Baseline ( ABG-1 ) PaCO2 values were similar between nCPAP and control groups with median values of 54.5 and 56.1 mm Hg , respectively .


There was a significant decline in PaCO2 in the nCPAP group ( median of -4.6 mm Hg [ 10th-90th quantile , -14.55 to 3.85 ] ) as compared with the control group ( median of 0.95 mm Hg [ -4.75 to 9.85 ] ; P = 0.015 ; 95 % confidence interval [ CI ] for location shift = -9.5 to -1.3 ) .


Within the control group , PaCO2 was similar from ABG-1 to ABG-2 ( median [ 10th-90th quantile ] = 56.1 mm Hg [ 47.2-67 .0 ] vs 56.6 mm Hg [ 46-68 .8 ] ; P = 0.52 ; 95 % CI for the median = -3.4 to 3.4 ) .


Forty percent of all patients received an airway before ABG-1 .


The baseline PaCO2 value of patients receiving an airway was not different from that of patients without an airway ( median [ 10th-90th quantile ] = 56.0 mm Hg [ 46.0-68 .4 ] vs 54.1 mm Hg [ 45.6-65 .6 ] , respectively ; P = 0.33 ; 95 % CI for location shift = -2.30 to 7.20 ) .


Deep sedation of TKA patients during SAB resulted in moderate hypercarbia ( mean and median PaCO2 = 55 ) .


There was a trend showing that nCPAP treatment reduced PaCO2 versus treatment for control group patients receiving standard airway management ; however , estimated treatment difference varied widely , from 1.4 to 12.6 mm Hg .


Among control group patients , the initial PaCO2 during deep sedation was similar to the PaCO2 when measured after a 30-minute period of continued deep sedation .


Finally , baseline PaCO2 among deeply sedated patients who received an airway was not different from that of patients who did not receive an airway .


Funnel technique is a method used for the insertion of screw into thoracic pedicle .


To evaluate the biomechanical characteristics of thoracic pedicle screw placement using the Funnel technique , trying to provide biomechanical basis for clinical application of this technology .


14 functional spinal units ( T6 to T10 ) were selected from thoracic spine specimens of 14 fresh adult cadavers , and randomly divided into two groups , including Funnel technique group ( n = 7 ) and Magerl technique group ( n = 7 ) .


The displacement-stiffness and pull-out strength in all kinds of position were tested and compared .


Two fixed groups were significantly higher than that of the intact state ( P < 0.05 ) in the spinal central axial direction , compression , anterior flexion , posterior bending , lateral bending , axial torsion , but there were no significant differences between two fixed groups ( P > 0.05 ) .


The mean pull-out strength in Funnel technique group ( 789.09 27.33 ) was lower than that in Magerl technique group ( P < 0.05 ) .


The Funnel technique for the insertion point of posterior bone is a safe and accurate technique for pedicle screw placement .


It exhibited no effects on the stiffness of spinal column , but decreased the pull-out strength of pedicle screw .


Therefore , the funnel technique in the thoracic spine affords an alternative for the standard screw placement .


Thoracic epidural analgesia ( TEA ) has a well-known effect on neurohormonal response .


Attenuation of stress response by post-operative epidural analgesia has shown beneficial effects such as lower pain scores and less immunological alterations .


Investigation of the combined effects of TEA and protective lung ventilation on pro-inflammatory cytokines and patients ' outcome after Ivor Lewis esophagectomy .


A randomized controlled study .


Academic medical center .


Thirty patients of the American Society of Anesthesiologists ( ASA ) I and II were randomly allocated into 2 groups : G1 ( n = 15 ) patients received general anesthesia and were mechanically ventilated with 9 mL/kg during 2 lung ventilations , reduced to 5 mL/kg and 5cm H2O positive end expiratory pressure ( PEEP ) during one lung ventilation ( OLV ) or GII ) ( n = 15 ) patients received TEA and the same general anesthesia and mechanical ventilation used in G1 .


Assessment parameters included hemodynamics , pain severity , total analgesic consumption , and measurement of interleukins ( IL ) ( IL-6 and IL-8 ) at baseline time after anesthetic induction ( TBaseline , ) ; at the end of the abdominal stage of the operation ( TAbdo , ) ; 15 minutes after initiation and at the end of OLV ( TOLV 15 ) and ( TOLV End ) respectively ; one and 20 hours after the end of the surgical procedure ( TPostop1 and TPostop20 ) , respectively , and patient 's outcome also recorded .


There was a significant reduction in mean arterial blood pressure ( MAP ) and pulse rate in GII during the intraoperative period , at Tabdo , TOLV15 , and TOLV End ( P < 0.05 ) .


The mean of systolic blood pressure ( SBP ) values were significantly lower in GII over all 3 post-operative days ( P = 0.001 ) , and the mean diastolic blood pressure ( DBP ) showed a significant reduction in GII for 16 hours post-operatively ( P = 0.001 ) .


The mean of heart rate values showed a significant reduction in GII over all 3 post-operative days in comparison to GI ( P = 0.001 ) .


The mean resting and dynamic VAS scores were significantly reduced in GII at all time periods studied in comparison to G1 ( P = 0.001 ) .


The daily PCA morphine consumption was markedly decreased in GII compared to GI in the first 3 days post-operatively ( P = 0.001 ) .


There were significant reductions in blood level of IL-6 and IL-8 in GII compared to G1 over the entire study period ( P < 0.05 ) .


There were no significant differences in post-operative adverse effects between the 2 groups ( P > 0.05 ) .


The duration of stay in PACU was significantly decreased in GII ( 10 2 days ) compared to GI ( 15 3 days ) ( P = 0.001 ) .


This study is limited by its sample size .


Our study concluded that TEA reduced the systemic pro-inflammatory response and provided optimal post-operative pain relief .


Although there were no significant differences in adverse events , there was a trend towards improved outcome .


Further clinical studies with larger numbers of patients are required .


Laparoscopic cholecystectomy ( LC ) , a gold standard procedure can be done without energized dissection ( ED ) .


We did a randomized study for the outcomes of LC done with ED or without ED , i.e. , with cold dissection ( CD ) .


At a tertiary level institution , open-ended prospective-randomized control study was conducted between September 2008 and June 2013 .


Consecutive , unselected , consenting candidates for LC were enrolled following standard ethics , informed consent , anesthesia , and clinical pathway protocol .


They were allocated to control group ( LC with ED ) or study group ( LC with CD , as per our published technique with the option for rescue ED ) .


The study points were based upon Clavien-Dindo grading of postoperative complications .


They were either , peri-operative events potentially affecting , hospital stay ( Grade I ) or Grade II-V , e.g. , peri-operative hemodynamic instability , needing intervention/blood transfusion , injury to biliary ducts/hollow viscous , postoperative biliary leak , postoperative re-intervention , re-hospitalization , mortality , and any adverse event during a 90-day follow-up period .


The data were prospectively collected in an integrated `` hospital information system '' that could be retrieved only by independent external coordinators .


Demographics , co-morbidities , and gallbladder inflammation profile of the control group ( n = 361 ) and study group ( n = 384 ) were comparable .


There was no rescue ED usage in the study group .


Hospital stay ( Grade I adverse outcome dependent ) was longer , i.e. , 1.6 1.03 in the control versus 1.35 1.2 days in the study group ( p < 0.001 ) .


Grade II-IV complications were significantly more ( p < 0.009 ) in control group .


There was one common bile duct ( CBD ) injury in each group .


The index bilio-enteric anastomosis for CBD injury in control group failed and needed a revision with multiple interventions .


There was one grade V adverse outcome , i.e. , mortality in the control group .


Avoiding the use of ED in LC is associated with better outcomes .


Surgical site infections ( SSIs ) are responsible for significant morbidity , mortality , and excess use of health care resources .


The preadmission antiseptic shower is accepted as an effective strategy for reducing the risk for SSIs .


The study analyzes the benefit of an innovative electronic patient alert system ( EAS ) for enhancing compliance with a preadmission showering protocol with 4 % chlorhexidine gluconate ( CHG ) .


After providing informed consent , 80 volunteers were randomized to 4 CHG showering groups .


Groups A1 and A2 showered twice .


Group A1 was prompted to shower via EAS .


Groups B1 and B2 showered 3 times .


Group B1 was prompted via EAS .


Subjects in groups A2 and B2 were not prompted ( non-EAS groups ) .


Skin-surface concentrations of CHG ( g/mL ) were analyzed using colorimetric assay at 5 separate anatomic sites .


Study personnel were blinded to the randomization code ; after final volunteer processing , the code was broken and individual groups were analyzed .


Mean composite CHG skin-surface concentrations were significantly higher ( p < 0.007 ) in EAS groups A1 ( 30.9 8.8 g/mL ) and B1 ( 29.0 8.3 g/mL ) compared with non-EAS groups A2 ( 10.5 3.9 g/mL ) and B2 ( 9.5 3.1 g/mL ) .


Overall , 66 % and 67 % reductions in CHG skin-surface concentrations were observed in non-EAS groups A2 and B2 compared with EAS study groups .


Analysis of returned ( unused ) CHG ( mL ) suggests that a wide variation in volume of biocide was used per shower in all groups .


The findings suggest that EAS was effective in enhancing patient compliance with a preadmission showering protocol , resulting in a significant ( p < 0.007 ) increase in skin-surface concentrations of CHG compared with non-EAS controls .


However , variation in amount of unused 4 % CHG suggests that rigorous standardization is required to maximize the benefits of this patient-centric interventional strategy .


To compare the efficacy and safety outcomes of bimanual microincision cataract surgery ( MICS ) versus 2.2-mm coaxial phacoemulsification assisted by Femtosecond LenSx ( Alcon-LenSx Inc. , Aliso Viejo , CA ) .


This prospective , randomized , observational , comparative case series comprised 50 cataractous eyes of 50 patients receiving femtosecond laser refractive lens surgery followed by a bimanual MICS technique with two 1-mm incisions ( 25 patients ) ( FemtoMICS group ) and a coaxial phacoemulsification technique with a 1-mm paracentesis and a 2.2-mm principal incision ( 25 patients ) ( FemtoCoaxial group ) .


The main outcomes measures were : ultrasound power , effective phacoemulsification time , postoperative spherical equivalent , higher-order aberrations ( corneal and internal ) , corneal thickness , endothelial cell count , macular thickness , and complications during and after surgery .


Both groups were absolutely comparable for all variables preoperatively .


Mean ultrasound power was 1.8 % 0.9 % for MICS and 14.7 % 4.9 % for 2.2-mm incisions ( P < .001 ) .


Effective phacoemulsification time values for MICS and 2.2-mm incisions were 1.5 0.9 and 4.5 2.9 sec , respectively ( P = .002 ) .


Mean postoperative spherical equivalent was 0.26 for FemtoMICS and 0.33 for FemtoCoaxial ( P > .05 ) .


The efficacy index at 1 month postoperatively was 160.2 % for FemtoMICS and 149 % for FemtoCoaxial .


No significant differences were found in corneal thickness , endothelial cell count , and macular thickness .


Complications included posterior capsule rupture ( 4 % ) and anterior capsule rupture with no posterior capsule tear ( 4 % ) for FemtoMICS and bridges due to incomplete capsulorhexis ( 4 % ) for FemtoCoaxial .


MICS and coaxial phacoemulsification techniques assisted by the Femtosecond LenSx achieved excellent safety and efficient outcomes .


