The number of glaucoma medications was decreased from 2.2 0.8 to 0.5 1.2 in MMC group ( p = 0.001 ) and from 2.6 1.0 to 0.5 0.7 in non-MMC group ( p < 0.001 ) .


Goniopuncture was performed in seven eyes ( 47 % ) in the MMC group , compared with 16 eyes ( 73 % ) in the non-MMC group ( p = 0.13 ) .


IOP < 10 mmHg was achieved in seven of 15 eyes in the MMC group and in two of 22 in the non-MMC group ( p = 0.009 ) .


Complication rate was low , and no difference between groups was evident .


Deep sclerectomy seems to be effective and safe in reducing IOP in patients with NTG .


Intraoperative use of MMC results in lower postoperative IOP 12-month postoperatively without increased rate of complications .


Vent-HeFT is a multicentre randomized trial designed to investigate the potential additive benefits of inspiratory muscle training ( IMT ) on aerobic training ( AT ) in patients with chronic heart failure ( CHF ) .


Forty-three CHF patients with a mean age of 5812 years , peak oxygen consumption ( peak VO2 ) 17.95 mL/kg/min , and LVEF 29.55 % were randomized to an AT/IMT group ( n = 21 ) or to an AT/SHAM group ( n = 22 ) in a 12-week exercise programme .


AT involved 45 min of ergometer training at 70-80 % of maximum heart rate , three times a week for both groups .


In the AT/IMT group , IMT was performed at 60 % of sustained maximal inspiratory pressure ( SPImax ) while in the AT/SHAM group it was performed at 10 % of SPImax , using a computer biofeedback trainer for 30 min , three times a week .


At baseline and at 3 months , patients were evaluated for exercise capacity , lung function , inspiratory muscle strength ( PImax ) and work capacity ( SPImax ) , quality of life ( QoL ) , LVEF and LV diameter , dyspnoea , C-reactive protein ( CRP ) , and NT-proBNP .


IMT resulted in a significantly higher benefit in SPImax ( P = 0.02 ) , QoL ( P = 0.002 ) , dyspnoea ( P = 0.004 ) , CRP ( P = 0.03 ) , and NT-proBNP ( P = 0.004 ) .


In both AT/IMT and AT/SHAM groups PImax ( P < 0.001 , P = 0.02 ) , peak VO2 ( P = 0.008 , P = 0.04 ) , and LVEF ( P = 0.005 , P = 0.002 ) improved significantly ; however , without an additional benefit for either of the groups .


This randomized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF .


These findings advocate for application of IMT in cardiac rehabilitation programmes .


Anaesthetists may fail to recognize and manage certain rare intraoperative events .


Simulation has been shown to be an effective educational adjunct to typical operating room-based education to train for these events .


It is yet unclear , however , why simulation has any benefit .


We hypothesize that learners who are allowed to manage a scenario independently and allowed to fail , thus causing simulated morbidity , will consequently perform better when re-exposed to a similar scenario .


Using a randomized , controlled , observer-blinded design , 24 first-year residents were exposed to an oxygen pipeline contamination scenario , either where patient harm occurred ( independent group , n = 12 ) or where a simulated attending anaesthetist intervened to prevent harm ( supervised group , n = 12 ) .


Residents were brought back 6 months later and exposed to a different scenario ( pipeline contamination ) with the same end point .


Participants ' proper treatment , time to diagnosis , and non-technical skills ( measured using the Anaesthetists ' Non-Technical Skills Checklist , ANTS ) were measured .


No participants provided proper treatment in the initial exposure .


In the repeat encounter 6 months later , 67 % in the independent group vs 17 % in the supervised group resumed adequate oxygen delivery ( P = 0.013 ) .


The independent group also had better ANTS scores [ median ( interquartile range ) : 42.3 ( 31.5-53 .1 ) vs 31.3 ( 21.6-41 ) , P = 0.015 ] .


There was no difference in time to treatment if proper management was provided [ 602 ( 490-820 ) vs 610 ( 420-800 ) s , P = 0.79 ] .


Allowing residents to practise independently in the simulation laboratory , and subsequently , allowing them to fail , can be an important part of simulation-based learning .


This is not feasible in real clinical practice but appears to have improved resident performance in this study .


The purposeful use of independent practice and its potentially negative outcomes thus sets simulation-based learning apart from traditional operating room learning .


Cardiovascular disease ( CVD ) and underlying atherosclerosis begin in childhood and are related to CVD risk factors .


This study evaluates tools and strategies to enhance adoption of new CVD risk reduction guidelines for children .


Thirty-two practices , recruited and supported by 2 primary care research networks , were cluster randomized to a multifaceted controlled intervention .


Practices were compared with guideline-based individual and composite measures for BMI , blood pressure ( BP ) , and tobacco .


Composite measures were constructed by summing the numerators and denominators of individual measures .


Preintervention and postintervention measures were assessed by medical record review of children ages 3 to 11 years .


Changes in measures ( pre-post and intervention versus control ) were compared .


The intervention group BP composite improved by 29.5 % , increasing from 49.7 % to 79.2 % , compared with the control group ( 49.5 % to 49.6 % ; P < .001 ) .


Intervention group BP interpretation improved by 61.1 % ( from 0.2 % to 61.3 % ) , compared with the control group ( 0.4 % to 0.6 % ; P < .001 ) .


The assessment of tobacco exposure or use for 5 - to 11-year-olds in the intervention group improved by 30.3 % ( from 3.4 % to 49.1 % ) versus the control group ( 0.6 % to 21.4 % ) ( P = .042 ) .


No significant change was seen in the BMI or tobacco composites measures .


The overall composite of 9 measures improved by 13.4 % ( from 48.2 % to 69.8 % ) for the intervention group versus the control group ( 47.4 % to 55.2 % ) ( P = .01 ) .


Significant improvement was demonstrated in the overall composite measure , the composite measure of BP , and tobacco assessment and advice for children aged 5 to 11 years .


Veliparib ( ABT-888 ) is a potent oral inhibitor of Poly ( ADP-ribose ) polymerase enzyme that is currently in development for the treatment of non-hematologic and hematologic malignancies .


This analysis characterizes the population pharmacokinetics of veliparib , including developing a structural pharmacokinetic model and testing patient demographics and covariates for potential influence on veliparib pharmacokinetics in patients with non-hematologic malignancies .


The analysis dataset included 3,542 veliparib concentration values from 325 patients with non-hematologic malignancies enrolled in three phase I and one phase II studies .


Population pharmacokinetic modeling was performed using NONMEM .


The likelihood ratio test was used for comparison of nested models , and visual predictive check was employed for model qualification .


Covariates tested included body size measures , creatinine clearance ( CLCR ) , formulation , age , sex , race , liver function tests , and coadministration with temozolomide .


A one-compartment model with first-order absorption and elimination adequately described veliparib pharmacokinetics .


The final model included fixed effects for CLCR on veliparib oral clearance ( CL/F ) and lean body mass ( LBM ) on volume of distribution ( V d/F ) .


CL/F and V d/F were 20.9 L/h ( for a CLCR of 100 mL/min ) and 173 L ( for an LBM of 56 kg ) , respectively .


Only LBM and CLCR were found to be determinants of veliparib V d/F and CL/F , respectively .


Dosage adjustments of veliparib on the basis of body size , age , sex , race , liver function , and temozolomide coadministration are not necessary in patients with non-hematologic malignancies .


This is the first study to characterize the population pharmacokinetics of veliparib , and the developed model will be used to conduct simulations and evaluate veliparib exposure-response relationships .


To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes .


Opportunistic addition to an established randomised double blind placebo controlled trial .


Christchurch , New Zealand , where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred , which caused widespread destruction , fatalities , and extensive psychological damage .


322 healthy adults ( 241 women ; 81 men ) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study ( VIDARIS ) between February 2010 and November 2011 .


Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly ( n = 161 ) or placebo ( n = 161 ) for a total of 18 months .


This is a post hoc analysis from the previously published VIDARIS trial .


The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011 , which was used as the index event .


The secondary end point was the number of `` psychological '' adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial .


308 participants completed the earthquake impact questionnaire ( n = 152 in the vitamin D group and 156 in the placebo group ) .


There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo .


There was also no difference in the overall adverse impact score between treatment groups ( ( 2 ) P = 0.44 ) .


The exception was that those in the vitamin D group experienced more adverse effects on family relationships ( 22 % v 13 % ; ( 2 ) P = 0.03 ) .


The number of psychological adverse events-such as fatigue , stress , anxiety , and insomnia-that participants reported at their usual monthly appointments was significantly higher after the earthquake ( ( 2 ) P = 0.007 ) but did not differ between treatment groups .


In this trial , vitamin D supplementation did not reduce the adverse impact of earthquakes in healthy adults .


Trial registration Australian New Zealand Clinical Trials Registry ( anzctr.org.au ) ACTRN12609000486224 .


Cumulative neurotoxicity is a prominent toxicity of oxaliplatin-based therapy .


Intravenous calcium and magnesium have been extensively used to reduce oxaliplatin-induced neurotoxicity .


This trial was designed to definitively test whether calcium/magnesium decreases oxaliplatin-related neurotoxicity .


In all , 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX ( fluorouracil , leucovorin , and oxaliplatin ) were randomly assigned to intravenous calcium/magnesium before and after oxaliplatin , a placebo before and after , or calcium/magnesium before and placebo after .


The primary end point was cumulative neurotoxicity measured by the sensory scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 tool .


There were no statistically significant neuropathy differences among the study arms as measured by the primary end point or additional measures of neuropathy , including clinician-determined measurement of the time to grade 2 neuropathy by using the National Cancer Institute Common Terminology Criteria for Adverse Events scale or an oxaliplatin-specific neuropathy scale .


In addition , calcium/magnesium did not substantially decrease oxaliplatin-induced acute neuropathy .


This study does not support using calcium/magnesium to protect against oxaliplatin-induced neurotoxicity .


To evaluate the effects of 0.3 mg or 0.5 mg of ranibizumab in eyes with macular telangiectasia type 2 without subretinal neovascularization .


Ten eyes were randomized to either 0.3 mg or 0.5 mg ranibizumab group in 1 eye only .


Study eye received ranibizumab at baseline and at Months 1 and 2 .


Injections at Months 3 , 4 , and 5 were at investigator 's discretion .


Participants were followed monthly through 6 months with best-corrected visual acuity , fluorescein angiography , and optical coherence tomography .


For study eyes at baseline , median best-corrected visual acuity letter score was 60 ( 20/64 Snellen equivalent ) and central subfield retinal thickness was 181.5 m. Median number of injections was six .


Median change in best-corrected visual acuity at Month 3 was 4 letters ( range : -5 to 9 letters ) at both doses in the study eye and 3 letters ( range : -10 to 5 letters ) in the untreated fellow eye .


At Month 3 , retinal leakage decreased 0.87 disk area and 0.76 disk area for 0.3 mg and 0.5 mg ranibizumab , respectively .


