Counter-advertising may help reduce the misleading influence of unhealthy food marketing and improve the accuracy of parents ' evaluations of how nutritious promoted food products are .


Glucagon-like peptide-1 ( GLP-1 ) may provide beneficial cardiovascular effects , possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake ( MGU ) .


We assessed the effects of GLP-1 on MGU in healthy subjects during normo - and hypoglycemia .


We included eighteen healthy men in two randomized , double-blinded , placebo-controlled cross-over studies .


MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo - ( plasma glucose ( PG ) : 4.5 mM , n = 10 ) and hypoglycemic clamps ( PG : 3.0 mM , n = 8 ) by positron emission tomography with ( 18 ) fluoro-deoxy-glucose ( ( 18 ) F-FDG ) as tracer .


In the normoglycemia study mean ( SD ) age was 253 years , and BMI was 22.60.6 kg/m ( 2 ) and in the hypoglycemia study the mean age was 232 years with a mean body mass index of 232 kg/m ( 2 ) .


GLP-1 did not change MGU during normoglycemia ( mean ( + / - SD ) 0.15 + / -0.04 and 0.16 + / -0.03 mol/g/min , P = 0.46 ) or during hypoglycemia ( 0.16 + / -0.03 and 0.13 + / -0.04 mol/g/min , P = 0.14 ) .


However , the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo - and hypoglycemia , ( P = 0.006 , r ( 2 ) = 0.64 and P = 0.018 , r ( 2 ) = 0.64 , respectively ) and changes in MGU correlated positively with the level of insulin resistance ( HOMA 2IR ) during hypoglycemia , P = 0.04 , r ( 2 ) = 0.54 .


GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study .


No differences in other circulating hormones or metabolites were found .


While GLP-1 does not affect overall MGU , GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU .


GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects .


ClinicalTrials.gov registration numbers : NCT00418288 : ( hypoglycemia ) and NCT00256256 : ( normoglycemia ) .


The effectiveness of non-invasive positive pressure ventilation ( NIV ) in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure ( ARF ) remains unclear .


We investigated if nocturnal NIV in these patients prolongs the time to readmission for respiratory causes or death ( primary endpoint ) in the following 12months .


201 COPD patients admitted to hospital with ARF and prolonged hypercapnia > 48h after termination of ventilatory support were randomised to NIV or standard treatment .


Secondary outcomes were daytime arterial blood gasses , transcutaneous PCO2 during the night , lung function , health-related quality-of-life ( HRQL ) , mood state , daily activities and dyspnoea .


1year after discharge , 65 % versus 64 % of patients ( NIV vs standard treatment ) were readmitted to hospital for respiratory causes or had died ; time to event was not different ( p = 0.85 ) .


Daytime PaCO2 was significantly improved in NIV versus standard treatment ( PaCO2 0.5 kPa ( 95 % CI 0.04 to 0.90 , p = 0.03 ) ) as was transcutaneous PCO2 during the night .


HRQL showed a trend ( p = 0.054 , Severe Respiratory Insufficiency questionnaire ) in favour of NIV .


Number of exacerbations , lung function , mood state , daily activity levels or dyspnoea was not significantly different .


We could not demonstrate an improvement in time to readmission or death by adding NIV for 1year in patients with prolonged hypercapnia after an episode of NIV for ARF .


There is no reason to believe the NIV was not effective since daytime PaCO2 and night-time PCO2 improved .


The trend for improvement in HRQL favouring NIV we believe nevertheless should be explored further .


NTR1100 .


This study evaluated the effect of either an intermediate application of adhesive resin or flowable resin application on the adhesion of particulate filler composite ( PFC ) to glass fiber-reinforced composite ( FRC ) .


Unidirectional , pre-impregnated S2-glass fiber bundles ( Dentapreg ) ( length : 40 mm ; thickness : 0.5 mm ) were obtained ( N = 30 , n = 10 per group ) and secured in translucent silicone material with the adhesion surface exposed and photopolymerized .


They were randomly divided into 3 groups for the following adhesion sequence : A ) FRC+PFC , B ) FRC + intermediate adhesive resin + PFC , C ) FRC + flowable resin + PFC. The PFC was applied in a polyethylene mold onto the FRC and photopolymerized .


PFCs were debonded from the FRC surface using shear bond test in a universal testing machine ( 1 mm/min ) .


After debonding , all specimens were analyzed using scanning electron microscopy to categorize the failure modes .


The data were statistically analyzed using one-way ANOVA and Tukey 's tests ( = 0.05 ) .


A significant difference was observed between the groups ( p < 0.05 ) .


The highest mean bond strength value was obtained with the application of an intermediate layer of adhesive resin ( group B : 19.4 1.1 MPa ) ( p < 0.05 ) followed by group A ( 14.1 0.6 MPa ) and group C ( 10.4 0.8 MPa ) , which were also significantly different from one another ( p < 0.05 ) .


Group A exclusively presented a combination of partial cohesive failure in the PFC and adhesive failure between the FRC and PFC. While group B showed large cohesive defects in the FRC , in group C , only small cohesive failures were observed in the FRC .


Based on the highest mean bond strength and the large cohesive failures within the FRC , application of an intermediate layer of adhesive resin on the S2-glass FRC surface prior to incremental build up of the PFC seems to be compulsory .


In vitro and retrospective clinical studies suggest an association between anaesthetic technique during primary breast cancer surgery and cancer outcome .


Apoptosis is an important step in the mechanism of breast cancer metastasis , but whether it is influenced by anaesthetic technique is unknown .


Using serum from breast cancer surgery patients randomized to receive distinct anaesthetic techniques , we investigated its effect on apoptosis in oestrogen receptor ( ER ) - negative breast cancer cells in vitro .


Women with biopsy-proven breast cancer were randomized to receive either propofol general anaesthesia with paravertebral analgesia ( PPA ) or standard sevoflurane general anaesthesia with opioid analgesia ( SGA ) in an ongoing , prospective clinical trial ( NCT 00418457 ) .


Serum from a randomly selected subset of these patients ( 10 PPA and 10 SGA ) who had donated 20 ml venous blood immediately before anaesthetic induction and at 1 h after operation was exposed to ER-negative MDA-MB-231 cells .


Apoptosis was measured using ApoLive-Glo Multiplex Assay .


Exposure of MDA-MB-231 cells to postoperative serum of PPA patients resulted in higher luminescence ratio ( apoptosis ) than SGA patients , median ( 25-75 % ) , 0.40 ( 0.35-0 .43 ) compared with 0.22 ( 0.21-0 .30 ) , respectively ( P = 0.001 ) .


The luminescence ratio of postoperative serum from SGA was reduced compared with preoperative SGA 0.22 ( 0.21-0 .30 ) compared with 0.3 ( 0.25-0 .35 ) ( P = 0.045 ) .


Serum from patients given sevoflurane anaesthesia and opioids for primary breast cancer surgery reduces apoptosis in ER-negative breast cancer cells to a greater extent than serum from patients given propofol-paravertebral anaesthesia .


Anaesthetic technique might affect the serum milieu in a manner that impacts cancer cell apoptosis , and thereby tumour metastasis .


There is uncertainty regarding the optimal dosing regimen for the resumption of warfarin after interruption for invasive procedures .


To determine the efficacy and safety of warfarin resumption with loading doses or with the most recent maintenance dose .


Patients receiving warfarin treatment and planned for invasive procedures with an expected hospital stay of 1 day were randomized to resume warfarin on the day of the procedure , defined as day 1 , with most recent maintenance dose or with 2 initial days of double maintenance dose .


Efficacy outcomes were proportion of international normalized ratio ( INR ) levels 2.0 on day 5 ( primary outcome ) and day 10 .


Safety outcomes were bleeding and thromboembolic events .


In addition , D-dimer levels were analyzed on days 5 and 10 in a subset of the population .


There were 49 patients analyzed in each group .


INR of 2.0 had been achieved by day 5 for 13 % in the maintenance-dose group and for 50 % in the loading-dose group ( relative risk [ RR ] 0.27 , 95 % confidence interval [ CI ] 0.10-0 .60 ) and by day 10 for 68 % and 87 % , respectively ( RR 0.78 , 95 % CI 0.65-1 .00 ) .


There were no thromboembolic events , and there was one major bleed before resumption of warfarin and one minor bleed , both in the maintenance-dose group .


There was no difference between the groups in the proportion of patients with excessive INRs or elevated D-dimer levels or in the median D-dimer level .


Resumption of warfarin after minor-moderately invasive procedures with two loading doses achieves therapeutic INR faster than does only maintenance dose .


To determine if self-reported anxiety levels decreased after tracheostomy placement in a sample of mechanically ventilated intensive care unit patients .


There is limited research regarding the impact of a tracheostomy on patients ' anxiety .


Elevated anxiety delays healing and contributes to long-term mental health complications .


This was a secondary analysis of data from a large clinical trial conducted in urban Minnesota .


Fifty-one of 116 patients received a tracheostomy .


Anxiety scores were obtained daily using the Visual Analog Scale-Anxiety .


Mixed model analysis was used to compare anxiety ratings pre - and post-tracheostomy .


There was no significant decrease in anxiety following tracheostomy after controlling for time and gender ( all p > .16 ) .


Age was the only variable to impact anxiety levels : anxiety scores increased as age increased ( p = .02 ) .


Prospective studies are needed to more accurately assess the impact of tracheostomy placement on patient anxiety and salient outcomes .


Myocardial iron overload leading to congestive heart failure ( HF ) or arrhythmias is a recognized complication in thalassemia patients undergoing chronic blood transfusion .


The relationship between myocardial iron load , subclinical systolic dysfunction , and clinical events remains less well known .


We studied a total of 77 subjects , comprising 37 thalassemia patients ( mean age : 24.2 5.5 years ) with a history of repeated blood transfusions , in addition to 40 age - and gender-matched controls ( mean age : 24 4.5 years ) .


Serum ferritin levels were checked in all subjects , as well as semiautomated quantification of left ventricular ( LV ) longitudinal , circumferential , and radial deformations assessed by two-dimensional ( 2D ) speckle tracking analysis .


Compared with the control group , thalassemia patients showed significantly larger LV mass index and lower myocardial deformations ( P < 0.05 ) , but left ventricular ejection fraction ( LVEF ) did not differ significantly ( P = 0.233 ) .


There was a significant linear correlation between serum ferritin level and longitudinal ( r = 0.44 , P = 0.0078 ) and radial strain ( r = -0.46 , P = 0.0051 ) , with optimal cutoff provided to be -15.48 % , -21.31 % , and 26.67 % for longitudinal , circumferential , and radial strain in predicting clinical events , respectively .


During a median of 802.5 days follow-up , 11 clinical composites ( HF incidence , ventricular tachyarrhythmia , and death ) occurred ( N = 9 subjects ) ; subjects with composites had significantly reduced longitudinal and radial strain compared to those without ( both P < 0.05 ) .


After adjusting for age , sex , serum ferritin level , and LV mass index , a worsening of longitudinal strain remained as an independent predictor of clinical events and death ( HR : 6.05 , P = 0.033 ) .