The FemtoMICS technique was surgically and statistically more efficient than the FemtoCoaxial technique .


MicroRNA-122 ( miR-122 ) is an important host factor for hepatitis C virus ( HCV ) and promotes HCV RNA accumulation .


Decreased intra-hepatic levels of miR-122 were observed in patients with hepatocellular carcinoma , suggesting a potential role of miR-122 in the development of HCC .


Miravirsen targets miR-122 and resulted in a dose dependent and prolonged decrease of HCV RNA levels in chronic hepatitis C patients .


The aim of this study was to establish the sustained virological response rate to peginterferon ( P ) and ribavirin ( R ) following miravirsen dosing and to assess long-term safety in patients treated with miravirsen .


In this multicenter , retrospective follow-up study we included 36 treatment nave patients with chronic hepatitis C genotype 1 who received five weekly subcutaneous injections with miravirsen or placebo over a 29-day period in a phase 2a study .


Patients were offered PR therapy 3weeks ( 3mg/kg group ) or 6weeks ( 5 or 7mg/kg group ) after completion of miravirsen or placebo dosing .


PR therapy was started in 14/36 patients of whom 12 had received miravirsen .


SVR was achieved in 7/12 patients previously dosed with miravirsen .


All patients dosed with 7mg/kg miravirsen who were subsequently treated with PR achieved SVR .


One patient had a prolonged undetectable HCV RNA period from week 14 to week 29 after baseline without subsequent antiviral therapy and relapsed thereafter .


None of the patients treated with anti-miR-122 developed HCC or other liver-related complications .


No long-term safety issues were observed among 27 miravirsen-treated patients .


Targeting miR-122 may be an effective and safe treatment strategy for HCV infection and should be investigated in larger clinical trials .


The efficacy of montelukast ( MONT ) , a cysteinyl leukotriene receptor antagonist , in nonasthmatic eosinophilic bronchitis ( NAEB ) , especially its influence on cough associated life quality is still indefinite .


We evaluated the efficacy of MONT combined with budesonide ( BUD ) as compared to BUD monotherapy in improving life quality , suppressing airway eosinophilia and cough remission in NAEB .


A prospective , open-labeled , multicenter , randomized controlled trial was conducted .


Patients with NAEB ( aged 18-75 years ) were randomized to inhaled BUD ( 200 g , bid ) or BUD plus oral MONT ( 10 g , qn ) for 4 weeks .


Leicester cough questionnaire ( LCQ ) life quality scores , cough visual analog scale ( CVAS ) scores , eosinophil differential ratio ( Eos ) , and eosinophil cationic protein ( ECP ) in induced sputum were monitored and compared .


The control and MONT groups contained 33 and 32 patients , respectively , with similar baseline characteristics .


Significant with-in group improvement in CVAS , LCQ scores , Eos , and ECP was observed in both groups during treatment .


After 2-week treatment , add-on treatment of MONT was significantly more effective than BUD monotherapy for CVAS decrease and LCQ scores improvement ( both P < 0.05 ) .


Similar results were seen at 4-week assessment ( both P < 0.05 ) .


4-week add-on therapy of MONT also resulted in a higher percentage of patients with normal sputum Eos ( < 2.5 % ) and greater decrease of ECP ( both P < 0.05 ) .


MONT combined with BUD was demonstrated cooperative effects in improvement of life quality , suppression of eosinophilic inflammation , and cough remission in patients with NAEB .


Adolescents living in South Africa are at high risk for HIV and other sexually transmitted diseases ( STDs ) .


The present study sought to identify correlates of curable STD incidence among a cohort of adolescents in Eastern Cape Province , South Africa .


Data were collected in conjunction with an HIV/STD prevention intervention randomized controlled trial .


At 54 months postintervention , curable STD incidence ( gonorrhea , chlamydial infection , and trichomoniasis ) was assayed and self-report measures of potential correlates of STD incidence were collected .


Participants were adolescents reporting at least 1 sexual partner in the past 3 months ( n = 659 ) .


As expected , univariate analyses revealed that girls were more likely than boys to have an STD .


In addition , intimate partner violence , unprotected sex , and having older partners were associated with incident STD .


In Poisson multiple regression analyses , sex ( risk ratio [ RR ] , 4.00 ; 95 % confidence interval [ CI ] , 2.51-6 .39 ) , intimate partner violence ( RR , 1.23 ; 95 % CI , 1.12-1 .35 ) , unprotected sex ( RR , 1.42 ; 95 % CI , 1.09-2 .01 ) , and multiple partners ( RR , 1.70 ; 95 % CI , 1.11-2 .61 ) , but not partner 's age ( RR , 1.00 ; 95 % CI , 0.94-1 .07 ) were associated with incident STD , adjusting for 42-month STD prevalence .


Binge drinking , forced sex , and age were unrelated to STD incidence in both analyses .


Interactions between sex and the hypothesized correlates were nonsignificant , suggesting that sex did not modify these relationships .


Interventions to reduce HIV/STD incidence among adolescents in South Africa should address the risk associated with sex , unprotected sex , intimate partner violence , and multiple partnerships .


To identify micronutrient deficiencies in patients with functional bowel diseases ( FBD ) and to reveal their correction with functional foods and probiotics .


The health status was evaluated in 90 patients aged 18 to 67 years with FBD .


All the patients were randomized into 3 groups according to the treatment regimen .


Group 1 took Amaltea goat 's milk 200 ml/day during basic therapy ; Group 2 received multispecies and multistrain RioFlora Balance probiotics in addition to the above components ; Group 3 ( a control group ) had traditional basic dietary therapy .


All the groups continued their treatment for 14 days .


The performed examinations have demonstrated that diet-based treatment fortified with goat 's milk and multispecies probiotics makes it possible to more promptly achieve remission and to level off clinical manifestations than in the control group .


The patients using multispecies probiotics versus the control group showed a reduction in fat-soluble vitamin deficiencies and a considerable improvement in quality of life .


FBD lacks a specific clinical picture and may be masked as lactase deficiency , which commonly leads to noticeable limitations in patients ' diet and favors the development of vitamin deficiency .


Of particular concern is the development of vitamin D deficiency in young patients , which may result in the early development of osteoporosis in the future .


To specify the composition of enzymes in the patients gives grounds to refuse restricted diets , and the dietary addition of functional foods ( goat 's milk fortified with vitamins and minerals ) , particularly in combination with multistrain probiotics , produces a pronounced clinical effect and eliminates fat-soluble vitamin deficiencies .


We examined the effect of the renin inhibitor , aliskiren , on renal blood flow ( RBF ) in patients with heart failure with reduced ejection fraction ( HFREF ) and decreased glomerular filtration rate ( GFR ) .


Renal blood flow is the main determinant of GFR in HFREF patients .


Both reduced GFR and RBF are associated with increased mortality .


Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals .


Patients with left ventricular ejection fraction 45 % and estimated GFR 30 to 75 mL/min per 1.73 m ( 2 ) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo .


Renal blood flow and GFR were measured using radioactive-labeled ( 125 ) I-iothalamate and ( 131 ) I-hippuran at baseline and 26 weeks .


After 41 patients were included , the trial was halted based on an interim safety analysis showing futility .


Mean age was 68 9 years , 82 % male , GFR ( 49 16 mL/min per 1.73 m ( 2 ) ) , RBF ( 294 77 mL/min per 1.73 m ( 2 ) ) , and NT-proBNP 999 ( 435-2040 ) pg/mL .


There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo ( -7.1 30 vs +14 54 mL/min per 1.73 m ( 2 ) ; P = .16 ) .


However , GFR decreased significantly in the aliskiren group compared with placebo ( -2.8 6.0 vs +4.4 9.6 mL/min per 1.73 m ( 2 ) ; P = .01 ) as did filtration fraction ( -2.2 3.3 vs +1.1 3.1 % ; P = .01 ) .


There were no significant differences in plasma aldosterone , NT-proBNP , urinary tubular markers , or adverse events .


Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase ( P = .007 ) .


Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction .


Coronary CT angiography ( CCTA ) has high sensitivity , with 3 recent randomized trials favorably comparing CCTA to standard-of-care .


Comparison to exercise stress ECG ( ExECG ) , the most available and least expensive standard-of-care worldwide , has not been systematically tested .


CT-COMPARE was a randomized , single-center trial of low-intermediate risk chest pain subjects undergoing CCTA or ExECG after the first negative troponin .


From March 2010 to April 2011 , 562 patients randomized to either dual-source CCTA ( n = 322 ) or ExECG ( n = 240 ) .


Primary endpoints were diagnostic performance for ACS , and hospital cost at 30 days .


Secondary endpoints were time-to-discharge , admission rates , and downstream resource utilization .


ACS occurred in 24 ( 4 % ) patients .


ExECG had 213 negative studies and 27 ( 26 % ) positive studies for ACS with sensitivity of 83 % [ 95 % CI : 36 , 99.6 % ] , specificity of 91 % [ CI : 86 , 94 % ] , and ROC AUC of 0.87 [ CI : 0.70 , 1 ] .


CCTA ( > 50 % stenosis considered positive ) had 288 negative studies and 18/35 ( 51 % ) positive studies with a sensitivity of 100 % [ CI : 81.5 , 100 ] , specificity of 94 % [ CI : 91.2 , 96.7 % ] , and ROC of 0.97 [ CI : 0.92 , 1.0 ; p = 0.2 ] .


Despite CCTA having higher odds of downstream testing ( OR 2.0 ) , 30 day per-patient cost was significantly lower for CCTA ( $ 2193 vs $ 2704 , p < 0.001 ) .


Length of stay for CCTA was significantly reduced ( 13.5 h [ 95 % CI : 11.2-15 .7 ] , ExECG 19.7 h [ 95 % CI : 17.4-22 .1 ] , p < 0.0005 ) , which drove the reduction in cost .


No patient had post-discharge cardiovascular events at 30 days .


CCTA had improved diagnostic performance compared to ExECG , combined with 35 % relative reduction in length-of-stay , and 20 % reduction in hospital costs .


These data lend further evidence that CCTA is useful as a first line assessment in emergency department chest pain .


Tivozanib hydrochloride ( tivozanib ) is a potent and selective tyrosine kinase inhibitor of all 3 vascular endothelial growth factor receptors with antitumor activity additive to 5-fluorouracil in preclinical models .


This study was conducted to determine maximum tolerated dose ( MTD ) , dose-limiting toxicities ( DLTs ) , pharmacokinetics ( PKs ) , and antitumor activity of escalating doses of tivozanib with a modified ( m ) FOLFOX-6 ( leucovorin , 5-fluorouracil [ 5-FU ] , and 85 mg/kg ( 2 ) oxaliplatin ) regimen in patients with advanced gastrointestinal tumors .


Tivozanib was administered orally once daily for 21 days in 28-day cycles , with mFOLFOX-6 administered every 14 days .


Patients were allowed to continue tivozanib after discontinuation of mFOLFOX-6 .


Thirty patients were assigned to tivozanib 0.5 mg ( n = 9 ) , 1.0 mg ( n = 3 ) , or 1.5 mg ( n = 18 ) with mFOLFOX-6 .


Patients received a median of 5.2 ( range , 0.03-26 .9 ) months of tivozanib .


DLTs were observed in 2 patients : Grade 3/4 transaminase level increases with tivozanib 0.5 mg , and Grade 3 dizziness with tivozanib 1.5 mg .


