To evaluate the effects of intravenous ( IV ) golimumab 2 mg/kg + methotrexate ( MTX ) on patient-reported measures of health-related quality of life ( HRQOL ) in patients with active rheumatoid arthritis ( RA ) despite prior MTX therapy .


In this randomized , multicenter , double-blind , placebo-controlled , phase III trial , adults with RA were randomly assigned to receive IV placebo ( n = 197 ) or golimumab 2 mg/kg ( n = 395 ) infusions at Week 0 , Week 4 , and every 8 weeks thereafter .


All patients continued stable oral MTX ( 15-25 mg/wk ) .


HRQOL assessments included Health Assessment Questionnaire-Disability Index ( HAQ-DI ; physical function ) , Medical Outcomes Study Short Form-36 questionnaire physical/mental component summary ( SF-36 PCS/MCS ) scores , EQ-5D assessment of current health state , Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-Fatigue ) questionnaire , and disease effect on productivity [ 10-cm visual analog scale ( VAS ) ] .


Mean HAQ-DI improvements from baseline were significantly greater with golimumab + MTX than placebo + MTX at Week 14 and Week 24 ( p < 0.001 ) .


Significantly greater improvements in all 8 individual SF-36 subscores and both the SF-36 PCS and MCS scores ( p < 0.001 ) also accompanied golimumab + MTX therapy .


Improved EQ-5D and EQ-5D VAS ( p < 0.001 ) and FACIT-Fatigue ( p < 0.001 ) scores were also observed for golimumab + MTX-treated patients at Week 12 , Week 16 , and Week 24 , and greater proportions of golimumab + MTX-treated patients had clinically meaningful improvements in these measures .


Greater reductions in disease effect on productivity were observed with golimumab + MTX versus placebo + MTX at Week 24 ( p < 0.001 ) .


Improvements in physical function , HRQOL , fatigue , and productivity significantly correlated with disease activity improvement .


In active RA , IV golimumab + MTX significantly improved physical function , HRQOL , fatigue , and productivity using multiple measurement tools ; all correlated with improvements in disease activity ( NCT00973479 , EudraCT 2008-006064-11 ) .


Previous studies have shown that heating the insulin injection site may accelerate insulin absorption .


We investigated the pharmacological profile of insulin administered with InsuPatch , a local skin-heating device .


In this randomized , crossover study carried out in 56 subjects with type 1 diabetes treated with insulin pump [ mean age 3213.5 years ; 23 women ; HbA1c :7.80.9 % ( 6210 mmol/mol ) ( mean + / - standard deviation ) ] .


Euglycemic glucose clamps were performed after administration of 0.15 units/kg of short-acting insulin analogues .


Each subject underwent three clamp procedures : two with the InsuPatch device ( day 1 and day 3 ) and one without the device ( day 1 control ) .


The primary endpoints were the following : ( 1 ) the change in the area under the curve ( AUC ) of insulin during the first 60 min post-insulin bolus on day 1 with the InsuPatch device versus day 1 control and ( 2 ) parameters to assess the safety of using the device .


The area under the curve of insulin during the initial 60 min ( insulin AUC ( 0-60 ) ) after insulin bolus was increased by 29.77 % on day 1 InsuPatch versus day 1 control ( p < 0.01 ) .


Maximal post-insulin bolus concentration was 57 mU/L on day 1 InsuPatch versus 47.6 mU/L on day 1 control ( p < 0.01 ) .


On day 3 InsuPatch , insulin AUC ( 0-60 ) was increased by 27.972 % versus day 1 InsuPatch ( p < 0.01 ) .


Maximal insulin concentration was 70.4 mU/L versus 57 mU/L , respectively ( p = 0.05 ) .


The use of the heating device upon administration of short-acting insulin analogues in pump-treated type 1 diabetic patients was found to enhance insulin absorption .


This heating device may therefore serve to achieve better meal insulin coverage .


Diagnosis of different parkinsonian syndromes is linked with high misdiagnosis rates and various confounding factors .


This is particularly problematic in its early stages .


With this in mind , the current pilot study aimed to distinguish between Idiopathic Parkinson 's Disease ( iPD ) , other Parkinsonian syndromes ( non-iPD ) and healthy subjects , by a breath test that analyzes the exhaled volatile organic compounds using a highly sensitive nanoarray .


Breath samples of 44 iPD , 16 non-iPD patients and 37 healthy controls were collected .


The samples were passed over a nanoarray and the resulting electrical signals were analyzed with discriminant factor analysis as well as by a K-fold cross-validation method , to test the accuracy of the model .


Comparison of non-iPD with iPD states yielded 88 % sensitivity , 88 % accuracy , and 88 % Receiver Operating Characteristic area under the curve in the training set samples with known identity .


The validation set of this comparison scored 81 % sensitivity and accuracy and 92 % negative predictive value .


Comparison between atypical parkinsonism states and healthy subjects scored 94 % sensitivity and 85 % accuracy in the training set samples with known identity .


The validation set of this comparison scored 81 % sensitivity and 78 % accuracy .


The obtained results were not affected by l-Dopa or MAO-B inhibitor treatment .


Exhaled breath analysis with nanoarray is a promising approach for a non-invasive , inexpensive , and portable technique for differentiation between different Parkinsonian states .


A larger cohort is required in order to establish the clinical usefulness of the method .


To compare treatment with metformin alone , metformin plus insulin and insulin alone in women with gestational diabetes ( GDM ) .


A total of 150 gestational diabetic patients who fulfilled the eligibility criteria were included in this prospective randomized control open labeled study .


A risk factor based screening was done followed by a GCT and then local GTT criteria from antenatal clinics .


They were initially divided into two groups with odd numbers assigned to metformin treatment and even numbers to insulin treatment .


Metformin and/or insulin treatment was given and target blood sugar levels aimed at FBS 100 mg/dl and postprandial levels 126 mg/dl .


Supplemental insulin was added to metformin treatment group to maintain the glycemic targets if required .


Patients were followed until delivery and maternal fetal outcomes and pharmacotherapeutic characteristics were recorded on a performa .


Less maternal weight gain was found in the metformin treated groups ( 9.8 1.5 kg [ metformin alone ] vs. 9.8 1.4 kg [ metformin plus insulin ] vs. 12.5 1.1 kg [ insulin alone ] P < 0.000 ) .


Preeclampsia was significantly less in metformin treated groups .


There were no perinatal deaths in the study .


Mean birth weight was significantly less in metformin treated groups ( 3.4 0.4 kg vs. 3.3 0.5 kg vs. 3.7 0.5 kg P < 0.01 ) .


Less neonatal morbidity was observed in metformin groups .


42.7 % of patients required supplemental insulin ( mean dose of 13.6 2 units ) in the metformin group .


Mean gestational age at which insulin was added was 31.8 5.9 weeks .


Metformin is an effective and cheap treatment option for women with gestational diabetes with or without supplemental insulin .


To study the effect of vasonit on the structural/functional state of erythrocyte cytoplasmic membrane in patients with ischemic stroke ( 11 ) using atomic-power microscopy in vitro .


We examined 45 patients with II .


Patients of the main group ( n = 30 ) received vasonit and standard treatment , 15 patients of the comparison group received only standard treatment .


To assess the severity of patient 's condition , we used the NIH stroke scale , modified Rankin scale , the Barthel index and the Rivermead Mobility index .


Dried erythrocyte preparations were made to study erythrocyte cytoplasmic membrane .


Scanning was performed using an atomic-power microscope manufactured by `` SOLVER P47-Pro '' ( NT-MDT , Russia ) .


A statistically significant positive dynamics of neurological deficit and patient 's functional state was found in the 14 '' day of the study .


A significant decrease in Young 's modulus value was identified in the main group that suggested the increase in the elasticity of erythrocyte cytoplasmic membrane .


Metformin is used to reduce pregnancy complications in women with polycystic ovary syndrome ( PCOS ) , although it is not approved for this indication and solid evidence is lacking .


Midpregnancy Doppler ultrasound is one of the best methods for prediction of adverse pregnancy outcome .


The objectives of the study were to investigate the following : 1 ) whether metformin treatment influenced the midpregnancy pulsatility index ( PI ) of the uterine artery ; 2 ) whether metabolic or endocrine factors affect the PI of the uterine artery of PCOS women ; and 3 ) whether PI predicted adverse pregnancy outcome in PCOS woman .


This is a substudy of a randomized , placebo-controlled , double-blind , multicenter study conducted at 11 secondary care centers .


We randomly assigned 273 pregnancies to receive metformin or placebo , from the first trimester of pregnancy to delivery .


In the present substudy , 231 pregnancies are included , ie , those who completed the ultrasound examinations .


Midpregnancy PI in the uterine artery related to metformin use , androgen levels , an oral glucose tolerance test , and insulin levels was measured .


We found no difference in the PI between the metformin and placebo groups .


In multivariate analyses , fasting serum glucose of the first and second trimester correlated positively to the midpregnancy PI .


Only in univariate analyses a weak correlation between androstenedione and PI was seen .


Metformin treatment did not affect uterine artery blood flow , measured by PI .


High fasting blood glucose correlated inversely to uterine artery blood flow .


The midpregnancy PI correlated positively to preeclampsia , hypertension , and gestational diabetes mellitus in PCOS pregnancies .


Androgen levels correlated only to PI in univariate analyses .


Erlotinib is a highly active epidermal growth factor receptor ( EGFR ) kinase inhibitor that is approved for first-line use in lung cancers harboring EGFR mutations .


Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease ( PD ) , although this has not been systematically studied to date .


Patients who had Response Evaluation Criteria In Solid Tumors-defined PD who were participating in 3 prospective trials of first-line erlotinib in advanced lung cancer were studied retrospectively , and the progression characteristics were compared between patients with and without EGFR-sensitizing mutations .


Factors were studied that influenced the time until treatment change ( TTC ) , defined as the time from PD to the start of a new systemic therapy or death .


The rate of tumor progression was assessed by comparing tumor measurements between the computed tomography scan obtained at the time of PD and the preceding scan .


In total , 92 eligible patients were studied , including 42 with and 50 without an EGFR-sensitizing mutation .


The EGFR-mutant cohort had a slower rate of progression ( P = .003 ) and a longer TTC ( P < .001 ) .


Among the patients with EGFR-mutant cancers , 28 ( 66 % ) continued single-agent erlotinib after PD , and 21 ( 50 % ) were able to delay a change in systemic therapy for > 3 months ; only 2 patients received local debulking therapy during that period .


Multivariate analysis of the patients with EGFR-mutant tumors demonstrated that a longer time to progression , a slower rate of progression , and a lack of new extrathoracic metastases were associated with a longer TTC .


A change in systemic therapy commonly can be delayed in patients with EGFR-mutant lung cancer who objectively progress on first-line erlotinib , particularly in those with a longer time to progression , a slow rate of progression , and a lack of new extrathoracic metastases .


