Understanding the intracellular mechanisms induced by remote ischemic preconditioning ( RIPC ) in the human left ventricle opens new possibilities for development of pharmacological cardioprotection against ischemia and reperfusion injury .


In this study we investigated the effects of RIPC on mitochondrial function , activation of pro-survival protein kinase Akt and microRNA expression in left ventricular biopsies from patients undergoing coronary artery bypass surgery ( CABG ) .


Sixty patients were randomized to control ( n = 30 ) or RIPC ( n = 30 ) .


A blood pressure cuff was applied to the arm of all patients preoperatively .


The cuff remained deflated in control group , whereas RIPC was performed by 3 cycles of cuff inflation to 200 mm Hg for 5 min , separated by 5 min deflation intervals .


Left ventricular biopsies were obtained before and 15 min after aortic declamping .


The primary outcome was mitochondrial respiration measured in situ .


Secondary outcomes were activation of protein kinase Akt , assessed by western immunoblotting , and expression of microRNAs assessed by array and real-time polymerase chain reaction .


Mitochondrial respiration was preserved during surgery in patients receiving RIPC ( +0.2 mol O2/min/g , p = 0.69 ) , and reduced by 15 % in controls ( -1.5 mol O2/min/g , p = 0.02 ) .


Furthermore , RIPC activated protein kinase Akt before aortic clamping ( difference from control +43.3 % , p = 0.04 ) , followed by increased phosphorylation of Akt substrates at reperfusion ( +26.8 % , p < 0.01 ) .


No differences were observed in microRNA expression .


RIPC preserves mitochondrial function and activates pro-survival protein kinase Akt in left ventricle of patients undergoing CABG .


Modulation of mitochondrial function and Akt activation should be further explored as cardioprotective drug targets .


http://www.clinicaltrials.gov , unique identifier : NCT01308138 .


In the management of attention-deficit hyperactivity disorder ( ADHD ) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses .


Studies with methylphenidate modified release long acting ( MPH-LA ) in children have reported the need for treatment optimization for improved outcomes .


We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized , placebo-controlled , multicenter 40-week study ( 9-week double-blind dose confirmation phase , 5-week open-label dose optimization phase , and 26-week double-blind maintenance of effect phase ) .


Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day ; up/down titrated to their optimal dose ( at which there was balance between control of symptoms and side effects ) of 40 , 60 , or 80 mg/day in increments of 20 mg/week by week 12 or 13 .


Safety was assessed by monitoring the adverse events ( AEs ) and serious AEs .


Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , Attention-Deficit Hyperactivity Disorder Rating Scale ( DSM-IV ADHD RS ) and Sheehan Disability Scale ( SDS ) total scores .


At the end of the dose confirmation phase , similar numbers of patients were treated optimally with each of the 40 , 60 , and 80 mg/day doses ( 152 , 177 , and 160 , respectively ) for MPH-LA .


Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 9.90 and 9.7 7.36 , respectively .


Dose optimization with MPH-LA ( 40 , 60 , or 80 mg/day ) improved treatment outcomes and was well-tolerated in adult ADHD patients .


The aim of this study was to compare the efficacy of combined intracervical Foley catheter and low-dose vaginal misoprostol with low-dose vaginal misoprostol alone for induction of labor .


This prospective non-blinded randomized controlled trial was conducted over a 2-year period in 126 pregnant women planned for induction of labor at a tertiary care centre .


Women at 28 gestational weeks with a singleton fetus in cephalic presentation , intact membranes and a Bishop score of 4 were randomized for labor induction with either a combination of Foley catheter and misoprostol or only misoprostol .


The primary outcome variable was the induction-to-delivery interval between the two groups .


The secondary outcome variables included rate of vaginal deliveries , uterine hyperstimulation , cesarean section rate , Apgar scores at 1 and 5 min , neonatal intensive care unit admissions and chorioamnionitis .


The mean induction-to-delivery interval and rate of vaginal deliveries were not significantly different between the groups ( 26.52 h in the combination group and 27.64 h in the misoprostol group , P = 0.65 ; 65.07 % and 65.07 % , respectively , P = 0.9 ) .


Uterine hyperstimulation and meconium-stained liquor were significantly more prevalent in the misoprostol group ( P = 0.001 ) .


Neonatal outcomes did not differ significantly between the groups .


The addition of Foley catheter to misoprostol did not cause any statistically significant benefit in reducing the induction-to-delivery time .


However , it reduced the incidence of uterine hyperstimulation and meconium-stained liquor .


The aim of this study was to investigate clinical efficacy and safety of Remifemin on peri-menopausal symptoms in endometriosis patients with a post-operative GnRH-a therapy .


We treated 116 women who had endometriosis with either Remifemin ( n = 56 ) 20 mg bid po or Tibolone ( n = 60 ) 2.5 mg qd po for 12 weeks after GnRH-a injection .


The efficacy was evaluated by Kupperman menopausal index ( KMI ) , and hot flash/sweating scores .


The safety parameters such as liver and renal functions , lipid profile , endometrial thickness , and serum sex hormone level , as well as the incidence of adverse events were recorded .


( 1 ) After GnRH-a therapy , KMI and hot flash/sweating scores in both groups increased significantly ( P < 0.05 ) but we found no significant difference for KMI ( 2.871.40 for Remifemin and 2.701.26 for Tibolone ) and hot flash/sweating scores ( 0.941.72 for Remifemin and 1.061.78 for Tibolone ) between the 2 groups ( P > 0.05 ) .


( 2 ) No statistical change was observed in liver or renal functions and lipid profile in both groups before and after the treatment ( P > 0.05 ) .


The post-therapeutic serum FSH , LH , and E2 level and endometrial thickness decreased remarkably in both groups ( P < 0.05 ) .


E2 level in the Remifemin group was obviously lower than that in the Tibolone group ( P < 0.05 ) , and FSH and LH levels were strongly higher ( P < 0.05 ) .


No significant difference in thickness were found in either group ( P > 0.05 ) .


The Remifemin group had far fewer adverse events than the Tibolone group ( P < 0.05 ) .


Compared with Tibolone , Remifemin had a similar clinical efficacy and was safer for the peri-menopausal symptoms induced by GnRH-a in endometriosis patients .


To assess the dose proportionality of azacitidine pharmacokinetics ( PK ) after single subcutaneous ( SC ) doses of 25-100 mg/m2 , and determine the effect of renal impairment on PK after single and multiple 75 mg/m2 SC azacitidine doses .


Multicenter , phase I , open-label , parallel group study .


Community clinics and major academic centers .


Twenty-seven patients with solid or hematologic malignancies .


Part 1 evaluated azacitidine dose proportionality in patients with normal renal function randomized to single 25 , 50 , 75 , or 100 mg/m2 SC doses .


The 75 mg/m2 dosing group received 4 additional days of SC azacitidine .


In Part 2 , patients with severe renal impairment ( creatinine clearance < 30 ml/min/1 .73 m2 Cockcroft-Gault adjusted ) received azacitidine 75 mg/m2 for 5 consecutive days .


PK parameters were determined using noncompartmental methods .


In patients with normal renal function ( n = 21 ) , azacitidine area under the plasma-time curve ( AUC0 - ) and maximum observed plasma concentration ( Cmax ) were dose proportional within the 25-100 mg/m2 range .


Concentration versus time profiles after single and multiple azacitidine 75 mg/m2 doses were similar in shape for patients with normal ( n = 6 ) or impaired renal function ( n = 6 ) , with higher mean concentrations in the latter group .


Higher mean exposures ( AUC0 - and Cmax ) in renally impaired patients were observed ; however , individual exposure values were , with few exceptions , within the same range in both groups .


No drug accumulation after multiple doses was observed in either group .


Terminal half-life and time to maximum plasma concentration were comparable between groups .


Azacitidine tolerability was similar in patients with normal or impaired renal function .


Azacitidine is dose proportional over the 25-100 mg/m2 dosing range .


Overall , renal impairment had no important effect on azacitidine PK .


Therefore , no initial azacitidine dose adjustment in patients with renal impairment is required .


The purpose of this study was to determine ( a ) whether among sober ( blood alcohol concentration [ BAC ] = .00 % ) drivers , being drug positive increases the drivers ' risk of being killed in a fatal crash ; ( b ) whether among drinking ( BAC > .00 % ) drivers , being drug positive increases the drivers ' risk of being killed in a fatal crash ; and ( c ) whether alcohol and other drugs interact in increasing crash risk .


We compared BACs for the 2006 , 2007 , and 2008 crash cases drawn from the U.S. Fatality Analysis Reporting System ( FARS ) with control drug and blood alcohol data from participants in the 2007 U.S. National Roadside Survey .


Only FARS drivers from states with drug information on 80 % or more of the drivers who also participated in the 2007 National Roadside Survey were selected .


For both sober and drinking drivers , being positive for a drug was found to increase the risk of being fatally injured .


When the drug-positive variable was separated into marijuana and other drugs , only the latter was found to contribute significantly to crash risk .


In all cases , the contribution of drugs other than alcohol to crash risk was significantly lower than that produced by alcohol .


Although overall , drugs contribute to crash risk regardless of the presence of alcohol , such a contribution is much lower than that by alcohol .


The lower contribution of drugs other than alcohol to crash risk relative to that of alcohol suggests caution in focusing too much on drugged driving , potentially diverting scarce resources from curbing drunk driving .


Patients with head and neck cancer undergoing surgery have a high occurrence of postoperative complications .


The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients , using an enhanced enteral formula with three different doses of arginine could improve nutritional variables as well as clinical outcome , depending of arginine dose .


A population of 84 patients with oral and laryngeal cancer was enrolled .


At surgery patients were randomly assigned to three different treatment groups , each one containing at less 28 patients .


Group I ( 28 patients ) received an enteral diet supplements with a low physiological dose of arginine ( 5.7 g per day ) , group II ( 28 patients ) received an isocaloric , isonitrogenous enteral formula with a medium dose of arginine ( 12.3 g per day ) and group III ( 28 patients ) received an isocaloric , isonitrogenous enteral formula with a high dose of arginine ( 18.9 g per day ) .


The length of postoperative stay had a trend to be better with high dose of arginine received ( 31.9 17.2 days in group I vs 27.8 15.2 days in group II vs 24.8 18.3 days in group III : p = 0.034 ) .


No differences were detected in postoperative infections complications and diarrhea .


Fistula was less frequent in groups II and III than I ( 10.7 % group I vs 3.6 % group II vs 3.6 % group III : p = 0.033 ) , The length of postoperative stay had a trend to be better with high dose of arginine received ( 31.9 17.2 days in group I vs 27.8 15.2 days in group II vs 24.8 18.3 days in group III : p = 0.034 ) .