Other Grade 3/4 adverse events included hypertension ( n = 8 ) , fatigue ( n = 8 ) , and neutropenia ( n = 6 ) .


MTD for tivozanib with mFOLFOX-6 was confirmed as 1.5 mg .


No PK interactions between tivozanib and mFOLFOX-6 were observed .


One patient had an ongoing clinical complete response , 10 had a partial response , and 11 obtained prolonged stable disease .


Tivozanib and mFOLFOX-6 is feasible and appears to be safe .


The recommended dose for tivozanib with mFOLFOX-6 is 1.5 mg/d .


Observed clinical activity merits further exploration in gastrointestinal tumors .


Although adiposity has been considered to be protective against hot flashes , newer data suggest positive relationships between hot flashes and adiposity .


No studies have been specifically designed to test whether weight loss reduces hot flashes .


This pilot study aimed to evaluate the feasibility , acceptability , and initial efficacy of behavioral weight loss in reducing hot flashes .


Forty overweight or obese women with hot flashes ( 4 hot flashes/d ) were randomized to either behavioral weight loss intervention or wait-list control .


Hot flashes were assessed before and after intervention via physiologic monitoring , diary , and questionnaire .


Comparisons of changes in hot flashes and anthropometrics between conditions were performed via Wilcoxon tests .


Study retention ( 83 % ) and intervention satisfaction ( 93.8 % ) were high .


Most women ( 74.1 % ) reported that hot flash reduction was a major motivator for losing weight .


Women randomized to the weight loss intervention lost more weight ( -8.86 kg ) than did women randomized to control ( +0.23 kg ; P < 0.0001 ) .


Women randomized to weight loss also showed greater reductions in questionnaire-reported hot flashes ( 2-wk hot flashes , -63.0 ) than did women in the control group ( -28.0 ; P = 0.03 ) - a difference not demonstrated in other hot flash measures .


Reductions in weight and hot flashes were significantly correlated ( eg , r = 0.47 , P = 0.006 ) .


This pilot study shows a behavioral weight loss program that is feasible , acceptable , and effective in producing weight loss among overweight or obese women with hot flashes .


Findings indicate the importance of a larger study designed to test behavioral weight loss for hot flash reduction .


Hot flash management could motivate women to engage in this health-promoting behavior .


The bioavailability of rifampicin ( RMP ) decreases by 30 % on interaction with isoniazid ( INH ) in stomach acid conditions , which can result in the development of drug resistance and treatment failure .


To compare the bioavailability in healthy volunteers of five anti-tuberculosis fixed-drug combinations ( FDCs ) used in China ( formulations A-E ) containing RMP and INH against single-drug formulations taken as reference .


Two - or three-period , two - or three-sequence crossover study of drugs .


Only RMP formulation E passed the bioequivalence criteria , with 90 % confidence intervals for the log-transformed ratios of AUC , AUC , and Cmax of respectively 89.9-103 .7 , 89.6-102 .2 and 87.7-107 .9 .


For INH , formulations A , B , C and D passed the bioequivalence test , but not product E , where the 90 % CIs of the log-transformed ratios of AUC , AUC , and Cmax were respectively 85.2-100 .7 , 85.2-100 .7 and 73.8-100 .9 .


According to the results of the bioequivalence analysis carried out in this study , RMP formulations A , B , C and D were not within the acceptable range and only formulation E passed the bioequivalence criteria of 80-125 % .


In comparison , four-test INH formulations ( A , B , C and D ) were bioequivalent to the corresponding single-drug formulation , while product E failed in the bioequivalence criteria .


In athletes , caffeine use is common although its effects on sleep have not been widely studied .


This randomised , double-blind , placebo-controlled crossover trial investigated the effects of late-afternoon caffeine and carbohydrate-electrolyte ( CEB ) co-ingestion on cycling performance and nocturnal sleep .


Six male cyclists/triathletes ( age 27.5 6.9 years ) completed an afternoon training session ( TS ; cycling 80 min ; 65 % VOmax ) followed by a 5 kJ kg ( -1 ) cycling time trial ( TT ) .


Caffeine ( split dose 2 3 mg kg ( -1 ) ) or placebo was administered 1 h prior and 40 min into the TS .


A 7.4 % CEB ( 3 ml kg ( -1 ) every 15 min ) was administered during the TS , followed 30 min after by a standardised evening meal .


Participants retired at their usual bedtime and indices of sleep duration and quality were monitored via polysomnography .


mean SD .


All participants performed better in the caffeine TT ( caffeine 19.7 3.3 ; placebo 20.5 3.5 min ; p = 0.006 ) , while ratings of perceived exertion ( caffeine 12.0 0.6 ; placebo 12.9 0.7 ; p = 0.004 ) and heart rate ( caffeine 175 6 ; placebo 167 11 bpm ; p = 0.085 ) were lower in the caffeine TS .


Caffeine intake induced significant disruptions to a number of sleep indices including increased sleep onset latency ( caffeine 51.1 34.7 ; placebo 10.2 4.2 min ; p = 0.028 ) and decreased sleep efficiency ( caffeine 76.1 19.6 ; placebo 91.5 4.2 % ; p = 0.028 ) , rapid eye movement sleep ( caffeine 62.1 19.6 ; placebo 85.8 24.7 min ; p = 0.028 ) and total sleep time ( caffeine 391 97 ; placebo 464 49 min ; p = 0.028 ) .


This study supports a performance-enhancing effect of caffeine , although athletes ( especially those using caffeine for late-afternoon/evening training and competition ) should consider its deleterious effects on sleep .


To study the effect of probiotic consumption on the faecal microbiota during and after antibiotic exposure .


A randomized , double-blind , placebo-controlled , parallel group study with a two species probiotic combination [ Lactobacillus acidophilus ( L. acidophilus ) ATCC 700396 and Bifidobacterium lactis ( B. lactis ) ATCC SD5220 ] on healthy adults during and after antibiotic treatment ( amoxicillin 875 and 125 mg clavulanate ) .


The dominant faecal microbiota was studied by real time-polymerase chain reaction to determine if this probiotic preparation could facilitate restoring the microbiota to its pre-antibiotic state and influence the prevalence of beta-lactam resistance .


Gastrointestinal symptoms were recorded by questionnaire and Bristol stool scale .


Subjects on the probiotic combination had significantly higher faecal counts of L. acidophilus ATCC 700396 and B. lactis at day 8 ( end of antibiotic treatment period ) vs those on placebo .


Furthermore , subjects on the probiotic combination had significantly higher faecal counts of L. acidophilus ATCC 700396 and B. lactis at Day 15 ( end of probiotic treatment ) vs those on placebo .


Lactobacillus counts remained stable in the probiotic group over the course of the study , while Clostridium XIV group was higher at the end of the study and closer to baseline levels ; this in contrast to the placebo group .


Beta-lactam resistance in creased after antibiotic exposure and was not different between both treatment groups .


Gastrointestinal symptoms were generally mild and did not differ between the treatment groups , which correlates with the generally small changes in the microbiota .


Consumption of the probiotic combination mainly leads to an increase in the faecal levels of the species included in the preparation .


Capecitabine and S-1 are orally administered fluorinated pyrimidines with high-level activity against metastatic breast cancer ( MBC ) .


This randomized , multicenter , phase II study compared the activities and safeties of the oral fluoropyrimidines , capecitabine and S-1 , in breast cancer patients .


Patients with MBC were randomly assigned to receive capecitabine 825g/m ( 2 ) twice daily on days 1-21 every 4weeks or S-1 40-60mg twice daily , according to body surface area , on days 1-28 every 6weeks .


The primary endpoint was progression-free survival ( PFS ) .


A total of 142 patients were enrolled and randomized to either capecitabine ( N = 73 ) or S-1 ( N = 69 ) .


Median PFS ( progression-free survival ) was 1.2 years for capecitabine and 1.3 years for S-1 , with a hazard ratio ( S-1 / capecitabine ) of 0.85 ( 95 % confidence interval [ CI ] 0.52-1 .38 ) ( P = 0.48 by log-rank ) .


The confirmed objective response rates were 24.0 % for capecitabine and 23.1 % for S-1 ( P = 0.938 ) .


The most common treatment-related adverse events were grade 1-2 in intensity .


Thrombocytopenia ( S-1 : 9.2 % , capecitabine : 1.4 % ; P = 0.040 ) and nausea ( S-1 : 26.2 % , capecitabine : 14.1 % ; P = 0.079 ) were more frequent in the S-1 group , while hand-foot syndrome occurred more often in the capecitabine group ( S-1 : 10.8 % , capecitabine : 25.4 % ; P = 0.029 ) .


The results of the current study demonstrate that both S-1 and capecitabine are effective and well-tolerated treatments in patients with MBC , while their adverse events were different .


They are both convenient , orally administered drugs , making them attractive agents for use in outpatient treatment .


Estimates of energy intake ( EI ) in humans have limited validity .


The objective was to test the accuracy and precision of the intake-balance method to estimate EI during weight gain induced by overfeeding .


In 2 studies of controlled overfeeding ( 1 inpatient study and 1 outpatient study ) , baseline energy requirements were determined by a doubly labeled water study and caloric titration to weight maintenance .


Overfeeding was prescribed as 140 % of baseline energy requirements for 56 d. Changes in weight , fat mass ( FM ) , and fat-free mass ( FFM ) were used to estimate change in energy stores ( ES ) .


Overfeeding EI was estimated as the sum of baseline energy requirements , thermic effect of food , and ES .


The estimated overfeeding EI was then compared with the actual EI consumed in the metabolic chamber during the last week of overfeeding .


In inpatient individuals , calculated EI during overfeeding determined from ES in FM and FFM was ( mean SD ) 3461 848 kcal/d , which was not significantly ( -29 273 kcal/d or 0.8 % ; limits of agreement : -564 , 505 kcal/d ; P = 0.78 ) different from the actual EI provided ( 3490 729 kcal/d ) .


Estimated EI determined from ES in weight closely estimated actual intake ( -7 193 kcal/d or 0.2 % ; limits of agreement : -386 , 370 kcal/d ; P = 0.9 ) .


In free-living individuals , estimated EI during overfeeding determined from ES in FM and FFM was 4123 500 kcal/d and underestimated actual EI ( 4286 488 kcal/d ; -162 301 kcal or 3.8 % ; limits of agreement : -751 , 427 kcal/d ; P = 0.003 ) .


Estimated EI determined from ES in weight also underestimated actual intake ( -159 270 kcal/d or 3.7 % ; limits of agreement : -688 , 370 kcal/d ; P = 0.001 ) .


The intake-balance method can be used to estimate EI during a period of weight gain as a result of 40 % overfeeding in individuals who are inpatients or free-living with only a slight underestimate of actual EI by 0.2-3 .8 % .


To use baseline computed tomographic ( CT ) angiography to analyze imaging and clinical end points in an Interventional Management of Stroke III cohort to identify patients who would benefit from endovascular stroke therapy .


The primary clinical end point was 90-day dichotomized modified Rankin Scale ( mRS ) score .


Secondary end points were 90-day mRS score distribution and 24-hour recanalization .


Prespecified subgroup was baseline proximal occlusions ( internal carotid , M1 , or basilar arteries ) .


Exploratory analyses were subsets with any occlusion and specific sites of occlusion ( two-sided = .01 ) .


Of 656 subjects , 306 ( 47 % ) underwent baseline CT angiography or magnetic resonance angiography .


