Interventions were more likely to occur contemporaneously with hypoventilation in the intervention group ( 2.26 ; 95 % CI , 1.34-3 .81 ) .


Interventions not in time with hypoventilation were associated with higher odds of oxygen desaturation less than 95 % ( odds ratio , 5.31 ; 95 % CI , 2.76-10 .22 ) .


Hypoventilation is common during sedation of pediatric emergency department patients .


This can be difficult to detect by current monitoring methods other than capnography .


Providers with access to capnography provided fewer but more timely interventions for hypoventilation .


This led to fewer episodes of hypoventilation and of oxygen desaturation .


Prospective , parallel-group , controlled , comparative randomized study .


To compare cement leakage rate and efficacy for vertebral body restoration of balloon kyphoplasty ( BK ) versus Kiva novel implant with polymethylmethacrylate ( PMMA ) for treating osteolytic vertebral body metastasis .


Minimally invasively vertebral augmentation techniques with PMMA are mostly performed for treating osteoporotic compression fractures .


The Kiva implant with PMMA offers better vertebral body restoration and less PMMA leakage than BK in osteoporotic fractures .


No previous study compared leakage rate and efficacy for vertebral body restoration in traditional BK and Kiva with PMMA in osteolytic vertebral body metastases .


This study examined 23 patients ( 71 13 yr ) with 41 osteolytic vertebral bodies , who received Kiva with low viscosity PMMA and 24 patients ( 70 11 yr ) with 43 vertebral body osteolyses , who were reinforced with BK and high viscosity PMMA .


All osteolyses were graded as Tomita 1 to 3 .


Anterior vertebral body height ratio ( AVBHr ) , posterior vertebral body height ratio ( PVBHr ) , and middle vertebral body height ratio ( MVBHr ) , Gardner kyphotic deformity , PMMA leakage and were measured and compared between the groups .


Visual analogue scale and Oswestry Disability Index were used for functional outcome evaluation .


No patient survived after 3 months .


Asymptomatic PMMA leakage occurred in 4 ( 9.3 % ) vertebrae in the BK group solely ( 2 to the spinal canal , in Tomita grade 3 osteolysis ) Anterior , posterior and middle vertebral body height ratio , Gardner angle improved insignificantly in both groups .


Visual anlogue scale and Oswestry Disability Index improved postoperatively similarly in both groups ( P < 0.001 ) .


BK and Kiva provided equally significant spinal pain relief in patients with cancer with osteolytic metastasis .


The absence of cement leakage in the Kiva group and absence of neurological complication in the BK group leakages reflects the safety of both augmentation techniques even in significant osteolysis .


The lack of cement leakage in the Kiva cases , although low viscosity PMMA was used , increases this implant safety in augmenting severely destructed thoracolumbar vertebrae and sacrum from osteolytic metastasis .


1 .


Unexplained painful physical symptoms are commonly reported by depressed patients .


The evidence suggests that dual-action antidepressants are potent in relieving pain in depression .


However , a direct comparison of the effects of selective serotonergic and selective noradrenergic antidepressants on painful symptoms has not been investigated so far .


Sixty patients who participated in the Genome-based Therapeutic Drugs for Depression study with a diagnosis of moderate or severe episodes of depression according to the International Classification of Diseases , 10th Revision , and the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria were involved .


All the participants were randomly allocated to receive nortriptyline or escitalopram .


The severity of depression was measured using the Montgomery-sberg Depression Rating Scale , the Hamilton Depression Rating Scale and the Beck Depression Inventory at weeks 0 , 2 , 4 , 6 and 8 .


The intensity of pain was measured on the Visual Analog Scale at the same points of the study .


At `` week 0 , '' 83.3 % of the patients later randomized to treatment with escitalopram and 86.7 % of those treated with nortriptyline reported at least one painful symptom .


A significant decrease of pain intensity was observed after 2 weeks of treatment .


The two groups did not differ in degree of pain reduction at weeks 2 , 4 , 6 and 8 in comparison to baseline values .


A 50 % reduction in pain intensity preceded the 50 % reduction of depression severity .


The intensity of pain at `` week 0 '' did not differ in remitted or nonremitted patients at week 8 .


Both selective serotonergic and selective noradrenergic antidepressants are equally effective in alleviations of painful physical symptoms of depression .


The presence of painful symptoms before the onset of treatment did not determine the final response .


The success of HIV programs relies on widely accessible HIV testing and counseling ( HTC ) services at health facilities as well as in the community .


Home-based HTC ( HB-HTC ) is a popular community-based approach to reach persons who do not test at health facilities .


Data comparing HB-HTC to other community-based HTC approaches are very limited .


This trial compares HB-HTC to mobile clinic HTC ( MC-HTC ) .


The trial was powered to test the hypothesis of higher HTC uptake in HB-HTC campaigns than in MC-HTC campaigns .


Twelve clusters were randomly allocated to HB-HTC or MC-HTC .


The six clusters in the HB-HTC group received 30 1-d multi-disease campaigns ( five villages per cluster ) that delivered services by going door-to-door , whereas the six clusters in MC-HTC group received campaigns involving community gatherings in the 30 villages with subsequent service provision in mobile clinics .


Time allocation and human resources were standardized and equal in both groups .


All individuals accessing the campaigns with unknown HIV status or whose last HIV test was > 12 wk ago and was negative were eligible .


All outcomes were assessed at the individual level .


Statistical analysis used multivariable logistic regression .


Odds ratios and p-values were adjusted for gender , age , and cluster effect .


Out of 3,197 participants from the 12 clusters , 2,563 ( 80.2 % ) were eligible ( HB-HTC : 1,171 ; MC-HTC : 1,392 ) .


The results for the primary outcomes were as follows .


Overall HTC uptake was higher in the HB-HTC group than in the MC-HTC group ( 92.5 % versus 86.7 % ; adjusted odds ratio [ aOR ] : 2.06 ; 95 % CI : 1.18-3 .60 ; p = 0.011 ) .


Among adolescents and adults 12 y , HTC uptake did not differ significantly between the two groups ; however , in children < 12 y , HTC uptake was higher in the HB-HTC arm ( 87.5 % versus 58.7 % ; aOR : 4.91 ; 95 % CI : 2.41-10 .0 ; p < 0.001 ) .


Out of those who took up HTC , 114 ( 4.9 % ) tested HIV-positive , 39 ( 3.6 % ) in the HB-HTC arm and 75 ( 6.2 % ) in the MC-HTC arm ( aOR : 0.64 ; 95 % CI : 0.48-0 .86 ; p = 0.002 ) .


Ten ( 25.6 % ) and 19 ( 25.3 % ) individuals in the HB-HTC and in the MC-HTC arms , respectively , linked to HIV care within 1 mo after testing positive .


Findings for secondary outcomes were as follows : HB-HTC reached more first-time testers , particularly among adolescents and young adults , and had a higher proportion of men among participants .


However , after adjusting for clustering , the difference in male participation was not significant anymore .


Age distribution among participants and immunological and clinical stages among persons newly diagnosed HIV-positive did not differ significantly between the two groups .


Major study limitations included the campaigns ' restriction to weekdays and a relatively low HIV prevalence among participants , the latter indicating that both arms may have reached an underexposed population .


This study demonstrates that both HB-HTC and MC-HTC can achieve high uptake of HTC .


The choice between these two community-based strategies will depend on the objective of the activity : HB-HTC was better in reaching children , individuals who had never tested before , and men , while MC-HTC detected more new HIV infections .


The low rate of linkage to care after a positive HIV test warrants future consideration of combining community-based HTC approaches with strategies to improve linkage to care for persons who test HIV-positive .


ClinicalTrials.gov NCT01459120 .


Please see later in the article for the Editors ' Summary .


Linifanib is a selective inhibitor of the vascular endothelial growth factor and platelet-derived growth factor family of tyrosine kinase inhibitors .


The purpose of this high-precision QT study was to evaluate the effects of linifanib on cardiac repolarization in patients with advanced metastatic tumors .


Enrolled patients ( n = 24 ) had measurable disease refractory to standard therapies , ECOG performance status of 0-1 , and adequate organ function .


Patients were randomized in a 2-sequence , 2-period crossover design .


Serial ECG measurements and pharmacokinetic samples were collected for each crossover period .


An intersection-union test was performed for time-matched baseline-adjusted QTcF intervals .


An exposure-response analysis was explored to correlate the plasma concentration and QTcF .


The maximum 95 % upper confidence bound for the baseline-adjusted QTcF was 4.3 ms at hour 3 at the maximum tolerated linifanib dose of 0.25 mg/kg .


Linifanib did not meet the regulatory threshold ( 10 ms ) for QT prolongation .


Exposure-response modeling showed that the QTcF change was not significant at the maximum plasma concentration .


Linifanib does not significantly affect cardiac repolarization in patients with advanced solid tumors .


Colorectal cancer is a major health burden .


Screening is recommended in many countries .


To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial .


Randomized clinical trial of 100,210 individuals aged 50 to 64 years , identified from the population of Oslo city and Telemark County , Norway .


Screening was performed in 1999-2000 ( 55-64-year age group ) and in 2001 ( 50-54-year age group ) , with follow-up ending December 31 , 2011 .


Of those selected , 1415 were excluded due to prior colorectal cancer , emigration , or death , and 3 could not be traced in the population registry .


Participants randomized to the screening group were invited to undergo screening .


Within the screening group , participants were randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing ( FOBT ) .


Participants with positive screening test results ( cancer , adenoma , polyp 10 mm , or positive FOBT ) were offered colonoscopy .


The control group received no intervention .


Colorectal cancer incidence and mortality .


A total of 98,792 participants were included in the intention-to-screen analyses , of whom 78,220 comprised the control group and 20,572 comprised the screening group ( 10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT ) .


Adherence with screening was 63 % .


After a median of 10.9 years , 71 participants died of colorectal cancer in the screening group vs 330 in the control group ( 31.4 vs 43.1 deaths per 100,000 person-years ; absolute rate difference , 11.7 [ 95 % CI , 3.0-20 .4 ] ; hazard ratio [ HR ] , 0.73 [ 95 % CI , 0.56-0 .94 ] ) .


Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group ( 112.6 vs 141.0 cases per 100,000 person-years ; absolute rate difference , 28.4 [ 95 % CI , 12.1-44 .7 ] ; HR , 0.80 [ 95 % CI , 0.70-0 .92 ] ) .


Colorectal cancer incidence was reduced in both the 50 - to 54-year age group ( HR , 0.68 ; 95 % CI , 0.49-0 .94 ) and the 55 - to 64-year age group ( HR , 0.83 ; 95 % CI , 0.71-0 .96 ) .


