At year 3 of follow-up , 27.3 % of Hispanic women who were normotensive at baseline had progressed to prehypertension , and 9.0 % had become hypertensive .


Among the prehypertensive participants at baseline , 30.4 % had progressed to hypertension .


Compared with normotensive Hispanic women , hypertensive participants had a higher number of cardiovascular risk factors : body mass index 30 kg/m ( 2 ) ( OR = 3.76 ; 95 % CI = 3.01-4 .71 ) , a family history of diabetes , stroke , and/or myocardial infarction ( OR = 1.12 ; 95 % CI 1.03-1 .23 ) , treated hypercholesterolemia ( OR = 1.57 ; 95 % CI = 1.23-1 .99 ) , treated diabetes ( OR = 2.04 ; 95 % CI = 1.40-2 .97 ) , and a history of cardiovascular disease ( OR = 2.04 ; 95 % CI = 1.58-2 .64 ) .


Hispanic women seem to experience an increased risk of incident hypertension in later adulthood .


On a practical level , recommendations for preventive care and population-wide adoption of health behaviors , such as community-focused campaigns to engage in physical activity , may contribute to reductions in hypertension risk factors .


Trial Number NCT00000611 .


Since the 1970s , MORA bioresonance therapy has globally been applied in the context of complementary medicine for various indications .


In this regard , practitioners also report successful application in smoking cessation .


The present study aims to verify these reports in a controlled study setting .


In order to achieve the aforementioned objective , we subjected the bioresonance method to a prospective , placebo-controlled , double-blind , parallel-group study involving 190 smokers .


In both study groups ( placebo n = 95 ; active bioresonance group ; n = 95 ) the course of treatment and study conditions were standardized .


1 week ( 77.2 % vs. 54.8 % ) , 2 weeks ( 62.4 % vs. 34.4 % ) , 1 month ( 51.1 % vs. 28.6 % ) , and 1 year ( 28.6 % vs. 16.1 % ) after treatment , the success rate in the verum group differed significantly from the results in the placebo group .


Also , the subjective health condition after treatment and subjective assessment of efficacy , polled after 1 week , were significantly more positive among participants in the active bioresonance therapy group than among those in the placebo group .


Adverse side effects were not observed .


According to the findings attained by this pilot study , bioresonance therapy is clinically effective in smoking cessation and does not show any adverse side effects .


Graves ' orbitopathy ( GO ) is a potentially sight-threatening disease for which available medical therapy is not uniformly successful .


Multiple case series suggest that rituximab ( RTX ) may be effective therapy for GO patients .


To determine the efficacy of RTX in GO .


It is a prospective , randomized , double-masked , placebo-controlled trial .


The study was conducted at a large academic private practice .


Twenty five patients with active moderate to severe GO were enrolled , and 21 completed the study to the primary endpoint .


Two RTX infusions ( 1000 mg each ) or two saline infusions were given 2 weeks apart .


The primary endpoint was a reduction in clinical activity score ( CAS ) assessed as a continuum and separately as improvement by 2 points at 24 weeks .


Secondary endpoints included success and failure rates , proportions showing clinically significant improvement in proptosis , lid fissure width , diplopia score , lagophthalmos and disease severity , and changes in those parameters , orbital fat / muscle volume and quality-of-life .


The treatment groups were similar in all parameters at baseline .


The last observation was carried forward if the patient discontinued prematurely .


No differences were found in the proportions of patients showing CAS improvement at 24 weeks ( 25 % placebo ; 31 % RTX , P = .75 ) or in CAS decrease from baseline to 24 or 52 weeks [ mean 1.5 points ( 1.8 SD ) placebo ; 1.2 ( 2 SD ) RTX at 24 weeks , P = .73 ] .


Similarly , there were no differences between groups in any of the secondary endpoints at either 24 or 52 weeks .


There were four adverse events ( AE ) in 3/12 placebo patients and 11 AE in 8/13 RTX-treated patients ; 5/6 moderate or severe AE occurred in the RTX group .


RTX offered no additional benefit over placebo to our patients with active and moderate to severe GO and carried with it non-negligible adverse effects .


Borderline personality disorder ( BPD ) is a severe and highly prevalent mental disorder .


Schema therapy ( ST ) has been found effective in the treatment of BPD and is commonly delivered through an individual format .


A group format ( group schema therapy , GST ) has also been developed .


GST has been found to speed up and amplify the treatment effects found for individual ST. Delivery in a group format may lead to improved cost-effectiveness .


An important question is how GST compares to treatment as usual ( TAU ) and what format for delivery of schema therapy ( format A ; intensive group therapy only , or format B ; a combination of group and individual therapy ) produces the best outcomes .


An international , multicentre randomized controlled trial ( RCT ) will be conducted with a minimum of fourteen participating centres .


Each centre will recruit multiple cohorts of at least sixteen patients .


GST formats as well as the orders in which they are delivered to successive cohorts will be balanced .


Within countries that contribute an uneven number of sites , the orders of GST formats will be balanced within a difference of one .


The RCT is designed to include a minimum of 448 patients with BPD .


The primary clinical outcome measure will be BPD severity .


Secondary clinical outcome measures will include measures of BPD and general psychiatric symptoms , schemas and schema modes , social functioning and quality of life .


Furthermore , an economic evaluation that consists of cost-effectiveness and cost-utility analyses will be performed using a societal perspective .


Lastly , additional investigations will be carried out that include an assessment of the integrity of GST , a qualitative study on patients ' and therapists ' experiences with GST , and studies on variables that might influence the effectiveness of GST .


This trial will compare GST to TAU for patients with BPD as well as two different formats for the delivery of GST .


By combining an evaluation of clinical effectiveness , an economic evaluation and additional investigations , it will contribute to an evidence-based understanding of which treatment should be offered to patients with BPD from clinical , economic , and stakeholders ' perspectives .


Netherlands Trial Register NTR2392 .


Registered 25 June 2010 .


Nonsteroidal anti-inflammatory drugs relieve osteoarthritis ( OA ) symptoms but cause adverse effects .


D-002 , a mixture of beeswax alcohols , is effective against experimental OA .


A pilot study found that D-002 ( 50 mg/day ) for 8 weeks improves OA symptoms .


The aim of this study was to investigate the effects of D-002 ( 50 to 100 mg/day ) administered for 6 weeks on OA symptoms .


Patients with OA symptoms were double-blindly randomized to D-002 ( 50 mg ) or placebo for 6 weeks .


Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index ( WOMAC ) and the visual analog scale ( VAS ) scores .


Patients without symptom improvement at week 3 were titrated to two daily tablets .


The primary outcome was the total WOMAC score .


WOMAC pain , joint stiffness and physical function scores , VAS score , and use of rescue medications were secondary outcomes .


All randomized patients ( n = 60 ) completed the study , and 23 experienced dose titration ( two in the D-002 and 21 in the placebo groups ) .


At study completion , D-002 reduced total WOMAC ( 65.4 % ) , pain ( 54.9 % ) , joint stiffness ( 76.8 % ) , and physical function ( 66.9 % ) WOMAC scores , and the VAS score ( 46.8 % ) versus placebo .


These reductions were significant beginning in the second week , and became enhanced during the trial .


The use of rescue medication by the D-002 ( 6/30 ) group was lower than that in the placebo ( 17/30 ) group .


The treatment was well tolerated .


Seven patients ( two in the D-002 and five in the placebo group ) reported adverse events .


These results indicate that D-002 ( 50 to 100 mg/day ) for 6 weeks ameliorated arthritic symptoms and was well tolerated .


To present the short-term follow-up findings of the Steps to Health study , a randomized trial to evaluate the effectiveness of two employee weight management programs offered within Duke University and the Health System .


A total of 550 obese ( body mass index , 30 kg/m2 ) employees were randomized 1:1 between January 2011 and June 2012 to the education-based Weight Management ( WM ) or the WM + arm , which focused on behavior modification .


Employees were contacted to complete a follow-up visit approximately 14 months after baseline .


There were no clinically , or statistically , meaningful differences between arms , but there were modest reductions in body mass index , and positive , meaningful changes in diet and physical activity for both arms .


The modest positive effects observed in this study may suggest that to achieve weight loss through the workplace more intensive interventions may be required .


Treatment of neonates and infants with adrenal insufficiency is unsatisfactory because unlicensed hydrocortisone formulations are used .


The objectives were to survey current hydrocortisone prescribing practice and develop a novel hydrocortisone formulation , Infacort .


The use of hydrocortisone by European pediatric endocrinologists was surveyed .


Based on this , an oral hydrocortisone granule formulation , Infacort , with taste masking was developed and evaluated in vitro and then in vivo in a phase I pharmacokinetic study .


The survey showed that pediatricians use a variety of unlicensed compounded adult medications at doses of between 0.5 and 5 mg .


Infacort was formulated with a taste-masking layer stable for at least 5 minutes in aqueous media and was produced in unit doses of 0.5 , 1 , 2 , and 5 mg .


Infacort 10 mg is the bioequivalent of a 10-mg hydrocortisone tablet ( mean area under the curve from zero to infinity [ AUC ( 0-inf ) ] ratio , 101 % ; 90 % confidence interval , 96-107 % ) .


Mean cortisol maximum concentration ( C ( max ) ) and AUC ( 0-inf ) values after administration of Infacort were linear with dose and dose proportional when adjusted for saturable plasma protein binding .


Subjects rated Infacort as `` not good or bad '' for smell ( 86 % ) , feel in the mouth ( 71 % ) , and taste ( 79 % ) .


No serious adverse events were reported .


This phase 1 study demonstrates that Infacort is safe , well tolerated , of neutral taste , bioequivalent to hydrocortisone licensed for adults , and shows dose proportionality with respect to cortisol exposure .


Infacort is expected to facilitate optimization of hydrocortisone dosing in neonates and children with adrenal insufficiency ; however , clinical studies will be required to demonstrate efficacy in this patient age group .


Late-onset infections commonly occur in extremely preterm infants and are associated with high rates of mortality and neurodevelopmental impairment .


Hand hygiene alone does not always achieve the desired clean hands , as microorganisms are still present more than 50 % of the time .


We hypothesize that glove use after hand hygiene may further decrease these infections .


To determine if nonsterile glove use after hand hygiene before all patient and intravenous catheter contact , compared with hand hygiene alone , prevents late-onset infections in preterm infants .


A prospective , single-center , clinical , randomized trial was conducted in infants admitted to the neonatal intensive care unit who weighed less than 1000 g and/or had a gestational age of less than 29 weeks and were less than 8 days old .


There were 175 eligible infants , of which 120 were enrolled during a 30-month period from December 8 , 2008 , to June 20 , 2011 .