Median change in central subfield retinal thickness was 1 m and -11 m for 0.3 mg and 0.5 mg ranibizumab , respectively .


Ranibizumab ( 0.3 mg or 0.5 mg ) decreases leakage secondary to macular telangiectasia type 2 , but accompanying improvements in best-corrected visual acuity appear similar to improvements in the untreated fellow eye where retinal thickness is relatively unchanged .


Patients with transient ischaemic attack ( TIA ) or stroke are at risk for cognitive impairment and dementia .


Currently , there is no known effective strategy to prevent this cognitive decline .


Increasing evidence exists that physical exercise is beneficial for cognitive function .


However , in patients with TIA or stroke who are at risk of cognitive impairment and dementia , only a few trials have been conducted .


In this study , we aim to investigate whether a physical exercise programme ( MoveIT ) can prevent cognitive decline in patients in the acute phase after a TIA or minor ischaemic stroke .


A single-blinded randomised controlled trial will be conducted to investigate the effect of an aerobic exercise programme on cognition compared with usual care .


120 adult patients with a TIA or minor ischaemic stroke less than 1 month ago will be randomly allocated to an exercise programme consisting of a 12-week aerobic exercise programme and regular follow-up visits to a specialised physiotherapist during the period of 1 year or to usual care .


Outcome measures will be assessed at the baseline , and at the 1-year and 2-year follow-up .


The primary outcome is cognitive functioning measured with the Montreal Cognitive Assessment ( MoCA ) test and with additional neuropsychological tests .


Secondary outcomes include maximal exercise capacity , self-reported physical activity and measures of secondary prevention .


The study received ethical approval from the VU University Amsterdam Ethics committee ( 2011/383 ) .


The results of this study will be published in peer-reviewed journals and presented at international conferences .


We will also disseminate the main results to our participants in a letter .


The Nederlands Trial Register NTR3884 .


To compare staples with subcuticular sutures for skin closure in emergency Cesarean sections ( CS ) .


One hundred and thirty women ( undergoing emergency CS without previous abdominal delivery ) were randomly assigned to either staples or subcuticular skin closure ( monocryl 3-0 ) .


Primary outcome of the study was cosmetic outcome [ as assessed by patient and independent observer : Patient Scar Assessment Scale ( PSAS ) and Observer Scar Assessment Scale ( OSAS ) , respectively ] , 6weeks post-operative .


Secondary outcomes were wound complications , operating time , post-operative pain ( visual analogue scale day 3 post-operative and patient assessment of pain in scar 6weeks post-operative ) , and duration of hospital stay .


112 women were available for evaluation of scar 6weeks post-operative .


Cosmetic result of staples was significantly better than subcuticular sutures ( PSAS and OSAS : p value 0.022 and 0.000 , respectively ) , with significantly lesser duration of surgery ( 24 vs. 32min : p value 0.000 ) and comparable post-operative pain ( pain on day 3 and 6weeks post-operatively : p value 0.474 and 0.179 , respectively ) and wound complications ( p value 0.737 ) .


However , duration of stay in hospital was increased ( 6 vs. 3days : p value 0.001 ) .


Staples are the method of choice for skin closure in emergency CS as they are significantly better than subcuticular sutures with respect to cosmesis and duration of surgery .


Post-operative pain and wound complications are comparable in two groups .


However , staples are associated with significantly increased duration of hospital stay .


Trial registered in clinical trial registry CTRI : REF/2013/05 / 005087 .


Chronic thoracic pain after cardiac surgery is prevalent ( 11 to 56 % ) and may affect patients ' physical and mental health status .


Despite its favorable pharmacokinetic and pharmacodynamic properties , high doses of remifentanil administered during surgery are reported to cause acute postoperative pain and increased requirements for analgesics .


Recently , an association between remifentanil use and the incidence of chronic thoracic pain in the long term was also reported .


Our objective is to investigate the influence of the intraoperative remifentanil on chronic postoperative pain in a prospective randomized controlled trial .


In this prospective , randomized , single-blind clinical trial , all patients ( N = 126 ) between 18 and 85 years undergoing cardiac surgery via sternotomy receive a continuous infusion of propofol together with intermittent intravenous fentanyl at predetermined times perioperatively .


Patients are randomized to receive either an additional continuous infusion of remifentanil ( 0.15 g ( -1 ) kgIBW ( -1 ) min ( -1 ) ) or additional fentanyl ( 200 to 500 g ) as needed during surgery.The primary end point is the prevalence of chronic thoracic pain 12 months after surgery .


Secondary end points include acute postoperative pain ; postoperative analgesic use ; chronic thoracic pain 3 and 6 months after surgery ; quality of life ( SF-12 ) at 3 , 6 and 12 months after surgery ; work productivity ; and use of health care .


In addition , thermal detection and pain thresholds are measured preoperatively , 3 days after surgery and 12 months after surgery using quantitative sensory testing ( QST ) .


Finally , the influence of several genetic variances on the different outcomes will be measured .


Chronic thoracic pain is prevalent after cardiac surgery , and research is needed to minimize the risk of chronic persistent postoperative pain , which is an invalidating , long-term complication of surgery .


The objective of this trial is to determine the influence of perioperative remifentanil on long-term pain outcomes for cardiac patients in a prospective randomized trial .


The results may be used to optimize perioperative analgesia techniques and , thereby , improve quality of life after cardiac surgery .


Clinicaltrials.gov NCT02031016 on 13 December 2013 .


To develop a reliable and safe laryngeal nerve conduction technique and to obtain consistent parameters as normal reference values .


A prospective single-arm study .


A nerve conduction test was performed on the contralateral normal side in 42 patients with unilateral vocal fold palsy .


The recording was performed in the intact thyroarytenoid muscle using a monopolar needle .


The electrical stimulation using a 37-mm monopolar needle was applied 3 cm below the lower margin of the cricoid cartilage , just lateral to the trachea and medial to the carotid artery , and its intensity was gradually increased until the amplitude of the electrical response reached the maximum level .


The latency of the evoked muscle response was acquired at the first evoked waveform deflection from the baseline .


The average latency of the recurrent laryngeal nerves was 1.980.26 ms. The latencies showed normal distribution according to the quantile-quantile plot and Kolmogorov-Smirnov test ( P = .098 ) .


There was no significant difference in latencies between the right and left recurrent laryngeal nerves .


Anthropometric factors including height and weight did not show any correlation with the latencies .


We developed a reliable and safe laryngeal nerve conduction technique and obtained normal reference values for the recurrent laryngeal nerve conduction study .


This laryngeal nerve conduction study can be an additional tool for detecting recurrent laryngeal nerve injury if it is performed in combination with the conventional laryngeal electromyography .


4 .


Because increased dopamine neurotransmission occurs with most antidepressants , and because antipsychotics cause behavioural supersensitivity to dopamine , short-term low-dose antipsychotic treatment was tested on depressed patients with an expectation of clinical improvement in the supersensitive phase following drug withdrawal .


This was a randomized , double-blind , placebo-controlled study of 48 patients who met criteria for DSM-IV ( ) Major Depressive Disorder , were in a Major Depressive Episode , and had a Hamilton Depression Rating Scale ( HAMD ) rating of 14 .


Half the participants received 0.25 mg oral haloperidol each day for 7 days , after which they received placebo daily for 4 weeks .


The other half received placebo throughout the trial .


One week after stopping the medication , the HAMD ratings of the drug-treated patients fell by 9.96 points , as compared to a reduction of 8.73 points in the placebo-treated patients , when comparing visits 1 and 4 .


There was no such difference when comparing visits 2 and 4 .


The differences were not significant , but indicated a trend .


One week after the medication was stopped , the Clinical Global Index fell 1.640.18 units for the medication-treated patients , compared to 1.120.26 units for the placebo group ( P = 0.05 ) .


The regimen was well tolerated .


Seven days of an ultra-low dose of 0.25 mg haloperidol , followed by withdrawal of haloperidol , resulted in clinical depression improvement greater than placebo and significantly decreased psychomotor retardation , consistent with haloperidol-induced behavioural supersensitivity to dopamine .


The sample was small .


More patients are needed in a future study .


To determine whether stereopsis of infants treated for monocular cataracts varies with the type of optical correction used .


Randomized prospective clinical trial .


The Infant Aphakia Treatment Study randomized 114 patients with unilateral cataracts at age 1-7 months to either primary intraocular lens ( IOL ) or contact lens correction .


At 4.5 years of age a masked examiner assessed stereopsis on these patients using 3 different tests : ( 1 ) Frisby ; ( 2 ) Randot Preschool ; and ( 3 ) Titmus Fly .


Twenty-eight patients ( 25 % ) had a positive response to at least 1 of the stereopsis tests .


There was no statistically significant difference in stereopsis between the 2 treatment groups : Frisby ( contact lens , 6 [ 11 % ] ; IOL , 7 [ 13 % ] ; P = .99 ) , Randot ( contact lens , 3 [ 6 % ] ; IOL , 1 [ 2 % ] ; P = .62 ) , or Titmus ( contact lens , 8 [ 15 % ] ; IOL , 13 [ 23 % ] ; P = .34 ) .


The median age at surgery for patients with stereopsis was younger than for those without stereopsis ( 1.2 vs 2.4 months ; P = .002 ) .


The median visual acuity for patients with stereopsis was better than for those without stereopsis ( 20/40 vs 20/252 ; P = .0003 ) .


The type of optical correction did not influence stereopsis outcomes .


However , 2 other factors did : age at surgery and visual acuity in the treated eye at age 4.5 years .


Early surgery for unilateral congenital cataract and the presence of visual acuity better than or equal to 20/40 appear to be more important than the type of initial optical correction used for the development of stereopsis .


Although the rate of bleeding among patients with atrial fibrillation ( AF ) taking novel oral anticoagulants in randomized controlled trials is described , the rate of bleeding with `` real-world '' use is uncertain .


We conducted a retrospective electronic medical record interrogation and subsequent chart review among patients within Intermountain Healthcare between October 2010 and November 2012 .


Patients were included if they had a diagnosis of AF and were receiving either dabigatran or rivaroxaban .


Rates of major bleeding were calculated .


Among 2579 patients , 13 ( 0.5 % ) experienced major bleeding ( 95 % confidence interval [ CI ] 0.23-0 .77 ) , 5 ( 0.19 % ) experienced intracranial hemorrhage ( 95 % CI 0.02-0 .36 ) , and 2 ( 0.08 % ) experienced fatal bleeding .


Of the 13 patients experiencing a major bleed , 8 ( 61.5 % ) would have been excluded from the Randomized Evaluation of Long-Term Anticoagulation Therapy ( RE-LY ) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET AF ) clinical trials .


We observed a rate of major bleeding similar to that reported in randomized clinical trials among patients with AF prescribed dabigatran or rivaroxaban .