The effectiveness of noninvasive positive pressure ventilation delivered by helmet ( H-NPPV ) as a weaning approach in patients with acute respiratory failure is unclear .


We randomly and evenly assigned 64 patients intubated for acute respiratory failure to conventional weaning with invasive mechanical ventilation ( IMV ) or H-NPPV .


The primary end point was a reduction in IMV duration by 6 days between the 2 groups .


Secondary end points were the occurrence of ventilator-associated pneumonia and major complications , duration of mechanical ventilation and weaning , intensive care unit and hospital length of stay , and survival .


The mean duration of IMV was significantly reduced in the H-NPPV group compared with the IMV group ( P < .0001 ) , without significant difference in duration of weaning ( P = .26 ) and total ventilatory support ( P = .45 ) .


In the H-NPPV group , the incidence of major complications was less than the IMV group ( P = .032 ) .


Compared with the H-NPPV group , the IMV group was associated with a greater incidence of VAP ( P = .018 ) and an increased risk of nosocomial pneumonia ( P = .049 ) .


The mortality rate was similar between the groups , with no significant difference in overall intensive care unit ( P = .47 ) or hospital length of stay ( P = .37 ) .


H-NPPV was well tolerated and effective in patients who were difficult to wean .


In laboratory studies , exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [ 1 ] .


We evaluated if exercise improves sexual desire , orgasm , and global sexual functioning in women experiencing antidepressant-induced sexual side effects .


Fifty-two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only .


They were randomized to complete either three weeks of exercise immediately before sexual activity ( 3/week ) or 3 weeks of exercise separate from sexual activity ( 3/week ) .


At the end of the first exercise arm , participants crossed to the other .


We measured sexual functioning , sexual satisfaction , depression , and physical health .


Exercise immediately prior to sexual activity significantly improved sexual desire and , for women with sexual dysfunction at baseline , global sexual function .


Scheduling regular sexual activity significantly improved orgasm function ; exercise did not increase this benefit .


Neither regular sexual activity nor exercise significantly changed sexual satisfaction .


Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants


Overweight and obesity during pregnancy represents a considerable health burden .


While research has focused on interventions to limit gestational weight gain , there is little information describing their impact on neonatal health .


Our aim was to investigate the effect on a range of pre-specified secondary neonatal outcomes of providing antenatal dietary and lifestyle advice to women who are overweight or obese .


We report a range of pre-specified secondary neonatal outcomes from a large randomised trial in which antenatal dietary and lifestyle advice was provided to women who were overweight or obese .


Pregnant women were eligible for participation with a body mass index of 25 kg/m ( 2 ) or over , and singleton gestation between 10 ( +0 ) and 20 ( +0 ) weeks .


Outcome measures included gestational age at birth ; Apgar score below 7 at 5 minutes of age ; need for resuscitation at birth ; birth weight above 4.5 kg or below 2.5 kg ; birth weight , length and head circumference ( and Z-scores ) ; admission to the nursery ; respiratory distress syndrome ; and postnatal length of stay .


Data relating to the primary outcome ( large for gestational age infants defined as birth weight above the 90th centile ) and birth weight above 4 kg have been reported previously .


Analyses used intention-to-treat principles .


In total , 2,142 infants were included in the analyses .


Infants born to women following lifestyle advice were significantly less likely to have birth weight above 4.5 kg ( 2.15 % versus 3.69 % ; adjusted risk ratio ( aRR ) = 0.59 ; 95 % confidence interval ( CI ) 0.36 to 0.98 ; P = 0.04 ) , or respiratory distress syndrome ( 1.22 % versus 2.57 % ; aRR = 0.47 ; 95 % CI 0.24 to 0.90 ; P = 0.02 ) , particularly moderate or severe disease , and had a shorter length of postnatal hospital stay ( 3.947.26 days versus 4.419.87 days ; adjusted ratio of means 0.89 ; 95 % CI 0.82 to 0.97 ; P = 0.006 ) compared with infants born to women who received Standard Care .


For women who are overweight or obese , antenatal dietary and lifestyle advice has health benefits for infants , without an increase in the risk of harm .


Continued follow-up into childhood will be important to assess the longer-term effects of a reduction in high infant birth weight on risk of child obesity .


Please see related articles : http://www.biomedcentral.com/1741-7015/12/161 and http://www.biomedcentral.com/1741-7015/12/201 .


Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ) .


Preclinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes .


In particular , it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights .


Here , we investigate whether glucocorticoids enhance the outcome of in vivo exposure-based group therapy of spider phobia .


In a double blind , block-randomized , placebo-controlled , between-subject study design , 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure-based group therapy .


Cortisol ( 20 mg ) or placebo was orally administered 1 hr before each therapy session .


Patients returned for a follow-up assessment one month after therapy .


Exposure-based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Questionnaire ( FSQ ) from pretreatment to immediate posttreatment and to follow-up .


The administration of cortisol to exposure therapy resulted in increased salivary cortisol concentrations and a significantly greater reduction in fear of spiders ( FSQ ) as compared to placebo at follow-up , but not immediately posttreatment .


Furthermore , cortisol-treated patients reported significantly less anxiety during standardized exposure to living spiders at follow-up than placebo-treated subjects .


Notably , groups did not differ in phobia-unrelated state-anxiety before and after the exposure sessions and at follow-up .


These findings indicate that adding cortisol to in vivo exposure-based group therapy of spider phobia enhances treatment outcome .


To investigate whether interventions that have positive effects on psychological symptoms and quality of life compared with usual care would also reduce days on sick leave .


A randomized controlled trial .


A large primary health care centre in Stockholm , Sweden .


Intervention .


Patients with common mental disorders were recruited by their GPs and randomized into one of two group interventions that took place in addition to usual care .


These group interventions were : ( a ) group cognitive behavioural therapy ( CBT ) , and ( b ) group multimodal intervention ( MMI ) .


Both types of intervention had previously shown significant effects on quality of life , and MMI had also shown significant effects on psychological symptoms .


Of the 245 randomized patients , 164 were employed and had taken sick leave periods of at least two weeks in length during the study period of two years .


They comprised the study group .


The odds , compared with usual care , for being sick-listed at different times relative to the date of randomization .


The mean number of days on sick leave increased steadily in the two years before randomization and decreased in the two years afterwards , showing the same pattern for all three groups .


The CBT and MMI interventions did not show the expected lower odds for sick-listing compared with usual care during the two-year follow-up .


Reduction in psychological symptoms and increased well-being did not seem to be enough to reduce sickness absence for patients with common mental problems in primary care .


The possibility of adding workplace-oriented interventions is discussed .


Medical nonpersistence is a worldwide problem of striking magnitude .


Although many fields of studies including epidemiology , sociology , and psychology try to identify determinants for medical nonpersistence , comprehensive research to explain medical nonpersistence from an economics perspective is rather scarce .


The aim of the study was to develop a conceptual framework that augments standard economic choice theory with psychological concepts of behavioral economics to understand how patients ' preferences for discontinuing with therapy arise over the course of the medical treatment .


The availability of such a framework allows the targeted design of mechanisms for intervention strategies .


Our conceptual framework models the patient as an active economic agent who evaluates the benefits and costs for continuing with therapy .


We argue that a combination of loss aversion and mental accounting operations explains why patients discontinue with therapy at a specific point in time .


We designed a randomized laboratory economic experiment with a student subject pool to investigate the behavioral predictions .


Subjects continue with therapy as long as experienced utility losses have to be compensated .


As soon as previous losses are evened out , subjects perceive the marginal benefit of persistence lower than in the beginning of the treatment .


Consequently , subjects start to discontinue with therapy .


Our results highlight that concepts of behavioral economics capture the dynamic structure of medical nonpersistence better than does standard economic choice theory .


We recommend that behavioral economics should be a mandatory part of the development of possible intervention strategies aimed at improving patients ' compliance and persistence behavior .


The aim of this placebo-controlled study was to evaluate the effects of pulsed and continuous ultrasound treatments combined with splint therapy on patients with mild and moderate idiopathic carpal tunnel syndrome .


The study included 46 carpal tunnel syndrome patients who were randomly divided into 3 groups .


The first group ( n = 15 ) received a 0 W/cm2 ultrasound treatment ( placebo ) ; the second group ( n = 16 ) received a 1.0 W/cm2 continuous ultrasound treatment and the third group ( n = 15 ) received a 1.0 W/cm2 1:4 pulsed ultrasound treatment 5 days a week for a total of 15 sessions .


All patients also wore night splints during treatment period .


Pre-treatment and post-treatment Visual Analogue Scale , Symptom Severity Scale and Functional Status Scale scores , median nerve motor conduction velocity and distal latency and sensory conduction velocities of the median nerve in the 2nd finger and palm were compared .


Clinicaltrials.gov : NCT02054247 .


There were significant improvements in all groups in terms of the post-treatment Functional Status Scale score ( p < 0.05 for all groups ) , Symptom Severity Scale score ( first group : p < 0.05 , second group : p < 0.01 , third group : p < 0.001 ) and Visual Analogue Scale score ( first and third groups : p < 0.01 , second group : p < 0.001 ) .


Sensory conduction velocities improved in the second and third groups ( p < 0.01 ) .


Distal latency in the 2nd finger showed improvement only in the third group ( p < 0.01 ) and action potential latency in the palm improved only in the second group ( p < 0.05 ) .


The results of this study suggest that splinting therapy combined with placebo and pulsed or continuous ultrasound have similar effects on clinical improvement .


Patients treated with continuous and pulsed ultrasound showed electrophysiological improvement ; however , the results were not superior to those of the placebo .


Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients , but rather on reports by clinicians in trials .


Given the potential for under-reporting , our aim was to compare reporting by patients and physicians of six toxicities ( anorexia , nausea , vomiting , constipation , diarrhea , and hair loss ) within three randomized trials .


In one trial , elderly patients with breast cancer received adjuvant chemotherapy ; in two trials , patients with advanced non-small-cell lung cancer received first-line treatment .


Toxicity was prospectively collected by investigators ( graded by National Cancer Institute Common Toxicity Criteria [ version 2.0 ] or Common Terminology Criteria for Adverse Events [ version 3 ] ) .


At the end of each cycle , patients completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaires , including toxicity-related symptom items .


Possible answers were `` not at all , '' `` a little , '' `` quite a bit , '' and `` very much . ''


Analysis was limited to the first three cycles .


For each toxicity , agreement between patients and physicians and under-reporting by physicians ( ie , toxicity reported by patients but not reported by physicians ) were calculated .


Overall , 1,090 patients ( 2,482 cycles ) were included .


Agreement between patients and physicians was low for all toxicities .


Toxicity rates reported by physicians were always lower than those reported by patients .


