The study completed accrual and all analyses are final .


This study is registered with ClinicalTrials.gov , number NCT01271803 .


129 patients were treated at ten dosing regimens combining vemurafenib and cobimetinib : 66 had recently progressed on vemurafenib and 63 had never received a BRAF inhibitor .


Dose-limiting toxic effects arose in four patients .


One patient on a schedule of vemurafenib 960 mg twice a day and cobimetinib 80 mg once a day 14/14 had grade 3 fatigue for more than 7 days ; one patient on a schedule of vemurafenib 960 mg twice a day and cobimetinib 60 mg once a day 21/7 had a grade 3 prolongation of QTc ; and two patients on a schedule of vemurafenib 960 mg twice a day and cobimetinib 60 mg 28/0 had dose-limiting toxic effects-one developed grade 3 stomatitis and fatigue and one developed arthralgia and myalgia .


The maximum tolerated dose was established as vemurafenib 960 mg twice a day in combination with cobimetinib 60 mg 21/7 .


Across all dosing regimens , the most common adverse events were diarrhoea ( 83 patients , 64 % ) , non-acneiform rash ( 77 patients , 60 % ) , liver enzyme abnormalities ( 64 patients , 50 % ) , fatigue ( 62 patients , 48 % ) , nausea ( 58 patients , 45 % ) , and photosensitivity ( 52 patients , 40 % ) .


Most adverse events were mild-to-moderate in severity .


The most common grade 3 or 4 adverse events were cutaneous squamous-cell carcinoma ( 12 patients , 9 % ; all grade 3 ) , raised amounts of alkaline phosphatase ( 11 patients , 9 % ] ) , and anaemia ( nine patients , 7 % ) .


Confirmed objective responses were recorded in ten ( 15 % ) of 66 patients who had recently progressed on vemurafenib , with a median progression-free survival of 28 months ( 95 % CI 26-34 ) .


Confirmed objective responses were noted in 55 ( 87 % ) of 63 patients who had never received a BRAF inhibitor , including six ( 10 % ) who had a complete response ; median progression-free survival was 137 months ( 95 % CI 101-175 ) .


The combination of vemurafenib and cobimetinib was safe and tolerable when administered at the respective maximum tolerated doses .


The combination has promising antitumour activity and further clinical development is warranted in patients with advanced BRAF ( V600 ) - mutated melanoma , particularly in those who have never received a BRAF inhibitor ; confirmatory clinical testing is ongoing .


F Hoffmann-La Roche/Genentech .


This study tested the hypothesis that early routine use of tranexamic acid ( TXA ) reduces mortality in a subset of the most critically injured trauma intensive care unit patients .


Consecutive trauma patients ( n = 1,217 ) who required emergency surgery ( OR ) and/or transfusions from August 2009 to January 2013 were reviewed .


At surgeon discretion , TXA was administered at a median of 97 minutes ( 1-g bolus then 1-g over 8 hours ) to 150 patients deemed high risk for hemorrhagic death .


With the use of propensity scores based on age , sex , traumatic brain injury ( TBI ) , mechanism of injury , systolic blood pressure , transfusion requirements , and Injury Severity Score ( ISS ) , these patients were matched to 150 non-TXA patients .


The study population was 43 years old , 86 % male , 54 % penetrating mechanism of injury , 25 % TBI , 28 ISS , with 22 % mortality .


OR was required in 78 % at 86 minutes , transfusion was required in 97 % at 36 minutes , and 75 % received both .


For TXA versus no TXA , more packed red blood cells and total fluid were required , and mortality was 27 % versus 17 % ( all p < 0.05 ) .


The effects of TXA were similar in those with or without TBI , although ISS , fluid , and mortality were all higher in the TBI group .


Mortality associated with TXA was influenced by the timing of administration ( p < 0.05 ) , but any benefit was eliminated in those who required more than 2,000-mL packed red blood cells , who presented with systolic blood pressure of less than 120 mm Hg or who required OR ( all p < 0.05 ) .


For the highest injury acuity patients , TXA was associated with increased , rather than reduced , mortality , no matter what time it was administered .


This lack of benefit can probably be attributed to the rapid availability of fluids and emergency OR at this trauma center .


Prospective studies are needed to further identify conditions that may override the benefits from TXA .


Therapeutic study , level IV .


This study aimed to examine the correlation of heart rate variability ( HRV ) and meridian electrical conductance among middle-aged women during an 8-week period of auricular acupressure ( AA ) treatment for weight reduction .


Sixty ( 60 ) subjects were randomized either to a control group ( n = 30 ) or to a treatment group with AA ( n = 30 ) .


Anthropometric parameters , HRV indices , and meridian levels were measured before treatment , at the 5th week , and 1 week after the 8-week treatment period .


Although no significant changes were observed in body weight ( BW ) and body-mass index ( BMI ) from baseline to 1 week after AA treatment , a significant decrease in Waist Circumference ( WC ) was observed in the acupressure group .


In contrast , the subjects ' BW , BMI , and WC were significantly increased from baseline to the 9th week in the control group .


With adjustment for baseline low frequencies ( LF ) of HRV , the LF at the 5th and 9th weeks in the acupressure groups was generally lower than that in the control group , with a p-value = 0.027 using the mixed linear model .


The meridian levels for Spleen , Bladder , and Gallbladder were significantly lower in the group subjected to acupressure than in the control group at the 5th week .


The results of the present study indicate that AA tends to inactivate the sympathetic nervous activity demonstrated by both HRV and meridian electrical conductance changes .


As a result , AA may modulate the autonomic nervous system to exert its physiological effect through the pathway of the meridian system .


The glycemic management of patients with type 2 diabetes mellitus ( T2DM ) and renal impairment is challenging , with few treatment options .


We investigated the effect of saxagliptin in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus ( SAVOR ) - Thrombolysis in Myocardial Infarction ( TIMI ) 53 trial according to baseline renal function .


Patients with T2DM at risk for cardiovascular events were stratified as having normal or mildly impaired renal function ( estimated glomerular filtration rate [ eGFR ] > 50 mL/min/1 .73 m ( 2 ) ; n = 13,916 ) , moderate renal impairment ( eGFR 30-50 mL/min/1 .73 m ( 2 ) ; n = 2,240 ) , or severe renal impairment ( eGFR < 30 mL/min/1 .73 m ( 2 ) ; n = 336 ) and randomized to receive saxagliptin or placebo .


The primary end point was cardiovascular death , myocardial infarction , or ischemic stroke .


After a median duration of 2 years , saxagliptin neither increased nor decreased the risk of the primary and secondary composite end points compared with placebo , irrespective of renal function ( all P for interactions 0.19 ) .


Overall , the risk of hospitalization for heart failure among the three eGFR groups of patients was 2.2 % ( referent ) , 7.4 % ( adjusted hazard ratio [ HR ] 2.38 [ 95 % CI 1.95-2 .91 ] , P < 0.001 ) , and 13.0 % ( adjusted HR 4.59 [ 95 % CI 3.28-6 .28 ] , P < 0.001 ) , respectively .


The relative risk of hospitalization for heart failure with saxagliptin was similar ( P for interaction = 0.43 ) in patients with eGFR > 50 mL/min/1 .73 m ( 2 ) ( HR 1.23 [ 95 % CI 0.99-1 .55 ] ) , eGFR 30-50 mL/min/1 .73 m ( 2 ) ( HR 1.46 [ 95 % CI 1.07-2 .00 ] ) , and in patients with eGFR < 30 ( HR 0.94 [ 95 % CI 0.52-1 .71 ] ) .


Patients with renal impairment achieved reductions in microalbuminuria with saxagliptin ( P = 0.041 ) that were similar to those of the overall trial population .


Saxagliptin did not affect the risk of ischemic cardiovascular events , increased the risk of heart failure hospitalization , and reduced progressive albuminuria , irrespective of baseline renal function .


High-dose statin loading is known to reduce periprocedural myocardial infarction and contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention .


However , the clinical role of high-dose statin loading in patients with acute heart failure ( AHF ) remains unknown .


In a prospective , single-center , randomized , controlled , open-label pilot study , patients hospitalized with AHF were randomly assigned to receive oral high-dose atorvastatin loading ( 80 mg for 3 days , followed by 10 mg/day until discharge ) or no statin therapy , on top of optimal HF treatment .


The primary outcome measures were changes to the level of biomarkers related to inflammation and renal injury from admission to hospital day 4 .


No significant changes in the levels of NT-proBNP ( -2,6274,956 vs. -2,9816,951 pg/ml , P = 0.845 ) , hsCRP ( -6.116.4 vs. -2.116.2 mg/L , P = 0.105 ) , cystatin C ( 0.0020.185 vs. 0.0090.216 mg/L , P = 0.904 ) , ACR ( -886.31,984.9 vs. -165.6825.2 mg/day , P = 0.124 ) were observed in either group .


In-hospital mortality ( 4.3 % vs. 3.8 % , P > 0.999 ) and all-cause mortality at 90 days ( 4.3 % vs. 3.8 % , P > 0.999 ) were not significantly different between groups .


This pilot study showed that oral high-dose atorvastatin loading may be used safely in patients with AHF , but is not effective in reducing the levels of circulating biomarkers related to inflammation and renal injury during hospitalization .


There is growing recognition of a syndrome of disturbed grief referred to as prolonged grief disorder ( PGD ) .


PGD is mostly studied in adults , but clinically significant PGD symptoms have also been observed in children and adolescents .


Yet , to date no effective treatment for childhood PGD exists .


The aims of this study are : ( 1 ) to investigate the effectiveness of Grief-Help , a nine-session cognitive-behavioural treatment for childhood PGD , combined with five sessions of parental counselling , immediately after the treatment and at three , six and twelve months follow-up ; ( 2 ) to examine tentative mediators of the effects of Grief-Help , ( i.e. , maladaptive cognitions and behaviours and positive parenting ) , and ( 3 ) to determine whether demographic variables , child personality , as well as symptoms of PGD , anxiety , and depression in parents moderate the treatment effectiveness .


We will conduct a Randomised Controlled Trial ( RCT ) in which 160 children and adolescents aged 8-18years are randomly allocated to cognitive behavioural Grief-Help or to a supportive counselling intervention ; both treatments are combined with five sessions of parental counselling .


We will recruit participants from clinics for mental health in the Netherlands .


The primary outcome measure will be the severity of Prolonged Grief Disorder symptoms according to the Inventory of Prolonged Grief for Children ( IPG-C ) .


Secondary outcomes will include PTSD , depression and parent-rated internalizing and externalizing problems .


Mediators like positive parenting and maladaptive cognitions and behaviours will be identified .


We will also examine possible moderators including demographic variables ( e.g. time since loss , cause of death ) , psychopathology symptoms in parents ( PGD , anxiety and depression ) and child personality .


