( 3 ) No obvious adverse reactions such as liver injury , renal injury , or skin allergy were observed .


Adjuvant treatment of GEGC could improve carcinoma of the large intestine patients with myelosuppression to some extent .


No relevant adverse reactions were found .


The health system responsiveness , defined as non-medical aspect of treatment relating to the protection of the patients ' legitimate rights , is the intrinsic goal of the WHO strategy for 21st century .


To describe the patients ' opinions on treatment they received in hospital , namely : admission to hospital , the role of patient in hospital treatment , course of treatment , medical workforce attitude , hospital environment , contact with family and friends , and the efficacy of hospital treatment in respect to responsiveness to patient 's needs and expectations ( dignity , autonomy , confidentiality , communication , prompt attention , social support , basic amenities and choice of provider ) .


The data were collected in 2012 from 998 former patients of the randomly selected 73 hospital in Poland .


Dignity : Over 80 % of patients experienced kindness , empathy , care and gentleness , and over 90 % of them had the sense of security in hospital , met with friendliness during the admission to hospital and never encountered inappropriate comments from medical staff .


Autonomy : About 80 % of patients accepted the active role of patients in hospital , they perceived they had influence on procedures related to hospitalization and course of treatment , and they felt medical staff responded to their requests and concerns .


Over 90 % of them had opportunity to communicate their concerns to medical staff and to discuss the course of treatment .


On the other hand , the explanation of the reason for the refusal to meet their requests was given to only 23 % of the patients interested .


Confidentiality : 70-80 % of patients declared the respect for privacy and confidentiality during collecting the health information and during medical examinations , and were not examined in presence of other people .


Nevertheless , only 23 % of patients examined so were asked of their consent .


Communication : About 90 % of patients declared they trusted their physician , received from him explanation regarding the course of treatment and information about further treatment after discharge from hospital , but physicians devoted the time and attention to only 70 % of them .


Prompt attention : Over 90 % of patients perceived simplicity of the formalities of admission to hospital , and short waiting for treatment and additional tests in hospital ( but only 50 % received explanation of reason if they waited long ) .


Nevertheless , 10 % of them % of them perceived they waited for admission to hospital too long , and over 20 % for admission to a ward as long .


Social support : The unlimited direct and phone contact with family and friends was declared by 96 % of patients .


Basic amenities : The high percentage of patients assessed positively the marking in hospital ( 97 % ) and cleanliness of linen ( 89 % ) , followed by the general indoor appearance room in which patient stayed , lack of noise ( 70-80 % ) , hospital meals , furniture ( 60-70 % ) , availability of personal hygienic articles ( 50-60 % ) , cleanliness of hospital room , toilet , showers and bathtubs , and availability of soap ( 40-50 % ) .


Choice of provider : Only 41 % of patients declared that they had influence on choice of the hospital .


Responsiveness of Polish hospital patient needs is similar to that of the OECD countries of the lowest health system responsiveness .


Compared to the Central European countries , the responsiveness in Polish hospitals is lower than that of Czech Republic and only slightly higher of those of Slovenia , Slovakia and Hungary .


Juvenile idiopathic arthritis ( JIA ) is the most common rheumatic disease in children .


Children with JIA are at risk of inflammation of the uvea in the eye ( uveitis ) .


Overall , 20 % to 25 % of paediatric uveitis is associated with JIA .


Major risk factors for development of uveitis in JIA are oligoarticular pattern of arthritis , an age at onset of arthritis of less than seven years of age , and antinuclear antibody positivity .


In the initial stages of mild to moderate inflammation the uveitis is asymptomatic .


This has led to current practice of screening all children with JIA for uveitis .


Approximately 12 % to 38 % of patients with JIA develop uveitis in seven years following onset of arthritis .


In 30 % to 50 % of children with JIA-associated uveitis structural complications are present at diagnosis .


Furthermore about 50 % to 75 % of those with severe uveitis will eventually develop visual impairment secondary to ocular complications such as cataract and glaucoma .


Defining the severity of inflammation and structural complications in uveitis patients is now possible following Standardised Uveitis Nomenclature ( SUN ) guidelines , and modified to incorporate the consensus of end point and outcome criteria into the design of randomised trials .


Despite current screening and therapeutic options ( pre-biologics ) 10 % to 15 % of children with JIA-associated uveitis may develop bilateral visual impairment and certified legally blind .


To date , there remains no controlled trial evidence of benefits of biologic therapy .


This study will randomise 154 patients aged 2 to 18 years with active JIA-associated uveitis ( despite methotrexate ( MTX ) treatment for at least 12 weeks ) .


All participants will be treated for 18 months , with follow up of 3 years from randomisation ( continuing on MTX throughout ) .


All participants will receive a stable dose of MTX and in addition either adalimumab ( 20 mg/0 .8 ml for patients < 30 kg or 40 mg/0 .8 ml for patients weighing 30 kg or more , subcutaneous ( s/c ) injection every 2 weeks based on body weight ) , or placebo ( 0.8 ml as appropriate according to body weight ) s/c injection every 2 weeks .


This is the first randomised controlled trial that will assess the clinical effectiveness , safety and cost effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis .


ISRCTN10065623 .


To estimate the associations between autism spectrum disorder ( ASD ) diagnoses and service use , caregiver time , and cost outcomes .


We used national data from the Medical Expenditure Panel Survey linked to the National Health Interview Survey and a study-specific survey to estimate the annual utilization and costs for health care , school , ASD-related therapy , family-coordinated services , as well as caregiver time in children aged 3 to 17 years , with and without parent-reported ASD .


Regression analyses estimated the association between ASD diagnosis and cost , controlling for child gender , age , race/ethnicity , insurance status , household income , country region and urban/rural classification , and non-ASD-related illnesses .


Children with parent-reported ASD had higher levels of health care office visits and prescription drug use compared with children without ASD ( P < .05 ) .


A greater proportion of children in the ASD group used special educational services ( 76 % vs. 7 % in the control group , P < .05 ) .


After adjusting for child demographic characteristics and non-ASD-associated illnesses , ASD was associated with $ 3020 ( 95 % confidence interval [ CI ] : $ 1017 - $ 4259 ) higher health care costs and $ 14,061 ( 95 % CI : $ 4390 - $ 24,302 ) higher aggregate non-health care costs , including $ 8610 ( 95 % CI : $ 6595 - $ 10,421 ) higher school costs .


In adjusted analyses , parents who reported that their child had ASD did not have significantly higher out-of-pocket costs or spend more time on caregiving activities compared with control parents .


The economic burden associated with ASD is substantial and can be measured across multiple sectors of our society .


Previous analyses that focused on health care underestimated this economic burden , particularly for school systems .


To compare the two different nutritional supports , enteral nutrition and parenteral nutrition in the aspects of nutritional conditions , immune status , the incidence of perioperative complications and quality of life impacts in pancreatic cancer .


For the pancreatic cancer patients which pancreaticoduodenectomy were performed from January 2007 to December 2008 in five high-volume medical centres , prospective , randomized controlled study was carried out .


The enrolled patients were randomly divided into enteral nutritional group ( EN group ) and parenteral nutritional group ( PN group ) .


Related indicators , such as nutritional conditions , immune status , incidence of complications , general status and quality of life were assessed .


The 200 patients were enrolled , while 178 cases which 90 patients in EN group and 88 patients in PN group were qualified to evaluate .


The 22 cases were dropped out .


For the mean hospital stay ( ( 23 13 ) days and ( 27 24 ) days respcectively ) , Karnofsky score and the life quality scoring , there are no statistical differences between the two groups .


In post-operation day 7 and day 10 , the prealbumin was ( 69 16 ) mg/L and ( 80 22 ) mg/L in EN group and it was ( 67 19 ) mg/L and ( 70 11 ) mg/L in PN group , which are all significantly decreased than preoperational levels ( ( 186 38 ) mg/L for enteral group and ( 179 37 ) mg/L for parenteral group , t = -2.24 , -2.13 , -2.23 , -2.20 , all P < 0.05 ) , but there was no statistically significant between the 2 groups ( P > 0.05 ) .


Other general indicators such as the albumin , hemoglobin , total bilirubin , blood urea nitrogen , serum creatinine , serum potassium and serum sodium , revealed no statistical differences in the 2 groups ( P > 0.05 ) ; The total lymphocytes , CD ( + ) 3CD ( + ) 4 and CD ( + ) 3CD ( + ) 8 lymphocytes in PN group was ( 0.687 0.065 ) 10 ( 9 ) / L , ( 0.363 0.029 ) 10 ( 9 ) / L , and ( 0.183 0.018 ) 10 ( 9 ) / L respectively in post-operation day 10 , which they are significantly decreased than in preoperational levels of PN group and the respective counterpart of EN group in post-operation day10 ( t = -2.04 -2.83 , P < 0.05 ) .


The 35 patients were suffered from different complications in the 2 groups , but there was no statistical differences among them ( P > 0.05 ) .


Enteral nutritional support could not decrease the incidence of perioperative complications in pancreatic cancer patient , but it can improve the immunonutrition status in comparison with parenteral nutrition .


Clustering of outcomes at centers involved in multicenter trials is a type of center effect .


The Consolidated Standards of Reporting Trials Statement recommends that multicenter randomized controlled trials ( RCTs ) should account for center effects in their analysis , however most do not .


The Early External Cephalic Version ( EECV ) trials published in 2003 and 2011 stratified by center at randomization , but did not account for center in the analyses , and due to the nature of the intervention and number of centers , may have been prone to center effects .


Using data from the EECV trials , we undertook an empirical study to compare various statistical approaches to account for center effect while estimating the impact of external cephalic version timing ( early or delayed ) on the outcomes of cesarean section , preterm birth , and non-cephalic presentation at the time of birth .


The data from the EECV pilot trial and the EECV2 trial were merged into one dataset .


Fisher 's exact method was used to test the overall effect of external cephalic version timing unadjusted for center effects .


Seven statistical models that accounted for center effects were applied to the data .


The models included : i ) the Mantel-Haenszel test , ii ) logistic regression with fixed center effect and fixed treatment effect , iii ) center-size weighted and iv ) un-weighted logistic regression with fixed center effect and fixed treatment-by-center interaction , iv ) logistic regression with random center effect and fixed treatment effect , v ) logistic regression with random center effect and random treatment-by-center interaction , and vi ) generalized estimating equations .


For each of the three outcomes of interest approaches to account for center effect did not alter the overall findings of the trial .


The results were similar for the majority of the methods used to adjust for center , illustrating the robustness of the findings .


Despite literature that suggests center effect can change the estimate of effect in multicenter trials , this empirical study does not show a difference in the outcomes of the EECV trials when accounting for center effect .


The EECV2 trial was registered on 30 July 30 2005 with Current Controlled Trials : ISRCTN 56498577 .


