Failure of the kidneys to excrete potassium as well as heparin-induced reduction of aldosterone synthesis put hemodialysis patients at risk of hyperkalemia .


It has not yet been clearly known whether hyperkalemia is also induced by low-molecular-weight ( LMW ) heparins .


This study aimed to evaluate the effect of switching UF heparin to LMW heparin enoxaparin , as an anticoagulant during hemodialysis , on serum potassium level in patients on hemodialysis .


In two hemodialysis units , 58 patients were randomly assigned into two groups , to receive two different anticoagulation protocols for 3 weeks ; one group continued to receive their routine dose of UF heparin , 5000 units , and the other received enoxaparin , 0.5 mg/kg , at the beginning of each hemodialysis session .


While there was no significant difference between baseline blood measurements of the two groups in terms of kidney function tests and electrolytes , following 3 weeks of the study , the mean serum potassium level decreased from 4.9 0.8 mEq/L to 4.5 0.5 mEq/L in the LMW heparin group ( P = .001 ) ; however , there was no change in the mean serum potassium level in those who continued to receive their usual dose of UF heparin .


In a subgroup analysis , diabetic patients in the enoxaparin group did not experience significant reduction in serum potassium levels .


Our study revealed the role of LMW heparins as a potential alternative to UF heparins in the hemodialysis patients with hyperkalemia .


Antidepressants are often the first-line treatment for depression in primary care .


However , not all patients respond to medication after an adequate dose and duration of treatment .


Currently , there are no estimates of the prevalence of treatment-resistant depression ( TRD ) from UK primary care .


To estimate the prevalence of TRD in UK primary care .


Design and setting Data were collected as part of a multicentre randomised controlled trial , from 73 general practices in UK primary care .


Potential participants ( aged 18-75 years who had received repeated prescriptions for antidepressants ) were identified from general practice records .


Those who agreed to be contacted were mailed a questionnaire that included questions on depressive symptoms ( Beck Depression Inventory [ BDI-II ] ) , and adherence to antidepressants .


Those who scored 14 on the BDI-II and had taken antidepressants for at least 6 weeks at an adequate dose were defined as treatment resistant .


A total of 2439 patients completed the questionnaire ( 84 % of those who agreed to be contacted ) , of whom 2129 had been prescribed an adequate dose of antidepressants for at least 6 weeks .


Seventy-seven per cent ( 95 % CI = 75 % to 79 % ) had a BDI score of 14 .


Fifty-five per cent ( 95 % CI = 53 % to 58 % ) ( n = 1177 ) met the study 's definition of TRD , of whom 67 % had taken their antidepressants for more than 12 months .


The high prevalence of TRD is an important challenge facing clinicians in UK primary care .


A more proactive approach to managing this patient population is required to improve outcome .


Cognitive enhancement resulting from nicotinic acetylcholine receptor stimulation may be evidenced by increased efficiency of the auditory-frontal cortex network of auditory discrimination , which is impaired in schizophrenia , a cognitive disorder associated with excessive tobacco use .


Investigating automatic ( preattentive ) detection of acoustic change with the mismatch negativity ( MMN ) brain event-related potential in response to nicotine in individuals with varying baseline levels of auditory discrimination may provide useful insight into the cholinergic regulation of this neural network and its potential amelioration with novel nicotinic agents .


Sixty healthy , non-smoking male volunteers were presented with an ` optimal ' multi-feature MMN paradigm in a randomized , placebo controlled double-blind design with 6mg of nicotine gum .


Participants with low , medium , and high baseline amplitudes responded differently to nicotine ( vs. placebo ) , and nicotine response was feature specific .


Whereas MMN in individuals with high amplitudes was diminished by nicotine , MMN increased in those with low amplitudes .


Nicotine effects were not shown in medium amplitude participants .


These findings provide preliminary support for the role of nicotinic neurotransmission in sensory memory processing of auditory change and suggest that nicotinic receptor modulation can both enhance and diminish change detection , depending on baseline MMN and its eliciting stimulus feature .


Community-acquired pneumonia ( CAP ) is considered the leading cause of death from infectious disease in developed countries , while complications of CAP - sepsis being the most common and challenging - increase the risk of mortality .


During the progression of sepsis , a state of neutrophil ` paralysis ' develops resulting in the impairment of neutrophil anti-microbial functions including : chemotaxis , production of reactive oxygen species , and formation of neutrophil extracellular traps ( NETs ) .


Mechanisms underlying defective neutrophil function remain elusive although NET formation has been implicated in the immunosuppression and increased rates of sepsis observed in neonates .


There is , however , increasing evidence that statins are able to modulate neutrophil function in sepsis as several systematic reviews have concluded that statins have a role in improving infection-related outcomes and mortality while , in vitro , statins have also been shown to boost NET formation in healthy individuals .


The ` SNOOPI ' trial is a phase 4 , randomised placebo-controlled trial .


The aim of this study is to determine whether oral treatment with simvastatin compared to placebo optimises neutrophil anti-microbial functions in elderly patients with septic pneumonia improving patient outcomes in the elderly .


The primary outcome will be NET production within 72 to 96 hours of treatment with simvastatin or placebo measured in response to a number of inflammatory mediators , including IL8 , f-Met-Leu-Phe and lipopolysaccharide .


Secondary outcomes include neutrophil migratory capacity ; reactive oxygen species production ; neutrophil phagocytic capacity ; safety and tolerability of simvastatin administration within this patient group ; biological markers of neutrophil activation , the inflammatory response , alveolar epithelial and endothelial injury ; systemic endothelial function biomarkers and pulmonary extracellular matrix degradation .


This study aims to recruit 60 patients admitted into Queen Elizabeth Hospital Birmingham NHS-Foundation Trust .


This study will investigate the ability of in vivo simvastatin therapy to modulate neutrophil anti-microbial functions in CAP-associated sepsis .


EudraCT number : 2012-003343-29 ( Trial Registered : 26 November 2012 ) .


The identification of patients at risk for developing left ventricular ( LV ) remodeling after acute myocardial infarction ( AMI ) has crucial prognostic implications .


The aims of this study were ( 1 ) to investigate the relationship between peak subepicardial and subendocardial twist and infarct transmurality , as assessed using contrast-enhanced magnetic resonance imaging , and ( 2 ) to evaluate the association between peak subepicardial and subendocardial twist and LV remodeling 6 months after AMI .


A total of 213 patients with ST-segment elevation AMIs who underwent three-dimensional echocardiography for LV volumes and functional assessment and two-dimensional speckle-tracking analysis for the evaluation of LV twist ( subendocardial vs subepicardial ) were retrospectively included .


A subgroup of 40 patients underwent magnetic resonance imaging within 2 months for infarct size quantification .


Peak subepicardial twist was strongly related to infarct size ( number of segments with transmural scar : r ( 2 ) = 0.526 , P < .001 ; total scar score : r ( 2 ) = 0.515 , P < .001 ) compared with peak subendocardial twist ( number of segments with transmural scar : r ( 2 ) = 0.379 , P < .001 ; total scar score : r ( 2 ) = 0.331 , P < .001 ) .


In the overall population , 44 patients ( 21 % ) developed significant LV remodeling at 6-month follow-up ( LV end-systolic volume increase 15 % ) .


These patients showed significantly more impaired peak subepicardial and subendocardial twist at baseline compared with patients without LV remodeling ( 4.5 1.3 vs 9.4 3.5 , P < .001 ; 7.0 3.2 vs 12.9 5.8 , P < .001 , respectively ) .


Importantly , peak subepicardial twist ( odds ratio , 0.241 ; 95 % confidence interval , 0.134-0 .431 ; P < .001 ) and peak troponin T ( odds ratio , 1.152 ; 95 % confidence interval , 1.006-1 .320 ; P = .041 ) were independently associated with the development of LV remodeling .


Peak subepicardial twist strongly reflects infarct transmurality as assessed with magnetic resonance imaging and is independently associated with LV remodeling after AMI .


To compare the clinical outcome of single implants which underwent immediate nonocclusal loading with implants subjected to early non-occlusal loading at 3 weeks , and implants conventionally loaded at 4 months .


One hundred and five patients in five private practices requiring a single implant-supported crown were randomised to immediate loading ( 35 patients ) , early loading ( 35 patients ) and conventional loading ( 35 patients ) groups .


To be immediately or early loaded , implants had to be inserted with a torque superior to 45 Ncm .


Immediately and early loaded implants received non-occluding temporary crows , whereas conventionally loaded implants were directly restored with definitive crowns .


Temporary crowns were replaced by definitive ones after 4 months .


Outcome measures were crown and implant failures , complications and peri-implant marginal bone level changes recorded by a blinded assessor .


Two patients dropped out from the immediate loading group up to 1-year post-loading .


Two implants failed , one in the immediately loaded and one in the early loaded group ( P = 0.601 ) .


One immediately loaded implant and two early loaded implants were affected by one complication each ( P = 0.162 ) .


Mean peri-implant marginal bone loss after 1 year was -0.1200.230 mm ( 95 % CI -0.35 , 0.10 ) for immediate , -0.3900.840 mm ( 95 % CI -1.23 , 0.45 ) for early and -0.2010.306 mm ( 95 % CI -0.51 ; 0.11 ) for conventionally loaded implants .


There were no statistically significant differences for any of the outcome measures between the three loading strategies up to 1-year post-loading .


No major clinical differences were observed with regard to implant survival , complications and marginal bone level changes when loading single implants immediately , early or conventionally .


Assess the effects of a home exercise programme , based on aerobic training and muscle strength training , in patients with cystic fibrosis ( CF ) , for a period of 3 months .


Randomised controlled clinical experiment , with an analysis of intention to treat including clinically stable patients with CF and of age 16 .


Assessments include : a 6 min walk test ( 6 MWT ) , one-repetition maximum strength test ( 1 RM ) , spirometry and quality of life questionnaires .


The patients randomised for the exercise group exercise group followed a home exercise protocol , supervised by telephone , while the control group maintained their usual activities .


41 Patients were included , 22 in the control group and 19 in the exercise group .


The exercise group presented a significant increase in muscle strength in upper limbs ( UULL ) on the 1 RM test .


There was no significant difference between groups on the scores for general quality of life and specifically for CF and in the distance walked on the 6 MWT .


The study demonstrated that a home exercise programme had positive effects in adult patients with CF , including gain in muscle strength in UULL .


No increase in tolerance to exercise was shown and improvement in the quality of life of the patients who received intervention .


Posttraumatic stress disorder ( PTSD ) is a chronic disabling illness , resulting from exposure to extreme traumatic event .


Although different pharmacologic agents are suggested for treatment of PTSD , none have been completely effective in eliminating symptoms .


The purpose of this study was to assess the use of baclofen as an add-on to citalopram in treatment of PTSD .


In this double-blind clinical trial , 40 Iranian combat veterans with PTSD were randomly assigned to 2 groups .


