In the present multicenter study analyzing a large cohort of healthy subjects and patients with hypertension , the normal range and the clinical relevance of multidirectional systolic parameters to evaluate global LV systolic function have been determined .


Curcumin revealed various health-beneficial properties in numerous studies .


However its bioavailability is low due to its limited intestinal uptake and rapid metabolism .


The aim of our project was to develop novel curcumin formulations with improved oral bioavailability and to study their safety as well as potential sex-differences .


In this crossover study , healthy subjects ( 13 women , 10 men ) took , in random order , a single oral dose of 500 mg curcuminoids as native powder , micronized powder , or liquid micelles .


Blood and urine samples were collected for 24 h and total curcuminoids and safety parameters were quantified .


Based on the area under the plasma concentration-time curve ( AUC ) , the micronized curcumin was 14 - , 5 - , and 9-fold and micellar curcumin 277 - , 114 - , and 185-fold better bioavailable than native curcumin in women , men , and all subjects , respectively .


Thus , women absorbed curcumin more efficiently than men .


All safety parameters remained within the reference ranges following the consumption of all formulations .


Both , the micronized powder and in particular the liquid micellar formulation of curcumin significantly improved its oral bioavailability without altering safety parameters and may thus be ideally suited to deliver curcumin in human intervention trials .


The observed sex differences in curcumin absorption warrant further investigation .


Late adolescence represents a developmental risk period when many youth become involved in multiple forms of high-risk behaviors with adverse consequences .


This study assessed the degree to which two such behaviors , adolescent sexual behaviors and gambling , were associated in a community-based sample with a large African-American presence .


Data are derived from a cohort study .


This study focuses on 427 African-American participants with complete information on gambling and sexual behaviors by age 18 ( 72 % of original cohort ) .


Gambling involvement and related problems were based on responses to the South Oaks Gambling Screen - Revised for Adolescents .


Several questions assessed sexual behaviors , including age of initiation .


Multivariable logistic regression models adjusted for demographics , intervention status , impulsivity , depressive and anxiety symptoms , and alcohol and illegal drug use .


Almost half of the sample ( 49 % , n = 211 ) had gambled at least once before age 18 .


More gamblers than non-gamblers had initiated sexual intercourse by age 18 ( aOR : 2.29 [ 1.16 , 4.52 ] ) .


Among those who had initiated sexual activity , more gamblers than non-gamblers with high impulsivity levels at age 13 ( vs. low impulsivity levels ) had become pregnant or had impregnated someone .


Among those who had initiated sexual activity by age 18 , more male gamblers had impregnated someone by age 18 as compared to female gamblers becoming pregnant .


Gambling and sexual behaviors often co-occur among adolescents .


Such findings prompt the need for the inclusion of gambling , an often overlooked risky behavior , in behavioral prevention/intervention programs targeting adolescents .


Laparoscopic and robotic sacrocolpopexy are widely used for pelvic organ prolapse ( POP ) treatment .


Evidence comparing outcomes and costs is lacking .


We compared costs and clinically relevant outcomes in women randomized to laparoscopic sacrocolpopexy compared with robotic sacrocolpopexy .


Participants with symptomatic stage POP II or greater , including significant apical support loss , were randomized to either laparoscopic or robotic sacrocolpopexy .


We compared surgical costs ( including costs for robot , initial hospitalization ) and rehospitalization within 6 weeks .


Secondary outcomes included postoperative pain , POP quantification , symptom severity and quality of life , and adverse events .


We randomized 78 women ( mean age 59 years ) : laparoscopic ( n = 38 ) and robotic ( n = 40 ) .


The robotic sacrocolpopexy group had higher initial hospital costs ( $ 19,616 compared with $ 11,573 , P < .001 ) and over 6 weeks , hospital costs remained higher for robotic sacrocolpopexy ( $ 20,898 compared with $ 12,170 , P < .001 ) .


When we excluded costs of robot purchase and maintenance , we did not detect a statistical difference in initial day of surgery costs of robotic compared with laparoscopic ( $ 12,586 compared with $ 11,573 ; P = .160 ) or hospital costs over 6 weeks ( $ 13,867 compared with $ 12,170 ; P = .060 ) .


The robotic group had longer operating room times ( 202.8 minutes compared with 178.4 minutes , P = .030 ) and higher pain scores 1 week after surgery ( 3.52.1 compared with 2.62.2 ; P = .044 ) .


There were no group differences in symptom bother by Pelvic Floor Distress Inventory , POP stage , or rate of adverse events .


Costs of robotic sacrocolpopexy are higher than laparoscopic , whereas short-term outcomes and complications are similar .


Primary cost differences resulted from robot maintenance and purchase costs .


Clinicaltrials.gov , www.clinicaltrials.gov , NCT01124916 .


I.


Proton pump inhibitor ( PPI ) increases the risk of decrease in bone mineral density ( BMD ) .


However , whether calcitrol improves this situation is unknown .


The current study investigates the effects of calcitriol on BMD in patients with esomeprazole therapy .


Three hundred and eighty-six participants with gastrointestinal ulcerations were enrolled and randomly assigned into controlled and supplemented groups .


Participants in the controlled group were prescribed esomeprazole ( 20mg/qd ) , while the supplemented group was prescribed esomeprazole ( 20mg/qd ) and calcitriol ( 2.5 g/qd ) .


BMD , serum levels of calcium , carboxy-terminal collagen crosslinks ( CTX ) , and alkaline-phosphatase ( ALP ) were assessed .


( 1 ) No significant between-group difference of age , gender , smoking , previous glucocorticoid use and hemoglobin level was found ; ( 2 ) after 10.60.8 d of PPI therapy , BMD T score in the controlled group was slightly increased compared with initial ( -1.250.08 versus -1.280.06 , p = 0.084 ) , while there was no change in the supplemented group ( -1.250.05 versus -1.260.03 , p = 0.308 ) ; ( 3 ) during study termination , calcium level in the supplemented group was slightly higher than the controlled group ( 2.050.03 mmol/L versus 2.010.05 mmol/L , p = 0.073 ) , while no significant differences of CTX ( 366.5743.71 pg/mL versus 373.1550.23 pg/mL , p = 0.036 ) and ALP were found among these two groups ( 50.479.32 U/L versus 52.2310.45 U/L , p = 0.075 ) .


Patients with gastrointestinal ulcerations with esomeprazole therapy , calcitriol supplement showed no efficacy on BMD changes .


Polycystic ovary syndrome ( PCOS ) is the most common endocrine cause of menstrual irregularities , hirsutism and acne .


Women with PCOS present elevated plasma insulin levels , both fasting and after a glucose load , as an indirect evidence of insulin resistance .


PCOS women may also present hypertension , low levels of HDL cholesterol , hypertriglyceridemia , visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk .


This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women .


PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated : menstrual cycle trend , hirsutism and acne , total cholesterolemia and HDL , triglyceridemia , fibrinogenemia , C-reactive protein , oral glucose tolerance test , glycated hemoglobin , FSH , LH , 17OH-progesterone , 17-estradiol , free and total testosterone , SHBG , DHEA-S , 4-androstenedione and adiponectin .


Treatment with pioglitazone improves the irregularities of menses and hirsutism .


Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases : adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased .


To determine the efficacy in reducing dentin hypersensitivity ( DHS ) of a combined in-office and home-use desensitizing system , each product containing 8 % arginine and calcium carbonate ( Test ) , following a dental scaling procedure , compared to the combination of a conventional prophylactic paste and a potassium nitrate dentifrice ( Control ) , in a group of patients with known dentin hypersensitivity .


An 8-week clinical study , with 50 subjects , was conducted in Piracicaba , So Paulo , Brazil , using a double-blind/two treatment design .


Air blast sensitivity assessments were used to compare the efficacy of the two approaches using both the Schiff scale as well as a Visual Analogue Scale ( VAS ) .


Immediately after prophylaxis , the Test treatment provided significant reduction in DHS when compared to baseline values ( VAS = 26.2 % and Schiff = 29.1 % ) , while for Control treatment this difference was not statistically significant ( VAS = 8.1 % and Schiff = 6.6 % ) .


The comparison between groups after prophylaxis showed a greater DHS reduction for the Test treatment ( P < 0.05 ) .


The reductions in DHS after 2 , 4 and 8 weeks were significant for both groups , however , when considering Schiff scale , the Test treatment provided greater DHS reduction after 2 weeks ( 44.5 % for Test versus 27.7 % for Control ) and 4 weeks ( 55.2 % for Test and 40.5 % for Control ) , while after 8 weeks there was no significant difference between groups ( 71.1 % for Test versus 61.1 % for Control ) .


To compare vision quality following phacoemulsification cataract extraction and implantation of a Big Bag or Akreos Adapt intraocular lens ( IOL ) in patients diagnosed with high myopia complicated with cataract .


This was a randomized prospective control study .


The patients with high myopia .


complicated with cataract , with axial length 28 mm , and corneal astigmatism 1D were enrolled and randomly divided into the Big Bag and Akreos Adapt IOL groups .


All patients underwent phacoemulsification cataract extraction and lens implantation .


At 3 months after surgery , intraocular high-order aberration was measured by a Tracey-iTrace wavefront aberrometer at a pupil diameter of 5 mm in an absolutely dark room and statistically compared between two groups .


The images of the anterior segment of eyes were photographed with a Scheimpflug camera using Penta-cam three-dimensional anterior segment analyzer .


The tilt and decentration of the IOL were calculated by Image-pro plus 6.0 imaging analysis software and statistically compared between two groups .


In total , 127 patients ( 127 eyes ) , including 52 males and 75 females , were enrolled in this study .


The total high-order aberration and coma in the Akreos Adapt group ( 59 eyes ) were significantly higher compared with those in the Big Bag ( P < 0.05 ) .


The clover and spherical aberration did not differ between the two groups ( P > 0.05 ) .


The horizontal and vertical decentration were significantly smaller in the Big Bag lens group than in the Akreos Adapt group ( both P < 0.05 ) , whereas the tilt of IOL did not significantly differ between the two groups ( P > 0.05 ) .


Both Big Bag and Akreos Adapt IOLs possess relatively good intraocular stability implanted in patients with high myopia .


Compared with the Akreos Adapt IOL , the Big Bag IOL presents with smaller intraocular high-order aberration .


Coma is the major difference between the two groups .


We hypothesized that the combination of bevacizumab , carboplatin , and pemetrexed will be an effective first-line regimen in fit , elderly patients with nonsquamous non-small-cell lung cancer .


Treatment-nave , stage IIIB/IV nonsquamous non-small-cell lung cancer patients more than 70 years old with good performance status ( Eastern Cooperative Oncology Group performance status 0-1 ) and adequate organ function were eligible .


