We conducted a double-blind randomized controlled trial in VLBW infants randomized to parenteral nutrition with the multicomponent ( study group ) or pure soybean oil emulsion ( control group ) from birth at a dose of 2 to 3 g kg ( -1 ) day ( -1 ) until the infants were receiving full enteral nutrition .


We assessed efficacy by growth rates and measuring plasma fatty acid profiles ( representative subset ) .


Safety was evaluated by assessing hematologic and biochemical parameters , potentially harmful phytosterol concentrations ( same subset ) , and clinical neonatal outcome parameters .


Ninety-six infants were included ( subsets n = 21 ) .


The multicomponent emulsion was associated with higher weight and head circumference z scores during admission .


Plasma eicosapentaenoic acid and docosahexaenoic acid concentrations were higher in the study group .


The hematological , biochemical , and neonatal outcomes were not different between groups , whereas the plasma concentrations of phytosterols were higher in the control group .


The multicomponent lipid emulsion was well tolerated and associated with improved growth and higher plasma fatty acid profiles in VLBW infants in comparison with the pure soybean oil emulsion .


Recently , intense pulsed light ( IPL ) and low-fluence Q-switched neodymium-doped yttrium aluminum ( LF-QS-Nd : YAG ) laser have been successfully used to treat melasma .


To evaluate the effectiveness and safety of combined novel fractionated IPL ( IPL-F ) with LF-QS-Nd : YAG laser in patients with melasma .


Twelve patients underwent 6 treatment sessions of concomitant IPL-F and LF-QS-Nd : YAG laser ( combination group ) , and 12 patients underwent 6 treatment session of IPL-F alone ( IPL only group ) .


Partial melasma area and severity index ( MASI ) scores were evaluated by 2 dermatologists using digital photography .


In the combination group , the partial MASI score has significantly decreased by 47 % at 1 month after the treatment ( p < .05 ) and 50 % at 2 months after the last treatment ( p < .01 ) .


At 1 month and 2 months after the treatment , the decrease in the partial MASI score of the combination group was significantly larger than that of the IPL only group ( p < .05 ) .


In both groups , treatment with IPL-F and LF-QS-Nd : YAG laser was well tolerated .


Our results suggest that the combination of the IPL-F with LF-QS-Nd : YAG laser may be an effective and safe modality for melasma patients .


Although serrated polyps may be precursors of colorectal cancer ( CRC ) , prospective data on the long-term CRC risk in individuals with serrated polyps are lacking .


In a population-based randomised trial , 12,955 individuals aged 50-64years were screened with flexible sigmoidoscopy , while 78220 individuals comprised the control arm .


We used Cox models to estimate HRs with 95 % CIs for CRC among individuals with 1 large serrated polyp ( 10mm in diameter ) , compared with individuals with adenomas at screening , and to population controls , and multivariate logistic regression to assess polyp risk factors for CRC .


A total of 103 individuals had large serrated polyps , of which 81 were included in the analyses .


Non-advanced adenomas were found in 1488 individuals , advanced adenomas in 701 .


Median follow-up was 10.9 years .


Compared with the control arm , the HR for CRC was 2.5 ( 95 % CI 0.8 to 7.8 ) in individuals with large serrated polyps , 2.0 ( 95 % CI 1.3 to 2.9 ) in individuals with advanced adenomas and 0.6 ( 95 % CI 0.4 to 1.1 ) in individuals with non-advanced adenomas .


A large serrated polyp was an independent risk factor for CRC , adjusted for histology , size and multiplicity of concomitant adenomas ( OR 3.3 ; 95 % CI 1.3 to 8.6 ) .


Twenty-three large serrated polyps found at screening were left in situ for a median of 11.0 years .


None developed into a malignant tumour .


Individuals with large serrated polyps have an increased risk of CRC , comparable with individuals with advanced adenomas .


However , this risk may not be related to malignant growth of the serrated polyp .


The Norwegian Colorectal Cancer Screening trial is registered at clinicaltrials.gov ( NCT00119912 ) .


Nonalcoholic fatty liver disease ( NAFLD ) is characterized by high intrahepatic triglyceride level .


It is associated with an increased prevalence of cardiovascular disease , independently of underlying cardiometabolic risk factors .


Metformin is used as a pharmacological treatment ; the adherence is low because of the presence of adverse effects .


Aerobic exercise could be an alternative therapy , but its effectiveness compared with metformin has not been established in the treatment of NAFLD .


The aim of this study was to establish the effectiveness of aerobic exercise and its influence in reducing cardiovascular risk in overweight or obese women with NAFLD .


Sedentary women 25-60 years old with body mass index ( BMI ) > 24.9 kg/m2 and liver fat content < 50 HU , were randomly divided into two parallel groups : exercise group ( EG ) or metformin group ( MG ) .


The EG performed an aerobic exercise program of 60 min/5 days / week at 60-85 % of heart rate reserve ; the MG took 1 g/day of metformin each morning .


The duration of the intervention was 12 weeks .


The liver fat content , metabolic and cardiorespiratory - fitness parameters were evaluated at the beginning and end of the program .


The study complied with the Helsinki ethics codes for human research .


The study included a sample of 16 women , with 8 per group .


The treatments modified the liver fat content by 14.6 % ( CI95 % 0.92 , 28.36 ) and 10.37 % ( CI95 % -1.74 , 22.48 ) for the EG and MG , respectively .


In the EG , the insulin levels and HOMA-IR decreased ( P < 0.05 ) , and the cardiovascular fitness improved .


An aerobic exercise program of 12 weeks with a volume training of 300 min/week and a moderate to vigorous intensity ( 60-85 % VO2peak ) modified the liver fat content and improved cardiovascular risk factors during the intervention .


Exercise contributed to a holistic approach by modifying a number of the components of metabolic syndrome , cardiorespiratory-fitness , and cardiovascular risk .


Brief interventions via the internet have been shown to reduce university students ' alcohol intake .


This study tested two smartphone applications ( apps ) targeting drinking choices on party occasions , with the goal of reducing problematic alcohol intake among Swedish university students .


Students were recruited via e-mails sent to student union members at two universities .


Those who gave informed consent , had a smartphone , and showed risky alcohol consumption according to the Alcohol Use Disorders Identification Test ( AUDIT ) were randomized into three groups .


Group 1 had access to the Swedish government alcohol monopoly 's app , Promillekoll , offering real-time estimated blood alcohol concentration ( eBAC ) calculation ; Group 2 had access to a web-based app , PartyPlanner , developed by the research group , offering real-time eBAC calculation with planning and follow-up functions ; and Group 3 participants were controls .


Follow-up was conducted at 7weeks .


Among 28574 students offered participation , 4823 agreed to join ; 415 were excluded due to incomplete data , and 1932 fulfilled eligibility criteria for randomization .


Attrition was 22.7-39 .3 percent , higher among heavier drinkers and highest in Group 2 .


Self-reported app use was higher in Group 1 ( 74 % ) compared to Group 2 ( 41 % ) .


Per-protocol analyses revealed only one significant time-by-group interaction , where Group 1 participants increased the frequency of their drinking occasions compared to controls ( p = 0.001 ) .


Secondary analyses by gender showed a significant difference among men in Group 1 for frequency of drinking occasions per week ( p = 0.001 ) , but not among women .


Among all participants , 29 percent showed high-risk drinking , over the recommended weekly drinking levels of 9 ( women ) and 14 ( men ) standard glasses .


Smartphone apps can make brief interventions available to large numbers of university students .


The apps studied using eBAC calculation did not , however , seem to affect alcohol consumption among university students and one app may have led to a negative effect among men .


Future research should : 1 ) explore ways to increase user retention , 2 ) include apps facilitating technical manipulation for evaluation of added components , 3 ) explore the effects of adapting app content to possible gender differences , and 4 ) offer additional interventions to high-risk users .


clinicaltrials.gov : NCT01958398 .


Evogliptin ( DA-1229 ) is a novel , potent , and selective dipeptidyl peptidase IV ( DPP-IV ) inhibitor in clinical development for the treatment of type 2 diabetes mellitus .


This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles and tolerability of evogliptin after repeated oral administration in healthy subjects .


A block-randomized , double-blind , placebo-controlled , multiple-dose , dose-escalation study was performed in a total of 30 subjects .


Repeated once-daily doses of 5 , 10 , or 20 mg evogliptin or the same doses of placebo were orally administered to ten subjects in each dosage group for 10 days .


Subjects in each group were randomized to receive evogliptin or placebo with a ratio of 8:2 .


Pharmacokinetics of evogliptin were evaluated , with its concentrations in serial plasma and urine samples collected following the first and last administrations .


DPP-IV activity and glucagon-like peptide-1 , glucose , and insulin levels were quantified to evaluate evogliptin 's pharmacodynamics on the first and last dosing days .


All participants completed the study without any serious or severe adverse event .


The evogliptin plasma concentration reached its peak within 4-5 hours and decreased relatively slowly , with a terminal elimination half-life of 33-39 hours .


Repeated administration resulted in a 1.4 - to 1.5-fold accumulation .


Evogliptin 's systemic exposure and inhibition of plasma DPP-IV activity increased in a dose-dependent manner .


Inhibition of DPP-IV activity > 80 % was sustained over 24 hours in all evogliptin dose groups and provided an increase in postprandial active glucagon-like peptide-1 levels by 1.5 - to 2.4-fold .


Postprandial glucose levels in the evogliptin-treated groups were reduced 20 % -35 % compared to placebo , but were not accompanied by increased insulin levels .


Repeated administration of evogliptin in healthy subjects was well tolerated and exhibited linear pharmacokinetics within the 5-20 mg dose range .


A once-daily regimen of 5-20 mg evogliptin effectively inhibited DPP-IV activity .


Taurine 's role in bile acid metabolism and anti-inflammatory activity could exert a protective effect on hepatobiliary complications associated with parenteral nutrition ( PN ) .


In this study , the effects of 2 amino acid solutions , with and without taurine , on liver function administered to nonacutely ill postsurgical patients as part of a short-term PN regimen were prospectively compared .


Adult patients randomly received ( double-blind ) Tauramin 10 % or a standard PN solution without taurine as the control ( 1.5 g amino acid/kg body weight [ bw ] / d ; infusion rate of 4 mg glucose/kg bw/d ) for a period of 5-30 days .


- Glutamyl transpeptidase ( GGT ) and other indicators of liver function , glucose metabolism , lipid profile , inflammation markers , and treatment safety data were collected .


Thirty-five patients receiving taurine PN and 39 receiving control PN were enrolled ( intention-to-treat [ ITT ] population ) .


Most patients ( n = 62 ) discontinued after day 7 of follow-up ( per-protocol [ PP ] population : n = 24 and n = 27 , respectively ) .


ITT patients with high GGT values after 5 days of PN comprised 68.6 % and 64.1 % , respectively .


