26.5 25 mm , P = .02 ; median visual analog scale 5 mm , IQR 2-14 .5 vs 20 mm , IQR 6.5-36 mm , P = .02 ) .


Visual analog scale pain scores trended lower in the experienced group when ice was applied ( experienced ice vs experienced control : mean visual analog scale 15.9 18.9 vs 25.1 22 mm , P = .15 ; median visual analog scale 8 mm , IQR 0.5-26 .5 vs 23 mm , IQR 3.5-40 mm , P = .08 ) .


There was no difference in first-attempt success between groups ( ice group : 85 % , control group : 82.5 % , P > .99 ) .


Only 3 subjects could not tolerate 3-min ice application .


Ice application before arterial puncture is well tolerated and reduces procedure-related pain .


( ClinicalTrials.gov NCT02065115 ) .


Melatonin levels decrease physiologically with age , and possibly with the transition to menopause .


The plausible influence of hormone therapy ( HT ) on melatonin is poorly understood .


The aim of this randomized , placebo-controlled , double-blind trial was to investigate the effect of HT administration on serum melatonin concentrations in late premenopausal and postmenopausal women .


Analyses were carried out among 17 late premenopausal and 18 postmenopausal healthy women who participated in a prospective HT study in Finland .


Serum melatonin was sampled at 20-min ( 21:00 -24:00 h ; 06:00 -09:00 h ) and 1-h ( 24:00 -06:00 h ) intervals at baseline and after 6 months with HT or placebo .


Melatonin levels and secretion profile after 6 months of HT compared to placebo .


Mean melatonin levels , mean melatonin exposure level ( area under curve , AUC ) and mean duration of melatonin secretion did not differ after 6 months with HT vs. placebo , irrespectively of the reproductive state .


However , in postmenopausal women the melatonin peak time ( acrophase ) was delayed by 2.4 h ( 2 h 21 min ) on average after 6 months with HT vs. placebo ( p < 0.05 ) .


No interaction between time and group was detected when melatonin level was modelled before or after treatment .


Administration of HT to postmenopausal women alters melatonin peak time , but not melatonin levels .


Further research on larger clinical samples is needed to better understand the effects of HT on melatonin profile .


There is good evidence for the benefits of short-term cognitive stimulation therapy for dementia but little is known about possible long-term effects .


To evaluate the effectiveness of maintenance cognitive stimulation therapy ( CST ) for people with dementia in a single-blind , pragmatic randomised controlled trial including a substudy with participants taking acetylcholinesterase inhibitors ( AChEIs ) .


The participants were 236 people with dementia from 9 care homes and 9 community services .


Prior to randomisation all participants received the 7-week , 14-session CST programme .


The intervention group received the weekly maintenance CST group programme for 24 weeks .


The control group received usual care .


Primary outcomes were cognition and quality of life ( clinical trial registration : ISRCTN26286067 ) .


For the intervention group at the 6-month primary end-point there were significant benefits for self-rated quality of life ( Quality of Life in Alzheimer 's Disease ( QoL-AD ) P = 0.03 ) .


At 3 months there were improvements for proxy-rated quality of life ( QoL-AD P = 0.01 , Dementia Quality of Life scale ( DEMQOL ) P = 0.03 ) and activities of daily living ( P = 0.04 ) .


The intervention subgroup taking AChEIs showed cognitive benefits ( on the Mini-Mental State Examination ) at 3 ( P = 0.03 ) and 6 months ( P = 0.03 ) .


Continuing CST improves quality of life ; and improves cognition for those taking AChEIs .


Physical inactivity and a poor diet predict lifestyle diseases such as diabetes , cardiovascular disease , and certain types of cancer .


Marked declines in physical activity occur during late adolescence , coinciding with the point at which many young people leave school and enter the workforce and begin to take greater control over their lifestyle behaviours .


The work outlined within this paper sought to test a theoretically-informed intervention aimed at supporting increased engagement in physical activity and healthy eating habits in young people at the point of transition from school to work or work-based learning .


As actively engaging young people in initiatives based on health messages is challenging , we also tested the efficacy of financial incentives in promoting initial engagement with the programme .


A three-arm cluster-randomised design was used .


Participants were school pupils from Year 11 and 13 ( i.e. , in their final year of study ) , aged 16-18years .


To reduce contamination effects , the unit of randomisation was school .


Participants were randomly allocated to receive ( i ) a 12-week behavioural support intervention consisting of six appointments , ( ii ) a behavioural support intervention plus incentives ( totalling 40 ) , or ( iii ) an information-only control group .


Behavioural support was provided by fitness advisors at local leisure centres following an initial consultation with a dietician .


Sessions focused on promoting habit formation through setting implementation intentions as part of an incremental goal setting process .


Consistent with self-determination theory , all advisors were trained to provide guidance in an autonomy-supportive manner so that they were equipped to create a social context supportive of autonomous forms of participant motivation .


The primary outcome was objectively assessed physical activity ( via GT1M accelerometers ) .


Secondary outcome measures were diet , motivation and habit strength .


Data were collected at baseline , post-intervention ( 12weeks ) and 12months .


Findings of this trial will provide valuable insight into the feasibility of promoting autonomous engagement in healthy physical activity and dietary habits among school leavers .


The research also provides much needed data and detailed information related to the use of incentives for the initial promotion of young peoples ' behaviour change during this important transition .


The trial is registered as Current Controlled Trials ISRCTN55839517 .


Hepatitis C virus ( HCV ) infection is associated with chronic inflammation and oxidative damage , with hepatic steatosis being common in genotype 3 cases .


Vitamin E , a potent antioxidant protective against oxidative stress-induced liver damage in vitro and in vivo , has beneficial effects on alanine aminotransferase ( ALT ) and histological outcomes in patients with non-alcoholic steatohepatitis .


To assess the effect of vitamin E on ALT status in patients with HCV genotype 3 .


This randomized , placebo-controlled , double-blind trial was conducted in a single tertiary-care hospital ( Rajavithi Hospital , Bangkok ) between 2010 and 2011 .


We included patients with HCV genotype 3 infection , unable to receive or tolerate , or did not respond to standard therapy .


Responders were defined as patients exhibiting a decrease in serum ALT of at least 5 % below the baseline value after 12 weeks of treatment .


Thirty-seven eligible patients were randomly assigned either to receive vitamin E 400 IU twice daily ( n = 19 ) or placebo ( n = 18 ; 1 dropped outearly ) for 12 weeks .


In all , 11 of 19 patients in the vitamin E group ( 57.8 % ) and 5 of 17 patients in the placebo group ( 29.4 % ) were ALT responders .


Among responders , serum ALT levels were greatly decreased in the vitamin E group ( reducing from 122.680.1 IU/L to 68.425.3 IU/L , p = 0.016 ) , when compared with the placebo group ( reducing from 89.240.6 IU/L to 73.630.6 IU/L , p > 0.05 ) .


Vitamin E treatment was well-tolerated with no serious adverse events in the present study .


Vitamin E treatment decreased serum ALT levels in patients with HCV genotype 3 .


Because of its good safety profile , vitamin E may be a worthwhile supportive therapy for patients with HCV particularly for those who were unable to achieve viral eradication by standard therapy .