Evidence supports peroneal nerve functional electrical stimulation ( FES ) as an effective alternative to ankle-foot orthoses ( AFO ) for treatment of foot drop poststroke , but few randomized controlled comparisons exist .


To compare changes in gait and quality of life ( QoL ) between FES and an AFO in individuals with foot drop poststroke .


In a multicenter randomized controlled trial ( ClinicalTrials.gov #NCT 01087957 ) with unblinded outcome assessments , 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months .


Primary endpoints : 10-Meter Walk Test ( 10MWT ) , a composite of the Mobility , Activities of Daily Living/Instrumental Activities of Daily Living , and Social Participation subscores on the Stroke Impact Scale ( SIS ) , and device-related serious adverse event rate .


Secondary endpoints : 6-Minute Walk Test , GaitRite Functional Ambulation Profile ( FAP ) , Modified Emory Functional Ambulation Profile ( mEFAP ) , Berg Balance Scale ( BBS ) , Timed Up and Go , individual SIS domains , and Stroke-Specific Quality of Life measures .


Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority .


A total of 399 subjects completed the study .


FES proved noninferior to the AFO for all primary endpoints .


Both the FES and AFO groups improved significantly on the 10MWT .


Within the FES group , significant improvements were found for SIS composite score , total mFEAP score , individual Floor and Obstacle course time scores of the mEFAP , FAP , and BBS , but again , no between-group differences were found .


Use of FES is equivalent to the AFO .


Further studies should examine whether FES enables better performance in tasks involving functional mobility , activities of daily living , and balance .


We evaluated changes in social capital following group-based cognitive processing therapy ( CPT ) for female survivors of sexual violence .


We compared CPT with individual support in a cluster-randomized trial in villages in South Kivu province , Democratic Republic of the Congo .


Local psychosocial assistants delivered the interventions from April through July 2011 .


We evaluated differences between CPT and individual support conditions for structural social capital ( i.e. , time spent with nonkin social network , group membership and participation , and the size of financial and instrumental support networks ) and emotional support seeking .


We analyzed intervention effects with longitudinal random effects models .


We obtained small to medium effect size differences for 2 study outcomes .


Women in the CPT villages increased group membership and participation at 6-month follow-up and emotional support seeking after the intervention compared with women in the individual support villages .


Results support the efficacy of group CPT to increase dimensions of social capital among survivors of sexual violence in a low-income conflict-affected context .


Gut microbiota provides beneficial effects under physiological conditions , but is able to contribute to inflammatory diseases in susceptible individuals .


Thus , we designed this study to test whether additional intake of symbiotic gel affects specific modifications of gut microbiota in patients with end-stage renal disease ( ESRD ) .


Eighteen patients with ESRD diagnosis with renal replacement therapy ( hemodialysis ) were included in this study .


They were randomly assigned to 2 treatment groups : ( 1 ) test group ( nutritional counseling + symbiotic ) and ( 2 ) control group ( nutritional counseling + placebo ) .


Clinical history and the evaluation of Gastrointestinal Symptom Rating Scale were performed .


Gut microbiota composition was analyzed by real-time polymerase chain reaction from fecal samples .


All subjects were followed for 2months .


Bifidobacterial counts were higher in the second samples ( mean : 5.51.72 log10 cells/g ) than in first samples ( 4.20.88 log 10cells/g ) in the patients of the test group ( P = .0344 ) .


Also , lactobacilli counts had a little decrease in the test group ( 2.30.75 to 2.00.88 log 10 cells/g ) and the control group ( 2.20.90 to 1.81.33 log 10 cells/g ) , between the first and the second samples .


Gastrointestinal symptoms scores ( scale 8-40 ) were reduced in the test group ( start 12 [ 10-14 ] and end 9 [ 8-10 ] ) compared with control group ( start 11 [ 8-21 ] and end 11 [ 9-15 ] ) .


Short-term symbiotic treatment in patients with ESRD can lead to the increase of Bifidobacterium counts , maintaining the intestinal microbial balance .


A longitudinal integration approach evaluated all radiographic scores assessed over 10 years , rather than only completer data , from 2 studies of adalimumab ( ADA ) for rheumatoid arthritis ( RA ) .


The DE019 ( methotrexate [ MTX ] - inadequate responders , longstanding RA ) and PREMIER ( MTX-naive , early RA ) studies , respectively , had 1 - or 2-year double-blind periods followed by 9 - or 8-year open-label extensions ( OLEs ) .


Patients received ADA MTX in both OLEs .


Radiographic progression was assessed using change from baseline in modified total Sharp score ( mTSS ) .


A mixed-effects model was used post hoc to evaluate repeated measurements of different data campaigns and to estimate mTSS through up to 10 years of treatment based on original randomization groups ( placebo [ PBO ] + MTX or standard dose ADA + MTX ) .


Data from patients with baseline and 1 postbaseline radiograph were included ( n = 327 for DE019 ; n = 452 for PREMIER ) .


Integrated and 10-year completer mTSS progression curves differed slightly .


In DE019 , for patients originally assigned PBO + MTX , accrued mTSS at year 10 was 6.6 units ( integrated model ) and 6.2 units ( completers ) .


For patients originally assigned ADA + MTX , accrued mTSS was 0.9 units by integrated analysis and 0.7 units in completers .


In PREMIER , for patients originally assigned PBO + MTX , accrued mTSS at year 10 was 11.2 units ( integrated analysis ) and 11.0 units ( completers ) .


For patients originally assigned ADA + MTX , accrued mTSS was 5.1 units ( integrated analysis ) and 4.0 units ( completers ) .


A higher radiographic progression rate was observed in patients who received delayed versus immediate ADA + MTX treatment .


Longitudinal integrated analysis provided robust estimates of radiographic progression that only slightly differed from completers-only scores and confirmed the effects .


We aimed to investigate the clinical significance of the activation of Yes-Associated Protein 1 ( YAP1 ) , a key downstream effector of Hippo tumor-suppressor pathway , in ovarian cancer .


A gene expression signature reflecting activation of YAP1 was developed from gene expression data of 267 samples from patients with ovarian cancer .


A refined ovarian cancer YAP1 signature was validated in an independent ovarian cancer cohort ( n = 185 ) .


Associations between the YAP1 signature and prognosis were assessed using Kaplan-Meier plots , the log-rank test , and a Cox proportional hazards model .


We identified a 612-gene expression signature reflecting YAP1 activation in ovarian cancer .


In multivariate analysis , the signature was an independent predictor of overall survival ( hazard ratio = 1.66 ; 95 % confidence interval = 1.1 to 2.53 ; p = 0.01 ) .


In subset analysis , the signature identified patients likely to benefit from taxane-based adjuvant chemotherapy .


Activation of YAP1 is significantly associated with prognosis and the YAP1 signature can predict response to taxane-based adjuvant chemotherapy in patients with ovarian cancer .


Epidemiology associates whole-grain ( WG ) consumption with several health benefits .


Mounting evidence suggests that WG wheat polyphenols play a role in mechanisms underlying health benefits .


The objective was to assess circulating concentration , excretion , and the physiologic role of WG wheat polyphenols in subjects with suboptimal dietary and lifestyle behaviors .


A placebo-controlled , parallel-group randomized trial with 80 healthy overweight/obese subjects with low intake of fruit and vegetables and sedentary lifestyle was performed .


Participants replaced precise portions of refined wheat ( RW ) with a fixed amount of selected WG wheat or RW products for 8 wk .


At baseline and every 4 wk , blood , urine , feces , and anthropometric and body composition measures were collected .


Profiles of phenolic acids in biological samples , plasma markers of metabolic disease and inflammation , and fecal microbiota composition were assessed .


WG consumption for 4-8 wk determined a 4-fold increase in serum dihydroferulic acid ( DHFA ) and a 2-fold increase in fecal ferulic acid ( FA ) compared with RW consumption ( no changes ) .


Similarly , urinary FA at 8 wk doubled the baseline concentration only in WG subjects .


Concomitant reduction in plasma tumor necrosis factor - ( TNF - ) after 8 wk and increased interleukin ( IL ) -10 only after 4 wk with WG compared with RW ( P = 0.04 ) were observed .


No significant change in plasma metabolic disease markers over the study period was observed , but a trend toward lower plasma plasminogen activator inhibitor 1 with higher excretion of FA and DHFA in the WG group was found .


Fecal FA was associated with baseline low Bifidobacteriales and Bacteroidetes abundances , whereas after WG consumption , it correlated with increased Bacteroidetes and Firmicutes but reduced Clostridium .


TNF - reduction correlated with increased Bacteroides and Lactobacillus .


No effect of dietary interventions on anthropometric measurements and body composition was found .


WG wheat consumption significantly increased excreted FA and circulating DHFA .


Bacterial communities influenced fecal FA and were modified by WG wheat consumption .


This trial was registered at clinicaltrials.gov as NCT01293175 .


Diarrhoea and respiratory infections are the two biggest causes of child death globally .


Handwashing with soap could substantially reduce diarrhoea and respiratory infections , but prevalence of adequate handwashing is low .


We tested whether a scalable village-level intervention based on emotional drivers of behaviour , rather than knowledge , could improve handwashing behaviour in rural India .


The study was done in Chittoor district in southern Andhra Pradesh , India , between May 24 , 2011 , and Sept 10 , 2012 .


Eligible villages had a population of 700-2000 people , a state-run primary school for children aged 8-13 years , and a preschool for children younger than 5 years .


14 villages ( clusters ) were selected , stratified by population size ( < 1200 vs > 1200 ) , and randomly assigned in a 1:1 ratio to intervention or control ( no intervention ) .


Clusters were enrolled by the study manager .


Random allocation was done by the study statistician using a random number generator .


The intervention included community and school-based events incorporating an animated film , skits , and public pledging ceremonies .


Outcomes were measured by direct observation in 20-25 households per village at baseline and at three follow-up visits ( 6 weeks , 6 months , and 12 months after the intervention ) .


Observers had no connection with the intervention and observers and participant households were told that the study was about domestic water use to reduce the risk of bias .


No other masking was possible .


The primary outcome was the proportion of handwashing with soap at key events ( after defecation , after cleaning a child 's bottom , before food preparation , and before eating ) at all follow-up visits .


The control villages received a shortened version of the intervention before the final follow-up round .


Outcome data are presented as village-level means .


Handwashing with soap at key events was rare at baseline in both the intervention and control groups ( 1 % [ SD 1 ] vs 2 % [ 1 ] ) .


At 6 weeks ' follow-up , handwashing with soap at key events was more common in the intervention group than in the control group ( 19 % [ SD 21 ] vs 4 % [ 2 ] ; difference 15 % , p = 0005 ) .


At the 6-month follow-up visit , the proportion handwashing with soap was 37 % ( SD 7 ) in the intervention group versus 6 % ( 3 ) in the control group ( difference 31 % ; p = 002 ) .