The mean change in GGT values with respect to the baseline values was 167 192 and 157 185 IU/L , respectively .


Low-density lipoprotein ( LDL ) cholesterol levels after 7 days of PN were significantly decreased in the taurine PN group of PP patients ( -2.83 30.9 vs 23.9 27.0 mg/dL for control PN ; P < .05 ) .


None of the adverse events reported ( taurine PN : n = 6 ; control PN : n = 7 ) were treatment related .


PN solutions with and without taurine had similar effects on liver function parameters , except for an LDL reduction in PN with taurine , when administered to nonacutely ill postsurgical patients in the short term ( 5-7 days ) .


Deep brain stimulation ( DBS ) improves motor symptoms in Parkinson 's disease ( PD ) , but questions remain regarding neuropsychological decrements sometimes associated with this treatment , including rates of statistically and clinically meaningful change , and whether there are differences in outcome related to surgical target .


Neuropsychological functioning was assessed in patients with Parkinson 's disease ( PD ) at baseline and after 6 months in a prospective , randomised , controlled study comparing best medical therapy ( BMT , n = 116 ) and bilateral deep brain stimulation ( DBS , n = 164 ) at either the subthalamic nucleus ( STN , n = 84 ) or globus pallidus interna ( GPi , n = 80 ) , using standardised neuropsychological tests .


Measures of functional outcomes were also administered .


Comparison of the two DBS targets revealed few significant group differences .


STN DBS was associated with greater mean reductions on some measures of processing speed , only one of which was statistically significant in comparison with stimulation of GPi .


GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility .


Compared to the group receiving BMT , the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory .


After calculating thresholds for statistically reliable change from data obtained from the BMT group , the combined DBS group also displayed higher rates of decline in neuropsychological test performance .


Among study completers , 18 ( 11 % ) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains , a significantly higher rate than in the BMT group ( 3 % ) .


This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life ( QOL ) .


The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up .


In those with PD , the likelihood of significant decline in neuropsychological functioning increases with DBS , affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL .


NCT00056563 and NCT01076452 .


Posttraumatic stress disorder ( PTSD ) and alcoholism are frequently comorbid , suggesting the possibility of overlapping neural substrates .


The neurokinin 1 ( NK1 ) receptor for substance P ( SP ) has been implicated in both stress - and alcohol-related behaviors .


The NK1 antagonist aprepitant , clinically available as a treatment for chemotherapy-induced nausea , offers a tool to probe a potential role of the SP/NK1 system in comorbid PTSD and alcoholism .


The aim of this study is to evaluate the efficacy of aprepitant for treatment of comorbid PTSD and alcoholism .


Fifty-three patients with PTSD and alcoholism were admitted for 4 weeks to an inpatient unit at the NIH Clinical Center and randomized to double-blind aprepitant ( 125 mg/day ; based on PET studies reporting > 90 % central receptor occupancy at this dose ) or placebo .


After reaching steady state , subjects were assessed for PTSD symptom severity , behavioral and neuroendocrine responses to stress and alcohol cues , and functional magnetic resonance imaging ( fMRI ) responses to stimuli with positive or negative emotional valence .


Aprepitant treatment had no effect on PTSD symptoms or subjective or physiological responses to stress or alcohol cues .


However , aprepitant robustly potentiated ventromedial prefrontal cortex ( mPFC ) fMRI responses to aversive visual stimuli .


Despite the lack of effect on PTSD symptoms and responses to stress/alcohol cues , NK1 antagonism activated the ventral mPFC , an area considered hypoactive in PTSD , during exposure to aversive stimuli .


Because this brain area is critically important for extinction of fear memories and in alcohol craving and relapse , our finding suggests that NK1 antagonism might be a useful pharmacological treatment to enhance extinction-based cue-exposure therapies .


The purpose of this study is to investigate the impact of cognitive group therapy and happiness training objectively in the local cerebral blood flow of patients with major depression ( MD ) .


The present research is semi-experimental to pre - and post-test with a control group .


Three groups were formed , and this number was incorporated in each group : 12 patients were chosen randomly ; the first group of depressed patients benefited from the combination of pharmacotherapy and sessions of cognitive group therapy ; the second group used a combination of pharmacotherapy and sessions of happiness training ; and a third group used only pharmacotherapy .


We compared cognitive-behavioural therapy and happiness training efficacy with only pharmacotherapy in MD patients .


We performed brain perfusion SPECT in each group , before and after each trial .


The study was conducted on 36 patients with MD ( 32 women and 4 men ; mean age : 41.22 9.08 ; range : 27-65 years ) .


There were significant differences regarding the two trial effects into two experimental groups ( p < 0/001 ) before and after trials , while such differences were not significant in the control group ( p > 0.05 ) .


In addition , there was significant difference among the regional cerebral blood flow in the frontal and prefrontal regions into two experimental groups before and after trials ( p < 0/001 ) , while such differences were not significant in the control group ( p > 0.05 ) .


This study demonstrated decreased cerebral perfusion in the frontal regions in MD patients , which increased following cognitive group therapy and happiness training .


Because of its availability , low costs , easy performance , and the objective semi-quantitative information supplied , brain perfusion SPECT scanning might be useful to assess the diagnosis and therapy efficacy .


Further exploration is needed to validate its clinical role .


In cases of exacerbation or crisis , myasthenia gravis ( MG ) patients can be treated with intravenous immunoglobulin ( IVIg ) , plasmapheresis , or immunoadsorption .


However , IVIg efficacy data in maintenance treatment are sparse .


We prospectively observed 16 index patients with chronic and insufficiently controlled MG under standard immunosuppressant therapy and symptomatic treatment .


The IVIg treatment response was measured using changes in quantitative myasthenia gravis ( QMG ) score and surrogates .


Based on these results , a sample size calculation for a future randomized , controlled trial ( RCT ) was simulated .


There was an enduring decline in QMG score and other parameters of about 50 % under IVIg maintenance treatment .


RCT sample size calculation results in 73 or 33 patients per arm to detect at least a 20 % vs. 30 % clinical difference in QMG score .


We recommend using the QMG score as a primary endpoint for an RCT of IVIg maintenance for chronic MG .


To evaluate the safety and efficacy of osmotic-controlled release oral delivery system ( OROS ) methylphenidate ( MPH ) HCl in adults with attention-deficit/hyperactivity disorder ( ADHD ) .


In this study , 284 adults with ADHD were randomized to OROS MPH or placebo .


During the 4-week titration period , patients were titrated from a starting dose of 18 mg once daily to an individually-optimized dose of up to 72 mg once daily in weekly 18-mg increments .


Patients continued on their individualized dose during the 4-week efficacy assessment period .


The primary efficacy endpoint was change in DSM-IV Total ADHD Symptoms subscale score of Conners ' Adult ADHD Rating Scale-Observer : Screening Version ( CAARS-O : SV ) from baseline to endpoint .


The mean change in DSM-IV Total ADHD Symptoms subscale score of CAARS-O : SV was significantly larger with OROS MPH compared with placebo ( P < 0.0001 , ANCOVA ) .


Similar results were observed for the majority of secondary endpoints , including CAARS-O : SV total score and other subscale scores .


Although treatment-emergent adverse events were reported more frequently in the OROS MPH group ( 81.8 % ) versus the placebo group ( 53.9 % ) , OROS-MPH showed a well-tolerated safety profile overall .


OROS MPH in a dose range of 18-72 mg once daily was effective and well-tolerated in adult patients with ADHD .


In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction , ischemic postconditioning has been shown to reduce infarct size , but the effect on clinical outcome has not been tested in a large randomized trial .


In addition , deferring stent implantation in the infarct-related lesion 1 to 3 days after acute opening of the infarct-related artery could have protective effects , by reducing the risk of injury caused by distal embolization and microvascular obstruction .


Finally , a considerable fraction of patients present with lesions in other coronary artery branches than the infarct-related artery .


Whether a strategy of complete or partial revascularization of these patients should be preferred remains uncertain .


The DANAMI 3 trial program was designed to investigate 3 different randomized treatment strategies in patients with ST-segment elevation myocardial infarction : ( 1 ) ischemic postconditioning versus conventional treatment with a primary end point of death and hospitalization for heart failure ; ( 2 ) deferring stent implantation in the infarct-related lesion versus conventional treatment with a primary end point of death , hospitalization for heart failure , reinfarction , and repeat revascularization ; and ( 3 ) treatment of the culprit lesion only versus fractional flow reserve-guided complete revascularization in patients with multivessel disease , with a primary end point of death , reinfarction , and repeat revascularization .


The DANAMI 3 trial program will determine whether either of 2 approaches to reduce reperfusion injury and distal microvascular obstruction with postconditioning or deferred stent implantation will translate into improved clinical outcome and whether patients with multivessel disease undergoing primary percutaneous coronary intervention will benefit from a strategy of complete or partial revascularization .


We aimed to investigate whether thrombus aspiration could preserve the index of microcirculatory resistance ( IMR ) after primary percutaneous coronary intervention ( PCI ) in patients with ST-elevation myocardial infarction ( STEMI ) .


Sixty-three patients with STEMI were randomised into two groups : primary PCI after thrombus aspiration ( aspiration group , n = 33 ) and primary PCI without thrombus aspiration ( non-aspiration group , n = 30 ) .


IMR was measured using a pressure-temperature sensor-tipped coronary wire .


Echocardiography was performed at baseline and at six-month follow-up .


No significant differences in baseline ejection fraction ( EF , 47.38.5 % vs. 49.57.8 % , p = 0.281 ) and baseline wall motion score index ( WMSI , 1.450.31 vs. 1.370.27 , p = 0.299 ) were observed between the two groups .


However , significant differences in IMR ( 23.510.2 U vs. 34.221.7 U , p = 0.018 ) , % E2 % 88 % 86EF ( follow-up EF - baseline EF ; 3.334.6 % vs. 0.731.9 % , p = 0.005 ) , and % E2 % 88 % 86WMSI ( follow-up WMSI - baseline WMSI ; -0.1210.16 vs. -0.0040.07 , p = 0.001 ) were observed between the two groups .


Thrombus aspiration as an adjunctive method to primary PCI for STEMI may preserve microvascular integrity and have beneficial effects on myocardial microcirculation .


The purpose of this study was to test the feasibility of a parent-briefing intervention for parents of hospitalized children with complex healthcare needs .


A phase I , single-group , posttest study .


There were 18 physicians , 25 nurses , and 31 parents who participated in the study .


Participants were asked to sit while carrying out the briefings with parents .


Parents and clinicians completed a feasibility questionnaire post briefings .


Sixty-eight briefings were carried out .


Parents and nurses evaluated the briefings in a favorable manner , whereas physicians ' ratings were mixed .


Further inquiry is recommended to understand the effects of a structured communication intervention on parent-professional decision-making practices .


