We registered 401 patients , 226 of whom were enrolled .


Results for 169 with KRAS wild-type are reported here , 78 ( 46 % ) assigned to intermittent cetuximab and 91 ( 54 % ) to continuous cetuximab .


64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis .


10-month failure-free survival was 50 % ( lower bound of 95 % CI 39 ) in the intermittent group versus 52 % ( lower bound of 95 % CI 41 ) in the continuous group ; median failure-free survival was 12.2 months ( 95 % CI 8.8-15 .6 ) and 14.3 months ( 10.7-20 .4 ) , respectively .


The most common grade 3-4 adverse events were skin rash ( 21 [ 27 % ] of 77 patients vs 20 [ 22 % ] of 92 patients ) , neutropenia ( 22 [ 29 % ] vs 30 [ 33 % ] ) , diarrhoea ( 14 [ 18 % ] vs 23 [ 25 % ] ) , and lethargy ( 20 [ 26 % ] vs 19 [ 21 % ] ) .


Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies .


Maintenance of biological monotherapy , with less cytotoxic chemotherapy within the first 6 months , in molecularly selected patients is promising and should be validated in phase 3 trials .


Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties .


We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function , and thrombus formation in healthy fire fighters .


In a double-blind randomized cross-over study , 16 healthy male fire fighters were exposed to wood smoke ( ~ 1 mg/m particulate matter concentration ) or filtered air for one hour during intermittent exercise .


Arterial pressure and stiffness were measured before and immediately after exposure , and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and - independent vasodilators 4-6 hours after exposure .


Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours , and platelet activation was measured using flow cytometry for up to 24 hours after the exposure .


Compared to filtered air , exposure to wood smoke increased blood carboxyhaemoglobin concentrations ( 1.3 % versus 0.8 % ; P < 0.001 ) , but had no effect on arterial pressure , augmentation index or pulse wave velocity ( P > 0.05 for all ) .


Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator ( P < 0.01 for all ) , there were no differences in blood flow responses to acetylcholine , sodium nitroprusside or verapamil between exposures ( P > 0.05 for all ) .


Following exposure to wood smoke , vasodilatation to bradykinin increased ( P = 0.003 ) , but there was no effect on bradykinin-induced tissue-plasminogen activator release , thrombus area or markers of platelet activation ( P > 0.05 for all ) .


Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function , or increase thrombus formation in fire fighters .


Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms , such as strenuous physical exertion and dehydration .


The New Nordic Diet ( NND ) has induced weight loss in a 26-week controlled intervention .


We aim to investigate whether high compliance and satisfaction can be maintained after the active intervention is discontinued thereby maintaining the health effects .


After 26 weeks of intervention with NND or Average Danish Diet ( ADD ) , 147 participants ( mean age 43 years and mean BMI 29.1 kg/m ) were followed for further 52 weeks .


All participants were encouraged to follow NND but without further guidance .


The study is registered with ClinicalTrials.gov , study id NCT01195610 .


One hundred and ten participants ( 75 % ) completed the follow-up .


Among participants previously randomised to NND ( NND group ) , dietary compliance and satisfaction decreased from 4.3 to 3.0 and from 4.8 to 4.0 , respectively ( both p < 0.0001 ) ( 1-5 point scale ) .


Among those originally randomised to ADD ( ADD group ) , satisfaction with NND was significantly higher than with ADD during follow-up ( 3.3 vs. 2.5 , p = 0.026 ) .


Weight losses during intervention of -6.2 kg and -3.0 kg were followed by regains of 4.6 kg ( SE 0.5 ) and 1.1 kg ( SE 0.7 ) for the NND group and ADD group , respectively [ adjusted difference ; mean ( 95 % CI ) : 1.8 kg ( 0.1-3 .4 ) , p = 0.041 ] .


Across diet groups , every 1 score higher in compliance with NND was associated with 0.90 kg less body weight regain ( p = 0.026 ) and those who increased physical activity regained 3.4 kg less compared to those who did not ( p < 0.0001 ) .


NND provides higher satisfaction , and body weight regain is reduced with higher compliance with NND and increased physical activity .


Advanced pancreatic cancer ( APC ) , beside its high mortality , causes the highest rates of venous thromboembolic events ( VTE ) .


Enoxaparin , a low molecular weight heparin ( LMWH ) , is effective in prevention and treatment of VTE .


Some small studies indicated that this benefit might extend to patients with cancer and probably prolong survival due to independent mechanisms .


We initiated this safety investigation to get feasibility information on intensified chemotherapy combined with LMWH in outpatients with APC treated in 1st line .


The trial was a prospective , open-label , single center investigation in outpatients with inoperable pancreatic cancer who were treated with intensified first-line chemotherapy along with concomitant application of subcutaneous LMWH .


The combined chemotherapy consisted of gemcitabine 1 g/m2 ( 30 min ) , 5-FU 750 mg/m2 ( 24 h ) , folinic acid 200 mg/m2 ( 30 min ) , and Cisplatin 30 mg/m2 ( 90 min ) on day 1 and 8 ; q3w for the first 12 weeks ( GFFC ) followed by gemcitabine alone in patients without cancer progression .


The simultaneous application of prophylactic enoxaparin started on day 1 of chemotherapy with a fixed dose of 40 mg daily .


Statistical analyses were performed using R 3.01 with software package CMPRSK and SPSS software v19 .0 .


The investigation was stopped after recruitment of 19 patients .


At this time 15 patients had completed the required 12 weeks of treatment .


Based on 71 cycles of GFFC + enoxaparin ( median 4/pt [ range : 2-4 ] ) and 108 cycles of single-agent gemcitabine + enoxaparin ( median 4/pt [ range : 0-18 ] ) the cumulative frequency of NCI-CTC toxicities grade 3/4 was below 10 % .


One case ( 5 % ) of a symptomatic non-lethal thromboembolic event was observed while receiving LMWH treatment .


No severe bleeding event as defined in the protocol has been observed .


The median overall survival was 10.05 [ 95 % CI : 8.67-18 .14 ] months .


The addition of enoxaparin to GFFC chemotherapy is feasible , safe and does not appear to affect the efficacy or the toxicity profile of the chemotherapy regimen in patients with advanced pancreatic adenocarcinoma .


Based on these findings we have initiated the randomized CONKO-004 trial to examine whether enoxaparin reduces the incidence of thromboembolic events or increases overall outcome .


Clinical Trials NCT01945879 .


Vorapaxar reduces cardiovascular death , myocardial infarction ( MI ) , or stroke in patients with previous MI while increasing bleeding .


Patients with diabetes mellitus ( DM ) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies .


The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized , double-blind , placebo-controlled trial of vorapaxar in patients with stable atherosclerosis .


We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI .


Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack , the analysis ( n = 16 896 ) excluded such patients .


The primary end point of cardiovascular death , MI , or stroke occurred more frequently in patients with DM than in patients without DM ( rates in placebo group : 14.3 % versus 7.6 % ; adjusted hazard ratio , 1.47 ; P < 0.001 ) .


In patients with DM ( n = 3623 ) , vorapaxar significantly reduced the primary end point ( 11.4 % versus 14.3 % ; hazard ratio , 0.73 [ 95 % confidence interval , 0.60-0 .89 ] ; P = 0.002 ) with a number needed to treat to avoid 1 major cardiovascular event of 29 .


The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM ( 4.4 % versus 2.6 % ; hazard ratio , 1.60 [ 95 % confidence interval , 1.07-2 .40 ] ) .


However , net clinical outcome integrating these 2 end points ( efficacy and safety ) was improved with vorapaxar ( hazard ratio , 0.79 [ 95 % confidence interval , 0.67-0 .93 ] ) .


In patients with previous MI and DM , the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events .


URL : http://www.clinicaltrials.gov .


Unique identifier : NCT00526474 .


To assess the efficacy and safety of eslicarbazepine acetate ( ESL ) as monotherapy in North American patients with partial-onset seizures ( POS ) .


This multicenter , randomized , double-blind `` withdrawal to monotherapy '' study used historical control data as the comparator .


Adults with POS medically uncontrolled by one to two antiepileptic drugs gradually converted to ESL monotherapy .


Following an 8-week baseline period , patients were randomized 2:1 to receive ESL 1,600 mg ( n = 128 ) or 1,200 mg QD ( n = 65 ) for 18 weeks .


The primary end point was the proportion of patients meeting predefined exit criteria ( signifying worsening seizure control ) .


Treatment was considered effective if the 95 % upper confidence limit ( UCL ) for the Kaplan-Meier estimated exit rate was lower than the exit rate threshold calculated from the historical control ( 65.3 % ) .


Kaplan-Meier estimated exit rates were : ESL 1,600 mg , 28.7 % ( 95 % CI 21.2-38 .1 % ) and 1,200 mg , 44.4 % ( 32.5-58 .3 % ) .


The difference between doses was not significant ( p = 0.07 ) .


For both doses , the 95 % UCLs for the exit rate were 65.3 % ; ESL monotherapy was considered superior to the historical control .


There was no statistically significant increase in the risk of study exit related to carbamazepine use .


Nine ( 7.6 % ) and five patients ( 8.3 % ) remained seizure-free during the 10-week monotherapy period , while taking ESL 1,600 and 1,200 mg , respectively .


The reductions in median standardized seizure frequency ( seizures per 28 days ) between baseline and the 18-week treatment period were : ESL 1,600 mg , 42 % and 1,200 mg , 31 % .


Treatment-emergent adverse events ( TEAEs ) occurring in 10 % of patients were dizziness , headache , fatigue , somnolence , nausea , and nasopharyngitis .


The TEAE most frequently leading to discontinuation was hyponatremia ( 2.1 % ) .


ESL was efficacious and well tolerated as monotherapy in North American patients , and led to a reduction in seizure frequency .


Exit rates for ESL 1,600 and 1,200 mg QD were superior to the historical control ; the difference in exit rates between doses was not statistically significant .


Interleukin 13 ( IL-13 ) is thought to play a key role as an effector cytokine in UC .


Anrukinzumab , a humanised antibody that inhibits human IL-13 , was evaluated for the treatment of UC .


In a multicentre , randomised , double-blind , placebo-controlled study , patients with active UC ( Mayo score 4 and < 10 ) were randomised to anrukinzumab 200 , 400 or 600mg or placebo .


Patients received five intravenous administrations over 14weeks .


The primary endpoint was fold change from baseline in faecal calprotectin ( FC ) at Week 14 .


Secondary endpoints included safety , pharmacokinetics and IL-13 levels .


The modified intention-to-treat population included 84 patients ( 21 patients/arm ) .


Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo .


The study had a high dropout rate , in part , related to lack of efficacy .


The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score , clinical response , clinical remission and proportion of subjects with mucosal healing .


