A total of 1493 patients were randomized ( 3:3:3:2 ) to 24 weeks of treatment with UMEC/VI 125/25 mcg , UMEC 125 mcg , VI 25 mcg , or placebo once-daily via dry powder inhaler .


Primary efficacy endpoint was trough forced expiratory volume in one second ( FEV1 ) on Day 169 ( 23-24 h post-dose ) .


Additional lung-function , symptomatic and health-related quality of life endpoints were also assessed .


Safety evaluations included : adverse events , vital signs , electrocardiography and clinical laboratory measurements .


All active treatments significantly improved trough FEV1 vs placebo ( 0.124-0 .238 L , all p < 0.001 ) .


Improvements with UMEC/VI 125/25 mcg were significantly greater than for UMEC 125 mcg or VI 25 mcg ( 0.079 L and 0.114 L ; both p0 .001 ) .


Improvements for UMEC/VI 125/25 mcg vs placebo were observed for the transition dyspnea index ( 1.0 unit ; p < 0.001 ) , rescue albuterol use at Weeks 1-24 ( -1.5 puffs/day ) and St. George 's Respiratory Questionnaire ( -3.60 units , p < 0.001 ) .


No safety signals were observed .


Once-daily UMEC/VI 125/25 mcg was well tolerated and provided greater improvements in lung function , health status , and dyspnea scores compared with monotherapy components and placebo over 24 weeks .


This study supports the use of UMEC/VI 125/25 mcg for the maintenance treatment of COPD .


protocol number : DB2113361 ; ClinicalTrials.gov identifier : NCT01313637 .


The set-back suture , an absorbable dermal suturing technique , purportedly improves wound eversion and cosmetic outcomes .


We sought to conduct a split-wound , prospective , randomized study to compare the cosmetic outcome and wound eversion achieved with the set-back suture and the buried vertical mattress suture ( BVMS ) .


A total of 46 surgical elliptical wounds were randomized to subcuticular closure with the set-back suture on half and the BVMS on the other .


Maximum eversion height and width were measured immediately postoperatively .


At 3 months , 2 blinded observers evaluated each scar using a 7-point Likert physician global scar assessment scale .


Subjects and observers also completed the validated Patient and Observer Scar Assessment Scale , where a score of 6 represents normal-appearing skin and 60 represents worst imaginable scar .


In all , 42 subjects completed the study .


The set-back suture provided statistically significant wound eversion .


On the Likert scale , observers rated the set-back suture side 1 point better than the BVMSside .


Both patient and observer total Patient and Observer Scar Assessment Scale scores were significantly lower for the set-back suture side ( subject mean 13.0 8.7 vs 16.2 12.0 [ P = .039 ] ; observer mean 24.5 10.4 vs 27.7 13.6 [ P = .028 ] , respectively ) .


Single institution experience and relatively short follow-up are limitations .


The set-back suture provides superior wound eversion and better cosmetic outcomes than the BVMS .


Macitentan is a novel dual endothelin ( ET ) -1 receptor antagonist to be used in patients with pulmonary arterial hypertension .


This study aimed to assess the pharmacokinetics ( PK ) and pharmacodynamics ( PD ) of macitentan after administration of multiple doses to healthy Korean male subjects .


A randomized , double-blind , placebo-controlled , multiple-ascending dose study was performed in 30 healthy male subjects receiving oral macitentan ( 3 , 10 , or 30 mg ) or placebo once daily for 10 days .


Plasma concentrations of macitentan , its active metabolite ACT-13277 , and ET-1 were evaluated .


Safety and tolerability measurements were conducted throughout the study .


The concentration-time profile of macitentan was characterized by slow absorption ( median time to maximum plasma concentration [ t ( max ) ] 9-10 h ) and slow elimination ( mean elimination half-life [ t ] 11-15 h ) .


After repeated doses of 3 , 10 , and 30 mg of macitentan over the course of 10 days , the peak concentration ( C ( max ) ) increased as the dose increased and the area under the plasma concentration-time curve during the dosing interval ( AUC ( ) ) increased in a dose-proportional manner .


Plasma concentrations showed approximately 1.5 - to 1.9-fold accumulation on day 10 compared with day 1 .


ACT-132577 showed higher levels of exposure than macitentan , its mean half-life was 46-48 h , and it accumulated 7 - to 12-fold .


Macitentan increased plasma ET-1 concentrations at all doses tested and was well tolerated and elicited no serious adverse events .


Multiple oral doses of 3 , 10 , and 30 mg of macitentan were well tolerated in healthy Korean subjects , and its pharmacokinetics correlated positively with ET-1 concentrations .


This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E ( gE ) with or without the adjuvant system AS01B .


In this phase II , single-blind , randomized , controlled study , adults aged 60years ( N = 714 ) received one dose of 100ggE/AS01B , two doses , two months apart , of 25 , 50 , or 100ggE/AS01B , or two doses of unadjuvanted 100ggE/saline .


Frequencies of CD4 ( + ) T cells expressing 2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA .


Frequencies of gE-specific CD4 ( + ) T cells were > 3-fold higher after two doses of all gE/AS01B formulations than after one dose of 100ggE/AS01B or two doses of 100ggE/saline .


Frequencies were comparable after two doses of 25 , 50 , or 100ggE/AS01B .


Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100ggE/AS01B and higher than in the other groups .


Immune responses persisted for at least 36 months .


Reactogenicities of all gE/AS01B formulations were similar but greater than with gE/saline .


The three formulations of gE/AS01B were immunogenic and well tolerated in adults aged 60years .


Two vaccinations with gE/AS01B induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses ( NCT00434577 ) .


In Denmark , guidelines on low back pain management are currently being implemented ; in association with this , a clinical trial is conducted .


A health economic evaluation is carried out alongside the clinical trial to assess the cost-effectiveness of an extended implementation strategy to increase the general practitioners ' adherence to the guidelines .


In addition to usual dissemination , the extended implementation strategy is composed of visits from a guideline facilitator , stratification tools , and feedback on guideline adherence .


The aim of this paper is to provide the considerations on the design of the health economic evaluation .


The economic evaluation is carried out alongside a cluster randomised controlled trial consisting of 60 general practices in the North Denmark Region .


An expected 1,200 patients between the age of 18 and 65 years with a low back pain diagnosis will be enrolled .


The economic evaluation comprises both a cost-effectiveness analyses and a cost-utility analysis .


Effectiveness measures include referral to secondary care , health-related quality of life measured by EQ-5D-5L , and disability measured by the Roland Morris disability questionnaire .


Cost measures include all relevant additional costs of the extended implementation strategy compared to usual implementation .


The economic evaluation will be performed from both a societal perspective and a health sector perspective with a 12-month time horizon .


It is expected that the extended implementation strategy will reduce the number of patients referred to secondary care .


It is hypothesised that the additional upfront cost of extended implementation will be counterbalanced by improvements in clinical practice and patient-related outcomes , thereby rendering the extended implementation strategy cost-effective .


ClinicalTrials.gov : NCT01699256 .


Many pathogenic processes and diseases are the result of an erroneous activation of the complement cascade and a number of inhibitors of complement have thus been examined for anti-inflammatory actions .


It was recently demonstrated that supraphysiological concentrations of the endogenous complement inhibitor MAp44 ( also denoted MAP1 ) protect against myocardial reperfusion injury .


In the present study , we examined the association between outcome after acute myocardial infarction ( MI ) and the plasma levels of MAp44 and its related proteins MASP-1 and MASP-3 in patients with first-time MI .


In addition , we compared plasma levels of MAp44 , MASP-1 , and MASP-3 in MI patients to levels in a healthy control group .


A total of 192 MI patients and 140 control persons were included .


Plasma samples were obtained and analysed with time-resolved immunofluorometric assays determining the plasma levels of MAp44 , MASP-1 , and MASP-3 .


The myocardial outcomes ( salvage index and final infarct size ) were measured by gated single-photon emission CT. .


MI patients had 18 % higher plasma levels of MAp44 ( IQR 11-25 % ) as compared to the healthy control group ( p < 0.001 .


However , neither salvage index ( Spearman rho -0.1 , p = 0.28 ) nor final infarct size ( Spearman rho 0.02 , p = 0.83 ) correlated with plasma levels of MAp44 .


Likewise , MASP-1 and MASP-3 were elevated in MI patients ( p = 0.002 and p < 0.001 ) , but the levels were not correlated to outcome .


Plasma levels of MAp44 , MASP-1 , and MASP-3 are significantly higher in patients with MI compared to healthy control persons , but are not associated with short-term outcome measured as salvage index and final infarct .


The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined .


We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy .


In this open-label , multicentre , phase 3 randomised controlled trial , patients were recruited from ten university hospitals throughout Spain .


Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria .


Patients were randomly assigned ( 1:1 ) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy ( range 76-82 Gy ; short-term androgen deprivation group ) or the same treatment followed by 24 months of adjuvant androgen deprivation ( long-term androgen deprivation group ) , stratified by prostate cancer risk group ( intermediate risk vs high risk ) and participating centre .


Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin ( 2 months before and 2 months combined with high-dose radiotherapy ) .


Anti-androgen therapy ( flutamide 750 mg per day or bicalutamide 50 mg per day ) was added during the first 2 months of treatment .


Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months .


The primary endpoint was biochemical disease-free survival .


Analysis was by intention to treat .


This study is registered with ClinicalTrials.gov , number NCT02175212 .


Between Nov 7 , 2005 , and Dec 20 , 2010 , 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation .


After a median follow-up of 63 months ( IQR 50-82 ) , 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment ( 90 % [ 95 % CI 87-92 ] vs 81 % [ 78-85 ] ; hazard ratio [ HR ] 188 [ 95 % CI 112-315 ] ; p = 001 ) .


5-year overall survival ( 95 % [ 95 % CI 93-97 ] vs 86 % [ 83-89 ] ; HR 248 [ 95 % CI 131-468 ] ; p = 0009 ) and 5-year metastasis-free survival ( 94 % [ 95 % CI 92-96 ] vs 83 % [ 80-86 ] ; HR 231 [ 95 % CI 123-385 ] ; p = 001 ) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group .


The effect of long-term androgen deprivation on biochemical disease-free survival , metastasis-free survival , and overall survival was more evident in patients with high-risk disease than in those with low-risk disease .


Grade 3 late rectal toxicity was noted in three ( 2 % ) of 177 patients in the long-term androgen deprivation group and two ( 1 % ) of 178 in the short-term androgen deprivation group ; grade 3-4 late urinary toxicity was noted in five ( 3 % ) patients in each group .


No deaths related to treatment were reported .


Compared with short-term androgen deprivation , 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer , particularly those with high-risk disease , with no increase in late radiation toxicity .


Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation .


Spanish National Health Investigation Fund , AstraZeneca .


