A significant post-treatment decrease ( p = 0.009 ) in vibration perception threshold ( VPT ) for left foot after active treatment was observed .


Present results highlight utility of NitroSense Derma Protect as controllable nitric oxide source for patients with DPN .


Exercise-induced adaptations of the human atria remain understudied , particularly early in the training process .


We examined the effects of short-term high-intensity interval training ( HIT ) and continuous moderate-intensity training ( CMT ) on left atrial ( LA ) systolic and diastolic function , relative to left ventricular ( LV ) function in young , healthy men , by speckle tracking echocardiography ( STE ) .


Fourteen untrained men ( mean age = 25 4 years ) were randomized to HIT or CMT , and assessed before and after six training sessions over a 12-day period .


HIT included 8-12 intervals of cycling for 60 s at 95-100 % of maximal aerobic power ( VOMAX ) , interspersed by 75 s of cycling at 10 % VOMAX .


CMT consisted of 90-120 min of cycling at 65 % VOMAX .


VOMAX increased following HIT and CMT by 11.5 and 5.5 % , respectively ( p < 0.05 ) .


Calculated plasma volume expanded 11 % following HIT and 10 % following CMT ( p < 0.005 ) .


Resting LV volumes and ejection fraction were unaltered following training .


Peak atrial longitudinal strain increased following HIT ( 41.8 5.2 % -47.1 3.7 % , p < 0.01 ) and CMT ( 38.5 4.6 % -41.7 6.0 % , p < 0.01 ) .


Atrial systolic strain rate increased following HIT ( 1.6 0.2 % / s-2 .0 0.3 % / s , p < 0.01 ) and CMT ( 1.6 0.2 % / s-1 .9 0.2 % / s , p < 0.01 ) .


LA function assessed by STE improves rapidly during short-term intensive exercise training .


To compare the effects of three methods of values clarification ( VCM ) : balance sheet ; rating and ranking ; and a discrete choice experiment ( DCE ) on decision-making about colorectal cancer ( CRC ) screening among adults in the US and Australia .


Using online panels managed by a survey research organization in the US and Australia , we recruited adults ages 50-75 at average risk for CRC for an online survey .


Those eligible were randomized to one of the three VCM tasks .


CRC screening options were described in terms of five key attributes : reduction in risk of CRC incidence and mortality ; nature of the screening test ; screening frequency ; complications from screening ; and chance of requiring a colonoscopy ( as initial or follow-up testing ) .


Main outcomes included self-reported most important attribute and unlabeled screening test preference by VCM and by country , assessed after the VCM .


A total of 920 participants were enrolled ; 51 % were Australian ; mean age was 59.0 ; 87.0 % were white ; 34.2 % had a 4-year college degree ; 42.8 % had household incomes less than $ 45,000 USD per year ; 44.9 % were up to date with CRC screening .


Most important attribute differed across VCM groups : the rating and ranking group was more likely to choose risk reduction as most important attribute ( 69.8 % ) than the balance sheet group ( 54.7 % ) or DCE ( 49.3 % ) , p < 0.0001 ; most important attribute did not vary by country ( p = 0.236 ) .


The fecal occult blood test ( FOBT ) - like test was the most frequently preferred test overall ( 55.9 % ) .


Unlabeled test choice did not differ meaningfully by VCM .


Australians were more likely to prefer the FOBT ( AU 66.2 % vs. US 45.1 % , OR 2.4 , 95 % CI 1.8 , 3.1 ) .


Few participants favored no screening ( US : 9.2 % , AU : 6.2 % ) .


Screening test attribute importance varied by VCM , but not by country .


FOBT was more commonly preferred by Australians than by Americans , but test preferences were heterogeneous in both countries .


Given the ubiquity of worrying as a consuming and distressing activity at both clinical and sub-clinical levels , it is important to develop theory-driven procedures that address worrying and allow worriers to manage this activity .


This paper describes the development and testing of a psychoeducation procedure based on mood-as-input hypothesis , which is a transdiagnostic model that describes a proximal mechanism for perseverative worrying .


The study used nonclinical participants meeting IAPT criteria indicating GAD symptomatology .


In 4 sessions , participants in experimental groups received psychoeducation about the basic principles of the mood-as-input hypothesis and received guidance on how to identify and change worry-relevant goal-directed decision rules and negative moods .


Participants in the psychoeducation conditions were compared with participants in a befriending control group .


Psychoeducation about the model significantly reduced PSWQ scores at follow-up compared with the befriending control condition ( a between-groups large effect size , Cohen 's d = 1.05 ) , and the homework tasks undertaken by the psychoeducation groups raised mood and reduced worry immediately .


At follow up 48.2 % of participants in the psychoeducation groups were below the recommended cut-off for identifying GAD symptomatology compared with 20 % of participants in the control condition .


This study was conducted on a small sample , high-worry student population , without a formal diagnosis .


This brief , low-intensity procedure is potentially adaptable to online or self-help procedures , and can be integrated into fuller cognitive therapy packages .


We evaluated the immunogenicity , efficacy , and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence .


This 6-site , 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16 .


We measured urine cocaine metabolites thrice weekly as the main outcome .


The 300 subjects ( 76 % male , 72 % African-American , mean age 46 years ) had smoked cocaine on average for 13 days monthly at baseline .


We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of 42 g/mL ( high IgG ) , which was attained by 67 % of the 130 vaccine subjects receiving five vaccinations .


Almost 3-times fewer high than low IgG subjects dropped out ( 7 % vs 20 % ) .


Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups ( placebo , high , low IgG ) , after week 8 , more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial ( 24 % vs 18 % ) , and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment ( OR = 3.02 ) , but neither were significant .


Injection site reactions of induration and tenderness differed between placebo and active vaccine , and the 29 serious adverse events did not lead to treatment related withdrawals , or deaths .


The vaccine was safe , but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence .


There is strong evidence of the efficacy of family psychosocial interventions for schizophrenia , but evidence of the role played by the attitudes of relatives in the therapeutic process is lacking .


To study the effect of a family intervention on family attitudes and to analyse their mediating role in the therapeutic process 50 patients with schizophrenia and their key relatives undergoing a trial on the efficacy of a family psychosocial intervention were studied by means of the Affective Style Coding System , the Scale of Empathy , and the Relational Control Coding System .


Specific statistical methods were used to determine the nature of the relationship of the relatives ' attitudes to the outcome of family intervention .


Family psychosocial intervention was associated with a reduction in relatives ' guilt induction and dominance and an improvement in empathy .


Empathy and lack of dominance were identified as independent mediators of the effect of family psychosocial intervention .


The change in empathy and dominance during the first 9months of the intervention predicted the outcome in the following 15months .


Relatives ' empathy and lack of dominance are mediators of the beneficial effect of family psychosocial intervention on patient 's outcome .


Cognitive-behavioral ( CB ) interventions improve outcomes for many pediatric health conditions , but little is known about which mechanisms mediate these outcomes .


The goal of this study was to identify whether changes in targeted process variables from baseline to 1 week posttreatment mediate improvement in outcomes in a randomized controlled trial of a brief CB intervention for idiopathic childhood abdominal pain .


Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to 1 of 2 conditions : a 3-session social learning and CB treatment ( N = 100 ) , or a 3-session educational intervention controlling for time and attention ( N = 100 ) .


Outcomes were assessed at 3 - , 6 - , and 12-month follow-ups .


The intervention focused on altering parental responses to pain and on increasing adaptive cognitions and coping strategies related to pain in both parents and children .


Multiple mediation analyses were applied to examine the extent to which the effects of the social learning and CB treatment condition on child gastrointestinal ( GI ) symptom severity and pain as reported by children and their parents were mediated by changes in targeted cognitive process variables and parents ' solicitous responses to their child 's pain symptoms .


Reductions in parents ' perceived threat regarding their child 's pain mediated reductions in both parent-reported and child-reported GI symptom severity and pain .


Reductions in children 's catastrophic cognitions mediated reductions in child-reported GI symptom severity but no other outcomes .


Reductions in parental solicitousness did not mediate outcomes .


Results suggest that reductions in reports of children 's pain and GI symptoms after a social learning and CB intervention were mediated at least in part by decreasing maladaptive parent and child cognitions .


To assess the nasal functions , nasal resistance , and olfactory function in middle turbinate surgery .


Randomized controlled trial .


This prospective controlled study was carried out on patients who underwent laminectomy for aeration of the middle turbinate .


Patients participating in the study were divided into two groups-group 1 : medial laminectomy ( n = 34 ) and group 2 : lateral laminectomy ( n = 38 ) .


Patients underwent the preoperative visual analogue score , sinonasal outcome test-22 ( SNOT-22 ) , peak nasal inspiratory flowmeter , and Connecticut Chemosensory Clinical Research Center smell test .


All patients were reevaluated 3 months after the operation .


