The study revealed that measures of FNE and FPE show distinct relationships with positive and negative social feedback which provides further evidence for the BFOE model in a laboratory setting .


The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain .


To determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo , after an initial 6-month nonrandomized treatment period on a vitamin K antagonist .


Randomized , double-blind trial ( treatment period , 18 months ; median follow-up , 24 months ) ; 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism ( ie , with no major risk factor for thrombosis ) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers .


Warfarin or placebo for 18 months .


The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization .


Secondary outcomes were the composite at 42 months ( treatment period plus 24-month follow-up ) , as well as each component of the composite , and death unrelated to pulmonary embolism or major bleeding , at 18 and 42 months .


After randomization , 4 patients were lost to follow-up , all after month 18 , and 1 withdrew due to an adverse event .


During the 18-month treatment period , the primary outcome occurred in 6 of 184 patients ( 3.3 % ) in the warfarin group and in 25 of 187 ( 13.5 % ) in the placebo group ( hazard ratio [ HR ] , 0.22 ; 95 % CI , 0.09-0 .55 ; P = .001 ) .


Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group ( HR , 0.15 ; 95 % CI , 0.05-0 .43 ) ; major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group ( HR , 3.96 ; 95 % CI , 0.44 to 35.89 ) .


During the 42-month entire study period ( including the study treatment and follow-up periods ) , the composite outcome occurred in 33 patients ( 20.8 % ) in the warfarin group and in 42 ( 24.0 % ) in the placebo group ( HR , 0.75 ; 95 % CI , 0.47-1 .18 ) .


Rates of recurrent venous thromboembolism , major bleeding , and unrelated death did not differ between groups .


Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment , an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo .


However , benefit was not maintained after discontinuation of anticoagulation therapy .


clinicaltrials.gov Identifier : NCT00740883 .


Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection .


The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection .


Substudy using data from a randomized controlled trial , the Procalcitonin And Survival Study 2006-2010 .


Nine multidisciplinary ICUs across Denmark .


A total of 1,200 critically ill patients .


Patients were randomly allocated to either a `` high exposure '' antibiotic therapy ( intervention arm , n = 604 ) or a `` standard exposure '' guided by current guidelines ( n = 596 ) .


Seventy-four patients met the endpoint , `` invasive Candida infection , '' 40 in the high exposure arm and 34 in standard exposure arm ( relative risk = 1.2 ; 95 % CI , 0.7-1 .8 ; p = 0.52 ) .


Among medical patients in the high exposure arm , the use of ciprofloxacin and piperacillin/tazobactam was 51 % and 75 % higher than in the standard exposure arm ; no difference in antibiotic exposure was observed between the randomized arms in surgical patients .


Among medical intensive care patients , invasive Candida infection was more frequent in the high exposure arm ( 6.2 % ; 27/437 ) than in standard exposure arm ( 3.3 % ; 14/424 ) ( hazard ratio = 1.9 ; 95 % CI , 1.0-3 .6 ; p = 0.05 ) .


Ciprofloxacin used at study entry independently predicted invasive Candida infection ( adjusted hazard ratio = 2.1 [ 1.1-4 .1 ] ) ; the risk gradually increased with duration of ciprofloxacin therapy : six of 384 in patients not exposed ( 1.6 % ) , eight of 212 ( 3.8 % ) when used for 1-2 days ( hazard ratio = 2.5 ; 95 % CI , 0.9-7 .3 ) , and 31 of 493 ( 6.3 % ) when used for 3 days ( hazard ratio = 3.8 ; 95 % CI , 1.6-9 .3 ; p = 0.002 ) .


Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin ( unadjusted hazard ratio = 3.7 ; 95 % CI , 1.6-8 .7 ; p = 0.003 ; adjusted hazard ratio , 3.4 ; 95 % CI , 1.4-8 .0 ; p = 0.006 ) .


High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients .


Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection .


Other antibiotics , such as meropenem , piperacillin/tazobactam , and cefuroxime , were not associated with such a risk .


A combination of aprepitant , a 5-HT3 receptor antagonist , and dexamethasone is recommended for the prophylaxis of acute or delayed emesis induced by chemotherapy containing anthracyclines plus cyclophosphamide in patients with breast cancer .


The aim of this study was to verify whether dexamethasone is superior to aprepitant in preventing delayed emesis in patients receiving the same prophylaxis for acute emesis .


A randomized double-blind study comparing aprepitant versus dexamethasone was completed in chemotherapy-naive patients with breast cancer treated with anthracyclines plus cyclophosphamide .


Before chemotherapy , all patients were treated with intravenous palonosetron 0.25 mg , dexamethasone 8 mg , and oral aprepitant 125 mg .


On days 2 and 3 , patients randomly received oral dexamethasone 4 mg twice per day or aprepitant 80 mg once per day .


Primary end point was rate of complete response ( ie , no vomiting or rescue treatment ) from days 2 to 5 after chemotherapy .


Of 580 enrolled patients , 551 were evaluable : 273 received dexamethasone , and 278 received aprepitant .


Day 1 complete response rates were similar : 87.6 % for dexamethasone and 84.9 % for aprepitant ( P < .39 ) .


From days 2 to 5 , complete response rates were the same with both antiemetic prophylaxes ( 79.5 % ; P < 1.00 ) , as were results of secondary end points ( ie , complete protection , total control , no vomiting , no nausea , score of Functional Living Index-Emesis ; P < .24 ) .


Incidences of insomnia ( 2.9 % v 0.4 % ; P < .02 ) and heartburn ( 8.1 % v 3.6 % ; P < .03 ) were significantly greater with dexamethasone on days 2 to 5 .


In patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy and receiving the same antiemetic prophylaxis for acute emesis , dexamethasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis .


Hyperkalemia is a common electrolyte abnormality that may be difficult to manage because of a lack of effective therapies .


Sodium zirconium cyclosilicate is a nonabsorbed cation exchanger that selectively binds potassium in the intestine .


To evaluate the efficacy and safety of zirconium cyclosilicate for 28 days in patients with hyperkalemia .


HARMONIZE was a phase 3 , multicenter , randomized , double-blind , placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia ( serum potassium 5.1 mEq/L ) recruited from 44 sites in the United States , Australia , and South Africa ( March-August 2014 ) .


Patients ( n = 258 ) received 10 g of zirconium cyclosilicate 3 times daily in the initial 48-hour open-label phase .


Patients ( n = 237 ) achieving normokalemia ( 3.5-5 .0 mEq/L ) were then randomized to receive zirconium cyclosilicate , 5 g ( n = 45 patients ) , 10 g ( n = 51 ) , or 15 g ( n = 56 ) , or placebo ( n = 85 ) daily for 28 days .


The primary end point was mean serum potassium level in each zirconium cyclosilicate group vs placebo during days 8-29 of the randomized phase .


In the open-label phase , serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours .


Median time to normalization was 2.2 hours , with 84 % of patients ( 95 % CI , 79 % -88 % ) achieving normokalemia by 24 hours and 98 % ( 95 % CI , 96 % -99 % ) by 48 hours .


In the randomized phase , serum potassium was significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs placebo ( 4.8 mEq/L [ 95 % CI , 4.6-4 .9 ] , 4.5 mEq/L [ 95 % CI , 4.4-4 .6 ] , and 4.4 mEq/L [ 95 % CI , 4.3-4 .5 ] for 5 g , 10 g , and 15 g ; 5.1 mEq/L [ 95 % CI , 5.0-5 .2 ] for placebo ; P < .001 for all comparisons ) .


The proportion of patients with mean potassium < 5.1 mEq/L during days 8-29 was significantly higher in all zirconium cyclosilicate groups vs placebo ( 36/45 [ 80 % ] , 45/50 [ 90 % ] , and 51/54 [ 94 % ] for the 5-g , 10-g , and 15-g groups , vs 38/82 [ 46 % ] with placebo ; P < .001 for each dose vs placebo ) .


Adverse events were comparable between zirconium cyclosilicate and placebo , although edema was more common in the 15-g group ( edema incidence : 2/85 [ 2 % ] , 1/45 [ 2 % ] , 3/51 [ 6 % ] , and 8/56 [ 14 % ] patients in the placebo , 5-g , 10-g , and 15-g groups ) .


Hypokalemia developed in 5/51 ( 10 % ) and 6/56 patients ( 11 % ) in the 10-g and 15-g zirconium cyclosilicate groups , vs none in the 5-g or placebo groups .


Among outpatients with hyperkalemia , open-label sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours ; compared with placebo , all 3 doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days .


Further studies are needed to evaluate the efficacy and safety of zirconium cyclosilicate beyond 4 weeks and to assess long-term clinical outcomes .


clinicaltrials.gov Identifier : NCT02088073 .


Video games have become popular in stroke rehabilitation ; however , the nature of this intervention is not fully understood .


To compare the number of ( a ) purposeful and nonpurposeful repetitions of the weaker upper extremity ( UE ) and ( b ) movement accelerations as assessed by accelerometer activity counts of the weaker and stronger UEs of individuals with chronic stroke while playing video games or participating in traditional therapy .


Twenty-nine individuals ( mean age 59 years , 1-7 years poststroke ) took part in a group intervention of video - games ( n = 15 ) or traditional therapy ( n = 14 ) as part of a randomized controlled trial .


During 1-2 sessions , participants were video-taped while wearing wrist accelerometers .


Assessors counted the number of repetitions and classified movements as purposeful or nonpurposeful using videotapes .


The weaker UE motor impairments were correlated to movement accelerations , to determine if participants were using their potential during the sessions .


Participants in the video game group performed a median of 271 purposeful movements and 37 970 activity counts compared to 48 purposeful movements and 14,872 activity counts in the traditional group ( z = -3.0 , P = .001 and z = -1.9 , P = .05 , respectively ) .


Participants in the traditional group performed a median of 26 nonpurposeful ( exercises ) compared with 0 in the video game group ( z = -4.2 , P = .000 ) .


Strong significant correlations were found between the motor ability of the weak UE to repetitions of participants in both groups ( r = .86 , P < .01 ) .


Participants with higher motor ability performed more repetitions .


Video games elicited more UE purposeful repetitions and higher acceleration of movement compared with traditional therapy in individuals with chronic stroke .


To determine whether scatter and grid laser photocoagulation ( laser ) adds benefit to ranibizumab injections in patients with macular edema from retinal vein occlusion ( RVO ) and to compare 0.5-mg with 2.0-mg ranibizumab .


Randomized , double-masked , controlled clinical trial .


Thirty-nine patients with central RVO ( CRVO ) and 42 with branch RVO ( BRVO ) .


Subjects were randomized to 0.5 mg or 2.0 mg ranibizumab every 4 weeks for 24 weeks and re-randomized to pro re nata ranibizumab plus laser or ranibizumab alone .