The main objective of this pilot study was to explore the effect of chiropractic high-velocity , low-amplitude ( HVLA ) manipulation on vertical jump height in young female athletes with talocrural joint dysfunction .


This was a randomized assessor-blind clinical pilot trial .


Twenty-two female handball players with talocrural joint dysfunction were randomized to receive either HVLA manipulation ( n = 11 ) or sham treatment ( n = 11 ) once a week during a 3-week period .


The main outcome was change in vertical jump height from baseline to follow-up within and between groups after 3 weeks .


Nineteen athletes completed the study .


After 3 weeks , the group receiving HVLA manipulation ( n = 11 ) had a statistically significant mean ( SD ) improvement in vertical jump height of 1.07 ( 1.23 ) cm ( P = .017 ) .


The sham treatment group ( n = 8 ) improved their vertical jump height by 0.59 ( 2.03 ) cm ( P = .436 ) .


The between groups ' change was 0.47 cm ( 95 % confidence interval , -1.31 to 2.26 ; P = .571 ) in favor of the group receiving HVLA manipulation .


Blinding and sham procedures were feasible , and there were no reported adverse events .


The results of this pilot study show that a larger-scale study is feasible .


Preliminary results suggest that chiropractic HVLA manipulation may increase vertical jump height in young female athletes with talocrural joint dysfunction .


However , the clinical result in favor of HVLA manipulation compared with sham treatment needs statistical confirmation in a larger randomized clinical trial .


To investigate whether a novel ultrasound device may be used with a simplified augmented reality technique , and to compare this device with conventional techniques during vascular access using a vascular phantom .


Prospective , randomized study .


Anesthesiology and Pain Medicine departments of a university-affiliated hospital .


20 physicians with no experience with ultrasound-guided techniques .


All participants performed the vascular access technique on the vascular phantom model using both a conventional device and the new ultrasound device .


Time and the number of redirections of the needle until aspiration of dye into a vessel of the vascular phantom were measured .


The median/interquartile range of time was 39.5 / 41.7 seconds versus 18.6 / 10.0 seconds ( P < 0.001 ) and number of redirections was 3/3 .5 versus 1/0 ( P < 0.001 ) for the conventional and novel ultrasound devices , respectively .


During vascular access in a vascular phantom model , the novel device decreased the time and the number of redirections significantly .


The device successfully improved the efficiency of the ultrasound-guided vascular access technique .


The mechanisms behind heterologous immunity and non-specific effects of vaccines on mortality are not well understood .


We examined associations between cytokine responses and subsequent mortality in low-birth-weight infants in Guinea-Bissau .


A low-birth-weight trial randomized children to Bacille Calmette-Gurin ( BCG ) at birth or later according to local policy .


Blood samples were obtained from a sub-group at age 6 weeks .


Interleukin ( IL ) -5 , IL-10 , IL-13 , interferon ( IFN ) - , and tumor necrosis factor ( TNF ) - were measured in whole-blood cell cultures stimulated with lipopolysaccharide ( LPS ) , phytohaemagglutinin ( PHA ) , or purified protein derivative ( PPD ) .


The outcome was mortality between bleeding and 1 year of age .


Non-linear associations between cytokine responses and mortality were examined .


Cytokine measurements were available from 390 children .


The mortality rate ( MR ) was high ( 6.8 / 100 person-years-observation ( PYO ) ) .


Both low and high cytokine responses to LPS and PHA were associated with high mortality ( MR up to 25/100 PYO in the lowest 10 % and 9.2 / 100 PYO in the highest 10 % ) .


In BCG-vaccinated children , higher IFN - responses to PPD were associated with better survival ( MR ratio = 0.43 ( 0.24-0 .77 ) ) .


Data presented a rare opportunity to explore associations between cytokine responses and mortality .


Both low and high cytokine responses were associated with high mortality ; a balanced response to invading pathogens seems preferable .


Hospitalization is an important outcome in pulmonary arterial hypertension ( PAH ) , shown previously to correlate with survival .


Using the Registry to Evaluate Early and Long-term PAH Disease Management ( REVEAL Registry ) , we sought to characterize first-time hospitalizations and their effect on subsequent hospitalization and survival in patients with newly diagnosed disease .


Patients with newly diagnosed PAH ( n = 862 , World Health Organization group 1 ) were evaluated for first-time hospitalization .


The hospitalizations were categorized as PAH related or PAH unrelated based on the case report form .


Categories for PAH-related and PAH-unrelated hospitalization were defined before independent review .


Patient demographics and disease characteristics are described as well as freedom from hospitalization and survival .


Of 862 patients , 490 ( 56.8 % ) had one or more hospitalizations postenrollment : 257 ( 52.4 % ) PAH related , 214 ( 43.7 % ) PAH unrelated , and 19 ( 3.9 % ) of undetermined causes .


The most common causes of PAH-related hospitalization were congestive heart failure and placement/removal of a central venous catheter .


Patients with PAH-related hospitalizations were more likely to receive parenteral therapy , be in functional class III/IV , and have higher risk scores before hospitalization at enrollment .


Following discharge , 25.4 % 3.2 % and 31.0 % 4.0 % of patients with PAH-related and PAH-unrelated first hospitalization , respectively , remained hospitalization-free for 3 years ( P = .11 ) .


Survival estimates at 3 years postdischarge were 56.8 % 3.5 % and 67.8 % 3.6 % ( P = .037 ) for patients with PAH-related and PAH-unrelated hospitalization , respectively .


In the REVEAL Registry , PAH-related hospitalization was associated with relatively more rehospitalizations and worse survival at 3 years .


ClinicalTrials.gov ; No. : NCT00370214 ; URL : www.clinicaltrials.gov .


Patients treated with oral anticoagulants have increased susceptibility to bleeding , and therefore any surgical medical procedure and especially oral surgery requires a therapeutic approach that minimizes bleeding effects in these patients .


The working hypothesis was based on studies of local application of tranexamic acid after maxillofacial interventions as effective therapeutic alternative for the prevention and control of bleeding .


The aim was to assess the effectiveness of the application of a gel solution tranexamic acid after tooth extraction in anticoagulated patients in terms of healing time and degree of healing .


The results indicate that application of tranexamic acid gel is very effective for consistency and maintenance in the place of action and shows its efficacy as a procoagulant material .


The application of a gel solution of tranexamic acid in oral anticoagulants patients ameliorates healing time and the bleeding time within the first 48-72 h.


The impact of food on relapse in ulcerative colitis has not been clearly defined .


The aim of this prospective , randomized-controlled study was to evaluate the impact of comprehensive dietary guidelines on the clinical course of the disease and quality of life in patients with ulcerative colitis .


Patients were allocated randomly to an intervention or a control group .


Participants in the intervention group were provided dietary guidelines in the form of an educational booklet that was recommended for use for 4-6 weeks during disease flare , that patients eat little and often ( four to six times a day ) , drink adequate fluids , decrease excess intake of fat , decrease simple carbohydrates and decrease high-fibre foods during flare.Validated and study-designed questionnaires were used to compare patients ' perceived quality of life , colitis activity scores and eating habits before and following the dietary advice provided .


Overall , 112 patients completed the study .


Study participants were asked to complete the Inflammatory Bowel Disease Questionnaire and Simple Clinical Colitis Activity Index together with the Food Frequency Questionnaire at 0 , 6 and 24 weeks .


At 24 weeks , there was a mean reduction in the Simple Clinical Colitis Activity Index score in the intervention group compared with an increase in the score in the control group [ -1.304 ( P = 0.0108 ) vs. 0.875 ( P = 0.0249 ) ] .


There was a mean increase in the Inflammatory Bowel Disease Questionnaire score in the intervention group compared with a reduction in the score in the control group [ 7.17 ( P = 0.126 ) vs. -3.44 ( P = 0.205 ) ] .


A total of 69 % of patients in the intervention group found the dietary advice significantly or moderately helpful .


The study suggests that there is likely to be a link between the dietary advice provided and symptomatic improvement .


The effect of diet may not occur through the addition or the elimination of single nutrients ; rather , each food consumed combines many nutrients that allow for a synergistic or an antagonistic action when present in a certain composition .


Intravitreal injection ( IVT ) is one of the most common vitreoretinal procedures , a large majority are performed with local anesthesia .


The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel .


A prospective clinical trial was conducted testing lidocaine gel in five preparations : 2 , 3.5 , 5 , 8 and 12 % .


Patients with macular degeneration , diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure .


Patients answered the visual analog scale for pain during the procedure .


Corneal and conjunctival was evaluated using the Oxford scale .


In total , 260 patients were randomized into five groups .


The mean pain scores ( standard deviation ) were 2.63 ( 1.68 ) in the 2 % group , 2.08 ( 1.35 ) in the 3.5 % ; 2.00 ( 1.65 ) in the 5 % , 1.93 ( 1.40 ) in the 8 % and 1.83 ( 1.35 ) in the 12 % group .


Mean pain score among all groups was similar ( p = 0.077 ) .


There was no significant difference between groups in regard to keratitis mean score ( p = 0.897 ) .


Lidocaine gel at concentrations from 2 to 12 % induced similar anesthetic effect for IVTs , without adverse effects on cornea and conjunctiva .


To evaluate the efficacy and safety of intravitreal bevacizumab ( Avastin ; Genentech , South San Francisco , CA ) in patients with neovascular age-related macular degeneration ( nAMD ) using 2 different treatment regimens in which patients were assessed clinically at up to 12-week intervals .


Randomized , controlled , noninferiority trial .


A total of 331 patients with nAMD .


Patients were treated with 1.25 mg intravitreal bevacizumab and followed up to 92 weeks .


They were randomized into 2 arms .


All patients received 3 loading doses 4 weeks apart and thereafter were assessed every 12 weeks until the end of the study .


One arm received a routine treatment at each 12-week assessment , and the other arm was treated at these assessments on an as-needed basis .


After the loading doses , patients in either arm who showed signs of disease activity had an additional assessment after 6 weeks and at that visit had top-up treatments on an as-needed basis .


Mean best-corrected visual acuity ( BCVA ) at 92 weeks .


At 92 weeks , patients who had treatments every 12 weeks had superior BCVA to those treated on an as-needed basis every 12 weeks ( P = 0.008 ) , with the regular treatment arm gaining a mean BCVA of 5.5 letters and the as-needed treatment arm gaining 0.6 letters .


The regular treatment arm of the study showed significantly improved outcomes with respect to 5 - , 10 - , and 15-letter changes in BCVA from baseline compared with the as-needed treatment arm , as well as superior reading speed .


In patients who completed the study , up to but not including week 92 , the mean number of treatments was 10.8 for the regular treatment arm and 9.1 for the as-needed treatment arm .


A treatment regimen with regular bevacizumab injections every 12 weeks after loading doses supplemented with as-needed top-up treatments produced a stable improvement in BCVA from baseline .