Psychosocial problems are highly prevalent among Dutch adolescents .


We have conducted a trial to test whether offering chat-based consultations could be of added value within the context of Dutch Youth Health Care .


This trial was ended prematurely because of recruitment issues .


The aim of this study is to learn from this failed trial and to provide more insight into non-participation .


Sources of data were non-participation forms , oral clarification , patient records , telephone interviews with adolescents that declined to participate , and a questionnaire-based process evaluation among nurses .


Non-participation appears to be a multi-factorial problem .


Of those 290 adolescents eligible to participate , the majority ( n = 165 , 57 % ) declined to do so .


Two-third of those ( n = 109 ) also refused usual care , which might be indicative of not wanting help and/or experiencing problems and the validity of the assessment instrument .


The other one-third ( n = 56 ) did enrol in usual care and indicated other reasons for non-participation , such as a preference for face-to-face consultations , the extensive information that was provided , and not liking the idea of being randomized .


This study shows that even if a trial fails , we can learn about the challenges of recruiting adolescents in intervention trials .


NL37668 .068.11 / METC11-3-077 .


To investigate the therapeutic effect of Yiqi Huaju Recipe ( YHR ) combined with routine therapy on the blood pressure , the blood pressure variability and other cardiovascular risk factors in hypertension patients complicated with metabolic syndrome ( MetS ) .


Totally 43 hypertension patients complicated with MetS were recruited in this study and randomly assigned to the treatment group ( 22 cases , treated with basic routine treatment + YHR ) and the control group ( 21 cases , treated with basic routine treatment + placebo ) .


The treatment course was 12 weeks .


Detected were parameters such as 24-h ambulatory blood pressure monitoring ( ABPM ) , body mass index ( BMI ) , waist circumference ( WC ) , waist to hip ratio ( WHR ) , homeostatic model assessment for insulin resistance ( HOMA-IR ) , fasting glycosylated hemoglobin A1c ( HbA1c ) , fasting plasma glucose ( FPG ) , 2 h postprandial plasma glucose ( 2 h PPG ) , fasting plasma insulin ( FPI ) , serum lipid , etc. .


The anthropometric parameters and plasma glucose levels ( except HbAlc ) were obviously lowered after treatment than before treatment in the treatment group ( P < 0.01 , P < 0.05 ) .


Besides , better effects were obtained in the WC , WHR , 2 h PPG , FPI and HOMA-IR ( P < 0.05 ) .


The average blood pressure amplitude , the blood pressure variability , and blood pressure load at any time point were more obviously improved in the two groups after treatment than before treatment ( P < 0.01 , P < 0.05 ) .


Besides , partial indices were better in the treatment group than in the control group ( P < 0.01 , P < 0.05 ) .


YHR combined with routine therapy exhibited better effect on reducing the blood pressure amplitude , the blood pressure variability , and the blood pressure load in hypertension patients complicated with MetS .


It could also effectively decrease the risk of other vascular disease .


Whether there are age-related changes in slow wave activity ( SWA ) rise time , a marker of homeostatic sleep drive , is unknown .


Additionally , although sleep medication use is highest among older adults , the quantitative electroencephalographic ( EEG ) profile of the most commonly prescribed sleep medication , zolpidem , in older adults is also unknown .


We therefore quantified age-related and regional brain differences in sleep EEG with and without zolpidem .


Thirteen healthy young adults aged 21.92.2 years and 12 healthy older adults aged 67.44.2 years participated in a randomized , double-blind , within-subject study that compared placebo to 5mg zolpidem .


Older adults showed a smaller rise in SWA and zolpidem increased age-related differences in SWA rise time such that age differences were observed earlier after latency to persistent sleep .


Age-related differences in EEG power differed by brain region .


Older , but not young , adults showed zolpidem-dependent reductions in theta and alpha frequencies .


Zolpidem decreased stage 1 in older adults and did not alter other age-related sleep architecture parameters .


SWA findings provide additional support for reduced homeostatic sleep drive or reduced ability to respond to sleep drive with age .


Consequences of reduced power in theta and alpha frequencies in older adults remain to be elucidated .


To assess the long-term effects of dietary interventions on glycemic control , need for diabetes medications , and remission of type 2 diabetes .


Originally , in a two-arm trial design , overweight , middle-aged men and women with newly diagnosed type 2 diabetes were randomized to a low-carbohydrate Mediterranean diet ( LCMD ; n = 108 ) or a low-fat diet ( n = 107 ) .


After 4 years , participants who were still free of diabetes medications were further followed up until the primary end point ( need of a diabetic drug ) ; remission of diabetes ( partial or complete ) and changes in weight , glycemic control , and cardiovascular risk factors were also evaluated .


The primary end point was reached in all participants after a total follow-up of 6.1 years in the low-fat group and 8.1 years in the LCMD group ; median survival time was 2.8 years ( 95 % CI 2.4-3 .2 ) and 4.8 years ( 4.3-5 .2 ) , respectively .


The unadjusted hazard ratio for the overall follow-up was 0.68 ( 0.50-0 .89 ; P < 0.001 ) .


LCMD participants were more likely to experience any remission ( partial or complete ) , with a prevalence of 14.7 % ( 13.0-16 .5 % ) during the first year and 5.0 % ( 4.4-5 .6 % ) during year 6 compared with 4.1 % ( 3.1-5 .0 % ) at year 1 and 0 % at year 6 in the low-fat diet group .


In patients with newly diagnosed type 2 diabetes , an LCMD resulted in a greater reduction of HbA1c levels , higher rate of diabetes remission , and delayed need for diabetes medication compared with a low-fat diet .


Many sub-Saharan African countries report high postpartum loss to follow-up of mother-baby pairs .


We aimed to determine whether interactive text messages improved rates of clinic attendance and early infant HIV testing in the Nyanza region of Kenya .


Parallel-group , unblinded , randomized controlled trial .


HIV-positive pregnant women at least 18 years old and enrolled in the prevention of mother-to-child transmission of HIV programme were randomized to receive either text messages ( SMS group , n = 195 ) or usual care ( n = 193 ) .


Messages were developed using formative focus group research informed by constructs of the Health Belief Model .


The SMS group received up to eight text messages before delivery ( depending on gestational age ) , and six messages postpartum .


Primary outcomes included maternal postpartum clinic attendance and virological infant HIV testing by 8 weeks postpartum .


The primary analyses were intention-to-treat .


Of the 388 enrolled women , 381 ( 98.2 % ) had final outcome information .


In the SMS group , 38 of 194 ( 19.6 % ) women attended a maternal postpartum clinic compared to 22 of 187 ( 11.8 % ) in the control group ( relative risk 1.66 , 95 % confidence interval 1.02-2 .70 ) .


HIV testing within 8 weeks was performed in 172 of 187 ( 92.0 % ) infants in the SMS group compared to 154 of 181 ( 85.1 % ) in the control group ( relative risk 1.08 , 95 % confidence interval 1.00-1 .16 ) .


Text messaging significantly improved maternal postpartum visit attendance , but overall return rates for these visits remained low .


In contrast , high rates of early infant HIV testing were achieved in both arms , with significantly higher testing rates in the SMS compared to the control infants .


To evaluate the clinical effectiveness and safety of Fangfeng Tongsheng Granule ( FTG ) in the treatment of upper respiratory infection ( superficial cold and interior heat syndrome , exterior and interior excess syndrome ) .


A randomized , double-blinded , multi-centered , placebo-parallel-controlled clinical trial was adopted .


Totally 324 patients were enrolled and assigned to two groups , 216 patients in the treatment group and 108 patients in the control group .


Those in the treatment group took FTG at the daily dose of 3 g , twice per day , the therapeutic course being 3 days .


Those with axillary temperature more than 37 degrees C took one more time before medication .


Those in the control group took simulated agent granules the same dose and dosage as the treatment group .


The effect of Chinese medical syndrome ( ECMS ) , the rate of temperature-dropping-to-normal ( RT ) , the time of temperature-dropping-to-normal ( TT ) , the curative effect of single symptom ( CESS ) and adverse reactions were observed .


Totally 203 completed the trial in the treatment group and 101 in the control group .


In the treatment group , the cured-effective rate was 55.67 % ( 113 / 101 ) , the total effective rate was 93.10 % ( 189/101 ) , the ECMS score decreased by 9.24 + / - 4.46 , while they were 5.94 % ( 6/101 ) , 36.63 % ( 37/101 ) , and 3.27 + / - 3.29 , respectively in the control group ( P < 0.01 ) .


The RT was 87.50 % ( 98/112 ) in the treatment group and 58.49 % ( 31/53 ) in the control group ( P < 0.01 ) .


The TT in the treatment group was superior to that of the control group ( P < 0.01 ) .


As for CESS , all of the three primary symptoms and nine secondary symptoms were improved more obviously in the treatment group than in the control group .


The integral decreased obviously , showing statistical difference ( P < 0.01 ) .


The decrease was more obvious in the treatment group than in the control group ( P < 0.01 ) .


There was no adverse event related to FTG .


FTG was effective and safe in treating upper respiratory infection ( superficial cold and interior heat syndrome , exterior and interior excess syndrome ) .


The Modifications of Diet in Renal Disease ( MDRD ) and Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) are 2 equations commonly used to estimate glomerular filtration rate ( eGFR ) .


The predictive performance offered by these equations , particularly in relation to clinical outcomes in elderly hypertensive patients , is not clear .


The Second Australian National Blood Pressure Study cohort was used to investigate the predictive performance of these 2 equations for long-term outcomes ( median 10.8 years ) in elderly treated hypertensive patients .


Both equations were used to calculate eGFR in 6,083 patients aged 65 years and classified as having chronic kidney disease ( CKD ) or no CKD ( eGFR 60ml/min/1 .73 m2 ) .


More patients were classified as having no CKD using the CKD-EPI equation compared with the MDRD equation ( 72.1 % vs. 69.4 % ; P = 0.001 ) .


Both equations performed similarly in risk prediction of all-cause and cardiovascular mortality with decreased eGFR , except for patients with baseline eGFR of 45-59ml / min/1 .73 m2 , where the CKD-EPI equation predicted higher risk of all-cause mortality compared with those with no CKD .


However , the magnitude of difference in risk prediction was too small to be clinically meaningful .


Both equations showed similar predictive performance .


However , we observed longer survival and no higher risk in those who were reclassified as having no CKD using the CKD-EPI equation , but these patients were classified earlier as having CKD using the MDRD equation .


There was no clinically relevant difference in predictive performance for long-term survival by eGFR calculated using either of these equations in this elderly hypertensive population .


Ischemic mitral regurgitation is associated with increased mortality and morbidity .


For surgical patients with moderate regurgitation , the benefits of adding mitral-valve repair to coronary-artery bypass grafting ( CABG ) are uncertain .


We randomly assigned 301 patients with moderate ischemic mitral regurgitation to CABG alone or CABG plus mitral-valve repair ( combined procedure ) .