Mean change from baseline best-corrected visual acuity ( BCVA ) at week 24 for BCVA at weeks 48 , 96 , and 144 for second randomization .


Mean improvement from baseline BCVA at week 24 was 15.5 and 15.8 letters in the 0.5-mg and 2.0-mg CRVO groups , and 12.1 and 14.6 letters in the 0.5-mg and 2.0-mg BRVO groups .


For CRVO , but not BRVO , there was significantly greater reduction from baseline mean central subfield thickness ( CST ) in the 2.0-mg versus 0.5-mg group ( 396.1 vs. 253.5 m ; P = 0.03 ) .


For the second randomization in CRVO patients , there was no significant difference from week 24 BCVA in the ranibizumab plus laser versus the ranibizumab only groups at week 48 ( -3.3 vs. 0.0 letters ) , week 96 ( +0.69 vs. -1.6 letters ) , or week 144 ( +0.4 vs. -6.7 letters ) , and a significant increase from week 24 mean CST at week 48 ( +94.7 vs. +15.2 m ; P = 0.05 ) but not weeks 96 or 144 .


For BRVO , there was a significant reduction from week 24 mean BCVA in ranibizumab plus laser versus ranibizumab at week 48 ( -7.5 vs. +2.8 ; P < 0.01 ) and week 96 ( -2.0 vs. +4.8 ; P < 0.03 ) , but not week 144 , and there were no differences in mean CST change from week 24 at weeks 48 , 96 , or 144 .


Laser failed to increase edema resolution or to reduce the ranibizumab injections between weeks 24 and 144 .


In patients with macular edema resulting from RVO , there was no short-term clinically significant benefit from monthly injections of 2.0-mg versus 0.5-mg ranibizumab injections and no long-term benefit in BCVA , resolution of edema , or number of ranibizumab injections obtained by addition of laser treatment to ranibizumab .


A UK study showed final height in Turner syndrome ( TS ) girls receiving growth hormone is affected by age at pubertal induction and oxandrolone ( Ox ) .


Using data from that study , we analysed the effect of timing of oral ethinylestradiol ( EE2 ) and Ox on height velocity ( HV ) , bone maturation and pubertal progression , and compared growth response in EE2-treated versus spontaneous puberty .


Analysis of HV , bone age and pubertal stage in 92 TS girls ( 7-13 years ) randomised to Ox ( 0.05 mg/kg/day ; max : 2.5 mg/day ) or placebo from 9 years , and EE2 ( year 1 : 2 g/day ; year 2 : 4 g/day ; year 3 : 6/8/10 g/day4 months ) or placebo at 12 years with EE2 at 14 years .


Girls enrolled at > 12.25 years received EE2 at 14 years ( ` late group ' ) .


Fifty-six girls were randomised to EE2 at 12 years ( n = 28 , 11 Ox ) or 14 years ( n = 28 , 13 Ox ) ; there were 19 girls in the late group ( 9 Ox ) and 17 girls with spontaneous puberty ( 10 Ox ) .


Girls receiving EE2 at 12 versus 14 years had faster bone maturation , but neither group showed acceleration .


Ox increased HV without altering bone maturation or pubertal progression .


Girls with spontaneous puberty had greater pubertal growth ( mean PHV 8.5 cm/year ; p < 0.001 ) and height gain ( p < 0.001 ) than EE2-treated girls despite similar mean enrolment height SD and dysmorphology scores .


Pubertal induction with EE2 does not replicate the acceleration observed in unaffected girls or TS girls with spontaneous puberty .


The purpose of this study was to investigate the long-term clinical course of normotensive preperimetric glaucoma ( PPG ) .


The medical records of 71 eyes of 71 patients with normotensive PPG who underwent intraocular pressure ( IOP ) - lowering therapy were reviewed retrospectively .


The patients had been regularly followed up at 3 - to 6-month intervals between 1996 and 2011 .


Progression was evaluated by comparing the structural changes of serial stereoscopic colour disc and red-free retinal nerve fibre layer ( RNFL ) photographs and by comparing serial visual field ( VF ) test results for functional changes .


Over an average follow-up period of 6.8 years , 41 eyes ( 57.7 % ) showed progression in either structural or functional evaluation .


Disc haemorrhage ( DH ) was observed significantly more frequently in the progressing group ( p < 0.005 ) ; however , there were no differences in mean age , gender ratio , follow-up period and ocular characteristics at baseline such as IOP , RNFL defects and global indices of VF between the non-progressing and progressing groups .


Thirty eyes ( 42.3 % ) showed significant angular widening of the localized RNFL defect towards the macula at a mean rate of approximately 1/year .


Perimetric glaucoma developed in 19 eyes ( 26.8 % ) , and the rate of change in the mean deviation was -0.23 dB/year .


Preperimetric glaucoma patients with DH or IOP reductions of < 20 % from the baseline had a higher probability of RNFL deterioration than patients without DH or IOP reductions of 20 % from the baseline by multivariate analysis .


Although the rates of change were typically slow , more than half of normotensive patients with PPG showed statistically significant progressive structural or functional changes in medically treated cases .


DH or IOP reductions of < 20 % from the baseline were shown as a significant risk factor for the progression of PPG .


Patients with heart failure ( HF ) who live in rural areas have less access to cardiac services than patients in urban areas .


We conducted a randomized , clinical trial to determine the impact of an educational intervention on the composite end point of HF rehospitalization and cardiac death in this population .


Patients ( n = 602 ; age , 6613 years ; 41 % female ; 51 % with systolic HF ) were randomized to 1 of 3 groups : control ( usual care ) , Fluid Watchers LITE , or Fluid Watchers PLUS .


Both intervention groups included a face-to-face education session delivered by a nurse focusing on self-care .


The LITE group received 2 follow-up phone calls , whereas the PLUS group received biweekly calls ( mean , 5.33.6 ; range , 1-19 ) until the nurse judged the patient to be adequately trained .


Over 2 years of follow-up , 35 % of patients ( n = 211 ) experienced cardiac death or hospitalization for HF , with no difference among the 3 groups in the proportion who experienced the combined clinical outcome ( P = 0.06 ) .


Although patients in the LITE group had reduced cardiac mortality compared with patients in the control group over the 2 years of follow-up ( 7.5 % and 17.7 % , respectively ; P = 0.003 ) , there was no significant difference in cardiac mortality between patients in the PLUS group and the control group .


A face-to-face education intervention did not significantly decrease the combined end point of cardiac death or hospitalization for HF .


Increasing the number of contacts between the patient and nurse did not significantly improve outcome .


http://www.clinicaltrials.gov .


Unique identifier : NCT00415545 .


Physical exercise could improve functional limitations , muscle mass , and health-related quality of life ( HRQoL ) in patients with cirrhosis .


The purpose of this study was to evaluate the efficacy and safety of an exercise programme and leucine supplementation to increase exercise capacity , muscle mass , and HRQoL in patients with cirrhosis .


Seventeen outpatients with cirrhosis were randomized to an exercise group ( n = 8 ) or a control group ( n = 9 ) in a pilot study .


The programme of moderate exercise was performed for 12 weeks under supervision of a physiotherapist .


All patients received oral leucine ( 10 g/day ) during the study .


At baseline and at the end of the study , we determined exercise capacity ( 6-min walk and 2-min step tests ) , anthropometric measurements , and HRQoL by Short Form-36 ( SF-36 ) questionnaire .


We also analyzed safety regarding complications of cirrhosis , liver and renal function , inflammatory response and oxidative stress .


In the exercise group , exercise capacity improved , as shown by the increase in the 6-min walk test from 365 ( 160-420 ) to 445 m ( 250-500 ) ( p = 0.01 ) , and in the 2-min step test ( p = 0.02 ) .


Lower thigh circumference also increased , from 41 ( 34-53 ) to 46 cm ( 36-56 ) ( p = 0.02 ) , and the domains of SF-36 general health ( p = 0.03 ) , vitality ( p = 0.01 ) and social function ( p = 0.04 ) improved significantly .


In the control group , no statistically significant changes were observed in any of the parameters .


We did not observe complications of cirrhosis in either group during the study .


A programme of moderate physical exercise together with leucine supplements in patients with cirrhosis is safe and improves exercise capacity , leg muscle mass and HRQoL .


Printed educational materials for clinician education are one of the most commonly used approaches for quality improvement .


The objective of this pragmatic cluster randomized trial was to evaluate the effectiveness of an educational toolkit focusing on cardiovascular disease screening and risk reduction in people with diabetes .


All 933,789 people aged 40 years with diagnosed diabetes in Ontario , Canada were studied using population-level administrative databases , with additional clinical outcome data collected from a random sample of 1,592 high risk patients .


Family practices were randomly assigned to receive the educational toolkit in June 2009 ( intervention group ) or May 2010 ( control group ) .


The primary outcome in the administrative data study , death or non-fatal myocardial infarction , occurred in 11,736 ( 2.5 % ) patients in the intervention group and 11,536 ( 2.5 % ) in the control group ( p = 0.77 ) .


The primary outcome in the clinical data study , use of a statin , occurred in 700 ( 88.1 % ) patients in the intervention group and 725 ( 90.1 % ) in the control group ( p = 0.26 ) .


Pre-specified secondary outcomes , including other clinical events , processes of care , and measures of risk factor control , were also not improved by the intervention .


A limitation is the high baseline rate of statin prescribing in this population .


The educational toolkit did not improve quality of care or cardiovascular outcomes in a population with diabetes .


Despite being relatively easy and inexpensive to implement , printed educational materials were not effective .


The study highlights the need for a rigorous and scientifically based approach to the development , dissemination , and evaluation of quality improvement interventions .


http://www.ClinicalTrials.gov NCT01411865 and NCT01026688 .


Increased consumption of omega-3 polyunsaturated fatty acids ( PUFA ) together with lifestyle measures and medications is recommended for the prevention of cardiovascular diseases .


However , the exact mechanisms underlying observed benefits are not well defined .


To this aim , we evaluated the effects of omega-3 PUFA in stable coronary artery disease ( CAD ) patients undergoing percutaneous coronary intervention ( PCI ) on lipoprotein associated phospholipase A2 ( Lp-PLA2 ) mass and activity and their relation to oxidized low-density lipoproteins ( oxy-LDL ) .


In a prospective , double-blind , placebo-controlled , randomized study Lp-PLA2 , oxy-LDL , myeloperoxidase and interleukin-6 were determined at baseline , 3-5 days and 30 days during administration of omega-3 PUFA 1g/day ( n = 30 ) or placebo ( n = 24 ) .


Treatment with omega-3 PUFA resulted in reduction of Lp-PLA2 mass by 10.7 % , activity by 9.3 ( p = 0.026 for both ) and oxy-LDL by 10.9 % ( p = 0.014 ) at 30 days , with no change in myeloperoxidase and interleukin-6 .


