Growth performance did not differ between groups before weaning , but SF-pCD pigs had higher ADG after weaning .


In response to Mhyo stimulation , numbers of IFN secreting PBMC and levels of interleukin 8 ( IL8 ) and IL10 in PBMC supernatants were significantly higher in SF-pCD pigs , as were Mhyo antibody levels in sera , and levels of IL1 , IL8 and IL12 in supernatants of PMA/Iono stimulated PBMC .


Under the conditions of this experiment , SF-pCD pigs demonstrated superior growth performance and enhanced humoral and cell-mediated immunity following vaccination .


Whether or not this reflects greater resistance or tolerance to infection is unknown but the ability to react positively to the vaccination provides evidence that SF-pCD pigs are a suitable alternative model for swine disease research .


Physical exercise is associated with enhanced production of reactive oxygen species , which if uncontrolled can result in tissue injury .


Phosphodiesterase type 5 inhibitors ( PDE5i ) exhibit protective effect against oxidative stress , both in animals and healthy/unhealthy humans .


However , the effect of a chronic administration of PDE5i , particularly combined with physical exercise , has never been investigated .


The present study was designed to evaluate the effect of the long-acting PDE5i tadalafil on oxidative status and muscle damage after exhaustive exercise in healthy males included in a double-blind crossover trial .


Tadalafil , having a putative antioxidant activity , may reduce oxidative damage after strenuous exercise .


Each volunteer randomly received two tablets of placebo or tadalafil ( 20 mg/day ) with 36 h of interval before performing exhaustive exercise .


After 2 weeks of washout , the volunteers were crossed over .


Blood samples were collected immediately before exercise , immediately after , and during recovery ( 15 , 30 , 60 min ) .


Plasma total antioxidant status , glutathione homeostasis ( GSH/GSSG ) , malondialdehyde ( MDA ) , protein carbonyls , creatine kinase ( CK ) , lactate dehydrogenase ( LDH ) and the inflammatory cytokine interleukin 6 were assessed .


Tadalafil administration per se affected redox homeostasis ( GSH/GSSG -36 % ; p < 0.05 ) , cellular ( CK +75 % and LDH +36 % ; p < 0.05 ) and oxidative damage ( MDA +41 % and protein carbonyls +50 % ; p < 0.05 ) markers .


The exhaustive exercise increased all the above-reported biochemical parameters , with subjects from the tadalafil group showing significantly higher values with respect to the placebo group .


A prolonged exposure to tadalafil decreases antioxidant capacity at resting condition , therefore making subjects more susceptible to the oxidative stress induced by an exhaustive bout of exercise .


To compare the clinical efficacy difference between electroacupuncture ( EA ) at qijie area combined with spine balance-regulating massage and medication for posterior circulation ischemia ( PCI ) .


One hundred cases of PCI were randomly divided into a treatment group ( 50 cases ) and a medication group ( 50 cases ) .


The treatment group was treated with EA at Baihui ( GV 20 ) , Sishencong ( EX-HN 1 ) , Fengchi ( GB 20 ) , Shenshu ( BL 23 ) , Danzhong ( CV 17 ) , etc. in qijie area combined with spine muscle-relieving massage and comprehensive chiropractic .


The medication group was treated with oral administration of nimodipine ( 30 mg per time , three treatments per day ) and vinpocetine injection with 500 mL of glucose injection or intravenous drip of 500 mL 0.9 % sodium chloride injection , once a day .


Ten treatments were taken as one course in both groups , and two courses were given .


The symptom score , mean resistance index ( RI ) of vertebral artery ( VA ) and basilar artery ( BA ) , mean velocity of blood flow ( Vm ) and comprehensive clinical efficacy were compared before and after treatment in two groups .


The cured and markedly effective rate was 79.6 % ( 39/49 ) in the treatment group , which was superior to 54.7 % ( 23/42 ) in the medication group ( P < 0.05 ) .


The symptom score was both significantly improved after treatment in two groups ( both P < 0.05 ) , which was more obvious in the treatment group ( P < 0.05 ) .


The RI of VA and BA , Vm of VA and BA were significantly improved after treatment in two groups ( all P < 0.05 ) , which were more obvious in the treatment group ( all P < 0.05 ) .


The electroacupuncture combined with spine balance-regulating massage has superior effect on improving mean velocity of blood flow and resistance index of vertebral artery and basilar artery as well as symptom score to medication , and is believed to be a safe and effective treatment for posterior circulation ischemia .


To determine the safety and effectiveness of intralesional tetracycline 2 % injection for the treatment of lower eyelid festoons .


The authors retrospectively reviewed the charts of all patients undergoing tetracycline 2 % injection of lower eyelid festoons at the Cole Eye Institute from August 2008 to August 2013 .


Charts were reviewed for patient demographic data , dose and number of tetracycline injections , follow-up interval , the presence of preinjection and postinjection photographs , and complications .


Charts without preinjection and postinjection photographs were excluded from review .


The preinjection and postinjection photographs were randomized , masked , and graded by 4 independent examiners .


Photographs were graded on a scale of 0 ( no festoon ) to 4 ( severe festoon ) .


Student t test was used for statistical analysis .


Eleven patients met inclusion criteria .


Each patient underwent bilateral injection .


Average follow up was 121 days ( range , 18-586 days ) .


Patients received up to 0.75 ml ( mean , 0.24 ml ) of tetracycline 2 % per side .


Average preinjection grade was 2.1 ( standard deviation , 0.89 ; range , 0-3 ) , and average postinjection grade was 1.2 ( standard deviation , 0.72 ; range , 0-2 ; p < 0.001 ) .


Three patients had follow up less than 60 days ( mean , 34 days ) , with an average preinjection grade of 1.96 and postinjection grade of 1.23 ( p < 0.001 ) .


Five patients had follow up between 60 and 100 days ( mean , 82 days ) , with an average preinjection grade of 2.18 and postinjection grade of 1.38 ( p < 0.001 ) .


Three patients had follow up longer than 100 days ( mean , 275 days ) , with an average preinjection grade of 2.08 and postinjection grade of 0.78 ( p < 0.001 ) .


Complications other than pain and bruising were not identified in any patient .


Intralesional tetracycline 2 % injection may offer a safe option to treat lower eyelid festoons .


Complications such as cutaneous ischemia or necrosis were not identified in any patient .


Further study may determine optimal treatment doses and intervals and detect infrequent but significant complications .


The Quality and Outcomes Framework in the United Kingdom ( UK ) National Health Service previously highlighted case finding of depression amongst patients with diabetes or coronary heart disease .


However , depression in older people remains under-recognized .


Comprehensive data for analyses of the association of depression in older age with other health and functional measures , and demographic factors from community populations within England , are lacking .


Secondary analyses of cross-sectional baseline survey data from the England arm of a randomised controlled trial of health risk appraisal for older people in Europe ; PRO-AGE study .


Data from 1085 community-dwelling non-disabled people aged 65 years or more from three group practices in suburban London contributed to this study .


Depressed mood was ascertained from the 5-item Mental Health Inventory Screening test .


Exploratory multivariable logistic regression was used to identify the strongest associations of depressed mood with a previous diagnosis of a specified physical/mental health condition , health and functional measures , and demographic factors .


Depressed mood occurred in 14 % ( 155/1085 ) of participants .


A previous diagnoses of depression ( OR 3.39 ; P < 0.001 ) and poor vision as determined from a Visual Function Questionnaire ( OR 2.37 ; P = 0.001 ) were amongst the strongest factors associated with depressed mood that were independent of functional impairment , other co-morbidities , and demographic factors .


A subgroup analyses on those without a previous diagnosis of depression also indicated that within this group , poor vision ( OR 2.51 ; P = 0.002 ) was amongst the strongest independent factors associated with depressed mood .


Previous case-finding strategies in primary care focussed on heart disease and diabetes but health-related conditions other than coronary heart disease and diabetes are also associated with an increased risk for depression .


Complex issues of multi-morbidity occur within aging populations .


` Risk ' factors that appeared stronger than those , such as , diabetes and coronary heart disease that until recently prompted for screening in the UK due to the QOF , were identified , and independent of other morbidities associated with depressed mood .


From the health and functional factors investigated , amongst the strongest factors associated with depressed mood was poor vision .


Consideration to case finding for depressed mood among older people with visual impairment might be justified .


To examine the association between preoperative quality of life ( QoL ) and postoperative adverse events in women treated for endometrial cancer .


760 women with apparent Stage I endometrial cancer were randomised into a clinical trial evaluating laparoscopic versus open surgery .


This analysis includes women with preoperative QoL measurements , from the Functional Assessment of Cancer Therapy-General ( FACT-G ) questionnaire , and who were followed up for at least 6 weeks after surgery ( n = 684 ) .


The outcomes for this study were defined as ( 1 ) the occurrence of moderate to severe adverse events within 6 months ( Common Toxicology Criteria ( CTC ) grade3 ) ; and ( 2 ) any serious adverse event ( SAE ) .


The association between preoperative QoL and the occurrence of AE was examined , after controlling for baseline comorbidity and other factors .


After adjusting for other factors , odds of occurrence of AE of CTC grade3 were significantly increased with each unit decrease in baseline FACT-G score ( OR = 1.02 , 95 % CI 1.00-1 .03 , p = 0.030 ) , which was driven by physical well-being ( PWB ) ( OR = 1.09 , 95 % CI 1.04-1 .13 , p = 0.0002 ) and functional well-being subscales ( FWB ) ( OR = 1.04 , 95 % CI 1.00-1 .07 , p = 0.035 ) .


Similarly , odds of SAE occurrence were significantly increased with each unit decrease in baseline FACT-G score ( OR = 1.02 , 95 % CI 1.01-1 .04 , p = 0.011 ) , baseline PWB ( OR = 1.11 , 95 % CI 1.06-1 .16 , p < 0.0001 ) or baseline FWB subscales ( OR = 1.05 , 95 % CI 1.01-1 .10 , p = 0.0077 ) .


Women with early endometrial cancer presenting with lower QoL prior to surgery are at higher risk of developing a serious adverse event following surgery .


Cancer Council Queensland , Cancer Council New South Wales , Cancer Council Victoria , Cancer Council , Western Australia ; NHMRC project grant 456110 ; Cancer Australia project grant 631523 ; The Women and Infants Research Foundation , Western Australia ; Royal Brisbane and Women 's Hospital Foundation ; Wesley Research Institute ; Gallipoli Research Foundation ; Gynetech ; TYCO Healthcare , Australia ; Johnson and Johnson Medical , Australia ; Hunter New England Centre for Gynaecological Cancer ; Genesis Oncology Trust ; and Smart Health Research Grant QLD Health .


