Rituximab-induced MIP-1 secretion depends on the combined presence of B cells and FcR-bearing cells , especially NK cells .


To compare a new low-dose levonorgestrel and ethinyl estradiol contraceptive patch ( Patch ) with a combination oral contraceptive ( Pill ; 100 micrograms levonorgestrel , 20 micrograms ethinyl estradiol ) regarding efficacy , safety , compliance , and unscheduled uterine bleeding .


Women ( 17-40 years ; body mass index 16-60 ) were randomized in a 3:1 ratio to one of two groups : Patch only ( 13 cycles ) or Pill ( six cycles ) followed by Patch ( seven cycles ) .


Investigators evaluated adverse events during cycles 2 , 4 , 6 , 9 , and 13 .


Participants recorded drug administration and uterine bleeding on daily diary cards .


Compliance was assessed by measuring levonorgestrel and ethinyl estradiol plasma levels .


Pearl Index ( pregnancies per 100 woman-years ) was calculated to evaluate efficacy .


Participants ( N = 1,504 ) were randomized to Patch ( n = 1,129 ) or Pill ( n = 375 ) .


Approximately 30 % were obese , more than 40 % were racial or ethnic minorities , and more than 55 % were new users of hormonal contraceptives .


Laboratory-verified noncompliance ( undetectable plasma drug levels ) was 11 % of Patch and 12.6 % of Pill users at cycle 6 .


Pearl Indices ( 95 % confidence intervals ) for the intention-to-treat population ( cycles 1-6 ) were 4.45 ( 2.34-6 .57 ) for Patch and 4.02 ( 0.50-7 .53 ) for Pill ; excluding laboratory-verified noncompliant participants , Pearl Indices were 2.82 ( 0.98-4 .67 ) for Patch and 3.80 ( 0.08-7 .52 ) for Pill ( differences not statistically significant ) .


Incidence of unscheduled bleeding and incidence and severity of adverse events were similar for both contraceptives ( no statistically significant difference ) .


Efficacy and safety of the new contraceptive Patch are comparable to those of a Pill .


Laboratory-verified noncompliance and bleeding profile are similar between the two treatments .


The Patch was well tolerated .


ClinicalTrials.gov , www.clinicaltrials.gov , NCT01181479 .


I.


Endocrine therapies include aromatase inhibitors and the selective estrogen receptor ( ER ) downregulator fulvestrant .


This study aimed to determine whether the reported efficacy of fulvestrant over anastrozole , and high - over low-dose fulvestrant , reflect distinct transcriptional responses .


Global gene expression profiles from ER-positive breast carcinomas before and during presurgical treatment with fulvestrant ( n = 22 ) or anastrozole ( n = 81 ) , and corresponding in vitro models , were compared .


Transcripts responding differently to fulvestrant and estrogen deprivation were identified and integrated using Gene Ontology , pathway and network analyses to evaluate their potential significance .


The overall transcriptional response to fulvestrant and estrogen deprivation was correlated ( r = 0.61 in presurgical studies , r = 0.87 in vitro ) , involving downregulation of estrogen-regulated and proliferation-associated genes .


The transcriptional response to fulvestrant was of greater magnitude than estrogen deprivation ( slope = 0.62 in presurgical studies , slope = 0.63 in vitro ) .


Comparative analyses identified 28 genes and 40 Gene Ontology categories affected differentially by fulvestrant .


Seventeen fulvestrant-specific genes , including CAV1/2 , SNAI2 , and NRP1 , associated with ER , androgen receptor ( AR ) , and TP53 , in a network regulating cell cycle , death , survival , and tumor morphology .


Eighteen genes responding differently to fulvestrant specifically predicted antiproliferative response to fulvestrant , but not anastrozole .


Transcriptional effects of low-dose fulvestrant correlated with high-dose treatment , but were of lower magnitude ( ratio = 0.29 ) .


The transcriptional response to fulvestrant has much in common with estrogen deprivation , but is stronger with distinctions potentially attributable to arrest of estrogen-independent ER activity and involvement of AR signaling .


Genes responding differently to fulvestrant may have predictive utility .


These data are consistent with the clinical efficacy of fulvestrant versus anastrozole and higher dosing regimens .


To compare the impact of varying fluidic parameters on intraoperative intraocular pressure ( IOP ) fluctuations and postoperative outcomes .


Prospective randomized study of 80 eyes undergoing cataract surgery that were randomly assigned to low ( aspiration flow rate : 20 cc/min ; bottle height : 90 cm ; vacuum : 400 mm Hg ) and high ( aspiration flow rate : 40 cc/min ; bottle height : 110 cm ; vacuum : 400 mm Hg ) fluidic parameter groups .


Real-time dynamic intraoperative IOP was measured during nuclear fragment removal .


Mean maximum and minimum IOP and percentage reduction in IOP from maximum were compared between groups .


Postoperatively , the rate of change in central corneal thickness and anterior chamber inflammation at days 1 and 7 , endothelial cell density at 3 months , and corneal clarity on day 1 were compared .


Minimum IOP in the low and high parameters groups was 35 4.0 and 34.5 6.8 mm Hg , respectively .


Maximum IOP in the low and high parameters groups was 69 3.0 and 85 1.2 mm Hg , respectively ( P < .002 ) .


Mean percent reduction from maximum was 59 % in the high parameters group compared to 41 % in the low parameters group , with the difference being statistically significant ( P < .002 ) .


Rate of change in central corneal thickness was greater in the high parameters group at postoperative days 1 and 7 ( P < .001 ) .


Anterior chamber inflammation and corneal clarity on the first postoperative day were significantly better in the low parameters group .


Higher aspiration flow rate and bottle heights are associated with high intraoperative IOPs of up to 85 mm Hg .


Prolonged elevated IOP during cataract surgery was found to have more anterior segment inflammation and more edematous corneas .


We compare monopolar vs bipolar transurethral resection of the prostate in patients with benign prostatic hyperplasia , focusing on functional outcomes as well as rates of bleeding complications and the transurethral resection syndrome .


A total of 137 patients with benign prostatic hyperplasia ( mean age 67 years , range 47 to 91 ) were prospectively randomly assigned to undergo monopolar ( 67 ) or bipolar ( 70 ) transurethral resection of the prostate .


Patient characteristics of the 2 groups were similar .


Hemoglobin ( as a marker of blood loss ) was measured preoperatively and perioperatively .


I-PSS , I-PSS-QoL score , maximal flow rate and post-void residual urine volume were assessed preoperatively and 3 and 12 months postoperatively .


Duration of surgery , indwelling catheter use and hospitalization were also documented , as were postoperative clot retention requiring removal by catheterization or surgery , and rates of bladder neck and/or urethral strictures .


No significant perioperative differences were found in duration of surgery , catheterization or hospitalization , or in blood loss or rates of blood transfusion and transurethral resection syndrome .


Postoperatively there were no significant differences in I-PSS or I-PSS-QoL scores , or rates of rehospitalization , clot retention , blood transfusions , reoperation or urethral strictures .


However , bladder neck stricture occurred significantly more often in the bipolar group ( 8.5 % vs 0 % , p = 0.02 ) .


The 3 and 12-month followup showed significant and equal improvement in micturition in the 2 groups .


Bipolar and monopolar transurethral resection of the prostate are effective and safe techniques for the surgical treatment of benign prostatic hyperplasia .


The only significant difference between them was a significantly higher rate of bladder neck strictures with bipolar resection of the prostate .


This study aimed ( 1 ) to determine whether scanner arm rotation causes significant movement of the head restraint and ( 2 ) to measure patient movement and its variation during the scan .


The iCAT scanner and a high-speed camera were used .


The 40 patients were divided into 2 groups : the open-eyed group and the blindfolded group .


The mean level of head restraint movement was 0.130 mm , with a significantly higher level at the beginning , probably owing to the accelerating arm .


Mean movement of patients was 1.135 mm and 1.119 mm in the open-eyed and blindfolded groups , respectively .


Patient movement was also significantly higher at the beginning of the scan , when noise and vibrations are likely to surprise the patient .


Patient instruction and a dry-run scan should be done by clinicians .


Manufacturers should consider separating the seat and head restraint from the rest of the scanner to avoid vibration transfer .


The objective of this prospectively randomized phase II trial ( Trial registration : EUCTR2004-004007-37-DE ) was to compare the clinical response of primary breast cancer patients to neoadjuvant therapy with letrozole alone ( LET ) or letrozole and zoledronic acid ( LET + ZOL ) .


Patients were randomly assigned to receive either LET 2.5 mg/day ( n = 79 ) or the combination of LET 2.5 mg/day and a total of seven infusions of ZOL 4 mg every 4 weeks ( n = 89 ) for 6 months .


Primary endpoint was clinical response rate as assessed by mammogram readings .


The study was terminated prematurely due to insufficient recruitment .


We report here on an exploratory analysis of this data .


Central assessment of tumor sizes during the treatment period was available for 131 patients ( 66 LET , 65 LET + ZOL ) .


Clinical responses ( complete or partial ) were seen in 54.5 % ( 95 % CI : 41.8-66 .9 ) of the patients in the LET arm and 69.2 % ( 95 % CI : 56.6-80 .1 ) of those in the LET + ZOL arm ( P = 0.106 ) .


A multivariate model showed an OR of 1.72 ( 95 % CI : 0.83-3 .59 ) for the experimental arm .


No increase in the clinical response rate was observed with the addition of ZOL to a neoadjuvant treatment regimen with LET .


However a trend towards a better reponse in the LET + ZOL arm could be observed .


This trend is consistent with previous studies that have investigated the addition of ZOL to chemotherapy , and it may support the evidence for a direct antitumor action of zoledronic acid .


To evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy .


This historical-controlled , double-blind study ( NCT00520741 ) enrolled patients aged 16-70 years on stable doses of 1-2 antiepileptic drugs ( AEDs ) and experiencing 2-40 partial-onset seizures per 28 days during the 8-week prospective Baseline .


Patients were randomized to lacosamide 400 or 300 mg/day ( 3:1 ratio ) , starting at 200 mg/day and titrated over 3 weeks to randomized dose .


Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase .


The primary assessment was the Kaplan-Meier-predicted percentage of patients on 400 mg/day in the full analysis set ( FAS ) meeting 1 predefined seizure-related exit criterion by day 112 , compared with the historical-control threshold ( 65.3 % ) .


Four hundred twenty-five patients were enrolled and were eligible for safety analyses ( 400 mg/day , n = 319 ; 300 mg/day , n = 106 ) .


A total of 271 ( 63.8 % ) of 425 patients completed the Lacosamide Maintenance Phase ( combined AED Withdrawal and Monotherapy Phases ) .