An increase in serum total IL-13 ( free and bound to anrukinzumab ) was observed for all anrukinzumab groups but not with placebo .


This suggests significant binding of anrukinzumab to IL-13 .


The safety profile was not different between the anrukinzumab and placebo groups .


A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13 .


ClinicalTrials.gov number NCT01284062 .


To investigate the changes in adrenocorticotropic hormone ( ACTH ) and cortisol in heroin addicts given Jitai tablet treatment during abstinence .


Double-blind , randomized , placebo-controlled clinical trial .


Drug Rehabilitation Bureau of Shanghai Police , China .


99 volunteers , including 69 heroin addicts and 30 healthy volunteers .


69 heroin addicts randomly divided into two groups : the Jitai tablet group , which comprised 34 heroin addicts given Jitai tablet treatment during abstinence , and the placebo group , which comprised 35 heroin addicts given placebo .


A control group consisted of 30 sex - and age-matched healthy volunteers .


ACTH and cortisol in plasma were measured in all groups at baseline and in the Jitai tablet and placebo groups on the third , seventh , and 14th days of abstinence .


Levels of both ACTH ( p < .01 ) and cortisol ( p < .001 ) were significantly higher in heroin addicts at baseline than in the healthy volunteers .


Jitai tablet treatment restored plasma cortisol levels to normal more rapidly than did placebo treatment ( p < .05 ) , but not ACTH levels .


A positive correlation between ACTH and cortisol values at baseline ( p < .01 ) was also found with withdrawal symptom scores and daily dosages of heroin .


Heroin addicts could respond to Jitai tablets through changes in the hypothalamus-pituitary-adrenal axis .


Former cancer patients ' quality of life can be improved by offering social comparison information .


Whether patients , however , benefit from the information may depend on how negative they perceive their present and their future .


We conducted a randomised experimental field study with a pre - and post-measurement .


Dutch former cancer patients - recruited through different media - were assigned to a social comparison intervention condition or a no-intervention control condition ( experimental condition n = 62 ; control condition n = 88 ; Mage = 52 years ) .


In the intervention condition , patients received a 20 min computer-tailored interview in audio format .


Patients ' present perceived life threat and future health expectations were measured at pretest .


Quality of life and life satisfaction after 2 months were the outcome variables .


The intervention increased life satisfaction only in patients who experienced a high present life threat ( [ Formula : see text ] = .08 ) and in patients who had negative future health expectations , the intervention increased quality of life ( [ Formula : see text ] = .05 ) .


Not all patients did benefit from the intervention ; for some patients , the social comparison intervention was even detrimental .


Moderator analyses seem necessary to evaluate psycho-social interventions for cancer patients .


At least 13 % of mothers experience depression in the first postnatal year , with accompanying feelings of despair and a range of debilitating symptoms .


Serious sequelae include disturbances in the mother-infant relationship and poor long-term cognitive and behavioural outcomes for the child .


Surprisingly , treatment of maternal symptoms of postnatal depression does not improve the mother-infant relationship for a majority of women .


Targeted interventions to improve the mother-infant relationship following postnatal depression are scarce and , of those that exist , the majority are not evaluated in randomised controlled trials .


This study aims to evaluate a brief targeted mother-infant intervention , to follow cognitive behavioural therapy treatment of postnatal depression , which has the potential to improve developmental outcomes of children of depressed mothers .


The proposed study is a two-arm randomised controlled trial with follow-up to 6 months .


One hundred participants will be recruited via referrals from health professionals including maternal and child health nurses and general practitioners , as well as self-referrals from women who have seen promotional materials for the study .


Women who meet inclusion criteria ( infant aged < 12 months , women 18 + years of age ) will complete the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV-TR Axis I Disorders .


Those with a clinical diagnosis of current major or minor depressive disorder and who do not meet exclusion criteria ( that is , currently receiving treatment for depression , significant difficulty with English , medium to high suicide risk , current self-harm , current substance abuse , current post-traumatic stress disorder , current manic/hypomanic episode or psychotic symptoms ) will be randomised to receive either a 4-session mother-infant intervention ( HUGS : Happiness Understanding Giving and Sharing ) or a 4-session attention placebo playgroup ( Playtime ) following a 12-session postnatal depression group treatment programme .


Primary outcome measures are the Parenting Stress Index ( self-report measure ) and the Parent-child Early Relational Assessment ( observational measure coded by a blinded observer ) .


Measurements are taken at baseline , after the postnatal depression programme , post-HUGS/Playtime , and at 6 months post-HUGS/Playtime .


This research addresses the need for specific treatment for mother-infant interactional difficulties following postnatal depression .


There is a need to investigate interventions in randomised trials to prevent detrimental effects on child development and make available evidence-based treatments .


Australia and New Zealand Clinical Trials Register : ACTRN12612001110875 .


Date Registered : 17 October 2012 .


Only limited data from large randomized clinical trials have been published on the long-term performance of second-generation drug-eluting stents in bifurcation lesions .


We investigated in patients in the randomized TWENTE trial the long-term safety and efficacy of treating bifurcation lesions with 2 widely applied second-generation drug-eluting stents , the zotarolimus-eluting Resolute stent ( Medtronic Inc , Santa Rosa , CA ) and the everolimus-eluting Xience V stent ( Abbott Vascular , Santa Clara , CA ) .


Three-year follow-up was available in 99.3 % .


Patients were categorized into treatment for 1 bifurcation lesion versus treatment for nonbifurcation lesions only .


Among the 1,391 patients of the TWENTE trial , 362 ( 26 % ) were treated for bifurcation lesions .


At 3-year follow-up , target-vessel failure did not differ between patients treated for bifurcation versus nonbifurcation lesions ( 13.1 % vs 12.6 % ; P = .84 ) , whereas the periprocedural myocardial infarction rate was higher in patients with bifurcation lesions ( 6.9 % vs 3.1 % ; P < .01 ) .


Of the 362 patients with bifurcation lesion treatment , 179 ( 49.4 % ) were treated with Resolute and 183 ( 50.6 % ) with Xience V.


There was no significant difference in target-vessel failure between the Resolute and Xience V groups with bifurcation treatment ( 13.6 % vs 12.6 % ; P = .78 ) , and their incidence of definite-or-probable stent thrombosis was low and similar ( 1.1 % vs 0.5 % , respectively ; P = .62 ) .


Despite a significant difference in periprocedural myocardial infarction , 3-year clinical outcome after implantation of second-generation stents was favorable and similar for patients with and without bifurcation lesions .


In addition , we observed no difference in long-term clinical outcome after bifurcation lesion treatment with Resolute and Xience V stents .


The aim was to evaluate , using urethral pressure reflectometry ( UPR ) , the effect of fesoterodine on urethral function in women with stress urinary incontinence ( SUI ) .


Women aged 18 to 65 years were eligible for this randomised , double-blind , placebo-controlled , crossover study if they had had clinically significant SUI or SUI-predominant mixed urinary incontinence for > 3 months .


Each participant received fesoterodine 4 mg , fesoterodine 8 mg , and placebo once daily for 7 days , with a 7 - to 10-day washout between treatments .


UPR was performed at baseline and 4 to 8 h after the last dose in each treatment period .


Participants completed a 3-day bladder diary before randomisation and during the last 3 days of each treatment period .


Of the 22 women randomly assigned and treated , 17 met the criteria for the primary efficacy analyses .


No statistically significant differences were seen between fesoterodine 4 mg or fesoterodine 8 mg and placebo in opening urethral pressure ( primary endpoint ) or other UPR endpoints .


No statistically significant differences were seen between either fesoterodine dose and placebo in the change from baseline in the bladder diary variables ( total urinary incontinence , SUI , or urgency urinary incontinence episodes per 24 h ) .


Adverse events were reported by 8 participants taking fesoterodine 4 mg , 17 taking fesoterodine 8 mg , and 8 taking placebo .


Fesoterodine did not affect urethral pressure or significantly decrease the number of incontinence episodes in women with SUI .


The UPR parameters showed no placebo effect , while there was a placebo effect of 60 % based on the bladder diary .


Insufficient asthma management leads to impaired health-related quality of life ( HRQL ) .


The aim of this study is to assess whether individualized self-management ( ISM ) support will improve HRQL in children with asthma compared to enhanced usual care ( EUC ) in Dutch general practices .


A cluster-randomized controlled trial with 9-month follow-up .


ISM is a nurse-led intervention that is optimized to the needs of children , leading to a written action plan .


Power calculation demanded inclusion of 170 children ( aged 6-11years ) diagnosed with asthma and active medication use .


Outcomes were HRQL of the child ( Paediatric Asthma Quality of Life Questionnaire , PAQLQ-s ) and several secondary outcomes .


Data of 29 children ( mean age 8.6 years , SD 1.7 ) were analyzed ; ISM ( n = 15 ) or EUC ( n = 14 ) .


Logistic regression analysis ( minimal clinical important difference ; MCID0 .5 ) and descriptive analyses were performed .


Despite high PAQLQ-s score at baseline ( median ISM 6.35 , EUC 6.02 ) , a substantial number of subjects from both groups showed MCID of HRQL ( ISM 33 % , EUC 57 % ) .


Treatment differences on HRQL were not significant ( OR 0.38 , 95 % CI 0.08 , 1.69 ) .


Secondary outcomes did not show significant differences either , with exception of PAQLQ-s symptoms domain score in favor of EUC .


Due to recruitment problems and underpowered analyses , no firm conclusions on the effectiveness of ISM support for childhood asthma in primary care could be drawn .


Still , this study can be considered a valuable pilot study and in the future , there might be better capacity in general practices to commit to such treatment .


Challenges remain to find ways to support patients with depression who have low levels of physical activity ( PA ) to overcome perceived barriers and enhance the perceived value of PA for preventing future relapse .


There is an evidence-base for behavioural activation ( BA ) for depression , which focuses on supporting patients to restore activities that have been avoided , but practitioners have no specific training in promoting PA. .


We aimed to design and evaluate an integrated BA and PA ( BAcPAc ) practitioner-led , written , self-help intervention to enhance both physical and mental health .


This study is informed by the Medical Research Council Complex Intervention Framework and describes a protocol for a pilot phase II randomised controlled trial ( RCT ) to test the feasibility and acceptability of the trial methods to inform a definitive phase III RCT .


Following development of the augmented written self-help intervention ( BAcPAc ) incorporating behavioural activation with physical activity promotion , depressed adults are randomised to receive up to 12 sessions over a maximum of 4months of either BAcPAc or behavioural activation alone within a written self-help format , which represents treatment as usual .


The study is located within two ` Improving Access to Psychological Therapies ' services in South West England , with both written self-help interventions supported by mental health paraprofessionals .