Infants were randomly assigned to receive care with nonsterile gloves after hand hygiene ( group A ) or care after hand hygiene alone ( group B ) before all patient and intravenous line ( central and peripheral ) contact .


Study intervention was continued while patients had central or peripheral venous access .


One or more episodes of late-onset ( > 72 hours of age ) infection in the bloodstream , urinary tract , or cerebrospinal fluid or necrotizing enterocolitis .


The 2 groups were similar in baseline demographic characteristics .


Late-onset invasive infection or necrotizing enterocolitis occurred in 32 % of infants ( 19 of 60 ) in group A compared with 45 % of infants ( 27 of 60 ) in group B ( difference , -12 % ; 95 % CI , -28 % to 6 % ; P = .13 ) .


In group A compared with group B , there were 53 % fewer gram-positive bloodstream infections ( 15 % [ 9 of 60 ] vs 32 % [ 19 of 60 ] ; difference , -17 % ; 95 % CI , -31 % to -1 % ; P = .03 ) and 64 % fewer central line-associated bloodstream infections ( 3.4 vs 9.4 per 1000 central line days ; ratio , 0.36 ; 95 % CI , 0.16 to 0.81 ; P = .01 ) .


Glove use after hand hygiene prior to patient and line contact is associated with fewer gram-positive bloodstream infections and possible central line-associated bloodstream infections in preterm infants .


This readily implementable infection control measure may result in decreased infections in high-risk preterm infants .


clinicaltrials.gov Identifier : NCT01729000 .


Retrospective analysis of prospectively collected follow-up data for 2.9 years .


To determine the natural history of subsequent morphometric fracture rates at adjacent levels ( one level above or below a previous known baseline fracture ) in a large patient database .


The long-term risk and risk factors for adjacent-level vertebral fractures in patients with osteoporosis are unknown .


The fracture intervention trial is a large randomized , placebo-controlled trial of alendronate treatment for osteoporosis .


Data from both bisphosphonate-treated and bisphosphonate-naive patients ( N = 1950 , vertebral fracture arm ) was analyzed to detect incident morphometric fracture rates .


During a mean follow-up of 2.9 years , 3.4 % of patients in the alendronate group and 7.4 % in the placebo group experienced adjacent-level vertebral fractures .


The annual rate of adjacent-level vertebral fractures was 1.2 % in the alendronate group , and 2.5 % in the placebo group ( overall , 1.8 % per year in both groups combined ) .


As expected , the thoracolumbar region ( defined as T11 , T12 , and L1 ) seemed to be the most prone to new adjacent-level fractures .


Among females with baseline prevalent fractures at the thoracolumbar junction , who subsequently experienced at least one new fracture anywhere along the spine ( N = 124 ) , 40.3 % had a new adjacent-level fracture in this region .


Older age at randomization , lower bone mineral density , inactivity , and placebo therapy were significantly associated with the development of adjacent-level fractures in univariate analysis ( P 0.05 ) .


Multivariate analysis indicated decreased odds of adjacent-level fractures with bisphosphonate therapy and higher bone mineral density , and increased odds with older age at randomization ( P 0.05 ) .


New vertebral fractures adjacent to prevalent fractures occurred relatively infrequently in this treatment trial of alendronate in females with osteoporosis , and were more common with older age at randomization , lower bone mineral density and placebo treatment .


Observational studies suggest that vitamin D may lower the risk of type 2 diabetes .


However , data from long-term trials are lacking .


The Vitamin D and Type 2 Diabetes ( D2d ) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes .


D2d was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) .


The final protocol was approved by the D2d Research Group , the data and safety monitoring board , and NIDDK .


Key eligibility criteria are age 30 years , BMI of 24 ( 22.5 for Asian Americans ) to 42 kg/m ( 2 ) , increased risk for diabetes ( defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association [ fasting glucose 100-125 mg/dL ( 5.5-6 .9 mmol/L ) , 2-h postload glucose after 75-g glucose load 140-199 mg/dL ( 7.7-11 .0 mmol/L ) , hemoglobin Ac 5.7-6 .4 % ( 39-46 mmol/mol ) ] ) , and no hyperparathyroidism , nephrolithiasis , or hypercalcemia .


D2d participants are randomized to once-daily vitamin D ( cholecalciferol 4,000 IU ) or placebo and followed for an average of 3 years .


The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D2d .


Recruitment was initiated at the end of 2013 .


D2d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type 2 diabetes .


Increasing numbers of patients are surviving critical illness , but survival may be associated with a constellation of physical and psychological sequelae that can cause ongoing disability and reduced health-related quality of life .


Limited evidence currently exists to guide the optimum structure , timing , and content of rehabilitation programmes .


There is a need to both develop and evaluate interventions to support and expedite recovery during the post-ICU discharge period .


This paper describes the construct development for a complex rehabilitation intervention intended to promote physical recovery following critical illness .


The intervention is currently being evaluated in a randomised trial ( ISRCTN09412438 ; funder Chief Scientists Office , Scotland ) .


The intervention was developed using the Medical Research Council ( MRC ) framework for developing complex healthcare interventions .


We ensured representation from a wide variety of stakeholders including content experts from multiple specialties , methodologists , and patient representation .


The intervention construct was initially based on literature review , local observational and audit work , qualitative studies with ICU survivors , and brainstorming activities .


Iterative refinement was aided by the publication of a National Institute for Health and Care Excellence guideline ( No. 83 ) , publicly available patient stories ( Healthtalkonline ) , a stakeholder event in collaboration with the James Lind Alliance , and local piloting .


Modelling and further work involved a feasibility trial and development of a novel generic rehabilitation assistant ( GRA ) role .


Several rounds of external peer review during successive funding applications also contributed to development .


The final construct for the complex intervention involved a dedicated GRA trained to pre-defined competencies across multiple rehabilitation domains ( physiotherapy , dietetics , occupational therapy , and speech/language therapy ) , with specific training in post-critical illness issues .


The intervention was from ICU discharge to 3 months post-discharge , including inpatient and post-hospital discharge elements .


Clear strategies to provide information to patients/families were included .


A detailed taxonomy was developed to define and describe the processes undertaken , and capture them during the trial .


The detailed process measure description , together with a range of patient , health service , and economic outcomes were successfully mapped on to the modified CONSORT recommendations for reporting non-pharmacologic trial interventions .


The MRC complex intervention framework was an effective guide to developing a novel post-ICU rehabilitation intervention .


Combining a clearly defined new healthcare role with a detailed taxonomy of process and activity enabled the intervention to be clearly described for the purpose of trial delivery and reporting .


These data will be useful when interpreting the results of the randomised trial , will increase internal and external trial validity , and help others implement the intervention if the intervention proves clinically and cost effective .


Foot musculoskeletal deficits are seldom addressed by preventive medicine despite their high prevalence in patients with diabetic polyneuropathy .


To investigate the effects of strengthening , stretching , and functional training on foot rollover process during gait .


A two-arm parallel-group randomized controlled trial with a blinded assessor was designed .


Fifty-five patients diagnosed with diabetic polyneuropathy , 45 to 65 years-old were recruited .


Exercises for foot-ankle and gait training were administered twice a week , for 12 weeks , to 26 patients assigned to the intervention group , while 29 patients assigned to control group received recommended standard medical care : pharmacological treatment for diabetes and foot care instructions .


Both groups were assessed after 12 weeks , and the intervention group at follow-up ( 24 weeks ) .


Primary outcomes involved foot rollover changes during gait , including peak pressure ( PP ) .


Secondary outcomes involved time-to-peak pressure ( TPP ) and pressure-time integral ( PTI ) in six foot-areas , mean center of pressure ( COP ) velocity , ankle kinematics and kinetics in the sagittal plane , intrinsic and extrinsic muscle function , and functional tests of foot and ankle .


Even though the intervention group primary outcome ( PP ) showed a not statistically significant change under the six foot areas , intention-to-treat comparisons yielded softening of heel strike ( delayed heel TPP , p = .03 ) , better eccentric control of forefoot contact ( decrease in ankle extensor moment , p < .01 ; increase in function of ankle dorsiflexion , p < .05 ) , earlier lateral forefoot contact with respect to medial forefoot ( TPP anticipation , p < .01 ) , and increased participation of hallux ( increased PP and PTI , p = .03 ) and toes ( increase in PTI , medium effect size ) .


A slower COP mean velocity ( p = .05 ) , and an increase in overall foot and ankle function ( p < .05 ) were also observed .


In most cases , the values returned to baseline after the follow-up ( p < .05 ) .


Intervention discreetly changed foot rollover towards a more physiological process , supported by improved plantar pressure distribution and better functional condition of the foot ankle complex .


Continuous monitoring of the foot status and patient education are necessary , and can contribute to preserving the integrity of foot muscles and joints impaired by polyneuropathy .


ClinicalTrials.gov Identifier : NCT01207284 , registered in 20th September 2010 .


In the Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease , all patients were at high cardiovascular risk , and a substantial proportion were hypertensive .


We performed a post-hoc analysis to explore the hypothesis that telmisartan has a differential action in hypertensive vs. nonhypertensive patients .


The primary four-fold endpoint ( composite of cardiovascular death , myocardial infarction ( MI ) , stroke , or hospitalization for heart failure ) , the secondary three-fold endpoint ( cardiovascular death , MI , and stroke ) , the individual components , new onset of left ventricular hypertrophy ( LVH ) , and new onset of albuminuria were analyzed .


There was no evidence for a significantly differential treatment effect of telmisartan in hypertensive and nonhypertensive patients for any endpoints , although the occurrence of the secondary three-fold endpoint was significantly lower in the telmisartan group ( 13.0 % ) compared with placebo ( 15.0 % , P < 0.05 ) only in hypertensive patients .


Moreover , data from this post-hoc analysis suggest that MI may be less frequent in hypertensive patients treated with telmisartan ( 3.8 vs. 5.1 % ; P < 0.05 ) .


Telmisartan may also reduce new onset of LVH ( nonhypertensive patients P < 0.05 ; hypertensive patients P < 0.001 ) in both subgroups , and new onset of microalbuminuria and macroalbuminuria in hypertensive patients ( P < 0.001 and P < 0.01 , respectively ) .


The effect of telmisartan in hypertensive and nonhypertensive patients at high cardiovascular risk was not different .


This post-hoc analysis suggests that MI may be further reduced by telmisartan in hypertensive patients .


Further investigations are needed to study the hypotheses raised by this explanatory analysis .


It is now recognized that preterm infants 28weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure .


However , this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency , with the result that intubation and delayed surfactant therapy are then required .