Among 284 patients in the 400 mg/day group in the FAS , 82 ( 28.9 % ) met 1 exit criterion ; the Kaplan-Meier-predicted exit percentage at day 112 for 400 mg/day ( 30.0 % ; 95 % confidence interval [ CI ] 24.6-35 .5 % ) was lower than the historical control .


When exit events , withdrawal due to treatment-emergent adverse events ( TEAEs ) , and withdrawal due to lack of efficacy were summed ( n = 90 ) , the predicted exit percentage ( 32.3 % ; 95 % CI 26.8-37 .8 % ) was also lower than the historical control .


Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change ( 75.4 % ) and Patient Global Impression of Change ( 74.3 % ) .


Overall , the most common ( > 10 % ) TEAEs were dizziness ( 24.0 % ) , headache ( 14.4 % ) , nausea ( 13.4 % ) , convulsion ( 11.5 % ) , somnolence ( 10.4 % ) , and fatigue ( 10.1 % ) ; most ( 74.1 % ) were mild-to-moderate in intensity .


Seventy-two patients ( 16.9 % ) discontinued due to TEAEs .


Seventeen patients ( 4 % , all receiving 400 mg/day ) experienced serious AEs .


Lacosamide 400 mg/day monotherapy was effective , with a favorable safety profile in patients with focal epilepsy .


Prolonged sitting time is detrimental for health .


Individuals with desk-based occupations tend to sit a great deal and sit-stand workstations have been identified as a potential strategy to reduce sitting time .


Hence , the objective of the current study was to examine the effects of using sit-stand workstations on office workers ' sitting time at work and over the whole day .


We conducted a randomized controlled trial pilot with crossover design and waiting list control in Sydney , Australia from September 2011 to July 2012 ( n = 42 ; 86 % female ; mean age 3811 years ) .


Participants used a sit-stand workstation for four weeks in the intervention condition .


In the time-matched control condition , participants received nothing and crossed over to the intervention condition after four weeks .


The primary outcomes , sitting , standing and walking time at work , were assessed before and after using the workstations with ActivPALs and self-report questionnaires .


Secondary outcomes , domain-specific sitting over the whole day , were assessed by self-report .


Linear mixed models estimated changes in outcomes adjusting for measurement time , study grouping and covariates .


Intervention participants significantly reduced objectively assessed time spent sitting at work by 73 min/workday ( 95 % CI : -106 , -39 ) and increased standing time at work by 65 min/workday ( 95 % CI : 47 , 83 ) ; these changes were significant relative to controls ( p = 0.004 and p < 0.001 , respectively ) .


Total sitting time significantly declined in intervention participants ( -80 min/workday ; 95 % CI : -155 , -4 ) .


This study shows that introducing sit-stand workstations in the office can reduce desk-based workers ' sitting time at work in the short term .


Larger scale studies on more representative samples are needed to determine the public health impact of sit-stand workstations .


ACTRN12612000072819 .


To determine whether falls can be prevented with minimally supervised exercise targeting potentially remediable fall risk factors , i.e. , poor balance , reduced leg muscle strength , and freezing of gait , in people with Parkinson disease .


Two hundred thirty-one people with Parkinson disease were randomized into exercise or usual-care control groups .


Exercises were practiced for 40 to 60 minutes , 3 times weekly for 6 months .


Primary outcomes were fall rates and proportion of fallers during the intervention period .


Secondary outcomes were physical ( balance , mobility , freezing of gait , habitual physical activity ) , psychological ( fear of falling , affect ) , and quality-of-life measures .


There was no significant difference between groups in the rate of falls ( incidence rate ratio [ IRR ] = 0.73 , 95 % confidence interval [ CI ] 0.45-1 .17 , p = 0.18 ) or proportion of fallers ( p = 0.45 ) .


Preplanned subgroup analysis revealed a significant interaction for disease severity ( p < 0.001 ) .


In the lower disease severity subgroup , there were fewer falls in the exercise group compared with controls ( IRR = 0.31 , 95 % CI 0.15-0 .62 , p < 0.001 ) , while in the higher disease severity subgroup , there was a trend toward more falls in the exercise group ( IRR = 1.61 , 95 % CI 0.86-3 .03 , p = 0.13 ) .


Postintervention , the exercise group scored significantly ( p < 0.05 ) better than controls on the Short Physical Performance Battery , sit-to-stand , fear of falling , affect , and quality of life , after adjusting for baseline performance .


An exercise program targeting balance , leg strength , and freezing of gait did not reduce falls but improved physical and psychological health .


Falls were reduced in people with milder disease but not in those with more severe Parkinson disease .


This study provides Class III evidence that for patients with Parkinson disease , a minimally supervised exercise program does not reduce fall risk .


This study lacked the precision to exclude a moderate reduction or modest increase in fall risk from exercise .


Australian New Zealand Clinical Trials Registry ( ACTRN12608000303347 ) .


Platelet aggregation is enhanced in firefighters following short bouts of work in thermal protective clothing ( TPC ) .


We sought to determine if aspirin therapy before and/or following exertion in TPC prevents platelet activation .


In a double-blind , placebo-controlled study , 102 firefighters were randomized to receive daily therapy ( 81 mg aspirin or placebo ) for 14 days before and a single dose ( 325 mg aspirin or placebo ) following exercise in TPC resulting in four potential assignments : aspirin before and after exercise ( AA ) , placebo before and after exercise ( PP ) , aspirin before and placebo after exercise ( AP ) , and placebo before and aspirin after exercise ( PA ) .


Platelet closure time ( PCT ) was measured with a platelet function analyzer before the 2-week treatment , after the 2 week treatment period , immediately after exercise , and 30 , 60 , and 90 minutes later .


Baseline PCT did not differ between groups .


PCT changed over time in all four groups ( p < 0.001 ) rising to a median of > 300 seconds [ IQR 99 , 300 ] in AA and > 300 [ 92 , 300 ] in AP prior to exercise .


Following exercise , median PCT decreased to in all groups .


Median PCT returned to > 300 seconds 30 minutes later in AA and AP and rose to 300 seconds in PA 60 minutes after exercise .


Daily aspirin therapy blunts platelet activation during exertional heat stress and single-dose aspirin therapy following exertional heat stress reduces platelet activation within 60 minutes .


Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet .


Improvement typically occurs soon after diet implementation .


This rapid response could result from low fuel supply ( calories ) , lower carbohydrate content of the weight-loss diet , and/or weight loss per se .


To differentiate these effects , glucose , insulin , C-peptide and glucagon were determined during the last 24 h of a 3-day period without food ( severe calorie restriction ) and a calorie-sufficient , carbohydrate-free diet .


Seven subjects with untreated type 2 diabetes were studied .


A randomized-crossover design with a 4-week washout period between arms was used .


Results from both the calorie-sufficient , carbohydrate-free diet and the 3-day fast were compared with the initial standard diet consisting of 55 % carbohydrate , 15 % protein and 30 % fat .


The overnight fasting glucose concentration decreased from 196 ( standard diet ) to 160 ( carbohydrate-free diet ) to 127 mg/dl ( fasting ) .


The 24 h glucose and insulin area responses decreased by 35 % and 48 % on day 3 of the carbohydrate-free diet , and by 49 % and 69 % after fasting .


Overnight basal insulin and glucagon remained unchanged .


Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations .


Carbohydrate restriction per se could account for 71 % of the reduction .


Insulin could not entirely explain the glucose responses .


In the absence of carbohydrate , the net insulin response was 28 % of the standard diet .


Glucagon did not contribute to the metabolic adaptations observed .


Exposure therapy in anorexia nervosa has preliminarily been shown to be effective for increasing food intake .


D-Cycloserine is a glutamatergic N-methyl-d-aspartate receptor agonist that has been shown to facilitate the benefits of exposure therapy for anxiety disorders by enhancing the emotional learning in the exposures ; therefore , we examined D-cycloserine-facilitation of exposure therapy to increase body mass index ( BMI ) in patients with anorexia nervosa .


Participants ( N = 36 ) with anorexia nervosa ( diagnosed via DSM-IV ) were recruited from a partial hospitalization eating disorder clinic between February 2013 and November 2013 .


Participants were randomly assigned to receive exposure therapy plus D-cycloserine ( n = 20 ) or placebo ( n = 16 ) .


Participants completed psychoeducation and 4 sessions of exposure therapy , with medication ( D-cycloserine vs placebo ) given prior to the first 3 exposure sessions .


They also completed a 1-month follow-up .


As hypothesized , participants in the D-cycloserine group showed a significantly greater increase in BMI than those in the placebo group ( Wilk = 0.86 , F3 ,32 = 2.20 , P = .043 , p ( 2 ) = 0.12 ) .


D-Cycloserine participants gained 3 pounds relative to 0.5 pounds in the placebo group .


Both groups experienced significantly decreased anxiety over the course of therapy ( Wilk = 0.80 , F3 ,32 = 3.32 , P = .023 , p ( 2 ) = 0.20 ) .


This study preliminarily demonstrates that D-cycloserine facilitates exposure therapy for anorexia nervosa , leading to increased weight gain .


A potential mechanism is that participants who receive D-cycloserine may generalize learning from within-session exposures to food intake during other similar meals , resulting in sustained increases in BMI .


Further research is needed to confirm these findings and test the putative mechanism that generalized learning from exposure therapy can increase BMI and stabilize a healthy weight .


ClinicalTrials.gov identifier : NCT01996644 .


A fixed-ratio combination of the basal insulin analogue insulin degludec and the glucagon-like peptide-1 ( GLP-1 ) analogue liraglutide has been developed as a once-daily injection for the treatment of type 2 diabetes .


We aimed to compare combined insulin degludec-liraglutide ( IDegLira ) with its components given alone in insulin-naive patients .


In this phase 3 , 26-week , open-label , randomised trial , adults with type 2 diabetes , HbA1c of 7-10 % ( inclusive ) , a BMI of 40 kg/m ( 2 ) or less , and treated with metformin with or without pioglitazone were randomly assigned ( 2:1:1 ) to daily injections of IDegLira , insulin degludec , or liraglutide ( 18 mg per day ) .


IDegLira and insulin degludec were titrated to achieve a self-measured prebreakfast plasma glucose concentration of 4-5 mmol/L .


The primary endpoint was change in HbA1c after 26 weeks of treatment , and the main objective was to assess the non-inferiority of IDegLira to insulin degludec ( with an upper 95 % CI margin of 03 % ) , and the superiority of IDegLira to liraglutide ( with a lower 95 % CI margin of 0 % ) .


This study is registered with ClinicalTrials.gov , number NCT01336023 .


1663 adults ( mean age 55 years [ SD 10 ] , HbA1c 83 % [ 09 ] , and BMI 312 kg/m ( 2 ) [ 48 ] ) were randomly assigned , 834 to IDegLira , 414 to insulin degludec , and 415 to liraglutide .


