After 24 weeks of treatment , mean changes in proteinuria were protein excretion of -508 , -376 , and -545 mg/d , respectively ( P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan ) .


Mean eGFR did not change significantly .


The incidence of adverse reactions was not different among the 3 groups ( P > 0.05 ) , and there were no severe adverse events in any group .


Results can not be generalized to those with nephrotic syndrome or reduced eGFR .


A manihot is a promising therapy for patients with primary kidney disease ( chronic kidney disease stages 1-2 ) with moderate proteinuria .


To prospectively evaluate the neuropsychological effect of levetiracetam ( LVT ) in comparison with carbamazepine ( CBZ ) and its efficacy and tolerability as a monotherapy in children with focal epilepsy .


A total of 121 out of 135 screened children ( 4-16 years ) were randomly assigned to LVT or CBZ groups in a multicenter , parallel-group , open-label trial .


The study 's primary endpoints were defined as the end of 52 weeks of treatment , followed by analysis of changes observed in a series of follow-up neurocognitive , behavioral , and emotional function tests performed during treatment in the per protocol population .


Drug efficacy and tolerability were also analyzed among the intention-to-treat ( ITT ) population ( ClinicalTrials.gov , number NCT02208492 ) .


Eighty-one patients ( 41 LVT , 40 CBZ ) from the randomly assigned ITT population of 121 children ( 57 LVT , 64 CBZ ) were followed up to their last visit .


No significant worsening or differences were noted between groups in neuropsychological tests , except for the Children 's Depression Inventory ( LVT -1.97 vs CBZ +1.43 , p = 0.027 , [ + ] improvement of function ) .


LVT-treated patients showed an improvement ( p = 0.004 ) in internalizing behavioral problems on the Korean Child Behavior Checklist .


Seizure-free outcomes were not different between the 2 groups ( CBZ 57.8 % vs LVT 66.7 % , p = 0.317 ) .


Neither LVT nor CBZ adversely affected neuropsychological function in pediatric patients .


Both medications were considered equally safe and effective as monotherapy in children with focal epilepsy .


This study provides Class II evidence that in patients with pediatric focal epilepsy , LVT and CBZ exhibit equivalent effects on neuropsychological function .


To compare the efficacy of 2 prophylaxis regimens before cataract surgery using topical antibiotics ( 1 hour before surgery versus the day before ) , both with povidone-iodine , with regard to reducing the preoperative conjunctival bacterial load .


Tertiary ophthalmic referral center , Munich , Germany .


Prospective comparative case series .


Eyes were treated with topical antibiotics and their conjunctival sac flush irrigated using 10 mL of povidone-iodine 1.0 % .


All eyes were randomized to receive either 4 applications of topical 3500 IU/mL neomycin sulfate/6000 IU/mL polymyxin-B sulfate within 1 hour preoperatively ( Group 1 ) or on the day before surgery ( Group 2 ) .


Conjunctival specimens were obtained at 4 timepoints : T0C untreated fellow eye ( control ) , T0 surgery eye ( after antibiotic prophylaxis but before povidone-iodine irrigation ) , T1 after povidone-iodine , and T2 at the conclusion of surgery .


All specimens were inoculated onto blood and chocolate-blood agar and into thioglycollate broth .


One hundred thirty-three eyes of 133 consecutive patients were included ( Group 1 , 64 eyes ; Group 2 , 69 eyes ) .


The antibiotic regimens were equally effective in reducing the aerobic and microaerophilic conjunctival flora ( Group 1 , P = .028 ; Group 2 , P = .000 ) , but had no significant effect on anaerobic bacteria ( Group 1 , P = .201 ; Group 2 , P = .117 ) .


Flush irrigation of the conjunctival sac using 10.0 mL povidone-iodine 1.0 % significantly decreased the conjunctival bacterial load in both groups .


Topical neomycin/polymyxin-B was equally effective in reducing the conjunctival bacterial load whether given 1 day or 1 hour before surgery .


The greatest effect was achieved by irrigating the conjunctival sac using povidone-iodine .


No author has a financial or proprietary interest in any material or method mentioned .


Assessment is a critical component of therapeutic intervention as it serves as the basis from which clinical goals and objectives are derived .


Unfortunately , there is a dearth of reliable group therapy assessment instruments , especially for children and preadolescents who have severe emotional disturbances .


The purpose of this study was to test reliability of a newly developed group therapy assessment instrument for use with children who have serious emotional disturbances that require placement in a residential or partial hospitalization treatment program .


After conducting an extensive literature review , the authors developed , refined , and tested a group therapy assessment tool for use in both music therapy and traditional therapy , measuring nine items : attention to task ( physical and verbal ) , eye contact , pro-social skills ( physical and verbal ) , empathy ( physical and verbal ) , and managing negative affect ( physical and verbal ) .


Six participants with a mean age of 9.5 ( SD = 1.85 ) years were randomly selected to test the group therapy assessment tool from a pool of 60 eligible children receiving group partial hospitalization therapy .


Participants were scored by three raters across two partial hospitalization therapy groups for inter-rater reliability .


Content and construct validity were also examined .


Intraclass Coefficients ( ICC ) averaged 0.994 across all nine items indicating excellent inter-rater reliability .


Content and construct validity was established and the instrument demonstrated good external validity potential .


The Beech Brook Therapy Assessment Instrument has demonstrated excellent inter-rater reliability in measuring important behaviors of functioning central in the treatment of youth with severe and emotional disturbances .


The measure has potential for wide utility and application in practice and research ; however , future studies are needed to establish external validity .


Breakthrough cancer pain typically has a rapid onset and relatively short duration .


Due to this temporal profile , it may not be adequately relieved by oral opioid analgesics .


The sublingual fentanyl orally disintegrating tablet is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid-onset analgesia , and which may be effective for breakthrough pain treatment .


A multicenter , randomized , placebo-controlled , double-blind comparative study was conducted to evaluate the efficacy and safety of the sublingual fentanyl tablet at optimized doses for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals .


The optimal dose was determined by open-label dose titration .


The efficacy and safety of a 12-week extended treatment were also evaluated .


Eleven of 42 subjects who received the sublingual fentanyl tablet experienced adverse drug reactions .


Common reactions were somnolence , constipation , nausea , and vomiting .


No serious adverse reactions occurred .


Sublingual fentanyl tablets at optimal doses and placebo were administered to 37 subjects in a double-blinded manner .


A significant analgesic effect of the sublingual fentanyl tablet was present compared to placebo at 30 min after administration .


The sublingual fentanyl tablet was also effective and safe during extended treatment , in which changes in basal opioid doses as well as sublingual fentanyl tablet doses were made as needed .


Sublingual fentanyl tablets at doses determined by titration were effective and safe for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals .


Extended treatment up to 12 weeks was also effective and safe .


Extensive decompression with laminectomy , where appropriate , is often still described as the method of choice when operating on degenerative lumbar spinal stenosis .


Nonetheless , tissue-sparing procedures are becoming more common .


Endoscopic techniques have become the standard in many areas because of the surgical advantages they offer and the benefits for rehabilitation .


One key issue when operating on the spine was the development of instruments to provide sufficient bone resection under continuous visual control .


This was achieved by using endoscopes for operations carried out in cases of spinal canal stenosis .


This study of patients with degenerative lumbar central spinal stenosis compares the results of spinal decompression using the full-endoscopic interlaminar technique ( FI ) with a conventional microsurgical laminotomy technique ( MI ) .


Prospective , randomized , controlled study .


135 patients with microsurgical or full-endoscopic decompression were followed up for 2 years .


Alongside general and specific parameters , the following measuring instruments were also used for the investigation : Visual Analog Scale ( VAS ) , German version of the North American Spine Society Instrument ( NASS ) , Oswestry Low-Back-Pain-Disability Questionnaire ( ODI ) .


Postoperatively 72 % of the patients no longer had leg pain or the pain was almost completely reduced and 21.2 % experienced occasional pain .


The clinical results were the same in both groups .


The rate of complications and revisions was significantly reduced in the FI Group .


The full-endoscopic techniques brought advantages in the following areas : operation , complications , traumatization , rehabilitation .


Lack of placebo control group .


The recorded results demonstrate that the full-endoscopic interlaminar bilateral decompression adopting a unilateral approach provides an adequate and safe supplement and alternative to the conventional microsurgical bilateral laminotomy technique when the indication criteria are fulfilled .


At the same time , it offers the advantages of a minimally invasive intervention .


The doctor-patient encounter ( DPE ) and associated patient expectations are potential confounders in open-label randomized trials of treatment efficacy .


It is therefore important to evaluate the effects of the DPE on study outcomes .


Four hundred participants with chronic low back pain ( LBP ) were randomized to four dose groups : 0 , 6 , 12 , or 18 sessions of spinal manipulation from a chiropractor .


Participants were treated three times per week for six weeks .


They received light massage control at visits when manipulation was not scheduled .


Treating chiropractors were instructed to have equal enthusiasm for both interventions .


A path analysis was conducted to determine the effects of dose , patient expectations of treatment success , and DPE on LBP intensity ( 100-point scale ) at the end of care ( 6 weeks ) and primary endpoint ( 12 weeks ) .


Direct , indirect , and total standardized effects ( total ) were computed .


Expectations and DPE were evaluated on Likert scales .


The DPE was assessed as patient-rated perception of chiropractor enthusiasm , confidence , comfort with care , and time spent .


The DPE was successfully balanced across groups , as were baseline expectations .


The principal finding was that the magnitude of the effects of DPE on LBP at 6 and 12 weeks ( | | total = 0.22 and 0.15 , p < .05 ) were comparable to the effects of dose of manipulation at those times ( | | total = 0.11 and 0.12 , p < .05 ) .


In addition , baseline expectations had no notable effect on follow-up LBP .


Subsequent expectations were affected by LBP , DPE , and dose ( p < .05 ) .


The DPE can have a relatively important effect on outcomes in open-label randomized trials of treatment efficacy .


Therefore , attempts should be made to balance the DPE across treatment groups and report degree of success in study publications .


We balanced the DPE across groups with minimal training of treatment providers .


ClinicalTrials.gov NCT00376350 .


To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU .


Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial .


Sixty-seven medical-surgical ICUs in six countries .


Three thousand seven hundred forty-six medical-surgical critically ill patients .


All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses .


Independent predictors for venous thromboembolism , proximal leg deep vein thrombosis , and pulmonary embolism developing during critical illness were assessed .


A total of 289 patients ( 7.7 % ) developed venous thromboembolism .


Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism ( hazard ratio , 1.64 ; 95 % CI , 1.03-2 .59 ; p = 0.04 ) and body mass index ( hazard ratio , 1.18 per 10-point increase ; 95 % CI , 1.04-1 .35 ; p = 0.01 ) .


Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis ( hazard ratio , 1.25 ; 95 % CI , 1.06-1 .46 ; p = 0.007 ) , which occurred in 182 patients ( 4.9 % ) .