Subclinical systolic dysfunction appears more likely in thalassemia subjects with a history of repeated blood transfusions , which further correlated with serum ferritin levels .


In addition , worsening LV myocardial deformation parameters may play an independent role in predicting clinical outcomes beyond traditional measures in this population .


To evaluate the efficacy of extracorporeal magnetic innervation ( ExMI ) as a treatment for primary dysmenorrhea compared with nonsteroidal anti-inflammatory drugs ( NSAIDs ) and combined oral contraceptives ( COCs ) .


The cases were randomized into three groups ( NSAID = 51 , ExMI = 53 , COC = 54 ) .


ExMI was applied for a total of 10 sessions .


Women in the NSAID group used an oral NSAID at the start of each menstruation .


Women in the COC group were given combined pills .


Of the treatment options , ExMI was applied for only a single period , whereas NSAID and COC use continued for 12 months .


At the first menstruation , visual analog scale ( VAS ) scores improved significantly in all groups ( p < 0.001 ) .


NSAIDs and COCs continued to show efficacy over the entire study period ( p < 0.05 ) .


However , in the ExMI group , VAS values increased from the first menstruation until 12 months .


The VAS score at the 12th month was significantly higher in the ExMI group than in the other groups ( p < 0.05 ) , but markedly lower than the pretreatment value ( 49.9 8.3 vs. 71.1 10.1 , p < 0.001 ) .


ExMI therapy might be a promising novel noninvasive option for primary dysmenorrhea .


Efficacy began to decline after 3 months , but continued for 12 months .


Physostigmine , a centrally acting acetylcholinesterase inhibitor , is most commonly used by anesthesiologists in the postanesthetic setting to reverse confusion caused by central anticholinergic medication effects .


It has also been proposed as a treatment for sleep-disordered breathing .


We investigated whether physostigmine was effective in decreasing the frequency of ventilatory arrhythmias produced during moderate sedation with midazolam and remifentanil during the conditions of breathing room air or 2 L/min nasal O2 .


Ten healthy male volunteers participated in this randomized , double-blind control trial of physostigmine ( 0.24 gkgmin ) versus placebo .


Moderate sedation was achieved with infusions of midazolam and remifentanil and monitored with full and processed electroencephalogram .


Analgesia was quantified with subjective pain score to thermal stimulation .


Ventilatory arrhythmias , as measured by the sedation apnea-hypopnea index ( S-AHI ) , were scored as the number of apneas and hypopneas during two 1-hour periods on room air or 2 L/min nasal O2 .


All subjects tolerated the sedation and physostigmine without significant adverse effects .


Sedation during placebo infusion resulted in clinically significant ( S-AHI > 15 ) ventilatory arrhythmias in 5 conditions in 3 subjects ( 2 on room air and then O2 , and 1 on O2 only ) .


Physostigmine did not significantly ( P > 0.46 ) reduce the total number of ventilatory arrhythmias on either room air or O2 ( 13.4 18.8 events/h [ mean SEM ] , 95 % confidence interval [ CI ] = -9.9 to 62.7 ; and 6.2 8.0 , 95 % CI = -3.1 to 28.7 , respectively ) .


Physostigmine did reduce the S-AHI in all 5 instances of clinically significant ventilatory arrhythmias ( S-AHI decreased by 67.0 22.2 ; CI = 29.2-111 .7 ; P = 0.04 ) .


Physostigmine does not appear to be useful as a pretreatment to prevent ventilatory arrhythmias during moderate sedation .


However , it may be useful as a treatment for clinically significant ventilatory arrhythmias during moderate sedation .


Low HDL cholesterol ( HDL-C ) and small HDL particle size may directly promote hyperglycemia .


We evaluated associations of HDL-C , apolipoprotein A-I ( apoA-I ) , and HDL-C/apoA-I with insulin secretion , insulin resistance , HbA1c , and long-term glycemic deterioration , reflected by initiation of pharmacologic glucose control .


The 5-year Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study followed 9,795 type 2 diabetic subjects .


We calculated baseline associations of fasting HDL-C , apoA-I , and HDL-C/apoA-I with HbA1c and , in those not taking exogenous insulin ( n = 8,271 ) , with estimated - cell function ( homeostasis model assessment of - cell function [ HOMA-B ] ) and insulin resistance ( HOMA-IR ) .


Among the 2,608 subjects prescribed lifestyle only , Cox proportional hazards analysis evaluated associations of HDL-C , apoA-I , and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents ( OHAs ) or insulin .


Adjusted for age and sex , baseline HDL-C , apoA-I , and HDL-C/apoA-I were inversely associated with HOMA-IR ( r = -0.233 , -0.134 , and -0.230 ; all P < 0.001 ; n = 8,271 ) but not related to HbA1c ( all P > 0.05 ; n = 9,795 ) .


ApoA-I was also inversely associated with HOMA-B ( r = -0.063 ; P = 0.002 ; n = 8,271 ) adjusted for age , sex , and HOMA-IR .


Prospectively , lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake ( per 1-SD lower : hazard ratio [ HR ] 1.13 [ CI 1.07-1 .19 ] , P < 0.001 ; and HR 1.16 [ CI 1.10-1 .23 ] , P < 0.001 , respectively ) and earlier uptake ( median 12.9 and 24.0 months , respectively , for quartile 1 vs. quartile 4 ; both P < 0.01 ) of OHAs and insulin , with no difference in HbA1c thresholds for initiation ( P = 0.87 and P = 0.81 ) .


Controlling for HOMA-IR and triglycerides lessened both associations , but HDL-C/apoA-I remained significant .


HDL-C , apoA-I , and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c .


However , lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control .


The obesity epidemic has spread to young adults , leading to significant public health implications later in adulthood .


Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic .


Few weight loss trials have been conducted in young adults .


It is unclear what weight loss strategies are beneficial in this population .


To describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You ( CITY ) study , which is a single center , randomized three-arm trial that compares the impact on weight loss of 1 ) a behavioral intervention that is delivered almost entirely via cell phone technology ( Cell Phone group ) ; and 2 ) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone ( Personal Coaching group ) , each compared to 3 ) a usual care , advice-only control condition .


A total of 365 community-dwelling overweight/obese adults aged 18-35 years were randomized to receive one of these three interventions for 24 months in parallel group design .


Study personnel assessing outcomes were blinded to group assignment .


The primary outcome is weight change at 24 [ corrected ] months .


We hypothesize that each active intervention will cause more weight loss than the usual care condition .


Study completion is anticipated in 2014 .


If effective , implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss .


ClinicalTrial.gov : NCT01092364 .


Subjective responses to alcohol represent a biologically based , genetically moderated , and clinically informative marker of alcoholism risk ; however , the physiology underlying this phenotype remains unclear .


This study tested whether subjective responses during alcohol administration predict neural responses to alcohol cues in the scanner and whether these neural responses differ between OPRM1 genotypes .


Twenty alcohol-dependent individuals were recruited ( 10 G-allele carriers ; 6 women ; Mage = 29.4 ) for a within-subjects alcohol administration in the laboratory and a functional magnetic resonance imaging session consisting of an alcohol taste cues task .


Laboratory assessments of alcohol high , liking , craving , and positive and negative reinforcement during alcohol administration were entered as predictors of neural response to the presentation of alcohol cues versus water cues in the scanner and further tested for OPRM1 genotype moderation ( whole-brain cluster-corrected at Z > 1.96 , p < .05 ) .


Alcohol craving during alcohol administration predicted less neural activity , whereas alcohol reinforcement predicted greater neural activity to alcohol cues versus water cues in regions including the precuneus , posterior cingulate gyrus , and lingual gyrus .


Alcohol high predicted greater neural activity to alcohol cues in regions including the precuneus and anterior cingulate cortex .


OPRM1 genotype was found to moderate these relationships .


No results were observed for alcohol liking .


This study provides initial evidence that subjective responses to alcohol , namely craving , high , and the reinforcing properties of alcohol , predict neural markers of alcohol cue reactivity .


These results support the validity of laboratory and neuroimaging measures of subjective responses to alcohol and offer an integration of these methods in a sample of alcohol-dependent individuals .


Vitamin D co-regulates the synthesis of sex hormones in part by interaction with its nuclear receptor .


The aim of this study was to determine whether there is an association of vitamin D concentration vs the level of sex hormones in elderly Polish individuals with different genotypes of the vitamin D receptor ( VDR ) gene .


Rs10735810 , rs1544410 , rs7975232 , and rs731236 polymorphisms of VDR , the serum sex hormone level , free estrogen index ( FEI ) and free androgen index ( FAI ) as well as vitamin D , were evaluated in 766 persons ( 362 women and 404 men ) selected from 5695 Polish population , aged 65-90years from the PolSenior survey .


We observed that women with GG ( rs731236 ) , TT ( rs7975232 ) , BB ( rs1544410 ) and FF ( rs10735810 ) genotypes were characterized by a significant correlation between vitamin D vs testosterone concentration and FAI value .


We found a significant correlation between testosterone level and FAI vs vitamin D concentration in men with heterozygote AG in the rs731236 polymorphism and in the GG ( rs7975232 ) , the BB ( rs1544410 ) , and the Ff ( rs10735810 ) genotypes .


In elderly selected Polish population with different genotypes of VDR polymorphisms , a statistically significant relationship between vitamin D concentration vs testosterone level was observed .


Evidence of effective treatment of childhood obesity in primary care settings is limited .


To examine the extent to which computerized clinical decision support ( CDS ) delivered to pediatric clinicians at the point of care of obese children , with or without individualized family coaching , improved body mass index ( BMI ; calculated as weight in kilograms divided by height in meters squared ) and quality of care .


We conducted a cluster-randomized , 3-arm clinical trial .


We enrolled 549 children aged 6 to 12 years with a BMI at the 95 % percentile or higher from 14 primary care practices in Massachusetts from October 1 , 2011 , through June 30 , 2012 .


Patients were followed up for 1 year ( last follow-up , August 30 , 2013 ) .


In intent-to-treat analyses , we used linear mixed-effects models to account for clustering by practice and within each person .


In 5 practices randomized to CDS , pediatric clinicians received decision support on obesity management , and patients and their families received an intervention for self-guided behavior change .


In 5 practices randomized to CDS + coaching , decision support was augmented by individualized family coaching .


The remaining 4 practices were randomized to usual care .


Smaller age-associated change in BMI and the Healthcare Effectiveness Data and Information Set ( HEDIS ) performance measures for obesity during the 1-year follow-up .


At baseline , mean ( SD ) patient age and BMI were 9.8 ( 1.9 ) years and 25.8 ( 4.3 ) , respectively .


At 1 year , we obtained BMI from 518 children ( 94.4 % ) and HEDIS measures from 491 visits ( 89.4 % ) .


The 3 randomization arms had different effects on BMI over time ( P = .04 ) .


Compared with the usual care arm , BMI increased less in children in the CDS arm during 1 year ( -0.51 [ 95 % CI , -0.91 to -0.11 ] ) .