There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups .


In Norway , once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening .


Screening was effective both in the 50 - to 54-year and the 55 - to 64-year age groups .


clinicaltrials.gov Identifier : NCT00119912 .


In observational studies , low serum 25-hydroxyvitamin D [ 25 ( OH ) D ] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease .


We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose ( IFG ) and/or impaired glucose tolerance ( IGT ) randomly assigned to 20,000 IU/week vitamin D3 or placebo .


An oral glucose tolerance test was performed at baseline and after 1 year .


Mean baseline serum 25 ( OH ) D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups , respectively , and increased by 45.8 nmol/L and 3.4 nmol/L , respectively .


With adjustment for baseline concentrations , no differences in measures of glucose metabolism , insulin secretion or sensitivity , blood pressure , or hs-CRP were found after 1 year .


There was a slight , but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group , but as there was also a decrease in HDL cholesterol , the change in the total/HDL cholesterol ratio did not differ significantly .


Only analyzing subjects with 25 ( OH ) D < 50 nmol/L did not change the results .


This study shows that vitamin D supplementation does not improve glycemic indices , blood pressure , or lipid status in subjects with IFG and/or IGT .


Faecal incontinence affects up to 8 % of adults .


Associated social isolation and subsequent depression can have devastating effects on quality of life ( QoL ) .


Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician .


There have been few well-designed , placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies .


Libertas , a robustly designed study will investigate the efficacy and safety of NRL001 ( 1R,2S-methoxamine ) , an 1 - adrenoceptor agonist , in the treatment of faecal incontinence .


Libertas is a multicentre , Phase II , double-blind , randomised , placebo-controlled , parallel group study .


Patient recruitment took place across 55 study centres in Europe .


Patients suffering with faecal incontinence were randomised into four groups ( approximately 110 each ) to receive once daily self-administered doses of NRL001 ( 5 , 7.5 or 10 mg or placebo in a suppository formulation ) for 8 weeks .


The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks , compared with placebo .


Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment ; safety and tolerability ; evaluation of plasma pharmacokinetics ; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events ; dose-response relationship ; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score ; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy .


Overall patient satisfaction with the treatment will also be evaluated .


This is the first randomised controlled study to investigate the efficacy and safety of a selective 1 - adrenoceptor agonist for the treatment of faecal incontinence .


Furthermore , this is the first time the impact of NRL001 on assessments of QoL , health outcomes and patient satisfaction will be assessed .


Innovative strategies were developed to meet the challenge of recruiting patients for this study , for example , media advertising , posters and mailshots as allowed by each study centre .


Propranolol therapy is changing the treatment paradigm for infantile hemangioma .


This study addresses the effect of propranolol therapy on the treatment of nasal infantile hemangioma ( NIH ) , an area that often does not respond to medical therapy .


To determine if propranolol treatment is associated with fewer invasive treatments for NIH .


Retrospective cohort study conducted within a single pediatric institution 's multidisciplinary vascular anomaly program for patients with NIH treated between January 1 , 2003 , and December 31 , 2011 .


Three NIH cohorts were compared : prepropranolol ( 20 in group 1 ; 2003-2009 ) , propranolol ( 25 in group 2 ; 2009-2011 ) , and nonpropranolol ( 13 in group 3 ; 2009-2011 ) treatment .


Analysis of systemic medical , laser , or surgical therapies for NIH .


The study plan was created to detect a change in invasive therapy for NIH .


Data collected included presenting age , sex , affected nasal subunits , infantile hemangioma morphologic characteristics , treatment type and number , and primary treating service .


An NIH grading system , based on nasal subunit involvement , helped quantify treatment change .


Descriptive statistics summarized data , and a Cox proportional hazards regression model evaluated propranolol use and the likelihood of invasive treatments ( surgical excision or laser ) .


Of the 95 patients identified , 58 met inclusion criteria : 20 in group 1 ( mean age ,4.8 months ) , 25 in group 2 ( mean age ,4.9 months ) , and 13 in group 3 ( mean age ,4.9 months ) .


Nasal infantile hemangiomas involved the nasal tip subunit in 33 of 58 patients ( 56.9 % ) .


Eight of 13 patients ( 61.5 % ) in group 3 frequently had small NIH ( grade 1 ) .


Patients in group 2 were less likely to undergo any invasive treatments ( relative risk , 0.44 ; 95 % CI , 0.27-0 .73 ) , have surgical excision only ( 0.45 ; 0.15-1 .38 ) , or undergo laser treatment only ( 0.44 ; 0.27-0 .78 ) compared with those in group 1 .


Patients with higher-grade NIH had more medical or invasive therapy , but invasive procedures were carried out in each subgroup defined by grade .


Patients with isolated propranolol-treated NIH were less likely to undergo invasive treatment , but despite its implementation , the need for invasive treatment was not totally supplanted by its use .


A number of studies have explored the effects of dietary nitrate on human health .


Nitrate in the blood can be recycled to nitric oxide , which is an essential mediator involved in many important biochemical mechanisms .


Nitric oxide is also formed in the body from l-arginine by nitric oxide synthase .


The aim of this study was to investigate whether genetic polymorphisms in endothelial nitric oxide synthase ( eNOS ) and genes involved in folate metabolism affect the concentration of serum nitrate , serum folate , and plasma total homocysteine in healthy individuals after folic acid supplementation .


In a randomized double-blind , crossover study , participants were given either folic acid 800 g/d ( n = 52 ) or placebo ( n = 51 ) for 2 wk .


Wash-out period was 2 wk .


Fasting blood samples were collected , DNA was extracted by salting-out method and the polymorphisms in eNOS synthase and folate genes were genotyped by polymerase chain reaction methods .


Measurement of serum nitrate and plasma total homocysteine ( p-tHcy ) concentration was done by high-performance liquid chromatography .


The concentration of serum nitrate did not change in individuals after folic acid supplements ( trial 1 ) ; however , the concentration of serum nitrate increased in the same individuals after placebo ( P = 0.01 ) ( trial 2 ) .


The individuals with three polymorphisms in eNOS gene had increased concentration of serum folate and decreased concentration of p-tHcy after folic acid supplementation .


Among the seven polymorphisms tested in folate metabolizing genes , serum nitrate concentration was significantly decreased only in DHFR del 19 gene variant .


A significant difference in the concentration of serum nitrate was detected among individuals with MTHFR C > T677 polymorphisms .


Polymorphisms in eNOS and folate genes affect the concentration of serum folate and p-tHcy but do not have any effect on the concentration of NO3 in healthy individuals after folic acid supplementation .


The aim of this study was to conduct a cost-utility analysis of the Education , Self-management and Upper Limb Exercise Training in People with RA ( EXTRA ) programme compared with usual care .


A within-trial incremental cost-utility analysis was conducted with 108 participants randomized to either the EXTRA programme ( n = 52 ) or usual care ( n = 56 ) .


A health care perspective was assumed for the primary analysis with a 36 week follow-up .


Resource use information was collected on interventions , medication , primary and secondary care contacts , private health care and social care costs .


Quality-adjusted life years ( QALYs ) were calculated from the EuroQol five-dimension three-level ( EQ-5D-3L ) questionnaire responses at baseline , 12 and 36 weeks .


Compared with usual care , total QALYs gained were higher in the EXTRA programme , leading to an increase of 0.0296 QALYs .


The mean National Health Service ( NHS ) costs per participant were slightly higher in the EXTRA programme ( by 82 ) , resulting in an incremental cost-effectiveness ratio of 2770 per additional QALY gained .


Thus the EXTRA programme was cost effective from an NHS perspective when assessed against the threshold of 20 000-30 000/QALY gained .


Overall , costs were lower in the EXTRA programme compared with usual care , suggesting it was the dominant treatment option from a societal perspective .


At a willingness-to-pay of 20 000/QALY gained , there was a 65 % probability that the EXTRA programme was the most cost-effective option .


These results were robust to sensitivity analyses accounting for missing data , changing the cost perspective and removing cost outliers .


The physiotherapist-led EXTRA programme represents a cost-effective use of resources compared with usual care and leads to lower health care costs and work absence .


International Standard Randomized Controlled Trial Number Register ; http://www.controlled-trials.com/isrctn/ ( ISRCTN14268051 ) .


Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs ( NSAIDs ) are sparse .


We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women , and that this association is stronger with greater cyclooxygenase ( cox ) -2 when compared with cox-1 inhibition .


Postmenopausal women enrolled in the Women 's Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs .


Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death , nonfatal myocardial infarction , or nonfatal stroke .


Secondary analyses considered the association of selective cox-2 inhibitors ( eg , celecoxib ) , nonselective agents with cox-2 > cox-1 inhibition ( eg , naproxen ) , and nonselective agents with cox-1 > cox-2 inhibition ( eg , ibuprofen ) with the primary outcome .


Overall , 160 801 participants were available for analysis ( mean follow-up , 11.2 years ) .


Regular NSAID use at some point in time was reported by 53 142 participants .


Regular NSAID use was associated with an increased hazard for cardiovascular events versus no NSAID use ( hazard ratio [ HR ] , 1.10 ; 95 % confidence interval , 1.06-1 .15 ; P < 0.001 ) .


Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events ( hazard ratio , 1.13 ; 1.04-1 .23 ; P = 0.004 and celecoxib only : HR , 1.13 ; 1.01-1 .27 ; P = 0.031 ) .


Among aspirin users , concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for cardiovascular events .


There was an increased risk for agents with cox-2 > cox-1 inhibition ( HR , 1.17 ; 1.10-1 .24 ; P < 0.001 and naproxen only : HR , 1.22 ; 1.12-1 .34 ; P < 0.001 ) .


This harmful association remained among concomitant aspirin users .


We did not observe a risk elevation for agents with cox-1 > cox-2 inhibition ( HR , 1.01 ; 0.95-1 .07 ; P = 0.884 and ibuprofen only : HR , 1.00 ; 0.93-1 .07 ; P = 0.996 ) .


Regular use of selective cox-2 inhibitors and nonselective NSAIDs with cox-2 > cox-1 inhibition showed a modestly increased hazard for cardiovascular events .


Nonselective agents with cox-1 > cox-2 inhibition were not associated with increased cardiovascular risk .


www.clinicaltrials.gov .


Unique identifier : NCT00000611 .


To gain insight into who is likely to benefit from activity-based therapy ( ABT ) , as assessed by secondary analysis of data obtained from a clinical trial .