Our results suggest that these patients could benefit from a high dose of arginine enhanced enteral formula to decrease length of hospital stay and fistula wound complications .


Changes in adolescent interpersonal behavior before and after an acute course of psychotherapy were investigated as outcomes and mediators of remission status in a previously described treatment study of depressed adolescents .


Maternal depressive symptoms were examined as moderators of the association between psychotherapy condition and changes in adolescents ' interpersonal behavior .


Adolescents ( n = 63 , mean age = 15.6 years , 77.8 % female , 84.1 % White ) engaged in videotaped interactions with their mothers before randomization to cognitive behavior therapy ( CBT ) , systemic behavior family therapy ( SBFT ) , or nondirective supportive therapy ( NST ) and after 12-16 weeks of treatment .


Adolescent involvement , problem solving , and dyadic conflict were examined .


Improvements in adolescent problem solving were significantly associated with CBT and SBFT .


Maternal depressive symptoms moderated the effect of CBT , but not SBFT , on adolescents ' problem solving ; adolescents experienced increases in problem solving only when their mothers had low or moderate levels of depressive symptoms .


Improvements in adolescents ' problem solving were associated with higher rates of remission across treatment conditions , but there were no significant indirect effects of SBFT on remission status through problem solving .


Exploratory analyses revealed a significant indirect effect of CBT on remission status through changes in adolescent problem solving , but only when maternal depressive symptoms at study entry were low .


Findings provide preliminary support for problem solving as an active treatment component of structured psychotherapies for depressed adolescents and suggest one pathway by which maternal depression may disrupt treatment efficacy for depressed adolescents treated with CBT .


A high prevalence of low back pain has persisted over the years despite extensive primary prevention initiatives among nurses ' aides .


Many single-faceted interventions addressing just one aspect of low back pain have been carried out at workplaces , but with low success rate .


This may be due to the multi-factorial origin of low back pain .


Participatory ergonomics , cognitive behavioral training and physical training have previously shown promising effects on prevention and rehabilitation of low back pain .


Therefore , the main aim of this study is to examine whether a multi-faceted workplace intervention consisting of participatory ergonomics , physical training and cognitive behavioral training can prevent low back pain and its consequences among nurses ' aides .


External resources for the participating workplace and a strong commitment from the management and the organization support the intervention .


To overcome implementation barriers within usual randomized controlled trial designed workplace interventions , this study uses a stepped-wedge cluster-randomized controlled trial design with 4 groups .


The intervention is delivered to the groups at random along four successive time periods three months apart .


The intervention lasts three months and integrates participatory ergonomics , physical training and cognitive behavioral training tailored to the target group .


Local physiotherapists and occupational therapists conduct the intervention after having received standardized training .


Primary outcomes are low back pain and its consequences measured monthly by text messages up to three months after initiation of the intervention .


Intervention effectiveness trials for preventing low back pain and its consequences in workplaces with physically demanding work are few , primarily single-faceted , with strict adherence to a traditional randomized controlled trial design that may hamper implementation and compliance , and have mostly been unsuccessful .


By using a stepped wedge design , and obtain high management commitment and support we intend to improve implementation and aim to establish the effectiveness of a multi-faceted intervention to prevent low back pain .


This study will potentially provide knowledge of prevention of low back pain and its consequences among nurses ' aides .


Results are expected to be published in 2015-2016 .


The study is registered as ISRCTN78113519 .


Evidence is accumulating that , similar to other ventral hernias , umbilical and epigastric hernias must be mesh repaired .


The difficulties involved in mesh placement and in mesh-related complications could be the reason many small abdominal hernias are still primary closed .


In laparoscopic repair , a mesh is placed intraperitoneally , while the most common procedure is open surgery is pre-peritoneal mesh placement .


A recently developed alternative method is the so-called patch repair , in this approach a mesh can be placed intraperitoneally through open surgery .


In theory , such patches are particularly suitable for small hernias due to a reduction in the required dissection .


This simple procedure is described in several studies .


It is still unclear whether this new approach is associated with an equal risk of recurrence and complications compared with pre-peritoneal meshes .


The material of the patch is in direct contact with intra-abdominal organs , it is unknown if this leads to more complications .


On the other hand , the smaller dissection in the pre-peritoneal plane may lead to a reduction in wound complications .


346 patients suffering from an umbilical or epigastric hernia will be included in a multi-centre patient-blinded trial , comparing mesh repair with patch repair .


Randomisation will take place for the two operation techniques .


The two devices investigated are a flat pre-peritoneal mesh and a Proceed Ventral Patch .


Stratification will occur per centre .


Post-operative evaluation will take place after 1 , 3 , 12 and 24 months .


The number of complications requiring treatment is the primary endpoint .


Secondary endpoints are Verbal Descriptor Scale ( VDS ) pain score and VDS cosmetic score , operation duration , recurrence and costs .


An intention to treat analysis will be performed .


This trial is one of the first in its kind , to compare different mesh devices in a randomized controlled setting .


The results will help to evaluate mesh repair for epigastric an umbilical hernia , and find a surgical method that minimizes the complication rate .


Netherlands Trail Registration ( NTR ) www.trialregister.nl 2010 NTR2514 NL33995 .060.10 .


The aim of this study was to map the sensitivity of the marginal and other conjunctival regions and to investigate changes in the sensitivity of these regions when determined in the morning and evening .


Thirty-five healthy , noncontact lens wearers ( 20 female , 15 male ; age 27.7 7.3 years ) were enrolled .


Mechanical sensitivity was measured at 8 locations on the ocular surface and adnexa ( cornea , marginal , bulbar , and tarsal conjunctiva ) using a Cochet-Bonnet esthesiometer ( 0.12-mm diameter filament ) .


A subgroup of 11 subjects ( 6 female , 5 male ; age 28.9 9.9 years ) returned after 12 hours when this protocol was repeated .


The cornea was found to be the most sensitive region ( all P < 0.001 ) .


The marginal conjunctiva showed greater sensitivity than did the bulbar and tarsal conjunctiva ( all P < 0.001 ) .


The temporal marginal conjunctiva was more sensitive than the central marginal conjunctiva ( all P < 0.05 ) .


No difference in marginal conjunctival sensitivity was found between upper and lower eyelids ( all P > 0.05 ) .


The upper tarsal conjunctiva was more sensitive than the lower tarsal conjunctiva ( P = 0.04 ) .


There was no significant difference in the sensitivity determined in the morning and the evening for any of the locations investigated ( Bonferroni adjusted , P > 0.006 ) .


This work has demonstrated that the marginal conjunctiva was the most sensitive of all the conjunctival regions and that this does not alter over the course of the day .


To compare 7 weeks of supervised physical rehabilitation with or without progressive strength training ( PST ) commenced early after fast-track total knee arthroplasty ( TKA ) on functional performance .


In total , 82 patients with a unilateral primary TKA were randomized to 2 different interventions : 7 weeks of supervised physical rehabilitation with PST ( PST group ) and without PST ( CON group ) commenced early after fast-track TKA .


The primary outcome was the maximal distance walked in 6 minutes ( 6-minute walk test ) .


Secondary outcomes were lower extremity strength and power , knee joint effusion and range of motion , knee pain , and self-reported disability and quality of life .


All outcome measures were assessed before TKA ( baseline ) and 4 , 8 , and 26 weeks after TKA .


There was no statistically significant difference between the PST and CON groups in the change score from baseline to the 8-week postoperative assessment ( primary end point ) for the 6-minute walk test with unadjusted baseline scores ( mean difference between groups : -11.3 meters [ 95 % confidence interval -45.4 , 22.7 ] ; analysis of variance P = 0.51 ) .


There were no statistically significant or clinically meaningful differences between groups in change scores from baseline to any other time point for all secondary outcomes .


The secondary outcome knee extension strength did not reach the level recorded before surgery in both groups .


Seven weeks of supervised physical rehabilitation with PST was not superior to 7 weeks of supervised physical rehabilitation without PST in improving functional performance , measured as the maximal walking distance in 6 minutes , at the primary end point 8 weeks after fast-track TKA .


Effective interventions to improve medication adherence are usually complex and expensive .


To assess the impact of a low-cost intervention designed to improve medication adherence and clinical outcomes in post-discharge patients with CVD .


A pilot RCT was conducted at a teaching hospital .


Intervention was based on the four-item Morisky Medication Adherence Scale ( MMAS-4 ) .


The primary outcome measure was medication adherence assessed using the eight-item MMAS at baseline , at 1 month post hospital discharge and re-assessed 1 year after hospital discharge .


Other outcomes included readmission and mortality rates .


61 patients were randomized to intervention ( n = 30 ) and control ( n = 31 ) groups .


The mean age of the patients was 61 years ( SD 12.73 ) , 52.5 % were males , and 57.4 % were married or living with a partner .


Mean number of prescribed medications per patient was 4.5 ( SD 3.3 ) .


Medication adherence was correlated to intervention ( p = 0.04 ) and after 1 month , 48.4 % of patients in the control group and 83.3 % in the intervention group were considered adherent .


However , this difference decreased after 1 year , when adherence was 34.8 % and 60.9 % , respectively .


Readmission and mortality rates were related to low adherence in both groups .


The intervention based on a validated patient self-report instrument for assessing adherence is a potentially effective method to improve adherent behavior and can be successfully used as a tool to guide adherence counseling in the clinical visit .


However , a larger study is required to assess the real impact of intervention on these outcomes .


This study investigated the clinical efficacy of electroacupuncture ( EA ) in inhibiting upper-extremity spasticity in chronic stroke patients , and also in mapping a unique preliminary acupoint-selection protocol .


Fifteen patients were divided into two groups : patients in the control group ( n = 6 ) received minimal acupuncture ( MA ) , and those in the experimental group ( n = 9 ) received EA .


Four acupoints , which include Neiguan ( PC6 ) , Shaohai ( HT3 ) , Zeqian ( Ex-UE , A32 ) , and Shounizhu ( EX-UE ) , were treated near the motor points of the muscles for elbow flexion , forearm pronation , and finger flexion .


Both groups were treated for twelve sessions , 20 minutes per session , for 6 weeks ( two sessions per week ) .


The outcome measures in this study included angle of muscle reaction ( R1 ) , passive range of motion ( R2 ) , and dynamic component ( R2-R1 ) .


In the experimental group , the R2-R1 of the elbow joint was significantly decreased at 1 ( P = 0.0079 ) , 3 ( P = 0.0013 ) , and 6 weeks ( P = 0.0149 ) after treatment compared with pretreatment levels ( P < 0.05 ) .


The between-group difference in the R2-R1 of the elbow joint after the 6-week treatment was statistically significant .


Combining the 6-week EA and standard rehabilitation treatment reduced the spasticity of the elbow for chronic stroke survivors .