Infants following this path are known to have a higher risk of adverse outcomes , including death , bronchopulmonary dysplasia and other morbidities .


In an effort to circumvent this problem , techniques of minimally-invasive surfactant therapy have been developed , in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure .


A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea ( the `` Hobart method '' ) has been shown to be feasible and potentially effective , and now requires evaluation in a randomised controlled trial .


This is a multicentre , randomised , masked , controlled trial in preterm infants 25-28 weeks gestation .


Infants are eligible if managed on continuous positive airway pressure without prior intubation , and requiring FiO20 .30 at an age 6hours .


Randomisation will be to receive exogenous surfactant ( 200mg/kg poractant alfa ) via the Hobart method , or sham treatment .


Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached ( FiO20 .45 , unremitting apnoea or persistent acidosis ) .


Primary outcome is the composite of death or physiological bronchopulmonary dysplasia , with secondary outcomes including incidence of death ; major neonatal morbidities ; durations of all modes of respiratory support and hospitalisation ; safety of the Hobart method ; and outcome at 2years .


A total of 606 infants will be enrolled .


The trial will be conducted in > 30 centres worldwide , and is expected to be completed by end-2017 .


Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants .


The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation .


Australia and New Zealand Clinical Trial Registry : ACTRN12611000916943 ; ClinicalTrials.gov : NCT02140580 .


Patients with excessive daytime sleepiness ( EDS ) are at high risk for driving accidents , and physicians are concerned by the effect of alerting drugs on driving skills of sleepy patients .


No study has up to now investigated the effect of modafinil ( a reference drug to treat EDS in patients with hypersomnia ) on on-road driving performance of patients suffering from central hypersomnia .


The objective is to evaluate in patients with central hypersomnia the effect of a wake-promoting drug on real driving performance and to assess the relationship between objective sleepiness and driving performance .


Randomized , crossover , double-blind placebo-controlled trial conducted among 13 patients with narcolepsy and 14 patients with idiopathic hypersomnia .


Patients were randomly assigned to receive modafinil ( 400 mg ) or placebo for 5 days prior to the driving test .


Each condition was separated by at least 3 weeks of washout .


Mean number of Inappropriate Line Crossings , Standard Deviation of Lateral Position of the vehicle and mean sleep latency in the Maintenance of Wakefulness Test were assessed .


Modafinil reduced the mean number of Inappropriate Line Crossings and Standard Deviation of Lateral Position of the vehicle compared to placebo ( F ( 1,25 ) = 4.88 , P < 0.05 and F ( 1,25 ) = 3.87 , P = 0.06 tendency ) .


Mean sleep latency at the Maintenance of Wakefulness Test significantly correlated with the mean number of Inappropriate Line Crossings ( r = -0.41 , P < 0.001 ) .


Modafinil improves driving performance in patients with narcolepsy and idiopathic hypersomnia .


The Maintenance of Wakefulness Test is a suitable clinical tool to assess fitness to drive in this population .


Healthy gut microflora is essential for oral tolerance and immunity .


A promising approach to preventing allergic diseases in genetically at-risk infants is to introduce administration of probiotics early in life when their immune system is still relatively immature .


In this follow-up study , we aim to determine if early-life supplementation with strains of probiotics has any long-term effect on allergic outcomes .


We analyzed the charts and electronic databases of the PROMPT ( Probiotics in Milk for the Prevention of Atopy Trial ) study cohort .


This cohort consisted of 253 infants at risk for allergy who were administered cow 's milk supplemented with or without probiotics from the first day of life to the age of 6 months .


The cohort was then followed up until the children were 5 years old and clinical outcomes were assessed .


Of the 253 children recruited into the study , 220 ( 87 % ) completed the follow-up .


At the age of 5 years , there were no significant differences between the groups in the proportion of children who had developed any asthma , allergic rhinitis , eczema , food allergy and sensitization to inhalant allergens .


Similar growth rates were observed in both groups .


The supplementation of probiotics in early childhood did not play a role in the prevention of allergic diseases .


Clinical/Key Message : Early-life supplementation with probiotics did not change allergic outcomes at 5 years of age .


To investigate the efficacy of erlotinib versus docetaxel in previously treated patients with advanced non-small-cell lung cancer ( NSCLC ) in an epidermal growth factor receptor ( EGFR ) - unselected patient population .


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


Secondary end points included overall survival ( OS ) , response rate , safety , and analyses on EGFR wild-type tumors .


Patients with stage IIIB or IV NSCLC , previous treatment with one or two chemotherapy regimens , evaluable or measurable disease , and performance status of 0 to 2 were eligible .


From August 2009 to July 2012 , 150 and 151 patients were randomly assigned to erlotinib ( 150 mg daily ) and docetaxel ( 60 mg/m ( 2 ) every 3 weeks ) , respectively .


EGFR wild-type NSCLC was present in 109 and 90 patients in the erlotinib and docetaxel groups , respectively .


Median PFS for erlotinib versus docetaxel was 2.0 v 3.2 months ( hazard ratio [ HR ] , 1.22 ; 95 % CI , 0.97 to 1.55 ; P = .09 ) , and median OS was 14.8 v 12.2 months ( HR , 0.91 ; 95 % CI , 0.68 to 1.22 ; P = .53 ) , respectively .


In a subset analysis of EGFR wild-type tumors , PFS for erlotinib versus docetaxel was 1.3 v 2.9 months ( HR , 1.45 ; 95 % CI , 1.09 to 1.94 ; P = .01 ) , and OS was 9.0 v 10.1 months ( HR , 0.98 ; 95 % CI , 0.69 to 1.39 ; P = .91 ) , respectively .


Erlotinib failed to show an improvement in PFS or OS compared with docetaxel in an EGFR-unselected patient population .


The OPUS study demonstrated that addition of cetuximab to 5-fluorouracil , folinic acid and oxaliplatin ( FOLFOX4 ) significantly improved objective response and progression-free survival ( PFS ) in the first-line treatment of patients with KRAS exon 2 wild-type metastatic colorectal cancer ( mCRC ) .


In patients with KRAS exon 2 mutations , a detrimental effect was seen upon addition of cetuximab to FOLFOX4 .


The current study reports outcomes in subgroups defined by extended RAS testing .


Samples from OPUS study KRAS exon 2 wild-type tumours were reanalysed for other RAS mutations in four additional KRAS codons ( exons 3-4 ) and six NRAS codons ( exons 2-4 ) using BEAMing .


A cutoff of 5 % mutant/wild-type sequences was selected to define RAS status ; we also report an analysis using a cutoff based on the technical lower limit for mutation identification ( 0.1 % ) .


Other RAS mutations were detected in 31/118 ( 26 % ) evaluable patients .


In the extended analysis of RAS wild-type tumours ( n = 87 ) , objective response was significantly improved by addition of cetuximab to FOLFOX4 ( 58 % versus 29 % ; odds ratio 3.33 [ 95 % confidence interval 1.36-8 .17 ] ; P = 0.0084 ) ; although limited by population size , there also appeared to be trends favouring the cetuximab arm in terms of PFS and overall survival in the RAS wild-type group compared with the RAS evaluable group .


There was no evidence that patients with other RAS mutations benefited from cetuximab , but small numbers precluded precise estimations of treatment effects .


In the combined population of patients with any RAS mutation ( KRAS exon 2 or other RAS ) , a clear detrimental effect was associated with addition of cetuximab to FOLFOX4 .


Patients with RAS-mutant mCRC , as defined by mutations in KRAS and NRAS exons 2-4 , derive no benefit and may be harmed by the addition of cetuximab to FOLFOX4 .


Restricting cetuximab administration to patients with RAS wild-type tumours will further tailor therapy to maximise benefit .


Refractory chronic low back pain ( CLBP ) often leads to treatment with long-term opioids .


Our goal was to describe the pharmaco-toxicological profile of opioid-treated CLBP patients and identify potential areas for care optimization .


Cross-sectional analysis .


Outpatient primary care .


CLBP patients prescribed 30 mg/d of morphine-equivalent dose ( MED ) for 3 months .


Self-reported clinical , medication ( verified ) and substance use , and urine drug testing ( UDT ) data were collected .


Participants ( N = 35 ) were 51.8 9.7 years old , 80 percent female with CLBP for 14.2 10.1 years , treated with opioids for 7.9 5.7 years , with severe disability ( Oswestry Disability Index score : 66.7 11.4 ) , and average pain score of 5.6 1.5 ( 0-10 rating scale ) .


Participants reported using tobacco ( N = 14 ) , alcohol ( N = 9 ) and illicit drugs or unprescribed medications ( N = 10 ) .


On average , participants took 13.4 6.8 daily medications , including 4.7 1.8 pain-modulating and 4.7 2.0 sedating medications .


Among prescribed opioids , 57.1 percent were long-acting and 91.4 percent were short-acting , with a total of 144.5 127.8 mg/d of MED .


Sixteen participants were prescribed benzodiazepines and/or zolpidem / zaleplon .


Fifteen participants had UDT positive for illicit drugs or unprescribed medications ; in addition , eight tested positive for alcohol and 19 for cotinine .


Compared to those with negative UDTs , those with positive UDTs ( N = 15 ) received lower daily `` total '' and `` extended release '' opioid doses , and were more likely to test positive for cotinine ( p < 0.05 ) .


Study findings corroborate existing evidence for high medication burden and high likelihood of substance misuse among opioid-treated CLBP patients .


Further research is needed to help understand causality and ways to optimize care and clinical outcomes .


Few prospective studies examine the impact of ethnicity or race on outcomes with lithium for bipolar disorder .


This exploratory study examines differences in lithium response and treatment outcomes in Hispanics , African Americans , and non-Hispanic whites with bipolar disorder in the Lithium Treatment Moderate Dose Use Study ( LiTMUS ) .


LiTMUS was a six-site randomized controlled trial of low-dose lithium added to optimized treatment ( OPT ; personalized , evidence-based pharmacotherapy ) vs. OPT alone in outpatients with bipolar disorder .


Of 283 participants , 47 African Americans , 39 Hispanics , and 175 non-Hispanic whites were examined .


We predicted minority groups would have more negative medication attitudes and higher attrition rates , but better clinical outcomes .


African Americans in the lithium group improved more on depression and life functioning compared to whites over the 6 month study .


African Americans in the OPT only group had marginal improvement on depression symptoms .


For Hispanics , satisfaction with life did not significantly improve in the OPT only group , in contrast to whites and African Americans who improved over time on all measures .


Attitudes toward medications did not differ across ethnic/racial groups .