Assessments will take place in both groups at baseline , after the treatment-phase and three , six and twelve months after the post-treatment assessment .


We aim to contribute to the improvement of mental health care for children and adolescents suffering from loss .


By comparing Grief-Help with supportive counselling , and by investigating mediators and moderators of its effectiveness we hope to provide new insights in the effects of interventions for bereaved children , and their mechanisms of change .


Netherlands Trial Register NTR3854 .


This randomized , single center , examiner-blind , controlled , parallel-group , 4-week clinical study compared the antiplaque/anti-gingivitis efficacy of an essential oil ( EO ) containing mouthrinse versus a 0.075 % cetylpyridinium chloride ( CPC ) containing mouthrinse .


A 5 % hydroalcohol solution was included as a control group .


165 systemically healthy volunteers ( 18-72 years of age ) , with mild to moderate plaque-related gingivitis were enrolled in this clinical trial ; 162 subjects completed the study .


At baseline and 4-week visits , subjects received an oral examination , gingivitis ( MGI ) , gingival bleeding ( BI ) and plaque ( PI ) assessments .


Following randomization , subjects began rinsing with 20 mL of the assigned mouthrinse for 30 seconds , in conjunction with their usual oral hygiene , twice daily for the duration of the study .


All rinses were well tolerated by the subjects .


EO was statistically significantly superior to CPC with a reduction in mean MGI of 5.9 % , and in mean PI of 6.4 % .


Statistically significant reductions in gingivitis , bleeding and plaque were observed for both EO and CPC when compared to the negative control ; mean MGI and mean PI were reduced by 13.0 % and 18.9 % for EO and by 7.6 % and 13.3 % for CPC .


EO also statistically significantly reduced the proportion of gingival bleeding sites compared to CPC by 7.6 % ( P = 0.012 ) and compared to control by 10.6 % ( P < 0.001 ) .


For the post hoc sitewise analyses , at 4 weeks , the mean percentage of healthy sites for EO , CPC and Control were 7.4 % , 1.1 % and 0.8 % , respectively and the mean percentage of virtually plaque free sites for EO , CPC and control were 5.4 % , 3.8 % and 0.4 % respectively .


The mean percentages of more inflamed gingival sites for EO , CPC and control were 20.4 % , 26.2 % and 45.7 % , respectively .


The mean percentage of tooth surfaces with heavier accumulations of plaque ( PI scores 3 ) was 50.9 % for EO , 56.1 % for CPC and 81.1 % for control .


Reduction of gingival inflammation and dental plaque was statistically significantly superior for EO compared to both 0.075 % CPC and negative control .


Both marketed antimicrobial mouthrinses showed a beneficial result in gingival health and in reducing plaque accumulation as early as 4 weeks .


To compare the benefits and harms of third-wave cognitive therapy versus mentalisation-based therapy in a small sample of depressed participants .


The trial was conducted at an outpatient psychiatric clinic for non-psychotic patients in Roskilde , Denmark .


44 consecutive adult participants diagnosed with major depressive disorder .


18weeks of third-wave cognitive therapy ( n = 22 ) versus 18weeks of mentalisation-based treatment ( n = 22 ) .


The primary outcome was the Hamilton Rating Scale for Depression ( HDRS ) at end of treatment ( 18weeks ) .


Secondary outcomes were : remission ( HDRS < 8 ) , Beck 's Depression Inventory , Symptom Checklist 90 Revised and The WHO-Five Well-being Index 1999 .


The trial inclusion lasted for about 2years as planned but only 44 out of the planned 84 participants were randomised .


Two mentalisation-based participants were lost to follow-up .


The unadjusted analysis showed that third-wave participants compared with mentalisation-based participants did not differ significantly regarding the 18weeks HDRS score ( 12.9 vs 17.0 ; mean difference -4.14 ; 95 % CI -8.30 to 0.03 ; p = 0.051 ) .


In the analysis adjusted for baseline HDRS score , the difference was favouring third-wave cognitive therapy ( p = 0.039 ) .


At 18weeks , five of the third-wave participants ( 22.7 % ) were in remission versus none of the mentalisation-based participants ( p = 0.049 ) .


We recorded no suicide attempts or suicides during the intervention period in any of the 44 participants .


No significant differences were found between the two intervention groups on the remaining secondary outcomes .


Third-wave cognitive therapy may be more effective than mentalisation-based therapy for depressive symptoms measured on the HDRS .


However , more randomised clinical trials are needed to assess the effects of third-wave cognitive therapy and mentalisation-based treatment for depression .


Registered with Clinical Trials government identifier : NCT01070134 .


Depression is a debilitating mental health problem that tends to run a chronic , recurrent course .


Even when effectively treated , relapse and recurrence rates remain high .


Accordingly , interventions need to focus not only on symptom reduction , but also on reducing the risk of relapse by targeting depression-related disturbances that persist into remission .


We are addressing this need by investigating the efficacy , acceptability and feasibility of a MEmory Specificity Training ( MEST ) programme , which directly targets an enduring cognitive marker of depression - reduced autobiographical memory specificity .


Promising pilot data suggest that training memory specificity ameliorates this disturbance and reduces depressive symptoms .


A larger , controlled trial is now needed to examine the efficacy of MEST .


This trial compares MEST to an education and support ( ES ) group , with an embedded mechanism study .


In a single blind , parallel cluster randomised controlled trial , 60 depressed individuals meeting diagnostic criteria for a current major depressive episode will be recruited from the community and clinical services .


Using a block randomisation procedure , groups of 5 to 8 participants will receive five weekly sessions of MEST ( n = 30 ) or education and support ( n = 30 ) .


Participants will be assessed immediately post-treatment , and at 3 - and 6-months post-treatment ( MEST group only for 6-month follow-up ) .


Depressive symptoms at 3-month follow-up will be the primary outcome .


Secondary outcomes will be change in depressive status and memory specificity at post-treatment and 3-months .


The 6-month follow-up of the MEST group will allow us to examine whether treatment gains are maintained .


An explanatory question will examine variables mediating improvement in depression symptoms post-treatment and at 3-month follow-up .


This trial will allow us to investigate the efficacy of MEST , whether treatment gains are maintained , and the mechanisms of change .


Evidence will be gathered regarding whether this treatment is feasible and acceptable as a low-intensity intervention .


If efficacy can be demonstrated , the results will support MEST as a treatment for depression and provide the foundation for a definitive trial .


NCT01882452 ( ClinicalTrials.gov ) , registered on 18 June 2013 .


To use Fourier-domain optical coherence tomography ( OCT ) to evaluate the wound characteristics of clear corneal incisions ( CCIs ) created with a metal or diamond blade in cataract surgery .


Department of Ophthalmology , Institute of Vision Research , Yonsei University College of Medicine , Seoul , South Korea .


Prospective comparative observational study .


Patients who had cataract surgery were randomized into 2 groups based on whether a metal blade ( Group 1 , 37 eyes ) or diamond blade ( Group 2 , 33 eyes ) was used to create a 2.8 mm temporal CCI .


One day , 1 week , and 1 month postoperatively , structural characteristics of the CCI were analyzed using RTVue-100 Fourier-domain OCT. .


Parameters included incision angle , corneal thickness , epithelial or endothelial gaps , and Descemet membrane detachment .


Visual acuity , surgically induced astigmatism ( SIA ) , and ocular aberrations were evaluated .


There was a significant difference in corneal thickness at the 1.0 mm temporal side from midpoint .


The mean uncorrected distance visual acuity in Group 2 ( 33 eyes ) improved significantly over time .


In both groups , corneal thickness at the midpoint , 1.0 mm temporal side , and 1.0 mm nasal side from the midpoint of the incision significantly decreased over time .


At all timepoints , temporal and nasal thickness in Group 2 was significantly greater than in Group 1 ( 37 eyes ) , with the exception of temporal thickness at 1 month .


In both groups , wound healing was reliable over time .


There were no significant between-group differences in SIA or changes in aberrations .


Corneal thickness at the incision site showed a significant difference between the 2 groups .


Both groups achieved structural stabilization .


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


Whereas emollients are integral to the long-term management of atopic dermatitis ( AD ) , the evidence for their efficacy in disease flares is limited .


We aimed to investigate the stand-alone efficacy of an emollient formulation with regard to improvement of the clinical symptoms , skin barrier function and reduction of pathogenic bacterial colonization in acute stage of AD .


Twenty AD volunteers aged 12-65 years with symmetric , mild to moderately severe inflammatory lesions on the forearms/arms were recruited for the study .


At inclusion , the forearms/arms of each volunteer were randomized to receive for 1 week either an o/w formulation containing licochalcone A ( Glycyrrhiza Inflata root extract ) , decanediol , menthoxypropanediol and -6 - fatty acids ( emollient arm ) or 1 % hydrocortisone ( HC arm ) ; after 1 week , the application of the emollient and HC were discontinued and the volunteers applied a w/o emollient containing licochalcone A and -6 - fatty acids on both arms for further 3 weeks .


The outcomes included reduction of the clinical and itch severity , decrease in S.aureus colonization , improvement of the barrier function , skin hydration and skin tolerability assessed after 1 week ( D7 ) and after 4 weeks ( D28 ) respectively .


In both arms , there was a significant decrease in the severity score , itch intensity , erythema and TEWL on D7 and D28 compared to baseline .


In addition , emollient use resulted in pronounced decrease in S.aureus colonization and significant increase of skin hydration on D7 .


The comparison of the outcomes , based on percentage change from baseline , showed no significant differences between the emollient and HC arm at any time point .


The results of the study indicate that the 1-week stand-alone application of an emollient , tailored to target inflammation , pruritus , compromised barrier function and pathogenic bacterial colonization may offer benefit for the improvement of mild to moderately severe localized flares of AD .


To determine whether a bundled intervention can increase detection of delirium and facilitate safer use of high-risk medications .


Pre-post interventional trial .


Large academic medical center .


Individuals aged 70 and older ( n = 19,949 ) admitted between May 1 , 2008 , September 30 , 2011 .


Individuals aged 80 and older admitted after April 26 , 2010 , received the intervention , those aged 80 and older admitted before were primary controls , and those aged 70 to 79 were concurrent controls .


The intervention uses a checklist promoting delirium prevention , recognition and management , and modifies the computerized provider order entry system to provide care focused on elderly adults .


Frequency of orders for activating the rapid response team for altered mental status , frequency of orders for haloperidol in excess of 0.5 mg or intravenous ( IV ) morphine in excess of 2 mg , and discharge disposition .


Participants receiving the intervention had a mean age of 86.1 4.6 ; 58.2 % were female .