Pulmonary embolism occurred in 47 patients ( 1.3 % ) and was associated with body mass index ( hazard ratio , 1.37 ; 95 % CI , 1.02-1 .83 ; p = 0.035 ) and vasopressor use ( hazard ratio , 1.84 ; 95 % CI , 1.01-3 .35 ; p = 0.046 ) .


Low-molecular-weight heparin ( in comparison to unfractionated heparin ) thromboprophylaxis lowered pulmonary embolism risk ( hazard ratio , 0.51 ; 95 % CI , 0.27-0 .95 ; p = 0.034 ) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis ( hazard ratio , 0.46 ; 95 % CI , 0.27-0 .77 ; p = 0.004 ) .


Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index , those with a personal or family history of venous thromboembolism , and those receiving vasopressors .


Alternate management or incremental risk reduction strategies may be needed in such patients .


We conducted this pilot randomized clinical trial to determine the feasibility of a large clinical trial aimed at testing whether early use of catheter ablation of ventricular tachycardia ( VT ) is superior to antiarrhythmic medications at reducing mortality .


Patients were enrolled at 4 sites if they had ischemic heart disease , an implantable cardioverter defibrillator ( ICD ) , and received 1 ICD shock or 3 antitachycardia pacing therapies for VT. .


Patients were randomized to 2 arms : ( 1 ) antiarrhythmic medication ( n = 14 ) and ( 2 ) catheter ablation ( n = 13 ) ; patients were followed at 3 and 6 months .


Endpoints included recurrent VT , time to first ICD therapy for VT , and death .


Of 243 screened patients , 27 were enrolled .


Main reasons for screen failures were : ( 1 ) patient was already on an antiarrhythmic medication ( 88 [ 41 % ] ) , ( 2 ) VT due to a reversible cause ( 23 [ 11 % ] ) , and ( 3 ) incessant VT ( 20 [ 9 % ] ) .


Fourteen patients had recurrent VT , 8 ( 62 % ) in the ablation arm and 6 ( 43 % ) in the antiarrhythmic medication arm .


Median time to recurrent VT was 75 days ( 25th , 75th : 51 , 89 ) in the ablation arm and 57 days ( 30 , 145 ) in the antiarrhythmic arm .


Four patients died , 2 in each arm .


This clinical trial shows that most patients in clinical practice have already failed antiarrhythmic drug therapy before catheter ablation is considered , and the VT recurrence rates and death in these patients are high .


For a large clinical trial to be feasible , factors limiting early consideration of catheter ablation need to be identified and addressed .


Anxiety , Depression and Somatoform ( ADSom ) disorders are highly prevalent in primary care .


Managing these disorders is time-consuming and requires strong commitment on behalf of the General Practitioners ( GPs ) .


Furthermore , the management of these patients is restricted by the high patient turnover rates in primary care practices , especially in the German health care system.In order to address this problem , we implement a complex , low-threshold intervention by an Advanced Practice Nurse ( APN ) using a mixture of case management and counseling techniques to promote self-management in these patients .


Here we present the protocol of the `` Self-Management Support for Anxiety , Depression and Somatoform Disorders in Primary Care '' ( SMADS ) - Study .


The study is designed as a cluster-randomized controlled trial , comparing an intervention and a control group of 10 primary care practices in each case .


We will compare the effectiveness of the intervention applied by an APN with usual GP-care .


A total of 340 participants will be enrolled in the study , 170 in either arm .


We use the Patient Health Questionnaire-German version ( PHQ-D ) as a screening tool for psychiatric symptoms , including patients with a score above 5 on any of the three symptom scales .


The primary outcome is self-efficacy , measured by the General Self-Efficacy Scale ( GSE ) , here used as a proxy for self-management .


As secondary outcomes we include the PHQ-D symptom load and questionnaires regarding coping with illness and health related quality of life .


Outcome assessments will be applied 8 weeks and 12 months after the baseline assessment .


The SMADS-study evaluates a complex , low threshold intervention for ambulatory patients presenting ADSom-symptoms , empowering them to better manage their condition , as well as improving their motivation to engage in self-help and health-seeking behaviour .


The benefit of the intervention will be substantiated , when patients can enhance their expected self-efficacy , reduce their symptom load and engage in more self-help activities to deal with their everyday lives .


After successfully evaluating this psychosocial intervention , a new health care model for the management of symptoms of anxiety , depression and somatoform disorders for ambulatory patients could emerge , supplementing the work of the GP .


Clinicaltrials.gov Identifier : NCT01726387 .


To compare the safety and efficacy of dexmedetomidine/propofol ( DP ) - total i.v. anaesthesia ( TIVA ) vs remifentanil/propofol ( RP ) - TIVA , both with spontaneous breathing , during airway foreign body ( FB ) removal in children .


Seventy-seven children undergoing rigid bronchoscopy for FB removal were randomly allocated to receive either RP-TIVA and spontaneous ventilation ( Group RP , n = 38 ) or DP-TIVA and spontaneous ventilation ( Group DP , n = 39 ) .


Heart rate , arterial pressure , pulse oxygen saturation ( Sp ( O2 ) ) , respiratory rate , end-tidal CO2 ( E ' ( CO2 ) ) , and induction time were recorded .


Adverse events , the intervention for these events , and postoperative care duration were also assessed .


The mean induction times were comparable between the two groups ( Group RP 12.2 min vs Group DP 13.1 min , P > 0.05 ) .


At the end of the procedure , the mean ( E ' ( CO2 ) ) was higher in Group RP ( Group RP 6.8 kPa vs Group DP 5.8 kPa , P < 0.001 ) , and respiratory rate was lower in Group RP ( Group RP 20.4 vs Group DP 35.8 , P < 0.001 ) .


Additionally , the perioperative haemodynamic profile was more stable in Group DP than that in Group RP .


The incidence rate of breath-holding and intervention were comparable between the two groups .


In the post-anaesthesia care unit ( PACU ) , no hypoxaemia was observed , and emergence time increased in Group DP ( Group DP 65.1 min vs Group RP 23.8 min , P < 0.0001 ) .


The incidence of cough in PACU was higher in Group RP ( Group RP 55.3 % vs Group DP 10.3 % , P < 0.0001 ) .


Compared with RP-TIVA , DP-TIVA provided more stable respiratory and haemodynamic profiles , but required a longer recovery time .


Clinical trial registration China Clinical Research Information Service , ChiCTR-TRC-13003018 .


PPARGC1A and PPARGCB encode transcriptional coactivators that regulate numerous metabolic processes .


We tested associations and treatment ( i.e. metformin or lifestyle modification ) interactions with metabolic traits in the Diabetes Prevention Program , a randomised controlled trial in persons at high risk of type 2 diabetes .


We used Tagger software to select 75 PPARGCA1 and 94 PPARGC1B tag single-nucleotide polymorphisms ( SNPs ) for analysis .


These SNPs were tested for associations with relevant cardiometabolic quantitative traits using generalised linear models .


Aggregate genetic effects were tested using the sequence kernel association test .


In aggregate , PPARGC1A variation was strongly associated with baseline triacylglycerol concentrations ( p = 2.910 ( -30 ) ) , BMI ( p = 2.010 ( -5 ) ) and visceral adiposity ( p = 1.910 ( -4 ) ) , as well as with changes in triacylglycerol concentrations ( p = 1.710 ( -5 ) ) and BMI ( p = 9.910 ( -5 ) ) from baseline to 1 year .


PPARGC1B variation was only associated with baseline subcutaneous adiposity ( p = 0.01 ) .


In individual SNP analyses , Gly482Ser ( rs8192678 , PPARGC1A ) was associated with accumulation of subcutaneous adiposity and worsening insulin resistance at 1 year ( both p < 0.05 ) , while rs2970852 ( PPARGC1A ) modified the effects of metformin on triacylglycerol levels ( p ( interaction ) = 0.04 ) .


These findings provide several novel and other confirmatory insights into the role of PPARGC1A variation with respect to diabetes-related metabolic traits .


ClinicalTrials.gov NCT00004992 .


The possible relationship between the circulating concentrations of T4 and GH sensitivity has not been elucidated .


The aim of this study is to evaluate the effect of levothyroxine supplementation on GH sensitivity in prepubertal boys with idiopathic short stature ( ISS ) .


We selected 28 prepubertal boys with ISS ( mean age 8.20.5 years ) and free T4 ( Ft4 ) concentrations between the 3rd and the 25th percentiles ( Ft4 : 0.8-1 .5 ng/dl ) .


They were randomly divided into two groups : Group A received thyroid supplementation ( 1-3g / kg/day ) for 120days , and Group B received placebo for the same period .


To evaluate GH sensitivity , an IGF-I generation test ( GH : 33g/kg/day sc for 3days ) was performed in both groups : under basal conditions , and after 120days of levothyroxine supplementation ( or placebo ) .


After thyroid supplementation , Group A had higher Ft4 concentrations compared with Group B ( 2.140.06 vs 1.480.06 ng/dl , p = 0.01 ) , their growth velocity was significantly higher ( 2.30.1 vs 1.50.2 cm/4months ) , and they exhibited a greater increase in IGF-I after GH administration ( Group A : 32.53.8 % vs Group B 17.32.6 % ) .


Supplementation with levothyroxine for 120days promotes an increase in growth velocity , and a greater IGF-I response to short-term GH administration in prepubertal boys with ISS and low-normal thyroid hormone concentrations .


Although conventional laparoscopic colectomy is a validated technique , laparoscopic natural-orifice specimen extraction ( NOSE ) colectomy might improve outcome .


This randomized clinical trial compared analgesia requirements , postoperative pain , anorectal function , inflammatory response and cosmesis in laparoscopic NOSE colectomy and conventional laparoscopic colectomy .


Patients were randomly assigned to undergo laparoscopic NOSE colectomy or conventional laparoscopic colectomy for left-sided colonic disease .


The primary endpoint was analgesia requirement .


Secondary endpoints were operative outcome , inflammatory response , anorectal function and cosmesis .


Forty patients were enrolled in the study , 20 in each group ( 15 with diverticulitis and 5 with colorectal cancer in each group ) .


A significant difference was observed in morphine analogue requirements ( 1 of 20 patients in the NOSE group versus 10 of 20 in the conventional group ; P = 0003 ) .


Patient-controlled epidural analgesia was lower in the NOSE group ( mean 116ml versus 221ml in the conventional group ; P < 0001 ) , as was paracetamol use ( mean 110 versus 170g respectively ; P < 0001 ) .


Postoperative pain scores were lower in the NOSE group : mean maximum visual analogue score of 35 versus 21 ( P < 0001 ) .


One week after hospital discharge , pain scores remained higher in the conventional group : 15 of 20 patients in the conventional group reported pain , compared with one of 20 in the NOSE group ( P < 0001 ) .