The first group received a combination treatment of 20 to 60 mg/d citalopram and 40 mg/d baclofen , and the second group received 20 to 60 mg/d citalopram plus placebo .


Symptom severity was assessed by Clinician-Administered PTSD Scale at the beginning of the study and after 2 , 4 , 6 , and 8 weeks .


Global Assessment of Functioning and Hamilton Rating Scale for Anxiety and Depression were also used at the same periods .


Data were analyzed with independent t test and paired t test using SPSS software version 13 ( IBM , Armonk , NY ) .


Twenty-three male patients ( baclofen group , 13 patients ; placebo group , 10 patients ) completed the study .


Dropout from the treatment was not caused by adverse effects of the new medications in any of the subjects .


Baclofen group showed significantly larger improvement in Clinician-Administered PTSD Scale total ( P = 0.040 ) , hyperarousal ( P = 0.020 ) , and avoidance ( 0.020 ) scores , Global Assessment of Functioning score ( 0.001 ) , depression ( P = 0.000 ) , and anxiety ( P = 0.000 ) after 8 weeks of treatment .


No intergroup difference was found in improvement of reexperience symptoms ( P = 0.740 ) .


Baclofen showed to be an effective add-on to selective serotonin reuptake inhibitors in treatment of PTSD for better symptom recovery and functional improvement .


We previously described the prognostic impact of tumor regression grading ( TRG ) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy ( CRT ) in the CAO/ARO/AIO -94 trial .


Here we report long-term results after a median follow-up of 132 months .


TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis , ranging from TRG 4 ( no viable tumor cells ) to TRG 0 ( no signs of regression ) .


Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence , distant metastasis , and disease-free survival ( DFS ) .


Ten-year cumulative incidence of distant metastasis and DFS were 10.5 % and 89.5 % for patients with TRG 4 ( complete regression ) , 29.3 % and 73.6 % for TRG 2 and 3 ( intermediate regression ) , and 39.6 % and 63 % for TRG 0 and 1 ( poor regression ) , respectively ( P = .005 and P = .008 , respectively ) .


On multivariable analysis , residual lymph node metastasis ( ypN + ) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis ( P < .001 and P = .035 , respectively ) and DFS ( P < .001 and P = .039 , respectively ) , whereas local recurrence was significantly affected by ypN status ( P < .001 ) and lymphatic invasion ( P = .026 ) .


Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters .


This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting .


The current standard for pain control following liver surgery is intravenous , patient-controlled analgesia ( IV PCA ) or epidural analgesia .


We have developed a modification of a regional technique called medial open transversus abdominis plane ( MOTAP ) catheter analgesia .


The MOTAP technique involves surgically placed catheters through the open surgical site into a plane between the internal oblique muscle and the transverse abdominis muscle superiorly .


The objective of this trial is to assess the efficacy of this technique .


This protocol describes a multicentre , prospective , blinded , randomized controlled trial .


One hundred and twenty patients scheduled for open liver resection through a subcostal incision will be enrolled .


All patients will have two MOTAP catheters placed at the conclusion of surgery .


Patients will be randomized to one of two parallel groups : experimental ( local anaesthetic through MOTAP catheters ) or placebo ( normal saline through MOTAP catheters ) .


Both groups will also receive IV PCA .


The primary endpoint is mean cumulative postoperative opioid consumption over the first 2 postoperative days ( 48 hours ) .


Secondary outcomes include pain intensity , patient functional outcomes , and the incidence of complications .


This trial has been approved by the ethics boards at participating centres and is currently enrolling patients .


Data collection will be completed by the end of 2014 with analysis mid-2015 and publication by the end of 2015 .


The study is registered with http://clinicaltrials.gov ( NCT01960049 ; 23 September 2013 ) .


Telephone-administered therapies have emerged as an alternative method of delivery for the treatment of depression , yet concerns persist that the use of the telephone may have a deleterious effect on therapeutic alliance .


The purpose of this study was to compare therapeutic alliance in clients receiving cognitive behavioral therapy ( CBT ) for depression by telephone ( T-CBT ) or face-to-face ( FtF-CBT ) .


We randomized 325 participants to receive 18 sessions of T-CBT or FtF-CBT .


The Working Alliance Inventory ( WAI ) was administered at Weeks 4 and 14 .


Depression was measured during treatment and over 1 year posttreatment follow-up using the Hamilton Rating Scale for Depression and Patient Health Questionnaire-9 .


There were no significant differences in client or therapist WAI between T-CBT or FtF-CBT ( Cohen 's f ranged from 0 to .013 , all ps > .05 ) .


All WAI scores predicted depression end of treatment outcomes ( Cohen 's f ranged from .009 to .06 , all ps < .02 ) .


The relationship between the WAI and depression outcomes did not vary by treatment group ( Cohen 's f ranged from 0 to .004 , ps > .07 ) .


The WAI did not significantly predict depression during posttreatment follow-up ( all ps > .12 ) .


Results from this analysis do not support the hypothesis that the use of the telephone to provide CBT reduces therapeutic alliance relative to FtF-CBT .


To design an educational activity and evaluate its effectiveness on increasing third-year pharmacy students ' knowledge and confidence to recommend self-care products to patients .


Faculty members created a self-care activity , the Amazing Self-Care Race , for educational use in a pharmaceutical care laboratory course .


Student teams worked competitively to complete 15 stations focused on self-care .


A complex , real-world case was presented at each station .


Student recommendations were presented to a facilitator .


Prior to and following the activity , students were invited to complete an online anonymous survey instrument .


Eighty-six students completed presurvey and postsurvey instruments to assess their knowledge and perceived confidence to recommend a self-care product to a patient prior to and following participation in the Amazing Self-Care Race .


Students demonstrated a significant increase in their ability and confidence to recommend self-care products following the activity ( p < 0.001 ) .


The Amazing Self-Care Race is an effective educational activity that increases student knowledge and confidence in self-care therapeutics .


The activity helped students to develop self-care skills , enabled them to learn through doing , encouraged them to synthesize information while making self-care recommendations , and helped them to develop confidence by thinking on their feet .


To determine the relationship between coronary plaque detected with coronary computed tomographic ( CT ) angiography and clinical parameters and cardiovascular risk factors in asymptomatic patients with diabetes .


All patients signed institutional review board-approved informed consent forms before enrollment .


Two hundred twenty-four asymptomatic diabetic patients ( 121 men ; mean patient age , 61.8 years ; mean duration of diabetes , 10.4 years ) underwent coronary CT angiography .


Total coronary artery wall volume in all three vessels was measured by using semiautomated software .


The coronary plaque volume index ( PVI ) was determined by dividing the wall volume by the coronary length .


The relationship between the PVI and cardiovascular risk factors was determined with multivariable analysis .


The mean PVI ( standard deviation ) was 11.2 mm ( 2 ) 2.7 .


The mean coronary artery calcium ( CAC ) score ( determined with the Agatston method ) was 382 ; 67 % of total plaque was noncalcified .


The PVI was related to age ( standardized = 0.32 , P < .001 ) , male sex ( standardized = 0.36 , P < .001 ) , body mass index ( BMI ) ( standardized = 0.26 , P < .001 ) , and duration of diabetes ( standardized = 0.14 , P = .03 ) .


A greater percentage of soft plaque was present in younger individuals with a shorter disease duration ( P = .02 ) .


The soft plaque percentage was directly related to BMI ( P = .002 ) .


Patients with discrepancies between CAC score and PVI rank quartiles had a higher percentage of soft and fibrous plaque ( 18.7 % 3.3 vs 17.4 % 3.5 [ P = .008 ] and 52.2 % 7.2 vs 47.2 % 8.8 [ P < .0001 ] , respectively ) .


In asymptomatic diabetic patients , BMI was the primary modifiable risk factor that was associated with total and soft coronary plaque as assessed with coronary CT angiography .


Walnut consumption is associated with reduced risk of coronary heart disease ( CHD ) .


We assessed the effect of walnuts on lipid and glucose metabolism , adipokines , inflammation and endothelial function in healthy Caucasian men and postmenopausal women 50years old .


Forty subjects ( meanSEM : age 601years , BMI 24.90.6 kg/m ( 2 ) ; 30 females ) were included in a controlled , cross-over study and randomized to receive first a walnut-enriched ( 43g/d ) and then a Western-type ( control ) diet or vice-versa , with each lasting 8weeks and separated by a 2-week wash-out .


At the beginning and end of each diet phase , measurements of fasting values , a mixed meal test and an assessment of postprandial endothelial function ( determination of microcirculation by peripheral artery tonometry ) were conducted .


Area under the curve ( AUC ) , incremental AUC ( iAUC ) and treatmenttime interaction ( shape of the curve ) were evaluated for postprandial triglycerides , VLDL-triglycerides , chylomicron-triglycerides , glucose and insulin .


Compared with the control diet , the walnut diet significantly reduced non-HDL-cholesterol ( walnut vs. control : -103 vs. -32 mg/dL ; p = 0.025 ) and apolipoprotein-B ( -5.01.3 vs. -0.21.1 mg/dL ; p = 0.009 ) after adjusting for age , gender , BMI and diet sequence .


Total cholesterol showed a trend toward reduction ( p = 0.073 ) .


Fasting VLDL-cholesterol , LDL-cholesterol , HDL-cholesterol , triglycerides and glucose , insulin , HOMA-IR , and HbA1c did not change significantly .


Similarly , fasting adipokines , C-reactive protein , biomarkers of endothelial dysfunction , postprandial lipid and glucose metabolism and endothelial function were unaffected .


Daily consumption of 43g of walnuts for 8weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B , which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk .


A subgroup of oropharyngeal squamous cell carcinoma ( OPC ) is infected with high-risk human papillomavirus ( HPV ) .


The object of this study is to evaluate the efficacy of adjuvant chemotherapy with S-1 , an oral 5-fluorouracil prodrug , on survival of patients with OPC according to HPV status .


Among OPC patients of stage III or IV who received definitive treatment from 1998 to 2008 , 38 who were confirmed tumor-free after primary treatment were analyzed .


Before 2003 , none of the patients received S-1 adjuvant chemotherapy ( S-1 ( - ) - group ) ; however , all patients who were eligible were administered S-1 ( S-1 ( + ) - group ) after 2003 .


The expression of thymidylate synthase ( TYMS ) involved in 5-FU metabolism was also examined in protein and mRNA levels .


Although there was a trend to disease-free and overall survival benefit in HPV-negative patients with S-1 , it did not achieve statistical significance ( P = .082 and P = .065 , respectively ) .


For the HPV-positive patients , the survivals were similar with or without S-1 administration .


TYMS-expression in HPV-positive OPC tissues was significantly higher than in HPV-negative ones in both protein and mRNA levels ( P = .0489 and P = .0446 , respectively ) .


