The mean annualised atrophy rate was significantly lower in patients in the simvastatin group ( 0288 % per year [ SD 0521 ] ) than in those in the placebo group ( 0584 % per year [ 0498 ] ) .


The adjusted difference in atrophy rate between groups was -0254 % per year ( 95 % CI -0422 to -0087 ; p = 0003 ) ; a 43 % reduction in annualised rate .


Simvastatin was well tolerated , with no differences between the placebo and simvastatin groups in proportions of participants who had serious adverse events ( 14 [ 20 % ] vs nine [ 13 % ] ) .


High-dose simvastatin reduced the annualised rate of whole-brain atrophy compared with placebo , and was well tolerated and safe .


These results support the advancement of this treatment to phase 3 testing .


The Moulton Foundation [ charity number 1109891 ] , Berkeley Foundation [ 268369 ] , the Multiple Sclerosis Trials Collaboration [ 1113598 ] , the Rosetrees Trust [ 298582 ] and a personal contribution from A Pidgley , UK National Institute of Health Research ( NIHR ) University College London Hospitals/UCL Biomedical Research Centres funding scheme .


Housing First has become a popular treatment model for homeless adults with mental illness , yet little is known about program participants ' early experiences or trajectories .


This study used a mixed methods design to examine participant changes in selected domains 6 months after enrollment in a Canadian field trial of Housing First .


The study sample included 301 participants receiving the Housing First intervention at the Toronto site of the At Home/Chez Soi project .


This study used a pre-post design to compare quantitative 6-month outcome data to baseline values in key domains and multivariate regression to identify baseline demographic , clinical or service use variables associated with observed changes in these domains .


In addition , qualitative data exploring participant and service provider perspectives and experiences was collected via stakeholder interviews and focus groups , and analyzed using thematic analysis .


The majority ( 60 to 72 % ) of participants followed the expected trajectory of improvement , with the remaining experiencing difficulties in community integration , mental health symptom severity , substance use , community functioning and quality of life 6 months after program enrollment .


Diagnosis of psychotic disorder was associated with a reduction in quality of life from baseline to 6-months , while substance use disorders were associated with reduced mental illness symptoms and substance use related problems and an improvement in quality of life .


Participants housed in independent housing at 6-months had greater improvements in community integration and quality of life , and greater reduction in mental illness symptoms , compared to those not independently housed .


The quality of the working alliance was positively associated with improvements in physical and psychological community integration and quality of life .


Qualitative data provided a unique window into the loneliness and isolation experienced by Housing First participants , as well as problems related to substance use and a need for life skills training and support .


Additional strategies can help support Housing First participants in the early stages of program participation and address potential causes of early difficulties , including lack of life skills and social isolation .


This study highlights the importance of early and ongoing evaluation , monitoring and program adaptations to address consumer support needs .


Current Controlled Trials ISRCTN42520374 .


In the UK around 22 % of men and 24 % of women are obese , and there are varying but worrying levels in other European countries .


Obesity is a chronic condition that carries an important health risk .


National guidelines , for use in England , on the management of people who are overweight or obese have been published by the National Institute for Health and Clinical Excellence ( NICE , 2006 ) .


NICE recommendations for primary care teams are : determine the degree of overweight and obesity ; assess lifestyle , comorbidities and willingness to change ; offer multicomponent management of overweight and obesity ; referral to external services when appropriate .


This study investigates a tailored intervention to improve the implementation of these recommendations by primary care teams .


The study is a cluster randomised controlled trial .


Primary care teams will be recruited from the East Midlands of England , and randomised into two study arms : 1 ) the study group , in which primary care teams are offered a set of tailored interventions to help implement the NICE guidelines for overweight and obesity ; or 2 ) the control group in which primary care teams continue to practice usual care .


The primary outcome is the proportion of overweight or obese patients for whom the primary care team adheres to the NICE guidelines .


Secondary outcomes include the proportion of patients with a record of lifestyle assessment , referral to external weight loss services , the proportion of obese patients who lose weight during the intervention period , and the mean weight change over the same period .


Although often recommended , the methods of tailoring implementation interventions to account for the determinants of practice are not well developed .


This study is part of a programme of studies seeking to develop the methods of tailored implementation .


Current Controlled Trials ISRCTN07457585 .


Registered 09/08/2013 .


Randomisation commenced 30/08/2013 .


A multicenter , randomized phase II trial , RECORD-3 , was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma .


RECORD-3 used a crossover treatment design .


The primary objective was to assess progression-free survival ( PFS ) noninferiority of first-line everolimus compared with first-line sunitinib .


Secondary end points included combined PFS for each sequence , overall survival ( OS ) , and safety .


Of 471 enrolled patients , 238 were randomly assigned to first-line everolimus followed by sunitinib , and 233 were randomly assigned to first-line sunitinib followed by everolimus .


The primary end point was not met ; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib ( hazard ratio [ HR ] , 1.4 ; 95 % CI , 1.2 to 1.8 ) .


Among patients who discontinued first-line , 108 ( 45 % ) crossed over from everolimus to second-line sunitinib , and 99 ( 43 % ) crossed over from sunitinib to second-line everolimus .


The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus ( HR , 1.3 ; 95 % CI , 0.9 to 1.7 ) .


The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus ( HR , 1.2 ; 95 % CI , 0.9 to 1.6 ) .


Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis ( 53 % and 57 % , respectively ) , fatigue ( 45 % and 51 % , respectively ) , and diarrhea ( 38 % and 57 % , respectively ) .


Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy .


The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression .


To report the refractive , topographic , and clinical outcomes 3 years after corneal collagen cross-linking ( CXL ) in eyes with progressive keratoconus .


Prospective , randomized controlled trial .


One hundred eyes with progressive keratoconus were randomized into the CXL treatment or control groups .


Cross-linking was performed by instilling riboflavin 0.1 % solution containing 20 % dextran for 15 minutes before and during the 30 minutes of ultraviolet A irradiation ( 3 mW/cm ( 2 ) ) .


Follow-up examinations were arranged at 3 , 6 , 12 , 24 , and 36 months .


The primary outcome measure was the maximum simulated keratometry value ( Kmax ) .


Other outcome measures were uncorrected visual acuity ( UCVA ; measured in logarithm of the minimum angle of resolution [ logMAR ] units ) , best spectacle-corrected visual acuity ( BSCVA ; measured in logMAR units ) , sphere and cylinder on subjective refraction , spherical equivalent , minimum simulated keratometry value , corneal thickness at the thinnest point , endothelial cell density , and intraocular pressure .


The results from 48 control and 46 treated eyes are reported .


In control eyes , Kmax increased by a mean of 1.200.28 diopters ( D ) , 1.700.36 D , and 1.750.38 D at 12 , 24 , and 36 months , respectively ( all P < 0.001 ) .


In treated eyes , Kmax flattened by-0 .720.15 D,-0 .960.16 D , and-1 .030.19 D at 12 , 24 , and 36 months , respectively ( all P < 0.001 ) .


The mean change in UCVA in the control group was +0.100.04 logMAR ( P = 0.034 ) at 36 months .


In the treatment group , both UCVA ( -0.150.06 logMAR ; P = 0.009 ) and BSCVA ( -0.090.03 logMAR ; P = 0.006 ) improved at 36 months .


There was a significant reduction in corneal thickness measured using computerized videokeratography in both groups at 36 months ( control group : -17.013.63 m , P < 0.001 ; treatment group : -19.525.06 m , P < 0.001 ) that was not observed in the treatment group using the manual pachymeter ( treatment group : +5.864.30 m , P = 0.181 ) .


The manifest cylinder increased by 1.170.49 D ( P = 0.020 ) in the control group at 36 months .


There were 2 eyes with minor complications that did not affect the final visual acuity .


At 36 months , there was a sustained improvement in Kmax , UCVA , and BSCVA after CXL , whereas eyes in the control group demonstrated further progression .


Ready-to-use therapeutic food ( RUTF ) has been found effective in treating severe acute malnutrition .


Vietnam 's National Institute of Nutrition ( NIN ) , the Institut de Recherche pour le Dveloppement ( IRD ) , and UNICEF collaborated to formulate a local RUTF called High-Energy Bar for Integrated Management of Acute Malnutrition ( HEBI ) .


RUTF might be useful to address malnutrition in HIV patients .


To compare the acceptability of the local RUTF and an imported RUTF among malnourished people with HIV in Vietnam Methods : The acceptability of HEBI and Plumpy'Nut was studied among 80 HIV-positive children and 80 HIV-positive adults .


In a crossover design , participants were randomly assigned to receive either Plumpy'Nut or HEBI for 2 weeks and were switched to the other product for the subsequent 2 weeks .


A third ( control ) group of about 40 HIV-positive participants in each study was randomly assigned to receive no RUTF .


Nurses took anthropometric measurements weekly , and the subjects or their caregivers monitored daily RUTF intake .


Children consumed 69 % of HEBI and 65 % of Plumpy'Nut ( p = .13 ) .


Adults consumed 91 % of HEBI and 81 % of Plumpy'Nut ( p = .059 ) .


Both children ( p = .058 ) and adults ( p .0001 ) preferred HEBI .


Significant gains were observed in percent weight ( p = .035 ) , weight-for-age ( p = .014 ) , and body mass index ( BMI ) - for-age ( p = .036 ) in children who received RUTF and in percent weight ( p = .017 ) and BMI ( p = .0048 ) in adults who received RUTF compared with the control groups .


In this study in Vietnam , both HEBI and Plumpy'Nut were found acceptable by people with HIV .


High-sensitivity cardiac troponin I ( cTnI ) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis .


We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome .


Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay .


First , in the Mechanism Cohort , 122 patients with aortic stenosis ( median age 71 , 67 % male , aortic valve area 1.0 0.4 cm ( 2 ) ) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular ( LV ) myocardial mass , function , and fibrosis .


The indexed LV mass and measures of replacement fibrosis ( late gadolinium enhancement ) were associated with cTnI concentrations independent of age , sex , coronary artery disease , aortic stenosis severity , and diastolic function .


In the separate Outcome Cohort , 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial , Impact of REgression ( SALTIRE ) study , had long-term follow-up for the occurrence of aortic valve replacement ( AVR ) and cardiovascular deaths .


Over a median follow-up of 10.6 years ( 1178 patient-years ) , 24 patients died from a cardiovascular cause and 60 patients had an AVR .


Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 ( 95 % CI , 1.22 to 2.55 ) independent of age , sex , systolic ejection fraction , and aortic stenosis severity .


In patients with aortic stenosis , plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death .


The combination of seawater baths and narrowband ultraviolet B ( NB-UVB ) is a known treatment for psoriasis .


This study evaluates two treatment regimens that combine bathing in geothermal seawater and NB-UVB therapy in comparison with NB-UVB monotherapy .