African Americans show some greater improvements with lithium than non-Hispanic whites , and Hispanics showed more consistent improvements in the lithium group .


The impact of low-dose lithium should be studied in a larger sample as there may be particular benefit for African Americans and Hispanics .


Given that the control group ( regardless of ethnicity/race ) had significant improvements , optimized treatment may be beneficial for any ethnic group .


Approximately 1 in 5 pregnant women in the United Kingdom are obese .


In addition to being associated generally with poor health , obesity is known to be a contributing factor to pregnancy and birth complications and the retention of gestational weight can lead to long term obesity.This paper describes the protocol for a cluster randomised trial to evaluate whether a weight management intervention for obese pregnant women is effective in reducing women 's Body Mass Index at 12 months following birth .


The study is a cluster randomised controlled trial involving 20 maternity units across England and Wales .


The units will be randomised , 10 to the intervention group and 10 to the control group .


570 pregnant women aged 18 years or over , with a Body Mass Index of + / = 30 ( kg/m2 ) and between 12 and 20 weeks gestation will be recruited .


Women allocated to the control group will receive usual care and two leaflets giving advice on diet and physical activity .


In addition to their usual care and the leaflets , women allocated to the intervention group will be offered to attend a weekly 1.5 hour weight management group , which combines expertise from Slimming World with clinical advice and supervision from National Health Service midwives , until 6 weeks postpartum.Participants will be followed up at 36 weeks gestation and at 6 weeks , 6 months and 12 months postpartum .


Body Mass Index at 12 months postpartum is the primary outcome .


Secondary outcomes include pregnancy weight gain , quality of life , mental health , waist-hip ratio , child weight centile , admission to neonatal unit , diet , physical activity levels , pregnancy and birth complications , social support , self-regulation and self-efficacy .


A cost effectiveness analysis and process evaluation will also be conducted .


This study will evaluate the effectiveness of a theory-based intervention developed for obese pregnant women .


If successful the intervention will equip women with the necessary knowledge and skills to enable them to make healthier choices for themselves and their unborn child .


Current Controlled Trials : ISRCTN25260464 Date of registration : 16th April 2010 .


Effective medicines have not been introduced for insulin resistance-related fatty liver .


The efficacy and safety of treatment between a combination of metformin and carnitine-orotate complex and metformin alone in a 12-week , double-blind , randomized , placebo-controlled study on drug-nave patients with impaired glucose metabolism and fatty liver were compared .


Fifty-two patients with fasting glucose 100-240mg / dL or glycosylated hemoglobin ( HbA1c ) 6.0 % and alanine aminotransferase ( ALT ) 40-250 IU/L were randomized to receive metformin ( 250mg t.i.d. ) , or metformin ( 250mg t.i.d. ) and carnitine-orotate complex ( 300mg t.i.d. ) for 12 weeks ( n = 26 per group ) .


The primary end-point was a change from baseline ALT level .


Secondary end-points were changes in fasting glucose , HbA1c , aspartate aminotransferase levels , mitochondrial DNA ( mtDNA ) copy number in the peripheral blood , and urinary output of 8-hydroxy-2 ' - deoxyguanosine , a marker of oxidative stress .


The combined treatment reduced ALT level significantly more than metformin alone ( -51.533.2 IU/Lvs -16.731.3 IU/L , P = 0.001 ) .


The HbA1c levels also decreased significantly in both groups but there was no significant difference between them ( -0.9 % 1.0 % vs -0.7 % 0.9 % ) .


Treatment with the complex decreased the urinary 8-hydroxy-2 ' - deoxyguanosine level and increased mtDNA copy number significantly compared with metformin alone ( both P < 0.05 ) .


No severe adverse events were observed .


A 12-week treatment with metformin and carnitine-orotate complex significantly improved liver function enzyme levels .


This was associated with changes in oxidative stress and mtDNA copy number compared with metformin alone in patients with impaired glucose metabolism and fatty liver ( clinical trial number : KCT0000193 ) .


There are limited therapeutic options to slow the progression of autosomal dominant polycystic kidney disease ( ADPKD ) .


Recent clinical studies indicate that somatostatin analogues are promising for treating polycystic liver disease and potentially also for the kidney phenotype .


We report on the design of the DIPAK 1 ( Developing Interventions to Halt Progression of ADPKD 1 ) Study , which will examine the efficacy of the somatostatin analogue lanreotide on preservation of kidney function in ADPKD .


The DIPAK 1 Study is an investigator-driven , randomized , multicenter , controlled , clinical trial .


We plan to enroll 300 individuals with ADPKD and estimated glomerular filtration rate ( eGFR ) of 30-60 mL/min/1 .73 m ( 2 ) who are aged 18-60 years .


Patients will be randomly assigned ( 1:1 ) to standard care or lanreotide , 120 mg , subcutaneously every 28 days for 120 weeks , in addition to standard care .


Main study outcome is the slope through serial eGFR measurements starting at week 12 until end of treatment for lanreotide versus standard care .


Secondary outcome parameters include change in eGFR from pretreatment versus 12 weeks after treatment cessation , change in kidney volume , change in liver volume , and change in quality of life .


Blood and urine will be collected and questionnaires will be filled in following a fixed scheme .


Magnetic resonance imaging will be performed for assessment of kidney and liver volume .


Assuming an average change in eGFR of 5.2 4.3 ( SD ) mL/min/1 .73 m ( 2 ) per year in untreated patients , 150 patients are needed in each group to detect a 30 % reduction in the rate of kidney function loss between treatment groups with 80 % power , 2-sided = 0.05 , and 20 % protocol violators and/or dropouts .


The design is an open randomized controlled trial and measurement of our primary end point does not begin at randomization .


The DIPAK 1 Study will show whether subcutaneous administration of lanreotide every 4 weeks attenuates disease progression in patients with ADPKD .


Exercise is important for fitness and recovery of older adults after hospitalization for treatment of cardiovascular disease .


Home-based , nurse-led exercise programs may be beneficial .


The aim of this study was to test the effects of a low-intensity , home-based exercise protocol led by an advanced practice nurse on health-related quality of life ( HRQOL ) , physical fitness , and left ventricular ejection fraction ( LVEF ) in older adults after hospital discharge with a cardiovascular disease diagnosis .


The study was randomized and single blinded .


Seventy-seven older adults ( 75 years old , mean = 80.68 years old ) were included ; 32 subjects in the intervention and 29 in the control group completed the study .


The low-intensity , home-based exercise protocol is composed of 14-type joint exercises and walking for 12 weeks .


The main outcome measures were assessments on the Medical Outcomes Study Short-Form-36 , the Senior Fitness Test , and LVEF at baseline and 12 weeks after hospital discharge .


After 12 weeks , the intervention group showed significant improvements in HRQOL ( physical functioning , role-physical , bodily pain , and vitality ; p < .05 ) as well as on the Senior Fitness Test ( chair stands , arm curls , Timed Up and Go , and 6-minute walk distance ; p < .05 ) ; there was no significant improvement in LVEF ( p = .56 ) .


The low-intensity , home-based exercise led by an advanced practice nurse was effective in improving HRQOL and physical fitness .


Adherence was high , and there were no adverse events related to exercise .


Tobacco use is responsible for the death of about 1 in 10 individuals worldwide .


Mindfulness training has shown preliminary efficacy as a behavioral treatment for smoking cessation .


Recent advances in mobile health suggest advantages to smartphone-based smoking cessation treatment including smartphone-based mindfulness training .


This study evaluates the efficacy of a smartphone app-based mindfulness training program for improving smoking cessation rates at 6-months follow-up .


A two-group parallel-randomized clinical trial with allocation concealment will be conducted .


Group assignment will be concealed from study researchers through to follow-up .


The study will be conducted by smartphone and online .


Daily smokers who are interested in quitting smoking and own a smartphone ( n = 140 ) will be recruited through study advertisements posted online .


After completion of a baseline survey , participants will be allocated randomly to the control or intervention group .


Participants in both groups will receive a 22-day smartphone-based treatment program for smoking .


Participants in the intervention group will receive mobile mindfulness training plus experience sampling .


Participants in the control group will receive experience sampling-only .


The primary outcome measure will be one-week point prevalence abstinence from smoking ( at 6-months follow-up ) assessed using carbon monoxide breath monitoring , which will be validated through smartphone-based video chat .


This is the first intervention study to evaluate smartphone-based delivery of mindfulness training for smoking cessation .


Such an intervention may provide treatment in-hand , in real-world contexts , to help individuals quit smoking .


Clinicaltrials.gov NCT02134509 .


Registered 7 May 2014 .


Triptans are a family of selective serotonin ( 5-HT1B / 1D ) receptor agonists that are widely used to treat acute migraine attacks .


Their efficacy is limited by side effects and the gastrointestinal manifestations of migraine .


To compare the efficacy of a single intravenous administration of propacetamol , a prodrug of paracetamol ( acetaminophen ) with a single dose of oral rizatriptan in treating acute migraine attacks .


Patients were selected from those who presented to the emergency room with a diagnosed migraine attack and who had not previously taken any analgesics .


They were randomized into 2 groups : treatment with a single 1g IV dose of propacetamol or with a single oral dose of 5mg rizatriptan .


Their Visual Analogue Scale ( VAS ) pain scores were assessed before and at 30 , 60 , and 120min after treatment .


The patients who received the propacetamol had significantly improved VAS scores at 60min compared to the rizatriptan group .


There were no significant differences in VAS scores at 30 or 120min post-treatment .


Propacetamol is either equivalent or superior in efficacy to rizatriptan for treating acute migraine attacks , while having the advantage of parenteral administration in patients whose migraines are accompanied by nausea and vomiting .


Onychomycosis , a fungal nail infection , can impact quality of life .


We sought to evaluate the efficacy and safety of tavaborole topical solution , 5 % for treatment of toenail onychomycosis .


In 2 phase-III trials , adults with distal subungual onychomycosis affecting 20 % to 60 % of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks .


The primary end point was complete cure of the target great toenail ( completely clear nail with negative mycology ) at week 52 .


Secondary end points included completely or almost clear nail , negative mycology , completely or almost clear nail plus negative mycology , and safety .


Rates of negative mycology ( 31.1 % -35.9 % vs 7.2 % -12.2 % ) and complete cure ( 6.5 % and 9.1 % vs 0.5 % and 1.5 % ) significantly favored tavaborole versus vehicle ( P .001 ) .


Completely or almost clear nail rates also significantly favored tavaborole versus vehicle ( 26.1 % -27.5 % vs 9.3 % -14.6 % ; P < .001 ) .