The CDS + coaching arm had a smaller magnitude of effect ( -0.34 [ 95 % CI , -0.75 to 0.07 ] ) .


We found substantially greater achievement of childhood obesity HEDIS measures in the CDS arm ( adjusted odds ratio , 2.28 [ 95 % CI , 1.15-4 .53 ] ) and CDS + coaching arm ( adjusted odds ratio , 2.60 [ 95 % CI , 1.25-5 .41 ] ) and higher use of HEDIS codes for nutrition or physical activity counseling ( CDS arm , 45 % ; CDS + coaching arm , 25 % ; P < .001 compared with usual care arm ) .


An intervention that included computerized CDS for pediatric clinicians and support for self-guided behavior change for families resulted in improved childhood BMI .


Both interventions improved the quality of care for childhood obesity .


clinicaltrials.gov Identifier : NCT01537510 .


Recent studies have shown that neutrophils may display an antigen-presenting function and inhibit lymphocyte proliferation by expressing programmed cell death 1 ligand 1 ( PD-L1 ) .


The current study was performed to investigate the effect of neutrophils and their pathophysiological significance during sepsis .


Neutrophil PD-L1 expression was determined in both septic mice ( n = 6 ) and patients ( n = 41 ) .


Neutrophils from septic mice were subtyped into PD-L1 and PD-L1 populations to determine their phenotypes and functions .


Septic neutrophils were cocultured with lymphocytes to observe the effect of septic neutrophils on lymphocyte apoptosis .


The PD-L1 level on neutrophils from septic mice was significantly up-regulated ( 21.41 4.76 % ) .


This level increased with the progression of sepsis and the migration of neutrophils from the bone marrow to the blood and peritoneal cavity .


The percentages of CD11a , CD62L , and C-C chemokine receptor type 2 were lower , whereas the percentages of CD16 and CD64 were higher on PD-L1 neutrophils than on PD-L1 neutrophils .


The migratory capacity of PD-L1 neutrophils was compromised .


Septic neutrophils induced lymphocyte apoptosis via a contact mechanism , and this process could be reversed by anti-PD-L1 antibody .


PD-L1 was also up-regulated on neutrophils from patients with severe sepsis ( 14.6 % [ 3.75 % , 42.1 % ] ) .


The levels were negatively correlated with the monocyte human leukocyte antigen-DR level and positively correlated with the severity of septic patients .


Neutrophil PD-L1 was a predictor for the prognosis of severe sepsis , with an area of 0.74 under the receiver operating curve .


PD-L1 is up-regulated on neutrophils during sepsis , which may be related to sepsis-induced immunosuppression .


Daylight photodynamic therapy ( DL-PDT ) of actinic keratosis ( AK ) has shown preliminary efficacy and safety results comparable to conventional photodynamic therapy ( c-PDT ) , using methyl aminolevulinate ( MAL ) cream .


To demonstrate the efficacy and safety of DL-PDT vs. c-PDT in treating mild facial/scalp AK .


This 24-week randomized , controlled , investigator-blinded , multicentre , intra-individual efficacy ( non-inferiority ) and safety ( superiority regarding pain ) study enrolled 100 subjects .


AKs on the face/scalp were treated once , with DL-PDT on one side and c-PDT on the contralateral side .


Primary end points for DL-PDT at week 12 were efficacy [ non-inferiority regarding complete lesion response ( mild AK ) ] and safety ( superiority regarding subject 's assessment of pain ) .


Lesions with complete response 12weeks after one treatment session were followed until week 24 .


The safety evaluation included incidence of adverse events .


Subject satisfaction was classified using a questionnaire .


At week 12 , the complete lesion response rate with DL-PDT was non-inferior to c-PDT ( 892 % vs. 928 % , respectively ; 95 % confidence interval -68 to -03 ) , confirmed by intention-to-treat analysis .


Additionally , regardless of the treatment used , 96 % of mild lesions were maintained in complete response 24weeks after the PDT session .


For DL-PDT , subject-reported pain was significantly lower ( 08 vs. 57 , respectively ; P < 0001 ) , with better tolerability and significantly higher subject satisfaction regarding convenience and outcome .


Daylight-mediated PDT was not inferior in efficacy to Metvix c-PDT ( mild AK response rate ) , better tolerated , nearly painless and more convenient for patients .


Brief motivational intervention ( BMI ) has shown promising results to reduce alcohol use in young adults .


Knowledge on mechanisms that predict BMI efficacy could potentially improve treatment effect sizes through data that optimize clinical training and implementation .


Particularly , little attention has been given to counselor influence on treatment mechanisms .


We investigated the influence of counselors on BMI efficacy in reducing alcohol use among non-treatment-seeking young men ( age 20 ) screened as hazardous drinkers .


Participants were randomly allocated to ( i ) a group receiving a single BMI from 1 of 18 counselors selected to maximize differences in several of their characteristics ( gender , professional status , clinical experience , and motivational interviewing [ MI ] experience ) or ( ii ) a control group receiving assessment only .


Drinking at 3-month follow-up was first compared between the BMI and control groups to assess efficacy .


Then , the influence of counselors ' characteristics ( i.e. , gender , professional status , clinical experience , MI experience , BMI attitudes , and expectancies ) and within-session behaviors ( i.e. , measured by the Motivational Interviewing Skill Code ) on outcome was tested in regression analyses .


There was a significant ( p = 0.02 ) decrease in alcohol use among the BMI group compared to the control group .


Counselors that were male , more experienced , that had more favorable BMI attitudes and expectancies , higher MI skills , but surprisingly less MI-consistent behaviors , had significantly better outcomes than the control group while their counterparts did not .


The current study demonstrated BMI efficacy on alcohol use reduction within a sample of non-treatment-seeking young adult males .


Moreover , BMI effect was related to interindividual differences among counselors , and results therefore provide recommendations for BMI training and implementation with similar populations .


Second-generation antipsychotics ( SGAs ) are among the first-line treatments for bipolar disorder and schizophrenia , but have a tendency to generate metabolic disturbances .


These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei .


In a clinical trial , we hypothesized that melatonin , a hormone that regulates the suprachiasmatic nucleus , could attenuate SGA-induced adverse metabolic effects .


In an eight-week , double-blind , randomized , placebo-controlled , parallel-group clinical trial , we evaluated the metabolic effect of melatonin in SGA-treated patients in terms of weight , blood pressure , lipid , glucose , body composition , and anthropometric measures .


A total of 44 patients treated with SGAs , 20 with bipolar disorder and 24 with schizophrenia , randomly received placebo ( n = 24 ) or melatonin 5 mg ( n = 20 ) .


The melatonin group showed a decrease in diastolic blood pressure ( 5.1 versus 1.1 mmHg for placebo , p = 0.003 ) and attenuated weight gain ( 1.5 versus 2.2 kg for placebo , F = 4.512 , p = 0.040 ) compared to the placebo group .


The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass ( 0.2 versus 2.7 kg , respectively , p = 0.032 ) and diastolic blood pressure ( 5.7 versus 5.5 mmHg , respectively , p = 0.001 ) were observed in the bipolar disorder and not in the schizophrenia group .


No adverse events were reported .


Our results show that melatonin is effective in attenuating SGAs ' adverse metabolic effects , particularly in bipolar disorder .


The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore .


Melatonin could become a safe and cost-effective therapeutic option to attenuate or prevent SGA metabolic effects .


EP42675 is a first-in-class , synthetic , parenteral , anticoagulant combining in a single molecule a direct thrombin inhibitor and an indirect factor Xa ( FXa ) inhibitor .


To investigate the safety , pharmacokinetics , and pharmacodynamics of EP42675 and its interaction with aspirin , clopidogrel , and unfractionated heparin ( UFH ) .


In study 1 , healthy male subjects were administered intravenously single-ascending doses ( 1-10 mg ) of EP42675 or placebo .


In study 2 , healthy male subjects were administered intravenously a single dose of 5 mg EP42675 on day 1 followed by oral administration of aspirin ( 100 mg ) and clopidogrel ( 75 mg ) once daily from day 8 to 21 .


On day 15 , a second dose of 5 mg EP42675 was administered , and subjects were then randomized to receive a single dose of UFH ( 30 or 60 IU kg ( -1 ) ) or placebo .


Mild bleedings were the only drug-related adverse events .


EP42675 pharmacokinetics were dose-proportional and characterized by a low clearance , a small volume of distribution , a long terminal half-life .


EP42675 pharmacodynamics were characterized by a long-lasting , dose-dependent increase in activated clotting time , ecarin clotting time , thrombin time , anti-FXa activity , activated partial thromboplastin time , prothrombin time , and a decrease in endogenous thrombin potential , measured by a thrombin generation test .


Dose-dependent additive effects were seen with UFH on coagulation tests .


EP42675 had no additive effect on the inhibition of platelet aggregation induced by aspirin and clopidogrel .


These results warrant further clinical development of this new class of anticoagulant .


Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities .


Allopurinol reduces the formation of free radicals , which potentially limits hypoxia-induced brain damage .


We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia .


We used data from a randomised , double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia ( NCT00189007 ) .


We studied 58 women in labour at term , with suspected fetal hypoxia prompting immediate delivery , in the intervention arm of the study .


Delivery rooms of 11 Dutch hospitals .


500 mg allopurinol , intravenously to the mother , immediately prior to delivery .


Drug disposition ( maternal plasma concentrations , cord blood concentrations ) and drug safety ( maternal and fetal adverse events ) .


Within 5 min after the end of maternal allopurinol infusion , target plasma concentrations of allopurinol of 2 mg/L were present in cord blood .


Of all analysed cord blood samples , 95 % ( 52/55 ) had a target allopurinol plasma concentration at the moment of delivery .


No adverse events were observed in the neonates .


Two mothers had a red and/or painful arm during infusion .


A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95 % of the fetuses at the moment of delivery , which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects .


The study is registered in the Dutch Trial Register ( NTR1383 ) and the Clinical Trials protocol registration system ( NCT00189007 ) .


A limited number of adrenaline auto-injectors are currently available .


Epipen and Anapen are available in Australia , New Zealand , UK and parts of Europe and Asia .


Few studies have compared the performance of these devices .


To compare the intuitiveness of use of these devices .


A secondary aim was to compare the ability to recall the use of each device after a period of 3months .


A random sample of 100 subjects nave to both the EpiPen and Anapen were recruited from staff and families attending Royal Children 's Hospital , Melbourne Australia .


Subjects were randomized to Anapen ( n = 53 ) or EpiPen ( n = 47 ) and asked to demonstrate use of a ` trainer ' device ( i ) prior to and ( ii ) after receiving training in its correct use .


A subset ( n = 32 ) participated in a follow-up study to evaluate ( iii ) the ability to recall correct use of each device .


Most subjects correctly demonstrated all steps in use of the EpiPen and Anapen both prior to ( 89 % vs. 79 % , p = 0.17 ) and after training on use ( 100 % vs. 100 % ) .