Sixty-eight psoriasis patients were randomly assigned to outpatient bathing in geothermal seawater combined with NB-UVB therapy three times a week , intensive daily treatment involving bathing in geothermal seawater combined with NB-UVB therapy , or NB-UVB therapy alone three times a week ; treatment period was 6 weeks .


Disease severity [ Psoriasis Area Severity Index ( PASI ) and Lattice System Physician 's Global Assessment scores ] , quality of life ( Dermatology Life Quality Index ) and histological changes were evaluated before , during and after treatment .


The primary end point was the proportion of patients who achieved PASI 75 at 6 weeks .


At 6 weeks , the percentage of patients who achieved PASI 75 and PASI 90 was significantly greater for both regimens , bathing in geothermal seawater three times a week ( 68.1 % and 18.2 % , respectively ) and intensive treatment with geothermal seawater ( 73.1 % and 42.3 % , respectively ) than for NB-UVB monotherapy ( 16.7 % and 0 % , respectively ) ( P < 0.05 in all comparisons ) .


Clinical improvement was paralleled by improvement in quality of life and histological score and a reduction in NB-UVB doses .


Bathing in geothermal seawater combined with NB-UVB therapy in psoriasis induces faster clinical and histological improvement , produces longer remission time and permits lower NB-UVB doses than UVB therapy alone .


n-3 polyunsaturated fatty acids ( contained in fish oil ) have been shown to beneficially influence infection rate and clinical outcomes in surgical patients probably due to their immunomodulatory action .


In contrast , study results of fish oil administration in critically ill patients are controversial .


The aim of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the prevalence of nosocomial infections and clinical outcomes in medical and surgical critically ill patients .


Prospective , multicenter , randomized , comparative , double-blind study .


Seventeen Spanish ICUs during 4 years .


A total of 159 medical and surgical intensive care patients with Acute Physiology and Chronic Health Evaluation II score more than or equal to 13 , expected to require total parenteral nutrition for at least 5 days .


Patients received total parenteral nutrition prepared either with a lipid emulsion containing 10 % fish oil or a fish oil-free lipid emulsion .


The prevalence of nosocomial infections was detected during 28 days of ICU stay .


Patients were followed 6 months after discharge from the ICU for length of hospital stay , hospital mortality , and 6-month mortality .


The number of patients with nosocomial infections was significantly reduced in the fish oil-receiving group ( 21.0 % vs 37.2 % , p = 0.035 ) and the predicted time free of infection was prolonged ( 21 2 vs 16 2 d , p = 0.03 ) .


No significant differences were detected for ICU , hospital , and 6-month mortality .


The results show that administration of n-3 polyunsaturated fatty acids reduces the risk of nosocomial infections and increases the predicted time free of infections in critically ill medical and surgical patients .


The administration of n-3 polyunsaturated fatty acids was safe and well tolerated .


The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis .


Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis .


We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms .


Laboratory and animal research plus prospective placebo-controlled randomized controlled trial ( NCT00529139 ) and retrospective analysis ( NCT00676897 ) .


Research laboratories of Hannover Medical School and Harvard Medical School .


Septic patients/C57Bl/6 mice and human endothelial cells .


Food and Drug Administration-approved library screening .


In a cell-based screen of more than 650 Food and Drug Administration-approved compounds , we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class ( referred to as statins ) that suppressed angiopoietin-2 .


Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase , which in turn activated PI3K-kinase .


Downstream of this signaling , PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter .


In septic mice , transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50 % .


Simvastatin had a similar effect , but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit .


To verify the link between statins and angiopoietin-2 in humans , we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2 .


3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis .


Given angiopoietin-2 's dual role as a biomarker and candidate disease mediator , early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage .


To evaluate the efficacy and safety of alogliptin added to insulin in Japanese patients with type 2 diabetes mellitus ( T2DM ) who are poorly controlled with insulin and diet or exercise .


This was a randomized , double-blind , 12-week comparative trial of alogliptin and insulin versus placebo and insulin in 179 patients with T2DM followed by a 40-week , open-label phase in 169 patients on alogliptin and insulin .


Change in glycated hemoglobin ( HbA1c ) from baseline to the end of double-blind phase ( week 12 ) .


The change in HbA1c ( least squares means ) from baseline to week 12 was -0.96 % for the alogliptin and insulin group and -0.29 % for the placebo and insulin group .


The point estimate ( 95 % confidence interval ) intergroup difference was -0.66 % ( [ -0.824 % , -0.503 % ] ) .


In the alogliptin and insulin group , HbA1c started to decrease from week 2 onward and peaked by week 12 .


The proportions of patients who achieved HbA1c < 8.0 , < 7.0 and < 6.0 % at week 12 were significantly higher in alogliptin and insulin group ( 73.0 , 23.3 and 1.1 % ) than in placebo and insulin group ( 25.0 , 5.7 and 0 % ) .


Incidences of adverse effects were comparable between groups , with no relevant increases in hypoglycemia or weight gain seen .


Alogliptin 25 mg/day was effective and well tolerated when added to insulin in Japanese patients with inadequately controlled T2DM .


Fifty percent of pregnancies in the United States are unintended despite numerous contraceptive methods available to women .


The only male contraceptive methods , vasectomy and condoms , are used by 10 % and 16 % of couples , respectively .


Prior studies have shown efficacy of male hormonal contraceptives in development , but few have evaluated patient acceptability and potential use if commercially available .


The objective of this study is to determine if a transdermal gel-based male hormonal contraceptive regimen , containing testosterone and Nestorone gels , would be acceptable to study participants as a primary contraceptive method .


As part of a three-arm , 6-month , double-blind , randomized controlled trial of testosterone and nestorone gels at two academic medical centers , subjects completed a questionnaire to assess the acceptability of the regimen .


Of the 99 men randomized , 79 provided data for analysis .


Overall , 56 % ( 44/79 ) of men were satisfied or extremely satisfied with this gel-based method of contraception , and 51 % ( 40/79 ) reported that they would recommend this method to others .


One third of subjects ( 26/79 ) reported that they would use this as their primary method of contraception if it were commercially available today .


However , men with concerns about sexually transmitted disease were significantly less satisfied than men without such concerns ( p = 0.03 ) .


A majority of the men who volunteered to participate in this trial of an experimental male hormonal contraceptive were satisfied with this transdermal male hormonal contraceptive .


If commercially available , a combination of topical nesterone and testosterone gels could provide a reversible , effective method of contraception that is appealing to men .


A substantial portion of men report they would use this transdermal male contraceptive regimen if commercially available .


This method would provide a novel , reversible method of contraception for men , whose current choices are limited to condoms and vasectomy .


The current study aimed to investigate the effects of eicosapentaenoic acid ( EPA ) - rich and docosahexaenoic acid ( DHA ) - rich supplementations on cognitive performance and functional brain activation .


A double-blind , counterbalanced , crossover design , with a 30-day washout period between two supplementation periods ( EPA-rich and DHA-rich ) was employed .


Functional magnetic resonance imaging scans were obtained during performance of Stroop and Spatial Working Memory tasks prior to supplementation and after each 30-day supplementation period .


Both supplementations resulted in reduced ratio of arachidonic acid to EPA levels .


Following the EPA-rich supplementation , there was a reduction in functional activation in the left anterior cingulate cortex and an increase in activation in the right precentral gyrus coupled with a reduction in reaction times on the colour-word Stroop task .


By contrast , the DHA-rich supplementation led to a significant increase in functional activation in the right precentral gyrus during the Stroop and Spatial Working Memory tasks , but there was no change in behavioural performance .


By extending the theory of neural efficiency to the within-subject neurocognitive effects of supplementation , we concluded that following the EPA-rich supplementation , participants ' brains worked ` less hard ' and achieved a better cognitive performance than prior to supplementation .


Conversely , the increase in functional activation and lack of improvement in time or accuracy of cognitive performance following DHA-rich supplementation may indicate that DHA-rich supplementation is less effective than EPA-rich supplementation in enhancing neurocognitive functioning after a 30-day supplementation period in the same group of individuals .


The occurrence of response shift ( RS ) in longitudinal health-related quality of life ( HRQoL ) studies , reflecting patient adaptation to disease , has already been demonstrated .


Several methods have been developed to detect the three different types of response shift ( RS ) , i.e. recalibration RS , 2 ) reprioritization RS , and 3 ) reconceptualization RS .


We investigated two complementary methods that characterize the occurrence of RS : factor analysis , comprising Principal Component Analysis ( PCA ) and Multiple Correspondence Analysis ( MCA ) , and a method of Item Response Theory ( IRT ) .


Breast cancer patients ( n = 381 ) completed the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires at baseline , immediately following surgery , and three and six months after surgery , according to the `` then-test/post-test '' design .


Recalibration was explored using MCA and a model of IRT , called the Linear Logistic Model with Relaxed Assumptions ( LLRA ) using the then-test method .


Principal Component Analysis ( PCA ) was used to explore reconceptualization and reprioritization .


MCA highlighted the main profiles of recalibration : patients with high HRQoL level report a slightly worse HRQoL level retrospectively and vice versa .


The LLRA model indicated a downward or upward recalibration for each dimension .


At six months , the recalibration effect was statistically significant for 11/22 dimensions of the QLQ-C30 and BR23 according to the LLRA model ( p 0.001 ) .


Regarding the QLQ-C30 , PCA indicated a reprioritization of symptom scales and reconceptualization via an increased correlation between functional scales .


Our findings demonstrate the usefulness of these analyses in characterizing the occurrence of RS .


MCA and IRT model had convergent results with then-test method to characterize recalibration component of RS .


PCA is an indirect method in investigating the reprioritization and reconceptualization components of RS .


Multidose steroid pretreatment is effective in preventing postextubation airway obstruction ( PEAO ) in adults , however controversy continues for children .


This study was designed as a randomized , placebo-controlled , double-blind trial to compare the effect of 24-h pretreatment with dexamethasone ( 24hPD ) versus 6-h pretreatment ( 6hPD ) on PEAO and reintubation in children at a tertiary care hospital in a developing economy .


Hundred twenty-four children ( 3 months to 12 years ) intubated for 48 h and planned to have extubation during next 24 h were randomized to receive 24hPD ( 0.5 mg/kg/dose , q6h , total of six doses ; n = 66 ) or 6hPD ( total of three doses ; n = 58 ) .


Patients with preexistent upper airway conditions , chronic respiratory diseases , steroid therapy in last 7 days , gastrointestinal bleeding , hypertension , and hyperglycemia and those likely to have poor airway reflexes were excluded .


The two groups were similar at baseline .


24hPD reduced the incidence of PEAO ( 43/66 versus 48/58 ; p = 0.027 ) with absolute risk reduction of 17 % .


It also reduced the incidence of reintubation , though nonsignificantly , by half [ 5/61 versus 9/58 ; relative risk ( RR ) , 1.09 ; 95 % confidence interval ( CI ) , 0.96-1 .25 ] .