The primary end point was the left ventricular end-systolic volume index ( LVESVI ) , a measure of left ventricular remodeling , at 1 year .


This end point was assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized as the lowest LVESVI rank .


At 1 year , the mean LVESVI among surviving patients was 46.122.4 ml per square meter of body-surface area in the CABG-alone group and 49.631.5 ml per square meter in the combined-procedure group ( mean change from baseline , -9.4 and -9.3 ml per square meter , respectively ) .


The rate of death was 6.7 % in the combined-procedure group and 7.3 % in the CABG-alone group ( hazard ratio with mitral-valve repair , 0.90 ; 95 % confidence interval , 0.38 to 2.12 ; P = 0.81 ) .


The rank-based assessment of LVESVI at 1 year ( incorporating deaths ) showed no significant between-group difference ( z score , 0.50 ; P = 0.61 ) .


The addition of mitral-valve repair was associated with a longer bypass time ( P < 0.001 ) , a longer hospital stay after surgery ( P = 0.002 ) , and more neurologic events ( P = 0.03 ) .


Moderate or severe mitral regurgitation was less common in the combined-procedure group than in the CABG-alone group ( 11.2 % vs. 31.0 % , P < 0.001 ) .


There were no significant between-group differences in major adverse cardiac or cerebrovascular events , deaths , readmissions , functional status , or quality of life at 1 year .


In patients with moderate ischemic mitral regurgitation , the addition of mitral-valve repair to CABG did not result in a higher degree of left ventricular reverse remodeling .


Mitral-valve repair was associated with a reduced prevalence of moderate or severe mitral regurgitation but an increased number of untoward events .


Thus , at 1 year , this trial did not show a clinically meaningful advantage of adding mitral-valve repair to CABG .


Longer-term follow-up may determine whether the lower prevalence of mitral regurgitation translates into a net clinical benefit .


( Funded by the National Institutes of Health and the Canadian Institutes of Health Research ; ClinicalTrials.gov number , NCT00806988 . )


To investigate the effects of stellate ganglion block ( SGB ) on the peri-operative vasomotor cytokine content and intrapulmonary shunt in patients with esophagus cancer who underwent thoracotomy .


Forty patients undergoing elective resection of esophageal cancer patients who had I ~ II American Society of Anesthesiologist ( ASA ) were randomly divided into total intravenous anesthesia group ( group N , n = 20 ) and total intravenous anesthesia combined with SGB group ( group S , n = 20 , 0.12 mL/kg 1 % lidocaine was used for SGB 10 min before induction ) .


Heart rate ( HR ) , mean arterial pressure ( MAP ) , central venous pressure ( CVP ) , mean pulmonary arterial pressure ( MPAP ) and continuous cardiac output ( CCO ) were continuously monitored .


The blood from internal jugular vein was drawn respectively before induction ( T0 ) , and 30 min ( T1 ) , 60 min ( T2 ) and 120 min ( T3 ) after one-lung ventilation ( OLV ) , and 30 min ( T4 ) after two-lung ventilation .


The contents of plasma endothelin ( ET ) , nitric oxide ( NO ) and calcitonin gene-related peptide ( CGRP ) were detected with enzyme linked immunosorbent assay ( ELISA ) .


Meanwhile , arterial and mixed venous blood samples were collected for determination of blood gas and calculation of intrapulmonary shunt fraction ( Qs/Qt ) .


During OLV , ET contents were increased significantly in two groups ( P < 0.05 ) , and no significant difference was presented ( P > 0.05 ) .


NO content in group S was obviously higher than in group N at T3 ( P < 0.05 ) , whereas CGRP content in group N was markedly lower than in group S at each time point ( P < 0.05 ) .


Qs/Qt was significantly increased in both groups after OLV , but there was no statistical significant regarding the Qs/Qt at each time point between two groups .


Total intravenous anesthesia combined with SGB is conducive to regulation of perioperative vasomotor cytokines in thoracotomy , and has little effect on intrapulmonary shunt at the time of OLV .


Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma .


The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma .


We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone ( carfilzomib group ) or lenalidomide and dexamethasone alone ( control group ) .


The primary end point was progression-free survival .


Progression-free survival was significantly improved with carfilzomib ( median , 26.3 months , vs. 17.6 months in the control group ; hazard ratio for progression or death , 0.69 ; 95 % confidence interval [ CI ] , 0.57 to 0.83 ; P = 0.0001 ) .


The median overall survival was not reached in either group at the interim analysis .


The Kaplan-Meier 24-month overall survival rates were 73.3 % and 65.0 % in the carfilzomib and control groups , respectively ( hazard ratio for death , 0.79 ; 95 % CI , 0.63 to 0.99 ; P = 0.04 ) .


The rates of overall response ( partial response or better ) were 87.1 % and 66.7 % in the carfilzomib and control groups , respectively ( P < 0.001 ; 31.8 % and 9.3 % of patients in the respective groups had a complete response or better ; 14.1 % and 4.3 % had a stringent complete response ) .


Adverse events of grade 3 or higher were reported in 83.7 % and 80.7 % of patients in the carfilzomib and control groups , respectively ; 15.3 % and 17.7 % of patients discontinued treatment owing to adverse events .


Patients in the carfilzomib group reported superior health-related quality of life .


In patients with relapsed multiple myeloma , the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile .


( Funded by Onyx Pharmaceuticals ; ClinicalTrials.gov number , NCT01080391 . )


One of the most important challenges in public health is to improve the quality of life in elders .


Aging may cause various disorders such as disabilities , high risk conditions and some chronic disease .


In this study the effect of educational intervention based on precede-proceed on quality of life in elders was examined .


This semi experimental study was carried out on 128 elders over 60 years in Zahedan that were randomly selected by multi-stage sampling method and divided in to control and intervention groups .


Data collection tool was a triploid questionnaire that included demographic data , questions of precede-proceed constructs and SF-36 questionnaire .


The validity and reliability of questionnaire confirmed by experts and Cranach 's Alpha coefficient ( 76 % ) .


After primary data collecting , educational intervention was performed and after nine months data was collected again and analyzed in spss .16 soft-ware using descriptive and analytical statistics .


The results showed that mean score of quality of life in participants was low and more than 61 % of them had a mean score less than 50 % .


After intervention the mean score of quality of life only in experimental group significantly increased from 47.72 to 58.90 .


Behavior and self-rated health were the strongest predictors for quality of life in this study .


Implementation educational intervention based on precedes-proceed model can improve quality of life in elders .


Elderly women and older elderly individuals compared with elderly men and younger elderly should be considering as an important risk factor for reducing HRQOL .


Yes-associated protein ( YAP1 ) is frequently reported to function as an oncogene in many types of cancer , but in breast cancer results remain controversial .


We set out to clarify the role of YAP1 in breast cancer by examining gene and protein expression in subgroups of patient material and by downregulating YAP1 in vitro and studying its role in response to the widely used anti-estrogen tamoxifen .


YAP1 protein intensity was scored as absent , weak , intermediate or strong in two primary breast cancer cohorts ( n = 144 and n = 564 ) and mRNA expression of YAP1 was evaluated in a gene expression dataset ( n = 1107 ) .


Recurrence-free survival was analysed using the log-rank test and Cox multivariate analysis was used to test for independence .


WST-1 assay was employed to measure cell viability and a luciferase ERE ( estrogen responsive element ) construct was used to study the effect of tamoxifen , following downregulation of YAP1 using siRNAs .


In the ER + ( Estrogen Receptor positive ) subgroup of the randomised cohort , YAP1 expression was inversely correlated to histological grade and proliferation ( p = 0.001 and p = 0.016 , respectively ) whereas in the ER - ( Estrogen Receptor negative ) subgroup YAP1 expression correlated positively to proliferation ( p = 0.005 ) .


Notably , low YAP1 mRNA was independently associated with decreased recurrence-free survival in the gene expression dataset , specifically for the luminal A subgroup ( p < 0.001 ) which includes low proliferating tumours of lower grade , usually associated with a good prognosis .


This subgroup specificity led us to hypothesize that YAP1 may be important for response to endocrine therapies , such as tamoxifen , extensively used for luminal A breast cancers .


In a tamoxifen randomised patient material , absent YAP1 protein expression was associated with impaired tamoxifen response which was significant upon interaction analysis ( p = 0.042 ) .


YAP1 downregulation resulted in increased progesterone receptor ( PgR ) expression and a delayed and weaker tamoxifen in support of the clinical data .


Decreased YAP1 expression is an independent prognostic factor for recurrence in the less aggressive luminal A breast cancer subgroup , likely due to the decreased tamoxifen sensitivity conferred by YAP1 downregulation .


Clinical validation of laboratory toothbrushing tests has important advantages .


It was , therefore , the aim to demonstrate correlation of tooth cleaning efficiency of a new robot brushing simulation technique with clinical plaque removal .


Clinical programme : 27 subjects received dental cleaning prior to 3-day-plaque-regrowth-interval .


Plaque was stained , photographically documented and scored using planimetrical index .


Subjects brushed teeth 33-47 with three techniques ( horizontal , rotating , vertical ) , each for 20s buccally and for 20s orally in 3 consecutive intervals .


The force was calibrated , the brushing technique was video supported .


Two different brushes were randomly assigned to the subject .


Robot programme : Clinical brushing programmes were transfered to a 6-axis-robot .


Artificial teeth 33-47 were covered with plaque-simulating substrate .


All brushing techniques were repeated 7 times , results were scored according to clinical planimetry .


All data underwent statistical analysis by t-test , U-test and multivariate analysis .


The individual clinical cleaning patterns are well reproduced by the robot programmes .


Differences in plaque removal are statistically significant for the two brushes , reproduced in clinical and robot data .


Multivariate analysis confirms the higher cleaning efficiency for anterior teeth and for the buccal sites .


The robot tooth brushing simulation programme showed good correlation with clinically standardized tooth brushing.This new robot brushing simulation programme can be used for rapid , reproducible laboratory testing of tooth cleaning .


Patients surviving stroke but who have significant impairment of function in the affected arm are at more risk of developing pain , stiffness and contractures .


The abnormal muscle activity , associated with post-stroke spasticity , is thought to be causally associated with the development of these complications .


Treatment of spasticity is currently delayed until a patient develops signs of these complications .


This protocol is for a phase II study that aims to identify whether using OnabotulinumtoxinA ( BoNT-A ) in combination with physiotherapy early post stroke when initial abnormal muscle activity is neurophysiologically identified can prevent loss of range at joints and improve functional outcomes.The trial uses a screening phase to identify which people are appropriate to be included in a double blind randomised placebo-controlled trial .


All patients admitted to Sandwell and West Birmingham NHS Trust Hospitals with a diagnosis of stroke will be screened to identify functional activity in the arm .


Those who have no function will be appropriate for further screening .


Patients who are screened and have abnormal muscle activity identified on EMG will be given electrical stimulation to forearm extensors for 3 months and randomised to have either injections of BoNT-A or normal saline .