The current study provides a rationale to plan a randomized trial to compare the efficacy of S-1 according to the HPV status in OPCs .


It is an inherent assumption in randomised controlled trials that the drug effect can be estimated by subtracting the response during placebo from the response during active drug treatment .


To test the assumption of additivity .


The primary hypothesis was that the total treatment effect is smaller than the sum of the drug effect and the placebo effect .


The secondary hypothesis was that non-additivity was most pronounced in participants with large placebo effects .


We used a within-subject randomised blinded balanced placebo design and included 48 healthy volunteers ( 50 % males ) , mean ( SD ) age 23.4 ( 6.2 ) years .


Experimental pain was induced by injections of hypertonic saline into the masseter muscle .


Participants received four injections with hypertonic saline along with lidocaine or matching placebo in randomised order : A : received hypertonic saline/told hypertonic saline ; B : received hypertonic saline + lidocaine/told hypertonic saline ; C : received hypertonic saline + placebo/told hypertonic saline + pain killer ; D : received hypertonic saline + lidocaine/told hypertonic saline + pain killer .


The primary outcome measure was the area under the curve ( AUC , mm ( 2 ) ) of pain intensity during injections .


There was a significant difference between the sum of the drug effect and the placebo effect ( mean AUC 6279 mm ( 2 ) ( 95 % CI , 4936-7622 ) ) and the total treatment effect ( mean AUC 5455 mm ( 2 ) ( 95 % CI , 4585-6324 ) ) ( P = 0.049 ) .


This difference was larger for participants with large versus small placebo effects ( P = 0.015 ) , and the difference correlated significantly with the size of the placebo effect ( r = 0.65 , P = 0.006 ) .


Although this study examined placebo effects and not the whole placebo response as in randomised controlled trials , it does suggest that the additivity assumption may be incorrect , and that the estimated drug effects in randomised controlled trials may be underestimated , particularly in studies reporting large placebo responses .


The implications for randomised controlled trials and systematic reviews need to be discussed .


Cardiovascular diseases ( CVD ) are a leading cause of death worldwide including the Middle East .


This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin .


Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines .


In this study , for the first time , the relationship between traditional cardiovascular risk factors , Metabolic Syndrome ( MetS ) and circulating level of adipokines in Arab ethnicity was investigated .


We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait .


Traditional cardiovascular risk factors such as blood pressure ( BP ) , low density lipoprotein ( LDL ) and triglyceride ( TG ) were measured .


Plasma levels of circulating Leptin , Plasminogen Activator Inhibitor ( PAI-1 ) visfatin , adiponectin , resistin and adipsin were assessed using the multiplexing immunobead-based assay .


Circulating levels of High sensitivity C-Reactive Protein ( hsCRP ) , Leptin , PAI-1 and adiponectin were significantly higher in Arab women than men ( p < 0.0001 ) .


In multi-variate analysis , the homeostasis model assessment-insulin resistance ( HOMA-IR ) and body mass index ( BMI ) showed strong association with most of the biomarkers ( p < 0.05 ) .


HsCRP showed significant association with all risk factors ( p < 0.05 ) .


Leptin , PAI-1 and adipsin showed significant positive correlation with BMI , unlike adiponectin which showed inverse correlation ( p < 0.05 ) .


Subjects in the highest tertile of leptin , PAI-1 and hsCRP had higher odds of having Metabolic Syndrome ( MetS ) ( odd ratio [ OR ] = 3.02 , 95 % confidence interval [ CI ] = 1.47-6 .19 ) and ( OR = 2.52 , 95 % CI = 1.45-4 .35 ) , ( OR = 4.26 , 95 % CI = 2.39-7 .59 ) respectively .


On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS ( OR = 0.22 , 95 % CI = 0.12-0 .40 ) .


Leptin , PAI-1 and hsCRP showed significant positive association with increased MetS components ( P-trend < 0.05 ) , while adiponectin was negatively associated with increased MetS components ( P-trend < 0.0001 ) .


Our results show positive association between hsCRP , leptin , PAI-1 with increased MetS components and increase the odds of having MetS .


Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS .


Overall , our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs .


Studies utilizing beta-hydroxy-beta-methylbutyrate ( HMB ) supplementation in trained populations are limited .


No long-term studies utilizing HMB free acid ( HMB-FA ) have been conducted .


Therefore , we investigated the effects of 12 weeks of HMB-FA supplementation on skeletal muscle hypertrophy , body composition , strength , and power in trained individuals .


We also determined the effects of HMB-FA on muscle damage and performance during an overreaching cycle .


A three-phase double-blind , placebo - and diet-controlled randomized intervention study was conducted .


Phase 1 was an 8-week-periodized resistance-training program ; Phase 2 was a 2-week overreaching cycle ; and Phase 3 was a 2-week taper .


Muscle mass , strength , and power were examined at weeks 0 , 4 , 8 , and 12 to assess the chronic effects of HMB-FA ; and assessment of these , as well as cortisol , testosterone , and creatine kinase ( CK ) was performed at weeks 9 and 10 of the overreaching cycle .


HMB-FA resulted in increased total strength ( bench press , squat , and deadlift combined ) over the 12-week training ( 77.1 18.4 vs. 25.3 22.0 kg , p < 0.001 ) ; a greater increase in vertical jump power ( 991 168 vs. 630 167 W , p < 0.001 ) ; and increased lean body mass gain ( 7.4 4.2 vs. 2.1 6.1 kg , p < 0.001 ) in HMB-FA - and placebo-supplemented groups , respectively .


During the overreaching cycle , HMB-FA attenuated increases in CK ( -6 91 vs. 277 229 IU/l , p < 0.001 ) and cortisol ( -0.2 2.9 vs. 4.5 1.7 g/dl , p < 0.003 ) in the HMB-FA - and placebo-supplemented groups , respectively .


These results suggest that HMB-FA enhances hypertrophy , strength , and power following chronic resistance training , and prevents decrements in performance following the overreaching .


The current study tested whether perceived social support serves as a mediator of anxiety and depressive symptom change following evidence-based anxiety treatment in the primary care setting .


Gender , age , and race were tested as moderators .


Data were obtained from 1004 adult patients ( age M = 43 , SD = 13 ; 71 % female ; 56 % White , 20 % Hispanic , 12 % Black ) who participated in a randomized effectiveness trial ( coordinated anxiety learning and management [ CALM ] study ) comparing evidence-based intervention ( cognitive-behavioral therapy and/or psychopharmacology ) to usual care in the primary care setting .


Patients were assessed with a battery of questionnaires at baseline , as well as at 6 , 12 , and 18 months following baseline .


Measures utilized in the mediation analyses included the Abbreviated Medical Outcomes ( MOS ) Social Support Survey , the Brief Symptom Index ( BSI ) - Somatic and Anxiety subscales , and the Patient Health Questionnaire ( PHQ-9 ) .


There was a mediating effect over time of perceived social support on symptom change following treatment , with stronger effects for 18-month depression than anxiety .


None of the mediating pathways were moderated by gender , age , or race .


Perceived social support may be central to anxiety and depressive symptom changes over time with evidence-based intervention in the primary care setting .


These findings possibly have important implications for development of anxiety interventions .


The article presents the results of psychosocial burdens in special educators ( specialists in the field of oligophrenopedagogy ) with intellectually disabled students .


In theoretical part , specific context of occupational stress in special educators was introduced .


Additionally , the need of broader research context regarding occupational stress and the risk of burnout in special educators working with intellectually disabled individuals were included .


The results were obtained using Plichta and Pyzalski 's Questionnaire of Occupational Burdens in Teaching ( QOBT ) .


The presented results are based on a research sample ( N = 100 ) of special educators ( female ) teaching intellectually disabled students attending special schools in the city of Ldz .


The obtained results were compared with the results coming from a large random sample of public school teachers working with non-intellectually disabled children from the Lodi voivodeship ( N = 429 ) and referred to the norms of QOBT .


The results show significant percentage of respondents obtaining high level of occupational burdens ( conflict situations - 45 % , organizational burdens - 31 % , lack of work sense - 40 % , global score - 40 % ) .


Seniority is not related to the level of burdens .


Some significant differences concerning the level of occupational burdens between both groups of teachers were found .


The study showed e.g. the strong need for supporting special educators in the workplace context and the need of implementing preventive and remedial measures at both individual and organizational levels ( especially in terms of improving personal relationships in a workplace ) .


Generally , the results show similarity of the stressors ' ranking in special educators and school teachers working with non-intellectually disabled children .


Chronic kidney disease ( CKD ) is public health concern even in Asian countries .


TRK-100STP , a sustained release tablet of an orally-active prostacyclin analogue , beraprost sodium , is suggested to suppress worsening of some parameters of renal filtration function , containing in slope of 1/serum creatinine ( 1/SCr ) vs. time in a phase II clinical trial .


We describe the design of the phase IIb/III trial of TRK-100STP , CASSIOPEIR ( CRF Asian Study with Oral PGI2 derivative for Evaluating Improvement of Renal function ) conducted in approximately 160 centers in China , Hong Kong , Japan , Malaysia , Republic of Korea , Taiwan , and Thailand .


A total of 750 patients ( n = 250 per group ) with primary glomerular disease or nephrosclerosis were planned to be enrolled .


Patients were randomized into one of three treatment groups in a double-bind , placebo-controlled manner : TRK-100STP 60 g b.i.d. ; TRK-100STP 120 g b.i.d. ; or placebo .


The treatment period is planned to last 2 to 4 years .


The primary efficacy endpoint is the renal composite endpoint including doubling of SCr and ESRD ( dialysis induction , renal transplantation , or increase in SCr to 6.0 mg/dL ) .


This trial targeting CKD patients is designed to ( a ) demonstrate the superiority of TRK-100STP over placebo using renal composite endpoints , ( b ) determine the recommended clinical dose , and ( c ) assess the safety of TRK-100STP in this population and setting .


ClinicalTrials.gov Identifier : NCT01090037 .


Indacaterol is a long-acting beta-2 agonist for once-daily treatment of COPD .


We evaluated the effects of indacaterol 150g on lung hyperinflation compared with placebo and open-label tiotropium 18g .


We measured physical activity during treatment with indacaterol 150g and matched placebo .


We performed a randomized , three-period , cross-over study ( 21days of treatment separated by two wash-out periods of 13days ) with indacaterol 150g or matching placebo and tiotropium 18g .


Lung function was assessed by body plethysmography and spirometry .


Physical activity was measured for one week by a multisensory armband at the end of both treatment periods with indacaterol/matched placebo .


The primary endpoint was peak inspiratory capacity at the end of each treatment period .


129 patients ( mean age , 61years ; mean post-bronchodilator FEV1 , 64 % ) , were randomized and 110 patients completed the study .


Peak inspiratory capacity was 0.22 L greater with Indacaterol at day 21 compared to placebo ( p < 0.001 ) .