The number of orders to activate the rapid response team for altered mental status increased in participants receiving the bundle and in controls ( odds ratio ( OR ) for the difference of differences = 1.23 ( 95 % confidence interval ( CI ) = 0.68-2 .24 , P = .49 ) ) .


Participants receiving the bundle were less likely to receive more than 0.5 mg of IV , intramuscular , or oral haloperidol ( OR = 0.60 , 95 % CI = 0.39-0 .91 , P = .02 ) and more than 2 mg of IV morphine ( OR = 0.52 , 95 % CI = 0.42-0 .63 , P < .001 ) .


Participants who received the bundle were more likely to be discharged home than to extended care facilities ( OR = 1.18 , 95 % CI = 1.04-1 .35 , P = .01 ) .


An intervention focused on delirium prevention and recognition by bedside staff combined with computerized decision support facilitates safer prescribing of high-risk medications and possibly results in less need for extended care .


The technical difficulty in the revascularization of the circumflex artery territory with off-pump surgery may compromise the outcome of this method in clinical follow-up .


We aimed to evaluate cardiac events in patients with stable coronary artery disease and severe obstruction of the circumflex system , undergoing coronary artery bypass grafting ( CABG ) with or without cardiopulmonary bypass .


MASS III was a single-centre study that evaluated 308 patients with multivessel coronary artery disease randomized to on-pump ( 153 ) or off-pump ( 155 ) CABG .


Of this total , 260 ( 84.4 % ) patients had , on coronary angiography , at least one 70 % obstruction in the circumflex territory ( 141 on-pump and 119 off-pump ) .


The combined outcome was death , myocardial infarction , target vessel revascularization ( angioplasty or surgery ) or hospitalization for cardiac causes .


Variables with possible associations ( P < 0.1 ) were included in the multivariate analysis .


The two groups were well matched for demographics and clinical and angiographic characteristics .


After 5 years of follow-up , off-pump CABG had higher combined events than on-pump had : 25 ( 21 % ) vs 17 ( 12 % ) , hazard ratio 1.88 , 95 % confidence interval 1.02-3 .48 , P = 0.041 .


In the multivariate model with the inclusion of the following variables : age ( P = 0.09 ) and complete revascularization ( P = 0.68 ) , off-pump surgery remained as a predictor of combined events in 5 years , P = 0.03 .


In patients with multivessel coronary artery disease and severe lesions in the circumflex territory , off-pump coronary artery bypass surgery resulted in a higher incidence of cardiac events at 5-year follow-up .


ISRCTN59539154 ( http://www.controlled-trials.com ) .


This clinical study was conducted to investigate the effects of dexmedetomidine ( DEX ) combined with propofol on vital signs and anaesthetic depth in patients .


Ninety patients with ASA 1-2 requiring painless colonoscopy for colonic polyps resection were randomized to receive DEX 0.3 micro ; g/kg ( group D , n = 45 ) followed by propofol 1 mg/kg or propofol 2 mg/kg ( group C , n = 45 ) , and according to the body activity and operation time , additional doses of propofol ( 0.2-0 .5 mg/kg ) were given .


The full recovery time , operation time , consumed dose of propofol , mean arterial pressure ( MAP ) , heart rate ( HR ) , hemoglobin oxygen saturation levels ( SPO ) and NTI were recorded .


The SPOrecover time and the consumed dose of propofol in group D were decreased compared to those in group C ( P < 0.01 ) .


The rate of the body activity in group D was lower than that in group C ( P < 0.05 ) .


The NTI in group C was lower than that in group D ( P < 0.05 ) .


The HR and MAP were similar in both groups .


Under Narcotrend monitoring , the value of DEX combined with low dose of propofol in colonoscopy for colonic polyps resection is to reach more reasonable depth of anesthesia to reduce adverse responses and the dose of propofol .


To estimate whether a continuous infusion of intraperitoneal local anaesthetic for 48hours following laparoscopic hysterectomy reduced the need for opioids delivered with a patient-controlled analgesia pump .


Double-blind randomised placebo-controlled trial .


District general hospital in the UK .


Women undergoing a laparoscopic hysterectomy for a benign indication .


Women were randomised to receive either 0.5 % levobupivicaine or 0.9 % normal saline via an ON-Q elastomeric pump for 48hours postoperatively .


The amount of opioids used via the patient-controlled analgesia pump was recorded and pain was measured using an 11-point Box Scale .


The primary outcome was the amount of patient-administered morphine used over the first 48 postoperative hours .


Secondary outcomes were length of hospital stay , oral analgesia use and level of patient-reported pain .


Sixty women participated and completed the trial .


There was no difference ( P = 0.59 ) in the median amount of patient-administered morphine used between the levobupivicaine ( 23mg ) and placebo ( 18.5 mg ) groups ; median group difference 3.0 ( 95 % CI -7.0 to 14.0 ) .


There was also no difference in the length of hospital stay with 40 % of the treatment group remaining in hospital > 48hours compared with 30 % of the placebo group ( P = 0.08 ) .


Pain scores at all postoperative time points remained similar , with a median group difference in pain scores of 1.0 ( 95 % CI -1.0 to 2.0 ) at the end of the first postoperative day .


Continuous infusion of 0.5 % levobupivicaine into the peritoneal cavity following laparoscopic hysterectomy does not have any opioid-sparing effects .


Screen-related behaviours are highly prevalent in schoolchildren .


Considering the adverse health effects and the relation of obesity and screen time in childhood , efforts to affect screen use in children are warranted .


Parents have been identified as an important influence on children 's screen time and therefore should be involved in prevention programmes .


The aim was to examine the mediating role of family-related factors on the effects of the school-based family-focused UP4FUN intervention aimed at screen time in 10 - to 12-year-old European children ( n child-parent dyads = 1940 ) .


A randomised controlled trial was conducted to test the six-week UP4FUN intervention in 10 - to 12-year-old children and one of their parents in five European countries in 2011 ( n child-parent dyads = 1940 ) .


Self-reported data of children were used to assess their TV and computer/game console time per day , and parents reported their physical activity , screen time and family-related factors associated with screen behaviours ( availability , permissiveness , monitoring , negotiation , rules , avoiding negative role modeling , and frequency of physically active family excursions ) .


Mediation analyses were performed using multi-level regression analyses ( child-school-country ) .


Almost all TV-specific and half of the computer-specific family-related factors were associated with children 's screen time .


However , the measured family-related factors did not mediate intervention effects on children 's TV and computer/game console use , because the intervention was not successful in changing these family-related factors .


Future screen-related interventions should aim to effectively target the home environment and parents ' practices related to children 's use of TV and computers to decrease children 's screen time .


The study is registered in the International Standard Randomised Controlled Trial Number Register ( registration number : ISRCTN34562078 ) .


To explore an optimal anesthesia method with less impact on hemodynamics and electrocardiogram ( ECG ) of old patients with coronary artery disease ( CHD ) during abdominal operation .


The 133 CHD patients waiting for abdominal operation were randomly divided into continuous epidural anesthesia ( EA ) group , general anesthesia group ( GA ) and combined spinal-epidural anesthesia ( CSEA ) group .


Continuous monitoring was carried out during operation and mean arterial pressure ( MAP ) , heart rate ( HR ) , oxygen saturation ( SaO2 ) , abnormal ECG were measured respectively at different time for comparison and the differences of the above hemodynamic parameters and abnormal ECG features were compared among the 3 groups .


At the 15 min and 30 min point after anesthesia , SaO2 in GA group was significantly increased compared to that in the EA group ( P < 0.05 ) .


At 15 min , 30 min and 60 min point after anesthesia , MAP in CSEA group was significantly increased compared to that in the EA group ( P < 0.05 ) .


At 30 min point after anesthesia , HR in CSEA group was increased significantly compared to the EA group ( P < 0.05 ) .


At 15 min and 30 min point after anesthesia , SaO2 in the CSEA group was increased significantly compare to the EA group ( P < 0.05 ) .


Compared with preanesthesia ( T0 ) in EA group , MAP , HR and SaO2 decreased significantly at 15 , 30 and 60 min after anesthesia ( P < 0.05 ) .


The fluctuation of the three parameters in GA and CSEA groups were relatively small ( P > 0.05 ) .


As well as the comparison of abnormal ECG among the 3 groups was concerned , the incidence of ST-T changes in GA and CSEA groups were significantly lower than that in EA group at the time of 15 min , 30 min and 60 min after anesthesia and at the time of surgery termination ( P < 0.05 , P < 0.01 ) .


The incidence of arrhythmia in GA and CSEA groups were significantly lower than that in EA group at the time of 15 min , 30 min and 60 min after anesthesia ( P < 0.05 , P < 0.01 ) .


Compared with T0 in the same group , the incidences of ST-T changes and arrhythmia in GA or CSEA group at the time of 15 , 30 and 60 min after anesthesia and at the time of surgery termination were significantly lower than that before anesthesia ( P < 0.05 , P < 0.01 ) .


GA and CSEA have less impact on hemodynamics and have smaller incidence of abnormal ECG of old CHD patients with abdominal operation .


Lower levels of global DNA methylation in tissue and blood have been associated with increased cancer risk .


Conversely , cross-sectional analyses of healthier lifestyle patterns have been associated with higher levels of global DNA methylation .


In this trial , we explored the associations between changes in lifestyle modifications ( diet , weight loss ) , metabolic markers , and global epigenetic biomarkers in white blood cells .


Study participants were Hispanic , African American , and Afro-Caribbean overweight and sedentary female breast cancer survivors ( n = 24 ) who participated in a larger randomized , crossover , pilot study of a 6-mo weight loss intervention and who had available blood specimens .


Anthropometric measures , a food-frequency questionnaire , and peripheral blood were collected at baseline , 6 mo , and 12 mo. .


Plasma samples were analyzed for metabolic markers ( insulin , glucose ) .


We measured DNA methylation of long interspersed nucleotide element 1 ( LINE-1 ) and satellite 2 by pyrosequencing and MethyLight , respectively , and global DNA methylation by the luminometric methylation assay ( LUMA ) .


DNA methylation of LINE-1 was statistically significantly elevated at 6 mo [ 75.5 % vs. 78.5 % ( P < 0.0001 ) ] and 12 mo [ 75.5 % vs. 77.7 % ( P < 0.0001 ) ] , compared to baseline .


Over a 12-mo period , changes in percentage body fat and plasma glucose concentrations were positively associated with LINE-1 DNA methylation ( = 0.19 , P = 0.001 ) and LUMA DNA methylation levels ( = 0.24 , P = 0.02 ) , respectively .


Similarly , 12-mo changes in dietary measures such as vegetable ( = 0.009 , P = 0.048 ) , protein ( = 0.04 , P = 0.001 ) , and total caloric ( = 0.05 , P = 0.01 ) intake were positively associated with changes in LUMA DNA methylation , as was intake of fruit positively associated with changes in LINE-1 DNA methylation ( = 0.004 , P = 0.02 ) .