The primary outcome measure is the action research arm test - a measure of arm function .


Further measures include spasticity , stiffness , muscle strength and fatigue as well as measures of quality of life , participation and caregiver strain .


ISRCTN57435427 , EudraCT2010-021257-39 , NCT01882556 .


To observe the efficacy and safety of Qizhi Jiangtang Capsule ( QJC ) in treating stage 3b diabetic kidney disease ( DKD ) patients with macroalbuminuria .


Patients who conformed to the diagnostic criteria of stage 3b DKD were randomly assigned to two groups according to random digital table , the experiment group and the control group , 84 in each group .


All patients received a two-week elution period , and then were treated with basic Western therapy .


Patients in the experiment group took QJC , 5 pills per time , 3 times a day , while those in the control group took Valsartan Capsule 160 mg each time , once daily .


The observation period of follow-ups was limited within 6 months , and the time points were set as the baseline , 1st month , 3rd month , and 6th month .


Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBS ) , 24 h urine protein quantitative ( 24 h UPQ ) , plasma albumin ( ALB ) , and serum creatinine ( SCr ) were detected and recorded , and estimated glomerular filtration rate ( eGFR ) was calculated .


The occurrence of hypoglycemic reaction , coagulation disorder , gastrointestinal tract reaction , allergy , hyperkalemia , doubling of creatinine , and overall adverse events were observed and recorded at same time .


Finally 81 patients in the experiment group and 80 patients in the control group were effectively included .


Compared with the baseline level , SBP and DBS obviously decreased in the control group at month 1 of treatment ( P < 0.05 ) , and more significantly decreased at month 6 of treatment ( P < 0.01 ) .


SBP at month 1 , 3 , and 6 of follow-ups ; DBS at month 6 of follow-ups was lower in the control group than in the experiment group ( P < 0.05 ) .


At month 1 , 3 , and 6 of follow-ups , 24 h UPQ of the experiment group was significantly lower than the baseline level ( P < 0.01 ) .


It was also significantly lower than the level of the control group at the same time point ( P < 0.05 ) .


There was no significant difference in 24 h UPQ at month 1 , 3 , and 6 of follow-ups between the control group and the baseline level ( P > 0.05 ) .


ALB of the experiment group showed an increasing trend .


It was significantly higher than the baseline level at month 6 ( P < 0.05 ) , which was also higher than that of the control group at same period ( P < 0.05 ) .


There was no significant difference in the ALB level in the control group ( P > 0.05 ) .


SCr of two groups showed an increasing trend .


SCr of the experiment group was significantly higher at month 1 , 3 , and 6 follow-ups than the baseline level ( P < 0.05 ) .


But the increment of SCr was higher in the control group than in the experimental group , and obviously higher than the baseline levels ( P < 0.05 ) .


eGFR of both groups showed a decreasing trend .


The decrement was higher in the control group than in the experimental group ( P < 0.05 ) .


The proportion of progression of renal functions at month 1 , 3 , and 6 of follow-ups in the experimental group was 0.0 % ( 0 case ) , 9.55 % ( 8 cases ) , and 21.4 % ( 18 cases ) , while they were 8.3 % ( 7 cases ) , 21.4 % ( 18 cases ) , and 40.5 % ( 34 cases ) in the control group .


There was no statistical difference in the proportion of progression of renal functions between the two groups at month 3 and 6 of follow-ups ( P < 0.05 ) .


There was no statistical difference in the incidence of adverse reactions between two groups ( P > 0.05 ) .


QJC could effectively reduce urinary protein of patients with stage 3b DKD , and delay the progression of renal functions .


To investigate and compare several quantification methods of myocardial perfusion measurements , paying special attention to the relation between the techniques and the required measurement duration .


Seven patients underwent contrast-enhanced rest and stress cardiac perfusion measurements at 3T .


Three slices were acquired in each patient and were divided into 16 segments , leading to 112 rest and stress data curves , which were analyzed using various tracer kinetic models as well as a model-free deconvolution .


Plasma flow , plasma volume , and myocardial perfusion reserve were analyzed for the complete acquisition as well as for the first pass data only .


Deconvolution analysis yielded stable results for both rest and stress analysis , while Fermi and one compartment models agree well for first pass data ( rest measurements only ) and prolonged data acquisition ( stress measurements only ) .


More complex models do not yield satisfactory results for the short measurement times investigated in this study .


When performing MRI-based quantification of myocardial perfusion , care must be taken that the method used is appropriate for the time frame under investigation .


When a numerical deconvolution is used instead of tracer kinetic models , more stable results are obtained .


Combining pharmacotherapies for tobacco-dependence treatment may increase smoking abstinence .


To determine efficacy and safety of varenicline and bupropion sustained-release ( SR ; combination therapy ) compared with varenicline ( monotherapy ) in cigarette smokers .


Randomized , blinded , placebo-controlled multicenter clinical trial with a 12-week treatment period and follow-up through week 52 conducted between October 2009 and April 2013 at 3 midwestern clinical research sites .


Five hundred six adult ( 18 years ) cigarette smokers were randomly assigned and 315 ( 62 % ) completed the study .


Twelve weeks of varenicline and bupropion SR or varenicline and placebo .


Primary outcome was abstinence rates at week 12 , defined as prolonged ( no smoking from 2 weeks after the target quit date ) abstinence and 7-day point-prevalence ( no smoking past 7 days ) abstinence .


Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52 .


Outcomes were biochemically confirmed .


At 12 weeks , 53.0 % of the combination therapy group achieved prolonged smoking abstinence and 56.2 % achieved 7-day point-prevalence smoking abstinence compared with 43.2 % and 48.6 % in varenicline monotherapy ( odds ratio [ OR ] , 1.49 ; 95 % CI , 1.05-2 .12 ; P = .03 and OR , 1.36 ; 95 % CI , 0.95-1 .93 ; P = .09 , respectively ) .


At 26 weeks , 36.6 % of the combination therapy group achieved prolonged and 38.2 % achieved 7-day point-prevalence smoking abstinence compared with 27.6 % and 31.9 % in varenicline monotherapy ( OR , 1.52 ; 95 % CI , 1.04-2 .22 ; P = .03 and OR , 1.32 ; 95 % CI , 0.91-1 .91 ; P = .14 , respectively ) .


At 52 weeks , 30.9 % of the combination therapy group achieved prolonged and 36.6 % achieved 7-day point-prevalence smoking abstinence compared with 24.5 % and 29.2 % in varenicline monotherapy ( OR , 1.39 ; 95 % CI , 0.93-2 .07 ; P = .11 and OR , 1.40 ; 95 % CI , 0.96-2 .05 ; P = .08 , respectively ) .


Participants receiving combination therapy reported more anxiety ( 7.2 % vs 3.1 % ; P = .04 ) and depressive symptoms ( 3.6 % vs 0.8 % ; P = .03 ) .


Among cigarette smokers , combined use of varenicline and bupropion , compared with varenicline alone , increased prolonged abstinence but not 7-day point prevalence at 12 and 26 weeks .


Neither outcome was significantly different at 52 weeks .


Further research is required to determine the role of combination therapy in smoking cessation .


clinicaltrials.gov Identifier : http://clinicaltrials.gov/show/NCT00935818 .


To study the efficacy of transdermal clonidine in the treatment of severe refractory hyperemesis gravidarum ( HG ) , the most severe illness of pregnancy .


The study had a randomised , double - blind , placebo-controlled , cross-over design ( RCT ) .


Single tertiary referral hospital after admission of patients .


Twelve women of gestational age 6-12 weeks and a major grade of HG clinical severity who were unresponsive to standard antiemetic treatment .


The patients were randomly treated with and without the active drug ( 5 mg patch ) for two consecutive periods of 5 days .


The patients were allocated to a random list to receive first placebo and then active drug or the other way round .


Other antiemetic drugs were administered on a scheduled or as-needed basis .


All patients received intravenous hydration and thiamine supplementation .


Pregnancy Unique Quantification of Emesis ( PUQE ) and visual analog scale ( VAS ) clinical scores , positive morning urine ketonuria , number of doses of standard antiemetic drugs required , and number of days off intravenous therapy were compared in the two periods .


Transdermal clonidine led to a significantly greater improvement compared with placebo of the primary ( PUQE score P = 0.026 CI 0.43-3 .24 ; VAS score P = 0.010 CI 2.17-12 .83 ) and secondary outcome measures .


A reduction of blood pressure was reported for systolic 6 mmHg P = 0.01 and diastolic 3 mmHg P = 0.055 .


This preliminary RCT demonstrates the efficacy of transdermal clonidine in the treatment of severe HG , leading to a significant reduction of symptoms and reducing the need for other supportive measures and medications .


Maternal obesity and gestational diabetes mellitus ( GDM ) may independently influence offspring fat mass and metabolic disease susceptibility .


In this pilot study , body composition and fat distribution in offspring from obese women with and without GDM and lean women were assessed within the 1st year of life , and maternal and newborn plasma factors were related to offspring adipose tissue distribution .


Serum and plasma samples from pregnant obese women with ( n = 16 ) or without ( n = 13 ) GDM and normoglycemic lean women ( n = 15 ) at 3rd trimester and offspring cord plasma were used for analyzing lipid profiles , insulin and adipokine levels .


At week-1 and 6 , month-4 and year-1 , offspring anthropometrics and skinfold thickness ( SFT ) were measured and abdominal subcutaneous ( SCA ) and preperitoneal adipose tissue ( PPA ) were determined by ultrasonography .


Cord insulin was significantly increased in the GDM group , whereas levels of cord leptin , total and high molecular weight ( HMW ) adiponectin were similar between the groups .


Neonates of the GDM group showed significantly higher SFT and fat mass until week-6 and significantly increased SCA at week-1 compared to the lean group that persisted as strong trend at week-6 .


Interestingly , PPA in neonates of the GDM group was significantly elevated at week-1 compared to both the lean and obese group .


At month-4 and year-1 , significant differences in adipose tissue growth between the groups were not observed .


Multiple linear regression analyses revealed that cord insulin levels are independently related to neonatal PPA that showed significant relation to PPA development at year-1 .


Maternal fasted C-peptide and HMW adiponectin levels at 3rd trimester emerged to be determinants for PPA at week-1 .


Maternal pregravid obesity combined with GDM leads to newborn hyperinsulinemia and increased offspring fat mass until week-6 , whereas pregravid obesity without GDM does not .


This strongly suggests the pivotal role of GDM in the adverse offspring outcome .


Maternal C-peptide and HMW adiponectin levels in pregnancy emerge to be predictive for elevated PPA in newborns and might be indicative for the obesity risk at later life .


Altogether , the findings from our pilot study warrant evaluation in long-term studies .


German Clinical Trials Register DRKS00004370 .