Similar results were observed for tiotropium .


Both bronchodilators also significantly improved other parameters of lung hyperinflation compared with placebo .


All parameters of physical activity were significantly increased during treatment with indacaterol versus placebo .


Indacaterol 150g improved lung hyperinflation in patients with moderate COPD , which was associated with an increase of physical activity .


ClinicalTrials.gov registration number : NCT01012765 .


Available drug treatments for bipolar disorder fail to reverse patients ' cognitive deficits .


Erythropoietin has neurotrophic actions and aids neurocognitive function .


The aim of the study was to investigate the potential of erythropoietin to treat cognitive dysfunction in bipolar disorder .


Patients with an ICD-10 diagnosis of bipolar disorder in remission were randomized , with stratification by age and gender , to receive 8 weekly erythropoietin ( 40,000 IU ) or saline ( sodium chloride [ NaCl ] , 0.9 % ) infusions in a double-blind , parallel-group design .


The first patient was randomized in September 2009 and last assessment was completed in October 2012 .


Patients were assessed at baseline and at weeks 9 and 14 .


The primary outcome was change in verbal memory indexed by the total words recalled across Rey Auditory Verbal Learning Test learning trials ( I-V ) from baseline to week 9 ; secondary outcomes were sustained attention and facial expression recognition ; and tertiary outcomes were attention , executive function , subjective cognitive function , and mood .


Analysis was by intention to treat , using repeated-measures analysis of covariance adjusted for stratification variables and mood .


The statistical threshold for which results were considered significant was P .05 ( 2-tailed ) .


44 patients were randomized ; given 1 dropout after baseline , results were analyzed for 43 patients ( erythropoietin : n = 23 ; saline : n = 20 ) .


There was no significant improvement of verbal memory in erythropoietin versus saline groups ( P = .10 ) .


However , erythropoietin enhanced sustained attention ( P = .001 ) , recognition of happy faces ( P = .03 ) , and speed of complex information processing across learning , attention , and executive function ( P = .01 ) .


These effects occurred in absence of changes in simple reaction times or mood ( P values .16 ) and were maintained after red blood cell normalization .


This is the first trial investigating erythropoietin to treat cognitive dysfunction in bipolar disorder .


The findings highlight erythropoietin as a candidate treatment for deficits in attention and executive function in bipolar disorder .


ClinicalTrials.gov identifier : NCT00916552 .


The objective was to compare retinal morphology and function following intravitreal injections of bevacizumab ( Avastin ) or triamcinolone ( Volon A ) in patients with early diabetic macular edema ( DME ) .


The study was planned as a randomized , prospective , interventional clinical trial .


A total of 30 diabetic patients with treatment-nave , clinically significant macular edema were included in this study and randomized to two equal groups .


One group initially received three injections of 2.5 mg bevacizumab in monthly intervals .


The second group received a single injection of 8 mg triamcinolone , followed by two sham interventions .


Functional and anatomic results were evaluated monthly using ETDRS vision charts and spectral-domain optical coherence tomography .


According to the study protocol , retreatment after 3 months was dependent on functional and anatomic outcome in a PRN regimen .


Baseline best corrected visual acuity ( BCVA ) was 0.30 logMAR and central retinal subfield thickness ( CSRT ) was 505m in the bevacizumab group and 0.32 logMAR and 490 m CSRT in the triamcinolone group .


After 3 months , BCVA improved to 0.23 logMAR ( bevacizumab ) and 358 m CRST and 0.26 logMAR ( triamcinolone ) and 308m CSRT .


After 12 months , BCVA further recovered in the bevacizumab group ( 0.18 logMAR ) but slightly decreased in the triamcinolone group ( 0.36 logMAR ) .


Intravitreal bevacizumab and triamcinolone are both equally effective in reducing CSRT in early DME .


After 6 months , rehabilitation of vision was comparable in both treatment arms , whereas at the final follow-up at month 12 , BCVA was superior in the bevacizumab than in the triamcinolone sample .


This may be related to cataract development following steroid treatment , as well as to substance-specific mechanisms within the angiogenic versus the inflammatory cascade .


To determine the prevalence and characteristics of fetal alcohol spectrum disorders ( FASD ) among first grade students ( 6 - to 7-year-olds ) in a representative Midwestern US community .


From a consented sample of 70.5 % of all first graders enrolled in public and private schools , an oversample of small children ( 25th percentile on height , weight , and head circumference ) and randomly selected control candidates were examined for physical growth , development , dysmorphology , cognition , and behavior .


The children 's mothers were interviewed for maternal risk .


Total dysmorphology scores differentiate significantly fetal alcohol syndrome ( FAS ) and partial FAS ( PFAS ) from one another and from unexposed controls .


Alcohol-related neurodevelopmental disorder ( ARND ) is not as clearly differentiated from controls .


Children who had FASD performed , on average , significantly worse on 7 cognitive and behavioral tests and measures .


The most predictive maternal risk variables in this community are late recognition of pregnancy , quantity of alcoholic drinks consumed 3 months before pregnancy , and quantity of drinking reported for the index child 's father .


From the final multidisciplinary case findings , 3 techniques were used to estimate prevalence .


FAS in this community likely ranges from 6 to 9 per 1000 children ( midpoint , 7.5 ) , PFAS from 11 to 17 per 1000 children ( midpoint , 14 ) , and the total rate of FASD is estimated at 24 to 48 per 1000 children , or 2.4 % to 4.8 % ( midpoint , 3.6 % ) .


Children who have FASD are more prevalent among first graders in this Midwestern city than predicted by previous , popular estimates .


Cancer-associated inflammation plays a driver role in pancreatic tumor development and progression .


Moreover , recent studies have implicated the inflammatory tumor microenvironment in modulating therapy response and inducing resistance .


The aim of this study is to investigate the prognostic and predictive value of the inflammatory biomarkers serum ferritin and C-reactive protein ( CRP ) in advanced pancreatic cancer patients .


We measured pretreatment serum ferritin and CRP levels in 159 patients with inoperable pancreatic cancer participating in a phase III trial .


Serum ferritin and CRP levels were examined for correlations with overall survival using Kaplan-Meier analysis .


When analyzed on a categorical basis , patients with higher ferritin ( > median ) or CRP ( > 25th percentile ) had shorter overall survival .


Moreover , the two biomarkers were not correlated suggesting independent mechanisms of production and release .


However , when patients were evaluated by their ferritin and CRP levels , only patients with elevation in both inflammatory biomarkers showed a significant decrease in overall survival .


Serum ferritin and CRP are independent prognostic factors for shorter survival in patients with inoperable pancreatic tumors .


Moreover , the evaluation of patients based on both biomarkers suggested that their prognostic value , although independent , reflected the broader state of cancer-associated inflammation .


Thus , serum ferritin and CRP should be further explored as clinical biomarkers .


To study efficacy and safety of baclofen for treatment of alcohol dependence .


32 patients with alcohol dependence had been randomized into one of two treatment groups ( 16 patients in each ) : patients of the 1st group were treated with baclofen ( 50 mg/day ) for 3 months while patients of the 2nd one received identically looking placebo .


All the study subjects were scheduled to come to the clinic on the weekly basis to control alcohol use and compliance with the study medications ( by riboflavin marker in urine ) and also - for psychiatric evaluations ( severity of craving for alcohol , anxiety and depression ) .


Alcohol use evaluated with the Time Line Follow Back technique and gamma-glutamiltranspeptidase activity in blood .


To assess anxiety Spielberger state-trait inventory and Hamilton scale were used .


Depression was assessed with Montgomery-Ashberg scale .


To evaluate carving for alcohol used Obsessive-Compulsive Drinking scale , Penn Alcohol Craving scale , and Visual Analog Scale of Craving .


Overall treatment effect assessed with the Clinical Global Impression scale .


The study design was double blind .


Baclofen did no differ significantly from placebo on either of primary or secondary outcome variables .


However , primary outcome variables of retention in treatment and drinking were slightly better in the baclofen group compared to placebo , and those differences were close to the level of statistical significance .


There were no differences between the groups in either rate of adverse events or liver enzymes activity which is an evidence of safety and good tolerability of baclofen in alcohol dependent patients .


Further studies of baclofen for alcohol dependence in the larger sample size are needed .


Pregabalin ( Lyrica ( ) ) is approved as an immediate-release ( IR ) formulation for administration twice ( BID ) or three times ( TID ) a day depending on indication .


Once daily ( QD ) dosing may be appropriate for ease of clinical use and patient convenience .


The objectives of this analysis were : ( 1 ) to evaluate the pharmacokinetics of pregabalin controlled-release ( CR ) administered with food relative to the pregabalin IR formulation administered fasted ; ( 2 ) to evaluate the pharmacokinetics of a two-tablet dose of pregabalin CR compared with the equivalent one-tablet dose of pregabalin CR ; and ( 3 ) to determine the safety and tolerability of multiple-dose administration of pregabalin CR and IR .


The pharmacokinetic properties of pregabalin CR were determined in four phase I , open-label , multiple-dose crossover studies ( 18-24 participants/study ) .


Pregabalin CR ( 82.5 , 165 , 330 or 660mg/day ) administered QD was compared with pregabalin IR ( 75 , 150 , 300 or 600mg/day , respectively ) administered either BID or TID .


Blood samples were collected up to 24h post-dose .


Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods .


Adverse events were monitored throughout all studies .


Eight-four healthy participants ( 19-55years of age ) received pregabalin .


For all pregabalin CR doses , total exposure was equivalent to the corresponding pregabalin IR dose .


Relative bioavailability of pregabalin CR was 93-97 % of pregabalin IR , and bioequivalence criteria with respect to the 24-h steady-state exposure ( area under the plasma concentration-time curve from 0 to 24h [ AUC24 ] ) were met .


Administration of a two-tablet dose of pregabalin CR was bioequivalent to one-tablet pregabalin CR .


The relative bioavailability of two-tablet pregabalin CR was 97-102 % of one-tablet pregabalin CR , and bioequivalence criteria with respect to AUC24 and peak plasma concentrations were met .


Pregabalin CR pharmacokinetic parameters were dose proportional following administration of 82.5-660mg / day pregabalin CR .


Pregabalin was well tolerated across studies , with no serious or severe adverse events .


Total daily exposure with multiple-dose pregabalin CR is equivalent to the corresponding pregabalin IR dose .


The radial artery ( RA ) is a useful conduit for coronary artery bypass grafting ( CABG ) but is susceptible to vasospasm during harvesting .


We evaluated the usefulness of fasudil , a Rho kinase inhibitor , in dilating the RA graft and increasing graft free flow ( GFF ) compared with the conventional graft-dilating agents papaverine and verapamil-nitroglycerin ( VG ) .


Between June 2012 and January 2013 , 45 patients with ischemic heart disease who underwent isolated CABG using the RA were enrolled and randomly assigned to fasudil ( n = 15 ) , papaverine ( n = 15 ) , or VG ( n = 15 ) .