Of 306 , 282 ( 92 % ) had arterial occlusions .


At baseline CT angiography , proximal occlusions ( n = 220 ) demonstrated no difference in primary outcome ( 41.3 % [ 62 of 150 ] endovascular vs 38 % [ 27 of 70 ] intravenous [ IV ] tissue-plasminogen activator [ tPA ] ; relative risk , 1.07 [ 99 % confidence interval : 0.67 , 1.70 ] ; P = .70 ) ; however , 24-hour recanalization rate was higher for endovascular treatment ( n = 167 ; 84.3 % [ 97 of 115 ] endovascular vs 56 % [ 29 of 52 ] IV tPA ; P < .001 ) .


Exploratory subgroup analysis for any occlusion at baseline CT angiography did not demonstrate significant differences between endovascular and IV tPA arms for primary outcome ( 44.7 % [ 85 of 190 ] vs 38 % [ 35 of 92 ] , P = .29 ) , although ordinal shift analysis of full mRS distribution demonstrated a trend toward more favorable outcome ( P = .011 ) .


Carotid T - or L-type occlusion ( terminal internal carotid artery [ ICA ] with M1 middle cerebral artery and/or A1 anterior cerebral artery involvement ) or tandem ( extracranial or intracranial ) ICA and M1 occlusion subgroup also showed a trend favoring endovascular treatment over IV tPA alone for primary outcome ( 26 % [ 12 of 46 ] vs 4 % [ one of 23 ] , P = .047 ) .


Significant differences were identified between treatment arms for 24-hour recanalization in proximal occlusions ; carotid T - or L-type and tandem ICA and M1 occlusions showed greater recanalization and a trend toward better outcome with endovascular treatment .


Vascular imaging should be mandated in future endovascular trials to identify such occlusions .


Online supplemental material is available for this article .


To investigate the potential antioxidant effects of Phyllanthus niruri ( P. niruri , Euphorbiaceae ) tea on healthy subjects .


Five non-smoking , male healthy volunteers , 20 to 31 years old , were enrolled .


Each subject was treated twice , following a randomized crossover fashion regarding the ingestion of P. niruri infusion ( 5 g/750 mL ) ( tea group ) or 750 mL of water ( control group ) .


Fasting venous blood samples were collected prior to and at 1 , 2 and 4 h after infusion drinking .


Samples were tested for plasmatic gallic acid and ascorbic acid levels , erythrocytic catalase and superoxide dismutase activities , and intracellular DCFH fluorescence in granulocytes , monocytes and lymphocytes .


Catalase and superoxide dismutase activities were not altered by tea ingestion .


Plasma levels of gallic acid were significantly increased at 1 , 2 and 4 h after P. niruri ingestion and plasma ascorbic acid at 1 h after P. niruri ingestion .


Ingestion of P. niruri tea is associated with a slight increase in antioxidant markers in human blood ( ascorbic acid and gallic acid ) , which may contribute to its pharmacological effects .


Black box warnings for young adults under the age of 25 years indicate that antidepressants may increase risk of suicide .


While underlying mechanisms for age-related treatment effects remain unclear , vagally mediated cardiovascular function may play a key role .


Decreased heart rate ( HR ) and an increase in its variability ( HRV ) improve one 's capacity to adapt to environmental stress and attenuate risk for suicide .


Using a double blind , randomized , placebo-controlled , crossover , experimental study , we examine whether a single dose of escitalopram ( 20 mg ) attenuates cardiovascular responses to stress under experimental conditions and determine whether age moderates these effects .


Forty-four healthy females received a single dose of escitalopram ( 20 mg ) and placebo treatment separated by a 1-week interval ( > 5 half-lives ) .


HR and high frequency HRV ( HF HRV normalized units ; 0.15-0 .40 Hz ) were measured during resting state and stress .


While escitalopram attenuated the increase in HR and increased HF HRV , these moderate to large effects were only significant in participants over 25 years of age .


No beneficial cardiovascular effects of escitalopram were observed in those under the age of 25 .


Maturational differences in the development of the prefrontal cortex -- a critical region in the central network of autonomic control -- may underpin these differential findings .


This study provides a theoretical framework on which future research on treatment-emergent suicidality in clinical populations could be based .


Clinical decision support has the potential to improve prevention of venous thromboembolism ( VTE ) .


The purpose of this prospective study was to analyze the effect of electronic reminders on thromboprophylaxis rates in wards to which patients were admitted and transferred .


The latter was of particular interest since patient handoffs are considered to be critical safety issues .


The trial involved two study periods in the six departments of a university hospital , three of which were randomly assigned to the intervention group displaying reminders during the second period .


At 6h after admission or transfer , the algorithm checked for prophylaxis orders within 0-30h of the patient 's arrival , increasing the specificity of the displayed reminders .


The significant impact of the reminders could be seen by prophylaxis orders placed 6-24h after admission ( increasing from 8.6 % ( 223/2579 ) to 12 % ( 307/2555 ) ; p < 0.0001 ) and transfer ( increasing from 2.4 % ( 39/1616 ) to 3.7 % ( 63/1682 ) ; p = 0.034 ) .


In admission wards , the rate of thromboprophylaxis increased from 62.4 % to 67.7 % ( p < 0.0001 ) , and in transfer wards it increased from 80.2 % to 84.3 % ( p = 0.0022 ) .


Overall , the rate of prophylaxis significantly increased in the intervention group from 69.2 % to 74.3 % ( p < 0.0001 ) .


No significant changes were observed in the control group .


Postponing prophylaxis checks to 6h after admissions and transfers reduced the number of reminders by 62 % and thereby minimized the risk of alert fatigue .


The reminders improved awareness of VTE prevention in both admission and transfer wards .


This approach may contribute to better quality of care and safer patient handoffs .


The aim of this study was to evaluate the effect of carbohydrate or glutamine supplementation , or a combination of the two , on the immune system and inflammatory parameters after exercise in simulated hypoxic conditions at 4500 m.


Nine men underwent three sessions of exercise at 70 % VO2peak until exhaustion as follows : 1 ) hypoxia with a placebo ; 2 ) hypoxia with 8 % maltodextrin ( 200 mL/20 min ) during exercise and for 2 h after ; and 3 ) hypoxia after 6 d of glutamine supplementation ( 20 g/d ) and supplementation with 8 % maltodextrin ( 200 mL/20 min ) during exercise and for 2 h after .


All procedures were randomized and double blind .


Blood was collected at rest , immediately before exercise , after the completion of exercise , and 2 h after recovery .


Glutamine , cortisol , cytokines , glucose , heat shock protein-70 , and erythropoietin were measured in serum , and the cytokine production from lymphocytes was measured .


Erythropoietin and interleukin ( IL ) -6 increased after exercise in the hypoxia group compared with baseline .


IL-6 was higher in the hypoxia group than pre-exercise after exercise and after 2 h recovery .


Cortisol did not change , whereas glucose was elevated post-exercise in the three groups compared with baseline and pre-exercise .


Glutamine increased in the hypoxia + carbohydrate + glutamine group after exercise compared with baseline .


Heat shock protein-70 increased post-exercise compared with baseline and pre-exercise and after recovery compared with pre-exercise , in the hypoxia + carbohydrate group .


No difference was observed in IL-2 and IL-6 production from lymphocytes .


IL-4 was reduced in the supplemented groups .


Carbohydrate or glutamine supplementation shifts the T helper ( Th ) 1/Th2 balance toward Th1 responses after exercise at a simulated altitude of 4500 m.


The nutritional strategies increased in IL-6 , suggesting an important anti-inflammatory effect .


In 2006 , Ethicon Inc. introduced a new minimally invasive single incision sling device for the surgical treatment of stress urinary incontinence , the Gynecare TVT Secur .


For device licensing , no new evidence of TVT Secur efficacy and safety was needed : rather evidence was provided of the long-term follow-up of patients who had a procedure using a predecate retropubic tension-free vaginal tape device .


Before adopting TVT Secur into our routine clinical practice , we decided to evaluate it .


The objective of our Canadian multi-centre pragmatic randomized controlled trial was to compare the effectiveness of the new single-incision device , TVT Secur , to the established TVT device , in terms of objective cure of stress urinary incontinence ( SUI ) at 12 months postoperatively .


Other outcomes included : complications , symptoms , and incontinence-related quality of life .


The sample size estimate for our trial was 300 , but the trial stopped early because of poor recruitment .


74 women participated ( 40 allocated to TVT Secur , 34 to TVT ) .


At 12 months postoperatively , 27/33 ( 82 % ) of TVT Secur group were cured , compared with 25/28 ( 89 % ) of the TVT group ( relative risk 0.92 , 95 % confidence interval 0.75 to 1.13 , p = 0.49 ) .


Most women reported little or no SUI symptoms ( 35/37 ( 95 % ) vs 29/30 ( 97 % ) , > 0.999 ) .


Quality of life improved significantly from baseline for both groups ( IIQ-7 mean change -25 for both groups ) but did not differ between groups ( p = 0.880 ) .


Our small randomized trial did not find statistically significant differences in outcomes between women allocated to the TVT Secur device versus those allocated to the TVT device for stress urinary incontinence .


Despite the discontinuation of TVT Secur in March 2013 for commercial reasons , the importance of our study lies in making evidence available for the many women who had a TVT Secur device implanted and their physicians who may be considering alternative treatments .


Our experience illustrates the difficulty of undertaking research on new licensed devices in a rapidly changing surgical specialty , and further highlights the need for research before licensing if surgeons and their patients are to be confident in the effectiveness and safety of new surgical devices .


ClinicalTrials.gov NCT00685217 , 22 May 2008 .


Prevention of alcohol , drug and tobacco misuse by young people is a key public health priority .


There is a need to develop the evidence base through rigorous evaluations of innovative approaches to substance misuse prevention .


The Strengthening Families Programme 10-14 is a universal family-based alcohol , drugs and tobacco prevention programme , which has achieved promising results in US trials , and which now requires cross-cultural assessment .


This paper therefore describes the protocol for a randomised controlled trial of the UK version of the Strengthening Families Programme 10-14 ( SFP 10-14 UK ) .


The trial comprises a pragmatic cluster randomised controlled effectiveness trial with families as the unit of randomisation , with embedded process and economic evaluations .


Participating families will be randomised to one of two treatment groups - usual care with full access to existing services ( control group ) , or usual care plus SFP 10-14 UK ( intervention group ) .


The trial has two primary outcomes - the number of occasions that young people report having drunk alcohol in the last 30 days , and drunkenness during the last 30 days , both dichotomised as ` never ' and ' 1-2 times or more ' .


The main follow-up is at 2 years past baseline , and short-term and intermediate outcomes are also measured at 9 and 15 months .


The results from this trial will provide evidence on the effectiveness and cost-effectiveness of an innovative universal family-based substance misuse prevention programme in a UK context .


Current Controlled Trials ISRCTN63550893 .


To investigate the effect that complications have on patients ' long-term quality of life ( QoL ) after curative colorectal cancer surgery .


Colorectal cancer surgery is a high risk , with approximately 1 in 3 patients suffering a complication .


The long-term consequences of postoperative complications are important but have poorly been documented .


The MRC-CLASICC trial ( laparoscopic-assisted vs open surgery for colorectal cancer ) included prospective evaluation of QoL using validated scoring questionnaires : EORTC QLQ-C30 / CR38 and EQ5D .