Since there is a lack of current evidence to support the compatibility of the most commonly used arterial blood gas syringes with the latest multi-parameter analyzers , the objective of this study was to assess the agreement of analyte values between three heparinized arterial blood gas syringes using three different analyzers .


Venous blood from 25 healthy volunteers was drawn into the study syringes ( BD Drihep A-Line , PICO50 , and Portex Line Draw Plus ) by four clinician volunteers in a random order ( 441 total ) and immediately ( < 15 minutes ) analyzed ( ABL800 FLEX , RAPIDPoint 500 , i-STAT System ) in a randomized order .


The Bland-Altman method was used to assess agreement of analyte values between the syringes for each analyzer .


The results by analyte and analyzer were compared across syringes using one-way ANOVA , and Tukey 's approach was used to identify statistically significant differences between pairs of syringes .


Comparison of the syringes ' mean differences and standard deviations showed close agreement for all three analyzers .


There were no statistically significant differences between syringes in 14 of the analytes for any of the analyzers ( p > 0.05 ) .


For RAPIDPoint and i-STAT , the Ca ( 2 + ) value was significantly less for A-Line than for the other syringes .


The value for Na ( + ) was significantly greater for the PICO50 than the A-Line and Line Draw syringes with the i-STAT .


Both results were within two standard deviations of the mean of the other two syringes and are not considered clinically significant ; however , comparisons were not made between the values from the different analyzers .


Dry-balanced lithium heparin ABG syringes used for blood draws should provide reliable results , regardless of syringe type , provided that the clinicians use proper pre-analytical techniques .


Pancreaticoduodenectomy ( PD ) is associated with a high incidence of postoperative complications including pancreatic fistula .


This randomized clinical trial compared the incidence of pancreatic fistula between the isolated Roux-en-Y ( IsoRY ) and conventional reconstruction ( CR ) methods .


Patients admitted for PD between June 2009 and September 2012 in a single centre were assigned randomly to CR or IsoRY .


The primary endpoint was the incidence of pancreatic fistula ( grade A-C ) defined according to the International Study Group on Pancreatic Fistula .


Secondary endpoints were complication rates , mortality and hospital stay .


Multiple logistic regression analysis was performed to identify factors associated with pancreatic fistula .


Some 153 patients were randomized , 76 to CR and 77 to IsoRY ; two patients from the IsoRY group were excluded after randomization .


Pancreatic fistula occurred in 26 patients ( 34 per cent ) in the CR group and 25 ( 33 per cent ) in the IsoRY group ( P = 0909 ) .


The number of patients with a clinically relevant pancreatic fistula ( grade B or C ) was similar in the two groups ( 10 and 11 patients respectively ; P = 0789 ) , as were complication rates ( 42 versus 40 per cent ; P = 0793 ) and mortality ( none in either group ; P = 0999 ) .


Soft pancreas was the only independent risk factor for pancreatic fistula ( odds ratio 442 , 95 per cent confidence interval 185 to 1053 ; P < 0001 ) .


This study showed that IsoRY reconstruction does not reduce the incidence of pancreatic fistula compared with CR .


NCT00915863 ( http://www.clinicaltrials.gov/ ) and UMIN000001967 ( http://www.umin.ac.jp/ ) .


Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function .


We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease .


In this randomised , double-blind , placebo-controlled trial , boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy , myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally , every other day for the first month and once daily thereafter , in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors ( ACEI ) or angiotensin receptor blockers ( ARB ) .


Computer-generated randomisation was done centrally using block sizes of four and six , and only the study statistician and the investigational pharmacy had the preset randomisation assignments .


The primary outcome was change in left ventricular circumferential strain ( Ecc ) at 12 months , a measure of contractile dysfunction .


Safety was established through serial serum potassium levels and measurement of cystatin C , a non-creatinine measure of kidney function .


This trial is registered with ClinicalTrials.gov , number NCT01521546 .


Between Jan 26 , 2012 , and July 3 , 2013 , 188 boys were screened and 42 were enrolled .


20 were randomly assigned to receive eplerenone and 22 to receive placebo , of whom 20 in the eplerenone group and 20 in the placebo group completed baseline , 6-month , and 12-month visits .


After 12 months , decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo ( median Ecc 10 [ IQR 03-22 ] vs 22 [ 13-31 ] ; p = 0020 ) .


Cystatin C concentrations remained normal in both groups , and all non-haemolysed blood samples showed normal potassium concentrations .


One 23-year-old patient in the placebo group died of fat embolism , and another patient in the placebo group withdrew from the trial to address long-standing digestive issues .


All other adverse events were mild : short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone , flushing occurred in one patient given placebo , and anxiety occurred in another patient given placebo .


In boys with Duchenne muscular dystrophy and preserved ejection fraction , addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function .


Early use of available drugs warrants consideration in this population at high risk of cardiac death , but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy .


BallouSkies , Parent Project for Muscular Dystrophy , US National Center for Advancing Translational Sciences , and US National Institutes of Health .


To monitor corneal epithelial healing under bandage contact lens ( BCL ) using ultrahigh-resolution optical coherence tomography ( UHR-OCT ) after pterygium surgery .


Thirty-nine eyes of 39 patients undergoing pterygium excision and conjunctival autografting were randomly allocated into 2 groups : 20 eyes were covered with silicone hydrogel BCLs at the end of surgery and 19 eyes served as a control .


Ultrahigh-resolution optical coherence tomography scans of the cornea were performed sequentially at 1 , 2 , and 3 days , and then every other day until the end of re-epithelialization after surgery .


Complete epithelial healing was verified with fluorescein staining examination after removal of BCLs .


Postsurgery pain was evaluated using the visual analog scale .


All BCLs were successfully fit without any contact lens-related complications .


Ultrahigh-resolution optical coherence images clearly revealed the architectural features of postoperative cornea with BCL in situ and showed epithelial healing process .


Ultrahigh-resolution optical coherence tomography imaging agreed with the fluorescein staining examinations in detecting corneal epithelial defect .


Based on the assessment by UHR-OCT , the average time course of re-epithelialization in the BCL group was 3.91.2 days , whereas in the control group , it was 5.71.8 days ( P = 0.001 ) .


Visual analog scale scoring showed lower pain levels in the BCL group comparing with the control group at each point of time ( all P < 0.05 ) .


Ultrahigh-resolution optical coherence tomography is an excellent tool in monitoring corneal epithelial healing under BCLs and determining the appropriate time for lens removal .


Silicone hydrogel BCL is recommended as an adjuvant therapy after pterygium surgery for its efficacy in improving re-epithelialization and postoperative comfort .


The Zwolle Risk Score ( ZRS ) identifies ST-elevation myocardial infarction ( STEMI ) patients treated with primary percutaneous coronary intervention ( PPCI ) eligible for early discharge .


We aimed to investigate whether baseline N-terminal pro-brain natriuretic peptide ( NT-proBNP ) is also able to identify these patients and could improve future risk strategies .


PPCI patients included in the Ongoing Tirofiban in Myocardial Infarction Evaluation ( On-TIME ) II study were candidates ( N = 861 ) .


We analyzed whether ZRS and baseline NT-proBNP predicted 30-day mortality and assessed the occurrence of major adverse cardiac events ( MACEs ) and major bleeding .


Receiver operating characteristic curve analysis was used to assess discriminative accuracy for ZRS , NT-pro-BNP , and their combination .


After multiple imputation , 845 patients were included .


Both ZRS > 3 ( hazard ratio [ HR ] = 9.42 ; P < 0.001 ) and log NT-pro-BNP ( HR = 2.61 ; P < 0.001 ) values were associated with 30-day mortality .


On multivariate analysis , both the ZRS ( HR = 1.41 ; 95 % confidence interval [ CI ] = 1.27 to 1.56 ; P < 0.001 ) and log NT-proBNP ( HR = 2.09 ; 95 % CI = 1.59 to 2.74 ; P < 0.001 ) independently predicted death at 30 days .


The area under the curve for 30-day mortality for combined ZRS/NT-proBNP was 0.94 ( 95 % CI = 0.90 to 0.99 ) , with optimal predictive values of a ZRS 2 and a NT-proBNP value of 200 pg/mL .


Using these cut-off values , 64 % of the study population could be identified as very low risk with zero mortality at 30 days follow-up and low occurrence of MACEs and major bleeding between 48 hours and 10 days ( 1.3 % and 0.6 % , respectively ) .


Baseline NT-proBNP identifies a large group of low-risk patients who may be eligible for early ( 48 - to 72-hour ) discharge , whereas optimal predictive accuracy is reached by the combination of both baseline NT-proBNP and ZRS .


Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm .


To evaluate the clinical effectiveness of a perioperative , cardiac output-guided hemodynamic therapy algorithm .


OPTIMISE was a pragmatic , multicenter , randomized , observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom .


An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014 .


Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope ( dopexamine ) infusion during and 6 hours following surgery ( n = 368 ) or to usual care ( n = 366 ) .


The primary outcome was a composite of predefined 30-day moderate or major complications and mortality .


Secondary outcomes were morbidity on day 7 ; infection , critical care-free days , and all-cause mortality at 30 days ; all-cause mortality at 180 days ; and length of hospital stay .


Baseline patient characteristics , clinical care , and volumes of intravenous fluid were similar between groups .


Care was nonadherent to the allocated treatment for less than 10 % of patients in each group .


The primary outcome occurred in 36.6 % of intervention and 43.4 % of usual care participants ( relative risk [ RR ] , 0.84 [ 95 % CI , 0.71-1 .01 ] ; absolute risk reduction , 6.8 % [ 95 % CI , -0.3 % to 13.9 % ] ; P = .07 ) .


There was no significant difference between groups for any secondary outcomes .


Five intervention patients ( 1.4 % ) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group .


Findings of the meta-analysis of 38 trials , including data from this study , suggest that the intervention is associated with fewer complications ( intervention , 488/1548 [ 31.5 % ] vs control , 614/1476 [ 41.6 % ] ; RR , 0.77 [ 95 % CI , 0.71-0 .83 ] ) and a nonsignificant reduction in hospital , 28-day , or 30-day mortality ( intervention , 159/3215 deaths [ 4.9 % ] vs control , 206/3160 deaths [ 6.5 % ] ; RR , 0.82 [ 95 % CI , 0.67-1 .01 ] ) and mortality at longest follow-up ( intervention , 267/3215 deaths [ 8.3 % ] vs control , 327/3160 deaths [ 10.3 % ] ; RR , 0.86 [ 95 % CI , 0.74-1 .00 ] ) .


In a randomized trial of high-risk patients undergoing major gastrointestinal surgery , use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality .


However , inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates .


isrctn.org Identifier : ISRCTN04386758 .