Two phase 3 , randomized , placebo-controlled trials demonstrated that low-dose paroxetine 7.5 mg reduced the frequency and severity of vasomotor symptoms ( VMS ) associated with menopause and had a favorable tolerability profile .


The impact of paroxetine 7.5 mg on body weight and sexual function was evaluated in a pooled analysis .


Postmenopausal women aged 40 years or older who had moderate to severe VMS were randomly assigned to receive paroxetine 7.5 mg or placebo once daily for 12 or 24 weeks .


Assessments included changes in body mass index ( BMI ) and weight , Arizona Sexual Experiences Scale score , Hot Flash-Related Daily Interference Scale sexuality subscore , and adverse events related to weight or sexual dysfunction .


Pooled efficacy and safety populations comprised 1,174 and 1,175 participants , respectively .


Baseline values were similar for median weight ( 75 kg ) , median BMI ( 28 kg/m ) , and the proportion of women with sexual dysfunction ( 58 % ) .


No clinically meaningful or statistically significant changes from baseline in weight or sexual function assessments occurred in the paroxetine 7.5 mg group .


Small but statistically significant increases in weight and BMI were observed in the placebo group only on week 4 .


No significant difference between treatment groups was observed in the proportion of participants who had 7 % or higher gain in body weight on week 4 , 12 , or 24 .


Rates of adverse events suggestive of sexual dysfunction were low and similar in both treatment groups .


Paroxetine 7.5 mg does not cause weight gain or negative changes in libido when used to treat menopause-associated VMS in postmenopausal women .


Some symptomatic degenerative conditions of the lumbar spine may be treated with spinal fusion if conservative treatment has failed .


The minimally invasive technique of transforaminal lumbar interbody fusion ( MIS TLIF ) is increasingly used but has been found to generate increased radiation exposure to the patient and staff .


Modern three-dimensional ( 3D ) C-arm devices are capable of providing conventional two-dimensional fluoroscopic images ( x-rays ) as well as 3D image sets for intraoperative navigation .


This study was designed to compare the radiation exposure between these two intraoperative imaging techniques in MIS TLIF procedures .


This study is a randomized controlled trial .


Forty participants scheduled to undergo monosegmental MIS TLIF will be recruited and randomly allocated to one of two groups with respect to the applied intraoperative imaging technique : conventional fluoroscopy ( FLUORO group ) and 3D fluoroscopy-based navigation combined with conventional fluoroscopy ( NAV group ) .


Furthermore , patients scheduled to undergo bisegmental MIS TLIF during the recruitment period for monosegmental MIS TLIF will be assessed for eligibility and will be randomly assigned separately .


The primary endpoint is the radiation exposure to the surgeon and is measured by dosimeter readings .


Secondary endpoints are the radiation exposure to the assistant surgeon , scrub nurse , anesthetist , patient , and C-arm as well as radiation exposure in relation to the body mass index of the patient .


Results of this randomized study will help to compare the radiation exposure to the operating staff and patient during MIS TLIF procedures using conventional fluoroscopy versus 3D fluoroscopy-based navigation combined with conventional fluoroscopy .


Furthermore , recommendations regarding the appropriate use of the investigated intraoperative imaging techniques will be made to improve radiation protection and to reduce radiation exposure .


Registration number of the German Clinical Trials Register : DRKS00004514 .


Registration date : 11 August 2012 .


The purpose of the study was to examine the relationship between ( 1 ) critical care nurses ' information-seeking behaviour and the non-routineness of tasks ; and ( 2 ) the extent to which nurses ' perception of their problem-solving abilities when completing patient care tasks , moderate the relationship between information-seeking behaviour and non-routineness of tasks .


A cross-sectional survey design was used .


A random sample ( n = 177 ) of critical care nurses working in hospital settings was selected from the College of Nurses of Ontario ( CNO ) database .


Descriptive statistics and multiple regression were used to analyze the data .


Previous information-seeking training ( p = 0.008 ) , non-routineness of the task ( p = 0.018 ) , and the perception of the problem-solving ability domain of personal control ( p = 0.040 ) had positive relationships with information-seeking behaviour .


The development of problem-solving skills such as personal control , in addition to information-seeking training is essential so critical care nurses will have the skills to aid their information needs when faced with the completion of non-routine tasks .


Current guidelines for transcutaneous oximetry measurement ( TCOM ) for the lower limb define tissue hypoxia as a transcutaneous oxygen partial pressure < 40 mmHg .


Values obtained with some newer machines and current research bring these reference values into question .


To determine ` normal ' TCOM values for the lower limb in healthy , non-smoking adults using the TCM400 oximeter with tc Sensor E5250 .


Thirty-two healthy , non-smoking volunteers had TCOM performed at six positions on the lower leg and foot .


Measurements were taken with subjects lying supine breathing air , then with leg elevated and whilst breathing 100 % oxygen .


Room-air TCOM values ( mean mmHg , 95 % confidence interval ( CI ) ) were : lateral leg 41.3 , CI 37.8 to 44.7 ; lateral malleolus 38.6 , CI 34.1 to 43.1 ; medial malleolus 43.9 , CI 40.2 to 47.6 ; dorsum , between first and second toe 39.3 , CI 35.9 to 42.7 ; dorsum , proximal to fifth metatarsal-phalangeal joint 46.4 , CI 43.4 to 49.3 ; plantar 52.3 , CI 49.6 to 55.1 .


Using the currently accepted value of less than 40 mmHg for tissue hypoxia , 24 of our 32 ` healthy ' subjects had at least one air sensor reading that would have been classified as hypoxic .


Seventeen subjects had TCOM values less than 100 mmHg when breathing 100 % normobaric oxygen .


Normal lower limb TCOM readings using the TCOM400 with tc Sensor E5250 may be lower than 40 mmHg , used to define tissue hypoxia , but consistent with the wide range of values found in the literature .


Because of the wide variability in TCOM at the different sensor sites we can not recommend one TCOM value as indicative of tissue hypoxia .


A thorough clinical assessment of the patient is essential to establish appropriateness for hyperbaric oxygen treatment , with TCOM used as an aid to help guide this decision , but not as an absolute diagnostic tool .


According to the proposed interference of N-acetylcysteine ( NAC ) with pathophysiologic processes of autistic disorders ( ADs ) , we aimed to assess the effectiveness and safety of NAC as an adjunct to risperidone in the treatment of ADs in a randomized , double-blind , clinical trial .


The participants were referred outpatients between 4 and 12 years of age with the diagnosis of ADs and a score of more than 12 on Aberrant Behavior Checklist-Community ( ABC-C ) Irritability subscale score .


The participants were randomized into 2 groups .


One group received risperidone plus NAC , and the other group received risperidone plus placebo .


The dose of risperidone was titrated between 1 and 2.0 mg/d , and the dose of NAC was 600 to 900 mg/d .


The main outcome was mean decrease in the ABC-C irritability subscale score from baseline at 5 and 10 weeks .


Changes in other subscales were considered as secondary outcome measures .


Forty patients completed the 10-week trial .


Baseline characteristics including age , sex and body weight , as well as baseline scores in 5 subscales did not demonstrate statistically significant difference between the 2 groups .