However , no significant effect was observed in the spasticity of the wrist joints .


The choice of acupoints and the frequency of EA have to be taken into account to achieve a positive treatment effect .


The correlation between acupoints and motor points provides a model of acupoint selection to improve spasticity .


The goal of this study is to determine whether bronchodilator ( BD ) response can be used as a reliable measure of asthma control by analyzing the effects of a short course of oral corticosteroids ( OC ) or placebo ( P ) on spirometry , sputum cytology and BD response in controlled asthma patients scoring less than 1.5 on the ACQ5 .


Seventy patients with moderate to severe asthma who were undergoing combination therapy and were considered to be controlled based on ACQ5 scores , but who exhibited persistent positive BD response , were randomly assigned to two groups , one receiving OC and the other P. Patients were evaluated before and after 2 weeks of treatment .


Intervention response ( comparison of FEV ( 1 ) before and after OC or P treatment ) was used as a measure of intervention efficacy , with values equal to or greater than 200mL considered positive .


Patients who received OC showed significant improvement in FEV ( 1 ) , and no longer exhibited a positive BD response .


Those in the P group showed no change .


In addition , sputum eosinophil counts significantly decreased in the OC group .


BD response can be used as a reliable measure of asthma control .


This study suggests that ACQ5 scores alone are not sufficient to fully assess asthma control , and that BD response should be included as an essential measurement in any algorithm of asthma control evaluation .


Previous research has demonstrated significant relationships between peri-shock pause and survival to discharge from out-of-hospital shockable cardiac arrest ( OHCA ) .


To determine the impact of peri-shock pause on survival from OHCA during the ROC PRIMED randomized controlled trial .


We included patients in the ROC PRIMED trial who suffered OHCA between June 2007 and November 2009 , presented with a shockable rhythm and had CPR process data for at least one shock .


We used multivariable logistic regression to determine the association between peri-shock pause duration and survival to hospital discharge .


Among 2006 patients studied , the median ( IQR ) shock pause duration was : pre-shock pause 15s ( 8 , 22 ) ; post-shock pause 6s ( 4 , 9 ) ; and peri-shock pause 22.0 s ( 14 , 31 ) .


After adjusting for Utstein predictors of survival as well as CPR quality measures , the odds of survival to hospital discharge were significantly higher for patients with pre-shock pause < 10s ( OR : 1.52 , 95 % CI : 1.09 , 2.11 ) and peri-shock pause < 20s ( OR : 1.82 , 95 % CI : 1.17 , 2.85 ) when compared to patients with pre-shock pause 20s and peri-shock pause 40s .


Post-shock pause was not significantly associated with survival to hospital discharge .


Results for neurologically intact survival ( Modified Rankin Score 3 ) were similar to our primary outcome .


In patients with cardiac arrest presenting in a shockable rhythm during the ROC PRIMED trial , shorter pre - and peri-shock pauses were significantly associated with higher odds of survival .


Future cardiopulmonary education and technology should focus on minimizing all peri-shock pauses .


In this study we assessed increased cortisol in Alzheimer 's disease ( AD ) patients .


The selective 11 -- hydroxysteroid dehydrogenase type 1 ( HSD-1 ) inhibitor ABT-384 blocked regeneration of active cortisol and this tests the hypothesis that intracellular hypercortisolism contributes to cognitive impairment .


In this double-blind , placebo - and active-controlled phase II study we examine the efficacy and safety of ABT-384 given 10 mg or 50 mg once daily , donepezil 10 mg once daily , or placebo for 12 weeks in subjects with mild-to-moderate AD .


The primary efficacy end point was the change from baseline to final evaluation on the 13-item Alzheimer 's Disease Assessment Scale-Cognitive subscale ( ADAS-Cog ) total score .


The study was terminated for futility after randomization of 267 subjects .


ABT-384 did not improve ADAS-Cog scores or any secondary end point ; however , donepezil significantly improved both cognition and functional end points .


Overall incidence of adverse events was similar among treatment groups .


ABT-384 , when tested at doses associated with complete brain HSD-1 inhibition , did not produce symptomatic improvement in AD .


Medical health care centres should aim at the application of a two-dimensional concept of quality -- technical quality and functional quality .


Technical quality means the compliance with norms and technical requirements which apply to medical services that are provided to patients .


This concerns medical standards , technology and the competence of medical staff .


Functional quality , which means the subjective estimate of patients , is an additional benefit for the patient and it becomes the best competitive advantage in conditions of comparable technical levels of provided medical services .


The patient will be satisfied with medical services if these elements are balanced .


The aim of the study was the evaluation of the quality of functional services in a specialist outpatient clinic in the Szczecin area by patients .


200 randomly-chosen patients of specialist outpatient clinics in Szczecin were asked to estimate the functional quality of services in specialist outpatient clinics .


A questionnaire was used .


The results were subjected to statistical analysis .


Most of the patients -- 51.3 % had confidence in their physician .


52.34 % of the patients claimed that their doctor was not interested in their problems .


Almost half of the respondents -- 47.92 % stated that there was no telephone contact with their doctor .


It is necessary to educate future physicians in problems of interpersonal communication .


Phase 3 randomized trials have shown that maintenance rituximab ( MR ) therapy or radioimmunotherapy ( RIT ) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma ( FL ) , but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework .


To evaluate and compare the economic impact of MR and RIT consolidation versus observation , respectively , following the first-line induction therapy for patients with advanced-stage FL .


We developed Markov models to estimate patients ' lifetime costs , quality-adjusted life-years ( QALYs ) , and life-years ( LYs ) after MR , RIT , and observation following frontline FL treatment from the US payer 's perspective .


Progression risks , adverse event probabilities , costs , and utilities were estimated from clinical data of Primary RItuximab and MAintenance ( PRIMA ) trial , Eastern Cooperative Oncology Group ( ECOG ) trial ( for MR ) , and First-line Indolent Trial ( for RIT ) and the published literature .


We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation .


Model robustness was addressed by one-way and probabilistic sensitivity analyses .


Compared with observation , MR provided an additional 1.089 QALYs ( 1.099 LYs ) and 1.399 QALYs ( 1.391 LYs ) on the basis of the PRIMA trial and the ECOG trial , respectively , and RIT provided an additional 1.026 QALYs ( 1.034 LYs ) .


The incremental cost per QALY gained was $ 40,335 ( PRIMA ) or $ 37,412 ( ECOG ) for MR and $ 40,851 for RIT .


MR and RIT had comparable incremental QALYs before first progression , whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias .


MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles .


The model results should be interpreted within the specific clinical settings of each trial .


Selection of MR , RIT , or observation should be based on patient characteristics and expected trade-offs for these alternatives .


To evaluate the effectiveness of a topically applied gel containing essential oils ( menthol and thymol ) and polyphenolic antioxidants ( phloretin and ferulic acid ) for reducing halitosis in dogs .


20 dogs .


A blinded crossover clinical trial was conducted .


Dogs received a dental cleaning and examination ( periodontal examination including periodontal probing and assessments of plaque , calculus , and gingivitis ) .


Owners then applied a gel ( active or placebo ) to oral soft tissues twice daily for a 4-week period .


Teeth of the dogs were cleaned again , and owners applied the other gel for a 4-week period .


Clinicians scored halitosis immediately after the initial cleaning and at 4 and 8 weeks , and owners scored halitosis weekly .


Halitosis assessment by clinicians revealed that both groups had improvement in halitosis scores .


Two dogs were removed because of owner noncompliance .


In the active-to-placebo group ( n = 9 ) , halitosis was significantly reduced during application of the active gel but increased during application of the placebo .


Seven of 9 owners reported increased halitosis when treatment was changed from the active gel to the placebo .


In the placebo-to-active group ( n = 9 ) , halitosis decreased during application of the placebo and continued to decrease during application of the active gel .


Seven of 9 owners reported a decrease in halitosis with the active gel .


An oral topically applied gel with essential oils and polyphenolic antioxidants applied daily after an initial professional dental cleaning decreased oral malodor in dogs .


The SNAP ( Smoking and Nicotine in Pregnancy ) trial compared nicotine replacement therapy ( NRT ) patches with placebo in pregnant smokers ; although NRT doubled cessation rates in the first 4 weeks , by delivery no differences in maternal smoking or birth outcomes were noted .


As a result , NRT used in standard doses during pregnancy is considered ineffective for smoking cessation .


Subsequent effects of NRT on the children of treated mothers are unknown because no trials have investigated the effect of gestational NRT use beyond birth .


To assess whether NRT use in pregnancy might cause harm to infants , we aimed to compare effects of NRT and placebo on infant development 2 years after delivery .


1050 pregnant smokers aged 16-45 years , at 12-24 weeks ' gestation , and smoking at least five cigarettes per day were recruited from seven hospitals in England between May 1 , 2007 , and Feb 26 , 2010 , and followed up until their infants were 2 years old .


Participants were randomly assigned ( 1:1 ) to receive up to 8-weeks treatment with NRT ( 15 mg/16 h transdermal patches ) or identically packaged and visually matched placebo patches ( all patches manufactured by and purchased at market rate from United Pharmaceuticals , Amman , Jordan ) , issued as two 4-week supplies ( 521 for NRT group , 529 for placebo group ) [ Corrected ] .


Randomisation was stratified by site with participants , health-care professionals , and research staff masked to treatment allocation .


The primary results for participants and infants at delivery were published in 2012 ; we present results from the trial cohort 2 years after birth .


After delivery , questionnaires were posted to participants and , if there was no response , to family physicians .


The primary outcome at 2 years was infants ' survival without developmental impairment ( ie , no disability or problems with behaviour or development ) .


Treatment groups were compared on an intention-to-treat basis .


The trial is registered with Controlled-Trials .


com , number ISRCTN07249128 .


Questionnaires were returned at 2 years for 891 ( 88 % ) of 1010 live singleton births ( 445 of ( 88 % ) 503 given NRT and 446 ( 88 % ) of 507 given placebo ) .


Because of missing data , developmental outcomes , including four infant deaths , were documented for 888 of ( 88 % ) 1010 singleton infants ; 445 ( 88 % ) of 503 infants in NRT group and 443 ( 87 % ) of 507 infants in placebo .


In the NRT group , 323 ( 73 % ) of 445 infants had no impairment compared with 290 ( 65 % ) of 443 infants in the placebo group ( odds ratio [ OR ] 1.40 , 95 % CI 1.05-1 .86 , p = 0.023 ) .


At 2 years , 15 ( 3 % ) of 521 mothers in the NRT group and nine ( 2 % ) of 529 mothers in the placebo groups self-reported prolonged smoking abstinence since a quit date set in pregnancy ( OR 1.71 , 95 % CI 0.74-3 .94 , p = 0.20 ) .