The Nurse-Family Partnership delivered by nurses has been found to produce long-term effects on maternal and child health in replicated randomized trials .


A persistent question is whether paraprofessional home visitors might produce comparable effects .


To examine the impact of prenatal and infancy/toddler home visits by paraprofessionals and by nurses on child development at child ages 6 and 9 years .


Randomized trial in public and private care settings in Denver , Colorado , of 735 low-income women and their first-born children ( 85 % of the mothers were unmarried ; 47 % were Hispanic , 35 % were non-Hispanic white , 15 % were African American , and 3 % were American Indian/Asian ) .


Home visits provided from pregnancy through child age 2 years delivered in one group by paraprofessionals and in the other by nurses .


Reports of children 's internalizing , externalizing , and total emotional/behavioral problems , and tests of children 's language , intelligence , attention , attention dysfunction , visual attention/task switching , working memory , and academic achievement .


We hypothesized that program effects on cognitive-related outcomes would be more pronounced among children born to mothers with low psychological resources .


We report paraprofessional-control and nurse-control differences with P < .10 given similar effects in a previous trial , earlier effects in this trial , and limited statistical power .


There were no significant paraprofessional effects on emotional/behavioral problems , but paraprofessional-visited children born to mothers with low psychological resources compared with control group counterparts exhibited fewer errors in visual attention/task switching at age 9 years ( effect size = -0.30 , P = .08 ) .


There were no statistically significant paraprofessional effects on other primary outcomes .


Nurse-visited children were less likely to be classified as having total emotional/behavioral problems at age 6 years ( relative risk [ RR ] = 0.45 , P = .08 ) , internalizing problems at age 9 years ( RR = 0.44 , P = .08 ) , and dysfunctional attention at age 9 years ( RR = 0.34 , P = .07 ) .


Nurse-visited children born to low-resource mothers compared with control-group counterparts had better receptive language averaged over ages 2 , 4 , and 6 years ( effect size = 0.30 , P = .01 ) and sustained attention averaged over ages 4 , 6 , and 9 years ( effect size = 0.36 , P = .006 ) .


There were no significant nurse effects on externalizing problems , intellectual functioning , and academic achievement .


Children born to low-resource mothers visited by paraprofessionals exhibited improvement in visual attention/task switching .


Nurse-visited children showed improved behavioral functioning , and those born to low-resource mothers benefited in language and attention but did not improve in intellectual functioning and academic achievement .


clinicaltrials.gov Identifier : NCT00438282 and NCT00438594 .


Inhaler mishandling is a common issue among patients suffering from asthma and is associated with poor clinical outcomes and greater consumption of health-care resources .


Ease of use can improve inhaler technique and , possibly , patients ' preference for their inhaler device , which in turn may lead to better adherence to therapy .


This study investigated usability characteristics of NEXThaler ( ) versus two other dry powder inhalers ( DPIs ; Diskus ( ) and Turbuhaler ( ) ) .


Sixty-six adult patients with asthma ( mean age 42.917.7 years ) and with no previous experience of using a DPI were included in a randomized crossover comparison of the three devices .


The main measures of usability were the number of steps failed for each device and the number of people who were able to use the device successfully ( effectiveness ) , the time it took patients to set up the device and the time to read the instructions for use ( IFU ; efficiency ) , and patient preferences ( satisfaction ) .


Inhaler technique was evaluated after the IFU leaflet was read .


NEXThaler was found to be superior to the other two DPIs in terms of the number of device use failures ( p < 0.001 ) , time to set up ( p < 0.001 ) , and time to read IFU ( p < 0.001 ) .


Additionally , the proportion of participants who completed a successful inhalation without any errors at all was significantly higher for NEXThaler than for Diskus and Turbuhaler ( p < 0.001 ) .


Patients rated NEXThaler as the easiest to use and most preferred inhaler to own ( p < 0.001 ) .


NEXThaler displayed better usability compared with Diskus and Turbuhaler .


The improved usability and higher satisfaction with the device may contribute to increased patient adherence to asthma treatment .


Randomized data support shorter radiotherapy courses for management of cancer-related symptoms in the palliative setting .


The purpose of this study was to evaluate the length of palliative radiotherapy before hospice enrollment among the elderly U.S. population , with a further focus on factors that influence the duration of radiation and the length of survival on hospice , including whether the duration of radiation was associated with length of survival on hospice .


A total of 6982 patients with breast , prostate , lung , or colorectal cancer who received a course of radiotherapy within 30days before hospice enrollment were identified within the Surveillance , Epidemiology , and End Results-Medicare linked database .


The primary end points included the duration of palliative radiotherapy and the time from hospice enrollment through death ( hospice duration ) .


Multivariate linear regression and multivariate Cox models evaluated factors associated with the length of radiotherapy course and hospice duration .


The median length of palliative radiotherapy was 14days , and the median hospice duration was 13days .


The course of palliative radiotherapy was longer than hospice duration in 48 % of the patients .


Breast and lung cancer were associated with longer courses of radiotherapy and shorter stays on hospice .


Patients treated in freestanding radiation centers had longer courses of radiotherapy .


For these groups , a longer radiotherapy course was not associated with longer hospice duration .


This study found relatively long courses of radiotherapy before short lengths of survival on hospice .


Future research is needed to identify barriers to shorter radiotherapy courses .


The once-daily oral factor Xa inhibitor , edoxaban , is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate-high stroke risk .


Limited data regarding cerebrovascular events with edoxaban were reported previously .


We analyzed the subtypes of cerebrovascular events in 21 105 patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 ( ENGAGE AF-TIMI 48 ) comparing outcomes among patients randomized to warfarin versus 2 edoxaban regimens ( high dose , low dose ) .


The primary end point for this prespecified analysis of cerebrovascular events was all stroke ( ischemic plus hemorrhagic ) , defined as an abrupt onset of focal neurological deficit because of infarction or bleeding with symptoms lasting 24 hours or fatal in < 24 hours .


Independent stroke neurologists unaware of treatment adjudicated all cerebrovascular events .


Patients randomized to high-dose edoxaban had fewer strokes on-treatment ( hazard ratio , 0.80 ; 95 % confidence interval , 0.65-0 .98 ) than warfarin ( median time-in-therapeutic range , 68.4 % ) ; patients in the low-dose edoxaban group had similar rates ( hazard ratio , 1.10 versus warfarin ; 95 % confidence interval , 0.91-1 .32 ) .


Rates of ischemic stroke or transient ischemic attack were similar with high-dose edoxaban ( 1.76 % per year ) and warfarin ( 1.73 % per year ; P = 0.81 ) , but more frequent with low-dose edoxaban ( 2.48 % per year ; P < 0.001 ) .


Both edoxaban regimens significantly reduced hemorrhagic stroke and other subtypes of intracranial bleeds .


In patients with atrial fibrillation , once-daily edoxaban was as effective as warfarin in preventing all strokes , with significant reductions in various subtypes of intracranial bleeding .


Ischemic cerebrovascular event rates were similar with high-dose edoxaban and warfarin , whereas low-dose edoxaban was less effective than warfarin .


http://www.clinicaltrials.gov .


Unique identifier : NCT00781391 .


The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids , alone or in conjunction with drotrecogin-alfa ( activated ) ( DrotAA ) , on the outcomes in septic shock patients .


We performed a sub-study of the PROWESS-Shock trial ( septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours ) .


A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression .


Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids , alone or in conjunction with DrotAA , on 28-day and 90-day all-cause mortality .


A total of 1695 patients were enrolled of which 49.5 % received intravenous steroids for treatment of septic shock at baseline ( DrotAA + steroids N = 436 ; DrotAA + no steroids N = 414 ; placebo + steroids N = 403 ; placebo + no steroids N = 442 ) .


The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo ( interaction p-value = 0.38 and p = 0.27 , respectively ) nor was a difference detected within each randomized treatment .


Similarly , the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy .


In patients with lung infection ( N = 744 ) , abdominal infection ( N = 510 ) , Gram-positive sepsis ( N = 420 ) and Gram-negative sepsis ( N = 461 ) , the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment .


In the present study of septic shock patients , after adjustment for treatment selection bias , we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo .


Clinicaltrials.gov NCT00604214 .


Registered 24 January 2008 .


Fibrin sealant ( FS ) is a biologically derived tissue adhesive for securing flaps .


The aim of the present randomized controlled clinical trial was to compare early wound healing by assessing interleukin-1 ( IL-1 ) and interleukin-8 ( IL-8 ) levels from gingival crevicular fluid ( GCF ) after using FS and suture for periodontal flap closure .


Thirty selected quadrants in 15 periodontitis patients were randomly assigned to either a test ( fibrining ) or control group ( suturing ) for flap closure .


IL-1 and IL-8 were assessed in GCF using enzyme-linked immunosorbent assay ( ELISA ) before and eight days after surgery .


Patients were recalled at 7 , 14 , 21days and 3months after surgery for clinical assessment .


There was a statistically significant decrease in IL-1 ( 84.8277.18 , 29.221.97 pg/l ) and IL-8 ( 57.9455.47 , 21.8221.93 pg/l ) levels in the test side after fibrining while there was an increase in the control side ( IL-1 31.4016.82 , 128.845.14 ; IL-8 31.4016.82 , 128.8345.14 pg/l ) ( p < 0.05 ) .


The change in concentration of IL-1 and IL-8 following intervention correlated significantly in both the sites .


Clinical parameters differed significantly only on the seventh day with less plaque and bleeding on the test sites .


Fibrin sealant enhances early wound healing by reducing inflammation after periodontal flap surgery .


Continuous lumbar plexus block ( LPB ) is a well-accepted technique for regional analgesia after THA .


However , many patients experience considerable quadriceps motor weakness with this technique , thus impairing their ability to achieve their physical therapy goals .


We asked whether L2 paravertebral block ( PVB ) provides better postoperative analgesia ( defined as decreased postoperative opioid consumption and lower pain scores ) , better preservation of motor function , and decreased length of hospital stay ( LOS ) compared to LPB in patients undergoing THA .


Sixty patients undergoing minimally invasive THA under standardized spinal anesthesia were enrolled in this randomized controlled study .


After exclusions , 53 patients were randomized into the L2 PVB ( n = 27 ) and LPB ( n = 26 ) groups .


Patient-controlled analgesia was available for 24 hours .


Motor and pain assessments were performed in the recovery room and at the end of 24 hours .


LOS was also noted .


Postoperative opioid consumption during the first 24 hours was less in the LPB group ( mean SD : 24 15 mg morphine ) than in the L2 PVB group ( 32 15 mg morphine ; p = 0.005 ) ; however , postoperative pain scores were not different between groups .


Postoperative motor and rehabilitation outcomes and LOS were also similar .