Rates of completely or almost clear nail plus negative mycology ( 15.3 % -17.9 % vs 1.5 % -3.9 % ) were significantly greater for tavaborole versus vehicle ( P < .001 ) .


Application-site reactions with tavaborole included exfoliation ( 2.7 % ) , erythema ( 1.6 % ) , and dermatitis ( 1.3 % ) .


Duration of follow-up is a limitation .


Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis .


Atrial fibrillation ( AF ) is frequently comorbid in patients receiving cardiac resynchronization therapy ( CRT ) , and suppression is typically difficult .


Herein , we sought to understand the benefit of atrial rhythm control in the setting of ventricular rate and regularity control induced by atrioventricular node ( AVN ) ablation .


Fifty-two patients with heart failure , persistent AF , left ventricular ( LV ) ejection fraction < 35 % , and left bundle branch block underwent cardiac resynchronization therapy ( CRT ) + AVN ablation , and were randomized to one of the following groups : ( 1 ) Atrial Rhythm Control ( ARC ) ; ( 2 ) AF .


Patients were subsequently followed for up to 1 year .


Similar numbers of patients in each group were lost to follow-up or have withdrawn ( ARC two ; AF three ) .


Rhythm control in four patients in the ARC group was inadequate .


Among the remaining patients , the incidence of death ( ARC = 1 , AF = 2 ) or left ventricular assist device + / - transplantation ( ARC = 2 , AF = 1 ) were similar .


Among the remaining patients ( ARC 16 , AF 19 ) , at 1 year , there were no significant differences in CRT response rate , Minnesota Living with Heart Failure survey score , 6-minute hall walk distance , ventricular tachyarrhythmia occurrence , or LV dimensions .


A significantly higher hospital encounter rate among ARC patients was attributable to efforts to maintain uniform atrial rhythm .


In this pilot study , no incremental benefit for ARC was apparent .


A larger study will be necessary to adequately examine these issues .


Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system ( RAAS ) blockade efficacy in non-diabetic nephropathy .


We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide , separately and in combination , added to RAAS blockade on residual albuminuria in patients with type 2 diabetic nephropathy .


In this multicentre , double-blind , placebo-controlled , crossover randomised trial , we included patients with type 2 diabetic nephropathy .


Main entry criteria were microalbuminaria or macroalbuminuria , and creatinine clearance of 30 mL/min or higher with less than 6 mL/min decline in the previous year .


We tested the separate and combined effects of sodium restriction ( dietary counselling in the outpatient setting ) and hydrochlorothiazide ( 50 mg daily ) , added to standardised maximal angiotensin-converting enzyme ( ACE ) inhibition ( lisinopril 40 mg daily ) , on albuminuria ( primary endpoint ) .


Patients were given hydrochlorothiazide ( 50 mg per day ) or placebo during four treatment periods of 6 weeks .


Both treatments were combined with regular sodium diet or sodium restriction ( target sodium intake 50 mmol Na ( + ) per day ) .


The 6-week treatment periods were done consecutively in a random order .


Patients were randomised in blocks of two patients .


The trial was analysed by intention to treat .


The trial is registered with TrialRegister.nl , number 2366 .


Of 89 eligible patients , 45 were included in the study .


Both sodium restriction and hydrochlorothiazide significantly reduced albuminuria , irrespective of treatment sequence .


Residual geometric mean albuminuria with baseline treatment was 711 mg per day ( 95 % CI 485-1043 ) ; it was significantly reduced by sodium restriction ( 393 mg per day [ 258-599 ] , p = 00002 ) , by hydrochlorothiazide ( 434 mg per day [ 306-618 ] , p = 00003 ) , and to the greatest extent by their combination ( 306 mg per day [ 203-461 ] , p < 00001 ) .


Orthostatic complaints were present in two patients ( 4 % ) during baseline treatment , five ( 11 % ) during addition of sodium restriction , five ( 11 % ) during hydrochlorothiazide treatment , and 12 ( 27 % ) during combination treatment .


No serious adverse events occurred .


We conclude that sodium restriction is an effective non-pharmacological intervention to increase RAAS blockade efficacy in type 2 diabetic nephropathy .


None .


Many patients have symptoms suggestive of coronary artery disease ( CAD ) and are often evaluated with the use of diagnostic testing , although there are limited data from randomized trials to guide care .


We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography ( CTA ) or to functional testing ( exercise electrocardiography , nuclear stress testing , or stress echocardiography ) .


The composite primary end point was death , myocardial infarction , hospitalization for unstable angina , or major procedural complication .


Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure .


The mean age of the patients was 60.88.3 years , 52.7 % were women , and 87.7 % had chest pain or dyspnea on exertion .


The mean pretest likelihood of obstructive CAD was 53.321.4 % .


Over a median follow-up period of 25 months , a primary end-point event occurred in 164 of 4996 patients in the CTA group ( 3.3 % ) and in 151 of 5007 ( 3.0 % ) in the functional-testing group ( adjusted hazard ratio , 1.04 ; 95 % confidence interval , 0.83 to 1.29 ; P = 0.75 ) .


CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing ( 3.4 % vs. 4.3 % , P = 0.02 ) , although more patients in the CTA group underwent catheterization within 90 days after randomization ( 12.2 % vs. 8.1 % ) .


The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group ( 10.0 mSv vs. 11.3 mSv ) , but 32.6 % of the patients in the functional-testing group had no exposure , so the overall exposure was higher in the CTA group ( mean , 12.0 mSv vs. 10.1 mSv ; P < 0.001 ) .


In symptomatic patients with suspected CAD who required noninvasive testing , a strategy of initial CTA , as compared with functional testing , did not improve clinical outcomes over a median follow-up of 2 years .


( Funded by the National Heart , Lung , and Blood Institute ; PROMISE ClinicalTrials.gov number , NCT01174550 . )


Electroencephalographic-based monitoring systems such as the bispectral index ( BIS ) may reduce anaesthetic overdose rates .


We hypothesised that goal-directed sevoflurane administration ( guided by BIS monitoring ) could reduce the sevoflurane plasma concentration ( SPC ) and intraoperative vasopressor doses during on-pump cardiac surgery .


A prospective , controlled , sequential two-arm clinical study .


German university medical centre with more than 2500 cardiac surgery interventions per year .


Sixty elective on-pump cardiac surgery patients .


In group Sevo1 .8 % ( n = 29 ) , the sedation depth was maintained with a sustained inspired concentration of sevoflurane 1.8 % before and during cardiopulmonary bypass ( CPB ) .


In group SevoBIS ( n = 31 ) , the inspired sevoflurane concentration was titrated to maintain a BIS target between 40 and 60 .


SPC during CPB and the intraoperative administration of noradrenaline .


Additional analyses were performed on intraoperative awareness , postoperative blood lactate concentration , duration of mechanical ventilation , intensive care unit length of stay and kidney injury .


Mean inspired sevoflurane concentration was 0.8 % in group SevoBIS , representing a 57.1 % reduction ( P < 0.001 ) compared with group Sevo1 .8 % .


The mean SPC was 42.3 gml ( -1 ) [ 95 % confidence interval ( CI ) 40.0 to 44.6 ] in group Sevo1 .8 % and 21.0 gml ( -1 ) ( 95 % CI 18.8 to 23.3 ) in group SevoBIS , representing a 50.2 % reduction ( P < 0.001 ) .


During CPB , the mean cumulative dose of noradrenaline administered was 13.48 gkg ( -1 ) ( 95 % CI 10.52 to 17.19 ) in group Sevo1 .8 % and 4.06 gkg ( -1 ) ( 95 % CI 2.67 to 5.97 ) in group SevoBIS ( P < 0.001 ) .


Pearson 's correlation coefficient ( between the cumulative applied dosage of sevoflurane calculated from the area under the curve of the SPC over time and the administered cumulative noradrenaline dose ) was 0.607 ( P < 0.001 ) .


No intraoperative awareness signs were detected .


BIS-guided titration of sevoflurane reduces the SPC and decreases noradrenaline administration compared with routine care during on-pump cardiac surgery .


Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects .


To report the 12-month extension of a phase II trial evaluating the efficacy , safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b ( IFNB-1b ) in relapsing-remitting multiple sclerosis ( RRMS ) .


In the randomized , multicenter , parallel-group , rater-blinded core study , 77 RRMS patients started IFNB-1b .


At month three they were randomized 11 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15 .


In the subsequent extension study , patients continued with unchanged medication for another 12 months .


Data at study end were compared to data at month three of the core study .


27 of 72 patients that finished the core study entered the extension study .


45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study .


The primary end point , the proportion of patients with new lesions on T2-weighted images was equal in both groups ( odds ratio 1.926 ; 95 % CI 0.265-14 .0007 ; p = 0.51 ) .


All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images , total number of Gd-enhancing lesions on T1-weighted images , volume of grey and white matter , EDSS , MSFC , relapse rate , number of relapse-free patients and neutralizing antibodies did not show significant differences either .


The combination therapy was well tolerated .


Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months .


ClinicalTrials.gov NCT01111656 .


Convergent biological , epidemiological , and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease ( PD ) .


To determine the safety , tolerability , and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial .


The Safety of Urate Elevation in PD ( SURE-PD ) study , a randomized , double-blind , placebo-controlled , dose-ranging trial of inosine , enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States .


Seventy-five consenting adults ( mean age , 62 years ; 55 % women ) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL ( the approximate population median ) were enrolled .


Participants were randomized to 1 of 3 treatment arms : placebo or inosine titrated to produce mild ( 6.1-7 .0 mg/dL ) or moderate ( 7.1-8 .0 mg/dL ) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day .


They were followed for up to 24 months ( median , 18 months ) while receiving the study drug plus 1 washout month .


The prespecified primary outcomes were absence of unacceptable serious adverse events ( safety ) , continued treatment without adverse event requiring dose reduction ( tolerability ) , and elevation of urate assessed serially in serum and once ( at 3 months ) in cerebrospinal fluid .


RESULTS Serious adverse events ( 17 ) , including infrequent cardiovascular events , occurred at the same or lower rates in the inosine groups relative to placebo .


No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis .


Treatment was tolerated by 95 % of participants at 6 months , and no participant withdrew because of an adverse event .


Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups ( P < .001 for each ) vs placebo , and cerebrospinal fluid urate level was greater in both inosine groups ( P = .006 and < .001 , respectively ) .


Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability .


Inosine was generally safe , tolerable , and effective in raising serum and cerebrospinal fluid urate levels in early PD .


The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD .


clinicaltrials.gov Identifier : NCT00833690 .


Endoscopic injection of a bulking agent is becoming a first-line treatment for low grade vesicoureteral reflux .