However , after 3months , significantly more participants correctly demonstrated use of EpiPen ( 87 % ) compared to Anapen ( 35 % ) ( p = 0.003 ) and critical errors that would likely result in failure to administer adrenaline were more common with Anapen ( 59 % vs. 13 % , p = 0.01 ) .


Most study participants correctly demonstrated the use of both devices without prior training .


There was greater attrition in correct use of Anapen compared to EpiPen over time .


Critical errors in administration were more likely with Anapen than EpiPen .


Pelvic organ prolapse is a common health problem : the lifetime risk of undergoing surgery for pelvic organ prolapse by the age of 85 years is 19 % .


Pelvic organ prolapse has significant negative effects on a woman 's quality of life .


Worldwide , vaginal hysterectomy is the leading treatment method for patients with symptomatic uterovaginal prolapse .


Several studies have shown that vaginal sacrospinous hysteropexy and laparoscopic sacrohysteropexy are safe and effective alternatives in treating uterine descent .


To date , it is unclear which of these techniques leads to the best operative result and the highest patient satisfaction .


Therefore , we conducted the LAVA trial .


The LAVA trial is a randomized controlled multicenter non-inferiority trial .


The study compares laparoscopic sacrohysteropexy with vaginal sacrospinous hysteropexy in women with uterine prolapse stage 2 or higher .


The primary outcome of this study is surgical success of the apical compartment at 1 and 5 years follow-up .


Secondary outcomes are subjective improvement on urogenital symptoms and quality of life ( assessed by disease-specific and general quality of life questionnaires ) , complications following surgery , hospital stay , post-operative recovery , sexual functioning and costs-effectiveness .


Evaluation will take place pre-operatively , and 6 weeks , 6 months , 12 months and annually till 60 months after surgery .


Validated questionnaires will be used.Analysis will be performed according to the intention to treat principle .


Based on comparable recurrence rates of 3 % and a non-inferiority margin of 10 % , 62 patients are needed in each arm to prove the hypothesis with a 95 % confidence interval .


The LAVA trial is a randomized controlled multicenter non-inferiority trial that will provide evidence whether the efficacy of laparoscopic sacrohysteropexy is non-inferior to vaginal sacrospinous hysteropexy in women with symptomatic uterine prolapse stage 2 or higher .


Netherlands Trial Register ( NTR ) : NTR4029 .


Since its introduction in 2007 , the use of 8-plates has gained great popularity for the correction of diverse deformities in skeletally immature patients .


In this study , we evaluate 2 different techniques of implant placement .


A consecutive series of patients with indication of guided growth around the knee ( femur or tibia ) were included in the study .


Patients were randomly divided in 2 groups , with 8-plate inserted using technique as described by Stevens ( group A ) versus technique modified from Paley ( group B ) .


We analyzed operative time , radiation exposure , incision size , and intraoperative complications .


Comparisons between groups were performed with a Mann-Whitney test .


A 2-tailed P-value < 0.05 was considered significant .


We evaluated a total of 31 procedures in 18 patients ( 16 in group A and 15 in group B ) .


Age and sex was similar in both groups ( P = 0.470 and 0.720 ) .


Operative time and radiation exposure was significantly lower in group B : 20 minutes ( range , 11.37 to 29.30 min ) versus 13.09 minutes ( range , 9.31 to 25 min ) ( P 0.009 ) , and 0.30 Gy ( range , 0.10 to 1.30 Gy ) versus 0.10 Gy ( range , 0.00 to 0.70 Gy ) ( P = 0.013 ) , respectively .


The incision size was also smaller in group B : 27 mm ( range , 23 to 29 mm ) versus 23 mm ( range , 18 to 24 mm ) ( P = 0.05 ) .


There were no intraoperative complications in any of the 2 groups .


Modified technique for 8-plate placement seems to reduce operative time , radiation exposure , and incision size for guided growth around the knee .


Level of evidence II-prospective randomized study .


Fast-track program has been applied in several surgical fields .


However , currently many surgical patients are elderly over 70 years of age , and discussion about the application of such protocols for elderly patients is inadequate .


The present study was designed to consider the safety and feasibility of application of a fast-track program after colorectal surgery in elderly patients .


A total of 76 elderly patients with colorectal cancer who underwent laparoscopic colorectal resection were randomly assigned to receive either the fast-track care program ( n = 40 ) or the conventional perioperative care protocol ( control group , n = 36 ) .


The fast track protocol included no preoperative mechanical bowel irrigation , immediate oral alimentation and earlier postoperative ambulation exercise .


The length of postoperative hospital stay , the length of time to regain bowel function and the rate of postoperative complications were compared between the two groups .


The length of time to regain bowel function , including the passage of flatus [ 32 ( 24-40 ) h vs 42 ( 32-52 ) h ] , and to start a liquid diet ( 13 [ 10-16 ] h v/s 43 [ 36-50 ] h ) were significantly shorter in patients receiving the fast track care protocol compared with those receiving the conventional care protocol .


A shorter duration of postoperative hospital stay was recorded in patients receiving the fast-track program than in those receiving conventional care [ 6 ( 5-7 ) days v/s 9.5 ( 7-12 ) days ] .


A reduced percentage of patients who developed general complications was also observed in the fast-track group ( 5.0 % v/s 18 % ) .


Fast-track after laparoscopic colorectal surgery can be safely applied in carefully selected elderly patients older than age 70 years .


The fast-track recovery program resulted in a more rapid postoperative recovery , earlier discharge from hospital and fewer general complications compared with a conventional postoperative protocol .


To test the hypothesis that inhaled nitric oxide ( iNO ) would lead to improved oxygenation and a decrease in duration of mechanical ventilation in pediatric patients with acute respiratory distress syndrome .


A total of 55 children with acute respiratory distress syndrome were enrolled from 9 centers .


Patients were randomized to iNO or placebo and remained on the study drug until death , they were free of ventilator support , or day 28 after the initiation of therapy .


Mean baseline oxygenation indexes ( OIs ) were 22.0 18.4 and 25.6 14.9 ( iNO and placebo groups , respectively , P = .27 ) .


There was a trend toward an improved OI in the iNO group compared with the placebo group at 4 hours that became significant at 12 hours .


There was no difference in the OI between groups at 24 hours .


Days alive and ventilator free at 28 days was greater in the iNO group , 14.2 8.1 and 9.1 9.5 days ( iNO and placebo groups , respectively , P = .05 ) .


Although overall survival at 28 days failed to reach statistical significance , 92 % ( 22 of 24 ) in the iNO group and 72 % ( 21 of 29 ) in the placebo group ( P = .07 ) , the rate of extracorporeal membrane oxygenation-free survival was significantly greater in those randomized to iNO 92 % ( 22 of 24 ) vs 52 % ( 15 of 29 ) for those receiving placebo ( P < .01 ) .


The use of iNO was associated with a significantly reduced duration of mechanical ventilation and significantly greater rate of extracorporeal membrane oxygenation-free survival .


To compare the clinical outcomes of sorafenib plus either erlotinib or placebo in patients with advanced hepatocellular carcinoma ( HCC ) in a multicenter , multinational , randomized , phase III trial .


Patients with advanced HCC and underlying Child-Pugh class A cirrhosis , who were naive to systemic treatment ( N = 720 ) , were randomly assigned to sorafenib plus either erlotinib ( n = 362 ) or placebo ( n = 358 ) .


The primary end point was overall survival ( OS ) .


Median OS was similar in the sorafenib plus erlotinib and sorafenib plus placebo groups ( 9.5 v 8.5 months , respectively ; hazard ratio [ HR ] , 0.929 ; P = .408 ) , as was median time to progression ( 3.2 v 4.0 months , respectively ; HR , 1.135 ; P = .18 ) .


In the sorafenib/erlotinib arm versus the sorafenib/placebo arm , the overall response rate trended higher ( 6.6 % v 3.9 % , respectively ; P = .102 ) , whereas the disease control rate was significantly lower ( 43.9 % v 52.5 % , respectively ; P = .021 ) .


The median durations of treatment with sorafenib were 86 days in the sorafenib/erlotinib arm and 123 days in the sorafenib/placebo arm .


In the sorafenib/erlotinib and sorafenib/placebo arms , the rates of treatment-emergent serious AEs ( 58.0 % v 54.6 % , respectively ) and drug-related serious AEs ( 21.0 % v 22.8 % , respectively ) were similar .


AEs matched the known safety profiles of both agents , but rates of rash/desquamation , anorexia , and diarrhea were higher in the sorafenib/erlotinib arm , whereas rates of alopecia and hand-foot skin reaction were higher in the sorafenib/placebo arm .


Withdrawal rates for AEs during cycles 1 to 3 were higher in the sorafenib/erlotinib arm .


Adding erlotinib to sorafenib did not improve survival in patients with advanced HCC .


Human 's life as well as medical professions consist of many moral dilemmas .


The aim of our study was to evaluate moral competences of midwifery students during their whole university education ( 3 year course ) based on their moral competences C-index .


We performed randomized single blinded 3-year follow-up trial of 72 midwifery students .


Standard Moral Judgment Test ( MJT ) By Georg Lind was used accompanied by own questionnaire .


Moral competences were calculated ( C-index ) according to Lind 's methodology .


Subjects were also divided into active and passive ethics training to search for differences .


C-index varied during studies insignificant ( p = 0.14 ) .


Randomized groups were equal at the beginning point , no significant differences were noticed .


Active ethics teaching did not increase C-index compared to controls in all measuring points ( P1-P4 , respectively p = 0,41 and p = 0,38 ) .


During 3 year studies at medical university moral competences measured by C-index varied insignificantly , but simultaneously the change in C-index was dependent on its value at the beginning of the trial .


There was not statistically significant influence of active ethic 's teaching compared to controls .


Among social factors parents have strongest influence on students ' morality , but growing role of Medical University in this hierarchy raises hopes for improvement in effectiveness of training in ethics .


The aim of this study was to examine whether EndoPredict ( EP ) , a novel genomic expression test , is effective in predicting local recurrence ( LR ) - free survival ( LRFS ) following surgery for breast cancer in postmenopausal women .


In addition , we examined whether EP may help tailor local therapy in these patients .


From January 1996 to June 2004 , 3714 postmenopausal patients were randomly assigned to either tamoxifen or tamoxifen followed by anastrozole within the prospective ABCSG 8 trial .


Using assay scores from EP , we classified breast tumour blocks as either low or high risk for recurrence .


Data were gathered from 1324 patients .


The median follow-up was 72.3 months and the cumulative incidence of LR was 2.6 % ( 0.4 % per year ) .


The risk of LR over a 10-year period among patients with high-risk lesions ( n = 683 ) was significantly higher ( LRFS = 91 % ) when compared with patients with low-risk lesions ( n = 641 ) ( 10-year LRFS = 97.5 % ) ( HR : 1.31 ( 1.16-1 .48 ) P < 0.005 ) .


The groups that received breast conservation surgery ( BCT ) and mastectomy ( MX ) had similar LR rates ( P = 0.879 ) .