The improvement in BCVA was broadly similar to that obtained in other studies using anti-vascular endothelial growth factor drugs with more frequent assessments and treatments .


To report our prospective comparison of clinical efficacy between multimodular flexible ureteroscope , PolyScope , and conventional flexible ureteroscope , both combined with holmium laser lithotripsy in managing renal stones < 3cm in diameter .


Between February 2011 and July 2014 , a total of 360 adult patients with renal stones were randomized in a single tertiary-care center trial .


For 180 patients in each arm , flexible ureteroscopy and holmium laser lithotripsy were done with either PolyScope or Olympus URF P-5 as control .


The primary end points were single-session stone fragmentation rate and stone-free rate .


The secondary end points comprised operation time , complication rate , and hospital stay .


Demographic and preoperative parameters were comparable between 2 groups .


For stones of different locations and sizes , single-session stone fragmentation rate of PolyScope was similar to that of URF P-5 .


However , for lower calyceal stones , URF P-5 was significantly better than PolyScope ( 82.0 % vs 69.2 % ; P = .022 ) .


No statistically significant difference existed in single-session or overall stone-free rate , complication rate , and hospital stay .


Mean operation time of PolyScope group was 92.620.2 minutes , 9minutes ( 10.8 % ) longer than that of URF P-5 group 83.317.1 minutes ( P < .01 ) .


PolyScope demonstrates similar overall stone clearance rate to a conventional flexible ureteroscope in managing renal calculi < 3cm in diameter , but for lower pole stones , it is of inferior efficacy and it is more skillfully demanding , taking longer operation time .


The purposes of this study were to use functional magnetic resonance imaging to investigate the immediate changes in functional connectivity ( FC ) between brain regions that process and modulate the pain experience after 3 different types of manual therapies ( MT ) and to identify reductions in experimentally induced myalgia and changes in local and remote pressure pain sensitivity .


Twenty-four participants ( 17 men ; mean age SD , 21.6 4.2 years ) who completed an exercise-injury protocol to induce low back pain were randomized into 3 groups : chiropractic spinal manipulation ( n = 6 ) , spinal mobilization ( n = 8 ) , or therapeutic touch ( n = 10 ) .


The primary outcome was the immediate change in FC as measured on functional magnetic resonance imaging between the following brain regions : somatosensory cortex , secondary somatosensory cortex , thalamus , anterior and posterior cingulate cortices , anterior and poster insula , and periaqueductal gray .


Secondary outcomes were immediate changes in pain intensity , measured with a 101-point numeric rating scale , and pain sensitivity , measured with a handheld dynamometer .


Repeated-measures analysis of variance models and correlation analyses were conducted to examine treatment effects and the relationship between within-person changes across outcome measures .


Changes in FC were found between several brain regions that were common to all 3 MT interventions .


Treatment-dependent changes in FC were also observed between several brain regions .


Improvement was seen in pain intensity after all interventions ( P < .05 ) with no difference between groups ( P > .05 ) .


There were no observed changes in pain sensitivity , or an association between primary and secondary outcome measures .


These results suggest that MTs ( chiropractic spinal manipulation , spinal mobilization , and therapeutic touch ) have an immediate effect on the FC between brain regions involved in processing and modulating the pain experience .


This suggests that neurophysiologic changes after MT may be an underlying mechanism of pain relief .


This study tested the hypothesis that pioglitazone reduces endothelin-1 activity in the forearm vasculature in non-diabetic patients with hypertension or hypercholesterolemia and variable degrees of insulin resistance .


We conducted a single center , randomized , double-blind , placebo controlled , cross-over trial in 80 patients with either hypertension or hypercholesterolemia and further classified as insulin-sensitive or insulin-resistant based on a published insulin sensitivity index .


Participants received pioglitazone 45 mg daily or matching placebo for eight weeks .


The main endpoint was the change in forearm vascular endothelin-1 activity , as assessed by intra-arterial infusion of the endothelin type A receptor blocker BQ-123 , measured at the end of each 8-week treatment period .


Pioglitazone lowered plasma insulin ( P < 0.001 ) , improved insulin sensitivity ( P < 0.001 ) , increased HDL ( P < 0.001 ) , and reduced triglycerides ( P = 0.003 ) , free fatty acids ( P = 0.005 ) , and C-reactive protein ( P = 0.001 ) .


However , pioglitazone did not affect the vasodilator response to BQ-123 in the whole group ( P = 0.618 ) and in the diagnosis or insulin sensitivity subgroups .


Hence , in non-diabetic patients with hypertension or hypercholesterolemia , PPAR activation with pioglitazone does not affect endothelin-1 activity , despite enhancing insulin sensitivity and reducing plasma insulin and C-reactive protein levels .


In non-diabetic patients with hypertension or hypercholesterolemia , pioglitazone improves insulin sensitivity , lipid profile , and inflammation but does not affect endothelin activity .


Our data suggest that the determinants of endothelin-1 vascular activity in vivo may differ and/or be more complex than those suggested by the results of previous in vitro studies .


There is a need for interventions to promote uptake of breast screening throughout Europe .


We performed a single-blind randomised controlled trial to test whether text-message reminders were effective .


Two thousand two hundred and forty women receiving their first breast screening invitation were included in the study and randomly assigned in a 1:1 ratio to receive either a normal invitation only ( n = 1118 ) or a normal invitation plus a text-message reminder 48h before their appointment ( n = 1122 ) .


In the intention-to-treat analysis , uptake of breast screening was 59.1 % among women in the normal invitation group and 64.4 % in the text-message reminder group ( ( 2 ) = 6.47 , odds ratio ( OR ) : 1.26 , 95 % confidence intervals ( CI ) : 1.05-1 .48 , P = 0.01 ) .


Of the 1122 women assigned to the text-message reminder group , only 456 ( 41 % ) had a mobile number recorded by their GP and were thereby sent a text .


In the per-protocol analysis , uptake by those in the control group who had a mobile number recorded on the GP system was 59.77 % and by those in the intervention group who were sent a reminder 71.7 % ( ( 2 ) = 14.12 , OR = 1.71 , 95 % CI = 1.29-2 .26 , P < 0.01 ) .


Sending women a text-message reminder before their first routine breast screening appointment significantly increased attendance .


This information can be used to allocate resources efficiently to improve uptake without exacerbating social inequalities .


Although exercise has been addressed as an adjuvant treatment for anxiety , depression and cancer-related symptoms , limited studies have evaluated the effectiveness of exercise in patients with lung cancer .


We recruited 116 patients from a medical centre in northern Taiwan , and randomly assigned them to either a walking-exercise group ( n = 58 ) or a usual-care group ( n = 58 ) .


We conducted a 12-week exercise programme that comprised home-based , moderate-intensity walking for 40min per day , 3 days per week , and weekly exercise counselling .


The outcome measures included the Hospital Anxiety and Depression Scale and the Taiwanese version of the MD Anderson Symptom Inventory .


We analysed the effects of the exercise programme on anxiety , depression and cancer-related symptoms by using a generalised estimating equation method .


The exercise group patients exhibited significant improvements in their anxiety levels over time ( P = 0.009 and 0.006 in the third and sixth months , respectively ) and depression ( P = 0.00006 and 0.004 in the third and sixth months , respectively ) than did the usual-care group patients .


The home-based walking exercise programme is a feasible and effective intervention method for managing anxiety and depression in lung cancer survivors and can be considered as an essential component of lung cancer rehabilitation .


To determine whether re-feeding of gastric residual volumes reduces the time needed to achieve full enteral feeding in preterm infants .


Parallel-group randomised controlled trial with a 1:1 allocation ratio .


Regional referral neonatal intensive care unit .


72 infants of gestational age 23 ( 0/7 ) to 28 ( 6/7 ) weeks receiving minimal enteral nutrition ( < 24 mL/kg/day ) during the first week after birth .


Infants were randomised to either be re-fed with gastric residual volumes ( Re-feeding group ) or receive fresh formula/human milk ( Fresh-feeding group ) whenever large gastric residual volumes were noted .


The primary efficacy end point was time to achieve full enteral feeding ( 120 mL/kg/day ) after randomisation .


The mean time to full enteral feeding was 10.0 days in the Re-feeding group and 11.3 days in the Fresh-feeding group ( mean difference favouring re-feeding : -1.3 days ; 95 % CI -2.9 to 0.3 ; p = 0.11 ) .


The composite safety end point of spontaneous intestinal perforation , surgical necrotising enterocolitis , or death occurred in 6 of 36 infants ( 17 % ) in the Re-feeding group versus 10 of 36 infants ( 28 % ) in the Fresh-feeding group ( p = 0.26 ) .


Re-feeding gastric residual volumes in extremely preterm infants does not reduce time to achieve full enteral feeding .


This trial suggests that re-feeding might be as safe as fresh feeding , but further research is needed , due to lack of sufficient statistical power in this study for safety analysis .


NCT01420263NCT01420263 .


Examination of arthroscopic skill requires evaluation tools that are valid and reliable with clear criteria for passing .


The Arthroscopic Surgery Skill Evaluation Tool was developed as a video-based assessment of technical skill with criteria for passing established by a panel of experts .


The purpose of this study was to test the validity and reliability of the Arthroscopic Surgery Skill Evaluation Tool as a pass-fail examination of arthroscopic skill .


Twenty-eight residents and two sports medicine faculty members were recorded performing diagnostic knee arthroscopy on a left and right cadaveric specimen in our arthroscopic skills laboratory .


Procedure videos were evaluated with use of the Arthroscopic Surgery Skill Evaluation Tool by two raters blind to subject identity .


Subjects were considered to pass the Arthroscopic Surgery Skill Evaluation Tool when they attained scores of 3 on all eight assessment domains .


The raters agreed on a pass-fail rating for fifty-five of sixty videos rated with an interclass correlation coefficient value of 0.83 .


Ten of thirty participants were assigned passing scores by both raters for both diagnostic arthroscopies performed in the laboratory .


Receiver operating characteristic analysis demonstrated that logging more than eighty arthroscopic cases or performing more than thirty-five arthroscopic knee cases was predictive of attaining a passing Arthroscopic Surgery Skill Evaluation Tool score on both procedures performed in the laboratory .


The Arthroscopic Surgery Skill Evaluation Tool is valid and reliable as a pass-fail examination of diagnostic arthroscopy of the knee in the simulation laboratory .


This study demonstrates that the Arthroscopic Surgery Skill Evaluation Tool may be a useful tool for pass-fail examination of diagnostic arthroscopy of the knee in the simulation laboratory .


Further study is necessary to determine whether the Arthroscopic Surgery Skill Evaluation Tool can be used for the assessment of multiple arthroscopic procedures and whether it can be used to evaluate arthroscopic procedures performed in the operating room .


To determine effect of change in urine excretion of isoflavonoids on cognitive change .