Measures assessed at 4 , 9 , and 12month follow-up include the following : CIS-R , PHQ-9 , accelerometer recorded ( 4months only ) and self-reported PA , body mass index , blood pressure , Insomnia Severity Index , quality of life , and health and social care service use .


Process evaluation will include analysis of recorded support sessions and patient and practitioner interviews .


At the time of writing the study has recruited 60 patients .


The feasibility outcomes will inform a definitive RCT to assess the clinical and cost-effectiveness of the augmented BAcPAc written self-help intervention to reduce depression and depressive relapse , and bring about improvements across a range of physical health outcomes .


Current Controlled Trials ISRCTN74390532 , 26.03.2013 .


Job rotation has often been used in situations where the level of exposure can not be reduced due to the characteristics of the job or through physical measures .


However , the effectiveness of the job rotation strategy at preventing musculoskeletal complaints lacks adequate scientific data .


A cluster randomized controlled trial will be used to investigate the effectiveness of job rotation to prevent musculoskeletal disorders in industrial workers .


The randomized cluster was based in characteristics of production sectors .


A total cluster will be 4 sectors , and 957 workers will be recruited from a textile industry and randomly allocated into intervention or control groups .


Both groups will receive training on ergonomics guidelines .


In addition , the intervention group will perform job rotation , switching between tasks with low , moderate , and high risk for musculoskeletal complaints .


The primary outcome will be the number of working hours lost due to sick leave by musculoskeletal injuries recorded in employee administrative data bases .


Secondary outcomes measured via survey include : body parts with musculoskeletal pain , the intensity of this pain , physical workload , fatigue , general health status , physical activity level , and work productivity .


Secondary outcome measures will be assessed at baseline and after 3 , 6 , 9 , and 12 months .


The cost-effectiveness analysis will be performed from the societal and company perspective .


Prevention of work-related musculoskeletal disorders is beneficial for workers , employers , and society .


The results of this study will provide new information about the effectiveness of job rotation as a strategy to reduce work-related musculoskeletal disorders .


NCT01979731 , November 3 , 2013 .


Avoidance of death , disability , dementia , and cognitive dysfunction ( DDCD ) are high priorities for people in aging societies .


Evidence is mounting that these conditions are associated with impaired glycemic control .


The aim of this study was to assess the strength of relationship between the degree of glucose elevation and the development of the composite elements of DDCD that impede successful/healthy aging in a population at high risk for cardiovascular disease .


DESIGN , SETTING , PARTICIPANTS , AND MAIN OUTCOME MEASURE : The relationship between baseline fasting plasma glucose values and DDCD was determined among 31 227 participants of the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE intolerant Subjects With Cardiovascular Disease studies followed up for a median of 4.7 years .


Several statistical models were used for the entire cohort and for those with and without normal fasting plasma glucose ( ie , < 5.6 mmol/L ) or a history of diabetes mellitus .


After adjusting for age and sex , a diagnosis of diabetes mellitus was associated with an approximately 1.6 greater odds of DDCD ; every 1 mmol/L higher baseline fasting plasma glucose value was associated with a 1.09 ( 95 % confidence interval 1.07 , 1.10 ) greater odds .


These associations persisted in the multivariate models ( a 1.08 95 % confidence interval 1.07 , 1.1 greater odds after adjustment for age , sex , education , and depression ) .


In individuals with high cardiovascular risk , a direct relationship exists between levels of dysglycemia and the risk of DDCD .


Further research is needed to understand the mechanisms underlying such an association and whether benefits can be derived from preventative strategies .


Cystic fibrosis-related diabetes is characterized by postprandial , rather than fasting , hyperglycemia .


Gastric emptying and the release of the incretin hormones [ glucagon-like peptide-1 ( GLP-1 ) and glucose dependent insulinotropic polypeptide ( GIP ) ] are central to postprandial glycemic control .


Lipolysis is required for fat to slow gastric emptying and stimulate incretin release .


We aimed to determine the effect of pancreatic enzyme replacement therapy ( PERT ) on postprandial glycemia in adolescents with cystic fibrosis ( CF ) .


This was a double-blinded randomized crossover trial .


Subjects consumed a high-fat pancake , with either PERT ( 50 000 IU lipase ) or placebo .


Gastric emptying was measured by a breath test and blood sampled frequently for plasma blood glucose , insulin , glucagon , GLP-1 , and GIP .


Data were also compared with seven healthy subjects .


Fourteen adolescents ( 13.1 2.7 y ) with pancreatic-insufficient CF and seven healthy age-matched controls participated in the study .


Postprandial hyperglycemia was measured as peak glucose and area under the curve for blood glucose at 240 minutes .


CF subjects had postprandial hyperglycemia compared with controls ( area under the curve , P < .0001 ) .


PERT reduced postprandial hyperglycemia ( P = .0002 ) , slowed gastric emptying ( P = .003 ) , and normalized GLP-1 and GIP secretion ( P < .001 for each ) when compared with placebo , without affecting insulin .


In young people with pancreatic insufficient CF , PERT markedly attenuates postprandial hyperglycemia by slowing gastric emptying and augmenting incretin hormone secretion .


To observe the effects of glutamine combined with ulinastatin on inflammatory response of patients with severe burn injury .


Sixty patients with severe burn injury admitted to our burn wards from January 2010 to December 2011 conforming to the study criteria were divided into control group ( C , n = 20 ) , glutamine group ( G , n = 20 ) , and glutamine combined with ulinastatin group ( G + U , n = 20 ) according to the random number table .


Another 10 healthy volunteers were chosen as normal control group ( NC ) .


Isonitrogenous and isocaloric nutrition supports were given to patients in groups C , G , and G + U from post burn day ( PBD ) 2.0.3 g/kg protein in the form of glutamine dipeptide was given to patients in group G for 10 days .


0.3 g/kg protein was given to patients in group G + U for 10 days with the same amount of glutamine dipeptide as that in group G , followed by intravenous injection of 100 kU ulinastatin ( once per 8 hours ) for 7 days during 10 days .


The nitrogen concentration of 24 h urine was determined with Kieldahl nitrogen determination method , and nitrogen balance was calculated one day before treatment and ten days after treatment .


Meanwhile , the levels of D-lactate in serum was determined by colorimetric method , the levels of diamine oxidase ( DAO ) , TNF - , and IL-6 by enzyme-linked immunosorbent assay , and LPS level by kinetic turbidimetric assay with TAL .


Above-mentioned indexes were also examined in group NC .


The wound healing rate on PBD 30 , total hospital stay days , and the incidence of burn sepsis of all burn patients were recorded .


Data were processed with one-way analysis of variance , LSD test , t test , and chi-square test .


Compared with that in group C [ ( -5.40 1.67 ) g/d ] , nitrogen balance in group G was significantly increased ten days after treatment [ ( -1.35 0.59 ) g/d , P < 0.01 ] .


The serum levels of D-lactate , DAO , LPS , TNF - , and IL-6 in group G ten days after treatment were significantly lower than those in group C ( P < 0.05 or P < 0.01 ) .


No statistically significant difference was observed in nitrogen balance and the serum levels of D-lactate , DAO between group G + U and group G ( P values all above 0.05 ) .


The serum levels of LPS , TNF - , and IL-6 in group G + U ten days after treatment were respectively ( 0.167 0.064 ) EU/mL , ( 43 14 ) pg/mL , ( 139 23 ) pg/mL , which were significantly lower than those in group G [ ( 0.240 0.079 ) EU/mL , ( 59 8 ) pg/mL , ( 195 31 ) pg/mL , respectively , P < 0.05 or P < 0.01 ] .


The would healing rate on PBD 30 and total hospital stay days in group G were respectively higher and shorter than those in group C ( P values all below 0.01 ) , but no statistically significant difference in the incidence of burn sepsis was found between them ( P > 0.05 ) .


The would healing rate on PBD 30 in group G+U [ ( 96 4 ) % ] was enhanced , and total hospital stay days [ ( 41 4 ) d ] were lowered than those in group G [ ( 88 7 ) % , ( 49 5 ) d , P values all below 0.01 ] .


The incidence of burn sepsis of patients in group G + U ( 5 % ) was significantly lower than that in group C ( 35 % , ( 2 ) = 6.234 , P < 0.05 ) .


Glutamine combined with ulinastatin treatment can alleviate damage to intestine after severe burn injury , lower the serum level of inflammatory cytokines , promote wound healing , and reduce the incidence of burn sepsis .


The Food Insulin Index ( FII ) is a novel algorithm for ranking foods on the basis of insulin responses in healthy subjects relative to an isoenergetic reference food .


Our aim was to compare postprandial glycemic responses in adults with type 1 diabetes who used both carbohydrate counting and the FII algorithm to estimate the insulin dosage for a variety of protein-containing foods .


A total of 11 adults on insulin pump therapy consumed six individual foods ( steak , battered fish , poached eggs , low-fat yoghurt , baked beans and peanuts ) on two occasions in random order , with the insulin dose determined once by the FII algorithm and once with carbohydrate counting .


Postprandial glycemia was measured in capillary blood glucose samples at 15-30 min intervals over 3h .


Researchers and participants were blinded to treatment .


Compared with carbohydrate counting , the FII algorithm significantly reduced the mean blood glucose level ( 5.70.2 vs 6.50.2 mmol/l , P = 0.003 ) and the mean change in blood glucose level ( -0.70.2 vs 0.10.2 mmol/l , P = 0.001 ) .


Peak blood glucose was reached earlier using the FII algorithm than using carbohydrate counting ( 345 vs 567min , P = 0.007 ) .


The risk of hypoglycemia was similar in both treatments ( 48 % vs 33 % for FII vs carbohydrate counting , respectively , P = 0.155 ) .


In adults with type 1 diabetes , compared with carbohydrate counting , the novel FII algorithm improved postprandial hyperglycemia after consumption of protein-containing foods .


To explore the safety in inguinal incarcerated hernia repair without use of antibiotics .


Retrospective statistical analysis was performed for a total 326 patients with inguinal incarcerated hernia repair at our hospital from January 2011 to July 2013 .


They were divided into 2 groups of non-using ( n = 192 ) and using ( n = 134 ) antibiotics .


Statistical analysis of early postoperative infection was performed for two groups .


The total incision infection had no statistical difference between two groups ( 7.29 % ( 14/192 ) vs 3.73 % ( 5/134 ) , 0.52 % ( 1/192 ) vs 1.49 % ( 2/134 ) , both P > 0.05 ) .


Further comparison of leukocyte count and neutrophil count at Day 3 showed no inter-group statistical difference ( ( 7.9 0.6 ) 10 ( 9 ) vs ( 7.8 0.7 ) 10 ( 9 ) / L , ( 4.9 0.5 ) 10 ( 9 ) vs ( 5.0 0.5 ) 10 ( 9 ) / L ; U = 1.344 , 1.777 ; P = 0.180 , 0.077 ) .