At the 12-month follow-up visit , after the control villages had received the shortened intervention , the proportion handwashing with soap was 29 % ( SD 9 ) in the intervention group and 29 % ( 13 ) in the control group .


This study shows that substantial increases in handwashing with soap can be achieved using a scalable intervention based on emotional drivers .


Wellcome Trust , SHARE .


A prospective , randomized , and double-blind study .


To compare the efficacy of ramosetron and palonosetron on preventing postoperative nausea and vomiting ( PONV ) associated with opioid-based intravenous patient-controlled analgesia ( IV-PCAopioid ) after lumbar spinal surgery .


IV-PCAopioid , an effective method to control pain after lumbar spinal surgery , accompanies PONV .


Ramosetron and palonosetron are novel 5-hydroxytryptamine 3 antagonists known to have longer action duration and higher receptor affinity than their congeners , whereas their relative efficacy has not been validated yet .


One hundred ninety-six patients were randomly and evenly allocated to receive either 0.3 mg of ramosetron or 0.075 mg of palonosetron 10 minutes before the end of operation .


Ramosetron or palonosetron were also added to the IV-PCAopioid , which was continuously infused for 48 hours postoperatively .


The incidence and intensity of PONV were serially assessed for 72 hours postoperatively .


Intensity of pain , volume of IV-PCAopioid consumption , use of rescue analgesics and antiemetics , and adverse events were also assessed .


The overall incidence of PONV was lower in the ramosetron group than the palonosetron group ( 50 % vs. 67 % , P = 0.014 ) without any intergroup difference in the incidence of vomiting .


Nausea intensity scores were also lower until 6 ( P = 0.041 ) and 24 hour ( P = 0.026 ) postoperatively in the ramosetron group than the palonosetron group .


Pain intensity scores were significantly lower in the ramosetron group than the palonosetron group for 72 hours postoperatively .


Ramosetron was superior to palonosetron in term of reducing the incidence and severity of nausea associated with IV-PCAopioid after lumbar spinal surgery .


This favorable influence of ramosetron on PONV was translated to significant postoperative pain reduction compared with palonosetron .


1 .


For patients with limited prognosis , some medication risks may outweigh the benefits , particularly when benefits take years to accrue ; statins are one example .


Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy .


To evaluate the safety , clinical , and cost impact of discontinuing statin medications for patients in the palliative care setting .


This was a multicenter , parallel-group , unblinded , pragmatic clinical trial .


Eligibility included adults with an estimated life expectancy of between 1 month and 1 year , statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease , recent deterioration in functional status , and no recent active cardiovascular disease .


Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year .


The study was conducted from June 3 , 2011 , to May 2 , 2013 .


All analyses were performed using an intent-to-treat approach .


Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group .


Patients in the continuation group continued to receive statins .


Outcomes included death within 60 days ( primary outcome ) , survival , cardiovascular events , performance status , quality of life ( QOL ) , symptoms , number of nonstatin medications , and cost savings .


A total of 381 patients were enrolled ; 189 of these were randomized to discontinue statins , and 192 were randomized to continue therapy .


Mean ( SD ) age was 74.1 ( 11.6 ) years , 22.0 % of the participants were cognitively impaired , and 48.8 % had cancer .


The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different ( 23.8 % vs 20.3 % ; 90 % CI , -3.5 % to 10.5 % ; P = .36 ) and did not meet the noninferiority end point .


Total QOL was better for the group discontinuing statin therapy ( mean McGill QOL score , 7.11 vs 6.85 ; P = .04 ) .


Few participants experienced cardiovascular events ( 13 in the discontinuation group vs 11 in the continuation group ) .


Mean cost savings were $ 3.37 per day and $ 716 per patient .


This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL , use of fewer nonstatin medications , and a corresponding reduction in medication costs .


Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted .


clinicaltrials.gov Identifier : NCT01415934 .


Several studies have shown that unnecessary right ventricular pacing has detrimental effects .


To evaluate whether minimization of ventricular pacing as compared with standard dual-chamber pacing ( DDD ) improves clinical outcomes in patients referred for pacemaker or implantable cardioverter-defibrillator ( ICD ) replacement .


In an international single-blind , multicenter , randomized controlled trial , we compared DDD with managed ventricular pacing ( MVP ) , a pacing mode developed to minimize ventricular pacing by promoting intrinsic atrioventricular conduction .


We included patients referred for device replacement with > 40 % ventricular pacing , no cardiac resynchronization therapy upgrade indication , no permanent atrial fibrillation ( AF ) , and no permanent complete atrioventricular block .


Follow-up was for 2 years .


The primary end point was cardiovascular hospitalization .


The intention-to-treat analysis was performed by using Kaplan-Meier method and the log-rank test .


We randomized 605 patients ( 556 referred for pacemaker and 49 referred for ICD replacement ; mean age 75 11 years ; 365 [ 60 % ] men , at 7.7 3.3 years from first device implantation ) to MVP ( n = 299 ) or DDD ( n = 306 ) .


We found no significant differences in the primary end point cardiovascular hospitalization ( MVP : 16.3 % vs DDD : 14.5 % ; P = .72 ) and the secondary end point persistent AF ( MVP : 15.4 % vs DDD : 11.2 % ; P = .08 ) , permanent AF ( MVP : 4.1 % vs DDD : 3.1 % ; P = .44 ) , and composite of death and cardiovascular hospitalization ( MVP : 23.9 % vs DDD : 20.2 % ; P = .48 ) .


MVP reduced right ventricular pacing ( median 5 % vs 86 % ; Wilcoxon , P < .0001 ) as compared with DDD .


In patients referred for pacemaker and ICD replacement with clinically well-tolerated long-term exposure to > 40 % ventricular pacing in the ventricle , a strategy to minimize ventricular pacing is not superior to standard DDD in reducing incidence of cardiovascular hospitalizations .


To compare gadobenate dimeglumine-enhanced magnetic resonance imaging ( MRI ) with gadopentetate dimeglumine-enhanced MRI , mammography , and ultrasound for breast cancer detection across different malignant lesion types and across different densities of breast tissue .


In all , 153 women with Breast Imaging Reporting and Data System ( BI-RADS ) 35 findings on mammography and/or ultrasound underwent identical breast MRI exams at 1.5 T with gadobenate dimeglumine and gadopentetate dimeglumine .


Images were evaluated by three independent blinded radiologists .


Mammography , ultrasound , and combined mammography and/or ultrasound findings were available for 108 , 109 , and 131 women .


Imaging findings were matched with histology data by a fourth , independent , blinded radiologist .


Malignant lesion detection rates and diagnostic performance were compared .


In all , 120 , 120 , and 140 confirmed malignant lesions were present in patients undergoing MRI + mammography , MRI + ultrasound , and MRI + mammography and/or ultrasound , respectively .


Significantly greater cancer detection rates were noted by all three readers for comparisons of gadobenate dimeglumine-enhanced MRI with mammography ( 15.817.5 % ; P < 0.0001 ) , ultrasound ( 18.320.0 % ; P < 0.0001 ) , and mammography and/or ultrasound ( 8.610.7 % ; P 0.0105 ) but not for comparisons of gadopentetate dimeglumine-enhanced MRI with conventional techniques ( P > 0.05 ) .


The false-positive detection rates were lower on gadobenate dimeglumine-enhanced MRI than on conventional imaging ( 4.05.5 % vs. 11.1 % at mammography ; 6.38.4 % vs. 15.5 % at ultrasound ) .


Significantly improved cancer detection on MRI was noted in heterogeneously dense breast ( 91.297.3 % on gadobenate dimeglumine-enhanced MRI vs. 77.284.9 % on gadopentetate dimeglumine-enhanced MRI vs. 71.9-84 .9 % with conventional techniques ) and for invasive cancers ( 93.296.2 % for invasive ductal carcinoma [ IDC ] on gadobenate dimeglumine-enhanced MRI vs. 79.788.5 % on gadopentetate dimeglumine-enhanced MRI vs. 77.084.4 % with conventional techniques ) .


Overall diagnostic performance for the detection of cancer was superior on gadobenate dimeglumine-enhanced MRI than on conventional imaging or gadopentetate dimeglumine-enhanced MRI .


Gadobenate dimeglumine-enhanced MRI significantly improves cancer detection compared to gadopentetate dimeglumine-enhanced MRI , mammography , and ultrasound in a selected group of patients undergoing breast MRI for preoperative staging or because of inconclusive findings at conventional imaging .


To observe the efficacy of combined use of brimonidine and betaxolol in treatment of primary open angle glaucoma ( POAG ) and ocular hypertension .


A total of 54 patients ( 90 eyes ) with POAG and ocular hypertension were randomly divided into three groups ( receiving betaxolol , brimonidine and combined administration of betaxolol and brimonidine respectively ) .


The administration was given twice daily in all groups ( 0.5 % betaxolol , 0.2 % brimonidine and 0.5 % betaxolol combined with 0.2 % brimonidine ) .


The changes in intraocular pressure ( IOP ) were observed before , and 2 , 4 , 6 , and 8 weeks after treatment .


In addition , the adverse reactions were also recorded post-treatment .


The mean IOPs at all the time points after treatment were significantly reduced compared with pre-treatment levels ( P < 0.05 ) .


Patients receiving brimonidine had a greater reduction in IOP compared with their counterparts in the betaxolol group but the difference was not statistically significant .


The IOP decline was significantly higher in the combined therapy group than in the other two groups ( P < 0.01 ) .


Few cases presented with slight discomfort , such as sensation of foreign bodies , ocular irritation , dizziness , headache , fatigue , and dryness of mouth and nose .


No severe adverse reactions were noted following administration .


Combined use of brimonidine and betaxolol is an efficacious treatment of reducing IOP without severe side effects .


Calcium aluminosilicate clay ( CASAD ) is a naturally occurring clay that serves as a cation exchange absorbent .


We hypothesized that oral administration of CASAD would reduce the rate of grade 3/4 diarrhea associated with irinotecan use for metastatic colorectal cancer ( CRC ) by adsorbing the SN-38 metabolite .


Patients receiving irinotecan-based chemotherapy were randomized equally between CASAD and placebo arms in this multicenter trial in order to assess differences in the proportions of patients with grade 3/4 diarrhea within 6 weeks .


Additionally , we compared symptom severity between the two arms using the M.D. Anderson Symptom Inventory .


Between May 2009 and May 2012 , 100 patients were enrolled .


In evaluable patients , 7 of 43 ( 16 % ) on the CASAD arm compared to 3 of 32 ( 9 % ) on the placebo arm experienced grade 3/4 diarrhea ( P = 0.70 ) .


The rate of any diarrhea among all patients was similar ( CASAD arm , 64 % vs. placebo arm , 70 % ) .


The rate of study dropout was 14 % in the CASAD arm and 38 % in the placebo arm ( P = 0.01 ) .


No differences were found in symptom severity , individual symptom items , and in serious adverse events between the two arms .