Repeated-measures analysis showed significant effect for time treatment interaction in irritability ( P = 0.01 ) and hyperactivity/noncompliance ( P = 0.02 ) subscales .


By week 10 , the NAC group showed significantly more reduction in irritability ( P = 0.02 ) and hyperactivity/noncompliance ( P = 0.01 ) subscales scores .


N-acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial therapeutic outcomes .


To determine the variability in treatment responses to antiemetic therapy ( ondansetron and dexamethasone vs ondansetron and dexamethasone plus aprepitant ) given with moderately emetogenic chemotherapy .


Post hoc subgroup analysis of data from a phase III , randomized , double-blind clinical trial evaluated whether the efficacy of aprepitant triple therapy ( ondansetron and dexamethasone plus aprepitant ) versus control ( ondansetron and dexamethasone ) varies by gender , age , or region in 848 men and women 18 years old with histologically confirmed malignancies and who were nave to moderately or highly emetogenic chemotherapeutic agents .


Endpoints compared were the incidences of no vomiting , complete response , and no use of rescue therapy , all during the overall period ( 0-120h ) .


Regardless of age , gender , or region , the aprepitant regimen provided better control for the no-vomiting and complete-response ( no vomiting , no rescue therapy ) endpoints .


The aprepitant regimen provided better control for the no-vomiting and complete-response ( no vomiting , no rescue therapy ) endpoints .


Overall response rates were higher in men and in older ( 55y ) patients , but treatment differences were greater among women and younger patients , known to be at increased chemotherapy-induced nausea and vomiting ( CINV ) risk .


Aprepitant showed a benefit versus control across regions , although the between-treatment difference appeared to be smaller for patients in Central/South America versus North America or international regions .


Although we acknowledge that subset numbers in this post hoc analysis may be too small to allow definitive conclusions , the data suggest that aprepitant triple therapy provides a benefit over control therapy for the prevention of CINV in patients receiving anthracycline and cyclophosphamide ( AC ) - or non-AC-based moderately emetogenic chemotherapy across age , gender , and region .


( Original trial results available at ClinicalTrials.gov : NCT00337727 . )


The - aminobutyric acid type B-receptor agonist lesogaberan ( AZD3355 ) has been developed for use in patients with gastroesophageal reflux disease ( GERD ) symptoms despite proton pump inhibitor ( PPI ) therapy ( partial responders ) .


This study aimed to explore the dose-response effect of lesogaberan on reflux episodes in partial responders .


In this randomized , single-centre , double-blind , crossover , placebo-controlled study , partial responders taking optimised PPI therapy were given 30 , 90 , 120 and 240mg doses of lesogaberan .


Each dose was given twice ( 12h apart ) during a 24-h period , during which impedance-pH measurements were taken .


Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis .


The effect of lesogaberan on the mean number of reflux episodes was dose-dependent , and all doses significantly reduced the mean number of reflux episodes relative to placebo .


Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes ( except the 30mg dose ) and weakly acid reflux episodes ( all doses ) significantly , relative to placebo .


Regardless of dose , lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [ mean reduction : 68.5 % ( 30mg ) , 54.2 % ( 90mg ) , 65.9 % ( 120mg ) , 72.1 % ( 240mg ) ; p < 0.05 except 90mg dose ] .


No adverse events led to discontinuation and no serious adverse events occurred during active treatment .


Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy , and these effects were significant versus placebo .


All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events .


ClinicalTrials.gov identifier : NCT01043185 .


The study was conducted to explore the effects of EGb 761 ( Dr. Willmar Schwabe GmbH & Co. .


KG , Karlsruhe , Germany ) on neuropsychiatric symptoms ( NPS ) and cognition in patients with mild cognitive impairment ( MCI ) .


One hundred and sixty patients with MCI who scored at least 6 on the 12-item Neuropsychiatric Inventory ( NPI ) were enrolled in this double-blind , multi-center trial and randomized to receive 240mg EGb 761 daily or placebo for a period of 24weeks .


Effects on NPS were assessed using the NPI , the state sub-score of the State-Trait Anxiety Inventory and the Geriatric Depression Scale .


Further outcome measures were the Trail-Making Test ( A/B ) for cognition and global ratings of change .


Statistical analyses followed the intention-to-treat principle .


The NPI composite score decreased by 7.04.5 ( mean , standard deviation ) points in the EGb 761-treated group and by 5.55.2 in the placebo group ( p = 0.001 ) .


Improvement by at least 4 points was found in 78.8 % of patients treated with EGb 761 and in 55.7 % of those receiving placebo ( p = 0.002 ) .


Superiority of EGb 761 over placebo ( p < 0.05 ) was also found for the State-Trait Anxiety Inventory score , the informants ' global impression of change , and both Trail-Making Test scores .


There were statistical trends favoring EGb 761 in the Geriatric Depression Scale and the patients ' global impression of change .


Adverse events ( all non-serious ) were reported by 37 patients taking EGb 761 and 36 patients receiving placebo .


EGb 761 improved NPS and cognitive performance in patients with MCI .


The drug was safe and well tolerated .


Ghrelin , which is a stomach-derived hormone , increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems .


Therefore , changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics .


We investigated whether ghrelin administration ( exogenous hyperghrelinemia ) mimics effects of fasting ( endogenous hyperghrelinemia ) on the hedonic response and activation of brain-reward systems to food .


In a crossover design , 22 healthy , nonobese adults ( 17 men ) underwent a functional magnetic resonance imaging ( fMRI ) food-picture evaluation task after a 16-h overnight fast ( Fasted-Saline ) or after eating breakfast 95 min before scanning ( 730 kcal , 14 % protein , 31 % fat , and 55 % carbohydrate ) and receiving a saline ( Fed-Saline ) or acyl ghrelin ( Fed-Ghrelin ) subcutaneous injection before scanning .


One male subject was excluded from the fMRI analysis because of excess head motion , which left 21 subjects with brain-activation data .


Compared with the Fed-Saline visit , both ghrelin administration to fed subjects ( Fed-Ghrelin ) and fasting ( Fasted-Saline ) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation .


Both fasting and ghrelin administration also increased hippocampus activation to high-energy - and low-energy-food pictures .


These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose , insulin , peptide YY , and glucagon-like peptide-1 .


Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens , caudate , anterior insula , or amygdala activation during the food-evaluation task or on auditory , motor , or visual cortex activation during a control task .


Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations .


Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss .


To explore the impact of race/ethnicity on efficacy and safety of twice-daily insulin lispro mix 75/25 ( LM75/25 ; 75 % lispro protamine suspension , 25 % insulin lispro ) and once daily insulin glargine ( GL ) .


More than 2,000 Patients with type 2 diabetes enrolled in the 24-week initiation phase of the DURABLE Trial .


Efficacy and safety variables at endpoint , including hemoglobin A1c ( HbA1c ) , self-monitored plasma glucose ( SMPG ) , and hypoglycemia , in each racial/ethnic group were compared to Caucasians within treatment groups .