Time to recovery from PEAO among non-reintubated patients was shorter among 24hPD patients ( p = 0.016 ) .


No adverse event was noted with dexamethasone use .


Intubation duration > 7 days and cuffed tracheal tubes were found to be independent risk factors for PEAO ( odds ratio 6 and 3.12 , respectively ) .


24-h pretreatment with multidose dexamethasone reduced the incidence of PEAO and the time to recover from it .


24hPD should be considered for high-risk children intubated for > 48 h in the study setting .


Further studies with larger sample size from different socioeconomic background are desirable to validate these findings .


Apolipoprotein C-III ( APOC3 ) is a key regulator of plasma triglyceride levels .


Elevated triglyceride levels are associated with a risk of adverse cardiovascular events and pancreatitis .


ISIS 304801 is a second-generation antisense inhibitor of APOC3 synthesis .


We conducted a randomized , double-blind , placebo-controlled , dose-ranging , phase 2 study to evaluate ISIS 304801 in untreated patients with fasting triglyceride levels between 350 mg per deciliter ( 4.0 mmol per liter ) and 2000 mg per deciliter ( 22.6 mmol per liter ) ( ISIS 304801 monotherapy cohort ) , as well as in patients receiving stable fibrate therapy who had fasting triglyceride levels between 225 mg per deciliter ( 2.5 mmol per liter ) and 2000 mg per deciliter ( ISIS 304801-fibrate cohort ) .


Eligible patients were randomly assigned to receive either ISIS 304801 , at doses ranging from 100 to 300 mg , or placebo , once weekly for 13 weeks .


The primary outcome was the percentage change in APOC3 level from baseline .


A total of 57 patients were treated in the ISIS 304801 monotherapy cohort ( 41 received active agent , and 16 received placebo ) , and 28 patients were treated in the ISIS 304801-fibrate cohort ( 20 received active agent , and 8 received placebo ) .


The mean ( SD ) baseline triglyceride levels in the two cohorts were 581291 mg per deciliter ( 6.63.3 mmol per liter ) and 376188 mg per deciliter ( 4.22.1 mmol per liter ) , respectively .


Treatment with ISIS 304801 resulted in dose-dependent and prolonged decreases in plasma APOC3 levels when the drug was administered as a single agent ( decreases of 40.032.0 % in the 100-mg group , 63.822.3 % in the 200-mg group , and 79.69.3 % in the 300-mg group , vs. an increase of 4.241.7 % in the placebo group ) and when it was administered as an add-on to fibrates ( decreases of 60.212.5 % in the 200-mg group and 70.913.0 % in the 300-mg group , vs. a decrease of 2.225.2 % in the placebo group ) .


Concordant reductions of 31.3 to 70.9 % were observed in triglyceride levels .


No safety concerns were identified in this short-term study .


We found that treatment with ISIS 304801 was associated with significant lowering of triglyceride levels , among patients with a broad range of baseline levels , through selective antisense inhibition of APOC3 synthesis .


( Funded by Isis Pharmaceuticals ; ClinicalTrials.gov number , NCT01529424 . )


Intravitreal triamcinolone acetonide ( IVTA ) is an effective treatment for recalcitrant diabetic macular oedema ( DMO ) .


It has been shown to improve vision with benefits persisting up to five years .


The most common initial side effect of IVTA treatment is rise in intraocular pressure , occurring in approximately 50 % of patients within the first 6 months of treatment .


We evaluated whether there is a correlation between the development of intraocular pressure rise and improvement in vision .


Analysis of individual data from 33 eyes of 33 participants treated with IVTA for DMO from a prospective , randomised , double-masked , placebo controlled trial .


The degree of intraocular pressure ( IOP ) rise was correlated with improvement in best-corrected visual acuity ( BCVA ) at 1 and 6 months .


The proportion of eyes gaining 5 or more logMAR letters was higher in eyes with greater IOP rise ( p = 0.044 ) .


Better absolute improvement in BCVA at 6 months ( p = 0.045 ) was also found in eyes with greater IOP rise .


Regression analyses revealed a correlation between IOP rise of 10 or more mmHg and absolute BCVA improvement at 6 months ( odds ratio 1.22 , 95 % confidence interval 1.01-1 .48 , p = 0.039 ) , but not at 1 month .


IOP rise and vision improvement appear to be correlated following IVTA for DMO , suggesting that the mechanisms that cause both may be linked .


Clinical trials.gov NCT00167518 , September 5 , 2005 .


During continuous venovenous haemofiltration ( CVVH ) , regional anticoagulation with citrate may be superior to heparin in terms of biocompatibility , since heparin as opposed to citrate may activate complement ( reflected by circulating C5a ) and induce neutrophil degranulation in the filter and myeloperoxidase ( MPO ) release from endothelium .


No anticoagulation ( n = 13 ) , unfractionated heparin ( n = 8 ) and trisodium citrate ( n = 17 ) regimens during CVVH were compared .


Blood samples were collected pre - and postfilter ; C5a , elastase and MPO were determined by ELISA .


Additionally , C5a was also measured in the ultrafiltrate .


In the heparin group , there was C5a production across the filter which most decreased over time as compared to other groups ( P = 0.007 ) .


There was also net production of elastase and MPO across the filter during heparin anticoagulation ( P = 0.049 or lower ) , while production was minimal and absent in the no anticoagulation and citrate group , respectively .


During heparin anticoagulation , plasma concentrations of MPO at the inlet increased in the first 10 minutes of CVVH ( P = 0.024 ) .


Citrate confers less filter-induced , potentially harmful complement activation and neutrophil degranulation and less endothelial activation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients .


Prospective , single-blinded , and randomized clinical trial .


This study evaluates the added benefit of promethazine administration as an anxiolytic adjunct to morphine analgesia in reducing acute low back pain ( LBP ) compared with morphine alone .


Acute LBP is one of the most common reasons for emergency department ( ED ) visits .


The optimal analgesic treatment for acute LBP remains controversial .


Anxiety relief has been shown to improve pain management in the ED setting .


We hypothesized that administration of the antihistamine promethazine as an anxiolytic adjunct to morphine analgesia will improve LBP management compared with morphine alone .


Fifty-nine adults , who were treated in our ED for severe acute LBP ( visual analogue scale 70 mm ) , were randomly enrolled in the study .


Thirty patients received slow infusion of intravenous ( IV ) morphine 0.1 mg/kg in normal saline and 29 patients received an analgesic regimen of IV morphine 0.1 mg/kg with promethazine 25 mg administered similarly .


Pain and anxiety levels were subjectively assessed by the patients on a 100-mm visual analogue scale before and after treatment .


Adverse event related to analgesia were recorded in real time .


After analgesia administration patients ' pain rating decreased by 43 mm in the morphine group and by 39 mm in the morphine/promethazine group ( P = 0.26 ) .


Similarly , patients ' anxiety decreased by 19 mm in the morphine group and by 13 mm in the morphine/promethazine group ( P = 0.37 ) .


The average ED stay was 78 minutes longer in the morphine/promethazine group ( P = 0.01 ) , due to the strong sedative effect of promethazine .


Patients ' satisfaction and the rate of adverse events were similar in both groups .


IV administration of morphine-promethazine regimen for pain and anxiety relief associated with acute LBP showed no advantage compared with IV morphine alone and significantly lengthened the overall ED stay .


Thus , we think that promethazine has no place in acute LBP management in the adult ED setting .


1 .


To evaluate the long-term effectiveness of presurgical therapy with GnRH analogues in patients who underwenthydrothermal endometrial ablation ( HTA ) for menorrhagia and assess the relationship between sonographically measured myometrium thickness and pelvic pain .


A prospective randomized control study comparing 15 women ( Group A ) with presurgical subcutaneous triptorelin depot injection before HTA with controls ( Group B , n = 15 ) .


Inclusion criteria were : recurrent menorrhagia , uterus length < 12 cm , no previous hormonal therapy for at least six month , and family plan completed .


Student 's t test was applied , as appropriate , to compare continuous variables .


Proportion were compared with chi-squared .


After 12 months of follow-up , Group A showed a significantly lower ( 0 % vs 20 % ; p = 0.03 ) failure rate after hydrothermoablation than the Group B and a generally higher successful rate at 24 and 48 months .


The discomfort , evaluated with VAS , showed a mean value of 47.6 + / - 15.9 + / - SD ) ; 96.7 % of women reported a mild-moderate postoperative pain .


No perioperative and late complications were recorded .


Presurgical treatment with GnRH analogues seems to improve long-term efficacy of HTA .


Perioperative pelvic pain seems to not be affected by myometrium thickness .


Data are inconsistent regarding the associations between age , age at diagnosis of diabetes , diabetes duration and subsequent vascular complications .


The associations between age ( or age at diagnosis ) , diabetes duration and major macrovascular events , all-cause death and major microvascular events were examined in 11,140 patients with type 2 diabetes randomly allocated to intensive or standard glucose control in the Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified Release Controlled Evaluation ( ADVANCE ) trial .


Rates were calculated by 5 year baseline age ( or age at diagnosis ) and diabetes duration strata .


Risks were estimated using Cox models adjusted for treatment assignment and HbA1c .


The mean age ( SD ) was 65.86.4 years , age at diagnosis was 57.88.7 years and diabetes duration was 7.96.4 years .


Diabetes duration was associated with the risk of macrovascular events ( HR 1.13 [ 95 % CI 1.08 , 1.17 ] ) , microvascular events ( 1.28 [ 1.23 , 1.33 ] ) and death ( 1.15 [ 1.10 , 1.20 ] ) whereas age ( or age at diagnosis ) was only associated with the risk of macrovascular events ( 1.33 [ 1.27 , 1.39 ] ) and death ( 1.56 [ 1.48 , 1.64 ] ) .


No interaction was observed between diabetes duration , age and the risk of macrovascular events or death ( both p > 0.4 ) .


However , an interaction was observed between diabetes duration , age and the risk of microvascular events ( p = 0.002 ) , such that the effects of increasing diabetes duration were greatest at younger rather than older age .


In patients with type 2 diabetes , age or age at diagnosis and diabetes duration are independently associated with macrovascular events and death whereas only diabetes duration is independently associated with microvascular events and this effect is greater in the youngest patients .


Electrotherapy , including theTENS and interferential current ( IFC ) is one of the most frequently used treatments in physical therapy in patients with low back pain .


The aim of this study was to assess the influence of TENS and IFC on pain relief and to compare the analgesic efficacy of the two currents .


Sixty patients aged 53.5 12.5 , with low back pain , were randomly divided into two groups : IFC ( gr .


I ) and TENS ( gr .


II ) .


Depending on the groups , patients were given series of ten 20-minute sessions using either IF orTENS currents .


In all patients VAS and Laitinen modified scale were taken before and after treatment .


