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


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


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


Overall , @/@ ( @ % ) assessable patients were RAS wild-type ( CAPOX , n = @ ; CAPOX-C , n = @ ) .


In this population , after a median follow-up of @ months , in line with the initial analysis , the addition of cetuximab was associated with numerically higher , but not statistically significant , rates of complete response ( @ % versus @ % , p = @ ) , @-year progression-free survival ( @ % versus @ % , hazard ratio ( HR ) @ , p = @ ) and @-year overall survival ( @ % versus @ % , HR @ , p = @ ) .


RAS mutations beyond KRAS exon @ and @ were identified in @ % 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 @ plantar with plantar fasciitis were randomly divided into a combined group ( n = @ ) , an extracorporeal shock wave group ( n = @ ) and an orthopaedic group ( n = @ ) .


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 @ weeks , @ month and @ months , respectively .


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


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


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


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 @ month or @ months ( P < @ ) .


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


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 < @ ) .


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 @ % of basal PaO@/FiO@ ratio , increase of @ % of PaCO@ , worsening of alertness , respiratory distress , SpO@ less than @ % , exhaustion ) .


Between February @ and @ , @ patients were randomized to CPAP and @ to Venturi mask .


The proportion of patients meeting ETI criteria in the CPAP group was significantly lower compared to those in the control group ( @/@ = @ % vs. @/@ = @ % , respectively , p < @ ; relative risk @ , @ % CI @-@ @ ; number needed to treat , @ ) 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 < @ ) .


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 @-@ patients were randomly allocated into two groups .


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


Anesthesia was induced with propofol and fentanyl and maintained with N@O-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 @ h after surgery .


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


@ ( @ % ) patients reported nausea and @ ( @ % ) patients had vomiting in group P while @ ( @ % ) patients had nausea and @ ( @ % ) patients complained of vomiting in group DP during @-@ h. Two patients in group P reported nausea while none in group PD during @-@ h. No patient had vomiting in either of the groups between @-@ 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 @ clusters of @ households with @ 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 @,@ respondents in @,@ households , of which @,@ ( @ % ) were male and included in the study .


In total , @ males or @ % ( @ % CI @-@ @ ) reported a soft or reducible swelling likely representing a hernia with four men having two masses .


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


On disability assessment , @ % 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 @st , @ , and December @st , @ .


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 @,@ DDI alerts were generated in the study period , with @ % accepted .


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


Overall , @ % ( @/@ ) 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 ( @ % , n = @ ) , cardiotoxicity ( @ % , n = @ ) , or sharp falls in blood pressure or significant hypotension ( @ % , n = @ ) .


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


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


Providers sometimes reported that patients had already taken interacting medications together ( @ % , n = @ ) , 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 = @ ) or TAC-sensitive but frequent relapsing nephrotic syndrome ( n = @ ) were randomly recruited in the present study .


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


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 @ patients was significantly improved after the triple-combination therapy , while the frequent relapse rate in the following @months 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 @year follow up by Kaplan-Meier plot .


Triple-combination therapy with Pre + TAC+CTX / MMF/LEF is effective for short-term response and @year 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 = @ ) , 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 -LSB- OR , @ ; @ % confidence interval ( CI ) , @-@ @ -RSB- , toenails if healthy ( OR , @ ; @ % CI , @-@ @ ) or had cancer ( OR , @ ; @ % CI , @-@ @ ) , hair if healthy ( OR , @ ; @ % CI , @-@ @ ) or had cancer ( OR , @ ; @ % CI , @-@ @ ) , and unused cancerous tissue ( OR , @ ; @ % CI , @-@ @ ) .


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


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


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


Children on PB had @ and children on AHA had @ statistically significant ( P < @ ) beneficial changes from baseline ( mean decreases ) : body mass index z-score ( PB ) ( -@ ) , systolic blood pressure ( PB ) ( -@ mm Hg ) , total cholesterol ( PB ) ( -@ mg/dL ) , low-density lipoprotein ( PB ) ( -@ mg/dL ) , high-sensitivity C-reactive protein ( PB ) ( -@ mg/L ) , insulin ( PB ) ( -@ uU/mL ) , myeloperoxidase ( PB/AHA ) ( -@ / @ pmol/L ) , mid-arm circumference ( PB/AHA ) ( -@ / -@ cm ) , weight ( PB/AHA ) ( -@ / -@ kg ) , and waist circumference ( AHA ) ( -@ cm ) .


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


The significant change favoring AHA was a @ % 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 @ sites in India .


Treatment-naive patients who were sputum-smear positive , HIV negative , and had pulmonary tuberculosis were randomly assigned ( @:@ ) , with centrally labelled , serially numbered bottles , to receive standard active tuberculosis treatment with either supplemental high-dose oral vitamin D@ ( four doses of @ mg at weeks @ , @ , @ , and @ ) 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 NCT@ .


Between Jan @ , @ , and Aug @ , @ , we randomly assigned @ participants to the vitamin D group ( n = @ ) or the placebo group ( n = @ ) , of whom @ participants ( n = @ and n = @ , respectively ) were included in the primary efficacy analysis .


Median time to culture conversion in the vitamin D group was @ days ( @ % CI @-@ ) versus @ days ( @-@ ) in the placebo group ( log-rank p = @ ) .


Three ( @ % ) patients died in the vitamin D group and one ( @ % ) 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 .


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


Data from @,@ patients with chronic obstructive pulmonary disease ( COPD ) were pooled from @ clinical studies of QVA@ , indacaterol and glycopyrronium of @ month 's duration with at least two of the treatment groups : QVA@ @/@g , glycopyrronium @g , indacaterol @g , placebo or tiotropium @g .


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 QVA@ versus placebo showed no significant increase in the overall risk for death ( HR -LSB- @ % confidence interval -RSB- : @ -LSB- @-@ @ -RSB- ) ; CCV events ( @ -LSB- @-@ @ -RSB- ) ; MACE ( @ -LSB- @-@ @ -RSB- ) ; pneumonia ( @ -LSB- @-@ @ -RSB- ) ; COPD exacerbations ( @ -LSB- @-@ @ -RSB- ) ; and AF/F ( @ -LSB- @-@ @ -RSB- ) .


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 QVA@ , 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 , @-armed , bilateral , @-month clinical trial following the American National Standards Institute ( ANSI ) standard for Toric IOLs .


Subjects implanted with a TECNIS toric IOL ( n = @ ) or a TECNIS @-piece control IOL ( ZCB@ ; n = @ ) .


Subjects underwent standard cataract surgery with IOL implantation .


The randomized control arm consisted of subjects requiring cylinder correction of @ to @ diopters ( D ) who were implanted with either toric ( ZCT@ ) or nontoric ( ZCB@ ) IOLs .


The open-label arm ( OLA ) consisted of subjects requiring cylinder correction of @ to @ D and implanted with ZCT@ , ZCT@ , or ZCT@ IOLs .


Assessments were at @ day , @ week , and @ , @ , and @ 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 < @ ) for ZCT@ eyes ( @ @ % ) versus ZCB@ eyes ( @ @ % ) .


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


A UCDVA of @/@ or better was achieved by @ % ( @/@ ) of ZCT@ eyes and by @ % ( @/@ ) of ZCB@ eyes ( P = @ ) .


In the OLA , @ % ( @/@ ) achieved @/@ or better UCDVA .


Mean UCDVA was @ @ for ZCT@ eyes and @ @ for ZCB@ eyes ( P = @ ) ; in the OLA , mean UCDVA was @ @ .


The BCDVA was @/@ or better for all eyes .


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


Lens rotation of @ or less occurred in @ % of toric eyes between @ and @ months and in @ % between @ and @ months , exceeding the ANSI standard for stability ( @ % of eyes with @ of rotation between visits ) .


Four lenses ( @ % ) 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 @ children ( @-@ yrs old ) with Down syndrome .


They were assigned randomly using sealed envelopes , with @ children allocated to the control group ( @ boys , @ girls ) and another @ children allocated to the study group ( @ boys , @ 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 @ 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 @ mos of the treatment program .


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


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


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


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


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


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


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


Mean elimination half-life was up to @h .


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 AUC@-tau on Day @ .


TAK-@ caused dose-dependent acid suppression .


On Day @ , mean @-h intragastric pH > @ holding time ratio ( HTR ) with @mg TAK-@ was @ % ( Japan ) and @ % ( UK ) , and mean night-time pH > @ HTR was @ % ( Japan ) and @ % ( UK ) .


TAK-@ 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-@ dose .


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


Clinicaltrials.gov identifiers : NCT@ and NCT@ .


PhaseIII DEFEND-@ investigated whether otelixizumab ( @ mg over @days ) preserved C-peptide secretion in patients with new-onset Type@ diabetes , focusing on adolescents ( @-@years ) .