It is unnecessary to use preventive antibiotics in patients undergoing tension-free repair with incarcerated inguinal hernia without high-risk infection or bowel necrosis .


To propose and evaluate a novel surgical approach with minimal trauma , termed interseptal bone reduction , combined with the use of a conventional orthodontic fixed appliance to accelerate canine retraction .


A split-mouth design study was conducted in 18 female subjects ( mean age , 21.9 years ) whose bilateral upper first premolars were extracted and who subsequently received canine distalization .


The extraction socket on the experimental side was deepened , and interseptal bone distal to the maxillary canine was reduced in thickness using a surgical bur ; conventional extraction was performed on the control side .


The canines were then distalized using elastomeric chains on both the labial and palatal sides , with a net force of 150 g.


The extent of canine movement and rotation was determined from study models , and the angulation was analyzed based on lateral cephalograms .


A Wilcoxon signed rank test demonstrated that the extent of canine movement in the mesio-distal direction after 3 months was significantly greater on the experimental side than on the control side ( 5.4 and 3.4 mm , respectively , P = .002 ) .


However , there was no statistically significant difference in canine angulation or rotation after 3 months between the experimental and control sides .


In combination with the use of conventional orthodontic appliances , interseptal bone reduction can enhance the rate of canine movement when interseptal bone is sufficiently reduced in both thickness and depth following surgical criteria .


Patients with left ventricular diastolic dysfunction ( LVDD ) are at increased risk of postoperative adverse events .


The primary aim of this study was to evaluate the safety and feasibility of using echocardiography-guided hemodynamic management ( EGHEM ) during surgery in subjects with LVDD compared to conventional management .


The feasibility of using echocardiography to direct a treatment algorithm and clinical outcomes were compared for safety between groups .


Subjects were screened for LVDD by preoperative transthoracic echocardiography ( TTE ) and randomized to the conventional or EGHEM group .


Subjects in EGHEM received hemodynamic management based on left ventricular filling patterns on transesophageal echocardiography ( TEE ) .


Primary outcomes measured were the feasibility to obtain TEE images and follow a TEE-based treatment algorithm .


Safety outcomes also compared the following clinical differences between groups : length of hospitalization , incidence of atrial fibrillation , congestive heart failure ( CHF ) , myocardial infarction , cerebrovascular accident , transient ischemic attack and renal failure measured 30 days postoperatively .


Population consisted of 28 surgical subjects ( 14 in conventional group and 14 in EGHEM group ) .


Mean subject age was 73.4 6.7 years ( 36 % male ) in conventional group and 65.9 14.4 years ( 36 % male ) in EGHEM group .


Procedures included orthopedic ( conventional = 29 % , EGHEM 36 % ) , general ( conventional = 50 % , EGHEM = 36 % ) , vascular ( conventional = 7 % , EGHEM = 21 % ) , and thoracic ( conventional = 14 % , EGHEM = 7 % ) .


There was no statistically significant difference in adverse clinical events between the 2 groups .


The EGHEM group had less CHF , atrial fibrillation , and shorter length of stay .


Echocardiography-guided hemodynamic management of patients with LVDD during surgery is feasible and may be a safe alternative to conventional management .


To analyze the efficacy and safety of combination of rh-endostatin ( Endostar ) with docetaxel treatment on patients of non-small cell lung cancer ( NSCLC ) who presented PD or intolerable toxicity in/after first-line chemotherapy .


A randomized , double-blind , placebo-controlled and multi-center clinical trial was conducted .


Patients with stage IIIB/IV of NSCLC experienced previous chemotherapy of one-regimen were screened for this trial .


A total of 68 cases were included in this study .


Single docetaxel and that combined with endostar were conducted in two arms .


The response , time to progression ( TTP ) and adverse effects were observed in both arms .


The objective response rate ( ORR ) and clinical benefit rate ( CBR ) were 0 and 62.5 % in the combined arm , along with 0 and 53.3 % in the single docetaxel arm , with a non-significant difference between the two groups ( all P > 0.05 ) , respectively .


The median TTPs in the combined and single docetaxel arms were 2.63 and 2.07 months , respectively ( P = 0.079 ) .


The median TTPs of the participants with progressive disease ( PD ) after first-line chemotherapy were 1.33 and 1.67 months in the combined and single docetaxel arms , respectively ( P = 0.946 ) .


The median TTPs of the participants with intolerant adverse effects in first-line chemotherapy were 4.70 months and 3.17 months in the combined and single docetaxel arms , respectively ( P = 0.070 ) .


The median TTPs of the patients with SD after 2 therapeutic cycles in the combined and single docetaxel arms were 6.23 months and 3.27 months , respectively ( P = 0.040 ) .


The differences between two arms were non-significant in adverse , serious adverse and cardiovascular adverse effects ( all P > 0.05 ) .


Endostar may prolong TTP in patients with advanced NSCLC benefited from docetaxel treatment without increased toxicities .


To assess subjective preference using three nasal hygiene systems : Strimar Original ( ) , Emcur ( ) and Sinus Rinse .


We used a prospective , single-blind , randomised , crossover study to compare three nasal hygiene systems : Strimar Original , Emcur and Sinus Rinse .


Eighteen adult volunteers were recruited and were asked to rate their experience over three days using three well-established nasal hygiene systems .


A standard visual analogue scale was used to assess five criteria : ( 1 ) simplicity of instructions ; ( 2 ) ease of use ; ( 3 ) comfort ; ( 4 ) perceived nasal clearance ( effectiveness ) and ( 5 ) single best overall system .


Strimar Original was found to have the easiest instructions to understand compared to the other two systems .


There was no significant difference between Strimar Original and Sinus Rinse with regards to ease of use but they were both significantly easier to use than Emcur ( p < 0.05 ) .


There was no statistically significant difference between the three systems when comparing the last three criteria .


There was no alteration in preference when the cost of each treatment was disclosed to the subjects , and no significant side effects were reported .


The instructions accompanying Strimar Original appeared to be the easiest to understand , while Strimar Original and Sinus Rinse were easier to use than Emcur .


Metastases-directed therapy ( MDT ) with surgery or stereotactic body radiotherapy ( SBRT ) is emerging as a new treatment option for prostate cancer ( PCa ) patients with a limited number of metastases ( 3 ) at recurrence - so called `` oligometastases '' .


One of the goals of this approach is to delay the start of palliative androgen deprivation therapy ( ADT ) , with its negative impact on quality of life .


However , the lack of a control group , selection bias and the use of adjuvant androgen deprivation therapy prevent strong conclusions from published studies.The aim of this multicenter randomized phase II trial is to assess the impact of MTD on the start of palliative ADT compared to patients undergoing active surveillance .


Patients with an oligometastatic recurrence , diagnosed on choline PET/CT after local treatment with curative intent , will be randomised in a 1:1 ratio between arm A : active surveillance only and arm B : MTD followed by active surveillance .


Patients will be stratified according to the location of metastasis ( node vs. bone metastases ) and PSA doubling time ( 3 vs. > 3 months ) .


Both surgery and SBRT are allowed as MDT .


Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression .


The primary endpoint is ADT-free survival .


ADT will be started in both arms at time of polymetastatic disease ( > 3 metastatic lesions ) , local progression or symptoms .


The secondary endpoints include progression-free survival , quality of life , toxicity and prostate-cancer specific survival .


This is the first randomized phase 2 trial assessing the possibility of deferring palliative ADT with MDT in oligometastatic PCa recurrence .


Clinicaltrials.gov identifier : NCT01558427 .


Sclerostin is secreted by osteocytes .


As a circulating inhibitor of the Wnt-signaling pathway it inhibits bone formation and contributes to the development of osteoporosis .


Sclerostin levels are elevated in patients with chronic kidney disease and end-stage renal disease .


Since data for patients after kidney transplantation are scarce , we have prospectively measured sclerostin levels before and during the first year after renal transplantation and have examined the association of sclerostin with parameters of bone mineral metabolism and with bone mineral density .


Sclerostin levels were measured by ELISA in 42 consecutive renal transplant recipients before and at defined intervals in the first year after transplantation .


Bone mineral density was measured by dual energy X-ray absorptiometry .


Pre-transplant serum sclerostin levels were elevated in all patients ( 61.8 32.3 pmol/l , normal range 20-30 pmol/l ) .


Within 15 days after transplantation and correlating with the improvement of renal function , sclerostin levels dropped to 21.0 14.7 pmol/l and subsequently increased to 23.8 14.9 and 28.0 16.8 pmol/l after 6 and 12 months , respectively ( P < 0.001 ) .


A linear mixed model indicated that pre-transplant sclerostin levels ( P < 0.001 ) and time after transplantation ( P < 0.001 ) were the most important predictors for the rise of post-transplant sclerostin levels .


No correlation was found between post-transplant sclerostin levels and bone mineral density .


The rapid reduction of elevated serum sclerostin levels shortly after kidney transplantation parallels the improvement of renal function , but contrasts with the more delayed improvement of hyperparathyroidism .


The normalization of both hormones could contribute to improved bone health after renal transplantation .


Lung age , a simple concept for patients to grasp , is frequently used as an aid in smoking cessation programs .


Lung age equations should be continuously updated and should be made relevant for target populations .


We observed how new lung age equations developed for Australian populations performed when utilizing the Burden of Obstructive Lung Disease ( BOLD ) - Australia dataset compared to more commonly used equations .


Data from a cross-sectional population study of noninstitutionalized Australians aged 40 years with analysis restricted to Caucasians < 75 years .


Lung age calculated using equations developed by Newbury et al. and Morris and Temple was compared with chronological age by smoking status and within smoking status .


There were 2,793 participants with a mean age of 57 ( 10 SD ) years .


More than half ( 52 % ) ever smoked , and 10.4 % were current smokers .


Prevalence of chronic obstructive pulmonary disease stage I or higher was 13.4 % ( 95 % confidence interval = 12.2 , 14.7 ) .


For both genders , newer Newbury equations estimated lung ages significantly higher than actual age across all smoking groups ( p < .05 ) .


Morris and Temple equations resulted in lung age estimates significantly lower than chronological age for nonsmokers ( p < .05 ) but no difference among current smokers .


Both equations showed exposure to smoking had lung ages higher than never-smokers ( p < .001 ) .


Lung age also increased with increased pack-years .


This supports the use of updated equations suited to the population of interest .


The Australian Newbury equations performed well in the BOLD-Australia dataset , providing more meaningful lung age profile compared to chronological age among smokers .


Using equations not developed or ideally suited for our population is likely to produce misleading results .


There is significant morbidity and mortality caused by the complications of osteoporosis , for which ageing is the greatest epidemiological risk factor .