Compared with placebo , patients receiving omega-3 PUFA had lower Lp-PLA2 mass by 9.42 % , activity by 9.2 ( p = 0.041 for both ) and oxy-LDL by 12.3 % ( p = 0.10 ) after one month , but not at 3-5 days .


There were no correlations between Lp-PLA2 and both myeloperoxidase and oxy-LDL throughout the study .


The multivariate model showed that only treatment with omega-3 PUFA and baseline myeloperoxidase levels were independent predictors of Lp-PLA2 mass changes at one month ( R ( 2 ) = 0.37 , P = 0.005 ) .


Administration of omega-3 PUFA can decrease Lp-PLA2 in patients with stable angina undergoing PCI .


This novel effect may contribute to the benefits derived from omega-3 PUF .


It is necessary to develop a new thrombolytic agent which can be used by a single bolus at first aid sites to decrease the time to reperfusion in clinical practice .


HTUPA , a genetically engineered new thrombolytic with a longer half-life , is well qualified .


We aim to compare the thrombolytic efficacy and safety of human tissue urokinase type plasminogen activator ( HTUPA ) to recombinant tissue plasminogen activator ( rt-PA ) in Chinese patients with acute myocardial infarction ( AMI ) .


AMI patients ( n = 221 ) were randomized to rt-PA ( a standard protocol ) or HTUPA ( 25 mg bolus ) treatment groups .


All patients also received oral aspirin and intravenous heparin .


Coronary angiography was performed 90 min after therapy initiation to determine infarct-related coronary artery ( IRA ) patency .


Clinical outcomes and changes of clotting variables , heart rate , blood pressure , left ventricular ejection fraction ( LVEF ) , and electrocardiogram were evaluated .


Patent IRA [ thrombolysis in myocardial infarction ( TIMI ) grade 2 or 3 ] was observed in 77 % of HTUPA-treated patients , compared to 76 % of rt-PA-treated patients ( P = 0.76 ) .


TIMI grade 3 patency rates were 52 % and 44 % in the HTUPA and rt-PA groups , respectively ( P = 0.37 ) .


The total patency rate was 77 % ( 86/111 patients ) in the HTUPA group and 73 % ( 80/110 patients ) in the rt-PA group ( P = 0.41 ) .


Adverse events were infrequent in both groups , and no significant differences were detected in mortality , re-occlusion rate , revascularization rate , adverse effects , clotting index , LVEF , or electrocardiogram between the two groups .


Intravenous HTUPA had a safe and efficacious profile as good as rt-PA in patients with AMI .


Uterine fibroids are the most common tumour in women of reproductive age .


By the time they are 50-years-old around 80 % of women will have developed one .


Of these , around half will experience symptoms which will impact negatively on their quality of life .


Hysterectomy is the traditional treatment for women with symptomatic fibroids .


For women who do not wish to undergo a hysterectomy , two invasive treatments are commonly available : myomectomy or uterine artery embolization ( UAE ) .


FEMME is a pragmatic , randomised , open , multi-centre trial examining the quality of life menstruating women with symptomatic fibroids experience after treatment with UAE or myomectomy .


After providing informed consent , 216 women with symptomatic fibroids from 43 NHS Hospital Trusts and Health Boards across the United Kingdom will undergo randomisation by a centralised computer system to treatment by either UAE or myomectomy .


A minimisation algorithm will be used in order to balance the groups with respect to the following three parameters : the longest dimension of the largest fibroid , the number of fibroids present , and whether the woman currently desires pregnancy.Using validated questionnaires the women 's quality of life will be compared between groups at six months , one year , two years and four years post-procedure , taking into account pre-procedure scores .


An economic evaluation will be conducted alongside the trial to determine the cost-effectiveness of UAE compared with myomectomy.Validated diaries will also be used to compare menstrual blood loss at the same time-points .


The plasma concentration of Anti-Mllerian hormone ( AMH ) , which will act as a proxy measurement of ovarian reserve , will be recorded before the woman has her procedure and then again at six weeks , six months , and twelve months afterwards .


Re-intervention rates will be recorded .


The FEMME trial 's primary outcome is the quality of life women with symptomatic uterine fibroids experience two years after they have been treated with either UAE or myomectomy , as measured by the disease-specific Uterine Fibroid Symptom Quality-of-Life ( UFS-QoL ) questionnaire .


Current Controlled Trials registration number : ISRCTN70772394 , registered on 2 March 2013 .


To evaluate the efficacy and safety of acupuncture for residual insomnia and other residual symptoms associated with major depressive disorder ( MDD ) .


150 participants having significant insomnia for more than 3 months and a history of MDD ( both based on DSM-IV-TR criteria ) were recruited from 4 psychiatric outpatient clinics in Hong Kong from May 2011 to August 2013 to receive 9 sessions of treatment over 3 weeks .


They were randomized to receive acupuncture , minimal acupuncture , or placebo acupuncture .


Primary outcome was sleep diary-derived sleep efficiency .


Secondary outcomes included other sleep diary parameters , actigraphy , anxiety and depressive symptoms , daytime functioning , and adverse events .


The mean difference in sleep diary-derived sleep efficiency at 1-week posttreatment was -1.40 ( 95 % CI , -7.08 to 4.28 ) between the acupuncture and minimal acupuncture groups and was 3.10 ( 95 % CI , -3.64 to 9.84 ) between the acupuncture and placebo acupuncture groups .


A ( 2 ) test showed that acupuncture produced a significantly higher proportion of participants achieving sleep-onset latency 30 minutes than did minimal acupuncture at 1-week posttreatment ( P = .04 ) .


However , there was no significant between-group difference in most of the other outcomes .


Treatment blinding was successful , as a majority of participants did not know which treatment they had received .


Acupuncture was well tolerated , but the efficacy was only mild and similar to that of minimal acupuncture and placebo acupuncture .


A high proportion of patients remained clinically significantly affected by insomnia after treatment .


The finding raises certain doubts about the value of acupuncture and underscores the difficulties in the treatment of residual insomnia in MDD .


ClinicalTrials.gov identifier : NCT01707706 .


The neuropeptide oxytocin is implicated in social processing , and recent research has begun to explore how gender relates to the reported effects .


This study examined the effects of oxytocin on social affective perception and learning .


Forty-seven male and female participants made judgments of faces during two different tasks , after being randomized to either double-blinded intranasal oxytocin or placebo .


In the first task , `` unseen '' affective stimuli were presented in a continuous flash suppression paradigm , and participants evaluated faces paired with these stimuli on dimensions of competence , trustworthiness , and warmth .


In the second task , participants learned affective associations between neutral faces and affective acts through a gossip learning procedure and later made affective ratings of the faces .


In both tasks , we found that gender moderated the effect of oxytocin , such that male participants in the oxytocin condition rated faces more negatively , compared with placebo .


The opposite pattern of findings emerged for female participants : they rated faces more positively in the oxytocin condition , compared with placebo .


These findings contribute to a small but growing body of research demonstrating differential effects of oxytocin in men and women .


A non-steroidal , anti-inflammatory moisturizing cream containing rhamnosoft , ceramides , and L-isoleucine ( ILE ) ( pro-AMP cream ) has been recently developed for the specific treatment of atopic eczema ( AE ) of the face .


In this trial , we evaluated the clinical efficacy and tolerability of pro-AMP cream in the treatment of facial AE in children in comparison with an emollient cream .


In a randomized , prospective , assessor-blinded , parallel groups ( 2:1 ) controlled trial , 107 children ( 72 allocated to pro-AMP cream and 35 allocated to control group ) with mild-to-moderate chronic AE of the face were enrolled .


Treatments were applied twice daily for a 6-week period .


Facial Eczema Severity Score ( ESS ) was evaluated at baseline , week 3 , and week 6 , by an assessor unaware of treatment allocation .


Investigators Global Assessment ( IGA ) score was assessed at week 3 and at week 6 .


Tolerability was evaluated at week 3 and at week 6 using a4-point score ( from 0 : low tolerability to 3 : very good tolerability ) .


At baseline ESS , mean ( SD ) was 6.1 ( 2.4 ) in the pro-AMP cream group and 5.3 ( 3 ) in the control group .


In the pro-AMP group , in comparison with baseline , ESS was significantly reduced to 2.5 ( -59 % ) after 3 wks and to 1.0 ( -84 % ) at week 6 ( p = 0.0001 ) .


In the control group , ESS was reduced to 3 ( -42 % ) at week 2 and to 2.6 ( -50 % ) at week 6 .


At week 6 , ESS in pro-AMP cream was significantly lower than the control group ( 1.0 vs. 2.6 ; p = 0.001 ) .


Both products were well tolerated .


Pro-AMP cream has shown to be effective in the treatment of mild-to moderate chronic lesion of AE of the face .


Clinical efficacy was greater in comparison with an emollient cream .


NTR4084 ) .


Survival rates after resection of advanced gastric cancer are extremely poor .


An increasing number of patients with gastric carcinomas ( GC ) are therefore being treated with preoperative chemotherapy .


We evaluated 36 month survival rate of GC patients that were treated by adding a neoadjuvant chemoradiotherapy before gastrostomy .


Patients with stage II or III gastric adenocarcinomas were enrolled .


The patients divided into two groups : ( A ) Neoadjuvant group that received concurrent chemoradiation before surgery ( 4,500 cGy of radiation at 180 cGy per day plus chemotherapy with cisplatin and 5-fluorouracil , in the first and the end four days of radiotherapy ) .


Resection was attempted 5 to 6 weeks after end of chemoradiotherapy .


( B ) Adjuvant group that received concurrent chemo-radiation after surgical resection .


Two ( 16.7 % ) patients out of 12 patients treated with neoadjuvant chemo-radiotherapy and 5 ( 38.5 % ) out of 13 in the surgery group survived after 36 months .


These rates were not significantly different with per protocol and intention-to-treat analysis .


The median survival time of patients in group A and B were 13.4 and 21.6 months , respectively , again not significantly different .


Survival was significantly greater in patients with well differentiated adenocarcinoma in group B than in group A ( p < 0.004 ) .


According to this study we suggest surgery then chemoradiotherapy for patients with well differentiated gastric adenocarcinoma rather than other approaches .


Additional studies with greater sample size and accurate matching relying on cancer molecular behavior are recommended .


This study assessed the impact of varying lenvatinib crystalline forms in 10-mg lenvatinib capsules on drug bioavailability in healthy volunteers .


Lenvatinib 10-mg capsules ( low C and high C forms ) .


This randomized , three-period - crossover study compared the pharmacokinetics and safety of two crystalline forms of capsules ( low C-form , < 4 % crystalline ; high C-form , 38 % crystalline ) to a standard ( ref Cform , 15 % crystalline ) .


59 subjects were evaluable for pharmacokinetics .