Our hypothesis-generating results suggest that lifestyle modifications may be associated with changes in global DNA methylation detectable at 6 and 12 mo. .


These biomarkers may be useful intermediate biomarkers to use in future intervention trials .


This trial was registered at clinicaltrials.gov as NCT00811824 .


Substance use problems in childhood and adolescence can severely impact youth 's physical and mental well-being .


When substance use is initiated early , the risk for moving from hazardous substance use to substance use disorders ( SUD ) is particularly high to developmentally induced biological and psychological vulnerability towards chronic trajectories in youth .


Thus , risk factors for developing SUD should be addressed early in life by adequate preventive measures reaching out to children , adolescents , and their families .


The study described in this protocol will test the effectiveness of the German adaptation of the Strengthening Families Program for Parents and Youth 10-14 ( SFP 10-14 ) aimed at ten to 14 year old adolescents and their caregivers .


The study is conducted in four large German cities by counselling centres in the areas of youth welfare , social work and addiction aid .


The effectiveness of the manualised group programme `` Familien Strken '' consisting of seven sessions and four booster-sessions is tested among N = 288 children and participating parents in a multicentre randomised controlled trial with standardised assessment instruments .


The control condition receives a minimal 2-hour intervention on parenting delivered in a school setting .


Data are collected shortly before and after as well as six and 18 months after the intervention .


We expect to replicate the favourable effects of the SFP 10-14 programme in the United States in the area of substance use initiation , family functioning and individual psychosocial adjustment .


The trial is expected to contribute to the growing literature on family-based preventive interventions , their effectiveness and feasibility .


It is in line with several other current European efforts aimed at strengthening families against the detrimental effects of substance abuse in youth .


The results of these trials will expand our knowledge on adapting evidence-based interventions and delivering them in diverse cultures and settings .


Current Controlled Trials ISRCTN90251787 .


There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease .


Aortic stiffness , an independent predictor of cardiovascular risk , and systemic and airway inflammation are increased in patients with the disease .


Statins modulate aortic stiffness and have anti-inflammatory properties .


A proof-of-principle , double-blind , randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease .


Stable patients ( n = 70 ) were randomized to simvastatin ( active ) or placebo .


Pre-treatment and post-treatment aortic stiffness , blood pressure , spirometry , and circulating and airway inflammatory mediators and lipids were measured .


A predefined subgroup analysis was performed where baseline aortic pulse wave velocity ( PWV ) was > 10 m/sec .


Total cholesterol dropped in the active group .


There was no significant change in aortic PWV between the active group and the placebo group ( -0.7 m/sec , P = 0.24 ) .


In those with aortic stiffness > 10 m/sec ( n = 22 ) , aortic PWV improved in the active group compared with the placebo group ( -2.8 m/sec , P = 0.03 ) .


Neither systemic nor airway inflammatory markers changed .


There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo , but in those with higher baseline aortic stiffness ( a higher risk group ) a significant and clinically relevant reduction in PWV was shown .


Depression , cognitive impairment , and other nonmotor symptoms ( NMSs ) are common early in Parkinson disease ( PD ) and may be in part due to disease-related dopamine deficiency .


Many patients with PD are treated with antidepressants for NMSs , and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied .


We report the effects of the addition of a monoamine oxidase B inhibitor , rasagiline , to antidepressant treatment in PD .


To evaluate the effect of rasagiline on depression , cognition , and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily ( ADAGIO ) study .


The ADAGIO study was a double-blind , placebo-controlled , delayed-start trial of rasagiline in de novo PD .


In this exploratory post hoc analysis , we analyzed patients taking an antidepressant during the 36-week phase 1 period , in which patients were randomized to rasagiline ( 1 or 2 mg/d ) or placebo .


We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo .


The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson 's Disease Rating Scale Nonmotor Experiences of Daily Living , the original Unified Parkinson 's Disease Rating Scale , and the Parkinson Fatigue Scale .


A total of 191 of the 1174 patients ( 16.3 % ) were treated with antidepressants during phase 1 and provided efficacy data .


Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group ( differences in Movement Disorder Society-sponsored revision of the Unified Parkinson 's Disease Rating Scale item-adjusted means [ SEs ] , -0.19 [ 0.10 ] , P = .048 , and -0.20 [ 0.05 ] , P < .001 , respectively ) .


Parkinson Fatigue Scale ( mean [ SE ] difference,-0 .42 [ 0.09 ] , P < .001 ) and daytime sleepiness ( mean [ SE ] difference,-0 .24 [ 0.09 ] , P = .006 ) scores also revealed significantly less worsening in the rasagiline group compared with placebo .


There was a nonsignificant trend toward less worsening in apathy and no significant between-group differences in anxiety or sleep .


The effect on depression remained significant after controlling for improvement in motor symptoms ( mean [ SE ] difference,-0 .23 [ 0.09 ] , P = .009 ) .


There were no serious adverse events in the combined rasagiline-antidepressant group suggestive of serotonin syndrome .


The combination of rasagiline and antidepressants in patients with de novo PD is associated with reduced worsening of a range of NMSs in preliminary analyses .


Adverse effects appear uncommon with this combination .


These findings suggest a role for dopamine-enhancing therapies in NMSs in early PD and encourage further study and confirmation .


clinicaltrials.gov Identifier : NCT00256204 .


The prevalence of obesity has markedly increased in patients with chronic kidney disease ( CKD ) .


Studies on the impact of exercise focusing on obese CKD patients are scarce .


Therefore , we aimed to investigate the effect of aerobic exercise performed either in an exercise centre or at home on visceral fat in overweight non-dialysed CKD patients .


Twenty-seven sedentary men ( 52.1 9.5 years , body mass index 30.4 3.8 kg/m ( 2 ) , estimated glomerular filtration rate ( eGFR ) 27.5 11.6 mL/min ) were randomly assigned to a centre-based exercise group ( n = 10 ) , home-based exercise group ( n = 8 ) or control group ( n = 9 ) .


The aerobic training was prescribed according to ventilatory threshold and performed three times per week during 12 weeks .


Body composition was assessed by dual energy X-ray absorptiometry ( DEXA ) and the distribution of abdominal fat by computed tomography .


In the centre-based group , visceral fat and waist circumference decreased 6.4 6.4 mm ( P < 0.01 ) and 2.0 2.3 cm ( P = 0.03 ) and leg lean mass increased 0.5 0.4 kg ( P < 0.01 ) .


No significant changes were observed in the home-based group .


Visceral fat increased 5.0 4.4 mm in the control group ( P = 0.01 ) .


In relation to the control , a group-by-time interaction was significant for visceral fat and waist circumference for both exercise groups and for leg lean mass for the centre-based group .


Mean blood pressure decreased in both exercise groups ( centre-based 13 % , P < 0.01 and home-based 10 % , P = 0.03 ) and eGFR increased 3.6 4.6 mL/min ( P = 0.03 ) in the centre-based group .


These parameters remained unchanged in the control group .


Centre-based aerobic exercise is an effective approach to reduce visceral fat besides promoting relevant clinical benefits in male overweight CKD patients .


Lowering intraocular pressure ( IOP ) is currently the only therapeutic approach in primary open-angle glaucoma .


and the fixed-combination medications are needed to achieve sufficiently low target IOP .


A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China .


In this study , we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension .


In this multicenter , randomized , double-masked , parallel controlled study , patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical - blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments .


Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03 % bimatoprost and 0.5 % timolol ( followed by vehicle for masking ) once daily at 19:00 P.M. and concurrent treatment was 0.03 % bimatoprost followed by 0.5 % timolol once daily at 19:00 P.M.


The primary efficacy variable was change from baseline in mean diurnal intraocular pressure ( IOP ) at week 4 visit in the intent-to-treat ( ITT ) population .


Primary analysis evaluated the non-inferiority of bimatoprost / timolol fixed combination to concurrent with respect to the primary variable using a confidence interval ( CI ) approach .


Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95 % CI for the between-treatment ( bimatoprost/timolol fixed combination minus concurrent ) difference was 1.5 mmHg .


Adverse events were collected and slit-lamp examinations were performed to assess safety .


Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher 's exact test .


Of the enrolled 235 patients , 121 patients were randomized to receive bimatoprost/timolol fixed combination and , 114 patients were randomized to receive concurrent treatment .


At baseline the mean value of mean diurnal IOP was ( 25.20 3.06 ) mmHg in the bimatoprost/timolol fixed combination group and ( 24.87 3.88 ) mmHg in the concurrent group .


The difference between the treatment groups was not statistically significant .


The mean change from baseline in mean diurnal IOP ( standard deviation ) in the bimatoprost/timolol fixed combination group was ( -9.38 4.66 ) mmHg and it was ( -8.93 4.25 ) mmHg in the concurrent group ( P < 0.01 ) .


The difference between the two treatment groups ( bimatoprost/timolol fixed combination minus concurrent ) in the change from baseline of mean diurnal IOP was -0.556 mmHg ( 95 % CI : -1.68 , 0.57 , P = 0.330 ) .


The upper limit of the 95 % CI was less than 1.5 mmHg , the predefined margin of non-inferiority .


Adverse events occurred in 26.4 % ( 32/121 ) of the bimatoprost/timolol fixed combination patients and 30.7 % ( 35/114 ) of the concurrent patients .


The most frequent adverse event was conjunctival hyperemia , which was reported as treatment related in 16.5 % ( 20/121 ) in the bimatoprost/timolol fixed combination group and 18.4 % ( 21/114 ) in the concurrent group ( P > 0.05 ) .


Bimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components .


Safety profiles were similar between the treatment groups .


The particle size and structure of masticated almonds have a significant impact on nutrient release ( bioaccessibility ) and digestion kinetics .


The goals of this study were to quantify the effects of mastication on the bioaccessibility of intracellular lipid of almond tissue and examine microstructural characteristics of masticated almonds .


In a randomized , subject-blind , crossover trial , 17 healthy subjects chewed natural almonds ( NAs ) or roasted almonds ( RAs ) in 4 separate mastication sessions .


Particle size distributions ( PSDs ) of the expectorated boluses were measured by using mechanical sieving and laser diffraction ( primary outcome ) .


The microstructure of masticated almonds , including the structural integrity of the cell walls ( i.e. , dietary fiber ) , was examined with microscopy .


Lipid bioaccessibility was predicted by using a theoretical model , based on almond particle size and cell dimensions , and then compared with empirically derived release data .


Intersubject variations ( n = 15 ; 2 subjects withdrew ) in PSDs of both NA and RA samples were small ( e.g. , laser diffraction ; CV : 12 % and 9 % , respectively ) .