For patients who reported toxicity ( any severity ) , under-reporting by physicians ranged from 40.7 % to 74.4 % .


Examining only patients who reported `` very much '' toxicity , under-reporting by physicians ranged from 13.0 % to 50.0 % .


Subjective toxicities are at high risk of under-reporting by physicians , even when prospectively collected within randomized trials .


This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials .


A randomized controlled trial showed that patients with grade III or IV internal hemorrhoids had similar symptomatic relief of symptoms up to 3 months following dearterialization with mucopexy or hemorrhoidectomy albeit with less postoperative pain after the former .


This study aimed to compare hemorrhoidal recurrence and chronic complications at 3-year follow-up .


This study was carried out on 40 patients with grade III or IV internal hemorrhoids previously enrolled to a randomized trial comparing dearterialization to hemorrhoidectomy .


Recurrence was defined as internal hemorrhoids diagnosed on proctoscopy .


Chronic complications were nonresolving adverse events related to surgery .


Outcome measures included patient-reported outcomes and quality of life measured by brief pain inventory ( BPI ) , SF-12 , and fecal incontinence surveys .


At median follow-up of 36 ( 27-43 ) months , 13 patients ( 32.5 % ) were lost to follow-up .


Patient-reported outcomes suggested no difference between dearterialization and hemorrhoidectomy in persistent symptoms , occurring in 1 ( 8.3 % ) vs. 2 ( 13.3 % ) patients ( p = 0.681 ) and in symptom recurrence , occurring in 6 ( 50 % ) vs. 4 ( 26.7 % ) patients ( p = 0.212 ) .


On proctoscopy , recurrence was seen in 2 ( 13.3 % ) vs. 1 ( 6.7 % ) patients ( p = 0.411 ) , all with index grade IV disease .


One patient in each arm required reoperation ( p = 0.869 ) .


Chronic complications were not seen in the dearterialization arm while they occurred in 2 ( 13.3 % ) hemorrhoidectomy patients ( p = 0.189 ) and included unhealed wound ( n = 1 ) , anal fissure ( n = 1 ) and fecal incontinence ( n = 1 ) .


There was a trend toward more patient reported than actual recurrence on proctoscopy ( 10 vs. 3 , p = 0.259 ) .


There was no difference in BPI , SF-12 , and fecal incontinence quality of life scores .


Recurrence rates did not differ significantly at 3-year follow-up and occurred in patients with index grade IV hemorrhoids .


Chronic complications occurred only after hemorrhoidectomy .


Premature discontinuation of antidepressant drugs is a frequent clinical problem .


Adverse effects are common , occur early on in treatment and are reported to be one of the main reasons for discontinuation of antidepressant treatment .


To investigate the association between adverse effects occurring in the first 2weeks of antidepressant treatment and discontinuation by 6weeks as the outcome .


To investigate the time profile of adverse effects induced by the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine over 12weeks of treatment .


Six hundred andone depressed individuals were randomly allocated to either citalopram ( 20mg daily ) or reboxetine ( 4mg twice daily ) .


A modified version of the Toronto Side Effects Scale was used to measure 14 physical symptoms at baseline ( medication free ) and at 2 , 6 and 12weeks after randomisation .


Individuals randomised to reboxetine reported a greater number of adverse effects and were more likely to stop treatment than individuals receiving citalopram .


Dizziness ( OR 1.83 ; 95 % CI 1.09 , 3.09 ; p = 0.02 ) and the total number of adverse effects ( OR 1.12 ; 95 % CI 1.00 , 1.25 ; p = 0.06 ) reported at 2weeks were associated with discontinuation from overall antidepressant treatment by 6weeks .


Reports of adverse effects tended to reduce throughout the 12weeks for both antidepressants .


The majority of adverse effects were not individually associated with discontinuation from antidepressant treatment .


Reports of physical symptoms tended to reduce over time .


The physical symptoms that did not reduce over time may represent symptoms of depression rather than antidepressant-induced adverse effects .


To compare the effect of slight and usual sedation on the prognosis and inflammatory marker levels in patients receiving mechanical ventilation in ICU .


We enrolled 78 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 48 h.


The patients were prospectively and randomly assigned to receive : slight sedation ( Richmond Agitation Sedation Score -1 to 0 , n = 38 patients ) or usual sedation ( Richmond Agitation Sedation Score -3 to -2 , n = 40 patients ) .


Sedative dosages , duration of mechanical ventilation , length of ICU stay , complications ( ventilator-associated pneumonia , tracheotomy ) , adverse reactions ( accidental extubation , reintubation , barotrauma ) and levels of inflammatory markers on the day of sedation time for 48 h were recorded .


When compared with the usual sedation group , duration of mechanical ventilation ( d ) ( 8 5 vs 13 8 , P < 0.05 ) and length of ICU stay ( d ) ( 12 10 vs 22 9 , P < 0.05 ) were significantly shorter in the slight sedation group .


The total doses of midazolam ( mg ) , propofol ( mg ) and fentany ( g ) were lower in the slight sedation group than those in the usual sedation group ( 275 85 vs 575 142 , 4 562 1 128 vs 7 434 1 712 and 2 332 1 458 vs 4 124 2 743 , P < 0.05 ) .


Accidental extubation ( 5 % vs 3 % ) , reintubation ( 5 % vs 10 % ) and barotraumas ( 3 % vs 8 % ) showed no differences between the 2 groups ( P > 0.05 ) .


In the slight sedation group , the incidences of ventilator-associated pneumonia ( 26 % vs 53 % ) and tracheotomy ( 18 % vs 48 % ) were significantly decreased compared with those in the usual group .


The levels of IL-1 ( 35 12 vs 47 18 , P < 0.05 ) ng/L , IL-6 ( 49 21 vs 62 27 , P < 0.05 ) ng/L , TNF - ( 39 16 vs 52 25 , P < 0.05 ) ng/L and CRP ( 95 41 vs 125 45 , P < 0.05 ) mg/L were also lower in the slight sedation group than those in the conventional group .


There were no differences in ICU mortality and 28 d-survival rate between the 2 groups .


Slight sedation was shown to reduce the length of mechanical ventilation and ICU stay .


It also decreased the levels of inflammatory markers while did n't increase the incidence of adverse reactions .


Combination antiretroviral therapy ( ART ) for HIV-1-infected individuals prevents sexual transmission if viral load is suppressed .


Participants were HIV-1-infected partners randomized to early ART ( CD4 350-550 ) in HPTN052 ( n = 886 , median follow-up = 2.1 years ) , a clinical trial of early ART to prevent sexual transmission of HIV-1 in serodiscordant couples at 13 sites in 9 countries .


Adherence was assessed through pill count ( dichotomized at < 95 % ) and through self-report items .


Predictors of adherence were mental health and general health perceptions , substance use , binge drinking , social support , sexual behaviors , and demographics .


Viral suppression was defined as HIV plasma viral load < 400 copies per milliliter .


Adherence counseling and couples ' counseling about safer sex were provided .


Logistic and linear regression models using generalized estimating equation for repeated measurements were used .


Through pill count , 82 % of participants were adherent at 1 month and 83.3 % at 1 year .


Mental health was the only psychosocial variable associated with adherence [ pill count , odds ratios ( OR ) = 1.05 , 95 % confidence intervals ( CIs ) : 1.00 to 1.11 ; self-report parameter estimate , OR = 0.02 , 95 % CI : 0.01 to 0.04 ] , although regional differences emerged .


Pill count ( OR = 1.19 , 95 % CI : 1.10 to 1.30 ) and self-report ( OR = 1.42 , 95 % CI : 1.14 to 1.77 ) adherence were associated with viral suppression .


Although adherence was high among individuals in stable relationships taking ART for prevention , mental health and adherence covaried .


Assessing and intervening on mental health in the context of promoting adherence to ART as prevention should be explored .


Adherence and couples ' counseling , feedback about viral suppression , and/or altruism may also help explain the magnitude of adherence observed .


To compare the difference of clinical efficacy on sleeping disorder in the children with encephalopathy between the combined therapy of acupuncture at head points and seed-pressure at ear points and the simple acupuncture at head points .


Thirty cases of sleeping disorder induced by encephalopathy werei randomized into an observation group and a control group , 15 cases in each one .


In the observation group , the combined therapy of acupuncture at head points and seed-pressure at ear points was adopted .


The head points in cluded Sishencong ( EX-HN 1 ) , Shenting ( GV 24 ) and Benshen ( GB 13 ) .


The ear points were the positive reactive sites in the cymba and cavum conchae .


In the control group , acupuncture was applied simply to the acupoints on the head .


The treatment was given once on every Tuesday and Friday a week separately , 30 min each time .


Totally , 16 treatments were required .


Children 's sleeping habit questionnaire ( CSHQ ) was used to observe the sleep improvements and the efficacy in the patients of the two groups .


In the observation group , the results of sleep resistance , sleep anxiety , night sleep wake , parasomnias , sleep dyspnea , daytime somnolence and the total score after treatment were all improved apparently as compared with those before treatment ( all P < 0.05 ) .


In the control group , the results of night sleep wake , parasomnias , daytime somnolence and the total score after treatment were improved apparently than those before treatment ( all P < 0.05 ) .


In the observation group , the results of sleep resistance , sleep dyspnea and the total score after treatment were better than those in the control group ( all P < 0.05 ) and the scores of sleep anxiety and daytime somnolence in the control group were better than those in the observation group after treatment ( both P < 0.05 ) .


The combined therapy of acupuncture at head points and seed-pressure at the positive reactive sites in the cymba and cavum conchae achieves the superior efficacy on sleep resistance and sleep dyspnea as compared with the simple acupuncture .


The efficacy of simple acupuncture is more satisfactory on sleep anxiety and daytime somnolence .


Lenalidomide , a weak substrate of P-glycoprotein ( P-gp ) in vitro , is an oral anticancer drug eliminated predominantly via renal excretion as unchanged compound .


The role of P-gp in lenalidomide disposition and the associated clinical relevance were evaluated .


Two phase I , crossover studies were conducted in healthy volunteers .


In Study 1 , subjects received lenalidomide ( 10 mg 7 days ) alone or with the P-gp substrate digoxin ( 0.5 mg on Day 5 ) .


In Study 2 , subjects received lenalidomide ( a single 25 mg dose ) alone , the P-gp inhibitor quinidine ( 300-600 mg twice-daily 5 days ) plus lenalidomide ( on Day 4 ) , the P-gp inhibitor/substrate temsirolimus ( a single 25 mg dose ) alone , or lenalidomide plus temsirolimus .


Pharmacokinetic and safety data were collected for lenalidomide and the co-administrated drugs .


There were no significant changes in the maximum concentration ( C max ) and area under the plasma concentration-time curve ( AUC ) of lenalidomide when co-administered with quinidine , digoxin , or temsirolimus .