Carboplatin area under the curve 6 , pemetrexed 500 mg/m , and bevacizumab 15 mg/kg were administered on day 1 of each 21-day cycle ( up to six cycles ) followed by maintenance pemetrexed and bevacizumab .


The primary end point of 6-month progression-free survival rate of at least 70 % was assessed using a one-stage binomial design .


Quality of life ( QOL ) questionnaires were administered .


Polymorphisms in genes encoding relevant proteins ( drug targets , transport , and metabolism proteins ) were correlated with treatment outcome .


Fifty-seven eligible patients were enrolled .


Median age was 74.5 years .


Median treatment cycles received was 6 .


The most common grade 3 or higher non-hematologic adverse events were fatigue ( 26 % ) and hypertension ( 11 % ) ; 16 % had grade 4 neutropenia and 6.5 % had grade 4 thrombocytopenia .


Three patients experienced grade 3/4 hemorrhagic events ( one pulmonary , two gastrointestinal ) .


Primary end point of PFS6 was 60 % ( 95 % confidence interval [ CI ] : 45.9-73 % ) .


Median PFS was 7.0 months ( 95 % CI : 5.9-10 .1 ) , median overall survival was 13.7 months ( 95 % CI : 9.4-16 .8 ) .


Polymorphic KDR and VEGFA variants correlated with survival and toxicity , respectively .


There was no significant change in overall QOL scores over time .


This regimen is feasible and did not decrease the QOL in this study population .


However , it did not meet the primary efficacy end point .


The aim of this study was to evaluate patient satisfaction and cost in spinal and general anesthesia for lumbar disc surgery .


The study was performed on 66 ASA class I-II patients with one level lumbar disc herniation ( LDH ) .


In this prospective study , patients were assigned randomly to either spinal anesthesia or general anesthesia groups .


Hemodynamic variables , intraoperative opioid requirements , postoperative pain scores and analgesic requirements and complications were recorded .


Patients were handed a questionnaire about the procedure they underwent to determine patient satisfaction .


The costs of preoperative and postoperative anesthesia procedures , medications , and hospitalization were calculated individually .


Spinal anesthesia and general anesthesia were similar concerning hemodynamic stability , first urination time , first mobilization time , postoperative analgesic requirement , and pain .


Patients in group S needed less additional dose of fentanyl intraoperatively than the patients in group G. Patient satisfaction was significantly higher in Group S when compared to Group G. Total cost was higher in Group G compared to Group S.


We conclude that successful LDH surgery can be performed using either anesthesia type .


As long as patients are selected carefully , spinal anesthesia is a safe , comfortable , and a more economical alternative .


This study aims to determine the difference between transcervical resection of septum ( TCRS ) and transcervical incision of septum ( TCIS ) in the improvement of reproductive prognosis .


Women with uterine septum in the Affiliated Hospital of Ningxia Medical University were retrospectively analyzed .


A statistical method was used according to operative time , postoperative menstruation , postoperative pregnancy rate , postoperative term delivery rate , and so on .


Compared with TCRS , the TCIS method decreased operative time , blood loss , and consumption of uterus distension medium .


No statistical difference was observed in operative complications between the two methods .


After TCIS , the incidence of uterine adhesion was low and the degree of endometrial epithelialisation was high by hysteroscopy review .


No statistical difference was observed in residual septum after the operation .


The total pregnancy rate after TCIS was higher than that of TCRS .


However , no statistical difference was observed in early and late pregnancy loss rates , preterm birth rate , and term birth rate .


TCIS exhibits advantages of decreasing operative time , blood loss , and consumption of uterus distension medium .


TCIS can reduce the incidence of uterine adhesion and can promote endometrial epithelialisation , which are the key factors to increase pregnancy rate after operation .


Major depressive disorder has been linked with inflammatory processes , but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial .


The authors tested the hypothesis that C-reactive protein ( CRP ) , a commonly available marker of systemic inflammation , predicts differential response to escitalopram ( a serotonin reuptake inhibitor ) and nortriptyline ( a norepinephrine reuptake inhibitor ) .


The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) study , a multicenter open-label randomized clinical trial .


CRP was measured with a high-sensitivity method in serum samples from 241 adult men and women with major depressive disorder randomly allocated to 12-week treatment with escitalopram ( N = 115 ) or nortriptyline ( N = 126 ) .


The primary outcome measure was the score on the Montgomery-sberg Depression Rating Scale ( MADRS ) , administered weekly .


CRP level at baseline differentially predicted treatment outcome with the two antidepressants ( CRP-drug interaction : = 3.27 , 95 % CI = 1.65 , 4.89 ) .


For patients with low levels of CRP ( < 1 mg/L ) , improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline .


For patients with higher CRP levels , improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram .


CRP and its interaction with medication explained more than 10 % of individual-level variance in treatment outcome .


An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice .


Chronic tension-type headache ( CTTH ) is a chronic syndrome characterized by frequent headache occurring more than 15 days per month .


The intensity and duration of headache pain can be very distressing and disabling on an individuals ' well-being .


The purpose of this study was to examine the applicability of sauna bathing as a new method of treatment for reducing pain in patients with CTTH .


Thirty-seven people who fulfilled the International Headache Society criteria for CTTH were randomly assigned into two groups .


The control group ( n = 20 ) received advice and education while the intervention group ( n = 17 ) received the same advice and attended a sauna regularly for 8 weeks .


Reductions in subjective pain were determined using the numerical pain rating scale ( NPRS ) .


Disturbance in sleep , depression as assessed by Beckman Disability Index ( BDI ) , and Headache Disability Index ( HDI ) were measured .


Mean change in headache intensity significantly differed between the sauna and control group by 1.27 ( 95 % confidence interval , 0.48-2 .07 ; F = 10.17 ; df = 1 , 117 ; p = 0.002 ) .


There was no statistically significant change in duration of headache or improvement in sleep , depression , or HDI between the sauna and control groups .


Regular sauna bathing is a simple , self-directed treatment that is effective for reducing headache pain intensity in CTTH .


Alpha adrenergic drugs are usually used in the treatment of erectile and ejaculatory dysfunction in humans .


The influence of such drugs on the seminal characteristics of wild animals has not been verified ; whereas their impact on the seminal characteristics and erectile and ejaculatory functions of collared peccaries ( Tayassu tajacu ) has already been determined .


This study aimed at investigating and comparing the effects of medetomidine and atipamezole on the seminal variables of collared peccaries undergoing electroejaculation as well as at determining whether these drugs affected the erectile and ejaculatory functions of this species .


A statistically significant difference in sperm concentration was observed between AP ( 100.0 26.0 106 sperm/ml ) and MP ( 220.2 49.8 106 sperm/ml ) ; however , both these treatments did not differ from P treatment ( 180.0 50.7 106 sperm/ml ) .


No statistically significant difference was observed among all treatments with regard to erectile function .


With regard to ejaculation time , no significant difference was observed between the MP and AP treatments ; however , when compared with the P treatment , AP exhibited a significantly higher difference .


When collared peccaries were anesthetized with propofol , neither medetomidine nor atipamezole significantly affected the characteristics of the semen or the erectile function , despite the fact that the AP treatment increased ejaculation time .


Therefore , the data indicate that using propofol alone is an effective anesthetic protocol for collecting semen in collared peccaries .


Other non-injectable anesthetic drugs , such as inhaled anesthetics , may be used in future research to collect semen from peccaries .


The currently proven time window for thrombolysis in ischemic stroke is 4.5 h. Beyond this , the risks and benefits of thrombolysis are uncertain .


To determine whether thrombolysis and reperfusion were beneficial after 4.5 h , we examined clinical and radiological outcomes in patients treated with tissue plasminogen activator or placebo within 4.5-6h , using data from the Echoplanar Imaging Thrombolytic Evaluation Trial .


In the Echoplanar Imaging Thrombolytic Evaluation Trial , ischemic stroke patients presenting three to six-hours after stroke onset were randomized to tissue plasminogen activator or placebo , without knowledge of magnetic resonance imaging results .


This analysis was restricted to patients treated between 4.5 and 6h .


The effect of tissue plasminogen activator and reperfusion on infarct growth between baseline diffusion-weighted imaging and day 90 T2 imaging was assessed , along with good neurological outcome ( 8 point reduction or reaching 0-1 at 90 days on National Institutes of Health Stroke Scale ) and functional outcome ( modified Rankin scale ) .


The effect of tissue plasminogen activator on reperfusion was also analyzed .


Sixty-nine patients were treated 4.5-6h after onset , and infarct growth was assessed in 63 .


Tissue plasminogen activator was associated with lower relative growth ( 94 % vs. 168 % , P = 0.03 ) and a trend to lower absolute growth ( -0.17 ml versus 9.6 ml , P = 0.07 ) .


Reperfusion was increased in the tissue plasminogen activator group ( 58 % versus 25 % , P = 0.03 ) and was associated with increased rates of good neurological ( 86 % versus 28 % P < 0.001 ) and functional ( modified Rankin scale 0-2 73 % versus 34 % , P = 0.01 ) outcomes .


Reperfusion was strongly associated with lower relative ( 80 % versus 189 % , P < 0.001 ) and absolute ( -2.5 ml versus 40ml , P < 0.001 ) infarct growth .


Thrombolysis 4.5-6h after stroke onset reduced infarct growth and increased the rate of reperfusion , which was associated with good neurological and functional outcome .


Tianeptine is widely used for controlling depressive symptoms .


The aim of this study was to evaluate the bioequivalence between the generic ( test ) formulation containing tianeptine sodium 12.5 mg and the branded ( reference ) formulation Stablon with regard to their pharmacokinetic profiles .


A randomized , two-sequence , two-treatment crossover study was conducted in healthy male Korean volunteers .


All of the enrolled subjects were allocated to one of two sequence groups .


They were administered a tablet of the test or reference formulation and then administered the alternative formulation after a 7-day washout period .


The blood samples were taken before dosing and at 0.33 , 0.67 , 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 6 , 8 , and 10 hours after dosing .


The plasma concentrations of tianeptine were analyzed using high-performance liquid chromatography with tandem mass spectrometer .


Tolerability was assessed throughout the study .


The pharmacokinetic parameters were assessed in the 40 subjects who completed the study .


The tianeptine C ( max ) for the test formulation was 283.13 57.58 ng/mL ( mean SD ) and that for the reference formulation was 272.50 59.00 ng/mL .


The AUC ( last ) of tianeptine was 803.24 180.94 ngh/mL for the test formulation and 792.27 180.93 ngh/mL for the reference formulation .


The geometric mean ratio ( % ) of the test to reference formulation was 104.04 ( 90 % CI , 99.66 - 108.61 ) for C ( max ) and 101.30 ( 98.01 - 104.71 ) for AUC ( last ) .


Clinically significant adverse events were not reported during the study .


The test and reference formulations of tianeptine were bioequivalent with regard to the pharmacokinetic parameters of Cmax and AUC ( last ) .