Significant differences in PSDs were found between these 2 almond forms ( P < 0.05 ) .


A small proportion of lipid was released from ruptured cells on fractured surfaces of masticated particles , as predicted by using the mathematical model ( 8.5 % and 11.3 % for NAs and RAs , respectively ) .


This low percentage of lipid bioaccessibility is attributable to the high proportion ( 35-40 % ) of large particles ( > 500 m ) in masticated almonds .


Microstructural examination of the almonds indicated that most intracellular lipid remained undisturbed in intact cells after mastication .


No adverse events were recorded .


Following mastication , most of the almond cells remained intact with lipid encapsulated by cell walls .


Thus , most of the lipid in masticated almonds is not immediately bioaccessible and remains unavailable for early stages of digestion .


The lipid encapsulation mechanism provides a convincing explanation for why almonds have a low metabolizable energy content and an attenuated impact on postprandial lipemia .


Neurocysticercosis causes a substantial burden of seizure disorders worldwide .


Treatment with either praziquantel or albendazole has suboptimum efficacy .


We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures .


We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations .


In this double-blind , placebo-controlled , phase 3 trial , patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole ( 15 mg/kg per day ) plus praziquantel ( 50 mg/kg per day ) , standard albendazole ( 15 mg/kg per day ) , or increased dose albendazole ( 225 mg/kg per day ) .


Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug .


Patients and investigators were masked to group assignment .


The primary outcome was complete cyst resolution on 6-month MRI .


Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group .


Analysis excluded patients lost to follow-up before the 6-month MRI .


This trial is registered with ClinicalTrials.gov , number NCT00441285 .


Between March 3 , 2010 and Nov 14 , 2011 , 124 patients were randomly assigned to study groups ( 41 to receive combined albendazole plus praziquantel [ 39 analysed ] , 43 standard albendazole [ 41 analysed ] , and 40 increased albendazole [ 38 analysed ] ) .


25 ( 64 % ) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 ( 37 % ) of 41 patients in the standard albendazole group ( rate ratio [ RR ] 175 , 95 % CI 110-279 , p = 0014 ) .


20 ( 53 % ) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 ( 37 % ) of 41 patients in the standard albendazole group ( RR 144 , 95 % CI 087-238 , p = 0151 ) .


No significant differences in adverse events were reported between treatment groups ( 18 in combined treatment group , 11 in standard albendazole group , and 19 in increased albendazole group ) .


Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects .


A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis .


National Institute of Neurological Disorders and Stroke ( NINDS ) , National Institutes of Health .


Critical illness results in disability and reduced health-related quality of life ( HRQOL ) , but the optimum timing and components of rehabilitation are uncertain .


To evaluate the effect of increasing physical and nutritional rehabilitation plus information delivered during the post-intensive care unit ( ICU ) acute hospital stay by dedicated rehabilitation assistants on subsequent mobility , HRQOL , and prevalent disabilities .


A parallel group , randomized clinical trial with blinded outcome assessment at 2 hospitals in Edinburgh , Scotland , of 240 patients discharged from the ICU between December 1 , 2010 , and January 31 , 2013 , who required at least 48 hours of mechanical ventilation .


Analysis for the primary outcome and other 3-month outcomes was performed between June and August 2013 ; for the 6 - and 12-month outcomes and the health economic evaluation , between March and April 2014 .


During the post-ICU hospital stay , both groups received physiotherapy and dietetic , occupational , and speech/language therapy , but patients in the intervention group received rehabilitation that typically increased the frequency of mobility and exercise therapies 2 - to 3-fold , increased dietetic assessment and treatment , used individualized goal setting , and provided greater illness-specific information .


Intervention group therapy was coordinated and delivered by a dedicated rehabilitation practitioner .


The Rivermead Mobility Index ( RMI ) ( range 0-15 ) at 3 months ; higher scores indicate greater mobility .


Secondary outcomes included HRQOL , psychological outcomes , self-reported symptoms , patient experience , and cost-effectiveness during a 12-month follow-up ( completed in February 2014 ) .


Median RMI at randomization was 3 ( interquartile range [ IQR ] , 1-6 ) and at 3 months was 13 ( IQR , 10-14 ) for the intervention and usual care groups ( mean difference , -0.2 [ 95 % CI , -1.3 to 0.9 ; P = .71 ] ) .


The HRQOL scores were unchanged by the intervention ( mean difference in the Physical Component Summary score , -0.1 [ 95 % CI , -3.3 to 3.1 ; P = .96 ] ; and in the Mental Component Summary score , 0.2 [ 95 % CI , -3.4 to 3.8 ; P = .91 ] ) .


No differences were found for self-reported symptoms of fatigue , pain , appetite , joint stiffness , or breathlessness .


Levels of anxiety , depression , and posttraumatic stress were similar , as were hand grip strength and the timed Up & Go test .


No differences were found at the 6 - or 12-month follow-up for any outcome measures .


However , patients in the intervention group reported greater satisfaction with physiotherapy , nutritional support , coordination of care , and information provision .


Post-ICU hospital-based rehabilitation , including increased physical and nutritional therapy plus information provision , did not improve physical recovery or HRQOL , but improved patient satisfaction with many aspects of recovery .


isrctn.com Identifier : ISRCTN09412438 .


The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes ( ACS ) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes ( PLATO ) trial .


The associations between sex subgroup and the primary composite outcomes , secondary outcomes , and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models .


Sex was not significantly associated with the probability of the primary composite endpoint [ adjusted hazard ratio ( HR ) : 1.02 ( 0.91-1 .16 ) ] , or other adverse cardiovascular endpoints .


Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2 % [ adjusted HR : 0.88 ( 0.74-1 .06 ) ] and men 9.4 vs. 11.1 % [ adjusted HR : 0.86 ( 0.76-0 .97 ) ] ( interaction P-value 0.78 ) , all-cause death in women 5.8 vs. 6.8 % [ adjusted HR : 0.90 ( 0.69-1 .16 ) ] and men 4.0 vs. 5.7 % [ adjusted HR : 0.80 ( 0.67-0 .96 ) ] ( interaction P-value 0.49 ) , and definite stent thrombosis in women 1.2 vs. 1.4 % [ adjusted HR : 0.71 ( 0.36-1 .38 ) ] and men 1.4 vs. 2.1 % [ adjusted HR : 0.63 ( 0.45-0 .89 ) ] ( interaction P-value 0.78 ) .


The treatments did not differ for PLATO-defined overall major bleeding complications in women [ adjusted HR : 1.01 ( 0.83-1 .23 ) ] or men [ adjusted HR : 1.10 ( 0.98-1 .24 ) ] .


Sex had no significant association with these outcomes ( interactions P = 0.43-0 .88 ) .


Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients .


Ticagrelor has a similar efficacy and safety profile in men and women .


Pulmonary rehabilitation is effective for patients with COPD , but its benefit is less clearly established in idiopathic pulmonary fibrosis ( IPF ) , especially in regard to levels of physical activity and health-related quality of life .


The objectives were to determine whether pulmonary rehabilitation increased physical activity as assessed by the International Physical Activity Questionnaire ( IPAQ ) , and improved quality of life and symptoms as assessed by the St George respiratory questionnaire for IPF ( SGRQ-I ) and the Borg dyspnea index ( BDI ) .


Subjects who met current criteria for IPF were randomized to a 3-month pulmonary rehabilitation program ( n = 11 ) or to a control group ( n = 10 ) .


The rehabilitation group participated in twice-weekly , 90-min exercise sessions ( 24 total sessions ) .


The control group maintained its preceding , normal physical activity .


All subjects underwent 6-min walk tests to assess the postexertion BDI .


The SGRQ-I and a 5-point self-assessment of health were completed at baseline , after 3 months of intervention or observation , and after 3-month follow-up .


All subjects completed the IPAQ weekly .


Subjects in the rehabilitation group maintained significantly higher levels of physical activity throughout the 3-month rehabilitation program ( rehabilitation : 51,364 57,713 [ mean SD ] metabolic equivalent of task-minutes ; control : 20,832 37,155 , P = .027 by 2-tailed Mann-Whitney test ) .


SGRQ-I symptom domain scores improved considerably by -9 22 in the rehabilitation group , whereas in the control group they worsened ( 16 12 rehabilitation compared with control , P = .013 by 2-tailed Mann-Whitney test ) .


During the 3-month follow-up , self-reported physical activity levels in the rehabilitation group were 14,428 8,884 metabolic equivalent of task-minutes and in the control group 16,923 32,620 ( P = .17 by 2-tailed Mann-Whitney test ) , demonstrating substantial reversal of activity in the rehabilitation group .


BDI scores after 6-min walk tests did not change significantly .


A 3-month rehabilitation program significantly improved symptoms ( SGRQ-I ) and physical activity levels ( IPAQ ) in subjects with IPF while they participated actively in the program .


( ClinicalTrials.gov registration NCT01118221 . )


To compare total laparoscopic hysterectomy ( TLH ) , total abdominal hysterectomy ( TAH ) and vaginal hysterectomy ( VH ) using electrosurgical bipolar vessel sealing ( EBVS ) technique regarding operative time , intra and postoperative complications .


The current prospective randomized controlled clinical trial was conducted at Ain-shams University maternity Hospital , Cairo , Egypt .


Ninety patients who were admitted from gynecologic outpatient clinic to undergo hysterectomy were enrolled .


The study population was randomized according to type of hysterectomy done into 3 groups : group 1 : VH ; group 2 : AH and group 3 : TLH .


EBVS was used in all groups .


Three staff members ' surgeons were also randomized to operate on the patients and they were all equally competent in all the procedures .


Main outcome measures were operative time , operative blood loss , operative complications , postoperative pain assessment using the visual analogue scale ( 0-10 ) , and the need for analgesics as well as the postoperative hospital stay .


Ninety patients were randomized to undergo VH , TAH or TLH for benign pathology using EBVS .


Postoperative pain score and the need for analgesia were least in TLH compared to the other two groups , ( p < 0.001 ) .


The hospital stay in TLH group was shorter than the other two groups , but there was no significant difference between VH group and TAH group with regard to hospital stay , ( p < 0.001 ) .


The total operative time was shortest in the VH group ( 100.4 35.8 min ) compared to TLH ( 126 42.7 min ) and TAH ( 123.6 44.5 min ) ( p = 0.033 ) .


The operative complications were more with VH and TAH groups .


The blood loss was more with VH ( p = 0.039 ) .


TLH had a longer operation time , yet , less blood loss , shorter hospital stay , less postoperative pain and fewer complications , compared to TAH and VH using EBVS .


Fibroblast growth factor 23 ( FGF23 ) is a hormone that regulates phosphorus and vitamin D metabolism .


Elevated FGF23 concentrations are associated with excess risk of cardiovascular disease .