Adverse events were not collected after delivery , but previously reported adverse pregnancy and birth outcomes were similar in the two groups .


Infants born to women who used NRT for smoking cessation in pregnancy were more likely to have unimpaired development .


NRT had no effect on prolonged abstinence from smoking but did cause a temporary doubling of smoking cessation shortly after randomisation during pregnancy , which could explain findings .


If findings are confirmed by subsequent research , this has potential implications for the management of smoking in pregnancy .


National Institute for Health Research Health Technology Assessment Programme .


Isotretinoin has been used in combination with oral psoralen + UVA ( PUVA ) and narrowband UVB ( NBUVB ) for treating psoriasis , especially in women of child-bearing age .


The efficacy of oral psoralen + sun exposure ( PUVAsol ) is comparable to that of PUVA .


This study was planned to compare the efficacy of oral PUVAsol with that of the combination of oral isotretinoin and PUVAsol in patients with chronic plaque psoriasis .


Forty patients with psoriasis vulgaris were randomized to two groups .


Group A ( control group ) received PUVAsol only .


Group B ( intervention group ) received PUVAsol + isotretinoin ( 0.5 mg/kg/day ) .


Psoriasis Area Severity Index ( PASI ) score was recorded at baseline and weeks 4 , 8 and 12 .


Dermatology Life Quality Index was assessed at baseline and 12 weeks .


The end point of the study was PASI 75 or 12 weeks , whichever came earlier .


Thirty-five patients completed the study .


There were statistically significant differences between the two study groups for the number of patients achieving the endpoint of PASI 75 , PASI scores at the end of 12 weeks , mean duration to achieve PASI 75 , number of PUVAsol sessions needed to achieve PASI75 and mean cumulative dosage of 8-methoxypsoralen needed to achieve PASI 75 .


The combination of isotretinoin with PUVAsol is more effective compared with PUVAsol alone for treating chronic plaque psoriasis .


Leisure-time physical activity ( LTPA ) and exercise training are essential parts of current guidelines for patients with coronary artery disease ( CAD ) .


However , the contributions of LTPA and exercise training to cardiovascular ( CV ) risk in CAD patients with type 2 diabetes ( T2D ) are not well established .


We examined the effects of LTPA ( n = 539 and n = 507 ; with and without T2D , respectively ) and 2-year controlled , home-based exercise training ( n = 63 plus 64 control subjects with T2D and n = 72 plus 68 control subjects without T2D ) on the CV risk profile and composite end point among CAD patients .


During the 2-year follow-up , patients with reduced LTPA at baseline had an increased risk of CV events ( adjusted hazard ratio 2.3 [ 95 % CI 1.1-5 .1 ; P = 0.033 ] , 2.1 [ 1.1-4 .2 ; P = 0.027 ] , and 2.0 [ 1.0-3 .9 ; P = 0.044 ] for no LTPA , LTPA irregularly , and LTPA two to three times weekly , respectively ) compared with those with LTPA more than three times weekly .


Among patients who completed the 2-year exercise intervention , exercise training resulted in favorable changes in exercise capacity both in CAD patients with T2D ( +0.2 0.8 vs. -0.1 0.8 MET , P = 0.030 ) and without T2D ( +0.3 0.7 vs. -0.1 0.5 MET , P = 0.002 ) as compared with the control group but did not have any significant effects on major metabolic or autonomic nervous system risk factors in CAD patients with or without T2D .


There is an inverse association between habitual LTPA and short-term CV outcome , but controlled , home-based exercise training has only minor effects on the CV risk profile in CAD patients with T2D .


Eating difficulty is a critical and common problem in head and neck cancer patients undergoing radiotherapy ( RT ) .


It leads to poor quality of life and extensive tube feeding use .


Nutri-jelly , a food gel with semisolid texture , water-releasing ability , and ready-to-eat by spoon , was recently developed to alleviate the trouble .


However , its efficacy was unknown .


This study investigated the potential effect of Nutri-jelly on health-related quality of life ( HRQOL ) and nasogastric tube feeding use .


A prospective quasi-randomized patients-preference controlled trial was conducted in 74 head and neck cancer patients .


Subjects in study and control groups ( 37 each ) had similar baseline HRQOL and body mass index and undergone definitive radiotherapy ( 25-35 RT fractions , 5,000-7 ,000 cGy ) .


Only study group received a 200-ml box of Nutri-jelly as daily supplement throughout radiotherapy .


HRQOL was scored by validated questionnaires .


The use of tube feeding was collected from medical records .


From 11 to 35 RT fractions , the study group maintained higher overall HRQOL score than that of control group ( p < 0.0001 ) .


Multiple physiologic and psychological aspects of HRQOL especially swallowing difficulty and overall eating problems were significantly improved in study as compared to control group .


Promisingly , the percentage of tube feeding use in study group ( 13.5 % ) was dramatically lower than control group ( 48.6 % ) .


Continuous supplementation of Nutri-jelly throughout radiotherapy may improve HRQOL and reduce tube feeding demand in head and neck cancer patients who preferred to take them .


Nutri-jelly could be an alternative for head and neck cancer patients who have eating difficulty during radiotherapy .


To perform the first randomized controlled trial comparing soft contact lens ( SCL ) with rigid gas-permeable lens ( RGPL ) wearing in infantile nystagmus ( IN ) , using spectacle wear as a baseline .


Randomized , controlled cross-over trial with an intention-to-treat design .


A total of 24 participants with IN ( 12 idiopathic , 12 with albinism ) .


Participants were randomized into 1 of 2 treatment arms receiving the following sequence of treatments ( 2-3 weeks for each treatment ) : ( A ) spectacles , SCL , RGPL , and spectacle wear ; or ( B ) spectacles , RGPL , SCL , and spectacle wear .


The main outcome measure was mean intensity of nystagmus at the null region viewing at 1.2 m. Secondary outcome measures included the same measure at 0.4 m viewing and across the horizontal meridian ( measured over a 30 range at 3 intervals ) for distance and near .


The nystagmus foveation characteristics were similarly assessed over 30 and at the null region at 1.2 m and 0.4 m viewing .


Visual outcome measures included best-corrected visual acuity ( BCVA ) at 4 m and 0.4 m , gaze-dependent visual acuity ( GDVA ) ( i.e. , visual acuity when maintaining gaze angles over a 30 range at 10 intervals ) at 4 m , and reading performance at 0.4 m derived from the Radner reading chart .


There were no significant differences between SCL and RGPL wearing for any nystagmus characteristics or compared with spectacle wearing .


The BCVA , reading acuity , and critical print size were significantly worse for SCL wearing compared with RGPL and baseline spectacle wear ( P < 0.05 ) , although mean differences were less than 1 logarithm of the minimum angle of resolution ( logMAR ) line .


Nystagmus was not significantly different during SCL and RGPL wearing in IN , and contact lens wearing does not significantly reduce nystagmus compared with baseline spectacle wearing .


The wearing of SCL leads to a small but statistically significant deterioration in visual function compared with both RGPL and spectacle wearing at baseline , although mean effect sizes were not clinically relevant .


The value of qigong in the treatment of chronic low back pain is unclear .


In a randomized controlled trial , we evaluated whether qigong is non-inferior to exercise therapy in patients with chronic low back pain .


German outpatients ( aged 46.710.4 ) with chronic low back pain [ mean visual analogue scale ( VAS ) , 53.912.5 mm ] were enrolled and randomly allocated in a 1:1 ratio to receive either qigong ( 64 patients , 12 sessions with 190min/week over 3 months ) or exercise therapy ( 63 patients , 12 sessions 160min/week ) .


The primary outcome measure was the average pain intensity over the last 7 days on a VAS ( 0-100mm , 0 = no pain , 100 = worst imaginable pain , non-inferiority margin = 5mm ) after 3 months .


Follow-up was measured after 6 and 12 months .


The mean adjusted low back pain intensity after 3 months was 34.8 mm [ 95 % confidence interval ( CI ) 29.5 ; 40.2 ] in the qigong group and 33.1 mm ( 95 % CI 27.7 ; 38.4 ) in the exercise group .


Non-inferiority of the qigong group compared with the exercise group failed to show statistical significance ( p = 0.204 ) .


In both groups , 10 patients reported suspected adverse reactions ( e.g. , muscle soreness , dizziness , pain ) the total number was comparable in both groups ( qigong n = 40 , exercise n = 44 ) .


Qigong was not proven to be non-inferior to exercise therapy in the treatment of chronic low back pain .


Its role in the prevention of chronic low back pain might be addressed in further studies .


Maintaining target hemoglobin ( Hb ) with minimal variability is a challenge in hemodialysis ( HD ) patients .


The aim of this study is to compare the long - and short-acting erythropoietin-stimulating agents such as Aranesp and Eprex in achieving these targets .


Randomized , prospective , open-labeled study of 24 weeks includes stable patients on HD > 3 months , age > 18 years , and on Eprex for > 3 months .


Patients were randomized into two groups : A - ( Aranesp group ) : HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly , by using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2 weeks ; B - ( Eprex group ) : patients continued on Eprex treatment .


Hemoglobin target was set at ( 105-125 g/l ) .


Primary end points were percentage of patients achieving target Hb , hemoglobin variability , and number of dose changes in each group .


This study consisted of 139 HD patients : 72 in the Aranesp and 67 in the Eprex-mean ( SD ) age 54 ( 16.2 ) years , 77 ( 55 % ) males .


About 46 % were diabetic .


Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex ( p = 0.006 ) .


Hb variability was less frequent in the Aranesp group ( p = 0.2 ) .


Mean number of dose changes was 1.3 ( 0.87 ) in the Aranesp and 1.9 ( 1.2 ) in the Eprex ( p < 0.001 ) .


There was 1 vascular access thrombosis in the Aranesp and 8 in the Eprex ( p < 0.001 ) .


There was no difference in hospitalization and death number between the 2 groups .


Aranesp Q weekly or every 2 weeks is more efficient in achieving target Hb , with less dose changes and minor vascular access complications .


The vertebral column is the most common site of bone metastases irrespective of the primary tumor .


Vertebral metastases are a major cause of motor deficit of the lower extremities .


The use of radiotherapy is the treatment of choice in these patients .


A temporary worsening of pain shortly during the course of palliative radiotherapy is clinically a common problem .


Steroid infusion has well-documented neuroprotective effects .


Our study objective is to evaluate the effect of pre-emptive infusion of methylprednisolone on pain flare and motor function in patients with vertebral metastases .


One hundred twenty patients with vertebral metastases received short-course external beam radiotherapy as high-voltage irradiation with a 6 MeV , via linear accelerator .