Radiotherapy ( RT ) after BCT significantly improved LRFS in the cohorts predicted by EP to be low-risk for LR ( received RT : n = 436 , 10-year LRFS 99.8 % ; did not receive RT : n = 63 , 10-year LRFS 83.6 % , P < 0.005 ) .


EndoPredict is an effective prognostic tool for predicting LRFS .


Among postmenopausal , low-risk patients , EP does not appear to be useful for tailoring local therapy .


Somatostatin ( SST ) receptors ( SSTRs ) are expressed in a number of tissues , including the adrenal cortex , but their role in cortisol secretion has not been well characterized .


The objective of the study was to investigate the expression of SSTRs in the adrenal cortex and cultured adrenocortical cells from primary pigmented nodular adrenocortical disease ( PPNAD ) tissues and to test the effect of a single injection of 100 g of the SST analog octreotide on cortisol secretion in patients with PPNAD .


The study was conducted at an academic research laboratory and clinical research center .


Expression of SSTRs was examined in 26 PPNAD tissues and the immortalized PPNAD cell line CAR47 .


Ten subjects with PPNAD underwent a randomized , single-blind , crossover study of their cortisol secretion every 30 minutes over 12 hours ( 6:00 pm to 6:00 am ) before and after the midnight administration of octreotide 100 g sc .


SSTRs expression was investigated by quantitative PCR and immunohistochemistry .


The CAR47 and primary cell lines were studied in vitro .


The data of the 10 patients were analyzed before and after the administration of octreotide .


All SSTRs , especially SSTR1-3 , were expressed in PPNAD at significantly higher levels than in normal adrenal .


SST was found to differentially regulate expression of its own receptors in the CAR47 cell line .


However , the administration of octreotide to patients with PPNAD did not significantly affect cortisol secretion .


SSTRs are overexpressed in PPNAD tissues in comparison with normal adrenal cortex .


Octreotide did not exert any significant effect on cortisol secretion in a short clinical pilot study in a small number of patients with PPNAD , but long-acting SST analogs targeting multiple SSTRs may be worth investigating in this condition .


By the age of sixteen , one in five children will sustain a mild traumatic brain injury also known as concussion .


Our research found that one in seven school children with mild traumatic brain injury suffer post-concussion syndrome symptoms for three months or longer .


Post-concussion syndrome is associated with significant disability in the child and his/her family and yet there are no evidence-based medical treatments available .


Melatonin has several potential mechanisms of action that could be useful following mild traumatic brain injury , including neuroprotective effects .


The aim of this study is to determine if treatment with melatonin improves post-concussion syndrome in youths following mild traumatic brain injury .


Our hypothesis is that treatment of post-concussion syndrome following mild traumatic brain injury with 3 or 10 mg of sublingual melatonin for 28 days will result in a decrease in post-concussion syndrome symptoms compared with placebo .


Ninety-nine youths with mild traumatic brain injury , aged between 13 and 18 years , who are symptomatic at 30 days post-injury will be recruited .


This study will be conducted as a randomized , double blind , placebo-controlled superiority trial of melatonin .


Three parallel treatment groups will be examined with a 1:1:1 allocation : sublingual melatonin 3 mg , sublingual melatonin 10 mg , and sublingual placebo .


Participants will receive treatment for 28 days .


The primary outcome is a change on the Post-Concussion Symptom Inventory ( Parent and Youth ) .


The secondary outcomes will include neurobehavioral function , health-related quality of life and sleep .


Neurophysiological and structural markers of change , using magnetic resonance imaging techniques and transcranial magnetic stimulation , will also be investigated .


Melatonin is a safe and well-tolerated agent that has many biological properties that may be useful following a traumatic brain injury .


This study will determine whether it is a useful treatment for children with post-concussion syndrome .


Recruitment commenced on 4 December 2014 .


This trial was registered on 6 June 2013 at ClinicalTrials.gov .


NCT01874847 .


Glucagon-like peptide-1 ( GLP-1 ) analogs have recently been promoted as antihyperglycemic agents in critically ill patients with systemic inflammation , but the effects of TNF - on glucose metabolism during GLP-1 administration are unknown .


The objective of the study was to determine whether the infusion of TNF - at high physiological levels impairs GLP-1 's effects on glucose metabolism .


This was a randomized , controlled , cross-over trial .


The study was conducted at a hospital clinical research laboratory .


Twelve healthy males ( aged 24 3 y ; body mass index 22.9 1.3 kg/m ( 2 ) ) .


After an overnight fast , either saline ( 0.9 % ) or recombinant human TNF - ( 1000 ng/m ( 2 ) h ) was infused from t = 0-6 hours .


At t = 2 hours , GLP-1 infusion ( 0.5 pmol/kg min ) began .


From t = 4-6 hours , the GLP-1 infusion rate was increased to 1.2 pmol/kg min .


Plasma glucose was clamped at 5 mmol/L throughout via a variable rate 20 % dextrose infusion .


Trials were 7-14 days apart .


Endogenous glucose production ( EGP ) was measured by the [ 6,6 - ( 2 ) H2 ] glucose isotope tracer dilution method .


GLP-1 infusion suppressed plasma glucagon ( P < .01 ) , elevated plasma insulin , and C-peptide ( P < .01 ) and suppressed EGP ( P < .001 ) during the saline infusion .


In contrast , the infusion of TNF - increased plasma TNF - and IL-6 , elevated body temperature , and blunted the GLP-1-induced suppression of EGP during high-dose GLP-1 infusion ( all P < .05 , TNF - vs saline ) .


However , TNF - infusion lowered plasma GLP-1 during high-dose GLP-1 infusion ( P < .001 ) .


TNF - induces systemic inflammation and reduces plasma GLP-1 , thereby reducing the suppression of EGP during GLP-1 infusion .


This may have clinical relevance if GLP-1 analog drugs are used for the treatment of hyperglycemia in critically ill patients .


To determine the efficacy and safety of azithromycin 1.5 % eye drops in a paediatric population with purulent bacterial conjunctivitis .


This was a multicentre , international , randomised , investigator-masked study in 286 children with purulent discharge and bulbar conjunctival injection .


Patients received either azithromycin 1.5 % eye drops ( twice daily for 3days ) or tobramycin 0.3 % eye drops ( every 2h for 2days , then four times daily for 5days ) .


Clinical signs were evaluated on day ( D ) 0 , 3 and 7 , and cultures on D0 and D7 .


The primary variable was the clinical cure ( absence of bulbar conjunctival injection and discharge ) on D3 in the worse eye for patients with positive cultures on D0 .


286 patients ( mean age 3.2 years ; range 1day-17years ) were included ; 203 had positive cultures on D0 .


Azithromycin was superior to tobramycin in clinical cure rate on D3 ( 47.1 % vs 28.7 % , p = 0.013 ) and was non-inferior to tobramycin on D7 ( 89.2 % vs 78.2 % , respectively ) .


Azithromycin treatment eradicated causative pathogens , including resistant species , with a similar resolution rate to tobramycin ( 89.8 % vs 87.2 % , respectively ) .


These results were confirmed in a subgroup of patients younger than 24months old .


Azithromycin 1.5 % eye drops provided a more rapid clinical cure than tobramycin 0.3 % eye drops in the treatment of purulent bacterial conjunctivitis in children , with a more convenient twice-a-day dosing regimen .


Mothers and children living in adverse contexts are at risk of premature death .


To determine the effect of prenatal and infant/toddler nurse home visiting on maternal and child mortality during a 2-decade period ( 1990-2011 ) .


A randomized clinical trial was designed originally to assess the home visiting program 's effect on pregnancy outcomes and maternal and child health through child age 2 years .


The study was conducted in a public system of obstetric and pediatric care in Memphis , Tennessee .


Participants included primarily African American women and their first live-born children living in highly disadvantaged urban neighborhoods , who were assigned to 1 of 4 treatment groups : treatment 1 ( transportation for prenatal care [ n = 166 ] ) , treatment 2 ( transportation plus developmental screening for infants and toddlers [ n = 514 ] ) , treatment 3 ( transportation plus prenatal/postpartum home visiting [ n = 230 ] ) , and treatment 4 ( transportation , screening , and prenatal , postpartum , and infant/toddler home visiting [ n = 228 ] ) .


Treatments 1 and 3 were included originally to increase statistical power for testing pregnancy outcomes .


For determining mortality , background information was available for all 1138 mothers assigned to all 4 treatments and all but 2 live-born children in treatments 2 and 4 ( n = 704 ) .


Inclusion of children in treatments 1 and 3 was not possible because background information was missing on too many children .


Nurses sought to improve the outcomes of pregnancy , children 's health and development , and mothers ' health and life-course with home visits beginning during pregnancy and continuing through child age 2 years .


All-cause mortality in mothers and preventable-cause mortality in children ( sudden infant death syndrome , unintentional injury , and homicide ) derived from the National Death Index .


The mean ( SE ) 21-year maternal all-cause mortality rate was 3.7 % ( 0.74 % ) in the combined control group ( treatments 1 and 2 ) , 0.4 % ( 0.43 % ) in treatment 3 , and 2.2 % ( 0.97 % ) in treatment 4 .


The survival contrast of treatments 1 and 2 combined with treatment 3 was significant ( P = .007 ) ; the contrast of treatments 1 and 2 combined with treatment 4 was not significant ( P = .19 ) , and the contrast of treatments 1 and 2 combined with treatments 3 and 4 combined was significant ( post hoc P = .008 ) .


At child age 20 years , the preventable-cause child mortality rate was 1.6 % ( 0.57 % ) in treatment 2 and 0.0 % ( SE not calculable ) in treatment 4 ; the survival contrast was significant ( P = .04 ) .


Prenatal and infant/toddler home visitation by nurses is a promising means of reducing all-cause mortality among mothers and preventable-cause mortality in their first-born children living in highly disadvantaged settings .


clinicaltrials.gov Identifier : NCT00708695 .


Radial artery ( RA ) was the second arterial graft introduced in clinical practice for myocardial revascularization .


The skeletonization technique of the left internal thoracic artery ( LITA ) may actually change the graft 's flow capacity with potential advantages .


This leads to the assumption that the behavior of the RA , as a coronary graft , is similar to that of the LITA , when skeletonized .


This study evaluated ` free ' aortic-coronary radial artery ( RA ) grafts , whether skeletonized or with adjacent tissues .


A prospective randomized study comparing 40 patients distributed into two groups was conducted .


In group I , we used skeletonized radial arteries ( 20 patients ) , and in group II , we used radial arteries with adjacent tissues ( 20 patients ) .


After the surgical procedure , patients underwent flow velocity measurements .


The main surgical variables were : RA internal diameter , RA length , and free blood flow in the radial artery .


The mean RA graft diameters as calculated using quantitative angiography in the immediate postoperative period were similar , as well as the flow velocity measurement variables .


On the other hand , coronary cineangiography showed the presence of occlusion in one RA graft and stenosis in five RA grafts in GII , while GI presented stenosis in only one RA graft ( p = 0.045 ) .


These results show that the morphological and pathological features , as well as the hemodynamic performance of the free radial artery grafts , whether prepared in a skeletonized manner or with adjacent tissues , are similar .