Sometimes a written advance directive contradicts the opinion of a health care proxy .


How this affects doctors ' decision making is unknown .


To quantify the influence of contradictory instructions on doctors ' decisions .


All the generalists and internists in French-speaking Switzerland were mailed the questionnaire .


Respondents ( 43.5 % ) evaluated three vignettes that described medical decisions for incapacitated patients .


Each vignette was produced in four versions : one with an advance directive , one with a proxy opinion , one with both , and one with neither ( control ) .


In the first vignette , the directive and proxy agreed on the recommendation to forgo a medical intervention ; in the second , the advance directive opposed , but the proxy favored the intervention ; and in the third , the roles were reversed .


Each doctor received one version of each vignette , attributed at random .


The outcome variables were the doctor 's decision to forgo the medical intervention and the rating of the decision as difficult .


Written advance directives and proxy opinions significantly influenced doctors ' decision making .


When both were available and concordant , they reinforced each other ( odds ratio [ OR ] of forgoing intervention 35.7 , P < 0.001 compared with no instruction ) .


When the directive and proxy disagreed , the resulting effect was to forgo the intervention ( ORs 2.1 and 2.2 for the two discordant vignettes , both P < 0.001 ) .


Discordance between instructions was associated with increased odds of doctors rating the decision as difficult ( both ORs 2.0 , P 0.001 ) .


Contradictions between advance directives and proxy opinions result in a weak preference for abstention from treatment and increase the difficulty of the decision .


To investigate the feasibility of a computer-based reading intervention completed by patients diagnosed with a brain tumor .


Patients were randomized to the intervention ( n = 43 ) or standard of care group ( n = 38 ) .


The intervention consisted of 30 sessions using Fast ForWord exercises in a game-like format .


Change in reading decoding scores over time since diagnosis was examined .


Gender , race , parent education , parent marital status , and age at diagnosis were examined as covariates .


17 patients ( 39.5 % ) were able to complete the target goal of 30 intervention sessions .


Females had significantly greater training time than males ( p = .022 ) .


Age at diagnosis was associated with average training time/session for females ( r = .485 , p = .041 ) .


No significant differences were found in reading scores between the randomized groups .


The study was well accepted by families and adherence by patients undergoing radiation therapy for medulloblastoma was moderate .


Suggestions for improved methodology are discussed .


To assess the efficacy of a heparin-surface-modified ( HSM ) hydrophobic acrylic intraocular lens ( IOL ) ( EC-1YH PAL ) and the same IOL without heparin coating ( EC-1Y-PAL ) by the flare and cell intensity in the anterior chamber after uneventful cataract surgery .


Department of Ophthalmology , Paracelsus Medical University Salzburg , Austria .


Comparative case series .


Routine phacoemulsification with randomized implantation of an HSM IOL in 1 eye ( HSM IOL group ) and an uncoated IOL ( uncoated IOL group ) in the fellow eye was performed .


Postoperative inflammation was assessed objectively using a laser flare-cell meter ( FM-600 ) preoperatively as well as 1 day and 1 and 3 months postoperatively .


Aqueous cells in the anterior chamber , distance visual acuities , and subjective manifest refraction were also evaluated at each visit .


One hundred eyes ( 50 patients ) were enrolled .


In both groups , the mean flare values increased significantly from preoperatively to 1 day postoperatively ( P < .001 ) and nearly reached preoperative values by 3 months postoperatively .


One day postoperatively , the mean flare value was statistically significantly lower in the HSM IOL group ( 14.92 photons per millisecond [ ph/ms ] 7.47 [ SD ] ) than in the uncoated IOL group ( mean 16.73 7.81 ph/ms ) ( P = .04 ) ; there was no statistically significant difference between groups 1 and 3 months postoperatively ( both P > .58 ) .


The HSM IOL group had a greater and quicker decrease in aqueous cells , reaching statistical significance 1 month postoperatively ( P = .01 ) .


The HSM IOL showed a significant lower inflammatory reaction in the early postoperative stage with a faster disappearance of inflammatory signs .


No author has a financial or proprietary interest in any material or method mentioned .


Propofol is commonly used for induction and maintenance of anesthesia , but pain at the site of intravenous injection is a clinical problem .


We studied the effectiveness of local cooling and pretreatment with lidocaine for prevention of injection pain of propofol .


A total of 226 adult patients scheduled to receive general anesthesia were assigned randomly to four groups : a control group receiving no prophylactic intervention , a cooling group receiving topical cooling , a lidocaine group receiving 1 mg x kg ( -1 ) lidocaine , and a lidocaine plus cooling group receiving topical cooling and 1 mg x kg ( -1 ) lidocaine .


A 20 gauge intravenous catheter was inserted into the peripheral vein at the radial side of the forearm .


After prophylactic intervention had been performed , 1-2 mg x kg ( -1 ) MCT/LCT propofol was injected .


Patients were asked to grade the pain as none , mild , moderate , or severe .


The incidence of propofol-induced pain was significantly higher in the control group ( 39 % ) than in the other three groups ( 17 % in the cooling group , 16 % in the lidocaine group and 8 % in the lidocaine plus cooling group ) .


However , there were no significant differences between the three groups with different prophylactic interventions .


The results suggest that cooling and pretreatment with lidocaine reduce the incidence of pain upon propofol injection .


Diabetes mellitus and heart failure frequently coexist .


However , few diabetes mellitus trials have prospectively evaluated and adjudicated heart failure as an end point .


A total of 16492 patients with type 2 diabetes mellitus and a history of , or at risk of , cardiovascular events were randomized to saxagliptin or placebo ( mean follow-up , 2.1 years ) .


The primary end point was the composite of cardiovascular death , myocardial infarction , or ischemic stroke .


Hospitalization for heart failure was a predefined component of the secondary end point .


Baseline N-terminal pro B-type natriuretic peptide was measured in 12301 patients .


More patients treated with saxagliptin ( 289 , 3.5 % ) were hospitalized for heart failure compared with placebo ( 228 , 2.8 % ; hazard ratio , 1.27 ; 95 % confidence intercal , 1.07-1 .51 ; P = 0.007 ) .


Corresponding rates at 12 months were 1.9 % versus 1.3 % ( hazard ratio , 1.46 ; 95 % confidence interval , 1.15-1 .88 ; P = 0.002 ) , with no significant difference thereafter ( time-varying interaction , P = 0.017 ) .


Subjects at greatest risk of hospitalization for heart failure had previous heart failure , an estimated glomerular filtration rate 60 mL/min , or elevated baseline levels of N-terminal pro B-type natriuretic peptide .


There was no evidence of heterogeneity between N-terminal pro B-type natriuretic peptide and saxagliptin ( P for interaction = 0.46 ) , although the absolute risk excess for heart failure with saxagliptin was greatest in the highest N-terminal pro B-type natriuretic peptide quartile ( 2.1 % ) .


Even in patients at high risk of hospitalization for heart failure , the risk of the primary and secondary end points were similar between treatment groups .


In the context of balanced primary and secondary end points , saxagliptin treatment was associated with an increased risk or hospitalization for heart failure .


This increase in risk was highest among patients with elevated levels of natriuretic peptides , previous heart failure , or chronic kidney disease .


http://www.clinicaltrials.gov .


Unique identifier : NCT01107886 .


Sturge-Weber syndrome ( SWS ) is characterized by port-wine stains ( PWS ) affecting the face , eyes , and central nervous system .


Pulsed dye laser ( PDL ) is the standard treatment for PWS .


Unfortunately , recurrence is frequent because of reformation and reperfusion of blood vessels .


We sought to assess the clinical efficacy of topical rapamycin combined with PDL in PWS of patients with SWS .


We conducted a phase II , randomized , double-blind , intraindividual placebo-controlled , clinical trial .


We recruited 23 patients with SWS and facial PWS ( 12 women ; median age 33 years , age range 17-65 years ) from the University Clinic of Navarra , Spain .


Four interventions were evaluated : placebo , PDL + placebo , rapamycin , and PDL + rapamycin .


Clinical and histologic responses were evaluated using a chromatographic computerized system , spectrometry , and histologic analyses at 6 , 12 , and 18 weeks after the intervention .


PDL + rapamycin yielded the lowest digital photographic image score and the lowest percentage of vessels in histologic analysis , and showed a statistically significant improvement compared with the other interventions .


The treatment was generally well tolerated .


PDL was only applied to the lateral parts of the PWS area .


Topical rapamycin associated with PDL seems to be an effective treatment for PWS in patients with SWS .


Sedative premedication is widely administered before surgery , but little clinical evidence supports its use .


To assess the efficacy of sedative premedication on perioperative patient experience .


A randomized clinical trial , the PremedX study , enrolled 1062 adult patients who were younger than 70 years and had been scheduled for various elective surgeries under general anesthesia at 5 French teaching hospitals ( in Marseille , Montpellier , Nimes , and Nice ) between January 2013 and June 2014 .


Neurosurgery , obstetrical , cardiac , and outpatient surgery were excluded .


Patients were randomized to 3 groups of 354 participants each to receive 2.5 mg of lorazepam , no premedication , or placebo .


The primary outcome was perioperative patient experience assessed 24 hours after surgery with a validated questionnaire ( Evaluation du Vcu de l'Anesthsie Generale ; EVAN-G ) describing 6 domains of satisfaction and a global index ( score range , 0-100 ; high scores represent high satisfaction ) ; secondary outcomes included time to extubation and early cognitive recovery .


A subgroup analysis was planned a priori in patients with a high level of preoperative anxiety .


Premedication with lorazepam did not improve the EVAN-G mean global index for overall level of patient satisfaction ( 72 [ 95 % CI , 70-73 ] ; n = 330 ) compared with no premedication ( 73 [ 95 % CI , 71-74 ] ; n = 319 ) or placebo ( 71 [ 95 % CI , 70-73 ] ; n = 322 ) ( P = .38 ) .


Among patients with heightened preoperative anxiety , there were no significant differences found in the EVAN-G mean global index between the lorazepam group ( 68 [ 95 % CI , 65-72 ] ; n = 87 ) and the no premedication group ( 73 [ 95 % CI , 69-77 ] ; n = 57 ) or the placebo group ( 70 [ 95 % CI , 67-72 ] ; n = 87 ) ( P = .18 ) .


Time to extubation was 17 minutes ( 95 % CI , 14-20 minutes ) in the lorazepam group , 12 minutes ( 95 % CI , 11-13 minutes ) for the no premedication group , and 13 minutes ( 95 % CI , 12-14 minutes ) for the placebo group ( P < .001 ) and the rate of early cognitive recovery was 51 % ( 95 % CI , 45 % -56 % ) , 71 % ( 95 % CI , 66 % -76 % ) , and 64 % ( 95 % CI , 59 % -69 % ) , respectively ( P < .001 ) .