Both formulations were tolerated by all of the participants .


Tinnitus is a result of hyper-activity/hyper-synchrony of auditory neurons coding the tinnitus frequency , which has developed to synchronous mass activity owing the lack of inhibition .


We assume that removal of exactly these frequency components from an auditory stimulus will cause the brain to reorganize around tonotopic regions coding the tinnitus frequency .


Based on this assumption a novel treatment for tonal tinnitus - tailor-made notched music training ( TMNMT ) ( Proc Natl Acad Sci USA 107:1207 -1210 , 2010 ; Ann N Y Acad Sci 1252:253 -258 , 2012 ; Frontiers Syst Neurosci 6:50 , 2012 ) has been introduced and will be tested in this clinical trial on a large number of tinnitus patients .


A randomized controlled trial ( RCT ) in parallel group design will be performed in a double-blinded manner .


The choice of the intervention we are going to apply is based on two `` proof of concept '' studies in humans ( Proc Natl Acad Sci USA 107:1207 -1210 , 2010 ; Ann N Y Acad Sci 1252:253 -258 , 2012 ; Frontiers Syst Neurosci 6:50 , 2012 ; PloS One 6 ( 9 ) : e24685 , 2011 ) and on a recent animal study ( Front Syst Neurosci 7:21 , 2013 ) .


The RCT includes 100 participants with chronic , tonal tinnitus who listened to tailor-made notched music ( TMNM ) for two hours a day for three months .


The effect of TMNMT is assessed by the tinnitus handicap questionnaire and visual analogue scales ( VAS ) measuring perceived tinnitus loudness , distress and handicap .


This is the first randomized controlled trial applying TMNMT on a larger number of patients with tonal tinnitus .


Our data will verify more securely and reliably the effectiveness of this kind of completely non-invasive and low-cost treatment approach on tonal tinnitus .


Current Controlled Trials ISRCTN04840953 .


Actinic damage is responsible for the development of multiple , recurrent non-melanoma skin cancers ( NMSCs ) , including actinic keratoses ( AKs ) .


Photodynamic therapy ( PDT ) and imiquimod cream ( IMIQ ) 5 % are recommended as field-directed treatment options .


To compare efficacy and safety of methyl aminolevulinate ( MAL ) - PDT vs. IMIQ 5 % in the prevention of new NMSCs development patients with field changes .


Patients with field cancerization of the face or scalp were randomized to receive MAL-PDT on one side , and IMIQ 5 % on the mirror field .


The primary endpoint was the number of new lesions on the treated fields during a 12-month follow-up period .


Secondary assessments included adverse events and patient preference .


Forty-four patients completed the study .


MAL-PDT and IMIQ did not differ concerning the primary endpoint , as there was no statistically significant difference in terms of development of new NMSCs at any point of follow-up .


Both treatment regimens were safe and well tolerated .


Patients ' preference based on the procedure , response rates and future choice favoured MAL-PDT .


MAL-PDT and IMIQ 5 % are safe and well-tolerated treatments that equally prevent development of new AKs in patients suffering from field changes .


MAL-PDT treatment appears to be superior in terms of patients ' preference .


DX-2930 is a human monoclonal antibody inhibitor of plasma kallikrein under investigation for long-term prophylaxis of hereditary angioedema .


To assess the safety , tolerability , pharmacokinetics , and pharmacodynamics of DX-2930 in healthy subjects .


A single-center , double-blinded study was performed in 32 healthy subjects randomized 3:1 to receive a single subcutaneous administration of DX-2930 or placebo within 1 of 4 sequential , ascending dose cohorts ( n = 8 each ) : 0.1 , 0.3 , 1.0 , or 3.0 mg/kg .


No dose-limiting toxicity was observed .


Headache was the most commonly reported treatment emergent adverse event ( AE ) , occurring at a rate of 25 % in the DX-2930 - and placebo-treated groups ; none were severe and all resolved .


There were no serious AEs , discontinuations owing to an AE , or deaths .


Two subjects had a severe AE reported as related to treatment by the blinded investigator ; the 2 AEs were asymptomatic creatinine phosphokinase elevations of 902 U/L in 1 subject receiving 0.1 mg/kg DX-2930 and 1,967 U/L in 1 subject receiving placebo .


For the 0.1 - , 0.3 - , 1.0 - , and 3.0-mg / kg dose groups , respectively , mean maximum plasma concentrations were 0.6 , 1.4 , 5.6 , and 14.5 g/mL and mean elimination half-lives were 20.6 , 16.8 , 17.6 , and 21.2 days .


Exploratory biomarker assays , involving exvivo activation of the kallikrein pathway , showed dose - and time-dependent inhibition of plasma kallikrein , with evidence of sustained bioactivity consistent with the pharmacokinetics profile .


A single administration of DX-2930 in healthy subjects up to doses of 3.0 mg/kg was well tolerated without dose-limiting toxicity .


Pharmacokinetic and pharmacodynamic data provide evidence fora long-acting biological effect relevant to long-term prophylaxis for hereditary angioedema with C1-inhibitor deficiency .


ClinicalTrials.gov identifier : NCT01923207 .


The impact of a text messaging-assisted lifestyle weight loss intervention on weight change among overweight adults in Beijing was examined .


It was a 6-month randomized two arm clinical trial .


The control group received a brief advice session after randomization .


The intervention group received three group sessions , five coaching calls , and a daily text message prompting participants to follow predetermined lifestyle goals .


A total of 123 participants were randomized .


At 6 months , controls gained 0.24 0.28 kg ( 0.21 % 0.38 % ) ( NS ) while intervention participants lost 1.6 0.28 kg ( 2.31 % 0.38 % ) ( p < 0.0001 ) .


Intervention participants decreased waist circumference ( WC ) ( -2.69 0.43 cm , p < 0.0001 ) , percent body fat ( % BF ) ( -0.66 % 0.19 % , p = 0.0007 ) , and systolic/diastolic blood pressure ( SBP/DBP ) significantly ( -1.71 1.12 / -3.24 0.87 mmHg ) , while the controls had no change in WC and % BF and increased SBP/DBP by 2.43 1.14 / 1.20 0.88 mmHg ( between groups : p = 0.01 / p = 0.0004 ) .


This text message-assisted lifestyle intervention was effective in reducing weight , WC , % BF , and improving BP .


Coupled with the scalable feature of the intervention , this finding is intriguing in light of the potential reach of the intervention for countries like China where mobile phone penetration is high and the obesity rate continues to rise .


Rheumatoid arthritis ( RA ) is a chronic autoimmune disease where TNF - is a central mediator of inflammation , and is cleaved from the cell surface by TACE/ADAM17 .


This metalloproteinase is also responsible for the release of soluble ( s ) CD163 .


Soluble CD163 reflects macrophage activation .


In RA , sCD163 has been suggested as a marker of disease activity and progression .


Our aim is to investigate sCD163 levels in early RA patients .


Soluble CD163 was measured by ELISA from 150 RA plasma samples from the OPERA trial .


Averaged disease duration was three months , prior to randomisation with methotrexate ( MTX ) and adalimumab ( DMARD+ADA ) or MTX and placebo ( DMARD+PLA ) .


Soluble CD163 levels were evaluated in relation to clinical disease parameters .


Plasma sCD163 at baseline was 2.39 mg/l ( 1.74 mg/l -3.18 mg/l ) , mean ( 95 % CI ) , vs healthy controls : 1.63 mg/l ( 1.54 mg/l - 1.73 mg/l ) , ( p < 0.001 ) .


After three months of treatment sCD163 levels decreased significantly ( average 23.5 % ) in both treatment groups .


Significant incremental sCD163 levels followed withdrawal of ADA after 12 months of treatment .


Baseline sCD163 correlated with CRP and all investigated disease activity markers ( = 0.16-0 .28 , p < 0.05 ) .


In the DMARD+PLA group baseline sCD163 also correlated with CRP during the follow-up period .


Soluble CD163 correlated with disease activity markers in early RA before treatment .


Plasma sCD163 may add to currently available disease measures by specifically reflecting changes in macrophage activity as evidenced by increasing levels following anti-TNF withdrawal , despite maintenance of a stable clinical condition achieved by conventional remedies .


It remains to be determined whether sCD163 is an early predictor of disease flare .


Whether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate .


In this prospective , randomized , controlled trial , we evaluated the effect on survival of elective node dissection ( ipsilateral neck dissection at the time of the primary surgery ) versus therapeutic node dissection ( watchful waiting followed by neck dissection for nodal relapse ) in patients with lateralized stage T1 or T2 oral squamous-cell carcinomas .


Primary and secondary end points were overall survival and disease-free survival , respectively .


Between 2004 and 2014 , a total of 596 patients were enrolled .


As prespecified by the data and safety monitoring committee , this report summarizes results for the first 500 patients ( 245 in the elective-surgery group and 255 in the therapeutic-surgery group ) , with a median follow-up of 39 months .


There were 81 recurrences and 50 deaths in the elective-surgery group and 146 recurrences and 79 deaths in the therapeutic-surgery group .


At 3 years , elective node dissection resulted in an improved rate of overall survival ( 80.0 % ; 95 % confidence interval [ CI ] , 74.1 to 85.8 ) , as compared with therapeutic dissection ( 67.5 % ; 95 % CI , 61.0 to 73.9 ) , for a hazard ratio for death of 0.64 in the elective-surgery group ( 95 % CI , 0.45 to 0.92 ; P = 0.01 by the log-rank test ) .


At that time , patients in the elective-surgery group also had a higher rate of disease-free survival than those in the therapeutic-surgery group ( 69.5 % vs. 45.9 % , P < 0.001 ) .


Elective node dissection was superior in most subgroups without significant interactions .


Rates of adverse events were 6.6 % and 3.6 % in the elective-surgery group and the therapeutic-surgery group , respectively .


Among patients with early-stage oral squamous-cell cancer , elective neck dissection resulted in higher rates of overall and disease-free survival than did therapeutic neck dissection .


( Funded by the Tata Memorial Centre ; ClinicalTrials.gov number , NCT00193765 . )


The goal of this study was to preliminarily test the efficacy of a telephone intervention , Family Intervention : Telephone Tracking , designed to assist stroke survivors and their primary caregivers during the first 6 months after stroke .


Forty-nine stroke survivors and their caregivers were randomly assigned to treatment as usual or treatment as usual plus the telephone intervention .


Global outcomes are reported for health care utilization , family functioning , and general functioning .


Family and general functioning were positively and significantly changed at 3 and 6 months .


Health care utilization was positively and significantly changed at 3 months .


Findings suggest that the model has the potential to decrease health care utilization and improve quality of life for stroke survivors and their caregivers .


Further study is warranted .


Transesophageal echocardiography has become a standard tool for evaluating left ventricular function during cardiac surgery .


However , the image quality varies widely between patients and examinations .