The study group comprised 72 consecutive patients .


The mean age of the patients was 31.039.7 , with a range of 17 to 54 years .


A total of 47.2 % ( n = 34 ) had medial and 52.8 % ( n = 38 ) had lateral laminectomy .


Bilateral turbinate intervention was performed in 27.8 % ( n = 20 ) , whereas unilateral middle turbinate intervention was performed in 72.3 % ( n = 52 ) .


Overall , both groups showed strong significant improvement over time in visual analogue scale results , SNOT-22 scores , peak flowmeter results , and olfactory function between preoperative and postoperative scores ( P < 0.001 ) .


There was no significant difference between the groups for all parameters ( P > 0.05 ) .


This study revealed that medial laminectomy for aeration of the middle turbinate was as effective as lateral laminectomy .


1b .


Laryngoscope , 125:1062 -1066 , 2015 .


Gabapentin enacarbil ( GEn ) is a prodrug of gabapentin and is approved in the United States in adults for the management of postherpetic neuralgia and in the United States and Japan for the treatment of moderate-to-severe primary restless legs syndrome .


This study examined the lack of effect of GEn on cardiac repolarization in accordance with International Conference on Harmonisation E14 guidance .


This was a randomized , double-blind , double-dummy , placebo - and active - controlled , crossover study in healthy adults ( age range , 18-50 years ) .


Study participants received the following in randomized order with a minimum 7-day washout period between treatments : placebo at 0 hours and GEn 1200 mg at 2 hours ( GEn 1200 mg group ) , placebo at 0 hours and GEn 6000 mg at 2 hours ( GEn 6000 mg group ) , placebo at 0 and 2 hours ( placebo group ) , moxifloxacin 400 mg ( active control group ) at 0 hours , and placebo at 2 hours ( moxifloxacin group ) .


Dose offsetting permitted moxifloxacin to be administered in the fasted state and GEn to be administered in the fed state .


Assessments included continuous ECG monitoring , pharmacokinetic parameters , and safety and tolerability profiles .


The primary end point was the change from baseline in the Fridericia corrected QT interval , at each time point , for the GEn 6000 mg and placebo groups .


Of 52 adults enrolled ( mean [ SD ] age , 30.8 [ 8.55 ] years ; 50 % women ) , 44 adults ( 85 % ) completed the study .


Forty-nine adults received GEn 1200 mg , 47 received GEn 6000 mg , 48 received placebo , and 47 received moxifloxacin .


The highest estimated ( upper limit of the 95 % CI ) model-adjusted difference in mean change from baseline in the Fridericia corrected QT interval between GEn and placebo was 3.55 ( 5.66 ) msec for 1200 mg and 1.20 ( 3.32 ) msec for 6000 mg .


Assay sensitivity was confirmed with moxifloxacin 400 mg .


The geometric mean ( % CV ) Cmax ( between-subject coefficient of variation ) was 7.49 ( 21.2 ) g/mL for GEn 1200 mg , 32.46 ( 23.9 ) g/mL for GEn 6000 mg , and 2.08 ( 24.5 ) g/mL for moxifloxacin 400 mg .


The most frequently reported adverse events with GEn 6000 mg were dizziness ( 30 % ) , feeling drunk ( 26 % ) , nausea ( 15 % ) , headache ( 13 % ) , and vomiting ( 13 % ) .


Single doses of GEn , up to 6000 mg , had no effect on cardiac repolarization in this thorough-QT study and are unlikely to cause clinically relevant QT prolongation in clinical use .


Assay sensitivity was confirmed with moxifloxacin as an active control .


ClinicalTrials.gov identifier : NCT01516372 .


Coronary vasodilator dysfunction has been reported after drug-eluting stent ( DES ) implantation .


Recent ESC guidelines suggest that transthoracic echocardiography ( TTE ) may be considered for assessment of coronary flow reserve ( CFR ) and microvascular disease in patients with stable angina , but its reliability has not been tested in patients with DES .


We sought to assess the agreement between TTE ( CFRTTE ) and invasive thermodilution-derived CFR ( CFRThermodilution ) as well as their association with index of microcirculatory resistance ( IMR ) in mid-term follow-up after percutaneous coronary intervention for acute coronary syndrome .


CFRTTE and CFRThermodilution were assessed 3 months after DES implantation in the left anterior descending artery in 24 patients .


Patients with haemodynamically significant epicardial stenosis ( fractional flow reserve < 0.75 ) were excluded .


Correlation between the two methods was good ( r = 0.71 , P < 0.001 ) , but CFRThermodilution ( mean SD ) tended to be higher ( 3.17 1.00 vs. 2.87 0.72 ; mean difference 0.29 , 95 % confidence interval -0.06 to 0.59 ) .


In Bland-Altman analysis , there was a trend towards a greater difference in the range of higher invasive values .


Nevertheless , TTE was successful in discriminating moderately impaired CFR ( 2.5 ) ( P = 0.001 ) and severely impaired CFR ( 2.0 ) ( P < 0.001 ) when compared with an invasive method .


No association between either CFR measurements vs. IMR measurement was detected , suggesting that in addition to microcirculatory function , CFR also accounts for epicardial vasodilator function in the absence of haemodynamically significant stenosis .


TTE is a feasible and reliable method for the assessment of CFR and vasodilator dysfunction after DES implantation .


Values obtained with this method successfully find abnormal CFR confirmed with the invasive thermodilution method .


Daily intake of 480 mg of BNO 1016 for 15 days is an effective treatment in acute viral rhinosinusitis .


The pooled efficacy data of two similar randomized placebo-controlled clinical trials were analyzed .


Safety was evaluated on the basis of the individual trials .


The efficacy analysis was based on 589 patients .


Treatment was performed orally with either 3 160 mg BNO 1016 ( n = 294 ) or 3 placebo ( n = 295 ) for 15 days .


In both trials patients underwent five visits to the investigational sites .


Symptoms were evaluated according to the EPOS 2012 guideline .


Ultrasonography was used to confirm the diagnosis at onset of treatment and the remission of symptoms at the last visit .


Efficacy was evaluated by the investigator as the mean major symptom score ( MSS ) at the end of treatment ( visit 5 , day 14 ) .


Patients reported symptoms and social/emotional consequences of rhinosinusitis using a quality of life questionnaire ( SNOT-20 GAV ) .


MSS improved during the treatment period by a mean of 10.02 1.61 score points to 2.47 2.55 for BNO 1016 and of 9.87 1.52 to 3.63 3.63 for placebo .


Differences between treatment groups at end of therapy ( 1.16 3.14 score points ; p < 0.0001 ) and patient-assessed quality of life ( p = 0.0015 ) were statistically significant in favor of BNO 1016 .


Rectal cancer continues to be devastating malignancy worldwide .


Sphincter preservation is the need of the hour .


Distal anastomosis is more prone to leaks .


Proximal diversion in form of ileostomy may be used to protect distal anastomosis .


To compare two groups of low anterior resection with and without diversion ileostomy in rectal cancer patients .


A prospective , hospital based study of 78 rectal carcinoma patients were taken for the study .


Inclusion criteria was operable rectal cancer 4-12 cm from anal verge .


Patients were randomized into two groups .


Group - A ( 34 patient ) patients with low anterior resection with ileostomy ( LAR with ileostomy ) ; Group - B ( 44 patients ) patients with low anterior resection without ileostomy ( LAR without ileostomy ) .


Quality of life was assessed by scoring done by self designed method .


A total score of 0-20 given for various parameters .


Skin excoriation was the commonest complication .


Stomal retraction and stomal obstruction was seen in 1 patient each ( 3 % ) .


Hypokalemia was the commonest electrolyte imbalance present in ileostomy group .


Anastomotic leak was present in 6 % of Group A and 11 % of Group B patients .


Mean time of closure of ileostomy was 16 4.3 weeks .


LAR with ileostomy has certain advantages over LAR without ileostomy in terms of anastomotic leak , postoperative ileus , resumption of diet , wound infection , small bowel obstruction and in terms mortality and recurrence .


However stoma related complications were main disadvantage in LAR with ileostomy .


Currently few evidence based interventions are available for the prevention of PTSD within the first weeks after trauma .


Increased risk for PTSD development is associated with dysregulated fear and stress responses prior to and shortly after trauma , as well as with a lack of perceived social support early after trauma .


Oxytocin is a potent regulator of these processes .


Therefore , we propose that oxytocin may be important in reducing adverse consequences of trauma .


The ` BONDS ' study is conducted in order to assess the efficacy of an early intervention with intranasal oxytocin for the prevention of PTSD .


In this multicenter double-blind randomized placebo-controlled trial we will recruit 220 Emergency Department patients at increased risk of PTSD .


Trauma-exposed patients are screened for increased PTSD risk with questionnaires assessing peri-traumatic distress and acute PTSD symptoms within 7 days after trauma .