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


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


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


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


Change from baseline C-peptide was not significantly different -LSB- = -@ nmol/l ( @ % CI -@ to @ ; P = @ ) -RSB- .


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-@ .


The @-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 : NCT@ .


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 @ patients ( @ in CHA-CHA and @ in conventional ( Conv . )


arm completed the treatment ) .


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


Patients in the control ( Conv . )


arm group were irradiated with a fd of @ Gy , five times a week to a total dose of @-@ Gy in the overall treatment time of @-@ 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 @ % and in Conv .


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


Tumour regression @ 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 @ year , @ years , and @ 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 @-year outcomes .


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


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 @ year , we present here predefined outcomes at @ years .


The study is registered with ClinicalTrials.gov , number NCT@ .


We screened @ patients , of whom @ were enrolled ( @ assigned to TAVR , @ assigned to SAVR ) .


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


At @ years , risk of death was @ % in the TAVR group compared with @ % in the SAVR group ( hazard ratio @ , @ % CI @-@ ; p = @ ) .


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


Moderate or severe aortic regurgitation occurred in @ ( @ % ) of @ patients in the TAVR group and two ( @ % ) of @ in the SAVR group ( p < @ ) , and was associated with increased @-year risk of mortality in the TAVR group ( @ % for moderate or severe aortic regurgitation vs @ % for those with mild aortic regurgitation or less ; p = @ ) .


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


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 .


Magnetic resonance imaging ( MRI ) and TTE images were retrospectively reviewed in @ consecutive patients with pulmonary hypertension .


RV and left ventricular volumes and ejection fractions were calculated using MRI .


TTE areas and indices of RV ejection fraction ( RVEF ) were compared .


The average age was @ @ years , with a majority of women ( @ % ) .


There was a wide range of mean pulmonary arterial pressures ( @-@ mm Hg ) and RV end-diastolic volumes ( @-@ mL ) , RVEFs ( @ % -@ % ) , and left ventricular ejection fractions ( @ % -@ % ) by MRI .


There was a strong association between TTE and MRI-derived parameters : RV end-diastolic area ( by TTE imaging ) and RV end-diastolic volume ( by MRI ) , R ( @ ) = @ ( P < @ ) ; RV fractional area change by TTE imaging and RVEF by MRI , R ( @ ) = @ ( P < @ ) ; and tricuspid annular plane systolic excursion by TTE imaging and RVEF by MRI , R ( @ ) = @ ( P < @ ) .


By receiver operating characteristic curve analysis , an RV fractional area change < @ % provided excellent discrimination of moderate systolic dysfunction ( RVEF < @ % ) , with an area under the curve of @ ( P < @ ) .


An RV end-diastolic area index of @cm ( @ ) / m ( @ ) provided excellent discrimination for moderate RV enlargement ( area under the curve , @ ; P < @ ) .


Echocardiographic estimates of RV volume ( by RV end-diastolic area ) and function ( by RV fractional area change and tricuspid annular plane systolic excursion ) offer good approximations of RV size and function in patients with pulmonary hypertension and allow the accurate discrimination of normal from abnormal .


Previous studies have focused on the effect of food advertisements on the caloric intake of children .


However , the role of individual susceptibility in this effect is unclear .


The aim of this study was to examine the role of impulsivity in the effect of advergames that promote energy-dense snacks on children 's snack intake .


First , impulsivity scores were assessed with a computer task .


Then a randomized between-subject design was conducted with @ children aged @ to @ years who played an advergame promoting either energy-dense snacks or nonfood products .


As an extra manipulation , half of the children in each condition were rewarded for refraining from eating , the other half were not .


Children could eat freely while playing the game .


Food intake was measured .


The children then completed questionnaire measures , and were weighed and measured .


Overall , playing an advergame containing food cues increased general caloric intake .


Furthermore , rewarding children to refrain from eating decreased their caloric intake .


Finally , rewarding impulsive children to refrain from eating had no influence when they were playing an advergame promoting energy-dense snacks , whereas it did lead to reduced intake among low impulsive children and children who played nonfood advergames .


Playing an advergame promoting energy-dense snacks contributes to increased caloric intake in children .


The advergame promoting energy-dense snacks overruled the inhibition task to refrain from eating among impulsive children , making it more difficult for them to refrain from eating .


The findings suggest that impulsivity plays an important role in susceptibility to food advertisements .


The EVEREST II ( Endovascular Valve Edge-to-Edge REpair STudy ) High-Risk registry and REALISM Continued Access Study High-Risk Arm are prospective registries of patients who received the MitraClip device ( Abbott Vascular , Santa Clara , California ) for mitral regurgitation ( MR ) in the United States .


The purpose of this study was to report @-month outcomes in high-risk patients treated with the percutaneous mitral valve edge-to-edge repair .


Patients with grades @ to @ + MR and a surgical mortality risk of @ % , based on the Society of Thoracic Surgeons risk calculator or the estimate of a surgeon coinvestigator following pre-specified protocol criteria , were enrolled .


In the studies , @ of @ patients completed @ months of follow-up .


Patients were elderly ( @ @ years of age ) , with @ % having functional MR and @ % having prior cardiac surgery .


The mitral valve device reduced MR to @ + in @ % of patients at discharge ( n = @ ; p < @ ) .


Major adverse events at @ days included death in @ % , myocardial infarction in @ % , and stroke in @ % .


At @ months , MR was @ + in @ % of patients ( n = @ ; p < @ ) .


From baseline to @ months , left ventricular ( LV ) end-diastolic volume improved from @ @ ml to @ @ ml ( n = @ ; p < @ ) and LV end-systolic volume improved from @ @ ml to @ @ ml ( n = @ ; p < @ ) .


New York Heart Association functional class improved from @ % in class III/IV at baseline to @ % in class I/II at @ months ( n = @ ; p < @ ) .


The @-item Short Form Health Survey physical and mental quality-of-life scores improved from baseline to @ months ( n = @ ; p < @ ) .


Annual hospitalization rate for heart failure fell from @ % pre-procedure to @ % post-procedure ( n = @ ; p < @ ) .


Kaplan-Meier survival estimate at @ months was @ % .


The percutaneous mitral valve device significantly reduced MR , improved clinical symptoms , and decreased LV dimensions at @ months in this high-surgical-risk cohort .


( Endovascular Valve Edge-to-Edge REpair STudy -LSB- EVERESTIIRCT -RSB- ; NCT@ ) .


The aim of this study was to compare health-related quality of life ( HRQoL ) scores obtained from the instrument Short Form ( SF ) -@ through the so-called SF-@D utilities , and those obtained from @D , in patients with ST-elevation myocardial infarction ( STEMI ) , and to evaluate the consequences in estimation of quality adjusted life years ( QALYs ) .


This was a sub-study of the Norwegian District Treatment of STEMI , in which patients with STEMI treated with tenecteplase , were randomized to early angioplasty or standard management ( n = @ ) .


HRQoL data were collected at all visits ( @ , @ , @ , @ and @ months ) .


All patients with complete data were included ( n = @ ) .


The score range was @-@ @ for SF-@D and @-@ @ for @D .


Mean utility scores from @D were higher and had different distribution compared to scores from SF-@D .


Mean QALY for the whole group was higher using @D than SF-@D ( @ vs. @ ) .


The incremental number of QALYs with early angioplasty compared to standard treatment was @ ( @ % CI : - @ to @ ) using SF-@D , and @ ( @ % CI : - @ to @ ) using the @D instrument .


Choice of instrument may influence HRQoL scores , but not necessarily the gain in QALYs .


Post-thrombotic syndrome ( PTS ) is a common and burdensome complication of deep venous thrombosis ( DVT ) .


Previous trials suggesting benefit of elastic compression stockings ( ECS ) to prevent PTS were small , single-centre studies without placebo control .


We aimed to assess the efficacy of ECS , compared with placebo stockings , for the prevention of PTS .


We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for @ years to prevent PTS after a first proximal DVT in centres in Canada and the USA .


Patients were randomly assigned to study groups with a web-based randomisation system .


Patients presenting with a first symptomatic , proximal DVT were potentially eligible to participate .


They were excluded if the use of compression stockings was contraindicated , they had an expected lifespan of less than @ months , geographical inaccessibility precluded return for follow-up visits , they were unable to apply stockings , or they received thrombolytic therapy for the initial treatment of acute DVT .


The primary outcome was PTS diagnosed at @ months or later using Ginsberg 's criteria ( leg pain and swelling of @ month duration ) .


We used a modified intention to treat Cox regression analysis , supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment .


This study is registered with ClinicalTrials.gov , number NCT@ , and Current Controlled Trials , number ISRCTN@ .


From @ to @ , @ patients were randomly assigned to receive active ECS and @ placebo ECS .


The cumulative incidence of PTS was @ % in active ECS versus @ % in placebo ECS ( hazard ratio adjusted for centre @ , @ % CI @-@ ; p = @ ) .


Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings .


ECS did not prevent PTS after a first proximal DVT , hence our findings do not support routine wearing of ECS after DVT .


The results of SYNTAX trial have been reported based on `` corelab '' calculated SS ( cSS ) .


It has been shown that reproducibility of SS is better among the core laboratory technicians than interventional cardiologists .


Thus , the prognostic value and clinical implication of the `` site '' SYNTAX SS ( sSS ) remain unknown .


The study sought to evaluate the prognostic value and clinical implication of the sSS after percutaneous coronary intervention ( PCI ) or coronary artery bypass graft ( CABG ) surgery in the randomized SYNTAX trial .


The sSS was calculated by the site investigators before randomization in the SYNTAX trial .


New tertiles based on the sSS were defined with low ( @ to @ ) , intermediate ( @ to @ ) , and high ( @ ) scores .


The clinical endpoints were compared between PCI and CABG by Kaplan-Meier estimates , log-rank comparison , and Cox regression analyses using the new tertiles .


The sSS-based SS II was calculated and its predictive performance was evaluated .


The mean difference in cSS and sSS is @ @ , with a mean absolute difference of @ @ .


In the overall cohort , using sSS there was a higher incidence of major adverse cardiac and cerebrovascular events ( MACCE ) at @-year follow-up in the PCI group for low ( @ % vs. @ % ; p = @ ) , intermediate ( @ % vs. @ % ; p = @ ) , and high ( @ % vs. @ % ; p = @ ) tertiles , compared with the CABG group .


Similarly , in the @-vessel disease subgroup , @-year MACCE rates were higher in PCI group in all tertiles .


Conversely , in the left main subgroup , MACCE rates were similar for PCI and CABG groups in all tertiles .


The sSS-based SS II ( c-index : @ ) had predictive performance similar to the cSS-based SS II ( c-index : @ ) , with net reclassification index of -@ ( p = @ ) .


Appropriate training and unbiased assessment are needed when using SS in clinical decision making .


sSS and tertiles based on sSS showed poor discrimination among low , intermediate , and high-risk groups .


However , combining clinical factors with sSS retained the predictive performance of SS II .


( SYNTAX Study : TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries ; NCT@ ) .


Epidemiologic evidence has suggested that diets with a high ratio of palmitic acid ( PA ) to oleic acid ( OA ) increase risk of cardiovascular disease ( CVD ) .


To gain additional insights into the relative effect of dietary fatty acids and their metabolism on CVD risk , we sought to identify a metabolomic signature that tracks with diet-induced changes in blood lipid concentrations and whole-body fat oxidation .


We applied comprehensive metabolomic profiling tools to biological specimens collected from @ healthy adults enrolled in a crossover trial that compared a @-wk high-palmitic acid ( HPA ) with a low-palmitic acid and high-oleic acid ( HOA ) diet .


A principal components analysis of the data set including @ variables measured in @ subjects in the fasted state identified one factor , the principal components analysis factor in the fasted state ( PCF@-Fasted ) , which was heavily weighted by the PA : OA ratio of serum and muscle lipids , that was affected by diet ( P < @ ; HPA greater than HOA ) .


One other factor , the additional principal components analysis factor in the fasted state ( PCF@-Fasted ) , reflected a wide range of acylcarnitines and was affected by diet in women only ( P = @ ; HPA greater than HOA ) .


HOA lowered the ratio of serum low-density lipoprotein to high-density lipoprotein ( LDL : HDL ) in men and women , and adjustment for the PCF@-Fasted abolished the effect .


In women only , adjustment for the PCF@-Fasted eliminated the HOA-diet effect on serum total - and LDL-cholesterol concentrations .


The respiratory exchange ratio in the fasted state was lower with the HPA diet ( P = @ ) , and the diet effect was eliminated after adjustment for the PCF@-Fasted .


The messenger RNA expression of the cholesterol regulatory gene insulin-induced gene-@ was higher with the HOA diet ( P = @ ) .


These results suggest that replacing dietary PA with OA reduces the blood LDL concentration and whole-body fat oxidation by modifying the saturation index of circulating and tissue lipids .


In women , these effects are also associated with a higher production and accumulation of acylcarnitines , possibly reflecting a shift in fat catabolism .


To observe the effect of qi benefiting stasis removing method ( QBSRM ) on systemic inflammatory response and coagulation function in multiple organ dysfunction syndrome ( MODS ) patients .


Totally @ MODS patients who were admitted to Affiliated Hospital of Nanjing University of Traditional Chinese Medicine between May @ to December @ were randomly assigned to two groups , the experimental group ( @ cases ) and the control group ( @ cases ) .


Patients in the control group were treated with routine Western therapy , while those in the experimental group additionally took decoction for benefiting qi removing stasis .


Inflammatory factors ( including interleukin-@ , interleukin-@ , tumor necrosis factor-alpha ) and coagulation parameters -LSB- including prothrombin time ( PT ) , activated partial thromboplastin time ( APTT ) , fibrinogen ( FIB ) , and D-dimer ( DD ) -RSB- were observed before treatment , and @ , @ , and @ days after treatment in the two groups .


At day @ after treatment , levels of interleukin-@ , interleukin-@ , and PT were significantly lower in the experimental group than in the control group ( P < @ ) .


At day @ after treatment , tumor necrosis factor-x and DD were significantly lower in the experimental group than in the control group ( P < @ ) .


There was no statistical difference in APTT or FIB at day @ , @ and @ after treatment ( P > @ ) .


QBSRM could relieve systemic inflammatory response and improve coagulation functions .


We previously found that the use of ezetimibe increased rapidly with different patterns between the United States ( US ) and Canada prior to the landmark Ezetimibe and Simvastatin in Hypercholesterolemia Enhance Atherosclerosis Regression ( ENHANCE ) trial , which was reported in January @ , and failed to show that the drug slowed the progression of atherosclerosis .


What is not known is how practice in the @ countries changed after the ENHANCE trial .


We examined ezetimibe use trends in the US and Canada before and after the reporting of the ENHANCE trial .


We conducted a population-based , retrospective , time-series analysis using the data collected by IMS Health in the US and CompuScript in Canada from January @ , @ , to December @ , @ .


The main outcome measure was monthly number of prescriptions for ezetimibe-containing products .


The monthly number of ezetimibe prescriptions/@ ,@ population rose from @ to @,@ in the US from November @ to January @ , then significantly declined to @/@ ,@ population by December @ after the release of the ENHANCE trial , a decrease of @ % ( P < @ ) .


In contrast , in Canada , use continuously rose from @ to @/@ ,@ population from June @ to December @ ( P = @ ) .


United States expenditures totaled $ @ billion in @ .


Ezetimibe remains commonly used in both the US and Canada .


Ezetimibe use has decreased in the US post-ENHANCE , whereas use has gradually but steadily increased in Canada .


The diverging patterns of ezetimibe use in the US and Canada require further investigation , as they reveal that a common evidence base is eliciting very different utilization patterns in neighboring countries .


To compare mean heart and left anterior descending coronary artery ( LAD ) doses ( NTDmean ) and positional reproducibility in larger-breasted women receiving left breast radiotherapy using supine voluntary deep-inspiratory breath-hold ( VBH ) and free-breathing prone techniques .


Following surgery for early breast cancer , patients with estimated breast volumes > @ cm ( @ ) underwent planning-CT scans in supine VBH and free-breathing prone positions .


Radiotherapy treatment plans were prepared , and mean heart and LAD doses were calculated .


Patients were randomised to receive one technique for fractions @-@ , before switching techniques for fractions @-@ ( @ Gy/@ fractions total ) .


Daily electronic portal imaging and alternate-day cone-beam CT ( CBCT ) imaging were performed .


The primary endpoint was the difference in mean LAD NTDmean between techniques .


Population systematic ( ) and random errors ( ) were estimated .


Within-patient comparisons between techniques used Wilcoxon signed-rank tests .


@ patients were recruited , with complete dosimetric data available for @ .


Mean heart and LAD NTDmean doses for VBH and prone treatments respectively were @ and @ ( p < @ ) and @ and @ ( p < @ ) .


Clip-based CBCT errors for VBH and prone respectively were @ mm and @ mm ( ) and @ mm and @ mm ( ) .


In larger-breasted women , supine VBH provided superior cardiac sparing and reproducibility than a free-breathing prone position .


Depression is common in diabetes and linked to adverse health outcomes .


This study evaluated the efficacy of a guided web-based intervention in reducing depression in adults with type @ and type @ diabetes .


A total of @ participants with diabetes and elevated depressive symptoms ( Center for Epidemiologic Studies Depression Scale -LSB- CES-D @ -RSB- ) were randomly assigned to the GET.ON Mood Enhancer Diabetes ( a guided self-help intervention , n = @ ) or a brief online unguided psychoeducation program for depression ( n = @ ) .