The aim of this study was to investigate the influence of the image quality on 5 commonly used 2-dimensional methods .


Transesophageal real-time 3-dimensional echocardiography ( 3DE ) served as a reference .


Left ventricular function was evaluated in 63 patients with sufficient real-time 3DE image quality .


The image quality was rated using the ratio of the visualized border divided by the total endocardial border .


These ratings were used to generate groups of poor ( 0 % -40 % ) , fair ( 41 % -70 % ) , and good ( 71 % -100 % ) image quality .


The ejection fraction ( EF ) , end-diastolic volume , and end-systolic volume were analyzed by the Simpson method of disks ( biplane and monoplane ) , eyeball method , Teichholz method , and speckle-tracking method .


Furthermore , the fractional area change was determined .


Each correlation with real-time 3DE was evaluated .


Correlations of the EF and volumes , respectively , as determined by long-axis view methods increased with improving image quality : the Simpson biplane method was found to be the most accurate method , with good image quality for the EF ( r = 0.946 ) and volumes ( end-diastolic volume , r = 0.962 ; end-systolic volume , r = 0.989 ) .


Correlations of the EF and fractional area change by short-axis view methods decreased with improving image quality , with the Teichholz EF found to be most accurate with poor ( r = 0.928 ) in contrast to good ( r = 0.699 ) image quality .


With good image quality , the Simpson biplane method is the most accurate 2-dimensional method for assessing the left ventricular EF .


Short-axis view methods , especially the Teichholz method yield better correlations with poor image quality .


The eyeball method was unaffected by image quality .


In this study , we aimed to evaluate the protective effect of tight glucose control during cardiopulmonary bypass on myocardium in adult nondiabetic patients undergoing isolated aortic valve replacement in a prospective and randomized trial .


Sixty-five adult nondiabetic patients undergoing selective isolated aortic valve replacement were enrolled and randomly assigned to an insulin group ( patients received a continuous insulin infusion during surgery ; n = 33 ) or a control group ( patients were not administered insulin unless their blood glucose level exceeded 200 mg/dL ; n = 32 ) .


Cardiac troponin I was assayed preoperatively , and then at 2 , 6 , 12 , 24 , and 48 hours after aortic cross-declamping .


The pre - , intra - , and postoperative relevant data of all selected patients were analyzed .


Tight glucose control reduced postoperative peak release by 48 % for cardiac troponin I compared with the control group ( 0.48 0.12 vs 0.71 0.17 ng/mL ; P < 0.0001 ) .


Patients with continuous insulin infusion had lower peak inotropic score during the first postoperative 24 hours and peak level of blood glucose ( 5.8 2.2 vs 8.2 3.1 g/kg/min ; P < 0.0001 ; 131.9 23.8 vs 191.1 38.5 mg/dL ; P < 0.001 , respectively ) , shorter duration of mechanical ventilation and intensive care unit stay and hospital stay compared with the control group ( 11.6 2.9 hours vs 14.8 3.5 hours ; P = 0.0002 ; 28.4 7.2 hours vs 36.5 7.8 hours ; P < 0.0001 ; 9.4 3.3 days vs 11.5 4.2 days ; P = 0.0283 , respectively ) .


Tight glucose control during cardiopulmonary bypass might provide myocardial protection in adult nondiabetic patients undergoing isolated aortic valve replacement .


The decision of whether to retain or remove a previously placed cervical cerclage in women who subsequently rupture fetal membranes in a premature gestation is controversial and all studies to date are retrospective .


We performed a multicenter randomized controlled trial of removal vs retention of cerclage in these patients to determine whether leaving the cerclage in place prolonged gestation and/or increased the risk of maternal or fetal infection .


A prospective randomized multicenter trial of 27 hospitals was performed .


Patients included were those with cerclage placement at 23 weeks 6 days in singleton or twin pregnancies , with subsequent spontaneous rupture of membranes between 22 weeks 0 days and 32 weeks 6 days .


Patients were randomized to retention or removal of cerclage .


Patients were then expectantly managed and delivered only for evidence of labor , chorioamnionitis , fetal distress , or other medical or obstetrical indications .


Management after 34 weeks was at the clinician 's discretion .


The initial sample size calculation determined that a total of 142 patients should be included but after a second interim analysis , futility calculations determined that the conditional power for showing statistical significance after randomizing 142 patients for the primary outcome of prolonging pregnancy was 22.8 % .


Thus the study was terminated after a total of 56 subjects were randomized with complete data available for analysis , 32 to removal and 24 to retention of cerclage .


There was no statistical significance in primary outcome of prolonging pregnancy by 1 week comparing the 2 groups ( removal 18/32 , 56.3 % ; retention 11/24 , 45.8 % ) P = .59 ; or chorioamnionitis ( removal 8/32 , 25.0 % ; retention 10/24 , 41.7 % ) P = .25 , respectively .


There was no statistical difference in composite neonatal outcomes ( removal 16/33 , 50 % ; retention 17/30 , 56 % ) , fetal/neonatal death ( removal 4/33 , 12 % ; retention 5/30 , 16 % ) ; or gestational age at delivery ( removal mean 200 days ; retention mean 198 days ) .


Statistically significant differences were not seen in prolongation of latency , infection , or composite neonatal outcomes .


However , there was a numerical trend in the direction of less infectious morbidity , with immediate removal of cerclage .


These findings may not have met statistical significance if the original sample size of 142 was obtained , however they provide valuable data suggesting that there may be no advantage to retaining a cerclage after preterm premature rupture of membranes and a possibility of increased infection with cerclage retention .


To compare the speed and accuracy of answering clinical questions using Google versus summary resources .


In 2011 and 2012 , 48 internal medicine interns from two classes at Rutgers University Robert Wood Johnson Medical School , who had been trained to use three evidence-based summary resources , performed four-minute computer searches to answer 10 clinical questions .


Half were randomized to initiate searches for answers to questions 1 to 5 using Google ; the other half initiated searches using a summary resource .


They then crossed over and used the other resource for questions 6 to 10 .


They documented the time spent searching and the resource where the answer was found .


Time to correct response and percentage of correct responses were compared between groups using t test and general estimating equations .


Of 480 questions administered , interns found answers for 393 ( 82 % ) .


Interns initiating searches in Google used a wider variety of resources than those starting with summary resources .


No significant difference was found in mean time to correct response ( 138.5 seconds for Google versus 136.1 seconds for summary resource ; P = .72 ) .


Mean correct response rate was 58.4 % for Google versus 61.5 % for summary resource ( mean difference -3.1 % ; 95 % CI -10.3 % to 4.2 % ; P = .40 ) .


The authors found no significant differences in speed or accuracy between searches initiated using Google versus summary resources .


Although summary resources are considered to provide the highest quality of evidence , improvements to allow for better speed and accuracy are needed .


To assess LASIK flaps made by femtosecond laser and mechanical microkeratome .


Clinical , prospective , randomized , masked study of 32 eyes ( 16 patients ) .


Both eyes of all patients were operated , each patient underwent different techniques for lasik .


Microkeratome Hansatome ( TM ) Bausch & Lomb ( group microkeratome ) was used in one eye and femtosecond laser Femto LDV ( TM ) Ziemer ( group femtosecond ) was used for the fellow eye .


Patients were selected from the Refractive Surgery service of the Eye Hospital of Paran between July 2010 and September 2010 .


Inclusion criteria were myopia less than 6.00 D , astigmatism less than 3.00 D , hyperopia less than 5.00 D , stable refraction over one year , corneal diameter smaller than 11 mm , discontinuation of contact lenses seven days before the preoperative evaluation , corrected visual acuity of at least 20/20 .


Eyes were randomly allocated for each technique .


The studied variables were : visual acuity with and without correction , residual refractive error , high order aberrations , low contrast visual acuity , complications and subjective patient preference .


All studied variables were similar between the two groups .


We could not demonstrate any difference between the studied groups .


Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1 - antihistamine in the morning and a sedating first-generation H1 - antihistamine , usually hydroxyzine , at night to enhance sleep .


But is this belief well founded ?


To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria ( CSU ) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night ( levocetirizine plus hydroxyzine ) vs. levocetirizine 20 mg daily ( levocetirizine monotherapy ) .


In this randomized , double-blind , cross-over study , 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each .


At the end of each treatment period , assessments were made of quality of life ( Chronic Urticaria Quality of Life Questionnaire , CU-Q2 oL ) , severity of urticaria symptoms ( Urticaria Activity Score , UAS ) , sleep disturbance during the night and daytime somnolence .


Both treatments significantly decreased UAS , night-time sleep disturbances and CU-Q2 oL scores ( P < 0001 ) without significant differences between the two .


Compared with baseline , daytime somnolence was significantly reduced by levocetirizine monotherapy ( P = 0006 ) but not by levocetirizine plus hydroxyzine ( P = 0218 ) .


Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy ( P = 0026 ) .


The widespread belief that sleep is aided by the addition of a sedating first-generation H1 - antihistamine , usually hydroxyzine , at night is not supported .


These results are in line with the urticaria guidelines , which state that first-line treatment for urticaria should be new-generation , nonsedating H1 - antihistamines only .


Lignin peroxidase is a cosmetic skin-lightening alternative that breaks down plant cell walls and melanin .


This research examined the topical efficacy of lignin peroxidase in pigment lightening .


Sixty women aged 18 to 65 years with mild to moderate facial dyspigmentation were enrolled for 12 weeks in 2 cohorts .


Cohort 1 applied lignin peroxidase to 1 randomized side of the face and nothing to the opposite side .


Cohort 2 applied lignin peroxidase to 1 facial side and generic hydroquinone to the other .


Investigator , subject , and dermospectrophotometer measurements were obtained .


In cohort 1 , improved skin texture ( P < .001 ) , roughness ( P < .001 ) , and overall appearance ( P = .002 ) was noted at week 2 with lignin peroxidase versus no treatment .


By week 12 , there was a decrease in spot size with lignin peroxidase versus no treatment ( P = .014 ) .


This was confirmed by a statistically significant reduction in melanin scores with the dermospectrophotometer on lignin peroxidase-treated side at weeks 4 , 8 , and 12 ( P = .003 ) and a similar reduction in Melasma Area Severity Index score .


Cohort 2 demonstrated parity between lignin peroxidase and hydroquinone , but lignin peroxidase was statistically superior in skin texture and roughness .


The sample size was limited .


Lignin peroxidase might be an over-the-counter skin-lightening preparation with efficacy parity to hydroquinone .


Increasing evidence suggests that stromal monocarboxylate transporter 4 ( MCT4 ) and carbonic anhydrase IX ( CA IX ) may play key roles in tumor development .


However , their clinical value remains largely unexplored in gastric cancer ( GC ) .


The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC .


Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies .


Expression was correlated with patient clinicopathologic characteristics and survival data .