Secondary analysis of results from a randomized controlled trial with delayed treatment design .


Outpatient program in a private , nonprofit rehabilitation hospital .


Volunteer sample of adults ( N = 38 ; 27 men ; 11 women ; age , 22-63y ) with chronic ( 12mo postinjury ) , motor-incomplete ( American Spinal Injury Association [ ASIA ] Impairment Scale [ AIS ] grade C or D ) spinal cord injury ( SCI ) .


A total of 9h/wk of ABT for 24 weeks including developmental sequencing ; resistance training ; repetitive , patterned motor activity ; and task-specific locomotor training .


Algorithms were used to guide group allocation , functional electrical stimulation utilization , and locomotor training progression .


Walking speed and endurance ( 10-meter walk test and 6-minute walk test ) and functional ambulation ( timed Up and Go test ) .


This secondary analysis identified likely responders to ABT on the basis of injury characteristics : AIS classification , time since injury , and initial walking ability .


Training effects were the most clinically significant in AIS grade D participants with injuries < 3 years in duration .


This information , along with information about preliminary responsiveness to therapy ( gains after 12wk ) , can help predict the degree of recovery likely from participation in an ABT program .


ABT has the potential to promote neurologic recovery and enhance walking ability in individuals with chronic , motor-incomplete SCI .


However , not everyone with goals of walking recovery will benefit .


Individuals with SCI should be advised of the time , effort , and resources required to undertake ABT .


Practitioners are encouraged to use the findings from this trial to assist prospective participants in establishing realistic expectations for recovery .


The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation .


To assess the association of digoxin with cardiovascular ( CV ) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF : A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets .


The primary outcome was a composite of CV morbidity and mortality .


Secondary outcomes included CV hospitalization and all-cause mortality or heart failure ( HF ) hospitalization .


Of the 614 patients , 608 ( 99 % ) completed the dose-adjustment phase .


Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up .


The median follow-up period was 2.9 years ( interquartile range 2.7-3 .0 years ) .


In total , 284 patients ( 46.7 % ) used digoxin after the dose-adjustment phase ( median dosage 0.250 mg ; interquartile range 0.0625-0 .750 mg ) .


These patients were more often women , previously admitted for HF , had an increased left ventricular end-systolic diameter , and more often randomized to strict rate control .


By using Cox proportional hazards regression analysis , the use of digoxin was not associated with an increased risk for the primary and secondary outcomes .


For the primary outcome , the 3-year estimated cumulative incidence was 12.9 % vs 13.4 % in the digoxin group vs the no-digoxin group ( unadjusted hazard ratio [ HR ] 0.97 ; 95 % confidence interval [ CI ] 0.62-1 .52 ) .


Incidence was 19.4 % vs. 19.5 % for CV hospitalization ( unadjusted HR 1.00 ; 95 % CI 0.69-1 .45 ) and 6.6 % vs. 9.9 % for all-cause mortality or HF hospitalization ( unadjusted HR 0.62 ; 95 % CI 0.34-1 .13 ) in the digoxin group vs the no-digoxin group .


The use of digoxin was not associated with increased morbidity and mortality .


Single-port access ( SPA ) laparoscopic ovarian cystectomy has been reported as a comparable procedure to conventional laparoscopy in terms of operative outcomes .


However , whether ovarian function after SPA laparoscopic surgery is similar to conventional laparoscopy is questioned due to the limitations in moving instruments .


The aim of this study was to evaluate whether the reduced port number affects the ovarian reserve after laparoscopic ovarian cystectomy .


This was a randomized controlled trial of 87 women with benign ovarian cyst , who attended a university hospital and were scheduled for laparoscopic ovarian cystectomy .


Women were randomized to SPA , two-port access ( TPA ) , or four-port access ( FPA ) laparoscopic groups .


The primary outcome was the serum anti-Mllerian hormone ( AMH ) levels : preoperative , 1 week , 1 month and 3 months after the operation .


Secondary outcomes were operative outcomes .


The mean serum AMH levels of preoperative , 1 week , 1 month and 3 months after laparoscopy were 4.42.9 , 2.72.2 , 2.31.9 , and 2.51.5 ng/mL ( in the SPA group ) , 3.62.5 , 2.32.2 , 2.63.2 , and 2.72.6 ng/mL ( in the TPA group ) , and 3.93.2 , 2.42.1 , 2.52.0 , and 2.82.2 ng/mL ( in the FPA group ) , respectively .


There was no statistically significant difference in the serial change of AMH levels among the SPA , TPA and FPA groups .


The laparoscopic ovarian cystectomy with reduced port number does not affect the serial change of ovarian reserve .


The SPA or TPA laparoscopy may be the alternative method to conventional laparoscopy in terms of ovarian reserve .


Studies reporting that budesonide is effective for the treatment of collagenous colitis have been small and differed in efficacy measures .


Mesalamine has been proposed as a treatment option for collagenous colitis , although its efficacy has never been investigated in placebo-controlled trials .


We performed a phase 3 , placebo-controlled , multicenter study to evaluate budesonide and mesalamine as short-term treatments for collagenous colitis .


Patients with active collagenous colitis were randomly assigned to groups given pH-modified release oral budesonide capsules ( 9 mg budesonide once daily , Budenofalk , n = 30 ) , mesalamine granules ( 3 g mesalamine once daily , Salofalk , n = 25 ) , or placebo for 8 weeks ( n = 37 ) in a double-blind , double-dummy fashion .


The study was conducted in 31 centers ( hospital clinics and private practices ) in Germany , Denmark , Lithuania , Spain , and the United Kingdom .


The primary end point was clinical remission at 8 weeks defined as 3 stools per day .


Secondary end points included clinical remission at 8 weeks , according to the Hjortswang-Criteria of disease activity , taking stool consistency into account .


A greater percentage of patients in the budesonide group were in clinical remission at week 8 than the placebo group ( intention-to-treat analysis , 80.0 % vs 59.5 % ; P = .072 ; per-protocol analysis , 84.8 % vs 60.6 % ; P = .046 ) .


Based on the Hjortswang-Criteria , 80.0 % of patients given budesonide achieved clinical remission compared with 37.8 % of patients given placebo ( P = .0006 ) ; 44.0 % of patients given mesalamine achieved clinical remission , but budesonide was superior to mesalamine ( P = .0035 ) .


Budesonide significantly improved stool consistency and mucosal histology , and alleviated abdominal pain .


The rate of adverse events did not differ among groups .


Oral budesonide ( 9 mg once daily ) is effective and safe for short-term treatment of collagenous colitis .


Short-term treatment with oral mesalamine ( 3 g once daily ) appears to be ineffective .


ClinicalTrials.gov number , NCT00450086 .


In a double-blind , placebo-controlled trial ( EudraCT identifier : 2006-001795-20 ) , the standardised quality ( SQ ) house dust mite ( HDM ) sublingual immunotherapy ( SLIT ) - tablet ( ALK , Denmark ) was investigated .


The trial included 604 subjects , 14 years , with mild-moderate HDM allergic asthma .


Subjects were randomised 1:1:1:1 to 1 , 3 or 6 SQ-HDM or placebo once daily .


The primary endpoint was reduction in inhaled corticosteroid ( ICS ) after one year .


ICS reduction , asthma quality of life questionnaire ( AQLQ ) and asthma control questionnaire ( ACQ ) score was analysed post hoc in a subgroup with daily ICS use of 400-800g and ACQ score of 1-1 .5 , corresponding to partly controlled asthma ( N = 108 ) .


The trial met its primary endpoint .


In the subgroup , the difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use was 327g ( p < 0.0001 ) , while it was 0.52 ( p = 0.010 ) for AQLQ .


The treatment effect on ICS reduction and AQLQ was increased for the subgroup versus the residual population ( ICS reduction : p < 0.001 ) ; AQLQ : p = 0.044 ) .


In this subgroup , including only patients with partly controlled asthma , the benefit of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for the less severe full population , both in terms of increased asthma control and improved quality of life .


Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV .


However , this treatment 's limitations include instability at room temperature .


A new epoprostenol formulation offers improved storage conditions and patient convenience .


The EPITOME-2 trial was an open-label , prospective , multicenter , single-arm , phase IIIb study .


Patients with pulmonary arterial hypertension on long-term , stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients ( Flolan ; GlaxoSmithKline , Durham , NC ) to epoprostenol with arginine and sucrose excipients ( Veletri ; Actelion Pharmaceuticals Ltd , Allschwil , Switzerland ) .


Patients were followed up for 3 months , and dose adjustments were recorded .


Efficacy measures included the 6-minute walk distance , hemodynamics assessed by right heart catheterization , and New York Heart Association functional class .


Safety and tolerability of the transition were also evaluated .


Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication .


Forty-two patients enrolled in the study , and 1 patient withdrew consent before treatment ; thus , 41 patients received treatment and completed the study .


Six patients required dose adjustments .


There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points .


Adverse events were those previously described with intravenous prostacyclin therapy .


Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience .


Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy , raised no new safety or tolerability concerns , and provided patients with an increased sense of treatment convenience .


Bronchopulmonary dysplasia ( BPD ) is one ofthe most significant complications among very-low-birth-weight ( VLBW ) premature infants .


Vitamin A deficiency increases the risk of BPD in VLBWinfants .


To assess the effect of vitamin A supplementation for prevention of bronchopulmonary dysplasia in VLBW premature Thai infants .


Randomized control trial .


Eighty premature infants weighing < 1,500 g who received mechanical ventilation or oxygen supplementation at 24 hours ofage-admitted to Neonatal units ofSrinagarind Hospital , Khon Kaen University , Khon Kaen , Thailand-were assigned to receive either intramuscular vitaminA 5 , 000 IU3 times/week ( treatment group ) or sham procedure ( control group ) for four weeks .


Serum vitamin A levels were measured before and after administration of the vitamin A.


The baseline of mean serum vitamin A levels were similar in both groups .


The mean serum level of vitamin A was significantly higher in the vitamin A supplemented infants than in the control infants on day 7 ( 1.41 + / - 0.48 vs. 0.92 +0.38 pmol / L , p < 0.001 ) , day 14 ( 1.48 + / - 0.90 vs. 0.96 + / - 0.36 micromol/L , p = 0.001 ) and day 28 ( 1.42 + / - 0.63 vs. 0.76 + / - 0.30 micromol/L , p < 0.001 ) after vitamin A supplementation .


None of the infants in the vitamin A supplemented group , compared to 5 % of the infants in the control group , had vitamin A level < 0.35 micromol/L , ( indicating severe vitamin A deficiency ) at 28 days .