Associations of FGF23 with stroke outcomes are less clear .


Using a case-cohort study design , we examined the association of baseline plasma FGF23 concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) study , a cohort of black and white adults aged 45 years .


FGF23 was measured in 615 participants who developed incident stroke ( cases ) and in 936 participants randomly selected from the REGARDS cohort ( comparison subcohort ) .


In multivariable-adjusted models , higher calcium and phosphorus concentrations , lower estimated glomerular filtration rate and higher urine albumin excretion were independently associated with higher FGF23 .


There was no statistically significant association of FGF23 with risk of all-cause stroke in Cox models adjusted for demographic factors and established stroke risk factors ( hazard ratio comparing fourth with first quartile 1.19 ; 95 % confidence interval , 0.78-1 .82 ) .


In prespecified models stratified by stroke subtypes , there was a graded association of FGF23 with risk of cardioembolic stroke in fully adjusted models ( quartile 1 , reference ; quartile 2 hazard ratio , 1.48 ; 95 % confidence interval , 0.63-3 .47 ; quartile 3 hazard ratio , 1.99 ; 95 % confidence interval , 0.89-4 .44 ; quartile 4 hazard ratio , 2.52 ; 95 % confidence interval , 1.08-5 .91 ) .


There were no statistically significant associations of FGF23 with other ischemic stroke subtypes or with hemorrhagic strokes .


Higher FGF23 concentrations were associated with higher risk of cardioembolic but not with other stroke subtypes in community-dwelling adults .


Additional studies should delineate reasons for these findings .


In patients undergoing regadenoson stress SPECT myocardial perfusion imaging ( MPI ) , the impact of the regimented administration of aminophylline on the cardiac-to-extracardiac photon activity ratio is unknown .


This is a substudy of the ASSUAGE trial ( NCT01250496 ) ; a double-blinded , randomized , placebo-controlled clinical trial which investigated the attenuation of regadenoson-related adverse effects using 75 mg of intravenous aminophylline vs placebo , administered 90 seconds following ( 99m ) Tc-tetrofosmin injection in patients undergoing regadenoson stress SPECT-MPI .


In subjects with normal MPI enrolled in the trial , we sampled from the antero-posterior planar projection of the post-stress scintigraphic data the mean photon activity in the myocardium , liver , bowel , and lungs .


The mean cardiac-to-extracardiac activity ratios were compared between patients randomized to aminophylline vs placebo .


We studied 158 eligible subjects , randomized to receive aminophylline ( n = 86 ) or placebo ( n = 72 ) .


The means of photon activity ratios of the heart-to-liver , heart-to-bowel , heart-to-lungs , inferior wall of the heart-to-liver , and inferior wall of the heart-to-bowel were not statistically different between those who received aminophylline vs placebo ( P values > .30 ) .


Only the time lapse between stress ( 99m ) Tc-tetrofosmin injection and stress SPECT acquisition independently correlated with higher heart-to-liver and heart-to-bowel activity ratios ( P values .01 ) .


Patients ' body mass index independently correlated with lower heart-to-lung ratio ( P = .009 ) .


The regimented intravenous aminophylline use following regadenoson stress does not significantly improve the cardiac-to-extracardiac photon activity ratio in patients undergoing regadenoson stress ( 99m ) Tc-tetrofosmin SPECT-MPI .


Physical inactivity is fourth in the list of risk factors for global mortality .


General practitioners are well placed to offer physical activity counseling but insufficient time is a barrier .


Although referral to an exercise specialist is an alternative , in Australia , these allied health professionals are only publicly funded to provide face-to-face counseling to patients who have an existing chronic illness .


Accordingly , this trial aims to determine the efficacy of GP referral of insufficiently active patients ( regardless of their chronic disease status ) for physical activity counseling ( either face-to-face or predominately via telephone ) by exercise specialists , based on patients ' objectively assessed physical activity levels , compared with usual care .


If the trial is efficacious , the equivalence and cost-effectiveness of face-to-face counseling versus telephone counseling will be assessed .


This three arm pragmatic randomized trial will involve the recruitment of 261 patients from primary care clinics in metropolitan and regional areas of New South Wales , Australia .


Insufficiently active ( less than 7000 steps/day ) consenting adult patients will be randomly assigned to : 1 ) five face-to-face counseling sessions , 2 ) one face-to-face counseling session followed by four telephone calls , or 3 ) a generic mailed physical activity brochure ( usual care ) .


The interventions will operationalize social cognitive theory via a behavior change counseling framework .


Participants will complete a survey and seven days of pedometry at baseline , and at three and 12 months post-randomization .


The primary analyses will be based on intention-to-treat principles and will compare : ( i ) mean change in average daily step counts between baseline and 12 months for the combined intervention group ( Group 1 : face-to-face , and Group 2 : telephone ) and usual care ( Group 3 ) ; ( ii ) step counts at 3 months post-randomization .


Secondary outcomes include : self-reported physical activity , sedentary behavior , quality of life , and depression .


If referral of primary care patients to exercise specialists increases physical activity , this process offers the prospect of systematically and sustainably reaching a large proportion of insufficiently active adults .


If shown to be efficacious this trial provides evidence to expand public funding beyond those with a chronic disease and for delivery via telephone as well as face-to-face consultations .


Australian New Zealand Clinical Trials Registry ACTRN12611000884909 .


Untreated advanced hepatocellular carcinoma ( HCC ) is linked to poor prognosis .


While sorafenib is the current recommended treatment for advanced HCC , radioembolisation ( RE ; also called selective internal radiation therapy or SIRT ) with yttrium-90 microspheres has shown efficacy in cohort studies .


However , there are no head-to-head trials comparing radiation therapy with yttrium-90 microspheres and sorafenib in advanced HCC .


The SARAH trial has been designed to compare the efficacy and safety of sorafenib therapy and RE using yttrium-90 resin microspheres ( SIR-Spheres ; Sirtex Medical Limited , North Sydney , Australia ) in patients with advanced HCC .


Quality of life ( QoL ) and cost-effectiveness will also be compared between therapies .


SARAH is a prospective , randomised , controlled , open-label , multicentre trial comparing the efficacy of RE with sorafenib in the treatment of patients with advanced HCC .


The trial aims to recruit adults with a life expectancy of > 3 months , Eastern Cooperative Oncology Group ( ECOG ) performance status 1 , and : advanced HCC according to the Barcelona criteria ( stage C ) or recurrent HCC after surgical or thermoablative treatment who are not eligible for surgical resection , liver transplantation or thermal ablation ; or two rounds of failed chemoembolisation .


Patients will be randomised 1:1 to receive either RE or sorafenib 400 mg twice daily .


All patients will be monitored for between 12 and 48 months following start of treatment .


The primary endpoint of the SARAH trial is overall survival ( OS ) .


Secondary endpoints include : adverse events , progression-free survival at 6 months ; tumour response rate ; general or liver disease-specific QoL scores ; and cost of each treatment strategy .


Assuming an increase in median OS of 4 months with RE versus sorafenib therapy , randomising at least 400 patients ( 200 in each treatment arm ) will be sufficient for 80 % power and a bilateral alpha risk of 5 % ; therefore , 440 patients will be enrolled to allow for 10 % loss of patients due to ineligibility .


The SARAH trial is the first randomised head-to-head study to compare RE with sorafenib in advanced HCC , and will establish the potential role of RE in HCC treatment guidelines .


ClinicalTrials.gov identifier NCT01482442 , first received 28 November 2011 .


To compare the safety and efficacy of combined therapy using sildenafil and tamsulosin for management of acute urinary retention ( AUR ) with tamsulosin alone in patients with benign prostate hyperplasia ( BPH ) .


101 patients were enrolled in a randomized placebo-controlled study from June 2009 to April 2012 .


Patients presenting with an initial episode of spontaneous AUR underwent urethral catheterization and then prospectively randomized to receive tamsulosin 0.4 mg plus sildenafil 50mg in group A and tamsulosin 0.4 mg plus placebo in group B for three days .


Urethral catheter was removed three days after medical treatment and patient 's ability to void assessed at the day after catheter removal and seven days later .


Patients who voided successfully were followed at least for three months .


Mean age of patients was 59.64 3.84 years in group A and 60.56 4.12 years in group B ( p value = 0.92 ) .


Mean prostate volume and mean residual urine were comparable between both groups ( p value = 0.74 and 0.42 , respectively ) .


Fifteen patients in group A ( success rate : 70 % ) and nineteen patients in group B ( success rate : 62.7 % ) had failed trial without catheter ( TWOC ) at 7th day following AUR ( p value = 0.3 ) .


No significant difference was noted between both groups regarding the rate of repeated AUR at one month and three month follow-up period ( p = 0.07 and p = 0.45 , respectively ) .


It seems that combination therapy by using 5-phosphodiesterase inhibitor and tamsulosin has no significant advantages to improve urinary retention versus tamsulosin alone .


Auto-Disable syringes are recommended for immunization because of their greater safety and preventing reuse .


In this study , the role of the syringe and needle gauge on the adverse events following Diphtheria , Tetanus toxoids and whole-cell Pertussis immunization was studied .


In this study , 1000 children from 2 months to 6 years of age , eligible for Diphtheria , Tetanus toxoids and whole-cell Pertussis immunization and who referred to 4 health centers , were randomized into 2 groups of regular syringe users ( the Auto-Disable syringe with a 23 gauge and 25 mm needle ) and new syringe users ( the disposable syringe with a 24 gauge and 25 mm needle ) .


Adverse events following immunization were evaluated on days 2 , 4 and 6 after immunization by visiting the children at their home and examining them .


The occurrence of the primary endpoint ( severe local reaction ) was found to be 2.1 % in all the children , 2.0 % in the children vaccinated with the Auto-Disable syringe and 2.2 % in the children vaccinated with the new syringe .


This difference is not significant ( P = 0.818 ) .


The evaluation of other milder adverse events ( secondary endpoints ) showed that the syringe type has no effect on the occurrence of these adverse events .


Syringe types and needle diameter played no role in precipitating the adverse events following immunization of the Diphtheria , Tetanus toxoids and whole-cell Pertussis vaccine .


To compare the long-term clinical and radiologic outcomes of temporomandibular joint osteoarthritis ( TMJ-OA ) treated with arthrocentesis plus platelet-rich plasma ( PRP ) versus arthrocentesis alone .


A randomized clinical trial in adult patients with TMJ-OA referred to the authors ' clinic from May 2012 through July 2013 was implemented .


The sample was composed of 30 consecutive patients with TMJ-OA treated randomly with arthrocentesis alone ( control group ) or initial arthrocentesis plus PRP injection and then 4 consecutive PRP injections ( study group ) .


The predictor variable was treatment technique .