Post hoc analysis of isoflavonoid exposure ( mean 2.7 years ) during the randomized , placebo-controlled , double-blind Women 's Isoflavone Soy Health trial .


General community .


Healthy postmenopausal women ( N = 350 ) .


Twenty-five grams of isoflavone-rich soy protein ( 91 mg of aglycone weight isoflavones : 52 mg genistein , 36 mg daidzein , 3 mg glycitein ) or milk protein-matched placebo provided daily .


Overnight urine excretion , fasting plasma levels of isoflavonoids , and cognitive function measured at baseline and endpoint .


Three hundred women ( age : mean 61 , range 45-92 ) completed both cognitive assessments and did not use hormone replacement therapy during the trial .


Mean on-trial change from baseline in urine excretion of isoflavonoids was not significantly associated with change in a composite score of global cognition ( P = .39 ) .


Secondary analyses indicated that change in urine excretion of isoflavonoids was inversely associated with change in a factor score representing general intelligence ( P = .02 ) but not with factor scores representing verbal or visual episodic memory .


Mean differences in this general intelligence factor score between women in the lowest and highest quartiles of isoflavonoid change were equivalent to an approximate 4.4-year age-associated decline .


Analyses based on plasma isoflavonoid levels yielded similar but attenuated results .


In healthy postmenopausal women , long-term changes in isoflavonoids are not associated with global cognition , supporting clinical trial results , although greater isoflavonoid exposure from dietary supplements is associated with decrements in general intelligence but not memory ; this finding requires confirmation in future studies .


To investigate the therapeutic value of Gastrografin in shortening duration of prolonged postoperative ileus ( PPOI ) after elective colorectal surgery .


Gut wall edema is central to the pathogenesis of PPOI .


Hyperosmotic , orally administered , water-soluble contrast media such as Gastrografin are theoretically capable of mitigating this edema .


A double-blinded , placebo-controlled , randomized trial was conducted .


Participants were allocated to receive 100 mL of Gastrografin ( Exposure Group ) or flavored distilled water ( Control Group ) administered enterally .


Other aspects of management were standardized .


Resolution of PPOI was assessed 12-hourly .


Eighty patients were randomized equally , with 5 in the Exposure Group and 4 in the Control Group excluded from analysis .


Participants were evenly matched at baseline .


Mean duration of PPOI did not differ between Exposure and Control Groups ( 83.7 vs 101.3 hours ; P = 0.191 ) .


When considering individual markers of PPOI resolution , Gastrografin did not affect time to resolution of nausea and vomiting ( 64.5 vs 74.3 hours ; P = 0.404 ) or consumption of oral diet ( 75.8 vs 90.0 hours ; P = 0.297 ) .


However , it accelerated time to flatus or stool ( 18.9 vs 32.7 hours ; P = 0.047 ) and time to resolution of abdominal distension ( 52.8 vs 77.7 hours ; P = 0.013 ) .


There were no significant differences between groups in nasogastric output ; analgesia , antiemetic , or fluid requirement ; complications ; or length of stay .


Gastrografin is not clinically useful in shortening an episode of PPOI characterized by upper and lower gastrointestinal symptoms .


It may however be of therapeutic benefit in the subset of PPOI patients who display lower gastrointestinal symptoms exclusively after surgery .


A randomized clinical trial is needed to evaluate what is the best photodynamic therapy ( PDT ) protocol to use for acute central serous chorioretinopathy .


To compare the efficacy and safety of a 50 % dose of verteporfin ( a method of PDT ) with the efficacy and safety of a 30 % dose for acute central serous chorioretinopathy .


A multicenter , noninferiority , double-masked , randomized , controlled , clinical trial in which 131 patients ( 131 eyes ) with acute central serous chorioretinopathy for less than 6 months were recruited with a follow-up of 12 months from university-based ophthalmology practices .


Patients were randomly assigned to either a 50 % dose of verteporfin ( the 50 % - dose PDT group ) or a 30 % dose ( the 30 % - dose PDT group ) .


The 2 primary outcome measures were the proportion of eyes with complete absorption of subretinal fluid and the proportion of eyes with complete disappearance of fluorescein leakage at 6 and 12 months .


The secondary outcome measures included the subretinal fluid recurrent rate , the fluorescein leakage recurrent rate at 12 months , the mean best-corrected visual acuity , the retinal thickness of the foveal center , and the maximum retinal thickness at each scheduled visit .


The noninferiority of the 30 % - dose PDT compared with the 50 % - dose PDT for the primary outcomes was not demonstrated .


The optical coherence tomography-based improvement rate in the 30 % - dose PDT group was less than that in the 50 % - dose PDT group both at 6 months ( 73.8 % vs 92.9 % ; = 0.0125 , P = .006 ) and at 12 months ( 75.4 % vs 94.6 % ; = 0.0125 , P = .004 ) .


The fluorescein angiography-based improvement rate in the 30 % - dose PDT group was less than that in the 50 % - dose PDT group both at 6 months ( 68.9 % vs 91.1 % ; = 0.0125 , P = .003 ) and at 12 months ( 68.9 % vs 92.9 % ; = 0.0125 , P = .001 ) .


The subretinal fluid recurrence rate in the 30 % - dose PDT group was greater than that in the 50 % - dose PDT group ( 24.0 % vs 5.7 % at 12 months ; P = .010 , determined by use of the log-rank test ) .


The fluorescein leakage recurrent rate in the 30 % - dose PDT group was significantly higher than that in the 50 % - dose PDT group ( 16.7 % vs 3.8 % at 12 months ; P = .03 , determined by use of the log-rank test ) .


No ocular adverse event was encountered in the study .


A 50 % dose of verteporfin may be more effective at resolving subretinal fluid and fluorescein leakage , and with better visual outcomes , than a 30 % dose for acute central serous chorioretinopathy .


clinicaltrials.gov Identifier : NCT01574430 .


Conventional Valsalva maneuver ( CV ) is a standardprocedure to exhibit reverse venous flow atsaphenofemoral junction ( SFJ ) by duplex ultrasonography ( DUS ) .


However some patients could not undergo CV during examination .


Compare blowing party balloon assisted Valsalva ( PBAV ) with CV for exhibiting the reverse venous flow at SFJ incompetence .


Forty patients who had symptoms and signs of suspected saphenofemoral junction incompetence were examined for venous reflux by DUS with two techniques of Valsalva maneuver PBAV and CV The design was a 2x2 cross-over study .


The patients were randomized to two sequences .


The first sequence performed CV before PBAV The second sequence performed PBAV before CV The timing for the instruction , reflux time , and total timing of examination were compared between the two sequences .


There was neither period effect nor treatment-period interaction .


Both PBAV and CV could equally identify SFJ reflux , but teaching time and total examination time in PBAV was shorter than CV .


PBAV is a new option to exhibit reverse venous flow at SFJ by DUS .


PBAV is easier and spend less time than CV


Obesity has long been associated with psoriasis and it is considered to be an independent risk factor for chronic heart diseases in these patients .


Recently , some of the biologic drugs used for psoriasis have been reported to cause increase in body weight .


It is currently not clear if this increased body weight seen in psoriasis patients on biologics leads to decrease in there efficacy or vice versa .


We carried out this study to see if reduction in body weight leads to increased efficacy of biologics in obese psoriasis patients .


To evaluate the effect of weight reduction by dietary control on treatment efficacy of biologics in obese patients as indicated by the Psoriasis Area and Severity Index ( PASI ) score .


Obese patients with psoriasis receiving biologic therapy , satisfying the inclusion criterion , were randomized in a 1:1 ratio to receive low-calorie diet versus normal diet ( control group ) .


We included 262 patients with moderate to severe , stable plaque psoriasis with a PASI score 20:50 on anti TNF - biologic therapy ( infliximab , etanercept , ustekinumab and adalimumab ) .


The patients in the dietary intervention group were given a low calorie diet ( 1000 kcal per day ) for 8 weeks to induce weight loss .


The treatment outcome was assessed using PASI .


The PASI scores were assessed at baseline and every 4 weeks up to week 24 .


There were no significant differences in age , sex distribution , body weight , body mass index , waist circumference , psoriasis duration , or PASI score between the two studied groups at base line .


At week 24 , the mean ( SD ) weight loss was 12.9 1.2 kg in the diet intervention group , and -1.5 0.5 kg in the control group .


The average improvement in mean PASI score was 84 % for the diet group , and 69 % for the control group .


PASI 75 was achieved by 85.9 % in the diet group , and 59.3 % in the control group ( p < 0.001 ) .


The mean ( SD ) body surface area values at week 24 were 3.3 4.4 % and 8.1 6.9 % in the diet group and control group .


Body weight reduction in obese patients on biologics may increase the efficacy of the drug .


Antenatal depression and anxiety are associated with adverse obstetric and mental health outcomes , yet practicable nonpharmacological therapies , particularly for the latter , are lacking .


Yoga incorporates relaxation and breathing techniques with postures that can be customized for pregnant women .


This study tested the efficacy of yoga as an intervention for reducing maternal anxiety during pregnancy .


Fifty-nine primiparous , low-risk pregnant women completed questionnaires assessing state ( State Trait Anxiety Inventory ; STAI-State ) , trait ( STAI-Trait ) , and pregnancy-specific anxiety ( Wijma Delivery Expectancy Questionnaire ; WDEQ ) and depression ( Edinburgh Postnatal Depression Scale ; EPDS ) before randomization ( baseline ) to either an 8-week course of antenatal yoga or treatment-as-usual ( TAU ) ; both groups repeated the questionnaires at follow-up .


The yoga group also completed pre - and postsession state anxiety and stress hormone assessments at both the first and last session of the 8-week course .


A single session of yoga reduced both subjective and physiological measures of state anxiety ( STAI-S and cortisol ) ; and this class-induced reduction in anxiety remained at the final session of the intervention .


Multiple linear regression analyses identified allocation to yoga as predictive of greater reduction in WDEQ scores ( B = -9.59 ; BCa 95 % CI = -18.25 to -0.43 ; P = .014 ; d = -0.57 ) , while allocation to TAU was predictive of significantly increased elevation in EPDS scores ( B = -3.06 ; BCa 95 % CI = -5.9 to -0.17 ; P = .042 ; d = -0.5 ) .


No significant differences were observed in state or trait anxiety scores between baseline and follow-up .


Antenatal yoga seems to be useful for reducing women 's anxieties toward childbirth and preventing increases in depressive symptomatology .


Vitamin D has wide-ranging effects on the immune system , and studies suggest that low serum vitamin D levels are associated with worse clinical outcomes in HIV .


Recent studies have identified an interaction between antiretrovirals used to treat HIV and reduced serum vitamin D levels , but these studies have been done in North American and European populations .