However , a larger number of non-obstructive lesions may be observed when RA is prepared with adjacent tissues .


Skeletal muscle from sedentary older adults exhibits reduced mitochondrial abundance and oxidative capacity .


The primary objective was to determine whether 8 weeks of combined training ( CT ) has a more robust effect than endurance training ( ET ) or resistance training ( RT ) on mitochondrial physiology in healthy young ( 18-30 years ) and older ( 65 years ) adults .


Thirty-four young and 31 older adults were randomly assigned to 8 weeks of ET , RT , and control/CT .


Control subjects completed 8 weeks of no exercise ( control ) followed by 8 weeks of CT. .


Body composition , skeletal muscle strength , and peak oxygen uptake were measured before and after the intervention .


Vastus lateralis muscle biopsy samples were obtained before and 48 hours after the intervention .


Mitochondrial physiology was evaluated by high-resolution respirometry and expression of mitochondrial proteins and transcription factors by quantitative PCR and immunoblotting .


ET and CT significantly increased oxidative capacity and expression of mitochondrial proteins and transcription factors .


All training modalities improved body composition , cardiorespiratory fitness , and skeletal muscle strength .


CT induced the most robust improvements in mitochondria-related outcomes and physical characteristics despite lower training volumes for the ET and RT components .


Importantly , most of the adaptations to training occurred independent of age .


Collectively , these results demonstrate that both ET and CT increase muscle mitochondrial abundance and capacity although CT induced the most robust improvements in the outcomes measured .


In conclusion , CT provides a robust exercise regimen to improve muscle mitochondrial outcomes and physical characteristics independent of age .


The efficacy of posttraumatic stress disorder ( PTSD ) treatments in psychosis has not been examined in a randomized clinical trial to our knowledge .


Psychosis is an exclusion criterion in most PTSD trials .


To examine the efficacy and safety of prolonged exposure ( PE ) therapy and eye movement desensitization and reprocessing ( EMDR ) therapy in patients with psychotic disorders and comorbid PTSD .


A single-blind randomized clinical trial with 3 arms ( N = 155 ) , including PE therapy , EMDR therapy , and waiting list ( WL ) of 13 outpatient mental health services among patients with a lifetime psychotic disorder and current chronic PTSD .


Baseline , posttreatment , and 6-month follow-up assessments were made .


Participants were randomized to receive 8 weekly 90-minute sessions of PE ( n = 53 ) , EMDR ( n = 55 ) , or WL ( n = 47 ) .


Standard protocols were used , and treatment was not preceded by stabilizing psychotherapeutic interventions .


Clinician-rated severity of PTSD symptoms , PTSD diagnosis , and full remission ( on the Clinician-Administered PTSD Scale ) were primary outcomes .


Self-reported PTSD symptoms and posttraumatic cognitions were secondary outcomes .


Data were analyzed as intent to treat with linear mixed models and generalized estimating equations .


Participants in the PE and EMDR conditions showed a greater reduction of PTSD symptoms than those in the WL condition .


Between-group effect sizes were 0.78 ( P < .001 ) in PE and 0.65 ( P = .001 ) in EMDR .


Participants in the PE condition ( 56.6 % ; odds ratio [ OR ] , 3.41 ; P = .006 ) or the EMDR condition ( 60.0 % ; OR , 3.92 ; P < .001 ) were significantly more likely to achieve loss of diagnosis during treatment than those in the WL condition ( 27.7 % ) .


Participants in the PE condition ( 28.3 % ; OR , 5.79 ; P = .01 ) , but not those in the EMDR condition ( 16.4 % ; OR , 2.87 ; P = .10 ) , were more likely to gain full remission than those in the WL condition ( 6.4 % ) .


Treatment effects were maintained at the 6-month follow-up in PE and EMDR .


Similar results were obtained regarding secondary outcomes .


There were no differences in severe adverse events between conditions ( 2 in PE , 1 in EMDR , and 4 in WL ) .


The PE therapy and EMDR therapy showed no difference in any of the outcomes and no difference in participant dropout ( 24.5 % in PE and 20.0 % in EMDR , P = .57 ) .


Standard PE and EMDR protocols are effective , safe , and feasible in patients with PTSD and severe psychotic disorders , including current symptoms .


A priori exclusion of individuals with psychosis from evidence-based PTSD treatments may not be justifiable .


isrctn.com Identifier : ISRCTN79584912 .


Until recently , non-specific low back pain ( NSLBP ) in adolescents was considered a rare phenomenon unlike in adults .


The last two decades has shown an increasing amount of research highlighting the prevalence in this age group .


Recent studies estimate lifetime prevalence at 7 % -80 % , point prevalence at 10 % -15 % , and prevalence of recurrent NSLBP at 13 % -36 % .


In Zimbabwe , there is dearth of literature on the magnitude of the problem in adolescents .


Therefore , the aims of the study were to determine the prevalence ( lifetime , point , recurrent ) and the nature of recurrent NSLBP reported by adolescents in secondary schools .


A cross-sectional study was conducted using a questionnaire .


A cluster sample of 544 adolescents ( age 13-19 years ) randomly derived from government schools participated in the study .


Lifetime prevalence , point prevalence and prevalence of recurrent NSLBP were presented as percentages of the total population .


Exact 95 % confidence intervals were given .


Chi-square test was used to evaluate the effect of gender and age on prevalence .


The students ' response rate was 97.8 % .


The lifetime prevalence was 42.9 % [ 95 % confidence interval = 40.8-44 .6 ] with no significant difference between sexes [ 2 ( 1 ) = 0.006 , p = 0.94 ] .


However , NSLBP peaked earlier in female students ( 13.9 years ) than in male students ( 15 years ) [ t ( 226 ) = 4.21 , p < 0.001 ] .


About 10 % of the adolescents reported having an episode of NSLBP on the day of the survey .


However , female students ( 14.2 % ) were more affected on the day [ 2 ( 1 ) = 11.2 , p < 0.001 ] .


Twenty-nine percent of the adolescents experienced recurrent NSLBP with 78 % experiencing at least three episodes in the last 12 months .


On average , recurrent NSLBP reported was mild in intensity ( 4.8 1.9 ) on the visual analogue scale ( VAS ) and short in duration .


Recurrent NSLBP was associated with sciatica in 20.9 % of adolescents .


NSLBP is a common occurrence among Zimbabwean adolescents in secondary schools .


It increases with chronological age and is recurrent in the minority of adolescents .


Although much of the symptomatology may be considered benign , the existence of recurrent NSLBP in adolescents before their work-life begins should be a concern to health professionals , teachers and parents .


We evaluated the efficacy of low-molecular-weight heparin ( LMWH ) relative to aspirin in preventing early neurologic deterioration ( END ) , venous thromboembolism ( VTE ) , and outcomes at 6months .


Patients were randomly assigned to receive either subcutaneous enoxaparin 4000 anti-factor Xa IU/0 .4 mL twice daily or oral aspirin 200mg daily for 10days .


After day 10 , all subjects received aspirin 100mg once daily for 6months .


We assessed whether LMWH was superior to aspirin in preventing END and VTE within the first 10days after index stroke and evaluated 6-month outcomes .


Of the total 1368 patients , 7.89 % suffered from END , and 2.85 % suffered from deep-vein thrombosis during the first 10days , with a significance difference between the LMWH group and aspirin group ( 3.95 % , 1.46 % versus 11.82 % , 4.23 % , respectively ) .


At 6months , there was a significant difference in the frequency of good outcomes among patients over the median age of 70years ( LMWH 63.8 % versus aspirin 44.6 % ) .


The benefit of LMWH was also significant in patients with symptomatic stenosis of the posterior circulation and basilar artery ( 75.2 % and 82 % for LMWH versus 40.5 % and 48 % for aspirin , respectively ) .


For patients with acute ischemic stroke , treatment with LMWH within 48hours of stroke until 10days later may reduce END and deep-vein thrombosis during the first 10days .


LMWH appears to have advantages over aspirin in certain subgroups , such as elderly patients and patients with posterior circulation and basilar artery stenosis .


Using simulation-based mastery learning , residents can be trained to achieve a predefined performance standard in resuscitation .


After mastery is achieved , performance degradation occurs over time .


Prior investigations have shown performance retention of 12-14 months following intensive simulation-based mastery learning sessions .


We sought to investigate the duration of mastery-level resuscitation performance retention after a single 1 - to 2-hour simulation-based mastery learning session .


Randomized , prospective trial .


Medical simulation laboratory .


Convenience sample of 42 pediatric residents .


Baseline resuscitation performance was determined on four standardized simulation scenarios .


After determination of baseline performance , each resident repeated each scenario , as needed , until mastery-level performance was achieved .


Residents were then randomized and retested 2 , 4 , or 6 months later .


Statistical analysis on scores at baseline and retesting were used to determine performances changes from baseline and performance retention over time .


Forty-two residents participated in the study ( 12 in 2 mo group , 14 in 4 mo group , and 16 in 6 mo group ) .


At baseline , postgraduate year-3 residents performed better than postgraduate year-1 residents ( p = 0.003 ) .


Overall performance on each of the four scenarios improved at retesting .


The percent of residents maintaining mastery-level performance showed a significant linear decline ( p = 0.039 ) , with a drop at each retesting interval ; 92 % retained mastery at 2 months , 71 % at 4 months , and 56 % at 6 months .


There was no difference in retention between postgraduate year-1 , postgraduate year-2 , and postgraduate year-3 residents ( p = 0.14 ) .


Residents displayed significant improvements in resuscitation performance after a single simulation-based mastery learning session , but performance declined over time , with less than 60 % retaining mastery-level performance at 6 months .


Our results suggest that relatively frequent refresher training is needed after a single simulation-based mastery learning session .


Additional research is needed to determine the duration of performance retention following any specific simulation-based mastery learning intervention .


Diabetic retinopathy ( DR ) is associated with a higher risk of renal and cardiovascular events .


We sought to compare the risk for renal versus cardiovascular ( CV ) outcomes , stratified by retinopathy severity .


ACCORD was a randomized trial of people with type 2 diabetes , at high-risk for CV disease .


A subgroup ( n = 3,369 from 71 clinics ) had stereoscopic fundus photographs graded centrally .


Participants were stratified at baseline to moderate/severe DR or no/mild DR and were monitored for renal and CV outcomes at follow-up visits over 4 years .


The composite renal outcome was composed of serum creatinine doubling , macroalbuminuria , or end-stage renal disease .


The composite CV outcome was the ACCORD trial primary outcome .


Competing risk techniques were used to estimate the relative risk ( RR ) of renal versus CV composite outcomes within each DR stratum .


The hazards ratio for doubling of serum creatinine and incident CV event in the moderate/severe DR versus no/mild DR strata were : 2.31 ( 95 % CI : 1.25-4 .26 ) and 1.98 ( 95 % CI : 1.49-2 .62 ) , respectively .


The RR of the two composite outcomes was highly similar in the no/mild DR stratum ( adjusted RR at 4 years for CV versus renal events = 0.96 , 95 % CI : 0.72-1 .28 ) and the moderate/severe DR stratum ( adjusted RR = 0.92 , 95 % CI : 0.64-1 .31 ) .