In addition to the short-course radiotherapy , 60 patients received pre-emptive methylprednisolone infusion ( 5 mg/kg ) the day just before initiation of radiotherapy ( Group 1 [ G1 ] ) .


The other 60 patients received short-course radiotherapy without pretreatment methylprednisolone infusion , and only normal saline was infused ( Group 2 [ G2 ] ) .


The Brief Pain Inventory , incidence of pain flare during radiotherapy , and motor functions were evaluated using the Tomita scale at the time of initial assessment , at the end of external beam radiotherapy , and after two weeks .


Four patients ( 6.6 % ) in G1 experienced pain flare compared with 12 patients ( 20 % ) in G2 during the two-week short-course radiotherapy .


The mean values of pain scores were significantly reduced in both groups at the end of radiotherapy ; the mean value of worst , average , and current pain scores in G1 remained statistically significant in comparison to pretreatment and G2 mean values two weeks later .


Significant increase was noticed in patients with normal motor and ambulatory status in G1 at two and four weeks of initial assessment .


Pre-emptive methylprednisolone infusion is an effective prophylactic agent in the prevention of radiation-induced pain flare and improves functional motor status after short-term radiotherapy in patients with vertebral metastases .


To evaluate the effectiveness of subconjunctival bevacizumab and topical bevacizumab in preventing neovascularisation on high-risk corneal grafts .


The randomised , controlled , parallel group study was carried out from February 2008 to April 2012 at Isra Postgraduate Institute of Ophthalmology and Yasin Eye Hospital , Karachi .


Eyes with high-risk corneal transplantation with corneal neovascularisation were included in the trial .


Patients were randomly allocated to 3 groups : A , B and C.


After penetrating keratoplasty , Group A patients received subconjunctival bevacizumab ( 2.5 mg / 0.1 ml ) , Group B , patients received sham injection , while Group C patients received topical bevacizumab ( 2.5 % , 25 mg/ml ) .


lt was self-administered 4 times a day for 24 weeks .


Group B was the control group .


Corneal neovascular invasion area was measured using mathematical software programme Mat Lab .


Data analyses were done using SPSS version 19 .


Of the total 122 patients , there were 41 ( 33.88 % ) each in Group A and B , while Group C had 40 ( 32.78 % ) patients .


Among the 3 groups , mean corneal neovascular invasion area was minimum in Group A ( n = 3 ; 6.23 % ) , while in Group B it was 12.3 % ( n = 5 ) .


Group C had the maximum corneal neovascular invasion area after 24 weks ( n = 11 ; 26.7 % ) .


Maximum number of patients ( n = 36 ; 87.80 % ) attained visual acuity of 6/36 or better in Group Afollowed by Group C ( n = 26 ; 65 % ) and Group B ( n = 17 ; 41.46 % ) .


Subconjunctival bevacizumab reduces the recurrence of neovascularisation and , thus , helps increasing the frequency of graft survival in cases of high-risk corneal transplants .


When used topically , it is less effective .


The acute consumption of dietary nitrate has been shown to improve exercise capacity in athletes , healthy adults and subjects with peripheral vascular disease .


Many COPD patients have reduced exercise capacity .


We hypothesized that acute nitrate consumption might increase incremental shuttle walk test ( ISWT ) distance in COPD subjects .


Eleven COPD subjects were randomly assigned to consume either a high nitrate or a matched , low nitrate beverage in a double-blind , randomized , placebo-controlled , crossover design .


ISWT distance was measured both before and 3 h after the beverage and change was recorded .


After a 7-day washout , ISWT distances were re-measured before and 3 h after the alternate beverage and changes were recorded .


We observed an increase in ISWT distance after consuming the high nitrate juice ( 25 m ) compared with a reduction after the low nitrate juice ( 14 m ) ( p < 0.01 ) .


This improvement in exercise capacity was associated with significant increases in serum nitrate ( p < 0.000005 ) and nitrite ( p < 0.01 ) levels and a significant lowering of resting blood pressure ( < 0.05 ) .


In patients with stable COPD , the acute consumption of dietary nitrate increased serum nitrate/nitrite levels and exercise capacity and was associated with a decrease in resting blood pressure .


Nitrate consumption might alter exercise capacity in COPD patients .


Induction chemotherapy is associated with anemia in non-small cell lung cancer ( NSCLC ) patients undergoing radiotherapy .


This randomized , open-label study compared the effect of sequential radiochemotherapy ( RCHT ) versus RCHT + epoetin alfa ( RCHT + EPO ) , with respect to 2-year overall survival ( OS ) .


Patients 18 years received sequential RCHT ; one arm also received EPO ( chemotherapy day 1 , when Hb < 12 g/dL ) .


Kaplan-Meier analysis with log-rank test , and Cox-regression methods were performed .


Of the 385 patients randomized ( RCHT + EPO : n = 195 ; RCHT : n = 190 ) , 78 ( RCTH + EPO : 46 [ 23.6 % ] ; RCHT : 32 [ 16.8 % ] ) were anemic at baseline .


Two-year OS was higher in RCHT + EPO-treated versus RCHT-treated ( 28.5 % [ 95 % CI : 22.2-35 .1 % ] versus 20.6 % [ 95 % CI : 15.1-26 .8 % ] [ p = 0.2278 ] ) , and requirement for RBC transfusion was lower ( 24/195 [ 12.3 % ] versus 61/190 [ 32.1 % ] ) .


In anemic ( baseline ) patients ( post hoc analysis ) , median survival was shorter in RCTH-treated ( 212 days ) versus RCHT + EPO-treated ( 343 days ) ( Hazard ratio = 1.62 [ 95 % CI : 0.99-2 .63 ] , p = 0.0525 ) .


Adverse events were documented in 72.7 % ( RCHT + EPO : 75.0 % ; RCHT : 70.5 % ) patients , and thrombovascular events ( TVEs ) in 45 patients ( RCHT + EPO : 16.7 % ; RCHT : 7.9 % ; p = 0.0099 ) .


A statistically non-significant trend for 2-year OS was observed in a sub-group of EPO-treated NSCLC-patients with baseline anemia , although this trend was not maintained in the overall population with inoperable NSCLC .


The aim of the study was to investigate the functional differences between N20m and P30m components of somatosensory-evoked magnetic cortical field ( SEF ) in young and senior subjects .


Twenty-nine healthy subjects , 13 younger ( mean age : 21.8 years ) and 16 senior ( 63.8 years ) , participated .


Magnetic fields were measured using a 160-channel , whole head MEG .


Single - and paired-pulse stimulations of 200 artifact-free MEG signal epochs were averaged separately .


We calculated how aging affects recovery function of SEFs .


The senior showed a prolonged N20m peak latency compared to the younger , although the P30m peak latency was not significantly different between groups .


The N20m ratios at 60 and 80 ms in the senior were significantly increased compared to the ratios in the younger ( 60 ms : P < 0.05 , 80 ms : P < 0.001 ) .


The P30m ratios at inter-stimulus interval ( ISI ) of 80 and 100 ms showed even disinhibition in the senior than in the younger ( P < 0.05 ) .


The younger also showed a significantly negative correlation between P30m and N20m components ' recovery curves ( R = 0.72 , P < 0.05 ) .


Aging-related changes that occurred in recovery functioning were the decrease in N20m component suppression and the increase in P30m component recovery , indicating that the N20m and P30m components have different functions in aging-related recovery changes .


Our results show that the N20m ratio at an ISI of 80 ms was significantly increased in the senior group , indicating that the second stimulus-evoked SEF was less inhibited by the initial stimulus at this ISI , suggesting less refractory effect or increased disinhibition .


Cell-saving devices ( CS ) are frequently used in cardiac surgery to reduce transfusion requirements , but convincing evidence from randomized clinical trials is missing .


Filtration of salvaged blood in combination with the CS is widely used to improve the quality of retransfused blood , but there are no data to justify this approach .


To determine the contribution of CS and filters on transfusion requirements , we performed a multicenter factorial randomized clinical trial in two academic and four nonacademic hospitals .


Patients undergoing elective coronary , valve , or combined surgical procedures were included .


The primary end point was the number of allogeneic blood products transfused in each group during hospital admission .


From 738 included patients , 716 patients completed the study ( CS + filter , 175 ; CS , 189 ; filter , 175 ; neither CS nor filter , 177 ) .


There was no significant effect of CS or filter on the total number of blood products ( fraction [ 95 % confidence interval ] : CS , 0.96 [ 0.79 , 1.18 ] ; filter , 1.17 [ 0.96 , 1.43 ] ) .


Use of a CS significantly reduced red blood cell transfusions within 24 hours ( 0.75 [ 0.61,0.92 ] ) , but not during hospital stay ( 0.86 [ 0.71 , 1.05 ] ) .


Use of a CS was significantly associated with increased transfusions of fresh frozen plasma ( 1.39 [ 1.04 , 1.86 ] ) , but not with platelets ( 1.25 [ 0.93 , 1.68 ] ) .


Use of a CS significantly reduced the percentage of patients who received any transfusion ( odds ratio [ 95 % confidence interval ] : 0.67 [ 0.49 , 0.91 ] ) , whereas filters did not ( 0.92 [ 0.68 , 1.25 ] ) .


Use of a CS , with or without a filter , does not reduce the total number of allogeneic blood products , but reduces the percentage of patients who need blood products during cardiac surgery .


A prospective clinical study assessing new vertebral compression fracture after previous treatment .


The purpose of this study was to investigate the incidence and associated risk factors of new symptomatic osteoporotic vertebral compression fractures ( OVCFs ) in patients treated by percutaneous vertebroplasty ( PVP ) and kyphoplasty ( PKP ) versus conservative treatment , and to elucidate our findings .


There are a lot of reports concerning the feasibility and efficacy of this minimally invasive procedure compared with conservative treatment , especially in pain soothing .


However , it is still unclear whether the risk of subsequent fracture has increased among operative treatment patients in the long term .


From November 2005 to July 2009 , 290 consecutive patients with 363 OVCFs were randomly selected for PVP/PKP or conservative treatment and evaluated with a mean follow-up of 49.4 months ( 36-80 months ) .


Some parameters were characterized and statistically compared in this study .


Telephone questionnaires , clinical reexamine , and plain radiographs were performed in the follow-up .


Thirty-one of 290 ( 10.7 % ) patients had experienced 42 newly developed symptomatic secondary OVCFs .


Among 169 operation ( 53.3 % vertebroplasty , 46.7 % kyphoplasty ) and 121 comparison patients , there is no significant statistical difference of new OVCFs incidence between the two groups calculated by patient proportion .


However , in separate , the rate of secondary adjacent fractures calculated by vertebral refracture number is significantly higher than non-adjacent levels in PVP/PKP group but no significant statistical difference was observed in conservative group .