Fewer of the premature infants in the vitamin A supplemented group required oxygen supplementation at 36 weeks postmenstrual age than in the control group albeit not statistically significant ( 22.5 vs. 35 % relative risk 0.71 ; 95 % CI 0.40 + / - 1.26 ; p = 0.21 ) .


Supplementation with vitamin A was also associated with a significant reduction in the duration ofintubation ( 10.8 + / - 3.1 days vitamin A supplemented group vs. 26.1 + / - 6.4 days control group , p = 0.03 ) , days on oxygen therapy ( 29.8 + / - 5.1 days vitamin A supplemented group vs. 58.2 + / - 9.1 days control group , p = 0.01 ) and length of hospital stay ( 61.9 + / - 4.2 days vitamin A supplemented group vs. 88.3 + / - 7.2 days control group , p = 0.002 ) .


The dose of vitamin A used in this study reduced biochemical evidence of vitamin A deficiency and , without complications , resulted in reducing duration of intubation , days of oxygen therapy , and length of hospital stay in premature infants suffering VLBW


Iodine contrast medium ( ICM ) is considered gold standard in endovascular revascularization procedures .


However , nephrotoxicity and hypersensitivity to ICM are causes that limit its indiscriminate use .


Carbon dioxide ( CO2 ) contrast angiography has been used as an alternative in patients with formal contraindication to ICM .


However , no studies to the present date have compared in a randomized and prospective way , outcomes of revascularization procedures performed with either ICM or CO2 in patients eligible for use of both contrasts .


Between April 2012 and April 2013 , 35 patients with peripheral arterial disease with arterial lesions classified as Trans-Atlantic Inter-Society Consensus A or B ( identified on preoperative angio computed tomography scan ) and adequate runoff underwent femoropopliteal revascularization by endovascular technique in a prospective , randomized , and controlled study .


Patients were randomized into 2 groups : CO2 group and ICM group , according to the contrast media selected of the procedure .


We evaluated the following outcomes in both groups : feasibility of the procedures , complications , surgical outcomes ( ankle-brachial index [ ABI ] ) , glomerular filtration rate using the Cockcroft-Gault formula , relationship between the volume of injected iodine and postoperative creatinine clearance , quality of the angiographic images obtained with CO2 , costs of the endovascular materials , and finally , cost of contrast agents .


We were able to perform the proposed procedures in all patients treated in this series ( ICM group and CO2 ) .


There were no CO2-related complications .


No procedures required conversion to open surgery .


Clinical results were satisfactory , with regression of ischemia and increased levels of ABI in both groups .


Variations in creatinine clearance levels showed a numerical increase in the CO2 group and a decrease in ICM group , however , with no statistically significant difference between the delta clearance in each group .


All CO2 arteriograms of the supragenicular arteries were graded as good or fair by both observers with high interobserver image quality concordance .


There was no statistical difference between endovascular material costs between the groups , but the contrast cost was significantly lower in CO2 group ( P < 0.001 ) .


The use of CO2 in patients with no restriction for ICM is an alternative that does not limit the feasibility of the procedures .


Similar outcomes were observed with CO2 when compared with the gold standard contrast ( ICM ) regarding quality of images produced , with no associated changes in creatinine clearance or hypersensitivity reactions and also allows a reduction in contrast-related costs in angioplasty procedures .


Negative emotional states and abnormal stress reactivity are central components in drug addiction .


The brain stress system in the amygdala is thought to play a key role in the maintenance of drug dependence through negative reinforcement .


Although acute heroin administration was found to reduce anxiety , craving , and stress hormone release , whether these effects are reflected in amygdala activity has not yet been investigated .


With a randomized , crossover , double-blind design , saline and heroin were administered to 22 heroin-dependent patients , whereas 17 healthy control subjects were included for the placebo administration only .


We used functional magnetic resonance imaging to investigate blood oxygen level-dependent responses during fearful faces processing .


Stress reactivity was measured by adrenocorticotropic hormone levels and by cortisol concentrations in serum and saliva 60 min after substance administration .


Anxiety and craving levels were assessed with self-report ratings .


Heroin administration acutely reduced the left amygdala response to fearful faces relative to the saline injection .


Patients receiving saline showed a significantly higher left amygdala response to fearful faces than healthy control subjects , whose activity did not differ from patients receiving heroin .


The left amygdala activity correlated significantly with scores on state-anxiety and levels of adrenocorticotropic hormone , serum cortisol , and saliva cortisol among all patients and control subjects .


Our results show a direct relation between the acute heroin effects on stress-related emotions , stress reactivity , and left amygdala response to negative facial expressions .


These findings provide new insights into the mechanisms underlying negative reinforcement in heroin addiction and the effects of regular heroin substitution .


Impairments of muscle function and strength in patients with primary hyperparathyroidism ( PHPT ) are rarely addressed , although decreased muscle function may contribute to increased fracture risk .


We aimed to assess the changes in muscle strength , muscle function , postural stability , quality of life ( QoL ) , and well-being during treatment with vitamin D or placebo before and after parathyroidectomy ( PTX ) in PHPT patients .


A randomized placebo-controlled trial .


We included 46 PHPT patients , mean age 58 ( range 29-77 ) years and 35 ( 76 % ) were women .


Daily treatment with 70g ( 2800IU ) cholecalciferol or placebo for 52 weeks .


Treatment was administered 26 weeks before PTX and continued for 26 weeks after PTX .


Changes in QoL and measures of muscle strength and function .


Preoperatively , 25-hydroxyvitamin D ( 25OHD ) increased significantly ( 50-94nmol / l ) compared with placebo ( 57-52nmol / l ) .


We did not measure any beneficial effects of supplementation with vitamin D compared with placebo regarding well-being , QoL , postural stability , muscle strength , or function .


In all patients , we measured marked improvements in QoL , well-being ( P < 0.01 ) , muscle strength in the knee flexion and extension ( P < 0.001 ) , and muscle function tests ( P < 0.01 ) after surgical cure .


Postural stability improved during standing with eyes closed ( P < 0.05 ) , but decreased with eyes open ( P < 0.05 ) .


Patients with PHPT and 25OHD levels around 50nmol/l did not benefit from vitamin D supplementation concerning muscle strength , muscle function , postural stability , well-being , or QoL .


Independent of preoperative 25OHD levels , PTX improved these parameters .


It has been assumed that the increase in urine calcium ( Ca ) that accompanies an increase in dietary protein was due to increased bone resorption .


However , studies using stable Ca isotopes have found that dietary protein increases Ca absorption without increasing bone resorption .


The objective of the study was to investigate the impact of a moderately high protein diet on bone mineral density ( BMD ) .


This was a randomized , double-blind , placebo-controlled trial of protein supplementation daily for 18 months .


The study was conducted at two institutional research centers .


Two hundred eight older women and men with a body mass index between 19 and 32 kg/m ( 2 ) and a self-reported protein intake between 0.6 and 1.0 g/kg participated in the study .


Subjects were asked to incorporate either a 45-g whey protein or isocaloric maltodextrin supplement into their usual diet for 18 months .


BMD by dual-energy x-ray absorptiometry , body composition , and markers of skeletal and mineral metabolism were measured at baseline and at 9 and 18 months .


There were no significant differences between groups for changes in L-spine BMD ( primary outcome ) or the other skeletal sites of interest .


Truncal lean mass was significantly higher in the protein group at 18 months ( P = .048 ) .


C-terminal telopeptide ( P = .0414 ) , IGF-1 ( P = .0054 ) , and urinary urea ( P < .001 ) were also higher in the protein group at the end of the study period .


There was no difference in estimated glomerular filtration rate at 18 months .


Our data suggest that protein supplementation above the recommended dietary allowance ( 0.8 g/kg ) may preserve fat-free mass without adversely affecting skeletal health or renal function in healthy older adults .


To assess whether add-back therapy with norethindrone acetate or norethindrone acetate plus conjugated equine estrogens is superior to maintain bone health in adolescents and young women using gonadotropin-releasing hormone agonists for endometriosis .


Gonadotropin-releasing hormone agonists are associated with deleterious effects on bone .


Hormonal add-back may mitigate these effects .


Adolescents and young women ( n = 51 ) received a random , double-blind assignment to add-back with norethindrone acetate ( 5 mg/day ) plus conjugated equine estrogens ( 0.625 mg/day ) or norethindrone acetate plus placebo for 12 months .


Body composition , bone mineral content , and bone mineral density ( BMD ) were obtained by dual-energy X-ray absorptiometry every 6 months .


Quality-of-life measures were collected every 3 months .


Intention-to-treat comparison of outcomes was conducted by repeated-measures analysis of variance .


Thirty-four adolescents and young women completed the trial ; dropouts did not differ from those who completed the trial .


Bone mineral density was normal at baseline .


At 12 months , total body bone mineral content and BMD had increased in the norethindrone acetate plus conjugated equine estrogens group ( bone mineral content +37 g , P < .001 and BMD +0.012 g/cm , P = .05 ) , but not in those receiving norethindrone acetate plus placebo ( bone mineral content P = .19 and BMD P = .95 ) .


Lean mass increased only in those receiving conjugated equine estrogens ( +1.4 kg , P = .001 ) .


Improvements in physical functioning domains of quality-of-life assessments were greater with norethindrone acetate plus conjugated equine estrogens ( P = .005 ) .


No differences were seen at the hip or lumbar spine by dual-energy X-ray absorptiometry .


No significant adverse events occurred .


Hormonal add-back successfully preserved bone health and improved quality of life for adolescents and young women with endometriosis during 12 months of gonadotropin-releasing hormone agonist therapy .


Combination norethindrone acetate plus conjugated equine estrogens add-back appears to be more effective for increasing total body bone mineral content , areal BMD , and lean mass than norethindrone acetate monotherapy .


ClinicalTrials.gov ; www.clinicaltrials.gov , NCT00474851 .


I.


Summarizes the frequency , type , and context of sexual assault in a large sample of first-year university women at three Canadian universities .


As part of a randomized controlled trial assessing the efficacy of a sexual assault resistance education program , baseline data were collected from women between ages of 17 and 24 using computerized surveys .


Participants ' experience with sexual victimization since the age of 14 years was assessed using the Sexual Experiences Survey -- Short Form Victimization ( SES-SFV ) .


Among 899 first-year university women ( mean age = 18.5 years ) , 58.7 % ( 95 % CI : 55.4 % , 62.0 % ) had experienced one or more forms of victimization since the age of 14 years , 35.0 % ( 95 % CI : 31.9 % , 38.3 % ) had experienced at least one completed or attempted rape , and 23.5 % ( 95 % CI : 20.7 % , 26.4 % ) had been raped .