High stromal MCT4 expression was detected in 72 of 143 ( 50.3 % ) GCs and high CA IX in 74 ( 51.7 % ) .


Both high stromal MCT4 and CA IX were correlated with advanced TNM stage ( p = 0.000 ; p = 0.000 ) .


High CA IX expression was positively related to depth of invasion ( p = 0.022 ) and positive lymph nodes ( p = 0.002 ) as well .


Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival ( OS ) ( HR and 95 % CI = 1.962 , 1.032-3 .729 , p = 0.040 ) and disease free survival ( DFS ) ( HR and 95 % CI = 2.081 , 1.158-3 .741 , p = 0.014 ) of GC patients .


However , high CA IX expression exhibited no significant predictive value .


These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression .


High stromal MCT4 heralds worse outcome of GC patient , suggesting a novel candidate prognostic marker and therapeutic target .


To study the prevalence of H. pylori CagA strain and the activity of associated gastritis in schoolchildren of Tyva Republic ( Russia ) .


The cohorts had been formed out of 1064 native and alien schoolchildren picked up by random in Tyva Republic in the ages from 7 to 17 years .


We determined IgG to H. pylori CagA antigen in serum ( 106 aliens and 112 natives ) .


Out them 59 Tuvins and 72 Europoids with dyspeptic complaints were provided with endoscopic tests including biopsy of mucosa of antrum and stomach body .


We had found ethnic peculiarities in the obtained indices in children , namely higher prevalence of the said strain of H. pylori and the absence of meaningful activity in antral sector and body of stomach in CagA-seropositive native children as compared to alien ones , in whom the activity of antral gastritis was higher than the activity in body of stomach .


To compare isoflurane and propofol for maintenance of anesthesia and quality of recovery in client-owned dogs with intracranial disease undergoing magnetic resonance imaging ( MRI ) .


Prospective , randomized , clinical trial .


Twenty-five client-owned dogs with intracranial pathology , 13 females and 12 males , ages 11months to 13years , weighing between 3.0 and 48.0 kg .


Each dog was randomly assigned to receive propofol or isoflurane for maintenance of anesthesia .


All dogs were not premedicated , were administered propofol intravenously to effect for induction , intubated and mechanically ventilated to maintain an end-tidal carbon dioxide tension 30-35mmHg ( 4.0-4 .7 kPa ) .


Temperature and cardiac output were measured pre - and post-MRI .


Scores for mentation , neurological status , ease of maintenance , and recovery were obtained pre - and post-anesthesia .


Pulse oximetry , end-tidal gases , arterial blood pressure , heart rate ( HR ) and requirements for dopamine administration to maintain mean arterial pressure ( MAP ) > 60mmHg were recorded throughout anesthesia .


End-tidal isoflurane concentration was 0.730.35 % and propofol infusion rate was 292119gkg ( -1 ) minute ( -1 ) .


Cardiac index was higher , while HR was lower , with propofol than isoflurane in dogs younger than 5years , but not in older dogs .


Dogs maintained with isoflurane were 14.7 times more likely to require dopamine than propofol dogs .


Mentation and maintenance scores and temperature were not different .


MAP and diastolic arterial pressure were higher in the propofol group .


Recovery scores were better with propofol , although times to extubation were similar .


Change in neurological score from pre - to post-anesthesia was not different between treatments .


Dogs maintained with propofol during MRI had higher arterial pressures , decreased requirements for dopamine , and better recovery scores , compared to dogs maintained with isoflurane .


Propofol anesthesia offered cardiovascular and recovery advantages over isoflurane during MRI in dogs with intracranial disease in this study .


This study reported on correlates of parental perception of their child 's weight status .


Associations between parental misperception ( i.e. , underestimation of the child 's weight ) and parental intention to improve their child 's overweight-related health behaviors and their child meeting guidelines regarding these behaviors were also investigated .


Baseline data from the population-based ` Be active , eat right study ' were used .


The population for analysis consisted of 630 overweight and 153 obese five year-old children and their parents .


Questionnaires were used to measure parental perception of the child 's weight status , correlates of misperception ( i.e. , child age , child gender , child BMI , parental age , parental gender , parental country of birth , parental educational level and parental weight status ) , overweight-related health behaviors ( i.e. , child playing outside , having breakfast , drinking sweet beverages , and watching TV ) , and parental intention to improve these behaviors .


Height and weight were measured using standardized protocols .


Multivariable logistic regression analyses were performed .


In total , 44.40 % of the parents misperceived their child 's weight status .


Parental misperception was associated with lower child BMI , the parent being the father , a foreign parental country of birth , and a lower parental education level ( p < 0.05 ) .


Parental misperception was not associated with parental intention to improve child overweight-related health behavior , nor with child meeting the guidelines of these behaviors .


This study showed that almost half of the parents with an overweight or obese child misperceived their child 's weight status .


A correct parental perception may be a small stepping-stone in improving the health of overweight and obese children .


To assess the beneficial effects of the components of lifestyle intervention in reducing incidence of diabetes in Asian Indian men with impaired glucose tolerance ( IGT ) in India .


This analysis was based on a 2 year prospective , randomized controlled primary prevention trial in a cohort of Asian Indian men with IGT ( n = 537 ) ( Clinical Trial No : NCT00819455 ) .


Intervention and control groups were given standard care advice at baseline .


Additionally , the intervention group received frequent , mobile phone based text message reminders on healthy lifestyle principles .


Dietary intake and physical activity habits were recorded by validated questionnaires .


The lifestyle goals were : reductions in consumption of carbohydrates , oil , portion size and body mass index of at least 1 unit ( 1 kg/m ( 2 ) ) from baseline and maintenance of good physical activity .


The association between diabetes and lifestyle goals achieved was assessed using multiple logistic regression analyses .


Changes in insulin sensitivity ( Matsuda 's insulin sensitivity index ) and oral disposition index during the follow-up were assessed .


At the end of the study , 123 ( 23.8 % ) participants developed diabetes .


The mean lifestyle score was higher in the intervention group compared with control ( 2.59 1.13 vs. 2.28 1.17 ; P = 0.002 ) .


Among the 5 lifestyle variables , significant improvements in the 3 dietary goal were seen with intervention .


Concomitant improvement in insulin sensitivity and oral disposition index was noted .


Higher lifestyle score was associated with lower risk of developing diabetes ( odds ratio : 0.54 [ 95 % CI : 0.44-0 .70 ] ; P < 0.0001 ) .


Beneficial effects of intervention were associated with increased compliance to lifestyle goals .


The plausible mechanism is through improvement in insulin sensitivity and beta cell preservation .


To investigate the safety and efficay of low-dose furosemide in the correction of oliguria in the patients undergoing gynecologic surgery .


A total of 120 patients , aged between 20 to 50 years old , who were scheduled to receive elective gynecological open surgery under general anesthesia , were randomly divided into 3 groups : the control group , furosemide 0.05 mg/kg ( F0 .5 ) group and furosemide 0.1 mg/kg ( F1 ) group ( n = 40 ) .


During surgery , blood volume and blood pressure was maintained in the normal range .


The urine volume was recorded every 30 minutes .


Oliguria was defined as the urine volume less than 0.5 mL / ( kg .


h ) , When oliguria was observed , flurosemide or saline was given to the patients based on the enrollment status .


If the patients were still oliguric 30 min later , the treatment was repeated .


The total time of surgery , net fluid infusion volume , urine volume per unit time per body weight at the completion of surgery , the incidence of intraoperative oliguria , the total amount of furosemide and the average specific gravity of urine were recorded .


There was no statistically significant difference in sex , age , fasting time , the total time of surgery and intraoperative net fluid infusion volume among the three groups ( P > 0.05 ) .


The urine volume per unit time per body weight in control group was significantly lower than that of the other two groups ( P < 0.01 ) .


The incidence of intraoperative oliguria in the three groups ( control , low dose , high dose groups ) were 52.5 % , 12.5 % and 0 % , respectively ( P < 0.01 ) .


Low-dose of furosemide could maintain normal urine volume and specific gravity of urine during gynecological surgery .


Ebola virus and Marburg virus cause serious disease outbreaks with high case fatality rates .


We aimed to assess the safety and immunogenicity of two investigational DNA vaccines , one ( EBO vaccine ) encoding Ebola virus Zaire and Sudan glycoproteins and one ( MAR ) encoding Marburg virus glycoprotein .


RV 247 was a phase 1b , double-blinded , randomised , placebo-controlled clinical trial in Kampala , Uganda to examine the safety and immunogenicity of the EBO and MAR vaccines given individually and concomitantly .


Healthy adult volunteers aged 18-50 years were randomly assigned ( 5:1 ) to receive three injections of vaccine or placebo at weeks 0 , 4 , and 8 , with vaccine allocations divided equally between three active vaccine groups : EBO vaccine only , MAR vaccine only , and both vaccines .


The primary study objective was to investigate the safety and tolerability of the vaccines , as assessed by local and systemic reactogenicity and adverse events .


We also assessed immunogenicity on the basis of antibody responses ( ELISA ) and T-cell responses ( ELISpot and intracellular cytokine staining assays ) 4 weeks after the third injection .


Participants and investigators were masked to group assignment .


Analysis was based on the intention-to-treat principle .


This trial is registered at ClinicalTrials.gov , number NCT00997607 .


108 participants were enrolled into the study between Nov 2 , 2009 , and April 15 , 2010 .


All 108 participants received at least one study injection ( including 100 who completed the injection schedule ) and were included in safety and tolerability analyses ; 107 for whom data were available were included in the immunogenicity analyses .


Study injections were well tolerated , with no significant differences in local or systemic reactions between groups .


The vaccines elicited antibody and T-cell responses specific to the glycoproteins received and we detected no differences between the separate and concomitant use of the two vaccines .


17 of 30 ( 57 % , 95 % CI 37-75 ) participants in the EBO vaccine group had an antibody response to the Ebola Zaire glycoprotein , as did 14 of 30 ( 47 % , 28-66 ) in the group that received both vaccines .


15 of 30 ( 50 % , 31-69 ) participants in the EBO vaccine group had an antibody response to the Ebola Sudan glycoprotein , as did 15 of 30 ( 50 % , 31-69 ) in the group that received both vaccines .


Nine of 29 ( 31 % , 15-51 ) participants in the MAR vaccine groups had an antibody response to the Marburg glycoprotein , as did seven of 30 ( 23 % , 10-42 ) in the group that received both vaccines .


19 of 30 ( 63 % , 44-80 ) participants in the EBO vaccine group had a T-cell response to the Ebola Zaire glycoprotein , as did 10 of 30 ( 33 % , 17-53 ) in the group that received both vaccines .


13 of 30 ( 43 % , 25-63 ) participants in the EBO vaccine group had a T-cell response to the Ebola Sudan glycoprotein , as did 10 of 30 ( 33 % , 17-53 ) in the group that received both vaccines .