After 2-weeks therapy there was improvement in the VAS and Laitinen scale ( all components ) in both groups , except for the part of the Laitinen scale on the reduction of activity in the group II ( TENS ) .


There was no statistically significant difference between the TENS and IF groups in reducing the intensity and other aspects of pain ( frequency , pain medication and activity limitation ) under the influence of therapy ( p > 0.05 ) .


Interferential current and TENS therapy are effective for pain relief in patients with low back pain .


The study showed equal analgesic efficacy of both treatments .


Limited options are available for the treatment of brittle nail syndrome .


To assess the efficacy and safety of topical cyclosporine emulsion ( CsAE ) versus emulsion ( vehicle ) alone in the treatment of brittle nail syndrome .


Twenty-four patients were randomized to topical CsAE emulsion or emulsion ( vehicle ) for 24 weeks .


Four fingernails of each patient were included ; the 2 most severe brittle nails and the second most normal nail were treated with the same medication .


The fourth nail , the most normal nail , remained untreated and was used to assess nail growth .


The prespecified primary endpoint was change from baseline in Physician Global Assessment ( PGA ) score ( 0 to 5 scale ) at each follow-up visit .


Safety evaluations were conducted at each visit .


In the intent-to-treat population ( n = 12 for each treatment arm ) , the PGA score for treated nails improved from baseline ( CsAE , 0.7 to 1.4 ; emulsion , 0.7 to 1.5 ; P < 0.05 for each ) , with no significant between-group differences .


Untreated nails did not improve in overall appearance ( 0.0 to 0.3 grade ; P > 0.05 ) .


Statistically and clinically significant improvement from baseline was reported for nail length/appearance in both CsAE and vehicle groups .


Sample size was relatively small .


The difference in PGA between treated and untreated nails was not analyzed .


Baseline disease severity may have been too mild , limiting detection of efficacy .


Both CsAE and emulsion vehicle applied topically appeared to improve signs and symptoms of brittle nail syndrome and were well tolerated .


These findings warrant corroboration in a larger population and inclusion of comparison with an inactive control and a higher concentration of CsAE , the former which may help in distinguishing the efficacy of vehicle emulsion from CsAE .


Phosphodiesterase ( PDE ) enzymes , including members of PDE4 , have been investigated in the regulation of endocrine and reproductive functions of ovaries .


In addition , selective inhibition of PDE4 enzyme has recently been implicated in the regulation of metabolism with positive effects on glucose homeostasis and weight reduction .


The aim of this study was to evaluate whether the PDE4 inhibitor roflumilast affects body weight and hormonal and metabolic status in obese women with polycystic ovary syndrome ( PCOS ) .


Design/Participants/Main Outcome Measures : A 12-week prospective randomized open-label study was conducted with 36 obese women with PCOS diagnosed by the National Eunice Kennedy Shriver Institute of Child Health and Human Development criteria that had been pretreated with metformin ( MET ) .


They were randomized to MET 1000 mg twice a day or combined treatment ( COM ) with MET 1000 mg twice a day and roflumilast 500 g every day .


The primary outcome was change in anthropometric measures of obesity .


Thirty-one patients ( aged 33.8 7.4 y , twice a day 36.4 5.1 kg/m ( 2 ) , mean SD ) completed the study : 16 on MET and 15 on COM .


Subjects treated with COM lost on average 4.2 2.8 kg compared with a 0.9 2.5 kg weight gain in the MET group ( P = .025 ) .


Body mass index decreased for 1.6 1.1 kg/m ( 2 ) in COM arm compared with increase for 0.9 2.4 kg/m ( 2 ) in the MET arm ( P = .046 ) .


Visceral adipose tissue area as assessed by dual-energy x-ray absorptiometry decreased from 136.7 37.8 to 121.2 36.2 cm ( 2 ) in the COM arm compared with an increase from 155.3 61.9 to 166.7 67.2 cm ( 2 ) in the MET arm ( P = .02 ) .


From baseline to study end , both treatment interventions resulted in a significant reduction of androstenedione ( P = .013 ) , free T ( P = .002 ) , and homeostasis model assessment for insulin resistance score ( P = .027 ) and a significant increase in SHBG ( P = .024 ) , although the between-treatment differences of the changes have not been statistically significant yet .


Roflumilast added to metformin reduced body weight in obese women with PCOS , primarily due to a loss of fat mass .


Randomized controlled trials specifically designed to assess inflammation-related outcomes in response to dairy consumption are lacking .


We investigated the impact of dairy food consumption on biomarkers of inflammation in healthy men and women with low-grade systemic inflammation .


In a multicenter randomized crossover study , 112 adult men and women with high-sensitivity C-reactive protein ( hs-CRP ) values > 1 mg/L consumed 3 servings/d of dairy ( 375 mL low-fat milk , 175 g low-fat yogurt , and 30 g regular-fat cheddar cheese ) or energy-matched control ( fruit juice , vegetable juice , cashews , and 1 cookie ) products as part of prudent 4-wk diets , each separated by a 4 - to 8-wk washout period .


Serum concentrations of inflammation biomarkers were measured at the beginning and end of each dietary phase .


Expression levels of key inflammatory genes and transcription factors in whole blood cells were assessed at the end of each diet by real-time polymerase chain reaction in a random subset of 53 subjects .


Analysis of within-diet changes ( post - vs. prediet values ) showed a significant reduction in hs-CRP concentrations after the control diet ( -11.7 % , P = 0.05 ) but no change after the dairy diet ( -7.3 % , P = 0.47 ) .


As a result , changes in hs-CRP differed between the dairy and control diets ( P = 0.04 ) .


Both the control and dairy diets similarly reduced interleukin-6 concentrations compared with diet-specific baseline values ( -17.6 % and -19.9 % , respectively ; P < 0.0001 for both , P = 0.77 for between-diet comparison ) .


No between - or within-diet difference was observed in adiponectin concentrations , and there was also no between-diet difference in the expression of inflammatory genes and transcription factors .


Consistent with data from previous work , these results suggest that short-term consumption of a combination of low - and high-fat dairy products as part of a healthy diet has no adverse effects on inflammation .


This trial was registered at www.clinicaltrials.gov as NCT01444326 .


Hepatic lipase ( HL ) plays a pivotal role in the metabolism of HDL and LDL .


Recent genome-wide association studies have identified common variants in the HL gene ( LIPC ) associated with HDL cholesterol .


We tested the effect of a common variant in LIPC on changes in blood lipids in response to weight-loss diets in the Preventing Overweight Using Novel Dietary Strategies Trial .


We genotyped LIPC rs2070895 in 743 overweight or obese adults aged 30-70 y ( 61 % women ) who were assigned to high-fat ( 40 % energy ) or low-fat ( 20 % energy ) diets for 2 y.


We measured serum concentrations of total cholesterol ( TC ) , triglycerides , LDL cholesterol , and HDL cholesterol at baseline and 2 y of intervention .


At 2 y of intervention , dietary fat modified effects of the variant on changes in serum TC , LDL cholesterol , and HDL cholesterol ( P-interaction : 0.0008 , 0.004 , and 0.03 , respectively ) .


In the low-fat group , as compared to the G allele , the A allele tended to be related to the decrease in TC and LDL cholesterol concentrations [ TC ( SE ) : -5.5 3.0 , P = 0.07 ; LDL cholesterol : -4.8 2.5 , P = 0.06 ] and a lower increase in HDL cholesterol concentrations ( SE : -1.37 0.69 , P = 0.048 ) , whereas an opposite effect in the high-fat diet group was evident [ TC ( SE ) : 7.3 2.7 , P = 0.008 ; LDL cholesterol : 4.1 2.3 , P = 0.07 ] , and there was no genetic effect on changes in HDL cholesterol concentrations ( P = 0.54 ) .


Dietary fat intake modifies the effect of a common variant in LIPC on changes in serum lipids during a long-term weight-loss intervention in overweight or obese adults .


This trial was registered at clinicaltrials.gov as NCT00072995 .


To explore the clinical efficacy of open-door cervical laminoplasty combined Modified Buyang Huanwu Decoction ( MBHD ) to treat cervical spinal canal stenosis ( CSCS ) .


Totally 32 CSCS patients were randomly assigned to two groups , Group A ( 17 cases , treated by laminoplasty ) and Group B ( 15 cases , treated by laminoplasty combined MBHD ) .


All patients received open-door cervical laminoplasty .


Those in Group B took MBHD additionally for 2 weeks after surgery .


The visual analogue scale ( VAS ) , the Japanese Orthopedic Association ( JOA ) score , and the neck disability index ( NDI ) were measured preoperative , postoperative 3 months and 12 months , respectively .


There was no statistical difference in preoperative VAS , JOA , or NDI ( P > 0.05 ) .


The VAS , JOA , and NDI were obviously improved 3 months and 12 months after surgery in the two groups , showing statistical difference when compared with before surgery in the same group ( P < 0.01 ) .


At 3 months after surgery the aforesaid indices in Group B were superior to those in Group A ( P < 0.05 ) .


There was no statistical difference in the aforesaid indices between the two groups at 12 months after surgery ( P > 0.05 ) .


MBHD favorably improved early recovery of neural functions of CSCS patients ( 3 months after surgery ) .


Increased levels of reactive oxygen species during and after surgery may affect inflammatory response , post-operative adhesion molecule formation , and hemodynamic stability .


The glutathione redox cycle is an important regulator in oxidative stress and its reduced forms scavenge free radicals .


N-acetyl cysteine , a precursor of reduced glutathione , is considered as a potentially therapeutic wide spectrum agent in clinical practice .


We therefore examined whether N-acetyl cysteine improves some biochemical parameters in cancer patients undergoing major abdominal surgery .


Thirty-three patients diagnosed with pancreas , stomach , rectum , colon malignancies , and undergoing major abdominal surgery at Ankara Numune Training and Research Hospital were randomly divided into two groups ; control ( CON ) and N-acetyl cysteine ( NAC ) .


The NAC group had 1,200mgN-acetyl cysteine starting two days before the operation day , in addition to isonitrogenous and isocaloric total parenteral nutrition of 1.2 g/kg protein , 25kcal/kg , and 60:40 carbohydrate/fat ratio .


Blood and urine samples were drawn two days before the operation , on operation day , and on the first , third , and fifth days post-operation .


Plasma malondialdehyde was significantly lower in the NAC group ( P < 0.001 ) .


N-acetyl cysteine treatment did not affect plasma levels of vitamin A , C or E.


The NAC group exhibited a higher ratio of reduced glutathione to oxidised glutathione ( P = 0.019 ) .


Urinary nitrate level was also significantly lower in the NAC group ( P = 0.016 ) .


The study demonstrated the clinical importance of N-acetyl cysteine supplementation on antioxidant parameters in abdominal surgery patients .


In these patients N-acetyl cysteine and vitamin administration can be considered as an effective method for improvement of oxidative status .