Among the 211 rape victims , 46.4 % ( 95 % CI : 39.7 % , 53.2 % ) had experienced more than one type of assault ( oral , vaginal , anal ) in a single incident or across multiple incidents .


More than three-quarters ( 79.6 % ; 95 % CI : 74.2 % , 85.1 % ) of the rapes occurred while women were incapacitated by alcohol or drugs .


One-third ( 33.3 % ) of women had previous self-defence training , but few ( 4.0 % ) had previous sexual assault education .


Findings from the first large Canadian study of university women since the 1990s indicate that a large proportion of women arrive on campuses with histories of sexual victimization , and they are generally unprepared for the perpetrators they may face during their academic years .


There is an urgent need for effective rape prevention programs on university campuses .


ClinicalTrials.gov NCT01338428 .


Registered 13 April 2011 .


Non-response bias is a major problem for the validity of survey answers .


Analyses of reasons for non-response in surveys with nursing home residents ( NHR ) are scarce .


The aim of this study was to develop reliable and valid categories which represent reasons for non-response in nursing homes using the `` Prozessmodell induktiver Kategorienbildung '' following Mayring ( 2010 ) .


Furthermore , characteristics of unit non-responder and responder were compared .


Forming of categories of reasons for non-response was conducted with 522 NHR , longitudinally .


Four major categories were identified ( general refusal , health reasons , accessibility , excessive demand ) and further 17 subcategories .


Unit-non-responder and responder did not differ in age and sex ; however follow-up non-responder showed differences in marital status , training qualification , and cognitive status .


The presented scheme of categories can be used to assess reasons for non-response in nursing homes .


Standardised assessment of reasons for non-response may contribute to higher response rates in this setting .


Many patients with quiescent Crohn 's disease are maintained on long-term treatment with azathioprine ( AZA ) , but controlled data are limited .


We aimed to evaluate the efficacy of AZA therapy for more than 4 years to maintain clinical remission .


We performed a randomized double-blind placebo-controlled AZA withdrawal trial with a follow-up period of 24 months .


Patients had to have continuous AZA therapy 4 years without exacerbation of disease during the 12 months before enrollment , and a Crohn 's disease activity index < 150 at baseline .


Patients were randomized to continue on AZA or switch to placebo .


The primary endpoint was time to clinical relapse during follow-up .


After inclusion of 52 patients , the trial was stopped prematurely due to slow recruitment .


During the 2-year follow-up , clinical relapse occurred in 4 of 26 ( 15 % ) patients on continued AZA and in 8 of 26 ( 31 % ) patients on placebo .


Time to clinical relapse averaged 22.3 months ( 95 % CI 20.6-24 .0 ) on AZA and 19.2 months ( 95 % CI 16.4-22 .1 ) on placebo ( p = 0.20 ) .


According to life-table analysis , the proportion of patients in remission after 12 and 24 months was 96 4 and 86 7 % in patients receiving AZA versus 76 8 and 68 9 % in patients receiving placebo ( month 12 , p = 0.035 ; month 24 , p = 0.30 ) .


A higher AZA dose at enrollment was an independent predictor for relapse ( p < 0.05 ) .


AZA withdrawal resulted in a significantly increased relapse risk after 1 year and a nonstatistically significant trend for relapse after 2 years .


Our results are in line with previous observations .


Suboptimal availability of circulating thyroid hormones may contribute to the high rate of treatment failures in bipolar disorder .


This study tested the efficacy of adjunctive treatment with supraphysiologic doses of levothyroxine in patients with bipolar depression and the hypothesis that women would display a better outcome compared to men .


The aims of this multicenter , 6-week , double-blind , randomized , placebo-controlled fixed-dose ( 300 g/d ) trial conducted from 2004 to 2009 were to assess efficacy and tolerability of levothyroxine adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication for patients with bipolar I or II disorder , currently depressed ( DSM-IV ) , and to investigate gender differences in treatment response .


The primary efficacy variable was mean change in Hamilton Depression Rating Scale ( HDRS ) score .


Of 74 patients enrolled in the study , 62 ( 35 with bipolar I ; mean age = 44.9 years ) were randomized .


Mean change in HDRS score from randomization to week 6 was larger in the levothyroxine group compared to the placebo group , with a 2.7-point difference ( decline of -7.8 [ 38.3 % ] vs -5.1 [ 25.5 % ] ; last-observation-carried-forward analysis ) .


The course of HDRS scores over time from randomization to week 6 was significantly different between groups at week 4 ( P = .046 ) but not at the end of the placebo-controlled phase ( P = .198 ) .


The secondary analysis of women ( n = 32 ) revealed a significant difference between groups in mean change in HDRS score ( -16.6 % placebo vs -42.4 % levothyroxine , P = .018 ) .


A mixed-effects model for repeated-measures analysis showed a significant between-group difference in HDRS score ( 6.8 , P = .012 ) for women .


High thyroid-stimulating hormone levels , indicating suboptimal levels of circulating thyroid hormones , were predictive for positive treatment outcome in women treated with levothyroxine in a linear regression model ( F3 = 3.47 ; P = .05 ) .


This trial demonstrated that patients treated with levothyroxine did numerically better than those treated with placebo ; however , the study failed to detect a statistically significant difference between the 2 groups in the primary outcome measure due to a high placebo response rate .


Previous findings that women show better improvement in depression scores with levothyroxine compared to men were confirmed .


ClinicalTrials.gov identifier : NCT01528839 .


Exercise training has been demonstrated to enhance physical function and to have a protective effect against functional limitations and disability in older adults .


The objective of this study was to determine whether the effects of a home-based , DVD-delivered exercise intervention on functional performance and limitations were maintained 6-month postintervention termination .


Follow-up assessments of functional performance and limitations were conducted in a sample of community-dwelling older adults ( N = 237 ) who participated in a 6-month randomized controlled exercise trial .


Participants were initially randomized to a DVD-delivered exercise intervention or an attentional control condition .


The Short Physical Performance Battery , measures of flexibility and strength , and functional limitations were assessed immediately before and after the intervention and then again 6 months later .


Analyses of covariance were conducted to examine changes in physical function between the two conditions at the end of the intervention to 6-month follow-up .


There were statistically significant adjusted group differences in the Short Physical Performance Battery ( ( 2 ) = 0.03 , p = .01 ) , upper-body strength ( ( 2 ) = 0.03 , p = .005 ) , and lower-body flexibility ( ( 2 ) = 0.02 , p = .05 ) , indicating that gains brought about by the intervention were maintained 6 months later .


A DVD-delivered exercise program specifically designed to target elements of functional fitness in older adults can produce clinically meaningful gains in physical function that are maintained beyond intervention cessation .


NEPA is a novel oral fixed-dose combination of netupitant ( NETU ) , a new highly selective neurokinin-1 ( NK1 ) receptor antagonist ( RA ) and palonosetron ( PALO ) , a pharmacologically and clinically distinct 5-hydroxytryptamine type 3 ( 5-HT3 ) RA .


This study was designed to determine the appropriate clinical dose of NETU to combine with PALO for evaluation in the phase 3 NEPA program .


This randomized , double-blind , parallel group study in 694 chemotherapy nave patients undergoing cisplatin-based chemotherapy for solid tumors compared three different oral doses of NETU ( 100 , 200 , and 300 mg ) + PALO 0.50 mg with oral PALO 0.50 mg , all given on day 1 .


A standard 3-day aprepitant ( APR ) + IV ondansetron ( OND ) 32 mg regimen was included as an exploratory arm .


All patients received oral dexamethasone on days 1-4 .


The primary efficacy endpoint was complete response ( CR : no emesis , no rescue medication ) during the overall ( 0-120 h ) phase .


All NEPA doses showed superior overall CR rates compared with PALO ( 87.4 % , 87.6 % , and 89.6 % for NEPA100 , NEPA200 , and NEPA300 , respectively versus 76.5 % PALO ; P < 0.050 ) with the highest NEPA300 dose studied showing an incremental benefit over lower NEPA doses for all efficacy endpoints .


NEPA300 was significantly more effective than PALO and numerically better than APR + OND for all secondary efficacy endpoints of no emesis , no significant nausea , and complete protection ( CR plus no significant nausea ) rates during the acute ( 0-24 h ) , delayed ( 25-120 h ) , and overall phases .


Adverse events were comparable across groups with no dose response .


The percent of patients developing electrocardiogram changes was also comparable .


Each NEPA dose provided superior prevention of chemotherapy-induced nausea and vomiting ( CINV ) compared with PALO following highly emetogenic chemotherapy ; however , NEPA300 was the best dose studied , with an advantage over lower doses for all efficacy endpoints .


The combination of NETU and PALO was well tolerated with a similar safety profile to PALO and APR + OND .


GSK1265744 ( 744 ) is an HIV-1 integrase inhibitor in clinical development as a long-acting ( LA ) injectable formulation .


This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular ( IM ) or subcutaneous injections .


This was a phase I , open-label , 9-cohort , parallel study of 744 in healthy subjects .


744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous .


Eight ( 6 active and 2 placebo ) male and female subjects participated in each of the first 7 cohorts .


All 8 subjects , 4 males and 4 females , received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling , respectively .


Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were 0.1 g/mL .


Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 ( cohort 8 ) and weeks 4 and 12 ( cohort 9 ) .


744 LA was generally safe and well tolerated after single injections .


A majority of subjects reported injection site reactions , all graded as mild in intensity .


Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing .


744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks .


Rectal and cervicovaginal tissue concentrations ranged from < 8 % to 28 % of corresponding plasma concentrations .


These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent .


The aim of this study was to investigate patient reported outcomes ( PROs ) of functional ability and health related quality of life ( HRQoL ) in patients with early ( rheumatoid ) arthritis during one year of remission steered treatment .


In this study , 610 patients with early rheumatoid arthritis ( RA ) or undifferentiated arthritis ( UA ) were treated with methotrexate ( MTX ) and tapered high dose of prednisone .


Patients in early remission ( Disease Activity Score ( DAS ) < 1.6 after 4 months ) tapered prednisone to zero and when in persistent remission , also tapered MTX .


Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone ( arm 1 ) or to MTX + adalimumab ( arm 2 ) .


Every 4 months , patients filled out the Health Assessment Questionnaire ( HAQ ) and the McMaster Toronto Arthritis Patient Preference Questionnaire ( MACTAR ) , the Short Form 36 ( SF-36 ) and visual analogue scales ( VAS ) .