Compared to placebo , CASAD use was safe but ineffective in preventing diarrhea in metastatic CRC patients treated with irinotecan-containing chemotherapy regimens .


There were no distinct signals in terms of patient symptoms between arms , but there was significantly more patient dropout in the placebo arm .


Future CASAD trials will focus on the active treatment of diarrhea .


Pulmonary hypertension ( PH ) associated with fibrotic idiopathic interstitial pneumonia ( IIP ; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia ) confers important additional morbidity and mortality .


To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group .


In a randomized , double-blind , placebo-controlled study , 60 patients with fibrotic IIP and right heart catheter confirmed PH were randomized 2:1 to bosentan ( n = 40 ) or placebo ( n = 20 ) .


The primary study endpoint was a fall from baseline pulmonary vascular resistance index ( PVRi ) of 20 % or more over 16 weeks .


Sixty patients ( 42 men ; mean age , 66.6 9.2 yr ) , with a mean pulmonary artery pressure of 36.0 ( 8.9 ) mm Hg , PVRi 13.0 ( 6.7 ) Wood Units/m ( 2 ) and reduced cardiac index of 2.21 ( 0.5 ) L/min/m ( 2 ) were recruited to the study .


Accounting for deaths and withdrawals , paired right heart catheter data were available for analysis in 39 patients ( bosentan = 25 , placebo = 14 ) .


No difference in the primary outcome was detected , with seven ( 28.0 % ) patients receiving bosentan , and four ( 28.6 % ) receiving placebo achieving a reduction in PVRi of greater than or equal to 20 % ( P = 0.97 ) at 16 weeks .


There was no change in functional capacity or symptoms between the two groups at 16 weeks , nor any difference in rates of serious adverse events or deaths ( three deaths in each group ) .


This study shows no difference in invasive pulmonary hemodynamics , functional capacity , or symptoms between the bosentan and placebo groups over 16 weeks .


Our data do not support the use of the dual endothelin-1 receptor antagonist , bosentan , in patients with PH and fibrotic IIP .


Clinical trial registered with www.clinicaltrials.gov ( NCT 00637065 ) .


The integrase inhibitor dolutegravir and nucleoside analogues abacavir and lamivudine are once-daily treatment options for HIV .


This study ( NCT01622790 ) evaluated , first , the bioequivalence ( BE ) of a fixed-dose combination ( FDC ) tablet containing dolutegravir 50 mg , abacavir 600 mg , and lamivudine 300 mg ( dolutegravir/abacavir/lamivudine FDC ) vs coadministered dolutegravir 50 mg and abacavir/lamivudine combination tablets ( Epzicom ) and , second , the effect of food on the dolutegravir/abacavir/lamivudine FDC tablet .


Study part A ( 66 healthy subjects ) was a single-dose , open-label , randomized , 2-period crossover study to evaluate the BE of the dolutegravir/abacavir/lamivudine FDC tablet and dolutegravir + abacavir/lamivudine tablets in the fasted state .


In study part B , 12 subjects from part A received the dolutegravir/abacavir/lamivudine FDC tablet with a high-fat meal .


BE and food effect were assessed by analysis of variance to determine the ratio of geometric least squares means and associated 90 % confidence intervals for key pharmacokinetic parameters for each of dolutegravir , abacavir , and lamivudine .


Sixty-two subjects completed part A.


The dolutegravir/abacavir/lamivudine tablet was bioequivalent to the dolutegravir + abacavir/lamivudine tablets ; 90 % confidence intervals for the geometric least squares mean ratios fell within the 0.8-1 .25 BE criteria .


The effect of food on the dolutegravir/abacavir/lamivudine FDC tablet was similar to previous food effects observed with the separate formulations .


The safety profile was comparable between treatments , with no observed serious or grade 3/4 adverse events .


The BE of the dolutegravir/abacavir/lamivudine FDC tablet was demonstrated ; it may be administered without regard to meals .


Crohn 's disease ( CD ) usually recurs after intestinal resection ; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence .


We investigated whether monitoring levels of fecal calprotectin ( FC ) can substitute for endoscopic analysis of the mucosa .


We analyzed data collected from 135 participants in a prospective , randomized , controlled trial , performed at 17 hospitals in Australia and 1 hospital in New Zealand , that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery .


Levels of FC , serum levels of C-reactive protein ( CRP ) , and Crohn 's disease activity index ( CDAI ) scores were measured before surgery and then at 6 , 12 , and 18 months after resection of all macroscopic Crohn 's disease .


Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients .


Levels of FC were measured in 319 samples from 135 patients .


The median FC level decreased from 1347 g/g before surgery to 166 g/g at 6 months after surgery , but was higher in patients with disease recurrence ( based on endoscopic analysis ; Rutgeerts score , i2 ) than in patients in remission ( 275 vs 72 g/g , respectively ; P < .001 ) .


Combined 6 - and 18-month levels of FC correlated with the presence ( r = 0.42 ; P < .001 ) and severity ( r = 0.44 ; P < .001 ) of CD recurrence , but the CRP level and CDAI score did not .


Levels of FC greater than 100 g/g indicated endoscopic recurrence with 89 % sensitivity and 58 % specificity , and a negative predictive value ( NPV ) of 91 % ; this means that colonoscopy could have been avoided in 47 % of patients .


Six months after surgery , FC levels less than 51 g/g in patients in endoscopic remission predicted maintenance of remission ( NPV , 79 % ) .


In patients with endoscopic recurrence at 6 months who stepped-up treatment , FC levels decreased from 324 g/g at 6 months to 180 g/g at 12 months and 109 g/g at 18 months .


In this analysis of data from a prospective clinical trial , FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection .


Its predictive value might be used to identify patients most likely to relapse .


After treatment for recurrence , the FC level can be used to monitor response to treatment .


It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score .


Systematic use of observational pain tools has been advocated as a means to improve pain management for care home residents with dementia .


Pain experts suggest that any observational tool should be used as part of a comprehensive pain management protocol , which should include score interpretation and verification with appropriately suggested treatments .


The Observational Pain Management Protocol ( Protocol ) was therefore developed .


This study aims to investigate the extent to which the implementation of this Protocol can improve pain management in care home residents with dementia .


In this two-group , single-blinded , cluster-randomized controlled trial , 122 care home residents with dementia and pain-related diagnoses will be recruited from eight care homes ( that is 15 to 16 residents from each care home ) .


Invitations will be sent to all local care homes who meet the home selection criteria .


The eight care homes will be randomly selected from all care homes that agree to join this trial .


They will then be randomized to either the control or experimental conditions .


Participants from each care home will be placed into their home 's corresponding group to avoid ` contamination ' effects across participants .


Each intervention cycle will take 16 weeks ( that is , baseline assessment and care home staff training for 4 weeks and Protocol implementation for 12 weeks ) .


The Protocol will guide the pain management of the participants in the experimental care homes .


Meanwhile , the control care homes will continue their usual pain management strategies .


Intervention effects will be measured weekly during the protocol implementation period and compared with the baseline measurements , as well as between the experimental and control conditions .


Although similar pain protocols have been suggested previously , the recommendations were based on experts ' opinions rather than evaluation of research studies .


The feasibility and effectiveness of this kind of pain management protocol , tailored to older people with dementia , remains unknown .


The findings of this trial will offer strong evidence that better strategies for pain management should be used in the care home daily routine .


The Chinese University of Hong Kong , Centre for Clinical Trials : CUHK-CCT00367 .


Dietary protein digestion and absorption is an important factor modulating muscle protein accretion .


However , there are few data available on the effects of coingesting other macronutrients with protein on digestion and absorption kinetics and the subsequent muscle protein synthetic response .


The objective of the study was to determine the impact of carbohydrate coingestion with protein on dietary protein digestion and absorption and muscle protein accretion in healthy young and older men .


Twenty-four healthy young ( aged 21 1 y , body mass index 21.8 0.5 kg/m ( 2 ) ) and 25 older ( aged 75 1 y , body mass index 25.4 0.6 kg/m ( 2 ) ) men received a primed continuous L - [ ring - ( 2 ) H5 ] - phenylalanine and L - [ ring-3 ,5 - ( 2 ) H2 ] - tyrosine infusion and ingested 20 g intrinsically L - [ 1 - ( 13 ) C ] - phenylalanine-labeled protein with ( Pro + CHO ) or without ( Pro ) 60 g carbohydrate .


Plasma samples and muscle biopsies were collected in a postabsorptive and postprandial state .


Carbohydrate coingestion delayed the appearance of exogenous phenylalanine in the circulation ( P = .001 ) .


Dietary protein-derived phenylalanine availability over the 5-hour postprandial period was lower in the older ( 62 2 % ) when compared with the young subjects ( 74 2 % ; P = .007 ) , with no differences between conditions ( P = .20 ) .


Carbohydrate coingestion did not modulate postprandial muscle protein synthesis rates ( 0.035 0.003 vs 0.043 0.004 and 0.033 0.002 vs 0.035 0.003 % / h after Pro vs Pro + CHO in the young and older group , respectively ) .


In accordance , no differences in muscle protein-bound L - [ 1 - ( 13 ) C ] - phenylalanine enrichments were observed between conditions ( 0.020 0.002 vs 0.020 0.002 and 0.019 0.003 vs 0.022 0.004 mole percent excess after Pro vs Pro + CHO in the young and older subjects , respectively ) .


Carbohydrate coingestion with protein delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion in healthy young or older men .


Intrusive thoughts and images are common across the adult lifespan , but vary in their consequences .


Understanding age-related experiences with intrusive thoughts is important for identifying risk and protective factors for intrusive thought problems across the adult lifespan .


This study characterized age trajectories for six aspects of experiences with intrusive thoughts using Internet data collection .


Participants ( N = 1427 ; ages 18-87 ) were randomly assigned to suppress ( i.e. keep out of mind ) or monitor an intrusive thought for one minute , and then later to monitor the thought for a second minute .


Participants tracked thought recurrences during each thinking period , then reported their positive and negative affects following each thinking period , as well as their effort expended in suppressing the thought and perceived difficulty controlling the intrusive thought .


Multilevel modeling and generalized estimating equations modeled the continuous relationships between age and each dependent variable .


As expected , older age was associated with less decline in positive affect while engaging with an intrusive thought .


Interestingly , older age was also associated with a sharper rise and fall of negative affect .


Suppression effort increased linearly with age ( though perceived difficulty did not ) .


Finally , no age differences were found in either the frequency or duration of the thought 's recurrence , adding to previous evidence that older adults function similarly to younger adults in their control of intrusive thoughts , despite certain age-related declines in cognitive functioning .


These findings suggest a dissociation between age-related changes in emotional versus cognitive characteristics of engaging with intrusive thoughts .


Screening to prevent sudden cardiac death remains a contentious topic in sport and exercise medicine .


The aim of this study was to assess whether the use of a standardised criteria tool improves the accuracy of ECG interpretation by physicians screening athletes .