Using a prospective cohort study design nested in a multinational clinical trial , we examined the effect of three combination antiretroviral ( cART ) regimens on serum vitamin D levels in 270 cART-nave , HIV-infected adults in nine diverse countries , ( Brazil , Haiti , Peru , Thailand , India , Malawi , South Africa , Zimbabwe and the United States ) .


We evaluated the change between baseline serum vitamin D levels and vitamin D levels 24 and 48 weeks after cART initiation .


Serum vitamin D levels decreased significantly from baseline to 24 weeks among those randomized to efavirenz/lamivudine/zidovudine ( mean change : -7.94 [ 95 % Confidence Interval ( CI ) -10.42 , -5.54 ] ng/ml ) and efavirenz/emtricitabine/tenofovir-DF ( mean change : -6.66 [ 95 % CI -9.40 , -3.92 ] ng/ml ) when compared to those randomized to atazanavir/emtricitabine/didanosine-EC ( mean change : -2.29 [ 95 % CI -4.83 , 0.25 ] ng/ml ) .


Vitamin D levels did not change significantly between week 24 and 48 .


Other factors that significantly affected serum vitamin D change included country ( p < 0.001 ) , season ( p < 0.001 ) and baseline vitamin D level ( p < 0.001 ) .


Efavirenz-containing cART regimens adversely affected vitamin D levels in patients from economically , geographically and racially diverse resource-limited settings .


This effect was most pronounced early after cART initiation .


Research is needed to define the role of Vitamin D supplementation in HIV care .


A collaborative care programme for depression in primary care has proven clinical effectiveness over a 12-months period .


Because depression tends to relapse and to chronic course , our aim was to determine whether the effectiveness observed in the first year persists during 3 years of monitoring .


Randomised controlled trial with twenty primary care centres were allocated to intervention group or usual care group .


The intervention consisted of a collaborative care programme with clinical , educational and organisational procedures .


Outcomes were monitored by a blinded interviewer at baseline , 12 and 36 months .


Clinical outcomes were response to treatment and remission rates , depression severity and health-related quality of life .


ISRCTN16384353 .


A total of 338 adult patients with major depression ( DSM-IV ) were assessed at baseline .


At 36 months , 137 patients in the intervention group and 97 in the control group were assessed ( attrition 31 % ) .


The severity of depression ( mean Patient Health Questionnaire-9 score ) was 0.95 points lower in the intervention group [ 6.31 versus 7.25 ; p = 0.324 ] .


The treatment response rate was 5.6 % higher in the intervention group than in the control group [ 66.4 % versus 60.8 % ; p = 0.379 ] and the remission rate was 9.2 % higher [ 57.7 % versus 48.5 % ; p = 0.164 ] .


No difference reached statistical significance .


The number of patients lost ( 31 % ) before follow-up may have introduced a bias .


Clinical benefits shown in the first year were not maintained beyond : at 36 months the differences between the control group and the intervention group reduced in all the analysed variables .


The Carotid Revascularization Endarterectomy Versus Stenting Trial ( CREST ) is a multicenter randomized trial of stenting versus endarterectomy in patients with symptomatic and asymptomatic carotid disease .


This study assesses management of vascular risk factors .


Management was provided by the patient 's physician , with biannual monitoring results collected by the local site .


Therapeutic targets were low-density lipoprotein , cholesterol < 100 mg/dL , systolic blood pressure < 140 mm Hg , fasting blood glucose < 126 mg/dL , and nonsmoking status .


Optimal control was defined as achieving all 4 goals concurrently .


Generalized estimating equations were used to compare risk factors at baseline with those observed in scheduled follow-up visits for up to 48 months .


In the analysis cohort of 2210 , significant improvements in risk-factor control were observed across risk factors for all follow-up visits compared with baseline .


At 48 months , achievement of the low-density lipoprotein cholesterol goal improved from 59.1 % to 73.6 % ( P < 0.001 ) , achievement of the systolic blood pressure goal improved from 51.6 % to 65.1 % ( P < 0.001 ) , achievement of the glucose goal improved from 74.9 % to 80.7 % ( P = 0.0101 ) , and nonsmoking improved from 74.4 % to 80.9 % ( P < 0.0001 ) .


The percentage with optimal risk-factor control also improved significantly , from 16.7 % to 36.2 % ( P < 0.001 ) , but nearly 2 of 3 study participants did not achieve optimal control during the study .


Site-based risk-factor control improved significantly in the first 6 months and over the long term in CREST but was often suboptimal .


Intensive medical management should be considered for future trials of carotid revascularization .


ClinicalTrials.gov .


Unique identifier : NCT00004732 .


To analyze the efficiency of the ALL-2009 protocol ( ClinicalTrials.gov NCT01 193933 ) in patients with T-cell leukemias , particularly the role of autologous hematopoietic stem cell transplantation ( auto-HSCT ) after non-myeloablative BEAM conditioning , followed by maintenance therapy .


Since 2009 , the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia ( T-ALL ) , the treatment results were assessed in 86 patients : 6 and 28 patients underwent allogeneic HSCT and auto-HSCT , respectively .


A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not .


For this , the median time from complete remission to the date of auto-HSCT was determined ( the median was 6 months ) .


Then to compare with the auto-HSCT group , only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group .


The achievement of complete remission in patients with thymic T-ALL ( 100 % ) was significantly higher than in those with early ( 85.7 % ) or mature ( 70 % ) variants .


The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction ( 7.4 and 10 % versus 0 ) and the patients with mature T-ALL had a.higher proportion of refractory forms ( 20 % versus 0 ) .


The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76 % , respectively .


After auto-HSCT , the risk of recurrence was 0 % versus 21 % after chemotherapy ( p = 0.03 ) .


The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups : 100 and 66 % , respectively ( p = 0.047 ) .


The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol , the basis for which is the principle of continuity of cytostatic effects , are exclusively optimistic .


Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning , followed by maintenance therapy , considerably reduces the risk of recurrence .


Orphans and vulnerable children ( OVC ) are at high risk for experiencing trauma and related psychosocial problems .


Despite this , no randomized clinical trials have studied evidence-based treatments for OVC in low-resource settings .


To evaluate the effectiveness of lay counselor-provided trauma-focused cognitive behavioral therapy ( TF-CBT ) to address trauma and stress-related symptoms among OVC in Lusaka , Zambia .


This randomized clinical trial compared TF-CBT and treatment as usual ( TAU ) ( varying by site ) for children recruited from August 1 , 2012 , through July 31 , 2013 , and treated until December 31 , 2013 , for trauma-related symptoms from 5 community sites within Lusaka , Zambia .


Children were aged 5 through 18 years and had experienced at least one traumatic event and reported significant trauma-related symptoms .


Analysis was with intent to treat .


The intervention group received 10 to 16 sessions of TF-CBT ( n = 131 ) .


The TAU group ( n = 126 ) received usual community services offered to OVC .


The primary outcome was mean item change in trauma and stress-related symptoms using a locally validated version of the UCLA Posttraumatic Stress Disorder Reaction Index ( range , 0-4 ) and functional impairment using a locally developed measure ( range , 0-4 ) .


Outcomes were measured at baseline and within 1 month after treatment completion or after a waiting period of approximately 4.5 months after baseline for TAU .


At follow-up , the mean item change in trauma symptom score was -1.54 ( 95 % CI , -1.81 to -1.27 ) , a reduction of 81.9 % , for the TF-CBT group and -0.37 ( 95 % CI , -0.57 to -0.17 ) , a reduction of 21.1 % , for the TAU group .


The mean item change for functioning was -0.76 ( 95 % CI , -0.98 to -0.54 ) , a reduction of 89.4 % , and -0.54 ( 95 % CI , -0.80 to -0.29 ) , a reduction of 68.3 % , for the TF-CBT and TAU groups , respectively .


The difference in change between groups was statistically significant for both outcomes ( P < .001 ) .


The effect size ( Cohen d ) was 2.39 for trauma symptoms and 0.34 for functioning .


Lay counselors participated in supervision and assessed whether the intervention was provided with fidelity in all 5 community settings .


The TF-CBT adapted for Zambia substantially decreased trauma and stress-related symptoms and produced a smaller improvement in functional impairment among OVC having experienced high levels of trauma .


clinicaltrials.gov Identifier : NCT01624298 .


To compare the astigmatism-reducing effect of a toric intraocular lens ( IOL ) and peripheral corneal relaxing incisions ( PCRIs ) .


Moorfields Eye Hospital NHS Foundation Trust , London , United Kingdom .


Prospective masked bilateral randomized study .


Cataract patients with a preoperative corneal astigmatism of 1.0 to 2.5 diopters ( D ) were included .


All patients received a toric IOL in 1 eye and a nontoric IOL plus a PCRI in the other eye .


Postoperative follow-up was at 1 hour , 1 month , and 6 months .


The uncorrected distance visual acuity , corrected distance visual acuity , autorefraction ( Topcon RM-8800 ) , and subjective refraction were recorded .


The IOL axis was assessed using retroillumination photographs .


The study enrolled 60 eyes of 30 patients .


The mean astigmatism vector reduction was 1.74 D 0.64 ( SD ) in the toric IOL group and 1.27 0.76 D in the PCRI group ; the difference was statistically significant ( P = .042 ) .


The mean absolute rotation of the toric IOL was 2.5 1.8 degrees ( maximum 6.3 degrees ) in the first 6 postoperative months .


Astigmatism increased in the PCRI group between the 1-month and 6-month follow-up ( mean 0.38 0.27 D ; maximum 1.00 D ) ( P < .001 ) .


Toric IOLs and PCRIs both reduced astigmatism ; however , toric IOLs reduced astigmatism to a higher extent and they were more predictable .


To evaluate the long-term efficacy and safety of certolizumab pegol ( CZP ) treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis ( RA ) patients who could not receive methotrexate ( MTX ) .


HIKARI double-blind ( DB ) patients were entered into an open-label extension ( OLE ) study .


Patients withdrawn at 16 weeks due to lack of efficacy and DB completers without a 24-week American College of Rheumatology ( ACR ) 20 response received CZP 200 mg every 2 weeks ( Q2W ) .


DB completers with 24-week ACR20 responses were randomized to CZP 200 mg Q2W or CZP 400 mg every 4 weeks .


The ACR20/ACR50/ACR70 response rates of DB completers ( n = 98 ) were 82.7 % / 56.1 % / 34.7 % at OLE entry , and 83.7 % / 65.3 % / 48.0 % at 52 weeks , respectively .


Other clinical , functional , and radiographic outcomes were sustained during long-term administration of CZP , even without MTX .


No new unexpected adverse events were observed during long-term CZP treatment .


The efficacy and safety of CZP treatment were similar between the two dosing schedules .


Long-term CZP administration is efficacious and safe for RA patients .


No obvious differences in clinical efficacy and safety were observed between the two dosing schedules .


The choice between two maintenace regimens adds flexibility in administration schedules for RA patients and physicians .