Asian patients had less ( LM75/25 : -1.46 % , P < .01 ; GL : -1.25 % , P < .01 ) and Hispanic patients had greater ( LM75/25 : -2.17 % ) HbA1c reduction from baseline vs Caucasian patients ( LM75/25 : -1.84 % ; GL : -1.78 % ) .


Fewer Asian ( LM75/25 : 20 % , P < .001 ; GL : 22 % , P < .001 ) and Hispanic patients ( LM75/25 : 40 % , P < .01 ) reached HbA1c target ( < 7 % ) vs Caucasian patients ( LM75/25 : 53 % ; GL : 44 % ) .


Fasting plasma glucose was similar among groups , postprandial glucose ( PPG ) with GL was lower for African patients post-breakfast and post-dinner and higher for Asian patients post-lunch .


Only PPG with LM75/25 was lower for Hispanic patients post-breakfast .


Weight gain was lower in Asian patients ( LM75 / 25 ) .


Insulin dose was higher for Asian ( LM75/25 and GL ) and lower for African patients ( GL ) .


Hypoglycemia rate was lower for Asian ( LM75/25 and GL ) and Hispanic patients ( LM75/25 ) .


There were significant efficacy and safety differences among racial/ethnic groups in the DURABLE trial .


These differences may be important in designing insulin based treatment plans .


Evidence suggests that the use of stimulation to increase corticomotor excitability improves hand function in persons with cervical spinal cord injury .


We assessed effects of a multiday application of 10-Hz repetitive transcranial magnetic stimulation ( rTMS ) applied to the corticomotor hand area combined with repetitive task practice ( RTP ) in participants with tetraplegia and neurologically healthy participants .


Using a double-blind , randomized , crossover design , 11 participants with chronic tetraplegia and 10 neurologically healthy participants received 3 sessions of 10-Hz rTMS + RTP and 3 sessions of sham-rTMS + RTP to the corticomotor hand region controlling the weaker hand .


Repetitive transcranial magnetic stimulation was interleaved with RTP of a skilled motor task between pulse trains .


Hand function ( Jebsen-Taylor Hand Function Test , pinch , and grasp strength ) and corticomotor excitability ( amplitude of motor-evoked potential ) were assessed before and after the rTMS + RTP and sham-rTMS + RTP phases .


We assessed significance , using paired t tests on pre-post differences , and effect sizes , using the standardized response mean .


RTMS+RTP was associated with larger effect sizes compared with sham-rTMS + RTP for improvement in Jebsen-Taylor Hand Function Test for both the trained hand ( standardized response mean = 0.85 and 0.42 , respectively ) and non-trained hand ( 0.55 and 0.31 , respectively ) , and for grasp strength of the trained hand in the group with cervical spinal cord injury ( 0.67 and 0.39 , respectively ) alone .


Effect sizes for all other measures were small and there were no statistical between-condition differences in the outcomes assessed .


Repetitive transcranial magnetic stimulation may be a valuable adjunct to RTP for improving hand function in persons with tetraplegia .


Higher stimulation dose ( frequency , intensity , and the number of sessions ) may be associated with larger effects .


( see Supplemental Digital Content 1 , http://links.lww.com/JNPT/A82 ) for more insights from the authors .


Obesity is a risk factor for atrial fibrillation .


Whether weight reduction and cardiometabolic risk factor management can reduce the burden of atrial fibrillation is not known .


To determine the effect of weight reduction and management of cardiometabolic risk factors on atrial fibrillation burden and cardiac structure .


Single-center , partially blinded , randomized controlled study conducted between June 2010 and December 2011 in Adelaide , Australia , among overweight and obese ambulatory patients ( N = 150 ) with symptomatic atrial fibrillation .


Patients underwent a median of 15 months of follow-up .


Patients were randomized to weight management ( intervention ) or general lifestyle advice ( control ) .


Both groups underwent intensive management of cardiometabolic risk factors .


The primary outcomes were Atrial Fibrillation Severity Scale scores : symptom burden and symptom severity .


Scores were measured every 3 months from baseline to 15 months .


Secondary outcomes performed at baseline and 12 months were total atrial fibrillation episodes and cumulative duration measured by 7-day Holter , echocardiographic left atrial area , and interventricular septal thickness .


Of 248 patients screened , 150 were randomized ( 75 per group ) and underwent follow-up .


The intervention group showed a significantly greater reduction , compared with the control group , in weight ( 14.3 and 3.6 kg , respectively ; P < .001 ) and in atrial fibrillation symptom burden scores ( 11.8 and 2.6 points , P < .001 ) , symptom severity scores ( 8.4 and 1.7 points , P < .001 ) , number of episodes ( 2.5 and no change , P = .01 ) , and cumulative duration ( 692-minute decline and 419-minute increase , P = .002 ) .


Additionally , there was a reduction in interventricular septal thickness in the intervention and control groups ( 1.1 and 0.6 mm , P = .02 ) and left atrial area ( 3.5 and 1.9 cm2 , P = .02 ) .


In this study , weight reduction with intensive risk factor management resulted in a reduction in atrial fibrillation symptom burden and severity and in beneficial cardiac remodeling .


These findings support therapy directed at weight and risk factors in the management of atrial fibrillation .


anzctr.org.au Identifier : ACTRN12610000497000 .


To evaluate whether evacetrapib prolongs QT intervals in healthy participants .


This was a single-center , randomized , active and placebo-controlled , 3-period , 6-sequence , and crossover study .


Participants were randomized to 1 of 6 treatment sequences in which they received 1 of 3 treatments : evacetrapib 1200 mg daily for 10 days ( supratherapeutic dose ) , moxifloxacin 400 mg for 1 day ( positive control ) , or placebo for 10 days in each of the 3 separate treatment periods .


Electrocardiographic parameters were recorded at time points specified in the protocol .


The primary end point was the comparison of evacetrapib effect on the population-corrected QT interval ( QTcP ) to that of placebo at 7 time points following dosing on day 10 .


An upper limit of the 2-sided 90 % confidence interval ( CI ) < 10 milliseconds confirmed the absence of significant effect .


Pharmacokinetic parameters were also calculated .


Subjects were predominantly male ( 73.2 % ) with a mean age of 43.1 years and a mean body mass index of 25.9 kg/m ( 2 ) .


For the primary analysis , the upper bound of the 2-sided 90 % CI for the mean difference between evacetrapib and placebo was < 10 milliseconds at all time points on day 10 .


Following administration of moxifloxacin , the QTcP increased by 5 milliseconds at all time points ( 2 , 3 , and 4 hours postdose ) .


Maximum plasma concentrations of evacetrapib occurred at a median time of approximately 2 hours , and the mean apparent elimination half-life was approximately 41 hours .


The area under the curve and Cmax achieved in this study were both 5-fold the values that are expected with the dose level being studied in a phase 3 cardiovascular outcome study .


A 1200-mg supratherapeutic dose of evacetrapib was considered to be well tolerated after 10 days of daily dosing in healthy participants .


Evacetrapib is not associated with QT interval prolongation , even at supratherapeutic doses .


A small literature suggests that pharmacotherapy may be useful in the prophylaxis of posttraumatic stress disorder in patients presenting with major trauma .


There is relatively little data , however , on the use of selective serotonin reuptake inhibitors ( SSRIs ) in this context .