Thus , in people with type 2 diabetes at high risk for cardiovascular disease , incident CV versus renal events was similar , irrespective of the severity of the DR. Further evaluation of the specificity of DR for microvascular versus macrovascular events in other populations is warranted .


We propose a new hybrid brain-computer interface ( BCI ) system that integrates two different EEG tasks : tactile selective attention ( TSA ) using a vibro-tactile stimulator on the left/right finger and motor imagery ( MI ) of left/right hand movement .


Event-related desynchronization ( ERD ) from the MI task and steady-state somatosensory evoked potential ( SSSEP ) from the TSA task are retrieved and combined into two hybrid senses .


One hybrid approach is to measure two tasks simultaneously ; the features of each task are combined for testing .


Another hybrid approach is to measure two tasks consecutively ( TSA first and MI next ) using only MI features .


For comparison with the hybrid approaches , the TSA and MI tasks are measured independently .


Using a total of 16 subject datasets , we analyzed the BCI classification performance for MI , TSA and two hybrid approaches in a comparative manner ; we found that the consecutive hybrid approach outperformed the others , yielding about a 10 % improvement in classification accuracy relative to MI alone .


It is understood that TSA may play a crucial role as a prestimulus in that it helps to generate earlier ERD prior to MI and thus sustains ERD longer and to a stronger degree ; this ERD may give more discriminative information than ERD in MI alone .


Overall , our proposed consecutive hybrid approach is very promising for the development of advanced BCI systems .


Despite the extraordinary scale up of HIV prevention , care and treatment services in sub-Saharan Africa ( SSA ) over the past decade , the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum .


Data from `` real-life '' settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum .


We are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy ( CIS ) using feasible , evidence-based , and practical interventions-including ( 1 ) point-of-care ( POC ) CD4 count testing , ( 2 ) accelerated antiretroviral therapy initiation for eligible individuals , and ( 3 ) SMS reminders for linkage to and retention in care-as compared to the standard of care ( SOC ) in Mozambique in improving linkage and retention among adults following HIV diagnosis .


A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives ( CIS + FI ) compared to the CIS without FI on study outcomes .


Randomization is done at the level of the study site , defined as a primary health facility .


Five sites are included from the City of Maputo and five from Inhambane Province .


Target enrollment is a total of 2,250 adults : 750 in the SOC arm , 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm ( average of 150 participants per site ) .


Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test .


Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted .


Study findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a `` real-life '' service delivery system in a SSA country severely impacted by HIV .


Clinicaltrials.gov , NCT01930084 .


High calcium intakes enhance fat loss under restricted energy intake .


Mechanisms explaining this may involve reduced dietary fat absorption , enhanced lipid utilization and ( or ) reductions in appetite .


This study aimed to assess the impact of 2 weeks of calcium supplementation on substrate utilization during exercise and appetite sensations at rest .


Thirteen physically active males completed two 14-d supplemental periods , in a double-blind , randomized crossover design separated by a 4-week washout period .


During supplementation , a test-drink was consumed daily containing 400 and 1400mg of calcium during control ( CON ) and high-calcium ( CAL ) periods , respectively .


Cycling-based exercise tests were conducted before and after each supplemental period to determine substrate utilization rates and circulating metabolic markers ( non-esterified fatty acid , glycerol , glucose and lactate concentrations ) across a range of exercise intensities .


Visual analog scales were completed in the fasting , rested state to determine subjective appetite sensations .


No significant differences between supplements were observed in lipid or carbohydrate utilization rates , nor in circulating metabolic markers ( both P > 0.05 ) .


Maximum rates of lipid utilization were 0.470.05 and 0.440.05 g/min for CON and CAL , respectively , prior to supplementation and 0.440.05 and 0.420.05 g/min , respectively , post-supplementation ( main effects of time , supplement and time x supplement interaction effect all P > 0.05 ) .


Furthermore , no significant differences were detected in any subjective appetite sensations ( all P > 0.05 ) .


Two weeks of calcium supplementation does not influence substrate utilization during exercise in physically active males .


The objective of the study was to evaluate the efficacy of 17 alpha-hydroxyprogesterone caproate ( 17OHP-C ) in prolonging gestation in patients with a short cervix and other risk factors for preterm delivery , such as previous preterm birth , cervical surgery , uterine anomalies , or prenatal diethylstilbestrol ( DES ) exposure .


This open-label , multicenter , randomized controlled trial included asymptomatic singleton pregnancies from 20 ( +0 ) through 31 ( +6 ) weeks of gestation with a cervical length less than 25 mm and a history of preterm delivery or cervical surgery or uterine malformation or prenatal DES exposure .


Randomization assigned them to receive ( or not ) 500 mg of intramuscular 17OHP-C weekly until 36 weeks .


The primary outcome was time from randomization to delivery .


After enrolling 105 patients , an interim analysis demonstrated the lack of efficacy of 17OHP-C in prolonging pregnancy .


The study was discontinued because of futility .


The groups were similar for maternal age , body mass index , parity , gestational age at inclusion , history of uterine anomalies , DES syndrome , previous preterm delivery or midtrimester abortion , and cervical length at randomization .


The enrollment-to-delivery interval did not differ between patients allocated to 17OHP-C ( n = 51 ) and those allocated to the control group ( n = 54 ) ( median [ interquartile range ] time to delivery : 77 [ 54-103 ] and 74 [ 52-99 ] days , respectively ) .


The rate of preterm delivery less than 37 ( 45 % vs 44 % , P > .99 ) , less than 34 ( 24 % vs 30 % , P = .51 ) , or less than 32 ( 14 % vs 20 % , P = .44 ) weeks was similar in patients allocated to 17OHP-C and those in the control group .


17OHP-C did not prolong pregnancy in women with singleton gestations , a sonographic short cervix , and other risk factors of preterm delivery ( prior history , uterine malformations , cervical surgery , or prenatal DES exposure ) .


The objectives of this trial were to investigate short-term changes in product usage , tobacco-related biomarkers of exposure , and subjective effects in smokers who switched to dissolvable tobacco ( Camel Orbs ) use .


Participants were randomized into 1 of 4 groups ( continued smoking , switched to consuming Orbs , switched to dual use of cigarettes and Orbs , and tobacco abstinent ) and confined for 6 days with dietary restrictions .


Most measurements were at baseline and days 1 , 3 , and 5 of intervention .


Mouth-level tar and nicotine exposures were estimated by filter tip analysis .


Twenty biomarkers were quantified in 24-hr urine ; 4 were quantified in blood/plasma ( carboxyhemoglobin , nicotine , cotinine , and thiocyanate ) .


Ratings for nicotine dependence and withdrawal symptoms were scored .


After 5 days , substantial and statistically significant reductions ( ~ 30 % -90 % ) in all biomarkers were observed in the Orbs and abstinent groups compared to baseline .


Numerous smaller reductions ( ~ 7 % -30 % ) were also noted in the continued smoking and dual-use groups ( generally similar in magnitude for both groups ) .


Subjective questionnaire findings indicated greater withdrawal discomfort levels throughout the intervention period for the nonsmoking groups .


For subjects that continued smoking , clinical confinement conditions did not significantly alter product use behavior and toxicant exposure profile compared to baseline .


Substantial reductions in toxicant exposure occurred for participants that did not smoke .


Cigarette smokers that switched to Orbs use showed reductions in all biomarkers , similar to abstinent group .


Changes in toxicant exposure for the dual-use group were similar to the continued-smoking group , consistent with minimal changes observed in that group 's product use behavior ( small reduction in cigarettes per day and small increase in Orbs use ) .


Our aim was to identify whether particular subgroups of patients had an unacceptably high risk of symptomatic intracranial hemorrhage or low chance of benefit when treated with alteplase ( recombinant tissue-type plasminogen activator ) .


Third International Stroke Trial was an international randomized trial of the intravenous ( IV ) recombinant plasminogen activator alteplase ( 0.9 mg/kg ) versus control in 3035 ( 1515 versus 1520 ) patients .


We analyzed the effect of recombinant tissue-type plasminogen activator on 6-month functional outcome , early death , and symptomatic intracranial hemorrhage ( both 7 days ) .


We tested for any differences in treatment effect between subgroups by a test of interaction .


Our 13 protocol prespecified subgroups were time to randomization , age , sex , stroke subtype , atrial fibrillation , early ischemic change ( clinician and expert panel ) , prior antiplatelet use , stroke severity , diastolic and systolic blood pressure at randomization , center 's thrombolysis experience , and trial phase .


Analyses were adjusted for key baseline prognostic factors .


There were no significant interactions in the subgroups analyzed that were consistent across all 3 outcomes .


Treatment with recombinant tissue-type plasminogen activator increased the odds of symptomatic intracranial hemorrhage by a greater amount in patients taking prior antiplatelets than those who were not ( P = 0.019 for test of interaction ) , but had no clear detrimental effect on functional outcome at 6 months in this group ( P = 0.781 for test of interaction ) .


Among the types of patient in the Third International Stroke Trial , this secondary analysis did not identify any subgroups for whom treatment should be avoided .


Given the limitations of the analysis , we found no clear evidence to avoid treatment in patients with prior ischemic stroke , diabetes mellitus , or hypertension .


http://www.controlled-trials.com .


Unique identifier : ISRCTN25765518 .


http://www.controlled-trials.com/ISRCTN25765518 .


Exercise training induces several beneficial effects in patients with chronic heart failure ( CHF ) .


This study investigated the effects of high-intensity aerobic interval training ( AIT ) compared with combined AIT and strength training ( COM ) on early ventilatory and metabolic recovery pattern after symptom-limited cardiopulmonary exercise testing ( CPET ) in CHF patients .


Stable CHF patients ( N = 42 ; 54 10 years [ mean SD ] , 35 males ) participated in an exercise training program for 12 weeks , 3 times per week .


Participants were randomly assigned to either AIT ( n = 20 ) or COM group ( n = 22 ) .


Cardiopulmonary exercise testing was performed before and after completion of the program .


Primary measurements included absolute and percentage difference of oxygen uptake , carbon dioxide output , minute ventilation ( ( Equation is included in full-text article . )


E ) , tidal volume ( VT ) , respiratory rate , and the first-degree slope of oxygen uptake ( ( Equation is included in full-text article . )


O2/t slope ) and carbon dioxide output ( ( Equation is included in full-text article . )


CO2/t slope ) during the first minute of recovery after maximal exercise .


The COM group had a greater improvement in the absolute and the percentage difference of ( Equation is included in full-text article . )


E ( P = .03 and P = .04 , respectively ) and respiratory rate ( P = .02 and P = .01 , respectively ) during the first minute of recovery period after exercise compared with the AIT group alone .


No significant changes were noted for VT measurements .


A significant increase in ( Equation is included in full-text article . )


CO2/t slope was observed in COM compared with the AIT group ( P = .01 ) .


There was a trend for a greater increase in ( Equation is included in full-text article . )


O2/t slope in the COM group ( P = .07 ) .