These were used to compare QoL at 3 , 6 , 18 , and 36 months to baseline values for patients categorized into 2 groups : ( i ) those suffering any complication and ( ii ) those suffering any of 5 common complications ( wound , chest , anastomotic leak , hemorrhage , and cardiac event ) .


A total of 614 of 794 CLASICC patients were suitable for inclusion .


Complications occurred in 215 ( 35.0 % ) patients , including : wound complications ( 61 , 9.9 % ) , chest infection ( 50 , 8.1 % ) , anastomotic leak ( 27 , 4.4 % ) , hemorrhage ( 14 , 2.3 % ) , and cardiac event ( 26 , 4.2 % ) .


Significant long-term differences in QoL between patients with and without complications were found for Physical and Social Function , Role Functioning , and Body Image on EORTC QLQ-C30 / QLQ-CR38 analysis and Mobility , Self-care , and Pain/Discomfort on EQ5D analysis .


No significant differences were seen for emotional/cognitive functioning , global QoL , financial difficulties , or future perspectives .


Risk factors of age , gender , ASA ( American Society of Anesthesiologists ) grade , and stoma moderated the impact of complications in the short - to medium-term QoL , but had less influence on long-term QoL .


Postoperative complications have adverse effects on long-term QoL , particularly for Physical , Role and Social Functioning , and Body Image , as well as for Mobility , Self-care , and Pain/Discomfort .


These findings should inform future preoperative counseling and health care planning .


Recent data indicate that hypertension is not well controlled in many populations throughout the world .


The factors that influence individual response to anti-hypertensive treatment need to be clarified .


Pulse wave velocity ( PWV ) , as a marker of arterial stiffness , has been demonstrated to have important relationships with BP progression ; however , little information is available on the role of PWV in blood pressure ( BP ) control .


We aimed to assess BP control during the run-in treatment period in the China Stroke Primary Prevention Trial ( CSPPT ) .


These analyses included a total of 3056 treated hypertensive subjects ( age : 59.67.5 years , male/female 1339/1717 ) with PWV measured at baseline .


The average BP at enrollment was 166/95mmHg , and declined to 141/85mmHg after short-term antihypertensive treatment ( a median follow-up of 20days ) .


There was an inverse relationship between PWV level and BP reduction during the treatment , most notably for systolic BP ( with estimated coefficients of -9.01 ( P < 0.001 ) for the top quartile , as compared to the bottom quartile ) .


The association did not differ significantly by gender or types of antihypertensive drugs .


Factors related to smaller BP decline were low baseline BP , high baseline PWV , high body mass index , high creatinine , use of fewer types of antihypertensive drug , high heart rate ( only for SBP ) , high homocysteine and low age ( only for DBP ) .


PWV appears to be an independent determinant of individual response to anti-hypertensive treatment .


To determine long-term safety and efficacy of adjunctive clobazam for patients with Lennox-Gastaut syndrome ( LGS ) .


Eligible patients from two randomized controlled trials ( Phase II OV-1002 and Phase III OV-1012 ) were able to enroll in open-label extension ( OLE ) study OV-1004 beginning in December 2005 and received clobazam until they discontinued ( mandatory at 2years for patients outside the United States ) or until study completion in March 2012 .


Patients in the United States could have received clobazam for 6years before it became commercially available .


Efficacy assessments included changes in rates of drop seizures and total seizures , responder rates ( 50 % , 75 % , or 100 % decreases in seizure frequency vs. baseline ) , sustained efficacy over time , concomitant antiepileptic drug ( AED ) use , and global evaluations .


Safety assessments included exposure to clobazam , laboratory assessments , physical and neurologic examinations , vital sign monitoring , electrocardiography monitoring , and adverse event reporting .


Of 267 patients who enrolled in the OLE , 188 ( 70 % ) completed the trial .


Two hundred seven patients were from the United States , which was the only country in which patients could be treated with clobazam for > 2years .


Forty-four patients were treated with clobazam for 5years , and 11 for 6years .


Because of the low number of Year 6 patients , this group is not reported separately .


Improvements in baseline seizure rates were very stable over the course of the study , with a median 85 % decrease in drop seizures at Year 1 , 87 % at Year 2 , 92 % at Year 3 , 97 % at Year 4 , and a 91 % decrease for patients who had reached Year 5 .


Similar results were observed for total seizures ( 79 % decrease at both Years 1 and 2 , 82 % decrease at Year 3 , 75 % decrease at Year 4 , and 85 % decrease at Year 5 ) .


Responder rates were also stable for the duration of the trial .


Of patients who had achieved a 50 % decrease in median drop-seizure frequency from baseline to Month 3 , 86 % still had that degree of drop-seizure reduction at Year 3 ( and 14 % lost their initial responses ) , and 47 % were drop-seizure-free .


Most patients who had achieved drop-seizure freedom in the original controlled trials remained drop-seizure-free in the OLE .


Based on parents ' and physicians ' ratings of global evaluations , 80 % of patients were `` very much improved '' or `` much improved '' after 3years .


Of the 43 patients with concomitant AED data who were treated for 5years , 30 % increased , 19 % decreased , and 51 % had no change in numbers of AEDs versus their Week 4 regimens .


The mean modal clobazam dosage was 0.90 mg/kg/day at Year 1 and 0.97 mg/kg/day at Year 5 , suggesting that study patients did not need significant increases in dosage over time .


The safety profile was what would be expected for clobazam for LGS patients over a 5-year span , and no new safety concerns developed over time .


In this largest and longest-running trial in LGS , adjunctive clobazam sustained seizure freedom and substantial seizure improvements at stable dosages through 3years of therapy in this difficult - to-treat patient population .


A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .


Limited capacity for social engagement is a core feature of autism spectrum disorder ( ASD ) , often evident early in the child 's development .


While these skills are difficult to train , there is some evidence that active involvement in music-making provides unique opportunities for social interaction between participants .


Family-centred music therapy ( FCMT ) endeavours to support social engagement between child and parent within active music-making , yet the extent of benefits provided is unknown .


This study investigated the impacts of FCMT on social engagement abilities .


Twenty-three children ( 36-60 months ) with severe ASD received either 16 weeks of FCMT in addition to their early intervention programmes ( n = 12 ) , or their early intervention programme only ( n = 11 ) .


Change in social engagement was measured with standardized parent-report assessments , parent interviews and clinician observation .


Intention-to-treat analysis for the Vineland Social Emotional Early Childhood Scale indicated a significant effect in favour of FCMT .


Thematic qualitative analysis of the parent interviews showed that the parent-child relationship grew stronger .


FCMT improves social interactions in the home and community and the parent-child relationship , but not language skills or general social responsiveness .


This study provides preliminary support for the use of FCMT to promote social engagement in children with severe ASD .


Insulin analogues have been developed to reduce the risk of hypoglycaemia in patients with diabetes who require insulin-based treatment , but their effect on this endpoint in patients with type 1 diabetes complicated by recurrent severe hypoglycaemia is unknown .


We compared the occurrence of severe hypoglycaemic episodes in such patients during treatment with insulin analogues or human insulin .


In this investigator-initiated , prospective , randomised , open-label , blinded-endpoint crossover trial at seven medical centres in Denmark , we recruited patients ( aged 18 years ) with type 1 diabetes ( diagnosed for > 5 years ) who had reported two or more episodes of severe hypoglycaemia in the preceding year .


Patients were randomly assigned ( 1:1 ) using computer-generated site-specific randomisation lists in blocks of four to treatment with basal-bolus therapy with either analogue insulin ( detemir and aspart ) or human insulin ( human neutral protamine Hagedorn and human regular ) in a balanced crossover design .


A 1-year plus 1-year treatment period was specified , consisting of two 3-month run-in periods , each followed by a 9-month maintenance period .


The primary endpoint was the number of validated episodes of severe hypoglycaemia ( defined by need for treatment assistance from others ) reported during the maintenance periods , analysed by intention to treat .


The study is registered with ClinicalTrials.gov , number NCT00346996 .


Between May 9 , 2007 , and Oct 30 , 2009 , 159 patients were randomly assigned .


18 patients discontinued during the first run-in period , leaving 141 patients in the intention-to-treat population .


136 severe hypoglycaemic episodes were reported during treatment with human insulin and 105 episodes were reported during treatment with insulin analogues , resulting in an absolute rate reduction of 0.51 episodes ( 95 % CI 0.19-0 .84 ) per patient-year with insulin analogues .


This result corresponds to a relative rate reduction of 29 % ( 95 % CI 11-48 ; p = 0.010 ) .


Treatment with insulin detemir and aspart in patients with type 1 diabetes and recurrent severe hypoglycaemia resulted in a clinically significant reduced rate of severe hypoglycaemia compared with human insulin .


Patients with the greatest chance of benefitting from improved insulin therapy should be offered treatment with insulin analogues and be included in future trials of new insulins .


Novo Nordisk A/S .


To evaluate the effects of humor therapy assessed using observational methods on agitation , engagement , positive behaviors , affect , and contentment .


Single-blind cluster randomized controlled trial .


A total of 35 Sydney nursing homes .


All eligible residents within geographically defined areas within each nursing home were invited to participate .


Professional `` ElderClowns '' provided 9 to 12 weekly humor therapy sessions , augmented by resident engagement by trained staff `` LaughterBosses . ''


Controls received usual care .


The Behavior Engagement Affect Measure ( BEAM ) touchpad observational tool was used to capture real-time behavioral data .


The tool assesses the duration in seconds of agitation , positive behavior toward others , engagement , and affect ( angry , anxious , happy , neutral , sad ) .


Seventeen nursing homes ( 189 residents ) received the intervention and 18 homes ( 209 residents ) received usual care .


Over 26 weeks , in comparison with controls , the humor therapy group decreased in duration of high agitation ( effect size = 0.168 and 0.129 at 13 and 26 weeks , respectively ) and increased in duration of happiness ( effect size = 0.4 and 0.236 at 13 and 26 weeks , respectively ) .


We confirmed that humor therapy decreases agitation and also showed that it increases happiness .


Researchers may consider evaluating impacts of nonpharmaceutical interventions on positive outcomes .


Computer-assisted observational measures should be considered , particularly for residents with dementia and when the reliability of staff is uncertain .


To investigate whether a histone deacetylase inhibitor ( HDACi ) would be effective in an in vitro model for the neurodegenerative disease Friedreich ataxia ( FRDA ) and to evaluate safety and surrogate markers of efficacy in a phase I clinical trial in patients .


We used a human FRDA neuronal cell model , derived from patient induced pluripotent stem cells , to determine the efficacy of a 2-aminobenzamide HDACi ( 109 ) as a modulator of FXN gene expression and chromatin histone modifications .


FRDA patients were dosed in 4 cohorts , ranging from 30mg/day to 240mg/day of the formulated drug product of HDACi 109 , RG2833 .


Patients were monitored for adverse effects as well as for increases in FXN mRNA , frataxin protein , and chromatin modification in blood cells .


In the neuronal cell model , HDACi 109/RG2833 increases FXN mRNA levels and frataxin protein , with concomitant changes in the epigenetic state of the gene .


Chromatin signatures indicate that histone H3 lysine 9 is a key residue for gene silencing through methylation and reactivation through acetylation , mediated by the HDACi .


Drug treatment in FRDA patients demonstrated increased FXN mRNA and H3 lysine 9 acetylation in peripheral blood mononuclear cells .


No safety issues were encountered .