The time interval of recompression after operative procedure was much shorter than that for comparison group ( 9.7 17.8 versus 22.4 7.99 months , p = 0.017 ) .


In addition , older age , gender , fracture times , location of original fracture segment , the amount of cement , cement leakage , operation modality ( PVP or PKP ) , and initial number of OVCFs were documented , but these were not the influencing factors in this study ( p > 0.05 ) .


Patients who had experienced PVP/PKP were not associated with an increased risk of recompression in new levels .


However , recompression in new levels of PVP/PKP group occurred much sooner than that of conservative group in the follow-up period .


The incidence of new vertebral fractures observed at adjacent levels was substantially higher but no sooner than at distant levels in PVP/PKP group .


No major risk factors involving new OVCFs have been found in this study and augmentation for sandwich situation is not necessary .


Viral load ( VL ) monitoring is recommended , but seldom performed , in resource-constrained countries .


RV288 is a US President 's Emergency Plan for AIDS Relief ( PEPFAR ) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count .


Analyses from Uganda are presented here .


In this cross-sectional , observational study , patients on first-line antiretroviral therapy ( ART ) ( efavirenz or nevirapine + zidovudine/lamivudine ) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load ( HIV-1 RNA ) , CD4 cell count and clinical chemistry tests .


Subjects were recruited by time on treatment : 6-12 , 13-24 or > 24 months .


Logistic regression modelling identified predictors of virological suppression .


Linear regression modelling identified predictors of CD4 cell count recovery on ART .


We found that 85.2 % of 325 subjects were virologically suppressed ( viral load < 47 HIV-1 RNA copies/ml ) .


There was no difference in the proportion of virologically suppressed subjects by time on treatment , yet CD4 counts were higher in each successive stratum .


Women had higher median CD4 counts than men overall ( 406 vs. 294 cells/L , respectively ; P < 0.0001 ) and in each time-on-treatment stratum .


In a multivariate logistic regression model , predictors of virological suppression included efavirenz use [ odds ratio ( OR ) 0.47 ; 95 % confidence interval ( CI ) 0.22-1 .02 ; P = 0.057 ] , lower cost of clinic visits ( OR 0.815 ; 95 % CI 0.66-1 .00 ; P = 0.05 ) , improvement in CD4 percentage ( OR 1.06 ; 95 % CI 1.014-1 .107 ; P = 0.009 ) , and care at Kayunga vs.Kangulamira ( OR 0.47 ; 95 % CI 0.23-0 .92 ; P = 0.035 ) .


In a multivariate linear regression model of covariates associated with CD4 count recovery , time on highly active antiretroviral therapy ( ART ) ( P < 0.0001 ) , patient satisfaction with care ( P = 0.038 ) , improvements in total lymphocyte count ( P < 0.0001 ) and haemoglobin concentration ( P = 0.05 ) were positively associated , whereas age at start of ART ( P = 0.0045 ) was negatively associated with this outcome .


High virological suppression rates are achievable on first-line ART in Uganda .


The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic .


CD4 cell reconstitution was positively associated with CD4 count at study visit , time on ART , satisfaction with care at clinic , haemoglobin concentration and total lymphocyte count and negatively associated with age .


The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction ( MI ) compared with more stable presentations .


This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI .


The Dual Antiplatelet Therapy Study , a randomized double-blind , placebo-controlled trial , compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting .


The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed .


The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events ( MACCE ) .


The primary safety endpoint was GUSTO ( Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries ) moderate or severe bleeding .


Of 11,648 randomized patients ( 9,961 treated with drug-eluting stents , 1,687 with bare-metal stents ) , 30.7 % presented with MI .


Between 12 and 30 months , continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation ( MI group , 0.5 % vs. 1.9 % , p < 0.001 ; no MI group , 0.4 % vs. 1.1 % , p < 0.001 ; interaction p = 0.69 ) .


The reduction in MACCE for continued thienopyridine was greater for patients with MI ( 3.9 % vs. 6.8 % ; p < 0.001 ) compared with those with no MI ( 4.4 % vs. 5.3 % ; p = 0.08 ; interaction p = 0.03 ) .


In both groups , continued thienopyridine reduced MI ( 2.2 % vs. 5.2 % , p < 0.001 for MI ; 2.1 % vs. 3.5 % , p < 0.001 for no MI ; interaction p = 0.15 ) but increased bleeding ( 1.9 % vs. 0.8 % , p = 0.005 for MI ; 2.6 % vs. 1.7 % , p = 0.007 for no MI ; interaction p = 0.21 ) .


Compared with 12 months of therapy , 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI , and increased bleeding .


( The Dual Antiplatelet Therapy Study [ The DAPT Study ] ; NCT00977938 ) .


Accurate restoration of mechanical alignment is an important factor in reconstructive surgery of the lower extremity .


Conventional intraoperative methods , such as using an electrocautery cable , provide only a momentary evaluation of alignment .


In this study , we evaluated a novel technique using a laser emitter , which projected the mechanical axis of the lower extremity , providing continuous intraoperative information on alignment .


Alignment of 16 cadaver lower extremities was measured using the electrocautery cable method , the laser method , and CT scan as the standard measurement .


The mechanical axis was defined by a line from the center of the femoral head to the center of the ankle .


For simplifying measurements the intersection with the tibial plateau was divided into percentages from the medial border ( 0 % ) to the lateral border ( 100 % ) .


For using the laser method a laser emitting and laser catching device was developed , which is positioned and centered on the femoral head and the ankle using an image intensifier .


By catching the laser on the knee region the actual mechanical axis is marked .


The data demonstrated good correlation of the laser method when compared to the cable method ( P = 0.44 ) .


Comparison of the average mechanical axis between cable method and CT ( P = 0.819 ) and laser method and CT ( P = 0.647 ) did not show a statistically significant difference .


Average radiation time in comparison between cable method and laser method showed a statistically significant difference ( P = 0.013 ) , with the laser method requiring more radiation time .


Determination of the mechanical axis during surgery remains a difficult clinical problem .


Restoration of alignment is an important prognostic factor for surgical outcome .


Based on these data , the laser method represents a simple , yet effective tool for continuous intraoperative evaluation of lower extremity alignment .


The objective of this study was to evaluate the protective effects of a new device for reducing perineal tears during vaginal childbirth .


A multicenter open randomized controlled trial ( RCT ) was performed in Helsingborg , Lund and Malm , Sweden consisting of 1148 women .


Women anticipating a vaginal delivery were either randomized to the intervention group ( n = 574 in which the perineal protection device was used , or a control group ( n = 574 ) , in which the perineal protection device was not used .


The main outcome measurements were incidence of vaginal and perineal tears ( 1st to 4th degree tears ) and adverse effects on the parturient and newborn .


The incidences of first - and second-degree tears of the vagina ( p = 0.018 ) and perineum ( p = 0.005 ) were significantly reduced in the intervention group compared with the controls .


In the intervention - and control group , 184 women ( 34.9 % ) and 142 ( 26.6 % ) showed no perineal tearing , respectively ( p = 0.034 ) .


Numbers needed to treat to avoid any perianal tearing was 12 .


The incidence of anal sphincter rupture ( ASR ) was the same in both groups ( n = 19 ; 3.4 % ) .


No negative effects on mother or child from using the device were observed .


The perineal protective device significantly reduced the incidence of first - and second-degree tears in the vagina and perineum during vaginal birth and also significantly increased the number of parturients with a fully intact posterior commissure .


No significant reduction of ASR and no negative effects of the device were observed .


DNA methylation has been linked to many important biological phenomena .


Researchers have recently begun to sequence bisulfite treated DNA to determine its pattern of methylation .


However , sequencing reads from bisulfite-converted DNA can vary significantly from the reference genome because of incomplete bisulfite conversion , genome variation , sequencing errors , and poor quality bases .


Therefore , it is often difficult to align reads to the correct locations in the reference genome .


Furthermore , bisulfite sequencing experiments have the additional complexity of having to estimate the DNA methylation levels within the sample .


Here , we present a highly accurate probabilistic algorithm , which is an extension of the Genomic Next-generation Universal MAPper to accommodate bisulfite sequencing data ( GNUMAP-bs ) , that addresses the computational problems associated with aligning bisulfite sequencing data to a reference genome .


GNUMAP-bs integrates uncertainty from read and mapping qualities to help resolve the difference between poor quality bases and the ambiguity inherent in bisulfite conversion .


We tested GNUMAP-bs and other commonly-used bisulfite alignment methods using both simulated and real bisulfite reads and found that GNUMAP-bs and other dynamic programming methods were more accurate than the more heuristic methods .


The GNUMAP-bs aligner is a highly accurate alignment approach for processing the data from bisulfite sequencing experiments .


The GNUMAP-bs algorithm is freely available for download at : http://dna.cs.byu.edu/gnumap .


The software runs on multiple threads and multiple processors to increase the alignment speed .


This study is an analysis of the pre-trial quality assurance ( QA ) exercises submitted by clinicians from radiotherapy ( RT ) centres across Europe and Canada to qualify for participation in the CONVERT trial .


QA exercises submitted by 64 clinicians at 64 RT centres were included in this analysis .


The exercises included the completion of a trial-specific questionnaire and submission of a treatment plan , for both trial arms , for a patient fitting the eligibility criteria of the trial .


This article describes the QA programme set up for the CONVERT trial and identifies deviations from the trial protocol .


Patient eligibility , disease and critical structure outlining and treatment planning technique were assessed .


Results from QA trial-specific questionnaires received between February 2008 and September 2011 , returned as part of the QA exercise , indicated that the majority of centres ( 70.3 % ) were using 6-MV photons and type B treatment planning system algorithms ( 57.8 % ) .


90.6 % of clinicians assessed submitted data for patients who fitted the eligibility criteria for the trial .


There were inconsistencies in outlining of gross tumour volume ( GTV ) and organs at risk , mainly heart and oesophagus , and in the use of margins around the GTV .


Such a QA programme helps to ensure that centres conform to trial protocol and should reduce inconsistencies in RT planning that may confound the results of the CONVERT trial .


Few studies reporting pre-trial QA have been published to date .


This article outlines the importance of such a QA programme in the context of multicentre Phase III studies .


Pelvic floor muscle exercises ( PFME ) are commonly recommended during pregnancy and after birth for both prevention and treatment of lower urinary tract symptoms ( LUTS ) .


Stress urinary incontinence has long been presumed to be associated with urethral hypermobility .


Pregnancy and delivery are known cause of increasing bladder neck descent ( BND ) .


The present study aimed to determine the effect of antenatal PFME on bladder neck descent in nulliparous pregnancy .


219 nulliparous women pregnant between 8-12 weeks were interviewed and then underwent transperineal ultrasound .