After 26 weeks , mean HbA1c had decreased by 19 % ( SD 11 ) to 64 % ( 10 ) with IDegLira , by 14 % ( 10 ) to 69 % ( 11 ) with insulin degludec , and by 13 % ( 11 ) to 70 % ( 12 ) with liraglutide .


IDegLira was non-inferior to insulin degludec ( estimated treatment difference -047 % , 95 % CI -058 to -036 , p < 00001 ) and superior to liraglutide ( -064 % , -075 to -053 , p < 00001 ) .


IDegLira was generally well tolerated ; fewer participants in the IDegLira group than in the liraglutide group reported gastrointestinal adverse events ( nausea 88 vs 197 % ) , although the insulin degludec group had the fewest participants with gastrointestinal adverse events ( nausea 36 % ) .


We noted no clinically relevant differences between treatments with respect to standard safety assessments , and the safety profile of IDegLira reflected those of its component parts .


The number of confirmed hypoglycaemic events per patient year was 18 for IDegLira , 02 for liraglutide , and 26 for insulin degludec .


Serious adverse events occurred in 19 ( 2 % ) of 825 patients in the IDegLira group , eight ( 2 % ) of 412 in the insulin degludec group , and 14 ( 3 % ) of 412 in the liraglutide group .


IDegLira combines the clinical advantages of basal insulin and GLP-1 receptor agonist treatment , resulting in improved glycaemic control compared with its components given alone .


Novo Nordisk .


This pilot study explores the feasibility of yoga as part of a treatment program for alcohol dependence .


Eighteen alcohol dependent patients were randomized to receive either treatment as usual or treatment as usual plus yoga .


Assessments were taken at baseline and six month follow-up .


` Riddargatan 1 ' : an outpatient alcohol treatment clinic located in Stockholm , Sweden .


Treatment as usual consisted of psychological and pharmacological interventions for alcohol dependence .


The 10-week yoga intervention included a weekly group yoga session .


Participants were encouraged to practice the yoga movements at home once per day .


Alcohol consumption ( timeline follow-back method , DSM-IV criteria for alcohol dependence , and the Short Alcohol Dependence Data questionnaire ) , affective symptoms ( the Hospital Anxiety and Depression Scale ) , quality of life ( Sheehan Disability Scale ) and stress ( the Perceived Stress Scale and saliva cortisol ) .


Yoga was found to be a feasible and well accepted adjunct treatment for alcohol dependence .


Alcohol consumption reduced more in the treatment as usual plus yoga group ( from 6.32 to 3.36 drinks per day ) compared to the treatment as usual only group ( from 3.42 to 3.08 drinks per day ) .


The difference was , however , not statistically significant ( p = 0.17 ) .


Larger studies are needed to adequately assess the efficacy and long-term effectiveness of yoga as an adjunct treatment for alcohol dependence .


The optimal timing of endocrine therapy in non-metastatic prostate cancer ( PCa ) is still an issue of debate .


A randomised , double-blind , parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-nave , non-metastatic PCa .


Kaplan-Meier analysis was used to estimate overall survival ( OS ) and multivariate Cox proportional hazard model was performed to analyse time-to-event ( death ) .


A total of 1218 patients were included into the Scandinavian Prostate Cancer Group ( SPCG ) -6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo .


Median follow-up was 14.6 years .


Overall , 866 ( 71.1 % ) patients died , 428 ( 70.5 % ) in the bicalutamide arm and 438 ( 71.7 % ) in the placebo arm , p = 0.87 .


Bicalutamide significantly improved OS in patient with locally advanced disease ( hazard ratios ( HR ) = 0.77 ( 95 % confidence interval ( CI ) : 0.63-0 .94 , p = 0.01 ) , regardless of baseline prostate-specific antigen ( PSA ) , with a survival benefit which was apparent throughout the study period .


In contrast , survival favoured randomisation to the placebo arm in patients with localised disease ( HR = 1.19 ( 95 % CI : 1.00-1 .43 ) , p = 0.056 ) .


However , a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation .


In multivariate Cox proportional hazard model , only including patients managed on watchful waiting as their standard of care ( n = 991 ) OS depended on age , World Health Organisation ( WHO ) grade , baseline PSA , clinical stage and randomised treatment .


Throughout the 14.6 year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa .


In contrast , patients with localised PCa and low PSA derived no survival benefit from early bicalutamide .


The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA .


Epidemiological studies suggest the existence of a relationship between aircraft noise exposure and increased risk for myocardial infarction and stroke .


Patients with established coronary artery disease and endothelial dysfunction are known to have more future cardiovascular events .


We therefore tested the effects of nocturnal aircraft noise on endothelial function in patients with or at high risk for coronary artery disease .


60 Patients ( 50p 1-3 vessels disease ; 10p with a high Framingham Score of 23 % ) were exposed in random and blinded order to aircraft noise and no noise conditions .


Noise was simulated in the patients ' bedroom and consisted of 60 events during one night .


Polygraphy was recorded during study nights , endothelial function ( flow-mediated dilation of the brachial artery ) , questionnaires and blood sampling were performed on the morning after each study night .


The mean sound pressure levels L eq ( 3 ) measured were 46.9 2.0 dB ( A ) in the Noise 60 nights and 39.2 3.1 dB ( A ) in the control nights .


Subjective sleep quality was markedly reduced by noise from 5.8 2.0 to 3.7 2.2 ( p < 0.001 ) .


FMD was significantly reduced ( from 9.6 4.3 to 7.9 3.7 % ; p < 0.001 ) and systolic blood pressure was increased ( from 129.5 16.5 to 133.6 17.9 mmHg ; p = 0.030 ) by noise .


The adverse vascular effects of noise were independent from sleep quality and self-reported noise sensitivity .


Nighttime aircraft noise markedly impairs endothelial function in patients with or at risk for cardiovascular disease .


These vascular effects appear to be independent from annoyance and attitude towards noise and may explain in part the cardiovascular side effects of nighttime aircraft noise .


Providing advice to wear good quality shoes with appropriate fit is one of the possibilities GPs have when treating patients with foot problems .


The aims of this study are to ( i ) determine which shoe characteristics are important when providing shoe advice ; ( ii ) develop a shoe advice leaflet and ( iii ) evaluate if women choose better shoes with the aid of the leaflet .


We performed a literature search on the effect of separate shoe characteristics on foot pathologies and kinematics and developed an information leaflet with the aid of multidisciplinary experts .


The leaflet was tested in a group of women aged 50 years or over who did not receive podiatric treatment or shoe advice in the year prior to the study .


The women were asked to select shoes ; half of them were provided with the leaflet .


Shoe characteristics were scored blinded for the condition by two podiatrists .


Data were analysed using a t-test for independent measures .


The developed leaflet contains nine shoe characteristics .


A total of 57 women ranging from 54 to 86 years old ( average 69 ) consented to participate in testing the efficacy of the leaflet .


Women using the leaflet ( n = 29 ) selected better shoes than without ( P = 0.049 ) .


Based on a literature search and expert opinion , we have developed an information leaflet for GPs to provide as a supplement to oral shoe advice .


Women using this leaflet were able to select shoes of better quality and better fit than women selecting shoes without using the leaflet .


Ideal anesthetic technique for renal allograft recipients should provide hemodynamic stability , optimum graft reperfusion and adequate analgesia .


Balanced anesthesia is preferred because renal nociception is conducted multi-segmentally and chronically ill ESRD patients have labile psychological profile .


Present study compared the efficacy ofdexmedetomidine with fentanyl administered via intravenous and epidural route before induction of general anesthesia .


Prospective , double blind randomized study , recruited sixty hemo-dynamically stable ESRD adults , 18-55 years , scheduled for elective live related renal transplantation .


Patients randomly received intravenous dexmedetomidine 0.5 g/kg followed by epidural dexmedetomidine 0.5 g/kg alongwith 5 ml ; 0.25 % ropivacaine or intravenous fentanyl 1 g/kg followed by epiduralfentanyl 1 g/kg alongwith 5 ml ; 0.25 % ropivacaine .


All patients received standardized general anaesthesia and continuous epidural ropivacaine 0.25 % ; 4-8 ml/hr .


Preoperative sedation , peri-operative haemodynamics , end tidal anaesthetic agent requirement , peri-operative fluid requirement , need for vasopressors , blood loss and early graft function was assessed .


80 % patients receiving intravenous dexmedetomidine did not require rescue midazolam for achieving satisfactory sedation before induction of general anaesthesia .


Dexmedetomidine significantly reduced propofol and end tidal inhalational agents requirement and need for rescue analgesics .


Early renal graft function ( onset time of diuresis after declamping , 24 hours urine output and serum creatinine levels ) was comparable .


There were no adverse sequelae .


Dexmedetomidine-based anaesthetic regimen versus fentanyl-based anaesthesia provided appropriate anxiolysis and analgesia for conducting invasive procedures and subsequent epidural administration of these agents reduced anaesthetic requirement and prolonged postoperative analgesia without compromising hemodynamics and respiratory parameters .


Further dose finding studies can be conducted in kidney transplant recipients .


The effect of the surgical site of DBS on balance and gait in Parkinson 's Disease ( PD ) is uncertain .


This is the first double-blind study of subjects randomized to either the STN ( N = 14 ) or GPi ( N = 14 ) who were assessed on a range of clinical balance measures .


Balance testing occurred before and 6 months postsurgery .


A control PD group was tested over the same period without surgery ( N = 9 ) .


All subjects were tested on and off medication and DBS subjects were also tested on and off DBS .


The Postural Instability and Gait Disability items of the UPDRS and additional functional tests , which we call the Balance and Gait scale , were assessed .


Activities of Balance Confidence and Activities of Daily Living questionnaires were also recorded .


Balance was not different between the best-treated states before and after DBS surgery for both sites .


Switching DBS on improved balance scores , and scores further improved with medication , compared to the off state .


The GPi group showed improved performance in the postsurgery off state and better ratings of balance confidence after surgery , compared to the STN group .


Clinical measures of balance function for both the STN and GPi sites showed that balance did not improve beyond the best medically treated state before surgery .


Both clinical balance testing in the off/off state and self-reported balance confidence after surgery showed better performance in the GPi than the STN group .


The scale-up of malaria rapid diagnostic tests ( RDTs ) is intended to improve case management of fever and targeting of artemisinin-based combination therapy .


Habitual presumptive treatment has hampered these intentions , suggesting a need for strategies to support behaviour change .


We aimed to assess the introduction of RDTs when packaged with basic or enhanced clinician training interventions in Cameroon .


We did a three-arm , stratified , cluster-randomised trial at 46 public and mission health facilities at two study sites in Cameroon to compare three approaches to malaria diagnosis .


Facilities were randomly assigned by a computer program in a 9:19:19 ratio to current practice with microscopy ( widely available , used as a control group ) ; RDTs with a basic ( 1 day ) clinician training intervention ; or RDTs with an enhanced ( 3 days ) clinician training intervention .