We prospectively compared the efficacy of 2 such products commercially available in Canada .


A total of 275 patients with documented grade I to V vesicoureteral reflux were prospectively enrolled in a comparative study between April 2005 and February 2011 to be randomly treated endoscopically with either polydimethylsiloxane ( Macroplastique ) or dextranomer/hyaluronic acid copolymer ( Deflux ) .


Of the ureters 202 were treated with polydimethylsiloxane and 197 with dextranomer/hyaluronic acid copolymer .


Patients were followed with voiding cystourethrography at 3 months and renal ultrasonography at 3 months and at 1 year .


Median followup was 4.3 years .


The primary outcome was surgical success ( resolution vs nonresolution ) , and secondary outcomes included occurrence of adverse events .


Vesicoureteral reflux was fully corrected in 182 of 202 ureters ( 90 % ) treated with polydimethylsiloxane , compared to 159 of 197 ( 81 % ) treated with dextranomer/hyaluronic acid copolymer ( p < 0.05 ) .


Obstruction was found in 5ureters .


Univariate and multivariate analyses did not allow identification of any characteristics that could explain the significant difference in the success rates except for the type of product used .


We present the largest known prospective evaluation comparing 2bulking agents for the treatment of vesicoureteral reflux .


Endoscopic injection of polydimethylsiloxane resulted in a better success rate than dextranomer/hyaluronic acid copolymer .


The rate of resolution obtained with the latter is lower than those previously published due to the inclusion of high grade reflux .


Economic evaluation is important for making decisions about resource allocation .


Few cost-utility or cost-effectiveness studies on breast hypertrophy have been reported in the medical literature .


The authors sought to determine the cost-utility of reduction mammaplasty in the Brazilian national health care system .


This randomized controlled study was conducted in a university-affiliated hospital .


Sixty patients with breast hypertrophy were enrolled prospectively and were assigned randomly to either the control group ( n = 30 patients who received follow-up for 6 months ) or the treatment group ( n = 30 patients who underwent reduction mammaplasty ) .


Direct costs were recorded , and the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) was administered to both groups at the beginning of the study ( preoperatively for the treatment group ) and 3 and 6 months postoperatively .


Utility was determined with Instrument 6D of the Brazilian version of the Short-Form Health Survey ( SF-6D ) , from the SF-36 data .


At the 6-month follow-up , the treatment group showed an improvement in utility , with an average direct cost of approximately 104 .


Reduction mammaplasty performed in the Brazilian national health care system provides a cost-utility ratio equivalent to approximately 142 per 1 quality-adjusted life year .


We aimed to compare the effectiveness of esmolol 1 mg/kg and lidocaine 1 mg/kg for injection pain and for the prevention of rocuronium-induced withdrawal response .


We enrolled a total of 81 patients in the study .


Patients were randomly assigned to receive either 10 mL of 0.9 % NaCl ( Group P ) , esmolol 1 mg/kg ( Group E ) , or lidocaine 1.0 mg/kg ( Group L ) .


A subparalyzing dose of rocuronium 0.05 mg / kg was administered to all patients and its effects were recorded .


Anesthesia was induced with intravenous propofol and intravenous rocuronium 0.5 mg/kg in all groups .


The withdrawal movements of the patient groups were subsequently graded .


There was a statistically significant difference in overall incidence of pain in group E and L compared to the placebo group after administrating the subparalyzed dose ( no pain response : Group E = 81.5 % , Group L = 77.8 % , Group P = 14.8 % ) ( P < 0.001 ) .


After intravenous administration of an intubating dose of rocuronium , the esmolol group had a significantly lower incidence of withdrawal movement than the other groups ( no response : Group E = 81.5 % , Group L = 63 % , Group P = 22.2 % ) ( P < 0.001 ) .


We found that esmolol significantly attenuates rocuronium-induced withdrawal movement and also reduces pain when used at subparalyzing doses .


Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding .


We aimed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated , stage IV , non-squamous non-small-cell lung cancer ( NSCLC ) .


We did this randomised , open-label , controlled phase 3 study at 103 sites in 20 countries .


Patients aged 18 years or older , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0-2 and adequate organ function , were randomly assigned 1:1 to treatment with a block randomisation scheme ( block size of four ) via a telephone-based interactive voice-response system or interactive web-response system .


Patients received either cisplatin 75 mg/m ( 2 ) and pemetrexed 500 mg/m ( 2 ) on day 1 of a 3-week cycle for a maximum of six cycles alone , or with necitumumab 800 mg on days 1 and 8 .


Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects .


Randomisation was stratified by smoking history , ECOG performance status , disease histology , and geographical region .


Patients and study investigators were not masked to group assignment .


The primary endpoint was overall survival .


Efficacy analyses were by intention to treat .


This trial is registered with ClinicalTrials.gov , number NCT00982111 .


Between Nov 11 , 2009 , and Feb 2 , 2011 , we randomly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin ( n = 315 ) or pemetrexed and cisplatin alone ( n = 318 ) .


Enrolment was stopped on Feb 2 , 2011 , after a recommendation from the independent data monitoring committee .


There was no significant difference in overall survival between treatment groups , with a median overall survival of 113 months ( 95 % CI 95-134 ) in the necitumumab plus pemetrexed and cisplatin group versus 115 months ( 101-131 ) in the pemetrexed and cisplatin group ( hazard ratio 101 [ 95 % CI 084-121 ] ; p = 096 ) .


The incidence of grade 3 or worse adverse events , including deaths , was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ; in particular , deaths regarded as related to study drug were reported in 15 ( 5 % ) of 304 patients in the necitumumab group versus nine ( 3 % ) of 312 patients in the pemetrexed and cisplatin group .


Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group ( 155 [ 51 % ] of 304 vs 127 [ 41 % ] of 312 patients ) .


Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3-4 rash ( 45 [ 15 % ] of 304 vs one [ < 1 % ] of 312 patients in the pemetrexed and cisplatin alone group ) , hypomagnesaemia ( 23 [ 8 % ] vs seven [ 2 % ] patients ) , and grade 3 or higher venous thromboembolic events ( 23 [ 8 % ] vs 11 [ 4 % ] patients ) than did those in the pemetrexed and cisplatin alone group .


Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC .


Unless future studies identify potentially useful predictive biomarkers , necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin .


Eli Lilly and Company .


Current guidelines recommend intensive low-density lipoprotein ( LDL ) cholesterol lowering with statins , with a target of 70 mg/dL ( 1.81 mmol/L ) LDL cholesterol for those with a very high risk of coronary artery events .


However , there is no multicenter study assessing the effect of intensive lipid-lowering therapy with statins on acute coronary syndrome ( ACS ) in a Chinese population with low baseline LDL cholesterol levels .


Patients ( n = 1355 ) with ACS were treated with a moderate dose of statin ( atorvastatin 10 mg/d , or equivalent dose of other statins , n = 675 ) or with an intensive dose of statin ( atorvastatin , 20 or 40 mg/d , or equivalent dose of other statins , n = 680 ) for 2 years .


The primary end points were cardiac death , non-fatal acute myocardial infarction ( MI ) , revascularization , ischemic stroke and documented unstable angina or severe heart failure requiring emergency hospitalization .


Baseline lipid levels were nearly identical in both groups with a mean LDL cholesterol level of 2.7 mmol/L ( 103 mg/dL ) .


At 3 months , LDL cholesterol levels declined 20.2 % in the moderate dose statin group and 26.6 % in the intensive statin group , respectively ( P < 0.001 ) .


In a 2-year follow-up , a primary end point event occurred in 20 patients in the moderate dose statin group and in 28 patients in the intensive statin group .


There was no significant between-group difference in the primary outcome ( hazard ratio , 1.39 ; 95 % confidence interval [ CI ] , 0.78-2 .46 ; P = 0.245 ) .


For ACS patients with a relatively low baseline LDL cholesterol level who received optimized current medication and interventional therapy , the incremental LDL cholesterol reduction of 6.4 % achieved by double-dose statin did not bring significant clinical effectiveness .


Response to cardiac resynchronization therapy is variable .


The aim of this study was to test the hypothesis that left ventricular ( LV ) lead position in proximity to myocardial scar is associated with less favorable outcomes .


A total of 149 patients were included in this substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial using echocardiographic radial strain for basal and middle LV segments and transverse strain for apical segments to estimate scar .


Sixty-four patients with high-dose rest ( 99m ) Tc sestamibi single-photon emission computed tomographic imaging were used for validation in 508 LV free-wall segments .


The relationship of LV lead position to segments estimated as scar was defined as concordant , adjacent , or remote .


The prespecified primary end point was heart failure hospitalization or death over 2 years .


Wall thickening < 10 % by radial strain in LV free wall segments was associated with absent ( 99m ) Tc sestamibi uptake indicative of scar with 77 % sensitivity and 89 % specificity and strain < 10 % was accordingly used as the surrogate for scar .


Event-free survival was most favorable in patients with nonischemic disease ( 79 % ) , similarly favorable in patients with ischemic disease and LV leads remote from scar ( 74 % ) , but significantly worse in patients with ischemic disease and LV leads adjacent to ( 61 % ) or within scar ( 41 % ) ( P = .004 ) .


Preserved wall thickening at the LV lead site was independently associated with favorable outcome and additive to pacing at the site of latest mechanical activation ( P = .001 ) and remained significant after adjusting for scar burden .


Echocardiographic speckle-tracking strain has the potential to estimate free wall scar in patients with ischemic cardiomyopathy and influence LV lead positioning away from scar to improve clinical outcomes after cardiac resynchronization therapy .


Tripterygium wilfordii Hook .


f. ( TwHF ) has been used for many years to induce the remission of Crohn 's disease in China .


To compare TwHF versus azathioprine for the prevention of postoperative recurrence in Crohn 's disease .


90 Crohn 's disease patients who had undergone resection were treated with TwHF 1.5 mg/kg/day or azathioprine 2.0 mg/kg/day .


The primary endpoint was clinical recurrence , and the secondary endpoint was endoscopic recurrence .


47 patients completed the trial .


Clinical recurrence was observed in 6/45 patients in the TwHF group and 4/45 patients in the azathioprine group at week 26 ( P = 0.74 ) .


At week 52 , 8/45 azathioprine patients and 12/45 TwHF patients had clinical recurrence ( P = 0.45 ) .


During the first 26 weeks , 56.8 % of the patients in the TwHF group versus 47.7 % in the azathioprine group experienced endoscopic recurrence ( P = 0.52 ) .


However , at week 52 , 74.4 % of patients in the TwHF group and 50 % in the azathioprine group had endoscopic recurrence ( P = 0.03 ) .