Baseline PTSD symptom severity scores and neuroendocrine and psychophysiological measures will be collected within 10 days after trauma .


Participants will be randomized to 7.5 days of intranasal oxytocin ( 40 IU ) or placebo twice a day .


Follow-up measurements at 1.5 , 3 and 6 months post-trauma are collected to assess PTSD symptom severity ( the primary outcome measure ) .


Other measures of symptoms of psychopathology , and neuroendocrine and psychophysiological disorders are secondary outcome measures .


We hypothesize that intranasal oxytocin administered early after trauma is an effective pharmacological strategy to prevent PTSD in individuals at increased risk , which is both safe and easily applicable .


Interindividual and contextual factors that may influence the effects of oxytocin treatment will be considered in the analysis of the results .


Netherlands Trial Registry : NTR3190 .


To evaluate whether the transillumination method increased the probability of appropriate tracheal tube ( TT ) placement compared with the main-stem method .


Prospective , randomized , controlled study .


Operating room , university hospital .


Eighty children < 2 years old scheduled for elective surgery undergoing general anesthesia .


Trachlight was used for the transillumination method .


After intubation , patients were randomly assigned to 1 of 2 groups : ( 1 ) deliberate bronchial intubation with subsequent withdrawal of the TT to 2 cm above the carina ( main-stem group ) or ( 2 ) transmitted visual signal from a bright light at the TT tip on the skin at the suprasternal notch after inserting the Trachlight into the TT ( transillumination group ) .


The TT tip position was assessed by chest radiograph after the procedure .


Appropriate TT placement was defined when the TT tip was located between the sternoclavicular junction and 1 cm above the carina .


Appropriate TT placement was found in 31 ( 80 % ) of 39 patients in the transillumination group and 26 ( 65 % ) of 40 in the main-stem group .


The transillumination method had higher rate of appropriate TT placement than the main-stem method ( P = .15 ; risk ratio , 1.22 ; 95 % confidence interval , 0.93-1 .61 ) .


Seven patients ( 18 % ) had proximal TT placement , and 1 ( 3 % ) had distal TT placement in the transillumination group .


In the main-stem group , 7 patients ( 18 % ) had proximal TT placement , and 7 ( 18 % ) had distal TT placement .


The transillumination method was reliable for appropriate TT placement in small children < 2 years old undergoing general anesthesia , although the transillumination method was not found to be better compared with the main-stem method .


Myocardial blood flow ( MBF ) quantification with dynamic SPECT could lead to widespread utilization of MBF imaging in clinical practice with little cost increase over current standard SPECT myocardial perfusion imaging .


This work evaluates the feasibility and operator-dependent variability of MBF and flow reserve measurements with ( 99m ) Tc-sestamibi ( MIBI ) dynamic SPECT imaging using a standard dual-head SPECT camera .


Twenty-eight patients underwent dipyridamole-stress and rest imaging with dynamic SPECT/CT acquisition .


Quantitative images were iteratively reconstructed with all physical corrections and then myocardial and arterial blood regions of interest ( ROI ) were defined semi-automatically .


A compartmental model was fitted to these ROI-sampled time-activity-curves , and flow-dependent MIBI extraction correction was applied to derive regional MBF values .


Myocardial flow reserve ( MFR ) was estimated as stress/rest MBF ratio .


MBF and MFR in low and high risk populations were evaluated for ability to detect disease .


Images were each processed twice ( 7 days apart ) by one expert and one novice operator to evaluate intra - and inter-operator variability of MBF and MFR measurement in the three coronary artery vascular territories .


Mean rest flow , stress flow , and MFR values were 0.83 , 1.82 mLminute ( -1 ) g ( -1 ) , and 2.45 , respectively .


For stress/rest MFR , the inter-operator reproducibility was r ( 2 ) = 0.86 with RPC = 1.1 .


Stress MBF and MFR were significantly reduced ( P < .05 ) in high risk ( n = 9 ) vs low risk populations ( n = 19 ) , indicating ability to detect disease .


For expert and novice operators very good intra-operator correlations of r ( 2 ) = 0.98 and 0.95 ( n = 168 , P < .001 ) were observed for combined rest and stress regional flow values .


Bland-Altman reproducibility coefficients ( RPC ) were 0.25 and 0.47 mLminute ( -1 ) g ( -1 ) for the expert and novice operators , respectively ( P < .001 ) .


Inter-operator correlation was r ( 2 ) = 0.91 and Bland-Altman RPC = 0.58 mLminute ( -1 ) g ( -1 ) ( n = 336 ) .


MBF and reserve measurements using ( 99m ) Tc-sestamibi on a traditional , two-headed camera with fast rotation and with quantitative dynamic SPECT appears to be feasible , warranting further investigation .


Cognitive impairment is an enduring and functionally relevant feature of early-onset schizophrenia ( EOS ) .


Cognitive remediation therapy ( CRT ) improves cognition and functional outcome in adults with schizophrenia , although data in adolescents with EOS remain scarce .


The purpose of this study is to examine the efficacy of CRT in improving cognition and functional outcomes in a sample of symptomatically stable but cognitively disabled adolescents with EOS .


We performed a randomized , controlled trial of individually delivered CRT plus treatment-as-usual compared with treatment-as-usual ( TAU ) .


Fifty adolescents with EOS were randomly assigned to receive CRT ( n = 25 ) or TAU ( n = 25 ) and were included in an intention-to-treat analysis .


Clinical symptoms and cognitive and functional performance were assessed before and after treatment in both groups and after 3 months in the CRT group .


Cognitive domains were defined according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia ( MATRICS ) consensus battery and averaged in a global cognitive composite score .


After CRT , significant improvements were found in verbal memory and executive functions , with medium-to-large effect sizes ( ES ) .


The derived cognitive composite score showed an improvement after the treatment , with a large ES .


This change was reliable in more than two-thirds of the treated patients .


Medium-sized ES were found for improvements after CRT in daily living and adaptive functioning , whereas large ES were observed for improvements in family burden .


With the exception of functional gains , these changes were maintained after 3 months .


CRT appears to be a useful intervention strategy for adolescents with EOS .


Cognitive improvements can be achieved through CRT , although further research is warranted to determine the durability of functional gains .


Clinical trial registration information-Cognitive Remediation Therapy ( CRT ) in Adolescents With EOS ; www.clinicaltrials.gov ; NCT01701609 .


Sentinel lymph node biopsy ( SLNB ) has become the gold standard for axillary staging .


Debate remains as to the optimal method of SLN detection .


Determine whether patients undergoing an SLNB required the addition of isosulfan blue dye to radioisotope when an SLN was identified on a preoperative lymphoscintigram .


A prospective randomized controlled trial comparing the combination of radioisotope and blue dye versus radioisotope alone was performed between March 2010 and September 2012 .


The trial protocol was registered with Current Controlled Trials .


Women with clinically and radiologically node-negative breast cancer with a positive preoperative lymphoscintigram were eligible for inclusion .


A total of 667 patients were included in the analysis with 342 patients receiving the combination ( blue dye and radioisotope ) and 325 patients receiving radioisotope alone .


The groups were evenly matched both demographically and pathologically .


The mean age was 48 years ( 48.3 vs 47.7 years ; P = 0.47 ) , the mean tumour size was 24.2 mm ( 24.3 mm vs 24.1 mm ; P = 0.7 ) and there was no statistically significant difference in the grade of the tumors between the 2 groups ( P = 0.58 ) .


There was no difference in the identification rate , nor was that in the number of nodes retrieved between the 2 groups ( P = 0.30 ) .


There was no difference in the number of positive lymph nodes that were identified between the 2 groups ( 23.8 % vs 22.1 % ; P = 0.64 ) .


This study failed to demonstrate an advantage with the addition of isosulfan blue dye to radioisotope in the identification of the SLN in the presence of a positive preoperative lymphoscintigram .


Substance misuse in those with severe mental health problems is common and associated with poor engagement in treatment and treatment outcomes .


Up to 44 % of those admitted into psychiatric inpatient facilities have coexisting substance-misuse problems .


However , this is not routinely addressed as part of their treatment plan .


A mental health admission may present a window of opportunity for inpatients to reevaluate the impact of their substance use .


This study will aim to evaluate the effectiveness of a targeted brief motivational intervention in improving engagement in treatment and to assess how feasible and acceptable this intervention is to inpatients and staff as a routine intervention .


This randomized controlled trial will use concealed randomization ; blind , independent assessment of outcome at 3 months ; characterization of refusers and dropouts ; and be analyzed according to the intention-to-treat principle .


After baseline assessments , eligible participants will be randomized either to the Brief Integrated Motivational Intervention plus Treatment As Usual , or Treatment as Usual alone .


Eligible participants will be those who are new admissions ; > 18 years ; ICD-10 diagnosis of - schizophrenia or related disorder , bipolar affective disorder , recurrent depressive disorder , and DSM-IV diagnosis of substance abuse or dependence over the last 3 months .