Of the total , 108 women were randomly assigned to a PFMT group , while 111 women to a control group .


The latter group received routine antenatal care .


For the intervention group , patients were taught about PFMT using visual biofeedback by transperineal ultrasound .


The PFMT regimen comprised a series of 15 contractions , and each contraction was heldfor 5 seconds , with 5 seconds rest between each contraction .


Patients were asked to repeat this regimen for 3 times after each meal .


At second trimester , third trimester , 3-month postpartum and 6-month postpartum , the subjects in both groups were interviewed and then underwent another ultrasound assessment .


Transperineal ultrasound was performed after bladder emptying , with the patient in the supine position .


Bladder neck position was measured at rest and on maximal valsava , and the differences yielded a numerical valueforBND .


The sample size was calculated with apower of80 % p < 0.05 was considered significant .


SPSS 15 .


Ofor windows ( SPSS Inc. , Chicago , Illinois ) was used for statistical analyses .


Demographic characteristics did not differ significantly between PFMT and control groups , showing effective randomization .


Mean age was 26.953.94 and 26.515.41 years for PFMT and control group , respectively ( p = 0.49 ) .


There were no significant differences in bladder symptoms between the two groups at the first visit .


In the first trimester , the average BND of the PFMT group was slightly higher than BND of the control group ( 14.16.9 mm and 12.26.7 mm respectively ( p = 0.04 ) ) .


When comparing delivery mode by using Pearson 's Chi-square test , there was no statistically significant difference between two groups ( p = 0.35 ) .


The mean fetal birth weight of women in the PFMTgroup was 3,084 grams and in the control group was 3,093 grams ( p = 0.88 ) .


At 6 monthspostpartum , 80 women of the PFMT group and 65 women of the control group returned for follow-up .


There were no differences regarding the prevalence ofL UTS between the groups at 6 months after delivery .


Women in the control group had a higher BND ( 16.46.6 mm ) than those in the PFMT group ( 13.97.3 mm , p = 0.03 ) .


This difference was also found in the subgroup of the women who delivered vaginally ( BND = 17.56.7 mm in the control group and 13.27.4 mm in the PFMTgroup , p = 0.006 ) .


Although postpartum prevalence of LUTS was no different between groups , this study has demonstrated that antenatal pelvic floor muscle exercises may reduce bladder neck mobility at 6 months after childbirth .


The significance of such an effect remains to be determined .


To investigate the clinical response of gastro-esophageal reflux disease ( GERD ) symptoms to exclusion diets based on food intolerance tests .


A double blind , randomized , controlled pilot trial was performed in 38 GERD patients partially or completely non-responders to proton pump inhibitors ( PPI ) treatment .


Fasting blood samples from each patients were obtained ; leukocytotoxic test was performed by incubating the blood with a panel of 60 food items to be tested .


The reaction of leukocytes ( rounding , vacuolization , lack of movement , flattening , fragmentation or disintegration of cell wall ) was then evaluated by optical microscopy and rated as follows : level 0 = negative , level 1 = slightly positive , level 2 = moderately positive , and level 3 = highly positive .


A `` true '' diet excluding food items inducing moderate-severe reactions , and a `` control '' diet including them was developed for each patient .


Then , twenty patients received the `` true '' diet and 18 the `` control '' diet ; after one month ( T1 ) symptoms severity was scored by the GERD impact scale ( GIS ) .


Hence , patients in the `` control '' group were switched to the `` true '' diet , and symptom severity was re-assessed after three months ( T2 ) .


At baseline ( T0 ) the mean GIS global score was 6.68 ( range : 5-12 ) with no difference between `` true '' and control group ( 6.6 1.19 vs 6.7 1.7 ) .


All patients reacted moderately/severely to at least 1 food ( range : 5-19 ) , with a significantly greater number of food substances inducing reaction in controls compared with the `` true '' diet group ( 11.6 vs 7.0 , P < 0.001 ) .


Food items more frequently involved were milk , lettuce , brewer 's yeast , pork , coffee , rice , sole asparagus , and tuna , followed by eggs , tomato , grain , shrimps , and chemical yeast .


At T1 both groups displayed a reduction of GIS score ( `` true '' group 3.3 1.7 , -50 % , P = 0.001 ; control group 4.9 2.8 , -26.9 % , P = 0.02 ) , although the GIS score was significantly lower in `` true '' vs `` control '' group ( P = 0.04 ) .


At T2 , after the diet switch , the `` control '' group showed a further reduction in GIS score ( 2.7 1.9 , -44.9 % , P = 0.01 ) , while the `` true '' group did not ( 2.6 1.8 , -21.3 % , P = 0.19 ) , so that the GIS scores did n't differ between the two groups .


Our results suggest that food intolerance may play a role in GERD symptoms development , and leucocytotoxic test-based exclusion diets may be a possible therapeutic approach when PPI are not effective or indicated .


Pediatric traumatic brain injury ( TBI ) contributes to impairments in functioning in everyday settings .


Evidence suggests that online family problem-solving therapy ( FPST ) may be effective in reducing adolescent behavioral morbidity .


This article examines the efficacy of Counselor-Assisted Problem Solving ( CAPS ) , a form of online FPST in improving long-term functional outcomes of adolescents with TBI relative to Internet resources only .


Children , aged 12 to 17 years , who were hospitalized in the previous 7 months for TBI were enrolled in a multisite , assessor-blinded randomized controlled trial .


Consented participants were randomly assigned to CAPS or an Internet resource comparison ( IRC ) condition .


Outcomes were assessed at baseline and at follow-ups 6 , 12 , and 18 months postbaseline .


The Child and Functional Assessment Scale and the Iowa Family Interaction Rating Scale ( IFIRS ) served as primary outcomes of child and family functioning respectively .


For the Child and Functional Assessment Scale total , we found a significant group time interaction , with less impaired functioning for the CAPS group than for the IRC group at the final follow-up .


Parent education moderated the efficacy of CAPS on overall rates of impairment and school/work functioning , with the advantage of CAPS over IRC evident at the final follow-up only for participants with less-educated parents .


Neither group differences nor group time interactions were found for the IFIRS .


Relatively brief , online treatment shortly after injury may result in long-term improvements in child functioning , particularly among families of lower socioeconomic status .


Clinical implementation of CAPS during the initial months postinjury should be considered .


The Troms Intervention Study on Preterms evaluates an early , sensitizing intervention given to parents of prematurely born children ( birth-weight < 2000g ) .


The current study investigated the potential influence of the intervention on children 's self-reported and parental proxy-reported quality of life ( QoL ) at children 's age of nine .


Participants were randomized to either intervention ( PI , n = 72 ) or preterm control ( PC , n = 74 ) in the neonatal care unit , while healthy term-born infants were recruited to a term reference group ( TR , n = 75 ) .


The intervention was a modified version of the Mother-Infant Transaction Program , and comprised eight one-hour sessions during the last week before discharge and four home visits at 1 , 2 , 4 and 12weeks post-discharge .


The two control groups received care in accordance with written guidelines drawn up at the hospital .


Participants and parents reported QoL independently on the Kinder Lebensqualitt Fragebogen ( KINDL ) questionnaire .


Differences between groups were analyzed by SPSS ; Linear Mixed Models and parent-child agreement were analyzed and compared by intra-class correlations within each group .


On average , children in all groups reported high levels of well-being .


The PI children reported better physical well-being than the PC children ( p = 0.002 ) .


In all other aspects of QoL both the PI and the PC children reported at similar levels as the term reference group .


PI parents reported better emotional wellbeing ( p = 0.05 ) and a higher level of contentment in school ( p = 0.003 ) compared with PC parents .


Parent-child agreement was significantly weaker in the PI group than in the PC group on dimensions such as emotional well-being and relationships with friends ( p < 0.05 ) .


PI parents reported QoL similar to parents of terms on all aspects except the subscale self-esteem , while PC parents generally reported moderately lower QoL than TR parents .


This early intervention appears to have generated long-lasting positive effects , improving perceived physical well-being among prematurely born children and parent 's perception of these children 's QoL in middle childhood .


Clinical Trials Gov NCT00222456 .


Colorectal cancer is an important public health problem in Spain .


Over the last decade , several regions have carried out screening programmes , but population participation rates remain below recommended European goals .


Reminders on electronic medical records have been identified as a low-cost and high-reach strategy to increase participation .


Further knowledge is needed about their effect in a population-based screening programme .


The main aim of this study is to evaluate the effectiveness of an electronic reminder to promote the participation in a population-based colorectal cancer screening programme .


Secondary aims are to learn population 's reasons for refusing to take part in the screening programme and to find out the health professionals ' opinion about the official programme implementation and on the new computerised tool .


This is a parallel randomised trial with a cross-sectional second stage .


all the invited subjects to participate in the public colorectal cancer screening programme that includes men and women aged between 50-69 , allocated to the eleven primary care centres of the study and all their health professionals .


The randomisation unit will be the primary care physician .


The intervention will consist of activating an electronic reminder , in the patient 's electronic medical record , in order to promote colorectal cancer screening , during a synchronous medical appointment , throughout the year that the intervention takes place .


A comparison of the screening rates will then take place , using the faecal occult blood test of the patients from the control and the intervention groups .


We will also take a questionnaire to know the opinions of the health professionals .


The main outcome is the screening status at the end of the study .


Data will be analysed with an intention-to-treat approach .


We expect that the introduction of specific reminders in electronic medical records , as a tool to facilitate and encourage direct referral by physicians and nurse practitioners to perform colorectal cancer screening will mean an increase in participation of the target population .


The introduction of this new software tool will have good acceptance and increase compliance with recommendations from health professionals .


Clinical Trials.gov identifier NCT01877018 .


In order to assess relationships between thyroid hormone status and findings on brain MRI , a subset of babies was recruited to a multi-centre randomised , placebo-controlled trial of levothyroxine ( LT4 ) supplementation for babies born before 28 weeks ' gestation ( known as the TIPIT study , for Thyroxine supplementation In Preterm InfanTs ) .


These infants were imaged at term-equivalence .


Forty-five TIPIT participants had brain MRI using diffusion tensor imaging ( DTI ) to estimate white matter development by apparent diffusion coefficient ( ADC ) , fractional anisotropy ( FA ) and tractography metrics of number and length of streamlines .


We made comparisons between babies with the lowest and highest plasma FT4 concentrations during the initial 4 weeks after birth .


There were no differences in DTI metrics between babies who had received LT4 supplementation and those who had received a placebo .


Among recipients of a placebo , babies in the lowest quartile of plasma-free thyroxine ( FT4 ) concentrations had significantly higher apparent diffusion coefficient measurements in the posterior corpus callosum and streamlines that were shorter and less numerous in the right internal capsule .