Neither the rate nor the capacity of lenalidomide renal excretion was affected by quinidine or temsirolimus , in addition lenalidomide absorption rate and bioavailability remained unchanged .


Furthermore , lenalidomide had no significant effect on blood C max and AUC of temsirolimus and its active metabolite sirolimus ( also a P-gp inhibitor/substrate ) .


The C max of digoxin was slightly higher ( +14 % ) when administered with lenalidomide versus placebo .


There were no other changes in digoxin pharmacokinetics upon co-administration with lenalidomide .


No remarkable safety findings were observed .


There are no clinically significant pharmacokinetic interactions between lenalidomide and substrates or inhibitors of P-gp .


To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation-induced skin reactions .


A total of 174 patients were randomized and participated in the study .


Patients received either cream 1 ( the natural oil-based emulsion containing allantoin ) or cream 2 ( aqueous cream ) .


Skin toxicity , pain , itching , and skin-related quality of life scores were collected for up to 4 weeks after radiation treatment .


Patients who received cream 1 had a significantly lower average level of Common Terminology Criteria for Adverse Events at week 3 ( P < .05 ) but had statistically higher average levels of skin toxicity at weeks 7 , 8 , and 9 ( all P < .001 ) .


Similar results were observed when skin toxicity was analyzed by grades .


With regards to pain , patients in the cream 2 group had a significantly higher average level of worst pain ( P < .05 ) and itching ( P = .046 ) compared with the cream 1 group at week 3 ; however , these differences were not observed at other weeks .


In addition , there was a strong trend for cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison with cream 1 ( P = .056 ) .


Overall , more participants in the cream 1 group were required to use another topical treatment at weeks 8 ( P = .049 ) and 9 ( P = .01 ) .


The natural oil-based emulsion containing allantoin seems to have similar effects for managing skin toxicity compared with aqueous cream up to week 5 ; however , it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion ( week 6 and beyond ) .


There were no major differences in pain , itching , and skin-related quality of life .


In light of these results , clinicians and patients can base their decision on costs and preferences .


Overall , aqueous cream seems to be a more preferred option .


Problem-based learning ( PBL ) is well established in medical education and beyond , and continues to be developed and explored .


Challenges include how to connect the somewhat abstract nature of classroom-based PBL with clinical practice and how to maintain learner engagement in the process of PBL over time .


A study was conducted to investigate the efficacy of decision-PBL ( D-PBL ) , a variant form of PBL that replaces linear PBL cases with virtual patients .


These Web-based interactive cases provided learners with a series of patient management pathways .


Learners were encouraged to consider and discuss courses of action , take their chosen management pathway , and experience the consequences of their decisions .


A Web-based application was essential to allow scenarios to respond dynamically to learners ' decisions , to deliver the scenarios to multiple PBL classrooms in the same timeframe , and to record centrally the paths taken by the PBL groups .


A randomized controlled trial in crossover design was run involving all learners ( N = 81 ) in the second year of the graduate entry stream for the undergraduate medicine program at St George 's University of London .


Learners were randomized to study groups ; half engaged in a D-PBL activity whereas the other half had a traditional linear PBL activity on the same subject material .


Groups alternated D-PBL and linear PBL over the semester .


The measure was mean cohort performance on specific face-to-face exam questions at the end of the semester .


D-PBL groups performed better than linear PBL groups on questions related to D-PBL with the difference being statistically significant for all questions .


Differences between the exam performances of the 2 groups were not statistically significant for the questions not related to D-PBL .


The effect sizes for D-PBL-related questions were large and positive ( > 0.6 ) except for 1 question that showed a medium positive effect size .


The effect sizes for questions not related to D-PBL were all small ( 0.3 ) with a mix of positive and negative values .


The efficacy of D-PBL was indicated by improved exam performance for learners who had D-PBL compared to those who had linear PBL .


This suggests that the use of D-PBL leads to better midterm learning outcomes than linear PBL , at least for learners with prior experience with linear PBL .


On the basis of tutor and student feedback , St George 's University of London and the University of Nicosia , Cyprus have replaced paper PBL cases for midstage undergraduate teaching with D-PBL virtual patients , and 6 more institutions in the ePBLnet partnership will be implementing D-PBL in Autumn 2015 .


The optimal dietary approach for weight loss and improving insulin sensitivity in adolescents is unknown .


This study aimed to explore the association between the estimated insulin demand of the diet , as measured by glycemic and insulin load , weight loss , percentage body fat and insulin sensitivity index ( ISI ) in obese adolescents with clinical features of insulin resistance and/or prediabetes after a 3 month lifestyle and metformin intervention .


Secondary data analysis of 91 adolescents ( median age 12.7 years ( range 10.1-17 .4 ) participating in a randomized controlled trial , known as RESIST ; ACTRN12608000416392 .


Weight change between baseline and 3 months was measured by BMI expressed as percentage of the 95th centile ( BMI % 95 ) .


Body composition was measured by dual energy X-ray absorptiometry and ISI was determined by an oral glucose tolerance test .


Higher dietary glycemic load and insulin load were associated with less weight loss ( BMI % 95 ) , adjusted for sex and pubertal stage , = 0.0466 , P = 0.007 and = 0.0124 , P = 0.040 , respectively .


Inclusion of total energy intake in the model explained observed associations between dietary glycemic load and insulin load and change in BMI % 95 .


Neither dietary glycemic load nor insulin load were associated with changes in percentage body fat or ISI .


Dietary glycemic index and macronutrient content ( % of total energy ) were not associated to changes in BMI % 95 , percentage body fat or ISI .


Reduced energy diet contributes to weight loss in obese , insulin resistant adolescents .


Diets with a lower insulin demand were associated with a lower energy intake and may hence assist with weight loss .


To investigate the safety of combining a 6-Hz primed low-frequency repetitive transcranial magnetic stimulation ( rTMS ) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy ( mCIMT ) program in children with congenital hemiparesis .


Phase 1 randomized , double-blinded , placebo-controlled pretest/posttest trial .


University academic facility and pediatric specialty hospital .


Subjects ( N = 19 ; age range , 8-17 y ) with congenital hemiparesis caused by ischemic stroke or periventricular leukomalacia .


No subject withdrew because of adverse events .


All subjects included completed the study .


Subjects were randomized to 1 of 2 groups : either real rTMS plus mCIMT ( n = 10 ) or sham rTMS plus mCIMT ( n = 9 ) .


Adverse events , physician assessment , ipsilateral hand function , stereognosis , cognitive function , subject report of symptoms assessment , and subject questionnaire .


No major adverse events occurred .


Minor adverse events were found in both groups .


The most common events were headaches ( real : 50 % , sham : 89 % ; P = .14 ) and cast irritation ( real : 30 % , sham : 44 % ; P = .65 ) .


No differences between groups in secondary cognitive and unaffected hand motor measures were found .


Primed rTMS can be used safely with mCIMT in congenital hemiparesis .


We provide new information on the use of rTMS in combination with mCIMT in children .


These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis .


Persons with serious mental illnesses ( SMI ) are more likely to die earlier than the general population , primarily due to increased medical burden , particularly from cardiovascular disease ( CVD ) .


Life Goals Collaborative Care ( LG-CC ) is designed to improve health outcomes in SMI through self-management , care management , and provider support .


This single-blind randomized controlled effectiveness study will determine whether patients with SMI receiving LG-CC compared to usual care ( UC ) experience improved physical health in 12 months .


Patients diagnosed with SMI and at least one CVD risk factor receiving care at a VA mental health clinic were randomized to LG-CC or UC .


LG-CC included five self-management sessions covering mental health symptom management reinforced through health behavior change , care coordination and health monitoring via a registry , and provider feedback .


The primary outcome is change in physical health-related quality of life score ( VR-12 ) from baseline to 12 months .


Secondary outcomes include changes in mental health-related quality of life , CVD risk factors ( blood pressure , BMI ) , and physical activity from baseline to 12 months later .


Out of 304 enrolled , 139 were randomized to LG-CC and 145 to UC .


Among patients completing baseline assessments ( N = 284 ) ; the mean age was 55.2 ( SD = 10.9 ; range 28-75 years ) , 15.6 % were women , the majority ( 62 % ) were diagnosed with depression , and the majority ( 63 % ) were diagnosed with hypertension or were overweight ( BMI mean SD = 33.3 6.3 ) .


Baseline VR-12 physical health component score was below population norms ( 50.0 SD = 10 ) at 33.4 11.0 .


Findings from this trial may inform initiatives to improve physical health for SMI patient populations .


Our aim was to identify moderators of the effects of a cognitive behavioral group-based prevention program ( CB group ) and CB bibliotherapy , relative to an educational brochure control condition and to one another , in a school-based effectiveness randomized controlled prevention trial .


378 adolescents ( M age = 15.5 , 68 % female ) with elevated depressive symptoms were randomized in one of three conditions and were assessed at pretest , posttest , and 6-month follow-up .


We tested the moderating effect of three individual ( baseline depressive symptoms , negative attributional style , substance use ) , three environmental ( negative life events , parental support , peer support ) , and two sociodemographic ( sex , age ) characteristics .


Baseline depressive symptoms interacted with condition and time .


Decomposition indicated that elevated baseline depressive symptoms amplified the effect of CB bibliotherapy at posttest ( but not 6-month follow-up ) relative to the control condition , but did not modify the effect of CB group relative to the control condition or relative to bibliotherapy .


Specifically , CB bibliotherapy resulted in lower posttest depressive symptoms than the control condition in individuals with elevated , but not average or low baseline symptoms .


We found no interaction effect for other putative moderators .


Our findings suggest that bibliotherapy is effective only in participants who have elevated depressive symptoms at baseline .


The fact that no study variable moderated the effects of CB group , which had a significant main effect in reducing depressive symptoms relative to the control condition , suggests that this indicated prevention intervention is effective for a wide range of adolescents .


Vitamin D deficiency is a common problem worldwide .


Several studies have shown an association between vitamin D deficiency and the increased risk of metabolic syndrome .


No previous study has compared the efficacy and safety of ergocalciferol at 40,000 versus 20,000 IU/week in patients with metabolic syndrome .


To evaluate the efficacy of ergocalciferol supplementation on serum 25-hydroxyvitamin D [ 25 ( OH ) D ] concentrations and to examine safety parameters in metabolic syndrome patients .


Outpatient department of Phramongkutklao Hospital , Bangkok , Thailand .


A randomized , double-blinded , parallel study was conducted in metabolic syndrome patients with vitamin D deficiency [ 25 ( OH ) D < 20 ng/mL ] .


Ninety patients were randomly assigned into three groups of 30 patients each .