Preventive medications to delay osteoporosis are available , but little is known about motivators to adhere to these in the context of a symptomless condition with evidence based on screening results .


To describe key perceptions that influence older women 's adherence and persistence with prescribed medication when identified to be at a higher than average risk of fracture .


A longitudinal qualitative study embedded within a multi-centre trial exploring the effectiveness of screening for prevention of fractures .


Primary care , Norfolk .


United Kingdom .


Thirty older women aged 70-85 years of age who were offered preventive medication for osteoporosis and agreed to undertake two interviews at 6 and 24 months post-first prescription .


There were no overall predictors of adherence which varied markedly over time .


Participants ' perceptions and motivations to persist with medication were influenced by six core themes : understanding adherence and non-adherence , motivations and self-care , appraising and prioritising risk , anticipating and managing side effects , problems of understanding , and decision making around medication .


Those engaged with supportive professionals could better tolerate and overcome barriers such as side-effects .


Many issues are raised following screening in a cohort of women who have not previously sought advice about their bone health .


Adherence to preventive medication for osteoporosis is complex and multifaceted .


Individual participant understanding , choice , risk and perceived need all interact to produce unpredictable patterns of usage and acceptability .


There are clear implications for practice and health professionals should not assume adherence in any older women prescribed medication for the prevention of osteoporosis .


The beliefs and motivations of participants and their healthcare providers regarding the need to establish acceptable medication regimes is key to promoting and sustaining adherence .


To evaluate the efficacy of Oraqix during scaling and root planing ( SRP ) in comparison with 20 % benzocaine and placebo .


15 patients requiring 4 sessions of SRP were enrolled .


For each patient , Oraqix , Hurricaine , vaseline or no anesthetic product were randomly assigned each to a quadrant .


Treatment pain was evaluated on a 100 mm Visual Analog Scale ( VAS ) and on a Verbal Rating Scale ( VRS ) .


The amount of product administered , the need to re-anesthetise , patient and operator satisfaction and the onset of side-effects were also recorded .


Oraqix was significantly better than nothing , with a reduction of VAS score to 13.3 units , but without significant differences with Vaseline or Hurricaine .


Oraqix was better in VRS reduction than not using any anesthetic ( p = 0.001 ) or using vaseline ( p = 0.024 ) , but similar to Hurricaine ( p = 0.232 ) .


Oraqix effectively controls pain in SRP procedures , with few side-effects and a good acceptance on the part of patients and clinicians .


Superficial fungal skin infections are treated using topical antifungals .


The aim of this study was to demonstrate the efficacy of a single application of 1 % terbinafine film-forming solution ( FFS ) versus placebo for the treatment of tinea pedis in the Chinese population .


Six centers in China randomized 290 patients in a 1:1 ratio to receive either 1 % terbinafine FFS or FFS vehicle ( placebo ) once on the affected foot/feet .


Efficacy assessments included microscopy and mycologic culture , and assessing clinical signs and symptoms at baseline , and at weeks 1 and 6 after the topical treatment .


All adverse events were recorded .


At week 6 , 1 % terbinafine FFS was superior to placebo for effective treatment rate ( 63 vs. 8 % ) ; clinical cure ( 30 vs. 6 % ) ; mycological cure ( 86 vs. 12 % ) ; negative microscopy ( 90 vs. 24 % ) ; and negative mycological culture ( 90 vs. 27 % ) : all p 0.001 and clinically relevant .


At week 6 , 1 % terbinafine FFS was clinically superior to placebo for the absence of : erythema ( 69 vs. 29 % ) ; desquamation ( 33 vs. 8 % ) ; and pruritus ( 70 vs. 30 % ) : all p 0.001 and clinically relevant .


At week 6 , differences in the average total signs and symptoms scores were significantly lower for 1 % terbinafine FFS versus placebo ( p 0.001 ) .


Both 1 % terbinafine FFS and placebo were safe and well tolerated based on adverse events and investigator and patient assessments .


This double-blind , randomized , multicenter study demonstrated one single topical application of 1 % terbinafine FFS was safe and effective in the treatment of tinea pedis in the Chinese population .


Postoperative nausea and vomiting ( PONV ) is common ; ondansetron is often used as prophylaxis or for breakthrough episodes .


Vestipitant is a neurokinin 1 ( NK-1 ) receptor antagonist that is effective for prophylaxis , but its efficacy for treating established PONV is unknown .


This study was performed to evaluate the efficacy and safety of vestipitant , compared with ondansetron for the treatment of breakthrough PONV in patients who had already received prophylactic ondansetron before surgery .


A multicentre , randomized , single-blind ( sponsor-open ) , parallel group study .


Of 527 surgical patients , 130 ( 25 % ) had breakthrough PONV and were equally randomized to one of six i.v. doses of vestipitant ( 4-36 mg ) or ondansetron 4 mg .


The primary endpoint was the rate of patients exhibiting complete response , defined as no emesis and no further rescue medication from 10 min after infusion up to 24 h after surgery or hospital discharge .


All doses of vestipitant were non-inferior to ondansetron in treating PONV after failed prophylaxis with ondansetron .


However , vestipitant was superior to ondansetron in decreasing episodes of postoperative emesis and retching .


The complete response rate analysis using Bayesian model averaging indicated that no vestipitant dose was superior to ondansetron .


Nausea numerical rating scale scores and the times-to-PONV or discharge were similar between the vestipitant and ondansetron treatment groups .


Although overall efficacy was non-inferior between vestipitant and ondansetron , the rate of emesis was lower with vestipitant .


These data suggest that vestipitant may be a useful agent for the management of PONV , similar to other NK-1 antagonists .


NCT01507194 .


To evaluate the impact of manual vibrocompression and nasotracheal suctioning on heart ( hr ) and respiratory ( rr ) rates , peripheral oxygen saturation ( SpO ( 2 ) ) , pain and respiratory distress in infants in the postoperative period of a cardiac surgery .


Randomized controlled trial , in which the assessments were performed by the same physiotherapist in two moments : before and after the procedure .


The infants were randomly divided into two groups : Intervention ( IG ) , with manual chest vibrocompression , nasotracheal suctioning and resting ; and Control CG ) , with 30 minutes of rest .


Cardiorespiratory data ( SpO ( 2 ) ; hr ; rr ) were monitored and the following scales were used : Neonatal Infant Pain Scale ( NIPS ) , for pain evaluation , and Bulletin of Silverman-Andersen ( BSA ) , for respiratory distress assessment .


The data were verified by analysis of variance ( ANOVA ) for repeated measures , being significant p < 0.05 .


20 infants with heart disease , ten in each group ( seven acyanotic and three cyanotic ) were enrolled , with ages ranging from zero to 12 months .


In the analysis of the interaction between group and time , there was a significant difference in the variation of SpO ( 2 ) ( p = 0.016 ) , without changes in the other variables .


Considering the main effect on time , only rr showed a significant difference ( p = 0.001 ) .


As for the group main effect , there were no statistical differences ( SpO ( 2 ) - p = 0.77 , hr - p = 0.14 , rr - p = 0.17 , NIPS - p = 0.49 and BSA - p = 0.51 ) .


The manual vibrocompression and the nasotracheal suctioning applied to infants in postoperative of cardiac surgery did not altered SpO ( 2 ) and rr , and did not trigger pain and respiratory distress .


In a subset of patients with asthma , standard-of-care treatment does not achieve disease control , highlighting the need for novel therapeutic approaches .


Lebrikizumab is a humanised , monoclonal antibody that binds to and blocks interleukin-13 activity .


LUTE and VERSE were replicate , randomised , double-blind , placebo-controlled studies , evaluating multiple doses of lebrikizumab in patients with uncontrolled asthma despite the use of medium-to-high-dose inhaled corticosteroid and a second controller .


Patients received lebrikizumab 37.5 , 125 , 250mg or placebo subcutaneously every fourweeks .


The primary endpoint was the rate of asthma exacerbations during the placebo-controlled period .


Analyses were performed on prespecified subgroups based on baseline serum periostin levels .


Following the discovery of a host-cell impurity in the study drug material , protocols were amended to convert from phase III to phase IIb .


Subsequently , dosing of study medication was discontinued early as a precautionary measure .


The data collected for analysis were from a placebo-controlled period of variable duration and pooled across both studies .


The median duration of treatment was approximately 24weeks .


Treatment with lebrikizumab reduced the rate of asthma exacerbations , which was more pronounced in the periostin-high patients ( all doses : 60 % reduction ) than in the periostin-low patients ( all doses : 5 % reduction ) ; no dose-response was evident .


Lung function also improved following lebrikizumab treatment , with greatest increase in FEV1 in periostin-high patients ( all doses : 9.1 % placebo-adjusted improvement ) compared with periostin-low patients ( all doses : 2.6 % placebo-adjusted improvement ) .


Lebrikizumab was well tolerated and no clinically important safety signals were observed .


These data are consistent with , and extend , previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and lung function in patients with moderate-to-severe asthma who remain uncontrolled despite current standard-of-care treatment .


The LUTE study was registered under NCT01545440 and the VERSE study under NCT01545453 at http://www.clinicaltrials.gov .


This study aimed to test whether a very early nutrition intervention delivered over the telephone was feasible and could improve outcomes amongst patients with upper gastrointestinal cancer .


Participants with a histologically proven new diagnosis of primary oesophageal or stomach cancer and who were to undergo surgery and/or chemotherapy were randomised to receive either standard nutrition care ( SC ) or early and intensive nutrition intervention ( NI ) over the telephone/face-to-face .


Participants were followed for 6 months .


The primary outcome was quality of life ( QoL ) , assessed using the European Organization for Research and Treatment of Cancer Global Quality of Life questionnaire C30 ( EORTC QLQ-C30 ) and the European Quality of Life Instrument ( EQ-5D ) tool ; secondary outcomes were nutritional status and survival .


Twenty-one participants were recruited ( 11 SC and 10 NI ) .


At baseline , the prevalence of malnutrition was 90 % .


Compared with SC , the NI group had a significantly higher EORTC global QoL score at the first mid-study follow-up ( coefficient ( 95 % CI ) 21.0 ( 12.1 , 29.9 ) adjusted for baseline , p < 0.001 ) and at 26 weeks ( 28.4 ( 21.3 , 35.4 ) adjusted for baseline , p < 0.001 ) .


Nutritional risk score was lower ( p < 0.001 ) , and loss of body weight attenuated ( p < 0.001 ) in the NI group compared with SC .


Six deaths occurred during the study , five in the SC group and one in the NI group ( p = 0.06 ) .


The mean time spent with a dietitian per contact was significantly less for the NI group compared with SC ( 16 ( 3 ) vs 40 ( 6 ) min per dietetic contact , p < 0.001 ) .