Design : Randomised control trial .


Study Population : General practitioners with an interest in sports medicine , sports physicians , sports medicine registrars and cardiologists from Australia and New Zealand were eligible to participate .


Outcome Measures : Accuracy , sensitivity , specificity and false-positive rates of screening ECG interpretation of athletes .


Intervention : A two-page standardised ECG criteria tool was provided to intervention participants .


Control participants undertook ` usual ' interpretation .


62 physicians , with a mean duration of practice of 16years , were randomised to intervention and control .


10 baseline and 30 postrandomisation athlete ECGs were interpreted by the participants .


Intervention participants were more likely to be correct : OR 1.72 ( 95 % CI 1.31 to 2.27 , p < 0.001 ) .


Correct ECG interpretation was higher in the intervention group , 88.4 % ( 95 % CI 85.7 % to 91.2 % ) , than in the control group , 82.2 % ( 95 % CI 78.8 % to 85.5 % ; p = 0.005 ) .


Sensitivity was 95 % in the intervention group and 92 % in the control group ( p = 0.4 ) , with specificity of 86 % and 78 % , respectively ( p = 0.006 ) .


There were 36 % fewer false positives in the intervention group ( p = 0.006 ) .


ECG interpretation in athletes can be improved by using a standardised ECG criteria tool .


Use of the tool results in lower false-positive rates ; this may have implications for screening recommendations .


ACTRN12612000641897 .


Anterior knee pain is a major cause of complaint in total knee arthroplasty ( TKA ) without patellar resurfacing .


The concept of improved patellar tracking and decreased retropatellar contact pressure for lateral retinacular release theoretically suggests that patients with lateral retinacular release in TKA would achieve a lower incidence of anterior knee pain when compared without lateral retinacular release .


We sought to determine ( 1 ) whether those patients who received a routine lateral retinacular release in TKA would attain lower incidence of anterior knee pain as compared to patients who received TKA without lateral retinacular release and ( 2 ) whether lateral retinacular release would increase the lateral retinacular release-related complications .


A total of 148 patients who underwent TKA with the use of the Gemini MK II mobile bearing were randomized to receive either routine lateral retinacular release ( intervention group ) or not ( control group ) .


Patients were assessed by the visual analogue scale for anterior knee pain , the Knee Society clinical scoring system of knee score and function score , and patellar score for clinical function .


Patients ' satisfaction and lateral retinacular release-related complications were also evaluated .


The overall incidence of anterior knee pain in the intervention group at 18 months follow-up was 5.6 % , while that of the control group was 20.6 % ( p = 0.009 ) .


No statistical difference was detected between the two groups in terms of lateral retinacular release-related complications ( n.s. ) , patients ' satisfaction ( n.s. ) , knee score ( n.s. ) , function score ( n.s. ) , and patellar score ( n.s. ) at 18 months follow-up .


The present study suggests that routine lateral retinacular release can reduce anterior knee pain and does not increase lateral retinacular release-related complications , in TKA with the use of the Gemini MK II mobile bearing without patellar resurfacing .


Therapeutic , Level I.


This study was undertaken to investigate whether a gradual reduction of the valve setting ( opening pressure ) decreases the complication rate in patients with idiopathic normal-pressure hydrocephalus ( iNPH ) treated with a ventriculoperitoneal ( VP ) shunt .


In this prospective double-blinded , randomized , controlled , dual-center study , a VP shunt with an adjustable valve was implanted in 68 patients with iNPH , randomized into two groups .


In one group ( the 20-4 group ) the valve setting was initially set to 20 cm HO and gradually reduced to 4 cm H2O over the course of the 6-month study period .


In the other group ( the 12 group ) , the valve was kept at a medium pressure setting of 12 cm HO during the whole study period .


The time to and type of complications ( hematoma , infection , and mechanical problems ) as well as overdrainage symptoms were recorded .


Symptoms , signs , and outcome were assessed by means of the iNPH scale and the NPH grading scale .


Six patients in the 20-4 group ( 22 % ) and 7 patients in the 12 group ( 23 % ) experienced a shunt complication ; 9 had subdural hematomas , 3 mechanical obstructions , and 1 infection ( no significant difference between groups ) .


The frequency of overdrainage symptoms was significantly higher for a valve setting 12 cm HO compared with a setting > 12 cm HO .


The 20-4 group had a higher improvement rate ( 88 % ) than the 12 group ( 62 % ) ( p = 0.032 ) .


There was no significant relationship between complications and body mass index , the use of an antisiphon device , or the use of anticoagulants .


Gradual lowering of the valve setting to a mean of 7 cm HO led to the same rate of shunt complications and overdrainage symptoms as a fixed valve setting at a mean of 13 cm HO but was associated with a significantly better outcome .


The combination of direct-acting antiviral agents in patients with chronic hepatitis C virus ( HCV ) infection has demonstrated clinical benefit ; however , evaluation of potential drug-drug interactions is required prior to therapy .


An open-label study assessed the pharmacokinetics and tolerability of the HCV NS5A replication complex inhibitor daclatasvir and the HCV NS3 protease inhibitor asunaprevir when co-administered in healthy subjects .


Daclatasvir 60mg once daily and asunaprevir 600mg twice daily were dosed for 7days alone followed by combination dosing for 14days at 30mg once daily and 200mg twice daily , respectively .


Further assessments were provided comparing exposures from the current study with those from studies in HCV-infected patients receiving either the same or higher doses of daclatasvir or asunaprevir administered alone or together .


Dose-normalized daclatasvir and asunaprevir morning exposures were comparable with control in healthy subjects , with geometric mean area under the concentration-time curve ratios of 1.202 ( 90 % CI 1.113-1 .298 ) and 0.868 ( 90 % CI 0.726-1 .038 ) , respectively .


In HCV patients daclatasvir and asunaprevir exposures were largely comparable , when administered together or alone .


Additional data support the conclusion that there is no clinically meaningful interaction between daclatasvir and asunaprevir in either healthy subjects or HCV-infected patients , including those also receiving peginterferon - / ribavirin , and that the combination of daclatasvir 60mg once daily and asunaprevir 200mg twice daily is generally well-tolerated .


Simplified informed consent forms have been successful in improving patient satisfaction and decreasing patient anxiety .


However , unsolved problems remain about whether these documents improve comprehension and satisfaction of patients with standard literacy skills .


s To investigate whether a detailed consent form explaining the key elements of informed consent , in comparison to a standard consent form , would increase the comprehension and satisfaction of adult cancer patients .


Patients who were eligible for the National Surgical Adjuvant Study of Breast Cancer ( protocol 01 ( N-SAS/BC -01 ) ) were randomly selected to receive one of the following four versions : detailed document with graphics , detailed document without graphics , standard document with graphics , and standard document without graphics .


The forms were written in plain language from the patients ' point of view .


A total of 85 patients were administered questionnaires via interview to assess levels of comprehension , satisfaction , and anxiety .


Patients demonstrated a strong understanding of information regarding treatment and research .


Patient comprehension did not differ significantly between the detailed document arms and the standard document arms .


Patient satisfaction level increased according to the amount of information presented in the consent form ; most patients preferred the detailed document with graphics .


Anxiety and accrual rates in the parent study were not affected by informed consent procedures .


Findings were limited to adults who had standard literacy skills and may not be generalizable to a population with lower literacy .


Informed consent can be a significant experience for a population with standard literacy skills , as long as the document is easily comprehensible .


Such information should be provided in a format that corresponds with patient needs , education levels , and preferences .


Providing additional Saturday rehabilitation can improve functional independence and health related quality of life at discharge and it may reduce patient length of stay , yet the economic implications are not known .


The aim of this study was to determine from a health service perspective if the provision of rehabilitation to inpatients on a Saturday in addition to Monday to Friday was cost effective compared to Monday to Friday rehabilitation alone .


Cost utility and cost effectiveness analyses were undertaken alongside a multi-center , single-blind randomized controlled trial with a 30-day follow up after discharge .


Participants were adults admitted for inpatient rehabilitation in two publicly funded metropolitan rehabilitation facilities .


The control group received usual care rehabilitation services from Monday to Friday and the intervention group received usual care plus an additional rehabilitation service on Saturday .


Incremental cost utility ratio was reported as cost per quality adjusted life year ( QALY ) gained and an incremental cost effectiveness ratio ( ICER ) was reported as cost for a minimal clinically important difference ( MCID ) in functional independence .


996 patients ( mean age 74 ( standard deviation 13 ) years ) were randomly assigned to the intervention ( n = 496 ) or the control group ( n = 500 ) .


Mean difference in cost of AUD$ 1,673 ( 95 % confidence interval ( CI ) -271 to 3,618 ) was a saving in favor of the intervention group .


The incremental cost utility ratio found a saving of AUD$ 41,825 ( 95 % CI -2,817 to 74,620 ) per QALY gained for the intervention group .


The ICER found a saving of AUD$ 16,003 ( 95 % CI -3,074 to 87,361 ) in achieving a MCID in functional independence for the intervention group .


If the willingness to pay per QALY gained or for a MCID in functional independence was zero dollars the probability of the intervention being cost effective was 96 % and 95 % , respectively .


A sensitivity analysis removing Saturday penalty rates did not significantly alter the outcome .


From a health service perspective , the provision of rehabilitation to inpatients on a Saturday in addition to Monday to Friday , compared to Monday to Friday rehabilitation alone , is likely to be cost saving per QALY gained and for a MCID in functional independence .


Australian and New Zealand Clinical Trials Registry November 2009 ACTRN12609000973213 .


The maximal effect of proton pump inhibitors ( PPI ) is reported to take 5 days .


However , most current protocols start PPI on the day of gastric endoscopic submucosal dissection ( ESD ) .


We aimed to evaluate the benefit of 5 days pretreatment with oral PPI before ESD to prevent bleeding .


This was a prospective randomized controlled trial .


Patients were administered oral rabeprazole 20 mg or placebo twice daily for 5 days before ESD .


Intravenous pantoprazole 40 mg was administered 2 h before ESD and at postprocedure day 1 , and then oral rabeprazole 20 mg was administered once daily .


Follow-up endoscopy was performed on days 1 and 30 .


Forty-eight-hour measurement of intragastric pH was performed in 26 patients .


The primary endpoint was major bleeding related to ESD .


One-hundred and twenty patients were enrolled .


Of these , 45 in the pretreatment and 53 in the placebo group were analyzed .


Each group had three cases of major bleeding .


There were no significant differences in the ulcer healing rate .


Intragastric pH percentage times greater than 4 , 5 , and 6 were 86.61 19.45 % , 83.30 22.06 % , and 76.86 25.35 % , respectively , in the pretreatment and 85.54 19.45 % , 84.08 27.11 % , and 81.53 27.81 % , respectively , in the placebo group , without significant differences .