Inflammatory responses were greater in patients undergoing NOSE colectomy : higher peak C-reactive protein and interleukin 6 levels were observed on postoperative day 2 ( P < 0001 ) and day 1 ( P = 0002 ) respectively .


Postoperative anorectal function , complications and hospital stay were similar in the two groups .


Laparoscopic NOSE colectomy was associated with less pain and lower analgesia requirements than the conventional laparoscopic extraction .


NCT01033838 ( http://www.clinicaltrials.gov ) .


This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure ( CHF ) , since the role of statins in CHF remains unclear .


The South koreAn Pitavastatin Heart FaIluRE ( SAPHIRE ) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin .


The low density lipoprotein cholesterol level decreased by 30 % in the pitavastatin group compared with 12 % in the pravastatin ( p < 0.05 ) group .


Left ventricular systolic dimensions decreased significantly by 9 % in the pitavastatin group and by 5 % in the pravastatin group .


Left ventricular ejection fraction ( EF ) improved significantly from 37 % to 42 % in the pitavastatin group and from 35 % to 39 % in the pravastatin group .


Although the extent of the EF change was greater in the pitavastatin group ( 16 % vs. 11 % ) than that in the pravastatin group , no significant difference was observed between the groups ( p = 0.386 ) .


Exercise capacity , evaluated by the 6-min walking test , improved significantly in the pravastatin group ( p < 0.001 ) , but no change was observed in the pitavastatin group ( p = 0.371 ) .


Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF .


However , only pravastatin significantly improved exercise capacity .


These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF .


Impetigo affects more than 110 million children worldwide at any one time .


The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance .


Few trials of systemic antibiotics are available to guide management of extensive impetigo .


As such , we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting .


In this randomised , controlled , non-inferiority trial , Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned ( 1:1:1 ) to receive benzathine benzylpenicillin ( weight-banded injection ) , twice-daily co-trimoxazole for 3 days ( 4 mg/kg plus 20 mg/kg per dose ) , or once-daily co-trimoxazole for 5 days ( 8 mg/kg plus 40 mg/kg per dose ) .


At every visit , participants were randomised in blocks of six and 12 , stratified by disease severity .


Randomisation was done by research nurses and codes were in sealed , sequentially numbered , opaque envelopes .


Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7 .


The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis .


This trial is registered with the Australian New Zealand Clinical Trials Registry , number ACTRN12609000858291 .


Between Nov 26 , 2009 , and Nov 20 , 2012 , 508 patients were randomly assigned to receive benzathine benzylpenicillin ( n = 165 [ 156 analysed ] ) , twice-daily co-trimoxazole for 3 days ( n = 175 [ 173 analysed ] ) , or once-daily co-trimoxazole for 5 days ( n = 168 [ 161 analysed ] ) .


Treatment was successful in 133 ( 85 % ) children who received benzathine benzylpenicillin and 283 ( 85 % ) who received pooled co-trimoxazole ( absolute difference 05 % ; 95 % CI -62 to 73 ) , showing non-inferiority of co-trimoxazole ( 10 % margin ) .


Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar .


Adverse events occurred in 54 participants , 49 ( 90 % ) of whom received benzathine benzylpenicillin .


Short-course co-trimoxazole is a non-inferior , alternative treatment to benzathine benzylpenicillin for impetigo ; it is palatable , pain-free , practical , and easily administered .


Australian National Health and Medical Research Council .


An unmet need exists for interferon-free and ribavirin-free treatments for chronic hepatitis C virus ( HCV ) infection .


In this study , we assessed all-oral therapy with daclatasvir ( NS5A replication complex inhibitor ) plus asunaprevir ( NS3 protease inhibitor ) in patients with genotype 1b infection , including those with high unmet needs or cirrhosis , or both .


We did this phase 3 , multicohort study ( HALLMARK-DUAL ) at 116 sites in 18 countries between May 11 , 2012 , and Oct 9 , 2013 .


Patients were adults with chronic HCV genotype 1b infection who were treatment-naive ; previous non-responders to peginterferon alfa plus ribavirin ; or medically ineligible for , previously intolerant of , or ineligible for and intolerant of peginterferon alfa plus ribavirin .


Treatment-naive patients were randomly assigned ( 2:1 ratio ) by an interactive voice-response system with a computer-generated random allocation sequence ( stratified by cirrhosis status ) to receive daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily or placebo for 12 weeks .


Patients and investigator sites were masked to treatment assignment and HCV RNA results to the end of week 12 .


The treatment-naive group assigned to daclatasvir plus asunaprevir continued open-label treatment to the end of week 24 ; participants assigned to placebo entered another daclatasvir plus asunaprevir study .


Non-responders and ineligible , intolerant , or ineligible and intolerant patients received open-label daclatasvir plus asunaprevir for 24 weeks .


The primary endpoint was sustained virological response at post-treatment week 12 .


Efficacy analyses were restricted to patients given daclatasvir plus asunaprevir .


This trial is registered with ClinicalTrials.gov , number NCT01581203 .


This study included 307 treatment-naive patients ( 205 received daclatasvir plus asunaprevir and 102 received placebo ; all randomly assigned patients received the intended treatment ) , 205 non-responders , and 235 ineligible , intolerant , or ineligible and intolerant patients .


Daclatasvir plus asunaprevir provided sustained virological response in 182 ( 90 % , 95 % CI 85-94 ) patients in the treatment-naive cohort , 168 ( 82 % , 77-87 ) in the non-responder cohort , and 192 ( 82 % , 77-87 ) in the ineligible , intolerant , or ineligible and intolerant cohort .


Serious adverse events occurred in 12 ( 6 % ) patients in the treatment-naive group ; 11 ( 5 % ) non-responders , and 16 ( 7 % ) ineligible , intolerant , or ineligible and intolerant patients ; adverse events leading to discontinuation ( most commonly reversible increases in alanine or aspartate aminotransferase ) occurred in six ( 3 % ) , two ( 1 % ) , and two ( 1 % ) patients , respectively , with no deaths recorded .


Grade 3 or 4 laboratory abnormalities were uncommon , with low incidences of aminotransferase increases during the first 12 weeks with daclatasvir plus asunaprevir and placebo in treatment-naive patients ( 2 % each ) .


Daclatasvir plus asunaprevir provided high sustained virological response rates in treatment-naive , non-responder , and ineligible , intolerant , or ineligible and intolerant patients , and was well tolerated in patients with HCV genotype 1b infection .


These results support the use of daclatasvir plus asunaprevir as an all-oral , interferon-free and ribavirin-free treatment option for patients with HCV genotype 1b infection , including those with cirrhosis .


Bristol-Myers Squibb .


To determine the normal variation in central retinal thickness asymmetry in healthy Caucasian adults using the posterior pole asymmetry analysis ( PPAA ) of a SPECTRALIS spectral-domain optical coherence tomography ( SD-OCT ) device .


Healthy Caucasian individuals aged between 18 and 45 years with a visual acuity of minimum 20/20 and a spherical equivalent between -1.5 and +1.5 diopters were recruited .


Retinal thickness and retinal nerve fiber layer thickness ( RNFL ) were using measured SPECTRALIS SD-OCT .


Inter - and intraocular differences in central retinal thickness were calculated using the PPAA .


The association between age , sex , and interocular asymmetry was evaluated by a linear model with Gaussian correlation structure .


A total of 105 individuals , 30 men and 75 women , were studied .


The mean age SD was 28.8 7.87 years .


The grand mean interocular retinal thickness asymmetry was 5.6 m ( 95 % confidence interval [ CI ] : 4.6-6 .5 ) and the grand mean intraocular retinal thickness asymmetry was 8.3 m ( 95 % CI : 6.8-9 .9 ) in the right eye and 8.4 m ( 95 % CI : 6.7-10 .0 ) in the left eye .


The highest local asymmetries were found in the nasal corners of macula were the posterior pole thickness map overlaps the temporal vascular arches .


A slight general age and sex effect on the mean interocular retinal thickness asymmetry was found to be respectively 0.04 m/year ( 95 % CI : 0.02-0 .06 m ) and 0.54 m ( 95 % CI : 0.19-0 .88 m ) for men compared with women .


Statistically significant physiological asymmetries in inter - and intraocular central retinal thickness exist .


This must be considered when early signs of glaucoma or other pathologies are evaluated based on the retinal thickness asymmetry .


( http://www.controlled-trials.com/isrctn/ number , ISRCTN09017572 . )


We seek to test the efficacy of noninvasive sphenopalatine ganglion block for the treatment of acute anterior headache in the emergency department ( ED ) using a novel noninvasive delivery device .


We conducted a randomized , double-blind , placebo-controlled trial evaluating bupivacaine anesthesia of the sphenopalatine ganglion for acute anterior or global-based headache .


This study was completed in 2 large academic EDs .


Bupivacaine or normal saline solution was delivered intranasally ( 0.3 mL per side ) with the Tx360 device .


Pain and nausea were measured at 0 , 5 , and 15 minutes by a 100-mm visual analog scale .


The primary endpoint was a 50 % reduction in pain at 15 minutes .


Telephone follow-up assessed 24-hour pain and nausea through a 0 - to 10-point verbal scale and adverse effects .


The median reported baseline pain in the bupivacaine group was 80 mm ( IQR 66 mm - 93 mm ) and 78.5 mm ( IQR 64 mm to 91.75 mm ) in the normal saline solution group .


A 50 % reduction in pain was achieved in 48.8 % of the bupivacaine group ( 20/41 patients ) versus 41.3 % in the normal saline solution group ( 19/46 patients ) , for an absolute risk difference of 7.5 % ( 95 % confidence interval [ CI ] -13 % to 27.1 % ) .


As a secondary outcome , at 24 hours , more patients in the bupivacaine group were headache free ( 24.7 % difference ; 95 % CI 2.6 % to 43.6 % ) and more were nausea free ( 16.9 % difference ; 95 % CI 0.8 % to 32.5 % ) .


For patients with acute anterior headache , sphenopalatine ganglion block with the Tx360 device with bupivacaine did not result in a significant increase in the proportion of patients achieving a greater than or equal to 50 % reduction in headache severity at 15 minutes compared with saline solution applied in the same manner .


Vibration anesthesia is an effective pain-reduction technique for facial cosmetic injections .


The analgesic effect of this method was tested in this study during facial dermal filler injections .


The study aimed to evaluate the safety and efficacy of vibration anesthesia for these facial injections .


This prospective study analyzed 41 patients who received dermal filler injections to the nasolabial folds , tear troughs , cheeks , and other facial sites .


The injections were administered in a randomly assigned split-face design .


One side of the patient 's face received vibration together with dermal filler injections , whereas the other side received dermal filler injections alone .


The patients completed a posttreatment questionnaire pertaining to injection pain , adverse effects , and preference for vibration with future dermal filler injections .