Patients ( or their carers ) and fieldworkers who administered surveys to obtain outcome data were masked to study group assignment .


The primary outcome was the proportion of patients treated in accordance with WHO malaria treatment guidelines , which is a composite indicator of whether patients were tested for malaria and given appropriate treatment consistent with the test result .


All analyses were by intention to treat .


This study is registered at ClinicalTrials.gov , number NCT01350752 .


The study took place between June 7 and Dec 14 , 2011 .


The analysis included 681 patients from nine facilities in the control group , 1632 patients from 18 facilities in the basic-training group , and 1669 from 19 facilities in the enhanced-training group .


The proportion of patients treated in accordance with malaria guidelines did not improve with either intervention ; the adjusted risk ratio ( RR ) for basic training compared with control was 104 ( 95 % CI 053-207 ; p = 090 ) , and for enhanced training compared with control was 117 ( 061-225 ; p = 062 ) .


Inappropriate use of antimalarial drugs after a negative test was reduced from 84 % ( 201/239 ) in the control group to 52 % ( 413/796 ) in the basic-training group ( unadjusted RR 063 , 028-143 ; p = 025 ) and to 31 % ( 232/759 ) in the enhanced-training group ( 029 , 011-077 ; p = 002 ) .


Enhanced clinician training , designed to translate knowledge into prescribing practice and improve quality of care , has the potential to halve overtreatment in public and mission health facilities in Cameroon .


Basic training is unlikely to be sufficient to support the behaviour change required for the introduction of RDTs .


To investigate individual patient data from a comprehensive trials programme to evaluate the safety and efficacy of the dipeptidyl peptidase-4 ( DPP-4 ) inhibitor linagliptin across a range of glucose-lowering regimens in a large elderly population with type 2 diabetes mellitus ( T2DM ) .


Data were pooled from individuals aged 65 years , who participated in seven phase III , placebo-controlled clinical trials of linagliptin ( 24-52 weeks ) .


Safety was assessed by incidence and severity of adverse events ( AEs ) with a focus on hypoglycaemia .


The primary efficacy endpoint was change in glycated haemoglobin ( HbA1c ) .


In total , 841 subjects received linagliptin 5 mg once a day and 490 received placebo .


At baseline , the population had a mean s.d. age of 71.0 4.6 years and a mean HbA1c concentration of 8.0 0.8 % ; 63.5 % of subjects received 2 antidiabetes drugs .


Overall AEs and drug-related AEs were experienced by similar proportions of patients ( linagliptin 71.3 , placebo 73.3 ; linagliptin 18.1 , placebo 19.8 % , respectively ) .


The incidence of investigator-reported hypoglycaemia was 21.4 % with linagliptin and 25.7 % with placebo .


Severe hypoglycaemic events were rare and there were fewer in the linagliptin group ( 1.0 vs. 1.8 % ) .


At week 24 , the placebo-corrected adjusted mean s.e. reduction in HbA1c with linagliptin was -0.62 0.06 % ( 95 % CI : -0.73 , -0.51 ) .


Data from this large cohort show that linagliptin is a well-tolerated and efficacious therapy for elderly patients with T2DM .


Treatment with linagliptin may support individualized treatment goals , while effectively managing the risk of hypoglycaemia or drug-related side effects .


We presented the pattern of health care consumption , and the utilization of available resources by describing the ecology of medical care in Beijing on a monthly basis and by describing the socio-demographic characteristics associated with receipt care in different settings .


A cohort of 6,592 adults , 15 years of age and older were sampled to estimate the number of urban-resident adults per 1,000 who visited a medical facility at least once in a month , by the method of three-stage stratified and cluster random sampling .


Separate logistic regression analyses assessed the association between those receiving care in different types of setting and their socio-demographic characteristics .


On average per 1,000 adults , 295 had at least one symptom , 217 considered seeking medical care , 173 consulted a physician , 129 visited western medical practitioners , 127 visited a hospital-based outpatient clinic , 78 visited traditional Chinese medical practitioners , 43 visited a primary care physician , 35 received care in an emergency department , 15 were hospitalized .


Health care seeking behaviors varied with socio-demographic characteristics , such as gender , age , ethnicity , resident census register , marital status , education , income , and health insurance status .


In term of primary care , the gate-keeping and referral roles of Community Health Centers have not yet been fully established in Beijing .


This study represents a first attempt to map the medical care ecology of Beijing urban population and provides timely baseline information for health care reform in China .


Vitamin E ( VE ) bonded polysulfone dialysis membranes have putative erythropoiesis stimulating agent ( ESA ) - sparing and anti-inflammatory properties based on data from a small number of studies .


We sought to investigate this in a large , prospective 12-month randomized controlled trial .


Two-hundred and sixty prevalent haemodialysis ( HD ) patients were randomized to dialysis with VE-bonded polysulfone membranes or non-VE-bonded equivalents .


All ESA-dosing was performed by means of a computer-based anaemia management decision support system .


Monthly data were used to calculate the ESA resistance index ( ERI ) and blood tests were performed at baseline , 6 and 12 months for measurement of C-reactive protein ( CRP ) levels .


Of the 260 patients , 123 were randomized to dialysis with the VE-membrane and 12-month data was available for 220 patients .


At the study population level , no beneficial effect of the VE membranes on the ERI or CRP levels was observed .


Post hoc analyses indicated that there was a significant fall in ERI for patients with the highest baseline ESA resistance dialysed with the VE ( 9.28 [ 7.70-12 .5 ] versus 7.70 [ 5.34-12 .7 ] IU/week/kg / g/dL Hb , P = 0.01 ) but not the control membranes ( 9.45 [ 7.62-12 .3 ] versus 8.14 [ 4.44-15 .6 ] IU/week/kg / g/dL Hb , P = 0.41 ) ; this was not attributable to changes in CRP levels .


Wholesale switching of all chronic HD patients to dialysis with VE-bonded polysulfone membranes appears not to be associated with improvements in ESA-responsiveness or CRP .


These membranes may have utility in patients with heightened ESA resistance .


Radiation Therapy Oncology Group ( RTOG ) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis ( BM ) treated with whole-brain radiation therapy ( WBRT ) and stereotactic radiosurgery ( SRS ) versus WBRT alone .


An improved prognostic index , the graded prognostic assessment ( GPA ) has been developed .


Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA , the conclusions may vary .


In this analysis , 252 of the 331 patients were evaluable by GPA .


Of those , 211 had lung cancer .


Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database .


Multiple Cox regression was used to compare survival between treatment groups , adjusting for GPA .


Treatment comparisons within subgroups were performed with the log-rank test .


A free online tool ( brainmetgpa.com ) simplified GPA use .


The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases ; however , there was a benefit for the subset of patients with GPA 3.5 to 4.0 ( median survival time [ MST ] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months , P = .05 ) regardless of the number of metastases .


Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS , the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months , respectively .


This secondary analysis of predominantly lung cancer patients , consistent with the original analysis , shows no survival advantage for the group overall when treated with WBRT and SRS ; however , in patients with high GPA ( 3.5-4 ) , there is a survival advantage regardless of whether they have 1 , 2 , or 3 BM .


This benefit did not extend to patients with lower GPA .


Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted .


Drug development and clinical decision making for patients with metastatic prostate cancer ( PC ) have been hindered by a lack of quantitative methods of assessing changes in bony disease burden that are associated with overall survival ( OS ) .


Bone scan index ( BSI ) , a quantitative imaging biomarker of bone tumor burden , is prognostic in men with metastatic PC .


We evaluated an automated method for BSI calculation for the association between BSI over time with clinical outcomes in a randomized double-blind trial of tasquinimod ( TASQ ) in men with metastatic castration-resistant PC ( mCRPC ) .


Bone scans collected during central review from the TASQ trial were analyzed retrospectively using EXINIbone ( BSI ) , an automated software package for BSI calculation .


Associations between BSI and other prognostic biomarkers , progression-free survival , OS , and treatment were evaluated over time .


Of 201 men ( 57 TASQ and 28 placebo ) , 85 contributed scans at baseline and week 12 of sufficient quality .


Baseline BSI correlated with prostate-specific antigen and alkaline phosphatase levels and was associated with OS in univariate ( hazard ratio [ HR ] = 1.42 , P = 0.013 ) and multivariate ( HR = 1.64 , P < 0.001 ) analyses .


BSI worsening at 12 weeks was prognostic for progression-free survival ( HR = 2.14 per BSI doubling , P < 0.001 ) and OS ( HR = 1.58 , P = 0.033 ) in multivariate analyses including baseline BSI and TASQ treatment .


TASQ delayed BSI progression .


BSI and BSI changes over time were independently associated with OS in men with mCRPC .


A delay in objective radiographic bone scan progression with TASQ is suggested ; prospective evaluation of BSI progression and response criteria in phase 3 trials of men with mCRPC is warranted .


Mortality following hip hemiarthroplasty is in the range of 10-40 % in the first year , with much attributed to post-operative complications .


One such complication is surgical site infection ( SSI ) , which at the start of this trial affected 4.68 % of patients in the UK having this operation .


Compared to SSI rates of elective hip surgery , at less than 1 % , this figure is elevated .


The aim of this quasi randomised controlled trial ( RCT ) is to determine if high dose antibiotic impregnated cement can reduce the SSI in patients at 12-months after hemiarthroplasty for intracapsular fractured neck of femur .


848 patients with an intracapsular fractured neck of femur requiring a hip hemiarthroplasty are been recruited into this two-centre double-blind quasi RCT .


Participants were recruited before surgery and quasi randomised to standard care or intervention group .


Participants , statistician and outcome assessors were blind to treatment allocation throughout the study .


The intervention consisted of high dose antibiotic impregnated cement consisting of 1 gram Clindamycin and 1 gram of Gentamicin .


The primary outcome is Health Protection Agency ( HPA ) defined deep surgical site infection at 12 months .


Secondary outcomes include HPA defined superficial surgical site infection at 30 days , 30 and 90-day mortality , length of hospital stay , critical care stay , and complications .


Large randomised controlled trials assessing the effectiveness of a surgical intervention are uncommon , particularly in the speciality of orthopaedics .


The results from this trial will inform evidence-based recommendations for antibiotic impregnated cement in the management of patients with a fractured neck of femur undergoing a hip hemiarthroplasty .


If high dose antibiotic impregnated cement is found to be an effective intervention , implementation into clinical practice could improve long-term outcomes for patients undergoing hip hemiarthroplasty .


Current Controlled Trials : ISRCTN25633145 .


To examine the influence of mechanical bowel preparation on surgical field visualization during laparoscopic hysterectomy .


The study 's primary outcome was the percentage of operations rated `` good '' or `` excellent '' in terms of surgical field visualization at the outset of the case by the primary surgeon .