Among patients undergoing elective surgery under general anesthesia , sedative premedication with lorazepam compared with placebo or no premedication did not improve the self-reported patient experience the day after surgery , but was associated with modestly prolonged time to extubation and a lower rate of early cognitive recovery .


The findings suggest a lack of benefit with routine use of lorazepam as sedative premedication in patients undergoing general anesthesia .


clinicaltrials.gov Identifier : NCT01901003 .


To investigate the effectiveness of a neck strengthening program on the isometric neck strength profile of male rugby union players .


Controlled laboratory study .


Professional rugby union club .


Fifteen professional and 10 semiprofessional rugby union players .


The 15 professional players undertook a 5-week neck strengthening intervention , which was performed twice per week , whereas the 10 semiprofessional players acted as the control group .


Isometric strength of the neck musculature was tested using a hand-held dynamometer , for flexion ( F ) , extension ( E ) , left-side flexion ( LSF ) , and right-side flexion ( RSF ) .


Preintervention and postintervention evaluations were undertaken .


No significant between-group differences in isometric neck strength were noted preintervention .


A significant main effect for time was observed ( P < 0.05 ) , whereby the intervention group increased isometric neck strength in all planes after the 5-week intervention ( F preintervention = 334.45 39.31 N vs F postintervention 396.05 75.55 N ; E preintervention = 606.19 97.34 vs E postintervention = 733.88 127.16 N ; LSF preintervention = 555.56 88.34 N vs LSF postintervention = 657.14 122.99 N ; RSF preintervention = 570.00 106.53 N vs RSF postintervention = 668.00 142.18 N ) .


No significant improvement in neck strength was observed for control group participants .


The results of the present study indicate that a 5-week neck strengthening program improves isometric neck strength in rugby union players , which may have implications for injury prevention , screening , and rehabilitation .


The strengthening program described in the present study may facilitate rehabilitation specialists in the development of neck injury prevention , screening , and rehabilitation protocols .


In the ` Tailored Implementation for Chronic Diseases ( TICD ) ' project , five tailored implementation programs to improve healthcare delivery in different chronic conditions have been developed .


These programs will be evaluated in distinct cluster-randomized controlled trials .


This protocol describes the process evaluation across these trials , which aims to identify determinants of change in chronic illness care , to examine the validity of the tailoring methods that were applied , and to analyze the association of implementation activities and the effectiveness of the program .


A multilevel approach was used to develop five tailored implementation interventions .


In order to guide the process evaluation in five distinct trials , the study protocols for the cluster randomized trials and the related process evaluations were developed simultaneously and iteratively .


The process evaluation comprises three main components : a structured survey with health professionals in the trials , semi-structured interviews with a purposeful sample of this study population , and standardized documentation of organizational practice characteristics .


Norway will only conduct the qualitative part of the analysis because the survey and documentation of practice characteristics are considered to be not feasible .


The evaluation is guided by ` logic models ' of the implementation programs : frameworks that specify the linkages between the strategies used , the determinants addressed by tailoring , and the anticipated outcomes .


Standardization of measures across trials is sought to facilitate analysis of aggregated data from the trials .


This process evaluation will need to find a balance between standardization of methods across trials and the tailoring of measures to the specificities of each trial .


Therapeutic hypothermia is the standard of care after perinatal asphyxia .


Preclinical studies show 50 % xenon improves outcome , if started early .


During a 32-patient study randomized between hypothermia only and hypothermia with xenon , 5 neonates were given xenon during retrieval using a closed-circuit incubator-mounted system .


Without xenon availability during retrieval , 50 % of eligible infants exceeded the 5-hour treatment window .


With the transportable system , 100 % were recruited .


Xenon delivery lasted 55 to 120 minutes , using 174 mL/h ( 117.5-193 .2 ) ( median [ interquartile range ] ) , after circuit priming ( 1300 mL ) .


Xenon delivery during ambulance retrieval was feasible , reduced starting delays , and used very little gas .


Detrimental effects of right ventricular ( RV ) apical pacing have directed the interest toward alternative pacing sites such as the RV mid-septum .


As safety data are scarce for implantable cardioverter defibrillator ( ICD ) recipients the study aims to evaluate ICD lead performance in the mid-septal position .


A total of 299 ICD recipients ( 79 % male , aged 65.2 12.1 years , 83 % primary prevention of sudden cardiac death ) were randomized to receive the RV ICD electrode either in a mid-septal ( n = 145 ) or apical ( n = 154 ) location .


Event-free survival was evaluated at 3 ( primary endpoint ) and 12 months ( secondary endpoint ) .


Events included a composite of lead revision , suboptimal right ventricular electrode performance ( including defibrillation thresholds ( DFT ) > 25 J ) or lead position not in accordance with randomized location .


Event-free survival at 3 ( 12 ) months was observed in 80.6 % ( 72.3 % ) of patients randomized to a mid-septal and in 82.2 % ( 72.1 % ) of patients randomized to an apical lead position , p = 0.726 ( p = 0.969 ) .


Pre-defined margins for non-inferiority were not reached at 3 or 12 months .


High DFT was found in 7 patients ( 5.0 % ) of the mid-septal and in 3 ( 2.2 % ) patients of the apical group ( p = 0.209 ) .


In ICD recipients electrode positioning to the RV mid-septum or the RV apex results in slightly different rates concerning the survival free of lead revision , suboptimal right ventricular electrode performance or non-randomized lead position .


Non-inferiority of the mid-septal lead location can not be concluded .


This should be taken into consideration when a mid-septal lead position is pursued .


ClinicalTrials.gov identifier NCT00745745 .


To make a randomized comparison of 2 consolidation treatment options ( two patient groups ) : 2 cycles of cytarabine in average ( Ig/m2 in Group 2 ) and standard ( 100 mg/mi2 in Group 1 ) doses in combination with idarubicin ( 8-12 mg/m2 ) and mitoxantrone ( 10 mg/m2 ) , after two 7 +3 induction cycles of daunorubicin ( 60 mg/mi2 ) and subsequent 6 cycles of maintenance therapy .


In January 2010 to October 2013 , a Russian multicenter trial was conducted to treat patients with acute myeloid leukemias ( AML ) in accordance with the AML-01 .10 protocol ( ClinicalTrials.gov Identifier : NCT01587430 ) .


The trial enrolled 243 AML patients from 21 centers , including 71 patients ( median age 38 years ) from the State Hematology Center , Ministry of Health of the Russian Federation ; 35 and 36 patients were randomized to Groups 1 and 2 , respectively .


The randomized groups were balanced by basic clinical and laboratory parameters .


Favorable , intermediate , and high cytogenetic prognoses were in 14 ( 21.9 % ) , 40 ( 62.5 % ) , and 10 ( 15.6 % ) patients , respectively .


Prior to treatment , 2 patients died ; one patient refused treatment .


Fifty-eight ( 85.3 % ) of the 68 patients achieved complete remission ( CR ) ; early deaths was in 2 ( 2.9 % ) and resistance in 8 ( 11.8 % ) .


Four ( 6.9 % ) patients died during CR .


Protocol deviations ( doses , intervals , and the number of cycles ) were recorded in 12 ( 20.7 % ) of the 58 patients .


Other 8 ( 11.8 % ) patients were switched to low-dose cytarabine because of complications , withdrawn from the protocol and not included into the analysis of randomized comparison .


Twenty allogeneic bone marrow transplantations ( allo-BMT ) ( 7 related , 12 unrelated , and 1 haploidentical ) were performed ; of them 15 allo-BMTs were done during first CR .


In the 68 patients , 3-year overall survival ( OS ) was 45.6 % ; relapse-free survival ( RFS ) was 41.5 % .


OS was 64.6 % in Group 1 and 58.3 % in Group 2 ; RFS was 62 and 38.8 % in Groups 1 and 2 , respectively ( p > 0.5 ) .


In the favorable , intermediate , and high prognosis groups , OS was 79.5 , 60 , and 31.1 % and RFS was 81.8 , 41.3 , and 33.3 % , respectively ( p = 0.1 ) .


The consolidation treatment option unchanged survival rates in the above risk groups .


Unachieved CR after the first cycle considerably decreased RFS ( 33.9 % versus 60 % ) and served as an indication for allo-BMT during first CP ( RFS without BMT was 0 ; that with BMT was 78 % ) .


No differences were found between both consolidation options according to long-term results .


Protocol deviations were recorded in one-third of the patients .


While implementing the protocol , the efficiency of treatment was high .


Allo-BMT during first CR substantially increased RFS if CP was not achieved after the first cycle .


We investigate the effect of 6 months aerobic training alone or in combination with diet on adiponectin in circulation and in adipose abdominal tissue ( AT ) in obese women .


Twenty obese subjects were randomized into a 24 weeks intervention : 1 ) training ( TR ) and 2 ) training and diet ( TRD ) .


Blood samples were collected at baseline , after 12 wk and 24 wk .


AT biopsies were obtained only at baseline and after 24 wk .


In the TRD group the fat loss was after 12 wk -13.74 % ( p < 0.01 ) and after 24 wk -21.82 % ( p < 0.01 ) with no changes in the TR group .


After 12 and 24 wk , VO2max was increased by 21.81-39 .54 % ( p < 0.05 ) in the TRD group and 18.09-40 .95 % in the TR group ( p < 0.05 ) .


After 12 wk , plasma adiponectin was raised only in the TRD group ( 55.8 % , p < 0.05 ) .


After 24 weeks , circulating adiponectin was elevated by 110.4 % ( p < 0.01 ) in the TRD group and by 27 % ( p < 0.05 ) in the TR group .


In AT biopsies , subjects in the TRD and TR groups exhibited a significant increase in adiponectin ( p < 0.05 and p < 0.01 , respectively ) .


The two indices HOMA-IR and HOMA-AD for assessing insulin resistance were strongly affected by protocols .


HOMA-IR decreased ( p < 0.05 ) only after 24 wk in the TRD group .


HOMA-AD increased in both groups after 12 ( p < 0.05 ) and 24 wk ( p < 0.01 ) .


Six months chronic aerobic exercise alone or combined with diet result in a significant increase in circulating and adipose tissue adiponectin levels in obese women independent of changes in body composition and/or in HOMA-IR .


Infantile spasms ( IS ) are a severe form of childhood epilepsy associated with autism spectrum disorders ( ASD ) in up to 35 % of cases .


The objective of this post hoc analysis of our randomized control trial was to determine whether rapid diagnosis and treatment of IS could limit the incidence of ASD while identifying risk factors related to ASD outcome .


Patients with IS were randomized in a standardized diagnostic and treatment protocol .


Clinical and electroencephalogram ( EEG ) evaluations were completed at all eight visits over 5 years , while cognitive evaluations were administered at 0 , 6 , 24 and 60 months , respectively .