The primary outcome was depressive symptoms severity ( CES-D ) .


The secondary outcomes included diabetes-specific emotional distress ( Problem Areas in Diabetes -LSB- PAID -RSB- scale ) and participant satisfaction ( adaption CSQ-@ ) .


Data were collected at baseline and @ months after randomization .


To identify differences in outcome between the groups , we used analyses of covariance with the baseline CES-D score as covariate on both intent-to-treat ( ITT ) and per-protocol ( PP ) basis .


Compared with the control group , the intervention group showed significantly less depressive symptom severity at posttreatment based on ITT ( d = @ ) and PP analyses ( d = @ ) .


The intervention participants displayed a significantly larger reduction in diabetes-specific emotional distress ( d = @ , ITT ) .


The intervention appeared to be acceptable to the participants ; @ % ( n = @ ) would recommend the training to a friend with diabetes in need of psychological help .


A guided , web-based intervention to reduce depression in adults with type @ and type @ diabetes is effective in reducing both depressive symptoms and diabetes-specific emotional distress .


Dietary sodium influences intermediate physiological traits in healthy adults independent of changes in blood pressure .


The purpose of this study was to test the hypothesis that dietary sodium affects cardiac autonomic modulation during mental stress .


In a prospective , randomized cross-over design separated by @ month between diets , @ normotensive healthy young adults ( F/M : @/@ , aged @-@ years ) consumed a @-day low ( @ mmol/day ) , normal ( @ mmol ) , and high ( @ mmol ) sodium diet followed by heart rate variability ( HRV ) recordings at rest and during @-min computerized mental arithmetic .


Women were studied in the low hormone phase of the menstrual cycle following each diet .


Diet did not affect resting blood pressure , but heart rate ( HR ) ( mean SE ) was @ @ , @ @ , and @ @ bpm in low , normal , and high sodium conditions , respectively ( analysis of variance P = @ ) .


For HRV , there was a main effect of sodium on resting SD of normalized RR intervals ( SDNN ) , square root of the mean squared difference of successive normalized RR intervals ( RMSSD ) , high frequency , low-frequency normalized units ( LFnu ) , and high-frequency normalized units ( HFnu ) ( P < @ for all ) .


The response to low sodium was most marked and consistent with sympathetic activation and reduced vagal activity , with increased LFnu and decreased SDNN , RMSSD , and HFnu compared to both normal and high sodium conditions ( P @ for all ) .


Dietary sodium-by-mental stress interactions were significant for mean NN , RMSSD , high-frequency power , LFnu , and low frequency/high frequency ratio ( P < @ for all ) .


The interactions signify that sodium restriction evoked an increase in resting sympathetic activity and reduced vagal activity to the extent that mental stress caused modest additional disruptions in autonomic balance .


Conversely , normal and high sodium evoked a reduction in resting sympathetic activity and incremental increase in resting vagal activity , which were disrupted to a greater extent during mental stress compared to low sodium .


We conclude that autonomic control of HRV at rest and during mental stress is altered by dietary sodium in healthy normotensive young adult men and women .


Beta-palmitate ( sn-@ palmitate ) mimics human milk fat , enabling easier digestion.Therefore , we hypothesized that infants consuming high beta-palmitate formula would have more frequent , softer stools and reduced crying compared to infants consuming low beta-palmitate formula .


Formula-fed infants were randomly assigned to receive either ( @ ) formula with high beta-palmitate ( HBP , n = @ ) or ( @ ) regular formula with a standard vegetable oil mix ( LBP , n = @ ) .


A matched group of breastfed infants served as a reference ( BF , n = @ ) .


Crying and stool characteristics data were recorded by the parents for @ days before the @ - and @-week visits .


We found no significant differences in the stool frequency or consistency between the two formula groups .


The percentage of crying infants in the LBP group was significantly higher than that in the HBP and BF groups during the evening at @ weeks ( @ % vs. @ % and @ % , p < @ ) and during the afternoon at @ weeks ( @ % vs. @ % and @ % , p < @ ) .


The infants fed HBP had significantly shorter crying durations when compared with infants fed LBP formula ( @ @ vs. @ @ min/day , respectively ; p = @ ) .


Our study indicates that consumption of a high beta-palmitate formula affects infant crying patterns during the first weeks of life .


Comparable to breastfeeding , it reduced crying duration and frequency , primarily during the afternoon and evening hours , thereby improving the well-being of formula-fed infants and their parents .


Acne vulgaris is a common inflammatory disorder of the skin that involves pilosebaceous units .


This study was conducted to compare the efficacy of oral azithromycin with oral doxycycline in the treatment of acne vulgaris in our population .


This randomized controlled trial was conducted in the dermatology department of Lady Reading Hospital , Peshawar from January to December @ .


All male and female patients of age ( @-@ years ) having moderate acne vulgaris on face only were included in the study .


Patients were randomly divided into two groups .


Patients in first group were given azithromycin @ mg daily before meal for @ consecutive days monthly for @ months while patients in second group were given doxycycline @ mg daily after meals for @ months .


Patients were followed up after taking treatment for three months to see the response of each drug .


Response was graded as excellent , good , moderate , mild and no response .


A total of @ patients equally divided in azithromycin and doxycycline groups .


Male to female ratio in azithromycin and doxycycline groups was @:@ and @:@ respectively .


Mean age in both groups was @ @ years and @ @ years respectively .


In azithromycin group , an excellent response was noted in @ ( @ % ) , and good response was observed in @ ( @ % ) patients .


In doxycycline group @ ( @ % ) patients had excellent and @ ( @ % ) patients had good response .


The difference being statistically significant .


Doxycycline is a better option fdr treatment of acne vulgaris as compared to azithromycin .


Residents often teach medical students , other residents , and patients .


However , few residents get feedback about their teaching .


This study 's objective was to determine if feedback from medical students increases resident teaching identity .


This was a stratified , single blinded , randomized controlled trial of an educational intervention .


Residents were stratified based on year of residency and then randomized to receive feedback by medical students or not .


Medical students evaluated resident teaching effectiveness by ranking resident ability to apply the five microskills for clinical teaching and to role model being an effective clinician .


Residents were surveyed to determine their level of teacher identity before and after the intervention .


Allocation concealment and intention to treat principles were used .


All residents ( n = @ ) that met inclusion criteria participated with complete response rate to both pre-intervention and post-intervention surveys .


There was no difference in teaching identity between residents who received feedback and those who did not , except in one subscale of the Teacher Identity Scale-global teaching identity , where residents who received medical student feedback scored lower .


There was no difference between intervention and control group in resident teaching identity over time .


The residents found feedback important .


This was a randomized controlled trial with strong methodology that helps advance understanding of the importance of medical student feedback on resident teaching .


No available treatments slow or halt progression of multiple system atrophy , which is a rare , progressive , fatal neurological disorder .


In a mouse model of multiple system atrophy , rifampicin inhibited formation of - synuclein fibrils , the neuropathological hallmark of the disease .


We aimed to assess the safety and efficacy of rifampicin in patients with multiple system atrophy .


In this randomised , double-blind , placebo-controlled trial we recruited participants aged @-@ years with possible or probable multiple system atrophy from ten US medical centres .


Eligible participants were randomly assigned ( @:@ ) via computer-generated permuted block randomisation to rifampicin @ mg twice daily or matching placebo ( @ mg riboflavin capsules ) , stratified by subtype ( parkinsonian vs cerebellar ) , with a block size of four .


The primary outcome was rate of change ( slope analysis ) from baseline to @ months in Unified Multiple System Atrophy Rating Scale ( UMSARS ) I score , analysed in all participants with at least one post-baseline measurement .


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


Between April @ , @ , and April @ , @ , we randomly assigned @ participants ( @ to rifampicin and @ to placebo ) .


Four participants in the rifampicin group and five in the placebo group withdrew from study prematurely .


Results of the preplanned interim analysis ( n = @ in each group ) of the primary endpoint showed that futility criteria had been met , and the trial was stopped ( the mean rate of change -LSB- slope analysis -RSB- of UMSARS I score was @ points -LSB- SD @ -RSB- per month in the rifampicin group vs @ points -LSB- @ -RSB- per month in the placebo group ; futility p = @ ; efficacy p = @ ) .


At the time of study termination , @ participants in the rifampicin group and @ in the placebo group had follow-up data and were included in the final analysis .


The primary endpoint was @ points ( SD @ ) per month for rifampicin and @ points ( @ ) per month for placebo ( difference @ , @ % CI -@ to @ ; p = @ ) .


Three ( @ % ) of @ participants in the rifampicin group and @ ( @ % ) of @ in the placebo group had one or more serious adverse events ; none was thought to be related to treatment .


Our results show that rifampicin does not slow or halt progression of multiple system atrophy .