The patients experienced both clinically and statistically significant pain reduction when a vibration stimulus was co-administered with the dermal filler injections .


No adverse events were reported .


The majority of the patients ( 95 % ) reported a preference for vibration anesthesia with subsequent dermal filler injections .


Vibration is a safe and effective method of achieving anesthesia during facial dermal filler injections .


This journal requires that authors assign a level of evidence to each article .


For a full description of these Evidence-Based Medicine ratings , please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


The Institute of Medicine recommends developing a broader workforce of mental health providers , including nontraditional providers , to expand services for older adults .


Cognitive behavior therapy ( CBT ) is effective for late-life generalized anxiety disorder ( GAD ) , but no study has examined outcomes with delivery by lay providers working under the supervision of licensed providers .


The current study examined the effects of CBT delivered by lay , bachelor-level providers ( BLP ) relative to Ph.D.-level expert providers ( PLP ) , and usual care ( UC ) in older adults with GAD .


Participants were 223 older adults ( mean age , 66.9 years ) with GAD recruited from primary care clinics at two sites and assigned randomly to BLP ( n = 76 ) , PLP ( n = 74 ) , or UC ( n = 73 ) .


Assessments occurred at baseline and 6 months .


CBT in BLP and PLP included core and elective modules ( 3 months : skills training ; 3 months : skills review ) delivered in person and by telephone , according to patient choice .


CBT in both BLP and PLP groups significantly improved GAD severity ( GAD Severity Scale ) , anxiety ( Spielberger State-Trait Anxiety Inventory ; Structured Interview Guide for the Hamilton Anxiety Scale ) , depression ( Patient Health Questionnaire ) , insomnia ( Insomnia Severity Index ) , and mental health quality of life ( Short-Form-12 ) , relative to UC .


Response rates defined by 20 % reduction from pre - to posttreatment in at least three of four primary outcomes were higher for study completers in BLP and PLP relative to UC ( BLP : 38.5 % ; PLP : 40.0 % ; UC : 19.1 % ) .


Lay providers , working under the supervision of licensed providers , can deliver effective CBT .


The benefit of statins in patients with acute aneurysmal subarachnoid haemorrhage is unclear .


We aimed to determine whether simvastatin 40 mg could improve the long-term outcome in patients with this disorder .


In this international , multicentre , randomised , double-blind trial , we enrolled patients aged 18-65 years with confirmatory evidence of an aneurysmal subarachnoid haemorrhage and presenting less than 96 h from ictus from 35 acute neurosurgical centres in nine countries .


Patients were randomly allocated ( 1:1 ) to receive either simvastatin 40 mg or placebo once a day for up to 21 days .


We used a computer-generated randomisation code to randomise patients in every centre by blocks of ten ( five simvastatin , five placebo ) .


Participants and investigators were masked to treatment assignment .


The primary outcome was the distribution of modified Rankin Scale ( mRS ) score obtained by questionnaire at 6 months .


Analyses were done on the intention-to-treat population .


This trial has been completed and is registered with Current Controlled Trials , number ISRCTN75948817 .


Between Jan 6 , 2007 , and Feb 1 , 2013 , apart from the period between May 15 , 2009 , and Feb 8 , 2011 , when recruitment was on hold , 803 patients were randomly assigned to receive either simvastatin 40 mg ( n = 391 ) or placebo ( n = 412 ) .


All patients were included in the intention-to-treat population .


782 ( 97 % ) patients had outcome data recorded at 6 months , of whom 560 ( 72 % ) were classed as having a favourable outcome , mRS 0-2 ( 271 patients in the simvastatin group vs 289 in the placebo group ) .


The primary ordinal analysis of the mRS , adjusted for age and World Federation of Neurological Surgeons grade on admission , gave a common odds ratio ( OR ) of 097 , 95 % CI 075-125 ; p = 0803 .


At 6 months , we recorded 37 ( 10 % ) deaths in the simvastatin group compared with 35 ( 9 % ) in the placebo group ( log-rank p = 0592 ) .


70 ( 18 % ) serious adverse events were reported in the simvastatin group compared with 74 ( 18 % ) in the placebo group .


No suspected unexpected serious adverse reactions were reported .


The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage .


Despite demonstrating no safety concerns , we conclude that patients with subarachnoid haemorrhage should not be treated routinely with simvastatin during the acute stages .


British Heart Foundation .


Although epidural analgesia has been used for postoperative pain control after total knee arthroplasty , its usefulness is being reevaluated because of possible adverse effects .


Recent studies have proven the efficacy of periarticular analgesic injection and its low prevalence of adverse effects .


The present study compares the clinical efficacies of epidural analgesia and periarticular injection after total knee arthroplasty .


This is a prospective , single-center , randomized controlled trial involving patients scheduled for unilateral total knee arthroplasty .


One hundred and eleven patients were randomly assigned to periarticular injection or epidural analgesia groups .


All patients were managed with spinal anesthesia .


The surgical technique and postoperative medication protocol were identical in both groups .


The primary outcome was postoperative pain at rest , quantified as the area under the curve of the scores on a visual analog pain scale to seventy-two hours postoperatively .


The Student t test and chi-square test were used to compare the data between groups .


In the intention-to-treat analysis , the periarticular injection group had a significantly lower area under the curve for pain score at rest ( 788.0 versus 1065.9 ; p = 0.0059 ) .


In the periarticular injection group , the mean knee flexion angle was small but significantly better at postoperative day 1 ( 64.2 versus 54.6 ; p = 0.0072 ) and postoperative day 2 ( 70.3 versus 64.6 ; p = 0.021 ) than in the epidural analgesia group .


The incidence of nausea at postoperative day 1 was significantly lower in the periarticular injection group ( 4.0 % versus 44.3 % ; p < 0.0001 ) .


Transient peroneal nerve palsy was frequently seen in the periarticular injection group ( 12.0 % versus 1.6 % ; p = 0.026 ) .


Compared with epidural analgesia , periarticular injection offers better postoperative pain relief , earlier recovery of knee flexion angle , and lower incidence of nausea .


Care should be taken to avoid transient peroneal nerve palsy when using periarticular injection .


Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence .


In 2013 the World Health Organization deemed hypertension as a global crisis as it is the leading risk factor attributed to global mortality .


Therefore , there is a great need for effective alternative treatment strategies to combat a condition that affects 40 % of adults worldwide .


Recently , the FlaxPAD Trial observed a significant reduction in systolic and diastolic blood pressure in hypertensive patients with peripheral arterial disease that consumed 30 g of milled flaxseed per day for one year .


However , these patients were already on anti-hypertensive medication .


Therefore , there is a need to assess if dietary flaxseed can effectively reduce blood pressure in the absence of peripheral arterial disease and anti-hypertensive medication in newly diagnosed hypertensive patients .


The HYPERFlax Trial is a parallel , superiority , phase II/III , randomized , double-blinded , controlled clinical trial .


St. Boniface Hospital and the Health Sciences Centre of Winnipeg , Canada , will recruit 100 participants newly diagnosed with stage 1 hypertension who have yet to be administered anti-hypertensive medication .


Participants will be randomly allocated with a 1:1 ratio into a flaxseed or control group and provided food products to consume daily for six months .


At baseline , two , four , and six months , participant assessments will include the primary outcome measure , averaged automated blood pressure , and secondary measures : 24-hour food recall , international physical activity questionnaire , anthropometrics , and blood and urine sampling for biochemical analysis .


Plasma will be assessed for lipids , metabolomics profiling , and molecules that regulate vascular tone .


Urine will be collected for metabolomics profiling .


With an estimated dropout rate of 20 % , the trial will have a power of 0.80 to detect differences between groups and across time , out of an effect size of 0.7 ( SD ) at an level of 0.05 .


This trial will determine if dietary flaxseed is efficacious over six months as an anti-hypertensive therapy in subjects newly diagnosed with hypertension .


If flaxseed can effectively reduce blood pressure as a monotherapy , then flaxseed will provide individuals on a global basis with a cost-effective food-based strategy to control hypertension .


NCT01952340 , Registered 24 September 2013 .


The indocyanine green dilution method is one of the methods available to estimate plasma volume , although some researchers have questioned the accuracy of this method .


We developed a new , physiologically based mathematical model of indocyanine green kinetics that more accurately represents indocyanine green kinetics during the first few minutes postinjection than what is assumed when using the traditional mono-exponential back-extrapolation method .


The mathematical model is used to develop an optimal back-extrapolation method for estimating plasma volume based on simulated indocyanine green kinetics obtained from the physiological model .


Results from a clinical study using the indocyanine green dilution method in 36 subjects with type 2 diabetes indicate that the estimated plasma volumes are considerably lower when using the traditional back-extrapolation method than when using the proposed back-extrapolation method ( mean ( standard deviation ) plasma volume = 26.8 ( 5.4 ) mL/kg for the traditional method vs 35.1 ( 7.0 ) mL/kg for the proposed method ) .


The results obtained using the proposed method are more consistent with previously reported plasma volume values .


Based on the more physiological representation of indocyanine green kinetics and greater consistency with previously reported plasma volume values , the new back-extrapolation method is proposed for use when estimating plasma volume using the indocyanine green dilution method .


Breastfed infants require supplementation with vitamin D ( vD ) , but little is known about the necessary dose .


This double blind trial evaluated four different doses of vD .


Exclusively breastfed infants ( N = 213 ) were randomized at 1 mo to one of four doses , which they received through 9 mo while receiving no formula .


The supplements provided daily 200 IU , 400 IU , 600 IU , or 800 IU of vD .


The primary endpoint was plasma 25 ( OH ) D level , and secondary outcomes were plasma parathyroid hormone and calcium , and illness incidence .


The study was conducted during winter at 41 N.


Most infants had low ( < 50 nmol/l ) 25 ( OH ) D levels at 1 mo , but with supplementation levels rose .


Overall , levels of 25 ( OH ) D differed significantly in proportion to vD dose .


There were no effects of vD on illness incidence or growth .


Low levels were common , with 7.8 % of levels being < 50 nmol/l and 15 infants having 2 to 4 low levels .


The four doses of vD produced different plasma levels of 25 ( OH ) D.


The higher doses were somewhat more efficacious in maintaining vD sufficiency in breastfed infants .


The findings support the recommended dose of 400 IU/d , and stress the need to start supplementation at birth .


It has been suggested that the development of maternal fever during epidural analgesia could be due to intrapartum infection .


We investigated whether antibiotic prophylaxis before epidural placement decreases the rate of epidural-related fever .


In this double-blind , placebo-controlled trial , 400 healthy nulliparous women requesting epidural analgesia were randomly assigned to receive either cefoxitin 2 g or placebo immediately preceding initiation of epidural labor analgesia .


Maternal tympanic temperature was measured hourly , and intrapartum fever was defined as a maternal temperature of 38C .


Neonates born to women with fever were evaluated for possible sepsis , and available placentas were evaluated for the presence of neutrophilic inflammation .