Change scores were compared between treatment groups .


The association with achieving remission was analyzed using linear mixed models .


During year 1 , patients who achieved early remission had the most improvement in PROs with scores comparable to the general population .


Patients in the randomization arms showed less improvement .


Scores were comparable between the arms .


There was a significant association between achieving remission and scores of HAQ , MACTAR and physical HRQoL .


In early arthritis , PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission .


In patients not in early remission , who were randomized to two strategy arms , PROs improved less , with similar scores in both treatment arms .


ISRCTN11916566 and EudraCT2006-006186-16 .


Addition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) whose symptoms are insufficiently controlled by bronchodilator monotherapy .


GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting 2-agonist indacaterol ( IND ) and the long-acting muscarinic antagonist glycopyrronium ( GLY ) versus IND alone in patients with moderate-to-severe COPD .


In this randomized , double-blind , parallel group , placebo-controlled , 12-week study , patients were randomized 1:1 to IND 150 g and GLY 50 g daily ( IND + GLY ) or IND 150 g daily and placebo ( IND + PBO ) ( all delivered via separate Breezhaler devices ) .


The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second ( FEV1 ) at week 12 .


Other end points included trough FEV1 at day 1 , FEV1 area under the curve from 30 minutes to 4 hours ( AUC30min-4h ) , peak FEV1 , inspiratory capacity and trough forced vital capacity ( FVC ) at day 1 and week 12 , and transition dyspnea index ( TDI ) focal score , COPD symptoms , and rescue medication use over 12 weeks .


A total of 449 patients were randomized ( IND + GLY , 226 ; IND + PBO , 223 ) ; 94 % completed the study .


On day 1 and at week 12 , IND + GLY significantly improved trough FEV1 versus IND + PBO , with treatment differences of 74 mL ( 95 % CI 46-101 mL ) and 64 mL ( 95 % CI 28-99 mL ) , respectively ( both P < 0.001 ) .


IND + GLY significantly improved postdose peak FEV1 , FEV1 AUC30min-4h , and trough FVC at day 1 and week 12 versus IND + PBO ( all P < 0.01 ) .


TDI focal score and COPD symptoms ( percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score ) were significantly improved with IND + GLY versus IND + PBO ( P < 0.05 ) .


The incidence of adverse events was similar for the two treatment groups .


In patients with moderate-to-severe COPD , once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1 , with significant improvements in patient-centered outcomes .


The DBCG 77C trial compared one year of tamoxifen in postmenopausal , steroid-receptor unknown , high-risk breast cancer patients to no adjuvant systemic therapy .


After a potential follow-up of 30years we report overall efficacy of the study and results according to subtypes subsequently assessed by immunohistochemistry and fluorescent in situ hybridisation ( FISH ) .


Between 1977 and 1982 , 1716 postmenopausal patients with tumours larger than 5cm or positive axillary nodes were randomly assigned to no systemic therapy or tamoxifen 30mg daily for one year .


Archival tumour tissue from 1515 patients was analysed and the hormone receptor positive ( estrogen receptor ( ER ) and/or progesterone receptor ( PR ) ) cancers were defined as luminal A if Ki67 low and HER2-negative ; as luminal B if Ki67 high or HER2-positive ; and otherwise as non-luminal-HER2 positive or triple negative .


In the intent-to-treat ( ITT ) population one year of tamoxifen improved the disease-free-survival ( DFS ) ( hazard ratio ( HR ) = 0.87 ; 95 % confidence interval ( CI ) 0.77-0 .98 ) , the Breast Cancer Recurrence Rate ( BCRR ) ( HR = 0.79 ; 0.69-0 .90 ) and reduced the breast-cancer-specific-mortality ( BCM ) ( HR = 0.83 ; 0.73-0 .93 ) .


BCRR were improved significantly by tamoxifen in luminal A ( HR = 0.66 ; 0.53-0 .84 ) and luminal B/HER2 - ( HR = 0.54 ; 0.39-0 .74 ) but not in the other subsets , and with similar results for BCM with 30years follow-up .


One year of treatment with tamoxifen significantly improves BCRR and BCM in postmenopausal patients with ER positive breast cancers .


The relative benefit from tamoxifen was not significantly different in luminal A and B subtypes .


The Danish Breast Cancer Cooperative Group ( DBCG ) prepared the original protocol ( DBCG 77C ) and was the sponsor of the study .


Funding was not provided to the participating departments .


The biomarker study was supported by grants from the Clinical Institute , Odense University .


For patients with advanced cancer , visits to the emergency department ( ED ) are common .


Such patients present to the ED with a specific profile of palliative care needs , including burdensome symptoms such as pain , dyspnea , or vomiting that can not be controlled in other settings and a lack of well-defined goals of care .


The goals of this study are : i ) to test the feasibility of recruiting , enrolling , and randomizing patients with serious illness in the ED ; and ii ) to evaluate the impact of ED-initiated palliative care on health care utilization , quality of life , and survival .


This is a protocol for a single center parallel , two-arm randomized controlled trial in ED patients with metastatic solid tumors comparing ED-initiated palliative care referral to a control group receiving usual care .


We plan to enroll 125 to 150 ED-advanced cancer patients at Mount Sinai Hospital in New York , USA , who meet the following criteria : i ) pass a brief cognitive screen ; ii ) speak fluent English or Spanish ; and iii ) have never been seen by palliative care .


We will use balanced block randomization in groups of 50 to assign patients to the intervention or control group after completion of a baseline questionnaire .


All research staff performing assessment or analysis will be blinded to patient assignment .


We will measure the impact of the palliative care intervention on the following outcomes : i ) timing and rate of palliative care consultation ; ii ) quality of life and depression at 12 weeks , measured using the FACT-G and PHQ-9 ; iii ) health care utilization ; and iv ) length of survival .


The primary analysis will be based on intention-to-treat .


This pilot randomized controlled trial will test the feasibility of recruiting , enrolling , and randomizing patients with advanced cancer in the ED , and provide a preliminary estimate of the impact of palliative care referral on health care utilization , quality of life , and survival .


Clinical Trials.gov identifier : NCT01358110 ( Entered 5/19/2011 ) .


The objective of this randomised trial was to compare surgical rotator cuff repair to simple decompression by acromioplasty and biceps tenotomy in patients older than 60 years of age with a mean follow-up of 4 years .


Tendon repair produces better functional outcomes than simple decompression and prevents progression towards cuff tear arthropathy in the longer term .


Of 130 initially included patients older than 60 years of age and having rotator cuff tears deemed amenable to surgical repair , 103 ( 79 % ) were evaluated after a mean of 4 years .


These patients had been randomly allocated to acromioplasty and tenotomy ( AT group , n = 49 ) or to acromioplasty , tenotomy , and tendon suture ( CR group , n = 54 ) .


The tear was distal in 41 patients , intermediate in 40 , and retracted in 22 .


At last follow-up , the evaluation included the clinical Constant 's Score , radiographs and , in the CR group , ultrasonography .


The complication rate was 4 % .


The mean Constant Score was 44 preoperatively ; values after 4 years were 76 overall ( P = 0.01 ) , 78 in the CR group , and 73 in the AT group ( P = 0.01 ) .


The tendon-healing rate as assessed using ultrasonography was 63 % .


The Constant Score was significantly better when tendon healing was achieved ( 82/73 , P < 0.001 ) .


In the AT group , the acromio-humeral distance was significantly shorter ( 6.9 mm/7 .8 mm , P = 0.03 ) and eccentric humeral head position was more common ( 44 % / 26 % , P = 0.01 ) .


Arthroscopic rotator cuff repair provides better functional outcomes than does simple decompression in patients older than 60 years and prevents cuff tear arthropathy with eccentric humeral head position in the medium term .


Tendon healing is the main determinant of outcomes after rotator cuff repair .


II , randomised trial .


Medication regimens for asthma are particularly vulnerable to adherence problems because of the requirement for long-term use and periods of symptom remission experienced by patients .


Pharmacists are suited to impact medication adherence given their training , skills , and frequent contact with patients .


The Empowering pharmacists in asthma management through interactive SMS ( EmPhAsIS ) trial involves an intervention leveraging mobile health ( mHealth ) technology to support community pharmacy practice with the hypothesis of improved medication adherence in asthma .


This study is a pragmatic pharmacy-based , cluster , randomized controlled trial with 12months of intervention delivery and follow-up .


Pharmacies ( the clusters ) will be randomized at a 1:1 ratio to provide intervention or usual care .


The EmPhAsIS intervention consists of patient asthma education , short message service ( SMS ) - based monthly assessment of adherence , and follow-up of non-adherent individuals by community pharmacists .


There are no inclusion or exclusion criteria for pharmacies .


Patients are eligible if they : are 14years of age or older , fill a prescription for inhaled corticosteroid ( either monotherapy or in a combination inhaler with long-acting beta-agonists ) , have been diagnosed with asthma , possess a mobile phone with SMS capabilities , and have no communication difficulties such as inability to communicate in English , or significant impairment in vision , hearing , or speech .


The primary outcome is adherence to inhaled corticosteroids ascertained by the medication possession ratio , the ratio of the days of medication supplied to days in a given time interval .


This study will also evaluate secondary outcomes including : asthma control , asthma-related quality of life , asthma-related hospital admissions , and use of reliever medications during the follow-up period .


A nested economic evaluation using a probabilistic decision-analytic model will be used to perform a cost-effectiveness analysis from the societal perspective of the intervention compared with usual care over a 10-year time horizon .


Considering the prevalence of asthma , the extent of the non-adherence problem in this disease , and the availability of effective treatments , there is a tremendous potential to reduce the burden of asthma through improving adherence .


This is the first study of an intervention based on mobile communication technology involving community pharmacists in asthma management .


ClinicalTrials.gov identifier : NCT02170883 ; date of registration : 19 June 2014 .


To determine if aspheric intraocular lens ( IOL ) implantation produces the same degree of postoperative ocular aberration and contrast sensitivity as spherical IOL implantation .


In this randomized prospective comparative study , 60 eyes of 30 cataract surgery patients were randomly assigned to receive a spherical IOL ( Rayner 620H ) in one eye and an aspheric IOL ( Rayner 920H ) in the contralateral eye .


All patients were examined at 1 month postoperatively .


Primary outcomes of contrast sensitivity and ocular wavefront higher order aberrations ( HOAs ) were assessed .


Aspheric IOLs ( median total HOAs 0.26 root mean square [ RMS ] ; range 0.13-0 .82 RMS ) produced significantly lower total HOAs than spherical IOLs ( median total HOAs 0.34 RMS ; range 0.18-1 .08 RMS ; p < 0.05 ) .