Autism was initially screened by means of the Checklist for Autism in Toddlers ( CHAT ) at 24 months , and formally assessed at the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule-Generic ( ADOS-G ) .


Of the 69 patients included in the study , 25 could not be assessed due to severe delay or death .


Eleven of the 42 patients screened with CHAT , were found to be at risk of an ASD outcome .


ADOS was performed in 44 and 10 were diagnosed with ASD .


The CHAT proved to correlate highly with the ADOS ( 80 % ppv ) .


Only patients with symptomatic IS developed ASD ( p = 0.003 ) .


Earlier diagnosis or successful treatment did not correlate with a reduced rate of ASD .


Other risk factors were identified such as having chronic epileptic discharges in the frontotemporal areas after disappearance of hypsarrhythmia ( p = 0.005 and p = 0.007 ) and being of nonwhite origin ( p = 0.009 ) .


ASD was only observed in children with sympyomatic IS .


Other clinical risk factors include chronic frontotemporal epileptic activity and being of non-white origin .


Early diagnosis and treatment did not prevent ASD as an outcome of IS .


However , patients at risk for ASD could be identified early on and should in the future benefit from early intervention to potentially improve their long-term outcome .


Examine a protective crumple zone effect of paranasal sinuses and nasal cavity on skull base fractures .


Randomized-control , cadaveric study .


In the experimental group ( n = 4 ) , the nasal cavity and bilateral sinuses of cadavers were obliterated with bone cement , whereas the control group ( n = 4 ) had native sinus architecture .


Increasing frontal , glabellar impacts were introduced .


Each impact event was examined with a high-speed video camera and sphenoid sinus pressure sensor .


After each impact , computed tomography scans were performed and fracture sites were analyzed .


The control group with intact sinuses showed statistically longer time duration , during which kinetic energy transfer occurred , and longer sphenoid wall pressure equilibrium time after an impact ( P < 0.05 ) .


In the experimental group , there were statistically higher fracture incidences of clivus , petrous portion of internal carotid , occipital bone , and foramen magnum ( P < 0.05 ) .


The type A pattern ( n = 6 ) had anterior skull base failure occurring before posterior skull base failure .


Type B pattern ( n = 2 ) , seen only in two experimental specimens , is marked by premature posterior skull base collapse occurring before anterior skull base failure with grossly disrupted posterior cranial fossa structures .


The presence of nasal cavity and paranasal sinuses behaves as a crumple zone to protect the cranial structures , preferentially posterior cranial fossa .


Obliteration of the nasal cavity and paranasal sinuses with bone cement significantly increased structural tolerance of the anterior cranial vault to frontal , glabellar impacts at the cost of premature , posterior cranial fossa failure .


The orexin-hypocretin system is important for translating peripheral metabolic signals and central neuronal inputs to a diverse range of behaviors , from feeding , motivation and arousal , to sleep and wakefulness .


Orexin signaling is thus an exciting potential therapeutic target for disorders of sleep , feeding , addiction , and stress .


Here , we investigated the low dose pharmacology of orexin receptor antagonist , SB-649868 , on neuroendocrine , sympathetic nervous system , and behavioral responses to insulin-induced hypoglycemic stress , in 24 healthy male subjects ( aged 18-45 years ; BMI 19.0-25 .9 kg/m ( 2 ) ) , using a randomized , double-blind , placebo-controlled , within-subject crossover design .


Alprazolam , a licensed benzodiazepine anxiolytic , was used as a positive comparator , as it has previously been validated using the insulin tolerance test ( ITT ) model in humans .


Of the primary endpoints , ITT induced defined increases in pulse rate , plasma cortisol , and adrenocorticotropic hormone in the placebo condition , but these responses were not significantly impacted by alprazolam or SB-649868 pre-treatment .


Of the secondary endpoints , ITT induced a defined increase in plasma concentrations of adrenaline , noradrenaline , growth hormone ( GH ) , and prolactin in the placebo condition .


Alprazolam pre-treatment significantly reduced the GH response to ITT ( p < 0.003 ) , the peak electromyography ( p < 0.0001 ) and galvanic skin response ( GSR , p = 0.04 ) to acoustic startle , the resting GSR ( p = 0.01 ) , and increased appetite following ITT ( p < 0.0005 ) .


SB-649868 pre-treatment produced no significant results .


We concluded that the ITT model may be informative for assessing the effects of drugs directly acting on the neuroendocrine or sympathetic nervous systems , but could not be validated for studying low dose orexin antagonist activity .


The purpose of the current study was to pilot-test a positive psychology intervention to improve adherence to diabetes management in adolescents with type 1 diabetes .


A total of 39 adolescents ( ages , 13-17 years ) with type 1 diabetes and their caregivers were randomized to a positive psychology intervention ( n = 20 ) or an attention control ( education ) intervention ( n = 19 ) .


The intervention condition used positive psychology exercises ( eg , gratitude , self-affirmation ) , small gifts , and parent affirmations to boost positive affect .


Outcomes included frequency of blood glucose monitoring , quality of life , and glycemic control .


No main effects for treatment were observed at the 6-month follow-up .


However , there was a significant association between adolescents ' levels of positive affect and measures of adherence , including self-report and meter downloads of glucose monitoring .


The results from the current study support the assertion that positive affect in the context of diabetes education is an important factor to consider in adolescents with type 1 diabetes .


The aim of this report is to describe the challenges , successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment ( START ) study .


START is a collaboration of many partners with central coordination provided by the protocol team , the statistical and data management centre ( SDMC ) , the International Network for Strategic Initiatives in Global HIV Trials ( INSIGHT ) network leadership , international coordinating centres and site coordinating centres .


The SDMC prepared reports on study accrual , baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial .


We describe the pattern of enrolment and challenges faced during the enrolment period of the trial .


An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites .


In August 2010 , funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013 .


Challenges to accrual included regulatory delays ( e.g. national/local ethics approval and drug importation approval ) and logistical obstacles ( e.g. execution of contracts with pharmaceutical companies , setting up of a central drug repository and translation of participant materials ) .


The personal engagement of investigators , strong central study coordination , and frequent and transparent communication with site investigators , community members and participants were key contributing factors to this success .


Accrual into START was completed in a timely fashion despite multiple challenges .


This success was attributable to the efforts of site investigators committed to maintaining study equipoise , transparent and responsive study coordination , and community involvement in problem-solving .


An emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders .


Adenosine agonists have been shown to have properties similar to those of dopamine antagonists ; there is a well-characterized interaction between adenosine and dopamine receptors in the ventral striatum , and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors .


Allopurinol increases adenosine levels in the brain , and hence is hypothesized to reduce the symptoms of mania .


Two randomized , placebo-controlled trials administering add-on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale ( YMRS ) scores for drug compared to placebo , while a more recent , relatively small , add-on study showed negative results .


Based on these data , our objective was to examine the efficacy of allopurinol as add-on treatment to mood stabilizers and/or antipsychotic agents in manic patients with bipolar disorder .


We performed a large , well-powered , multicenter , six-week , randomized , placebo-controlled trial of allopurinol added to mood stabilizers and/or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode .


Both groups showed improvement on the YMRS ( effect size of 1.5 for placebo and 1.6 for allopurinol ) , with no difference observed between groups on YMRS scores ( t = 0.28 , p = 0.78 ) .


There was no difference in the proportion of patients who responded to treatment ( defined as showing at least 50 % improvement in YMRS score ) between the two groups ( p = 0.92 ) , or in dropout rates ( p = 0.84 ) .


None of our patients received lithium .


However , the side effects of lithium and its narrow therapeutic index made the use of lithium less common and , therefore , our study results reflect common current clinical practice .


In the present study , we used a variety of antipsychotic and/or mood stabilizing treatments , to which we added allopurinol ; one might hypothesize that add-on allopurinol has a different effect in combination with different antipsychotic agents or mood stabilizers .


The findings of this large , well-powered study do not support add-on allopurinol as a treatment for acute mania .


This study did not test the efficacy of allopurinol as monotherapy .


The objective was to investigate the potential protective effects of two conditioning methods , on myocardial ischemic and reperfusion injury in relation to cardiac surgery .


Totally 68 patients were randomly assigned to either a control group ( n = 23 ) , a remote ischemic preconditioning ( RIPC ) group ( n = 23 ) or a glucagon-like peptide-1 ( GLP-1 ) analogue group ( n = 22 ) .


The RIPC protocol consisted of three cycles of upper limb ischemia .


The GLP-1 analogue protocol consisted of intravenous infusion with exenatide .


The primary endpoint was postoperative cardiac enzyme release .


The other secondary endpoints were metabolic parameters related to myocardial ischemia , measured using microdialysis technique , as well as other operative - and postoperative data .


Postoperative cardiac enzyme release indicated a possible beneficial effect of the interventions , but the difference did not reach statistical significance .


RIPC showed a trend toward lower levels ( p = 0.07 ) .


We managed to establish a functional myocardial microdialysis model , but we were unable to demonstrate clear protective effects .


We were in this prospective randomized proof-of-concept trial , unable to show distinct protective effects of the studied conditioning methods .


However , this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique .


Laparoscopic cholecystectomy performed during low intraabdominal pressure ( < 12 mm Hg ) is associated with significantly less postoperative pain than standard pressure ( 12 mm Hg ) .


The impact on surgical space conditions and safety of operating at lower pressures has not been adequately described , but deep neuromuscular blockade may be beneficial .


We investigated if deep muscle relaxation would be associated with a higher proportion of procedures with `` optimal '' surgical space conditions compared with moderate relaxation during low-pressure ( 8 mm Hg ) laparoscopic cholecystectomy .


In this assessor-blinded study , 48 patients undergoing elective laparoscopic cholecystectomy were administered rocuronium for neuromuscular blockade and randomized to either deep neuromuscular blockade ( rocuronium bolus plus infusion maintaining a posttetanic count 0-1 ) or moderate neuromuscular blockade ( rocuronium repeat bolus only for inadequate surgical conditions with spontaneous recovery of neuromuscular function ) .


Patients received anesthesia with propofol , remifentanil , and rocuronium .


The primary outcome was the proportion of procedures with optimal surgical space conditions ( assessed by the surgeon as 1 on a 4-point scale ) .


Secondary outcomes included the proportion of procedures completed at pneumoperitoneum 8 mm Hg and surgical space conditions on dissection of the gallbladder ( numeric rating scale 0-100 ; 0 = optimal surgical space conditions ; 100 = unacceptable surgical space conditions ) .


Optimal surgical space conditions during the entire procedure were observed in 7 of 25 patients allocated to deep neuromuscular blockade and in 1 of 23 patients allocated to moderate blockade ( P = 0.05 ) with an absolute difference of 24 % between the groups ( 95 % confidence interval , 4 % -43 % ) .