The outcome variables were visual analog scale evaluations ( masticatory efficiency , joint sounds , and pain complaints ) , maximal interincisal opening , and cone-beam computed tomographic ( CBCT ) findings .


Outcome variables were recorded preoperatively and 12 months postoperatively .


Descriptive and bivariate statistics were computed , and significance was set at a P value less than .05 .


The paired t and Student t tests were used for intragroup and intergroup comparisons , respectively .


The sample was composed of 47 joints of 30 patients with OA ( control group : 15 joints of 12 patients ; mean age , 35.08 14.84 yr ; study group : 32 joints of 18 patients ; mean age , 32.22 14.32 yr ) .


Joint sounds and general pain complaints decreased statistically in the 2 groups , whereas masticatory efficiency , painless interincisal opening , and lateral motion increased statistically only in the study group .


However , only masticatory efficiency showed statistically greater improvement in the study group compared with the control group .


CBCT evaluations showed that reparative remodeling of the osseous abnormalities occurred at rates of 87.5 and 46.6 % in the study and control groups , respectively .


These findings suggested that arthrocentesis and PRP injections constitute a safe and promising method for the treatment of TMJ-OA that is superior to arthrocentesis alone .


Cerebral palsy is the most common cause of physical disability in childhood .


Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation .


The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered ( one on one ) physiotherapy rehabilitation .


With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework , it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes , encouraging providers to offer flexible models of physiotherapy delivery .


This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years .


An assessor-masked , block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy .


A sample size of 30 ( 15 in each study arm ) will be recruited .


Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities ( three exercises to be performed three times a week ) .


Study groups will be compared at baseline ( T1 ) , then at 10 weeks ( T2 , efficacy ) and 26 weeks ( T3 , retention ) post Botulinum Toxin-A injections .


Primary outcomes will be caregiver/s perception of and satisfaction with their child 's occupational performance goals ( Canadian Occupational Performance Measure ) and quality of gait ( Edinburgh Visual Gait Score ) with a range of secondary outcomes across domains of the International Classification of Disability , Functioning and Health .


This paper outlines the study protocol including theoretical basis , study hypotheses and outcome measures for this assessor-masked , randomised comparison trial comparing group versus individual models of physiotherapy following intramuscular injections of Botulinum Toxin-A to the lower limbs for ambulant children with cerebral palsy .


ACTRN12611000454976 .


Amino acids are well known to be key effectors of gut protein turnover .


We recently reported that enteral delivery of proteins markedly stimulated global duodenal protein synthesis in carbohydrate-fed healthy humans , but specifically affected proteins remain unknown .


We aimed to assess the influence of an enteral protein supply on the duodenal mucosal proteome in carbohydrate-fed humans .


Six healthy volunteers received for 5 h , on 2 occasions and in random order , either an enteral infusion of maltodextrins alone ( 0.25 g kg h ) mimicking the fed state or maltodextrins with a protein powder ( 0.14 g proteins kg h ) .


Endoscopic duodenal biopsy specimens were then collected and frozen until analysis .


A 2-dimensional polyacrylamide gel electrophoresis-based comparative proteomics analysis was then performed , and differentially expressed proteins ( at least 1.5-fold change ; Student 's t test , P < 0.05 ) were identified by mass spectrometry .


Protein expression changes were confirmed by Western blot analysis .


Thirty-two protein spots were differentially expressed after protein delivery compared with maltodextrins alone : 28 and 4 spots were up - or downregulated , respectively .


Among the 22 identified proteins , 11 upregulated proteins were involved either in the cytoskeleton ( ezrin , moesin , plastin 1 , lamin B1 , vimentin , and - actin ) or in protein biosynthesis ( glutamyl-prolyl-transfer RNA synthetase , glutaminyl-transfer RNA synthetase , elongation factor 2 , elongation factor 1 , and eukaryotic translation and initiation factor 3 subunit f ) .


Enteral delivery of proteins altered the duodenal mucosal proteome and mainly stimulated the expression of proteins involved in cytoskeleton and protein biosynthesis .


These results suggest that protein supply may affect intestinal morphology by stimulating actin cytoskeleton remodeling .


Physical activity ( PA ) and nutrition are the cornerstones of diabetes management .


Several reviews and meta-analyses report that PA independently produces clinically important improvements in glucose control in people with Type 2 diabetes .


However , it remains unclear what the optimal strategies are to increase PA behaviour in people with Type 2 diabetes in routine primary care .


This study will determine whether an evidence-informed multifaceted behaviour change intervention ( Movement as Medicine for Type 2 Diabetes ) targeting both consultation behaviour of primary healthcare professionals and PA behaviour in adults with Type 2 diabetes is both acceptable and feasible in the primary care setting .


An open pilot study conducted in two primary care practices ( phase one ) will assess acceptability , feasibility and fidelity .


Ongoing feedback from participating primary healthcare professionals and patients will provide opportunities for systematic adaptation and refinement of the intervention and study procedures .


A two-arm parallel group clustered pilot randomised controlled trial with patients from participating primary care practices in North East England will assess acceptability , feasibility , and fidelity of the intervention ( versus usual clinical care ) and trial processes over a 12-month period .


Consultation behaviour involving fidelity of intervention delivery , diabetes and PA related knowledge , attitudes/beliefs , intentions and self-efficacy for delivering a behaviour change intervention targeting PA behaviour will be assessed in primary healthcare professionals .


We will rehearse the collection of outcome data ( with the focus on data yield and quality ) for a future definitive trial , through outcome assessment at baseline , one , six and twelve months .


An embedded qualitative process evaluation and treatment fidelity assessment will explore issues around intervention implementation and assess whether intervention components can be reliably and faithfully delivered in routine primary care .


Movement as Medicine for Type 2 Diabetes will address an important gap in the evidence-base , that is , the need for interventions to increase free-living PA behaviour in adults with Type 2 diabetes .


The multifaceted intervention incorporates an online accredited training programme for primary healthcare professionals and represents , to the best of our knowledge , the first of its kind in the United Kingdom .


This study will establish whether the multifaceted behavioural intervention is acceptable and feasible in routine primary care .


Movement as Medicine for Type 2 Diabetes ( MaMT2D ) was registered with Current Controlled Trials on the 14th January 2012 : ISRCTN67997502 .


The first primary care practice was randomised on the 5th October 2012 .


Dengue shock syndrome ( DSS ) fluid resuscitation by following the World Health Organization ( WHO ) guideline usually required large volumes of Ringer lactate ( RL ) that might induce secondary fluid overload .


Our objective was to compare the effectiveness of the recommended volume of RL versus a smaller volume of a hypertonic sodium lactate solution ( HSL ) in children with DSS .


The primary end point was to evaluate the effect of HSL on endothelial cell inflammation , assessed by soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) measurements .


Secondarily , we considered the effectiveness of HSL in restoring hemodynamic fluid balance , acid-base status , and sodium and chloride balances , as well as in-hospital survival .


A prospective randomized single-blind clinical trial including 50 DSS children was conducted in the Pediatrics Department of Hasan Sadikin Hospital , Bandung , Indonesia .


Only pediatric patients ( 2 to 14 years old ) fulfilling the WHO criteria for DSS and new to resuscitation treatments were eligible .


Patients were resuscitated with either HSL ( 5 ml/kg/BW in 15 minutes followed by 1 ml/kg/BW / h for 12 hours ) , or RL ( 20 ml/kg/BW in 15 minutes followed by decreasing doses of 10 , 7 , 5 , and 3 ml/kg BW/h for 12 hours ) .


In total , 50 patients were randomized and included in outcome and adverse-event analysis ; 46 patients ( 8.20.5 years ; 24.91.9 kg ; meanSEM ) completed the protocol and were fully analyzed ( 24 and 22 subjects in the HSL and RL groups , respectively ) .


Baseline ( prebolus ) data were similar in both groups .


Hemodynamic recovery , plasma expansion , clinical outcome , and survival rate were not significantly different in the two groups , whereas fluid accumulation was one third lower in the HSL than in the RL group .


Moreover , HSL was responsible for a partial recovery from endothelial dysfunction , as indicated by the significant decrease in sVCAM-1 .


Similar hemodynamic shock recovery and plasma expansion were achieved in both groups despite much lower fluid intake and fluid accumulation in the HSL group .


ClinicalTrials.gov NCT00966628 .


Registered 26 August 2009 .


`` Nudges '' that influence decision making through subtle cognitive mechanisms have been shown to be highly effective in a wide range of applications , but there have been few experiments to improve clinical practice .


To investigate the use of a behavioral `` nudge '' based on the principle of public commitment in encouraging the judicious use of antibiotics for acute respiratory infections ( ARIs ) .


Randomized clinical trial in 5 outpatient primary care clinics .


A total of 954 adults had ARI visits during the study timeframe : 449 patients were treated by clinicians randomized to the posted commitment letter ( 335 in the baseline period , 114 in the intervention period ) ; 505 patients were treated by clinicians randomized to standard practice control ( 384 baseline , 121 intervention ) .


The intervention consisted of displaying poster-sized commitment letters in examination rooms for 12 weeks .


These letters , featuring clinician photographs and signatures , stated their commitment to avoid inappropriate antibiotic prescribing for ARIs .


Antibiotic prescribing rates for antibiotic-inappropriate ARI diagnoses in baseline and intervention periods , adjusted for patient age , sex , and insurance status .


Baseline rates were 43.5 % and 42.8 % for control and poster , respectively .


During the intervention period , inappropriate prescribing rates increased to 52.7 % for controls but decreased to 33.7 % in the posted commitment letter condition .


Controlling for baseline prescribing rates , we found that the posted commitment letter resulted in a 19.7 absolute percentage reduction in inappropriate antibiotic prescribing rate relative to control ( P = .02 ) .


There was no evidence of diagnostic coding shift , and rates of appropriate antibiotic prescriptions did not diminish over time .


Displaying poster-sized commitment letters in examination rooms decreased inappropriate antibiotic prescribing for ARIs .


The effect of this simple , low-cost intervention is comparable in magnitude to costlier , more intensive quality-improvement efforts .


clinicaltrials.gov identifier : NCT01767064 .


Blood loss after cardiac surgery can be caused by impaired platelet ( PLT ) function after cardiopulmonary bypass .


Desmopressin or 1-deamino-8-D-arginine vasopressin ( DDAVP ) is a synthetic analog of vasopressin .


DDAVP can increase the level of von Willebrand factor and coagulation factor VIII , thus it may enhance PLT function and improve coagulation .


In this study , we assessed the effects of DDAVP on PLT aggregation and blood loss in patients undergoing cardiac surgery .


A total of 102 patients undergoing valvular heart surgery ( from October 2010 to June 2011 ) were divided into DDAVP group ( n = 52 ) and control group ( n = 50 ) .