In our randomised , controlled , phase 3 trial NeOAdjuvant Herceptin ( NOAH ) trial in women with HER2-positive locally advanced or inflammatory breast cancer , neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival .


We report updated results from our primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy .


We did this multicentre , open-label , randomised trial in women with HER2-positive locally advanced or inflammatory breast cancer .


Participants were randomly assigned ( 1:1 ) , by computer program with a minimisation technique , to receive neoadjuvant chemotherapy alone or with 1 year of trastuzumab ( concurrently with neoadjuvant chemotherapy and continued after surgery ) .


A parallel group with HER2-negative disease was included and received neoadjuvant chemotherapy alone .


Our primary endpoint was event-free survival .


Analysis was by intention to treat .


This study is registered at www.controlled-trials.com , ISRCTN86043495 .


Between June 20 , 2002 , and Dec 12 , 2005 , we enrolled 235 patients with HER2-positive disease , of whom 118 received chemotherapy alone and 117 received chemotherapy plus trastuzumab .


99 additional patients with HER2-negative disease were included in the parallel cohort .


After a median follow-up of 5.4 years ( IQR 3.1-6 .8 ) the event-free-survival benefit from the addition of trastuzumab to chemotherapy was maintained in patients with HER2-positive disease .


5 year event-free survival was 58 % ( 95 % CI 48-66 ) in patients in the trastuzumab group and 43 % ( 34-52 ) in those in the chemotherapy group ; the unadjusted hazard ratio ( HR ) for event-free survival between the two randomised HER2-positive treatment groups was 0.64 ( 95 % CI 0.44-0 .93 ; two-sided log-rank p = 0.016 ) .


Event-free survival was strongly associated with pathological complete remission in patients given trastuzumab .


Of the 68 patients with a pathological complete response ( 45 with trastuzumab and 23 with chemotherapy alone ) , the HR for event-free survival between those with and without trastuzumab was 0.29 ( 95 % CI 0.11-0 .78 ) .


During follow-up only four cardiovascular adverse events were regarded by the investigator to be drug-related ( grade 2 lymphostasis and grade 2 lymphoedema , each in one patient in the trastuzumab group , and grade 2 thrombosis and grade 2 deep vein thrombosis , each in one patient in the chemotherapy-alone group ) .


These results show a sustained benefit in event-free survival from trastuzumab-containing neoadjuvant therapy followed by adjuvant trastuzumab in patients with locally advanced or inflammatory breast cancer , and provide new insight into the association between pathological complete remission and long-term outcomes in HER2-positive disease .


A better understanding of the stroke risk factors in children with congenital heart disease ( CHD ) could inform stroke prevention strategies .


We analyzed pediatric stroke associated with CHD in a large community-based case-control study .


From 2.5 million children ( aged < 20 years ) enrolled in a Northern California integrated healthcare plan , we identified children with ischemic and hemorrhagic strokes and randomly selected age - and facility-matched stroke-free controls ( 3 per case ) .


We determined exposure to CHD ( diagnosed before stroke ) and used conditional logistic regression to analyze stroke risk factors .


CHD was identified in 15 of 412 cases ( 4 % ) versus 7 of 1236 controls ( 0.6 % ) .


Cases of childhood stroke ( occurring between ages 29 days to 20 years ) with CHD had 19-fold ( odds ratio , 19 ; 95 % confidence interval 4.2-83 ) increased stroke risk compared to controls .


History of CHD surgery was associated with > 30-fold ( odds ratio , 31 ; confidence interval 4-241 ) increased risk of stroke in children with CHD when compared with controls .


After excluding perioperative strokes , the history of CHD surgery still increased the childhood stroke risk ( odds ratio , 13 ; confidence interval 1.5-114 ) .


The majority of children with stroke and CHD were outpatients at the time of stroke , and almost half the cases who underwent cardiac surgery had their stroke > 5 years after the most recent procedure .


An estimated 7 % of ischemic and 2 % of hemorrhagic childhood strokes in the population were attributable to CHD .


CHD is an important childhood stroke risk factor .


Children who undergo CHD surgery remain at elevated risk outside the perioperative period and would benefit from optimized long-term stroke prevention strategies .


To analyze differences in the cost of treatment for infants randomized to primary intraocular lens ( IOL ) implantation versus optical correction with a contact lens ( CL ) after unilateral cataract surgery in the Infant Aphakia Treatment Study ( IATS ) .


Retrospective cost analysis of a prospective , randomized clinical trial based on Georgia Medicaid reimbursement data as well as actual costs of supplies used during the study , adjusted for inflation .


The IATS is a multicenter ( n = 12 ) , randomized clinical trial comparing the optical treatment of aphakia with either primary IOL implantation ( n = 57 ) or CL correction ( n = 57 ) in 114 infants with unilateral congenital cataract .


One hundred fourteen infants underwent unilateral cataract surgery and were either corrected optically by primary IOL implantation at the time of surgery or were corrected with a CL after surgery .


The mean cost of cataract surgery and all additional surgeries , examinations , and supplies used up to 5 years of age .


The 5-year treatment cost of an infant with a unilateral congenital cataract corrected optically with an IOL was $ 27 090 versus $ 25 331 for a patient treated with a CL after initial cataract surgery .


The total cost of supplies was $ 3204 in the IOL group versus $ 7728 in the CL group .


Unilateral cataract surgery in infancy coupled with primary IOL implantation is approximately 7 % more expensive than aphakia and CL correction .


Patient costs are more than double with CL versus IOL treatment .


Paclitaxel and gemcitabine ( PG ) combination chemotherapy is effective as a maintenance chemotherapeutic regimen in metastatic breast cancer ( MBC ) patients because it increases progression-free survival ( PFS ) , which increases overall survival ( OS ) .


The primary purpose of our study was to investigate the association between genetic polymorphisms in the genes involved in PG pathways and clinical outcomes in MBC patients treated with PG chemotherapy .


A total of 324 MBC patients were enrolled in this prospective multicenter trial of PG as the first-line chemotherapy .


Eighty-five of the 324 patients from two institutes were available for analysis of single nucleotide polymorphisms ( SNPs ) .


Germline DNA was extracted from peripheral blood mononuclear cells .


Thirty-eight SNPs in 15 candidate genes selected from pathways that may influence the metabolism and transport of , or sensitivity , to PG were analysed .


The median PFS and OS of all 324 patients were 8.7 months ( 95 % confidence interval [ CI ] : 7.5-9 .6 months ) and 26.9 months ( 95 % CI : 23.6-30 .1 months ) , respectively .


An SNP in SLC28A3 ( rs7867504 , C/T ) was associated with OS ( CC or CT versus TT : 37 versus 21 months , p = 0.027 , hazard ratio [ HR ] 2.6 , 95 % CI : 1.1-6 .3 ) .


SLC29A1 GA haplotype had a significantly shorter OS ( p = 0.030 , HR 3.391 , 95 % CI : 1.13-10 .19 ) .


RRM1 ( ribonucleotide reductase large subunit M1 ) SNP ( rs9937 ) , and haplotypes ATAA and ATGA were significantly associated with neurotoxicity .


Genetic polymorphisms in SLC28A3 , SLC29A1 and RRM1 can influence the clinical outcome of MBC patients treated with PG chemotherapy .


Further studies on the functional mechanisms relating to these germline polymorphisms in these genes are warranted .


JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient .


In this Phase 3 , multicenter , randomized , open-label , parallel-group study , we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis .


A total of 230 patients with a serum phosphate 1.97 and < 3.23 mmol/L were randomized to JTT-751 ( dose adjusted between 1.5 and 6.0 g/day ) or sevelamer hydrochloride ( dose adjusted between 3.0 and 9.0 g/day ) for 12 weeks .


The primary outcome was change in serum phosphate from baseline to end of treatment .


Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone ( PTH ) .


The changes in ferritin , transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes .


Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group , establishing non-inferiority of JTT-751 compared with sevelamer ( least squares mean , -0.03 mmol/L ; 95 % confidence interval , -0.13 to 0.07 mmol/L ) .


Corrected serum calcium increased and PTH decreased from baseline within both groups ; changes between groups were similar .


Gastrointestinal disorders were the most common adverse events in both groups ; the incidence of diarrhea was higher in the JTT-751 group , while constipation occurred frequently in the sevelamer group .


Treatment with JTT-751 resulted in significant relative increases in serum ferritin and transferrin saturation .


Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia .


Differential adverse effects were observed ; biochemical markers of iron status increased in patients treated with JTT-751 .


CTI-111433 ( The Japan Pharmaceutical Information Center at : http / / www.clinicaltrials.jp ) .


Date of registration : 7 March 2011 .


Little is known as to whether primary care teams ' perceptions of how well they have implemented the Chronic Care Model ( CCM ) corresponds with their patients ' own experience of chronic illness care .


We examined the extent to which practice members ' perceptions of how well they organized to deliver care consistent with the CCM were associated with their patients ' perceptions of the chronic illness care they have received .


Analysis of baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM in small , community-based primary care practices .


All practice `` members '' ( i.e. , physician providers , non-physician providers , and staff ) completed the Assessment of Chronic Illness Care ( ACIC ) survey and adult patients with 1 or more chronic illnesses completed the Patient Assessment of Chronic Illness Care ( PACIC ) questionnaire .


Two sets of hierarchical linear regression models accounting for nesting of practice members ( N = 283 ) and patients ( N = 1,769 ) within 39 practices assessed the association between practice member perspectives of CCM implementation ( ACIC scores ) and patients ' perspectives of CCM ( PACIC ) .


ACIC summary score was not significantly associated with PACIC summary score or most of PACIC subscale scores , but four of the ACIC subscales [ Self-management Support ( p < 0.05 ) ; Community Linkages ( p < 0.02 ) , Delivery System Design ( p < 0.02 ) , and Organizational Support ( p < 0.02 ) ] were consistently associated with PACIC summary score and the majority of PACIC subscale scores after controlling for patient characteristics .


The magnitude of the coefficients , however , indicates that the level of association is weak .


The ACIC and PACIC scales appear to provide complementary and relatively unique assessments of how well clinical services are aligned with the CCM .


Our findings underscore the importance of assessing both patient and practice member perspectives when evaluating quality of chronic illness care .


NCT00482768 .


Copper IUD is a long term and reversible contraception which equals tubal ligation in terms of sterilization .


One of the barriers to using this contraception method is the fear and the pain associated with its insertion .


Eutectic mixture of local anesthetics ( EMLA ) 5 % is a local anesthetic that contains 25 mg lidocaine and 25 mg of prilocaine per gram .


Application of topical analgesic cream to the cervix for laser surgery , hysteroscopy and hysterosalpingography is known Aims : this study aimed to determine the effect of EMLA on IUD insertion pain .


This triple blind clinical trial was conducted on 92 women in a clinic in Hamedan in 2012 .