Drug exposure inducing epigenetic changes in neurons in vitro is comparable to the exposure required in patients to see epigenetic changes in circulating lymphoid cells and increases in gene expression .


These findings provide a proof of concept for the development of an epigenetic therapy for this fatal neurological disease .


To evaluate the effectiveness and tolerability of an experimental 9.5 % hydrogen peroxide whitening strip relative to a placebo control over a three-week period .


In this parallel-design , double-blind clinical trial , 54 adult volunteers were randomized to an experimental 9.5 % hydrogen peroxide whitening strip or placebo strip balancing for age and baseline tooth color , and received treatment .


Strips were worn on the maxillary arch 30 minutes daily for 20 days .


Efficacy was measured objectively as L * a * b * color change from digital images at Days 4 , 7 , 15 , and 21 .


As early as Day 4 and at all subsequent visits , the 9.5 % strip group experienced significant ( p < 0.004 ) color improvement relative to placebo for b * and L * color parameters .


The amount of color improvement increased with continuing peroxide strip use .


Mean SE between-group differences in Ab * were -0.6 0.16 , -0.8 0.15 , -1.6 0.19 , and -1.9 0.20 at Days 4 , 7 , 15 , and 21 , respectively .


Similar results were noted for AL * .


Minor tooth sensitivity was the most common adverse event , as reported by 12 % of subjects in the 9.5 % strip group and 11 % of subjects in the placebo group .


No subjects discontinued treatment due to an adverse event .


This placebo-controlled clinical trial demonstrated that an experimental 9.5 % hydrogen peroxide strip yielded significant tooth whitening relative to a placebo strip as early as after three days of product use .


Although previous studies have found reminder/recall to be effective in increasing immunization rates , little guidance exists regarding the specific ages at which it is optimal to send reminder/recall notices .


To assess the relative effectiveness of centralized reminder/recall strategies targeting age-specific vaccination milestones among children in urban areas during June 2008-June 2009 .


Three reminder/recall strategies used capabilities of the Michigan Care Improvement Registry ( MCIR ) , a statewide immunization information system : a 7-month recall strategy , a 12-month reminder strategy , and a 19-month recall strategy .


Eligible children were randomized to notification ( intervention ) or no notification groups ( control ) .


Primary study outcomes included MCIR-recorded immunization activity ( administration of 1 new dose , entry of 1 historic dose , entry of immunization waiver ) within 60 days following each notification cycle .


A total of 10,175 children were included : 2,072 for the 7-month recall , 3,502 for the 12-month reminder , and 4,601 for the 19-month recall .


Immunization activity was similar between notification versus no notification groups at both 7 and 12 months .


Significantly more 19-month-old children in the recall group ( 26 % ) had immunization activity compared to their counterparts who did not receive a recall notification ( 19 % ) .


Although recall notifications can positively affect immunization activity , the effect may vary by targeted age group .


Many 7 - and 12-month-olds had immunization activity following reminder/recall ; however , levels of activity were similar irrespective of notification , suggesting that these groups were likely to receive medical care or immunization services without prompting .


To investigate whether DTI allows assessment of renal impairment and pathology in patients with chronic glomerulonephritis .


Seventy-five patients and 20 healthy volunteers were enrolled in this study .


Renal function and kidney biopsies were evaluated .


For DTI , a respiratory-triggered coronal EPI sequence was performed ( TR , 1400 ms ; TE , 76 ms ; diffusion direction , 6 ; NEX , 4 ; b values , 0 and 600 s/mm2 ; slices thickness , 6 mm , with no intersection gap ) .


Renal ADC and FA values were calculated and compared between the groups .


Correlations between ADC/FA and histopathology were evaluated .


ADC values decreased with increased stages .


ADC differences in renal parenchyma at different disease stages were found , with the exception of the control group compared with stage 1 patients ; similar results were obtained for FA .


ADC values in the cortex and medulla in stage 1-3 patients were both statistically different , similar to the FA values .


A significant negative correlation was found between the percentage of glomerulosclerosis and FA in the renal cortex ( r = -0.74 ) , similar to the degree of tubulointerstitial fibrosis with FA in the medulla ( r = -0.76 ) .


ADC and FA values are correlated with the degree of renal impairment , the percentage of glomerulosclerosis , and area of interstitial fibrosis .


DTI can be used to assess renal function impairment in patients with chronic glomerulonephritis .


ADC and FA values were correlated with tubulointerstitial fibrosis and glomerulosclerosis .


Identification of renal impairment is helpful for timely treatment .


DTI can be used for non-invasive assessment of renal pathology .


Posttraumatic stress disorder ( PTSD ) is associated with abnormal functioning of the hypothalamic-pituitary-adrenal ( HPA ) axis ; however , limited research has examined whether cortisol levels change following successful PTSD treatment .


The current study examined the impact of successful PTSD treatment on the cortisol awakening response ( CAR ) .


Twenty-nine adults participating in a treatment trial for chronic PTSD provided saliva samples ( upon waking , and 30 - , 45 - , and 60 min postwaking ) before and after receiving either prolonged exposure therapy or sertraline .


PTSD responder status ( i.e. , loss or retention of a PTSD diagnosis ) served as the predictor variable .


Outcome measures included area under the curve with respect to ground and increase , reflecting total cortisol output and HPA axis reactivity , respectively .


A series of hierarchical regressions revealed no significant main effects of PTSD responder status for either CAR outcome .


However , a significant gender by treatment response interaction for cortisol reactivity revealed that female treatment nonresponders displayed higher cortisol reactivity following treatment than female responders , whereas cortisol reactivity did not change pre - to posttreatment for male responders .


Findings remained after controlling for age , trauma history , baseline medication status , baseline PTSD , and baseline depressive symptoms .


Loss of a PTSD diagnosis may contribute to decreased cortisol reactivity in females .


Neuroendocrine changes following treatment may emerge only for specific subgroups , highlighting the importance of exploring treatment moderators .


Abundant evidence suggests that allelic variation in the serotonin transporter-linked polymorphic region ( 5-HTTLPR ) influences susceptibility to stress and its affective consequences due to brain serotonergic vulnerability .


Based on recent assumptions , the present study examined whether the 5-HTTLPR genotype may also interact with a vulnerability to chronic stress experience ( conceptualized by trait neuroticism ) in order to influence sleep quality and , additionally , whether this is influenced by brain serotonergic manipulations .


In a well-balanced experimental design , homozygous S-allele ( n = 57 ) and L-allele ( n = 54 ) genotypes with high and low chronic stress vulnerability ( neuroticism ) were first assessed for general past sleep quality during a month before onset of the experiment .


Then subjects were assessed for sleep quality following 7 days of tryptophan ( 3.0 g/day ) or placebo intake .


Although high neuroticism was significantly related to a higher frequency of stressful life events and daily hassles , it did not interact with the 5-HTTLPR genotype on general past sleep quality .


However , as expected , a 7 day period of tryptophan administration was exclusively associated with better sleep quality scores in the S ' / S ' genotype with high trait neuroticism .


Current findings suggest that 5-HTTLPR does not directly interact with stress vulnerability in order to influence sleep quality .


Instead , based on current and previous findings , it is suggested that the S ' / S ' 5-HTTLPR genotype promotes the risk for stress-related sleep disturbances because of an increased susceptibility to the depressogenic consequences of stress .


Accordingly , by way of reducing depressive symptomatology , tryptophan augmentation may particularly improve sleep quality in stress-vulnerable individuals carrying the 5-HTTLPR S-allele .


By using orthogonal design method to optimnize prescription of pulsed electric field at Jiaji ( EX - B 2 ) points for spinal cord injury ( SCI ) .


Fifty six patients of SCI were selected , in which 36 cases were divided into orthogonal design trial and 20 cases were into clinical verification .


With 36 patients who received orthogonal design trial , Frankel grading scale was used as observation index to screen optimal prescription of pulsed electric field .


Pulse frequency ( factor A ) included low frequency ( factor A ( I ) , 10 ( 2 ) Hz ) .


moderate frequency ( factor A ( II ) , 10 ( 4 ) Hz ) and high frequency ( factor A ( III ) , 10 ( 3 ) Hz ) ; pulse amplitude ( factor B ) included 0-30 V ( factor B ) , 0-60 V ( factor B ( II ) ) and 0-90 V ( factor B ( III ) ) ; pulse width ( factor C ) included 0.1 ms ( factor C ( I ) ) .


0.6 ms ( factor C ( II ) ) and 0.9 ms ( factor C ( III ) ) ; acupuncture time ( factor D ) included one month ( DI ) , three months ( D ( II ) ) and five months ( D ( III ) ) .


Twenty patients were used for clinical efficacy observation and the effects of screened optimal pre scription of pulsed electric field at Jiaji ( EX-B 2 ) points combined with regular rehabilitation training on spasm se - verity , score of sensory and motor functions , Barthel index and Frankel score were observed .


( 1 ) As results of orthogonal design trial , the optimal prescription was A ( III ) B ( III ) , C ( I ) , D ( III ) , which were high frequency ( 10 ( 3 ) Hz ) , 0-90 V of pulse amplitude , 0.4 ms of pulse width and 5 months of treatment time .


( 2 ) As results of 20 patient clinical verification , Ashworth score , tendon reflex and clonus were all significantly improved ( P < 0.001 , P < 0.01 ) , the scores of sensory and motor functions were evidently improvedtl ( P < 0.001 , P < 0.05 ) , and Barthel in dex and Frankel score were also enhanced ( P < 0.001 , P < 0.05 ) .


The optimal prescription of pulsed electric field at Jiaji ( EX-B 2 ) points for spinal cord injury is high frequency ( 10 & Hz ) , 0-90 V of pulse amplitude , 0.4 ms of pulse width and 5 months of treatment time .


The optimal prescription of pulsed electric field at Jiaji ( EX-B 2 ) points combined with regular rehabilitation could obviously improve spasm severity , enhance senso - ry and motor functions , and ameliorate activity of daily life and Frankel score .


To compare the impacts of electroacu puncture ( EA ) and moxibustion ( Mox ) on the prima ry gastrointestinal symptoms and the expressions of colonic mucosa-associated neuropeptide substance P ( SP ) and vasoactive intestinal peptide ( VIP ) in patients with either diarrhea-predominant or constipation-predominant irritable bowel syndrome ( IBS-D and IBS-C , respectively ) .


Eighty-five IBS patients were randomly allocated to the EA and Mox groups .


Zusanli ( ST 36 ) and Shangjuxu ( ST 37 ) were selected as acupoints for electroacupuncture or warm moxibustion treatment once a day for 14 consecutive days .


Before and after the treatment sessions , a Visual Analog Pain Scale and the Bristol Stool Form Scale were used to evaluate gastrointestinal symptoms .


There were four dropout cases , leaving 81 participants ( 41 with IBS-D and 40 with IBS-C ) who volunteered to undergo colonoscopy before and after the treatment sessions .


During colonoscopy , sigmoid mucosa were collected to detect SP and VIP expression using immunohistochemistry assay .


Both EA and Mox treatments were effective at relieving abdominal pain in IBS-D and IBS-C patients .


However , Mox was more effective at reducing diarrhea in IBS-D patients , whereas EA was more effective at improving constipation in IBS-C patients .


EA and Mox treatments both down-regulated the abnormally increased SP and VIP expression in the colonic mucosa , with no significant difference shown between the two treatments .


Both EA and Mox treatments are effective at ameliorating gastrointestinal symptoms by reducing SP and VIP expression in the colonic mucosa of IBS patients .