The primary outcome is engagement in treatment for substance misuse , and secondary outcomes include readiness to change substance misuse together with a cost-effectiveness analysis .


Qualitative interviews with staff and participants will assess the acceptability of the intervention .


This pilot randomized trial will provide the first robust evidence base for inpatient care of people with severe mental health problems and co-morbid substance misuse and provide the groundwork for confirmatory trials to evaluate a potentially feasible , cost-effective , and easy-to-implement treatment option that may be readily integrated into standard inpatient and community-based care .


ISRCTN43548483 Date of ISRCTN assignation : 4/17/2014 .


To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol , The Evaluation of Choline Fenofibrate ( ABT-335 ) on Carotid Intima-Media Thickness ( cIMT ) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy ( FIRST ) trial evaluated the effects of fenofibric acid ( FA ) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin .


This multicenter , double-blind , placebo-controlled study was performed in patients with mixed dyslipidemia ( fasting triglycerides , 150 mg/dL ; high-density lipoprotein cholesterol , 45 [ men ] or 55 mg/dL [ women ] ; low-density lipoprotein cholesterol , 100 mg/dL once and averaging 105 mg/dL ) and a history of coronary heart disease or risk equivalent .


Patients on background atorvastatin ( continued on starting dose or titrated to 40 mg , if needed ) were randomized to FA 135 mg or placebo .


The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT , measured by ultrasound .


In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy , rate of change in posterior-wall cIMT was similar with FA plus atorvastatin ( -0.006 mm/y ) versus atorvastatin monotherapy ( 0.000 mm/y ; P = 0.22 ) .


FA plus atorvastatin was favored ( P < 0.05 ) in 5 of 24 prespecified subgroups : age 60 years , history of coronary artery disease , cIMT > 0.795 mm , triglycerides 170 to 235 mg/dL , and statin use at entry .


Adverse events were consistent with the known safety profiles of both drugs ; however , FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy ( 6.5 % versus 0.9 % ) .


Compared with atorvastatin monotherapy , FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia .


The role of glycemic index ( GI ) and foods with negative attributes related to GI as part of a weight loss regimen has not been thoroughly assessed in free-living individuals .


This study examined the effects of a dietary prescription for energy intake modification , GI , and potato consumption on weight loss , dietary prescription adherence , body composition , and glucose control in a free-living , self-selecting overweight population .


Ninety overweight ( body mass index [ BMI ] 29.6 3.9 ) men and women were randomly assigned to one of 3 groups for 12 weeks .


Two groups were counseled to reduce their energy intake by 500 kcal/day and consume diets that were predominantly composed of either low - or high-GI foods ( low glycemic index energy reduced [ LGI-ER ] or high glycemic index energy reduced [ HGI-ER ] diet , respectively ) .


The third group received no energy restriction , GI provision , or nutritional counseling .


All groups were instructed to consume 5-7 servings of potatoes per week .


Changes in weight , body composition , glucose tolerance , and triglycerides were determined at baseline and 12 weeks .


There were no significant differences in weight loss or changes in body composition between the groups ; however , modest weight loss and body composition changes were seen from week 0 to week 12 for all groups ( p < 0.05 ) .


Difficulty achieving the prescribed GI diets was evident in this free-living setting .


There were no significant changes within or among treatments for fasting concentrations of triglycerides , glucose tolerance , insulin , or insulin sensitivity .


The results indicate that in a free-living population of men and women , weight loss is associated with energy intake reduction .


Potato intake did not cause weight gain and following either a high - or low-GI dietary prescription was difficult for free-living subjects , emphasizing the complex nature of changing dietary patterns .


This prospective , randomized , single-blinded study evaluates the effectiveness of the ultrasound-guided bilateral thoracic paravertebral ( BTPV ) block for providing postoperative pain control in children undergoing the Nuss procedure .


Thirty American Society of Anesthesiologists I-II children with pectus excavatum , scheduled for the Nuss procedure , were enrolled at West China Hospital of Sichuan University .


The patients were randomly allocated into the BTPV block group or the control group .


In the BTPV group , 0.25 % ropivacaine 0.5 mL/kg with 1:200,000 epinephrine was injected under ultrasound guidance on each side at the level of the fifth thoracic vertebra .


Postoperative pain was evaluated in both groups for the first 48 hours .


Total opioid administered and cumulative attempts on the patient/parent-controlled intravenous analgesia ( PCA ) pump were recorded .


Postoperative negative behavioral changes in the children were evaluated on postoperative days 1 , 7 , and 30 , respectively , using the posthospital behavior questionnaire .


The pain scores were significantly reduced in the postanesthesia care unit and for the first 48 hours postoperatively in the BTPV group compared to the control group ( P < 0.01 ) .


The sufentanil use in the postanesthesia care unit was significantly greater in the control group [ mean ( SD ) , 0.2 ( 0 ) mcg/kg ] compared to the BTPV group [ mean ( SD ) , 0.05 ( 0.06 ) mcg/kg ] ( P < 0.01 ) .


The postoperative sufentanil use was significantly higher in the control group during the first 24 hours ( P < 0.01 ) .


Numbers of attempts on the PCA pump were significantly greater in the control group ( P < 0.01 ) .


The posthospital behavior questionnaire score was lower in the BTPV group on day 1 , day 7 , and 1 month , respectively ( P < 0.01 ) .


Ultrasound-guided BTPV block provides improved postoperative analgesia for children undergoing the Nuss procedure as compared with intravenous PCA and decreases the incidence of postoperative behavioral disturbance .


Tumour shrinkage ( TS ) increases the possibility of resection in metastatic colorectal cancer ( mCRC ) and may improve tumour-related symptoms .


Here we report prespecified secondary response-related end-points and exploratory TS/resection outcomes for patients with RAS wild-type ( WT ) tumours ( no mutations in KRAS/NRAS exons 2/3/4 ) from the PRIME study ( NCT00364013 ) .


PRIME was a randomised phase 3 study comparing first-line panitumumab + FOLFOX4 versus FOLFOX4 in mCRC patients .


Tumour response analyses were conducted to compare response rates and their impact on survival outcomes .


Overall , 505 patients had RAS WT mCRC .


More patients receiving panitumumab + FOLFOX4 versus FOLFOX4 had 30 % ( 59 % versus 38 % ; P < 0.001 ) or 20 % ( 72 % versus 57 % ; P < 0.001 ) TS at week 8 ( early TS ) ; consistent TS benefits were observed over the first 40weeks of treatment .


Objective response rate ( P = 0.003 ) , duration of response ( P = 0.0027 ) , depth of response ( P = 0.0149 ) , progression-free survival ( PFS ; P = 0.0015 ) and overall survival ( OS ; P = 0.0057 ) were improved in the panitumumab + FOLFOX4 group .


Both early TS and resection were associated with improved PFS and OS .


2-year OS rates for patients who did ( n = 64 ) versus did not ( n = 441 ) undergo resection were 88 % versus 40 % ; 2-year OS rates for patients who did ( n = 45 ) versus did not ( n = 460 ) undergo complete resection were 96 % versus 41 % .


More patients receiving panitumumab + FOLFOX4 versus FOLFOX4 had 30 % or 20 % TS at week 8 ; PFS and OS were also improved with panitumumab + FOLFOX4 .


The clinical value of achieving early TS in mCRC warrants further investigation .


This was a randomized , placebo-controlled , double-blind , sequential , ascending-dose study to assess the safety , tolerability , pharmacokinetics , and pharmacodynamics of multiple oral doses of apixaban in healthy Japanese male subjects .


The study was conducted using three sequential dose panels : apixaban 2.5 mg , 5 mg , and 10 mg given twice daily .


For each dose panel , subjects were randomly assigned to receive oral apixaban ( n = 6 ) or matching placebo ( n = 2 ) for 7 days .


The pharmacokinetics of apixaban and effect on pharmacodynamic variables ( clotting assays and anti-Xa activity ) were assessed on day 1 and day 7 of treatment .


Safety was assessed throughout the study .


Only after the preceding dose was confirmed to be safe and well-tolerated subjects were enrolled into the next-higher-dose panel .


Apixaban was safe and well-tolerated in these healthy Japanese male subjects across the doses evaluated .


On day 7 , peak plasma concentrations were reached ~ 3 hours postdose , and increases in peak plasma concentration ( C ( max ) ) , trough plasma concentration , and area under the plasma concentration-time curve across one dosing interval ( 12 hours ) were tested dose-proportional across the dose range .


A modest degree of accumulation was observed that was similar for all doses ( accumulation index of 1.7 to 2.0 ) , and renal clearance was consistent across doses ( 0.91 L/h - 1.07 L/h ) .