After applying the cream on the cervix , pain in three steps , after using Tenaculum , after inserting hystrometr and after inserting IUD and removing IUD insertion tube were assessed with visual analog scale and were compared in EMLA group and placebo group Statistical analysis used to determine and compare the pain of independent t tests , Mann-Whitney U test and repeated measures analysis of variance and chi-square tests to determine the homogeneity of variables and Fisher 's exact test was used .


Insertion hystrometr was determined as the most painful IUD insertion .


The mean pain at step 2 ( inserting hystrometr ) was ( 3.112.53 ) in EMLA group , ( 5.232.31 ) in placebo group .


EMLA cream significantly reduced the pain after using tenaculum ( P < 0.001 ) , pain inserting Hystrometr ( P < 0.001 ) and pain at IUD insertion and removing insertion tube ( P < 0.001 ) CONCLUSIONS : Topical Application of EMLA 5 % cream as a topical anesthetic on the cervix before insertion IUD reduced the pain during this procedure .


To evaluate how much the improvement of lower urinary tract symptoms ( LUTS ) affects sexual function and which storage symptoms or voiding symptoms have the greatest effect on sexual function .


A total of 187 patients were enrolled in this study .


Patients were randomly assigned to receive either tamsulosin 0.2 mg ( group A ) or tamsulosin 0.2 mg and solifenacin 5 mg ( group B ) .


At 4 weeks and 12 weeks , the LUTS and sexual function of the patients were evaluated by use of the International Index of Erectile Function-5 ( IIEF5 ) , International Prostate Symptom Score ( IPSS ) , Overactive Bladder Symptom Score ( OABSS ) questionnaire , uroflowmetry , and bladder scan .


Both groups A and B showed statistically significant improvements in IPSS , OABSS , and quality of life ( QoL ) .


Group A showed improved maximum flow rate , mean flow rate , and residual urine volume by time .


Group B did not show an improvement in flow rate or residual urine volume but total voiding volume increased with time .


The IIEF5 score was not improved in either group .


In group A , the IIEF5 score dropped from 13.66 4.97 to 11.93 6.14 after 12 weeks ( p = 0.072 ) .


Group B showed a decline in the IIEF5 score from 13.19 5.91 to 12.45 6.38 ( p = 0.299 ) .


Although group B showed a relatively smaller decrease in the IIEF5 score , the difference between the two groups was not significant ( p = 0.696 ) .


Tamsulosin monotherapy and combination therapy with solifenacin did not improve erectile function despite improvements in voiding symptoms and QoL .


The improvement in storage symptoms did not affect erectile function .


We evaluate the effect of the protoconized anemia therapy on adverse events using the Hb and ferritin levels of individual patients undergoing maintenance hemodialysis ( MHD ) .


Design : A randomized , parallel group , multi-center study .


Two hundred sixty-six MHD patients .


Intervention group : The doses of erythropoietin , iron , and vitamin C were adjusted every month based on the ferritin and hemoglobin ( Hb ) levels according to the protocol .


Non-intervention group : The attending physician determined the doses of erythropoietin and iron .


The maintenance rate of target Hb and ferritin levels were significantly higher in the Intervention group than in the Non-intervention group .


The frequency of hospitalization was significantly lower for patients with a higher maintenance rate of target Hb levels than for those with a lower maintenance rate .


Using an anemia treatment protocol according to the individual Hb and ferritin levels of hemodialysis patients might stabilize the Hb and ferritin levels , which in turn could contribute to the lower frequency of adverse events in MHD patients .


The impact of long-acting calcium channel blocker ( CCB ) administration on serial changes in left ventricular ( LV ) function and morphology in hypertensive patients with LV hypertrophy remains unclear .


This study attempted to clarify this impact by comparing the effects of administration of azelnidipine with that of amlodipine using conventional and speckle tracking echocardiography .


An equal number ( 16 ) of 32 hypertensive patients was prospectively assigned to a group administered 5 mg of amlodipine/day or a group administered 16 mg of azelnidipine/day .


LV function and morphology was examined by conventional and speckle tracking echocardiography at baseline and at 1 , 3 , 6 , and 12 months after treatment initiation .


Both groups were found to have experienced a significant decrease in systolic blood pressure by 1 month after treatment initiation ; a significant reduction in septal thickness and LV mass index at 6 and 12 months .


Transmitral flow E/A ratio and early diastolic mitral annular velocity at lateral wall significantly improved at 12 months .


On the other hand , a significant improvement of global longitudinal strain was observed earlier than the above indexes at 3 , 6 , and 12 months .


Ar-A duration difference was significantly decreased at 3 months .


The global circumferential strain improved significantly at 3 months , but there were no significant changes in mid - / apical circumferential and radial strains throughout the study period .


Azelnidipine has beneficial effects on LV mass regression , transmitral flow , tissue Doppler , and LV longitudinal strain that are comparable to those of amlodipine on the same parameters .


To observe the clinical efficacy of sodium cromoglicate eye drops combined with Yupingfeng granules in the treatment of allergic conjunctivitis .


A total of 118 patients with allergic conjunctivitis were randomly divided into a combined sodium cromoglicate and Yupingfeng Granule ( treatment ) group ( n = 74 ) and a sodium cromoglicate ( control ) group ( n = 44 ) .


Clinical efficacy of the two treatments was evaluated by observing the changes in patients ' symptoms and physical signs before and after their respective treatments .


Following treatment , the symptoms and physical signs related to allergic conjunctivitis were significantly alleviated in all 118 cases .


The total efficacy of the combined sodium cromoglicate and Yupingfeng granule treatment was 91.9 % , which was significantly higher than the value of 75.0 % obtained with sodium cromoglicate alone ( P < 0.05 ) .


Combined therapy of sodium cromoglicate eye drops and Yupingfeng granules had a high efficacy and no significant adverse reactions .


Therefore , this treatment deserves to be considered for wide application in clinical settings .


To examine if implicit emotion regulation ( occurring outside of awareness ) is related to binge eating disorder ( BED ) symptomatology and explicit emotion regulation ( occurring within awareness ) , and can be altered via intervention .


Implicit emotion regulation was assessed via the Emotion Conflict Task ( ECT ) among a group of adults with BED .


Study 1 correlated BED symptomatology and explicit emotion regulation with ECT performance at baseline ( BL ) and after receiving BED treatment ( PT ) .


Study 2 generated effect sizes comparing ECT performance at BL and PT with healthy ( non-eating disordered ) controls ( HC ) .


Study 1 yielded significant correlations ( p < .05 ) between both BED symptomatology and explicit emotion regulation with ECT performance .


Study 2 found that compared to BL ECT performance , PT shifted ( d = -.27 ) , closer to HC .


Preliminary results suggest a ) BED symptomatology and explicit emotion regulation are associated with ECT performance , and b ) PT ECT performance normalized after BED treatment .


Implicit emotion regulation may be a BED treatment mechanism because psychotherapy , directly or indirectly , decreased sensitivity to implicit emotional conflict .


Further understanding implicit emotion regulation may refine conceptualizations and effective BED treatments .


The purpose of our study was to investigate the effects of Kinesio Taping ( ) Application with Complex Decongestive Therapy ( CDT ) in patients with lymphedema .


45 patients were randomly divided into 3 groups ( CDT including Bandage , CDT including Bandage + Kinesio Tape ( ) , CDT including Kinesio Tape ( ) without bandage ) .


Assessments included the severity of the symptoms such as pain , discomfort , heaviness , tension , stiffness and weakness .


Bilateral circumference measurements were done for evaluation of the edema .


Symptoms were decreased in all three groups ( p < 0.05 ) .


CDT was found effective only during treatment in arm volume ( p < 0.05 ) .


Kinesio Taping ( ) applied with CDT had effect of decreasing edema after 10 days of treatment period ( p < 0.05 ) and for control period ( p < 0.05 ) .


Only the application of Kinesio Taping ( ) group also had significant decrease at edema ( p < 0.05 ) .


Kinesio Taping ( ) Application along with CDT may have a better effect on decreasing lymphedema which can stimulate the reduction of edema for long term effects .


To study the efficacy of short-term educational intervention for parents of preschool children with anxiety .


Forty-nine children with Spence Preschool Anxiety Scale ( SPAS ) scores of 48 were randomly divided into intervention and control groups .


The children 's parents in the intervention group received a collective curriculum on children 's anxiety management six times , while the control group was only followed up .


All children were evaluated for anxiety by the SPAS 3 and 6 months later , and then the results were compared between the two groups .


The test was completed in 21 cases of the intervention group and 22 cases of the control group .


At month 3 , the intervention group had a significantly lower percentage of children with SPAS scores of 48 than the control group ( 62 % vs 91 % ; P < 0.05 ) , and this percentage was also significantly lower in the intervention group than in the control group at month 6 ( 52 % vs 82 % ; P < 0.05 ) .


At month 3 , the intervention group had a significantly reduced mean SPAS score , which was significantly lower than that of the control group ( 69 12 vs 81 12 ; P < 0.01 ) .


At month 6 , both groups showed significant decreases in SPAS score , but still the SPAS score was significantly lower in the intervention group than in the control group ( 65 13 vs 78 13 ; P < 0.01 ) .


Early short-term education for parents can relieve their preschool children 's anxiety effectively , but the long-term effect needs to be evaluated by follow-up .


To report penile integrity measures , including stretched penile length ( SPL ) , from a randomized , double-blind , double-dummy , placebo-controlled trial evaluating treatment with tadalafil initiated after nerve-sparing radical prostatectomy ( nsRP ) .


Patients aged 68 years were randomized after nsRP 1:1:1 to 9-month double-blind treatment ( DBT ) with tadalafil 5 mg once daily ( OaD ) , 20-mg tadalafil on-demand ( `` pro-re-nata '' ; PRN ) , or placebo , followed by 6-week drug-free washout and 3-month open-label OaD treatment .


Secondary outcome measures included the change in SPL from pre-nsRP to the end of DBT ( analysis of covariance adjusting for treatment , country , baseline , age , and nerve-sparing score ) , responses to Sexual Encounter Profile ( SEP ) questions 1-3 ( mixed models for repeated measures adjusting for treatment , country , visit , visit-treatment-interaction , age ) , and Standardized Morning Erection Question ( Cochran-Mantel-Haenszel test adjusted for age and country ) .


Four hundred twenty-three patients were randomized to tadalafil OaD ( N = 139 ) , tadalafil PRN ( N = 143 ) , and placebo ( N = 141 ) .


Greater retainment of SPL was observed with tadalafil OaD vs placebo at the end of DBT ( least-square mean [ 95 % confidence interval ] difference OaD vs placebo , 4.1 mm [ 0.4 to 7.8 mm ] ; P = .032 ) .


No significant effects on SPL were found for tadalafil PRN vs placebo , or for the nerve-sparing score .


Penile tumescence ( SEP1 ) and ability for vaginal insertion ( SEP2 ) significantly improved vs placebo at the end of double-blind and open-label treatment for patients randomized to tadalafil OaD only .