The aim of this study was to assess the usefulness of colour duplex sonography ( CDS ) - guided temporal artery biopsy ( TAB ) for the diagnosis of GCA in patients with suspected GCA .


From September 2009 through December 2012 , 112 consecutive patients with suspected GCA were randomized to undergo CDS-guided TAB or standard TAB .


All patients underwent temporal artery physical examination and temporal artery CDS prior to TAB .


CDS of the temporal artery was performed by the same ultrasonographer , who was unaware of the patient 's clinical data , and all TABs were evaluated by the same pathologist .


Seven patients in whom biopsy failed to sample temporal artery tissue were excluded from the analysis .


Fifty patients were randomized to undergo CDS-guided TAB and 55 patients to standard TAB .


Except for a younger age in patients who underwent standard TAB ( P = 0.026 ) , no significant differences were observed between the two groups .


There were no significant differences in the frequencies of positive TAB for classic transmural inflammation ( 28 % vs 18.2 % ) or for periadventitial small vessel vasculitis and/or vasa vasorum vasculitis ( 6 % vs 14.5 % ) between the two groups .


No significant differences in the frequency of positive TAB in the two groups were observed when we excluded the patients treated with glucocorticoids and when we stratified the patients of the two groups for the presence or absence of the halo sign .


Our study showed that CDS-guided TAB did not improve the sensitivity of TAB for diagnosing GCA .


The importance of interactions between the host and gut microbiota in the pathogenesis of irritable bowel syndrome ( IBS ) is becoming increasingly apparent .


Probiotics offer a potential new treatment for IBS , but current results are conflicting , largely as a result of poorly designed trials and nonstandardisation of outcome measures .


To assess the efficacy of a liquid , multi-strain probiotic ( Symprove ) in IBS .


A single-centre , randomised , double-blind , placebo-controlled trial of adult patients with symptomatic IBS .


Patients received 12 weeks of treatment with the probiotic or placebo ( 1 mL/kg/day ) .


The primary efficacy measure was the difference in change in the IBS symptom severity score ( IBS-SSS ) between probiotic vs. placebo at week 12 .


Secondary outcome measures included change in the IBS quality of life ( IBS-QOL ) score and change in the IBS-SSS symptom component scores .


A total of 186 patients were randomised and 152 patients completed the study .


The mean change in IBS-SSS was -63.3 probiotic vs. -28.3 placebo .


The mean difference in the IBS-SSS was statistically significant [ -35.0 ( 95 % CI ; -62.03 , -7.87 ) ; P = 0.01 ] .


There was no significant improvement in the IBS-QOL .


No serious adverse events were reported .


The multi-strain probiotic was associated with a statistically significant improvement in overall symptom severity in patients with IBS , and was well tolerated .


These results suggest this probiotic confers benefit in IBS and deserves further investigation ( ISRCTN identifier : 77512412 ) .


Bevacizumab , a humanized monoclonal antibody against vascular endothelial growth factor , has shown increased pathological complete response rates when added to neoadjuvant chemotherapy .


In various cancer types , bevacizumab treatment was accompanied by an increased risk of bleedings and other surgical complications .


We assessed associated surgical complications .


In the GeparQuinto trial , 1,948 patients were randomized to receive four cycles epirubicin/cyclophosphamide ( EC , 90/600mg/m ( 2 ) q3w ) followed by four cycles docetaxel ( D , 100mg/m ( 2 ) q3w ) each with ( ECB-DB ) or without ( EC-D ) bevacizumab ( B , 15mg/kg q3w ) concurrent with chemotherapy .


Surgery had to be performed not earlier than 28days after the last bevacizumab infusion , but within days 21 and 35 after the last chemotherapy .


In 743 ( 38.1 % ) patients , a surgical complication ( bleedings , hematomas , necrosis , wound infections , abscess ) was documented prospectively .


Baseline characteristics of the patients were well balanced between both arms .


The breast-conserving surgery ( BCS ) rate ( N = 502 ) was 69.1 % ( EC-D ) and 71.9 % ( ECB-DB ; p = 0.464 ) .


The first surgical procedure was performed at a median of 29 ( EC-D ) and 34days ( ECB-DB ) after last chemotherapy with or without bevacizumab infusion ( p < 0.001 ) .


Surgical complications were documented in 38 ( 10.9 % ; EC-D ) and 59 ( 15.0 % ; ECB-DB ) patients ( p = 0.103 ) .


Surgical complications were significantly higher after ECD-DB only in patients treated with BCS ( N = 53 ; p = 0.029 ) or in those requiring repeat surgery in order achieve clear margins ( N = 23 ; p = 0.037 ) compared to the EC-D group .


Addition of bevacizumab to neoadjuvant chemotherapy might be associated with an increased risk for surgical complications in patients treated with BCS or after repeated surgeries .


Whether convective therapies allow better control of serum phosphate ( P ) is still undefined , and no data are available concerning on-line haemofiltration ( HF ) .


The objectives of the study are to evaluate the effect of convective treatments ( CTs ) on P levels in comparison with low-flux haemodialysis ( HD ) and to evaluate the correlates of serum phosphate in a post hoc analysis of a randomized clinical trial .


This analysis was performed in the database of a multicentre , open label and randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD ( 70 patients ) or CTs : on-line pre-dilution HF ( 36 patients ) or on-line pre-dilution haemodiafiltration ( 40 patients ) .


CTs did not affect P ( P = 0.526 ) , calcium ( Ca ) ( P = 0.849 ) and parathyroid hormone levels ( P = 0.622 ) .


P levels were associated with the use of phosphate binders including aluminium-based phosphate binders ( P < 0.001 ) and sevelamer ( P < 0.001 ) , pre-dialysis bicarbonate levels ( P < 0.001 ) and pre-dialysis blood K levels ( P < 0.001 ) .


On multivariate analysis ( generalized linear model ) , serum P was again largely unassociated with CTs ( P = 0.631 ) .


Notably , participating centres were by far the strongest independent correlate of serum P , explaining 45.3 % of the variance of serum P over the trial and this association was confirmed at multivariate analysis .


Bicarbonate ( P < 0.001 ) and , to a weaker extent , serum K ( P = 0.032 ) were independently related to serum P.


In comparison with low-flux HD , CTs did not significantly affect serum P levels .


Participating centres were the main source of P variability during the trial followed by treatment with phosphate binders , serum bicarbonate and , to a weak extent , serum potassium levels ( ClinicalTrials.gov Identifier : NCT011583309 ) .


Fine particulate matter ( PM ) air pollution is associated with numerous adverse health effects , including increased blood pressure ( BP ) and vascular dysfunction .


Coarse PM substantially contributes to global air pollution , yet differs in characteristics from fine particles and is currently not regulated .


However , the cardiovascular ( CV ) impacts of coarse PM exposure remain largely unknown .


Our goal was to elucidate whether coarse PM , like fine PM , is itself capable of eliciting adverse CV responses .


We performed a randomized double-blind crossover study in which 32 healthy adults ( 25.9 6.6 years of age ) were exposed to concentrated ambient coarse particles ( CAP ; 76.2 51.5 g/m ( 3 ) ) in a rural location and filtered air ( FA ) for 2 hr .


We measured CV outcomes during , immediately after , and 2 hr postexposures .


Both systolic ( mean difference = 0.32 mmHg ; 95 % CI : 0.05 , 0.58 ; p = 0.021 ) and diastolic BP ( 0.27 mmHg ; 95 % CI : 0.003 , 0.53 ; p = 0.05 ) linearly increased per 10 min of exposure during the inhalation of coarse CAP when compared with changes during FA exposure .


Heart rate was on average higher ( 4.1 bpm ; 95 % CI : 3.06 , 5.12 ; p < 0.0001 ) and the ratio of low-to-high frequency heart rate variability increased ( 0.24 ; 95 % CI : 0.07 , 0.41 ; p = 0.007 ) during coarse particle versus FA exposure .


Other outcomes ( brachial flow-mediated dilatation , microvascular reactive hyperemia index , aortic hemodynamics , pulse wave velocity ) were not differentially altered by the exposures .


Inhalation of coarse PM from a rural location is associated with a rapid elevation in BP and heart rate during exposure , likely due to the triggering of autonomic imbalance .


These findings add mechanistic evidence supporting the biological plausibility that coarse particles could contribute to the triggering of acute CV events .


There have been repeated calls from health professionals and policy-makers to clarify the side-effects of the increasingly popular consumption trend of alcohol mixed with energy drinks ( AmED ) .


There is a dearth of research assessing the differential effects of AmED relative to alcohol by comparing self-reported psychological and physiological outcomes whilst under the influence of these substances .


The aim of the present study was to examine the acute effects of a moderate alcohol and energy drink ( ED ) dose on self-reported psychological and physiological outcomes .


Using a single-blind , placebo-controlled , crossover design , 28 adults completed four sessions where they were administered : ( i ) 0.50 g/kg alcohol , ( ii ) 3.57 mL/kg ED , ( iii ) AmED , and ( iv ) placebo .


Participants independently completed the Profile of Mood States and a Somatic Symptom Scale at baseline and at 30 and 125min after beverage administration .


Breath alcohol concentration peaked at .068 % and .067 % in the alcohol and AmED conditions , respectively .


There were no interactive alcohol and ED effects on self-reported psychological outcomes .


Treatment effects for physiological outcomes generally only related to alcohol or ED administration , with the exception of a moderate magnitude decrease in heart palpitation ratings following alcohol relative to AmED .


Decreased muscular tension ratings were evident when the two constituents were consumed separately relative to placebo .


The results provide evidence of few subjective changes in physiological and psychological state after consuming AmED relative to alcohol .


The majority of treatment-based changes arose from the independent effects of alcohol or ED , rather than being modified by their interaction .


However , research extending into higher dosage domains is required to increase outcome generalisability for consumers in the night-time economy .


This randomized , controlled , single-blinded multicenter study evaluated the efficacy of latest-generation fibrin sealant containing synthetic aprotinin as fibrinolysis inhibitor as supportive treatment for hemostasis after elective partial hepatectomy .


Adult subjects undergoing resection of at least one liver segment were assigned to treatment with fibrin sealant or manual compression with a surgical gauze swab if persistent oozing necessitated additional hemostatic measures after primary control of arterial and venous bleeding .


The primary outcome measure was the proportion of subjects with intraoperative hemostasis at 4 min after start of randomized treatment application .


Secondary efficacy outcome measures included intraoperative hemostasis at 6 , 8 , and 10 min , intra - and postoperative rebleedings , transfusion requirements , and drainage volume .


Seventy subjects were randomized .


Hemostasis at 4 min was achieved in 29/35 ( 82.9 % ) fibrin sealant subjects compared with 13/35 ( 37.1 % ) control subjects ( p < 0.001 ) .


Significantly more fibrin sealant subjects achieved hemostasis at 6 ( p < 0.001 ) , 8 ( p = 0.028 ) , and 10 min ( p = 0.017 ) .


The number of rebleedings was low in both study arms .


Transfusion requirements and 48-h drainage volumes were similar between the study arms .


No adverse events related to study treatment were reported .


Fibrin sealant was shown to be safe and superior to manual compression in the control of parenchymal bleeding after hepatic resection .


The use of synthetic aprotinin as fibrinolysis inhibitor further improves the safety margin of fibrin sealant by eliminating the risk of transmission of bovine spongiform encephalopathy and other bovine pathogens .