Laparoscopic cholecystectomy was completed at pneumoperitoneum 8 mm Hg in 15 of 25 and 8 of 23 patients in the deep and moderate group , respectively ( 95 % confidence interval , -2 % to 53 % ; P = 0.08 ) .


Surgical space conditions during dissection of the gallbladder assessed by use of the numeric rating scale were 20 ( 10-50 ) ( median [ 25 % -75 % range ] ) in the deep neuromuscular blockade group and 30 ( 10-50 ) in the moderate group ( P = 0.58 ; Wilcoxon-Mann-Whitney odds , 1.2 ; 95 % confidence interval , 0.6-2 .5 ) .


No operations were converted to laparotomy .


Deep neuromuscular blockade was associated with surgical space conditions that were marginally better than with moderate muscle relaxation during low-pressure laparoscopic cholecystectomy .


This study aimed to ascertain whether training-induced muscle hypertrophy is accompanied by an increase in the aponeurosis width , and to infer its impact on the training-induced increase in the pennation angle .


Eleven young men completed a resistance training program of unilateral knee extensions for 12 weeks .


Before and after training , anatomical cross-sectional area ( ACSA ) of the vastus lateralis and its distal aponeurosis width in the transverse plane were measured with magnetic resonance imaging .


The pennation angle and fascicle length were also determined with ultrasonography at the midbelly of the muscle .


The effect of change in aponeurosis width on the magnitude of training-induced increase in pennation angle was estimated by using a parallelepipedon model .


After the training , there were significant increases in ACSA ( 10.7 7.6 % ) , pennation angle ( 10.8 7.3 % ) and aponeurosis width ( 1.9 3.1 % ) , whereas no significant change was found in the fascicle length .


The model simulation shows that the increase in aponeurosis width by 1.9 % reduces the magnitude of increase in pennation angle by only 0.4 .


These results indicate that ( 1 ) the aponeurosis width of the vastus lateralis increases after 12 weeks of resistance training and ( 2 ) the increase in the aponeurosis width accompanying muscle hypertrophy by the amount of ~ 10 % does not substantially affect the increase in pennation angle .


Physical rehabilitation programs for kidney transplant recipients are not routinely personalized to patients ' physical and emotional health , which could result in a potentially limited health impact , shorter-term participation , and an overall low success rate .


We conducted an internal review board-approved randomized prospective study involving a 12-month supervised multidisciplinary rehabilitation program ( GH method ) initiated after kidney transplantation in obese recipients ( body mass index > 30 ) .


The new method incorporates 3 major components : physical exercise , behavioral interventions , and nutritional guidance .


We compared 9 patients who underwent supervised rehabilitation with 8 patients who underwent standard care .


Patients were followed up after the start of the intervention , and multiple assessments were performed .


The adherence to training and follow-up was 100 % in the intervention group , compared with 25 % at 12 months in the control group .


There was a trend for a higher glomerular filtration rate in the intervention group compared with the control group ( 55.5 18.6 mL/min/1 .73 m ( 2 ) vs 38.8 18.9 mL/min/1 .73 m ( 2 ) , P = .06 ) .


The quality of life ( SF-36 ) mean score improved more in the intervention group compared with the control group ( 583 13 vs 436 22 , P = .008 ) .


There was a significantly higher employment rate in the intervention group , 77.7 % at 12 months compared with 12.5 % in the control group ( P = .02 ) .


Our preliminary results suggest that this comprehensive approach to physical rehabilitation can improve adherence , kidney function , quality of life , and employment rate for obese patients after kidney transplantation .


In cystic fibrosis ( CF ) , the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa .


Pathogens subsequently descend to the lower airways , with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease .


Unlike conventional aerosols , vibrating aerosols applied with the PARI Sinus nebulizer deposit drugs into the paranasal sinuses .


This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage .


To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage ; and on patient quality of life , measured with the Sino-Nasal Outcome Test ( SNOT-20 ) , and otologic and renal safety and tolerability .


Patients were randomized to inhalation of tobramycin ( 80 mg/2 mL ) or placebo ( 2 mL isotonic saline ) once daily ( 4 minutes/nostril ) with the PARI Sinus nebulizer over 28 days , with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days .


Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline .


Nine patients participated , six initially receiving tobramycin and three placebo .


Sinonasal inhalation was well tolerated , with serum tobramycin < 0.5 mg/L and stable creatinine .


P. aeruginosa quantity decreased in four of six ( 67 % ) patients given tobramycin , compared with zero of three given placebo ( non-significant ) .


SNOT-20 scores were significantly lower in the tobramycin than in the placebo group ( P = 0.033 ) .


Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.


The orodispersible house dust mite ( HDM ) sublingual immunotherapy ( SLIT ) - tablet ( ALK , Denmark ) is being developed for the treatment of HDM respiratory allergic disease .


The objective of the 2 phase I trials was to investigate tolerability and the acceptable dose range of HDM SLIT-tablet treatment in adults and children with HDM respiratory allergic disease .


The trials were randomized , multiple-dose , dose-escalation , double-blind , placebo-controlled phase I trials including patients with HDM-induced asthma , with or without rhinoconjunctivitis .


Both trials were registered in EudraCT ( Trial 1 : 2005-002151-41 ; Trial 2 : 2007-000402-67 ) .


Trial 1 included 71 adults ( 18-63 years ) and trial 2 included 72 children ( 5-14 years ) .


Both trials included 6 dose groups that were randomized 3:1 to active treatment or placebo once daily for 28 days .


Adverse events ( AEs ) were coded in MedDRA ( version 8.1 or later ) .


Immunological variables included specific IgE and IgE-blocking factor .


No serious AEs were reported .


In trial 1 ( maximum dose , 32 development units [ DU ] ) , 1 patient in the 16 DU group discontinued due to AEs .


The entire 32 DU group was discontinued as 1 patient had a severe adverse reaction .


In trial 2 ( maximum dose , 12 DU ) , no patients discontinued prematurely .


The most frequently reported AEs were mild application-site related events .


The total number of events was dose-related within each trial .


HDM SLIT-tablet treatment induced changes in immunological parameters in a dose-dependent manner .


These trials demonstrate that doses up to 12 DU of HDM SLIT-tablet were tolerated in the selected populations , and thus are suitable for further clinical investigations in adults and children with HDM respiratory allergic disease .


To investigate the feasibility and safety of pH capsule to monitor pH in patients with gastroesophageal reflux disease ( GERD ) .


Ninety-one patients with symptoms suggestive of GERD were enrolled in this study , 46 of whom were randomized to the pH capsule group ; the remaining 45 patients used the conventional catheter and pH capsule simultaneously .


The pH data and traces were recorded via automatic analysis , and capsule detachment was assessed using X-ray images .


All of the patients were required to complete a questionnaire regarding tolerance with the capsule .


The capsules were successfully attached on the first attempt , and no early detachment of the capsules was observed .


Compared to the 24-h pH data recorded with the conventional catheter , the data collected with the pH capsule showed no significant differences in 24-h esophageal acid exposure .


The measurements of esophageal acid exposure over 24 h collected with the two devices showed a significant correlation ( r ( 2 ) = 0.996 , P < 0.001 ) .


Capsule detachment occurred spontaneously in 89 patients , and 2 capsules required endoscopic removal due to chest pain .


The capsule was associated with less interference with daily activity .


The wireless pH capsule provides a feasible and safe method for monitoring gastroesophageal reflux and therefore may serve as an important tool for diagnosing GERD .


Male circumcision is a primary HIV-1 prevention intervention for men , but whether the procedure reduces the risk of syphilis among men and their female partners is uncertain .


We aimed to assess whether male circumcision was associated with incident syphilis in men and in their female partners .


In this large prospective cohort study , participants were members of Kenyan and Ugandan HIV-1 serodiscordant heterosexual couples enrolled in a randomised safety and efficacy clinical trial of pre-exposure prophylaxis for HIV-1 prevention ( the Partners PrEP Study ) .


Participants attended monthly or quarterly follow-up visits for up to 36 months .


Annually , syphilis serology testing was done and male circumcision status was assessed .


We used multivariate Andersen-Gill survival methods , adjusted for age , sexual behaviour , and plasma HIV RNA levels of the HIV-infected partner .


4716 HIV-1 serodiscordant couples ( 38 % ) with a man with HIV were followed for a median of 275 years .


At enrolment , 1575 ( 53 % ) men with HIV and 560 ( 32 % ) men without HIV were circumcised ; an additional 69 ( 4 % ) men with HIV and 132 ( 5 % ) men without HIV were circumcised during study follow-up .


221 incident syphilis infections were reported : 46 ( 21 % ) in men with HIV ( incidence 110 per 100 person-years ) , 76 ( 34 % ) in men without HIV ( 109 ) , 54 ( 24 % ) in women with HIV ( 077 ) , and 45 ( 24 % ) in women without HIV ( 111 ) .


Male circumcision was associated with a 42 % reduction in incident syphilis in men ( adjusted hazard ratio [ aHR ] 058 , 95 % CI 037-091 ) including a 62 % reduction in men with HIV ( 038 , 018-081 ) , and a non-significant reduction in incident syphilis in men without HIV ( 064 , 036-111 ) .


In women , circumcision of their male partners was associated with a 59 % reduction in incident syphilis ( aHR 041 , 95 % CI 025-069 ) , including a 75 % reduction in women without HIV ( 025 , 008-076 ) and a 48 % reduction in women with HIV ( 052 , 027-097 ) .


Male circumcision was associated with decreased risk of incident syphilis in men and women .


If confirmed , these results suggest that medical male circumcision could substantially reduce incidence of syphilis and its sequelae .


Bill & Melinda Gates Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development .


Telomere length in blood or buccal cell DNA has been associated with risk of various cancers .


Glioma can be a highly malignant brain tumor and has few known risk factors .


Genetic variants in or near RTEL1 and TERT , key components of telomere biology , are associated with glioma risk .


Therefore , we evaluated the association between relative telomere length ( RTL ) and glioma in a prospective study .


We performed a nested case-control study within the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial .


RTL was determined by quantitative PCR on blood or buccal cell DNA obtained at least 2 years prior to diagnosis from 101 individuals with glioma cases .


Healthy controls ( n = 198 ) were matched to cases ( 2:1 ) on age , gender , smoking status , calendar year , and DNA source .


Conditional logistic regression was used to investigate the association between RTL and glioma .


As expected , RTL declined with increasing age in both cases and controls .


There was no statistically significant association between RTL and glioma overall .


An analysis stratified by gender suggested that short RTL ( 1st tertile ) in males was associated with glioma ( odds ratio , [ OR ] = 2.29 , 95 % confidence interval [ CI ] 1.02-5 .11 ) ; this association was not observed for females ( OR = 0.41 , 95 % CI 0.14-1 .17 ) .