Fasudil ( 2.67 mmol/L ) , papaverine ( 1.0 mmol/L ) mixed with heparinized blood , or VG ( 30 mol/L each of verapamil and nitroglycerin ) was injected intraluminally into the RA graft after harvesting .


Main outcome measures were RA GFF , hemodynamic changes , and histopathologic examination of the RA .


In the fasudil group , GFF increased significantly ( p < 0.001 ) from 36.8 20.4 at baseline to 148.0 88.3 mL/min after injection .


GFF increased significantly ( p < 0.001 ) from 36.0 19.0 to 72.3 36.7 mL/min in the papaverine group and increased significantly ( p < 0.001 ) from 39.5 23.3 to 64.3 29.9 mL/min in the VG group .


The GFF was significantly higher ( p = 0.001 ) in fasudil-treated RA than in papaverine - or VG-treated RA .


Histopathologically , RA graft diameter was markedly increased after fasudil injection , and the structure of the multiple elastic lamellae was intact .


Blood pressure did not change significantly after drug injection in all groups .


Fasudil exhibited a very potent vasodilatory effect on the RA compared with conventional papaverine or VG , resulting in increased GFF .


This agent is useful for dilating RA grafts in CABG .


The objective of this pilot trial was to evaluate the safety and efficacy of AKL1 , a patented botanical formulation containing extracts of Picrorhiza kurroa , Ginkgo biloba , and Zingiber officinale , as add-on therapy for patients with chronic obstructive pulmonary disease ( COPD ) and chronic cough .


This randomized , double-blind , placebo-controlled trial enrolled male and female patients > 18 years old with COPD and Leicester Cough Questionnaire ( LCQ ) score of < 18 .


The 10-week study period comprised a 2-week single-blind placebo run-in period followed by add-on treatment with AKL1 or placebo twice daily for 8 weeks .


The primary study endpoint was the change from week 0 to week 8 in cough-related health status , as assessed by the LCQ .


Of 33 patients enrolled , 20 were randomized to AKL1 and 13 to placebo .


Patients included 19 ( 58 % ) men and 14 ( 42 % ) women of mean ( standard deviation [ SD ] ) age of 67 ( 9.4 ) years ; 15 ( 45 % ) patients were smokers and 16 ( 49 % ) were ex-smokers .


The mean ( SD ) change from baseline in LCQ score at 8 weeks was 2.3 ( 4.9 ) in the AKL1 group and 0.6 ( 3.7 ) in the placebo group , with mean difference in change of 1.8 ( 95 % confidence interval : -1.5 to 5.1 ; P = 0.28 ) .


The St George 's Respiratory Questionnaire score improved substantially in the AKL1 treatment group by a mean ( SD ) of -7.7 ( 11.7 ) versus worsening in the placebo group ( +1.5 [ 9.3 ] ) , with mean difference in change of -9.2 ( 95 % confidence interval : -19.0 to 0.6 ; P = 0.064 ) .


There were no significant differences between treatment groups in change from baseline to week 8 in other patient-reported measures , lung function , or the 6-minute walk distance .


Further study is needed with a larger patient population and over a longer duration to better assess the effects of add-on therapy with AKL1 in COPD .


Smokers with depressive symptoms have more difficulty quitting smoking than the general population of smokers .


The present study examines a web-based treatment using acceptance and commitment therapy ( ACT ) for smokers with depressive symptoms .


The study aimed to determine participant receptivity to the intervention and its effects on smoking cessation , acceptance of internal cues , and depressive symptoms .


Smokers who had positive screening results for depressive symptoms at baseline ( n = 94 ) were selected from a randomized controlled trial ( N = 222 ) comparing web-based ACT for smoking cessation ( WebQuit.org ) with Smokefree.gov .


Forty-five participants ( 48 % ) completed the three-month follow-up .


Compared to Smokefree.gov , WebQuit participants spent significantly more time on site ( p = .001 ) and had higher acceptance of physical cravings ( p = .033 ) .


While not significant , WebQuit participants were more engaged and satisfied with their program and were more accepting of internal cues overall .


There was preliminary evidence that WebQuit participants had higher quit rates ( 20 % versus 12 % ) and lower depressive symptoms at follow-up ( 45 % versus 56 % ) than those in Smokefree.gov .


This was the first study of web-based ACT for smoking cessation among smokers with depressive symptoms , with promising evidence of receptivity , efficacy , impact on a theory-based change process , and possible secondary effects on depression .


A fully powered trial of the ACT WebQuit.org intervention specifically for depressed smokers is needed .


This was part of a clinical trial registered as NCT # 01166334 at www.clinicaltrials.gov .


Students in German medical schools frequently complain that the subject ` clinical examination ' is not taught in a satisfying manner due to time constraints and lack of personnel resources .


While the effectiveness and efficiency of practice-oriented teaching in small groups using near-peer teaching has been shown , it is rarely used in German medical schools .


We investigated whether adding a new near-peer teaching course developed with student input plus patient examination under supervision in small groups improves basic clinical examination skills in third year medical students compared to a traditional clinical examination course alone .


Third year medical students registered for the mandatory curricular clinical examination course at the medical faculty of the Technische Universitt Mnchen were invited to participate in a randomised trial with blinded outcome assessment .


Students were randomised to the control group participating in the established curricular physical examination course or to the intervention group , which received additional near-peer teaching for the same content .


The learning success was verified by a voluntary objective structured clinical examination ( OSCE ) .


A total of 84 students were randomised and 53 ( 63 % ) participated in the final OSCE .


Students in the control group scored a median of 57 % ( 25th percentile 47 % , 75th percentile 61 % ) of the maximum possible total points of the OSCE compared to 77 % ( 73 % , 80 % ; p < 0.001 ) for students in the intervention group .


Only two students in the intervention group received a lower score than the best student in the control group .


Adding a near-peer teaching course to the routine course significantly improved the clinical examination skills of medical students in an efficient manner in the context of a resource-constrained setting .


A prospective randomized study .


To compare occupational radiation exposure to the surgeon , as well as the patient , during posterior lumbar spine instrumentation in 10 navigated cases ( navigated ) versus 11 cases using the freehand technique ( non-navigated ) .


The use of navigation increases the accuracy of posterior lumbar instrumentation.A further speculated benefit of navigation is the reduction of radiation exposure of the surgeon .


However , this has so far not been evaluated in such comparative manner .


Radiation exposure to the surgeon was measured by digital dosimeters placed at the level of the eye , chest , and dominant forearm .


Radiation exposure was measured from the time of positioning of the patient to the end of the procedure both for navigated ( intraoperative 3-dimensional [ 3D ] fluoroscopy-based ) and non-navigated ( 2-dimensional fluoroscopy-guided ) freehand posterior lumbar spine instrumentations .


A 3D fluoroscopic scan was routinely performed at the end of the procedure for all patients .


Patients were distributed evenly in the 2 groups in terms of sex , age , body mass index , and the number of operated levels .


The accumulated radiation dose for the surgeon was significantly higher in the non-navigated group ; up to 9.96 times .


The radiation dose for the patient was higher with the freehand technique , 1884.8 cGycm ( non-navigated ) versus 887 cGycm ( navigated ) , without reaching a statistically significant level .


Radiation exposure to the surgeon during pedicle screw placement with the freehand technique is up to 9.96 times greater than with the use of navigation .


In the latter group , the only radiation exposure comes from the preoperative-level control and positioning of the 3D C-arm before 3D fluoroscopic acquisition .


Furthermore , neuronavigation also reduces the cumulative dose for the patient .


2 .


Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation .


We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2 ' - deoxycytodine ( decitabine ) can reverse resistance to carboplatin in women with relapsed ovarian cancer .


Patients progressing 6-12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin ( AUC 6 ) on day 8 , every 28 days or carboplatin alone .


The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma .


After a pre-defined interim analysis , the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated with the combination .


Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin and carboplatin/decitabine , respectively .


Grade 3/4 neutropenia was more common with the combination ( 60 % vs 15.4 % ) as was G2/3 carboplatin hypersensitivity ( 47 % vs 21 % ) .


With this schedule , the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partially platinum-sensitive ovarian cancer and is difficult to deliver .


Patient-selection strategies , different schedules and other demethylating agents should be considered in future combination studies .


To evaluate the impact of Playworks on students ' physical activity during recess .


Twenty-seven elementary schools from six U.S. cities were grouped into blocks and randomly assigned to implement Playworks ( treatment ) or not ( control ) during an entire school year ( either 2010-2011 or 2011-2012 ) .


Study data were collected at the end of the school year only .


Fourth - and 5th-grade students ( n = 2278 ) reported on their physical activity during recess , and a subset ( n = 1537 ) wore accelerometers during recess .


Teachers ( n = 111 ) also reported on their students ' physical activity during recess .


A significantly higher percentage of teachers in treatment schools reported that their students engaged in an intense physical activity during recess ( p = 0.01 ) .


Marginally significant differences between treatment and control groups were found for the mean number of accelerometer intensity counts recorded per minute during recess ( p = 0.10 ) and the mean percentage of time spent in vigorous physical activity during recess ( p = 0.07 ) .


No significant differences were found for student reports about their physical activity during recess ( p = 0.92 ) .


Teachers in Playworks schools reported that students were more active during recess , but accelerometer and student survey measures showed either no impacts or marginally significant impacts .


Adults with intellectual disability ( ID ) are physically very inactive .


This study will compare two approaches to increasing physical activity in adults with ID : a lifestyle physical activity ( light-moderate intensity ) approach and a structured exercise ( moderate-vigorous intensity ) approach .


The trial will compare the short-term ( 3-month ) and long-term ( 9-month ) outcomes and sustainability of each approach with a usual-care control group .


A three-arm randomised controlled trial ( RCT ) will be conducted .


Ninety adults with ID aged 18-55 will be randomly assigned to one of three groups : 1 ) a lifestyle physical activity group ( n = 30 ) , 2 ) a structured exercise group ( n = 30 ) , or 3 ) a usual care control group ( n = 30 ) .


Participants in both groups will receive a 12-week intervention delivered by exercise specialists in the community with disability service staff , after which intervention will continue for 6months , delivered by disability service staff only .


Primary outcomes are aerobic fitness , 12-hour energy expenditure , and proxy-reported everyday physical activity .


Secondary outcomes include objectively assessed physical activity and sedentary behaviour , intervention compliance , functional walking capacity , participation in domestic activities , muscle strength , body composition , psychosocial outcomes , quality of life and health care costs .


The trial results will determine the effectiveness and sustainability of two approaches to increasing physical activity and exercise among adults with ID .


ISRCTN77889248 ( 18 April 2012 ) .


Poor nutritional quality of complementary foods often limits growth .


Animal source foods , such as milk or meat , are often unaffordable .