Additional measures included assessment of visualization during the case and patient perioperative comfort .


The study was powered to detect a 20 % absolute difference in the proportion of cases rated as `` good '' or `` excellent . ''


Seventy-three patients were assigned to mechanical bowel preparation and 73 to no mechanical bowel preparation .


The groups were comparable regarding patient and surgery characteristics .


No differences were found for this rating between groups ( mechanical bowel preparation , 64 of 73 patients [ 87.7 % ] , compared with no mechanical bowel preparation , 60 of 73 patients [ 82.2 % ] , P = .36 ) .


Surgeons guessed patient assignment correctly 59 % of the time ( 42 of 71 patients ) with mechanical bowel preparation and 55 % of the time ( 41 of 75 patients ) with no mechanical bowel preparation .


Mechanical bowel preparation is well-tolerated but does not influence surgical field visualization for laparoscopic hysterectomy .


ClinialTrials.gov , www.clinicaltrials.gov , NCT01576965 .


Idiotypes ( Ids ) , the unique portions of tumor immunoglobulins , can serve as targets for passive and active immunotherapies for lymphoma .


We performed a multicenter , randomized trial comparing a specific vaccine ( MyVax ) , comprising Id chemically coupled to keyhole limpet hemocyanin ( KLH ) plus granulocyte macrophage colony-stimulating factor ( GM-CSF ) to a control immunotherapy with KLH plus GM-CSF .


Patients with previously untreated advanced-stage follicular lymphoma ( FL ) received eight cycles of chemotherapy with cyclophosphamide , vincristine , and prednisone .


Those achieving sustained partial or complete remission ( n = 287 [ 44 % ] ) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy .


Anti-Id antibody responses ( humoral immune responses [ IRs ] ) were measured before each immunization .


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


Secondary end points included IR and time to subsequent antilymphoma therapy .


At a median follow-up of 58 months , no significant difference was observed in either PFS or time to next therapy between the two arms .


In the MyVax group ( n = 195 ) , anti-Id IRs were observed in 41 % of patients , with a median PFS of 40 months , significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy .


This trial failed to demonstrate clinical benefit of specific immunotherapy .


The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes .


Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study .


The poly ( ADP-ribose ) polymerase inhibitor olaparib has shown antitumour activity in patients with platinum-sensitive , recurrent , high-grade serous ovarian cancer with or without BRCA1 or BRCA2 mutations .


The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy , followed by olaparib maintenance monotherapy , versus chemotherapy alone in patients with platinum-sensitive , recurrent , high-grade serous ovarian cancer .


In this randomised , open-label , phase 2 study , adult patients with platinum-sensitive , recurrent , high-grade serous ovarian cancer who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months before randomisation received either olaparib ( 200 mg capsules twice daily , administered orally on days 1-10 of each 21-day cycle ) plus paclitaxel ( 175 mg/m ( 2 ) , administered intravenously on day 1 ) and carboplatin ( area under the curve [ AUC ] 4 mg/mL per min , according to the Calvert formula , administered intravenously on day 1 ) , then olaparib monotherapy ( 400 mg capsules twice daily , given continuously ) until progression ( the olaparib plus chemotherapy group ) , or paclitaxel ( 175 mg/m ( 2 ) on day 1 ) and carboplatin ( AUC 6 mg/mL per min on day 1 ) then no further treatment ( the chemotherapy alone group ) .


Randomisation was done by an interactive voice response system , stratified by number of previous platinum-containing regimens received and time to disease progression after the previous platinum regimen .


The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 , analysed by intention to treat .


Prespecified exploratory analyses included efficacy by BRCA mutation status , assessed retrospectively .


This study is registered with ClinicalTrials.gov , number NCT01081951 , and has been completed .


Between Feb 12 and July 30 , 2010 , 173 patients at 43 investigational sites in 12 countries were enrolled into the study , of whom 162 were eligible and were randomly assigned to the two treatment groups ( 81 to the olaparib plus chemotherapy group and 81 to the chemotherapy alone group ) .


Of these randomised patients , 156 were treated in the combination phase ( 81 in the olaparib plus chemotherapy group and 75 in the chemotherapy alone group ) and 121 continued to the maintenance or no further treatment phase ( 66 in the olaparib plus chemotherapy group and 55 in the chemotherapy alone group ) .


BRCA mutation status was known for 107 patients ( either at baseline or determined retrospectively ) : 41 ( 38 % ) of 107 had a BRCA mutation ( 20 in the olaparib plus chemotherapy group and 21 in the chemotherapy alone group ) .


Progression-free survival was significantly longer in the olaparib plus chemotherapy group ( median 12.2 months [ 95 % CI 9.7-15 .0 ] ) than in the chemotherapy alone group ( median 9.6 months [ 95 % CI 9.1-9 .7 ) ( HR 0.51 [ 95 % CI 0.34-0 .77 ] ; p = 0.0012 ) , especially in patients with BRCA mutations ( HR 0.21 [ 0.08-0 .55 ] ; p = 0.0015 ) .


In the combination phase , adverse events that were reported at least 10 % more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia ( 60 [ 74 % ] of 81 vs 44 [ 59 % ] of 75 ) , nausea ( 56 [ 69 % ] vs 43 [ 57 % ] ) , neutropenia ( 40 [ 49 % ] vs 29 [ 39 % ] ) , diarrhoea ( 34 [ 42 % ] vs 20 [ 27 % ] ) , headache ( 27 [ 33 % ] vs seven [ 9 % ] ) , peripheral neuropathy ( 25 [ 31 % ] vs 14 [ 19 % ] ) , and dyspepsia ( 21 [ 26 % ] vs 9 [ 12 % ] ) ; most were of mild-to-moderate intensity .


The most common grade 3 or higher adverse events during the combination phase were neutropenia ( in 35 [ 43 % ] of 81 patients in the olaparib plus chemotherapy group vs 26 [ 35 % ] of 75 in the chemotherapy alone group ) and anaemia ( seven [ 9 % ] vs five [ 7 % ] ) .


Serious adverse events were reported in 12 ( 15 % ) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 ( 21 % ) patients in the chemotherapy alone group .


Olaparib plus paclitaxel and carboplatin followed by maintenance monotherapy significantly improved progression-free survival versus paclitaxel plus carboplatin alone , with the greatest clinical benefit in BRCA-mutated patients , and had an acceptable and manageable tolerability profile .


AstraZeneca .


Budesonide is a potent corticosteroid commonly prescribed for management of inflammation in chronic rhinosinusitis ( CRS ) .


The standard for prescribing budesonide is via impregnated nasal saline irrigation ( INSI ) , although recently the mucosal atomization device ( MAD ) has emerged as a theoretically superior method of distributing medication into the sinuses .


The MAD atomizes medication into small droplets and this is thought to enhance absorption and improve bioavailability .


However , no studies have shown whether enhanced absorption and improved bioavailability of budesonide via MAD causes adrenal suppression .


The objective of this study is to determine whether budesonide via MAD affects the hypothalamic-pituitary-adrenal ( HPA ) axis .


Twenty CRS patients were recruited from a tertiary rhinology clinic and randomized to take budesonide ( 1 mg ) via MAD or via INSI twice a day for 60 days .


The adrenocorticotropic hormone ( ACTH ) stimulation test and 22-item Sinonasal Outcomes Test ( SNOT-22 ) questionnaire were administered on days 1 , 30 , and 60 of the study .


Plasma budesonide and cortisol levels were simultaneously quantified using a high-performance liquid chromatography-tandem mass spectrometry technique .


There was no indication of adrenal suppression in either group ( n = 20 ) based on ACTH stimulation test results nor was there significant plasma budesonide levels detected in either group .


Quality of life , as indicated by SNOT-22 , did not differ between groups at 60 days ( p = 0.404 ; 95 % confidence interval [ CI ] , -37.2 to 15.9 ) , but SNOT-22 scores for patients using MAD did show statistically significant improvement at 60 days compared to baseline ( p = 0.02 ) .


The MAD is likely a safe and effective method of delivering budesonide to the sinuses in the short term .


The purpose of this study was to investigate the predictive values of baseline and changes in cystatin C ( CysC ) and its derived equations for short-term adverse outcomes and the effect of nesiritide therapy on CysC in acute decompensated heart failure ( ADHF ) .


Newer renal biomarkers or their derived estimates of renal function have demonstrated long-term prognostic value in chronic heart failure .


CysC levels were measured in sequential plasma samples from 811 subjects with ADHF who were enrolled in the ASCEND-HF ( Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure ) biomarker sub-study ( randomized to nesiritide therapy vs. placebo ) , and followed for all-cause death ( 180 days ) and recurrent hospital stay ( 30 days ) .


Median CysC levels were 1.49 ( interquartile range [ IQR ] : 1.20 to 1.96 ) mg/l at baseline , 1.56 ( IQR : 1.28 to 2.13 ) mg/l at 48 to 72 h , and 1.58 ( IQR : 1.24 to 2.11 ) mg/l at 30 days .


Higher baseline ( but not follow-up ) CysC levels were associated with increased risk of 30-day adverse events and less improvement in dyspnea after 24 h as well as 180-day mortality , although not incremental to blood urea nitrogen .


Worsening renal function ( defined as a 0.3 mg/l increase in CysC ) occurred in 161 of 701 ( 23 % ) patients , but it was not predictive of adverse events .


Changes in CysC levels were similar between the nesiritide and placebo groups .


Our findings confirmed the prognostic value of baseline CysC levels in the setting of ADHF .


However , worsening renal function based on CysC rise was not predictive of adverse events .


Nesiritide did not worsen renal function compared with placebo .


Pharmacokinetic ( PK ) and pharmacodynamic ( PD ) data are limited for artesunate ( AS ) and amodiaquine ( AQ ) in uncomplicated Plasmodium falciparum .


From 2007-8 , 54 P. falciparum-infected , Kenyan adults were assigned randomly fixed dose ( FD ) ASAQ ( n = 26 ) or non-fixed ( NF ) ASAQ ( n = 28 ) .


Total doses were 600 mg AS ( both arms ) + 1,620 mg ( FD ) or 1,836 mg ( NF ) AQ .


Follow-up extended over 28 days .


PK data were collected for AS , dihydroartemisinin ( DHA ) , AS + DHA combined as DHA equivalents ( DHAeq ) , AQ , desethylamodiaquine ( DAQ ) , and their relationships assessed against the PD collected data consisting of parasitological efficacy , adverse events ( AEs ) , and the Bazett 's corrected QTinterval ( QTcB ) .


Mean AUC 0-72 of dihydroartemisinin equivalents ( DHAeq ) when administered as a fixed dose ( FD ) compared to NF dose were similar : 24.2 4.6 vs 26.46.9 mol * h/L ( p = 0.68 ) Parasite clearance rates were also similar after 24 hrs : 17/25 ( 68 % ) vs 18/28 ( 64.3 % ) ( p = 0.86 ) , as well as at 48 hrs : 25/8 ( 100 % ) vs 26 ( 92.9 % ) / 28 ( p = 0.49 ) .