Our study demonstrates that use of a LPB results in slightly less morphine consumption but comparable pain scores when compared with continuous L2 PVB .


No difference was noted in terms of motor preservation or LOS .


Although the difference in morphine consumption was only slightly in favor of the LPB group , the advantage of L2 PVBs noted by previous authors as preservation of motor function , was not seen .


At our institute where LPBs have been performed for years , there seems to be no real advantage in switching to L2 PVBs .


However , L2 PVB could be a reasonable alternative for operators who are wary of LPBs due to their high potential for complications and/or requiring advanced skills for its placement .


But , since L2 PVBs are relatively new , not much is known about their complication profile .


We recommend a thorough understanding of both techniques before attempting to place them .


Level I , therapeutic study .


See Instructions for Authors for a complete description of levels of evidence .


Annually approximately 100.000 patients undergo a laparotomy in the Netherlands .


About 15,000 of these patients will develop an incisional hernia .


Both open and laparoscopic surgical repair have been proven to be safe .


However , the most effective treatment of incisional hernias remains unclear .


This study , the ` INCH-trial ' , comparing cost-effectiveness of open and laparoscopic incisional hernia repair , is therefore needed .


A randomized multi-center clinical trial comparing cost-effectiveness of open and laparoscopic repair of incisional hernias .


Patients with a symptomatic incisional hernia , eligible for laparoscopic and open incisional hernia repair .


Only surgeons , experienced in both open and laparoscopic incisional hernia repair , will participate in the INCH trial .


During incisional hernia repair , a mesh is placed under or on top of the fascia , with a minimal overlap of 5 cm .


Primary endpoint is length of hospital stay after an incisional hernia repair .


Secondary endpoints are time to full recovery within three months after index surgery , post-operative complications , recurrences , mortality and quality of life.Our hypothesis is that laparoscopic incisional hernia repair comes with a significant shorter hospital stay compared to open incisional hernia repair .


A difference of two days is considered significant .


One-hunderd-and-thirty-five patients are enrolled in each treatment arm .


The economic evaluation will be performed from a societal perspective .


Primary outcomes are costs per patient related to time-to-recovery and quality of life.The main goal of the trial is to establish whether laparoscopic incisional hernia repair is superior to conventional open incisional hernia repair in terms of cost-effectiveness .


This is measured through length of hospital stay and quality of life .


Secondary endpoints are re-operation rate due to post-operative complications or recurrences , mortality and quality of life .


The difference in time to full recovery between the two treatment strategies is thought to be in favor of laparoscopic incisional hernia repair .


Laparoscopic incisional hernia repair is therefore expected to be a more cost-effective approach .


Netherlands Trial register : NTR2808 .


Oxygen consumption may be impaired in critically ill patients .


To evaluate the effect of intravenous thiamine on oxygen consumption ( [ Formula : see text ] o2 ) in critically ill patients .


This was a small , exploratory open-label pilot study conducted in the intensive care units at a tertiary care medical center .


Critically ill adults requiring mechanical ventilation were screened for enrollment .


Oxygen consumption ( [ Formula : see text ] o2 ) and cardiac index ( CI ) were recorded continuously for 9 hours .


After 3 hours of baseline data collection , 200 mg of intravenous thiamine was administered .


The outcome was change in [ Formula : see text ] o2 after thiamine administration .


Twenty patients were enrolled and 3 were excluded because of incomplete [ Formula : see text ] o2 data , leaving 17 patients for analysis .


There was a trend toward increase in [ Formula : see text ] o2 after thiamine administration ( 16.3 ml/min , SE 8.5 ; P = 0.052 ) .


After preplanned adjustment for changes in CI in case of a delivery-dependent state in some patients ( with exclusion of one additional patient because of missing CI data ) , this became statistically significant ( 16.9 ml/min , SE 8.6 ; P = 0.047 ) .


In patients with average CI greater than our cohort 's mean value of 3 L/min/m ( 2 ) , [ Formula : see text ] o2 increased by 70.9 ml/min ( 16 ; P < 0.0001 ) after thiamine .


Thiamine had no effect in patients with reduced CI ( < 2.4 L/min/m ( 2 ) ) .


There was no association between initial thiamine level and change in [ Formula : see text ] o2 after thiamine administration .


The administration of a single dose of thiamine was associated with a trend toward increase in [ Formula : see text ] o2 in critically ill patients .


There was a significant increase in [ Formula : see text ] o2 in those patients with preserved or elevated CI .


Further study is needed to better characterize the role of thiamine in oxygen extraction .


Clinical trial registered with www.clinicaltrials.gov ( NCT01462279 ) .


To assess the efficacy of aromatic essential oils on neck pain .


Sixty participants with a history of neck pain and Neck Disability Index ( NDI ) score > 10 % were selected and randomly divided into control and experimental groups .


Motion analysis laboratory at Hungkuang University .


For the experimental group , the intervention included 3 % concentration cream composed of four essential oils : marjoram , black pepper , lavender , and peppermint .


For the control group , only an unscented cream was provided .


For 4 weeks , all patients applied 2g cream directly to the affected area daily after showering or bathing .


Assessment was performed by using a visual analogue scale ( VAS ) , NDI , pressure pain threshold ( PPT ) evaluated with a pressure meter , and neck-joint range evaluated with Motion Analysis System ( MAS ) .


A t-test statistical analysis by SPSS statistical software indicated that VAS scores improved significantly for both groups ( p < 0.05 ) .


In addition , the experimental group had improved pain tolerance in the left upper trapezius ( meanstandard deviation , 2.962.54 ) and right upper trapezius ( 2.882.90 ) as measured by the PPT .


According to the NDI , the experimental group also showed significant improvement ( p = 0.02 ) .


Comparison of MAS values before and after the intervention showed significant improvement in the 10 motion areas in the experimental group .


This finding suggests that the experimental group had better results than the control group .


The essential oil cream developed in this study can be used to improve neck pain .


This study appears to be the first to quantify this by using PPT and MAS .


Few studies have evaluated interventions to improve quality of life ( QOL ) for Latina breast cancer survivors and caregivers .


Following best practices in community-based participatory research ( CBPR ) , we established a multi-level partnership among Latina survivors , caregivers , community-based organizations ( CBOs ) , clinicians , and researchers to evaluate a survivor-caregiver QOL intervention .


A CBO in the mid-Atlantic region , Nueva Vida , developed a patient-caregiver program called Cuidando a mis Cuidadores ( Caring for My Caregivers ) , to improve outcomes important to Latina cancer survivors and their families .


Together with an academic partner , Nueva Vida and three CBOs established a multi-level team of researchers , clinicians , Latina cancer survivors , and caregivers to conduct a national randomized trial to compare the patient-caregiver program to usual care .


Incorporating team feedback and programmatic considerations , we adapted the prior patient-caregiver program into an 8-session patient - and caregiver-centered intervention that includes skill-building workshops such as managing stress , communication , self-care , social well-being , and impact of cancer on sexual intimacy .


We will measure QOL domains with the patient-reported outcomes measurement information system , dyadic communication between the survivor and caregiver , and survivors ' adherence to recommended cancer care .


To integrate the intervention within each CBO , we conducted interactive training on the protection of human subjects , qualitative interviewing , and intervention delivery .


The development and engagement process for our QOL intervention study is innovative because it is both informed by and directly impacts underserved Latina survivors and caregivers .


The CBPR-based process demonstrates successful multi-level patient engagement through collaboration among researchers , clinicians , community partners , survivors , and caregivers .


This study evaluated change in health-related quality of life ( HRQOL ) associated with ongoing weight change among patients with type 2 diabetes mellitus ( T2DM ) treated with dapagliflozin , a highly selective sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor that lowers blood glucose by increasing urinary glucose excretion and is associated with body weight reductions .


Patients with T2DM who had inadequate glycaemic control on metformin ( MET ) alone were enrolled in a 24-week , double-blind , randomized , placebo-controlled study with a 78-week extension to evaluate the effect of dapagliflozin + MET on body weight .


Patients also completed the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes Weight Questionnaire-9 ( SHIELD-WQ-9 ) , a weight change-related HRQOL survey .


Difference in proportions of patients treated with dapagliflozin 10mg + MET ( n = 89 ) or placebo + MET ( n = 91 ) who reported improvement in HRQOL was analysed with Fisher 's exact test .


Dapagliflozin patients had significantly greater weight loss than placebo patients over 102weeks ( p < 0.05 ) .


This corresponded to a numerically greater proportion of dapagliflozin-treated patients reporting ongoing weight loss and associated improvements in most HRQOL domains at three different evaluation points ( weeks 24 , 50 and 102 ) than placebo-treated patients .


In a post-hoc analysis among patients who reported ongoing weight loss regardless of treatment arm , a significantly greater proportion of patients reporting weight loss versus weight gain reported improvements in physical health , self-esteem and overall HRQOL at weeks 24 , 50 and 102 .


Dapagliflozin-induced weight loss was associated with improvement in overall HRQOL .


Overall , ongoing weight loss was associated with improvements in several HRQOL domains compared with weight gain .


Care services for older people are provided with the expectation of supporting carers in their caregiving role .


The aim of the study is to investigate the association between the utilisation of care services by older people and the caregiving experience .


Cross-sectional design , involving a cohort of family carers ( n = 119 ) of frail older people ( 70 years ) enrolled in a clinical trial of frailty treatment in metropolitan Sydney from 2008 to 2011 .


The caregiving experience was measured in five domains : health , daily schedule , finance , family support and self-esteem ( Caregiver Reaction Assessment tool ) .


Multivariate regression analysis demonstrated an association between the utilisation of residential respite care and financial strain ( = -0.613 , P = 0.049 ) , after controlling for functional ability , co-residence and age .


There is a need to consider carers ' financial barriers and concerns in regards to the utilisation of respite care services .


We examine improvement and worsening in quality of life ( QOL ) in terms of proportions achieving minimum clinically important change ( MCID ) , and factors related to MCID , in patients with temporal lobe epilepsy randomized to medical or surgical treatment .


Eighty patients with temporal lobe epilepsy randomized to surgical ( n ( 1 ) = 40 ) or medical ( n ( 2 ) = 40 ) therapy were followed for 12 months , reporting QOL at baseline , and at 6 and 12 months .


Previously established thresholds for MCID across various general and epilepsy-specific QOL instruments were used to determine meaningful improvement ( positive MCID ) or worsening ( negative MCID ) .


Generalized linear mixed-effects models were used to compare MCID in both groups .


At 6 months , 56.0 % of patients in the surgical group achieved positive MCID on the Quality of Life in Epilepsy ( QOLIE ) -89 , as compared to 11.0 % of those in the medical group ( p < 0.001 ) .