A dose of DDAVP ( 0.3 g/kg ) was administered to the patients intravenously when they were being re-warmed .


At the same time , an equal volume of saline was given to the patients in the control group .


PLT aggregation rate was measured with the AggRAM four-way PLT aggregation measurement instrument .


The blood loss and transfusion , hemoglobin levels , PLT counts , and urine outputs at different time were recorded and compared .


The postoperative blood loss in the first 6 h was significantly reduced in DDAVP group ( 202 119 ml vs. 258 143 ml , P = 0.023 ) .


The incidence of fresh frozen plasma ( FFP ) transfusion was decreased postoperatively in DDAVP group ( 3.8 % vs. 12 % , P = 0.015 ) .


There was no significant difference in the PLT aggregation , urine volumes , red blood cell transfusions and blood loss after 24 h between two groups .


A single dose of DDAVP can reduce the first 6 h blood loss and FFP transfusion postoperatively in patients undergoing valvular heart surgery , but has no effect on PLT aggregation .


Combined BRAF and MEK inhibition , as compared with BRAF inhibition alone , delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K mutations .


In this phase 3 trial , we randomly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation to receive a combination of dabrafenib ( 150 mg orally twice daily ) and trametinib ( 2 mg orally once daily ) or dabrafenib and placebo .


The primary end point was progression-free survival .


Secondary end points included overall survival , response rate , response duration , and safety .


A preplanned interim overall survival analysis was conducted .


The median progression-free survival was 9.3 months in the dabrafenib-trametinib group and 8.8 months in the dabrafenib-only group ( hazard ratio for progression or death in the dabrafenib-trametinib group , 0.75 ; 95 % confidence interval [ CI ] , 0.57 to 0.99 ; P = 0.03 ) .


The overall response rate was 67 % in the dabrafenib-trametinib group and 51 % in the dabrafenib-only group ( P = 0.002 ) .


At 6 months , the interim overall survival rate was 93 % with dabrafenib-trametinib and 85 % with dabrafenib alone ( hazard ratio for death , 0.63 ; 95 % CI , 0.42 to 0.94 ; P = 0.02 ) .


However , a specified efficacy-stopping boundary ( two-sided P = 0.00028 ) was not crossed .


Rates of adverse events were similar in the two groups , although more dose modifications occurred in the dabrafenib-trametinib group .


The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib-trametinib group than in the dabrafenib-only group ( 2 % vs. 9 % ) , whereas pyrexia occurred in more patients ( 51 % vs. 28 % ) and was more often severe ( grade 3 , 6 % vs. 2 % ) in the dabrafenib-trametinib group .


A combination of dabrafenib and trametinib , as compared with dabrafenib alone , improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations .


( Funded by GlaxoSmithKline ; Clinical Trials.gov number , NCT01584648 . )


To compare the efficacy and safety between tension-free vaginal tape obturator technique ( TVT-O ) and TVT-O with biofeedback pelvic floor electrical stimulation on the therapy of female stress urinary incontinence .


In this prospective study , 120 female patients of female stress urinary incontinence were enrolled from January 2012 to December 2013 .


The patients were randomly assigned to two groups , 60 in group A received TVT-O alone , while 60 in group B not only received TVT-O but also received biofeedback pelvic floor electrical stimulation .


All the patients were followed up for 12 months to assess the efficacy and safety of the two procedures .


Subjective indices [ total volume of urine ( TV ) , the total frequency of urination ( TOV ) , the total leakage of urine events ( TL ) , urinary incontinence related quality of life questionnaire ( I-QOL ) , International Advisory Committee on urinary incontinence urinary incontinence questionnaire short form scale ( ICI-Q-SF ) ] and objective indices [ Valsalva leak point pressure ( VLPP ) , maximum flow rate ( MFR ) , residual urine volume ( RUV ) , pad test ] were analyzed .


Overall , the cure rate was 75 % at 1 year follow-up for group A and 88.33 % for group B ( P < 0.05 ) .


The effective rate was 16.67 % for group A and 10 % for group B ( P < 0.05 ) .


The ineffective rate was 8.33 % for group A and 1.67 % for group B ( P < 0.05 ) .


TV , I-QOL , ICI-Q-SF , VLPP and pad test in group B were superior to group A ( P < 0.05 ) .


Pelvic floor electrical stimulation biofeedback therapy could improve the curative effects of TVT-O on the treatment of female stress urinary incontinence .


The hypothesis that covered stents are superior to bare-metal stents ( BMS ) in long femoropopliteal artery disease was tested .


The one-year results of the VIASTAR trial revealed a patency benefit of covered stents in the treatment-per-protocol ( TPP ) analysis only .


A prospective , randomized , single-blind , multicenter study evaluated 141 patients with symptomatic peripheral arterial disease ( PAD ) after treatment with heparin-bonded covered stents ( VIABAHN ( ) Endoprosthesis ) or BMS .


Clinical outcomes and patency rates were assessed at 1 , 6 , 12 , and 24 months .


Mean lesion length was 19.0 6.3 cm in the VIABAHN ( ) versus 17.3 6.6 cm in the BMS group .


The 24-month primary patency rates in the VIABAHN ( ) and BMS group were : intention-to-treat 63.1 ( 95 % CI 0.52-0 .76 ) versus 41.2 % ( 95 % CI 0.29-0 .57 ; log rank p = 0.04 ) and TPP 69.4 ( 95 % CI 0.58-0 .83 ) versus 40.0 % ( 95 % CI 0.28-0 .56 ; log rank p = 0.004 ) .


Freedom from target-lesion-revascularization ( TLR ) was 79.4 ( 95 % CI 0.70-0 .90 ) versus 73.0 % ( 95 % CI 0.63-0 .85 ) for VIABAHN ( ) versus BMS ( log rank p = 0.37 ) .


For the TPP group in lesions 20 cm , the 24-month patency rates were 65.2 ( 95 % CI 0.50-0 .85 ) versus 26.7 % ( 95 % CI 0.12-0 .59 ; log rank p = 0.004 ) for VIABAHN ( ) versus BMS , and freedom from TLR was 80.0 ( 95 % CI 0.68-0 .94 ) versus 61.9 % ( 95 % CI 0.44-0 .87 ; log rank p = 0.13 ) .


The ankle brachial index was 0.89 0.18 versus 0.91 0.17 ( p = 0.76 ) at 24-month in the VIABAHN ( ) versus the BMS group , respectively .


At 24-month , this trial in PAD patients with long femoropopliteal lesions demonstrated a significantly improved primary patency rate for heparin-bonded covered stents compared to BMS , however , without a significant impact on clinical outcomes and TLR rate ( Reg .


Nr .


ISRCTN48164244 ) .


The treat-to-target ( T2T ) approach to the care of patients with rheumatoid arthritis involves using validated metrics to measure disease activity , frequent follow-up visits for patients with moderate to high disease activity , and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores .


The study described is a newly launched cluster-randomized behavioral intervention to assess the feasibility and effectiveness of the T2T approach in US rheumatology practices .


It is designed to identify patient and provider barriers to implementing T2T management .


This initial paper focuses on the novel study design and methods created to provide these insights .


This trial cluster-randomizes rheumatology practices from the existing Corrona network of private and academic sites rather than patients within sites or individual investigators to provide either T2T or usual care ( UC ) for qualified patients who meet the 2010 revised American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis and have moderate to high disease activity .


Specific medication choices are left to the investigator and patient , rather than being specified in the protocol .


Enrollment is expected to be completed by the end of 2013 , with 30 practices randomized and enrolling a minimum of 530 patients .


During the 12-month follow-up , visits are mandated as frequently as monthly in patients with active disease in the T2T group and every 3 months for the UC group .


Safety data are collected at each visit .


The coprimary endpoints include a comparison of the proportion of patients achieving low disease activity in the T2T and UC groups and assessment of the feasibility of implementing T2T in rheumatology practices , specifically assessment of the rates of treatment acceleration , frequency of visits , time to next visit conditional on disease activity , and probability of acceleration conditional on disease activity in the 2 groups .


This cluster-randomized behavioral intervention study will provide valuable insights on the outcomes and feasibility of employing a T2T treatment approach in clinical practice in the United States .


NCT01407419 .


We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage ( ICH ) to better inform clinicians and researchers in their efforts to improve outcomes for patients .


We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials ( INTERACT1 and 2 , respectively ) .


The study group was divided into a derivation cohort ( INTERACT2 , n = 964 ) and a validation cohort ( INTERACT1 , n = 346 ) .


Multivariable logistic regression was used to identify factors associated with clinically significant ( 6 mL ) increase in hematoma volume at 24 hours after symptom onset .


A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model .


A 24-point BRAIN score was derived from INTERACT2 ( C-statistic , 0.73 ) based on baseline ICH volume ( mL per score , 10 = 0 , 10-20 = 5 , > 20 = 7 ) , recurrent ICH ( yes = 4 ) , anticoagulation with warfarin at symptom onset ( yes = 6 ) , intraventricular extension ( yes = 2 ) , and number of hours to baseline computed tomography from symptom onset ( 1 = 5 , 1-2 = 4 , 2-3 = 3 , 3-4 = 2 , 4-5 = 1 , > 5 = 0 ) predicted the probability of ICH growth ( ranging from 3.4 % for 0 point to 85.8 % for 24 points ) with good discrimination ( C-statistic , 0.73 ) and calibration ( Hosmer-Lemeshow P = 0.82 ) in INTERACT1 .


The simple BRAIN score predicts the probability of hematoma growth in ICH .


This could be used to improve risk stratification for research and clinical practice .


http://www.clinicaltrials.gov .


Unique identifier : NCT00226096 and NCT00716079 .


The aim of this trial was to compare functional capacity , pulmonary shunt fraction and clinical outcomes between patients undergoing pleurotomy with a pleural drain inserted in the sub-xyphoid position and patients with a pleural drain placed in the intercostal position after off-pump coronary artery bypass surgery .


Patients were randomized into two groups according to the pleural drain site : Group II ( n = 33 intercostal pleural drain ) ; and Group SI ( n = 35 sub-xyphoid pleural drain ) .


Functional capacity was assessed by the distance covered on the 6-min walking test performed preoperatively and on postoperative day ( POD ) 5 ; in addition , pulmonary function test was determined preoperatively and on POD 1 and 5 .


Pulmonary shunt fraction was evaluated preoperatively and on POD 1 , and clinical outcomes were recorded throughout the study .


Group SI had better preservation of lung volumes and capacities in POD compared with Group II ( P < 0.05 ) .


Pulmonary shunt fraction increased in both groups postoperatively ; however , Group SI showed a smaller pulmonary shunt fraction ( 0.26 0.04 vs 0.21 0.04 % ; P = 0.0014 ) .