Mean FD vs NF DAQ AUC0-28 were 27.63.19 vs 32.75.53 mg * h/L ( p = 0.0005 ) .


Two PCR-proven new infections occurred on Day ( D ) 28 for estimated , in vivo , DAQ minimum inhibitory concentrations of 15.2 and 27.5 ng/mL .


Combining the FD and NF arms , the mean QTcB at D2 +4 hrs increased significantly ( p = 0.0059 ) vs baseline : 420 vs410 ms ( = 9.02 ( 95 % confidence interval 2.72-15 .31 ms ) , explained by falling heart rates , increasing DAQ concentrations and female sex in a general linear mixed effects model .


Ten of 108 ( 9.26 % ) AEs ( 5/arm ) reported by 37/54 ( 68.5 % ) patients were possibly or probably drug related .


Severe , asymptomatic neutropaenia developed in 2/47 ( 4.25 % ) patients on D28 : 574/L ( vsD0 : 5,075 / L ) , and 777/L ( vsD0 : 3,778 / L ) .


Tolerability of both formulations was good .


For QTcB , a parameter for ECG modifications , increases were modest and due to rising DAQ concentrations and falling heart rates as malaria resolved .


Rapid parasite clearance rates and no resistant infections suggest effective pharmacokinetics of both formulations .


To compare the operative outcomes of patients undergoing either single-port or multiport laparoscopic hysterectomy ( LH ) .


Two hundred fifty-six women scheduled for LH for symptomatic myoma and/or adenomyosis from 8 tertiary teaching hospitals were randomized to single-port or multiport groups .


Primary outcome was conversion and/or complication proportion of the planned procedure to determine whether the success proportion of the single-port approach was not inferior to that of the multiport approach .


Secondary outcomes were postoperative pain and operative scar .


Demographic parameters including age , body mass index , parity , and history of vaginal and cesarean delivery were comparable between the 2 groups .


The primary outcome of a combined conversion and/or complication rate was similar between the single-port and multiport groups at 8 % and 10.3 % , respectively .


Conversions were similar between the groups with 4 % of single-port cases and .8 % of multiport cases .


Transfusions were the most frequent complication required in 4.0 % of single-port cases and 7.9 % of multiport cases , with no difference between the groups .


Concerning secondary outcomes , postoperative pain score and patient and observer scar assessment were not different between the 2 groups .


Although not a specific outcome measure , there was no difference between the groups in blood loss , operative time , and postoperative hospital stay .


Single-port LH is not inferior to multiport LH in terms of conversion and/or complications rates , including transfusion .


However , the single-port approach did not have any advantage over multiport LH with regard to pain or cosmetic outcomes .


These findings were demonstrated by multi-institutional surgeons in Korea .


In Europe , gastric cancer remains diagnosed at advanced stage ( serosal and/or lymph node involvement ) .


Despite curative management combining perioperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection , 5-year survival rates of T3 and/or N + patients remain under 30 % .


More than 50 % of recurrences are peritoneal and/or locoregional .


The use of adjuvant hyperthermic intraperitoneal chemotherapy that eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences , was extensively evaluated by several randomized trials conducted in Asia .


Two meta-analysis reported that adjuvant hyperthermic intraperitoneal chemotherapy significantly reduces the peritoneal recurrences and significantly improves the overall survival .


As it was previously done for the evaluation of the extension of lymph node dissection , it seems very important to validate on European or caucasian patients the results observed in trials performed in Asia .


GASTRICHIP is a prospective , open , randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of hyperthermic intraperitoneal chemotherapy with oxaliplatin on patients with gastric cancer involving the serosa and/or lymph node involvement and/or with positive cytology at peritoneal washing , treated with perioperative systemic chemotherapy and D1-D2 curative gastrectomy .


Peroperatively , at the end of curative surgery , patients will be randomized after preoperatively written consent has been given for participation .


Primary endpoint will be overall survival from the date of surgery to the date of death or to the end of follow-up ( 5 years ) .


Secondary endpoint will be 3 - and 5-year recurrence-free survival , site of recurrence , morbidity , and quality of life .


An ancillary study will compare the incidence of positive peritoneal cytology pre - and post-gastrectomy in two arms of the study , and assess its impact on 5-year survival .


The number of patients to be randomized was calculated to be 306 .


EudraCT number : 2012-005748-12 , ClinicalTrials.gov identifier : NCT01882933 .


Transoral esophagogastric fundoplication ( TF ) can decrease or eliminate features of gastroesophageal reflux disease ( GERD ) in some patients whose symptoms persist despite proton pump inhibitor ( PPI ) therapy .


We performed a prospective , sham-controlled trial to determine if TF reduced troublesome regurgitation to a greater extent than PPIs in patients with GERD .


We screened 696 patients with troublesome regurgitation despite daily PPI use with 3 validated GERD-specific symptom scales , on and off PPIs .


Those with at least troublesome regurgitation ( based on the Montreal definition ) on PPIs underwent barium swallow , esophagogastroduodenoscopy , 48-hour esophageal pH monitoring ( off PPIs ) , and high-resolution esophageal manometry analyses .


Patients with GERD and hiatal hernias 2 cm were randomly assigned to groups that underwent TF and then received 6 months of placebo ( n = 87 ) , or sham surgery and 6 months of once - or twice-daily omeprazole ( controls , n = 42 ) .


Patients were blinded to therapy during follow-up period and reassessed at 2 , 12 , and 26 weeks .


At 6 months , patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy .


By intention-to-treat analysis , TF eliminated troublesome regurgitation in a larger proportion of patients ( 67 % ) than PPIs ( 45 % ) ( P = .023 ) .


A larger proportion of controls had no response at 3 months ( 36 % ) than subjects that received TF ( 11 % ; P = .004 ) .


Control of esophageal pH improved after TF ( mean 9.3 % before and 6.3 % after ; P < .001 ) , but not after sham surgery ( mean 8.6 % before and 8.9 % after ) .


Subjects from both groups who completed the protocol had similar reductions in GERD symptom scores .


Severe complications were rare ( 3 subjects receiving TF and 1 receiving the sham surgery ) .


TF was an effective treatment for patients with GERD symptoms , particularly in those with persistent regurgitation despite PPI therapy , based on evaluation 6 months after the procedure .


Clinicaltrials.gov no : NCT01136980 .


To compare 2 short-term , community caregiver training interventions for preschool-aged children with Autism Spectrum Disorder who had low resources .


Low resource was defined by the US Department of Housing and Urban Development low-income index or 1 `` indicator , '' ( e.g. , Medicaid eligibility ) .


Child outcomes focused on joint engagement , joint attention , and play .


Participants included 112 families of a child who had Autism Spectrum Disorder who met criteria for being low-resourced and who were randomly assigned to 1 of 2 3-month interventions , group caregiver education or individualized caregiver-mediated intervention ( CMM ) .


Children were assessed for social communication skills pre - and post-treatment , and followed up at 3 months .


All children improved in joint engagement and initiating joint attention , with significantly greater improvement by the CMM group .


Outcomes on play skills were mixed , with improvement of symbolic play for the CMM group and no change in functional play skills .


Joint engagement maintained over time for the CMM group , and initiating joint attention maintained for both groups over time .


This study is among the first randomized trials comparing 2 active interventions with a large sample of low-resourced families .


Results suggest improvements in core autism deficits of joint engagement , joint attention , and symbolic play with relatively brief , caregiver-mediated interventions , but additional support is necessary to maintain and generalize these gains over time .


Appetitive and aversive processes share a number of features such as their relevance for action and learning .


On a neural level , reward and its predictors are associated with increased firing of dopaminergic neurons , whereas punishment processing has been linked to the serotonergic system and to decreases in dopamine transmission .


Recent data indicate , however , that the dopaminergic system also responds to aversive stimuli and associated actions .


In this pharmacological functional magnetic resonance imaging study , we investigated the contribution of the dopaminergic system to reward and punishment processing in humans .


Two groups of participants received either placebo or the dopamine precursor levodopa and were scanned during alternating reward and punishment anticipation blocks .


Levodopa administration increased striatal activations for cues presented in punishment blocks .


In an interaction with individual personality scores , levodopa also enhanced striatal activation for punishment-predictive compared with neutral cues in participants scoring higher on the novelty-seeking dimension .


These data support recent indications that dopamine contributes to punishment processing and suggest that the novelty-seeking trait is a measure of susceptibility to drug effects on motivation .


These findings are also consistent with the possibility of an inverted U-shaped response function of dopamine in the striatum , suggesting an optimal level of dopamine release for motivational processing .


Internet-based interventions ( IBI ) are effective in treating depression .


However , uptake rates in routine care are still limited .


Hence , this study aimed to ( 1 ) assess the acceptance of IBIs in primary care patients with depressive symptoms and to ( 2 ) examine the effects of a brief acceptance facilitating intervention in the form of an informational video on patients ' acceptance of IBIs .


Primary care patients ( N = 128 ) with Minor or Major Depression were randomly assigned to an intervention ( IG ) or control group ( CG ) .


Patients in the IG were shown a brief informational video about IBIs before receiving a questionnaire that assessed their acceptance of IBIs and other secondary outcomes .


Patients of the CG filled out the questionnaire immediately .


Baseline acceptance of IBIs in the CG was high for 6.3 % , moderate for 53.1 % and low for 40.6 % of patients .


Acceptance of IBIs was significantly higher in the IG when compared to the CG ( d = .71 , 95 % - CI : .09 -2.91 ) .


Except for social influence and the general attitude towards psychological treatment , all secondary outcomes were also significantly improved ( e.g. effort - ( d = .40 ) and performance-expectancy : d = .65 ; knowledge about Internet interventions d = .35 ) .


Depression of the participants was only assessed using a self-report measure ( PHQ-9 ) .


Primary care patients ' acceptance of IBIs for depressive symptoms was low but could be increased significantly using a brief acceptance facilitating intervention on the basis of an informational video .


Future studies should further examine the potential of acceptance facilitating interventions for patients and health care providers to exploit the public health impact of IBIs .


Dissemination of psychotherapeutic modules to local counselors seems a key requirement for coping with mental health disasters in conflict regions .


We tested a train-the-trainer ( TTT ) dissemination model for the treatment of posttraumatic stress disorder ( PTSD ) .


We randomly assigned widowed or orphaned survivors of the 1994 Rwandan genocide with a PTSD diagnosis to narrative exposure therapy ( NET ) treatment ( NET-1 , n = 38 ) or to a 6-month waiting list ( WL ) condition to be followed by treatment ( WL/NET -2 , n = 38 ) .