Whether early antiretroviral therapy ( ART ) initiation could impact sexual risk behaviours remains to be documented .


We aimed to investigate changes in sexual behaviours within the 24 months following an early versus standard ART initiation in HIV-positive adults with high CD4 counts .


We used data from a prospective behavioural study nested in a randomized controlled trial of early ART ( Temprano-ANRS12136 ) .


Time trends in sexual behaviours from enrolment in the trial ( M0 ) to 12-month ( M12 ) and 24-month ( M24 ) visits were measured and compared , using Generalized Estimating Equations models , between participants randomly assigned either to initiate ART immediately ( early ART ) or to defer ART initiation until on-going WHO starting criteria are met ( standard ART ) .


Indicators of sexual behaviours included 1 ) sexual activity in the past year , 2 ) multiple partnership in the past year , 3 ) unprotected sex at last intercourse and 4 ) risky sex ( i.e. unprotected sex with a partner of HIV negative/unknown status ) at last intercourse .


Analyses included 1952 participants ( 975 with early ART and 977 with standard ART ; overall median baseline CD4 count : 469/mm ( 3 ) ) .


Among participants with early ART , significant decreases were found between M0 and M24 in sexual activity ( Odds Ratio [ OR ] 0.72 , 95 % Confidence Interval [ 95 % CI ] 0.57-0 .92 ) , multiple partnership ( OR 0.57 , 95 % CI 0.41-0 .79 ) , unprotected sex ( OR 0.59 , 95 % CI 0.47-0 .75 ) and risky sex ( OR 0.58 , 95 % CI 0.45-0 .76 ) .


Among participants with standard ART , sexual behaviours showed similar trends over time .


These decreases mostly occurred within the 12 months following enrolment in the trial in both groups and prior to ART initiation in participants with standard ART .


For unprotected sex and risky sex , decreases were or tended to be more pronounced among patients reporting that their last sexual partner was non-cohabiting .


In these sub-Saharan adults with high CD4 counts , entry into HIV care , rather than ART initiation , resulted in decreased sexual activity and risky sexual behaviours .


We did not observe any evidence of a risk compensation phenomenon associated with early ART initiation .


These results illustrate the potential behavioural preventive effect of early entry into care , which goes hand in hand with early ART initiation .


Oropharyngeal dysphagia ( OD ) is a major gastrointestinal motility disorder that causes severe nutritional and respiratory complications in elderly and neurological patients .


In an earlier study , we found that stimulation of pharyngeal sensory neurons by capsaicinoids acting on transient receptor potential vanilloid 1 ( TRPV1 ) improved the swallow response of dysphagic patients .


The aim of this study was to explore the effect of piperine , a dual TRPV1/TRPA1 agonist , on the swallow response of dysphagic patients .


A videofluoroscopic study was performed to assess the signs of impaired safety and efficacy of swallow and the swallow response of 40 dysphagic patients while swallowing one series of nectar control boluses and two series of nectar boluses supplemented with piperine .


Patients were randomized into two groups : one group received 150 M piperine and the other group received 1 mM .


Piperine improved the safety of swallow by : ( a ) reducing the prevalence of unsafe swallows by -34.48 % ( P = 0.004 ) at 150 M and -57.19 % ( P < 0.001 ) at 1 mM , and the severity score of the penetration-aspiration scale from 3.25 0.51 to 1.85 0.27 ( P = 0.003 , 1 mM ) ; and ( b ) shortening the time to laryngeal vestibule closure from 0.366 0.024 to 0.270 0.022 s with 150 M piperine ( P < 0.001 ) and from 0.380 0.032 to 0.306 0.028 s with 1 mM piperine ( P < 0.05 ) .


Supplementing the alimentary bolus with piperine speeds swallow response and strongly improves safety of swallow in patients with OD , with a maximal therapeutic effect at 1 mM .


Our results suggest that activation of TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation strategy for dysphagic patients .


We performed an open-label , multicenter , phase 3 study of the safety and efficacy of twice-daily telaprevir in treatment-naive patients with chronic hepatitis C virus ( HCV ) genotype 1 infection , including those with cirrhosis .


Patients were randomly assigned to groups treated with telaprevir 1125 mg twice daily or 750 mg every 8 hours plus peginterferon alfa-2a and ribavirin for 12 weeks ; patients were then treated with peginterferon alfa-2a and ribavirin alone for 12 weeks if their level of HCV RNA at week 4 was < 25 IU/mL or for 36 weeks if their level was higher .


The primary objective was to demonstrate noninferiority of telaprevir twice daily versus every 8 hours in producing a sustained virological response 12 weeks after the end of therapy ( SVR12 ) ( based on a -11 % lower limit of the 95 % lower confidence interval for the difference between groups ) .


At baseline , of 740 patients , 85 % had levels of HCV RNA 800,000 IU/mL , 28 % had fibrosis ( F3-F4 ) , 14 % had cirrhosis ( F4 ) , 57 % were infected with HCV genotype 1a , and 71 % had the non-CC IL28B genotype .


Of patients who were treated with telaprevir twice daily , 74.3 % achieved SVR12 compared with 72.8 % of patients who were treated with telaprevir every 8 hours ( difference in response , 1.5 % ; 95 % confidence interval , -4.9 % to 12.0 % ) , so telaprevir twice daily is noninferior to telaprevir every 8 hours .


All subgroups of patients who were treated with telaprevir twice daily versus those who were treated every 8 hours had similar rates of SVR12 .


The most frequent adverse events ( AEs ) in the telaprevir phase were fatigue ( 47 % ) , pruritus ( 43 % ) , anemia ( 42 % ) , nausea ( 37 % ) , rash ( 35 % ) , and headache ( 26 % ) ; serious AEs were reported in 9 % of patients .


Rates of AEs and serious AEs were similar or slightly higher among patients treated with telaprevir every 8 hours .


Based on a phase 3 trial , telaprevir twice daily is noninferior to every 8 hours in producing SVR12 , with similar levels of safety and tolerability .


These results support use of telaprevir twice daily in patients with chronic HCV genotype 1 infection , including those with cirrhosis .


ClinicalTrials.gov , Number : NCT01241760 .


Radiotherapy has a good effect in palliation of painful bone metastases , with a pain response rate of more than 60 % .


However , shortly after treatment , in approximately 40 % of patients a temporary pain flare occurs , which is defined as a two-point increase of the worst pain score on an 11-point rating scale compared to baseline , without a decrease in analgesic intake , or a 25 % increase in analgesic intake without a decrease in worst pain score , compared to baseline .


A pain flare has a negative impact on daily functioning and mood of patients .


It is thought to be caused by periostial edema after radiotherapy .


Dexamethasone might diminish this edema and thereby reduce the incidence of pain flare .


Two non-randomized studies suggest that dexamethasone reduces the incidence of a pain flare by 50 % .


The aim of this trial is to study the effectiveness of dexamethasone to prevent a pain flare after palliative radiotherapy for painful bone metastases and to determine the optimal dose schedule .


This study is a three-armed , double-blind , placebo-controlled multicenter trial .


We aim to include 411 patients with uncomplicated painful bone metastases from any type of primary solid tumor who receive short schedule radiotherapy ( all conventional treatment schedules from one to six fractions ) .


Arm 1 consists of daily placebo for four days , arm 2 starts with 8mg dexamethasone before the ( first ) radiotherapy and three days placebo thereafter .


Arm 3 consists of four days 8mg dexamethasone .


The primary endpoint is the occurrence of a pain flare .


Secondary endpoints are pain , quality of life and side-effects of dexamethasone versus placebo .


Patients complete a questionnaire ( Brief Pain Inventory with two added questions about side-effects of medication , the EORTC QLQ-C15-PAL and QLQ-BM22 for quality of life ) at baseline , daily for two weeks and lastly at four weeks .


This study will show whether dexamethasone is effective in preventing a pain flare after palliative radiotherapy for painful bone metastases and , if so , to determine the optimal dose .


This study is registered at ClinicalTrials.gov : NCT01669499 .


HIV infection is associated with a greater risk for fasting hyperinsulinemia , impaired glucose tolerance , and higher incidence rates for vascular disease , myocardial infarction , or stroke despite effective combination antiretroviral therapy ( cART ) .


The underlying mechanism ( s ) may involve chronic low-grade systemic inflammation and immune cell activation .


Dipeptidyl peptidase-4 inhibitors ( sitagliptin ) improve glucose tolerance and may possess immunomodulatory effects because leukocyte CD26 cell surface receptors express dipeptidyl peptidase-4 activity .


Sitagliptin will reduce inflammatory and immune cell activation markers known to be elevated in cART-treated HIV-infected ( HIV + ) adults with impaired glucose tolerance .


This was designed as a prospective , randomized , placebo-controlled , double-blind trial of sitagliptin in HIV + adults .


The setting was an academic medical center .


Patients were cART-treated HIV + men and women ( n = 36 ) with stable HIV disease and impaired glucose tolerance .


Interventions included sitagliptin 100 mg/d or placebo for 8 weeks .


At baseline and week 8 , plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 concentrations ( ELISA ) , oral glucose tolerance , and abdominal sc adipose mRNA expression for M1 macrophage markers ( monocyte chemotactic protein-1 , EGF-like module-containing , mucin-like hormone receptor 1 ) .


Sitagliptin reduced glucose area under the curve ( P = .002 ) and improved oral glucose insulin sensitivity index ( P = .04 ) more than placebo .


Sitagliptin reduced plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 levels more than placebo ( P < .009 ) .


Adipose tissue monocyte chemotactic protein-1 mRNA abundance declined significantly more ( P = .01 ) , and adipose EGF-like module-containing , mucin-like hormone receptor 1 mRNA expression tended to decline more ( P = .19 ) in sitagliptin than placebo .


Sitagliptin had beneficial systemic and adipose anti-inflammatory effects in cART-treated HIV + adults with impaired glucose tolerance .


Large-scale , long-term studies should determine whether sitagliptin reduces cardiovascular risk and events in HIV + adults .


The purpose of this study was to compare the effects of manual therapy with exercise to kinesiotaping with exercise for patients with subacromial impingement syndrome .


Randomized clinical before and after trial was used .


Fifty-four patients diagnosed as having subacromial impingement syndrome who were referred for outpatient treatment were included .


Eligible patients ( between 30 and 60 years old , with unilateral shoulder pain ) were randomly allocated to 2 study groups : kinesiotaping with exercise ( n = 28 ) or manual therapy with exercise ( n = 26 ) .


In addition , patients were advised to use cold packs 5 times per day to control for pain .


Visual analog scale for pain , Disability of Arm and Shoulder Questionnaire for function , and diagnostic ultrasound assessment for supraspinatus tendon thickness were used as main outcome measures .


Assessments were applied at the baseline and after completing 6 weeks of related interventions .


At the baseline , there was no difference between the 2 group characteristics ( P > .05 ) .


There were significant differences in both groups before and after treatment in terms of pain decrease and improvement of Disability of Arm and Shoulder Questionnaire scores ( P < .05 ) .


No difference was observed on ultrasound for tendon thickness after treatment in both groups ( P > .05 ) .


The only difference between the groups was at night pain , resulting in favor of the kinesiotaping with exercise group ( P < .05 ) .


For the group of subjects studied , no differences were found between kinesiotaping with exercise and manual therapy with exercise .


Both treatments may have similar results in reducing pain and disability in subacromial impingement in 6 weeks .