24 week , double-blind placebo controlled study .


31 participants presenting immediately after trauma , and meeting diagnostic criteria for full or partial acute stress disorder were randomized to treatment with 10-20 mg of escitalopram or placebo daily for 24 weeks .


2 participants were excluded from the analysis due to early drop out , leaving 29 participants ( escitalopram = 12 , placebo = 17 ) for inclusion in an intent - to - treat analysis .


Participants were followed up until 56 weeks , and assessed with the Clinician Administered PTSD Scale ( CAPS ) .


A mixed model repeated measures analysis of variance ( RMANOVA ) was undertaken to determine the efficacy of the intervention on the CAPS score .


There was a significant reduction in CAPS score over the course of treatment ( F ( 7 , 142 ) = 41.58 , p < 0.001 ) in both the escitalopram and placebo groups , with a greater reduction in CAPS score in the placebo group F ( 7 , 142 ) = 2.12 , p = 0.045 .


There were improvements on all secondary measures , including the Clinical Global Impressions scale , and scales assessing depression , anxiety and disability .


Only functional disability outcomes ( F ( 7 , 141 ) = 2.13 , p = .04 ) , were significantly different between treatment and placebo groups .


In the sample as a whole , improvement in scores were maintained at the 52 week follow-up .


Side effects were comparable between the groups .


These data are consistent with other recent work indicating that the SSRIs may not be efficacious in the prevention of PTSD .


Nevertheless , the small sample size and baseline differences between groups limit the explanatory power of the study .


Although a consideration of the possibility of medication prophylaxis in PTSD remains important , both from conceptual and clinical perspectives , caution is needed with regards to the use of SSRIs until their efficacy can be proven .


Clinical Trials NCT00300313 .


Prevention of rejection after renal transplantation requires treatment with immunosuppressive drugs .


Data on their in vivo effects on T - and B-cell phenotype and function are limited .


In a randomized double-blind placebo-controlled study to prevent renal allograft rejection , patients were treated with tacrolimus , mycophenolate mofetil ( MMF ) , steroids , and a single dose of rituximab or placebo during transplant surgery .


In a subset of patients , we analyzed the number and phenotype of peripheral T and B cells by multiparameter flow cytometry before transplantation , and at 3 , 6 , 12 , and 24 months after transplantation .


In patients treated with tacrolimus/MMF/steroids the proportion of central memory CD4 + and CD8 + T cells was higher at 3 months post-transplant compared to pre-transplant levels .


In addition , the ratio between the percentage of central memory CD4 + and CD4 + regulatory T cells was significantly higher up to 24 months post-transplant compared to pre-transplant levels .


Interestingly , treatment with tacrolimus/MMF/steroids resulted in a shift toward a more memory-like B-cell phenotype post-transplant .


Addition of a single dose of rituximab resulted in a long-lasting B-cell depletion .


At 12 months post-transplant , the small fraction of repopulated B cells consisted of a high percentage of transitional B cells .


Rituximab treatment had no effect on the T-cell phenotype and function post-transplant .


Renal transplant recipients treated with tacrolimus/MMF/steroids show an altered memory T and B-cell compartment post-transplant .


Additional B-cell depletion by rituximab leads to a relative increase of transitional and memory-like B cells , without affecting T-cell phenotype and function .


ClinicalTrials.gov NCT00565331 .


Relapse rates following cognitive behavioral therapy ( CBT ) for alcohol dependence are high .


Continuing care programs can prolong therapeutic effects but are underutilized .


Thus , there is need to explore options having greater accessibility .


This randomized controlled trial tested the efficacy of a novel , fully automated continuing care program , Alcohol Therapeutic Interactive Voice Response ( ATIVR ) .


ATIVR enables daily monitoring of alcohol consumption and associated variables , offers targeted feedback , and facilitates use of coping skills .


Upon completing 12weeks of group CBT for alcohol dependence , participants were randomly assigned to either four months of ATIVR ( n = 81 ) or usual care ( n = 77 ) .


Drinking behavior was assessed pre - and post-CBT , then at 2weeks , 2months , 4months , and 12months post-randomization .


Drinking days per week increased over time for the control group but not the intervention group .


There were no significant differences between groups on the other alcohol-related outcome measures .


Comparisons on the subset of participants abstinent at the end of CBT ( n = 72 ) showed higher rates of continuous abstinence in the experimental group .


Effect sizes for the other outcome variables were moderate but not significant in this subgroup .


For continuing care , ATIVR shows some promise as a tool that may help clients maintain gains achieved during outpatient treatment .


However , ATIVR may not be adequate for clients who have not achieved treatment goals at the time of discharge .


The Amberg-Schwandorf Algorithm for Primary Triage ( ASAV ) is a novel primary triage concept specifically for physician manned emergency medical services ( EMS ) systems .


In this study , we determined the diagnostic reliability and the time requirements of ASAV triage .


Seven hundred eighty triage runs performed by 76 trained EMS providers of varying professional qualification were included into the study .


Patients were simulated using human dummies with written vital signs sheets .


Triage results were compared to a standard solution , which was developed in a modified Delphi procedure .


Test performance parameters ( e.g. sensitivity , specificity , likelihood ratios ( LR ) , under-triage , and over-triage ) were calculated .


Time measurements comprised the complete triage and tagging process and included the time span for walking to the subsequent patient .


Results were compared to those published for mSTaRT .


Additionally , a subgroup analysis was performed for employment status ( career/volunteer ) , team qualification , and previous triage training .


For red patients , ASAV sensitivity was 87 % , specificity 91 % , positive LR 9.7 , negative LR 0.139 , over-triage 6 % , and under-triage 10 % .


There were no significant differences related to mSTaRT .


Per patient , ASAV triage required a mean of 35.4 sec ( 75th percentile 46 sec , 90th percentile 58 sec ) .


Volunteers needed slightly more time to perform triage than EMS professionals .


Previous mSTaRT training of the provider reduced under-triage significantly .


There were significant differences in time requirements for triage depending on the expected triage category .


The ASAV is a specific concept for primary triage in physician governed EMS systems .


It may detect red patients reliably .


The test performance criteria are comparable to that of mSTaRT , whereas ASAV triage might be accomplished slightly faster .


From the data , there was no evidence for a clinically significant reliability difference between typical staffing of mobile intensive care units , patient transport ambulances , or disaster response volunteers .


Up to now , there is no clinical validation of either triage concept .


Therefore , reality based evaluation studies are needed .


Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes , probably through effects on energy balance .


Recent genome-wide association studies identified variants in circadian rhythm-related genes ( CRY2 and MTNR1B ) associated with glucose homeostasis .


We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial , the POUNDS ( Preventing Overweight Using Novel Dietary Strategies ) LOST Trial .


The variants CRY2 rs11605924 ( n = 721 ) and MTNR1B rs10830963 ( n = 722 ) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients .


Respiratory quotient ( RQ ) and resting metabolic rate ( RMR ) were measured .


By 2 y of diet intervention , the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ ( P = 0.03 ) and a greater increase in RMR and RMR/kg ( both P = 0.04 ) .