On the QOLIE-31 , 62.0 % of the surgical group and 17.0 % of the medical group achieved positive MCID ( p < 0.001 ) .


Substantially more medically treated patients exhibited clinically significant worsening in QOL , as compared with those surgically treated .


The respective medical versus surgical proportions with worsening were 36.67 % versus 13.8 % in QOLIE31 , 20 % versus 15 % in Health Utility Index-III ( HUI-III ) , and 30 % versus 19 % in Short Form-36 ( SF-36 ) Mental Composite Score ( MCS ) .


The number of patients who need to undergo surgery for one additional person to have a meaningful improvement in the QOLIE-31 is two ( number needed to treat = 2 ) .


The results also favored surgery using the generic HUI-III instrument , but not with the mental of physical function subscales of the SF-36 .


Significantly more patients in the surgical group achieved meaningful improvement in epilepsy-specific measures of QOL at 6 and 12 months compared to those in the medical group .


Substantially more patients in the medical therapy group exhibited clinically significant worsening in their QOL assessed with epilepsy-specific and generic instruments .


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


To evaluate feasibility and potential effectiveness of a patient decision aid ( PtDA ) for patients and a preference report for surgeons to reduce wait times and improve decision quality in patients with osteoarthritis considering total knee replacement .


A prospective two-arm pilot randomized controlled trial .


Patients with osteoarthritis were eligible if they understood English and were referred for surgical consultation about an initial total knee arthroplasty at a Canadian orthopaedic joint assessment clinic .


Patients were randomized to the PtDA intervention or usual education .


The intervention was an osteoarthritis PtDA for patients and a one-page preference report summarizing patients ' clinical and decisional data for their surgeon .


The main feasibility outcomes were rates of recruitment and questionnaire completion ; the preliminary effectiveness outcomes were wait times and decision quality .


Of 180 patients eligible for surgical consultation , 142 ( 79 % ) were recruited and randomized to the PtDA intervention ( n = 71 ) or usual education ( n = 71 ) .


Data collection yielded a 93 % questionnaire completion rate with less than 1 % missing items .


After one year , 13 % of patients remained on the surgical wait list .


The median time from referral to being off the wait list ( censored using survival analysis techniques ) was 33.4 weeks for the PtDA group ( n = 69 , 95 % CI : 26.0 , 41.4 ) and 33.0 weeks for usual education ( n = 71 , 95 % CI : 26.1 , 39.9 ) .


Patients exposed to the PtDA had higher decision quality based on knowledge ( 71 % versus 47 % ; p < 0.0001 ) and quality decision being an informed choice that is consistent with their values for option outcomes ( 56.4 % versus 25.0 % ; p < 0.001 ) .


Recruitment of patients with osteoarthritis considering surgery and data collection were feasible .


As some patients remained on the surgical waiting list after one year , follow-up should be extended to two years .


Patients exposed to the PtDA achieved higher decision quality compared to those receiving usual education but there was no difference in wait for surgery .


ClinicalTrials.Gov NCT00743951 .


While surgery and perioperative smoking cessation interventions may motivate patients to quit smoking in the short term , it is unknown how often this translates into permanent cessation .


In this study , we sought to determine the rates of long-term smoking cessation after a perioperative smoking cessation intervention and predictors of successful cessation at 1 year .


We previously reported short-term results from a perioperative randomized controlled trial comparing usual care with an intervention involving ( 1 ) brief counseling by the preadmission nurse , ( 2 ) smoking cessation brochures , ( 3 ) referral to a telephone quitline , and ( 4 ) a free 6-week supply of transdermal nicotine replacement .


We now report our 1-year follow-up outcomes .


Between October 2010 and April 2012 , 168 patients were randomized .


At 1 year , 127 patients ( 76 % ) were available for follow-up telephone interview .


Smoking cessation occurred in 8 % of control patients compared with 25 % of patients in the intervention group ( relative risk , 3.0 ; 95 % confidence interval [ CI ] , 1.2-7 .8 ; P = 0.018 ) .


The number needed-to-treat to achieve smoking cessation for 1 patient at 1 year postoperatively was 5.9 ( 95 % CI , 3.4-25 .9 ) .


Multivariable logistic regression modeling found that the intervention ( P = 0.020 ) and lower nicotine dependency at baseline ( P < 0.001 ) were predictive of success at smoking cessation at 1 year .


Poisson regression showed that adjusted for nicotine dependency , those randomized to the intervention group were 2.7 times ( 95 % CI , 1.1-6 .7 ; P = 0.028 ) more likely to achieve long-term cessation than those in the control group .


Adjusted for randomization group , a low level of nicotine dependency resulted in a relative risk of quitting of 5.1 ( 95 % CI , 2.0-12 .8 ; P = 0.001 ) .


This study demonstrates that an intervention designed for a busy preadmission clinic results in decreased smoking rates not only around the time of surgery but also continued benefit in smoking cessation at 1 year .


Perioperative care providers have a unique opportunity to assist patients in smoking cessation and achieve long-lasting results .


The aim of this study was to investigate whether more sickness absence is reported in countries with higher income inequality than elsewhere , and whether the level of income inequality moderates the association between psycho-social job demands and sickness absence .


Our analysis is based on the Fifth European Working Conditions Survey that compared 23 European countries .


We performed multi-level regression analysis .


On the macro-level of analysis we included the Gini-Index as measure of inequality .


On the micro-level of analysis we followed the Karasek-Theorell model and included three scales for psychological job demands , physical job demands , and decision latitude in the model .


The model was stratified by sex .


We found that , in countries with high income inequality , workers report significantly more sickness absence than workers in countries with low income inequality .


In addition we found that the level of income inequality moderates the relationship between psychological job demands and sickness absence .


High psychological job demands are significantly more strongly related to more days of sickness absence in countries with low income inequality than in countries with high income inequality .


As the nature and causal pathways of cross-level interaction effects still can not be fully explained , we argue that future research should aim to explore such causal pathways .


In accordance with WHO recommendations we argue that inequalities should be reduced .


In addition we state that , particularly in countries with low levels of income inequality , policies should aim to reduce psychological job demands .


This study sought to assess the 2-year outcomes of the population included in the EXAMINATION ( Everolimus-Eluting Stents Versus Bare-Metal Stents in ST-Segment Elevation Myocardial Infarction ) trial beyond the 1-year prescription period of dual antiplatelet therapy .


The EXAMINATION trial compared the performance of everolimus-eluting stents ( EES ) versus bare-metal stents ( BMS ) in an all-comer ST-segment elevation myocardial infarction ( STEMI ) population .


This was a multicenter , multinational , prospective , randomized , single-blind , controlled trial in patients with STEMI .


The primary endpoint , which was the combined endpoint of all-cause death , any recurrent myocardial infarction , and any revascularization , and the endpoints target lesion revascularization and stent thrombosis were assessed at 2 years .


Between December 31 , 2008 , and May 15 , 2010 , 1,498 patients were randomized to receive EES ( n = 751 ) or BMS ( n = 747 ) .


Compliance with dual antiplatelet regimen was reduced at 2 years to a similar degree ( 17.3 % vs. 17.2 % , p = 0.91 ) .


At 2 years , the primary endpoint occurred in 108 ( 14.4 % ) patients of the EES group and in 129 ( 17.3 % ) patients of the BMS group ( p = 0.11 ) .


Rate of target lesion revascularization was significantly lower in the EES group than in the BMS group ( 2.9 % vs. 5.6 % ; p = 0.009 ) .


Rates of definite and definite or probable stent thrombosis were also significantly reduced in the EES group ( 0.8 % vs. 2.1 % ; p = 0.03 , and 1.3 % vs. 2.8 % ; p = 0.04 , respectively ) .


The 2-year follow-up of the EXAMINATION trial confirms the safety and efficacy of the EES compared with BMS in the setting of STEMI .


Specifically , both rates of target lesion revascularization and stent thrombosis were reduced in recipients of EES without any signs of late attrition for either of these endpoints .


( A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction : EXAMINATION Study ; NCT00828087 ) .


The purpose of this study was to evaluate prevalence , progression , treatment , and outcome of silent coronary artery disease ( CAD ) in asymptomatic patients with diabetes ( DM ) at high coronary risk .


Despite the close association of diabetes and CAD , general CAD screening in asymptomatic patients with DM is discouraged even though outcome data in patients at high coronary risk are lacking .


Prospective multicenter outcome study-with a pilot randomized treatment substudy .


The study comprised 400 asymptomatic patients with DM ( type 2 ) without history or symptoms of CAD at high CAD risk .


They underwent clinical evaluation and myocardial perfusion single-photon emission computed tomography ( MPS ) at baseline and after 2 years .


Patients with normal MPS received usual care ; those with abnormal MPS received medical or combined invasive and medical management .


An abnormal MPS was found in 87 of 400 patients ( 22 % ) .


In patients with normal MPS , MACE occurred in 2.9 % and ischemia or new scar in 3.2 % .


Patients with abnormal MPS had more MACE ( 9.8 % ; hazard ratio : 3.44 ; 95 % confidence interval [ CI ] : 1.32 to 8.95 ; p = 0.011 ) and ischemia or new scar ( 34.2 % ; odds ratio : 15.91 ; 95 % CI : 7.24 to 38.03 ; p < 0.001 ) despite therapy , resulting in `` overt or silent CAD progression '' of 35.6 % versus 4.6 % ( odds ratio : 11.53 ; 95 % CI : 5.63 to 24.70 ; p < 0.001 ) .


Patients with abnormal MPS randomized to medical versus invasive-medical strategies had similar event rates ( p = 0.215 ) , but more ischemic or new scar findings ( 54.3 % vs. 15.8 % ; p < 0.001 ) .


High-risk asymptomatic patients with DM and normal MPS ( 78 % ) have a low rate of first manifestations of CAD .


Patients with abnormal MPS at baseline ( 22 % ) have a 7-fold higher rate of progression to `` overt or silent CAD , '' despite therapy .


Randomized patients ' outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone .


( Trial of Invasive versus Medical therapy of Early coronary artery disease in Diabetes Mellitus ISRCTN87953632 ) .


Chronic obstructive pulmonary disease ( COPD ) is associated with eosinophilic airway inflammation in 10-20 % of patients .


Benralizumab , an anti-interleukin-5 receptor monoclonal antibody , depletes blood and sputum eosinophils .


We aimed to establish whether benralizumab reduces acute exacerbations of COPD in patients with eosinophilia and COPD .


We did this randomised , double-blind , placebo-controlled , phase 2a study between Nov 18 , 2010 , and July 13 , 2013 , at 26 sites in the UK , Poland , Germany , Canada , the USA , Denmark , and Spain .