Contrast sensitivity was significantly better with aspheric IOLs ( median contrast sensitivity 1.8 log units ; range 1.35-1 .8 log units ) than with spherical IOLs ( median contrast sensitivity 1.65 log units ; range 1.35-1 .8 log units ; p < 0.05 ) .


When compared with a structurally ( platform and material ) similar spherical IOL ( Rayner 620H ) , aspheric IOLs ( Rayner 920H ) appear to significantly reduce HOAs and yield better levels of contrast sensitivity under photopic conditions .


The aim of this study was to evaluate , under farm conditions , the use of a teat sealant in addition to whole herd dry cow antibiotic therapy on the risk of clinical mastitis in dairy cattle at pasture , and to evaluate the impact of dry period length on that risk and the impact of the teat sealant on that risk .


Dairy cows in three herds which used routine whole herd antibiotic therapy were randomly assigned to receive either treatment with an internal teat sealant ( n = 322 ) or no additional treatment ( n = 313 ) at drying-off between March and May 2010 .


All clinical mastitis cases during the dry period and to the end of the subsequent lactation were recorded by farm staff ; factors affecting risk of clinical mastitis were then analysed using a Cox proportional hazards model .


Median duration of the dry period was 112 days with > 25 % of cows having a dry period > 130 days .


The incidence risk of mastitis during lactation for cows treated with teat sealant was 9.9 ( 95 % CI = 6.9-13 .7 ) cases per 100 cows compared with 17.9 ( 95 % CI = 13.8-22 .6 ) cases per 100 cows for cows treated with antibiotic alone .


The addition of a teat sealant to dry cow antibiotic therapy decreased the risk of clinical mastitis only in the first 33 days after calving ( Hazard risk 0.24 ( 95 % CI = 0.12-0 .48 ) ) .


Length of dry period did not significantly affect the risk of clinical mastitis , or the effect of adding teat sealant to dry cow antibiotic therapy on the risk of clinical mastitis .


In these herds where , based on the mastitis history , whole herd antibiotic therapy had been recommended , the use of a teat sealant significantly reduced the risk of clinical mastitis .


This effect was limited to the first 33 days after calving ; subsequently there was no significant effect of treatment .


There was no effect of dry period length on risk of clinical mastitis , nor any significant interaction with treatment .


Combination therapy with teat sealant and antibiotic was effective under New Zealand conditions in herds using whole herd antibiotic treatment at drying off .


Teat sealant reduced risk of clinical mastitis in cattle with dry periods substantially longer than 100 days , and there was no evidence that this effect changed as dry period length increased .


To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus ( SLE ) who require cyclophosphamide therapy , to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment , and to investigate the safety of triptorelin .


In this randomized , double-blind , placebo-controlled , dose-escalation study , female patients ages < 21 years were randomized 4:1 to receive triptorelin ( n = 25 ) or placebo ( n = 6 ) .


The starting doses of triptorelin were 25 , 50 , 75 , and 100 g/kg , and the dose was escalated until complete ovarian suppression was maintained .


The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90 % of the patients , as determined by gonadotropin-releasing hormone agonist stimulation testing .


The secondary outcome was the period of time required to achieve ovarian suppression , as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment .


Treatment with triptorelin at a weight-adjusted dose of 120 g/kg body weight provided sustained complete ovarian suppression in 90 % of the patients .


After administration of the initial dose of triptorelin , 22 days were required to achieve complete ovarian suppression .


The rates of adverse events ( AEs ) and serious adverse events ( SAEs ) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group ( for AEs , 189 versus 362 ; for SAEs , 2.1 versus 8.5 ) .


High doses of triptorelin are needed to achieve and maintain complete ovarian suppression , but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE .


Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued .


To examine the association between baseline body mass index ( BMI ) , and disease-free survival ( DFS ) and overall survival ( OS ) in a large French early-stage breast cancer population included in the UNICANCER Programme d'Action Concert Sein-01 ( PACS01 ) and PACS04 phase III randomised trials .


After a median follow-up of 5.9 years , this report analyses 4996 patients with node-positive breast cancer , and randomly assigned to adjuvant anthracycline-based chemotherapy combined or not with taxanes .


Univariate analyses were used to study the effects of well known prognostic factors and BMI on DFS and OS .


BMI was obtained at baseline , before chemotherapy initiation , and obesity was defined as a BMI30kg/m ( 2 ) .


Cox proportional hazards regression models were secondly used to assess the influence of BMI after adjusting for other factors .


Exhaustive analysis of the dose intensity delivered was also studied for comparison between obese and non-obese patients .


Obese patients initially present with more advanced disease at diagnosis compared to non-obese patients .


By univariate analysis , obesity was moderately associated with poorer DFS ( hazard ratio ( HR ) = 1.18 [ 1.01-1 .39 ] P = 0.04 ) , but mostly with poorer OS ( HR = 1.38 [ 1.13-1 .69 ] P = 0.002 ) .


Delivered dose intensity of anthracyclines and taxanes was not significantly different between obese and non-obese patients .


After adjustment for disease characteristics , BMI had no influence either on DFS or OS .


This report suggests that in a French population , obesity has no impact on breast cancer prognosis when modern adjuvant chemotherapy , at the appropriate dose intensity , is delivered .


We demonstrated the effectiveness of an accelerated hepatitis B vaccination schedule in drug users .


We compared the long-term effectiveness of accelerated ( 0-1-2 months ) and standard ( 0-1-6 months ) hepatitis B vaccination schedules in preventing hepatitis B virus ( HBV ) infections and anti-hepatitis B ( anti-HBs ) antibody loss during 2-year follow-up in 707 drug users ( HIV and HBV negative at enrollment and completed 3 vaccine doses ) from February 2004 to October 2009 .


Drug users in the accelerated schedule group had significantly lower HBV infection rates , but had a similar rate of anti-HBs antibody loss compared with the standard schedule group over 2 years of follow-up .


No chronic HBV infections were observed .


Hepatitis C positivity at enrollment and age younger than 40 years were independent risk factors for HBV infection and antibody loss , respectively .


An accelerated vaccination schedule was more preferable than a standard vaccination schedule in preventing HBV infections in drug users .


To overcome the disadvantages of a standard vaccination schedule , an accelerated vaccination schedule should be considered in drug users with low adherence .


Our study should be repeated in different cohorts to validate our findings and establish the role of an accelerated schedule in hepatitis B vaccination guidelines for drug users .


Insect bite hypersensitivity ( IBH ) is a common cause of pruritus in horses , but there are few controlled studies on the efficacy of allergen-specific immunotherapy ( ASIT ) .


Atopic dermatitis and IBH can present with overlapping clinical signs ; multiple insect and environmental allergens could be indicated in these horses to achieve effective hyposensitization .


Although the success of ASIT using Culicoides spp .


whole-body extracts is controversial , there are no controlled studies published that clearly show benefit from this form of therapy .


The objective was to evaluate the efficacy of ASIT in horses with IBH using commercially available extracts and tests .


Twenty horses with seasonal pruritus and positive intradermal reactions to a whole Culicoides extract .


An enzyme-linked immunosorbent assay test ( Allercept ( ) ) was used to detect concurrent allergen-specific IgE for other insects and environmental allergens .


The ASIT was formulated by adding the relevant serologically positive allergens to the Culicoides extract .


After randomization , 10 horses received ASIT and the rest a placebo solution .


Clinical response was assessed every 4 months during 1 year using a clinical scoring system based on the severity of four clinical signs at 10 different body regions .


Horses were not stabled and , to minimize dropouts , an insect repellent was used weekly in both groups .


Differences in clinical scores between groups were nonsignificant at any re-evaluation , while both groups improved to a similar extent , probably due to the insecticide treatment .


Using commercially available extracts and tests , we could not demonstrate a beneficial effect of 1 year multiple ASIT in nonstabled horses with IBH .


Expanded access to efficacious interventions is needed for women living with human immunodeficiency virus ( WLH ) in the United States .


Availability of `` prevention with ( human immunodeficiency virus [ HIV ) ] positives '' interventions in rural/remote and low HIV prevalence areas remains limited , leaving WLH in these communities few options for receiving effective behavioral interventions such as Healthy Relationships ( HR ) .


Offering such programs via videoconferencing groups ( VGs ) may expand access .


This analysis tests the effectiveness of HR-VG ( versus wait-list control ) for reducing sexual risk behavior among WLH and explores intervention satisfaction .


In this randomized controlled trial unprotected vaginal/anal sex occasions over the prior 3 months reported at the 6-month follow-up were compared across randomization groups through zero-inflated Poisson regression modeling , controlling for unprotected sex at baseline .


Seventy-one WLH were randomized and completed the baseline assessment ( n = 36 intervention and n = 35 control ) ; 59 ( 83 % in each group ) had follow-up data .


Among those who engaged in unprotected sex at 6-month follow-up , intervention participants had approximately seven fewer unprotected occasions than control participants ( 95 % confidence interval 5.43-7 .43 ) .


Intervention participants reported high levels of satisfaction with HR-VG ; 84 % reported being `` very satisfied '' overall .


This study found promising evidence for effective dissemination of HIV risk reduction interventions via VGs .


Important next steps will be to determine whether VGs are effective with other subpopulations of people living with HIV ( i.e. , men and non-English speakers ) and to assess cost-effectiveness .


Possibilities for using VGs to expand access to other psychosocial and behavioral interventions and reduce stigma are discussed .


We determined the efficacy and cost-effectiveness of adding an evidence-based Internet behavioral weight loss intervention alone or combined with optional group sessions to ShapeUp Rhode Island 2011 ( SURI ) , a 3-month statewide wellness campaign .


We randomized participants ( n = 230 ; body mass index = 34.3 6.8 kg/m ( 2 ) ; 84 % female ) to the standard SURI program ( S ) or to 1 of 2 enhanced programs : SURI plus Internet behavioral program ( SI ) or SI plus optional group sessions ( SIG ) .


The primary outcome was weight loss at the end of the 3-month program .


Weight losses differed among all 3 conditions ( S : 1.1 % 0.9 % ; SI : 4.2 % 0.6 % ; SIG : 6.1 % 0.6 % ; Ps .04 ) .


Both SI and SIG increased the percentage of individuals who achieved a 5 % weight loss ( SI : 42 % ; SIG : 54 % ; S : 7 % ; Ps < .001 ) .


Cost per kilogram of weight loss was similar for S ( $ 39 ) and SI ( $ 35 ) ; both were lower than SIG ( $ 114 ) .