The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ ( P = 0.01 ) but was not related to changes in RMR and RMR/kg .


In addition , we found significant gene-diet fat interactions for both CRY2 ( P-interaction = 0.02 ) and MTNR1B ( P-interaction < 0.001 ) in relation to 2-y changes in RQ .


Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure , and dietary fat intake may modify the genetic effects .


This trial was registered at www.clinicaltrials.gov as NCT00072995 .


In the literature , chronic groin pain ( i.e. lasting > 3 months ) occurs in about 10 % of patients who undergo inguinal hernioplasty with prosthesis ; it is characterized by a broad range of symptoms , and is relative to individual perceptions of pain .


In 2-5 % of cases , the painful symptomatology is so intense that it interferes with daily activities , and can be debilitating in 0.5-6 % of cases .


The best known cause of inguinodynia is neuropathy , due to implication of one or more inguinal nerves ( iliohypogastric , ilioinguinal , and genitofemoral nerves ) into fibroblastic processes ; or from nervous stimulation caused by prosthetic material on adjacent nervous trunks .


Many therapeutic strategies have been proposed to treat chronic groin pain , including intra-operative prophylactic neurectomy .


The purpose of our study was to perform a comparative analysis between outcomes from wide resections of inguinal nerves versus those from simple nervous section ( or minimal resection ) .


We considered 350 patients who had undergone inguinal prosthetic hernioplasty with Trabucco 's technique between 2004 and 2010 .


Wide nervous resection ( removal of nerve segments 3-8 cm in length ) was performed in 180 .


The other 170 patients underwent simple section or minimal resection .


All patients were checked 1 week , 1 month , and 1 year after surgery .


Group 1 : At 1-week follow-up , 63 patients ( 35 % ) reported no pain , 113 ( 63 % ) reported moderate pain , and 4 ( 2 % ) intense pain ; 1 month after the procedure , 152 patients ( 84.4 % ) reported no pain , 25 ( 14 % ) complained of moderate pain , and 3 ( 1.6 % ) of severe pain ; 1 year after surgery , only 1 patient ( 0.5 % ) complained of constant pain .


Group 2 : At 1 week follow-up , 48 patients ( 28 % ) reported no pain , 101 ( 59 % ) reported moderate pain , and 21 ( 13 % ) intense pain ; 1 month after the procedure , 81 patients ( 47.6 % ) had no pain , 72 ( 42.4 % ) complained of moderate pain , and 17 ( 10 % ) of severe pain ; 1 year after surgery , 11 patients ( 6.5 % ) had constant pain , and two of them were re-admitted for surgery .


The lower incidence of chronic pain after long nervous resection is statistically significant ( 0.5 vs. 6.5 % ; p = 0.006 ) ; the incidence of moderate pain 1 month after operation is also lower ( 14 vs. 42.4 % ; p < 0.0001 ) ; patients who underwent a long resection experienced faster resolution of pain symptomatology , during a month .


Also noteworthy is the lower incidence of intense pain in the short and medium term ( after 1 week , 13 vs. 2 % , p = 0.0005 ; after 1 month , 10 vs. 1.6 % , p = 0.0018 ) .


The prophylactic wide resection of selected segments of inguinal nerves , despite the apparent paradox of greater tissue damage , appears more effective than simple section at preventing postoperative inguinodynia , given both the lower incidence and the faster resolution of painful symptomatology .


Cardiogenic shock ( CS ) is the leading cause of death in patients hospitalized with acute myocardial infarction ( AMI ) .


Biomarkers might help in risk stratification and understanding of pathophysiology .


Preliminary data suggests that patients with CS face a profound increase in the osteocyte-derived hormone fibroblast growth factor 23 ( FGF-23 ) , which acts as a negative regulator of serum phosphate levels .


The present study aimed to assess the predictive role of FGF-23 for clinical outcome in a large cohort of CS patients with and without renal dysfunction .


In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II ( IABP-SHOCK II ) trial , 600 patients with CS complicating AMI were assigned to therapy with or without IABP .


Our predefined biomarker substudy included 182 patients .


Blood sampling was performed in a standardized procedure at three different time points ( day 1 ( day of admission ) , day 2 and day 3 ) .


Differences in outcome of patients with FGF-23 levels <and> median were compared by log-rank testing .


Stepwise logistic regression modeling was performed to identify predictors of death at 30 days and Cox regression analysis for time to death during the first year .


At all three time points , nonsurvivors had significantly higher FGF-23 levels compared to survivors ( P < 0.001 for all ) .


Patients with FGF-23 levels above the median ( 395 RU/mL [ interquartile range 102 ; 2,395 ] ) were characterized by an increased 30-day mortality and 1-year mortality .


In multivariable analysis FGF-23 levels remained independent predictors for 30-day ( odds ratio per 10log 1.80 , 95 % confidence interval ( CI ) 1.11 to 2.92 ; P = 0.02 ) and 1-year mortality ( hazard ratio 1.50 , 95 % CI 1.11 to 2.04 , P = 0.009 ) .


After stratifying the patients according to their baseline serum creatinine levels , the negative prognostic association of increased FGF-23 was only significant in those with serum creatinine greater than median .


In CS , high levels of FGF-23 are independently related to a poor clinical outcome .


However , this prognostic association appears only to apply in patients with impaired renal function .


ClinicalTrials.gov NCT00491036 .


Registered 22 June 2007 .


To determine whether a weight-bearing physical activity intervention improves measures of bone density , size and strength in a pre - and early pubertal cohort of black South African children .


Twenty two school children ( 9.71.1 years ) were cluster randomised into an exercise ( EX ; n = 12 ) and control ( CON ; n = 10 ) group .


EX children performed a weight-bearing exercise program for 20 weeks .


CON children continued their regular activities .


Whole body DXA and tibial peripheral QCT scans were obtained .


Urine was analysed for concentrations of cross-linked N-telopeptides of Type I collagen ( NTX ) .


Changes in 4 % volumetric BMD , area and strength were greater in EX than CON .


At the 38 % site , change in bone area and density was greater in EX than CON .


The greater change in periosteal circumference in the EX groups also resulted in a greater change in cortical thickness of the tibia compared to the CON group .


NTX concentration was lower in the EX group than the CON group after the intervention .


This study documents for the first time the beneficial response of trabecular and cortical bone of black children to a weight bearing exercise intervention .


p38 MAPK inhibition has potential myocardial protective effects .


We assessed losmapimod , a potent oral p38 MAPK inhibitor , in patients with non-ST-segment elevation myocardial infarction ( NSTEMI ) in a double-blind , randomised , placebo-controlled trial .


From October , 2009 , to November , 2011 , NSTEMI patients were assigned oral losmapimod ( 75 mg or 150 mg loading dose followed by 75 mg twice daily ) or matching placebo in a 3:3:2 ratio .


Safety outcomes were serious adverse events and alanine aminotransferase ( ALT ) concentrations over 12 weeks , and cardiac events ( death , myocardial infarction , recurrent ischaemia , stroke , and heart failure ) at 90 days .


Efficacy outcomes were high-sensitivity C-reactive protein ( hsCRP ) and B-type natriuretic peptide ( BNP ) concentrations at 72 h and 12 weeks , and troponin I area under the curve ( AUC ) over 72 h.