Local affordable alternatives are needed .


We evaluate the efficacy of 2 newly developed , rice-based complementary food products : WinFood ( WF ) with small fish and edible spiders and WinFood-Lite ( WF-L ) fortified with small fish , against 2 existing fortified corn-soy blend products , CSB + ( purely plant based ) and CSB + + ( 8 % dried skimmed milk ) .


In total , 419 infants aged 6 mo were enrolled in this randomized , single-blinded study for 9 mo , designed primarily to assess increments in fat-free mass by a deuterium dilution technique and change in plasma ferritin and soluble transferrin receptor .


Secondary endpoints were changes in anthropometric variables , including knee-heel length .


Data were analyzed by the intention-to-treat approach .


There was no difference in fat-free mass increment in WF or WF-L compared with CSB + [ WF : +0.04 kg ( 95 % CI : -0.20 , 0.28 kg ) ; WF-L : +0.14 kg ( 95 % CI : -0.10 , 0.38 kg ) ] or CSB + + [ WF : -0.03 kg ( 95 % CI : -0.27 , 0.21 kg ) ; WF-L : +0.07 kg ( 95 % CI : -0.18 , 0.31 kg ) ] and no effect on iron status .


The 1.7-mm ( 95 % CI : -0.1 , 3.5 mm ) greater increase in knee-heel length in WF-L than in CSB + was not significant .


No difference was found between the locally produced products ( WF and WF-L ) and the CSBs .


Micronutrient fortification may be necessary , and small fish may be an affordable alternative to milk to improve complementary foods .


The dietary role of edible spiders needs to be further explored .


This trial was registered at controlled-trials .


com as ISRCTN19918531 .


To compare the effectiveness and safety of two glycemic control regimens in stable critical care patients receiving parenteral nutrition ( PN ) .


Prospective , randomized open-label clinical trial .


Eligible postoperative critical care patients in the ICU began PN on the first to the seventh day of ICU admission .


The PN admixture included regular insulin , in doses sufficient to maintain 3 or more goal blood glucose ( BG ) levels between 110 and 180mg/dl .


After 3 to 5days of PN containing regular insulin , patients were randomized to 3 more days of regular insulin at the same dose or 80 % of their total daily regular insulin dose provided in PN solution as glargine insulin .


Capillary BG monitoring was performed every 6hours .


Twenty one patients were randomized to each treatment group .


Median APACHE II scores were not significantly different between the two groups within the first 24-hour of ICU admission .


There were no significant differences between the two groups at day 3 for mean daily dextrose ( 306.946.2 vs. 305.252.2 g ; p = 0.913 ) or insulin ( 18.38.8 vs. 19.510.0 units ; p = 0.696 ) doses .


The percentage of BG values in the goal ( 110-180mg / dl ) , hyperglycemic ( > 180mg/dl ) , and hypoglycemic ( < 70mg/dl ) BG levels were similar between the two groups ( 69.0 % vs. 66.7 % , p = 0.567 ; 11.9 % vs. 11.1 % , p = 0.780 ; 0 % vs. 1.6 % , p = 0.124 , respectively ) .


Mean daily BG levels were not significantly different between the two groups on each of the 3 study days ( day 1 : 14020 vs. 13125mg/dl , p = 0.194 ; day 2 : 13620 vs. 14018mg/dl , p = 0.498 ; day 3 : 14215 vs. 14019mg/dl ; p = 0.741 ) .


These data suggest that , compared with regular insulin added to PN , glargine insulin results in similar glycemic control and rates of hyperglycemia and hypoglycemia in stable critical care patients .


Everolimus synergistically enhances taxane-induced cytotoxicity in breast cancer cells in vitro and in vivo in addition to demonstrating a direct antiproliferative activity .


We aim to determine pharmacodynamics changes and response of adding everolimus to standard neoadjuvant chemotherapy in triple-negative breast cancer ( TNBC ) .


Phase II study in patients with primary TNBC randomized to T-FEC ( paclitaxel 80 mg/m ( 2 ) i.v. weekly for 12 weeks , followed by 5-fluorouracil 500 mg/m ( 2 ) , epirubicin 100 mg/m ( 2 ) , and cyclophosphamide 500 mg/m ( 2 ) every 3 weeks for four cycles ) versus TR-FEC ( paclitaxel 80 mg/m ( 2 ) i.v. and everolimus 30 mg PO weekly for 12 weeks , followed by FEC ) .


Tumor samples were collected to assess molecular changes in the PI3K/AKT/mTOR pathway , at baseline , 48 h , 12 weeks , and at surgery by reverse phase protein arrays ( RPPA ) .


Clinical end points included 12-week clinical response rate ( 12-week RR ) , pathological complete response ( pCR ) , and toxicity .


Sixty-two patients were registered , and 50 were randomized , 27 received T-FEC , and 23 received TR-FEC .


Median age was 48 ( range 31-75 ) .


There was downregulation of the mTOR pathway at 48 h in the TR-FEC arm .


Twelve-week RR by ultrasound were 29.6 % versus 47.8 % , ( P = 0.075 ) , and pCR were 25.9 % versus 30.4 % ( P = 0.76 ) for T-FEC and TR-FEC , respectively .


mTOR downregulation at 48 h did not correlate with 12-week RR in the TR-FEC group ( P = 0.58 ) .


Main NCI grade 3/4 toxicities included anemia , neutropenia , rash/desquamation , and vomiting in both arms .


There was one case of grade 3 pneumonitis in the TR-FEC arm .


No grade 3/4 stomatitis occurred .


The addition of everolimus to paclitaxel was well tolerated .


Everolimus downregulated mTOR signaling but downregulation of mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group .


NCT00499603 .


Pain after total knee arthroplasty ( TKA ) is usually severe .


Recently , the usefulness of local periarticular injection analgesia ( PAI ) and peripheral nerve block ( PNB ) has been reported .


We report a prospective blinded randomized trial of PAI versus PNB in patients undergoing primary TKA , in accordance with the CONSORT statement 2010 .


A total of 210 patients undergoing TKA under spinal anesthesia were randomized to receive PNB group or PAI group .


In the PNB group , femoral nerve block and sciatic nerve block were performed .


In the PAI group , a special mixture containing ropivacaine , saline , epinephrine , morphine hydrochloride , and dexamethasone was injected into the periarticular soft tissue .


Pain intensity at rest was assessed using a numerical rating scale ( NRS : 0-10 ) after surgery .


Use of a diclofenac sodium suppository ( 25mg ) was allowed for all patients at any time after surgery , and the diclofenac sodium suppository usage was assessed .


The NRS for patient satisfaction at 48 hours after surgery was examined .


The average NRS for pain at rest up to 48 hours after surgery was low in both groups .


Within 48 hours after surgery , the diclofenac sodium suppository usage was similar in both groups .


There were no significant differences in the NRS for patient satisfaction in both groups .


The analgesic effects of PAI and PNB are similar .


PAI may be considered superior to PNB because it is easier to perform .


Therapeutic Level 1 .


Most patients with heart failure are diagnosed and managed in primary care , however , underdiagnosis and undertreatment are common .


We assessed whether implementation of a diagnostic-therapeutic strategy improves functionality , health-related quality of life , and uptake of heart failure medication in primary care .


A selective screening study followed by a single-blind cluster randomized trial in primary care .


The study population consists of patients aged 65 years or over who presented themselves to the general practitioner in the previous 12 months with shortness of breath on exertion .


Patients already known with established heart failure , confirmed by echocardiography , are excluded .


Diagnostic investigations include history taking , physical examination , electrocardiography , and serum N-terminal pro B-type natriuretic peptide levels .


Only participants with an abnormal electrocardiogram or an N-terminal pro B-type natriuretic peptide level exceeding the exclusionary cutpoint for non-acute onset heart failure ( > 15 pmol/L ( 125 pg/ml ) ) will undergo open-access echocardiography .


The diagnosis of heart failure ( with reduced or preserved ejection fraction ) is established by an expert panel consisting of two cardiologists and a general practitioner , according to the criteria of the European Society of Cardiology guidelines.Patients with newly established heart failure are allocated to either the ` care as usual ' group or the ` intervention ' group .


Randomization is at the level of the general practitioner .


In the intervention group general practitioners receive a single half-day training in heart failure management and the use of a structured up-titration scheme .


All participants fill out quality of life questionnaires at baseline and after six months of follow-up .


A six-minute walking test will be performed in patients with heart failure .


Information on medication and hospitalization rates is extracted from the electronic medical files of the general practitioners .


This study will provide information on the prevalence of unrecognized heart failure in elderly with shortness of breath on exertion , and the randomized comparison will reveal whether management based on a half-day training of general practitioners in the practical application of an up-titration scheme results in improvements in functionality , health-related quality of life , and uptake of heart failure medication in heart failure patients compared to care as usual .


ClinicalTrials.gov NCT01202006 .


To determine the effects of constant exposure to cattle persistently infected ( PI ) with bovine viral diarrhea virus ( BVDV ) on health and performance of feedlot cattle .


3 controlled trials .


Crossbred feedlot cattle ( trial 1 , n = 184 ; trial 2 , 138 ; trial 3 , 138 ) .


Weaned calves were or were not vaccinated against BVDV at feedlot arrival ( trial 1 ) or 2 ( trial 2 ) or 3 ( trial 3 ) weeks before feedlot arrival .


During trial 1 , half of the calves were commingled with PI cattle throughout the feeding period .


During trial 2 , 63 calves were exposed to PI cattle before weaning and all calves were exposed to PI cattle throughout the feeding period .


During trial 3 , all study calves were exposed to PI cattle throughout the feeding period .


Morbidity and mortality rates and average daily gain ( ADG ) data were analyzed .


During trial 1 , calves maintained with PI cattle had a higher morbidity rate regardless of BVDV vaccination than did calves not exposed to PI cattle ; however , for calves maintained with PI cattle , the morbidity rate for those vaccinated against BVDV was less than that for those not vaccinated against BVDV .


During trial 2 , calves exposed to PI cattle before weaning or vaccinated against BVDV had lower morbidity and mortality rates and increased ADG , compared with those for calves not exposed to PI cattle before weaning or vaccinated against BVDV .


During trial 3 , health and performance did not vary between calves that were and were not vaccinated against BVDV .


Exposure of cattle to BVDV naturally or through vaccination before or at feedlot arrival mitigated the negative effects of constant exposure to PI cattle .


The efficacy of a slow-release insecticidal and repellent collar containing 10 % imidacloprid and 4.5 % flumethrin ( Seresto , Bayer Animal Health ) in preventing Leishmania infantum infection was evaluated in a large population of dogs living in a hyper-endemic area of Sicily ( Italy ) .


A total of 219 dogs , negative for L. infantum were enrolled in a multicentre , controlled study .