Although weight losses were greatest at the end of SURI with optional group sessions , the addition of an Internet behavioral program was the most cost-effective method to enhance weight losses .


Individuals with major depressive disorder ( MDD ) are characterized by maladaptive responses to both positive and negative outcomes , which have been linked to localized abnormal activations in cortical and striatal brain regions .


However , the exact neural circuitry implicated in such abnormalities remains largely unexplored .


In this study 26 unmedicated adults with MDD and 29 matched healthy controls ( HCs ) completed a monetary incentive delay task during functional magnetic resonance imaging ( fMRI ) .


Psychophysiological interaction ( PPI ) analyses probed group differences in connectivity separately in response to positive and negative outcomes ( i.e. monetary gains and penalties ) .


Relative to HCs , MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex ( dACC ) in response to monetary gains , yet increased connectivity between the caudate and a different , more rostral , dACC subregion in response to monetary penalties .


Moreover , exploratory analyses of 14 MDD patients who completed a 12-week , double-blind , placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later .


These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD , and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response .


Given the role of cortico-striatal circuitry in encoding action-outcome contingencies , such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD .


To assess the performance of QuantiFERON-TB Gold In-Tube ( QFT-GIT ) test for active tuberculosis ( TB ) in HIV adults , and its variation over time in patients on antiretroviral therapy ( ART ) and/or isoniazide preventive therapy ( IPT ) .


Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization , with or without a 6-month IPT .


Performance of QFT-GIT for detecting active TB at baseline in the first 50 % participants , and 12-month incidence of conversion/reversion in the first 25 % participants were assessed .


QFT-GIT threshold for positivity was 0.35 IU/ml .


Among the 975 first participants ( median baseline CD4 count 383/mm3 , positive QFT-GIT test 35 % ) , 2.7 % had active TB at baseline .


QFT-GIT sensitivity , specificity , positive and negative predictive value for active TB were 88.0 % , 66.6 % , 6.5 % and 99.5 % .


For the 444 patients with a second test at 12 months , rates for conversion and reversion were 9.3 % and 14 % .


Reversion was more frequent in patients without ART and younger patients .


IPT and early ART were not associated with reversion/conversion .


A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed , thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases .


ClinicalTrials.gov NCT00495651 .


The aim of the work is to study histomorphometric and histochemical properties of jaw bone loss in patients with full or partial edentulism , need to restoring their dentition integrity by dental implantation .


Cytological studies were carried out in 83 patients , among which normal bone mass was observed in 28 patients ( 17 women and 11 men ) , osteopenia in 26 patients ( 17 women and 9 men ) , osteoporosis in 29 ( 19 women and 10 men ) patients .


Histological examination of bone biopsies were performed in 76 patients , among which normal bone mass was observed in 22 ( 16 women and 6 men , osteopenia in 26 patients ( 17 women and 9 men ) , osteoporosis in 28 ( 19 women and 9 men ) patients .


Histomorphometric analysis of `` implant-bone '' contact in the entire length of the joint in patients with normal bone mass was 61.8 + / - 3.7 % , with osteopenia was 51.6 + / - 3.0 % , with osteoporosis was 46.1 + / - 2.8 % .


The intensity of bone remodeling in patients with normal bone mass was 2.7 + / - 0.19 , in patients with osteopenia was 2.2 + / - 0.14 , in patients with osteoporosis was 1.8 + / - 0.11 .


This demonstrates the significant difference between the patients with normal bone mass and osteoporotic patients .


The `` implant-bone '' interface in osteoporotic patients was significantly lower than in patients with normal bone mass .


Histomorphometric studies and quantitative histochemical analysis revealed that the decrease of bone mineral mass in patients often combined with a decrease of the `` implant surface-bone '' site contact area , with atrophy and with hypoplasia of perimplant tissues .


Since the 1990s , fluorouracil-based adjuvant chemotherapy has significantly reduced the risk of tumour recurrence in patients with stage III colon cancer .


We aimed to assess whether the addition of cetuximab to standard adjuvant oxaliplatin , fluorouracil , and leucovorin chemotherapy ( FOLFOX4 ) in patients with stage III colon cancer improved disease-free survival ( DFS ) .


For this open-label , randomised phase 3 study done in nine European countries , we enrolled patients through an interactive voice response system to the central randomisation centre , with a central stratified permuted block randomisation procedure .


We randomly assigned patients with resected ( R0 ) stage III disease ( 1:1 ) to receive 12 cycles of FOLFOX4 twice a week with or without cetuximab .


Patients were stratified by N-status ( N1 vs N2 ) , T-status ( T1-3 vs T4 ) , and obstruction or perforation status ( no obstruction and no perforation vs obstruction or perforation or both ) .


A protocol amendment ( applied in June , 2008 , after 2096 patients had been randomly assigned to treatment-restricted enrolment to patients with tumours wild-type at codons 12 and 13 in exon 2 of the KRAS gene ( KRAS exon 2 wild-type ) .


The primary endpoint was DFS .


Analysis was intention to treat in all patients with KRAS exon 2 wild-type tumours .


The study is registered at EudraCT , number 2005-003463-23 .


Between Dec 22 , 2005 , and Nov 5 , 2009 , 2559 patients from 340 sites in Europe were randomly assigned .


Of these patients , 1602 had KRAS exon 2 wild-type tumours ( intention-to-treat population ) , 791 in the FOLFOX4 plus cetuximab group and 811 in the FOLFOX4 group .


Median follow-up was 33 years ( IQR 32-34 ) .


In the experimental and control groups , DFS was similar in the intention-to-treat population ( hazard ratio [ HR ] 105 ; 95 % CI 085-129 ; p = 066 ) , and in patients with KRAS exon 2/BRAF wild-type ( n = 984 , HR 099 ; 95 % CI 076-128 ) or KRAS exon 2-mutated tumours ( n = 742 , HR 106 ; 95 % CI 082-137 ) .


We noted heterogeneous responses to the addition of cetuximab in preplanned subgroup analyses .


Grade 3 or 4 acne-like rash ( in 209 of 785 patients [ 27 % ] vs four of 805 [ < 1 % ] ) , diarrhoea ( 113 [ 14 % ] vs 70 [ 9 % ] ) , mucositis ( 63 [ 8 % ] vs 10 [ 1 % ] ) , and infusion-related reactions ( 55 [ 7 % ] vs 30 [ 4 % ] ) were more frequent in patients treated with FOLFOX4 plus cetuximab than in those patients who received FOLFOX4 alone .


The addition of cetuximab to FOLFOX4 did not improve DFS compared with FOLFOX4 alone in patients with KRAS exon 2 wild-type resected stage III colon cancer .


This trial can not conclude on the benefit of cetuximab in the studied population , but the heterogeneity of response suggests that further investigation of the role of FOLFOX4 plus cetuximab in specific patient subgroups is warranted .


Fdration Francophone de Cancrologie Digestive ( FFCD ) , Merck KGaA , and Sanofi-Aventis .


Low back pain is highly prevalent and a significant public health burden in Western society .


Feasibility studies suggest personalised pedometer-driven walking is an acceptable and effective motivating tool in the management of chronic low back pain ( CLBP12weeks ) .


The proposed study will investigate pedometer-driven walking as a low cost , easily accessible , and sustainable means of physical activity to improve disability and clinical outcomes for people with CLBP in Saskatchewan , Canada .


A fully-powered single-blinded randomised controlled trial will compare back care advice and education with back care advice and education followed by a 12-week pedometer-driven walking programme in adults with CLBP .


Adults with self-reported CLBP will be recruited from the community and screened for elibility .


Two-hundred participants will be randomly allocated to one of two intervention groups .


All participants will receive a single back care advice and education session with a physiotherapist .


Participants in the walking group will also receive a physiotherapist-facilitated pedometer based walking programme .


The physiotherapist will facilitate the participant to monitor and progress the walking programme , by phone , on a weekly basis over 10weeks following two face-to-face sessions .


Outcome measures of self-reported disability , physical activity , participants ' low back pain beliefs/perceptions , quality of life and direct/indirect cost estimates will be gathered at baseline , three months , six months , and 12months by a different physiotherapist blinded to group allocation .


Following intervention , focus groups will be used to explore participants ' thoughts and experiences of pedometer-driven walking as a management tool for CLBP .


This paper describes the design of a community-based RCT to determine the effectiveness of a pedometer-driven walking programme in the management of CLBP .


United States National Institutes of Health Clinical Trails registry ( http://ClinicalTrails.gov/ ) No .


NCT02284958 .


Registered on 27 ( th ) October 2014 ) .


This randomised , open label , phase I , immunotherapeutic study investigated the effects of interleukin ( IL ) -2 , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , recombinant human growth hormone ( rhGH ) , and therapeutic immunisation ( a Clade B DNA vaccine ) on combination antiretroviral therapy ( cART ) - treated HIV-1-infected individuals , with the objective to reverse residual T-cell dysfunction .


Twelve HIV-1 ( + ) patients on suppressive cART with baseline CD4 T-cell counts > 400 cells/mm ( 3 ) blood were randomised into one of three groups : ( 1 ) vaccine , IL-2 , GM-CSF and rhGH ( n = 3 ) ; ( 2 ) vaccine alone ( n = 4 ) ; or ( 3 ) IL-2 , GM-CSF and rhGH ( n = 5 ) .


Samples were collected at weeks 0 , 1 , 2 , 4 , 6 , 8 , 12 , 16 , 24 and 48 .


Interferon ( IFN ) - , IL-2 , IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24 , Nef , Rev , and Tat peptides ; and detailed T-cell immunophenotyping was undertaken by flow cytometry .


Proviral DNA was also measured .


Median baseline CD4 T-cell count was 757 cells/mm ( 3 ) ( interquartile range [ IQR ] 567-886 cells/mm ( 3 ) ) , median age 48 years ( IQR 42-51 years ) , and plasma HIV-1-RNA < 50 copies/ml for all subjects .


Patients who received vaccine plus IL-2 , GM-CSF and rhGH ( group 1 ) showed the most marked changes .


Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells ( p = 0.0083 ) and improved CD4/CD8 T-cell ratios ( p = 0.0033 ) .


This was accompanied by a significant reduction in expression of CD38 on CD4 T cells ( p = 0.0194 ) , significantly increased IFN - and IL-2 production in response to Gag ( p = 0.0122 ) and elevated IFN - production in response to Tat ( p = 0.041 ) at week 48 compared to baseline .


Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline , with some reductions in proviral DNA .