Adults aged 40-85 years , with moderate-to-severe COPD , at least one acute exacerbation of COPD , and a sputum eosinophil count of 30 % or more within the previous year , were randomly assigned ( 1:1 ) via computer-generated permuted block randomisation ( block size of four ) , with an interactive voice or web-response system , to receive placebo or 100 mg benralizumab subcutaneously , every 4 weeks ( three doses ) , then every 8 weeks ( five doses ) over 48 weeks .


Study site personnel included in study assessments , participants , and data analysts , were masked to treatment allocation .


The primary endpoint was the annualised rate of acute exacerbations of COPD at week 56 , defined as the number of acute exacerbations divided by total duration of person-year follow-up .


Secondary and exploratory endpoints included COPD-specific Saint George 's Respiratory Questionnaire ( SGRQ-C ) , Chronic Respiratory Questionnaire self-administered standardised format ( CRQ-SAS ) , pre-bronchodilator forced expiratory volume in 1 second ( FEV1 ) , and safety .


We did a prespecified subgroup analysis by baseline blood eosinophil count .


Analyses were by intention to treat and per-protocol .


This trial is registered with ClinicalTrials.gov , number NCT01227278 .


We randomly assigned 101 patients to receive placebo ( n = 50 ) or benralizumab ( n = 51 ) , of whom 88 ( 87 % ) patients completed the study .


Six patients who completed the study were excluded from the per-protocol population because of major protocol violations ; the per-protocol population thus included 82 patients .


Benralizumab did not reduce the annualised rate of acute exacerbations of COPD compared with placebo in the per-protocol population , with rates of 095 ( 068-129 ; n = 40 ) versus 092 ( 067-125 ; n = 42 ) .


Mean pre-bronchodilator FEV1 change from baseline to week 56 was -006 L ( SD 024 ) with placebo , and 013 L ( 041 ) with benralizumab ( p = 0014 ) .


Numerical , albeit non-significant , improvement in acute exacerbations of COPD , SGRQ-C , CRQ-SAS , and FEV1 were greater in benralizumab-treated patients with baseline blood eosinophil concentrations of 200 cells per L or more or 300 cells per L or more .


Incidence of treatment-emergent adverse events was similar between the two groups , with the most common events being respiratory disorders ( 31 [ 62 % ] of 50 patients given placebo vs 32 [ 63 % ] of 51 given benralizumab ) and infections ( 28 [ 56 % ] vs 27 [ 53 % ] ) .


A higher incidence of serious treatment-emergent adverse events were recorded in patients in the benralizumab group than in those in the placebo group ( 14 vs nine patients ) , although none of these events were considered by the investigator to be benralizumab related .


Compared with placebo , benralizumab did not reduce the rate of acute exacerbations of COPD .


However , the results of prespecified subgroup analysis support further investigation of benralizumab in patients with COPD and eosinophilia .


MedImmune .


Limited data are available from controlled studies on biomarkers of maternal vitamin B-12 status .


We sought to quantify the effects of pregnancy and lactation on the vitamin B-12 status response to a known and highly controlled vitamin B-12 intake .


As part of a 10-12 wk feeding trial , pregnant ( 26-29 wk gestation ; n = 26 ) , lactating ( 5 wk postpartum ; n = 28 ) , and control ( nonpregnant , nonlactating ; n = 21 ) women consumed vitamin B-12 amounts of 8.6 g/d [ mixed diet ( 6 g/d ) plus a prenatal multivitamin supplement ( 2.6 g/d ) ] .


Serum vitamin B-12 , holotranscobalamin ( bioactive form of vitamin B-12 ) , methylmalonic acid ( MMA ) , and homocysteine were measured at baseline and study-end .


All participants achieved adequate vitamin B-12 status in response to the study dose .


Compared with control women , pregnant women had lower serum vitamin B-12 ( -21 % ; P = 0.02 ) at study-end , whereas lactating women had higher ( P = 0.04 ) serum vitamin B-12 throughout the study ( +26 % at study-end ) .


Consumption of the study vitamin B-12 dose increased serum holotranscobalamin in all reproductive groups ( +16 -42 % ; P 0.009 ) .


At study-end , pregnant ( vs. control ) women had a higher holotranscobalamin-to-vitamin B-12 ratio ( P = 0.04 ) with 30 % ( vs. 20 % ) of total vitamin B-12 in the bioactive form .


Serum MMA increased during pregnancy ( +50 % ; P < 0.001 ) but did not differ by reproductive state at study-end .


Serum homocysteine increased in pregnant women ( +15 % ; P = 0.009 ) but decreased in control and lactating women ( -16 -17 % ; P < 0.001 ) .


Despite these changes , pregnant women had 20 % lower serum homocysteine than the other 2 groups at study-end ( P 0.02 ) .


Pregnancy and lactation alter vitamin B-12 status in a manner consistent with enhanced vitamin B-12 supply to the child .


Consumption of the study vitamin B-12 dose ( 3 times the RDA ) increased the bioactive form of vitamin B-12 , suggesting that women in these reproductive states may benefit from vitamin B-12 intakes exceeding current recommendations .


This trial was registered at clinicaltrials.gov as NCT01127022 .


Early mortality for HIV-positive people starting antiretroviral therapy ( ART ) remains high in resource-limited settings , with tuberculosis the most important cause .


Existing rapid diagnostic tests for tuberculosis lack sensitivity among HIV-positive people , and consequently , tuberculosis treatment is either delayed or started empirically ( without bacteriological confirmation ) .


We developed a management algorithm for ambulatory HIV-positive people , based on body mass index and point-of-care tests for haemoglobin and urine lipoarabinomannan ( LAM ) , to identify those at high risk of tuberculosis and mortality .


We designed a clinical trial to test whether implementation of this algorithm reduces six-month mortality among HIV-positive people with advanced immunosuppression .


The TB Fast Track study is an open , pragmatic , cluster randomised superiority trial , with 24 primary health clinics randomised to implement the intervention or standard of care .


Adults ( aged 18years ) with a CD4 count of 150 cells/L or less , who have not received any tuberculosis treatment in the last three months , or ART in the last six months , are eligible .


In intervention clinics , the study algorithm is used to classify individuals as at high , medium or low probability of tuberculosis .


Those classified as high probability start tuberculosis treatment immediately , followed by ART after two weeks .


Medium-probability patients follow the South African guidelines for test-negative tuberculosis and are reviewed within a week , to be re-categorised as low or high probability .


Low-probability patients start ART as soon as possible .


The primary outcome is all-cause mortality at six months .


Secondary outcomes include severe morbidity , time to ART start and cost-effectiveness .


This trial will test whether a primary care-friendly management algorithm will enable nurses to identify HIV-positive patients at the highest risk of tuberculosis , to facilitate prompt treatment and reduce early mortality .


There remains an urgent need for better diagnostic tests for tuberculosis , especially for people with advanced HIV disease , which may render empirical treatment unnecessary .


This trial was registered with Current Controlled Trials ( identifier : ISRCTN35344604 ) on 12 September 2012 .


Guidelines recommend gradual weight loss for the treatment of obesity , indicative of a widely held opinion that weight lost rapidly is more quickly regained .


We aimed to investigate the effect of the rate of weight loss on the rate of regain in obese people .


For this two phase , randomised , non-masked , dietary intervention trial in a Melbourne metropolitan hospital , we enrolled 204 participants ( 51 men and 153 women ) aged 1870 years with a BMI between 30 and 45 kg/m2 .


During phase 1 , we randomly assigned ( 1:1 ) participants with a block design ( block sizes of 2 , 4 , and 6 ) to account for sex , age , and BMI , to either a 12-week rapid weight loss or a 36-week gradual programme , both aimed at 15 % weight loss .


We placed participants who lost 125 % or more weight during phase 1 on a weight maintenance diet for 144 weeks ( phase 2 ) .


The primary outcome was mean weight loss maintained at week 144 of phase 2 .


We investigated the primary outcome by both completers only and intention-to-treat analyses .


This study is registered with the Australian New Zealand Clinical Trials Registry , number ACTRN12611000190909 .


200 participants were randomly assigned to the gradual weight loss ( n = 103 ) or rapid weight loss ( n = 97 ) programme between Aug 8 , 2008 , and March 9 , 2010 .


After phase 1 , 51 ( 50 % ) participants in the gradual weight loss group and 76 ( 81 % ) in the rapid weight loss group achieved 125 % or more weight loss in the allocated time and started phase 2 .


At the end of phase 2 , both gradual weight loss and rapid weight loss participants who completed the study ( n = 43 in gradual weight loss and n = 61 in rapid weight loss ) had regained most of their lost weight ( gradual weight loss 712 % regain , 95 % CI 581843 vs rapid weight loss 705 % , 578832 ) .


Intention-to-treat analysis showed similar results ( gradual weight loss 763 % regain , 95 % CI 652874 vs rapid weight loss 763 % , 658868 ) .


In phase 1 , one participant in the rapid weight loss group developed cholecystitis , requiring cholecystectomy .


In phase 2 , two participants in the rapid weight loss group developed cancer .


The rate of weight loss does not affect the proportion of weight regained within 144 weeks .


These findings are not consistent with present dietary guidelines which recommend gradual over rapid weight loss , based on the belief that rapid weight loss is more quickly regained .


The Australian National Health and Medical Research Council and the Sir Edward Dunlop Medical Research Foundation .


NSABP P-1 provides an opportunity to examine the association of behavioral factors with prospectively monitored cancer incidence and interactions with tamoxifen .


From 1992 to 1997 , 13,388 women with estimated 5-year breast cancer risk greater than 1.66 % or a history of lobular carcinoma in situ ( 87 % younger than age 65 ; 67 % postmenopausal ) were randomly assigned to tamoxifen versus placebo .


Invasive breast cancer , lung cancer , colon cancer , and endometrial cancer were analyzed with Cox regression .


Predictors were baseline cigarette smoking , leisure-time physical activity , alcohol consumption , and established risk factors .


At median 7 years follow-up , we observed 395 , 66 , 35 , and 74 breast cancer , lung cancer , colon cancer , and endometrial cancer , respectively .


Women who had smoked were at increased risk of breast cancer ( P = 0.007 ; HR = 1.3 for 15-35 years smoking , HR = 1.6 for 35 years ) , lung cancer ( P < 0.001 ; HR = 3.9 for 15-35 years , HR = 18.4 for 35 years ) , and colon cancer ( P < 0.001 ; HR = 5.1 for 35 years ) versus never-smokers .


Low activity predicted increased breast cancer risk only among women assigned to placebo ( P = 0.021 activity main effect , P = 0.013 activity-treatment interaction ; HR = 1.4 for the placebo group ) and endometrial cancer among all women ( P = 0.026 , HR = 1.7 ) .