Test/reference ratios of the geometric least squares means ( LSM ) and 90 % confidence intervals ( CI ) for AUC0-t ( t up to 120 hours ) , AUC0 - , and Cmax for low C-form vs. ref C-form were 101 ( 94.8 , 107 ) , 101 ( 95.3 , 107 ) , and 98.7 ( 88.6 , 110 ) , respectively ; and for high C-form vs. ref C-form were 96.0 ( 92.1 , 100 ) , 96.5 ( 92.5 , 101 ) , and 90.6 ( 83.5 , 98.4 ) , respectively .


The incidence of treatment-emergent adverse events ( TEAE ) and treatment-related adverse events ( TRAE ) were comparable between all formulations ( TEAE range 20-24 % ; TRAE range 15-19 % ) .


One serious TRAE ( spontaneous abortion ) occurred in the low C-form group .


For both comparisons , the 90 % CIs of the test/reference ratios were within the regulatory acceptance range ( 80-125 % ) , suggesting that both test formulations ( low Cform and high C-form ) were bioequivalent to the reference formulation for Cmax , AUC0-t , and AUC0 - .


The effect of internal mammary and medial supraclavicular lymph-node irradiation ( regional nodal irradiation ) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown .


We randomly assigned women who had a centrally or medially located primary tumor , irrespective of axillary involvement , or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation ( nodal-irradiation group ) or whole-breast or thoracic-wall irradiation alone ( control group ) .


The primary end point was overall survival .


Secondary end points were the rates of disease-free survival , survival free from distant disease , and death from breast cancer .


Between 1996 and 2004 , a total of 4004 patients underwent randomization .


The majority of patients ( 76.1 % ) underwent breast-conserving surgery .


After mastectomy , 73.4 % of the patients in both groups underwent chest-wall irradiation .


Nearly all patients with node-positive disease ( 99.0 % ) and 66.3 % of patients with node-negative disease received adjuvant systemic treatment .


At a median follow-up of 10.9 years , 811 patients had died .


At 10 years , overall survival was 82.3 % in the nodal-irradiation group and 80.7 % in the control group ( hazard ratio for death with nodal irradiation , 0.87 ; 95 % confidence interval [ CI ] , 0.76 to 1.00 ; P = 0.06 ) .


The rate of disease-free survival was 72.1 % in the nodal-irradiation group and 69.1 % in the control group ( hazard ratio for disease progression or death , 0.89 ; 95 % CI , 0.80 to 1.00 ; P = 0.04 ) , the rate of distant disease-free survival was 78.0 % versus 75.0 % ( hazard ratio , 0.86 ; 95 % CI , 0.76 to 0.98 ; P = 0.02 ) , and breast-cancer mortality was 12.5 % versus 14.4 % ( hazard ratio , 0.82 ; 95 % CI , 0.70 to 0.97 ; P = 0.02 ) .


Acute side effects of regional nodal irradiation were modest .


In patients with early-stage breast cancer , irradiation of the regional nodes had a marginal effect on overall survival .


Disease-free survival and distant disease-free survival were improved , and breast-cancer mortality was reduced .


( Funded by Fonds Cancer ; ClinicalTrials.gov number , NCT00002851 . )


Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations , but it is uncertain whether benefits outweigh disadvantages .


We directly compared the psychological/quality-of-life consequences of such an approach to family history ( FH ) - based testing .


In a randomized controlled trial of BRCA1/2 gene-mutation testing in the Ashkenazi Jewish ( AJ ) population , we compared testing all participants in the population screening ( PS ) arm with testing those fulfilling standard FH-based clinical criteria ( FH arm ) .


Following a targeted community campaign , AJ participants older than 18 years were recruited by self-referral after pretest genetic counseling .


The effects of BRCA1/2 genetic testing on acceptability , psychological impact , and quality-of-life measures were assessed by random effects regression analysis .


All statistical tests were two-sided .


One thousand , one hundred sixty-eight AJ individuals were counseled , 1042 consented , 1034 were randomly assigned ( 691 women , 343 men ) , and 1017 were eligible for analysis .


Mean age was 54.3 ( SD = 14.66 ) years .


Thirteen BRCA1/2 carriers were identified in the PS arm , nine in the FH arm .


Five more carriers were detected among FH-negative FH-arm participants following study completion .


There were no statistically significant differences between the FH and PS arms at seven days or three months on measures of anxiety , depression , health anxiety , distress , uncertainty , and quality-of-life .


Contrast tests indicated that overall anxiety ( P = .0001 ) and uncertainty ( P = .005 ) associated with genetic testing decreased ; positive experience scores increased ( P = .0001 ) ; quality-of-life and health anxiety did not change with time .


Overall , 56 % of carriers did not fulfill clinical criteria for genetic testing , and the BRCA1/2 prevalence was 2.45 % .


Compared with FH-based testing , population-based genetic testing in Ashkenazi Jews does n't adversely affect short-term psychological/quality-of-life outcomes and may detect 56 % additional BRCA carriers .


The use of nicotine replacement therapy before quitting smoking is called nicotine preloading .


Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking ( quit day ) aiming to reduce withdrawal symptoms and craving .


However , other , more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after .


Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward .


A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed .


This is a study protocol for a multicenter , non-blinded , randomized controlled trial based in the United Kingdom , enrolling 1786 smokers who want to quit , funded by the National Institute for Health Research , Health Technology Assessment program , and sponsored by the University of Oxford .


Participants will primarily be recruited through general practices and smoking cessation clinics , and randomized ( 1:1 ) either to use 21 mg nicotine patches , or not , for four weeks before quitting , whilst smoking as normal .


All participants will be referred to receive standard smoking cessation service support .


Follow-ups will take place at one week , four weeks , six months and 12 months after quit day .


The primary outcome will be prolonged , biochemically verified six-month abstinence .


Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration , side effects , costs of treatment , and markers of potential mediators and moderators of the preloading effect .


This large trial will add substantially to evidence on the effectiveness of nicotine preloading , but also on its cost effectiveness and potential mediators , which have not been investigated in detail previously .


A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample , and the multicentre design means that knowledge can be shared between recruitment teams .


The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice .


Current Controlled Trials ISRCTN33031001 .


Registered 27 April 2012 .


Sirolimus-eluting stents ( SES ) with a biodegradable polymer coating have demonstrated promising results but have not been compared to SES with a durable polymer in high-risk patients .


We compared the efficacy of these 2 stent types in patients with acute myocardial infarction ( STEMI ) .


One thousand one hundred ninety-two STEMI patients were randomized to receive SES coated with biodegradable ( n = 596 ) or durable polymer ( n = 596 ) .


The study end-point was the composite of major adverse cardiac events ( MACE ) including all-cause death , recurrent myocardial infarction ( MI ) , or target lesion revascularization ( TLR ) at 1-year follow-up .


Secondary end-points included individual components of primary end-point and stent thrombosis .


Compared with durable polymer SES , the noninferiority of SES with biodegradable polymer coating was established by an absolute risk difference of 0.9 % in the primary end-point ( 12.4 % vs. 13.3 % , P = 0.67 ) and an upper limit of one-sided 95 % confidence interval ( CI ) of 2.96 % ( P for noninferiority = 0.001 ) .


Rate of death , recurrent MI , and TLR were 7.9 % and 8.6 % ( HR : 0.92 ; 95 % CI : 0.61-1 .38 , P = 0.67 ) , 2.9 % and 3.5 % ( HR : 0.80 ; 95 % CI : 0.42-1 .54 , P = 0.51 ) , and 2.0 % and 3.2 % ( HR : 0.62 ; 95 % CI : 0.30-1 .30 , P = 0.20 ) in the biodegradable polymer SES and durable polymer SES group at 1-year clinical follow-up , respectively .


Despite similar rates of 30-day ARC definite/probable stent thrombosis , late stent thrombosis ( stent thrombosis occurring beyond 30 days ) was lower with biodegradable polymer SES ( 0.7 % vs. 2.2 % , P = 0.028 ) .


In patients undergoing primary PCI for STEMI , the use of biodegradable polymer SES was associated with noninferior 1-year rates of MACE compared with durable polymer SES .


To compare the efficacy differences between acupuncture-moxibustion and physiotherapy interventions in improving proprioception of athletes with lateral collateral ligament injury of the ankle joint .


Thirty patients with injured lateral collateral ligament of ankle joint were randomly divided into acupuncture group ( n = 15 ) and physiotherapy group ( n = 15 ) .


Patients of the acupuncture group were treated by acupuncture and moxibustion stimulation of Qiuxu ( GB40 ) , Kunlun ( BL 60 ) , Shenmai ( BL 62 ) , Jiexi ( ST 41 ) , and Ashi-points , etc. , and those of the physiotherapy group treated with TDP irradiation of the regional lateral malleolus .


The treatment of the two groups was conducted once the other day , 3 times each week , continuously for 8 weeks .


Before and after the treatment , the ankle-joint 's active and passive repositioning error angles were measured by using a joint angle ruler .


The average error angle values of active and passive reposition tests of the injured ankle-joint were 4.98 + / - 1.11 and 4.78 + / - 1.3 before the treatment , and 3.67 + / - 0.58 and 3.51 + / - 0.64 after the treatment , respectively in the acupuncture group , being reduced significantly after the treatment ( both P < 0.01 ) .


No significant changes of the average error angle values of both active and passive reposition tests of the ankle-joint were found after the treatment in the physiotherapy group ( P > 0.05 ) .


Comparison between two groups showed that the average error angle , average active and passive reposition angles of the injured ankle in the acupuncture group were evidently lower than those in the physiotherapy group ( P < 0.01 ) .


Acupuncture and moxibustion can effectively improve the proprioception of the injured lateral collateral ligament of the ankle joint in athletes , which is superior to conventional physiotherapy in the therapeutic effect .


Several studies show that psychological treatments relieve symptoms for patients suffering from irritable bowel syndrome ( IBS ) .


However , there are no consistent findings that show what patient characteristics make a psychological treatment more or less likely to result in improvement .


We have previously conducted a study of a newly developed internet-delivered cognitive behavioral therapy ( ICBT ) that emphasized exposure to IBS symptoms and IBS-related situations and reduced symptom-related avoidance .


The study showed that the treatment led to improvement in IBS symptoms compared to a waiting list and that treatment gains were maintained over a 15-18 month follow-up period .


The aim of the present study was to investigate several possible predictors of short - and long-term treatment outcome in terms of symptom improvement , based on data collected in the previously conducted treatment trial .


Demographics , comorbid psychological distress , IBS-related fear and avoidance behaviors , and IBS-related disability were investigated as predictors of treatment outcome in the sample consisting of 79 participants diagnosed with IBS who had undergone 10 weeks of ICBT .


Predictors that were significantly correlated with symptom levels at post-treatment and follow-up were entered into multiple regression analyses that controlled for pre-treatment symptom levels .