Group 1 was given two capsules of placebo/week , group 2 was given ergocalciferol 20,000 IU/week , and group 3 was given ergocalciferol 40,000 IU/week for 8 weeks .


serum 25 ( OH ) D concentrations , serum calcium , safety , and corrected QT ( QTc ) interval .


Of the 90 patients enrolled , 84 patients completed the study .


At the end of the study , the mean serum 25 ( OH ) D in groups 2 and 3 significantly increased from the baseline ( 15.1 and 14.3 to 26.8 and 30.0 ng/mL , respectively ) .


The increase in serum 25 ( OH ) D in groups 2 and 3 were comparable and significantly greater than that of the placebo group .


The percentage number of patients achieving normal vitamin D levels in groups 1 , 2 and 3 were 3.3 , 33.3 , and 60.0 % , respectively , which were significantly different between groups ( p < 0.001 ) .


Adverse reactions in both ergocalciferol treatment groups were not different from the placebo group ( p > 0.05 ) .


Serum calcium levels did not change within and between groups of treatment .


No significant change in QTc was observed in any patient .


Both 20,000 and 40,000 IU/week of ergocalciferol supplementation for 8 weeks were able to increase serum 25 ( OH ) D concentrations significantly .


However , more patients in the ergocalciferol 40,000 IU/week treatment group achieved a normal serum 25 ( OH ) D level than in the group which received 20,000 IU/week .


Clinicians would have informed of choosing the dosing regimen of ergocalciferol in metabolic syndrome patients .


Cross-cultural translation , adaptation , and psychometric testing .


To cross-culturally translate and adapt the Roland-Morris Disability Questionnaire ( RMDQ ) into Modern Standard Arabic and examine its validity with Arabic-speaking patients with low back pain ( LBP ) .


The English RMDQ is valid , reliable , and commonly used to assess LBP disability in clinical practice and research .


There is no valid and reliable version of the RMDQ in Modern Standard Arabic .


The RMDQ was forward translated and back translated .


An expert committee of musculoskeletal physiotherapists reviewed the translation .


Eight patients with LBP evaluated item-by-item comprehensibility .


Ten patients piloted the RMDQ for overall comprehensibility and acceptability .


Seventeen bilingual patients tested the agreement of the Arabic and English RMDQs .


Two-hundred one patients completed the RMDQ and the visual analogue scale .


Sixty-four patients were followed-up for test-retest reliability .


Translation of most items was uncontroversial .


The expert committee found the Arabic RMDQ clinically and culturally appropriate .


They reviewed item 11 , addressing bending and kneeling , because this has a clinical significance and cultural/religious implication regarding prayer positions .


All patients reported that it was easy to understand and complete .


The Arabic RMDQ had high overall agreement with the English RMDQ for the global score ( intraclass correlation coefficient [ ICC ] = 0.925 ; 0.811-0 .972 ) .


Kappa statistics showed good item-by-item agreement ( none 0.30 ) .


Mean ( SD ) RMDQ and visual analog scale scores of 201 patients were 10.53 ( 4.80 ) and 5.11 ( 2.28 ) , respectively .


The RMDQ had a low correlation against pain intensity ( r = 0.259 ; P < 0.01 ) .


A Cronbach of 0.729 showed high internal consistency .


Test-retest reliability of the Arabic RMDQ was good ( ICC = 0.900 ; 95 % confidence interval , 0.753-0 .951 ) .


Kappa statistics were high for 18 items and fair for 6 .


The Arabic version of the RMDQ has good comprehensibility and acceptability , high internal consistency and reliability , low correlation against pain intensity , and good agreement with the English RMDQ .


We recommend its use with Arabic-speaking patients with LBP .


3 .


Biologic drugs are expensive treatments used in rheumatoid arthritis ( RA ) .


Switching among them is common practice in patients who have had an inadequate response or intolerable adverse events .


The National Institute of Health and Clinical Excellence ( NICE ) UK , which aims to curtail postcode prescribing , has provided guidance on the sequential prescription of these drugs .


This study sought to evaluate the extent to which rheumatology centres across the Midlands were complying with NICE guidance on the switching of biologic drugs in RA , as well as analyse the various prescribing patterns of these drugs .


Data was collected via a web-based tool on RA patients who had undergone at least one switch of a biologic drug during 2011 .


The standards specified in NICE technology appraisals ( TA130 , TA186 , TA195 , TA198 , and TA225 ) were used to assess compliance with NICE guidance .


Descriptive statistical analysis was performed .


There were 335 biologic drug switches in 317 patients .


The most common reason given for switching to a drug was NICE guidelines ( 242 , 72.2 % ) , followed by Physician 's choice ( 122 , 33.4 % ) .


Lack of effect was the most common reason for discontinuing a drug ( 224 , 67 % ) .


For patients on Rituximab , Methotrexate was used in 133 switches ( 76.9 % of the time ) .


Overall NICE compliance for all units was 65 % ( range 50 to 100 % ) , with anti-TNF to anti-TNF switches for inefficacy making up the majority of non-compliant switches .


This study draws attention to the enigma and disparity of commissioning and prescribing of biologic drugs in RA .


Currently the evidence would not support switching of a biologic drug for non-clinical purposes such as economic pressures .


Flexibility in prescribing should be encouraged : biologic therapy should be individualised based on the mode of action and likely tolerability of these drugs .


Further work should focus on the evidence for using particular sequences of biologic drugs .


To determine whether infusions with intravenous immunoglobulin ( IVIg ) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo .


A single-centre , randomised , double-blind , placebo-controlled trial .


A tertiary centre for recurrent miscarriage in Copenhagen , Denmark .


A group of 82 women with unexplained secondary recurrent miscarriage and at least four miscarriages .


Women were randomly assigned to repeated infusions with IVIg or placebo ( albumin ) from the time of positive pregnancy test to gestational week 15 or pregnancy loss .


Primary outcome was birth with neonatal survival in all randomised women .


In the intention-to-treat analyses , live birth rates were 23/42 ( 54.8 % ) in the IVIg and 20/40 ( 50.0 % ) in the placebo group , relative risk 1.11 ( 95 % CI 0.70-1 .74 ) .


In a per protocol analysis , almost identical results were found .


The median gestational length at delivery was higher in the IVIg than the placebo group ( 282 versus 272 days , P = 0.02 ) but the mean birthweight was not significantly increased .


In this trial , which is the largest so far , IVIg did not increase the live birth rate in patients with secondary recurrent miscarriage and the treatment can not be recommended in clinical practice .


Hypertension , hyperlipidemia , and diabetes are significant , but often preventable , contributors to cardiovascular disease ( CVD ) risk .


Medication and behavioral nonadherence are significant barriers to successful hypertension , hyperlidemia , and diabetes management .


Our objective was to describe the theoretical framework underlying a tailored behavioral and educational pharmacist-administered intervention for achieving CVD risk reduction .


Adults with poorly controlled hypertension and/or hyperlipidemia were enrolled from three outpatient primary care clinics associated with the Durham Veterans Affairs Medical Center ( Durham , NC ) .


Participants were randomly assigned to receive a pharmacist-administered , tailored , 1-year telephone-based intervention or usual care .


The goal of the study was to reduce the risk for CVD through a theory-driven intervention to increase medication adherence and improve health behaviors .


Enrollment began in November 2011 and is ongoing .


The target sample size is 500 patients .


The Cardiovascular Intervention Improvement Telemedicine Study ( CITIES ) intervention has been designed with a strong theoretical underpinning .


The theoretical foundation and intervention are designed to encourage patients with multiple comorbidities and poorly controlled CVD risk factors to engage in home-based monitoring and tailored telephone-based interventions .


Evidence suggests that clinical pharmacist-administered telephone-based interventions may be efficiently integrated into primary care for patients with poorly controlled CVD risk factors .


Dose-dense weekly paclitaxel ( Taxol ) and carboplatin ( dd-TC ) improved survival compared with conventional tri-weekly paclitaxel and carboplatin ( c-TC ) as a first-line chemotherapy for newly diagnosed stage II-IV ovarian cancer in the Japanese Gynecologic Oncology Group 3016 trial .


We report the quality-of-life ( QoL ) results from this trial .


A total of 637 patients were randomly assigned to receive c-TC or dd-TC ( c-TC , n = 319 ; dd-TC , n = 312 ) and were asked to complete a QoL assessment at baseline , just after the third and sixth chemotherapy cycles , and at 12 months after randomization .


QoL was assessed using Functional Assessment of Cancer Therapy ( FACT ) - general ( FACT-G ) , FACT-taxane subscale ( FACT-T ) , and FACT-ovary subscale ( FACT-Ov ) .


The overall QoL and that according to each subscale were analyzed using mixed-effects models adjusted for treatment and time .


Baseline QoL assessment was completed by 204 out of 319 ( 63.9 % ) and 200 out of 312 ( 64.1 % ) patients in the c-TC and dd-TC groups , respectively .


In these groups , the compliance rates with regard to QoL assessment were 74.5 % and 73.0 % , respectively , after three chemotherapy cycles ; 86.8 % and 86.9 % , respectively , after six chemotherapy cycles ; and 74.2 % and 71.6 % , respectively , at 12 months after randomization .


The overall QoL did not differ significantly between the two treatment groups up to 12 months after randomization ( P = 0.46 ) .


However , QoL according to the FACT-T subscale was significantly lower in the dd-TC group than in the c-TC group ( P = 0.02 ) .


dd-TC does not decrease overall QoL compared with c-TC .


The accuracy of physical examination techniques in detecting liver disease is unclear .


We sought to determine the perceived location of the lower liver border via scratch , percussion , palpation and ballottement with novice medical student examiners , compared with ultrasound localisation .


Five novice medical students learnt four liver examination techniques and measured the lower liver border in 19 healthy volunteers .


The difference between the examination technique and ultrasound ( bias ) and limits of agreement of each method were estimated by mixed linear models and shown using Bland-Altman - like plots .


All techniques had similar bias for the lower liver border , between 1.6 and 1.9 cm superior to the ultrasound measurement .


Percussion had the smallest variability with increasing liver size .


Limits of agreement were wide for all techniques , smallest for palpation ( 6.04 cm ) and largest for scratch ( 7.2 cm ) compared to the mean liver distance of 8 cm .


Conclusion There was no difference in bias between the scratch , percussion , palpation and ballottement techniques regarding the lower liver border .


All techniques had very wide limits of agreement , although palpation had the smallest .


Liver size examination by novice medical students in healthy subjects is unreliable .


Further research is needed using examiners with a different level of expertise and participants of varying body habitus and confirmed liver disease .


To evaluate the dose-response relationship of a novel recombinant human FSH ( rhFSH ; FE 999049 ) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment ; and prospectively study the influence of initial antimllerian hormone ( AMH ) concentrations .