Exposure-dependent prolongation of prothrombin time , activated partial thromboplastin time , modified prothrombin time , and increases in anti-Xa activity were observed after single and multiple doses of apixaban .


Apixaban was safe and well-tolerated in healthy Japanese subjects .


The pharmacokinetic profile of apixaban following multiple twice-daily doses was linear , and exposure parameters such as C ( max ) , observed at ~ 3 hours post-dose , and area under the plasma concentration-time curve increased in a dose-proportional manner .


Pharmacodynamic profiles closely followed the apixaban plasma concentration-time profiles .


An intervention was designed to introduce rapid diagnostics tests for malaria ( mRDTs ) into registered drug shops in Uganda to encourage rational and appropriate treatment of malaria with artemisinin-based combination therapy ( ACT ) .


We conducted participatory training of drug shop vendors and implemented supporting interventions to orientate local communities ( patients ) and the public sector ( health facility staff and district officials ) to the behavioral changes in diagnosis , treatment and referral being introduced in drug shops .


The intervention was designed to be evaluated through a cluster randomized trial .


In this paper , we present detailed design , implementation and evaluation experiences in order to help inform future studies of a complex nature .


Three preparatory studies ( formative , baseline and willingness-to-pay ) were conducted to explore perceptions on diagnosis and treatment of malaria at drug shops , and affordable prices for mRDTs and ACTs in order to inform the design of the intervention and implementation modalities .


The intervention required careful design with the intention to be acceptable , sustainable and effective .


Critical components of intervention were : community sensitization and creating awareness , training of drug shop vendors to diagnose malaria with mRDTs , treat and refer customers to formal health facilities , giving pre-referral rectal artesunate and improved record-keeping .


The primary outcome was the proportion of patients receiving appropriately-targeted treatment with ACT , evaluated against microscopy on a research blood slide .


Introducing mRDTs in drug shops may seem simple , but our experience of intervention design , conduct and evaluation showed this to be a complex process requiring multiple interventions and evaluation components drawing from a combination of epidemiological , social science and health economics methodologies .


The trial was conducted in phases sequenced such that each benefited from the other .


The main challenges in designing this trial were maintaining a balance between a robust intervention to support effective behaviour change and introducing practices that would be sustainable in a real-life situation in tropical Africa ; as well as achieving a detailed evaluation without inadvertently influencing prescribing behaviour .


NCT01194557 registered with ClinicalTrials.gov 2 September 2010 .


To identify risk factors for recurrent urinary tract infection ( UTI ) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis .


This 2-year , multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux ( VUR ) receiving placebo in the RIVUR ( Randomized Intervention for Vesicoureteral Reflux ) study and 195 children with no VUR observed in the CUTIE ( Careful Urinary Tract Infection Evaluation ) study .


Primary exposure was presence of VUR ; secondary exposures included bladder and bowel dysfunction ( BBD ) , age , and race .


Outcomes were recurrent febrile or symptomatic urinary tract infection ( F/SUTI ) and renal scarring .


Children with VUR had higher 2-year rates of recurrent F/SUTI ( Kaplan-Meier estimate 25.4 % compared with 17.3 % for VUR and no VUR , respectively ) .


Other factors associated with recurrent F/SUTI included presence of BBD at baseline ( adjusted hazard ratio : 2.07 [ 95 % confidence interval ( CI ) : 1.09-3 .93 ] ) and presence of renal scarring on the baseline ( 99m ) Tc-labeled dimercaptosuccinic acid scan ( adjusted hazard ratio : 2.88 [ 95 % CI : 1.22-6 .80 ] ) .


Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI ( 56 % ) .


At the end of the 2-year follow-up period , 8 ( 5.6 % ) children in the no VUR group and 24 ( 10.2 % ) in the VUR group had renal scars , but the difference was not statistically significant ( adjusted odds ratio : 2.05 [ 95 % CI : 0.86-4 .87 ] ) .


VUR and BBD are risk factors for recurrent UTI , especially when they appear in combination .


Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD .


Exercise intolerance is a hallmark of heart failure , but factors associated with impaired exercise capacity in heart failure with preserved ejection fraction are unclear .


We hypothesized that in heart failure with preserved ejection fraction , the severity of resting ventricular and vascular dysfunction are associated with impairment in exercise tolerance as assessed by peak oxygen consumption .


Subjects with heart failure with preserved ejection fraction enrolled in the PhosphodiesteRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart Failure ( RELAX ) clinical trial ( n = 216 ) underwent baseline Doppler echocardiography , cardiopulmonary exercise testing , and cardiac MRI .


RELAX participants were elderly ( median age 69 years ) and 48 % were women .


Ejection fraction ( 60 % ) and stroke volume ( 77 mL ) were normal , while diastolic dysfunction ( medial E/e ' , 16 ; deceleration time , 185 ms ; left atrial volume , 44 mL/m ( 2 ) ) and increased arterial load ( arterial elastance , 1.51 mm Hg/mL ) were evident .


Peak oxygen consumption was reduced ( 11.7 mLkg ( -1 ) min ( -1 ) , 1141 mL/min ) and age , sex , body mass index , hemoglobin , and chronotropic response collectively explained 64 % of the variance in raw peak oxygen consumption ( mL/min ) .


After adjustment for these variables , left ventricular structure ( diastolic dimension [ 1.5 % , P = 0.008 ] and left ventricular mass [ 1.6 % , P = 0.008 ] ) , resting stroke volume ( 2.0 % , P = 0.002 ) , left ventricular diastolic dysfunction ( deceleration time [ 0.9 % , P = 0.03 ] and E/e ' [ 1.4 % , P = 0.009 ] ) , and arterial function ( arterial elastance [ 2.1 % , P = 0.002 ] and systemic arterial compliance [ 1.5 % , P = 0.007 ] ) , each explained only a small additional portion of the variance in peak oxygen consumption .


In heart failure with preserved ejection fraction , potentially modifiable factors ( obesity , anemia , and chronotropic incompetence ) are strongly associated with exercise capacity , whereas resting measures of ventricular and vascular structure and function are not .


http://www.clinicaltrials.gov .


Unique identifier : NCT00763867 .


Epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs ) show great efficacy in patients with advanced non-small cell lung cancer ( NSCLC ) with EGFR mutations .


The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown .


In this open-label , phase II study , patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations ( either exon 19 deletion or L858R point mutation ) were assigned randomly to receive pemetrexed ( 500mg/m ( 2 ) ) and carboplatin ( AUC = 5 ) , administered every 21days for 4 cycles , followed with or without gefitinib ( 250mg/day ) for 6months .


The primary end point was disease-free survival ( DFS ) .


From August 2008 to September 2011 , 60 patients were included in our center .


DFS was significantly longer among those who received pemetrexed and carboplatin ( PC ) - gefitinib than among those who received PC alone [ hazard ratio ( HR ) , 0.37 ; 95 % confidence interval ( CI ) 0.16-0 .85 ; P = 0.014 ; median , 39.8 vs. 27.0 months ] .


The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and 54.2 % in the PC alone group .


The rates of 2-year overall survival ( OS ) were 92.4 % in the PC-gefitinib group and 77.4 % in the PC alone group ( HR , 0.37 ; 95 % CI 0.12-1 .11 , P = 0.076 ) .


The most common adverse event was rash ( 43.3 % , 13/30 ) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated .


The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations .


Inflammation is fundamental to the development of atherosclerosis .


We examined the effect of anti-inflammatory doses of salicylate on endothelium-dependent vasodilation , a biomarker of cardiovascular risk , in a broad range of subjects .


We performed a randomized , double-blind , placebo-controlled crossover trial evaluating the effects of 4 weeks of high-dose salsalate ( disalicylate ) therapy on endothelium-dependent flow-mediated and endothelium-independent vasodilation .


Fifty-eight subjects , including 17 with metabolic syndrome , 13 with atherosclerosis , and 28 healthy controls , were studied .


Among all subjects , endothelium-dependent flow-mediated vasodilation decreased after salsalate compared with placebo therapy ( P = 0.01 ) , whereas nitroglycerin-mediated , endothelium-independent vasodilation was unchanged ( P = 0.97 ) .


Endothelium-dependent flow-mediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels ( n = 31 , P < 0.02 ) but not in subjects with subtherapeutic levels ( P > 0.2 ) .


Salsalate therapy , particularly when therapeutic salicylate levels are achieved , impairs endothelium-dependent vasodilation in a broad range of subjects .


These data raise concern about the possible deleterious effects of anti-inflammatory doses of salsalate on cardiovascular risk .


www.clinicaltrials.gov .


Unique Identifiers : NCT00760019 and NCT00762827 .


Effective strategies to address risk factors of non-communicable diseases are required to curtail the expanding costs of health care .


This trial tested the effectiveness over one year of a minimal intervention targeting multiple health behaviours ( diet , physical activity , alcohol and smoking ) in a general practice setting , through the provision of personalised , computer-tailored feedback .