This prospective study did not identify significant associations between RTL and glioma risk , but there may be gender-specific differences .


Larger , prospective studies are needed to evaluate these findings .


The philtral column and dimple are especially important in patients with cleft lip .


Recently , we have found that , at maximal puckering , the appearance of the philtrum worsens although the philtral column is well formed at rest .


In this study , we explore the effectiveness of the coronal muscle splitting technique in a microform cleft lip through comparative analysis of the postoperative results between the control group ( patients without coronal muscle splitting ) and the study group ( patients with coronal muscle splitting ) .


Philtral reconstruction was performed in 24 patients with microform cleft lip between March 2006 and March 2010 .


The philtrum was reconstructed in 12 patients using the coronal muscle splitting technique and in the other 12 patients without this technique .


The convexity of the philtral column and the dimpling of the philtrum were evaluated at rest and at maximal puckering through digital photographs and videos taken preoperatively and postoperatively .


In addition , we compared the postoperative results between the 2 groups using the paired t-test .


Postoperative evaluation was done at 6 to 48 months ( mean , 25 mo ) .


There was no statistically significant difference in the shape of the philtral column and the philtral dimple between the 2 groups preoperatively ( P > 0.05 ) .


Reconstruction of the philtral column in the study group rendered better results than in the control group at both rest and maximal puckering ( P < 0.001 and P < 0.001 ) .


Reconstruction of the philtral dimple in the study group rendered better results than in the control group at both rest and maximal puckering ( P = 0.018 and 0.035 ) .


The coronal muscle splitting technique offers more esthetic and functional results in the formation of the philtral column and dimple both at rest and at maximal puckering than in the control group in cases of philtral reconstruction of the microform cleft lip .


The construct of ` preparation for future learning ' ( PFL ) is understood as the ability to learn new information from available resources , relate new learning to past experiences and demonstrate innovation and flexibility in problem solving .


Preparation for future learning has been proposed as a key competence of adaptive expertise .


There is a need for educators to ensure that opportunities are provided for students to develop PFL ability and that assessments accurately measure the development of this form of competence .


The objective of this research was to compare the relative impacts of basic science instruction and clinically focused instruction on performance on a PFL assessment ( PFLA ) .


This study employed a ` double transfer ' design .


Fifty-one pre-clerkship students were randomly assigned to either basic science instruction or clinically focused instruction to learn four categories of disease .


After completing an initial assessment on the learned material , all participants received clinically focused instruction for four novel diseases and completed a PFLA .


The data from the initial assessment and the PFLA were submitted to independent-sample t-tests .


Meanstandard deviation [ SD ] scores on the diagnostic cases in the initial assessment were similar for participants in the basic science ( 0.650.11 ) and clinical learning ( 0.620.11 ) conditions .


The difference was not significant ( t [ 42 ] = 0.90 , p = 0.37 , d = 0.27 ) .


Analysis of the diagnostic cases on the PFLA revealed significantly higher meanSD scores for participants in the basic science learning condition ( 0.720.14 ) compared with those in the clinical learning condition ( 0.630.15 ) ( t [ 42 ] = 2.02 , p = 0.05 , d = 0.62 ) .


Our results show that the inclusion of basic science instruction enhanced the learning of novel related content .


We discuss this finding within the broader context of research on basic science instruction , development of adaptive expertise and assessment in medical education .


This study assessed whether a cycle of `` routine '' therapeutic drug monitoring ( TDM ) for imatinib dosage individualization , targeting an imatinib trough plasma concentration ( C min ) of 1,000 ng/ml ( tolerance : 750-1 ,500 ng/ml ) , could improve clinical outcomes in chronic myelogenous leukemia ( CML ) patients , compared with TDM use only in case of problems ( `` rescue '' TDM ) .


Imatinib concentration monitoring evaluation was a multicenter randomized controlled trial including adult patients in chronic or accelerated phase CML receiving imatinib since less than 5years .


Patients were allocated 1:1 to `` routine TDM '' or `` rescue TDM . ''


The primary endpoint was a combined outcome ( failure - and toxicity-free survival with continuation on imatinib ) over 1-year follow-up , analyzed in intention-to-treat ( ISRCTN31181395 ) .


Among 56 patients ( 55 evaluable ) , 14/27 ( 52 % ) receiving `` routine TDM '' remained event-free versus 16/28 ( 57 % ) `` rescue TDM '' controls ( P = 0.69 ) .


In the `` routine TDM '' arm , dosage recommendations were correctly adopted in 14 patients ( median C min : 895ng/ml ) , who had fewer unfavorable events ( 28 % ) than the 13 not receiving the advised dosage ( 77 % ; P = 0.03 ; median C min : 648ng/ml ) .


This first target concentration intervention trial could not formally demonstrate a benefit of `` routine TDM '' because of small patient number and surprisingly limited prescriber 's adherence to dosage recommendations .


Favorable outcomes were , however , found in patients actually elected for target dosing .


This study thus shows first prospective indication for TDM being a useful tool to guide drug dosage and shift decisions .


The study design and analysis provide an interesting paradigm for future randomized TDM trials on targeted anticancer agents .


Computed tomography ( CT ) scans of the lumbar spine ( CTLS ) have demonstrated a higher level of accuracy than plain films and have been used to assess patients with spinal disorder when magnetic resonance imaging is not available .


Nevertheless , radiation exposure remains a serious safety concern .


Iterative reconstruction ( IR ) decreases the CT radiation dose for diagnostic imaging .


However , the feasibility of using IR in CTLS is unclear .


To evaluate the imaging quality and diagnostic reliability of CTLS with IR .


A prospective study .


All patients from outpatient departments who suffered from spinal disorders and were referred for CTLS .


In acquired CT images , the signal-to-noise ratio ( SNR ) of the dural sac ( DS ) , intervertebral disc ( IVD ) , psoas muscle ( PM ) , and L5 vertebral body , the contrast-to-noise ratio between the DS and IVD ( D-D CNR ) , and the subjective imaging qualities were compared across groups .


Interobserver agreement was evaluated with kappa values .


Patients receiving low radiation CTLS were divided into three groups .


A 150 mAs tube current with 120 kVp tube voltage was used with Group A and a 230 mAs tube current with 100 kVp tube voltage with Group B. Intended end radiation exposure was 50 % less than that of the control group .


Tube modulation was active for all groups .


The images of the two low-radiation groups were reconstructed by IR ; those of the control group by filtered back-projection ( FBP ) .


The SNRs of the DS , IVD , PM , BM , and D-D CNR of Group A were not inferior to those of the control group .


All SNRs and D-D CNRs for Group B were inferior to those of the control group .


Except for that of the facet joint , all subjective imaging ratings for anatomic regions were equivalent between Groups A and B. Interobserver agreement was highest for the control group ( 0.72-0 .88 ) , followed by Group A ( 0.69-0 .83 ) and B ( 0.55-0 .83 ) .


Fifty percent tube current reduction combined with IR provides equivalent diagnostic accuracy and improved patient safety when compared with conventional CTLS .


Our results support its use as a screening tool .


With the tube modulation technique , further adjustments in weighting IR and FBP algorithms based on body mass index become unnecessary .


The clinical benefits of using icodextrin during acute peritonitis in peritoneal dialysis are uncertain .


On the premise that high glucose concentration might jeopardize the peritoneal defense during peritonitis , icodextrin administration during acute peritonitis could have the potential to improve the peritonitis outcome whilst improving ultrafiltration .


We conducted a single-center , open-label , randomized controlled trial in which 53 adult continuous ambulatory peritoneal dialysis patients underwent randomization to receive either icodextrin or original glucose-based dialysis solution .


The primary outcome measure was the peritoneal dialyzate white cell count on Day 3 .


Secondary outcome measures comprised the need of additional hypertonic exchanges , fluid control as denoted by changes in body weight , and the clinical outcome of peritonitis including 30-day and 120-day all-cause mortality .


Between icodextrin and control treatment groups , there were no statistically significant differences in the peritoneal dialyzate white cell count on day ( 1829 versus 987/mm ( 3 ) , P = 0.13 ) .


There was neither improvement in primary cure rate ( 31.8 versus 32.3 % , P = 1.00 ) , nor was there any change in 120-day mortality after icodextrin use ( 13.6 versus 12.9 % , P = 1.00 ) .


However , requirement of hypertonic dialysis exchange was much more frequent in the control group than in those randomized to icodextrin ( 35.5 versus 0 % , P = 0.001 ) .


Body weight did not change significantly in the icodextrin group , but body weight in the control group increased from 63.3 14.5 kg at baseline to 64.2 14.2 kg at Day 5 ( P = 0.0002 ) and 65.2 14.1 kg at Day 10 ( P < 0.0001 ) .


As compared with glucose-based peritoneal dialysis solution , use of icodextrin achieved better ultrafiltration and fluid control during acute peritonitis complicating continuous ambulatory peritoneal dialysis , although we found no evidence of a worthwhile clinical benefit on peritonitis resolution .


( ClinicalTrial.gov number , NCT0104446 [ ClinicalTrial.gov ] . )


Maternal risk factors for fetal alcohol spectrum disorders ( FASD ) in Italy and Mediterranean cultures need clarification , as there are few studies and most are plagued by inaccurate reporting of antenatal alcohol use .


Maternal interviews ( n = 905 ) were carried out in a population-based study of the prevalence and characteristics of FASD in the Lazio region of Italy which provided data for multivariate case control comparisons and multiple correlation models .


Case control findings from interviews seven years post-partum indicate that mothers of children with FASD are significantly more likely than randomly-selected controls or community mothers to : be shorter ; have higher body mass indexes ( BMI ) ; be married to a man with legal problems ; report more drinking three months pre-pregnancy ; engage in more current drinking and drinking alone ; and have alcohol problems in her family .


Logistic regression analysis of multiple candidate predictors of a FASD diagnosis indicates that alcohol problems in the child 's family is the most significant risk factor , making a diagnosis within the continuum of FASD 9 times more likely ( 95 % C.I. = 1.6 to 50.7 ) .


Sequential multiple regression analysis of the child 's neuropsychological performance also identifies alcohol problems in the child 's family as the only significant maternal risk variable ( p < .001 ) when controlling for other potential risk factors .


Underreporting of prenatal alcohol use has been demonstrated among Italian and other Mediterranean antenatal samples , and it was suspected in this sample .


Nevertheless , several significant maternal risk factors for FASD have been identified .


To compare the efficacy and safety of new insulin glargine 300 units/mL ( Gla-300 ) with glargine 100 units/mL ( Gla-100 ) in people with type 2 diabetes using basal insulin ( 42 units/day ) plus oral antihyperglycemic drugs ( OADs ) .


EDITION 2 was a multicenter , open-label , two-arm study .


Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months .


The primary end point was change in HbA1c .