To compare the 24-h changes of intraocular pressure ( IOP ) and mean ocular perfusion pressure ( MOPP ) obtained with tafluprost versus travoprost in patients with normal-tension glaucoma ( NTG ) .


This study is a randomized crossover study of 50 patients newly diagnosed with NTG who received either tafluprost or travoprost given once at 9 PM for 2 months , after which they were crossed over to the other medication for another 2 months .


IOP and blood pressure were measured for 24h before starting the treatment and after finishing the first and second treatment periods .


Forty-one patients completed the study .


The mean ( standard deviation ) 24-h IOP was 16.82.0 mmHg at baseline , 14.42.2 mmHg on tafluprost , and 13.61.8 mmHg on travoprost .


Both prostaglandin monotherapies significantly reduced mean 24-h IOP as compared with baseline ( P < 0.001 , P < 0.001 , respectively ) , and travoprost demonstrated a lower mean 24-h IOP than tafluprost ( P = 0.044 ) .


Both treatments significantly reduced the IOP from baseline at every point over 24h .


At 3 individual time points , travoprost provided a lower IOP than tafluprost : at 4 PM ( 13.82.7 vs. 14.82.6 mmHg , P = 0.041 ) , at 6 PM ( 13.52.5 vs. 14.42.5 mmHg , P = 0.006 ) , and at 8 PM ( 13.32.5 vs. 14.52.4 mmHg , P = 0.029 ) .


Both tafluprost and travoprost significantly increased the 24-h MOPP ( P = 0.008 , P = 0.002 , respectively ) , and travoprost demonstrated a greater 24-h MOPP than tafluprost ( P = 0.027 ) .


Both tafluprost and travoprost were effective in lowering IOP and increasing MOPP throughout 24h in NTG .


However , travoprost reduced IOP greater than tafluprost in the late afternoon and evening .


Guanidinoacetic acid ( GAA ) is an intermediate in the biosynthesis of creatine ( Cr ) , yet its use in human nutrition is limited due to a lack of a clear understanding of its ' dose-response effect .


Thus , the purpose of this study was to investigate the effect of three different dosages of GAA ( 1.2 , 2.4 and 4.8 g/day ) administered for 6 weeks on serum and urinary variables related to GAA metabolism .


Forty-eight healthy volunteers participated in the randomized , placebo-controlled , double-blind , repeated-measure study .


At baseline , after 1 , 2 , 4 and 6 weeks , participants provided both fasting blood samples and 24-h urine .


GAA intervention significantly increased serum and urinary GAA , Cr and creatinine as compared to placebo ( P < 0.05 ) .


Differences were found for serum GAA and Cr responses between the three GAA dosages , with high-dose GAA resulting in a greater increase ( P < 0.05 ) in the plasma concentration of both variables as compared to other GAA dosages .


In GAA groups , fasting plasma total homocysteine ( T-Hcy ) increased by 3.5 mol/L on average at post-administration , yet no dose-response differences were found between trials .


Serum B vitamins were not affected by either placebo or GAA intervention ( P > 0.05 ) .


Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine .


ClinicalTrials.gov , identification number NCT01133899 .


The objective of this trial was to assess which type of warm-up has the highest effect on virtual reality ( VR ) laparoscopy performance .


The following warm-up strategies were applied : a hands-on exercise ( group 1 ) , a cognitive exercise ( group 2 ) , and no warm-up ( control , group 3 ) .


This is a 3-arm randomized controlled trial .


The trial was conducted at the department of surgery of the University Hospital Basel in Switzerland .


A total of 94 participants , all laypersons without any surgical or VR experience , completed the study .


A total of 96 participants were randomized , 31 to group 1 , 31 to group 2 , and 32 to group 3 .


There were 2 postrandomization exclusions .


In the multivariate analysis , we found no evidence that the intervention had an effect on VR performance as represented by 6 calculated subscores of accuracy , time , and path length for ( 1 ) camera manipulation and ( 2 ) hand-eye coordination combined with 2-handed maneuvers ( p = 0.795 ) .


Neither the comparison of the average of the intervention groups ( groups 1 and 2 ) vs control ( group 3 ) nor the pairwise comparisons revealed any significant differences in VR performance , neither multivariate nor univariate .


VR performance improved with increasing performance score in the cognitive exercise warm-up ( iPad 3D puzzle ) for accuracy , time , and path length in the camera navigation task .


We were unable to show an effect of the 2 tested warm-up strategies on VR performance in laypersons .


We are currently designing a follow-up study including surgeons rather than laypersons with a longer warm-up exercise , which is more closely related to the final task .


The purpose of this study was to retrospectively explore the relationship between human epidermal growth factor receptor 2 ( HER2 ) messenger RNA ( mRNA ) expression and efficacy in patients receiving trastuzumab plus docetaxel ( HT ) or trastuzumab emtansine ( T-DM1 ) .


Patients with HER2-positive , locally advanced or metastatic breast cancer ( MBC ) were randomly assigned to HT ( n = 70 ) or T-DM1 ( n = 67 ) .


HER2 status was assessed locally using immunohistochemistry or fluorescence in situ hybridization and confirmed retrospectively by central testing .


HER2 mRNA expression was assessed using quantitative reverse transcriptase polymerase chain reaction .


HER2 mRNA levels were obtained for 116/137 patients ( HT = 61 ; T-DM1 = 55 ) .


Median pretreatment HER2 mRNA was 8.9 .


The risk of disease progression in the overall population was lower with T-DM1 than with HT ( hazard ratio ( HR ) = 0.59 ; 95 % confidence interval ( CI ) 0.36 to 0.97 ) .


This effect was more pronounced in patients with HER2 mRNAmedian ( HR = 0.39 ; 95 % CI 0.18 to 0.85 ) versus < median ( HR = 0.85 ; 95 % CI 0.44 to 1.67 ) .


In the T-DM1 arm , median progression-free survival ( PFS ) was not reached in patients with HER2 mRNAmedian and was 10.6 months in patients with HER2 mRNA < median .


In the HT arm , PFS was 8.8 versus 9.8 months in patients with HER2 mRNAmedian versus < median , respectively .


The effect of HER2 mRNA expression on objective response rates was less pronounced .


This exploratory analysis suggests that while overall , patients with HER2-positive MBC show improved PFS with T-DM1 relative to HT , the effect is enhanced in patients with tumor HER2 mRNAmedian .


ClinicalTrials.gov NCT00679341 .


The behavioral outcome of food ingestion is a complex process that involves psychological and biological factors .


Avocados are nutrient dense with properties that may favorably impact energy balance .


This study sought to evaluate if incorporating approximately one half of a Hass avocado by addition or inclusion into a lunch meal will influence post-ingestive satiety , glucose and insulin response , and subsequent energy intake among overweight adults .


This was a randomized 33 single-blind crossover design study with 26 healthy overweight adults ( mean SD age 40.811.0 years and BMI 28.12.4 kg/m ) .


Participants consumed a standardized breakfast followed by 1 of 3 lunch test meals [ Control ( C ) , avocado-free ; Avocado Inclusive ( AI ) ; and , Avocado Added ( AA ) ] .


Participants rated five appetite sensations using a visual analog scale ( VAS ) before lunch and at specific intervals over 5 hours following the start of the test meal .


Blood glucose and insulin were measured before lunch and at specific intervals over 3 hours following the start of the test meal .


Mixed models were used to compare differences among the 3 test meals , and the area under the curve ( AUC ( 0-xh ) ) was computed for the VAS and biological measures .


There were significant differences in the AUC ( 0-5h ) for the self-reported feelings of satisfaction ( P = 0.04 ) and desire to eat ( P = 0.05 ) in the mixed model analysis .


Compared to the C test meal , the AA test meal increased satisfaction by 23 % ( P = 0.05 ) and decreased the desire to eat by 28 % ( P = 0.04 ) for the AUC ( 0-5h ) .


For the AUC ( 0-3h ) , the AA test meal increased satisfaction by 26 % ( P = 0.02 ) and decreased the desire to eat by 40 % ( P = 0.01 ) as compared to the C test meal .


Compared to the AI meal , the AUC ( 0-3h ) for blood insulin was higher in the C and AA meals ( P = 0.04 and P = 0.05 , respectively ) .


The addition of approximately one half of a Hass avocado at a lunch meal can influence post-ingestive satiety over a subsequent 3 and 5 hour period in overweight adults .


A caveat to these findings is that the avocado contained an additional 112 kcal , which may have accounted for the observed increase in satisfaction and decreased desire to eat .


Future trials are warranted to evaluate the effects of avocado intake on weight management in adults of varying BMIs and among insulin resistant individuals .


We explored associations between mitochondrial DNA ( mtDNA ) haplogroups , epidermal nerve fiber density ( ENFD ) , and HIV-associated sensory neuropathy ( HIV-SN ) in a randomized trial of Thai patients initiating antiretroviral therapy ( ART ) .


The South East Asia Research Collaboration with Hawaii 003 study evaluated toxicity of nucleoside reverse transcriptase inhibitors ( stavudine vs. zidovudine vs. tenofovir ) .


We present secondary analyses of mtDNA haplogroups and ENFD changes .


ENFD , peripheral blood mononuclear cell mitochondrial complex I and IV , and 8-oxo-deoxyguanine ( 8-oxo-dG ) were quantified .


Peripheral blood mononuclear cell mtDNA sequences were obtained for haplogroup determination .


Multivariate regression of ENFD change was performed .


Paired ENFD was available from 118 patients .


Median age , CD4 cell count , and height at entry were 34 years , 172 cells/l , and 162 cm , respectively .


Major haplogroups included M ( 42 % ) , F ( 21 % ) , and B ( 16 % ) .


Baseline ENFD , CD4 cell count , randomized ART , and biomarkers did not differ by haplogroup .


Haplogroup B patients were older ( P = 0.02 ) at baseline , and had an increase in median ENFD ( +1.5 vs. -2.9 fibers/mm ; P = 0.03 ) and 8-oxo-dG break frequency ( +0.05 vs. 0.00 ; P = 0.05 ) compared to other haplogroups .


In a multivariate model , haplogroup B was associated with increased ENFD ( = 3.5 , P = 0.009 ) at week 24 , whereas older age ( P = 0.02 ) , higher baseline CD4 cell count , ( P = 0.03 ) , higher complex I level ( P = 0.03 ) , and higher ENFD ( P < 0.001 ) at baseline were all associated with decreased ENFD .


Three of the six HIV-SN cases were haplogroup B ( P = 0.05 ) .


Thai persons belonging to mtDNA haplogroup B had increased ENFD and 8-oxo-dG on ART , and were more likely to develop HIV-SN .


These results suggest that mtDNA variation influences early oxidative damage and ENFD changes .