15 of 29 ( 52 % , 33-71 ) participants in the MAR vaccine group had a T-cell response to the Marburg glycoprotein , as did 13 of 30 ( 43 % , 25-63 ) in the group that received both vaccines .


This study is the first Ebola or Marburg vaccine trial done in Africa , and the results show that , given separately or together , both vaccines were well tolerated and elicited antigen-specific humoral and cellular immune responses .


These findings have contributed to the accelerated development of more potent Ebola virus vaccines that encode the same wild-type glycoprotein antigens as the EBO vaccine , which are being assessed during the 2014 Ebola virus disease outbreak in west Africa .


US Department of Defense Infectious Disease Clinical Research Program and US National Institutes of Health Intramural Research Program .


Cure of lung cancer is impossible without local tumour control .


This can be compromised by accelerated repopulation of tumour cells during radiotherapy and chemotherapy .


A strategy to minimise accelerated repopulation might improve local control .


We investigated whether concurrent chemo-radiotherapy could be given safely over four weeks .


We conducted a randomised phase II trial in which patients with inoperable Stage III Non-Small Cell Lung Cancer ( NSCLC ) received a radical radiation dose over four weeks rather than conventional fractionation .


Treatment was given either sequentially or concurrently with three to four cycles of cisplatinum and vinorelbine .


130 patients with inoperable stage III NSCLC and PS 0-1 were randomised to receive cisplatinum and vinorelbine with either sequential or concurrent chemo-radiation using 55Gy in 20 fractions over four weeks .


The primary end-point was treatment related mortality .


Secondary end-points were toxicity and survival .


Treatment related mortality was : 2.9 % ( exact 95 % confidence interval [ CI ] 0.36-10 .2 % ) and 1.7 % ( exact 95 % CI 0.043-9 .1 % ) for the Concurrent and Sequential group respectively ; relative risk ( RR ) 1.25 ; ( 95 % CI 0.55 , 2.84 ) .


Toxicity was similar between arms ; grade 3 or worse oesophagitis was 8.8 % versus 8.5 % ; RR 1.02 ( 95 % CI 0.58 , 1.79 ) .


OS HR was 0.92 ; 95 % CI ( 0.60-1 .39 ; p = 0.682 ) .


The 2 year overall survival rates were : 50 % versus 46 % ; RR 1.06 ( 95 % CI 0.77 , 1.46 ) for Concurrent versus Sequential .


A strategy to minimise the effects of accelerated repopulation using accelerated hypofractionated radiotherapy with chemotherapy is feasible , and reasonably safe for patients with stage III NSCLC .


The reported two year survival is promising and suggests that a four week regime of radiotherapy should be compared with conventionally fractionated radiotherapy in an adequately powered randomised controlled phase III trial .


In this paper , we describe a trial protocol used to assess feasibility related to : study administration ( recruitment , randomization , retention , compliance , eligibility criteria , suitability of protocol instructions and data collection questionnaires ) ; resource and data management ( suitability of site , time and budget allocation , management of personnel and data ) ; intervention fidelity ( treatment dose , violations ) ; and effect size .


Pressure injury can lead to increases in hospital length of stay and cost .


The sacrum is identified as one of the most common anatomical pressure injury sites for hospitalized patients .


Silicone foam border dressings have been proposed as one strategy to reduce pressure injury incidence ; however , rigorous testing of benefit in a general medical-surgical population is required .


Randomized controlled trial .


Eighty patients will be recruited after assessment of high risk of pressure injury in a large tertiary hospital in south-east Queensland , Australia .


Eligible , consenting participants will be randomly allocated to either a control group ( routine care ) or an intervention group ( routine care and a sacral prophylactic dressing ) .


The primary outcomes comprise feasibility criteria as identified above .


The secondary measure is the presence and severity of sacral pressure injury via blind assessment of digital photographs .


Research ethics approval was received in October 2013 .


Prophylactic dressings applied to the sacrum may be an effective method for reducing pressure injury in high-risk general medical-surgical patients .


However , more rigorous studies to confirm benefit are required .


This pilot study will determine the feasibility and effect size to inform a larger randomized controlled trial .


Group cognitive behavioural intervention ( CBI ) is effective in reducing low-back pain and disability in comparison to advice in primary care .


The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance .


In this multicentre trial , 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices .


Participants were randomised to advice ( control n = 233 ) or advice plus CBI ( n = 468 ) .


Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment .


We estimated the complier average causal effect ( CACE ) of treatment .


Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat ( ITT ) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire ( CACE : 1.6 points , 95 % CI 0.51 to 2.74 ; ITT : 1.3 points , 95 % CI 0.55 to 2.07 ) , the Modified Von Korff disability score ( CACE : 12.1 points , 95 % CI 6.07 to 18.17 ; ITT : 8.6 points , 95 % CI 4.58 to 12.64 ) and the Modified von Korff pain score ( CACE : 10.4 points , 95 % CI 4.64 to 16.10 ; ITT : 7.0 points , 95 % CI 3.26 to 10.74 ) .


People who were non-compliant were younger and had higher pain scores at randomisation .


Treatment compliance is important in the effectiveness of group CBI .


Younger people and those with more pain are at greater risk of non-compliance .


Current Controlled Trials ISRCTN54717854 .


The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs ( NSAIDs ) .


Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals , thus enhancing the protective function of the gastric mucosa .


However , it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy .


The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment .


We studied 479 patients who required continuous NSAID treatment .


The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 g of misoprostol three times per day for 12 weeks .


The primary endpoint of the analysis was the occurrence rate of gastric ulcers , as determined by endoscopy after 12 weeks of therapy .


Of the 479 patients in the study , 242 received rebamipide , and 237 received misoprostol .


Ultimately , 44 patients ( 18.6 % ) withdrew from the misoprostol group and 25 patients ( 10.3 % ) withdrew from the rebamipide group .


There was a significant difference in withdrawal rate between the two groups ( p = 0.0103 ) .


The per protocol analysis set was not valid because of the dropout rate of the misoprostol group ; thus , the intention to treat ( ITT ) analysis set is the main set for the efficacy analysis in this study .


After 12 weeks , the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups ( 20.3 % vs 21.9 % , p = 0.6497 ) according to ITT analysis .


In addition , the therapeutic failure rate was similar in the rebamipide and misoprostol groups ( 13.6 % vs 13.1 % , p = 0.8580 ) .


The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group ( p = 0.0002 ) .


The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group ( p = 0.0258 ) .


Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration .


When the possibility of poor compliance and the potential adverse effects of misoprostol are considered , rebamipide appears to be a clinically effective and safe alternative .


The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children ( 7-11 years ) and adolescents ( 12-17 years ) with major depressive disorder ( MDD ) .


Patients ( n = 337 ) in this 36 week study ( 10 week acute and 26 week extension treatment ) received duloxetine ( 60-120mg once daily [ QD ] , n = 117 ) , fluoxetine ( 20-40mg QD , n = 117 ) , or placebo ( n = 103 ) .


Measures included : Children 's Depression Rating Scale-Revised ( CDRS-R ) , treatment-emergent adverse events ( TEAEs ) , and Columbia-Suicide Severity Rating Scale ( C-SSRS ) .


Neither active drug ( duloxetine or fluoxetine ) separated significantly ( p < 0.05 ) from placebo on mean change from baseline to end-point ( 10 weeks ) on the CDRS-R total score .


There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs ( SAEs ) , total TEAEs , or discontinuation for AE during acute treatment .


There were no completed suicides or deaths , and no clinically significant electrocardiogram ( ECG ) abnormalities observed during the study .


One fluoxetine and one duloxetine patient experienced alanine aminotransferase ( ALT ) three or more times the upper limit of normal , which resolved during the study .


A total of 8 ( 7.1 % ) duloxetine patients , 7 ( 6.8 % ) placebo patients , and 9 ( 8.0 % ) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment .


Of the patients with suicidal ideation at baseline , 15/19 ( 79 % ) duloxetine , 19/19 ( 100 % ) placebo , and 16/19 ( 84 % ) fluoxetine had improvement in suicidal ideation at end-point during acute treatment .


One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study .


Trial results were inconclusive , as neither the investigational drug ( duloxetine ) nor the active control ( fluoxetine ) separated from placebo on the CDRS-R at 10 weeks .


No new duloxetine safety signals were identified relative to those seen in adults .


Clinical Trial Registry Number : NCT00849901 .


The 2014 Eighth Joint National Committee panel recommendations for management of high blood pressure ( BP ) recommend a systolic BP threshold for initiation of drug therapy and a therapeutic target of < 150 mm Hg in those60 years of age , a departure from prior recommendations of < 140 mm Hg .


However , it is not known whether this is an optimal choice , especially for the large population with coronary artery disease ( CAD ) .


This study sought to evaluate optimal BP in patients60 years of age .


Patients 60 years of age or older with CAD and baseline systolic BP > 150 mm Hg randomized to a treatment strategy on the basis of either atenolol/hydrochlorothiazide or verapamil-SR ( sustained release ) / trandolapril in INVEST ( INternational VErapamil SR Trandolapril STudy ) were categorized into 3 groups on the basis of achieved on-treatment systolic BP : group 1 , < 140 mm Hg ; group 2 , 140 to < 150 mm Hg ; and group 3,150 mm Hg .


Primary outcome was first occurrence of all-cause death , nonfatal myocardial infarction ( MI ) , or nonfatal stroke .


Secondary outcomes were all-cause mortality , cardiovascular mortality , total MI , nonfatal MI , total stroke , nonfatal stroke , heart failure , or revascularization , tabulated separately .


Outcomes for each group were compared in unadjusted and multiple propensity score-adjusted models .


Among 8,354 patients included in this analysis with an accumulated 22,308 patient-years of follow-up , 4,787 ( 57 % ) achieved systolic BP of < 140 mm Hg ( group 1 ) , 1,747 ( 21 % ) achieved systolic BP of 140 to < 150 mm Hg ( group 2 ) , and 1,820 ( 22 % ) achieved systolic BP of150 mm Hg ( group 3 ) .


In unadjusted models , group 1 had the lowest rates of the primary outcome ( 9.36 % vs. 12.71 % vs. 21.32 % ; p < 0.0001 ) , all-cause mortality ( 7.92 % vs. 10.07 % vs. 16.81 % ; p < 0.0001 ) , cardiovascular mortality ( 3.26 % vs. 4.58 % vs. 7.80 % ; p < 0.0001 ) , MI ( 1.07 % vs. 1.03 % vs. 2.91 % ; p < 0.0001 ) , total stroke ( 1.19 % vs. 2.63 % vs. 3.85 % ; p < 0.0001 ) , and nonfatal stroke ( 0.86 % vs 1.89 % vs 2.86 % ; p < 0.0001 ) compared with groups 2 and 3 , respectively .