While effective in preventing stroke in patients with atrial fibrillation ( AF ) , warfarin is limited by a narrow therapeutic profile , a need for lifelong coagulation monitoring , and multiple drug and diet interactions .


To determine whether a local strategy of mechanical left atrial appendage ( LAA ) closure was noninferior to warfarin .


PROTECT AF was a multicenter , randomized ( 2:1 ) , unblinded , Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor ( CHADS2 score 1 ) .


Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012 .


Noninferiority required a posterior probability greater than 97.5 % and superiority a probability of 95 % or greater ; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups .


Left atrial appendage closure with the device ( n = 463 ) or warfarin ( n = 244 ; target international normalized ratio , 2-3 ) .


A composite efficacy end point including stroke , systemic embolism , and cardiovascular/unexplained death , analyzed by intention-to-treat .


At a mean ( SD ) follow-up of 3.8 ( 1.7 ) years ( 2621 patient-years ) , there were 39 events among 463 patients ( 8.4 % ) in the device group for a primary event rate of 2.3 events per 100 patient-years , compared with 34 events among 244 patients ( 13.9 % ) for a primary event rate of 3.8 events per 100 patient-years with warfarin ( rate ratio , 0.60 ; 95 % credible interval , 0.41-1 .05 ) , meeting prespecified criteria for both noninferiority ( posterior probability , > 99.9 % ) and superiority ( posterior probability , 96.0 % ) .


Patients in the device group demonstrated lower rates of both cardiovascular mortality ( 1.0 events per 100 patient-years for the device group [ 17/463 patients , 3.7 % ] vs 2.4 events per 100 patient-years with warfarin [ 22/244 patients , 9.0 % ] ; hazard ratio [ HR ] , 0.40 ; 95 % CI , 0.21-0 .75 ; P = .005 ) and all-cause mortality ( 3.2 events per 100 patient-years for the device group [ 57/466 patients , 12.3 % ] vs 4.8 events per 100 patient-years with warfarin [ 44/244 patients , 18.0 % ] ; HR , 0.66 ; 95 % CI , 0.45-0 .98 ; P = .04 ) .


After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke , percutaneous LAA closure met criteria for both noninferiority and superiority , compared with warfarin , for preventing the combined outcome of stroke , systemic embolism , and cardiovascular death , as well as superiority for cardiovascular and all-cause mortality .


clinicaltrials.gov Identifier : NCT00129545 .


Despite great reduction of in-stent restenosis , first-generation drug-eluting stents ( DESs ) have increased the risk of late stent thrombosis due to delayed endothelialization .


Arsenic trioxide , a natural substance that could inhibit cell proliferation and induce cell apoptosis , seems to be a promising surrogate of sirolimus to improve DES performance .


This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent ( AES ) , compared with traditional sirolimus-eluting stent ( SES ) .


Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group .


The primary endpoint was target vessel failure ( TVF ) , and the second endpoint includes rates of all-cause death , cardiac death or myocardial infarction , target lesion revascularization ( TLR ) by telephone visit and late luminal loss ( LLL ) at 9-month by angiographic follow-up .


From July 2007 to 2009 , 212 patients were enrolled and randomized 1:1 to receive either AES or SES .


At 2 years of follow-up , TVF rate was similar between AES and SES group ( 6.67 % vs. 5.83 % , P = 0.980 ) .


Frequency of all-cause death was significantly lower in AES group ( 0 vs. 4.85 % , P = 0.028 ) .


There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis , but greater in-stent LLL was observed for AES group ( 0.29 0.52 mm vs. 0.10 0.25 mm , P = 0.008 ) .


After 2 years of follow-up , AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions .


Raltegravir is an HIV-1 integrase inhibitor approved for use in adults , children and infants 4 weeks of age .


As alternatives to the original film-coated tablet , a chewable ethylcellulose ( EC ) tablet and oral granules for suspension ( GFS ) have been developed for use in children .


The purpose of this study was to evaluate these formulations in adults prior to use in paediatric studies .


This open-label , 4-period , randomized , crossover study investigated the safety , tolerability and pharmacokinetics of raltegravir paediatric formulations and the effect of a high-fat meal on EC tablet pharmacokinetics in healthy adults .


In a balanced , crossover design ( with a 4-day washout between treatments ) , 12 subjects received one 400 mg film-coated tablet ( fasted ) , four 100 mg EC tablets ( fasted ) , one 400 mg GFS dose ( fasted ) and four 100 mg EC tablets ( after a high-fat meal ) .


AUC0 - and Cmax were 2.6-fold and 4.6-fold higher for GFS and 1.8-fold and 3.2-fold higher for EC versus film-coated tablets .


The geometric mean C12h values for the GFS formulation ( 162 nM ) and the EC tablet ( 134 nM ) were similar to that of the film-coated tablet ( 149 nM ) .


Administration with a high-fat meal increased C12h , decreased Cmax and delayed Tmax for the EC tablet , but did not affect AUC0 - .


There were no serious adverse events ( AEs ) and no discontinuations due to drug-related clinical or laboratory AEs .


Both paediatric formulations demonstrate moderately higher AUC0 - and Cmax , and similar C12h compared with the film-coated tablet .


These data support the use of raltegravir GFS and EC formulations in paediatric studies .


To determine the effect of neonatal caffeine treatment on rates of developmental coordination disorder ( DCD ) .


Children in the Caffeine for Apnea of Prematurity trial were assessed for motor performance ( Movement Assessment Battery for Children [ MABC ] ) , clinical signs of cerebral palsy , and Full-Scale IQ at 5 years of age by staff who were unaware of the children 's treatment group .


DCD was defined as MABC < 5th percentile in children with a Full-Scale IQ > 69 who did not have a diagnosis of cerebral palsy .


There were 1433 children with known MABC corrected-age percentile as well as known Full-Scale IQ at 5 years and cerebral palsy status , of whom 735 had been randomly assigned to caffeine and 698 to placebo therapy .


The rate of DCD was lower in those treated with caffeine ( 11.3 % ) than in the placebo group ( 15.2 % ) ( OR adjusted for center and baseline covariates , 0.71 , 95 % CI , 0.52-0 .97 ; P = .032 ) .


Neonatal caffeine therapy for apnea of prematurity reduces the rate of DCD at 5 years of age .


As more children have DCD than have cerebral palsy , this is an important additional benefit from neonatal caffeine treatment .


To determine whether exercise training might exert anti-inflammatory effect by reducing HMGB1 levels in women with breast cancer ( BC ) .


We analyzed monocentric data from the DIANA ( DIET AND ANDROGENS ) -5 PROJECT .


Study population consisted of 94 patients randomized into two groups : 61 patients ( 53 + / - 8 yrs , training group ) were assigned to a structured exercise training intervention ( 3 times/week for the first 3 months , and once / week for the following 9 months ) ; whereas 33 patients ( 52 + / - 7 yrs , control group ) followed only the general indications to adhere to the life-style intervention suggestions of the DIANA protocol .


At study entry and after 12 months , all patients underwent cardiopulmonary exercise testing , biochemical as - sessment [ HMGB1 , high-sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) ] ; and lipid and glycemic profile .


There were no significant differences between groups in baseline clinical and inflammatory profile .


Among the training group , only 19/61 patients had high adherence to the exercise intervention .


After stratifying the study population according to the level of adhesion to the exer - cise intervention , 1-year HMGB1 levels were lower among patients more adherent to exercise ( p for trend = 0.001 ) .


Further adjusting for age , body mass index and baseline values , 1-year HMGB1 levels remained significantly and inversely associated to the level of adhesion to the exercise intervention ( B = -0.97 , SE = 0.43 , p = 0.01 ) .


Moderate intensity exercise training in BC survivors is associated with reduced HMGB1 levels that are proportional to the level of adhesion to the exercise intervention , independently from other classical inflammatory molecules , suggesting an exercise-induced anti-inflammatory effect mediated by HMGB1 .


According to the literature , 40 % of injuries affecting school-age children are sports related .


The role of physical education students , as future teachers , seems to be of high importance in terms of protecting children 's safety during sports classes .


The aim is to evaluate the level of basic life support ( BLS ) knowledge and skills in physical education students instructed with the use of different methods .


Second-year physical education students ( n = 104 , M age = 200.6 years ) were randomly assigned to three groups : experimental 1 ( E1 ) , experimental 2 ( E2 ) , and control ( C ) .


Group E1 students participated in a 2-hour BLS course based on computer-assisted presentations .


Group E2 trainees practiced BLS algorithm in pairs during a 2-hour course .


No manikins were used in both intervention groups .


Students of Group C were asked to learn BLS algorithm on their own .


All groups fulfilled a 10-question multiple-choice test on BLS at the beginning and the end of the experiment .


After completing the course participants performed BLS on a manikin .


The results of knowledge test were not significant before an experiment but differed essentially among the groups afterward ( analysis of variance contrast analysis , p < .05 ) .


Regardless of teaching method used , no significant differences were found among the students in preparatory BLS actions and cardiopulmonary resuscitation ( CPR ) performance on a manikin .


The level of CPR performance was very low in all groups .


Students of both intervention groups improved their BLS knowledge after the training .


Teaching methods used in the current study seemed to be ineffective in terms of practical CPR skills .


Access to greater number of modern manikins should improve the BLS training in physical education students .


Moreover , permanent consultation on instructional methods with emergency medicine experts is recommended for university teachers .


This study evaluated the efficacy and safety of levosimendan , a positive inotropic drug with vasodilator effects , given intravenously to patients with acutely decompensated heart failure ( ADHF ) .


We performed 2 sequential trials , the first to develop a new measure of efficacy in 100 patients , and the second to use this measure to evaluate levosimendan in an additional 600 patients .


Patients admitted with ADHF received placebo or intravenous levosimendan for 24 h in addition to standard treatment .


The primary endpoint was a composite that evaluated changes in clinical status during the first 5 days after randomization .


In the 600-patient trial , more levosimendan than placebo patients ( 58 vs. 44 ) were improved at all 3 pre-specified time points ( 6 h , 24 h , and 5 days ) , whereas fewer levosimendan patients ( 58 vs. 82 ) experienced clinical worsening ( p = 0.015 for the difference between the groups ) .


These differences were apparent , despite more frequent intensification of adjunctive therapy in the placebo group ( 79 vs. 45 patients ) .


Improvements in patient self-assessment and declines in B-type natriuretic peptide levels with levosimendan persisted for 5 days and were associated with reduced length of stay ( p = 0.009 ) .


Similar findings were present in the 100-patient pilot trial .


Levosimendan was associated with more frequent hypotension and cardiac arrhythmias during the infusion period and a numerically higher risk of death across the 2 trials ( 49 of 350 on a regimen of levosimendan vs. 40 of 350 on a regimen of placebo at 90 days , p = 0.29 ) .


In patients with ADHF , intravenous levosimendan provided rapid and durable symptomatic relief .


As dosed in this trial , levosimendan was associated with an increased risk of adverse cardiovascular events .