Randomized , controlled , assessor-blinded , AMH-stratified ( low : 5.0-14 .9 pmol/L [ 0.7 - < 2.1 ng/mL ] ; high : 15.0-44 .9 pmol/L [ 2.1-6 .3 ng/mL ] ) trial .


Seven infertility centers in four countries .


Two hundred sixty-five women aged 37 years .


Controlled ovarian stimulation with either 5.2 , 6.9 , 8.6 , 10.3 , or 12.1 g of rhFSH , or 11 g ( 150 IU ) of follitropin alfa in a GnRH antagonist cycle .


Number of oocytes retrieved .


The number of oocytes retrieved increased in an rhFSH dose-dependent manner , from 5.2 3.3 oocytes with 5.2 g/d to 12.2 5.9 with 12.1 g/d .


The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata , demonstrating that a 10 % increase in dose resulted in 0.5 ( 95 % confidence interval 0.2-0 .7 ) and 1.0 ( 95 % confidence interval 0.7-1 .3 ) more oocytes in the low and high AMH stratum , respectively .


Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata .


No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata .


Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum .


Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner .


The availability of blastocysts is less influenced by the rhFSH dose and AMH level .


NCT01426386 .


The aim of this study was to evaluate the feasibility and safety of nonoperative treatment of acute nonperforated appendicitis with antibiotics in children .


A pilot randomized controlled trial was performed comparing nonoperative treatment with antibiotics versus surgery for acute appendicitis in children .


Patients with imaging-confirmed acute nonperforated appendicitis who would normally have had emergency appendectomy were randomized either to treatment with antibiotics or to surgery .


Follow-up was for 1 year .


Fifty patients were enrolled ; 26 were randomized to surgery and 24 to nonoperative treatment with antibiotics .


All children in the surgery group had histopathologically confirmed acute appendicitis , and there were no significant complications in this group .


Two of 24 patients in the nonoperative treatment group had appendectomy within the time of primary antibiotic treatment and 1 patient after 9 months for recurrent acute appendicitis .


Another 6 patients have had an appendectomy due to recurrent abdominal pain ( n = 5 ) or parental wish ( n = 1 ) during the follow-up period ; none of these 6 patients had evidence of appendicitis on histopathological examination .


Twenty-two of 24 patients ( 92 % ) treated with antibiotics had initial resolution of symptoms .


Of these 22 , only 1 patient ( 5 % ) had recurrence of acute appendicitis during follow-up .


Overall , 62 % of patients have not had an appendectomy during the follow-up period .


This pilot trial suggests that nonoperative treatment of acute appendicitis in children is feasible and safe and that further investigation of nonoperative treatment is warranted .


The prevalence of sleep disorders increases with age .


Sleep disorders may have serious health implications and may be related to serious underlying diseases .


Many older people use hypnotics , like benzodiazepines , although these medications have serious side effects and often lead to habituation .


Acetaminophen is one of the most frequently used off-label drugs for sleep disorders , although little is known about its effects .


Our objective is to investigate whether acetaminophen is effective in treating self-reported sleep disorders in older people .


Participants , aged 65 years or older ( n = 150 ) , who have sleep disorders will be randomized for treatment with either acetaminophen 1000 mg or placebo , once daily at bedtime in a double-blind design .


Eligible patients should be able to give informed consent , should not be cognitively impaired ( Minimal Mental State Examination ( MMSE ) score20 ) , should not have pain , and should not use acetaminophen on a regular basis because of pain complaints .


The study will take three weeks to complete .


During these three weeks , the participants register their sleep behavior in a sleep diary .


The participants will use the study medication during the second and third week .


The primary endpoint will be the self-reported sleep disorders at the end of week three , as measured by means of the Insomnia Severity Index ( ISI ) .


To validate these subjective sleep parameters against objectively measured indices of the sleep-wake pattern , we will measure the periods of wakefulness and sleep in a subgroup of participants , using an actigraph worn on the wrist during the entire study period .


The proposed study will contribute to our knowledge about the treatment of sleep disorders in an older population .


There is a need for treatments for sleep disorders without serious adverse effects .


Acetaminophen might be a simple and inexpensive alternative for the regimes that are currently used with older people .


The Netherlands National Trial Register NTR2747 .


Modified vaccinia virus Ankara ( MVA ) is a promising viral vector platform for the development of an H5N1 influenza vaccine .


Preclinical assessment of MVA-based H5N1 vaccines showed their immunogenicity and safety in different animal models .


We aimed to assess the safety and immunogenicity of the MVA-haemagglutinin-based H5N1 vaccine MVA-H5-sfMR in healthy individuals .


In a single-centre , double-blind phase 1/2a study , young volunteers ( aged 18-28 years ) were randomly assigned with a computer-generated list in equal numbers to one of eight groups and were given one injection or two injections intramuscularly at an interval of 4 weeks of a standard dose ( 10 ( 8 ) plaque forming units [ pfu ] ) or a ten times lower dose ( 10 ( 7 ) pfu ) of the MVA-H5-sfMR ( vector encoding the haemagglutinin gene of influenza A/Vietnam/1194 / 2004 virus [ H5N1 subtype ] ) or MVA-F6-sfMR ( empty vector ) vaccine .


Volunteers and physicians who examined and administered the vaccine were masked to vaccine assignment .


Individuals who received the MVA-H5-sfMR vaccine were eligible for a booster immunisation 1 year after the first immunisation .


Primary endpoint was safety .


Secondary outcome was immunogenicity .


The trial is registered with the Dutch Trial Register , number NTR3401 .


79 of 80 individuals who were enrolled completed the study .


No serious adverse events were identified .


11 individuals reported severe headache and lightheadedness , erythema nodosum , respiratory illness ( accompanied by influenza-like symptoms ) , sore throat , or injection-site reaction .


Most of the volunteers had one or more local ( itch , pain , redness , and swelling ) and systemic reactions ( rise in body temperature , headache , myalgia , arthralgia , chills , malaise , and fatigue ) after the first , second , and booster immunisations .


Individuals who received the 10 ( 7 ) dose had fewer systemic reactions .


The MVA-H5-sfMR vaccine at 10 ( 8 ) pfu induced significantly higher antibody responses after one and two immunisations than did 10 ( 7 ) pfu when assessed with haemagglutination inhibition geometric mean titre at 8 weeks against H5N1 A/Vietnam/1194 / 2004 ( 302 [ SD 38 ] vs 92 [ 23 ] and 1081 [ 24 ] vs 158 [ 32 ] ) .


27 of 39 eligible individuals were enrolled in the booster immunisation study .


A single shot of MVA-H5-sfMR 10 ( 8 ) pfu prime immunisation resulted in higher antibody responses after the booster immunisation than did two shots of MVA-H5-sfMR at the ten times lower dose .


The MVA-based H5N1 vaccine was well tolerated and immunogenic and therefore the vaccine candidates arising from the MVA platform hold great promise for rapid development in response to a future influenza pandemic threat .


However , the immunogenicity of this vaccine needs to be compared with conventional H5N1 inactivated non-adjuvanted vaccine candidates in head-to-head clinical trials .


European Research Council .


This two-part phase 2 study evaluated the efficacy and safety of panitumumab , a fully human anti-epidermal growth factor receptor monoclonal antibody , combined with carboplatin/paclitaxel in patients with previously untreated advanced non-small-cell lung cancer .


In part 1 , patients were sequentially enrolled to receive paclitaxel 200 mg/m ( 2 ) and carboplatin ( area under the concentration-versus-time curve , 6 mg/min/ml ) plus panitumumab ( 1.0 , 2.0 , or 2.5 mg/kg ) .


In part 2 , patients were randomized 2:1 to receive paclitaxel/carboplatin with ( arm A ) or without ( arm B ) the maximum tolerated dose of panitumumab identified in part 1 .


Primary endpoints in parts 1 and 2 were the incidence of dose-limiting toxicities and time to progression ( TTP ) , respectively .


In part 1 , four of 19 patients had dose-limiting toxicities : three at 2.0 mg/kg ( fatigue , pain in extremity , dyspepsia ) and one at 2.5 mg/kg ( rash ) .


The maximum tolerated dose was not reached ; panitumumab 2.5 mg/kg was selected for part 2 .


In part 2 , TTP was 18.1 weeks ( 95 % confidence interval [ CI ] , 13.6-23 .3 ) in arm A and 23.0 weeks ( 95 % CI , 15.9-24 .1 ) in arm B ( hazard ratio , 0.9 ; 90 % CI , 0.66-1 .21 ; p = 0.555 ) .


Progression-free survival in arms A and B was 17.6 weeks and 18.3 weeks , respectively , and the objective response rate was 15.2 % and 11.1 % .


Adverse events occurring more frequently in arm A than in arm B included skin toxicity , diarrhea , stomatitis , vomiting , and dizziness .


Exploratory analyses did not demonstrate associations between potential biomarkers and outcomes .


Although toxicity was predictable and manageable , the addition of panitumumab to paclitaxel/carboplatin did not improve TTP in patients with previously untreated advanced non-small-cell lung cancer .


Lung volume reduction surgery improves quality of life , exercise capacity , and survival in selected patients but is accompanied by significant morbidity .


Bronchoscopic approaches may provide similar benefits with less morbidity .


In a randomized , sham procedure controlled , double-blind trial , 277 subjects were enrolled at 36 centers .


Patients had emphysema , airflow obstruction , hyperinflation , and severe dyspnea .


The primary effectiveness measure was a significant improvement in disease-related quality of life ( St. George 's Respiratory Questionnaire ) and changes in lobar lung volumes .


The primary safety measure was a comparison of serious adverse events .


There were 6/121 ( 5.0 % ) responders in the treatment group at 6 months , significantly > 1/134 ( 0.7 % ) in the control group [ Bayesian credible intervals ( BCI ) , 0.05 % , 9.21 % ] .


Lobar volume changes were significantly different with an average decrease in the treated lobes of -224 mL compared with -17 mL for the control group ( BCI , -272 , -143 ) .


The proportion of responders in St. George 's Respiratory Questionnaire was not greater in the treatment group .


There were significantly more subjects with a serious adverse event in the treatment group ( n = 20 or 14.1 % ) compared with the control group ( n = 5 or 3.7 % ) ( BCI , 4.0 , 17.1 ) , but most were neither procedure nor device related .


This trial had technical and statistical success but partial-bilateral endobronchial valve occlusion did not obtain clinically meaningful results .


Safety results were acceptable and compare favorably to lung volume reduction surgery and other bronchial valve studies .


Further studies need to focus on improved patient selection and a different treatment algorithm .


ClinicalTrials.gov NCT00475007 .


Lung volume reduction surgery improves survival in selected patients with emphysema , and has generated interest in bronchoscopic approaches that might achieve the same effect with less morbidity and mortality .


Previous trials with endobronchial valves have yielded modest group benefits because when collateral ventilation is present it prevents lobar atelectasis .