There were measures within each domain , i.e. , comorbid psychological distress , IBS-related fear and avoidance behaviors , and IBS-related disability , with the exception of demographic data , that were correlated with the symptom levels at post-treatment and follow-up .


However , when these were entered into a multiple regression analyses that controlled for pre-treatment levels , none remained a significant predictor of the post-treatment and follow-up symptomatic status .


The study did not find any individual characteristics that made patients more or less likely to respond to the exposure-based ICBT .


The finding that comorbid psychological distress did not predict outcome is in accordance with previous studies .


Reliable predictors for response to any type of psychological treatment for IBS remain to be established .


To evaluate the effect of luteal phase progesterone support on pregnancy rates in women with polycystic ovary syndrome ( PCOS ) who were treated for clomiphene citrate-resistant anovulatory infertility with ovulation induction and intrauterine insemination ( OI / IUI ) .


This randomized study included 110 clomiphene citrate-resistant PCOS patients .


All patients underwent ovulation induction with recombinant follicle-stimulating hormone and intrauterine insemination , up to 3 cycles , and were randomized into 2 groups : ( 1 ) luteal support with progesterone or ( 2 ) a control group .


The main outcomes were clinical pregnancy rates and live birth rates per cycle .


Demographic data were not different between the study and control groups .


Cycle characteristics were found to be homogeneous between groups .


A total of 38 pregnancies were achieved ( 15.5 % pregnancy rate per cycle ) .


The clinical pregnancy rate and live birth rate per cycle in progesterone supported cycles were 18.9 % and 16.8 % , respectively .


There might be a clinical benefit of luteal progesterone supplementation on OI/IUI cycles for women with PCOS .


Although we did not reach a statistically significant difference between the 2 groups , luteal-supported cycles demonstrated a 6.7 % higher clinical pregnancy rate and 6.1 % higher live birth rate .


Dementia-care mapping ( DCM ) is a cyclic intervention aiming at reducing neuropsychiatric symptoms in people with dementia in nursing homes .


Alongside an 18-month cluster-randomized controlled trial in which we studied the effectiveness of DCM on residents and staff outcomes , we investigated differences in costs of care between DCM and usual care in nursing homes .


Dementia special care units were randomly assigned to DCM or usual care .


Nurses from the intervention care homes received DCM training , a DCM organizational briefing day and conducted the 4-months DCM-intervention twice during the study .


A single DCM cycle consists of observation , feedback to the staff , and action plans for the residents .


We measured costs related to health care consumption , falls and psychotropic drug use at the resident level and absenteeism at the staff level .


Data were extracted from resident files and the nursing home records .


Prizes were determined using the Dutch manual of health care cost and the cost prices delivered by a pharmacy and a nursing home .


Total costs were evaluated by means of linear mixed-effect models for longitudinal data , with the unit as a random effect to correct for dependencies within units .


34 units from 11 nursing homes , including 318 residents and 376 nursing staff members participated in the cost analyses .


Analyses showed no difference in total costs .


However certain changes within costs could be noticed .


The intervention group showed lower costs associated with outpatient hospital appointments over time ( p = 0.05 ) than the control group .


In both groups , the number of falls , costs associated with the elderly-care physician and nurse practitioner increased equally during the study ( p < 0.02 ) .


DCM is a cost-neutral intervention .


It effectively reduces outpatient hospital appointments compared to usual care .


Other considerations than costs , such as nursing homes ' preferences , may determine whether they adopt the DCM method .


Dutch Trials Registry NTR2314 .


Although catheter ablation of isthmus-dependent atrial flutter ( AFL ) is successful at eliminating the target arrhythmia , many patients subsequently experience new-onset atrial fibrillation ( AF ) .


The aim of this study was to determine whether AF can be prevented by prophylactic pulmonary vein ablation in patients with AFL .


A prospective , single-blind , randomized clinical trial in patients whose sole arrhythmia was AFL without AF was conducted .


Patients were randomized to cavotricuspid isthmus ablation alone or with concomitant pulmonary vein isolation .


All patients received an implantable cardiac monitor .


Fifty patients completed the trial , and patients were well matched .


Isthmus ablation was successful in all patients ; pulmonary vein isolation was successful in 25 ( 100 % ) randomized patients .


Procedure ( P < .0001 ) and fluoroscopy ( P < .0001 ) times were longer in the combined ablation group .


More patients in the isthmus ablation-only group experienced new-onset AF during follow-up ( 52 % vs. 12 % ; P = .003 ) .


The 1-year AF burden also favored the combined ablation group compared with the isthmus ablation-only group ( 8.3 % vs. 4.0 % ; P = .034 ) .


In the isthmus ablation-only group , 8 ( 32 % ) patients subsequently underwent another ablation for AF .


The performance of pulmonary vein isolation and male sex were independent predictors of freedom from AF .


In the PREVENT-AF Study I randomized clinical trial of patients in whom only typical AFL had been observed clinically , the addition of pulmonary vein isolation to cavotricuspid isthmus ablation resulted in a marked reduction of new-onset AF during clinical follow-up as assessed with a continuous implantable cardiac monitor .


Severe acute pancreatitis is a life-threatening disease .


Patients with peripancreatic necrotic infection often require surgical removal of necrotic infected tissue and a wide debridement will cause blood loss and worsen the condition .


To assess whether treatment with NovoSeven , a recombinant activated FVII ( rFVIIa ) , could improve coagulation function and therefore reduce blood loss , blood transfusion and all-cause mortality during necrosectomy in patients with infected necrosis secondary to severe acute pancreatitis .


Severe acute pancreatitis patients admitted to Nanjing Jinling Hospital for necrosectomy were enrolled and randomized to receive either standard treatment or standard treatment plus an intravenous infusion of rFVIIa ( 40g per kilogram of body weight per hour ) before operation .


The prospectively defined primary end points were perioperative coagulation parameters ( prothrombin time , activated partial thromboplastin time ) , blood transfusion unit and blood loss .


The secondary end points were operation time , ICU stay and all-cause mortality at 28days after the operation .


A total of 64 patients were enrolled ( 31 in the rFVIIa group and 33 in the control group ) .


Treatment with rFVIIa was associated with a reduction in operation time , red blood cell and fresh froze plasma transfusion , blood loss and prothrombin time compared to the control group ( p < 0.05 for all ) .


Activated partial thromboplastin time and mortality were similar between the two groups ( P > 0.05 ) .


Treatment with rFVIIa significantly improved the extrinsic coagulation function in patients with severe acute pancreatitis and was associated with decreased risk of bleeding .


However , rFVIIa did not improve intrinsic coagulation or reduce over-cause mortality .


ChiCTR-TRC-1300389 .


The aim is to determine , from the patient 's perspective , what constitutes a good hand-off procedure in the emergency department ( ED ) .


The secondary purpose is to evaluate what impact a formalized hand-off had on patient knowledge , throughput and customer service


This study used a randomized controlled clinical trial involving two unique hand-off approaches and a convenience sample .


The study alternated between the current hand-off process that documented the process but not specific elements ( referred to as the informal process ) to one using the IPASS the BATON process ( considered the formal process ) .


Consenting patients completed a 12-question validated questionnaire on how the process was perceived by patients and about their understanding why they waited in the ED .


Statistical analysis using SPSS calculated descriptive frequencies and t-tests .


In total 107 patients were enrolled : 50 in the informal and 57 in the formal group .


Most patients had positive answers to the customer survey .


There were significant differences between formal and informal groups : recalling the oncoming and outgoing physician coming to the patient 's bed ( p = 0.000 ) , with more formal group recalling that than informal group patients ; the oncoming physician introducing him/herself ( p = 0.01 ) , with more from the formal group answering yes and the physician discussing tests and implications with formal group patients ( p = 0.02 ) .


This study was done at an urban inner city ED , a fact that may have skewed its results .


A comparison of suburban and rural EDs would make the results stronger .


It also reflected a very high level of customer satisfaction within the ED .


This lack of variance may have meant that the correlation between customer service and handoffs was missed or underrepresented .


There was no codified observation of either those using the IPASS the BATON script or those using informal procedures , so no comparison of level and types of information given between the two groups was done .


There could have been a bias of those attending who had internalized the IPASS the BATON procedures and used them even when they were assigned to the informal group .


A hand off from one physician to the next in the emergency department is best done using a formalized process .


IPASS the BATON is a useful tool for hand off in the ED in part because it involved the patient in the process .


The formal hand off increased communication between patient and doctor as its use increased the patient 's opportunity to ask and respond to questions .


The researchers evaluated an ED physician specific hand-off process and illustrate the value and impact of involving patients in the hand-off process .


To compare the efficacy of a shorter interval ( 24hours ) between misoprostol and mifepristone administration with that of the conventional dosing interval ( 48hours ) for second-trimester termination of pregnancy ( TOP ) .


This was a prospective randomized , controlled , open-label study of 98 healthy women opting for mid-trimester TOP .


The women were randomized to receive 200mg mifepristone orally , followed 24hours ( Group 1 ) or 48hours ( Group 2 ) later by misoprostol ( 800g , then 400g every 3hours ) .


The primary outcome measure was the percentage of successful abortions within 24hours .


Secondary outcome measures were the induction-to-abortion interval ( measured from misoprostol administration ) and the frequencies of complications and adverse effects .


The rate of successful abortions was similar with the 24-hour and 48-hour dosing intervals ( 95.8 % and 93.6 % , respectively ; P = 0.38 ) .


The mean induction-to-abortion interval was also comparable between the 2 groups ( 8.64.1 hours versus 8.73.9 hours ; P = 0.37 ) .


Nulliparous women and women with a pregnancy duration of 16weeks or more had a longer induction-to-abortion interval in both groups .


The 24-hour dosing interval between misoprostol and mifepristone administration seems to be as effective as the 48-hour dosing interval for second trimester TOP .


Clinical Trial Registry India : CTRI/2011/05 / 001770 .


The effects of combined aerobic and resistance exercise training on central arterial stiffness and gait velocity in patients with chronic poststroke hemiparesis were investigated .


Twenty-six patients with chronic poststroke hemiparesis were randomly assigned to either the combined aerobic and resistance exercise group ( n = 14 ) or the control group ( n = 12 ) .


The exercise intervention group received a combined aerobic and resistance exercise training ( 1 hr/day , three times/week for 16 wks ) , whereas the control group received usual care .


Central arterial stiffness was determined by pulse wave velocity and augmentation index .


Gait velocity was assessed using the 6-min walk test , 10-m walk test , and the Timed Up-and-Go test .


Patients in the exercise intervention group had greater improvement of mean pulse wave velocity ( P < 0.001 ) , augmentation index ( P = 0.048 ) , and gait velocity ( 6-min walk test , P < 0.001 ; 10-m walk test , P < 0.001 ) than did patients in the control group .