( Evaluation of Intravenous Levosimendan Efficacy in the Short Term Treatment of Decompensated Chronic Heart Failure ; NCT00048425 ) .


To compare the treatment outcome of tamsulosin 0.4 mg ( TAM ) with or without solifenacin 5 mg ( SOL ) for the most bothersome symptom in male lower urinary tract symptoms ( LUTS ) with overactive bladder ( OAB ) .


Male LUTS/OAB ( 50 years ) patients who had a total International Prostate Symptom Score ( I-PSS ) of 12 , I-PSS urgency-related question of 2 , and quality of life ( QoL ) of 3 points were enrolled .


Patients who complained of storage symptoms as the most bothersome were included in the ` storage ' group .


Patients who complained of voiding symptoms as the most bothersome were included in the ` voiding ' group .


The change in the I-PSS was compared between the two groups 4 weeks after commencing treatment .


In the storage group , 172 were able to finish this study ( TAM : 88 , TAM + SOL : 84 ) .


The improvement of I-PSS and QoL with TAM + SOL was significantly greater than with TAM alone ( p < 0.001 ) .


In the voiding group , 108 were able to finish the study ( TAM : 54 , TAM + SOL : 54 ) .


The improvement of I-PSS and QoL with TAM alone was significantly greater than with TAM + SOL ( p < 0.001 ) .


The most bothersome symptom in male LUTS/OAB should be considered when choosing the appropriate medical treatment .


Multiple phase-2 trials in men with biochemically-recurrent prostate cancer ( BRPC ) have assessed the impact of nonhormonal agents on PSA kinetics .


We have previously demonstrated that changes in PSA kinetics correlate with metastasis-free survival ; however , it is unknown whether these changes also correlate with overall survival ( OS ) .


We performed a combined retrospective analysis of 146 men with BRPC treated on phase-2 trials using one of four investigational drugs : lenalidomide ( n = 60 ) , marimastat ( n = 39 ) , ATN-224 ( n = 22 ) and imatinib ( n = 25 ) .


We examined factors influencing OS , including within-subject changes in PSA kinetics ( PSA slope , PSA doubling time and PSA velocity ) , before and 6 months after treatment initiation .


After a median follow-up of 83.1 months , 49 of 146 men had died .


In univariate Cox regression analysis , two factors were associated with OS : baseline PSA velocity and change in PSA velocity on therapy .


In a landmark multivariable model , stratified by study ( which controlled for age , Gleason score , type of local therapy and use of androgen-deprivation therapy prior to metastases ) , baseline PSA velocity and increase in PSA velocity on therapy remained independent predictors of OS .


Median OS for men with an increase in PSA velocity on treatment was 115.4 months and was not reached for men with a decrease in PSA velocity ( hazard ratio = 0.47 , 95 % confidence interval 0.25-0 .88 ; P = 0.02 ) .


This hypothesis-generating study suggests that within-subject changes in PSA velocity after initiation of nonhormonal therapy may correlate with OS in men with BRPC .


If validated in prospective trials , change in PSA velocity may represent a reasonable intermediate end point for screening new agents in these patients .


The aims of the present study were to evaluate the efficacy of and compliance with a new device for autoinflation in the treatment of persistent otitis media with effusion ( OME ) in young children .


Forty-five children with persistent OME with a bilateral type B or C2 tympanogram for at least three months and history of subjective hearing loss , waiting for grommet surgery , were randomised to a treatment and a control group .


Twenty-three children aged between three and eight years started as the treatment group with the new device for autoinflation .


Another 22 children , aged between two and eight years were included as controls .


After a period of four weeks , a cross-over was performed .


Both groups underwent otomicroscopy , tympanometry and audiometry at inclusion and after one and two months for the evaluation of treatment efficiency .


The primary outcome measurements were improvement in middle-ear pressure and hearing thresholds at eight weeks .


Both groups were then followed up for another 10 months .


In the treatment group , the mean middle-ear pressure for both ears and the mean hearing thresholds for the best ear improved by 166 daPa ( p < 0.0001 ) and 6 dB ( p < 0.0001 ) , respectively after four weeks , while in the control group , non-significant alterations were observed .


After the cross-over of the control group to treatment , equivalent improvements in the mean middle-ear pressure and the mean hearing thresholds of 187 daPa ( p < 0.0001 ) and 7 dB ( p < 0.01 ) , respectively were achieved also in this group .


After treatment in both groups at eight weeks , four of 45 children were submitted to grommet surgery .


During the long-term follow-up another five children were submitted to surgery due to recurrence of disease .


All the children managed to perform the manoeuvre and no side-effects were detected .


The device demonstrated efficiency in improving both middle-ear pressure and hearing thresholds in most children after four weeks of treatment .


It might therefore be possible to consider this method of autoinflation in children with persistent OME during the watchful waiting period .


The negative consequences of unhealthy weight gain and the high likelihood of pediatric obesity tracking into adulthood highlight the importance of targeting youth who are ` at risk ' of obesity .


The aim of this paper is to report the rationale and study protocol for the ` Active Teen Leaders Avoiding Screen-time ' ( ATLAS ) obesity prevention intervention for adolescent boys living in low-income communities .


The ATLAS intervention will be evaluated using a cluster randomized controlled trial in 14 secondary schools in the state of New South Wales ( NSW ) , Australia ( 2012 to 2014 ) .


ATLAS is an 8-month multi-component , school-based program informed by self-determination theory and social cognitive theory .


The intervention consists of teacher professional development , enhanced school-sport sessions , researcher-led seminars , lunch-time physical activity mentoring sessions , pedometers for self-monitoring , provision of equipment to schools , parental newsletters , and a smartphone application and website .


Assessments were conducted at baseline and will be completed again at 9 - and 18-months from baseline .


Primary outcomes are body mass index ( BMI ) and waist circumference .


Secondary outcomes include BMI z-scores , body fat ( bioelectrical impedance analysis ) , physical activity ( accelerometers ) , muscular fitness ( grip strength and push-ups ) , screen-time , sugar-sweetened beverage consumption , resistance training skill competency , daytime sleepiness , subjective well-being , physical self-perception , pathological video gaming , and aggression .


Hypothesized mediators of behavior change will also be explored .


ATLAS is an innovative school-based intervention designed to improve the health behaviors and related outcomes of adolescent males in low-income communities .


Our recent work indicates that endogenous opioid activity influences analgesic responses to opioid medications .


This secondary analysis evaluated whether endogenous opioid activity is associated with degree of opioid analgesic adverse effects , and whether chronic pain status and sex affect these adverse effects .


Using a double-blind , randomized , placebo-controlled , crossover design , 51 subjects with chronic low back pain and 38 healthy controls participated in 3 separate sessions , undergoing 2 laboratory-evoked pain tasks ( ischemic and thermal ) after receiving placebo , naloxone , or morphine .


Endogenous opioid system function was indexed by the difference in pain responses between the placebo and naloxone conditions .


These measures were examined for associations with morphine-related adverse effects .


Chronic pain subjects reported significantly greater itching and unpleasant bodily sensations with morphine than controls ( P < 0.05 ) .


Across groups , only 6 of 112 possible associations between adverse effects and blockade effects were significant .


For the ischemic task , higher endogenous opioid function was associated with greater itching ( visual analog scale [ VAS ] ; P < 0.05 ) , numbness ( tolerance ; P < 0.001 ) , dry mouth ( tolerance ; P < 0.05 ) , and unpleasant bodily sensations ( VAS ; P < 0.05 ) .


For the thermal task , higher endogenous opioid function was associated with greater numbness ( VAS ; P < 0.05 ) and feeling carefree ( VAS ; P < 0.05 ) .


There were no significant main or interaction effects of chronic pain status or sex on these findings .


No consistent relationships were observed between endogenous opioid function and morphine-related adverse effects .


This is in stark contrast to our previous observation of strong relationships between elevated endogenous opioid function and smaller morphine analgesic effects .


A new core biopsy needle for endoscopic ultrasound ( EUS ) - guided sampling has recently been developed .


The aim of this prospective multicenter study was to compare this needle with a standard needle in patients with solid pancreatic masses .


Consecutive patients with solid pancreatic masses referred to 17 centers for EUS-guided sampling were included .


Each patient had two passes with a standard 22G needle and a single pass with a 22G core needle performed in a randomized order .


Samples from both needles were separately processed for liquid-based cytology and cell-block preparation and were assessed independently by two blinded expert pathologists .


The primary endpoint was the accuracy of the detection of malignancy .


The reference standard was based on further cytohistological analysis obtained under ultrasound or computed tomography scanning , endoscopic or surgical guidance , and/or by clinical follow-up with repeated imaging examinations for at least 12 months .


The secondary endpoints were the rate of technical failure and the quality of the cytohistological samples obtained .


Of the 80 patients included ( 49 men ; mean age 67.111.1 ) , 87.5 % had final malignant diagnoses ( adenocarcinoma n = 62 , 77.5 % ) .


There was no difference between the needles in diagnostic accuracy ( standard needle 92.5 % vs. core needle 90 % ; P = 0.68 ) or technical failure .


Both pathologists found the overall sample quality significantly better for the standard needle ( expert 1 , P = 0.009 ; expert 2 , P = 0.002 ) .


The diagnostic accuracy of EUS sampling for solid pancreatic masses using standard and core needles seems comparable but with a better overall histological sample quality for the former .


ClinicalTrial.gov identifier : NCT01479803 .


The purpose of this study was to evaluate the safety and efficacy of three different intravenous ( IV ) doses of palonosetron compared with placebo for the prevention of postoperative nausea and vomiting ( PONV ) in children undergoing dental rehabilitation under general anesthesia ( DRGA ) in the first 24 hours after discharge .


A total of 286 children who were classified with an American Society of Anesthesiologists physical status of I and II , between three and 13 years old ( mean = 6.13 years old ) , and undergoing DRGA were enrolled in this study .


The children were randomized to receive one of the three doses of palonosetron ( 0.0025 mg , 0.0050 mg , or 0.0075 mg ) or placebo immediately before induction of anesthesia .


Compared with placebo , the incidence of PONV was significantly lower in the palonosetron groups ( P < .05 ) .


However , there were no statistically significant differences among the palonosetron groups regarding the number of children with PONV during all time periods after anesthesia ( P < .05 ) .


A single 0.0025 mg intravenous dose of palonosetron is recommended for further evaluation , as it appears to be an effective dose for prevention of postoperative nausea and vomiting in children undergoing dental rehabilitation under general anesthesia .


To assess bacillus Calmette-Gurin maintenance treatment schedule for non-muscle invasive bladder cancer at 2 years , using one-third of the full dose and fewer instillations every 3 months or 6 months .


This was a prospective , randomized , multicenter study .


All patients had an intermediate - or high-risk non-muscle invasive bladder cancer .


They received three weekly instillations of one-third dose bacillus Calmette-Gurin every 6 months ( group I ) and two weekly instillations every 3 months ( group II ) during 3 years .