The losmapimod groups were pooled for analysis .


This trial is registered with ClinicalTrials.gov , number NCT00910962 .


Of 535 patients enrolled , 526 ( 98 % ) received at least one dose of study treatment ( losmapimod n = 388 and placebo n = 138 ) .


Safety outcomes did not differ between groups .


HsCRP concentrations at 72 h were lower in the losmapimod group than in the placebo group ( geometric mean 641 nmol/L , 95 % CI 530-776 vs 1108 nmol/L , 831-1477 ; p = 00009 ) but were similar at 12 weeks .


Early geometric mean BNP concentrations were similar at 72 h but significantly lower in the losmapimod group at 12 weeks ( 372 ng/L , 95 % CI 323-429 vs 494 ng/L , 387-630 ; p = 004 ) .


Mean troponin I AUC values did not differ .


p38 MAPK inhibition with oral losmapimod was well tolerated in NSTEMI patients and might improve outcomes after acute coronary syndromes .


GlaxoSmithKline .


Timely access to general practitioner ( GP ) care is a recognized strategy to address avoidable hospitalization .


Little is known about patients seeking planned ( decided ahead ) and unplanned ( decided on day ) GP visits .


The Patient Journey Record System ( PaJR ) provides a biopsychosocial real-time monitoring and support service to chronically ill and older people over 65 who may be at risk of an avoidable hospital admission .


This study aims to describe reported profiles associated with planned and unplanned GP visits during the week in the PaJR database of regular outbound phone calls made by Care Guides to multi-morbid older patients .


One hundred fifty consecutive patients with one or more chronic condition ( including chronic obstructive pulmonary disease , heart/vascular disease , heart failure and/or diabetes ) , one or more hospital admission in previous year , and consecutively recruited from hospital discharge , out-of-hour care and GP practices comprised the study sample .


Using a semistructured script , Care Guides telephoned the patients approximately every 3 week days , and entered call data into the PaJR database in 2011 .


The PaJR project identified and prompted unplanned visits according to its algorithms .


Logistic regression modelling and descriptive statistics identified significant predictors of planned and unplanned visits and patterns of GP visits on weekdays reported in calls .


In 5096 telephone calls , unplanned versus planned GP visits were predicted by change in health state , significant symptom concerns , poor self-rated health , bodily pain and concerns about caregiver or intimates .


Calls not reporting visits had significantly fewer of these features .


Planned visits were associated with general and medication concerns , reduced social participation and feeling down .


Planned visits were highest on Monday and trended downwards to Fridays .


Unplanned visits were reported at the same rate each weekday and more frequently when the interval between calls was 3 days .


The PaJR project Care Guides advised patients to make unplanned visits in 6.3 % of calls and advised planned GP visits in 2.5 % of calls .


Unplanned GP visits consistently indicated a significant change to worse health with planned visits presenting less acuity in this study of older multi-morbid patients in general practice , when monitored by regular calls at about every 3 days .


The PaJR study actively prompted GP visits according to its algorithms .


Assessing and predicting acuity in older multi-morbid patients appears to be a promising strategy to improve access to primary care , and thus to reducing avoidable hospital utilization .


Further research is needed to investigate the topic on a wider scale .


This study sought to evaluate the relationship between post-stent strut apposition and follow-up strut coverage using contour plot optical coherence tomographic analysis .


Tracking the fate of interested regions of struts at different time points has not been investigated .


Post-intervention and 6-month follow-up optical coherence tomographic evaluations were performed in 82 patients treated with biolimus - ( n = 37 ) or sirolimus-eluting stents ( n = 45 ) .


Post-stent apposition was classified as embedded , apposed , or malapposed .


For volumetric stent evaluation , the post-intervention strut-artery distance and the neointimal thickness at follow-up were measured as a function of the circumferential arc length and longitudinal stent length .


Computer-generated contour plots of the strut-artery distance and neointimal thickness were compared .


The percentages of embedded and malapposed struts after intervention were 1.8 % ( Interquartile range [ IQR ] : 0.6 % to 6.2 % ) and 2.3 % ( IQR : 0.5 % to 5.2 % ) , respectively .


The percentages of uncovered and malapposed struts at 6 months were 16.0 % ( IQR : 7.4 % to 33.3 % ) and 0 % ( IQR : 0 % to 0.7 % ) , respectively .


The percentage of uncovered struts at 6 months varied significantly with post-stent strut apposition ( 0 % [ IQR : 0 % to 11.4 % ] in embedded , 16.3 % [ IQR : 8.1 % to 31.3 % ] in apposed , and 26.8 % [ IQR : 0 % to 56.3 % ] in malapposed , p < 0.001 for all pairwise comparisons ) .


In lesions without tissue prolapse , embedded struts were all covered ( 100 % covered struts ) compared with those with tissue prolapse ( 76.8 % covered , p < 0.001 ) .


The optical coherence tomography-guided optimization of stent strut apposition enhances strut coverage at follow-up .


This comprehensive method for evaluating strut apposition may provide more useful information to understanding the serial changes in strut coverage .


( Neointimal Coverage After Implantation of Biolimus Eluting Stent With Biodegradable Polymer : Optical Coherence Tomographic Assessment According to the Treatment of Dyslipidemia and Hypertension and the Types of Implanted Drug-Eluting Stents ; NCT01502904 ) .


Despite investments in infrastructure and evidence for high acceptability , few mHealth interventions have been implemented in sub-Saharan Africa .


We sought to ( 1 ) identify predictors of uptake of an mHealth application for a low-literacy population of people living with HIV ( PLWH ) in rural Uganda and ( 2 ) evaluate the efficacy of various short message service ( SMS ) text message formats to optimize the balance between confidentiality and accessibility .


The trial evaluated the efficacy of a SMS text messaging app to notify PLWH of their laboratory results and request return to care for those with abnormal test results .


Participants with a normal laboratory result received a single SMS text message indicating results were normal .


Participants with an abnormal test result were randomized to 1 of 3 message formats designed to evaluate trade-offs between clarity and privacy : ( 1 ) an SMS text message that stated results were abnormal and requested return to clinic ( `` direct '' ) , ( 2 ) the same message protected by a 4-digit PIN code ( `` PIN '' ) , and ( 3 ) the message `` ABCDEFG '' explained at enrollment to indicate abnormal results ( `` coded '' ) .


Outcomes of interest were ( 1 ) self-reported receipt of the SMS text message , ( 2 ) accurate identification of the message , and ( 3 ) return to care within 7 days ( for abnormal results ) or on the date of the scheduled appointment ( for normal results ) .


We fit regression models for each outcome with the following explanatory variables : sociodemographic characteristics , CD4 count result , ability to read a complete sentence , ability to access a test message on enrollment , and format of SMS text message .


Seventy-two percent ( 234/385 ) of participants successfully receiving a message , 87.6 % ( 219/250 ) correctly identified the message format , and 60.8 % ( 234/385 ) returned to clinic at the requested time .


Among participants with abnormal tests results ( 138/385 , 35.8 % ) , the strongest predictors of reported message receipt were the ability to read a complete sentence and a demonstrated ability to access a test message on enrollment .