The primary outcome was maternal fever during epidural analgesia .


Thirty-eight percent of women in the cefoxitin group and 40 % of women in the placebo group developed fever ( P = 0.68 ) .


The risk difference ( 95 % confidence interval ) for fever 38C during labor ( antibiotic versus placebo ) was -2.0 % ( -11.5 to 7.5 ) , and for fever > 39C during labor was -1.5 % ( -4.7 to 1.7 ) .


Approximately half of each study group had placental neutrophilic inflammation , but administration of cefoxitin had no significant effect on any grade of neutrophilic inflammation .


Fever developed significantly more often in the women with placental neutrophilic inflammation compared with those without such inflammation ( 73/158 vs 33/144 , P < 0.001 ; risk difference 23 % [ 95 % confidence interval , 13.0-34 .0 ] ) .


There were no significant differences in any neonatal outcomes between the antibiotic and placebo study groups .


Sepsis was not diagnosed in any of the infants .


There were no neonatal deaths .


Fever during labor epidural analgesia is associated with placental inflammation , but fever and placental inflammation were not reduced with antibiotic prophylaxis .


This finding suggests that infection is unlikely to be the cause in its development .


To determine whether the use of quantitative personal exposure measurements in experimental research would result in better estimates of the associations between static and time-varying magnetic field exposure and neurocognitive test performance than when exposure categories were based solely on distance to the magnetic field source .


In our original analysis , based on distance to the magnet of a 7 T MRI scanner , an effect of exposure to static magnetic fields was observed .


We performed a sensitivity analysis of test performance on a reaction task and line bisection task with different exposure measures that were derived from personal real-time measurements .


The exposure measures were highly comparable , and almost all models resulted in significant associations between exposure to time-varying magnetic fields within a static magnetic field and performance on a reaction and line bisection task .


In a controlled experimental setup , distance to the bore is a good proxy for personal exposure when placing subjects at fixed positions with standardized head movements in the magnetic stray fields of a 7 T MRI .


Use of a magnetic field dosimeter is , however , important for estimating quantitative exposure response associations .


The aim of this study was to compare biweekly and monthly evolocumab with placebo and oral ezetimibe in patientswith hypercholesterolemia in a phase III trial .


Evolocumab , a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , significantly reduced LDL-C in phase II trials .


Patients 18 to 80 years of age with fasting low-density lipoprotein cholesterol ( LDL-C ) 100 and < 190 mg/dl and Framingham risk scores10 % were randomized ( 1:1:1:1:2:2 ) to oral placebo and subcutaneous ( SC ) placebo biweekly ; oral placebo and SC placebo monthly ; ezetimibe and SC placebo biweekly ; ezetimibe and SC placebo monthly ; oral placebo and evolocumab 140 mg biweekly ; or oral placebo and evolocumab 420 mg monthly .


A total of 614 patients were randomized and administered doses .


Evolocumab treatment reduced LDL-C from baseline , on average , by 55 % to 57 % more than placebo and 38 % to 40 % more than ezetimibe ( p < 0.001 for all comparisons ) .


Evolocumab treatment also favorably altered other lipoprotein levels .


Treatment-emergent adverse events ( AEs ) , muscle-related AEs , and laboratory abnormalities were comparable across treatment groups .


In the largest monotherapy trial using a PCSK9 inhibitor to date , evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia .


( Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing LipidLevels-2 [ MENDEL-2 ] ; NCT01763827 ) .


The modern classroom is an inherently sedentary environment .


Virtual Field Trips ( VFTs ) using interactive whiteboards to explore virtual scenes are a potential method of converting sedentary class-time into physically active teaching .


This pilot aimed to assess the effects of a developed VFT on physical activity and learning in primary-school children .


Participants ( n = 85 ) were randomly assigned to a ) a 30-minute physically active London 2012 Olympics-themed VFT , or b ) a 30-minute sedentary version of the same VFT .


Activity was measured using GT1M Actigraphs , content recall was assessed with a quiz and user evaluations were gained from teacher and pupil questionnaires .


Pupils in the active VFT displayed significantly less sedentary time ( p < 0.001 ) , and significantly more light ( p < 0.001 ) , moderate ( p = 0.01 ) and vigorous physical activity ( p < 0.001 ) than sedentary VFT pupils .


No differences in content recall were found between intervention groups : suggesting that adding physical activity into classroom teaching may not compromise attainment .


High acceptability was found in teachers and active VFT students rated their session significantly higher than sedentary pupils ( p < 0.002 ) .


This one-day pilot provides early evidence of the ability of VFTs to convert sedentary academic time into active time .


Longitudinal research is needed to assess prolonged effects of active VFTs in reducing sedentary time .


To compare biofeedback-guided pelvic floor exercise therapy ( BFT ) with the use of oral polyethylene glycol ( PEG ) for the treatment of obstructive defecation .


A total of 88 subjects were assigned to treatment with either BFT ( n = 44 ) or oral PEG ( n = 44 ) .


Constipation symptoms ( including difficult evacuation , hard stool , digitation necessity , incomplete emptying sensation , laxative dependence , perianal pain at defecation , and constipation satisfaction ) , Wexner Scores , and quality of life scores were assessed after 1 , 3 , and 6 mo. .


At the 6 mo follow-up , the symptoms of the BFT group patients showed significantly greater improvements compared with the PEG group regarding difficult evacuation , hard stools , digitation necessity , laxative dependence , perianal pain at defecation , constipation satisfaction , Wexner Constipation Score , and quality of life score ( P < 0.05 ) .


The quality of life score of the BFT group at the final follow-up time ( 6 mo ) was 80 2.2 .


After a complete course of training , improvements in the clinical symptoms of the BFT group were markedly improved ( P < 0.05 ) , and the Wexner Constipation Scores were greatly decreased compared with the oral PEG group ( P < 0.05 ) .


We concluded that manometric biofeedback-guided pelvic floor exercise training is superior to oral polyethylene glycol therapy for obstructive defecation .


The ability to physically perform at high altitude may require unique strategies to acclimatize before exposure .


The effect of acute hypoxic exposure on the metabolic response of the skeletal muscle may provide insight into the value of short-term preacclimatization strategies .


To determine the human skeletal muscle response to a single acute bout of exercise in a hypoxic environment on metabolic gene expression .


Eleven recreationally active male participants ( 24 4 years , 173 20 cm , 82 12 kg , 15.2 7.1 % fat , 4.0 0.6 L/min maximal oxygen consumption ) completed two 1-hour cycling exercise trials at 60 % of peak power followed by 4 hours of recovery in ambient environmental conditions ( 975 m ) and at normobaric hypoxic conditions simulating 3000 m in a randomized counterbalanced order .


Muscle biopsies were obtained from the vastus lateralis before exercise and 4 hours after exercise for real-time polymerase chain reaction analysis of select metabolic genes .


Gene expression of hypoxia-inducible factor 1 alpha , cytochrome c oxidase subunit 4 , peroxisome proliferator-activated receptor gamma coactivator 1 alpha , hexokinase , phosphofructokinase , mitochondrial fission 1 , and mitofusin-2 increased with exercise ( P < .05 ) but did not differ with hypoxic exposure ( P > .05 ) .


Optic atrophy 1 did not increase with exercise or differ between environmental conditions ( P > .05 ) .


The improvements in mitochondrial function reported with intermittent hypoxic training may not be explained by a single acute hypoxic exposure , and thus it appears that a longer period of preacclimatization than a single exposure may be required .


The current phase II clinical study was conducted to evaluate the efficacy and safety of weekly docetaxel alone , and weekly docetaxel-plus-oxaliplatin , as a second-line chemotherapy in patients with cisplatin-refractory advanced gastric cancer .


We enrolled patients with histologically confirmed gastric adenocarcinoma whose disease had progressed after cisplatin-based regimens .


Patients were randomly assigned to receive docetaxel alone ( 36 mg/m ( 2 ) , days 1 and 8 ) or docetaxel ( 36 mg/m ( 2 ) , days 1 and 8 ) and oxaliplatin ( 80 mg/m ( 2 ) , day 1 ) combination therapy every three weeks .


This trial was terminated early due to poor patient accrual rate .


From January 2009 to January 2012 , a total of 52 patients were enrolled in the current study from six centers : 27 patients in the docetaxel monotherapy arm and 25 patients in the docetaxel/oxaliplatin combination arm .


Fifty-two patients were assessable for efficacy , and response rates as follows ( response rate : 14.8 % in the monotherapy arm , 24.0 % in the combination arm ; disease control rate : 48.1 % in the monotherapy arm , 76.0 % in the combination arm .


The median progression-free survival was 2.0 ( 95 % confidence interval = 1.2-2 .9 ) months in the monotherapy arm and 4.9 ( 95 % confidence interval = 3.6-6 .6 ) months in the combination arm ( p = 0.002 ) .


The most common grade 3 or 4 adverse event was neutropenia ( 14 % for monotherapy versus 32 % for combination ) .


No treatment-related mortality was observed .


Weekly docetaxel and weekly docetaxel-plus-oxalipaltin regimens were found to be well-tolerated and effective as a second-line chemotherapy for patients with advanced gastric cancer .


We conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome ( BOS ) post lung transplantation .


We compared azithromycin ( 250mg alternate days , 12weeks ) with placebo .


Primary outcome was FEV1 change at 12weeks .


48 patients were randomised ; ( 25 azithromycin , 23 placebo ) .


It was established , post randomisation that two did not have BOS .


46 patients were analysed as intention to treat ( ITT ) with 33 ` Completers ' .


ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal .


The ITT analysis ( n = 46 , 177 observations ) estimated mean difference in FEV1 between treatments ( azithromycin minus placebo ) was 0.035 L , with a 95 % CI of -0.112 L to 0.182 L ( p = 0.6 ) .


Five withdrawals , who were identified at the end of the study as having been randomised to placebo ( four with rapid loss in FEV1 , one withdrawn consent ) had received rescue open-label azithromycin , with improvement in subsequent FEV1 at 12weeks .


Study Completers showed an estimated mean difference in FEV1 between treatment groups ( azithromycin minus placebo ) of 0.278 L , with 95 % CI for the mean difference : 0.170 L to 0.386 L ( p = < 0.001 ) .


Nine of 23 ITT patients in the azithromycin group had 10 % gain in FEV1 from baseline .


No patients in the placebo group had 10 % gain in FEV1 from baseline while on placebo ( p = 0.002 ) .


Seven serious adverse events , three azithromycin , four in the placebo group , were deemed unrelated to study medication .


Azithromycin therapy improves FEV1 in patients with BOS and appears superior to placebo .


This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS .


EU-CTR , 2006-000485-36 / GB .


Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions .


To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores .


We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis .


After a 3-day esomeprazole infusion , patients with Rockall scores 6 were randomised into the oral double-dose group ( n = 93 ) or the oral standard-dose group ( n = 94 ) to receive 11days of oral esomeprazole 40mg twice daily or once daily , respectively .


The patients with Rockall scores < 6 served as controls ( n = 89 ) ; they received 11days of oral esomeprazole 40mg once daily .


Thereafter , all patients received oral esomeprazole 40mg once daily for two more weeks until the end of the 28-day study period .


The primary end point was peptic ulcer rebleeding .


Among patients with Rockall scores 6 , the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group ( p = 0.02 , log-rank test ) .


The proportion of patients free from recurrent bleeding during the 4th-28th day in the oral double-dose group remained lower than that of the group with Rockall scores < 6 ( p = 0.03 , log-rank test ) .


Among patients with Rockall scores 6 , the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group ( 4th-28th day : 10.8 % vs 28.7 % , p = 0.002 ) .


Double oral esomeprazole at 40mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores 6 .


NCT01591083 .


Postoperative blood loss in patients after total knee arthroplasty may cause local and systemic complications and influence clinical outcome .


The aim of this study was to assess whether fibrin glue or tranexamic acid reduced blood loss compared with routine hemostasis in patients undergoing total knee arthroplasty .


A randomized , single-center , parallel , open clinical trial was performed in adult patients undergoing primary total knee arthroplasty .


Patients were divided into four groups .


Group 1 received fibrin glue manufactured by the Blood and Tissue Bank of Catalonia , Group 2 received Tissucol ( fibrinogen and thrombin ) , Group 3 received intravenous tranexamic acid , and Group 4 ( control ) had no treatment other than routine hemostasis .


The primary outcome was total blood loss collected in drains after surgery .


Secondary outcomes were the calculated hidden blood loss , transfusion rate , preoperative and postoperative hemoglobin , number of blood units transfused , adverse events , and mortality .


One hundred and seventy-two patients were included .


The mean total blood loss ( and standard deviation ) collected in drains was 553.9 321.5 mL for Group 1 , 567.8 299.3 mL for Group 2 , 244.1 223.4 mL for Group 3 , and 563.5 269.7 mL for Group 4 .


In comparison with the control group , Group 3 had significantly lower total blood loss ( p < 0.001 ) , but it was not significantly lower in Groups 1 and 2 .


The overall rate of patients who had a blood transfusion was 21.1 % ( thirty-five of 166 patients analyzed per protocol ) .


Two patients required transfusion in Group 3 compared with twelve patients in Group 4 ( p = 0.015 ) .


No significant difference was observed between the two fibrin glue groups and the control group with regard to the need for transfusion .


There was no difference between groups with regard to the percentage of adverse events .


Neither type of fibrin glue was more effective than routine hemostasis in reducing postoperative bleeding and transfusion requirements , and we no longer use them .


However , this trial supports findings from previous studies showing that intravenous tranexamic acid can decrease postoperative blood loss .


Type 1 diabetes ( T1D ) results from destruction of pancreatic cells by autoreactive effector T cells .


We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes in effector T cells and prolonged preservation of endogenous insulin secretion by the remaining cells in patients with newly diagnosed T1D .


In a multicenter , randomized , double-blind , placebo-controlled trial , we compared alefacept ( two 12-week courses of 15 mg/wk i.m. , separated by a 12-week pause ) with placebo in patients with recent onset of T1D .


Endpoints were assessed at 24 months and included meal-stimulated C-peptide AUC , insulin use , hypoglycemic events , and immunologic responses .


A total of 49 patients were enrolled .


At 24 months , or 15 months after the last dose of alefacept , both the 4-hour and the 2-hour C-peptide AUCs were significantly greater in the treatment group than in the control group ( P = 0.002 and 0.015 , respectively ) .


Exogenous insulin requirements were lower ( P = 0.002 ) and rates of major hypoglycemic events were about 50 % reduced ( P < 0.001 ) in the alefacept group compared with placebo at 24 months .


There was no apparent between-group difference in glycemic control or adverse events .


Alefacept treatment depleted CD4 + and CD8 + central memory T cells ( Tcm ) and effector memory T cells ( Tem ) ( P < 0.01 ) , preserved Tregs , increased the ratios of Treg to Tem and Tcm ( P < 0.01 ) , and increased the percentage of PD-1 + CD4 + Tem and Tcm ( P < 0.01 ) .


In patients with newly diagnosed T1D , two 12-week courses of alefacept preserved C-peptide secretion , reduced insulin use and hypoglycemic events , and induced favorable immunologic profiles at 24 months , well over 1 year after cessation of therapy .


https://clinicaltrials.gov/ NCT00965458 .


NIH and Astellas .


Millions of patients were treated with the sirolimus-eluting Cypher and the paclitaxel-eluting Taxus coronary stents with potential late-occurring increase in event rates .


Therefore , the long-term outcome follow-up is of major clinical interest .


In total , 2.098 unselected patients with ST-segment elevation myocardial infarction ( STEMI ) , non-STEMI , stable or unstable angina pectoris were randomized to receive Cypher ( n = 1.065 ) or Taxus ( n = 1.033 ) stents and were followed for 5 years .


The primary end-point ; the composite of cardiac death , myocardial infarction and target vessel revascularization ( major adverse cardiac event , MACE ) , occurred in 467 patients ( 22.3 % ) ; Cypher n = 222 ( 20.8 % ) , Taxus n = 245 ( 23.7 % ) , ns .


Definite and probable stent thrombosis occurred in 107 patients ( 5.1 % ) ; Cypher n = 51 ( 4.8 % ) , Taxus n = 56 ( 5.4 % ) , ns .


No statistically significant differences were found in the elements of the primary end-point or in other secondary end-points between the two stent groups .


After one year , the annual rates of stent thrombosis and MACE remained constant .


During 5-year follow-up , the Cypher and the Taxus coronary stents had similar clinical outcome with no signs of increasing rates of adverse events over time .


Lysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism .


We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency , an underappreciated cause of cirrhosis and severe dyslipidemia .


In this multicenter , randomized , double-blind , placebo-controlled study involving 66 patients , we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa ( administered intravenously at a dose of 1 mg per kilogram of body weight every other week ) ; the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients .


The primary end point was normalization of the alanine aminotransferase level .


Secondary end points included additional disease-related efficacy assessments , safety , and side-effect profile .


Substantial disease burden at baseline included a very high level of low-density lipoprotein cholesterol ( 190 mg per deciliter ) in 38 of 66 patients ( 58 % ) and cirrhosis in 10 of 32 patients ( 31 % ) who underwent biopsy .


A total of 65 of the 66 patients who underwent randomization completed the double-blind portion of the trial and continued with open-label treatment .


At 20 weeks , the alanine aminotransferase level was normal in 11 of 36 patients ( 31 % ) in the sebelipase alfa group and in 2 of 30 ( 7 % ) in the placebo group ( P = 0.03 ) , with mean changes from baseline of -58 U per liter versus -7 U per liter ( P < 0.001 ) .


With respect to prespecified key secondary efficacy end points , we observed improvements in lipid levels and reduction in hepatic fat content ( P < 0.001 for all comparisons , except P = 0.04 for triglycerides ) .


The number of patients with adverse events was similar in the two groups ; most events were mild and were considered by the investigator to be unrelated to treatment .


Sebelipase alfa therapy resulted in a reduction in multiple disease-related hepatic and lipid abnormalities in children and adults with lysosomal acid lipase deficiency .


( Funded by Synageva BioPharma and others ; ARISE ClinicalTrials.gov number , NCT01757184 . )


Cryosurgery is the most common treatment for actinic keratosis ( AK ) in the United States .


Efficacy with cryosurgery is variable , and is a modality for treating individual , visible lesions while failing to treat subclinical lesions .


FIELD Study 1 ( NCT01541553 ) is a phase 3 , multicenter , randomized , double-blind study that evaluated the short - ( 11-week ) and long - ( 12-month ) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol mebutate gel , versus cryosurgery followed by vehicle .


Overall , 329 patients were randomized to ingenol mebutate 0.015 % gel ( n = 167 ) or vehicle ( n = 162 ) 3 weeks after cryosurgery .


Baseline characteristics were balanced across groups .


At week 11 , complete clearance rate ( 100 % ) in the treatment area was higher for ingenol mebutate gel compared with vehicle ( 60.5 % vs 49.4 % , respectively ; P = .04 ) .


Mean percentage reduction in number of AKs versus baseline was also numerically higher for ingenol mebutate gel ( 82.7 % vs 75.6 % ) .


A general reduction from baseline lesion count was observed 3 weeks after cryosurgery .


Treatment after cryosurgery was well tolerated .


Short-term ( 11-week ) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher than with cryosurgery alone .


To evaluate the contraction pattern of masticatory muscles during sustained clenching tasks with or without experimental pain induced by glutamate injection into the masseter muscle .


It was hypothesized that acute muscle pain could induce compensatory changes in the electromyographic ( EMG ) activity of the masticatory muscles .


Fifteen volunteers ( seven males , mean age SD = 29.7 1.1 years ; eight females , mean age SD = 23.5 1.2 years ) were recruited in a crossover experimental study .


All subjects participated in two randomized 20-minute experimental sessions .


Each subject was asked to clench at 25 % of the maximum voluntary contraction ( MVC ) .


After 10 minutes , isotonic saline or glutamate was injected in random order into the right masseter .


EMG activity ( root mean square [ RMS ] and mean power frequency [ MPF ] ) was assessed in the masseter and anterior temporalis muscles on both sides .


Pain and fatigue were assessed by 0-10 numeric rating scales ( NRS ) every minute .


Differences between conditions ( isotonic saline vs glutamate ) for all the outcome parameters were analyzed by using a mixed effect model .


The EMG activity of the masticatory muscles and pain and fatigue scores were not dependent on isotonic saline/glutamate injection ( all P > .05 ) .


The RMS in the temporalis and masseter muscles increased with time ( right masseter P = 0.001 , left masseter P = .004 , right temporalis P = .22 , left temporalis P = .006 ) , whereas the MPF decreased ( right masseter P = .0001 , left masseter P < .0001 , right temporalis P = .51 , left temporalis P = .0005 ) .


Scores for fatigue and pain increased during the experimental sessions ( all P < .05 ) .


Intramuscular injection of glutamate caused more pain than isotonic saline but did not affect the contraction pattern of the masticatory muscles during a sustained clenching task .


This finding strongly suggests the adaptive capacity of the stomatognathic system in the presence of acute nociceptive inputs .


The purpose of this study was to investigate the hypothesis that dietary supplementation with rice bran fermented with Lentinus edodes ( rice bran exo-biopolymer , RBEP ) , a substance known to contain arabinoxylan , enhances natural killer ( NK ) cell activity and modulates cytokine production in healthy adults .


This study was designed in a randomized , double-blind , placebo-controlled , and parallel-group format .