The main secondary end point was percentage of participants with one or more nocturnal confirmed ( 3.9 mmol/L [ 70 mg/dL ] ) or severe hypoglycemic events from week 9 to month 6 .


Randomized participants ( n = 811 ) had a mean ( SD ) HbAc of 8.24 % ( 0.82 ) and BMI of 34.8 kg/m ( 2 ) ( 6.4 ) .


Glycemic control improved similarly with both basal insulins ; least squares mean ( SD ) reduction from baseline was -0.57 % ( 0.09 ) for Gla-300 and -0.56 % ( 0.09 ) for Gla-100 ( mean difference -0.01 % [ 95 % CI -0.14 to 0.12 ] ) , with 10 % higher dose of Gla-300 .


Less nocturnal confirmed ( 3.9 mmol/L [ 70 mg/dL ] ) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 ( relative risk 0.77 [ 95 % CI 0.61-0 .99 ] ; P = 0.038 ) and during the first 8 weeks .


Fewer nocturnal and any time ( 24 h ) hypoglycemic events were reported during the entire 6-month period .


Weight gain was lower with Gla-300 than with Gla-100 ( P = 0.015 ) .


No between-treatment differences in safety parameters were identified .


Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day .


The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody ( ANCA ) - associated vasculitides .


However , even when patients receive maintenance treatment with azathioprine or methotrexate , the relapse rate remains high .


Rituximab may help to maintain remission .


Patients with newly diagnosed or relapsing granulomatosis with polyangiitis , microscopic polyangiitis , or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were randomly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6 , 12 , and 18 after study entry or daily azathioprine until month 22 .


The primary end point at month 28 was the rate of major relapse ( the reappearance of disease activity or worsening , with a Birmingham Vasculitis Activity Score > 0 , and involvement of one or more major organs , disease-related life-threatening events , or both ) .


The 115 enrolled patients ( 87 with granulomatosis with polyangiitis , 23 with microscopic polyangiitis , and 5 with renal-limited ANCA-associated vasculitis ) received azathioprine ( 58 patients ) or rituximab ( 57 patients ) .


At month 28 , major relapse had occurred in 17 patients in the azathioprine group ( 29 % ) and in 3 patients in the rituximab group ( 5 % ) ( hazard ratio for relapse , 6.61 ; 95 % confidence interval , 1.56 to 27.96 ; P = 0.002 ) .


The frequencies of severe adverse events were similar in the two groups .


Twenty-five patients in each group ( P = 0.92 ) had severe adverse events ; there were 44 events in the azathioprine group and 45 in the rituximab group .


Eight patients in the azathioprine group and 11 in the rituximab group had severe infections , and cancer developed in 2 patients in the azathioprine group and 1 in the rituximab group .


Two patients in the azathioprine group died ( 1 from sepsis and 1 from pancreatic cancer ) .


More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine .


( Funded by the French Ministry of Health ; MAINRITSAN ClinicalTrials.gov number , NCT00748644 ; EudraCT number , 2008-002846-51 . )


In the Prevention of Malaria and HIV disease in Tororo pediatrics trial , HIV-infected Ugandan children randomized to receive lopinavir/ritonavir ( LPV/r ) - based antiretroviral therapy ( ART ) experienced a lower incidence of malaria compared with children receiving nonnucleoside reverse transcriptase inhibitor ( NNRTI ) - based ART .


Here we present the results of the noninferiority analysis of virologic efficacy and comparison of immunologic outcomes .


ART-naive or - experienced ( HIV RNA < 400 copies/mL ) children aged 2 months to 6 years received either LPV/r or NNRTI-based ART .


The proportion of children with virologic suppression ( HIV RNA < 400 copies/mL ) at 48 weeks was compared using a prespecified noninferiority margin of -11 % in per-protocol analysis .


Time to virologic failure by 96 weeks , change in CD4 counts and percentages , and incidence of adverse event rates were also compared .


Of 185 children enrolled , 91 initiated LPV/r and 92 initiated NNRTI-based ART .


At baseline , the median age was 3.1 years ( range , 0.4-5 .9 ) , and 131 ( 71 % ) children were ART-naive .


The proportion of children with virologic suppression at 48 weeks was 80 % ( 67/84 ) in the LPV/r arm vs. 76 % ( 59/78 ) in the NNRTI arm , a difference of 4 % ( 95 % confidence interval : -9 % to +17 % ) .


Time to virologic failure , CD4 changes , and the incidence of Division of AIDS grade III/IV adverse events were similar between arms .


LPV/r-based ART was not associated with worse virologic efficacy , immunologic efficacy , or adverse event rates compared with NNRTI-based ART .


Considering these results and the reduction in malaria incidence associated with LPV/r previously reported for this trial , wider use of LPV/r to treat HIV-infected African children in similar malaria-endemic settings could be considered .


The impact of the age of first Plasmodium falciparum infection on the rate of acquisition of immunity to malaria and on the immune correlates of protection has proven difficult to elucidate .


A randomized , double-blind , placebo-controlled trial using monthly chemoprophylaxis with sulphadoxine-pyrimethamine plus artesunate was conducted to modify the age of first P. falciparum erythrocytic exposure in infancy and assess antibodies and malaria risk over two years .


Participants ( n = 349 ) were enrolled at birth to one of three groups : late exposure , early exposure and control group , and were followed up for malaria morbidity and immunological analyses at birth , 2.5 , 5.5 , 10.5 , 15 and 24 months of age .


Total IgG , IgG subclasses and IgM responses to MSP-1 ( 19 ) , AMA-1 , and EBA-175 were measured by ELISA , and IgG against variant antigens on the surface of infected erythrocytes by flow cytometry .


Factors affecting antibody responses in relation to chemoprophylaxis and malaria incidence were evaluated .


Generally , antibody responses did not vary significantly between exposure groups except for levels of IgM to EBA-175 , and seropositivity of IgG1 and IgG3 to MSP-1 ( 19 ) .


Previous and current malaria infections were strongly associated with increased IgG against MSP-1 ( 19 ) , EBA-175 and AMA-1 ( p < 0.0001 ) .


After adjusting for exposure , only higher levels of anti-EBA-175 IgG were significantly associated with reduced clinical malaria incidence ( IRR 0.67 , p = 0.0178 ) .


Overall , the age of first P. falciparum infection did not influence the magnitude and breadth of IgG responses , but previous exposure was critical for antibody acquisition .


IgG responses to EBA-175 were the strongest correlate of protection against clinical malaria .


ClinicalTrials.gov : NCT00231452 .


Worldwide , 200 million adults undergo major noncardiac surgery annually , and 10 million of these patients will have a major vascular complication .


Low-dose clonidine and low-dose acetyl-salicylic acid ( ASA ) may prevent major perioperative vascular complications .


We therefore initiated the POISE-2 trial to establish the perioperative effects of these 2 interventions .


The POISE-2 trial is a 2 2 factorial randomized controlled trial of low-dose ASA vs. placebo and low-dose clonidine vs. placebo in 10,000 patients at risk for a perioperative cardiovascular event who are undergoing noncardiac surgery .


Both study drugs are initiated prior to surgery ( goal 2-4 hours ) and are continued after surgery .


Patients , health care providers , data collectors , and outcome adjudicators are blinded to treatment allocation .


The primary outcome is a composite of mortality and nonfatal myocardial infarction at 30 days after randomization .


To date , the POISE-2 trial has recruited more than 9,000 patients from 135 centers in 23 countries .


Among the first 7,500 patients recruited , patients ' mean age was 68.2 years , 53.4 % were male , 34.0 % had a history of vascular disease , and 38.3 % had diabetes that was treated .


Participants had orthopedic ( 38.1 % ) , general ( 27.0 % ) , urologic or gynecologic ( 17.2 % ) , vascular ( 6.6 % ) , thoracic ( 5.7 % ) , and other ( 5.4 % ) surgery .


POISE-2 is a large international trial that will rigorously evaluate the effects of low-dose clonidine and ASA in patients having noncardiac surgery .


Onychomycosis is a therapeutic challenge because of the toxicities of systemic medications .


This has led to the investigation of light-based technologies for safe and effective alternative treatment modalities .


The purpose of this study was to determine the safety and efficacy of 4 treatments with a 1,320-nm neodymium : yttrium aluminum garnet ( Nd : YAG ) laser in improving the appearance of onychomycosis .


This study was a 24-week , single-center randomized placebo-controlled study .


Ten subjects were enrolled with culture-proven , bilateral great toenail onychomycosis .


The subjects received 4 treatments with the 1,320-nm Nd : YAG laser to the treatment toenail on Days 1 , 7 , 14 , and 60 .


The control toenail received a sham treatment of cryogen cooling only .


Mycologic cultures were obtained at 3-month follow-up visits .


Fifty percent of mycologic cultures were negative at the 3-month follow-up after 4 laser treatments .


Toenails had improvement in subungual debris , hypertrophy , and yellowing .


Patient satisfaction was upheld as assessed by the Nail Quality of Life Questionnaire .


The 1,320-nm Nd : YAG laser may be a safe and effective therapy for improving the appearance of onychomycosis .


Additional therapy may be necessary to enhance long-term results .


Further investigation needs to explore the optimal treatment settings and the most effective treatment schedule .


Spaceflight studies and ground-based analogues of microgravity indicate a weakening of human immunity .


Mannan-binding lectin ( MBL ) and H - , L - , and M-ficolin together constitute the lectin pathway and mediate the clearance of pathogens through complement activation .


We hypothesized that simulated microgravity may weaken human innate immune functions and studied the impact of 6 head-down tilted bed rest ( HDT ) for 21 d on MBL and ficolin levels .


Within a 6-mo period , seven men underwent two periods of HDT .


Blood samples were analyzed for MBL , H - , L - , and M-ficolin , mannose-binding lectin-associated protein of 44 kDa ( MAp44 ) , and collectin liver 1 ( CL-L1 ) by time-resolved immunofluorometric assays ( TRIFMA ) .


We observed well-defined individual preintervention levels of MBL and ficolins .


Remarkably similar intraindividual changes occurred for MBL and MBL levels decreased ( mean 282 ng ml ) in the recovery phase .


Conversely , CL-L1 , a protein with MBL-like properties , increased ( mean 102 ng ml ) during the recovery phase .


M-ficolin increased ( mean 79 ng ml ) within the first 2 d of HDT , followed by a decrease ( mean 112 ng ml ) during the recovery phase .


L-ficolin increased ( mean 304 ng ml ) during HDT , while H-ficolin was essentially unaffected .


MAp44 , a down-regulator of the lectin pathway , decreased initially ( mean 78 ng ml ) in the recovery phase followed by an increase ( mean 131 ng ml ) .


Alterations in MBL and ficolin levels were modest and with our current knowledge do not lead to overt immunodeficiency .


Pronounced changes occurred when the subjects resumed the upright position .