Participants with an abnormal result who could read a complete sentence were also more likely to accurately identify the message format ( AOR 4.54 , 95 % CI 1.42-14 .47 , P = .01 ) and return to clinic appropriately ( AOR 3.81 , 95 % CI 1.61-9 .03 , P = .002 ) .


Those who were sent a PIN-protected message were less likely to identify the message ( AOR 0.11 , 95 % CI 0.03-0 .44 , P = .002 ) or return within 7 days ( AOR 0.26 , 95 % CI 0.10-0 .66 , P = .005 ) .


Gender , age , and socioeconomic characteristics did not predict any outcomes and there were no differences in outcomes between those receiving direct or coded messages .


Confirmed literacy at the time of enrollment was a robust predictor of SMS text message receipt , identification , and appropriate response for PLWH in rural Uganda .


PIN-protected messages reduced odds of clinic return , but coded messages were as effective as direct messages and might augment privacy .


Clinicaltrials.gov NCT 01579214 ; https://clinicaltrials.gov/ct2/show/NCT01579214 ( Archived by WebCite at http://www.webcitation.org/6Ww8R4sKq ) .


Velcalcetide , also known as AMG 416 , is a novel , long-acting selective peptide agonist of the calcium sensing receptor .


It is being developed as an intravenous treatment of secondary hyperparathyroidism ( SHPT ) in hemodialysis patients with chronic kidney disease-mineral and bone disorder .


To assess the safety , tolerability , pharmacokinetics and pharmacodynamics of velcalcetide in healthy male volunteers .


The study was a double-blind , randomized , placebo-controlled , single-dose , dose-escalation study in healthy males aged 18-45 years conducted at a single center .


Each cohort included eight subjects randomized 6:2 to velcalcetide or placebo .


Velcalcetide at 0.5 , 2 , 5 and 10 mg or placebo was administered intravenously .


Measurements included plasma ionized calcium ( iCa ) , serum total calcium , intact parathyroid hormone ( iPTH ) , phosphorus and fibroblast growth factor-23 ( FGF23 ) , 1,25-dihydroxyvitamin D , calcitonin and urine creatinine , calcium and phosphorus and plasma pharmacokinetics for velcalcetide .


Vital signs , safety biochemical and hematological indices , and adverse events were monitored throughout the study .


Intravenous administration of velcalcetide was well tolerated with no adverse reaction of nausea , vomiting or diarrhea reported .


Velcalcetide mediated dose-dependent decreases in serum iPTH at 30 min , FGF23 at 24 h and iCa at 12 h post dose ( P < 0.05 ) and in urine fractional excretion of phosphorus and increases in tubular reabsorption of phosphorus .


Velcalcetide plasma exposure increased in a dose-related manner and the terminal elimination of half-life was comparable across the dose range evaluated and ranged from 18.4 to 20.0 h.


Single IV doses of velcalcetide were well tolerated and associated with rapid , sustained , dose-dependent reductions in serum PTH .


The results support further evaluation of velcalcetide as a treatment for SHPT in hemodialysis patients .


It is unclear whether endoscopic mediastinal lymph node ( LN ) staging techniques are equivalent to surgical mediastinal staging ( SMS ) techniques in patients with potentially operable non-small cell lung cancer ( NSCLC ) .


A total of 166 patients with confirmed or suspected NSCLC who required SMS based on current guidelines were enrolled in this prospective controlled trial comparing endosonographic mediastinal LN staging with SMS .


Each patient served as his or her own control .


All patients underwent endobronchial ultrasound ( EBUS ) , endoscopic ultrasound ( EUS ) , and SMS during a single procedure .


Results of EBUS , EUS , and combined EBUS/EUS were compared with SMS ( gold standard ) and in patients with negative LN staging results , with LN sampling at pulmonary resection .


EBUS , EUS , combined EBUS/EUS , and SMS sampled a mean of 2.2 , 1.7 , 3.9 , and 3.1 LN stations , respectively .


The prevalence of mediastinal nodal disease ( N2/N3 ) was 32 % ( 53 of 166 patients ) .


The sensitivity , negative predictive value , and diagnostic accuracy of the endoscopic staging modalities , respectively , were EBUS , 72 % ( 95 % CI , 0.58-0 .83 ) , 88 % ( 0.81-0 .93 ) , and 91 % ( 0.85-0 .95 ) ; EUS , 62 % ( 0.48-0 .75 ) , 85 % ( 0.78-0 .91 ) , and 88 % ( 0.82-0 .92 ) ; and combined EBUS/EUS , 91 % ( 0.79-0 .97 ) , 96 % ( 0.90-0 .99 ) , and 97 % ( 0.93-0 .99 ) .


Endosonography was diagnostic for N2/N3/M1 disease in 24 patients in whom SMS findings were negative , preventing futile thoracotomy in an additional 14 % of patients .


The combined EBUS/EUS procedure can replace surgical mediastinal staging in patients with potentially resectable NSCLC .


Additionally , endosonography leads to improved staging compared with SMS because it allows the biopsy of LNs and metastases unattainable with SMS techniques .


ClinicalTrials.gov ; No. : NCT01011595 ; URL : www.clinicaltrials.gov .


To examine whether ( 1 ) the ` What Do You Drink ' ( WDYD ) intervention resulted in drinking refusal self-efficacy ( DRSE ) changes directly after the intervention , and if so , whether these changes sustained at six-months follow-up and ( 2 ) DRSE was related to alcohol use over time , and if so , whether the strength of these relationships differed across conditions .


Insight herein can help explain the sustained preventive effects of the WDYD intervention on alcohol use , as reported previously .


Alcohol use and DRSE data were collected from 907 participants ( 60.3 % male ; M = 20.8 ( SD = 1.7 ) in a two-arm parallel group randomized controlled trial applying ecological momentary assessment with 30 time-points .


Participants were randomized to the experimental ( n = 456 : WDYD intervention ) or control condition ( n = 451 : no intervention ) .


Latent Growth Curve ( LGC ) analyses that modeled individual change in DRSE over time by condition revealed that participants in the experimental condition experienced a higher social pressure DRSE compared to participants in the control condition at six-months follow-up .


Moreover , LGC analyses with time-varying covariates revealed that DRSE was negatively related to weekly alcohol consumption and social pressure DRSE to frequency of binge drinking .


The WDYD intervention did not affect the strength of these relationships .


The WDYD intervention increased the level of social pressure DRSE directly after the intervention that sustained at six-months follow-up .


This change is likely to be responsible for the sustained preventive effects of the WDYD intervention on alcohol use , as reported previously .


The objective is to compare the analgesic effects of diclofenac , acetaminophen , and acupuncture in urolithiasis-driven renal colic pain relief .


Renal colic patients were divided randomly into 3 groups .


Patients in group I ( n = 40 ) were treated with intravenous acetaminophen , those in group II ( n = 41 ) with acupuncture , and those in group III ( n = 40 ) with a 75-mg intramuscular injection diclofenac sodium .


Visual analogue scale ( VAS ) and verbal rating scale ( VRS ) were used to assess pain intensity after 10 , 30 , 60 , and 120 minutes .