Patients in the exercise intervention group also had greater improvements in physical fitness component ( grip strength , P < 0.001 ; muscular strength of upper and lower limbs , P < 0.027 ; flexibility , P < 0.001 ) when compared with control patients .


The combined aerobic and resistance exercise program significantly reduced central arterial stiffness and increased gait velocity in patients with chronic poststroke hemiparesis .


To evaluate whether levels of corneal subbasal nerve fiber length ( SNFL ) in dry eye disease ( DED ) could prognosticate the level of improvement in signs and symptoms after treatment .


Phase IV , double-masked , randomized clinical trial .


Sixty patients with meibomian gland dysfunction-associated DED and 27 age-matched controls .


Patients with DED were randomized to receive topical artificial tears , loteprednol etabonate 0.5 % , or loteprednol etabonate 0.5 % / tobramycin 0.3 % twice daily for 4 weeks .


At baseline , in vivo confocal microscopy of central cornea was performed in both eyes .


Patients with DED were divided into 2 subgroups : those with low baseline SNFL and those with near-normal baseline SNFL for this purpose ( the cutoff point : the mean SNFL in controls minus 2 standard deviations ) .


Clinical signs and symptoms at baseline and after 4 weeks of treatment were compared between the subgroups with low and near-normal SNFL for all therapeutic groups .


Symptom questionnaires , corneal fluorescein staining ( CFS ) , conjunctival staining with lissamine green , tear break-up time , Schirmer 's test , and SNFL .


In patients with DED , baseline SNFL ( 17.065.78 mm/mm ( 2 ) ) was significantly lower than in controls ( 23.683.42 mm/mm ( 2 ) , P = 0.001 ) .


In the artificial tear and loteprednol groups , although no significant improvement in any sign or symptom was noted in patients with low baseline SNFL ( < 16.84 mm/mm ( 2 ) ) , subjects with near-normal baseline SNFL ( 16.84 mm/mm ( 2 ) ) showed significant improvement in both symptoms and CFS score ( all P < 0.05 ) .


In the loteprednol/tobramycin group , no significant change was evident for any sign or symptom in either subgroup of low or near-normal baseline SNFL .


Significant improvements in CFS and patient symptomatology after DED treatment were evident only in the subgroup with near-normal corneal SNFL .


Consideration of SNFL may assist in explaining the variability of patients ' response to DED therapy .


To evaluate the effect mechanism of warm acupuncture combined with auricular point sticking therapy and its efficacy on insomnia by monitoring the level of brain neurotransmitters in the insomnia patients .


One hundred and thirty patients with insomnia were randomized into an observation group and a control group , 65 cases in each one .


In the observation group , based on the treating principle of warming yang and benefiting qi , acupuncture was applied to Xinshu ( BL 15 ) , Pishu ( BL 20 ) , Shenshu ( BL 23 ) , Yaoyangguan ( GV 3 ) , Baihui ( GV 20 ) , Neiguan ( PC 6 ) and Shenmen ( HT 7 ) .


Warm acupuncture was supplemented at Xinshu ( BL 15 ) , Pishu ( BL 20 ) , Shenshu ( BL 23 ) and Yaoyangguan ( GV 3 ) .


The treatment was given once every day .


In the control group , estazolam tablets , 0.5 to 1 mg were prescribed for oral administration , 30 min before sleep at night .


The treatment of 14 days was taken as one session and 2 sessions were required in the two groups .


The encephal of luctuograph technology was used to observe the sleep quality and brain neurotransmitters before and after treatment in the two groups and the efficacy was compared between the two groups .


The total effective rate was 83.1 % ( 54/65 ) in the observation group and 87.7 % ( 57/65 ) in the control group .


The efficacy was similar between the two groups ( P > 0.05 ) .


In the observation group , after treatment , 5-HT and GABA/Glu were all increased compared with those before treatment ( P < 0.05 , P < 0.01 ) and norepinephrine ( NE ) was reduced compared with that before treatment ( P < 0.05 ) .


The level of each index did not change significantly before and after treatment in the control group ( all P > 0.05 ) .


The regulations of 5-HT , GABA/Glu in the observation group were superior to those in the control group ( all P < 0.05 ) .


The combined therapy of warm acupuncture and auricular point sticking method for warming yang and benefiting qi effectively improves brain neurotransmitters and essentially improves sleep quality of the patients with insomnia differentiated as yang deficiency pattern .


To compare long-term outcomes and retreatment rates for patients with Dupuytren disease who underwent needle aponeurotomy ( NA ) combined with a series of triamcinolone acetonide injections or underwent NA alone as part of a prior randomized controlled trial .


During this follow-up study , 44 of 47 participants in the original study were examined as needed between 6 and 53 months from their initial procedure .


Those who had not been reassessed within 18 months of the original NA were asked to return for follow-up .


The average total active extension deficit ( TAED ) of previously treated joints was compared between groups 7 to 12 , 13 to 24 , 25 to 36 , and 37 to 48 months following treatment .


Timing of retreatment ( if performed ) was recorded .


Forty-four participants returned for assessment an average of 4.8 times over 53months .


Mean TAED was significantly less in needle aponeurotomy triamcinolone injection patients at 6 months and between 13 and 24 months .


Sixty-two percent of NA group patients and 30 % of needle aponeurotomy triamcinolone injection patients returned for a second treatment on the same digit ( s ) ( retreatment ) .


This difference was not significant .


Mean time to retreatment and mean TAED immediately prior to retreatment did not differ significantly between groups .


Kaplan-Meier survival estimates demonstrated a significantly higher percentage of NA group patients expected to return for retreatment by 24 but not by 36 months .


Younger age , more than one joint treated at the initial NA , and TAED severity throughout the follow-up period were associated with earlier retreatment .


Serial triamcinolone injections combined with NA was associated with lower TAED for up to 24 months .


A larger study would more accurately quantify the potential benefits of combining triamcinolone injections with NA for treatment of Dupuytren disease .


Therapeutic III .


Increasing levels of physical activity in mothers have long-term health benefits for the mother and family .


The study aimed to evaluate the effect of a six-month , physical activity RCT for mothers of young children .


Women were recruited via playgroups and randomly assigned to intervention ( n = 394 ) or control group ( n = 322 ) .


The intervention group received a six-month multi-strategy programme delivered via playgroups in Perth , Australia .


measures were mean minutes per week of moderate ( M ) and vigorous ( V ) intensity physical activity ( PA ) , and number of days/week of muscle strength exercises .


The intervention had a significant effect on mean time for vigorous ( p = 0.008 ) , moderate ( p = 0.023 ) and total physical activity ( p = 0.001 ) when compared to the control group .


The intervention group increased their vigorous activity by a mean of 24min/week , moderate activity by 23min/week and total physical activity by 72min/week .


A relatively minimum home based intervention was able to demonstrate modest but statistically significant improvements in physical activity in a hard to reach group .


These changes if maintained over a longer period are likely to improve the health of mothers and have a positive impact on their partners and children .


Australian and New Zealand Clinical Trials Registry ACTRN12609000735257 .


To present longitudinal changes in Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) scores during 25-week treatment with enzalutamide or placebo in men with progressive metastatic castration-resistant prostate cancer ( mCRPC ) after chemotherapy in the AFFIRM trial .


Patients were randomly assigned to enzalutamide 160 mg/day or placebo .


FACT-P was completed before randomization , at weeks 13 , 17 , 21 , and 25 , and every 12 weeks thereafter while on study treatment .


Longitudinal changes in FACT-P scores from baseline to 25 weeks were analyzed using a mixed effects model for repeated measures ( MMRM ) , with a pattern mixture model ( PMM ) applied as secondary analysis to address non-ignorable missing data .


Cumulative distribution function ( CDF ) plots were generated and different methodological approaches and models for handling missing data were applied .


Due to the exploratory nature of the analyses , adjustments for multiple comparisons were not made .


AFFIRM is registered with ClinicalTrials.gov , number NCT00974311 .


The intention-to-treat FACT-P population included 938 patients ( enzalutamide , n = 674 ; placebo n = 264 ) with evaluable FACT-P assessments at baseline and 1 post-baseline assessment .


After 25 weeks , the mean FACT-P total score decreased by 1.52 points with enzalutamide compared with 13.73 points with placebo ( P < 0.001 ) .


In addition , significant treatment differences at week 25 favoring enzalutamide were evident for all FACT-P subscales and indices , whether analyzed by MMRM or PMM .


CDF plots revealed differences favoring enzalutamide compared with placebo across the full range of possible response levels for FACT-P total and all disease - and symptom-specific subscales/indices .


In men with progressive mCRPC after docetaxel-based chemotherapy , enzalutamide is superior to placebo in health-related quality-of-life outcomes , regardless of analysis model or threshold selected for meaningful response .


NCT00974311 .


Arterial access is a major site of bleeding complications after invasive coronary procedures .


Among strategies to decrease vascular complications , the radial approach is an established one .


Vascular closure devices provide more comfort to patients and decrease hemostasis and need for bed rest .


However , the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications , requiring evidence through adequately designed randomized trials .


The aim of this study is to compare the radial versus femoral approach using a vascular closure device for the incidence of arterial puncture site vascular complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy .


ARISE is a national , multicenter , non-inferiority randomized clinical trial .


Two hundred patients with non-ST-segment elevation acute coronary syndrome will be randomized to either radial or femoral access using a vascular closure device .


The primary outcome is the occurrence of vascular complications at an arterial puncture site 30days after the procedure , including major bleeding , retroperitoneal hematoma , compartment syndrome , hematoma5cm , pseudoaneurysm , arterio-venous fistula , infection , limb ischemia , arterial occlusion , adjacent nerve injury or the need for vascular surgical repair .


Enrollment was initiated in September 2012 , and until October 2013 91 patients were included .


The inclusion phase is expected to last until the second half of 2014 .


The ARISE trial will help define the role of a vascular closure device as a bleeding avoidance strategy in patients with NSTEACS .


ClinicalTrials.gov identifier : NCT01653587 .


Preclinical studies indicate that oxytocin is anorexigenic and has beneficial metabolic effects .


Oxytocin effects on nutrition and metabolism in humans are not well defined .


It was hypothesized that oxytocin would reduce caloric intake and appetite and alter levels of appetite-regulating hormones .


Metabolic effects of oxytocin were also explored .


A randomized , placebo-controlled crossover study of single-dose intranasal oxytocin ( 24 IU ) in 25 fasting healthy men was performed .


After oxytocin/placebo , subjects selected breakfast from a menu and were given double portions .


Caloric content of food consumed was measured .


Visual analog scales were used to assess appetite , and blood was drawn for appetite-regulating hormones , insulin , and glucose before and after oxytocin/placebo .


Indirect calorimetry assessed resting energy expenditure ( REE ) and substrate utilization .


Oxytocin reduced caloric intake with a preferential effect on fat intake and increased levels of the anorexigenic hormone cholecystokinin without affecting appetite or other appetite-regulating hormones .