We did a single-centre , double-blind sham-controlled trial in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax .


We enrolled stable outpatients with chronic obstructive pulmonary disease who had a forced expiratory volume in 1 s ( FEV1 ) of less than 50 % predicted , significant hyperinflation ( total lung capacity > 100 % and residual volume > 150 % ) , a restricted exercise capacity ( 6 min walking distance < 450 m ) , and substantial breathlessness ( MRC dyspnoea score 3 ) .


Participants were randomised ( 1:1 ) by computer-generated sequence to receive either valves placed to achieve unilateral lobar occlusion ( bronchoscopic lung volume reduction ) or a bronchoscopy with sham valve placement ( control ) .


Patients and researchers were masked to treatment allocation .


The study was powered to detect a 15 % improvement in the primary endpoint , the FEV1 3 months after the procedure .


Analysis was on an intention-to-treat basis .


The trial is registered at controlled-trials .


com , ISRCTN04761234 .


50 patients ( 62 % male , FEV1 [ % predicted ] mean 317 % [ SD 102 ] ) were enrolled to receive valves ( n = 25 ) or sham valve placement ( control , n = 25 ) between March 1 , 2012 , and Sept 30 , 2013 .


In the bronchoscopic lung volume reduction group , FEV1 increased by a median 877 % ( IQR 227-3585 ) versus 288 % ( 0-851 ) in the control group ( Mann-Whitney p = 00326 ) .


There were two deaths in the bronchoscopic lung volume reduction group and one control patient was unable to attend for follow-up assessment because of a prolonged pneumothorax .


Unilateral lobar occlusion with endobronchial valves in patients with heterogeneous emphysema and intact interlobar fissures produces significant improvements in lung function .


There is a risk of significant complications and further trials are needed that compare valve placement with lung volume reduction surgery .


Efficacy and Mechanism Evaluation Programme , funded by the Medical Research Council ( MRC ) and managed by the National Institute for Health Research ( NIHR ) on behalf of the MRC-NIHR partnership .


To determine the effects of decreased ankle-foot dorsiflexion ( A-Fdf ) range of motion ( ROM ) on gait kinematics in children with spastic cerebral palsy ( SCP ) .


All participants were children with spastic cerebral palsy ( n = 10 ) who walked with knee flexion in midstance .


Data were collected over 2-5 sessions , at 3-monthly intervals .


A-Fdf ROM was quantified using a custom-designed hand-held ankle dynamometer that exerted 4 Nm at the ankle .


Ankle-foot and knee angles during gait were quantified on sagittal video recordings .


Linear regression ( cross-sectional analysis ) and General Estimation Equation analysis ( longitudinal analysis ) were performed to assess relationships between ( change in ) A-Fdf ROM and ( change in ) ankle-foot and knee angle during gait .


Cross-sectional analysis showed a positive relationship between A-Fdf ROM and both ankle-foot angle in midstance and terminal swing .


Longitudinal analysis showed a positive relationship between individual decreases in A-Fdf ROM and increases of knee flexion during gait ( lowest knee angle in terminal stance and angle in terminal swing ) .


For this subgroup of SCP children , our results indicate that while changes in ankle angles during gait are unrelated to changes in A-Fdf ROM , changes in knee angles are related to changes in A-Fdf ROM .


After stroke , pneumonia is a relevant medical complication that can be precipitated by aspiration of saliva , liquids , or solid food .


Swallowing difficulty and aspiration occur in a significant proportion of stroke survivors .


Cough , an important mechanism protecting the lungs from inhaled materials , can be impaired in stroke survivors , and the likely cause for this impairment is central weakness of the respiratory musculature .


Thus , respiratory muscle training in acute stroke may be useful in the recovery of respiratory muscle and cough function , and may thereby reduce the risk of pneumonia .


The present study is a pilot study , aimed at investigating the validity and feasibility of this approach by exploring effect size , safety , and patient acceptability of the intervention .


Adults with moderate to severe stroke impairment ( National Institutes of Health Stroke Scale ( NIHSS ) score 5 to 25 at the time of admission ) are recruited within 2weeks of stroke onset .


Participants must be able to perform voluntary respiratory maneuvers .


Excluded are patients with increased intracranial pressure , uncontrolled hypertension , neuromuscular conditions other than stroke , medical history of asthma or chronic obstructive pulmonary disease , and recent cardiac events .


Participants are randomized to receive inspiratory , expiratory , or sham respiratory training over a 4-week period , by using commercially available threshold resistance devices .


Participants and caregivers , but not study investigators , are blind to treatment allocation .


All participants receive medical care and stroke rehabilitation according to the usual standard of care .


The following assessments are conducted at baseline , 4weeks , and 12weeks : Voluntary and reflex cough flow measurements , forced spirometry , respiratory muscle strength tests , incidence of pneumonia , assessments of safety parameters , and self-reported activity of daily living .


The primary outcome is peak expiratory cough flow of voluntary cough , a parameter indicating the effectiveness of cough .


Secondary outcomes are incidence of pneumonia , peak expiratory cough flow of reflex cough , and maximum inspiratory and expiratory mouth pressures .


Various novel pharmacologic and nonpharmacologic approaches for preventing stroke-associated pneumonia are currently being researched .


This study investigates a novel strategy based on an exercise intervention for cough rehabilitation .


Current Controlled Trials ISRCTN40298220 .


Bleeding after percutaneous coronary intervention ( PCI ) is more common in women than in men .


However , the relationship of sex and bleeding with outcomes is less well studied .


We examined the sex-related differences in the incidence of bleeding and its association with in-hospital outcomes among 96,637 patients undergoing PCI enrolled in the BMC2 registry ( 2010-2012 ) .


Women had higher bleeding rate than did men ( 3.9 % vs 1.8 % ) and thus received more blood transfusions ( 59 % vs 41 % ) .


Both men ( odds ratio [ OR ] 2.25 , 95 % CI 1.70-2 .97 ) and women ( OR 3.13 , 95 % CI 2.42-4 .07 ) who bled had higher risk-adjusted death compared with their counterparts without bleeding .


Although there was no difference in adjusted mortality between women and men without bleeding ( OR 1.14 , 95 % CI 0.99-1 .32 ) , among patients who bled , adjusted death was higher in women ( OR 1.28 , 95 % CI 1.11-1 .47 ) .


Among patients with bleeding , transfusion was associated with similar increased risk of death in both men ( OR 2.00 , 95 % CI 1.23-3 .25 ) and women ( OR 2.18 , 95 % CI 1.31-3 .63 ) compared with their counterparts without transfusion ( s ) .


Post-PCI bleeding was more common and associated with higher-than-expected in-hospital death in women compared with men with bleeding .


This trend for higher death in women with bleeding was independent of transfusion .


Quality efforts geared toward reducing bleeding in general , with a special focus on women , need to be explored to help reduce post PCI-bleeding and mortality and decrease sex-related disparity in adverse events .


This randomized , double-blind study evaluates the efficacy and tolerability of agomelatine , using fluoxetine as an active comparator , in Asian patients suffering from moderate to severe major depressive disorder ( MDD ) .


Patients were randomly assigned to receive either agomelatine ( 25-50mg / day , n = 314 ) or fluoxetine ( 20-40mg / day , n = 314 ) during an 8-week treatment period .


The main outcome measure was the change in Hamilton Depression Rating Scale 17 items ( HAM-D17 ) scores .


Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness ( CGI-S ) and Improvement of illness ( CGI-I ) , patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire ( LSEQ ) and anxiety using the Hamilton Anxiety Rating Scale ( HAM-A ) scores .


Tolerability and safety evaluations were based on emergent adverse events .


Agomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population .


Mean changes over 8 weeks were clinically relevant and similar in both groups ( -14.87.3 and -15.08.1 on HAM-D17 scale in agomelatine and fluoxetine groups , respectively ) .


The between-group difference reached statistical significance on non-inferiority test ( p = 0.015 ) .


Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups .


The two treatments were equally effective on the symptoms of both anxiety and sleep .


The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population .


Agomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients .


Icotinib , an oral epidermal growth factor receptor tyrosine kinase inhibitor , has proved effectiveness in xenografted nude mice .


Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time , including dose proportionality , food effect , and tolerability .


Two studies were conducted in total of 22 healthy subjects : a randomized , two-Latin-square crossover , dose proportional study ( n = 12 ) and a randomized two-way crossover food-effect study ( n = 10 ) .


Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3 .5 h after single dose and then declined with a mean t1/2 of 6.02-7 .83 h. Over the dose range of 100-600 mg , AUC values were proportional to dose and Cmax showed a slight saturation when dose increases .


Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib .


After dosing 400 mg of Icotinib with high-fat and high-calorie meal , mean Cmax and AUC were significantly increased by 59 and 79 % , respectively .


Three subjects experienced four adverse events ( rash , increase in AST and ALT , and external injury ) .


Rash and increased levels of AST and ALT were considered as drug-related .


No serious adverse events were reported .


The current work demonstrated that Icotinib was well tolerated in healthy male subjects ( n = 22 ) over the dose range of 100-600 mg with or without food .


Icotinib exposure , expressed in AUC , was proportionally increased with dose over the above dose range .


Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects .


To compare safety and efficacy of insulin glargine and liraglutide in patients with type 2 diabetes ( T2DM ) .


This randomized , multinational , open-label trial included subjects treated for T2DM with metforminsulphonylurea , who had glycated haemoglobin ( HbA1c ) levels of 7.5-12 % .


Subjects were assigned to 24weeks of insulin glargine , titrated to target fasting plasma glucose of 4.0-5 .5 mmol/L or liraglutide , escalated to the highest approved clinical dose of 1.8 mg daily .


The trial was powered to detect superiority of glargine over liraglutide in percentage of people reaching HbA1c < 7 % .


The mean [ standard deviation ( s.d. ) ] age of the participants was 57 ( 9 ) years , the duration of diabetes was 9 ( 6 ) years , body mass index was 31.9 ( 4.2 ) kg/m ( 2 ) and HbA1c level was 9.0 ( 1.1 ) % .


Equal numbers ( n = 489 ) were allocated to glargine and liraglutide .


Similar numbers of subjects in both groups attained an HbA1c level of < 7 % ( 48.4 vs. 45.9 % ) ; therefore , superiority of glargine over liraglutide was not observed ( p = 0.44 ) .


Subjects treated with glargine had greater reductions of HbA1c [ -1.94 % ( 0.05 ) and -1.79 % ( 0.05 ) ; p = 0.019 ] and fasting plasma glucose [ 6.2 ( 1.6 ) and 7.9 ( 2.2 ) mmol/L ; p < 0.001 ] than those receiving liraglutide .


The liraglutide group reported a greater number of gastrointestinal treatment-emergent adverse events ( p < 0.001 ) .