This pilot study has shown the potential of a novel telephone-based early and intensive dietetic model of care for newly diagnosed upper gastrointestinal cancer patients .


We investigated the potential benefits of early tracheotomy performed before day eight of mechanical ventilation ( MV ) compared with late tracheotomy ( from day 14 if it still indicated ) in reducing mortality , days of MV , days of sedation and ICU length of stay ( LOS ) .


Randomized controlled trial ( RCT ) including all-consecutive ICU admitted patients requiring seven or more days of MV .


Between days five to seven of MV , before randomization , the attending physician ( AP ) was consulted about the expected duration of MV and acceptance of tracheotomy according to randomization .


Only accepted patients received tracheotomy as result of randomization .


An intention to treat analysis was performed including patients accepted for the AP and those rejected without exclusion criteria .


A total of 489 patients were included in the RCT .


Of 245 patients randomized to the early group , the procedure was performed for 167 patients ( 68.2 % ) whereas in the 244 patients randomized to the late group was performed for 135 patients ( 55.3 % ) ( P < 0.004 ) .


Mortality at day 90 was similar in both groups ( 25.7 % versus 29.9 % ) , but duration of sedation was shorter in the early tracheotomy group median 11 days ( range 2 to 92 ) days compared to 14 days ( range 0 to 79 ) in the late group ( P < 0.02 ) .


The AP accepted the protocol of randomization in 205 cases ( 42 % ) , 101 were included in early group and 104 in the late group .


In these subgroup of patients ( per-protocol analysis ) no differences existed in mortality at day 90 between the two groups , but the early group had more ventilator-free days , less duration of sedation and less LOS , than the late group .


This study shows that early tracheotomy reduces the days of sedation in patients undergoing MV , but was underpowered to prove any other benefit .


In those patients selected by their attending physicians as potential candidates for a tracheotomy , an early procedure can lessen the days of MV , the days of sedation and LOS .


However , the imprecision of physicians to select patients who will require prolonged MV challenges the potential benefits of early tracheotomy .


Controlled-Trials .


com ISRCTN22208087 .


Registered 27 March 2014 .


Fear of Falling ( FoF ) is commonly reported among older adults ( up to 50 % ) and can impact negatively on physical and social activities , mood and quality of life .


This paper explores the development , acceptability and feasibility of a cognitive behavioural therapy intervention ( CBTi ) for FoF .


The process evaluation of the CBTi development phase of an RCT ( conducted in the UK ) reported here , used ethnographic methods .


Data included : interviews with patients and carers ( n = 16 ) , clinic staff ( n = 6 ) and the psychologists developing the CBTi ( n = 3 ) ; observational field notes and transcripts of intervention development meetings ( n = 9 ) and stakeholder engagement meetings ( n = 2 ) ; and informal discussions with staff developing the CBTi ( n = 8 ) .


Data collection and thematic analysis were guided by Normalisation Process Theory ( NPT ) .


The process evaluation showed two domains of work necessary to develop a CBTi that made sense to stakeholders , and that could be delivered as part of an RCT .


For the psychologists developing the content of the CBTi , a growing understanding of the complexity of FoF highlighted the need for an individualised rather than a manualised intervention .


For the research team , the work involved adapting the structures and processes of the RCT to address preliminary concerns over the acceptability and feasibility of the proposed CBTi .


Theory-based approaches to process evaluation can sensitise researchers to contested understandings about proposed interventions that could undermine implementation .


Drawing on the coherence construct of NPT , this study emphasises the nature and extent of work required to ensure an intervention makes sufficient sense to key stakeholders in order to maximise chances of successful implementation .


To determine whether a novel guarded 33-gauge injection device can make the intravitreal injection procedure faster and more comfortable for patients .


Single-center , prospective , randomized interventional study .


Seventy participants receiving bilateral injections on the same day had one eye injected with the 33-gauge injection device without a speculum and the other eye injected with a standard 30-gauge needle using a speculum .


Length of time needed for the injection procedure was assessed , and subjects were asked to complete a questionnaire regarding their comfort level with each device during the injection procedure as well as immediately after , later that evening , and the next day .


Intravitreal injections using the 33-gauge injection device were significantly faster , but there was no significant difference in the incidence or levels of pain between the two needle types .


The 33-gauge injection device may offer advantages over a standard 30-gauge needle when performing an intravitreal injection .


Human motivation and decision-making is influenced by the interaction of Pavlovian and instrumental systems .


The neurotransmitters dopamine and serotonin have been suggested to play a major role in motivation and decision-making , but how they affect this interaction in humans is largely unknown .


We investigated the effect of these neurotransmitters in a general Pavlovian-to-instrumental transfer ( PIT ) task which measured the nonspecific effect of appetitive and aversive Pavlovian cues on instrumental responses .


For that purpose , we used selective dietary depletion of the amino acid precursors of serotonin and dopamine : tryptophan ( n = 34 ) and tyrosine/phenylalanine ( n = 35 ) , respectively , and compared the performance of these groups to a control group ( n = 34 ) receiving a nondepleted ( balanced ) amino acid drink .


We found that PIT differed between groups : Relative to the control group that exhibited only appetitive PIT , we found reduced appetitive PIT in the tyrosine/phenylalanine-depleted group and enhanced aversive PIT in the tryptophan-depleted group .


These results demonstrate a differential involvement of serotonin and dopamine in motivated behavior .


They suggest that reductions in serotonin enhance the motivational influence of aversive stimuli on instrumental behavior and do not affect the influence of appetitive stimuli , while reductions in dopamine diminish the influence of appetitive stimuli .


No conclusions could be drawn about how dopamine affects the influence of aversive stimuli .


The interplay of both neurotransmitter systems allows for flexible and adaptive responses depending on the behavioral context .


Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways .


While traditional formulations of inhaled steroids settle predominantly in the large airways , newer formulations with an extra-fine particle size have a more peripheral pattern of deposition .


Specifically treating distal airway inflammation may improve asthma control .


30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia .


Following 2weeks of prednisolone 30mg , patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320g twice daily or placebo in addition to usual maintenance therapy for 8weeks .


The primary outcome measure was sputum eosinophil count at week 8 .


Alveolar nitric oxide was measured as a marker of distal airway inflammation .


There was continued suppression of differential sputum eosinophil counts with ciclesonide ( median 2.3 % ) but not placebo ( median 4.5 % ) though the between-group difference was not significant .


When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant ( 1.4 % vs 4.5 % , p = 0.028 ) .


Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance .


These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory , and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid .


Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate , with additional tests of small airway function .


NCT01171365 .


Protocol available at http://www.clinicaltrials.gov .


Plasma adiponectin levels are reduced in type 2 diabetes mellitus ( T2DM ) and other insulin-resistant states .


We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance ( IGT ) subjects were associated with improved insulin sensitivity ( SI ) and glucose tolerance status .


A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years .


Pioglitazone reduced IGT conversion to diabetes by 72 % in association with improved - cell function by 64 % ( insulin secretion/insulin resistance index ) and increased tissue sensitivity by 88 % ( Matsuda index ) .


In pioglitazone-treated subjects , plasma adiponectin concentration increased threefold from 13 0.5 to 38 2.5 g/mL ( P < 0.001 ) and was strongly correlated with the improvement in SI ( r = 0.436 , P < 0.001 ) and modestly correlated with glucose area under the curve during oral glucose tolerance test ( r = 0.238 , P < 0.005 ) and insulin secretion/insulin resistance index ( r = 0.306 , P < 0.005 ) .


The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM .


In the placebo group , plasma adiponectin did not change and was not correlated with changes in glucose levels .


There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group .


Baseline adiponectin does not predict the response to pioglitazone .


The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin .


Although CRC is the third most commonly diagnosed cancer in the United States , second-line CRC treatment is limited .


In this trial we examined the efficacy and safety of linifanib , an oral , potent , selective tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor families , with mFOLFOX6 , compared with bevacizumab and mFOLFOX6 , in previously treated metastatic CRC .


One hundred forty-eight patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab ( 10 mg/kg , intravenous ) , low-dose linifanib ( 7.5 mg ) , or high-dose linifanib ( 12.5 mg ) , with mFOLFOX6 .


The primary end point was progression-free survival ( PFS ) .


Secondary objectives included overall survival ( OS ) , objective response rate ( ORR ) , and safety .


No statistically significant differences in PFS occurred between bevacizumab and linifanib doses ( low , hazard ratio [ HR ] , 1.453 [ 95 % confidence interval [ CI ] , 0.830-2 .539 ] ; high , HR , 1.257 [ 95 % CI , 0.672-2 .351 ] ) .


Median OS values were similar for bevacizumab and high-dose linifanib ( bevacizumab , 16.5 months [ 95 % CI , 13.0-not available ] ; high-dose linifanib , 16.4 months [ 95 % CI , 11.9-21 .7 ] ; low-dose linifanib , 12.0 months [ 95 % CI , 10.1-13 .0 ] ) .


ORRs were similar ( bevacizumab , 34.7 % [ 95 % CI , 21.7-49 .6 ] ; low-dose linifanib , 24.0 % [ 95 % CI , 13.1-38 .2 ] ; high-dose linifanib , 22.4 % [ 95 % CI , 11.8-36 .6 ] ) .


Median cycles of 5-fluorouracil were reduced in the linifanib arms , versus the bevacizumab arm .


Grade 3/4 adverse event occurrences were more frequent with linifanib .


Palmar-plantar erythrodysesthesia , hypothyroidism , and thrombocytopenia were more common with high-dose linifanib than bevacizumab .


Combining linifanib with mFOLFOX6 as a second-line treatment for metastatic CRC did not improve PFS , radiographic findings , or duration of response versus bevacizumab and mFOLFOX6 .


Adolescent substance use and delinquency are major public health problems .


Although community-based prevention strategies have been recommended to produce population-level reductions in rates of substance use and delinquency , few models show evidence of effectiveness .


To test the efficacy of a community-based prevention system , Communities That Care ( CTC ) , in reducing community rates of problem behaviors , particularly effects on specific profiles of adolescent substance use and delinquency in eighth - and tenth-graders .


Twenty-four communities were randomized to CTC intervention or control groups .


Data were collected from 14,099 8th - and 10th-grade students in these communities using anonymous cross-sectional surveys in 2004 and 2010 and analyzed in 2012 .


Outcomes were four different profiles of self-reported substance use and delinquency in 8th grade and five profiles in 10th grade .


In the cross-sectional 2010 data , there was no intervention effect on the probability of experimenting with substances or of substance use coupled with delinquent activities for either grade .


However , tenth-graders in intervention communities were significantly less likely to be alcohol users than those in control communities ( OR = 0.69 , CI = 0.48 , 1.00 ) .