Among LT4-supplemented babies , those who had plasma FT4 concentrations in the highest quartile had significantly lower apparent diffusion coefficient values in the left occipital lobe , higher fractional anisotropy in the anterior corpus callosum and longer and more numerous streamlines in the anterior corpus callosum .


DTI variables were not associated with allocation of placebo or thyroid supplementation .


Markers of poorly organised brain microstructure were associated with low plasma FT4 concentrations after birth .


The findings suggest that plasma FT4 concentrations affect brain development in very immature infants and that the effect of LT4 supplementation for immature babies with low FT4 plasma concentrations warrants further study .


Periodontitis is an inflammatory process in response to dental biofilm and leads to periodontal tissue destruction .


The aim of this study was the comparison of outcomes using either an enamel matrix derivative ( EMD ) or a nanocrystalline hydroxyapatite ( NHA ) in regenerative periodontal therapy after 6 and 12 months .


Using a parallel group , prospective randomized study design , we enrolled 19 patients in each group .


The primary outcome was bone fill after 12 months .


Attachment gain , probing pocket depth ( PPD ) reduction , and recession were secondary variables .


Additionally , early wound healing and adverse events were assessed .


Data analysis included test of noninferiority of NHA group ( test ) compared to EMD group ( reference ) in bone fill .


Differences in means of secondary variables were compared by paired t-test , frequency data by exact ( 2 ) test .


Both groups showed significant bone fill , reduction of PPD , increase in recession , and gain of attachment after 6 and 12 months .


No significant differences between groups were found at any time point .


Adverse events were comparable between both groups with a tendency of more complaints in the NHA group .


The clinical outcomes were similar in both groups .


EMD could have some advantage compared to NHA regarding patients comfort and adverse events .


The trial is registered with ClinicalTrials.gov NCT00757159 .


Recent neuroimaging studies on poststroke aphasia revealed maladaptive cortical changes in both hemispheres , yet their functional contribution in language recovery remains elusive .


The aim of this study was to evaluate the long-term efficacy of dual-hemisphere repetitive transcranial magnetic stimulation ( rTMS ) on poststroke aphasia .


Thirty patients with subacute poststroke nonfluent aphasia were randomly allocated to receive real or sham rTMS .


Each patient received 1000 rTMS pulses ( 1 Hz at 110 % of resting motor threshold [ rMT ] over the right unaffected Broca 's area and 1000 pulses ( 20 Hz at 80 % rMT ) over the left affected Broca 's area for 10 consecutive days followed by speech/language training .


The language section of the Hemispheric Stroke Scale ( HSS ) , the Stroke Aphasic Depression Questionnaire-Hospital Version ( SADQ-H ) , and the National Institutes of Health Stroke Scale ( NIHSS ) were measured before , immediately after the 10 sessions , and 1 and 2 months after the last session .


At baseline , there were no significant differences between groups in demographic and clinical rating scales .


However , there was a significantly greater improvement in the HSS language score as well as in the SADQ-H after real rTMS compared with sham rTMS , which remained significant 2 months after the end of the treatment sessions .


This is the first clinical study of dual-hemisphere rTMS in poststroke aphasia .


Combining dual-hemisphere rTMS with language training might be a feasible treatment for nonfluent aphasia ; further multicenter studies are needed to confirm this result .


The randomized , phase III AVAPERL trial evaluated the safety and efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous nonsmall-cell lung cancer ( nsNSCLC ) .


Progression-free survival ( PFS ) was significantly prolonged with bevacizumab-pemetrexed , but overall survival ( OS ) data were immature .


In this article , we report an independent , updated analysis of survival outcomes in AVAPERL .


Patients with advanced nsNSCLC received first-line bevacizumab ( 7.5 mg/kg ) , cisplatin ( 75 mg/m ( 2 ) ) , and pemetrexed ( 500 mg/m ( 2 ) ) every 3 weeks ( q3w ) for four cycles .


Nonprogressing patients were randomized to maintenance bevacizumab ( 7.5 mg/kg ) or bevacizumab-pemetrexed ( 500 mg/m ( 2 ) ) q3w until progression or consent withdrawal .


The primary end point of the trial was PFS ; in this independent OS analysis , participating study centers were contacted to collect survival data on patients still alive at the time of the first analysis .


A total of 376 patients received induction treatment .


Disease control was confirmed in 71.9 % of patients ; 253 patients were randomized to maintenance treatment with bevacizumab ( n = 125 ) or bevacizumab-pemetrexed ( n = 128 ) .


At a median follow-up of 14.8 months , patients allocated to bevacizumab-pemetrexed had significantly improved PFS versus those on bevacizumab when measured from randomization [ 7.4 versus 3.7 months , hazard ratio ( HR ) , 0.57 , 95 % confidence interval ( CI ) 0.44-0 .75 ) ; P < 0.0001 ] .


OS events occurred in 58 % of all patients .


OS was numerically longer with bevacizumab-pemetrexed versus bevacizumab when measured from randomization [ 17.1 versus 13.2 months , HR 0.87 ( 0.63-1 .21 ) ; P = 0.29 ] .


Second-line therapy was administered in 77 % and 70 % of patients in the bevacizumab and bevacizumab-pemetrexed arms , respectively .


No new adverse events were reported during this updated analysis .


In an unselected population of nsNSCLC patients achieving disease control on platinum-based induction therapy , maintenance with bevacizumab-pemetrexed was associated with a nonsignificant increase in OS over bevacizumab alone .


Preoperative airway assessment in Denmark is based on a non-specific clinical assessment left to the discretion of the responsible anesthesiologist .


The DIFFICAIR trial compares the effect of using a systematic and consistent airway assessment versus a non-specific clinical assessment on the frequency of unanticipated difficult airway management.To prevent outcome bias and selective reporting , we hereby present a detailed statistical analysis plan as an amendment ( update ) to the previously published protocol for the DIFFICAIR trial .


The DIFFICAIR trial is a stratified , parallel group , cluster ( cluster = department ) randomized multicenter trial involving 28 departments of anesthesia in Denmark randomized to airway assessment either by the Simplified Airway Risk Index ( SARI ) or by a usual non-specific assessment .


Data from patients ' preoperative airway assessment are registered in the Danish Anesthesia Database .


An objective score for intubation grading the severity , that is the severity of the intubations , as well as the frequency of unanticipated difficult intubation , is measured for each group.Primary outcome measures are the fraction of unanticipated difficult and easy intubations.The database is programmed so that the registration of the SARI is mandatory for the intervention group but invisible to controls.Data recruitment was commenced in October 2012 and ended in ultimo December 2013 .


We intend to increase the transparency of the data analyses regarding the DIFFICAIR trial by an a priori publication of a statistical analysis plan .


ClinicalTrials.gov : NCT01718561 .


To assess the effect of an electronic health record-based transitional care intervention involving automated alerts to primary care providers and staff when older adults were discharged from the hospital .


Randomized controlled trial .


Large multispecialty group practice .


Individuals aged 65 and older discharged from hospital to home .


In addition to notifying primary care providers about the individual 's recent discharge , the system provided information about new drugs added during the inpatient stay , warnings about drug-drug interactions , recommendations for dose changes and laboratory monitoring of high-risk medications , and alerts to the primary care provider 's support staff to schedule a posthospitalization office visit .


An outpatient office visit with a primary care provider after discharge and rehospitalization within 30 days after discharge .


Of the 1,870 discharges in the intervention group , 27.7 % had an office visit with a primary care provider within 7 days of discharge .


Of the 1,791 discharges in the control group , 28.3 % had an office visit with a primary care provider within 7 days of discharge .


In the intervention group , 18.8 % experienced a rehospitalization within the 30-day period after discharge , compared with 19.9 % in the control group .


The hazard ratio for an office visit with a primary care physician did not significantly differ between the intervention and control groups .


The hazard ratio for rehospitalization in the 30-day period after hospital discharge in the intervention versus the control group was 0.94 ( 95 % confidence interval = 0.81-1 .1 ) .


This electronic health record-based intervention did not have a significant effect on the timeliness of office visits to primary care providers after hospitalization or risk of rehospitalization .


Psychological stress may alter immune function by activating physiological stress pathways .


Building on our previous study , in which we report that stress management training led to an altered self-reported and cortisol response to psychological stress in patients with rheumatoid arthritis ( RA ) , we explored the effects of this stress management intervention on the immune response to a psychological stress task in patients with RA .


In this study , 74 patients with RA , who were randomly assigned to either a control group or a group that received short stress management training , performed the Trier Social Stress Test ( TSST ) 1 week after the intervention and at a 9-week follow-up .


Stress-induced changes in levels of key cytokines involved in stress and inflammatory processes ( for example , interleukin ( IL ) -6 and IL-8 ) were assessed .


Basal and stress-induced cytokine levels were not significantly different in patients in the intervention and control groups one week after treatment , but stress-induced IL-8 levels were lower in patients in the intervention group than in the control group at the follow-up assessment .


In line with our previous findings of lower stress-induced cortisol levels at the follow-up of stress management intervention , this is the first study to show that relatively short stress management training might also alter stress-induced IL-8 levels in patients with RA .


These results might help to determine the role of immunological mediators in stress and disease .


The Netherlands National Trial Register ( NTR1193 )


The use of intravenous regional anesthesia ( IVRA ) is limited by pain resulting from the application of tourniquets and postoperative pain .


To assess the efficacy of low-level laser therapy added to IVRA for improving pain related to surgical fixation of distal radius fractures .


The present double-blinded , placebo-controlled , randomized clinical trial involved 48 patients who were undergoing surgical fixation of distal radius fractures .


Participants were randomly assigned to either an intervention group ( n = 24 ) , who received 808 nm laser irradiation as 4 Jpoint for 20 s over ipsilateral three nerve roots in the cervical region corresponding to C5-C8 vertebrae , and 808 nm laser irradiation as 0.1 Jcm2 for 5 min in a tangential scanning mode over the affected extremity ; or a control group ( n = 24 ) , who underwent the same protocol and timing of laser probe application with the laser switched off .


Both groups received the same IVRA protocol using 2 % lidocaine .


The mean visual analogue scale scores were significantly lower in the laser-assisted group than in the lidocaine-only group on all measurements during and after operation ( P < 0.05 ) .


The mean time to the first need for fentanyl administration during the operation was longer in the laser group ( P = 0.04 ) .


The total amount of fentanyl administered to patients was significantly lower in the laser-assisted group ( P = 0.003 ) .


The laser group needed significantly less pethidine for pain relief ( P = 0.001 ) and at a later time ( P = 0.002 ) compared with the lidocaine-only group .


There was no difference between the groups in terms of mean arterial pressure and heart rate .