Moderate alcohol ( > 0-1 drink/day ) was associated with decreased risk of colon cancer ( P = 0.019 ; HR = 0.35 ) versus no alcohol .


There were no other significant associations between these behaviors and cancer risk .


Among women with elevated risk of breast cancer , smoking has an even greater impact on breast cancer risk than observed in past studies in the general population .


Women who smoke or are inactive should be informed of the increased risk of multiple types of cancer .


Extensive-stage small-cell lung cancer ( SCLC ) patients who progress after platinum-based chemotherapy are traditionally categorized as platinum sensitive ( progression 90 days from last platinum dose ) or refractory ( progression < 90 days ) , a practice arising from seminal observations of worse survival in refractory patients .


Subsequent trials accounted for platinum sensitivity , resulting in higher sample sizes and increased resource use .


To assess whether platinum-sensitivity status remains associated with outcomes , patient-level data from recent Southwest Oncology Group trials in second - and/or third-line extensive-stage SCLC were pooled .


Hazard ratios ( HRs ) for progression-free survival ( PFS ) and overall survival ( OS ) accounting for platinum sensitivity were calculated using unadjusted and adjusted Cox Proportional Hazard models .


Recursive partitioning was performed to define prognostic risk groups .


Of 329 patients , 151 were platinum sensitive and 178 refractory .


HRs from unadjusted Cox PFS and OS models for refractory versus sensitive disease were 1.0 ( 95 % confidence interval , 0.81-1 .25 ; p = 0.98 ) and 1.24 ( 0.99-1 .57 ; p = 0.06 ) , respectively .


Adjusted Cox models showed that only elevated serum lactate dehydrogenase ( HR , 2.04 ; p < 0.001 ) , males ( HR , 1.36 ; p = 0.04 ) , performance status of 1 ( HR , 1.25 ; p = 0.02 ) , and weight loss greater than or equal to 5 % ( 1.53 , p = 0.01 ) were independently associated with OS .


Platinum-sensitivity status was not associated with PFS ( HR , 1.11 ; p = 0.49 ) or OS ( HR , 1.25 ; p = 0.14 ) , except in a model that excluded 36 patients who received more than one prior chemotherapy regimen ( HR , 1.34 ; p = 0.049 ) .


Prognostic groups with differential OS outcomes ( high , intermediate , and poor risk ) were identified .


Platinum-sensitivity status may no longer be strongly associated with PFS or OS in at least one multivariate model .


Validation of prognostic risk groups identified here is warranted .


These data have critical implications in the design of future SCLC trials .


To evaluate the effectiveness of a hydrogel sealant versus a suture in preventing fluid egress after wound leakage in cataract surgery .


Twenty-four ophthalmic clinical practices in the United States .


Prospective randomized parallel-arm controlled multicenter subject-masked study .


Healthy patients having uneventful clear corneal incision ( CCI ) cataract surgery were eligible for the study .


Spontaneous and provoked fluid egress from wounds was evaluated at the time of surgery using a calibrated force gauge .


Eyes with leakage were randomized to receive a hydrogel sealant ( Resure ) or a nylon suture at the main incision site .


Incision leakage was reevaluated 1 , 3 , 7 , and 28 days postoperatively .


Of 500 eyes , 488 had leakage at the time of cataract surgery .


The leak was spontaneous in 244 cases ( 48.8 % ) , and 488 ( 97.6 % ) of all incisions leaked with 1.0 ounce or less of applied force .


After randomization , 12 ( 4.1 % ) of 295 eyes in the sealant group and 60 ( 34.1 % ) of 176 eyes in the suture group had wound leakage with provocation ( P < .0001 ) .


The overall incidence of adverse ocular events was statistically significantly lower in the sealant group than in the suture group ( P < .05 ) .


In this study , 97.6 % of CCIs leaked after cataract surgery .


The hydrogel sealant was safe and effective and better than a suture for the intraoperative management of CCIs with leakage as seen on Seidel testing and for the prevention of postoperative fluid egress .


Various methods are used to assess the height of sensory block to touch under spinal anesthesia for cesarean section .


We tested a novel , inexpensive , miniature , user-dependent plastic neurological wheel against the user-independent Neurotip mounted Neuropen .


Patients received either spinal or combined spinal-epidural anesthesia .


For each patient assessment , the devices were randomly assigned to one of two independent investigators .


The order of device application was randomly permuted .


Neither researcher was involved with anesthetic care .


At 5-min intervals for 20 min after spinal injection , and again at the end of the operation , the levels of block to loss-of-touch sensation were assessed .


While one investigator evaluated the block , the other left the operating room and vice versa .


Mixed-effects regression and Bland-Altman analysis were used to weigh agreement between devices .


The mean difference in level-to-touch was 0.04 ( 95 % CI -0.18 , 0.27 ) dermatome levels .


Measurement error standard deviation associated with the Neurotip mounted Neuropen and plastic neurological wheel was 1.36 ( 95 % CI 1.26 , 1.41 ) and 1.33 ( 95 % CI 1.26 , 1.46 ) dermatome levels , respectively .


The difference in measurement error standard deviation was -0.03 ( 95 % CI -0.16 , 0.24 ) .


This evidence excludes the possibility , with 95 % confidence , of clinically significant bias or measurement error differences between methods .


Occasional wide variances in dermatome level were observed with both instruments at the initial assessment only .


The compact plastic neurological wheel is as clinically reliable as the Neurotip mounted Neuropen .


To determine the effects of rumen-protected choline ( RPC ) on health and reproduction in dairy cows .


A total of 298 primi - and multiparous German Holstein cows of a high-production dairy herd ( average daily milk yield : 32 l ) were assigned randomly to a control or treatment group and were hand fed with 0 or 60 g/d of RPC as ReaShure , respectively , from 21 days before expected calving to 21 days post partum ( p. p. ) as a top dressing .


Health data was analyzed for the incidence of fever within the first 10 days in milk ( DIM ) as well as the incidence of diseases and the culling rate within the first 200 DIM .


Reproduction data were evaluated in terms of the calving data , uterine involution on days 10 , 21 and 42 p. p. , uterine cytology at day 42 p. p. , progesterone concentrations during weeks 3 and 5 p. p. and certain fertility measures .


In the statistical analysis , it was differentiated between the control and treatment groups and between primi - and multiparous animals , and their interactions were analyzed .


The treatment group had less cows with subclinical endometritis , higher sickness rates after day 100 p. p. , lower numbers of stillbirths and more cyclic cows in week 5 p. p. compared to the control group ( p < 0.05 ) .


Primipara in contrast to multipara had fever more frequently , higher rates of subclinical ketosis p. p. , metritis and lameness , higher numbers of sick cows in the first 30 DIM , higher rates of stillbirths and dystocia , showed impaired involution of the uterus on day 10 p. p. , fewer animals were cyclic during week 5 p. p. and less animals were culled ( p < 0.05 ) .


Statistically significant interactions indicated that more heifers of the treatment group were lame , more heifers of the control group developed fever and subclinical endometritis , cows of the treatment group suffered more metritis and were sick more often in the first 30 DIM , and cows of the control group had more dystocia ( p < 0.05 ) .


Overall , supplementing RPC had only minor effects on the health status and reproduction .


Further research in other dairy herds should focus on this topic .


Individuals with a strong family history of colorectal cancer have significant risk for colorectal cancer , although adherence to colonoscopy screening in these groups remains low .


This study assessed whether a tailored telephone counseling intervention can increase adherence to colonoscopy in members of high-risk families in a randomized , controlled trial .


Eligible participants were recruited from two national cancer registries if they had a first-degree relative with colorectal cancer under age 60 or multiple affected family members , which included families that met the Amsterdam criteria for hereditary non-polyposis colon cancer ( HNPCC ) , and if they were due for colonoscopy within 24 months .


Participants were randomized to receive a tailored telephone intervention grounded in behavioral theory or a mailed packet with general information about screening .


Colonoscopy status was assessed through follow-up surveys and endoscopy reports .


Cox proportional hazards models were used to assess intervention effect .


Of the 632 participants ( ages 25-80 ) , 60 % were female , the majority were White , non-Hispanic , educated , and had health insurance .


Colonoscopy adherence increased 11 percentage points in the tailored telephone intervention group , compared with no significant change in the mailed group .


The telephone intervention was associated with a 32 % increase in screening adherence compared with the mailed intervention ( HR , 1.32 ; P = 0.01 ) .


A tailored telephone intervention can effectively increase colonoscopy adherence in high-risk persons .


This intervention has the potential for broad dissemination to healthcare organizations or other high-risk populations .


Increasing adherence to colonoscopy among persons with increased colorectal cancer risk could effectively reduce incidence and mortality from this disease .


Hepatitis E virus ( HEV ) is a leading cause of acute hepatitis .


The long-term efficacy of a hepatitis E vaccine needs to be determined .


In an initial efficacy study , we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine ( vaccine group ; 56,302 participants ) or a hepatitis B vaccine ( control group ; 56,302 participants ) .


The vaccines were administered at 0 , 1 , and 6 months , and the participants were followed for 19 months .


In this extended follow-up study , the treatment assignments of all participants remained double-blinded , and follow-up assessments of efficacy , immunogenicity , and safety were continued for up to 4.5 years .


During the 4.5-year study period , 60 cases of hepatitis E were identified ; 7 cases were confirmed in the vaccine group ( 0.3 cases per 10,000 person-years ) , and 53 cases in the control group ( 2.1 cases per 10,000 person-years ) , representing a vaccine efficacy of 86.8 % ( 95 % confidence interval , 71 to 94 ) in the modified intention-to-treat analysis , rather than ( 95 % confidence interval , 71 to 84 ) [ corrected ] .


Of the participants who were assessed for immunogenicity and were seronegative at baseline , 87 % of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years ; HEV antibody titers developed in 9 % in the control group .


The rate of adverse events was similar in the two groups .


Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years .


( Funded by the Chinese Ministry of Science and Technology and others ; ClinicalTrials.gov number , NCT01014845 . )


Exercise can improve physical fitness in children and adults with congenital heart disease .


We hypothesized that exercise training would not lead to adverse cardiac remodelling in this population .


This multi-centre randomized controlled trial included children and young adults ( 10 to 25 years ) with either corrected tetralogy of Fallot or Fontan circulation .


The exercise-group was enrolled in a 12 week standardized aerobic dynamic exercise training program .


The control-group continued their life-style and received care as usual .


Both groups underwent cardiopulmonary exercise testing , cardiac magnetic resonance imaging ( MRI ) , echocardiography and neurohormonal assessment , within 2 weeks before and 2 weeks after the intervention period .


Fifty-six patients were randomized to the exercise-group and 37 to the control-group .