Cross-sectional population surveys showed evidence of CTC effects in reducing tenth-grade alcohol users but not experimenters .


A community-wide reduction in adolescent alcohol use is important because alcohol is the most commonly used illicit substance during adolescence , and early initiation of alcohol use has been associated with alcohol-related disorders in adulthood .


Failure to find hypothesized effects on experimenters qualifies these results .


Perineural dexamethasone prolongs the duration of single-injection peripheral nerve block when added to the local anesthetic solution .


Postulated systemic mechanisms of action along with theoretical safety concerns have prompted the investigation of intravenous dexamethasone as an alternative , with decidedly mixed results .


We aimed to confirm that addition of intravenous dexamethasone will prolong the duration of analgesia after single-injection supraclavicular block compared with conventional long-acting local anesthetic alone or in combination with perineural dexamethasone for ambulatory upper extremity surgery .


Seventy-five patients were randomized to receive supraclavicular block using 30-mL bupivacaine 0.5 % alone ( Control ) , with concomitant intravenous dexamethasone 8 mg ( DexIV ) , or with perineural dexamethasone 8 mg ( DexP ) .


Duration of analgesia was designated as the primary outcome .


To test our hypothesis , the superiority of DexIV was first compared with Control and then with DexP .


Motor block duration , pain scores , opioid consumption , opioid-related side effects , patient satisfaction , and block-related complications were also analyzed .


Twenty-five patients per group were analyzed .


The duration of analgesia ( mean [ 95 % confidence interval ] ) was prolonged in the DexIV group ( 25 hours [ 17.632.4 ] ) compared with Control ( 13.2 hours [ 11.515.0 ] ; P < 0.001 ) but similar to the DexP group ( 25 hours [ 19.530.5 ] ; P = 1 ) .


[ corrected ] Both DexIV and DexP had reduced pain scores , reduced postoperative opioid consumption , and improved satisfaction compared with Control .


In a single-injection supraclavicular block with long-acting local anesthetic , the effectiveness of intravenous dexamethasone in prolonging the duration of analgesia seems similar to perineural dexamethasone .


This prospective , multicenter , randomized clinical trial was performed to compare the effectiveness of the bioprosthesis Surgisis Gold ( Cook Biotech , Inc , West Lafayette , IN ) to suture closure alone in reinforcing the abdominal wall after open Roux-en-Y gastric bypass ( RYGB ) .


A total of 402 adult patients ( body mass index 35kg/m ( 2 ) ) scheduled to undergo open RYGB procedures were randomized to receive either Surgisis Gold placed as a sublay directly under and opposed to the posterior rectus fascia without intervening preperitoneal fat or suture closure alone .


Peri - and postoperative complications were tracked .


Incisional hernia formation in each group was examined at 6weeks , 3 , 6 , and 9months , and 1 and 2years after RYGB .


A total of 380 ( 78 male ; 302 female ) patients with a mean age of 45years ( range 18-69 ) and a mean BMI of 48 ( range 35-79 ) underwent RYGB .


There were no differences in patient demographics or comorbidities between groups .


Placement of the Surgisis Gold increased operating time by an average of 14minutes .


Complications were more common in the Surgisis Gold group with significantly more wound events and seroma formation compared with the suture closure alone group .


At final follow-up , 32 of 185 ( 17 % ) of patients in the reinforced arm and 38 of 195 ( 20 % ) in the suture alone arm developed an incisional hernia ( P = .6 ) .


In this challenging patient population , the use of Surgisis Gold for reinforcing the abdominal wall after open RYGB was not shown to be greatly different from a primary suture repair .


Weight loss induced only by exercise is frequently less than expected , possibly because of compensatory changes in energy intake and/or energy expenditure .


The purpose of the Examination of Mechanisms ( E-MECHANIC ) of Exercise-Induced Weight Compensation trial is to examine whether increased energy intake and/or reduced spontaneous activity or energy expenditure ( outside of structured exercise ) account for the less than expected , exercise-associated weight loss .


E-MECHANIC is a three-arm , 6-month randomized ( 1:1:1 ) controlled trial .


The two intervention arms are exercise doses that reflect current recommendations for ( 1 ) general health ( 8 kcal/kg body weight per week ( 8 KKW ) , about 900 kcal/wk ) and ( 2 ) weight loss ( 20 KKW , about 2,250 kcal/wk ) .


The third arm , a nonexercise control group , will receive health information only .


The sample will include a combined total of 198sedentary , overweight or obese ( body mass index : 25 kg/m to 45 kg/m ) men and women ages 18 to 65 years .


The exercise dose will be supervised and tightly controlled in an exercise training laboratory .


The primary outcome variables are energy intake , which will be measured using doubly labeled water ( adjusted for change in energy stores ) and laboratory-based food intake tests , and the discrepancy between expected weight loss and observed weight loss .


Secondary outcomes include changes in resting metabolic rate ( adjusted for change in body mass ) , activity levels ( excluding structured exercise ) and body composition .


In an effort to guide the development of future interventions , the participants will be behaviorally phenotyped and defined as those who do compensate ( that is , fail to lose the amount of weight expected ) or do not compensate ( that is , lose the amount of weight expected or more ) .


In this study , we will attempt to identify underlying mechanisms to explain why exercise elicits less weight loss than expected .


This information will guide the development of interventions to increase exercise-induced weight loss and maximize weight loss retention and related health benefits .


ClinicalTrials.gov ID : NCT01264406 ( registration date : 20 December 2010 ) .


We aimed to evaluate whether atrial electromechanical delay ( AEMD ) measured by tissue Doppler imaging ( TDI ) , which is an indicator for structural and electrical remodelling of the atria , is prolonged in patients with active or inactive acromegaly , or both , compared with a control group .


A total of 34 patients with acromegaly ( 18 active/16 inactive ) and 35 patients as a control group were enrolled .


Both intra - and inter-AEMD were calculated by TDI .


The correlation between clinical variables and AEMD were analyzed .


Both inter-AEMD and right and left intra-AEMD were prolonged in patients with acromegaly compared with the control group ( P < 0.001 , P < 0.001 , and P = 0.004 , respectively ) .


Also , patients with active acromegaly showed higher inter-AEMD and right intra-AEMD compared with patients with inactive acromegaly ( P < 0.05 ) .


There was no significant difference in left intra-AEMD between patients with active acromegaly and those with inactive acromegaly ( P = 0.977 ) .


The growth hormone and insulin-like growth factor ( IGF-1 ) levels positively correlated with inter-AEMD ( r = 0.577 ; P < 0.001 ; r = 0.614 ; P < 0.001 , respectively ) .


Additionally , we found that inter-AEMD was significantly and positively correlated with relationship between maximal values of passive mitral inflow ( E , PW-Doppler ) and lateral early diastolic mitral annular velocities ( e ' , TDI ) ( r = 0.316 ; P = 0.008 ) .


Only the serum IGF-1 level was independently associated with inter-AEMD in multivariate linear regression analysis ( = 0.500 ; P = 0.011 ) .


Our study findings showed that both inter - and intra-AEMD are prolonged in patients with acromegaly .


Also , AEMD was observed to be more prolonged in patients with active acromegaly than in those with inactive acromegaly .


IGF-1 was an independent predictor of inter - AEMD in patients with acromegaly .


Being a noninvasive , inexpensive , and simple technique , AEMD may be used as an indicator for atrial electrical and structural remodelling in patients with acromegaly .


Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes .


3-arm double-blind randomized trial .


Participants assigned in a 2:2:3 ratio to 17 estradiol 0.5 mg/day ( n = 97 ) , venlafaxine XR 75 mg/day ( n = 96 ) , or placebo ( n = 146 ) for 8 weeks .


Academic research centers .


339 community-dwelling perimenopausal and postmenopausal women with 2 bothersome hot flashes per day .


Insomnia symptoms ( Insomnia Severity Index [ ISI ] ) and sleep quality ( Pittsburgh Sleep Quality Index [ PSQI ] ) at baseline , week 4 and 8 ; 325 women ( 96 % ) provided ISI data and 312 women ( 92 % ) provided PSQI data at baseline and follow-up .


At baseline , mean ( SD ) hot flash frequency was 8.1 / day ( 5.3 ) , mean ISI was 11.1 ( 6.0 ) , and mean PSQI was 7.5 ( 3.4 ) .


Mean ( 95 % CI ) change from baseline in ISI at week 8 was -4.1 points ( -5.3 to -3.0 ) with estradiol , -5.0 points ( -6.1 to -3.9 ) with venlafaxine , and -3.0 points ( -3.8 to -2.3 ) with placebo ( P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine ) .


Mean ( 95 % CI ) change from baseline in PSQI at week 8 was -2.2 points ( -2.8 to -1.6 ) with estradiol , -2.3 points ( -2.9 to -1.6 ) with venlafaxine , and -1.2 points ( -1.7 to -0.8 ) with placebo ( P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine ) .


Among perimenopausal and postmenopausal women with hot flashes , both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality .


NCT01418209 at www.clinicaltrials.gov .


To compare the vaginal cytology of ovulating and non-ovulating queens .


The study group comprised 15 queens showing behavioural oestrus .


Ovulation was induced in 7 ( dioestrus group ) and 8 were left untreated ( postoestrus group ) .


Vaginal smears were collected from all animals prior to ovariohysterectomy on day 7 .


Epithelial cells were classified as basal-parabasal , intermediate , superficial , or anucleated superficial cells and counted using computer-assisted image analysis .


From each smear , 50 representative vaginal epithelial cells were chosen .


Digital images of cells were taken and cell area , cytoplasm area , nucleus area , cell diameter , cell perimeter , nucleus/cytoplasm ratio and red-green-blue ( RGB ) values were measured using image analysis software .


Measurement data were compared between groups .


Ovulation induction was successful in all animals .


The swabbing procedure in oestrus did not induce ovulation in any postoestrus queens .


Mean duration of oestrus was 6.65 0.44 and 4.71 0.32 days ( P > 0.05 ) in the postoestrus and dioestrus queens , respectively .


Intermediate cell count averaged 21.43 % in dioestrus cats and 10.76 % in postoestrus cats ( P < 0.05 ) .


Epithelial cells in the postoestrus group had higher cell area , cytoplasm area , cell diameter and cell perimeter measurements ( P < 0.01 ) .


Red ( 90.9 1.6 ) , green ( 76.1 1.3 ) and blue ( 83.6 1.4 ) channel values in postoestrus were higher than the values ( 81.3 0.8 , 65.8 0.9 and 74.0 0.7 , respectively ) in dioestrus ( P < 0.01 ) .


Induction of ovulation in oestrus queens results in a significant increase in the number of intermediate cells and a significant decrease in both the dimensions and RGB values of vaginal epithelial cells on day 7 .