Dogs were divided into two homogeneous groups , defined as G1 ( n = 102 ) and G2 ( n = 117 ) .


Before the start of the sand fly season , dogs in G1 were treated with the collar while animals in G2 were left untreated , serving as negative controls .


Dogs were serially sampled on day D90 , D180 , D210 and D300 in order to assess Leishmania infection by IFAT , PCR on skin ( D210-D300 ) and bone marrow ( D300 ) and cytology on bone marrow aspirate ( D300 ) .


Three dogs ( 2.9 % ) in G1 and 41 ( 40.2 % ) in G2 became positive for L. infantum in at least one of the diagnostic tests employed in the study .


The number of seropositive dogs in G2 increased in the course of the study from 15 ( D90 ) to 41 ( D300 ) , with some of them also positive in other diagnostic tests .


Eight ( 19.6 % ) of the seropositive dogs in G2 showed an increase in antibody titers ranging from 1:160 to 1:1,280 .


At the last follow-up , some of dogs in G2 displayed overt clinical signs suggestive of leishmaniosis .


The mean incidence density rate at the final follow-up was 4.0 % for G1 and 60.7 % for G2 , leading to a mean efficacy of the collar in protecting dogs at both sites of 93.4 % .


The slow-release collar tested in this study was shown to be safe and highly effective in preventing L. infantum infection in a large population of dogs .


Protection conferred by a single collar ( up to eight months ) spanned an entire sand fly season in a hyper-endemic area of southern Italy .


The regular use of collars , at least during the sand fly season , may represent a reliable and sustainable strategy for the prevention of leishmaniosis in dogs living in or travelling to an endemic area .


Meaningful delays occurred in the Interventional Management of Stroke ( IMS ) III trial .


Analysis of the work flow will identify factors contributing to the in-hospital delays .


In the endovascular arm of the IMS III trial , the following time intervals were calculated : stroke onset to emergency department arrival ; emergency department to computed tomography ( CT ) ; CT to intravenous tissue plasminogen activator start ; intravenous tissue plasminogen activator start to randomization ; randomization to groin puncture ; groin puncture to thrombus identification ; thrombus identification to start of endovascular therapy ; and start of endovascular therapy to reperfusion .


The effects of enrollment time , CT angiography use , interhospital transfers , and intubation on work flow were evaluated .


Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture ( median 84 minutes ) and start of endovascular therapy to reperfusion ( median 85 minutes ) .


The CT to groin puncture time was significantly shorter during working hours than after .


Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period .


Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times .


Transfer of patients resulted in a longer onset to reperfusion time compared with those treated in the same center .


Age , sex , National Institutes of Health Stroke Scale score , and intubation did not affect delays .


Important delays were identified before reperfusion in the IMS III trial .


Delays decreased as the trial progressed .


Use of CT angiography and endovascular treatment in the same center were associated with time savings .


These data may help in optimizing work flow in current and future endovascular trials .


http://www.clinicaltrials.gov .


Unique identifier : NCT00359424 .


Dosages of vitamin D necessary to prevent or treat vitamin D deficiency in children remain to be clarified .


To determine the effects of vitamin D3 1000 IU/d on serum 25-hydroxyvitamin D [ 25 ( OH ) D ] , PTH , and markers of bone turnover ( osteocalcin and collagen type 1 cross-linked C-telopeptide ) in black children and white children , and to explore whether there is a threshold level of 25 ( OH ) D associated with maximal suppression of serum PTH concentration .


Healthy 8 - to 14-year-old Pittsburgh-area black ( n = 84 ) and white ( n = 73 ) children not receiving vitamin supplements , enrolled from October through March from 2008 through 2011 , were randomized to vitamin D3 1000 IU or placebo daily for 6 months .


The mean baseline concentration of 25 ( OH ) D was < 20 ng/mL in both the vitamin D-supplemented group and the placebo group ( 19.8 7.6 and 18.8 6.9 ng/mL , respectively ) .


The mean concentration was higher in the supplemented group than in the placebo group at 2 months ( 26.4 8.1 vs 18.9 8.1 ng/mL ; P < .0001 ) and also at 6 months ( 26.7 7.6 vs 22.4 7.3 ; P = .003 ) , after adjusting for baseline 25 ( OH ) D , race , gender , pubertal status , dietary vitamin D intake , body mass index , and sunlight exposure .


Increases were only significant in black children , when examined by race .


The association between 25 ( OH ) D and PTH concentrations was inverse and linear , without evidence of a plateau .


Overall , vitamin D supplementation had no effect on PTH and bone turnover .


Vitamin D3 supplementation with 1000 IU/d in children with mean baseline 25 ( OH ) D concentration < 20 ng/mL effectively raised their mean 25 ( OH ) D concentration to 20 ng/mL but failed to reach 30 ng/mL .


Vitamin D supplementation had no effect on PTH concentrations .


Vitamin D may be a regulator of skeletal muscle function , although human trials investigating this hypothesis are limited to predominantly elderly populations .


We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function .


Participants ( n = 29 ) received an oral dose of 10,000 IU day ( -1 ) vitamin D3 ( VITD ) or a visually identical placebo ( PLB ) for 3 months .


Serum 25 [ OH ] D and intact parathyroid hormone ( iPTH ) were measured at baseline and at week 4 , 8 and 12 .


Muscle function was assessed in n = 22 participants by isokinetic dynamometry and percutaneous isometric electromyostimulation at baseline and at week 6 and 12 .


Baseline mean total serum 25 [ OH ] D was 40 17 and 41 20 nmol L ( -1 ) for PLB and VITD , respectively .


VITD showed a significant improvement in total 25 [ OH ] D at week 4 ( 150 31 nmol L ( -1 ) ) that remained elevated throughout the trial ( P < 0.005 ) .


Contrastingly , PLB showed a significant decrease in 25 [ OH ] D at week 12 ( 25 15 nmol L ( -1 ) ) compared with baseline .


Despite marked increases in total serum 25 [ OH ] D in VITD and a decrease in PLB , there were no significant changes in any of the muscle function outcome measures at week 6 or 12 for either group ( P > 0.05 ) .


Elevating total serum 25 [ OH ] D to concentrations > 120 nmol L ( -1 ) has no effect on skeletal muscle function .


We postulate that skeletal muscle function is only perturbed in conditions of severe deficiency ( < 12.5 nmol L ( -1 ) ) .


The addition of bevacizumab to paclitaxel or capecitabine has demonstrated improved progression-free survival ( PFS ) and objective response rate ( ORR ) as compared with chemotherapy alone in patients with HER2-negative locally recurrent or metastatic breast cancer ( LR/MBC ) .


We evaluated the efficacy and safety of first-line therapy of paclitaxel and bevacizumab with or without capecitabine in patients with HER2-negative LR/MBC .


In this multicentre , open-label , randomised phase II trial , women with HER2-negative LR/MBC were randomly assigned in a 1:1 ratio to paclitaxel ( 90 mg/m2 intravenously [ IV ] on days 1 , 8 , and 15 ) and bevacizumab ( 10 mg/kg IV on days 1 and 15 ) every 4 weeks for six cycles , followed by bevacizumab ( 15 mg/kg IV on day 1 ) every 3 weeks ( AT ) or to paclitaxel ( 90 mg/m2 IV on days 1 and 8 ) , bevacizumab ( 15 mg/kg IV on day 1 ) and capecitabine ( 825 mg/m2 orally twice daily on days 114 ) every 3 weeks for eight cycles , followed by bevacizumab and capecitabine at the same doses every 3 weeks ( ATX ) .


The primary end-point was investigator-assessed PFS .


Secondary end-points included ORR , duration of response , overall survival ( OS ) and safety .


Exploratory analyses were conducted to evaluate the impact of capecitabine on OS and to validate a novel prognostic model .


This trial is registered with EudraCT , number 2006-006058-83 .


Median PFS was significantly longer in ATX as compared with AT ( 11.2 months versus 8.4 months ; stratified hazard ratio ( HR ) , 0.52 ; 95 % confidence interval ( CI ) , 0.410.67 ; p < 0.0001 ) .


The ORR in ATX patients with measurable disease ( n = 268 ) was higher than that in AT ( 69 % versus 51 % ; p = 0.01 ) .


The median duration of response was 6.8 versus 5.4 months for , respectively , ATX and AT ( p < 0.0001 ) .


Median OS was 24.2 months for ATX and 23.1 months for AT ( p = 0.53 ) .


The increased rate of grade 34 adverse events related to the addition of capecitabine , being hand-foot syndrome ( 34 % versus 0 % for AT ) and neutropenia ( 20 % versus 12 % for AT ) , generally did not preclude continuation of treatment .


Exploratory analyses indicated that ( 1 ) patients receiving capecitabine at some line for treatment have significantly improved OS and ( 2 ) a prognostic model can classify patients into three risk groups associated with OS .


In patients with HER2-negative LR/MBC , addition of capecitabine to paclitaxel and bevacizumab significantly improved PFS , ORR and response duration .


This combination was reasonably well tolerated and may be considered of use as first-line treatment in rapidly progressive disease .


F. Hoffmann-La Roche Ltd , the Netherlands .


We investigated the determinants and clinical correlations of MRI-detected brain volume loss ( BVL ) among patients with relapsing-remitting multiple sclerosis from the phase 3 trials of fingolimod : FREEDOMS , FREEDOMS II , and TRANSFORMS .


Post hoc analyses were conducted in the intent-to-treat populations from each trial and in a combined dataset of 3,635 patients from the trials and their extensions .


The relationship between brain volume changes and demographic , clinical , and MRI parameters was studied in pairwise correlations ( Pearson ) and in multiple regression models .


The relative frequency of confirmed disability progression was evaluated in the combined dataset by strata of concurrent BVL at up to 4 years .


Increasing age , disease duration , T2 lesion volume , T1-hypointense lesion volume , and disability were associated with reduced brain volume ( p < 0.001 , all ) .


The strongest individual baseline predictors of on-study BVL were T2 lesion volume , gadolinium-enhancing lesion count , and T1-hypointense lesion volume ( p < 0.01 , all ) .


During each study , BVL correlated most strongly with cumulative gadolinium-enhancing lesion count , new/enlarged T2 lesion count ( p < 0.001 , both ) , and number of confirmed on-study relapses ( p < 0.01 ) .


Over 4 years in the combined dataset ( mean exposure to study drug , 2.4 years ) , confirmed disability progression was most frequent in patients with greatest BVL .


Rate of BVL in patients during the fingolimod trials correlated with disease severity at baseline and new disease activity on study , and was associated with worsening disability .


To study the changes in cortisol levels during and after cardiac surgery after an inductive dose of either etomidate or thiopentone and their consequences .


A prospective , randomized , double-blinded study was conducted in 26 patients undergoing elective cardiac surgery .


They received either etomidate or thiopentone for induction .