Expert therapists trained a first dissemination generation of local Rwandan psychologists in NET complemented by 2 sessions of interpersonal psychotherapy modules .


Under the supervision of the experts , these Rwandan psychologists ( a ) provided NET to the NET-1 participants and ( b ) subsequently trained and supervised a second generation of local psychologists .


This second dissemination generation provided treatment to the WL/NET -2 group .


The primary outcome measure was the Clinician-Administered PTSD Scale total score before therapy and at 3 - and 12-month follow-ups .


At the 3-month follow-up , the NET-1 participants suffered significantly and substantially less from PTSD symptoms than the participants in the WL group .


The treatment gains of NET-1 were maintained and increased at follow-up , with a within-group effect size of Cohen 's d = 1.47 at the 12-month follow-up .


After treatment by the second dissemination generation of therapists , the WL/NET -2 participants improved to an extent similar to that of the NET-1 group at follow-ups , with an effect size of Cohen 's d = 1.37 at the 12-month follow-up .


A TTT model of PTSD treatment dissemination can be effective in resource-poor postconflict societies .


This trial evaluated the efficacy of maintenance erlotinib , an epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , after first-line chemotherapy .


Eligible patients had high-risk International Federation of Gynecology and Obstetrics stage I or stage II to IV epithelial ovarian , primary peritoneal , or fallopian tube cancer and were not selected for EGFR expression .


All patients underwent first-line platinum-based chemotherapy ( CT ) and showed no signs of progression at the end of CT. .


Patients were randomly assigned to maintenance erlotinib 150 mg orally daily for 2 years or to observation .


EGFR immunohistochemistry ( IHC ) , fluorescent in situ hybridization ( FISH ) , and mutation analyses were performed in 318 patients .


Between October 2005 and February 2008 , 835 patients were randomly assigned ( median follow-up , 51 months ) .


Twenty-six percent of the patients stopped erlotinib as a result of adverse effects ( of these , 67 % were due to rash ) .


For erlotinib and observation , respectively , the median progression-free survival was 12.7 and 12.4 months ( hazard ratio [ HR ] , 1.05 ; 95 % CI , 0.90 to 1.23 ) , and the median overall survival was 50.8 and 59.1 months ( HR , 0.99 ; 95 % CI , 0.81 to 1.20 months ) , respectively .


No subgroup could be identified with improved effect of erlotinib , based on IHC or FISH for EGFR , or mutations in genes related to the EGFR pathway , or on rash during erlotinib therapy .


However , patients with a positive FISH EGFR score had a worse overall survival ( 46.1 months ) than those with a negative score ( 67.0 months ; HR , 1.56 ; 95 % CI , 1.01 to 2.40 ; P = .044 ) .


Global health/quality-of-life scores showed a significant difference during the first year ( P = .0102 ) in favor of the observation arm .


Maintenance erlotinib after first-line treatment in ovarian cancer did not improve progression-free or overall survival .


To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation ( APBI ) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID ( Randomized Trial of Accelerated Partial Breast Irradiation ) trial .


Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3years .


Adverse cosmesis was defined as a score of fair or poor .


Cosmetic deterioration was defined as any adverse change in score from baseline to 3years .


The analysis is based on data from the previously reported interim analysis .


Logistic regression models were used to assess the association ofrisk factors for these outcomes among all patients and those treated with APBI only .


Clinicopathologic characteristics were similar between subjects randomized to APBI ( n = 569 ) or whole-breast irradiation ( n = 539 ) .


For all subjects , factors associated with adverse cosmesis at 3years were older age , central/inner tumor location , breast infection , smoking , seroma volume , breast volume , and use of APBI ; factors associated with cosmetic deterioration were smoking , seroma volume , and use of APBI ( P < .05 ) .


For APBI subjects , tumor location , smoking , age , and seroma volume were associated with adverse cosmesis ( P < .05 ) , and smoking was associated with cosmetic deterioration ( P = .02 ) .


An independent association between the V95/whole-breast volume ratio and adverse cosmesis ( P = .28 ) or cosmetic deterioration ( P = .07 ) was not detected .


On further exploration a V95/whole-breast volume ratio < 0.15 was associated with a lower risk of cosmetic deterioration ( p = .04 ) , but this accounted for only 11 % of patients .


In the RAPID trial , a number of patient tumor and treatment-related factors , including the use of APBI , were associated with adverse cosmesis and cosmetic deterioration .


For patients treated with APBI alone , the high-dose treatment volume was not independently associated with an adverse cosmetic outcome , and a useful clinical threshold could not be identified .


Oral mucositis ( OM ) is a painful complication of radiation therapy ( RT ) for head and neck cancer ( H&NC ) .


OM can compromise nutrition , require opioid analgesics and hospitalization for pain control , and lead to treatment interruptions .


Based on the role of inflammatory pathways in OM pathogenesis , we investigated effect of cyclooxygenase-2 ( COX-2 ) inhibition on severity and morbidity of OM .


In this double-blind placebo-controlled trial , 40 H&NC patients were randomized to daily use of 200 mg celecoxib or placebo , for the duration of RT. .


Clinical OM , normalcy of diet , pain scores , and analgesic use were assessed 2-3 times/week by blinded investigators during the 6-7 week RT period , using validated scales .


Twenty subjects were randomized to each arm , which were similar with respect to tumor location , radiation dose , and concomitant chemotherapy .


In both arms , mucositis and pain scores increased over course of RT. .


Intention-to-treat analyses demonstrated no significant difference in mean Oral Mucositis Assessment Scale ( OMAS ) scores at 5000 cGy ( primary endpoint ) .


There was also no difference between the two arms in mean OMAS scores over the period of RT , mean worst pain scores , mean normalcy of diet scores , or mean daily opioid medication use in IV morphine equivalents .


There were no adverse events attributed to celecoxib use .


Daily use of a selective COX-2 inhibitor , during period of RT for H&NC , did not reduce the severity of clinical OM , pain , dietary compromise or use of opioid analgesics .


These findings also have implications for celecoxib use in H&NC treatment regimens ( NCT00698204 ) .


A proportion of HIV-positive people have condomless sex .


Antiretroviral treatment ( ART ) reduces infectiousness , but a substantial proportion of HIV-diagnosed people are not yet on ART .


We describe baseline self-reported risk behaviours in ART-nave Strategic Timing of AntiRetroviral Treatment ( START ) trial participants .


All START participants completed a risk behaviour questionnaire .


Data were collected on sociodemographics , lifestyle factors , health and wellbeing status and clinical status .


Recent sexual behaviour and HIV transmission beliefs in the context of ART were also assessed .


The primary interest was in condomless sex with serodifferent partners ( CLS-D ) in the past two months .


A total of 4601 of 4685 HIV-positive participants ( 98 % ) completed the questionnaire [ 2559 men who have sex with men ( MSM ) , 803 heterosexual men and 1239 women ] .


Region of recruitment was Europe/Israel , 33 % ; South America/Mexico , 25 % ; Africa , 22 % ; other , 21 % .


Median age was 36 years [ interquartile range ( IQR ) 29 , 44 years ] .


Forty-five per cent reported white ethnicity and 31 % black ethnicity .


Two per cent had HIV viral load < 50 HIV-1 RNA copies/mL .


Seventeen per cent ( 767 of 4601 ) reported CLS-D ; 20 % of MSM compared with 10 % of heterosexual men and 14 % of women .


MSM were also more likely to report multiple CLS-D partners .


Possible risk limitation measures ( reported by more than half of those who had CLS-D ) were seropositioning ( receptive anal CLS-D only ) or withdrawal ( insertive anal CLS-D always without ejaculation ) .


CLS-D was more commonly reported by participants from South America/Mexico and North America compared with Europe ; among heterosexual men and women CLS-D was also more commonly reported among participants from Africa compared with Europe .


Knowledge of ART impact on transmission risk was low .


A substantial minority recruited to the START study reported CLS-D at baseline .


CLS-D reporting was higher in MSM than heterosexuals and varied significantly according to region of recruitment .


A substantial proportion of MSM reporting CLS-D appear to take transmission risk limitation measures .


It has been shown that the myocutaneous latissimus dorsi flap volume and consistency remain mainly the same regardless the nerve is cut or not in breast reconstruction .


It is controversial how big an impact the flap innervation has on the muscle activity of the flap .


The aim of the study was to prospectively evaluate the influence of latissimus dorsi flap innervation on the functional and aesthetic outcome of delayed breast reconstruction .


Between 2007 and 2008 , 28 breast reconstructions were performed and randomly divided into denervation group ( surgical denervation by excision of 1 cm of proximal thoracodorsal nerve , n = 14 ) and innervation group ( thoracodorsal nerve saved intact , n = 14 ) .


Patients were clinically evaluated and a questionnaire considering functional and aesthetic outcome was filled 1-year after operation .


Muscular twitching , pain , tightness , shape and symmetry of the breasts were evaluated .


In addition , the mobility of the shoulder joint on the operated side was evaluated and the patients self-estimated the activities of daily living .


There was no significant difference in latissimus dorsi flap twitching , pain and tightness of the breast and symmetry and shape of the breasts between denervated and innervated groups .


The shoulder joint mobility was not found to be changed significantly in either of the groups and there were no limitations in activities of daily living .


Thoracodorsal nerve division or preservation does not significantly affect muscle contraction activity of the latissimus dorsi flap and distortion of the breast when latissimus dorsi muscle humeral insertion is also detached .


Therefore , both cutting and saving the nerve are justified in latissimus dorsi flap breast reconstruction depending on whether the humeral insertion of the muscle is preserved intact or divided and the flap islanded .


The study shows that there is no tangible benefit in dividing the nerve when the flap is islanded .


Clinical trial has been registered in public trials registry .


Trial registry name is ` The significance of latissimus dorsi flap innervation in delayed breast reconstruction ' .


Registration number is NCT01239524 and URL is https://register.clinicaltrials.gov .


We examined the effect of caffeine ingestion on muscle torque production and muscle activity at different contraction speeds in trained men .


10 men ( mean age SD = 22 1.1 years ) volunteered to participate .


A double-blind , randomized cross-over design was used .


Sixty minutes postingestion of caffeine ( 6 mg kg ( -1 ) ) or placebo , participants completed 6 repetitions of isokientic knee extension at 3 angular velocities ( 30s ( -1 ) , 150s ( -1 ) , 300s ( -1 ) ) from which peak torque was determined .


Electromyographic activity of the vastus medialis was also collected .


Repeated measures analysis of variance indicated that muscle torque production was significantly higher ( P = 0.02 ) with caffeine compared with placebo .


A significant ( P = 0.02 ) substance by velocity interaction for muscle activity indicated significantly higher vastus medialis muscle activity in the presence of caffeine versus placebo , and this difference was amplified as angular velocity increased .