In multiple propensity score-adjusted models , compared with the reference group of < 140 mm Hg ( group 1 ) , the risk of cardiovascular mortality ( adjusted hazard ratio [ HR ] : 1.34 ; 95 % confidence interval [ CI ] : 1.01 to 1.77 ; p = 0.04 ) , total stroke ( adjusted HR : 1.89 ; 95 % CI : 1.26 to 2.82 ; p = 0.002 ) and nonfatal stroke ( adjusted HR : 1.70 ; 95 % CI : 1.06 to 2.72 ; p = 0.03 ) was increased in the group with BP of 140 to < 150 mm Hg , whereas the risk of primary outcome , all-cause mortality , cardiovascular mortality , total MI , nonfatal MI , total stroke , and nonfatal stroke was increased in the group with BP150 mm Hg .


In hypertensive patients with CAD who are60 years of age , achieving a BP target of 140 to < 150mm Hg as recommended by the JNC-8 panel was associated with less benefit than the previously recommended target of < 140 mm Hg .


After cardiac surgery , patients receive large amounts of fluid in the Intensive Care Unit ( ICU ) .


We plan to conduct a multi-centre randomised controlled trial , of a conservative fluid regime , in patients after cardiac surgery , and have reported results of a feasibility study that evaluated efficacy and safety of the proposed regime .


After ethical approval , a single-centre , prospectively randomised interventional study was undertaken .


Participants were randomised to either usual care , or to a protocolised algorithm , utilising stroke volume variation , to guide fluid administration to patients who were deemed to have inadequate cardiac output and were likely to be volume responsive .


The study protocol lasted from ICU admission to de-sedation or 24 h , whichever occurred first .


We randomised 144 subjects over 9 months .


Less bolus fluid and less total overall fluid volume was administered in the intervention group ( median ( IQR ) 1620 ml ( 500-3410 ) and 2525 ml ( 1440-5250 ; P < 0.001 ) , compared with the usual care group ( 2050 ml ( 910-4280 ) and 2980 ml ( 2070-6580 ; P = 0.001 ) , from ICU admission to extubation .


There was no significant difference in incidence of acute kidney injury or the average amount of fluid administered to the usual care group at the beginning compared with the end of the study .


It is both possible and safe to achieve a significant reduction in the amount of fluid administered to patients , allocated to a conservative fluid protocol .


These results suggest that a planned multi-centre study is both justified and feasible .


Australia New Zealand Clinical Trials Registry www.anzctr.org.au ( ACTRN12612000754842 ) .


Dexmedetomidine can prolong the duration of local anesthetics , but the effect of retrobulbar dexmedetomidine on the potency of ropivacaine for retrobulbar block has not been investigated .


Our study was designed to determine the effect of retrobulbar dexmedetomidine on ropivacaine for retrobulbar block in children .


A group of 90 children aged 10-16 years scheduled for vitreoretinal surgery who received retrobulbar block were randomly assigned to 1 of 3 groups : group L ( retrobulbar ropivacaine ) , group LD1 ( ropivacaine plus 0.5 g.kg-1 dexmedetomidine ) , or group LD2 ( ropivacaine plus 1 g.kg-1 dexmedetomidine ) .


The minimum local anesthetic concentration ( MLAC ) was determined according to a Dixon-Massey protocol .


The primary endpoint of the study was MLAC .


Secondary outcomes were duration of postoperative analgesia , postoperative pain scores , dexmedetomidine side effects , and time to hospital discharge .


The MLAC values of retrobulbar ropivacaine were 0.314 % , 0.259 % , and 0.246 % in groups L , LD1 , and LD2 , respectively .


The median ( interquartile range ) durations of analgesia in the postoperative period were 66 ( 54-117 ) , 89 ( 40-157 ) , and 168 ( 120-194 ) minutes in groups L , LD1 , and LD2 , respectively ( L vs LD1 or LD2 , p < 0.05 ) .


Wake-up time was significantly increased in groups LD1 and LD2 .


Retrobulbar dexmedetomidine reduces the MLAC values of ropivacaine and improves postoperative analgesia in children without any neurologic side effects .


Empathy improves our ability to communicate in social interactions and motivates prosocial behavior .


The neuropeptides arginine vasopressin and oxytocin play key roles in socioemotional processes such as pair bonding and parental care , which suggests that they may be involved in empathic processing .


We investigated how vasopressin and oxytocin affect empathic responding in a randomized , double-blind , placebo controlled , between-subjects study design .


We also examined the moderating role of parental warmth , as reported in the early family environment , on empathic responding following vasopressin , oxytocin , or placebo administration .


Among participants who reported higher levels of paternal warmth ( but not maternal warmth ) , vasopressin ( vs. placebo and oxytocin ) increased ratings of empathic concern after viewing distressing and uplifting videos .


No main or interaction effects were found for individuals who received oxytocin .


Vasopressin has a role in enhancing empathy among individuals who received higher levels of paternal warmth .


NCT01680718 .


Levels of stool fatty acid soaps and beneficial bacteria differ between formula-fed and breast-fed infants ; addition of specific formula ingredients may reduce these differences .


This study evaluated the effects of a term infant formula containing high sn-2 palmitate term infant formula ( sn-2 ) or an identical formula supplemented with oligofructose ( OF ) at 2 concentrations ( sn-2 +3 g/L OF , sn-2 +5 g/L OF ) on stool composition , stool characteristics , and fecal bifidobacteria .


Healthy , term formula-fed infants 7 to 14 days old ( n = 300 ) were randomized in a double-blind manner to receive standard formula ( control ) , sn-2 , sn-2 +3 g/L OF , or sn-2 +5 g/L OF for 8 weeks .


Human milk ( HM ) - fed infants ( n = 75 ) were studied in parallel .


Stool samples were collected from all subjects at week 8 for fatty acid soaps and mineral content , and from a subset at baseline and week 8 for bifidobacteria .


Stool characteristics were assessed via 3-day diary .


The sn-2 group had 46 % less stool soap palmitate ( P < 0.001 ) and softer stools than control ( 20 % more mushy soft stools , P = 0.026 ; 50 % fewer formed stools , P = 0.003 ) .


Addition of OF resulted in even fewer formed stools versus control ( 65 % fewer for sn-2 +3 g/L OF , 79 % fewer for sn-2 +5 g/L OF ) , with 5 g/L OF more closely resembling that of HM-fed infants .


Both sn-2 ( P < 0.05 ) and sn-2 with OF groups ( P < 0.01 ) had significantly higher fecal bifidobacteria concentrations than control at week 8 , not differing from HM-fed infants .


High sn-2-palmitate formulas led to reduced stool soaps , softer stools , and increased bifidobacteria , whereas addition of OF further improved stool consistency .


Those modifications brought outcomes in formula-fed infants closer to that in HM-fed infants .


Targeting the epidermal-growth-factor-receptor ( EGFR ) in non-small cell lung cancer ( NSCLC ) is an established treatment option with less toxicity compared to conventional chemotherapy .


This study was undertaken to determine whether Erlotinib is non-inferior compared to chemotherapy as a first-line therapy in unselected elderly patients .


Patients 70 years with untreated , metastatic NSCLC were randomized to Erlotinib ( E ) , 150 mg/day or Carboplatin ( AUC5 ) plus Vinorelbine ( 25mg/m ( 2 ) on days 1 and 8 ) every three weeks ( CV ) .


Primary endpoint was progression-free survival ( PFS ) .


After progression , crossover was strongly recommended .


Secondary endpoints were duration of response , 1-year survival , overall survival ( OS ) , response rate ( RR ) , quality of life ( FACT-L ) , assessment of comorbidities by simplified comorbidity score ( SCS ) and Charlsons ' comorbidity score , safety and assessment of molecular markers .


Between June 2006 and August 2008 284 pts were randomized to E ( 144 ) and CV ( 140 ) .


PFS was significantly inferior with E ( median PFS 2.4 versus 4.6 months [ HR 1.6 , 75 % CI 1.22-2 .09 , p : 0.0005 ] ) as well as RR ( 7.8 % v 28.3 % , p : 0.0001 ) .


No significant difference in OS appeared ( median E : 7.3 months versus CV : 8.4 months , HR : 1.24 [ 75 % CI 0.9-1 .71 ] ) .


In never smokers PFS ( median PFS : 3.7 v 4.3 m , E v CV , HR 0.72 , 75 % CI 0.35-1 .48 ) and OS ( median : 16.5 versus 17 months , HR 0.99 [ 75 % CI 0.38-2 .57 ] ) were comparable .


More skin toxicity and diarrhea was seen with E compared to more myelotoxicity , neurotoxicity and constipation with CV .


Less severe adverse events were observed with E ( 81 v 102 , E v CV ) .


CV had an increased efficacy compared with E in an unselected population of elderly patients with advanced NSCLC .


In the BRIM-3 trial , vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF ( V600 ) mutation-positive melanoma .


We present an extended follow-up analysis of the total population and in the BRAF ( V600E ) and BRAF ( V600K ) mutation subgroups .


Patients older than 18 years , with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF ( V600 ) mutations were eligible .


Patients also had to have a life expectancy of at least 3 months , an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 , and adequate haematological , hepatic , and renal function .


Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib ( 960 mg orally twice daily ) or dacarbazine ( 1000 mg/m ( 2 ) of body surface area intravenously every 3 weeks ) .


Coprimary endpoints were overall survival and progression-free survival , analysed in the intention-to-treat population ( n = 675 ) , with data censored at crossover .


A sensitivity analysis was done .


This trial is registered with ClinicalTrials.gov , NCT01006980 .


675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4 , 2010 , and Dec 16 , 2010.337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine .


Median follow-up was 125 months ( IQR 77-160 ) on vemurafenib and 95 months ( 31-147 ) on dacarbazine .


83 ( 25 % ) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib .


Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group ( 136 months [ 95 % CI 120-152 ] vs 97 months [ 79-128 ] ; hazard ratio [ HR ] 070 [ 95 % CI 057-087 ] ; p = 00008 ) , as was median progression-free survival ( 69 months [ 95 % CI 61-70 ] vs 16 months [ 16-21 ] ; HR 038 [ 95 % CI 032-046 ] ; p < 00001 ) .


For the 598 ( 91 % ) patients with BRAF ( V600E ) disease , median overall survival in the vemurafenib group was 133 months ( 95 % CI 119-149 ) compared with 100 months ( 80-140 ) in the dacarbazine group ( HR 075 [ 95 % CI 060-093 ] ; p = 00085 ) ; median progression-free survival was 69 months ( 95 % CI 62-70 ) and 16 months ( 16-21 ) , respectively ( HR 039 [ 95 % CI 033-047 ] ; p < 00001 ) .