Patients who had attended a general practice in the previous 6 months were recruited from 21 general practitioners in Brisbane , Australia .


Baseline data were collected using self-reports on adherence to ten health behaviours and summarised into a health score from 0 to 10 .


This randomised controlled trial used a 22 factorial design , with one arm randomising subjects to the intervention or control group .


The other arm was either feedback at baseline ( single contact ) or an additional assessment with feedback at 3 months ( dual contact ) .


As such , 4 study groups created were , to which participants were randomised blindly : A. Intervention with single contact ; B. Intervention with dual contact ; C. Control with single contact and D. Control with dual contact .


All participants were assessed again at 12 months .


Of the 4676 participants randomised , 3065 completed questionnaires at 12 months .


Both single and dual contact groups improved their 10 item health scores ( +0.31 and +0.49 respectively ) relative to control group outcomes ( +0.02 ; p < 0.01 ) .


Improvement in adherence to guidelines for fish intake , type of milk consumed , vegetable and fruit intake , and alcohol intake were observed in single and dual contact intervention groups ( p < 0.01 ) .


Both intervention groups showed greater improvement than controls for individual health behaviours , apart from red meat intake , smoking behaviour , physical activity and body weight .


Interestingly , there was an improvement in reported non-smoking rates in both intervention and control groups ( 3 % single contact ; 4.5 % dual contact ) .


Small but meaningful long-term changes in health behaviours can be achieved with a low-intensity intervention , which may reduce health care costs if implemented on a large scale .


Further research is needed to better understand the mechanism by which maintenance of behaviour change can be achieved .


The Australian New Zealand Clinical Trials Registry : ACTRN12611001213932 .


( 9 ) - Tetrahydrocannabinol has been shown to modulate anxiety and facilitate the extinction of fear by inhibiting amygdala reactivity .


Since functional coupling between the amygdala and prefrontal cortex is implicated in affective processes , it is possible that ( 9 ) - tetrahydrocannabinol affects amygdala-prefrontal cortex functional connectivity in ways that differ across amygdala subregions : basolateral , centromedial , and superficial .


The aim of the study was to examine the effects of ( 9 ) - tetrahydrocannabinol on functional connectivity between amygdala subregions and the prefrontal cortex during socio-emotional threat in healthy adults using a double-blind , placebo-controlled , within-subjects design .


Sixteen subjects completed a functional magnetic resonance imaging task designed to probe amygdala responses to social threat .


Amygdala subregion-prefrontal cortex functional connectivity was compared between ( 9 ) - tetrahydrocannabinol and placebo using generalized psychophysiological interaction analyses .


Findings indicated that ( 9 ) - tetrahydrocannabinol enhanced basolateral and superficial amygdala connectivity to the rostral anterior cingulate/medial prefrontal cortex .


These effects , including ( 9 ) - tetrahydrocannabinol 's potential ability to reduce threat perception or enhance socio-emotional regulation , may help understand the neurocircuitry of affect .


A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane .


C-X-C motif chemokine 13 ( CXCL13 ) is central in this process as it attracts C-X-C chemokine receptor type 5 ( CXCR5 ) - expressing B cells and T follicular helper cells to the follicle .


We here examine the role of CXCL13 and its association with disease in patients with treatment-nave early rheumatoid arthritis .


Plasma samples from patients in the OPERA trial were examined for CXCL13 at treatment initiation and after 6 months of treatment with either methotrexate plus placebo ( DMARD ) ( n = 37 ) or methotrexate plus adalimumab ( DMARD + ADA ) ( n = 39 ) .


Treatment outcome was evaluated after 1 and 2 years .


CXCL13 plasma levels in healthy volunteers ( n = 38 ) were also examined .


Baseline CXCL13 plasma levels were increased in early rheumatoid arthritis patients in comparison with healthy volunteers .


Also , plasma CXCL13 correlated positively with disease activity parameters ; swollen joint count 28 ( rho = 0.34 ) and 40 ( rho = 0.39 ) , visual analog score ( rho = 0.38 ) and simplified disease activity index ( rho = 0.25 ) ( all P < 0.05 ) .


CXCL13 levels decreased a significantly twofold more in the DMARD + ADA group than in the DMARD group .


Baseline CXCL13 plasma levels in the DMARD group correlated inversely with disease activity parameters ; disease activity score in 28 joints , four variables , C-reactive protein based ( DAS28CRP ) ( rho = 0.58 , P < 0.05 ) at 12 months .


High baseline CXCL13 was associated with remission ( DAS28CRP less than 2.6 ) after 2 years .


In treatment-nave early rheumatoid arthritis patients , plasma CXCL13 levels were associated with joint inflammation .


Furthermore , patients with high baseline plasma CXCL13 levels had an improved chance of remission after 2 years .


We propose that high CXCL13 concentrations indicate recent onset of inflammation that may respond better to early aggressive treatment .


Thus , high levels of CXCL13 could reflect the ` the window of opportunity ' for optimal treatment effect .


Clinicaltrial.gov NCT00660647 .


Registered 10 April 2008 .


Strategies to implement post exposure prophylaxis ( PEP ) in case of an anthrax bioterror event are needed .


To increase the number of doses of vaccine available we evaluated reducing the amount of vaccine administered at each of the vaccinations , and reducing the number of doses administered .


Healthy male and non-pregnant female subjects between the ages of 18 and 65 were enrolled and randomized 1:1:1:1 to one of four study arms to receive 0.5 mL ( standard dose ) of vaccine subcutaneously ( SQ ) at : ( A ) days 0 , 14 ; ( B ) days 0 and 28 ; ( C ) days 0 , 14 , and 28 ; or ( D ) 0.25 mL at days 0 , 14 , and 28 .


A booster was provided on day 180 .


Safety was assessed after each dose .


Blood was obtained on days 0 , 7 , 14 , 21 , 28 , 35 , 42 , 49 , 56 , 63 , 70 , 84 , 100 , 180 , and 201 and both Toxin Neutralizing antibody and anti-PA IgG antibody measured .


Almost all subjects developed some local reactions with 46-64 % reported to be of moderate severity and 3.3 % severe during the primary series .


Vaccine groups that included a day 14 dose induced a 4 fold antibody rise in more subjects on days 21 , 28 , and 35 than the arm without a day 14 dose .


However , schedules with a full day 28 dose induced higher peak levels of antibody that persisted longer .


The half dose regimen did not induce antibody as well as the full dose study arms .


Depending on the extent of the outbreak , effectiveness of antibiotics and availability of vaccine , the full dose 0 , 28 or 0 , 14 , 28 schedules may have advantages .


The development of specific screening programs for individuals with a family history of colorectal cancer ( CRC ) is a priority .


This study evaluates the diagnostic performance of serum soluble CD26 ( sCD26 ) in family-risk individuals and compares this marker with the faecal immunochemical test for the detection of advanced neoplasia ( AN ) ( CRC or advanced adenomas ; AA ) .


Five hundred and sixteen asymptomatic individuals with at least one first-degree relative with CRC were included .


Serum sCD26 was measured in all the individuals who also underwent a colonoscopy ( 53 AA and four cancer cases were found ) and a faecal immunochemical test .


Setting specificity to 90 % and 95 % , respectively , sCD26 showed a sensitivity of 39.6 % and 28.3 % for AA , and of 42.1 % and 28.1 % for AN .


The combination of sCD26 and the faecal test detected AA and AN with a 52.8 % and 56.1 % sensitivity , corresponding to 93.5 % specificity .


The combination of serum sCD26 and the faecal blood test could result a valuable strategy for detecting AN in familial-risk CRC screening .


Ramosetron is a new selective 5-hydroxytryptamine type 3 ( 5-HT3 ) receptor antagonist that reportedly has more potent antiemetic effects than other 5-HT3 receptor antagonists .


The aim of this study was to determine the effect of ramosetron pretreatment on gastric emptying using the 13C-acetic acid breath test .


Ten healthy male and female volunteers participated in this randomized , twoway crossover study .


After they had fasted overnight , the subjects were randomly assigned to receive 0.1 mg ramosetron 1 hour before ingestion of a test meal ( 200 kcal per 200 mL , containing 100 mg 13C acetate ) or to receive the test meal alone .


Under both conditions , breath samples were collected for 150 min following ingestion of the meal .


Statistical comparison of the parameters between the two test conditions was performed .


No significant differences in the calculated parameters , including T 1/2 , T lag , GEC or and , were observed between the two test conditions .


The present study revealed that 0.1 mg ramosetron had no significant effect on the rate of gastric emptying .


Thus , our results suggest that ramosetron can be administered safely , without gastrointestinal adverse effects , even to terminal cancer patients with delayed or accelerated gastric emptying abnormality .


Although children with acute lymphoblastic leukemia ( ALL ) mount immune responses after vaccination with the trivalent influenza vaccine ( TIV ) , these responses are lower compared to controls .