Acute caffeine ingestion improves muscle performance and increases muscle activity during short-duration maximal dynamic contractions .


Performance improvements after caffeine ( CAF ) ingestion are well documented when using a 1-d protocol .


In numerous competitions such as the Tour de France , Tour de Ski , world championships , and National College Athletic Association championships , athletes compete for several days in a row .


To date , no studies have investigated the effects of CAF when competing for consecutive days in a row .


This study aimed to investigate the effects of placebo ( PLA ) and two different CAF doses ( 3 and 4.5 mgkg body mass ) on performance in a 10-min all-out , cross-country , double poling ergometer test ( C-PT ) 2 d in a row .


Eight highly trained male cross-country skiers ( VO2max-run , 78.5 1.6 mLkgmin ) participated in the study , which was a randomized , double-blind , PLA-controlled , crossover design .


Performance was assessed as distance covered during a 10-min all-out C-PT .


Oral ingestion of CAF or PLA was consumed 75 min before the all-out C-PT .


Poling distance was improved after CAF ingestions compared with that after PLA on both days .


The improvements on day 1 were 4.0 % ( 90 % confidence limits , 3.3 ) and 4.0 % 2.9 % for both CAF doses , respectively ( P < 0.05 ) , whereas improvements on day 2 were 5.0 % 3.6 % and 5.1 % 2.8 % for CAF3 and CAF4 .5 , respectively , compared with those for PLA .


Improved performance was associated with increased HR , adrenaline concentration , blood lactate concentration , and VO2 consumption after CAF ingestion .


Furthermore , performance was elevated despite higher creatine kinase concentration and muscular pain at arrival on day 2 for both CAF doses .


Both CAF doses improved performance in the 10-min all-out C-PT compared with PLA over two consecutive days .


Therefore , CAF seems useful for athletes competing over consecutive days despite higher muscle damage occurring after enhanced performance on the first day .


When compared with more traditional instructional methods , Game-based e-learning ( GbEl ) promises a higher motivation of learners by presenting contents in an interactive , rule-based and competitive way .


Most recent systematic reviews and meta-analysis of studies on Game-based learning and GbEl in the medical professions have shown limited effects of these instructional methods .


To compare the effectiveness on the learning outcome of a Game-based e-learning ( GbEl ) instruction with a conventional script-based instruction in the teaching of phase contrast microscopy urinalysis under routine training conditions of undergraduate medical students .


A randomized controlled trial was conducted with 145 medical students in their third year of training in the Department of Urology at the University Medical Center Freiburg , Germany .


82 subjects where allocated for training with an educational adventure-game ( GbEl group ) and 69 subjects for conventional training with a written script-based approach ( script group ) .


Learning outcome was measured with a 34 item single choice test .


Students ' attitudes were collected by a questionnaire regarding fun with the training , motivation to continue the training and self-assessment of acquired knowledge .


The students in the GbEl group achieved significantly better results in the cognitive knowledge test than the students in the script group : the mean score was 28.6 for the GbEl group and 26.0 for the script group of a total of 34.0 points with a Cohen 's d effect size of 0.71 ( ITT analysis ) .


Attitudes towards the recent learning experience were significantly more positive with GbEl .


Students reported to have more fun while learning with the game when compared to the script-based approach .


Game-based e-learning is more effective than a script-based approach for the training of urinalysis in regard to cognitive learning outcome and has a high positive motivational impact on learning .


Game-based e-learning can be used as an effective teaching method for self-instruction .


Depression is a high prevalence disorder , displaying high rates of lifetime incidence , early age onset , high chronicity , and role impairment .


In Ireland 12-month prevalence of depression has been reported to be 10.3 % .


A large percentage of affected individuals have no medical diagnosis nor seek treatment .


Cognitive Behavior Therapy ( CBT ) has established itself as an option for the treatment of depression .


Many Irish adults with depression find it difficult to access evidence-based CBT , this is due to several factors , like stigma and costs .


However , systematic factors including the shortage of trained professionals and the relative underdevelopment of services also make access difficult.Stepped-care can increase access to evidence-based CBT .


One option is tailored internet-delivered treatment programs .


Preliminary research from Ireland needs now to include large-scale studies on effectiveness .


Thus the current study seeks to examine the potential of an internet-delivered low-intensity treatment for symptoms of depression in an Irish adult community sample .


The study is a randomized controlled trial of an online CBT ( iCBT ) program for the treatment of adults with depressive symptoms .


The trial will include an active treatment group and a waiting-list control group .


The active condition will consist of 8 weekly modules of iCBT , with post-session feedback support .


Participants in the waiting list will receive access to the treatment at week 8 .


Participants will complete the Beck Depression Inventory ( BDI-II ) and eligibility criteria will also apply .


Primary outcomes are depressive symptoms .


Secondary outcomes include quality of life indicators , significant events and satisfaction with online treatment .


Data will be collected at baseline and at post-treatment , week 8 , and at follow-up week 20 ( 3-months ) and week 32 ( 6-months ) .


Analysis will be conducted on the intention-to-treat basis .


The study seeks to evaluate the effectiveness of an online delivered treatment for depression in a community sample of Irish adults with symptoms of depression .


The study will be a first contribution and depending on the sample recruited the results may be generalizable to people with similar difficulties in Ireland and may therefore give insight into the potential of low-intensity interventions for Irish people with depressive symptoms .


Current Controlled Trials ISRCTN03704676 .


DOI : 10.1186 / ISRCTN03704676 .


Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children .


We investigated the associations between breakfast consumption ( frequency and content ) and risk markers for type 2 diabetes ( particularly insulin resistance and glycaemia ) and cardiovascular disease in children .


We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years .


Participants provided information on breakfast frequency , had measurements of body composition , and gave fasting blood samples for measurements of blood lipids , insulin , glucose , and glycated haemoglobin ( HbA1c ) .


A subgroup of 2,004 children also completed a 24-hour dietary recall .


Among 4,116 children studied , 3,056 ( 74 % ) ate breakfast daily , 450 ( 11 % ) most days , 372 ( 9 % ) some days , and 238 ( 6 % ) not usually .


Graded associations between breakfast frequency and risk markers were observed ; children who reported not usually having breakfast had higher fasting insulin ( percent difference 26.4 % , 95 % CI 16.6 % -37.0 % ) , insulin resistance ( percent difference 26.7 % , 95 % CI 17.0 % -37.2 % ) , HbA1c ( percent difference 1.2 % , 95 % CI 0.4 % -2.0 % ) , glucose ( percent difference 1.0 % , 95 % CI 0.0 % -2.0 % ) , and urate ( percent difference 6 % , 95 % CI 3 % -10 % ) than those who reported having breakfast daily ; these differences were little affected by adjustment for adiposity , socioeconomic status , and physical activity levels .


When the higher levels of triglyceride , systolic blood pressure , and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity , the differences were no longer significant .


Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types ( p for heterogeneity < 0.01 ) .


Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers .


Children who ate breakfast daily , particularly a high fibre cereal breakfast , had a more favourable type 2 diabetes risk profile .


Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk .


Please see later in the article for the Editors ' Summary .


The goal of this study was to determine if a robotic dry laboratory curriculum for gynecology and urology residents improved their basic robotic skills .


After the institution-specific institutional review board approval or exemption , 165 residents from 8 gynecology and/or urology programs were enrolled .


Residents underwent standardized robotic orientation followed by dry laboratory testing on 4 unique robotic tasks .


Residents were block randomized by program to unstructured or structured training programs .


Regardless of group , residents were expected to practice for 15 minutes twice monthly over 7 months .


Errors , time to completion , and objective structured assessment of technical skills global rating scores were recorded for each task before and after the training period .


Statistics were calculated using the Student t tests , Pearson correlation , and analysis of variance with STATA systems ( version 11.2 ) .


A total of 99 residents completed both the pretraining and posttraining testing .


A mean of 4 ( range , 0-15 ) 15-minute training sessions per resident was self-reported .


The structured group had faster posttraining times on the transection task , although the unstructured group had higher posttraining scores on the knot-tying task .


Overall , the residents ' robotic skills improved after participating in a dry laboratory curriculum ; however , robotic availability , duty hour restrictions , and clinical responsibilities limit the curriculum implementation .


More than 50 % of children in Nepal are malnourished .


Economic growth and poverty reduction are not always sufficient to improve the health and nutritional status of children .


Heifer Nepal uses livestock training as a tool for community development and poverty alleviation but does not directly address child health and nutrition .


To systematically assess the effects of Heifer activities on child health and nutrition .


The study was a 2-year , longitudinal , randomized , controlled trial in six communities in Nepal ( both Terai and hills ) , pair-matched for specific characteristics , randomly assigned to receive Heifer community development activities at baseline ( intervention ) or 1 year ( control ) .


At 6-month intervals over a period of 2 years , child anthropometric and comprehensive household surveys were performed .


Four hundred fifteen households were enrolled containing 607 children 6 months to 5 years of age .


The intervention and control communities were equivalent for baseline socioeconomic status , household size , ownership of land and animals , and child nutrition and health .


At 12 months ( prior to animal donations ) , the Terai intervention group had improved child weight ( p = .04 ) , improved child height ( p = .05 ) , and reduced sick days ( p = .03 ) , as well as increased household income ( p = .004 ) , increased ownership of animals ( p = .04 ) and land ( p = .04 ) , and improved sanitation practices ( p < .01 ) .


In all districts , longer participation in Heifer activities corresponded to more improvement in child height-for-age z-scores .


Heifer interventions resulted in improved socioeconomic status and household income per family member .


Children under 60 months of age in the intervention group had greater incremental improvement in height-for-age and weight-for-age z-scores than children in the control group , and longer participation in Heifer activities was associated with better growth .


Poverty alleviation programs , such as Heifer , may indirectly benefit child growth .


To evaluate whether anticholinergic medication contributes to early recovery of continence and improvement of other voiding symptoms after radical prostatectomy ( RP ) .


A total of 78 patients with clinically localized prostate cancer who had incontinence at 1 week after RP were enrolled prospectively .


The patients were allocated to one of the 2 groups : group 1 ( - adrenergic agonist [ midodrine ] plus an anticholinergic [ solifenacin ] ) or group 2 ( - adrenergic agonist only ) .


A urodynamic study and the International Continence Society male Short Form questionnaire were completed preoperatively and 4 months after RP .


One-hour pad test and 3-day frequency volume chart at 1 and 4 months after medication were also analyzed .


The rate of continence , defined as being pad free , did not differ between the groups at 4 months ( both 71.8 % ; P > .05 ) .


However , the decreased value of mean weight of daily pads worn by groups 1 and 2 were 51.5 vs 11.7 g , respectively ( P = .005 ) .


The incontinence ( P = .008 ) and quality of life ( P = .044 ) subscale scores significantly worsened in group 2 , whereas they remained unchanged in group 1 .