Chronic post-surgical pain ( CPSP ) is a not uncommon complication after mastectomy , with a reported incidence between 20 % and 68 % .


Careful dissection , the use of minimally invasive surgical techniques , and attempts to reduce the associated inflammatory and hyperalgesic responses are suggested methods to prevent CPSP .


To determine if the use of perioperative lidocaine infusion is associated with decreased incidence of CPSP after mastectomy .


Double-blind , placebo-controlled randomized trial .


This is a secondary analysis of data from 61 out of 71 patients who underwent mastectomy for breast cancer .


Patients were randomized to either placebo ( Group P ; n = 27 ) or intravenous lidocaine ( Group L ; n = 34 , bolus 1.5 mg/kg at induction , then infusion at 2 mg/kg/hr , up to 2 hours after the end of surgery ) in a prospective double-blind design .


CPSP was assessed at 6 months after surgery .


Stepwise logistic regression analysis was performed to assess the efficacy of lidocaine .


Overall 12 ( 20 % ) patients developed CPSP , 8 ( 30 % ) in the placebo group and 4 ( 12 % ) in the lidocaine group .


Predictive factors for CPSP that remained significant after multivariate analysis included lidocaine ( associated with a 20-fold decrease in CPSP , P = 0.013 ) , breast implant placement ( associated with a 16-fold increase in CPSP , P = 0.034 ) , and radiotherapy ( associated with a 29-fold increase in CPSP , P = 0.008 ) .


Small sample size .


Perioperative lidocaine administration was associated with a decreased incidence of CPSP , while breast implant placement and radiotherapy were associated with an increased incidence .


These findings suggest a protective effect of lidocaine on CPSP development in mastectomy patients .


To compare quality of survival in `` standard-risk '' medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy , combined with a chemotherapy regimen common to both treatment arms , in the PNET4 randomised controlled trial .


Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function , health status , behavior , health-related quality of life , and medical , educational , employment , and social information .


Pre - and postoperative neurologic status and serial heights and weights were also recorded .


Data were provided by 151 of 244 eligible survivors ( 62 % ) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years .


Compared with standard radiation therapy , hyperfractionated radiation therapy was associated with lower ( ie , better ) z-scores for executive function in all participants ( mean intergroup difference 0.48 SDs , 95 % confidence interval 0.16-0 .81 , P = .004 ) , but health status , behavioral difficulties , and health-related quality of life z-scores were similar in the 2 treatment arms .


Data on hearing impairment were equivocal .


Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores ( mean intergroup difference 0.43 SDs , 95 % confidence interval 0.10-0 .76 , P = .011 ) .


Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status , behavior , or quality of life .


The aim of this study was to identify gender specific physical activity correlates in Danish preschool children , using a socioecological approach .


This was a cross-sectional study conducted in Odense , Denmark .


The gender specific models were based on data from 174 boys and 177 girls , 5-6 years of age and enrolled in 40 randomly selected preschools .


Percentage of total daily time spent in moderate and vigorously physical activity ( MVPA ) was measured using ActiGraph accelerometers over 5 preschool days and 2 days off .


Thirty-nine potential correlates of child MVPA across 5 domains were tested for associations with gender specific MVPA .


The gender specific models consistently identified motor coordination and the parents ' perceptions of their child 's activity preferences during free play to be positively associated with MVPA .


Days with rain or no preschool attendance were negatively associated with MVPA .


For boys , rural area and the size of the preschool playground were positively associated with MVPA , whereas for girls , it was the age and the relative preschool indoor area .


Individual and overall environmental correlates of MVPA were identified .


However , most correlates were not or only weakly related to MVPA .


It is possible that the interaction with peers and surrounding adults might contribute the most to preschool child MVPA .


Based on findings that major depressive disorder ( MDD ) is associated to decreased dorsolateral prefrontal cortical ( DLPFC ) activity ; interventions that increase DLPFC activity might theoretically present antidepressant effects .


Two of them are cognitive control therapy ( CCT ) , a neurocognitive intervention that uses computer-based working memory exercises , and transcranial direct current stimulation ( tDCS ) , which delivers weak , electric direct currents over the scalp .


We investigated whether tDCS enhanced the effects of CCT in a double-blind trial , in which participants were randomized to sham tDCS and CCT ( n = 17 ) vs. active tDCS and CCT ( n = 20 ) .


CCT and tDCS were applied for 10 consecutive workdays .


Clinicaltrials.gov identifier : NCT01434836 .


Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up , with a response rate of approximately 25 % .


Older patients and those who presented better performance in the task throughout the trial ( possibly indicating greater engagement and activation of the DLPFC ) had greater depression improvement in the combined treatment group .


Our exploratory findings should be further confirmed in prospective controlled trials .


CCT and tDCS combined might be beneficial for older depressed patients , particularly for those who have cognitive resources to adequately learn and improve task performance over time .


This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy .


To evaluate if the use of Valleylab mode ( `` V mode '' ) ( Covidien , Mansfield , MA ) electrothermal energy for colpotomy during total laparoscopic hysterectomy ( LH ) results in a smaller margin of thermal injury to the upper vagina compared with traditional cut/coagulate ( cut/coag ) electrothermal energy .


Prospective randomized clinical trial ( Canadian Task Force classification I ) .


University medical center .


A total of 101 subjects who underwent LH between June 2010 and August2012 .


Subjects were randomized to colpotomy by V mode electrothermal energy or cut/coag electrothermal energy .


The primary end point was the median depth of thermal injury measured in millimeters .


The secondary end points included the proportion of subjects who developed granulation tissue , induration , infection , or dehiscence at the vaginal cuff at 4weeks , 3months , or 6months postoperatively .


There was no significant difference in the median depth of thermal injury in the cut/coag and V mode arms ( anterior margin : 0.68 mm vs 0.63 mm [ p = .94 ] , posterior margin : 0.66 mm vs 0.70 mm [ p = .87 ] , respectively ) .


Twenty-seven percent of subjects in each arm developed at least 1 of the clinical end points at 4weeks , 3months , or 6months postoperatively ( granulation tissue : 6 % -18 % vs 8 % -21 % , induration : 0 % -2 % vs 4 % -5 % , infection : 0 % -4 % vs 0 % -10 % , dehiscence : 2 % vs 0 % in the cut/coag and V mode arms , respectively ) , with no difference between arms ( p = 1.0 ) .


The V mode does not reduce the depth of thermal injury compared with cut/coag electrothermal energy when used for colpotomy incision during total laparoscopic hysterectomy ( Clinical Trials.gov ID : NCT02080546 ) .


To evaluate the antimicrobial activity of a new , transparent composite film dressing , whose adhesive contains chlorhexidine gluconate ( CHG ) , against the native microflora present on human skin .


CHG-containing adhesive film dressings and non-antimicrobial control film dressings were applied to the skin on the backs of healthy human volunteers without antiseptic preparation .


Dressings were removed 1 , 4 or 7 days after application .


The bacterial populations underneath were measured by quantitative cultures ( cylinder-scrub technique ) and compared with one another as a function of time .


The mean baseline microflora recovery was 3.24 log10 cfu/cm ( 2 ) .


The mean log reductions from baseline measured from underneath the CHG-containing dressings were 0.87 , 0.78 and 1.30 log10 cfu/cm ( 2 ) on days 1 , 4 and 7 , respectively , compared with log reductions of 0.67 , -0.87 and -1.29 log10 cfu/cm ( 2 ) from underneath the control film dressings .


There was no significant difference between the log reductions of the two treatments on day 1 , but on days 4 and 7 the log reduction associated with the CHG adhesive was significantly higher than that associated with the control adhesive .


The adhesive containing CHG was associated with a sustained antimicrobial effect that was not present in the control .


Incorporating the antimicrobial into the adhesive layer confers upon it bactericidal properties in marked contrast to the non-antimicrobial adhesive , which contributed to bacterial proliferation when the wear time was 4 days .


Third-generation coronary drug-eluting stents ( DES ) with biodegradable polymers have been designed to improve safety and efficacy .


We designed a large scale registry-based randomized clinical trial to compare 2 third-generation DES : a thin strut , cobalt-chromium DES with silicon carbide-coating releasing sirolimus from a biodegradable polymer ( O-SES , Orsiro ; Biotronik , Blach , Switzerland ) with the stainless steel biodegradable polymer biolimus-eluting Nobori stents ( N-BES , Nobori ; Terumo , Tokyo , Japan ) in an all-comer patient population .


The multicenter SORT OUT VII trial ( NCT01879358 ) randomly assigned 2,530 patients to treatment with biodegradable polymer O-SES or biodegradable polymer N-BES at 3 sites in Western Denmark .


Patients were eligible , if they were 18 years old ; had chronic stable coronary artery disease or acute coronary syndromes ; and 1 coronary lesion with > 50 % diameter stenosis , requiring treatment with a DES .


The primary end point target lesion failure is a composite of cardiac death , myocardial infarction ( not related to other than index lesion ) , or target lesion revascularization within 12 months .


Clinically , driven event detection based on Danish registries will be used .


An event rate of 6.5 % is assumed in each stent group .


With a sample size of 1,157 patients in each treatment arm , a 2-group large-sample normal approximation test of proportions with a 1-sided 5 % significance level will have 90 % power to detect noninferiority of the O-SES compared with the N-BES with a predetermined noninferiority margin of 3.0 % .


The SORT OUT VII trial will determine whether the biodegradable polymers O-SES is noninferior to the N-BES with respect to driven event .


Nivolumab , a fully human IgG4 PD-1 immune checkpoint inhibitor antibody , can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors .


We assessed the efficacy and safety of nivolumab compared with investigator 's choice of chemotherapy ( ICC ) as a second-line or later-line treatment in patients with advanced melanoma .


In this randomised , controlled , open-label , phase 3 trial , we recruited patients at 90 sites in 14 countries .


Eligible patients were 18 years or older , had unresectable or metastatic melanoma , and progressed after ipilimumab , or ipilimumab and a BRAF inhibitor if they were BRAF ( V 600 ) mutation-positive .


Participating investigators randomly assigned ( with an interactive voice response system ) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC ( dacarbazine 1000 mg/m ( 2 ) every 3 weeks or paclitaxel 175 mg/m ( 2 ) combined with carboplatin area under the curve 6 every 3 weeks ) until progression or unacceptable toxic effects .


We stratified randomisation by BRAF mutation status , tumour expression of PD-L1 , and previous best overall response to ipilimumab .


We used permuted blocks ( block size of six ) within each stratum .


Primary endpoints were the proportion of patients who had an objective response and overall survival .


Treatment was given open-label , but those doing tumour assessments were masked to treatment assignment .


We assessed objective responses per-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks , and safety in all patients who had had at least one dose of treatment .


The trial is closed and this is the first interim analysis , reporting the objective response primary endpoint .


This study is registered with ClinicalTrials.gov , number NCT01721746 .