There was no effect of oxytocin on REE .


Oxytocin resulted in a shift from carbohydrate to fat utilization and improved insulin sensitivity .


Intranasal oxytocin reduces caloric intake and has beneficial metabolic effects in men without concerning side effects .


The efficacy and safety of sustained oxytocin administration in the treatment of obesity warrants investigation .


Benzodiazepines ( BZDs ) are the first-line drugs in alcohol-withdrawal syndrome ( AWS ) .


Baclofen , a gamma-aminobutyric acidB ( GABAB ) agonist , controls withdrawal symptoms without causing significant adverse effects .


The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS .


This was a randomized , open label , standard controlled , parallel group study of cost-effectiveness analysis ( CEA ) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS .


Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol ( CIWA-Ar ) scores .


Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone .


Both direct and indirect medical costs were considered and the CEA was analyzed in both patient 's perspective and third-party perspective .


The average cost-effectiveness ratio ( ACER ) in patient 's perspective of baclofen and chlordiazepoxide was Rs .


5,308.61 and Rs .


2,951.95 per symptom-free day , respectively .


The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs .


895.01 and Rs .


476.29 per symptom-free day , respectively .


Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test ( U = 253.50 , P = 0.03 ) .


Both study drugs provided relief of withdrawal symptoms .


Chlordiazepoxide was more cost-effective than baclofen .


Baclofen was relatively less effective and more expensive than chlordiazepoxide .


This study was aimed to assess the outcome of Ilioinguinal , Iliohypogastric block and wound infiltration with 0.75 % ropivacaine on pain perception , first analgesic request and hospital stay following inguinal Lichtenstein mesh repair .


This was a prospective , randomized , double-blind study with 60 patients undergoing inguinal hernioplasty under general anesthesia .


Patients were randomly allocated to one of the two groups by the sealed envelope method .


Group 1 ( n = 30 ) received nerve blocks and incision infiltration with 0.75 % ropivacaine while group 2 ( n = 30 ) received isotonic saline .


Postoperatively pain intensity , time of demand for the first analgesic and duration of hospital stay were assessed .


Median Visual Analog Scale ( VAS ) score of group 1 was 4 ( high = 6 , low = 3 ) while for group 2 was 5.50 ( high = 8 , low = 4 ) and the p value was < 0.001 .


Mean time for the demand of the first analgesic was prolonged from 1.191.05 h to 5.311.14 h with the p value of < 0.0005 , while the mean time of hospital stay was reduced from 22.53.30 h to 14.12.99 h with the p value of < 0.0005 .


Preemptive analgesia with 0.75 % ropivacaine causes significant reduction in pain perception , request for an analgesic and hospital stay .


Therefore it is advisable before inguinal hernioplasty .


The use of intensity-modulated radiotherapy ( IMRT ) in breast cancer reduces clinician-assessed breast tissue toxicity including fibrosis , telangectasia and sub-optimal cosmesis .


Patient reported outcome measures ( PROMs ) are also important as they provide the patient 's perspective .


This longitudinal study reports on ( a ) the effect of forward planned field-in-field IMRT ( simple IMRT ) on PROMs compared to standard RT at 5 years after RT , ( b ) factors affecting PROMs at 5years after RT and ( c ) the trend of PROMs over 5 years of follow up .


PROMs were assessed at baseline ( pre-RT ) , 6 , 24 and 60 months after completion of RT using global health ( EORTC QLQ C30 ) and 4 breast symptom questions ( BR23 ) .


Also , 4 breast RT-specific questions were included at 6 , 24 and 60 months : change in skin appearance , firmness to touch , reduction in breast size and overall change in breast appearance since RT. .


The benefits of simple IMRT over standard RT at 5 years after RT were assessed using standard t-test for global health and logistic regression analysis for breast symptom questions and breast RT-specific questions .


Clinical factors affecting PROMs at 5 years were investigated using a multivariate analysis .


A repeated mixed model was applied to explore the trend over time for each of PROMs .


( 89 % ) 727/815 , 84 % , 81 % and 61 % patients completed questionnaires at baseline , 6 , 24 and 60 months respectively .


Patients reported worse toxicity for all four BR23 breast symptoms at 6 months , which then improved over time ( p < 0.0001 ) .


They also reported improvement in skin appearance and breast hardness over time ( p < 0.0001 ) , with no significant change for breast shrinkage ( p = 0.47 ) and overall breast appearance ( p = 0.13 ) .


At 5years , PROMs assessments did not demonstrate a benefit for simple IMRT over standard radiotherapy .


Large breast volume , young age , baseline surgical cosmesis and post-operative infection were the most important variables to affect PROMs .


This study was unable to demonstrate the benefits of IMRT on PROMs at 5years .


PROMs are influenced by non-radiotherapy factors and surgical factors should be optimised to improve patients ' outcome .


Only a small proportion of patients report moderate-severe breast changes post radiotherapy , with most PROMs improving over time .


The difference in clinician assessment and PROMs outcome requires further investigation .


Sacral nerve stimulation ( SNS ) is a well established therapy for faecal incontinence ( FI ) .


Percutaneous tibial nerve stimulation ( PTNS ) is a newer , less invasive , treatment .


The effectiveness and acceptability of these treatments have not been compared systematically .


An investigator-blinded randomized pilot trial of PTNS versus SNS with a parallel qualitative study was performed .


Quantitative clinical outcomes and qualitative data from patient interviews were collected for both interventions .


Forty patients ( 39 women ; mean age 59 years ) met the eligibility criteria ; 23 were randomized to receive SNS and 17 to PTNS .


Fifteen patients progressed to permanent SNS implantation and 16 received a full course of PTNS .


Within-group effect sizes were marginally greater for SNS than for PTNS on available-case analysis .


Mean ( s.d. ) FI episodes per week at baseline , and 3 and 6 months of follow-up were : 114 ( 120 ) , 40 ( 40 ) and 49 ( 69 ) respectively for SNS compared with 106 ( 112 ) , 58 ( 69 ) and 63 ( 69 ) for PTNS .


Mean ( s.d. ) Cleveland Clinic Incontinence Score values at baseline , and 3 and 6 months were : 162 ( 30 ) , 111 ( 52 ) and 104 ( 56 ) for SNS versus 151 ( 27 ) , 117 ( 44 ) and 121 ( 52 ) for PTNS .


Improvement of at least 50 per cent in FI episodes per week at 6 months was seen in 11 of 18 patients in the SNS group compared with seven of 15 in the PTNS group .


Effect estimates for SNS with chronic implanted stimulation were larger ( 10 of 15 patients at 6 months ) .


Disease-specific and generic quality-of-life improvements complemented clinical outcome data .


Qualitative analysis of interview data suggested that both treatments had high acceptability amongst patients .


In the short term , both SNS and PTNS provide some clinical benefit to patients with FI .


Registration numbers : 2010-018728-15 and 10479 ( http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=10479 ) .


To assess efficacy and safety of fulranumab , a fully human monoclonal antibody against nerve growth factor , in patients with diabetic peripheral neuropathic pain ( DPNP ) .


In this phase II , double-blind , placebo-controlled trial , patients with moderate to severe DPNP were randomized to treatments with fulranumab ( 1 , 3 , or 10 mg ) or placebo administered subcutaneously every 4 weeks .


Because of early study termination ( clinical hold ) by the US Food and Drug Administration , 77 ( intent-to-treat ) of the planned 200 patients were enrolled .


The primary endpoint , the mean reduction of average daily pain at week 12 compared with baseline , showed a positive dose-response relationship ( p = 0.014 , 1-sided ) ; the pair-wise comparison between the 10-mg group and placebo was significant ( unadjusted p = 0.040 , 2-sided ) .


An exploratory responder analysis revealed that a greater proportion of patients in the 10-mg group reported 30 % reduction in the average DPNP intensity compared with placebo at week 12 ( p = 0.006 ) .


Although not statistically significant , several secondary endpoints showed directionally similar results to the primary efficacy dose-response relationship .


During the combined efficacy and safety extension phases , the top 3 treatment-emergent adverse events in the combined fulranumab group were arthralgia ( 11 % ) , edema peripheral ( 11 % ) , and diarrhea ( 9 % ) .


No cases of joint replacement or death were reported .


Despite early study termination , fulranumab treatment resulted in dose-dependent efficacy and was generally well tolerated .


This study provides Class I evidence that in patients with DPNP , fulranumab 10 mg reduces pain by 1.2 points on an 11-point scale compared with placebo .


Angiogenesis is a valid target in the treatment of epithelial ovarian cancer .


Trebananib inhibits the binding of angiopoietins 1 and 2 to the Tie2 receptor , and thereby inhibits angiogenesis .


We aimed to assess whether the addition of trebananib to single-agent weekly paclitaxel in patients with recurrent epithelial ovarian cancer improved progression-free survival .


For this randomised , double-blind phase 3 study undertaken between Nov 10 , 2010 , and Nov 19 , 2012 , we enrolled women with recurrent epithelial ovarian cancer from 32 countries .


Patient eligibility criteria included having been treated with three or fewer previous regimens , and a platinum-free interval of less than 12 months .


We enrolled patients with a computerised interactive voice response system , and patients were randomly assigned using a permuted block method ( block size of four ) in a 1:1 ratio to receive weekly intravenous paclitaxel ( 80 mg/m ( 2 ) ) plus either weekly masked intravenous placebo or trebananib ( 15 mg/kg ) .


Patients were stratified on the basis of platinum-free interval ( 0 and 6 months vs > 6 and 12 months ) , presence or absence of measurable disease , and region ( North America , western Europe and Australia , or rest of world ) .


The sponsor , investigators , site staff , and patients were masked to the treatment assignment .


The primary endpoint was progression-free survival assessed in the intention-to-treat population .


The trial is registered with ClinicalTrials.gov , NCT01204749 , and is no longer accruing patients .


919 patients were enrolled , of whom 461 were randomly assigned to the trebananib group and 458 to the placebo group .


Median progression-free survival was significantly longer in the trebananib group than in the placebo group ( 72 months [ 58-74 ] vs 54 months [ 95 % CI 43-55 ] , respectively , hazard ratio 066 , 95 % CI 057-077 , p < 00001 ) .


Incidence of grade 3 or higher adverse events was similar between treatment groups ( 244 [ 54 % ] of 452 patients in the placebo group vs 258 [ 56 % ] of 461 patients in the trebananib group ) .


Trebananib was associated with more adverse event-related treatment discontinuations than was placebo ( 77 [ 17 % ] patients vs 27 [ 6 % ] , respectively ) and higher incidences of oedema ( 294 [ 64 % ] patients had any-grade oedema in the trebananib group vs 127 [ 28 % ] patients in the placebo group ) .