Despite the negative result , the trial does provide information that could be useful in the design of future studies assessing potential disease modifying therapies in patients with multiple system atrophy .


There is no consensus on what type of arthroplasty is best for the treatment of complex proximal humeral fractures in elderly patients .


The purpose of this prospective study was to compare the outcomes of reverse shoulder arthroplasty ( RSA ) and hemiarthroplasty ( HA ) .


Sixty-two patients older than @ years were randomized to RSA ( @ patients ) and HA ( @ patients ) .


One HA patient died at @ year , and she was excluded .


The mean follow-up was @ months ( range , @-@ months ) .


Compared with HA patients , RSA patients had significantly higher ( P = @ ) mean University of California-Los Angeles ( @ vs @ ) and Constant ( @ vs @ ) scores , forward elevation ( @ vs @ ) , and abduction ( @ vs @ ) but no difference in internal rotation ( @ vs @ ; P = @ ) .


The Disabilities of the Arm , Shoulder , and Hand score was higher in the HA patients ( @ vs @ ; P = @ ) .


In the HA group , @ % of tuberosities healed and @ % resorbed .


Patients with failure of tuberosities had significantly worse functional outcomes .


There were @ complications ( intraoperative humeral fracture and superficial infection ) .


One patient was manipulated under general anesthesia because of postoperative stiffness .


Six patients with HA had proximal migration that required revision to RSA .


In the RSA group , @ % of tuberosities healed and @ % resorbed .


Functional outcome was irrespective of healing of the tuberosities .


Notching was observed in only @ RSA patient .


One patient developed a hematoma and another a deep infection requiring a @-stage revision to another RSA .


RSA resulted in better pain and function and lower revision rate .


Revision from HA to RSA does not appear to improve outcomes .


This study examined the feasibility of a prototype Web-based acceptance and commitment therapy ( ACT ) program for preventing mental health problems among college students .


Undergraduate first-year students ( N = @ ) participated between May and November @ .


Participants were randomized to ACT or a waitlist , with assessments conducted at baseline , posttherapy , and @-week follow-up .


Waitlist participants accessed the program after the second assessment .


Program usability/usage data indicated high program acceptability .


Significant improvements were found for ACT knowledge , education values , and depression with ACT relative to waitlist .


Subgroup analyses indicated that ACT decreased depression and anxiety relative to waitlist among students with at least minimal distress .


Within the ACT condition , significant improvements were observed from baseline to @-week follow-up on all outcome and process measures .


Results provide preliminary support for the feasibility of a Web-based ACT prevention program .


Breast International Group ( BIG ) @-@ is a randomised phase III trial that tested the effect of adding docetaxel , either in sequence to or in combination with anthracycline-based adjuvant chemotherapy , in women with node-positive breast cancer ( BC ) .


Here , we present the @-year final trial safety and efficacy analyses .


We also report an exploratory analysis on the predictive value of Ki@ for docetaxel efficacy , in the BIG @-@ and using a pooled analysis of three other randomised trials .


@ patients were randomly assigned in a @ trial design to one of four treatments .


The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival ( DFS ) .


Secondary objectives included comparisons of sequential docetaxel versus sequential control arm , safety and overall survival ( OS ) .


Ki@ expression was centrally evaluated by immunohistochemistry .


After a median follow-up of @ years , the addition of docetaxel did not significantly improve DFS or OS ( hazard ratio ( HR ) = @ , @ % confidence interval ( CI ) = @-@ @ ; P = @ and HR = @ , @ % CI = @-@ @ ; P = @ , respectively ) .


Sequential docetaxel did not improve DFS compared to the sequential control arm ( HR = @ , @ % CI = @-@ @ ; P = @ ) .


In oestrogen receptor ( ER ) - positive tumours with Ki@ % , the addition of docetaxel resulted in @ % improvement in @-year OS ( P = @ , test for interaction = @ ) .


In a multivariate model , there was a trend for improved DFS and OS in ER-positive patients with high Ki@ and treated with docetaxel ( HR = @ , @ % CI = @-@ @ ; P = @ and HR = @ , @ % CI = @-@ @ ; P = @ , respectively ) .


A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours ( interaction test P = @ ) .


The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at @years .


However , an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC .


A wide range of herbal plants have been reported to treat various gynecological problems of women .


This study was set out to investigate the effect of ginger ( Zingiber officinale ) on heavy menstrual bleeding ( HMB ) in high school girls .


Ninety-two young women who experienced HMB and met the inclusion criteria were recruited in this study .


Participants were evaluated for six consecutive menstrual cycles .


During @ assessment cycles , their HMB was confirmed by Pictorial Blood Assessment Chart .


They were then randomly allocated to two study groups to receive either ginger or placebo capsules .


The participants filled in the same chart during three intervention cycles .


The level of menstrual blood loss dramatically declined during the three intervention cycles in ginger-receiving group .


The decrease of blood loss in ginger-receiving group was significantly more remarkable than that of participants receiving placebo ( p < @ ) .


Minimum number of participants reported adverse effects .


HMB is highly prevalent among young women .


Considering the significance of appropriate and timely treatment and also the importance of prevention of unwanted consequences , ginger may be considered as an effective therapeutic option for HMB .


Early oral feeding ( EOF ) following colorectal surgery can accelerate patient recovery and shorten hospital stay .


However , some patients are intolerable to postoperative early oral feeding .


The aim of this study was to evaluate the tolerability of EOF following laparoscopic colorectal cancer surgery and the effects of intravenous lidocaine .


The cohort in this randomized , placebo-controlled trial ( ClinicalTrial.gov , NCT@ ) comprised of @ patients undergoing elective laparoscopic colorectal cancer surgery .


For patients randomized to the lidocaine group , a loading dose of @mg/kg lidocaine prior to skin incision , and a continuous dose of @mg/kg/h lidocaine with @mg ketorolac ( non-steroidal anti-inflammatory drug ) ( in normal saline , total @mL ) was administered for @h .


Patients randomized to the placebo group received a loading dose of @mL saline and a continuous dose of @mg ketorolac in @mL saline .


The primary outcome measure was prevalence of postoperative nausea/vomiting and intolerance to EOF .


Altogether , @ patients completed the study and were analyzed .


Postoperative nausea and vomiting were higher in the control group but did not reach statistical significance ( P = @ ) .


Tolerability of EOF was @ % in the lidocaine group and @ % in the control group ( P = @ ) .


There was no difference in postoperative pain , opioid consumption , bowel function recovery or postoperative hospital stay .


Perioperative intravenous lidocaine administered for laparoscopic colorectal cancer surgery might reduce postoperative nausea and vomiting .


However , a high tolerability to EOF following colorectal surgery can be achieved by laparoscopic surgery alone without other supportive treatment .


Developing and evaluating interventions for patients with age-associated disorders is a rising field in psychotherapy research .


Its methodological challenges include the high between-subject variability and the wealth of influencing factors associated with longer lifetime .


Latent change score modeling ( LCSM ) , a technique based on structural equation modeling , may be well suited to analyzing longitudinal data sets obtained in clinical trials .


Here , we used LCSM to evaluate the antidepressant effect of a combined cognitive behavioral/cognitive rehabilitation ( CB/CR ) intervention in Alzheimer 's disease ( AD ) .


LCSM was applied to predict the change in depressive symptoms from baseline as an outcome of the CORDIAL study , a randomized controlled trial involving @ patients with mild AD .


The participants underwent either the CORDIAL CB/CR program or standard treatment .


Using LCSM , the model best predicting changes in Geriatric Depression Scale scores was determined based on this data set .


The best fit was achieved by a model predicting a decline in depressive symptoms between before and after testing .


Assignment to the intervention group as well as female gender revealed significant effects in model fit indices , which remained stable at @ - and @-month follow-up examinations .


The pre-post effect was pronounced for patients with clinically relevant depressive symptoms at baseline .


LCSM confirmed the antidepressant effect of the CORDIAL therapy program , which was limited to women .


The effect was pronounced in patients with clinically relevant depressive symptoms at baseline .


Methodologically , LCSM appears well suited to analyzing longitudinal data from clinical trials in aged populations , by accounting for the high between-subject variability and providing information on the differential indication of the probed intervention .


The aim of this study is to examine the relationship between time in the therapeutic range ( TTR ) and clinical outcomes in heart failure patients in sinus rhythm treated with warfarin .


We used data from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction ( WARCEF ) trial to assess the relationship of TTR with the WARCEF primary outcome ( ischemic stroke , intracerebral hemorrhage , or death ) , with death alone , ischemic stroke alone , major hemorrhage alone , and net clinical benefit ( primary outcome and major hemorrhage combined ) .


Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR , low TTR , and aspirin-treated patients , with TTR being treated as a time-dependent covariate .


A total of @ patients were included in the analyses ; among whom @ were randomized to warfarin and @ were randomized to aspirin .