For the 57 ( 9 % ) patients with BRAF ( V600K ) disease , median overall survival in the vemurafenib group was 145 months ( 95 % CI 112-not estimable ) compared with 76 months ( 61-166 ) in the dacarbazine group ( HR 043 [ 95 % CI 021-090 ] ; p = 0024 ) ; median progression-free survival was 59 months ( 95 % CI 44-90 ) and 17 months ( 14-29 ) , respectively ( HR 030 [ 95 % CI 016-056 ] ; p < 00001 ) .


The most frequent grade 3-4 events were cutaneous squamous-cell carcinoma ( 65 [ 19 % ] of 337 patients ) and keratoacanthomas ( 34 [ 10 % ] ) , rash ( 30 [ 9 % ] ) , and abnormal liver function tests ( 38 [ 11 % ] ) in the vemurafenib group and neutropenia ( 26 [ 9 % ] of 287 patients ) in the dacarbazine group .


Eight ( 2 % ) patients in the vemurafenib group and seven ( 2 % ) in the dacarbazine group had grade 5 events .


Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF ( V600E ) mutation and in patients with the less common BRAF ( V600K ) mutation .


F Hoffmann-La Roche-Genentech .


This study investigated the effect of exposure to television food advertising on accessibility of food-related cognitions and motivation to eat .


We initially developed a word stem completion task to measure accessibility of food-related cognitions .


In two subsequent experiments , 160 female undergraduate students ( Experiment 1 ) and 124 overweight or obese community-dwelling women ( Experiment 2 ) viewed a series of television commercials advertising either food or non-food products .


They then completed the word stem task and also rated their desire to eat .


Exposure to televised food advertisements led to the completion of word stems with more food - and eating-related words in both experiments .


It also increased self-reported desire to eat , but only for overweight and obese individuals ( Experiment 2 ) .


In both samples , there was a positive association between accessibility of food-related cognitions and reported desire to eat , following priming with television food advertisements .


We conclude that an increased activation of food-related cognitions may provide a mechanism for the link between food advertising and consumption .


This has implications for tackling pathological ( over ) eating .


The study aims to determine whether the route of insulin administration influences glycaemic variability and inflammatory or neurohormonal markers in patients with type 2 diabetes and congestive heart failure ( CHF ) exacerbation .


Patients ( n = 65 ) were randomized to intravenous ( IV ) insulin ( duration 48 h ) or subcutaneous ( SQ ) insulin .


Inflammatory cytokines and markers of lipid oxidation , high-frequency heart rate variability ( n = 27 ) and cardiac impedance ( pre-ejection period , n = 28 ) were used to estimate parasympathetic and sympathetic tone in patients with valid cardiac data .


Glycaemic variability was measured using a continuous glucose monitor .


Mean glucose was lower ( 7.71.2 vs 9.42.7 mmol/L , p = 0.004 ) , coefficient of variation was higher ( p = 0.03 ) and glycaemic lability index was similar on day 1 in the IV group compared with the SQ group , but groups were similar by day 2 .


The IV group had more confirmed hypoglycaemia ( p = 0.005 ) .


There were no differences in hospital readmission or hospital length of stay between groups .


There were no differences in CHF biomarkers , heart rate variability or pre-ejection period between groups .


Increasing log glycaemic lability index was associated with lower on-treatment pre-ejection period ( p = 0.03 ) while increasing coefficient of variation was associated with increasing brain natriuretic peptide ( p = 0.004 ) and paroxonase-1 ( p = 0.02 ) .


Other univariable analyses were not significant .


There were modest , transient differences in glucose control between IV and SQ insulin in hospitalized CHF patients .


However , the analyses do not support a link between insulin route and inflammatory markers or autonomic tone .


Further study is needed to assess outcomes in hospitalized CHF patients .


New vaccines containing highly conserved Streptococcus pneumoniae proteins such as pneumolysin toxoid ( dPly ) and histidine-triad protein D ( PhtD ) are being developed to provide broader protection against pneumococcal disease .


This study evaluated the safety , reactogenicity and immunogenicity of different pneumococcal protein-containing formulations in adults .


In a phase I double-blind study ( www.clinicaltrials.gov : NCT00707798 ) , healthy adults ( 18-40 years ) were randomized ( 1:2:2:2:2:2:2 ) to receive two doses of one of six investigational vaccine formulations 2 months apart , or a single dose of the control 23-valent pneumococcal polysaccharide vaccine ( 23PPV ; Pneumovax23 , Sanofi Pasteur MSD ) followed by placebo .


The investigational formulations contained dPly alone ( 10 or 30 g ) , or both dPly and PhtD ( 10 or 30 g each ) alone or combined with the polysaccharide conjugates of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ; Synflorix , GlaxoSmithKline Vaccines ) .


Two groups primed with a formulation containing dPly and PhtD ( 10 or 30 g each ) continued to the follow-up phase II study ( NCT00896064 ) , in which they received a booster dose at 5-9 months after primary vaccination .


Of 156 enrolled and vaccinated adults , 146 completed the primary immunization and 43 adults received a booster dose .


During primary and booster vaccination , for any formulation , 8.9 % of doses were followed by grade 3 solicited local or general adverse events .


No fever > 39.5 C ( oral temperature ) was reported .


Unsolicited adverse events considered causally related to vaccination were reported following 33.3 % of investigational vaccine doses .


No serious adverse events were reported for adults receiving investigational vaccine formulations .


Formulations containing dPly with or without PhtD were immunogenic for these antigens ; polysaccharide conjugate-containing formulations were also immunogenic for those 10 polysaccharides .


Investigational vaccine formulations containing dPly and PhtD were well tolerated and immunogenic when administered to healthy adults as standalone protein vaccine or combined with PHiD-CV conjugates .


Early identification ( EI ) and brief interventions ( BIs ) for risky drinkers are effective tools in primary care .


Lack of time in daily practice has been identified as one of the main barriers to implementation of BI .


There is growing evidence that facilitated access by primary healthcare professionals ( PHCPs ) to a web-based BI can be a time-saving alternative to standard face-to-face BIs , but there is as yet no evidence about the effectiveness of this approach relative to conventional BI .


The main aim of this study is to test non-inferiority of facilitation to a web-based BI for risky drinkers delivered by PHCP against face-to-face BI .


A randomised controlled non-inferiority trial comparing both interventions will be performed in primary care health centres in Catalonia , Spain .


Unselected adult patients attending participating centres will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test ( AUDIT-C ) alcohol screening questionnaire .


Participants with positive results will be requested online to complete a trial module including consent , baseline assessment and randomisation to either face-to-face BI by the practitioner or BI via the alcohol reduction website .


Follow-up assessment of risky drinking will be undertaken online at 3 months and 1 year using the full AUDIT and D5-EQD5 scale .


Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10 % .


Assuming reduction of 30 % of risky drinkers receiving standard intervention , 1000 patients will be required to give 90 % power to reject the null hypothesis .


The protocol was approved by the Ethics Commmittee of IDIAP Jordi Gol i Gurina P14/028 .


The findings of the trial will be disseminated through peer-reviewed journals , national and international conference presentations .


ClinicalTrials.gov NCT02082990 .


The hyperglycemic response to surgery may be a risk factor for cognitive dysfunction .


We hypothesize that strict maintenance of normoglycemia during cardiac surgery preserves postoperative cognitive function .


As part of a larger randomized , single-blind , interventional efficacy study on the effects of hyperinsulinemic glucose control in cardiac surgery ( NCT00524472 ) , consenting patients were randomly assigned to receive combined administration of insulin and glucose , titrated to preserve normoglycemia ( 3.5-6 .1 mmol L ( -1 ) ; experimental group ) , or standard metabolic care ( blood glucose 3.5-10 mmol L ( -1 ) ; control group ) , during open heart surgery .


The patients ' cognitive function was assessed during three home visits , approximately two weeks before the operation , and two months and seven months after surgery .


The following tests were performed : Rey Auditory Verbal Learning Task ( RAVLT for verbal learning and memory ) , Digit Span Task ( working memory ) , Trail Making A & B ( visuomotor tracking and attention ) , and the Word Pair Task ( implicit memory ) .


Questionnaires measuring specific traits known to affect cognitive performance , such as self-esteem , depression , chronic stress and social support , were also administered .


The primary outcome was to assess the effect of hyperinsulinemic-normoglycemic clamp therapy versus standard therapy on specific cognitive parameters in patients receiving normoglycemic clamp , or standard metabolic care .


Twenty-six patients completed the study with 14 patients in the normoglycemia and 12 patients in the control group .


Multiple analysis of covariance ( MANCOVA ) for the RAVLT showed a significant effect for the interaction of group by visit ( F = 4.07 , p = 0.035 ) , and group by visit by recall ( F = 2.21 , p = 0.04 ) .


The differences occurred at the second and third visit .


MANCOVA for the digit span task , trail making and word pair association test showed no significant effect .


Preserving intraoperative normoglycemia by intravenous insulin and glucose may prevent the impairment of memory function , both short and long-term , after cardiac surgery .


Cardiovascular disease and cancer are leading causes of mortality for people with a history of alcohol or other substance use disorders .


These chronic diseases share the same four primary behavioural risk factors i.e. excessive alcohol use , smoking , low intake of fruit and vegetables and physical inactivity .


In addition to addressing problematic alcohol use , there is the potential for substance abuse treatment services to also address these other behaviours .


Healthy Recovery is an 8-session group-based intervention that targets these multiple behavioural health risk factors and was developed specifically for people attending substance abuse treatment .


This protocol describes a Cancer Institute NSW funded study that assesses the effectiveness of delivering Healthy Recovery for people who are attending residential alcohol and other substance abuse treatment .


The study uses a stepped wedge randomised controlled design , where randomisation occurs at the service level .


Participants will be recruited from residential rehabilitation programs provided by The Australian Salvation Army .


All participants who ( 1 ) currently smoke tobacco and ( 2 ) are expected to be in the residential program for the duration of the 5-week intervention will be asked to participate in the study .


Those participants residing at the facilities assigned to the treatment condition will complete Healthy Recovery .


The intervention is manual guided and will be delivered over a 5-week period , with participants attending 8 group sessions .


All participants will continue to complete The Salvation Army residential program , a predominantly 12-step based , modified therapeutic community .


Participants in the control condition will complete treatment as usual .


Research staff blind to treatment allocation will complete the primary and secondary outcome assessments at baseline and then at weeks 8 , 20 and 32 weeks post intervention .


This study will provide comprehensive data on the effect of delivering a healthy lifestyle intervention ( i.e. Healthy Recovery ) within a residential substance abuse setting .


If shown to be effective , this intervention can be disseminated within other residential substance abuse programs .


Australian and New Zealand Clinical Trials Register ( ANZCTR ) : ACTRN12615000165583 .


Registered 19 ( th ) February 2015 .


Appropriate pain management may positively affect outcome following hip fractures .


Positioning patients for spinal anesthesia ( SA ) can be extremely painful .


Peripheral nerve blockades are gaining popularity in this setting .