Recently , a high dose ( HD ) TIV was found to increase the level of antibody response in elderly patients compared to the standard dose ( SD ) TIV .


We hypothesized that the HD TIV would be well-tolerated and more immunogenic compared to the SD TIV in pediatric subjects with ALL .


This was a randomized , double-blind , phase I safety trial comparing the HD to the SD TIV in children with ALL .


Our secondary objective was immunogenicity .


Subjects were randomized 2:1 to receive either the HD ( 60 g ) or the SD ( 15 g ) TIV .


Local and systemic reactions were solicited , hemagglutinin inhibition titers to influenza virus antigens were measured , and monitoring labs were collected prior to and/or after each vaccination .


Fifty subjects were enrolled ( 34 HD , 16 SD ) .


Mean age was 8.5 years ; 63 % were male , and 80 % were in maintenance therapy .


There were no significant differences reported in local or systemic symptoms .


No severe adverse events were attributed to vaccination .


No significant differences between the HD and SD TIV groups were noted for immune responses .


No differences were noted between the HD and SD TIV groups for solicited systemic and local reactions .


Since this study was not powered for immunogenicity , a phase II trial is needed to determine the immunogenicity of HD versus SD TIV in the pediatric ALL population .


The objective of this study was to evaluate the efficacy of subcutaneous ( SC ) sedation using midazolam with and without ketamine in non-cooperative pediatric patients undergoing dental treatment .


A prospective , randomized , controlled , double-blind , crossover pilot clinical trial was carried out in 13 children , aged between 17-46 months , ASA l , Frankl 1 .


Two sedation schemes were administered SC : Midazolam alone ( M ) , and a combination of Midazolam-Ketamine ( MK ) .


Both regimens were administered to the same patient in two consecutive treatment sessions , in accordance with a random assignment .


Overall behavior , movement , and crying were assessed according to the modified Houpt scale .


Heart rate , blood pressure , blood oxygen saturation , and possible side effects were also monitored .


The percentage of non-crying children was always higher in the treatment with MK compared with the treatment with M , but without a significant statistical difference .


Regarding variable body movement , the percentage of children without movement was higher in the MK group , although only up to minute 10 ; no significant differences were found at 20 , 30 , and 40 minutes , and from minute 40 , body movement was lower in the M group .


Midazolam alone and the midazolam-ketamine combination administered subcutaneously resulted in a safe and efficient pharmacological method for providing moderate sedation to non-cooperative pediatric patients undergoing dental treatment .


During atrial fibrillation ( AF ) , conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular ( AV ) node can not be used .


We aimed at evaluating changes in AV nodal properties during administration of metoprolol from electrocardiogram data , and to support our findings with simulated data based on results from an electrophysiological study .


Sixty patients ( age 71 9 years , 42 men ) with permanent AF were included in the RATe control in Atrial Fibrillation ( RATAF ) study .


Two 15 min segments , during baseline and metoprolol administration , starting at 2 pm were analysed in this study .


Atrial fibrillatory rate ( AFR ) , heart rate ( HR ) , and AV nodal parameters were assessed .


The AV nodal parameters account for the probability of an impulse not taking the fast pathway , the absolute refractory periods of the slow and fast pathways ( aRPs and aRPf ) , representing the functional refractory period , and their respective prolongation in refractory period .


In addition , simulated RR series were generated that mimic metoprolol administration through prolonged AV conduction interval and AV node effective refractory period .


During metoprolol administration , AFR and HR were significantly decreased and aRP was significantly prolonged in both pathways ( aRPs : 337 60 vs. 398 79 ms , P < 0.01 ; aRPf : 430 91 vs. 517 100 ms , P < 0.01 ) .


Similar results were found for the simulated RR series , both aRPs and aRPf being prolonged with metoprolol ( aRPs : 413 33 vs. 437 43 ms , P = 0.01 ; aRPf : 465 40 vs. 502 69 ms , P = 0.02 ) .


The AV nodal parameters reflect expected changes after metoprolol administration , i.e. a prolongation in functional refractory period .


The simulations confirmed that aRPs and aRPf may serve as an estimate of the functional refractory period .


Early handling alters adult behavioral responses to palatable food and to its withdrawal following a period of chronic exposure .


However , the central mechanisms involved in this phenomenon are not known .


Since neonatal handling has persistent effects on stress and anxiety responses , we hypothesized that its involvement in the aforementioned association may be associated with differential neuroadaptations in the amygdala during withdrawal periods .


Litters were randomized into two groups : handled ( H , removed from their dam for 10min per day from the first to the tenth postnatal day and placed in an incubator at 32C ) and non-handled ( NH ) .


Experiment 1 : on PNDs 80-100 , females were assigned to receive palatable food + rat chow for 15 or 30 days , and these two groups were compared in terms of palatable food preference , body weight and abdominal fat deposition .


In Experiment 2 , H and NH rats were exposed to a chronic diet of palatable food + rat chow for 15 days , followed by ( a ) no withdrawal , ( b ) 24h withdrawal from palatable food ( receiving only rat chow ) or ( c ) 7-day withdrawal from palatable food ( receiving only rat chow ) .


Body weight , 10-min rebound palatable food intake , abdominal fat deposition , serum corticosterone as well as TH and pCREB levels in the amygdala were then compared between groups .


Experiment 1-chronic exposure to palatable food induces comparable metabolic effects after 15 and 30 days .


Experiment 2-neonatal handling is associated with a peculiar response to palatable food withdrawal following chronic exposure for 15 days .


Rats exposed to early handling ingested less of this food after a 24h withdrawal period , and displayed increased amygdala TH and pCREB levels .


Variations in the neonatal environment affect both behavioral responses and amygdala neuroadaptation to acute withdrawal from a palatable diet .


These findings contribute to the comprehension of the mechanisms that link early life events and altered feeding behavior and related morbidities such as obesity in adulthood .


Hyperuricemia is a risk factor for the onset of chronic kidney disease ( CKD ) and is significantly associated with the progression of CKD .


However , there is no sufficient evidence by interventional research supporting a cause-effect relationship .


Hyperuricemic patients without gouty arthritis , whose serum urate ( SUA ) concentration is 8.0 mg/dL and who have a complication , are treated by pharmacotherapy in addition to lifestyle guidance .


Nevertheless , there is no evidence that rationalizes pharmacotherapy for patients with hyperuricemia who have no complication and whose SUA concentration is below 9.0 mg/dL .


The FEATHER ( FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 ) study is a prospective , multicenter , double-blind , randomized , placebo-controlled trial of febuxostat-a novel , nonpurine , selective , xanthine oxidase inhibitor .


The present study will enroll , at 64 medical institutions in Japan , 400 Japanese patients aged 20 years or older who have hyperuricemia without gouty arthritis , who present CKD stage 3 , and whose SUA concentration is 7.1-10 .0 mg/dL .


Patients are randomly assigned to either the febuxostat or the control group , in which febuxostat tablets and placebo are administered orally , respectively .


The dosage of the study drugs should be one 10-mg tablet/day at weeks 1 to 4 after study initiation , increased to one 20-mg tablet/day at weeks 5 to 8 , and elevated to one 40-mg tablet/day at week 9 and then maintained until week 108 .


The primary endpoint is estimated glomerular filtration rate ( eGFR ) slope .


The secondary endpoints include the amount and percent rate of change in eGFR from baseline to week 108 , the amount and percent rate of change in SUA concentration from baseline to week 108 , the proportion of patients who achieved an SUA concentration6 .0 mg/dL , and the incidence of renal function deterioration .


The present study aims to examine whether febuxostat prevents a further reduction in renal function as assessed with eGFR in subjects and will ( 1 ) provide evidence to indicate the inverse association between a reduction in SUA concentration and an improvement in renal function and ( 2 ) rationalize pharmacotherapy for subjects and clarify its clinical relevance .


UMIN Identifier : UMIN000008343 .


To compare the efficacy and safety of cutting balloon angioplasty ( CBA ) versus high-pressure balloon angioplasty ( HPBA ) for the treatment of hemodialysis autogenous fistula stenoses resistant to conventional percutaneous transluminal angioplasty ( PTA ) .


In a prospective , randomized clinical trial involving patients with dysfunctional , stenotic hemodialysis arteriovenous fistulas ( AVFs ) , patients were randomized to receive CBA or HPBA if conventional PTA had suboptimal results ( ie , residual stenosis > 30 % ) .


A total of 516 patients consented to participate in the study from October 2008 to September 2011 , 85 % of whom ( n = 439 ) had technically successful conventional PTA .


The remaining 71 patients ( mean age , 60 y ; 49 men ) with suboptimal PTA results were eventually randomized : 36 to the CBA arm and 35 to the HPBA arm .


Primary and secondary target lesion patencies were determined by Kaplan-Meier analysis .