The median ( interquartile range ) follow-up duration was @ ( @-@ @ ) years .


Mean ( SD ) age was @ years , with @ % being men .


The mean ( SD ) TTR was @ % ( @ % ) .


Increasing TTR was significantly associated with reduction in primary outcome ( adjusted P < @ ) , death alone ( adjusted P = @ ) , and improved net clinical benefit ( adjusted P < @ ) .


A similar trend was observed for the other @ outcomes , but significance was not reached ( adjusted P = @ for ischemic stroke and adjusted P = @ for major hemorrhage ) .


In patients with heart failure in sinus rhythm , increasing TTR is associated with better outcome and improved net clinical benefit .


Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants .


To assess the adequacy of different amounts of local anesthetics ( LA ) in infraclavicular blockade ( ICB ) under ultrasonographic ( US ) guidance and neurostimulation and compare them to the conventional doses under neurostimulation ( NS ) .


In this study @ patients scheduled for upper limb surgery and suitable for ICB were randomly allocated to @ of @ groups : group NS ( NS alone group @ ml/kg LA ) , group FD ( full-dose US group @ ml/kg LA ) , group @ ( @ % reduced dose LA @ ml/kg ) , group @ ( @ ml/kg LA ) and group @ ( @ ml/kg LA ) .


The ICB was performed under US in conjunction with NS in all groups except group NS in which neurostimulation was used alone .


When necessary local anesthetic supplementation to the operation site was administered during surgery and propofol infusion for sedation ensued .


Evaluation of sensory and motor block was performed for each terminal nerve ( i.e. radial , ulnar , median and musculocutaneous nerves ) .


Block quality ( assessing the need for rescue LA and propofol sedation ) and duration of the block were documented .


None of the patients in the FD and @ groups required any supplementation or sedation , whereas LA supplementation rates were @ % in group @ and @ % in groups @ and NS .


The propofol sedation rates were @ % in group NS , @ % in group @ and @ % in group @ .


Sensory block was significantly better in groups FD , @ and NS at @ min .


A complete block was achieved more rapidly in all nerve territories in the full-dose group ( p = @ ) .


Block duration was longest in group FD and was significantly longer in group @ than in the other two groups ( p = @ ) .


The results show that US guidance is more effective in maintenance of successful ICB than neurostimulation guidance alone and a reduction of LA doses even to @ % of conventionally used doses seems possible with US guidance .


This article is published in English .


This study aimed to compare the effectiveness and safety of triphasic combined oral contraceptives ( OCs ) containing ethinyl estradiol ( EE ) and norgestimate ( NGM ) and biphasic combined OCs containing EE and desogestrel ( DSG ) in the treatment of mild to moderate acne .


This was an investigator-blinded , randomized , parallel group trial conducted at @ centers in Thailand .


Female subjects @-@ years old were assigned to one or the other OCs and evaluated for efficacy and safety parameters at the baseline visit and after @ , @ and @ months of treatment .


Among @ randomized subjects , data from @ subjects in the EE/NGM group and @ subjects in the EE/DSG group were analyzed .


After @ months of treatment with EE/NGM and EE/DSG , no differences between formulations were found for the decrease in total acne lesion counts ( @ % vs. @ % , respectively , p = @ ) or facial improvement score .


More women using EE/NGM showed a decrease in severity of facial seborrhea than those using EE/DSG ( p = @ ) .


No changes in weight were noted in either group as compared to baseline .


Multiphasic OCs containing EE/NGM and EE/DSG provided comparable efficacy and tolerability in the treatment of acne .


However , EE/NGM had a more beneficial effect on facial seborrhea reduction than EE/DSG .


EE/NGM and EE/DSG are multiphasic OCs , which were shown to be clinically equally effective for mild to moderate facial acne , and the multiphasic combined OC with NGM was more effective for women with facial seborrhea .


Clinicians may apply the results of this study when considering treatment options for facial acne and seborrhea .


Forehead and glabella rhytides are treated mostly with neurotoxins , although some practitioners prefer the concurrent use of fillers .


It has been suggested that combination treatments can result in a better overall improvement .


To compare the safety and effectiveness of treatment of forehead and glabellar lines with botulinum toxin A alone versus botulinum toxin A and filler .


Split-face , randomized control trial .


Twenty subjects with forehead/glabellar rhytide complex ( static and dynamic creases ) enrolled .


Subjects were randomized and injected with botulinum toxin alone on one side of the forehead/glabella and hyaluronic acid filler followed by botulinum toxin on the other side .


Blinded ratings were obtained to assess the effectiveness of treatment for static and dynamic rhytides , respectively , at @-week , @-week , @-month , and @-month follow-up visits .


Subjects performed a self-evaluation at the end of the study .


Adverse events were recorded .


Ratings of both treatments showed comparable efficacy , with @ % of subjects experiencing improvement from baseline regardless of treatment type at weeks @ , @ , and @ .


Combination treatment produced longer-lasting results in dynamic forehead wrinkles , and greater static and dynamic wrinkle reduction in the glabella at week @ .


Subject self-evaluations showed that both treatments were effective , with a nominal preference for combination treatment .


Glabella and forehead lines can be effectively and safely reduced with neurotoxin alone as well as neurotoxin in combination with fillers .


Combination treatment may provide a slightly better cumulative benefit and also increase the persistence of effect .


Remote ischemic preconditioning ( RIPC ) by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting ( CABG ) .


Activation of signal transducer and activator of transcription @ ( STAT@ ) in left ventricular ( LV ) myocardium at early reperfusion is associated with such protection .


Autophagy , i.e. , removal of dysfunctional cellular components through lysosomes , has been proposed as one mechanism of cardioprotection .


Therefore , we analyzed whether or not the protection by RIPC is associated with activated autophagy .


CABG patients were randomized to undergo RIPC ( @ min blood pressure cuff inflation/@ min deflation ) or placebo ( cuff deflated ) before skin incision ( n = @/@ ) .


Transmural myocardial biopsies were taken from the LV before cardioplegia ( baseline ) and at early ( @-@ min ) reperfusion .


RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve ( @ versus @ ng/ml @ h , p = @ ) .


Western blotting for beclin-@-phosphorylation and protein expression of autophagy-related gene @-@ ( ATG@-@ ) complex , light chain @ ( LC@ ) , parkin , and p@ was performed .


STAT@ - , STAT@ - and extracellular signal-regulated protein kinase @/@ ( ERK@/@ ) - phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion .


Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo .


STAT@-phosphorylation was greater at early reperfusion only with RIPC ( @-fold , p = @ ) .


STAT@ - and ERK@/@-phosphorylation were greater at early reperfusion with placebo and RIPC ( @-fold versus baseline , p@ @ ) .


Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion .


The aim of this study was to evaluate the treatment effect of diquafosol @ % with preservative-free sodium hyaluronate @ % eye drops in dry eye syndrome .


In total , @ patients with dry eye syndrome were divided randomly into @ groups .


Group @ ( @ patients ) was treated @ times daily with preserved sodium hyaluronate @ % , group @ ( @ patients ) was treated @ times daily with diquafosol @ % , and group @ ( @ patients ) was treated @ times daily with diquafosol @ % and preservative-free sodium hyaluronate @ % eye drops for @ months .


Ocular surface disease index ( OSDI ) score , tear film break-up time , Schirmer I test , corneal fluorescein staining , and impression cytology were evaluated .


There were significant improvements in the OSDI score , tear film break-up time , Schirmer I score , fluorescein and Rose Bengal staining , goblet cell density , and impression cytological findings in groups @ and @ compared with those for group @ in patients with dry eye syndrome at @ , @ , and @ months ( P < @ ) .


There were statistically significant improvements in the OSDI score ( -@ @ , -@ @ ; P = @ ) , fluorescein ( -@ @ , -@ @ ; P = @ ) , and Rose Bengal staining ( -@ @ , -@ @ ; P = @ ) , goblet cell density ( @ @ , @ @ ; P = @ ) , and impression cytological findings ( -@ @ , -@ @ ; P = @ ) in group @ compared with those in group @ at @ months .


Treatment with diquafosol @ % with preservative-free sodium hyaluronate @ % was more effective than diquafosol @ % monotherapy or treatment with preserved sodium hyaluronate @ % in dry eye syndrome .


Preservative-free sodium hyaluronate @ % eye drops can increase the effect of diquafosol @ % in dry eye syndrome .


The aim of this prospective comparative study was to compare outcomes and complications of humeral diaphyseal fracture non-unions managed with humerus interlocking nail ( HIL ) and locking compression plate ( LCP ) .


@ patients with non-union of humeral diaphyseal fractures were included in this study and were randomly allocated in two groups ; group A had @ cases treated with HIL and group B had @ cases treated with LCP .


Clinico-radiological assessments were done for each case up to @-year follow-up period .