TwHF was less effective in maintaining endoscopic remission at week 52 , even though TwHF was comparable to azathioprine for preventing postoperative clinical recurrence .


To test the efficacy of meaning-centered group psychotherapy ( MCGP ) to reduce psychological distress and improve spiritual well-being in patients with advanced or terminal cancer .


Patients with advanced cancer ( N = 253 ) were randomly assigned to manualized eight-session interventions of either MCGP or supportive group psychotherapy ( SGP ) .


Patients were assessed before and after completing the treatment and 2 months after treatment .


The primary outcome measures were spiritual well-being and overall quality of life , with secondary outcome measures assessing depression , hopelessness , desire for hastened death , anxiety , and physical symptom distress .


Hierarchical linear models that included a priori covariates and only participants who attended three sessions indicated a significant group time interaction for most outcome variables .


Specifically , patients receiving MCGP showed significantly greater improvement in spiritual well-being and quality of life and significantly greater reductions in depression , hopelessness , desire for hastened death , and physical symptom distress compared with those receiving SGP .


No group differences were observed for changes in anxiety .


Analyses that included all patients , regardless of whether they attended any treatment sessions ( ie , intent-to-treat analyses ) , and no covariates still showed significant treatment effects ( ie , greater benefit for patients receiving MCGP v SGP ) for quality of life , depression , and hopelessness but not for other outcome variables .


This large randomized controlled study provides strong support for the efficacy of MCGP as a treatment for psychological and existential or spiritual distress in patients with advanced cancer .


We investigated the contribution of electrocortical stimulation ( ECS ) , induced high gamma electrocorticography ( hgECoG ) and functional magnetic resonance imaging ( fMRI ) for the localization of somatosensory and language cortex .


23 Epileptic patients with subdural electrodes underwent a protocol of somatosensory stimulation and/or an auditory semantic decision task .


14 Patients did the same protocol with fMRI prior to implantation .


ECS resulted in the identification of thumb somatosensory cortex in 12/16 patients .


Taking ECS as a gold standard , hgECoG and fMRI identified 53.6 / 33 % of true positive and 4/12 % of false positive contacts , respectively .


The hgECoG false positive sites were all found in the hand area of the post-central gyrus .


ECS localized language-related sites in 7/12 patients with hgECoG and fMRI showing 50/64 % of true positive and 8/23 % of false positive contacts , respectively .


All but one of the hgECoG/fMRI false positive contacts were located in plausible language areas .


Four patients showed post-surgical impairments : the resection included the sites positively indicated by ECS , hgECoG and fMRI in 3 patients and a positive hgECoG site in one patient .


HgECoG and fMRI provide additional localization information in patients who can not sufficiently collaborate during ECS .


HgECoG and fMRI make the cortical mapping procedure more flexible not only by identifying priority cortical sites for ECS or when ECS is not feasible , but also when ECS does not provide any result .


Tissue factor ( TF ) expression is increased in inflammatory atherosclerotic plaques and has been related to their thrombogenicity .


Blood-borne TF has been also demonstrated to contribute to thrombogenesis .


However , few studies have evaluated the association of circulating levels of TF with stroke .


We investigated the association of baseline circulating levels of TF with stroke events occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort .


Using a nested case-cohort design , a center-stratified random sample of 839 subjects ( 66 % women ; age range , 35-71 years ) was selected as subcohort and compared with 292 strokes in a mean follow-up of 9 years .


Blood samples were collected at baseline in citrate , plasma was stored in liquid nitrogen and TF was measured by ELISA ( IMUBIND , TF ELISA , Instrumentation Laboratory , Milan , Italy ) .


The odd ratios and 95 % confidence intervals , adjusted by relevant confounders ( covariates of TF ) and stratified by center , were estimated by a Cox regression model using Prentice method .


Individuals in the highest compared with the lowest quartile of TF plasma levels had significantly increased risk of stroke ( odds ratioIVvsI quartile , 2.01 ; 95 % confidence interval , 1.25-3 .23 ) .


The association was independent from several potential confounders ( odds ratioIVvsI quartile , 1.91 ; 95 % confidence interval , 1.15-3 .19 ) .


No differences were observed between men and women .


The increase in risk was restricted to ischemic strokes ( odds ratioIVvsI quartile , 2.13 ; 95 % confidence interval , 1.10-4 .12 ; fully adjusted model ) , whereas high levels of TF were not associated with the risk of hemorrhagic stroke ( odds ratioIVvsI quartile , 1.12 ; 95 % confidence interval , 0.49-2 .55 ; fully adjusted model ) .


Our data provide evidence that elevated levels of circulating TF are potential risk factors for ischemic strokes .


Recently , the usefulness of neuromuscular electrical stimulation and repetitive transcranial magnetic stimulation for poststroke dysphagia has been reported .


However , there is no report that describes the effectiveness of functional magnetic stimulation ( FMS ) for dysphagia .


The purpose of this study is to clarify the effectiveness of FMS for poststroke dysphagia .


Twenty poststroke dysphagic patients ( age at treatment : 51-80 years ; interval between onset of stroke and treatment : 6 to 36 months ) were randomly assigned to a real group or a sham group .


In the real group , FMS of 30 Hz was applied for suprahyoid muscles in a 20-sec train using a parabolic coil for 10 min ( total 1200 pulses ) .


In the sham group , sham stimulation was applied for 10 min at the same site .


Swallowing function was evaluated by the timed water swallow test , interswallow interval ( ISI ) , swallowing volume velocity ( speed ) , and volume per swallow ( capacity ) were measured before and after stimulation .


All patients completed the stimulation and none showed any adverse reactions throughout the stimulation .


The improvement of speed and capacity of swallowing after stimulation was significantly larger in the real group compared with the sham group ( all p < 0.05 ) .


However , no significant difference in the ISI was found between the groups .


FMS using a parabolic coil can potentially improve swallowing function in poststroke dysphagic patients .


To observe the clinical efficacy and safety of Traditional Chinese Medicine ( TCM ) combined with Western Medicine ( WM ) in patients with diabetic acute ischemic stroke .


Ninety patients with diabetic acute ischemic stroke were randomly divided into a treatment group and a control group .


The 45 patients in the treatment group were given standardized treatment with TCM combined with WM. They received corresponding oral Chinese decoctions three times daily , according to their TCM syndromes , along with basic western medical treatment .


The 45 patients in the control group were given non-standardized treatment with TCM combined with WM. They received an oral Chinese decoction for promotion of blood circulation to inhibit hemostasis , regardless of their TCM syndromes , along with basic western medical treatment .


The treatments lasted for 4 weeks .


Scores were evaluated on the National Institutes of Health Stroke Scale ( NIHSS ) score , activity of daily life ( ADL ) scores , and TCM symptoms before treatment and 2 and 4 weeks after treatment .


Analysis of variance for repeated measurements showed that there were significant differences in NIHSS and ADL score before and after treatment in both groups ( P < 0.05 ) .


There were also significant differences between the scores at 2 and 4 weeks after treatment .


There were significant differences in TCM syndrome scores before and after treatment in both groups ( P < 0.05 ) .


The X2 test showed no statistically significant difference in the incidence of adverse reactions between the two groups ( P > 0.05 ) .


Standardized treatment was superior to non-standardized treatment for clinical efficacy of TCM combined with WM in patients with diabetic acute ischemic stroke , and the superiority was more obvious in improving neural dysfunction , ADL score , and TCM symptoms .


The adverse reactions were similar in the two treatment groups .


Subacromial impingement syndrome is the most frequent cause of shoulder problems which themselves affect 1 in 3 adults .


Management commonly includes exercise and corticosteroid injection .


However , the few existing trials of exercise or corticosteroid injection for subacromial impingement syndrome are mostly small , of poor quality , and focus only on short-term results .


Exercise packages tend to be standardised rather than individualised and progressed .


There has been much recent interest in improving outcome from corticosteroid injections by using musculoskeletal ultrasound to guide injections .


However , there are no high-quality trials comparing ultrasound-guided and blind corticosteroid injection in subacromial impingement syndrome .


This trial will investigate how to optimise the outcome of subacromial impingement syndrome from exercise ( standardised advice and information leaflet versus physiotherapist-led exercise ) and from subacromial corticosteroid injection ( blind versus ultrasound-guided ) , and provide long-term follow-up data on clinical and cost-effectiveness .


The study design is a 2x2 factorial randomised controlled trial .


252 adults with subacromial impingement syndrome will be recruited from two musculoskeletal Clinical Assessment and Treatment Services at the primary-secondary care interface in Staffordshire , UK .


Participants will be randomised on a 1:1:1:1 basis to one of four treatment groups : ( 1 ) ultrasound-guided subacromial corticosteroid injection and a physiotherapist-led exercise programme , ( 2 ) ultrasound-guided subacromial corticosteroid injection and an advice and exercise leaflet , ( 3 ) blind subacromial corticosteroid injection and a physiotherapist-led exercise programme , or ( 4 ) blind subacromial corticosteroid injection and an advice and exercise leaflet .


The primary intention-to-treat analysis will be the mean differences in Shoulder Pain and Disability Index ( SPADI ) scores at 6 weeks for the comparison between injection interventions and at 6 months for the comparison between exercise interventions .


Although independence of treatment effects is assumed , the magnitude of any interaction effect will be examined ( but is not intended for the main analyses ) .


Secondary outcomes will include comparison of long-term outcomes ( 12 months ) and cost-effectiveness .


A secondary per protocol analysis will also be performed .


This protocol paper presents detail of the rationale , design , methods and operational aspects of the SUPPORT trial .


Current controlled trials ISRCTN42399123 .


Pre-clinical work suggests that upper thoracic spinal cord stimulation ( SCS ) may have therapeutic effects in the treatment of heart failure ( HF ) .


We therefore aim to assess the safety and feasibility of SCS in HF patients .


A prospective , randomized , double-blind , crossover pilot study was conducted in symptomatic HF patients receiving optimal medical therapy .


Patients were implanted with an SCS system and randomized to an SCS-ACTIVE , delivered at 90 % paraesthesia threshold , or an SCS-INACTIVE phase for 3 months , followed by a 1-month washout period and crossover to the alternative phase .


The safety of SCS therapy was assessed by death and cardiac events .


Implantable cardioverter defibrillator ( ICD ) function in the presence of SCS was tested by defibrillation testing during SCS system implant and review of real-time and stored electrograms during follow-up .


The efficacy of SCS therapy was assessed by changes in patient symptoms , LV function , and BNP level .


Nine patients were investigated .


In all cases , ICD sensing , detection , and therapy delivery were unaffected by SCS .