The ability for successful sexual intercourse ( SEP3 ) significantly improved with tadalafil OaD vs placebo only during DBT .


The distribution of Standardized Morning Erection Question responses was different at the end of DBT ( P = .045 ) ; 34.2 % of patients on tadalafil OaD , 50.0 % on tadalafil PRN , and 56.5 % on placebo reported absence of morning erections .


These data suggest the early initiation of tadalafil OaD protects from penile length loss and may contribute to protection from structural cavernosal changes after nsRP .


Efficacy and safety of first-line axitinib/paclitaxel/carboplatin versus bevacizumab/paclitaxel/carboplatin in advanced non-squamous non-small-cell lung cancer ( NSCLC ) was evaluated .


Patients with stage IIIB/IV disease stratified by adjuvant therapy and gender were randomised 1 : 1 to axitinib ( 5 mg twice daily ) or bevacizumab [ 15 mg/kg every 3 weeks ( Q3W ) ] , both with paclitaxel ( 200 mg/m ( 2 ) Q3W ) / carboplatin ( AUC 6 mg min/ml Q3W ) .


The trial was discontinued after preliminary analysis .


Median progression-free survival ( primary end point ) for axitinib ( N = 58 ) and bevacizumab ( N = 60 ) , respectively , was 5.7 and 6.1 months [ hazard ratio ( HR ) 1.09 , 95 % confidence interval ( CI ) 0.68-1 .76 ; one-sided stratified P = 0.64 ] ; median overall survival was 10.6 and 13.3 months ( HR 1.12 , 95 % CI 0.74-1 .69 ; one-sided stratified P = 0.70 ) .


Objective response rates ( 95 % CI ) were 29.3 % ( 18.1-42 .7 ) and 43.3 % ( 30.6-56 .8 ) , respectively ; risk ratio 0.676 ( 95 % CI 0.41-1 .11 ; one-sided stratified P = 0.94 ) .


The most common grade 3/4 adverse events included neutropenia ( 28 % versus 20 % ) , fatigue ( 14 % versus 7 % ) , and hypertension ( 14 % versus 5 % ) .


Patient-reported outcomes based on the EORTC QLQ-C30 were similar between arms .


In patients with advanced non-squamous NSCLC , axitinib/paclitaxel/carboplatin did not improve efficacy versus bevacizumab/paclitaxel/carboplatin , and was less well tolerated .


To evaluate the effect of resistance training ( RT ) on non alcoholic liver disease ( NAFLD ) patients .


A randomized clinical trial enrolling NAFLD patients without secondary liver disease ( e.g. , without hepatitis B virus , hepatitis C virus or excessive alcohol consumption ) .


Patients were randomly allocated either to RT , three times weekly , for 3 mo or a control arm consisting of home stretching .


The RT included leg press , chest press , seated rowing , latissimus pull down etc. with 8-12 repetitions , 3 sets for each exercise , for a total duration of 40 min .


Hepatic ultrasound , fasting blood tests , anthropometrics and body composition by dual energy X-ray absorptiometry were assessed .


At baseline and follow-up , patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake .


Steatosis was quantified by the hepatorenal-ultrasound index ( HRI ) representing the ratio between the brightness level of the liver and the right kidney .


The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy .


Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching .


After dropout or exclusion from analysis because of protocol violation ( weight change > 3 kg ) , thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol .


All baseline characteristics were similar for the two treatment groups with respect to demographics , anthropometrics and body composition , blood tests and liver steatosis on imaging .


HRI score was reduced significantly in the RT arm as compared to the stretching arm ( -0.25 0.37 vs -0.05 0.28 , P = 0.017 ) .


The RT arm had a significantly higher reduction in total , trunk and android fat with increase in lean body mass .


There was no correlation between the reduction in HRI in the RT arm and weight change during the study , but it was positively correlated with the change in trunk fat ( r = 0.37 , P = 0.048 ) .


The RT arm had a significant reduction in serum ferritin and total cholesterol .


There was no significant difference between arms in dietary changes and these did not correlate with HRI change .


Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin .


RT may serve as a complement to treatment of NAFLD .


There are limited data on prognosis and outcomes of patients with new-onset atrial fibrillation ( AF ) compared with those with a prior history of AF .


We conducted a comparison of these 2 groups in the AFFIRM trial .


New-onset AF was the qualifying arrhythmia in 1,391 patients ( 34 % ) .


Compared with patients with prior history of AF , patients with new-onset AF were more likely to have a history of heart failure .


There was no mortality difference between rate control ( RaC ) and rhythm control ( RhC ) among patients with new-onset AF ( 17 % vs 20 % , P = .152 ) .


In the univariate model , new-onset AF was associated with increased risk of mortality compared with history of prior AF ( RaC unadjusted hazard ratio [ HR ] 1.36 [ P = .010 ] , RhC unadjusted HR 1.39 [ P = .003 ] ) .


However , after multivariate adjustments , new-onset AF did not carry an increased risk of mortality ( RaC adjusted HR 1.14 [ P = .370 ] , RhC adjusted HR 1.16 [ P = .248 ] ) .


Subjects with new-onset AF randomized to the RhC arm were more likely to remain in normal sinus rhythm at follow-up ( adjusted HR 0.79 , P = .012 ) compared with patients with prior history of AF .


In a multivariable analysis adjusting for confounders , new-onset AF was not associated with increased mortality compared with prior history of AF regardless of the treatment strategy .


Patients with new-onset AF treated with the rhythm control strategy were more likely to remain in normal sinus rhythm on follow-up .


Previous studies have shown a positive effect of zinc as an adjunctive therapy on reducing depressive symptoms .


However , to our knowledge , no study has examined the effect of zinc monotherapy on mood .


The aim of the present study was to determine the effects of zinc monotherapy on depressive symptoms and serum brain-derived neurotrophic factor ( BDNF ) levels in overweight or obese subjects .


Fifty overweight or obese subjects were randomly assigned into two groups and received either 30 mg zinc or placebo daily for 12 weeks .


At baseline and post-intervention , depression severity was assessed using Beck depression inventory II ( BDI II ) , and serum BDNF and zinc levels were determined by enzyme-linked immunosorbent assay and atomic absorption spectrophotometry , respectively .


The trial was completed with 46 subjects .


After a 12-week supplementation , serum zinc and BDNF levels increased significantly in the zinc-supplemented group compared with the placebo group .


BDI scores declined in both the groups at the end of the study , but reduction in the zinc-supplemented group was significantly higher than the placebo group .


More analysis revealed that following supplementation , BDI scores decreased in subgroup of subjects with depressive symptoms ( BDI 10 ) ( n = 30 ) , but did not change in the subgroup of non-depressed subjects ( BDI < 10 ) ( n = 16 ) .


Moreover , a significant inverse correlation was observed between serum BDNF levels and depression severity in all participants .


Interestingly , a significant positive correlation was found between serum BDNF and zinc levels at baseline .


Zinc monotherapy improves mood in overweight or obese subjects most likely through increasing BDNF levels .


Gastroparesis is a well-known complication to diabetes mellitus ( DM ) .


Dietary advice is considered to be of importance to reduce gastrointestinal ( GI ) symptoms in patients with diabetic gastroparesis , but no randomized controlled trials exist .


Our aim was to compare GI symptoms in insulin treated DM subjects with gastroparesis eating a diet with small particle size ( `` intervention diet '' ) with the recommended diet for DM ( `` control diet '' ) .


56 subjects with insulin treated DM and gastroparesis were randomized to the intervention diet or the control diet .


The patients received dietary advice by a dietitian at 7 occasions during 20 weeks .


GI symptom severity , nutrient intake and glycemic control were measured before and after the intervention .


A significantly greater reduction of the severity of the key gastroparetic symptoms-nausea/vomiting ( P = 0.01 ) , postprandial fullness ( P = 0.02 ) and bloating ( P = 0.006 ) - were seen in patients who received the intervention diet compared with the control diet , and this was also true for regurgitation/heartburn ( P = 0.02 ) , but not for abdominal pain .


Anxiety was reduced after the intervention diet , but not after the control diet , whereas no effect on depression or quality of life was noted in any of the groups .


A higher fat intake in the intervention group was noted , but otherwise no differences in body weight , HbA1c or nutrient intake were seen .


A small particle diet improves the key symptoms of gastroparesis in patients with diabetes mellitus .


( ClinicalTrials.gov NCT01557296 ) .


To evaluate if an opiate sparing multimodal regimen of dexamethasone , gabapentin , ibuprofen and paracetamol had better analgesic effect , less side effects and was safe compared to a traditional morphine and paracetamol regimen after cardiac surgery .


Open-label , prospective randomized controlled trial .


180 patients undergoing cardiac procedures through median sternotomy , were included in the period march 2007-August 2009.151 patients were available for analysis .


Pain was assessed with the 11-numeric rating scale ( 11-NRS ) .


Patients in the multimodal group demonstrated significantly lower average pain scores from the day of surgery throughout the third postoperative day .


Extensive nausea and vomiting , was found in no patient in the multimodal group but in 13 patients in the morphine group , p < 0.001 .


Postoperative rise in individual creatinine levels demonstrated a non-significant rise in the multimodal group , 33.053.4 vs. 19.948.5 , p = 0.133 .


Patients in the multimodal group suffered less major in-hospital events in crude numbers : myocardial infarction ( MI ) ( 1 vs. 2 , p = 0.54 ) , stroke ( 0 vs. 3 , p = 0.075 ) , dialysis ( 1 vs. 2 , p = 0.54 ) , and gastrointestinal ( GI ) bleeding ( 0 vs. 1 , p = 0.31 ) .


30-day mortality was 1 vs. 2 , p = 0.54 .


In patients undergoing cardiac surgery , a multimodal regimen offered significantly better analgesia than a traditional opiate regimen .


Nausea and vomiting complaints were significantly reduced .


No safety issues were observed with the multimodal regimen .


Clinicaltrials.gov identifier : NCT01966172 .


Antiretroviral drug regimen choice may influence changes in body composition .


The objective of this study was to compare changes in body composition between ritonavir-boosted atazanavir ( ATV/r ) and ritonavir-boosted lopinavir ( LPV/r ) over 96 weeks using data from a substudy of CASTLE , which compared once-daily ATV/r with twice-daily LPV/r , both in combination with tenofovir disoproxil fumarate/emtricitabine in treatment-nave patients with HIV-1 infection .


We examined 224 patients ( 125 on ATV/r ; 99 on LPV/r ) at baseline , 48 and 96 weeks using dual-energy X-ray absorptiometry and computerised tomography .


In the lowest baseline body mass index ( BMI ) group , there were significantly greater gains at week 96 for ATV/r than for LPV/r in subcutaneous adipose tissue and in visceral adipose tissue ( VAT ) .