Primary outcome measures ( time to fracture union , union rate ) and secondary outcome measures ( functional outcome and complication such as infection , malunion , delayed union , implant failure , joint stiffness and iatrogenic radial nerve palsy ) were compared between both the groups .


Disabilities of the arm , shoulder and hand ( DASH ) scoring and Steward and Hundley 's scoring system were used to assess functional outcome of the fracture fixation .


There was no significant difference ( p = @ ) in terms of mean fracture union time between group A ( @ @ weeks ) and group B ( @ @ weeks ) .


Group A had @ % union rate and group B had @ % union rate ( p = @ ) .


At the @-year follow-up visit , there was no significant difference found between both the groups regarding range of motion of shoulder and elbow joint .


There was no significant difference found in final functional outcomes between both the groups on comparing DASH score ( p = @ ) and Steward and Hundley 's score ( p = @ ) .


In terms of complications , there was insignificant difference found between both the groups .


This study concludes that both the implants can be used in non-union of humeral shaft fractures with good functional outcomes and acceptable rate of complications .


The aim of the study was to compare the efficacy of a microorganism-binding ( MB ) dressing with a silver-containing hydrofiber ( SCH ) dressing in controlling the bacterial loads of heavily colonised or locally infected chronic venous leg ulcers , before surgical management with homologous skin grafts .


A randomised comparative single centre study recruited patients presenting with hard-to-heal critically colonised or locally infected leg ulcers , who could be treated with skin grafting .


Inclusion criteria included ; ulcers of vascular aetiology , over @ years old , a wound duration @ months and ankle brachial index ( ABPI ) > @ .


Patients were randomly assigned to treatment with SCH dressings ( Aquacel Ag ) or MB dressing ( Cutimed Sorbact ) .


Dressings were changed daily over a four-day observation period , after which they were taken for a skin grafting procedure .


Swab samples from ulcer beds were taken in order to quantify the bacterial load at inclusion ( D@ ) and at the end of the observation period day @ ( D@ ) .


No antibiotics were administered before or during the evaluation period .


Both groups ( n = @ SCH , n = @ MB ) were similar in gender , age , pathophysiology ( both had @ patients with venous leg ulcers and @ with arterial leg ulcers ) , ulcer surface , ulcer duration , treatment-related pain and initial bacterial load .


Analysing bacterial load variation showed a significant reduction of bacterial burden at D@ in both groups .


In the SCH group , we found an average bacterial load reduction of @ % , with an average reduction of @ % in the MB group ( p < @ ) .


No serious adverse events were reported .


Our evaluation confirmed that MB and SCH dressings are effective in reducing the bacterial burden in critically colonised or locally infected chronic leg ulcers , without inducing adverse events , with MB dressings significantly more effective .


The effectiveness of antimicrobial prophylaxis ( AMP ) in the prevention of surgical site infection ( SSI ) following thyroid and parathyroid surgery remains uncertain .


The objective of this prospective randomized controlled trial ( Ito-RCT@ ) was to assess the effectiveness of AMP in clean neck surgery performed to treat thyroid and parathyroid disease .


Participants comprised patients scheduled for clean neck surgery for thyroid and parathyroid disease at Ito Hospital .


Patients whose surgery included sternotomy or resection of the trachea , larynx , pharynx , or esophagus were excluded .


AMP consisted of @ g of piperacillin ( PIPC ) ( group A , n = @ ) or @ g of cefazolin ( CEZ ) ( group B , n = @ ) administered intravenously immediately after endotracheal intubation .


Patients in the control group ( Group C , n = @,@ ) did not receive AMP .


Statistical analysis was performed to compare the AMP group ( Group A + Group B ) with the control group ( Group C ) .


Drug-induced acute reactions correlated to PIPC or CEZ did not occur in the AMP group .


No significant differences in the postoperative incidence of liver or renal dysfunction were seen between the AMP and control groups .


Postoperative incidence of urinary tract infection was significantly higher in the control group ( p = @ ) .


The incidence of SSI events was very low , with only @ event ( @ % ) in the AMP group and @ events ( @ % ) in the control group , and this difference between groups was not significant ( p = @ ) .


AMP is not necessary to prevent SSI after clean thyroid or parathyroid surgery .


To investigate how suppression of endogenous testosterone during an @-week strength training period influences the activity of satellite cells and myonuclei .


Twenty-two moderately trained young men participated in this randomized , placebo-controlled , and double-blinded intervention study .


The participants were randomized to treatment with a GnRH analogue , goserelin ( n = @ ) , which suppresses testosterone or placebo ( n = @ ) for @ weeks .


The strength training period of @ weeks started after @ weeks of treatment and included exercises for all major muscles .


Biopsies were obtained from the mid-portion of the vastus lateralis muscle .


Testosterone resting level in goserelin was @-@ times lower compared with placebo , and the training-induced increase in the level of testosterone was abolished in goserelin .


Training increased satellite cells number in type II fibres by @ % in placebo and by @ % in goserelin ( P < @ ) , whereas the myonuclear number significantly increased by @ % in type II fibres in placebo and remained unchanged in goserelin ( P < @ ) .


No changes in satellite cells and myonuclei were seen in type I fibres in either group .


Data from the microarray analysis indicated that low testosterone affects the bone morphogenetic proteins signalling , which might regulate proliferation vs. differentiation of satellite cells .


Eight weeks of strength training enhances the myonuclear number in type II fibres , and this is largely blocked by the suppression of testosterone .


The data indicate that low testosterone levels could reduce the differentiation of satellite cells to myonuclei via the bone morphogenetic proteins signalling pathway , resulting in reduced increases in lean leg mass .


A previous pilot trial evaluating computer-based training for cognitive-behavioral therapy ( CBT@CBT ) in @ heterogeneous substance users ( alcohol , marijuana , cocaine , and opioids ) demonstrated preliminary support for its efficacy in the context of a community-based outpatient clinic .


The authors conducted a more definitive trial in a larger , more homogeneous sample .


In this randomized clinical trial , @ cocaine-dependent individuals maintained on methadone were randomly assigned to standard methadone maintenance or methadone maintenance with weekly access to CBT@CBT , with seven modules delivered within an @-week trial .


Treatment retention and data availability were high and comparable across the treatment conditions .


Participants assigned to the CBT@CBT condition were significantly more likely to attain @ or more consecutive weeks of abstinence from cocaine ( @ % compared with @ % ; p < @ , odds ratio = @ ) .


The group assigned to CBT@CBT also had better outcomes on most dimensions , including urine specimens negative for all drugs , but these reached statistical significance only for individuals completing the @-week trial ( N = @ ) .


Follow-up data collected @ months after treatment termination were available for @ % of the randomized sample ; these data indicate continued improvement for those assigned to the CBT@CBT group , replicating previous findings regarding its durability .


This trial replicates earlier findings indicating that CBT@CBT is an effective adjunct to addiction treatment with durable effects .


CBT@CBT is an easily disseminable strategy for broadening the availability of CBT , even in challenging populations such as cocaine-dependent individuals enrolled in methadone maintenance programs .


Hepatitis C virus ( HCV ) genotype @ accounts for about @ % of global HCV infections .


Because interferon-containing treatments for genotype @ infection have low efficacy and poor tolerability , an unmet need exists for effective all-oral regimens .


We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir , an NS@A inhibitor , and paritaprevir ( ABT-@ ) , an NS@/@A protease inhibitor dosed with ritonavir ( ombitasvir plus paritaprevir plus ritonavir ) , given with or without ribavirin .


In this multicentre ongoing phase @b , randomised , open-label combination trial ( PEARL-I ) , patients were recruited from academic , public , and private hospitals and clinics in France , Hungary , Italy , Poland , Romania , Spain , Turkey , and the USA .


Eligible participants were aged @-@ years with non-cirrhotic , chronic HCV genotype @ infection ( documented @ months before screening ) and plasma HCV RNA levels higher than @,@ IU/mL .


Previously untreated ( treatment-naive ) patients were randomly assigned ( @:@ ) by computer-generated randomisation lists to receive once-daily ombitasvir ( @ mg ) plus paritaprevir ( @ mg ) plus ritonavir ( @ mg ) with or without weight-based ribavirin for @ weeks .


Previously treated ( treatment-experienced ) patients who had received pegylated interferon plus ribavirin all received the ribavirin-containing regimen .


The primary endpoint was a sustained virological response ( HCV RNA < @ IU/mL ) @ weeks after the end of treatment ( SVR@ ) .


Analysis was by intention to treat .


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


Between Aug @ , @ , and Nov @ , @ , @ patients with HCV infection were screened , of whom @ were infected with genotype @ patients were randomly assigned to treatment and received at least one dose of study medication ; @ patients were treatment-naive , of whom @ received ombitasvir plus paritaprevir plus ritonavir and @ received ombitasvir plus paritaprevir plus ritonavir with ribavirin , and @ treatment-experienced patients received the ribavirin-containing regimen .