During follow-up , one patient died and one was hospitalized for HF while in the SCS-INACTIVE phase , and two patients had HF hospitalizations during the SCS-ACTIVE phase .


Symptoms were improved in the majority of patients with SCS , while markers of cardiac structure and function were , in aggregate , unchanged .


This study shows that an SCS system can be safely implanted in patients with advanced HF and that the SCS system does not interfere with ICD function .


A recent noninferiority randomized trial showed that in terms of clinical effectiveness imiquimod was superior and topical fluorouracil noninferior to methylaminolaevulinate photodynamic therapy ( MAL-PDT ) for treatment of superficial basal-cell carcinoma ( sBCC ) .


Although it was expected that MAL-PDT would be more costly than either cream , a full cost-effectiveness analysis is necessary to determine the balance between effectiveness and costs .


To determine whether imiquimod or topical fluorouracil are cost-effective treatments for sBCC compared with MAL-PDT .


An economic evaluation was performed from a healthcare perspective .


Data on resource use and costs were collected alongside the randomized clinical trial .


The incremental cost-effectiveness ratio was expressed as the incremental costs per additional patient free of tumour recurrence .


At 12 months follow-up , the total mean costs for MAL-PDT were 680 , for imiquimod cream 526 and for topical fluorouracil cream 388 .


Both imiquimod and topical fluorouracil were cost-effective treatments compared with MAL-PDT .


Comparing costs and effectiveness of both creams led to a incremental investment of 4451 to achieve an additional patient free of tumour recurrence .


The acceptability curve showed that , for a threshold value of 4451 , the probability of imiquimod being more cost-effective than topical fluorouracil was 50 % .


Based on the 12 months follow-up results , imiquimod and topical fluorouracil cream are more cost-effective than MAL-PDT for treatment of sBCC .


Hence , substituting MAL-PDT with either imiquimod or topical fluorouracil results in cost savings ; these savings will be larger for topical fluorouracil .


Long-term follow-up effectiveness data are necessary to confirm the cost-effectiveness of imiquimod vs. topical 5-fluorouracil cream .


Due to increasing resistance to antibiotics and rising incidence of oral diseases , there is a need for alternative treatment modalities to combat oral diseases .


The aim of the present study was to access the effect of Aloe vera mouthwash on the dental plaque in the experimental period of 4 days and to compare it with the bench mark control chlorhexidine and placebo ( saline water ) .


A total of 300 systemically healthy subjects were randomly allocated into 3 groups : Aloe vera mouthwash group ( n = 100 ) , control group ( = 100 ) - chlorhexidene group and saline water-Placebo ( n = 100 ) .


To begin with , Gingival index ( GI ) and plaque index ( PI ) were recorded .


Then , baseline plaque scores were brought to zero by professionally cleaning the teeth with scaling and polishing .


After randomization of the participants into three groups they were refrained from regular mechanical oral hygiene measures .


Subjects were asked to swish with respective mouthwash ( Aloe vera mouthwash , 0.2 % chlorhexidine gluconate mouthwash , or normal saline ) as per therapeutic dose for 4 days .


The results showed that Aloe vera mouthrinse is equally effective in reducing plaque as Chlorhexidine compared to placebo over a period of 4 days .


There was a significant reduction on plaque in Aloe vera and chlorhexidine groups and no statistically significant difference was observed among them ( p > 0.05 ) .


Aloe vera mouthwash showed no side effects .


The results of the present study indicated that Aloe vera may prove an effective mouthwash due to its ability in reducing dental plaque .


The phase 3 MONET1 study evaluated motesanib ( a small-molecule inhibitor of vascular endothelial growth factor receptors ) plus carboplatin/paclitaxel versus placebo plus carboplatin/paclitaxel as first-line therapy for advanced non-small-cell lung cancer ( NSCLC ) .


Treatment and enrollment of patients with squamous histology were permanently discontinued following higher early mortality and gross hemoptysis in those with squamous NSCLC who received motesanib .


Enrollment of patients with nonsquamous histology was temporarily halted , but resumed following a protocol amendment ( Scagliotti et al. .


J Clin Oncol .


2012 ; 30:2829 -2836 ) .


Herein , we report data from the squamous cohort .


Patients with stage IIIB/IV or recurrent squamous NSCLC ( without prior systemic therapy for advanced disease ) received up to six 3-week cycles of chemotherapy ( carboplatin , area under the curve 6 mg/mLmin/paclitaxel , 200 mg/m ) and were randomized 1:1 to receive motesanib 125 mg ( Arm A ) or placebo ( Arm B ) once daily .


The primary end point was overall survival .


Three-hundred and sixty patients with squamous NSCLC were randomized ( Arm A , n = 182 ; Arm B , n = 178 ) between July 2007 and November 2008 .


Twenty-three patients ( 13 % ) in Arm A and 10 ( 6 % ) in Arm B had fatal adverse events within the first 60 days of treatment .


Among these , six patients in Arm A , but none in Arm B , had fatal bleeding events .


At final analysis , serious adverse events had occurred in 47 % of patients in Arm A and 29 % of patients in Arm B. Median overall survival was similar in Arms A and B ( 11.1 versus 10.7 months ) .


Motesanib plus carboplatin/paclitaxel had unacceptable toxicity compared with carboplatin/paclitaxel alone in patients with advanced squamous NSCLC .


Roux-en-Y gastric bypass may lead to impaired calcium uptake .


Therefore , operation-specific effects of gastric bypass and vertical banded gastroplasty on bone mineral density ( BMD ) were examined in a randomized clinical trial .


Bone resorption markers and mechanisms of decreased calcium uptake after gastric bypass were investigated using blood and endoscopic samples from two additional patient cohorts .


Total BMD and non-weight-bearing skull BMD were measured by dual-energy X-ray absorptiometry at baseline , and 1 and 6years after gastric bypass or vertical banded gastroplasty in patients who were not receiving calcium supplements .


Bone resorption markers in serum and calcium uptake mechanisms in jejunal mucosa biopsies were analysed after gastric bypass by proteomics including radioimmunoassay , gel electrophoresis and mass spectrometry .


One year after surgery , weight loss was similar after gastric bypass and vertical banded gastroplasty .


There was a moderate decrease in skull BMD after gastric bypass , but not after vertical banded gastroplasty ( P < 0001 ) .


Between 1 and 6years after gastric bypass , skull BMD and total BMD continued to decrease ( P = 0001 ) .


C-terminal telopeptide levels in serum had increased twofold by 18months after gastric bypass .


Proteomic analysis of the jejunal mucosa revealed decreased levels of heat-shock protein 90 , a co-activator of the vitamin D receptor , after gastric bypass .


Despite increased vitamin D receptor levels , expression of the vitamin D receptor-regulated calcium transporter protein TRPV6 decreased .


BMD decreases independently of weight after gastric bypass .


Bone loss might be attributed to impaired calcium absorption caused by decreased activation of vitamin D-dependent calcium absorption mechanisms mediated by heat-shock protein 90 and TRPV6 .


The metastatic status of regional lymph nodes is the most relevant prognostic factor in breast cancer , melanoma , and other solid organ tumors with a lymphatic spread .


The current gold standard for detection and targeted excision of the sentinel lymph node is preoperative lymphoscintigraphy with technetium Tc 99m .


Because of the worldwide shortage of technetium Tc 99m , physicians are looking for nonradioactive dyes for sentinel lymph node labeling .


Based on several retrospective studies , the fluorescent dye indocyanine green is considered a possible alternative to technetium Tc 99m .


To analyze the feasibility and clinical benefit of intraoperative near infrared fluorescence sentinel lymph node excision ( SLNE ) compared with standard technetium Tc 99m-guided SLNE using malignant melanoma in which SLNE is firmly established .


Analysis of a prospective clinical trial at the Skin Cancer Center , University Hospital Essen .


Eighty patients with malignant melanoma on the trunk or extremities ( upper and lower ) who were scheduled to undergo SLNE were included in this study from January 1 , 2013 , to June 27 , 2014 .


Concordance of preoperative and intraoperative sentinel lymph node detection rates .


During the study period , 80 patients were operated on with an additional intraoperative application of a near infrared fluorescent dye .


In these 80 surgical procedures , 147 SLNs were excised .


Detection of a technetium Tc 99m-marked SLN before surgery was possible in all cases .


Intraoperative visualization of the SLN by indocyanine green before skin incision was successful in only 17 of 80 patients ( 21 % ) .


The number of SLNs identified using the near infrared fluorescence technique in the operative site after skin incision and initial tissue preparation was 141 of 147 ( 96 % ) .


Among patients in whom the lymph node basin can not be predicted correctly ( eg , in cutaneous melanoma on the trunk ) , the use of indocyanine green for SLN detection is severely limited compared with SLNE using standard technique guided by technetium Tc 99m .


Therefore , SLNE with the use of radiocolloid , followed if possible by single-photon emission computed tomography , remains the gold standard .


German Clinical Trials Register identifier DRKS00004619 .


Osteoporosis and atherosclerosis are the two most common diseases in postmenopausal women .


In most cases , they are simultaneously present in the same individual and commonly lead to bone fracture or cardiovascular disease ( CVD ) .


Bisphosphonates ( BPs ) are frequently used in the treatment of osteoporosis and have the ability to increase lumbar spine bone mineral density ( L-BMD ) .


BPs may also protect against CVD .


A single monthly 50-mg dose of minodronate ( monthly minodronate ) is now common practice and is highly anticipated to reduce the incidence of both bone fracture and CVD .


A useful approach to independently predicting CVD is brachial-ankle pulse wave velocity ( baPWV ) .


Here , we directly compared the effects of monthly minodronate with those of a standard single weekly 35-mg dose of alendronate ( weekly alendronate ) on L-BMD and baPWV in postmenopausal women with osteoporosis across a 12-month period .


Thirty-eight postmenopausal women with osteoporosis were randomized into two treatment groups ( group 1 , weekly alendronate , n = 19 ; group 2 , monthly minodronate , n = 19 ) .


L-BMD and baPWV were assessed at baseline and 12-month follow-up .


At the end of the 12-month period , increases in L-BMD were similar between group 1 ( 7.6 % ) and group 2 ( 8.5 % ) , but baPWV was significantly reduced in group 2 compared with group 1 .


The change in baPWV during the study period showed a significant negative correlation with the change in L-BMD .


Changes in L-BMD in the monthly minodronate and weekly alendronate groups are generally comparable .


Good control of changes in L-BMD in the postmenopausal phase might be associated with regression of CVD .


Monthly minodronate is a promising new BP and potential first-line drug for the treatment of osteoporosis in postmenopausal women .