The mean ( s.d. ) weight change was +2.0 ( 4.0 ) kg for glargine and -3.0 ( 3.6 ) kg for liraglutide ( p < 0.001 ) .


Symptomatic hypoglycaemia was more common with glargine ( p < 0.001 ) .


A greater number of subjects in the liraglutide arm withdrew as a result of adverse events ( p < 0.001 ) .


Adding either insulin glargine or liraglutide to subjects with poorly controlled T2DM reduces HbA1c substantially , with nearly half of subjects reaching target levels of 7 % .


The lung volume reduction ( LVR ) coil is a minimally invasive bronchoscopic nitinol device designed to reduce hyperinflation and improve elastic recoil in severe emphysema .


We investigated the feasibility , safety and efficacy of LVR coil treatment in a prospective multicentre cohort trial in patients with severe emphysema .


Patients were treated in 11 centres .


Safety was evaluated by recording all adverse events , efficacy by the St George 's Respiratory Questionnaire ( SGRQ ) as primary endpoint , and pulmonary function testing , modified Medical Research Council dyspnoea score ( mMRC ) and 6-min walk distance ( 6MWD ) up to 12months after the final treatment .


Sixty patients ( 60.97.5 years , forced expiratory volume in 1s ( FEV ( 1 ) ) 30.26.3 % pred ) were bronchoscopically treated with coils ( 55 bilateral , 5 unilateral ) , with a median of 10 ( range 5-15 ) coils per lobe .


Within 30days post-treatment , seven chronic obstructive pulmonary disease exacerbations ( 6.1 % ) , six pneumonias ( 5.2 % ) , four pneumothoraces ( 3.5 % ) and one haemoptysis ( 0.9 % ) occurred as serious adverse events .


At 6 and 12months , respectively , SGRQ was -12.112.9 and -11.113.3 points , 6MWD was +29.774.1 m and +51.476 m , FEV ( 1 ) was +0.110.20 L and +0.110.30 L , and RV ( residual volume ) was -0.650.90 L and -0.710.81 L ( all p < 0.01 ) .


Post hoc analyses showed significant responses for SGRQ , 6MWD and RV in patients with both heterogeneous and homogeneous emphysema .


LVR coil treatment results in significant clinical improvements in patients with severe emphysema , with a good safety profile and sustained results for up to 1year .


NCT01328899 .


Whole grain ( WG ) options are often limited in schools , which may impact rural , low-income students who rely on school meals for a substantial portion of their food intake .


This study examined the changes in the availability and quantity of WG and refined grain foods offered in schools participating in the Creating Healthy , Active and Nurturing Growing-up Environments ( CHANGE ) study , a randomized , controlled intervention among rural communities ( 4 intervention and 4 control ) .


Foods were assessed using production records , recipes , and nutrition labels from breakfast and lunch over 1 week during fall 2008 and spring 2009 .


Key informant interviews were conducted with school food service directors in the spring 2009 .


The CHANGE intervention schools significantly increased the average percent of school days WGs were offered ( p = .047 ) and the amount of WGs offered/food item ( ounces ) at lunch compared with control schools ( p = .02 ) .


There was a significant decrease in the percent of students with access to refined grains at lunch compared with control schools ( p = .049 ) , although there were no significant differences in WG availability during breakfast .


The CHANGE schools improved WG availability , enabling student 's WG consumption to be closer to national recommendations .


To evaluate the clinical value of iodine [ 131I ] metuximab infusion combined with transcatheter arterial chemoembolization ( TACE ) for treating cases of post-intervention relapse of mid or advanced stage hepatocellular carcinoma ( HCC ) .


Sixty patients who were diagnosed between March 2009 and June 2010 with relapse of mid or advanced stage HCC following previous intervention with various standard clinical methods were recruited for study .


The patients were randomly and equally divided into a control treatment group ( CG ; receiving TACE therapy alone ) and an experimental treatment group ( TG ; receiving TACE combined with iodine [ 131I ] metuximab injection ) .


For all patients , licartin was first perfused into the tumor feeding artery and then the TACE procedure was performed 20 min later .


Liver function markers and routine blood parameters , including alpha-fetoprotein ( AFP ) and clotting time , were examined at one week and one month after the treatment .


Enhanced computed tomography or magnetic resonance imaging of the liver was performed at one month after treatment and thereafter on a bi-monthly follow-up schedule .


The World Health Organization 's tumor evaluation standard was used to assess the therapeutic effects in each group .


Results of laboratory tests ( pre - and post-treatment ) , reported complications , and side-effects were evaluated for their contributions to time of tumor progression ( TTP ) and survival time .


Patients in the TG and CG groups had similar blood cell counts at pre-operative and 1-week postoperative time points .


The TG group showed a significantly reduced level of AFP following treatment , but it was not significantly different from the level in the CG group .


The TG group did however show significantly different levels of liver functional parameters ( all P less than 0.05 ) and significantly higher TTP ( 4.84 + / -4.11 vs. CG : 2.54 + / -2.08 months ; t = -2.13 , P less than 0.05 ) and average survival time ( 7.05 vs. 5.15 months ; x2 = 4.24 , P = 0.039 ) .


The rates of partial response ( PR ) , slight remission ( MR ) , unchanged status ( SD ) and progressive disease ( PD ) were 16.7 % , 37.5 % , 25.0 % and 20.8 % in the TG group , and 8.7 % , 17.4 % , 21.7 % and 52.2 % in the CG group .


The therapeutic effect rate ( CR + PR + MR ) and reaction rate ( CR + PR + MR + SD ) was significantly different between the two groups ( P = 0.048 ) .


No serious adverse effects were reported .


TACE combined with iodine [ 131I ] metuximab injection is a safe and effective procedure for prolonging the survival and TTP of patients with HCC relapse following prior therapeutic intervention .


Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation .


First efficacy results of the nicotine vaccine 3 ' - AmNic-rEPA ( NicVAX ) showed that only a subgroup of the top 30 % antibody responders achieved higher abstinence rates than placebo .


The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention .


Randomized placebo-controlled trial .


Two research centres ( Maastricht University Medical Centre and Slotervaart Hospital ) in the Netherlands .


A total of 558 smokers were assigned randomly to six injections with NicVAX ( n = 278 ) or placebo ( n = 280 ) both co-administered with open label varenicline and behavioural support .


Outcomes were prolonged carbon monoxide-validated abstinence from weeks 9 to 52 ( primary ) and weeks 37 to 52 ( secondary ) .


We also performed a pre-planned subgroup analysis in the top 30 % antibody responders .


There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [ 27.7 versus 30.0 % , odds ratio ( OR ) = 0.89 , 95 % confidence interval ( CI ) = 0.62-1 .29 ] or weeks 37 to 52 ( 33.8 versus 33.2 % , OR = 1.03 , 95 % CI = 0.73-1 .46 ) .


The top 30 % antibody responders , compared to the placebo group , showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 ( 42.2 versus 33.2 % , OR = 1.47 , 95 % CI = 0.89-2 .42 ) .


The nicotine vaccine , NicVAX , does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support .


Acting coherently upon stimuli requires some kind of integration of stimulus and response features across various distinct cortical feature maps ( one aspect of the binding problem ) .


Although the process of feature binding proper seems rather automatic , recent studies revealed that the management of stimulus-response bindings is less efficient in populations with impaired cognitive-control processes .


Here , we investigated whether the cognitive control of stimulus-response feature bindings ( `` event files '' ) in healthy participants is affected by non-invasive brain stimulation ( tDCS ) of the dorsolateral prefrontal cortex ( DLPFC ) - a main component of the cognitive-control network .


In different sessions , participants received anodal , cathodal , or sham tDCS ( 2 mA , 20 min ) while performing an audio-visual event-file task assessing the creation and retrieval of stimulus-stimulus and stimulus-response feature bindings .


The general findings from this task indicate that performance suffers when some , but not all of the features are repeated ( the so-called partial repetition cost ) .


Stimulation over the right , but not the left DLPFC reduced control of stimulus-response bindings and produced outcome patterns similar to those previously observed in autistic children , people with lower fluid intelligence , and older adults .


This finding provides empirical support for a role of the right DLPFC in feature-binding management , which might consist in preventing the stimulus-induced activation of previously created , but now task-irrelevant , episodic bindings .


From a methodological perspective , the finding may suggest that tDCS could be used as a temporary , reversible `` brain lesion '' generator in healthy subjects , enabling experimental investigation of how the brain works .


To assess in a randomized study the patient-centred outcome of two guided surgery systems ( mucosa or bone supported ) compared to conventional implant placement , in fully edentulous patients .


Fifty-nine patients ( 72 jaws ) with edentulous maxillas and / or mandibles , were consecutively recruited and randomly assigned to one of the treatment groups .


Outcome measures were the Dutch version of the McGill Pain Questionnaire ( MPQ-DLV ) , the Health-related quality of life instrument ( HRQOL ) , visual analogue scales ( VAS ) , the duration of the procedure , and the analgesic doses taken each day .


Three hundred and fourteen implants were placed successfully .


No statistical differences could be shown between treatment groups on pain response ( MPQ-DLV ) , treatment perception ( VAS ) or number or kind of pain killers .


For the HRQOLI-instrument , a significant difference was found between the Materialise Mucosa and Materialise Bone group at day 1 ( p = 0.02 ) and day 2 ( p = 0.01 ) .


For the duration of the surgery , a statistical difference ( p = 0.005 ) was found between the Materialise mucosa and the Mental group , in favour of the first .


In this study little difference could be found in the patient outcome variables of the different treatment groups .


However there was a tendency for patients treated with conventional flapped implant placement to experience the pain for a longer period of time .


The snatch-farrowed porcine-colostrum-deprived ( SF-pCD ) pig model , in which neonates are raised on commercially available bovine colostrum , is an alternative model for porcine infectious disease research .


It is not known if SF-pCD pigs possess growth performance and immunity comparable to conventional , farm-raised pigs .


The current experiment compared growth performance and immune responses of SF-pCD pigs to their farm-raised siblings following Mycoplasma hyopneumoniae ( Mhyo ) vaccination .


Twelve SF-pCD and 13 farm-raised siblings were vaccinated on day 7 ( D7 ) and D26 of age .


Body weights were measured once or twice weekly and average daily gain ( ADG ) was calculated .


Peripheral blood mononuclear cells ( PBMC ) were isolated on D40 .


Cytokine secretion from PBMC stimulated with Mhyo antigen or phorbol myristate acetate plus ionomycin ( PMA/Iono ) was assessed using a multiplexed fluorescent microsphere immunoassay ( FMIA ) .


Additionally , interferon gamma ( IFN ) secretion from stimulated PBMC was assessed using ELISPOT .


Mhyo IgG titers were measured by an ELISA in D40 sera .