Grade 3 or higher adverse events included ascites ( 34 [ 8 % ] in the placebo group vs 52 [ 11 % ] in the trebananib group ) , neutropenia ( 40 [ 9 % ] vs 26 [ 6 % ] ) , and abdominal pain ( 21 [ 5 % ] vs 22 [ 5 % ] ) .


We recorded serious adverse events in 125 ( 28 % ) patients in the placebo group and 159 ( 34 % ) patients in the trebananib group .


There was a difference of 2 % or less in class-specific adverse events associated with anti-VEGF therapy ( hypertension , proteinuria , wound-healing complications , thrombotic events , gastrointestinal perforations ) , except bleeding , which was more common in the placebo group than in the trebananib group ( 75 [ 17 % ] vs 46 [ 10 % ] ) .


Inhibition of angiopoietins 1 and 2 with trebananib provided a clinically meaningful prolongation in progression-free survival .


This non-VEGF anti-angiogenesis option for women with recurrent epithelial ovarian cancer should be investigated in other settings and in combination with additional agents .


Although oedema was increased , typical anti-VEGF associated adverse events were not prominent .


Amgen .


A close correlation exists between positron emission tomography ( PET ) - determined histamine H1 - receptor occupancy ( H1 RO ) and the incidence of sedation .


Antihistamines with H1 RO < 20 % are classified as non-sedating .


The objective was to compare the H1 RO of bilastine , a second generation antihistamine , with that of hydroxyzine .


This randomized , double-blind , crossover study used PET imaging with [ ( 11 ) C ] - doxepin to evaluate H1 RO in 12 healthy males ( mean age 26.2 years ) , after single oral administration of bilastine ( 20mg ) , hydroxyzine ( 25mg ) or placebo .


Binding potentials and H1 ROs were calculated in five cerebral cortex regions of interest : frontal , occipital , parietal , temporal , insula .


Plasma bilastine concentrations , subjective sedation ( visual analogue scale ) , objective psychomotor performance ( digital symbol substitution test ) , physiological variables and safety ( adverse events , AEs ) , were also evaluated .


The mean binding potential of all five regions of interest ( total binding potential ) was significantly greater with bilastine than hydroxyzine ( mean value 0.26 vs. 0.13 , P < 0.01 ; mean difference and 95 % CI -0.130 [ -0.155 , 0.105 ] ) .


There was no significant difference between bilastine and placebo .


Overall H1 RO by bilastine was significantly lower than that by hydroxyzine ( mean value -3.92 % vs. 53.95 % , P < 0.01 ; mean difference and 95 % CI 57.870 % [ 42.664 % , 73.075 % ] ) .


There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values .


No significant between-treatment differences were observed for sedation and psychomotor performance .


Twenty-six non-serious AEs were reported .


Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine .


A single oral dose of bilastine 20mg had minimal H1 RO , was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs , thus satisfying relevant subjective , objective and PET criteria as a non-sedating antihistamine .


The Whole Systems Demonstrator was a large , pragmatic , cluster randomised trial that compared telehealth with usual care among 3,230 patients with long-term conditions in three areas of England .


Telehealth involved the regular transmission of physiological information such as blood glucose to health professionals working remotely .


We examined whether telehealth led to changes in glycosylated haemoglobin ( HbA1c ) among the subset of patients with type 2 diabetes .


The general practice electronic medical record was used as the source of information on HbA1c .


Effects on HbA1c were assessed using a repeated measures model that included all HbA1c readings recorded during the 12-month trial period , and adjusted for differences in HbA1c readings recorded before recruitment .


Secondary analysis averaged multiple HbA1c readings recorded for each individual during the trial period .


513 of the 3,230 participants were identified as having type 2 diabetes and thus were included in the study .


Telehealth was associated with lower HbA1c than usual care during the trial period ( difference 0.21 % or 2.3 mmol/mol , 95 % CI , 0.04 % to 0.38 % , p = 0.013 ) .


Among the 457 patients in the secondary analysis , mean HbA1c showed little change for controls following recruitment , but fell for intervention patients from 8.38 % to 8.15 % ( 68 to 66 mmol/mol ) .


A higher proportion of intervention patients than controls had HbA1c below the 7.5 % ( 58 mmol/mol ) threshold that was targeted by general practices ( 30.4 % vs. 38.0 % ) .


This difference , however , did not quite reach statistical significance ( adjusted odds ratio 1.63 , 95 % CI , 0.99 to 2.68 , p = 0.053 ) .


Telehealth modestly improved glycaemic control in patients with type 2 diabetes over 12 months .


The scale of the improvements is consistent with previous meta-analyses , but was relatively modest and seems unlikely to produce significant patient benefit .


International Standard Randomized Controlled Trial Number Register ISRCTN43002091 .


To evaluate the effect of calorie restriction-induced weight loss with or without aerobic exercise on liver fat .


Thirty-three adults with visceral adiposity were divided into calorie restriction ( CR ; n = 18 ) or CR and aerobic exercise ( CR + Ex ; n = 15 ) groups .


Target energy intake was 25kcal/kg of ideal body weight .


The CR + Ex group had a targeted exercise time of 300min/wk or more at lactate threshold intensity for 12 weeks .


Reductions in body weight ( CR , -5.3 0.8 kg ; CR + Ex , -5.1 0.7 kg ) , fat mass ( CR , -4.9 0.9 kg ; CR + Ex , -4.4 0.6 kg ) , and visceral fat ( CR , -24 5cm2 ; CR + Ex , -37 5cm2 ) were not statistically different between groups .


Liver fat decreased significantly in both groups , with no difference between groups .


Change in maximal oxygen uptake was significantly greater in the CR + Ex group than in the CR group ( CR , -0.7 0.7 mL/kg/min ; CR + Ex , 2.9 1.0 mL/kg/min ) .


Both CR and CR + Ex resulted in an improved reduction in liver fat ; however , there was no additive effect of exercise training .


One hypothesis suggests that the differential response to ondansetron - and serotonin-specific re-uptake inhibitors ( SSRIs ) may be due to a functional polymorphism of the 5 ' - HTTLPR promoter region in SLC6A4 , the gene that codes for the serotonin transporter ( 5-HTT ) .


The LL 5 ' - HTTLPR genotype is postulated to be specifically sensitive to the effects of ondansetron with SS/SL 5 ' - HTTLPR genotypes sensitive to SSRIs .


This study tests this hypothesis by matching nontreatment-seeking alcohol-dependent ( AD ) individuals with LL genotype to ondansetron and SS/SL genotypes to the SSRI sertraline , and mismatching them assessing naturalistic and bar-laboratory alcohol drinking .


Seventy-seven AD individuals were randomized to 1 of 2 counterbalanced arms to receive sertraline 200 mg/d or ondansetron 0.5 mg/d for 3 weeks followed by an alcohol self-administration experiment ( ASAE ) and then received placebo for 3 weeks followed by a second ASAE .


Individuals then received the alternate drug for 3 weeks followed by a third ASAE .


Drinks per drinking day ( DDD with drinks in standard drinking units ) for 7 days prior to each ASAE and milliliters consumed during each ASAE were the primary outcomes .


Fifty-five participants completed the study .


The genotype order interaction was significant , F ( 1 , 47 ) = 8.42 , p = 0.006 , for DDD .


Three analyses of covariance were conducted for DDD during the week before each ASAE .


Ondansetron compared to sertraline resulted in a significant reduction in DDD during the week before the first , F ( 1 , 47 ) = 7.64 , p = 0.008 , but not the third ASAE .


There was no difference in milliliters consumed during each ASAE .


This study modestly supports the hypothesis that ondansetron may reduce DDD in AD individuals with the LL genotype as measured naturalistically .


By contrast , there was no support that ondansetron reduces drinking during the ASAEs or that sertraline reduces alcohol use in individuals who have SS/SL genotypes .


We provide limited support that ondansetron may reduce drinking in nontreatment-seeking individuals with the LL genotype .


No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery .


To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery .


In this multicenter trial , we enrolled 240 patients at high risk for acute kidney injury , as identified by a Cleveland Clinic Foundation score of 6 or higher , between August 2013 and June 2014 at 4 hospitals in Germany .


We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning ( control ) .


All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle .


Patients received either remote ischemic preconditioning ( 3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia ) or sham remote ischemic preconditioning ( control ) , both via blood pressure cuff inflation .


The primary end point was the rate of acute kidney injury defined by Kidney Disease : Improving Global Outcomes criteria within the first 72 hours after cardiac surgery .


Secondary end points included use of renal replacement therapy , duration of intensive care unit stay , occurrence of myocardial infarction and stroke , in-hospital and 30-day mortality , and change in acute kidney injury biomarkers .


Acute kidney injury was significantly reduced with remote ischemic preconditioning ( 45 of 120 patients [ 37.5 % ] ) compared with control ( 63 of 120 patients [ 52.5 % ] ; absolute risk reduction , 15 % ; 95 % CI , 2.56 % -27.44 % ; P = .02 ) .


Fewer patients receiving remote ischemic preconditioning received renal replacement therapy ( 7 [ 5.8 % ] vs 19 [ 15.8 % ] ; absolute risk reduction , 10 % ; 95 % CI , 2.25 % -17.75 % ; P = .01 ) , and remote ischemic preconditioning reduced intensive care unit stay ( 3 days [ interquartile range , 2-5 ] ) vs 4 days ( interquartile range , 2-7 ) ( P = .04 ) .


There was no significant effect of remote ischemic preconditioning on myocardial infarction , stroke , or mortality .


Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor-binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery ( remote ischemic preconditioning , 0.36 vs control , 0.97 ng/mL2/1000 ; difference , 0.61 ; 95 % CI , 0.27-0 .86 ; P < .001 ) .


No adverse events were reported with remote ischemic preconditioning .


Among high-risk patients undergoing cardiac surgery , remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy .


The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation .


German Clinical Trials Register Identifier : DRKS00005333 .


Parasitological confirmation is now recommended for all cases of suspected malaria .


The roll-out of rapid diagnostic tests ( RDTs ) is hoped to enable this goal in low resource settings through point of care testing .


However , simply making RDTs available has not led to high uptake of the tests or adherence to results by clinicians , with malaria continuing to be overdiagnosed in many settings .


We undertook to design an evidence-based intervention package that would be sufficient to support the introduction of RDTs at dispensaries in Tanzania , to be evaluated through the Targeting Artemisinin Combination Therapy ( TACT ) cluster randomised controlled trial .


We describe five steps in our intervention design : formative research , review of existing evidence and theory , a workshop to define the intervention approach and content and results of formative research , engagement with behaviour change theory and literature , detailed design of intervention materials and piloting and pretesting of intervention materials .


This involved fieldwork with a total of 19 health workers and 212 community members in northeast Tanzania .


The formative research suggested that RDTs were a potential source of conflict in the health worker-patient interaction , but that health workers used various techniques to resolve this , including provision of antimalarial drugs for RDT-negative patients .