Between Dec 21 , 2012 , and Jan 10 , 2014 , we screened 631 patients , randomly allocating 272 patients to nivolumab and 133 to ICC .


Confirmed objective responses were reported in 38 ( 317 % , 95 % CI 235-408 ) of the first 120 patients in the nivolumab group versus five ( 106 % , 35-231 ) of 47 patients in the ICC group .


Grade 3-4 adverse events related to nivolumab included increased lipase ( three [ 1 % ] of 268 patients ) , increased alanine aminotransferase , anaemia , and fatigue ( two [ 1 % ] each ) ; for ICC , these included neutropenia ( 14 [ 14 % ] of 102 ) , thrombocytopenia ( six [ 6 % ] ) , and anaemia ( five [ 5 % ] ) .


We noted grade 3-4 drug-related serious adverse events in 12 ( 5 % ) nivolumab-treated patients and nine ( 9 % ) patients in the ICC group .


No treatment-related deaths occurred .


Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor .


Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need .


Bristol-Myers Squibb .


To investigate the effect of stretch-and-flow voice therapy on vocal function and handicap .


Randomized controlled trial .


Participants with primary muscle tension dysphonia were randomly assigned to experimental or control groups .


Experimental participants received vocal hygiene education followed by 6 weeks of stretch-and-flow voice therapy .


Control participants received vocal hygiene education only .


Outcome variables consisted of a measure of vocal handicap ( Voice Handicap Index [ VHI ] ) , maximum phonation time , s/z ratio , and acoustic measures .


All measures were obtained at baseline prior to treatment and within 2 weeks posttreatment or at the end of the control period .


The pre - to posttreatment measurement change ( delta ) was applied to statistical analyses .


A multivariate analysis of variance revealed significant group differences in pre-to-post changes on measures of VHI , maximum phonation time , and cepstral peak prominence ( CPP ) in connected speech and vowels ( P = 0.003 , 0.013 , 0.025 , and 0.017 respectively ) , with a significant reduction of VHI ( Cohen 's d = 1.6 ) , increase in maximum phonation time ( Cohen 's d = 1.2 ) , increase of CPP in connected speech ( Cohen 's d = 1.2 ) , and increase of CPP in vowels ( Cohen 's d = 1.1 ) in the experimental group compared to the control group .


This preliminary small sample randomized controlled trial found significantly greater improvement in vocal handicap , maximum phonation time , and acoustic measures of vocal function after participants received stretch-and-flow voice therapy compared to participants receiving vocal hygiene education alone .


Additional research incorporating larger samples will be needed to confirm and further investigate these findings .


1b .


To examine the impact of providing rapid diagnostic tests for malaria on fever management in private drug retail shops where most poor rural people with fever present , with the aim of reducing current massive overdiagnosis and overtreatment of malaria .


Cluster randomized trial of 24 clusters of shops .


Dangme West , a poor rural district of Ghana .


Shops and their clients , both adults and children .


Providing rapid diagnostic tests with realistic training .


The primary outcome was the proportion of clients testing negative for malaria by a double-read research blood slide who received an artemisinin combination therapy or other antimalarial .


Secondary outcomes were use of antibiotics and antipyretics , and safety .


Of 4603 clients , 3424 ( 74.4 % ) tested negative by double-read research slides .


The proportion of slide-negative clients who received any antimalarial was 590/1854 ( 32 % ) in the intervention arm and 1378/1570 ( 88 % ) in the control arm ( adjusted risk ratio 0.41 ( 95 % CI 0.29 to 0.58 ) , P < 0.0001 ) .


Treatment was in high agreement with rapid diagnostic test result .


Of those who were slide-positive , 690/787 ( 87.8 % ) in the intervention arm and 347/392 ( 88.5 % ) in the control arm received an artemisinin combination therapy ( adjusted risk ratio 0.96 ( 0.84 to 1.09 ) ) .


There was no evidence of antibiotics being substituted for antimalarials .


Overall , 1954/2641 ( 74 % ) clients in the intervention arm and 539/1962 ( 27 % ) in the control arm received appropriate treatment ( adjusted risk ratio 2.39 ( 1.69 to 3.39 ) , P < 0.0001 ) .


No safety concerns were identified .


Most patients with fever in Africa present to the private sector .


In this trial , providing rapid diagnostic tests for malaria in the private drug retail sector significantly reduced dispensing of antimalarials to patients without malaria , did not reduce prescribing of antimalarials to true malaria cases , and appeared safe .


Rapid diagnostic tests should be considered for the informal private drug retail sector.Registration Clinicaltrials.gov NCT01907672 .


Stringent control of proteolytic activity represents a major therapeutic approach for wound-bed preparation .


We tested whether a protease-modulating polyacrylate - ( PA - ) containing hydrogel resulted in a more efficient wound-bed preparation of venous leg ulcers when compared to an amorphous hydrogel without known protease-modulating properties .


Patients were randomized to the polyacrylate-based hydrogel ( n = 34 ) or to an amorphous hydrogel ( n = 41 ) .


Wound beds were evaluated by three blinded experts using photographs taken on days 0 , 7 and 14 .


After 14 days of treatment there was an absolute decrease in fibrin and necrotic tissue of 37.6 29.9 percentage points in the PA-based hydrogel group and by 16.8 23.0 percentage points in the amorphous hydrogel group .


The absolute increase in the proportion of ulcer area covered by granulation tissue was 36.0 27.4 percentage points in the PA-based hydrogel group and 14.5 22.0 percentage points in the control group .


The differences between the groups were significant ( decrease in fibrin and necrotic tissue P = 0.004 and increase in granulation tissue P = 0.0005 , respectively ) .


In particular , long-standing wounds profited from the treatment with the PA-based hydrogel .


These data suggest that PA-based hydrogel dressings can stimulate normalization of the wound environment , particularly in hard-to-heal ulcers .


To determine the efficacy of a multivalent modified-live virus ( MLV ) vaccine containing a Mannheimia haemolytica toxoid to reduce pneumonia and mortality rate when administered to calves challenge exposed with virulent Bibersteinia trehalosi .


Animals-74 Holstein calves .


Calves were assigned to 2 treatment groups .


Calves in the control group ( n = 36 ) were vaccinated by SC administration of 2 mL of a commercial 5-way MLV vaccine , and calves in the other group ( 38 ) were vaccinated by SC administration of a 2-mL dose of a 5-way MLV vaccine containing M haemolytica toxoid ( day 0 ) .


On day 21 , calves were transtracheally administered B trehalosi .


Serum was obtained for analysis of antibody titers against M haemolytica leukotoxin .


Nasopharyngeal swab specimens were collected from calves 1 day before vaccination ( day -1 ) and challenge exposure ( day 20 ) and cultured to detect bacterial respiratory pathogens .


Clinical scores , rectal temperature , and death attributable to the challenge-exposure organism were recorded for 6 days after challenge exposure .


Remaining calves were euthanized at the end of the study .


Necropsy was performed on all calves , and lung lesion scores were recorded .


Calves vaccinated with the MLV vaccine containing M haemolytica toxoid had significantly lower lung lesion scores , mortality rate , and clinical scores for respiratory disease , compared with results for control calves .


Administration of a multivalent MLV vaccine containing M haemolytica toxoid protected calves against challenge exposure with virulent B trehalosi by reducing the mortality rate , lung lesion scores , and clinical scores for respiratory disease .


To investigate phone follow-up with a semiquantitative urine pregnancy test and symptom checklist as a replacement for universal clinic follow-up after medical abortion .


One thousand four hundred thirty-three women seeking early medical abortion at four hospitals in Vietnam were randomized to clinic or phone follow-up .


Women allocated to clinic follow-up returned to the hospital for confirmation of abortion outcome 2 weeks after mifepristone administration .


Women assigned to phone follow-up completed a semiquantitative pregnancy test at initial visit to determine baseline human chorionic gonadotropin range and again at home 2 weeks later .


Clinic staff called women to review the pregnancy test results and symptom checklist .


Women who screened positive were referred to the clinic .


Effectiveness , feasibility , and acceptability of the follow-up methods were assessed .


The rate of ongoing pregnancy was not significantly different between the two groups ( clinic : 2.7 % phone , 2.5 % , relative risk 0.9 , 95 % confidence interval 0.99-1 .02 ) .


Eighty-five percent of women in the phone group did not need an additional clinic visit .


Phone follow-up was highly effective in screening for ongoing pregnancy with a sensitivity and specificity of 92.8 % and 90.6 % , respectively .


Specificity of the pregnancy test alone ( eg , without the symptom checklist ) was higher ( 95.7 % ) .


Phone follow-up offers a feasible and effective approach to identify women with ongoing pregnancy after early medical abortion .


When used with the semiquantitative pregnancy test , the symptom checklist offered no additional benefit and decreased the specificity of the screening .


Given its effectiveness and ease of use , the semiquantitative pregnancy test alone could replace routine clinic follow-up after early medical abortion .


ClinicalTrials.gov , www.clinicaltrials.gov , NCT01150422 .


I.


Weight loss interventions often present small mean weight changes over time , despite the fact that a substantial proportion of the participants lost more weight .


This effect is often leveled out by the substantial proportion of participants who gained weight during the trial .


The aim of this study is to identify and describe distinct subgroups of participants with different weight change trajectories during and after a weight loss intervention .


We used data from a weight loss intervention that was part of a randomized controlled trial on the preventive effect of a tailor-made weight loss intervention and oral glucosamine sulfate on the incidence of knee osteoarthritis in 407 overweight women aged 50 to 60years .


Latent class growth analysis ( LCGA ) was used to identify subgroups of participants with different weight change trajectories over time .


Using LCGA , we identified three subgroups with different trajectories of weight change , one large group ( n = 298 ) with almost no change over time , and two smaller groups ( both n = 48 ) , of which one represents participants who steadily gained weight over time , whereas the other represents participants who steadily lost weight over time .


Participants that had relatively low body weight around their 40th year of life and that gained weight in the year preceding the study were most likely to belong to the group that lost weight .


LCGA was a suitable method to identify three distinct groups of participants with different trajectories of weight change .


Low body weight at age 40 and weight gain in the year preceding the study were associated with a higher chance of membership of thegroup that lost weight .


It seems weight loss that occurred during this weight loss intervention was mostly recently gained weight .


To analyze the clinical characteristics of a serous retinopathy associated with mitogen-activated protein kinase kinase ( MEK ) inhibition with binimetinib treatment for metastatic cutaneous melanoma ( CM ) and uveal melanoma ( UM ) , and to determine possible pathogenetic mechanisms that may lead to this retinopathy .


Prospective observational , cohort-based , cross-sectional study .


Thirty CM patients and 5 UM patients treated with the MEK inhibitor binimetinib ( CM ) or a combination of binimetinib and the protein kinase C inhibitor sotrastaurin ( UM ) .