Preprocedural administration of rabeprazole offers no additional benefit over postprocedural administration alone in preventing major bleeding after gastric ESD .


To determine the relationship between type three secretion genotype and fluoroquinolone resistance for P. aeruginosa strains isolated from microbial keratitis during the Steroids for Corneal Ulcers Trial ( SCUT ) and for two laboratory strains , PA103 and PAO1 .


Confirmed P. aeruginosa isolates from the SCUT were divided into exoU ( + ) or exoU ( - ) .


The exoU ( + ) strains contained the gene encoding ExoU , a powerful phospholipase toxin delivered into host cells by the type three secretion system .


Isolates were then assessed for susceptibility to fluoroquinolone , cephalosporin , and aminoglycoside antibiotics using disk diffusion assays .


Etest was used to determine the MIC of moxifloxacin and other fluoroquinolones .


Laboratory isolates in which the exoU gene was added or deleted were also tested .


A significantly higher proportion of exoU ( + ) strains were resistant to ciprofloxacin ( p = 0.001 ) , gatifloxacin ( p = 0.003 ) , and ofloxacin ( p = 0.002 ) compared to exoU ( - ) isolates .


There was no significant difference between exoU ( + ) or exoU ( - ) negative isolates with respect to susceptibility to other antibiotics except gentamicin .


Infections involving resistant exoU ( + ) strains trended towards worse clinical outcome .


Deletion or acquisition of exoU in laboratory isolates did not affect fluoroquinolone susceptibility .


Fluoroquinolone susceptibility of P. aeruginosa isolated from the SCUT is consistent with previous studies showing elevated resistance involving exoU encoding ( cytotoxic ) strains , and suggest worse clinical outcome from infections involving resistant isolates .


Determination of exoU expression in clinical isolates of P. aeruginosa may be helpful in directing clinical management of patients with microbial keratitis .


Few evidence-based interventions address adolescent relationship abuse in clinical settings .


This cluster randomized controlled trial tested the effectiveness of a brief relationship abuse education and counseling intervention in school health centers ( SHCs ) .


In 2012-2013 , 11 SHCs ( 10 clusters ) were randomized to intervention ( SHC providers received training to implement ) or standard-of-care control condition .


Among 1062 eligible students ages 14 to 19 years at 8 SHCs who continued participation after randomization , 1011 completed computer-assisted surveys before a clinic visit ; 939 completed surveys 3 months later ( 93 % retention ) .


Intervention versus control adjusted mean differences ( 95 % confidence interval ) on changes in primary outcomes were not statistically significant : recognition of abuse = 0.10 ( -0.02 to 0.22 ) ; intentions to intervene = 0.03 ( -0.09 to 0.15 ) ; and knowledge of resources = 0.18 ( -0.06 to 0.42 ) .


Intervention participants had improved recognition of sexual coercion compared with controls ( adjusted mean difference = 0.10 [ 0.01 to 0.18 ] ) .


In exploratory analyses adjusting for intensity of intervention uptake , intervention effects were significant for increased knowledge of relationship abuse resources and self-efficacy to use harm reduction behaviors .


Among participants reporting relationship abuse at baseline , intervention participants were less likely to report such abuse at follow-up ( mean risk difference = -0.17 [ -0.21 to -0.12 ] ) .


Adolescents in intervention clinics who reported ever being in an unhealthy relationship were more likely to report disclosing this during the SHC visit ( adjusted odds ratio = 2.77 [ 1.29 to 5.95 ] ) .


This is the first evidence of the potential benefit of a SHC intervention to address abusive relationships among adolescents .


To assess bacterial colonization following balloon uterine stent placement in the uterus for 30 days .


Prospective randomized controlled study .


Tertiary medical center .


Sixty-eight women scheduled for hysteroscopy .


Women who were undergoing hysteroscopic surgery were randomly assigned to receive a balloon uterine stent or not .


Before starting surgery , the uterine cavity was swabbed for bacterial culture .


The device was placed in the uterus after surgery in the stent group .


After 30 days , the stent was removed and sent for culture and the uterine cavity also swabbed and cultured .


The uterine cavities of the control patients were swabbed before and 30 days after surgery .


The primary outcome was the incidence of bacterial colonization of the uterus .


Secondary outcomes were pain intensity and species of colonizing bacteria .


Excluding eight women , 30 women in each group were included in this analysis .


In the stent group , three women ( 10.0 % ) demonstrated bacterial colonization before surgery compared with nine women ( 30.0 % ) after 30 days .


In the control group , four ( 13.3 % ) and ten ( 33.3 % ) women had microorganisms detected in the uterus before and after 30 days after surgery , respectively .


In neither group did the percentage of women with uterine microorganisms increase significantly after 30 days .


The percentages of women with uterine bacterial colonization before and 30 days after surgery were similar between both groups .


Balloon uterine stents may be placed after surgery for up to 30 days without increasing bacterial colonization .


ClinicalTrials.gov ( www.clinicaltrials.gov ) NCT01167296 .


RAS mutations predict resistance to anti-epidermal growthfactor receptor ( EGFR ) monoclonal antibodies in metastatic colorectal cancer .


We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial .


Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type , and randomly assigned to capecitabine plus oxaliplatin ( CAPOX ) followed by chemoradiotherapy , surgery and adjuvant CAPOX or the same regimen plus cetuximab ( CAPOX-C ) .


Of these , four had a mutation of NRAS exon 3 , and 84 were retrospectively analysed for additional KRAS ( exon 4 ) and NRAS ( exons 2/4 ) mutations by using bi-directional Sanger sequencing .


The effect of cetuximab on study end-points in the RAS wild-type population was analysed .


Eleven ( 13 % ) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 ( 11 % ) or NRAS exons 2/4 ( 2 % ) .


Overall , 78/149 ( 52 % ) assessable patients were RAS wild-type ( CAPOX , n = 40 ; CAPOX-C , n = 38 ) .


In this population , after a median follow-up of 63.8 months , in line with the initial analysis , the addition of cetuximab was associated with numerically higher , but not statistically significant , rates of complete response ( 15.8 % versus 7.5 % , p = 0.31 ) , 5-year progression-free survival ( 75.5 % versus 67.5 % , hazard ratio ( HR ) 0.61 , p = 0.25 ) and 5-year overall survival ( 83.8 % versus 70 % , HR 0.54 , p = 0.20 ) .


RAS mutations beyond KRAS exon 2 and 3 were identified in 17 % of locally advanced rectal cancer patients .


Given the small sample size , no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted .


To observe the therapeutic effect of extracorporeal shock wave combined with orthopaedic insole on plantar fasciitis .


A total of 153 plantar with plantar fasciitis were randomly divided into a combined group ( n = 51 ) , an extracorporeal shock wave group ( n = 53 ) and an orthopaedic group ( n = 49 ) .


The combined group received treatment of both extracorporeal shock wave and orthopaedic insole while the extracorporeal shock wave or the orthopaedic group only received the treatment of extracorporeal shock wave or orthopaedic insole .


The therapeutic parameters such as visual analogue scale ( VAS ) scores , continued walking time and thickness of the plantar fascia were monitored before and aft er the treatment for 2 weeks , 1 month and 3 months , respectively .


The VAS scores in the 3 groups were all reduced after the treatment compared with the corresponding scores before the therapy ( P < 0.05 ) .


The VAS score in the extracorporeal shock wave group was greater than that in the orthopedic group after the treatment for 2 weeks .


The VAS score in the combined group was smaller than that in the orthopedic group after the treatment for 2 weeks and 3 months ( P < 0.05 ) .


The VAS scores in the orthopedic group and the combined group were smaller than those in the extracorporeal shock wave group after the treatment for 1 month or 3 months ( P < 0.05 ) .


The continued walking time and thickness of the plantar fascia was improved after the treatment ( P < 0.05 ) .


The cure rate and total effective rate in the combination group were obviously greater than those in the two other groups .


The cure rate in the orthopedic group was greater than that in the extracorporeal shock wave group ( P < 0.05 ) .


Extracorporeal shock wave combined with orthopaedic insole therapy is an effective method to treat plantar fasciitis .


It is recommended to spread in clinic .


The efficacy of noninvasive continuous positive airway pressure ( CPAP ) to improve outcomes in severe hypoxemic acute respiratory failure ( hARF ) due to pneumonia has not been clearly established .


The aim of this study was to compare CPAP vs. oxygen therapy to reduce the risk of meeting criteria for endotracheal intubation ( ETI ) .


In a multicenter randomized controlled trial conducted in four Italian centers patients with severe hARF due to pneumonia were randomized to receive helmet CPAP ( CPAP group ) or oxygen delivered with a Venturi mask ( control group ) .


The primary endpoint was the percentage of patients meeting criteria for ETI , including either one or more major criteria ( respiratory arrest , respiratory pauses with unconsciousness , severe hemodynamic instability , intolerance ) or at least two minor criteria ( reduction of at least 30 % of basal PaO2/FiO2 ratio , increase of 20 % of PaCO2 , worsening of alertness , respiratory distress , SpO2 less than 90 % , exhaustion ) .


Between February 2010 and 2013 , 40 patients were randomized to CPAP and 41 to Venturi mask .


The proportion of patients meeting ETI criteria in the CPAP group was significantly lower compared to those in the control group ( 6/40 = 15 % vs. 26/41 = 63 % , respectively , p < 0.001 ; relative risk 0.24 , 95 % CI 0.11-0 .51 ; number needed to treat , 2 ) two patients were intubated in the CPAP group and one in the control group .


The CPAP group showed a faster and greater improvement in oxygenation in comparison to controls ( p < 0.001 ) .


In either study group , no relevant adverse events were detected .


Helmet CPAP reduces the risk of meeting ETI criteria compared to oxygen therapy in patients with severe hARF due to pneumonia .


This randomized double-blind study was designed to compare palonosetron with palonosetron-dexamethasone combination for prevention of post operative nausea and vomiting ( PONV ) in patients undergoing laparoscopic cholecystectomy .


Eighty-four adult ASA 1-2 patients were randomly allocated into two groups .


Group P patients received 0.075 mg palonosetron and group PD patients received 0.075 mg palonosetron and 8 mg dexamethasone intravenously before induction of anesthesia .


Anesthesia was induced with propofol and fentanyl and maintained with N2O-isoflurane in oxygen .


All patients received port-site infiltration with bupivacaine and intravenous diclofenac for postoperative analgesia .


Metoclopramide was used as rescue antiemetic .


Patients were observed for the incidence of PONV and requirement of rescue antiemetic for 48 h after surgery .


The complete response rate ( no vomiting ) was significantly higher in group DP as compared to group P between 0-24 h ( P = 0.004 ) .


18 ( 42.9 % ) patients reported nausea and 14 ( 33.3 % ) patients had vomiting in group P while 6 ( 14.4 % ) patients had nausea and 5 ( 11.9 % ) patients complained of vomiting in group DP during 0-24 h. Two patients in group P reported nausea while none in group PD during 24-48 h. No patient had vomiting in either of the groups between 24-48 h.