In previously untreated patients , SVR@ rates were @ % ( @/@ -LSB- @ % CI @-@ -RSB- ) in the ribavirin-containing regimen and @ % ( @/@ -LSB- @ % CI @-@ -RSB- ) in the ribavirin-free regimen .


No statistically significant differences in SVR@ rates were noted between the treatment-naive groups ( mean difference -@ % -LSB- @ % CI -@ to @ -RSB- ; p = @ ) .


All treatment-experienced patients achieved SVR@ ( @/@ ; @ % -LSB- @ % CI @-@ -RSB- ) .


In the ribavirin-free group , two ( @ % ) of @ treatment-naive patients had virological relapse , and one ( @ % ) of @ had virological breakthrough ; no virological failures were recorded in the ribavirin-containing regimen .


The most common adverse event was headache ( @ -LSB- @ % -RSB- of @ treatment-experienced patients and @ -LSB- @ % -RSB- of @ treatment-naive patients ) .


No adverse event-related discontinuations or dose interruptions of study medications , including ribavirin , were noted , and only four patients ( @ % ) of @ receiving ribavirin required dose modification for haemoglobin less than @ g/L or anaemia .


An interferon-free regimen of ombitasvir plus paritaprevir plus ritonavir with or without ribavirin achieved high sustained virological response rates at @ weeks after the end of treatment and was generally well tolerated , with low rates of anaemia and treatment discontinuation in non-cirrhotic previously untreated and previously treated patients with HCV genotype @ infection .


Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators ( ICDs ) .


We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing .


In this single-blind , randomised , multicentre , non-inferiority trial ( Shockless IMPLant Evaluation -LSB- SIMPLE -RSB- ) , we recruited patients aged older than @ years receiving their first ICD for standard indications at @ hospitals in @ countries worldwide .


Exclusion criteria included pregnancy , awaiting transplantation , particpation in another randomised trial , unavailability for follow-up , or if it was expected that the ICD would have to be implanted on the right-hand side of the chest .


Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned ( @:@ ) using a computer-generated sequence to have either defibrillation testing ( testing group ) or not ( no-testing group ) .


We used random block sizes to conceal treatment allocation from the patients , and randomisation was stratified by clinical centre .


Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock ( ie , a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation ) .


The non-inferiority margin was a hazard ratio ( HR ) of @ calculated from a proportional hazards model with no-testing versus testing as the only covariate ; if the upper bound of the @ % CI was less than @ , we concluded that ICD insertion without testing was non-inferior to ICD with testing .


We examined safety with two , @ day , adverse event outcome clusters .


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


Between Jan @ , @ , and April @ , @ , of @ eligible patients , @ were randomly assigned to defibrillation testing and @ to no-testing , and followed up for a mean of @ years ( SD @ ) .


The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients ( @ -LSB- @ % per year -RSB- ) in the no-testing group than patients who did receive it ( @ -LSB- @ % per year -RSB- ; HR @ , @ % CI @-@ ; pnon-inferiority < @ ) .


The first safety composite outcome occurred in @ ( @ % ) of @ patients with no-testing and in @ ( @ % ) of @ patients with defibrillation testing , p = @ .


The second , pre-specified safety composite outcome , which included only events most likely to be directly caused by testing , occurred in @ % of patients with no-testing and in @ % with defibrillation testing , p = @ .


Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event ( in @ -LSB- @ % -RSB- of @ patients in the no-testing group vs @ -LSB- @ % -RSB- of @ patients in the testing group , p = @ ) .


Routine defibrillation testing at the time of ICD implantation is generally well tolerated , but does not improve shock efficacy or reduce arrhythmic death .


Artemisinin-based combination therapy ( ACT ) has become the standard of care for the treatment of uncomplicated Plasmodium falciparum malaria .


Although several ACT regimens are approved , data guiding optimal choices of ACTs are limited .


We compared short - and long-term outcomes in a cohort of young Ugandan children randomized to @ leading ACTs .


Overall , @ children were randomized to artemether-lumefantrine or dihydroartemisinin-piperaquine ( DP ) at the time of the first episode of uncomplicated malaria ( median age , @ months ) .


The same treatment was given for all subsequent episodes of uncomplicated malaria and children were followed until they reached @ years of age .


The cohort included a subgroup that was human immunodeficiency virus ( HIV ) infected ( n = @ ) or HIV exposed ( n = @ ) and prescribed trimethoprim-sulfamethoxazole ( TMP-SMX ) prophylaxis .


Outcomes included time to recurrent malaria following individual treatments and the overall incidences of treatments for malaria , complicated malaria , and hospitalizations .


Among children not prescribed TMP-SMX prophylaxis , @ treatments for malaria were given over @ person-years following randomization .


Treatment with DP was associated with a lower hazard of recurrent malaria over the @ days after treatment ( hazard ratio , @ ; @ % confidence interval -LSB- CI -RSB- , @ -@ ; P < @ ) .


Children randomized to DP had a lower incidence of all treatments for malaria ( incidence rate ratio -LSB- IRR -RSB- , @ ; @ % CI , @ -@ ; P = @ ) , complicated malaria ( IRR , @ ; @ % CI , @ -@ ; P < @ ) , and hospitalizations ( IRR , @ ; @ % CI , @ -@ ; P = @ ) .


Among children prescribed TMP-SMX prophylaxis , there were no significant differences in longitudinal outcomes .


Compared to artemether-lumefantrine , the use of DP to treat uncomplicated malaria delayed the time to recurrent malaria and reduced the incidences of treatments for malaria , complicated malaria , and hospitalizations .


The study aimed to investigate the effectiveness of a web-based therapy programme , ` Move it to improve it ' ( Mitii ( ) ) , in children with unilateral cerebral palsy ( UCP ) on occupational performance , upper limb function , and visual perception .


Participants ( n = @ ) were matched in pairs and randomized to intervention ( Mitii for @wks ; @ males , mean age @y @mo -LSB- @y @mo -RSB- , Manual Ability Classification System level I = @ , II = @ , III = @ ) or control ( standard care ; @ males , mean age @y @mo -LSB- @y @mo -RSB- , Manual Ability Classification System level I = @ , II = @ ) .


Outcomes were the Assessment of Motor and Process Skills ( AMPS ) , Assisting Hand Assessment , Jebsen-Taylor Test of Hand Function ( JTTHF ) , Melbourne Assessment of Unilateral Upper Limb Function ( MUUL ) , Canadian Occupational Performance Measure ( COPM ) , and Test of Visual Perceptual Skills ( TVPS-@ ) .


Participants completed on average @ hours of Mitii ( range @-@ @ h ) .


The Mitii group demonstrated significantly greater post-intervention scores than the comparison group on the AMPS , JTTHF dominant upper limb , COPM , and TVPS-@ .


The differences between groups were not clinically significant .


There were no differences between groups on measures of impaired upper limb function .


Mitii delivers individualized , web-based therapy at home and has potential to increase therapy dose .


Mitii can be considered as an option to enhance occupational performance and visual perception for children with UCP .


Inappropriate implantable cardioverter defibrillators ( ICD ) therapies have been associated with multiple adverse effects , including worse quality of life and prognosis .


We evaluated the possibility of predicting atrial fibrillation ( AF ) - related inappropriate ICD shocks through continuous monitoring of device diagnostics .


@ ICD patients were prospectively followed in an observational research by @ Italian cardiology centres .


Device diagnostics stored daily information on AF duration and ventricular rate ( VR ) during AF .


Uncontrolled VR was defined as mean VR > @ beats per minute ( bpm ) and maximum VR > @ bpm .


Expert electrophysiologists reviewed the ventricular tachycardia/ventricular fibrillation ( VT/VF ) episodes electrograms , stored in the device memory , and classified appropriate detections , inappropriate detection mechanisms and ICD therapy outcomes .


Over a median follow-up of @ months , @ ( @ % ) patients suffered spontaneous VT/VF , which were treated by ICD shocks in a subgroup of @ ( @ % ) patients .


Inappropriate detections occurred in @ ( @ % ) patients , and inappropriate ICD shocks in @ ( @ % ) patients .


AF was the cause of inappropriate shocks in @ patients .


AF caused @ inappropriate shocks : @ % of all inappropriate shocks .


The likelihood of experiencing AF-related inappropriate shocks was @ % at @ year and @ % at @ years .


Uncontrolled VR during AF proved to be an independent predictor of AF-related inappropriate shocks ( OR = @ , p = @ ) ; an alarm set at a VR > @ bpm or @ bpm was associated with prediction of AF-related inappropriate shocks with a sensitivity of @ % or @ % , respectively .


AF is the most common cause of inappropriate shocks in ICD patients .


Continuous remote monitoring of VR during AF would promptly and efficiently predict AF-related inappropriate shocks .