Eighty healthy participants with white blood cell counts of 4,000-8 ,000 cells/L were randomly assigned to take six capsules per day of either 3 g RBEP or 3 g placebo for 8 weeks .


Three participants in the placebo group were excluded after initiation of the protocol ; no severe adverse effects from RBEP supplementation were reported .


NK cell activity of peripheral blood mononuclear cells was measured using nonradioactive cytotoxicity assay kits and serum cytokine concentrations included interferon ( IFN ) - , tumor necrosis factor ( TNF ) - , interleukin ( IL ) -2 , IL-4 , IL-10 , and IL-12 were measured by Bio-Plex cytokine assay kit .


This study was registered with the Clinical Research Information Service ( KCT0000536 ) .


Supplementation of RBEP significantly increased IFN - production compared with the placebo group ( P = 0.012 ) .


However , RBEP supplementation did not affect either NK cell activity or cytokine levels , including IL-2 , IL-4 , IL-10 , IL-12 , and TNF - , compared with the placebo group .


The data obtained in this study indicate that RBEP supplementation increases IFN - secretion without causing significant adverse effects , and thus may be beneficial to healthy individuals .


This new rice bran-derived product may therefore be potentially useful to include in the formulation of solid and liquid foods designed for treatment and prevention of pathological states associated with defective immune responses .


Inflammation contributes to the pathogenesis of psoriasis as well as atrial fibrillation .


The impact of psoriasis and its association with new-onset atrial fibrillation was assessed in hypertensive patients with left ventricular hypertrophy ( LVH ) .


The predictive value of baseline or incident psoriasis for new-onset atrial fibrillation was evaluated in 7099 hypertensive patients with electrocardiographic LVH with no history of atrial fibrillation or other cardiovascular disease , in sinus rhythm on their baseline electrocardiogram .


A total of 154 patients ( 2.2 % ) had or developed psoriasis and new-onset atrial fibrillation occurred in 506 patients ( 7.1 % ) during a mean follow-up of 4.7 1.1 years .


At baseline , the psoriasis patients were younger ( 65 7 vs. 67 7 years ) and had less left ventricle hypertrophy by ECG Sokolow-Lyon voltage ( 27.6 9.7 vs. 30.1 10.4 mm ) ; higher hemoglobin ( 6.3 2.2 vs. 6.0 2.7 mmol/l ) and prevalence of diabetes ( 20.6 vs. 12.8 % , P 0.004 ) than patients without psoriasis .


In multivariable Cox analysis , adjusting for age , sex , hemoglobin , diabetes , time-varying SBP , heart rate , study treatment and Sokolow-Lyon hypertrophy , psoriasis , treated as a time-varying covariate , was associated with a two-fold higher risk of new-onset atrial fibrillation [ hazard ratio : 1.97 ( 95 % confidence interval ( CI ) : 1.18-3 .30 ) , P = 0.01 ] .


Propensity-matched analysis yielded similar results ( odds ratio : 3.49 , 95 % CI 1.24-9 .81 , P = 0.018 ) .


Psoriasis has a similar prevalence in hypertensive patients as in the general population .


Psoriasis independently predicted new-onset atrial fibrillation despite lower age and electrocardiographic LVH in psoriasis patients than in patients without psoriasis .


Many patients with relapsing-remitting multiple sclerosis ( MS ) treated with high-dose interferon - ( IFN ) develop serum binding antibodies ( BAb ) and neutralizing antibodies ( NAb ) .


NAb reduces the biological activity of IFN , which contributes to clinical failure in these patients .


We investigated whether access to antibody ( Ab ) test results would alter usual care of ( IFN ) - treated patients and whether BAb could predict NAb .


This was a randomized , controlled , open-label , parallel-group , multicenter study in patients with multiple sclerosis .


Subjects ( n = 1358 ) were randomly assigned to Ab testing or usual care .


BAb and NAb titres were measured using standard assays .


Primary and secondary outcomes were the proportion of patients whose IFN therapy changed and the type of and reasons for therapy changes .


Therapy changes differed between the Ab testing and usual care arms ( 19.6 % and 14.0 % , respectively ; p = 0004 ) .


Results from Ab testing were more frequently reported as the reason for therapy change in the Ab testing arm than in the usual care arm ( p < 0.0001 ) .


NAb and BAb positivity significantly increased the likelihood of therapy change and reduced IFN-associated adverse events .


BAb titres were a significant predictor of NAb positivity ( p = 0.0012 ) .


Initial BAb-positive and NAb-positive status in both study arms had a significant impact on the overall number of patients with a therapy change ( p < 0.05 ) .


Access to Ab test results impacted therapy management .


BAb titres can predict NAb positivity in patients on high-dose IFN .


The aim of this report was to clinically and radiographically evaluate changes to the hard and soft tissues around implants placed in extraction sockets grafted with medical grade calcium sulfate hemihydrate ( MGCSH ) mixed with platelet-rich plasma ( PRP ) and a collagen resorbable plug after one year of function .


This evaluation was part of a previous study conducted to evaluate extraction socket grafts .


Fourteen subjects out of 16 were evaluated .


After tooth extraction , eight subjects received MGCSH mixed with PRP in the extraction sockets ( test group ) , and six subjects received collagen resorbable plug dressing material ( control group ) .


After three months of bone healing , dental implants were placed .


Three months after implant installation , provisional restorations were placed and implants were loaded in function for one month followed by definitive restorations .


Follow-up examinations and intraoral digital radiographs were made at baseline and one year after definitive restorations to evaluate the marginal bone level in each subject .


At the one-year follow-up , the survival and success rate was 100 % for all implants .


There was no statistically significant difference in the amount of vertical bone loss between groups after 1 year ( p > 0.05 ) .


For the test group , there was a mean mesial bone loss of -0.8 + / - 0.6 mm and a mean distal bone loss of -0.5 + / - 0.4 mm .


For the control group , there was a mean mesial bone loss of -1.1 + / - 0.7 mm and a mean distal bone loss of -0.6 + / - 0.6 mm .


At the one-year follow-up , the implant placement in grafted sockets was not affected by the type of the graft material .


Implants placed in sockets grafted with MGCSH mixed with PRP showed less marginal bone loss after one year in comparison to those with collagen resorbable grafts .


Patients with HIV on antiretroviral therapy might benefit from regimen simplification to reduce pill burden and dosing frequency .


We aimed to assess the safety and efficacy of simplifying the treatment regimen for adults with virologically suppressed HIV infection from a ritonavir-boosted protease inhibitor and emtricitabine plus tenofovir disoproxil fumarate ( tenofovir ) regimen to coformulated elvitegravir , cobicistat , emtricitabine , and tenofovir .


STRATEGY-PI is a 96 week , international , multicentre , randomised , open-label , phase 3b trial in which HIV-infected adults with a plasma HIV-1 RNA viral load of less than 50 copies per mL for at least 6 months who were taking a ritonavir-boosted protease inhibitor with emtricitabine plus tenofovir were randomly assigned ( 2:1 ) either to switch to coformulated elvitegravir , cobicistat , emtricitabine , and tenofovir or to continue on their existing regimen .


Key eligibility criteria included no history of virological failure , no resistance to emtricitabine and tenofovir , and creatinine clearance of 70 mL/min or higher .


Neither participants nor investigators were masked to group allocation .


The primary endpoint was the proportion of participants with a viral load of less than 50 copies per mL at week 48 , based on a US Food and Drug Administration snapshot algorithm for the modified intention-to-treat population , which excluded major protocol violations ( prohibited resistance or not receiving a protease inhibitor at baseline ) .


We prespecified non-inferiority with a 12 % margin ; if non-inferiority was established , superiority was tested as per a prespecified sequential testing procedure .


This trial is registered at ClinicalTrials.gov , number NCT01475838 .


Between Dec 12 , 2011 , and Dec 20 , 2012 , 433 participants were randomly assigned and received at least one dose of study drug .


Of these participants , 293 were assigned to switch to the simplified regimen ( switch group ) and 140 to remain on their existing regimen ( no-switch group ) ; after exclusions , 290 and 139 participants , respectively , were analysed in the modified intention-to-treat population .


At week 48 , 272 ( 938 % ) of 290 participants in the switch group maintained a viral load of less than 50 copies per mL , compared with 121 ( 871 % ) of 139 in the no-switch group ( difference 67 % , 95 % CI 04-137 ; p = 0025 ) .


The statistical superiority of the simplified regimen was mainly caused by a higher proportion of participants in the no-switch group than in the switch group discontinuing treatment for non-virological reasons ; virological failure was rare in both groups ( two [ 1 % ] of 290 vs two [ 1 % ] of 139 ) .


We did not detect any treatment-emergent resistance in either group .


Adverse events leading to discontinuation were rare in both groups ( six [ 2 % ] of 293 vs four [ 3 % ] of 140 ) .


Switching to the simplified regimen was associated with a small , non-progressive increase from baseline in serum creatinine concentration .


Nausea was more common in the switch group than in the no-switch group , but rates of diarrhoea and bloating decreased compared with baseline from week 4 to week 48 in the switch group , whereas there were generally no changes for these symptoms in the no-switch group .


Coformulated elvitegravir , cobicistat , emtricitabine , and tenofovir might be a useful regimen simplification option for virologically supressed adults with HIV taking a multitablet ritonavir-boosted protease inhibitor regimen .


Gilead Sciences .


The aim of this study is to assess the efficacy of an initial dose of ribavirin administered before a 48-week course of treatment with peg-IFN + ribavirin in treatment-nave patients and in patients after previous failure of CHC treatment .


A total of 103 patients with chronic hepatitis C infected with genotype 1 HCV were qualified to the study .


Study patients were randomised to receive one of two treatments : A - RBV for 4 weeks followed by combined therapy with peg-IFN alpha-2a + RBV for 48 weeks ( n = 73 ) , or B - combined therapy with peg-IFN alpha-2a + RBV for 48 weeks ( n = 30 ) .


SVR 24 was observed in 44 % patients in group A and in group 40 % patients in group B ( 40 % ) , p > 0.05 .


Comparing subgroups of the naive patients , it was found that the SVR24 value was higher in group A than group B ( 57 % vs. 47 % , p > 0.05 ) .


In the re-therapy subgroups , higher treatment response rates in patients not responding earlier was found in group A than group B ( 39 % vs. 16 % , p > 0.05 ) .


No significant advantage was found in the use of a priming method over a standard regimen .


However , it could be recommended in patients with a total lack of response to peg-IFN and ribavirin when no other therapeutic options are available .


Vitamin D deficiency affects 1 billion people globally .


It has an important role in bone homeostasis , brain development and modulation of the immune system and yet the impact of antenatal vitamin D deficiency on infant outcomes is poorly understood .


We assessed the association of 25 - hydroxyvitamin D levels ( 25-OHD ) in late pregnancy and early infant growth and developmental outcomes in rural Vietnam .