By week 96 , patients with lowest baseline CD4 cell counts on ATV/r had 28 % increases in VAT versus 14 % reductions for patients receiving LPV/r .


Those with the lowest baseline BMI on ATV/r had 19 % increases in VAT versus reductions of 5 % for patients on LPV/r .


In the highest baseline BMI group , the mean increase in triglycerides was 6 and 70 % in the ATV/r and LPV/r arms , respectively .


Compared with baseline , an increase in proportion of patients with high waist circumference ( WC ) / high triglycerides at 96 weeks was noted in both treatment arms , but this increase was numerically greater with LVP/r ( 18 % ) than with ATV/r ( 11 % ) .


Truncal fat gains on ATV/r primarily led to increases in WC , which may reflect return to health , while on LPV/r increases in WC and triglycerides occurred .


Changes in body composition with antiretroviral therapy are influenced by treatment choice and baseline characteristics .


To establish the cost-effectiveness of long-term humidification therapy ( LTHT ) added to usual care for patients with moderate or severe chronic obstructive pulmonary disease or bronchiectasis .


Resource usage in a 12-month clinical trial of LTHT was estimated from hospital records , patient diaries , and the equipment supplier .


Health state utility values were derived from the St. Georges Respiratory Questionnaire ( SGRQ ) total score .


All patients who remained in the trial for 12 months and who had at least 90 days of diary records were included ( 87 of 108 ) .


Clinical costs were NZ $ 3973 ( 95 % confidence interval [ CI ] $ 1614 - $ 6332 ) for the control group and NZ $ 3331 ( 95 % CI $ 948 - $ 6920 ) for the intervention group .


The mean health benefit per patient was -6.9 SGRQ units ( 95 % CI -13.0 to -7.2 ; P < 0.05 ) or +0.0678 quality-adjusted life-years ( 95 % CI 0.001-0 .135 ) .


With the intervention costing NZ $ 2059 annually , the mean cost per quality-adjusted life-year was NZ $ 20,902 ( US $ 18,907 ) and the bootstrap median was NZ $ 19,749 ( 2.5 th percentile - $ 40,923 , 97.5 th percentile $ 221,275 ) .


At a willingness-to-pay ( WTP ) threshold of NZ $ 30,000 , the probability of cost-effectiveness was 61 % , ranging from 49 % to 72 % as the cost of LTHT was varied by 30 % .


At a WTP of NZ $ 20,000 , the probability was 49 % ( range 34 % -61 % ) .


LTHT is moderately cost-effective for patients with moderate to severe chronic obstructive pulmonary disease or bronchiectasis at a WTP threshold that is acceptable for public funding of medicines in New Zealand .


These findings must be interpreted with caution because of the modest size of the clinical study , necessary lack of blinding in the clinical trial , and uncertainty in estimating health state utility from the SQRQ .


To evaluate whether clinically relevant concentrations of stimulated C-peptide in response to a mixed-meal tolerance test can be detected after almost 30 years of diabetes in people included in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort .


Mixed-meal tolerance tests were performed in a sample of 58 people .


C-peptide levels were measured using a chemiluminescent immunoassay .


This sample size assured a high probability of detecting C-peptide response if the true prevalence was at least 5 % , a level that would justify the subsequent assessment of C-peptide in the entire cohort .


Of the 58 participants , 17 % showed a definite response , defined as one or more post-stimulus concentrations of C-peptide > 0.03 nmol/l , and measurable concentrations were found in all participants .


These results show that a stimulated C-peptide response can be measured in some people with long-term Type 1 diabetes .


Further investigation of all participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study will help relate long-term residual C-peptide response to glycaemia over time and provide insight into the relevance of this response in terms of insulin dose , severe hypoglycaemia , retinopathy , nephropathy and macrovascular disease .


Establishing the clinical relevance of long-term C-peptide responses is important in understanding the impact that therapy to preserve or improve - cell function may have in patients with long-term Type 1 diabetes .


To clarify the effectiveness of Chinese herbal fomentation in treating chronic neck pain by means of changes in cervical kinematics .


Seventy-six patients with chronic neck pain were included in the study and were randomized into two groups based on the random number generator of the SPSS software : fomentation combined with Chinese herbal ( Group 1 ) and fomentation without any medicine ( Group 2 ) .


In both groups , the fomentation lasted for 60 min and heated to 35 C , once a day for 28 consecutive days .


Standard lateral radiographs of the cervical spine were obtained including the neutral , full flexion , and full extension positions .


Before and after intervention , the following parameters were used to evaluate the changes in kinematics : range of motion ( ROM ) , sagittal alignment and instantaneous center of rotation ( ICR ) .


After treatment , the ROM was signifcantly higher than that of before treatment in Group 1 ( 51.5 , 95 % CI : 49.8-55 .9 ; P < 0.05 ) .


There was no significant difference between before and after treatment in Group 2 ( P > 0.05 ) .


Although C2-C7 cervical alignment was increased in both groups after treatment , no significant difference was detected between before and after treatment ( P > 0.05 ) .


For Group 1 , the significant X coordinate variation was only observed at C5/C6 level ( 38.1 ; 95 % CI : 34.0 , 42.1 ; P < 0.05 ) .


There was a significant upward trend in the Y coordinate of the ICR at C5/C6 ( -30.5 ; 95 % CI : -34.3 , -26.8 ; P < 0.05 ) and C6/C7 after treatment ( -6.1 ; 95 % CI : -6.7 , -5.4 ; P < 0.05 ) .


For Group 2 , the ICR location of each level was not statistically different between the pre - and post-treatment ( P > 0.05 ) .


Chinese herbal fomentation could improve abnormal mobility in terms of ROM and ICR .


Chinese herbal fomentation might be an effective treatment for chronic neck pain .


Theoretically , salt supplementation should promote diuresis through increasing the glomerular filtration rate ( GFR ) during treatment of acute decompensated heart failure ( ADHF ) even with low-dose furosemide ; however , there is little evidence to support this idea .


This was a prospective , randomized , open-label , controlled trial that compared the diuretic effectiveness of salt infusion with that of glucose infusion supplemented with low-dose furosemide in 44 consecutive patients with ADHF .


Patients were randomly administered 1.7 % hypertonic saline solution supplemented with 40 mg furosemide ( salt infusion group ) or glucose supplemented with 40 mg furosemide ( glucose infusion group ) .


Our major end points were 24-hour urinary volume and GFR .


Urinary volume was greater in the salt infusion group than in the glucose infusion group ( 2,701 920 vs 1,777 797 mL ; P < .001 ) .


There was no significant difference in the estimated GFR at baseline .


Creatinine clearance for 24 h was greater in the salt infusion group than in the glucose infusion group ( 63.5 52.6 vs 39.0 26.3 mL min ( -1 ) 1.73 m ( -2 ) ; P = .048 ) .


Salt supplementation rather than salt restriction evoked favorable diuresis through increasing GFR .


The findings support an efficacious novel approach of the treatment of ADHF .


To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder .


Adults meeting DSM-IV-TR criteria for bipolar I disorder and currently experiencing a major depressive episode while taking at least 4 weeks of conventional maintenance medication were enrolled in a placebo-controlled evaluation of adjunctive armodafinil 150 or 200 mg ( conducted January 2010-March 2012 ) .


The primary efficacy measure was change from baseline to week 8 on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated ( IDS-C30 ) total score in the 150-mg armodafinil group versus placebo .


Of 786 patients screened , 433 were randomized ( placebo , n = 199 ; armodafinil 150 mg , n = 201 ; armodafinil 200 mg , n = 33 ) .


The 200-mg armodafinil group was discontinued by protocol amendment due to lower than expected patient enrollment .


For the 150-mg armodafinil group versus placebo , there was a significantly greater decrease in least squares mean ( standard error of mean [ SEM ] ) IDS-C30 total score at week 8 ( -21.7 [ 1.1 ] vs -17.9 [ 1.1 ] ; P = .0097 ; Cohen d therapeutic effect size = 0.28 ) .


The proportion of IDS-C30 responders ( 50 % decrease from baseline ) was significantly higher for the 150-mg armodafinil group versus placebo at final visit ( 46 % [ 91/197 ] vs 34 % [ 67/196 ] ; P = .0147 ) .


The proportion of IDS-C30 remitters ( total score 11 ) was 21 % ( 42/197 ) for armodafinil 150 mg versus 17 % ( 34/196 ) for placebo ( P = .3343 ) at final visit .


Adverse events ( AEs ) observed in > 5 % of either the armodafinil 150 mg or placebo groups and more frequently with 150 mg armodafinil were diarrhea ( 9 % [ 17/198 ] vs 7 % [ 13/199 ] ) , and nausea ( 6 % [ 11/198 ] vs 5 % [ 9/199 ] ) , respectively .


In the 200-mg armodafinil group , there were 2 serious AEs ( n = 1 , hepatic failure leading to death ; n = 1 , acute hepatitis ) .


The death was not considered related to study treatment .


Adjunctive armodafinil 150 mg significantly improved symptoms of major depressive episodes associated with bipolar I disorder versus placebo and was generally well tolerated .


ClinicalTrials.gov identifier : NCT01072929 .


Despite the reported detrimental effects of international air travel on physical performance , a paucity of interventions have been scientifically tested and confirmed to benefit travelling athletes .


Consequently , the aim of the present study was to examine the effects of sleep hygiene and artificial bright light interventions on physical performance following simulated international travel .


In a randomized crossover design , 13 physically active males completed 24 h of simulated international travel with ( INT ) and without ( CON ) the interventions .


The mild hypoxia and cramped conditions typically encountered during commercial air travel were simulated in a normobaric , hypoxic room .


Physical performance , subjective jet-lag symptoms and mood states were assessed in the morning and evening on the day prior to and for two days post-travel .


Sleep quantity and quality were monitored throughout each trial .


Sleep duration was significantly reduced during travel in both trials ( P < 0.01 ) , though total sleep duration during and following travel was almost significantly greater ( P = 0.06 ) in INT ( 17.0 ( 16.2-17 .8 ) h ) compared to CON ( 15.7 ( 14.9-16 .5 ) h ) .


Maximal-sprint and countermovement jump ( P < 0.05 ) , but not Yo-Yo Intermittent Recovery level 1 test ( P > 0.05 ) performance , were significantly reduced the evening of day 1 and 2 post-travel , with no differences between trials ( P > 0.05 ) .


Furthermore , vigour was significantly greater ( P = 0.04 ) the morning of day 2 in INT [ 5.3 ( 3.9-6 .7 ) ] compared to CON [ 2.8 ( 1.4-4 .2 ) ] , and subjective jet-lag symptoms and mood states were significantly worse on day 2 in CON only ( P < 0.05 ) .


Whilst reducing travel-induced sleep disruption may attenuate travel fatigue , no improvements in the recovery of physical performance were apparent .


The purpose of this study was to determine if 6-min walk test data assists in treatment decisions for patients withheart failure .