Varenicline carries a black box warning for neuropsychiatric adverse events .


We examined varenicline use and past history of major depressive disorder ( MDD ) on depressive symptoms during smoking cessation .


This is a secondary analysis of two smoking cessation studies in 152 postmenopausal women who received placebo or nicotine patch , or 78 women who received varenicline with relaxation .


Lifetime history of MDD ( LH-MDD ) was assessed at baseline and women with current MDD were excluded .


Center for Epidemiologic Study Depression scale ( CESD ) measured depressive symptoms at baseline , 6 and 12 weeks .


Baseline CESD scores were 5.3 +4.4 .


Those with a LH-MDD reported higher CESD scores ( p > .001 ) .


Those taking varenicline reported lower scores over all time periods compared to nicotine or placebo ( p < .01 ) .


The differences between varenicline and the other treatments remained when controlling for LH-MDD , indicating an independent effect .


CESD scores were associated with concurrent smoking status ( p < .001 ) , and with withdrawal symptoms ( p < .001 ) .


CESD score were lower in those receiving varenicline , whether this is due to an anti-depressant effect , subject selection , use of relaxation or another cause is unknown .


Varenicline does not increase depressive symptoms during smoking cessation in postmenopausal women without current MDD .


Subjects with a LH-MDD are susceptible to developing depressive symptoms during smoking cessation , regardless of pharmacologic aid .


Pharmacologic aids did not increase depression symptoms in this select population of postmenopausal women without current depression .


Smoking cessation does increase depressive symptoms in those with LH-MDD , though the degree of increase was not clinically meaningful .


Previous research suggests that testosterone ( T ) plays a key role in shaping competitive and aggressive behavior in humans , possibly by modulating threat-related neural circuitry .


However , this research has been limited by the use of T augmentation that fails to account for baseline differences and has been conducted exclusively in women .


Thus , the extent to which normal physiologic concentrations of T affect threat-related brain function in men remains unknown .


In the current study , we use a novel two-step pharmacologic challenge protocol to overcome these limitations and to evaluate causal modulation of threat - and aggression-related neural circuits by T in healthy young men ( n = 16 ) .


First , we controlled for baseline differences in T through administration of a gonadotropin releasing hormone antagonist .


Once a common baseline was established across participants , we then administered T to within the normal physiologic range .


During this second step of the protocol we acquired functional neuroimaging data to examine the impact of T augmentation on neural circuitry supporting threat and aggression .


Gonadotropin releasing hormone antagonism successfully reduced circulating concentrations of T and brought subjects to a common baseline .


Administration of T rapidly increased circulating T concentrations and was associated with heightened reactivity of the amygdala , hypothalamus , and periaqueductal grey to angry facial expressions .


These findings provide novel causal evidence that T rapidly potentiates the response of neural circuits mediating threat processing and aggressive behavior in men .


Survivors of ischemic stroke/transient ischemic attack ( TIA ) are at high risk for other vascular events .


We evaluated the impact of 2 types of case management ( hard touch with pharmacist or soft touch with nurse ) added to usual care on global vascular risk .


This is a prespecified secondary analysis of a 6-month trial conducted in outpatients with recent stroke/TIA who received usual care and were randomized to additional monthly visits with either nurse case managers ( who counseled patients , monitored risk factors , and communicated results to primary care physicians ) or pharmacist case managers ( who were also able to independently prescribe according to treatment algorithms ) .


The Framingham Risk Score [ FRS ] ) and the Cardiovascular Disease Life Expectancy Model ( CDLEM ) were used to estimate 10-year risk of any vascular event at baseline , 6 months ( trial conclusion ) , and 12 months ( 6 months after last trial visit ) .


Mean age of the 275 evaluable patients was 67.6 years .


Both study arms were well balanced at baseline and exhibited reductions in absolute global vascular risk estimates at 6 months : median 4.8 % ( Interquartile range ( IQR ) 0.3 % -11.3 % ) for the pharmacist arm versus 5.1 % ( IQR 1.9 % -12.5 % ) for the nurse arm on the FRS ( P = .44 between arms ) and median 10.0 % ( 0.1 % -31.6 % ) versus 12.5 % ( 2.1 % -30.5 % ) on the CDLEM ( P = .37 ) .


These reductions persisted at 12 months : median 6.4 % ( 1.2 % -11.6 % ) versus 5.5 % ( 2.0 % -12.0 % ) for the FRS ( P = .83 ) and median 8.4 % ( 0.1 % -28.3 % ) versus 13.1 % ( 1.6 % -31.6 % ) on the CDLEM ( P = .20 ) .


Case management by nonphysician providers is associated with improved global vascular risk in patients with recent stroke/TIA .


Reductions achieved during the active phase of the trial persisted after trial conclusion .


The aim of this study was to compare the effects of ethyl chloride and placebo sprays for reducing pain induced by needle electromyography and changes in parameters of the motor unit action potential during needle electromyography of the upper extremity .


Sixty patients were randomized into the ethyl chloride or placebo spray groups .


In both groups , spray was applied just before needle electromyography of the flexor carpi radialis , and a visual analog scale to evaluate the pain of needle electromyography and a five-point Likert scale for patient satisfaction and preference for reexamination were compared between the two groups .


Then , changes in the amplitude , phases , turns , and duration of the motor unit action potential during needle electromyography of the biceps brachii were compared before and after spraying in each group .


The visual analog scale was significantly lower , and patient satisfaction and preference for reexamination were significantly higher in the ethyl chloride spray group .


Among the parameters of the motor unit action potential , there were no significant changes except for an increased duration after spraying with ethyl chloride .


Ethyl chloride spray can effectively reduce pain , but it must be used with caution because it may affect parameters of the motor unit action potential during needle electromyography .


L-Menthol stimulates cutaneous thermoreceptors and induces cool sensations improving thermal comfort but has also been linked to heat storage responses .


Therefore , L-Menthol application could lead to a conflict in behavioural and thermoregulatory drivers improving comfort but leading to a higher rate of deep body temperature rise ; the present study examined this possibility .


Six untrained male participants ( age 21 [ 1 ] years ; height 1.80 [ 0.07 ] m ; mass 78.9 [ 6.9 ] kg ; surface area 1.98 [ 0.13 ] m2 ) took part .


They completed three trials in hot conditions ( 34 C ) where their clothing was sprayed ( CONTROL-SPRAY or MENTHOL-SPRAY ) or not sprayed ( CONTROL ) after a fixed intensity exercise period ( 15-minutes ) , which induced thermal discomfort , before completing a 5 km treadmill time trial ( TT ) .


Thermal perception ( thermal sensation and comfort ; TS , TC ) , thermal responses ( aural temperature [ Tau ] , skin temperature [ Tskin ] ) , perceived exertion ( RPE ) , heart rate , pacing ( 1 km split time ) and performance ( TT completion time ) were measured .


MENTHOL-SPRAY induced improvements in TS ( up to 3 km of TT ) and TC ( up to 1 km ) with Tau showing a tendency to be higher than CONTROL-SPRAY ( +0.20 [ 0.29 ] C ) and CONTROL condition ( 0.30 [ 0.34 ] C ) ; this was not statistically significant and the rate of rise in Tau was linear .


Tau was continuing to rise between the 4th and 5th kilometre of the TT .


The other variables were unchanged .


TT completion time and pace were not different : CONTROL 27.92 [ 1.65 ] , CONTROL-SPRAY 28.10 [ 1.12 ] , MENTHOL-SPRAY 27.53 [ 2.85 ] minutes .


Spraying L-MENTHOL prior to exercise in the heat culminated in improved perception but not altered performance .


Emergence of artemisinin resistance has raised concerns that the most potent anti-malarial drug may be under threat .


Artesunate-amodiaquine ( AS-AQ ) and artemether-lumefantrine ( AL ) are , respectively , the first - and second-line treatments for uncomplicated falciparum malaria in Cte d'Ivoire .


Constant monitoring by National Malaria Control Programme ( NMCP ) of drug efficacy is an important tool in establishing rational anti-malarial drug policies in Cte d'Ivoire .


In an open label , randomized controlled clinical trial , children and adults were randomized to receive AS-AQ or AL. .


Both drug regimens were given for three days , and follow-up was for 42 days .


The primary endpoint was the 42-day cure rate and was defined as proportion of patients with PCR-corrected cure rate after 42 days of follow-up .


A total of 383 patients who were attending the Anonkoua-koute ( Abidjan ) , Petit Paris ( Korhogo ) and Libreville ( Man ) hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive AS-AQ ( 188 ) and AL ( 195 ) .


The intention-to-treat analysis showed effectiveness rates of 94.7 % and 96.4 % for AS-AQ and AL , respectively on day 42 .


After adjustment for PCR , these rates were 96.8 % and 99 % , respectively .


At day 42 , in per-protocol analysis , Adequate clinical and parasitological response ( ACPR ) PCR uncorrected was 97.8 % and 97.4 % for AS-AQ and AL , respectively .


The PCR adjusted ACPR was 100 % for each combination and both regimens were well tolerated .


This study has shown the high efficacy of AS-AQ in patients of all ages with acute uncomplicated falciparum malaria and AS-AQ was non-inferior to AL. .


Continuous efficacy monitoring is recommended .


Hypertension management strategies have traditionally focused on `` tailored therapy '' and `` stepped-care '' approaches .


These tend to be costly and time consuming and often fail to achieve adequate blood pressure ( BP ) control .


The TRIUMPH study aims to investigate the effectiveness , cost-effectiveness , and acceptability of early use of a 3-in-1 BP-lowering pill ( `` Triple Pill '' ) compared with usual care for the management of hypertension .


The prospective , open , randomized controlled clinical trial ( n = 700 ) will compare Triple Pill-based strategy to usual care among individuals with persistent mild-to-moderate hypertension ( systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg , or systolic BP > 130 mm Hg and/or diastolic BP > 80 mm Hg in patients with diabetes or chronic kidney disease ) on no or minimal drug therapy .


The study will be conducted within approximately 20 hospital-based clinics in India .


Participants will be randomized to the Triple Pill ( initially strength 1-telmisartan 20 mg , amlodipine 2.5 mg , hydrochlorothiazide 6.25 mg , with the option of subsequent titration to strength 2-telmisartan 40 mg , amlodipine 5 mg , hydrochlorothiazide 12.5 mg ) or continued usual care .


Participants will be followed up for 6 months .


The primary outcome is the proportion of participants achieving target BP at the end follow-up .


This study will determine whether early use of a low-dose triple combination therapy has the potential to address some of the challenges in hypertension control through earlier achievement of BP control , better adherence , and fewer adverse effects , in the context of less intensive clinical follow-up .


The study aim was , for the first time , to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy ( IgAN ) .