A prospective cohort study of 960 women who had previously participated in a double-blind cluster randomized controlled trial of antenatal micronutrient supplementation in rural Vietnam was undertaken .


Maternal 25-OHD concentration was measured at 32 weeks gestation , and infants were followed until 6 months of age .


Main outcome measures were cognitive , motor , socio-emotional and language scores using the Bayley Scales of Infant Development , 3rd edition , and infant length-for-age z scores at 6 months of age .


60 % ( 582/960 ) of women had 25-OHD levels < 75 nmol/L at 32 weeks gestation .


Infants born to women with 25-OHD deficiency ( < 37.5 nmol/L ) had reduced developmental language scores compared to those born to women who were vitamin D replete ( 75 nmol/L ) ( Mean Difference ( MD ) -3.48 , 95 % Confidence Interval ( CI ) -5.67 to -1.28 ) .


For every 25 nmol increase in 25-OHD concentration in late pregnancy , infant length-for-age z scores at 6 months of age decreased by 0.08 ( 95 % CI -0.15 to -0.02 ) .


Low maternal 25 - hydroxyvitamin D levels during late pregnancy are of concern in rural Vietnam , and are associated with reduced language developmental outcomes at 6 months of age .


Our findings strengthen the evidence for giving vitamin D supplementation during pregnancy .


Poor management of chronic medical treatments may result in severe health consequences for patients as well as costs for society .


Non-adherence is common among patients with type 2 diabetes .


Interventions by community pharmacists may assist in improving adherence and consequently health outcomes for patients with type 2 diabetes .


The study aimed to investigate whether a comprehensive and a brief individually targeted intervention for patients with type 2 diabetes could improve implementation of drug therapy in Danish community pharmacies .


The interventions intended to give patients more competence and support to improve adherence and self-management in order to reach treatment goals for diabetes and blood pressure as well as goals for patient perceived outcomes .


This study was an RCT , comparing two interventions ; basic intervention ( BI ) and extended intervention ( EI ) .


The intervention model sought to identify drug-related problems as well as issues experienced by patients in relation to medicines use , and consequently find individually tailored solutions to address the identified problems .


The trial included five pharmacies ; five pharmacists and five pharmaconomists , and 205 patients ; BI ( 39 patients ) , EI ( 41 patients ) , Control ( 125 patients ) .


Patient reported systolic blood pressure improved in both groups and significantly in the EI group compared to the control group ( P = 0.020 ) .


Increase in disease-related knowledge was higher in the EI group compared to the control group ( P = 0.006 ) , but not in the BI group ( P = 0.139 ) .


Except for quality of life , the EI group reported significantly higher improvement in all aspects of beneficial effects from participating in the trial when compared to the control group .


No significant differences were detected for changes in hospital admissions or in doctor visits .


The two intervention groups reported significantly higher satisfaction with all aspects of patient satisfaction with pharmacy staff in the project than control patients .


The study showed improvement in patient health , well-being , knowledge , and satisfaction as a result of the trial , particularly for the EI group .


Thus a program comprising patient narratives , problem and resource identification , and multi-dimensional individually tailored patient medication management solutions seems to be an appropriate intervention to ensure outcome improvement of non-adherent patients .


The 4-stage approach ( 4-SA ) is used as a didactic method for teaching practical skills in international courses on resuscitation and the structured care of trauma patients .


The aim of this study was to evaluate objective and subjective learning success of a video-assisted 4-SA in teaching undergraduate medical students .


The participants were medical students learning the principles of the acute treatment of trauma patients in their multidiscipline course on emergency and intensive care medicine .


The participants were quasi - randomly divided into two groups .


The 4-SA was used in both groups .


In the control group , all four steps were presented by an instructor .


In the study group , the first two steps were presented as a video .


At the end of the course a 5-minute objective , structured clinical examination ( OSCE ) of a simulated trauma patient was conducted .


The test results were divided into objective results obtained through a checklist with 9 dichotomous items and the assessment of the global performance rated subjectively by the examiner on a Likert scale from 1 to 6 .


313 students were recruited ; the results of 256 were suitable for analysis .


The OSCE results were excellent in both groups and did not differ significantly ( control group : median 9 , interquantil range ( IQR ) 8-9 , study group : median 9 , IQR 8-9 ; p = 0.29 ) .


The global performance was rated significantly better for the study group ( median 1 , IQR 1-2 vs. median 2 , IQR 1-3 ; p < 0.01 ) .


The relative knowledge increase , stated by the students in their evaluation after the course , was greater in the study group ( 85 % vs. 80 % ) .


It is possible to employ video assistance in the classical 4-SA with comparable objective test results in an OSCE .


The global performance was significantly improved with use of video assistance .


Although anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration ( AMD ) results in improved vision overall , loss of substantial vision can occur .


Understanding the processes that lead to loss of vision may lead to preventive strategies .


To determine the incidence , characteristics , causes , and baseline predictors of sustained visual acuity loss after 2 years of treatment with ranibizumab or bevacizumab for neovascular AMD .


A cohort study within a randomized clinical trial of participants in the Comparison of Age-Related Macular Degeneration Treatments Trials ( CATT ) .


Participants were randomly assigned to treatment with ranibizumab or bevacizumab and to 2 years of monthly or as needed injections or monthly injections for 1 year and as needed injections the following year .


Sustained visual acuity loss , defined as loss of 15 or more letters from baseline at weeks 88 and 104 .


Among 1030 participants , 61 eyes ( 5.9 % ) developed sustained visual acuity loss in 2 years .


Within this group , visual acuity decreased gradually over time , with a mean decrease of 2 , 19 , and 33 letters from baseline at 4 weeks , 1 year , and 2 years , respectively .


At 2 years , eyes with sustained visual acuity loss had more scarring ( 60.0 % vs 41.4 % , P = .007 ) , more geographic atrophy ( GA ) ( 31.6 % vs 20.7 % , P = .004 ) , larger lesions ( 16 vs 8 mm2 , P < .001 ) , and higher proportions of intraretinal fluid ( 82.5 % vs 51.0 % , P < .001 ) , subretinal hyperreflective material ( 84.5 % vs 44.2 % , P < .001 ) , retinal thinning ( 43.3 % vs 23.0 % , P < .001 ) , and thickening ( 20.0 % vs 12.1 % , P < .001 ) .


Likely causes of sustained visual acuity loss included foveal scarring ( 44.3 % ) , pigmentary abnormalities ( 27.9 % ) , and foveal GA ( 11.5 % ) .


Baseline factors independently associated with a higher incidence of sustained visual acuity loss were the presence of nonfoveal GA ( odds ratio [ OR ] , 2.86 ; 95 % CI , 1.35-6 .08 ; P = .006 ) , larger area of choroidal neovascularization ( OR for a > 4-disc area vs 1-disc area , 3.91 ; 95 % CI , 1.70-9 .03 ; P = .007 ) , and bevacizumab treatment ( OR , 1.83 ; 95 % CI , 1.07-3 .14 ; P = .03 ) .


Sustained visual acuity loss was relatively rare in CATT .


The development of foveal scar , pigmentary abnormalities , or GA contributed to most of the sustained visual acuity loss .


Risk was 3 % higher among eyes treated with bevacizumab .


Treatment that targeted the prevention of scarring or GA may improve vision outcomes .


clinicaltrials.gov Identifier : NCT00593450 .


To compare 2 digital flexible ureteroscopes in a randomized , prospective , clinical trial ; the complementary metal oxide semiconductor-based Gyrus ACMI/Olympus Invisio DUR-D and the charged coupled device-based Olympus URF-V .


Patients scheduled for ureteroscopy were prospectively enrolled and randomized between the DUR-D and URF-V .


Patient demographics , laser and total procedure time , laser energy , lower pole time , and difficulties encountered were recorded .


The visibility and maneuverability were rated on a scale of 0-10 .


A total of 101 patients ( 58 women ) with a mean age of 49.5 years ( 20-80 years ) were enrolled .


Laser lithotripsy ( mean stone size , 11.8 mm ) was performed in 88 patients , 10 underwent stone basketing , and 3 had diagnostic ureteroscopy .


For the DUR-D and URF-V , the mean total operative time ( 26.5 vs 25 minutes ) , laser time ( 12.5 vs 13 minutes ) , lower pole time ( 9 vs 11 minutes ) , and basket time ( 14.5 vs 13 minutes ) were comparable .


In 3 of 45 ( 6.6 % ) and 6 of 56 ( 10.7 % ) cases , the stone could not be reached with the DUR-D and URF-V , respectively .


A fiberoptic scope ( URF-P5 ) reached the stone in all cases .


On a scale of 0-10 , the mean visibility was 6.86 and 8.73 ( P < .01 ) and the maneuverability was 7.18 and 8.17 ( P < .01 ) for DUR-D and URF-V , respectively .


There were 8 repairs , 4 for each scope .


The DUR-D averaged 11.25 cases per repair and the URF-V averaged 14 .


The URF-V offered better visibility and maneuverability compared with the DUR-D .


Both had similar failure rates compared with the previous study with fiberoptic scopes .


Ability to perform basic daily activity represented by functional status ( FNS ) before surgery can be assessed in the clinic for determining health status of the patient .


We sought to study the effect of FNS on postoperative outcomes after carotid endarterectomy ( CEA ) in a national data set .


National Surgical Quality Improvement Project is a national data set , which includes data from > 300 hospitals .


Patients who underwent CEA were identified by Current Procedural Terminology code and divided into 3 categories based on FNS : independent , partially dependent , and dependent .


Thirty-day postoperative stroke , death , and other postoperative complications were identified as the study end point .


We used multivariate logistic regression to estimate odds ratio for outcomes while controlling for sex , race , diabetes mellitus , cardiovascular disease , smoking , and other confounders .


Of 19 748 CEAs , 19 348 ( 97.97 % ) were functionally independent , 377 ( 1.99 % ) were functionally partially dependent , and 23 ( 0.12 % ) were functionallydependent .


In functionally independent group , there were 196 ( 1.01 % ) strokes , 84 ( 0.43 % ) deaths , and 1416 ( 7.17 % ) other complications , whereas in the functionally partially dependent group , there were 14 ( 3.71 % ) strokes , 10 ( 2.65 % ) deaths , and 80 ( 21.22 % ) other complications .


In multivariable risk-adjusted model , using functionally independent as reference , functionally partially dependent was associated with death ( odds ratio , 3.3 ; 95 % confidence interval , 1.6-6 .8 ; P < 0.001 ) , stroke ( odds ratio , 3 ; 95 % confidence interval , 1.7-5 .4 ; P < 0.001 ) , and other complications ( odds ratio , 2.5 ; 95 % confidence interval , 1.9-3 .2 ; P < 0.001 ) .


In this national data set , patient 's inability to perform basic activities of independent living is associated with adverse postoperative outcomes after CEA .