We assessed changes between the pre - and the post-intervention period for the exercise group compared to the changes in the control-group .


Peak load increased significantly in the exercise-group compared to the control-group ( exercise-group 6.9 11.8 W ; control-group 0.8 13.9 W ; p = 0.047 ) .


There were no adverse events linked to the study .


Ventricular systolic parameters , cardiac dimensions and neurohormonal markers during follow-up did not change in patients allocated to the exercise-group and control-group .


Although there were some isolated minor changes in inflow parameters , there was no consistent pattern of changes , indicating a lack of true change in the diastolic function .


We demonstrated that no clinically relevant adverse cardiac remodelling occurred after 12 weeks of exercise training in patients with either corrected tetralogy of Fallot or Fontan circulation .


www.trialregister.nl , identification NTR2731 .


To compare the efficacy of simulation-based training between the Mimic dV - Trainer and traditional dry lab da Vinci robot training .


A prospective randomized study analyzing the performance of 20 robotics-naive participants .


Participants were enrolled in an online da Vinci Intuitive Surgical didactic training module , followed by training in use of the da Vinci standard surgical robot .


Spatial ability tests were performed as well .


Participants were randomly assigned to 1 of 2 training conditions : performance of 3 Fundamentals of Laparoscopic Surgery dry lab tasks using the da Vinci or performance of 4 dV-Trainer tasks .


Participants in both groups performed all tasks to empirically establish proficiency criterion .


Participants then performed the transfer task , a cystotomy closure using the daVinci robot on a live animal ( swine ) model .


The performance of robotic tasks was blindly assessed by a panel of experienced surgeons using objective tracking data and using the validated Global Evaluative Assessment of Robotic Surgery ( GEARS ) , a structured assessment tool .


No statistically significant difference in surgeon performance was found between the 2 training conditions , dV-Trainer and da Vinci robot .


Analysis of a 95 % confidence interval for the difference in means ( -0.803 to 0.543 ) indicated that the 2 methods are unlikely to differ to an extent that would be clinically meaningful .


Based on the results of this study , a curriculum on the dV - Trainer was shown to be comparable to traditional da Vinci robot training .


Therefore , we have identified that training on a virtual reality system may be an alternative to live animal training for future robotic surgeons .


Previously , we showed that high-dose early initiated inhaled corticosteroids during respiratory syncytial virus bronchiolitis partially and transiently prevents subsequent recurrent wheeze .


Here , we study treatment effect on lung function at age 6 .


This is a 6-year follow-up report of a randomized placebo-controlled trial , in which 185 infants hospitalized for respiratory syncytial virus bronchiolitis were treated with early initiated , high-dose inhaled beclomethasone ( n = 86 ) or placebo ( n = 99 ) for 3 months .


The primary outcome was forced expiratory volume in 1 second as percentage predicted .


Secondary outcomes were bronchial hyperresponsiveness , physician-diagnosed asthma , hay fever and eczema .


Possible toxicity was assessed by linear growth measurements .


At age 6 , no significant differences were found in mean forced expiratory volume in 1 second percentage predicted between beclomethasone-treated and placebo-treated patients ( 91.4 vs. 93.4 , mean difference 2.05 ( 95 % confidence interval : -1.98 to 6.08 ) .


The proportion of bronchial hyperresponsiveness , physician-diagnosed asthma , parent reported hay fever and eczema was comparable between groups .


There were no differences in linear growth .


Early initiated prolonged treatment with high-dose inhaled beclomethasone during hospitalization for respiratory syncytial virus infection during infancy did not improve the long-term respiratory outcome , but was safe .


We investigated changes in anisometropia and aniso-axial length with myopia progression in the Correction of Myopia Evaluation Trial ( COMET ) cohort .


Of 469 myopic children , 6 to < 12 years old , enrolled in COMET , 358 were followed for 13 years .


Cycloplegic autorefraction and axial length ( AL ) in each eye were measured annually .


The COMET eligibility required anisometropia ( interocular difference in spherical equivalent refraction ) of 1.00 diopter ( D ) .


For each child , a linear regression line was fit to anisometropia data by visit , and the regression slope b was used as the rate of change .


Logistic regression was applied to identify factors for significant changes in anisometropia ( b 0.05 D/y , or a cumulative increase in anisometropia 0.50 D over 10 years ) .


Similar analyses were applied to aniso-AL .


A total of 358/469 ( 76.3 % ) children had refractions at baseline and the 13-year visit .


The mean ( SD ) amount of anisometropia increased from 0.24 D ( 0.22 D ) at baseline to 0.49 D ( 0.46 D ) at the 13-year visit .


A total of 319/358 ( 89.1 % ) had slopes | b | < 0.05 D/y and 39 ( 10.9 % ) had slopes | b | 0.05 D/y , with only one negative slope .


Similarly , 334/358 ( 93.3 % ) children had little change in aniso-AL over time .


The correlation between changes in anisometropia and aniso-AL over 13 years was 0.39 ( P < 0.001 ) .


The correlation between changes in anisometropia and myopia progression was significant ( r = -0.36 , P < 0.001 ) .


No correlation was found between baseline anisometropia and myopia progression ( r = -0.02 , P = 0.68 ) .


Myopia and axial length progressed at a similar rate in both eyes for most children in COMET during the period of fast progression and eventual stabilization .


These results may be more generalizable to school-aged myopic children with limited anisometropia at baseline .


( ClinicalTrials.gov number , NCT00000113 . )


Given the long natural history of prostate cancer , we assessed differing graphical formats for imparting knowledge about the longitudinal risks of prostate cancer recurrence with or without ` hormone ' or ` androgen deprivation ' therapy .


Male volunteers without a history of prostate cancer were randomized to 1 of 8 risk communication instruments that depicted the likelihood of prostate cancer returning or spreading over 1 , 2 , and 3 years .


The tools differed in format ( line , pie , bar , or pictograph ) and whether the graph also included no numbers , 1 number ( indicating the number of affected individuals ) , or 2 numbers ( indicting both the number affected and the number unaffected ) .


The main outcome variables evaluated were graphical preference and knowledge .


A total of 420 men were recruited ; respondents were least familiar and experienced with pictographs ( P < 0.0001 ) , and only 10 % preferred this particular format .


Overall accuracy ranged from 79 % to 92 % , and when assessed across all graphical subtypes , the addition of numerical information did not improve verbatim knowledge ( P = 0.1 ) .


Self-reported numeracy was a strong predictor of accuracy of responses ( odds ratio [ OR ] = 2.6 , P = 0.008 ) , and the impact of high numeracy varied across graphical type , having a greater impact on line ( OR = 5.1 ; 95 % confidence interval [ CI ] = 1.6-16 ; P = 0.04 ) and pie charts ( OR = 7.1 ; 95 % CI = 2.6-19 ; P = 0.01 ) , without an impact on pictographs ( OR = 0.4 ; 95 % CI = 0.1-1 .7 ; P = 0.17 ) or bar charts ( OR = 0.5 ; 95 % CI = 0.1-1 .8 ; P = 0.24 ) .


For longitudinal presentation of risk , baseline numeracy was strongly prognostic for outcome .


However , the addition of numbers to risk graphs improved only the delivery of verbatim knowledge for subjects with lower numeracy .


Although subjects reported the least familiarity with pictographs , they were one of the most effective means of transferring information regardless of numeracy .


Warfarin is the most widely used oral anticoagulant worldwide , but serious bleeding complications are common .


We tested whether genetic variants can identify patients who are at increased risk of bleeding with warfarin and , consequently , those who would derive a greater safety benefit with a direct oral anticoagulant rather than warfarin .


ENGAGE AF-TIMI 48 was a randomised , double-blind trial in which patients with atrial fibrillation were assigned to warfarin to achieve a target international normalised ratio of 20-30 , or to higher-dose ( 60 mg ) or lower-dose ( 30 mg ) edoxaban once daily .


A subgroup of patients was included in a prespecified genetic analysis and genotyped for variants in CYP2C9 and VKORC1 .


The results were used to create three genotype functional bins ( normal , sensitive , and highly sensitive responders to warfarin ) .


This trial is registered with ClinicalTrials.gov , number NCT00781391 .


14,348 patients were included in the genetic analysis .


Of 4833 taking warfarin , 2982 ( 617 % ) were classified as normal responders , 1711 ( 354 % ) as sensitive responders , and 140 ( 29 % ) as highly sensitive responders .


Compared with normal responders , sensitive and highly sensitive responders spent greater proportions of time over-anticoagulated in the first 90 days of treatment ( median 22 % , IQR 0-202 ; 84 % , 0-258 ; and 183 % , 0-326 ; ptrend < 00001 ) and had increased risks of bleeding with warfarin ( sensitive responders hazard ratio 131 , 95 % CI 105-164 , p = 00179 ; highly sensitive responders 266 , 169-419 , p < 00001 ) .


Genotype added independent information beyond clinical risk scoring .


During the first 90 days , when compared with warfarin , treatment with edoxaban reduced bleeding more so in sensitive and highly sensitive responders than in normal responders ( higher-dose edoxaban pinteraction = 00066 ; lower-dose edoxaban pinteraction = 00036 ) .


After 90 days , the reduction in bleeding risk with edoxaban versus warfarin was similarly beneficial across genotypes .


CYP2C9 and VKORC1 genotypes identify patients who are more likely to experience early bleeding with warfarin and who derive a greater early safety benefit from edoxaban compared with warfarin .


Daiichi Sankyo .


Research shows that multilevel factors influence healthcare delivery and patient outcomes .


The study goal was to examine how clinic type [ academic medical center ( AMC ) or federally qualified health center ( FQHC ) ] and patient characteristics influence time to resolution ( TTR ) among individuals with an abnormal cancer-screening test enrolled in a patient navigation ( PN ) intervention .


Data were obtained from the Ohio Patient Navigation Research Project , a group-randomized trial of 862 patients from 18 clinics in Columbus , Ohio .


TTR of patient after an abnormal breast , cervical , or colorectal screening test and the clinics ' patient and provider characteristics were obtained .


Descriptive statistics and Cox shared frailty proportional hazards regression models of TTR were used .


The mean patient age was 44.8 years and 71 % of patients were white .


In models adjusted for study arm , FQHC patients had a 39 % lower rate of resolution than AMC patients ( P = 0.004 ) .


Patient factors of having a college education , private insurance , higher income , and being older were significantly associated with lower TTR .


After adjustment for factors that substantially affected the effect of clinic type ( patient insurance status , education level , and age ) , clinic type was not significantly associated with TTR .


These results suggest that TTR among individuals participating in PN programs are influenced by multiple socioeconomic patient-level factors rather than clinic type .


Consequently , PN interventions should be tailored to address socioeconomic status factors that influence TTR .