Serum cortisol levels were measured preoperatively , and then at 2 - , 4 - , 8 - , and 24-hour All of the patients received standard anesthesia and surgery .


The data also included patients perioperative management and outcome .


There is no difference in patients ' characteristics .


The baseline plasma morning cortisols in the two groups were comparable ( 11.7 7.5 mcg/dL in etomidate group vs. 12.0 8.2 mcg/dL in thiopentone group ) .


In both groups , during surgery , the cortisol levels rose to higher levels and reached peak levels at four to eight hours and related to surgical stress .


At all times , the etomidate group had lower cortisol levels but only at 8-hour the etomidate group had significantly lower cortisol level ( 39.9 14.2 vs. 65.9 20.0 mcg/dL ) .


At 24 hours , in both groups , cortisol levels were lower than at 8-hour but did not return to normal baseline levels .


There were no differences in the dose of inotropic use and ICU stay .


However surprisingly the etomidate group had shorter hospital stay .


A single dose of etomidate usedfor induction in elective cardiac patients can partially and reversibly inhibit of the cortisol synthesis for , at least , 24 hours , but its association with any hemodynamic consequences can not be concluded .


ClinicalTrials.gov as NCT01495949 .


To observe improved effects of Jingjin acupuncture on fine activity of hemiplegic hand in recovery period of stroke .


Fifty cases were randomly divided into an observation group and a control group , 25 cases in each one .


Regular western medicine treatment , rehabilitation training and regular acupuncture ( in which Shuigou ( GV 26 ) , Baihui ( GV 20 ) , Neiguan ( PC 6 ) , etc. were selected ) were applied in both groups .


Additionally , muscles in palm side of affected hand , dorsal metacarpophalangeal joints and proximal interphalangeal joints were treated with acupuncture in the observation group , once every other day and electroacupuncture was applied when arrival of qi was acquired .


Baxie ( EX-UE 9 ) in the affected hand were needled in the control group , and electroacupuncture was added when arrival of qi was acquired .


Ten days of treatment was considered a treatment course , and after two courses Lindmark score , Brunnstrom movement function grade , joint range of hand and Barthel index ( BI ) were observed in two groups .


Compared before the treatment , the Lindmark score in two groups were both improved after the treatment ( both P < 0.01 ) .


Compared with the control group , the motor coordination ability , sensory function and total score of Lindmark in observation group were obviously improved ( differences before and after treatment : 8.24 + / - 3.07 vs 6.84 + / - 2.43 , 3.52 + / - 2.33 vs 2.16 + / - 2.12 , 11.76 + / - 3.55 vs 9.00 + / - 3.62 , all P < 0.05 ) .


The Brunnstrom movement function grade was significantly improved in both groups after treatment ( both P < 0.01 ) , which was more obvious in the observation group ( P < 0.05 ) .


The joint range of hemiplegic hand was improved in both groups after treatment ( both P < 0.01 ) , which was more obvious in the observation group [ differences before and after treatment : ( 25.35 + / - 10.91 ) degrees vs ( 18.65 + / - 7.86 ) degrees , p < 0.05 ] .


The score of BI was also significantly improved after treatment in two groups ( both P < 0.01 ) .


The Jingjin acupuncture could effectively improve fine activity of hemiplegic hand in recovery period of stroke prove daily life ability .


This study aimed to explore the possible mechanism of spironolactone in reduction of atrial fibrosis in elderly patients with atrial fibrillation .


67 patients with atrial fibrillation and 30 matching patients with sinus rhythm were included into this study , in which the former patients were randomly divided into the conventional treatment group ( 33 cases ) and spironolactone ( 20 mg/d ) treatment group ( 34 cases ) .


They underwent follow-ups for 6 months .


The levels of serum aldosterone , PICP ( propeptide of type I procollagen ) and CITP ( carboxy-terminal cross-linking telopeptide of type I collagen ) were determined before and after treatment .


The concentrations of serum PICP , CITP and aldosterone and left atrial size in the atrial fibrillation group were all higher than the control group ( t values were 7.982 , 5.950 , 9.309 , 9.050 , respectively , p < 0.01 ) , with a significant statistical difference .


The concentrations of serum PICP and aldosterone were both positively corelated to the left atrial size in the atrial fibrillation group ( r values were 0.302 and 0.369 , respectively ) .


The levels of serum aldosterone and PICP after treatment were both decreased compared to those before treatment in the spironolactone treatment group and conventional treatment group , especially in the spironolactone treatment group .


There were statistical differences in the levels of serum aldosterone and PICP after treatment between the two groups ( t values were 2.872 and 3.054 , respectively , p < 0.01 ) .


Spironolactone could reduce the levels of serum aldosterone and PICP in patients with atrial fibrillation , so as to reduce the atrial fibrosis and delay the occurrence and development of atrial fibrillation .


The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence .


Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins .


This study evaluated the adjunctive use of the MarginProbe device ( Dune Medical Devices Ltd , Caesarea , Israel ) in providing real-time intraoperative assessment of lumpectomy margins .


This multicenter randomized trial enrolled patients with nonpalpable breast malignancies .


The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment .


After specimen removal and inspection , patients were randomized to device or control arms .


In the device arm , MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins .


Intraoperative imaging was used in both arms ; no intraoperative pathology assessment was permitted .


In total , 596 patients were enrolled .


False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms , respectively .


All positive margins on positive main specimens were resected in 62 % ( 101 of 163 ) of cases in the device arm , versus 22 % ( 33 of 147 ) in the control arm ( p < 0.001 ) .


A total of 19.8 % ( 59 of 298 ) of patients in the device arm underwent a reexcision procedure compared with 25.8 % ( 77 of 298 ) in the control arm ( 6 % absolute , 23 % relative reduction ) .


The difference in tissue volume removed was not significant .


Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons ' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment , reducing the number of patients requiring reexcision .


MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system .


To determine the prevalence of impaired olfaction in individuals presenting for cardiac surgery and the independent association between impaired olfaction and postoperative delirium and cognitive decline .


Nested prospective cohort study .


Academic hospital .


Individuals undergoing coronary artery bypass , valve surgery , or both ( n = 165 ) .


Olfaction was measured using the Brief Smell Identification Test , with impaired olfaction defined as an olfactory score below the fifth percentile of normative data .


Delirium was assessed using a validated chart review method .


Cognitive performance was assessed using a neuropsychological testing battery at baseline and 4 to 6 weeks after surgery .


Impaired olfaction was identified in 54 of 165 participants ( 33 % ) before surgery .


Impaired olfaction was associated with greater adjusted risk of postoperative delirium ( relative risk = 1.90 , 95 % confidence interval = 1.17-3 .09 , P = .009 ) .


There was no association between impaired olfaction and change in composite cognitive score in the overall study population .


Impaired olfaction is prevalent in individuals undergoing cardiac surgery and is associated with greater adjusted risk of postoperative delirium but not cognitive decline .


Impaired olfaction may identify unrecognized vulnerability to postoperative delirium in individuals undergoing cardiac surgery .


WHO recommends daily co-trimoxazole for children born to HIV-infected mothers from 6 weeks of age until breastfeeding cessation and exclusion of HIV infection .


We have previously reported on the effectiveness of continuation of co-trimoxazole prophylaxis up to age 2 years in these children .


We assessed the protective efficacy and safety of prolonging co-trimoxazole prophylaxis until age 4 years in HIV-exposed children .


We undertook an open-label randomised controlled trial alongside two observational cohorts in eastern Uganda , an area with high HIV prevalence , malaria transmission intensity , and antifolate resistance .


We enrolled HIV-exposed infants between 6 weeks and 9 months of age and prescribed them daily co-trimoxazole until breastfeeding cessation and HIV-status confirmation .


At the end of breastfeeding , children who remained HIV-uninfected were randomly assigned ( 1:1 ) to discontinue co-trimoxazole or to continue taking it up to age 2 years .


At age 2 years , children who continued co-trimoxazole prophylaxis were randomly assigned ( 1:1 ) to discontinue or continue prophylaxis from age 2 years to age 4 years .


The primary outcome was incidence of malaria ( defined as the number of treatments for new episodes of malaria diagnosed with positive thick smear ) at age 4 years .


For additional comparisons , we observed 48 HIV-infected children who took continuous co-trimoxazole prophylaxis and 100 HIV-unexposed uninfected children who never received prophylaxis .


We measured grade 3 and 4 serious adverse events and hospital admissions .


All children were followed up to age 5 years and all analyses were by intention to treat .


This study is registered with ClinicalTrials.gov , number NCT00527800 .


203 HIV-exposed infants were enrolled between Aug 10 , 2007 , and March 28 , 2008 .


After breastfeeding ended , 185 children were not infected with HIV and were randomly assigned to stop ( n = 87 ) or continue ( n = 98 ) co-trimoxazole up to age 2 years .


At age 2 years , 91 HIV-exposed children who had remained on co-trimoxazole prophylaxis were randomly assigned to discontinue ( n = 46 ) or continue ( n = 45 ) co-trimoxazole from age 2 years to age 4 years .


We recorded 243 malaria episodes ( 291 per person-years ) in the 45 HIV-exposed children assigned to continue co-trimoxazole until age 4 years compared with 503 episodes ( 560 per person-years ) in the 46 children assigned to stop co-trimoxazole at age 2 years ( incidence rate ratio 053 , 95 % CI 039-071 ; p < 00001 ) .


There was no evidence of malaria incidence rebound in the year after discontinuation of co-trimoxazole in the HIV-exposed children who stopped co-trimoxazole at age 2 years , but incidence increased significantly in HIV-exposed children who stopped co-trimoxazole at age 4 years ( odds ratio 178 , 95 % CI 119-266 ; p = 0005 ) .


Incidence of grade 3 or 4 serious adverse events , hospital admissions , or deaths did not significantly differ between HIV-exposed , HIV-unexposed , and HIV-infected children .


We aimed to determine the relationship between blood lactate , carboxy-hemoglobin ( COHb ) levels and the severity of clinical findings in patients with CO poisoning .


Patients over 18 years old and of both gender who were admitted to Emergency Department with the diagnosis of CO poisoning between 10.02.2008 and 17.03.2011 were enrolled in this study .


Detailed physical examination of each patient was performed , patients and their relatives were informed about the study and written consents were noted .


The levels of consciousness , physical examination findings , electrocardiographic findings , Glasgow Coma Scale ( GCS ) scores , laboratory results ( lactate , COHb , CK-MB , Troponin-I levels ) and applied treatments [ normobaric oxygen therapy ( NBOT ) , hyperbaric oxygen therapy ( HBOT ) ] were recorded to standart data entry form for each patient .


`` SPSS for Windows version 18 '' package program was used for statistical analysis of the data .


Total 201 patients were included in this study .


Thirty five patients ( 17.4 % ) received HBOT and lactate ; COHb , CKMB , Troponin-I levels of this group were higher than the other patients .