The requirement of rescue antiemetic was also less in group DP as compared to group P. Patients in group DP required less postoperative analgesia and were more satisfied with PONV treatment than group P patients .


The palonosetron-dexamethasone combination was more effective as compared to only palonosetron for reducing PONV after laparoscopic cholecystectomy .


A large number of unrepaired inguinal hernias is expected in sub-Saharan Africa where late presentation often results in incarceration , strangulation , or giant scrotal hernias .


However , no representative population-based data are available to quantify the prevalence of hernias .


We present data on groin masses in Sierra Leone to estimate prevalence , barriers to care , and associated disability .


A cluster randomized , cross-sectional household survey of 75 clusters of 25 households with 2 respondents each was designed to calculate the prevalence of and disability caused by groin hernias in Sierra Leone using a verbal head-to-toe examination .


Barriers to hernia repairs were assessed by asking participants the main reason for delay in surgical care .


Information was obtained from 3,645 respondents in 1,843 households , of which 1,669 ( 46 % ) were male and included in the study .


In total , 117 males or 7.01 % ( 95 % CI 5.64-8 .38 ) reported a soft or reducible swelling likely representing a hernia with four men having two masses .


Of the 93.2 % who indicated the need for health care , only 22.2 % underwent a procedure , citing limited funds ( 59.0 % ) as the major barrier to care .


On disability assessment , 20.2 % were not able to work secondary to the groin swelling .


The results indicate groin masses represent a major burden for the male population in Sierra Leone .


Improving access to surgical care for adult patients with hernias and early intervention for children will be vital to address the burden of disease and prevent complications or limitations of daily activity .


Health IT can play a major role in improving patient safety .


Computerized physician order entry with decision support can alert providers to potential prescribing errors .


However , too many alerts can result in providers ignoring and overriding clinically important ones .


To evaluate the appropriateness of providers ' drug-drug interaction ( DDI ) alert overrides , the reasons why they chose to override these alerts , and what actions they took as a consequence of the alert .


A cross-sectional , observational study of DDI alerts generated over a three-year period between January 1st , 2009 , and December 31st , 2011 .


Primary care practices affiliated with two Harvard teaching hospitals .


The DDI alerts were screened to minimize the number of clinically unimportant warnings .


A total of 24,849 DDI alerts were generated in the study period , with 40 % accepted .


The top 62 providers with the highest override rate were identified and eight overrides randomly selected for each ( a total of 496 alert overrides for 438 patients , 3.3 % of the sample ) .


Overall , 68.2 % ( 338/496 ) of the DDI alert overrides were considered appropriate .


Among inappropriate overrides , the therapeutic combinations put patients at increased risk of several specific conditions including : serotonin syndrome ( 21.5 % , n = 34 ) , cardiotoxicity ( 16.5 % , n = 26 ) , or sharp falls in blood pressure or significant hypotension ( 28.5 % , n = 45 ) .


A small number of drugs and DDIs accounted for a disproportionate share of alert overrides .


Of the 121 appropriate alert overrides where the provider indicated they would `` monitor as recommended '' , a detailed chart review revealed that only 35.5 % ( n = 43 ) actually did .


Providers sometimes reported that patients had already taken interacting medications together ( 15.7 % , n = 78 ) , despite no evidence to confirm this .


We found that providers continue to override important and useful alerts that are likely to cause serious patient injuries , even when relatively few false positive alerts are displayed .


The treatment strategy for steroid-resistant nephrotic syndrome remains uncertain at present , especially in those with calcineurin inhibitor resistance or intolerance .


To date , few studies have been published using multiple combination therapy of immunosuppressive reagents for children with calcineurin inhibitor-resistant or - intolerant nephrotic syndrome .


Eighteen consecutive children with steroid - and tacrolimus ( TAC ) - resistant ( n = 10 ) or TAC-sensitive but frequent relapsing nephrotic syndrome ( n = 8 ) were randomly recruited in the present study .


All of them received further triple-combination therapy by cyclophosphamide ( CTX , n = 6 ) , mycophenolate mofetil ( MMF , n = 5 ) or leflunomide ( LEF , n = 7 ) .


Their clinical data were collected and efficacy of triple-combination therapy was evaluated .


Compared with previous double-combination therapy of prednisone ( Pre ) and TAC , the short-term remission rate in all 18 patients was significantly improved after the triple-combination therapy , while the frequent relapse rate in the following 12months was also significantly decreased .


Among three different subgroups with CTX , MMF or LEF therapy , no significant difference was found in short-term remission rate and the relapse rate within 1year follow up by Kaplan-Meier plot .


Triple-combination therapy with Pre + TAC+CTX / MMF/LEF is effective for short-term response and 1year remission , without significant additional side-effects seen in children with steroid-resistant and tacrolimus-resistant or tacrolimus-sensitive but frequently relapsing nephrotic syndrome .


Further study for evaluating long-term efficacy and safety of triple-combination therapy with Pre + TAC+CTX / MMF/LEF would be necessary for these patients .


Biospecimen collection from diverse populations can advance cancer disparities research , but is currently underrepresented .


We partnered with a community-based clinic serving Cantonese-speaking Chinese Americans to develop and revise an educational seminar on biospecimen collection .


Through a randomized controlled trial ( n = 395 ) , the intervention seminar was compared with a control seminar ( cancer prevention ) on change in willingness to donate biospecimens .


At baseline , many were willing to donate a biospecimen ( saliva , urine , hair , toenails , blood , unused cancerous tissue ) whether healthy or hypothetically had cancer .


Also , many would donate because future generations would benefit , and few had concerns about donation .


In logistic regression analyses , there was an intervention effect for willingness to donate : urine if had cancer [ OR , 2.2 ; 95 % confidence interval ( CI ) , 1.3-3 .7 ] , toenails if healthy ( OR , 2.1 ; 95 % CI , 1.4-3 .2 ) or had cancer ( OR , 2.3 ; 95 % CI , 2.0-2 .7 ) , hair if healthy ( OR , 1.8 ; 95 % CI , 1.3-2 .5 ) or had cancer ( OR , 2.8 ; 95 % CI , 1.9-4 .0 ) , and unused cancerous tissue ( OR , 1.8 ; 95 % CI , 1.2-2 .9 ) .


There was also an intervention effect for donating because future generations would benefit ( OR , 2.0 ; 95 % CI , 1.4-3 .0 ) , and this attitude was a strong independent predictor for willingness to donate all biospecimens , whether healthy or had cancer ( OR , 2.9-4 .2 ) .


Cantonese-speaking Chinese American participants of an educational seminar on biospecimen collection showed greater increases in willingness to donate biospecimens and donating for the benefit of future generations , than participants who attended a control seminar .


Donating for the benefit of future generations is a theme that should be incorporated in messages that encourage biospecimen donation for Chinese Americans .


To perform a randomized trial to determine whether there is cardiovascular disease ( CVD ) risk reduction from a plant-based ( PB ) , no-added-fat diet and the American Heart Association ( AHA ) diet in children .


A 4-week ( April 20 , 2013 to May 18 , 2013 ) , prospective randomized trial was undertaken in a large , Midwestern hospital system 's predominantly middle class outpatient pediatric practices .


Thirty children ( 9-18 years of age ) parent pairs with a last recorded child body mass index > 95th percentile and child cholesterol > 169 mg/dL were randomized to PB or AHA with weekly 2-hour classes of nutrition education .


Children on PB had 9 and children on AHA had 4 statistically significant ( P < .05 ) beneficial changes from baseline ( mean decreases ) : body mass index z-score ( PB ) ( -0.14 ) , systolic blood pressure ( PB ) ( -6.43 mm Hg ) , total cholesterol ( PB ) ( -22.5 mg/dL ) , low-density lipoprotein ( PB ) ( -13.14 mg/dL ) , high-sensitivity C-reactive protein ( PB ) ( -2.09 mg/L ) , insulin ( PB ) ( -5.42 uU/mL ) , myeloperoxidase ( PB/AHA ) ( -75.34 / 69.23 pmol/L ) , mid-arm circumference ( PB/AHA ) ( -2.02 / -1.55 cm ) , weight ( PB/AHA ) ( -3.05 / -1.14 kg ) , and waist circumference ( AHA ) ( -2.96 cm ) .


Adults on PB and AHA had 7 and 2 , respectively , statistically significant ( P < .05 ) beneficial changes .


The significant change favoring AHA was a 1 % difference in children 's waist circumference .


Difficulty shopping for food for the PB was the only statistically significant acceptability barrier .


PB and the AHA in both children and adults demonstrated potentially beneficial changes from baseline in risk factors for CVD .


Future larger , long-term randomized trials with easily accessible PB foods will further define the role of the PB in preventing CVD .


Vitamin D has immunomodulatory effects that might aid clearance of mycobacterial infection .


We aimed to assess whether vitamin D supplementation would reduce time to sputum culture conversion in patients with active tuberculosis .


We did this randomised , double-blind , placebo-controlled , superiority trial at 13 sites in India .


Treatment-naive patients who were sputum-smear positive , HIV negative , and had pulmonary tuberculosis were randomly assigned ( 1:1 ) , with centrally labelled , serially numbered bottles , to receive standard active tuberculosis treatment with either supplemental high-dose oral vitamin D3 ( four doses of 25 mg at weeks 0 , 2 , 4 , and 6 ) or placebo .


Neither the patients nor the clinical and laboratory investigators and personnel were aware of treatment assignment .


The primary efficacy outcome was time to sputum culture conversion .


Analysis was by modified intention to treat .


This trial is registered with ClinicalTrials.gov , number NCT00366470 .


Between Jan 20 , 2010 , and Aug 23 , 2011 , we randomly assigned 247 participants to the vitamin D group ( n = 121 ) or the placebo group ( n = 126 ) , of whom 211 participants ( n = 101 and n = 110 , respectively ) were included in the primary efficacy analysis .


Median time to culture conversion in the vitamin D group was 430 days ( 95 % CI 333-528 ) versus 420 days ( 339-501 ) in the placebo group ( log-rank p = 095 ) .


Three ( 2 % ) patients died in the vitamin D group and one ( 1 % ) patient died in the placebo group ; no death was considered attributable to the study intervention .


No patients had hypercalcaemia .


Our findings show that vitamin D supplementation did not reduce time to sputum culture conversion .


Further studies should investigate the role of vitamin D in prevention or reactivation of tuberculosis infection .


Dalhousie University and Infectious Diseases Training and Research Centre .


To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium ( QVA149 ) and its monocomponents ; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety databases .


Data from 11,404 patients with chronic obstructive pulmonary disease ( COPD ) were pooled from 14 clinical studies of QVA149 , indacaterol and glycopyrronium of 3 month 's duration with at least two of the treatment groups : QVA149 110/50g , glycopyrronium 50g , indacaterol 150g , placebo or tiotropium 18g .