The addition of strength training to AIT induces significant beneficial effects in terms of ventilatory and metabolic recovery kinetics than AIT alone in CHF patients , possibly indicating greater ventilatory efficiency and metabolic improvement .


The DBCG-IMN is a nationwide population-based cohort study on the effect of internal mammary node radiotherapy ( IMN-RT ) in patients with node positive early breast cancer .


Due to the risk of RT-induced heart disease , only patients with right-sided breast cancer received IMN-RT , whereas patients with left-sided breast cancer did not .


At seven-year median follow-up , a 3 % gain in overall survival with IMN-RT has been reported .


This study estimates IMN doses and doses to organs at risk ( OAR ) in patients from the DBCG-IMN .


Numbers needed to harm ( NNH ) if patients with left-sided breast cancer had received IMN-RT are compared to the number needed to treat ( NNT ) .


Ten percent of CT-guided treatment plans from the DBCG-IMN patients were selected randomly .


IMNs and OAR were contoured in 68 planning CT scans .


Dose distributions were re-calculated .


IMNs and OAR dose estimates were compared in right-sided versus left-sided breast cancer patients .


In six left-sided patients , IMN-RT was simulated , and OAR doses were compared to those in the original plan .


The NNH resulting from the change in mean heart dose ( MHD ) was calculated using a published model for risk of RT-related ischemic heart death .


In original plans , the absolute difference between right - and left-sided V90 % to the IMNs was 38.0 % [ 95 % confidence interval ( 5.5 % ; 70.5 % ) , p < 0.05 ] .


Heart doses were higher in left-sided plans .


With IMN-RT simulation without regard to OAR constraints , MHD increased 4.8 Gy ( 0.9 Gy ; 8.7 Gy ) , p < 0.05 .


Resulting NNHs from ischemic heart death were consistently larger than the NNT with IMN-RT .


Refraining from IMN-RT on the left side may have spared some ischemic heart deaths .


Assuming left-sided patients benefit as much from IMN-RT as right-sided patients , the benefits from IMN-RT outweigh the costs in terms of ischemic heart death .


To investigate the impact and mechanisms of vitamin D deficiency ( VDD ) on the outcome of elderly patients with diffuse large B-cell lymphoma ( DLBCL ) .


Three hundred fifty-nine pretreatment 25-hydroxyvitamin D3 ( 25 [ OH ] D3 ) serum levels from the RICOVER-60 study ( Six Versus Eight Cycles of Biweekly CHOP-14 With or Without Rituximab in Elderly Patients With Aggressive CD20 + B-Cell Lymphomas ) and 63 from the RICOVER-noRTh study ( an amendment to the RICOVER-60 study in which patients received six cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone administered at an interval of 2 weeks plus two cycles of rituximab [ R-CHOP-14 ] , but without radiotherapy ) were determined by chemoluminescent immunoassay .


Rituximab-mediated cellular cytotoxicity ( RMCC ) was assessed by lactate dehydrogenase release assay of CD20 + Daudi cells .


RICOVER-60 patients with VDD ( 8 ng/mL ) and vitamin D levels more than 8 ng/mL treated with rituximab had 3-year event-free survival ( EFS ) of 59 % and 79 % and 3-year overall survival ( OS ) of 70 % and 82 % , respectively .


These differences were significant in a multivariable analysis adjusting for International Prognostic Index risk factors with a hazard ratio ( HR ) of 2.1 ( P = .008 ) for EFS and 1.9 ( P = .040 ) for OS .


EFS was not significantly different in patients with vitamin D levels 8 or more than 8 ng/mL ( HR , 1.2 ; P = .388 ) treated without rituximab .


This was confirmed in an independent validation set of 63 RICOVER-noRTh patients .


RMCC increased significantly ( P < .001 ) in seven of seven individuals with VDD after substitution and normalization of their vitamin D levels .


VDD is a risk factor for elderly patients with DLBCL treated with R-CHOP .


That VDD impairs RMCC and substitution improves RMCC strongly suggests that vitamin D substitution enhances rituximab efficacy , which must be confirmed in appropriately designed prospective trials addressing VDD and substitution not only in DLBCL , but also in malignancies treated with other antibodies , of which the major mechanism of action is antibody-dependent cellular cytotoxicity ( eg , trastuzumab in breast cancer and cetuximab in colorectal cancer ) .


Several additives have been suggested to enhance analgesic effect of local anesthetic agents to decrease the adverse effects of them and increase the degree of satisfaction .


We designed this randomized double-blind controlled study to evaluate the analgesic efficacy of the neostigmine added to bupivacaine using spinal anesthesia in patients undergoing lower limb orthopedic surgery .


Sixty patients 18-80 yr old American Society of Anesthesiologists ( ASA ) physical status I or II , scheduled for femur surgery under spinal anesthesia , were recruited in a prospective , double-blinded , randomized way .


The patients were randomly allocated to one of two groups of 30 each .


The neostigmine group ( group N ) received bupivacaine 20 mg combined with 25 g neostigmine , and the placebo group ( group C ) received bupivacaine 20 mg combined with 0.5 ml distilled water ( intrathecally ) 5 minutes prior to surgery .


The time to the first analgesic request , analgesic requirement in the first 12 hours after surgery , the duration of sensory and motor blockade , the incidence of adverse effects such as nausea , vomiting , hypotension , ephedrine requirements , bradycardia , and hypoxemia were recorded .


Patients receiving neostigmine had a significantly prolonged duration of motor block ( C95 % CI 30.27 to 87.65 ; P < 0.001 ) and sensory block ( C95 % CI 101.04 to 224.64 ; P < 0.001 ) compared to the control group .


The difference of the mean time to the first analgesic request was also significantly longer in neostigmine group ( C95 % CI 83.139 to 208.526 ; P < 0.001 ) .


The total analgesic consumption during the first 12 hours after surgery was devoid of any significant difference between groups N and C ( p = 0.41 ) .


The two groups were not significantly different in terms of intraoperative and postoperative side effects .


Intrathecal neostigmine 25 g with bupivacaine caused a prolonged time to the first analgesic request and its use was not associated with any side effects .


To analyze pomegranate extract ( POMx ) effects on serum and on human HMDM atherogenicity in simvastatin - treated hypercholesterolemic patients .


Patients were randomly assigned to receive either simvastatin ( 20 mg/day ) + vegan placebo pill ( n = 11 ) , or simvastatin ( 20 mg/day ) + POMx pill ( 1g/day , n = 12 ) .


Fasting blood samples were collected at baseline and after 1 and 2 months of therapy .


HMDM were collected from 3 patients in each group at baseline and after 2 months of therapy , as well as from 3 healthy subjects .


After 2 months of therapy , serum LDL-cholesterol levels significantly decreased , by 23 % , in the simvastatin + placebo group , and by 26 % in the simvastatin + POMx group .


Simvastatin + POMx therapy increased serum thiols concentration by 6 % .


Patients ' HMDM reactive oxygen species ( ROS ) levels were significantly increased , by 69 % , vs. healthy subjects HMDM .


After 2 months of therapy , HMDM ROS levels decreased by 18 % in the simvastatin + placebo group , whereas in the simvastatin + POMx group it decreased by up to 30 % .


A novel finding was the triglycerides levels in the patients ' HMDM at baseline which were significantly higher , by 71 % , vs. healthy subjects HMDM .


The simvastatin + POMx , but not the simvastatin + placebo therapy , significantly reduced macrophage triglycerides content by 48 % , vs. baseline levels .


In addition , whereas the simvastatin + placebo therapy significantly decreased the patients ' HMDM cholesterol biosynthesis rate by 33 % , the simvastatin + POMx therapy further decreased it , by 44 % .


The addition of POMx to simvastatin therapy in hypercholesterolemic patients improved oxidative stress and lipid status in the patient 's serum and in their HMDM .


These anti-atherogenic effects could reduce the risk for atherosclerosis development .


To estimate the incremental cost-effectiveness of tuberculosis ( TB ) screening and isoniazid preventive therapy ( IPT ) among human immunodeficiency virus ( HIV ) infected adults in Rio de Janeiro , Brazil .


We used decision analysis , populated by data from a cluster-randomized trial , to project the costs ( in 2010 USD ) and effectiveness ( in disability-adjusted life years [ DALYs ] averted ) of training health care workers to implement the tuberculin skin test ( TST ) , followed by IPT for TST-positive patients with no evidence of active TB .


This intervention was compared to a baseline of usual care .


We used time horizons of 1 year for the intervention and 20 years for disease outcomes , with all future DALYs and medical costs discounted at 3 % per year .


Providing this intervention to 100 people would avert 1.14 discounted DALYs ( 1.57 undiscounted DALYs ) .


The median estimated incremental cost-effectiveness ratio was $ 2273 ( IQR $ 1779 - $ 3135 ) per DALY averted , less than Brazil 's 2010 per capita gross domestic product ( GDP ) of $ 11,700 .


Results were most sensitive to the cost of providing the training .


Training health care workers to screen HIV-infected adults with TST and provide IPT to those with latent tuberculous infection can be considered cost-effective relative to the Brazilian GDP per capita .


The present study is an open-label extension ( OLE ) aimed at evaluating the effect of 100 mg/day of phosphatidylserine enriched with docosahexaenoic acid ( PS-DHA ) on cognitive performance in nondemented elderly individuals with memory complaints .


From the participants who completed the core study , 122 continued with a 15-week OLE .


Efficacy was assessed using a computerized tool and the Clinical Global Impression of Change ( CGI-C ) rating scale .


A significant improvement in sustained attention and memory recognition was observed in the PS-DHA nave group , while the PS-DHA continuers maintained their cognitive status .


Additionally , a significant improvement in CGI-C was observed in the nave group .


The results demonstrate that consumption of 100 mg/day of PS-DHA might be associated with improving or maintaining cognitive status in elderly subjects with memory complaints .


To evaluate the effects of terazosin and tolterodine on ureteral stent discomfort .


Of 163 patients assessed for eligibility , 104 patients were randomly assigned to receive placebo , 2 mg of terazosin twice daily , 2 mg of tolterodine daily , or both terazosin plus tolterodine during the stenting period .


Prior to stenting and at stent removal , the International Prostate Symptom Score ( IPSS ) , the IPSS quality of life ( QoL ) subscore and the Visual Analog Scale for Pain were determined .


The patients also reported their analgesic use during the stenting period .


Ninety-four patients completed the study .


We noted significant decreases in the total IPSS scores ( p = 0.002 ) , irritative subscore ( p = 0.039 ) , QoL ( p = 0.001 ) , flank pain ( p = 0.013 ) , voiding pain ( p = 0.01 ) and amount of analgesics used ( p = 0.02 ) in the groups .


However , neither the obstructive subscore nor the suprapubic pain improved significantly ( p = 0.251 and p = 0.522 , respectively ) .


The patients receiving terazosin plus tolterodine experienced significant reductions in the total IPSS , irritative symptoms , QoL , flank pain , voiding pain and decreased analgesics use compared with those patients receiving placebo .