In the two schedules we assessed efficacy , tolerance , leukocyturia and prostate-specific antigen .


No significant difference was observed between the two groups for recurrence at 6 , 12 or 18 months .


At 2 years , tumor recurrence was observed in 10.9 % and muscle invasion in 2.9 % of cases .


Bacillus Calmette-Gurin tolerance was comparable - the adverse events score was 0.8 in group I and 1 in group II ( P = 0.242 ) .


No statistical correlation was observed between the adverse events score over 2 years , either for leukocyturia ( P = 0.8891 ) or prostate-specific antigen level ( P = 0.7155 ) .


Leukocyturia level was not significantly associated with tumor recurrence or progression .


One-third dose maintenance bacillus Calmette-Gurin is effective with no impact on tumor recurrence or muscle invasion .


Furthermore , there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months .


In clinical practice , the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus Calmette-Gurin toxicity .


To evaluate the usefulness of velocity ratio ( VR ) in patients with low gradient severe aortic stenosis ( LGSAS ) and preserved EF .


LGSAS despite preserved EF represents a clinically challenging entity .


Reliance on mean pressure gradient ( MPG ) may underestimate stenosis severity as has been reported in the context of paradoxical low flow , LGSAS .


On the other hand , grading of stenosis severity by aortic valve area ( AVA ) may overrate stenosis severity due to erroneous underestimation of LV outflow tract ( LVOT ) diameter , small body size or inconsistencies in cut-off values for severe stenosis .


We hypothesised that VR may have conceptual advantages over MPG and AVA , predict clinical outcomes and thereby be useful in the management of patients with LGSAS .


Patients from the prospective Simvastatin and Ezetimibe in Aortic Stenosis ( SEAS ) study with an AVA < 1.0 cm ( 2 ) , MPG40mmHg and EF55 % and asymptomatic at baseline were stratified according to VR with a cut-off value of 0.25 .


Outcomes were evaluated according to aortic valve-related events and cardiovascular death .


Of 435 patients with LGSAS , 197 ( 45 % ) had VR < 0.25 suggesting severe and 238 ( 55 % ) had VR0 .25 suggesting non-severe stenosis .


Aortic valve-related events ( mean follow-up 4214months ) were more frequent in patients with VR < 0.25 ( 57 % vs 41 % ; p < 0.001 ) as was cardiovascular death within the first 24months ( p < 0.05 ) .


In multivariable Cox regression analysis , MPG was the strongest independent predictor of aortic valve events ( p < 0.001 ) followed by VR ( p < 0.02 ) .


Adjusting AVA by VR increased predictive accuracy for aortic valve events ( area under the receiver operating curve 0.62 ( 95 % CI 0.57 to 0.67 ) vs 0.56 ( 95 % CI 0.51 to 0.61 ) for AVA , p = 0.02 ) with net reclassification improvement calculated at 0.36 ( 95 % CI 0.17 to 0.54 , p < 0.001 ) .


VR did not improve the prediction of clinical events by MPG .


In the difficult setting of LGSAS , VR shows a strong association with valve-related events and-although not outperforming MPG-may be particularly useful in guiding clinical management .


NCT00092677 .


The objective was to assess the long-term safety profile of dual-release hydrocortisone ( DR-HC ) in patients with adrenal insufficiency ( AI ) .


Randomised , open-label , crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each ( stage 1 ) followed by two consecutive , prospective , open-label studies of DR-HC for 6 months ( stage 2 ) and 18 months ( stage 3 ) at five university clinics in Sweden .


Sixty-four adults with primary AI started stage 1 , and an additional 16 entered stage 3 .


Patients received DR-HC 20-40mg once daily and hydrocortisone 20-40mg divided into three daily doses ( stage 1 only ) .


Main outcome measures were adverse events ( AEs ) and intercurrent illness ( self-reported hydrocortisone use during illness ) .


In stage 1 , patients had a median 1.5 ( range , 1-9 ) intercurrent illness events with DR-HC and 1.0 ( 1-8 ) with thrice-daily hydrocortisone .


AEs during stage 1 were not related to the cortisol exposure-time profile .


The percentage of patients with one or more AEs during stage 1 ( 73.4 % with DR-HC ; 65.6 % with thrice-daily hydrocortisone ) decreased during stage 2 , when all patients received DR-HC ( 51 % in the first 3 months ; 54 % in the second 3 months ) .


In stages 1-3 combined , 19 patients experienced 27 serious AEs , equating to 18.6 serious AEs/100 patient-years of DR-HC exposure .


This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy .


Low-fat and low-carbohydrate weight-loss diets can have a beneficial effect on longitudinal measures of blood pressure and blood lipids .


We aimed to assess longitudinal changes in blood pressure and blood lipids in a population of premenopausal women .


We hypothesized that results may differ by level of adherence to the respective diet protocol and baseline presence of hypertension or hyperlipidemia .


Overweight or obese premenopausal women were randomized to a low-fat ( n = 41 ) or low-carbohydrate ( n = 38 ) diet .


As part of the 52-week Lifestyle Eating and Fitness ( LEAF ) intervention trial , we fit linear mixed models to determine whether a change in outcome differed by treatment arm .


Within-group trends in blood pressure and blood lipids did not differ ( p > 0.30 ) .


Across study arms , there was a significant decrease in systolic blood pressure ( SBP , 3mm Hg , p = 0.01 ) over time , but diastolic blood pressure ( DBP ) did not change significantly over the course of the study .


Blood lipids ( total cholesterol [ TC ] , low-density lipoproteins [ LDL ] , and high-density lipoproteins [ HDL ] ) all exhibited nonlinear trends over time ( p < 0.01 ) ; each decreased initially but returned to levels comparable to baseline by study conclusion ( p > 0.20 ) .


We observed a decline in SBP among women who were hypertensive at baseline ( p < 0.01 ) , but hypercholesterolemia at baseline did not affect trends in blood lipids ( p > 0.40 ) .


Our results support that dietary interventions may be efficacious for lowering blood pressure and blood lipids among overweight or obese premenopausal women .


However , a decrease in SBP was the only favorable change that was sustained in this study population .


These changes can be maintained over the course of a 1-year intervention , yet changes in blood lipids may be less sustainable .


Intrafraction tumour motion in helical tomotherapy was investigated by comparing pre - and mid-fraction CT scans in patients with early non-small cell lung carcinoma ( NSCLC ) to assess the efficacy of a 7-mm margin around gross tumour volumes ( GTVs ) in stereotactic body radiation therapy ( SBRT ) .


Thirty patients with early-stage NSCLC received SBRT in four or five fractions for a total of 141 treatments .


A slow positron emission tomography/CT scan was fused with the simulation CT to determine the GTV .


A planning target volume was created by placing an isotropic margin of 7mm around the GTV .


Data were retrospectively analyzed to assess translational tumour positional changes along the x , y and z axes and vector changes in millimeters from the pretreatment megavoltage ( MV ) - CT to the mid-fraction MV-CT .


Average movements for all 141 treatment days along the x , y and z axes were 0.52.3 , -0.33.0 and 0.93.0 mm , respectively .


Average movements for each patient along the x , y and z axes were 0.51.5 , -0.22.0 and 0.91.9 mm , respectively .


Average vector displacement was 4.32.4 mm for all treatment days and 4.21.7 mm for each patient .


Of 141 treatments , 137 ( 97.2 % ) fell within 7.0 mm in all axes .


The addition of a 7-mm margin to the GTV for patients receiving SBRT for NSCLC using tomotherapy is adequate to account for tumour movement .


Mid-fraction CT scans proved to be valuable in assessing intrafraction tumour motion .


Standard varenicline tartrate dosing was formulated to avoid adverse effects ( primarily nausea ) , but some patients may be underdosed .


To our knowledge , no evidence-based guidance exists for physicians considering increasing varenicline dose if there is no response to the standard dosage .


To determine whether increasing varenicline dose in patients showing no response to the standard dosage improves treatment efficacy .


In a double-blind randomized placebo-controlled trial , 503 smokers attending a stop smoking clinic commenced varenicline use 3 weeks before their target quit date ( TQD ) .


Two hundred participants reporting no strong nausea , no clear reduction in smoking enjoyment , and less than 50 % reduction in their baseline smoking on day 12 received additional tablets of varenicline or placebo .


All participants began standard varenicline tartrate dosing , gradually increasing to 2 mg/d .


Dose increases of twice-daily varenicline ( 0.5 mg ) or placebo took place on days 12 , 15 , and 18 ( up to a maximum of 5 mg/d ) .


Participants rated their smoking enjoyment during the prequit period and withdrawal symptoms weekly for the first 4 weeks after the TQD .


Continuous validated abstinence rates were assessed at 1 , 4 , and 12 weeks after the TQD .


The dose increase reduced smoking enjoyment during the prequit period , with mean ( SD ) ratings of 1.7 ( 0.8 ) for varenicline vs 2.1 ( 0.7 ) for placebo ( P = .001 ) .


It had no effect on the mean ( SD ) frequency of urges to smoke at 1 week after the TQD , their strength , or the severity of withdrawal symptoms : these ratings for varenicline vs placebo were 2.7 ( 1.1 ) vs 2.6 ( 0.9 ) ( P = .90 ) , 2.6 ( 1.1 ) vs 2.8 ( 1.0 ) ( P = .36 ) , and 1.5 ( 0.4 ) vs 1.6 ( 0.5 ) ( P = .30 ) , respectively .


The dose increase also had no effect on smoking cessation rates for varenicline vs placebo at 1 week ( 37 [ 37.0 % ] vs 48 [ 48.0 % ] , P = .14 ) , 4 weeks ( 51 [ 51.0 % ] vs 59 [ 59.0 % ] , P = .32 ) , and 12 weeks ( 26 [ 26.0 % ] vs 23 [ 23.0 % ] , P = .61 ) after the TQD .


There was significantly more nausea ( P < .001 ) and vomiting ( P < .001 ) reported in the varenicline arm than in the placebo arm .


Increasing varenicline dose in smokers with low response to the drug had no significant effect on tobacco withdrawal symptoms or smoking cessation .


Physicians often consider increasing the medication dose if there is no response to the standard dosage .


This approach may not work with varenicline .


clinicaltrials.gov Identifier : NCT01206010 .


To assess the efficacy of the cytoprotective neuropeptide cortexin in the complex treatment in acute and early rehabilitation stages of ischemic stroke ( II ) .


A multicenter prospective double-blind placebo-controlled trial has been carried out .


Two hundreds and seventy-two patients with II have been enrolled in the trial .


Cortexin was administered in low doses ( 10 mg three times a day intramuscular , using the following schemes : group 1 : 2 courses of cortexin ; group 2 : 1 course of cortexin with the following course of placebo ; group 3 : two courses of placebo .


The duration of treatment was 70 days .


Patients were examined during 4 visits using clinical tests and instrumental methods .