Overall hazard ratio ( HR ) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction , inhaled corticosteroid use , cardiovascular risk factors , sex , age and body mass index for death , serious cases of cardio - and cerebrovascular ( CCV ) events , major adverse cardiovascular events ( MACEs ) , pneumonia , COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation ( AF/F ) .


The HR for QVA149 versus placebo showed no significant increase in the overall risk for death ( HR [ 95 % confidence interval ] : 0.93 [ 0.34-2 .54 ] ) ; CCV events ( 0.60 [ 0.29-1 .24 ] ) ; MACE ( 1.04 [ 0.45-2 .42 ] ) ; pneumonia ( 1.10 [ 0.54-2 .25 ] ) ; COPD exacerbations ( 0.60 [ 0.40-0 .91 ] ) ; and AF/F ( 1.03 [ 0.49-2 .18 ] ) .


Similar results were observed for indacaterol , glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups .


There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149 , and it had a comparable safety profile as its monocomponents and tiotropium versus placebo .


To evaluate safety and effectiveness of the TECNIS toric intraocular lenses ( IOLs ) .


Prospective , multicenter , 2-armed , bilateral , 6-month clinical trial following the American National Standards Institute ( ANSI ) standard for Toric IOLs .


Subjects implanted with a TECNIS toric IOL ( n = 172 ) or a TECNIS 1-piece control IOL ( ZCB00 ; n = 93 ) .


Subjects underwent standard cataract surgery with IOL implantation .


The randomized control arm consisted of subjects requiring cylinder correction of 0.75 to 1.50 diopters ( D ) who were implanted with either toric ( ZCT150 ) or nontoric ( ZCB00 ) IOLs .


The open-label arm ( OLA ) consisted of subjects requiring cylinder correction of 1.50 to 3.62 D and implanted with ZCT225 , ZCT300 , or ZCT400 IOLs .


Assessments were at 1 day , 1 week , and 1 , 3 , and 6 months and included uncorrected distance visual acuity ( UCDVA ) and best-corrected distance visual acuity ( BCDVA ) , manifest refraction , keratometry , adverse events , spectacle use , and photographic documentation of IOL rotational stability .


Mean percent reduction in cylinder ( standard deviation ) was statistically significantly greater ( P < 0.0001 ) for ZCT150 eyes ( 74.53 72.25 % ) versus ZCB00 eyes ( 31.61 78.73 % ) .


In the OLA , mean percent reduction in cylinder was 76.27 33.09 % .


A UCDVA of 20/20 or better was achieved by 43.6 % ( 44/101 ) of ZCT150 eyes and by 23.7 % ( 22/93 ) of ZCB00 eyes ( P = 0.0026 ) .


In the OLA , 38.0 % ( 27/71 ) achieved 20/20 or better UCDVA .


Mean UCDVA was 0.10 0.14 for ZCT150 eyes and 0.16 0.16 for ZCB00 eyes ( P = 0.0009 ) ; in the OLA , mean UCDVA was 0.11 0.12 .


The BCDVA was 20/40 or better for all eyes .


Mean absolute lens rotation between visits for toric eyes pooled was less than 3 .


Lens rotation of 5 or less occurred in 92.9 % of toric eyes between 1 and 3 months and in 94.1 % between 3 and 6 months , exceeding the ANSI standard for stability ( 90 % of eyes with 5 of rotation between visits ) .


Four lenses ( 2.3 % ) were repositioned during the study .


The TECNIS toric IOLs successfully reduce ocular astigmatism and are a safe and effective treatment for cataract patients with corneal astigmatism .


The purpose of this study was to determine whether whole-body vibration training could improve standing balance and muscle strength in children with Down syndrome .


This study was a randomized controlled trial studying 30 children ( 8-10 yrs old ) with Down syndrome .


They were assigned randomly using sealed envelopes , with 15 children allocated to the control group ( 9 boys , 6 girls ) and another 15 children allocated to the study group ( 8 boys , 7 girls ) .


The control group received a designed physical therapy program , whereas the study group received the same program given to the control group in addition to whole-body vibration training .


Both groups received the treatment sessions three times per week for 6 successive months .


Measurement of stability indices by using the Biodex Stability System as well as muscle strength of the knee flexors and extensors by using a handheld dynamometer was done before and after the 6 mos of the treatment program .


Each group demonstrated significant improvements in stability indices and muscle strength after treatment ( P < 0.05 ) , with significantly greater improvements seen in the study group when compared with the control group ( P < 0.05 ) .


Whole-body vibration may be a useful intervention modality to improve balance and muscle strength in children with Down syndrome .


TAK-438 ( vonoprazan ) is a potassium-competitive acid blocker that reversibly inhibits gastric H ( + ) , K ( + ) - ATPase .


To evaluate the safety , tolerability , pharmacokinetics and pharmacodynamics of TAK-438 in healthy Japanese and non-Japanese men .


In two Phase I , randomised , double-blind , placebo-controlled studies , healthy men ( Japan N = 60 ; UK N = 48 ) received TAK-438 10-40mg once daily at a fixed dose level for 7 consecutive days .


Assessments included safety , tolerability , pharmacokinetics and pharmacodynamics ( intragastric pH ) .


Plasma concentration-time profiles of TAK-438 at all dose levels showed rapid absorption ( median Tmax 2h ) .


Mean elimination half-life was up to 9h .


Exposure was slightly greater than dose proportional , with no apparent time-dependent inhibition of metabolism .


There was no important difference between the two studies in AUC0-tau on Day 7 .


TAK-438 caused dose-dependent acid suppression .


On Day 7 , mean 24-h intragastric pH > 4 holding time ratio ( HTR ) with 40mg TAK-438 was 100 % ( Japan ) and 93.2 % ( UK ) , and mean night-time pH > 4 HTR was 100 % ( Japan ) and 90.4 % ( UK ) .


TAK-438 was well tolerated .


The frequency of adverse events was similar at all dose levels and there were no serious adverse events .


There were no important increases in serum alanine transaminase activity .


Serum gastrin and pepsinogen I and II concentrations increased with TAK-438 dose .


TAK-438 in multiple rising oral dose levels of 10-40mg once daily for 7days was safe and well tolerated in healthy men and caused rapid , profound and sustained suppression of gastric acid secretion throughout each 24-h dosing interval .


Clinicaltrials.gov identifiers : NCT02123953 and NCT02141711 .


PhaseIII DEFEND-2 investigated whether otelixizumab ( 3.1 mg over 8days ) preserved C-peptide secretion in patients with new-onset Type1 diabetes , focusing on adolescents ( 12-17years ) .


One hundred and seventy-nine patients ( 54 adolescents ) were randomized to otelixizumab or placebo .


The primary endpoint was change in 2-h mixed-meal-stimulated C-peptide area under the curve at month12 .


Enrolment was suspended in April 2011 following negative efficacy results from DEFEND-1 .


DEFEND-2 terminated early after 12months ' efficacy and safety follow-up .


Change from baseline C-peptide was not significantly different [ = -0.09 nmol/l ( 95 % CI -0.17 to 0 ; P = 0.051 ) ] .


No differential C-peptide effect was seen for otelixizumab in adolescents and more adverse events were reported .


Efficacy and tolerability of otelixizumab was similar to DEFEND-1 .


The 3.1-mg dose was non-efficacious in adults and adolescents .


Further investigation of the mechanism of action seen at higher doses and therapeutic window is required .


Clinical Trials Registry No : NCT00763451 .


Evaluation of the efficacy and toxicity of split-course accelerated hyperfractionated irradiation ( CHA-CHA ) as a sole treatment for advanced head and neck ( H&N ) cancer patients .


We enrolled 101 patients ( 39 in CHA-CHA and 37 in conventional ( Conv . )


arm completed the treatment ) .


The CHA-CHA arm patients were irradiated twice a day , 7 days a week , using a fraction dose ( fd ) of 1.6 Gy up to 64 Gy with an 8-day gap in midterm .


Patients in the control ( Conv . )


arm group were irradiated with a fd of 2 Gy , five times a week to a total dose of 72-74 Gy in the overall treatment time of 50-53 days .


Quality of life ( QOL ) and acute mucosal reaction were evaluated during radiotherapy ( RT ) .


After RT , we followed the effect of treatment , QOL , performance status and adverse effects of radiation .


For statistical analysis mainly a hierarchical multilevel modelling was used .


QOL was most deteriorated in the CHA-CHA arm ; the CHA-CHA scheme also caused a relatively stronger acute injury .


There were no significant differences in late adverse effects .


In the CHA-CHA arm in 35 % and in Conv .


arm in 30 % of patients , disease was controlled during follow-up .


Tumour regression 1 year after the treatment was significantly better in the CHA-CHA arm .


However , the overall survival rate analysis did not show significant difference between both arms .


Despite differences in treatment results , we can not conclude that split-course accelerated hyperfractionated irradiation is superior to conventionally fractionated RT as a sole treatment for advanced H&N cancer patients .


Obtained results in the context of published data support the statement that altered fractionations alone do not give an advantage for advanced H&N cancer patients .


The Placement of Aortic Transcatheter Valves ( PARTNER ) trial showed that mortality at 1 year , 2 years , and 3 years is much the same with transcatheter aortic valve replacement ( TAVR ) or surgical aortic valve replacement ( SAVR ) for high-risk patients with aortic stenosis .


We report here the 5-year outcomes .


We did this randomised controlled trial at 25 hospitals , in Canada ( two ) , Germany ( one ) , and the USA ( 23 ) .


We used a computer-generated randomisation sequence to randomly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-expandable bovine pericardial tissue valve by either a transfemoral or transapical approach .


Patients and their treating physicians were not masked to treatment allocation .


The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year , we present here predefined outcomes at 5 years .


The study is registered with ClinicalTrials.gov , number NCT00530894 .


We screened 3105 patients , of whom 699 were enrolled ( 348 assigned to TAVR , 351 assigned to SAVR ) .


Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 117 % .


At 5 years , risk of death was 678 % in the TAVR group compared with 624 % in the SAVR group ( hazard ratio 104 , 95 % CI 086-124 ; p = 076 ) .


We recorded no structural valve deterioration requiring surgical valve replacement in either group .


Moderate or severe aortic regurgitation occurred in 40 ( 14 % ) of 280 patients in the TAVR group and two ( 1 % ) of 228 in the SAVR group ( p < 00001 ) , and was associated with increased 5-year risk of mortality in the TAVR group ( 724 % for moderate or severe aortic regurgitation vs 566 % for those with mild aortic regurgitation or less ; p = 0003 ) .


Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes .


Edwards Lifesciences .


Transthoracic echocardiographic ( TTE ) imaging is the mainstay of clinical practice for evaluating right ventricular ( RV ) size and function , but its accuracy in patients with pulmonary hypertension has not been well validated .