Clinical success rates were 100 % in both arms .


Primary target lesion patency rates at 6 months were 66.4 % and 39.9 % for CBA and HPBA , respectively ( P = .01 ) .


Secondary target lesion patency rates at 6 months were 96.5 % for CBA and 80.0 % for HPBA ( P = .03 ) .


There was a single major complication of venous perforation following CBA .


The 30-day mortality rate was 1.4 % , with one non-procedure-related death in the HPBA group .


Primary and secondary target lesion patency rates of CBA were statistically superior to those of HPBA following suboptimal conventional PTA .


For AVF stenoses resistant to conventional PTA , CBA may be a better second-line treatment given its superior patency rates .


To assess the efficacy and safety of aranidipine versus retard-released felodipine in Chinese patients with mild-to-moderate essential hypertension .


This was a multicenter , randomized , double-blind , placebo and active antihypertensive drug parallel-controlled study .


After 2 weeks of placebo run-in period , 315 patients at 6 centers with diastolic blood pressure ( DBP ) between 95 to 109 mm Hg ( 1 mm Hg = 0.133 kPa ) while systolic blood pressure ( SBP ) below 180 mm Hg were randomized to receive aranidipine 5-20 mg/d ( n = 126 ) or retard-released felodipine 5-10 mg/d ( n = 126 ) for 12 weeks .


Others ( n = 63 ) received placebo for 4 weeks .


Their blood pressures were evaluated at baseline and the end of Weeks 4 , 8 and 12 .


After a 12-week treatment , SBP decreased from 148.8 10.7 mm Hg to ( 132.8 11.2 ) mm Hg while DBP dropped from ( 98.4 2.8 ) mm Hg to ( 83.9 7.5 ) mm Hg .


There were significant differences with the baseline values ( P < 0.0001 ) .


After a 4-week treatment , the reductions of SBP in aranidipine and retard-released felodipine groups were ( 12.1 11.0 ) mm Hg and ( 12.2 11.2 ) mm Hg while the reductions of DBP in two groups ( 11.8 6.9 ) mm Hg and ( 12.1 7.9 ) mm Hg respectively .


The reductions of SBP and DBP in two groups were ( 2.3 8.4 ) mm Hg and ( 4.0 5.1 ) mm Hg and they were significantly superior to that in placebo group ( P < 0.0001 ) .


But no significant difference existed between aranidipine and retard-released felodipine groups .


Also no significant differences were found between these two antihypertensive therapy groups at the end of Weeks 4 , 8 and 12 in the reduction of blood pressure , total response rate and blood pressure control rate .


But 20 mg daily aranidipine was significantly superior to 10 mg daily retard-released felodipine in the control rates of SBP and DBP .


Adverse events occurred at 24.22 % and 29.92 % in aranidipine and retard-released felodipine groups respectively ( P = 0.305 ) .


Administration of aranidipine 5-20 mg/d can effectively control blood pressure and is not inferior to retard-released felodipine 5-10 mg/d .


The efficacy of 20 mg/d aranidipine is superior to that of retard-released felodipine 5-10 mg/d .


And the effectiveness and safety of aranidipine are similar to those of retard-released felodipine .


The Tisseel/Tissucol for mesh fixation in Lichtenstein hernia repair ( TIMELI ) study showed that mesh fixation with human fibrin sealant during inguinal hernia repair significantly reduced moderate-severe complications of pain 12months post-operatively compared with sutures .


Further analyses may assist surgeons by investigating predictors of post-surgical complications and identifying patients that may benefit from Tisseel/Tissucol intervention .


Univariate and multivariate analyses identified risk factors for combined pain , numbness and groin discomfort ( PND ) visual analogue scale ( VAS ) score 12months post-operatively .


Variables tested were : fixation method , age , employment status , physical activity , nerve handling , PND VAS score at pre-operative visit and 1week post-operatively .


The effect of fixation technique on separate PND outcomes 12months post-surgery was also assessed .


Analyses included the intention-to-treat ( ITT ) population and a subpopulation with pre-operative PND VAS > 30mm .


316 patients were included in the ITT , with 130 patients in the subpopulation with pre-operative PND VAS > 30 .


Multivariate analysis identified mesh fixation with sutures , worsening pre-operative PND and worsening PND 1week post-surgery as significant predictors of 12-month PND in the ITT population ; mesh fixation with sutures was a significant predictor of 12-month PND in the pre-operative PND VAS > 30 subpopulation ( p < 0.05 ) .


Mesh fixation with Tisseel/Tissucol resulted in significantly less numbness and a lower intensity of groin discomfort compared with sutures at 12months ; there was no difference in pain between the treatment groups .


Pre-operative discomfort may be an important predictor of post-operative pain , numbness and discomfort .


Tisseel/Tissucol may improve long-term morbidity over conventional sutures in these patients .


To determine whether abagovomab induces protective immune responses in ovarian cancer patients in first clinical remission .


The present analysis is a substudy of monoclonal antibody immunotherapy for malignancies of the ovary by subcutaneous abagovomab trial ( NCT00418574 ) .


The study included 129 patients , 91 in the abagovomab arm and 38 in the placebo arm .


Circulating CA125-specific cytotoxic T lymphocytes ( CTL ) were measured by a flow cytometry-based interferon - producing assay .


Human antimouse antibody and anti-anti-idiotypic ( Ab3 ) were assessed by ELISA .


Patients were evaluated before starting the treatment and at different time points during induction and maintenance phases .


A similar percentage of patients in both the placebo and abagovomab arms had CA125-specific CTL ( 26.3 and 31.8 % , respectively ; p = 0.673 by Fisher 's exact test ) .


Patients with CA125-specific CTL in both arms tended to have an increased relapse-free survival ( RFS , log-rank test p = 0.095 ) compared to patients without .


Patients ( n = 27 ) in the abagovomab arm without CA125-specific CTL but that developed Ab3 above the cutoff ( defined as median Ab3 level at week 22 ) had a prolonged RFS compared to patients ( n = 24 ) that did not develop Ab3 above the cutoff ( log-rank test p = 0.019 ) .


Abagovomab does not induce CA125-specific CTL .


However , patients with CA125-specific CTL perform better than patients without , irrespective of abagovomab treatment .


Abagovomab-induced Ab3 associate with prolonged RFS in patients without CA125-specific CTL .


Further studies are needed to confirm these data and to assess the potential utility of these immunological findings as a tool for patient selection in clinical trial .


Indoor exposure to fine particulate matter ( PM2 .5 ) from outdoor sources is a major health concern , especially in highly polluted developing countries such as China .


Few studies have evaluated the effectiveness of indoor air purification on the improvement of cardiopulmonary health in these areas .


This study sought to evaluate whether a short-term indoor air purifier intervention improves cardiopulmonary health .


We conducted a randomized , double-blind crossover trial among 35 healthy college students in Shanghai , China , in 2014 .


These students lived in dormitories that were randomized into 2 groups and alternated the use of true or sham air purifiers for 48 h with a 2-week washout interval .


We measured 14 circulating biomarkers of inflammation , coagulation , and vasoconstriction ; lung function ; blood pressure ( BP ) ; and fractional exhaled nitric .


We applied linear mixed-effect models to evaluate the effect of the intervention on health outcome variables .


On average , air purification resulted in a 57 % reduction in PM2 .5 concentration , from 96.2 to 41.3 g/m3 , within hours of operation .


Air purification was significantly associated with decreases in geometric means of several circulating inflammatory and thrombogenic biomarkers , including 17.5 % in monocyte chemoattractant protein-1 , 68.1 % in interleukin-1 , 32.8 % in myeloperoxidase , and 64.9 % in soluble CD40 ligand .


Furthermore , systolic BP , diastolic BP , and fractional exhaled nitrous oxide were significantly decreased by 2.7 % , 4.8 % , and 17.0 % in geometric mean , respectively .


The impacts on lung function and vasoconstriction biomarkers were beneficial but not statistically significant .


This intervention study demonstrated clear cardiopulmonary benefits of indoor air purification among young , healthy adults in a Chinese city with severe ambient particulate air pollution .


( Intervention Study on the Health Impact of Air Filters in Chinese Adults ; NCT02239744 ) .


To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women .


Multicentre randomised trial .


We utilised a central telephone randomisation server , with computer generated schedule , balanced variable blocks , and stratification for parity , body mass index ( BMI ) category , and hospital .


Three public maternity hospitals across South Australia .


2212 women with a singleton pregnancy , between 10 +0 and 20 +0 weeks ' gestation , and BMI 25 .


1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff ; 1104 were randomised to standard care and received pregnancy care according to local guidelines , which did not include such information .


Incidence of infants born large for gestational age ( birth weight 90th centile for gestation and sex ) .


Prespecified secondary outcomes included birth weight > 4000 g , hypertension , pre-eclampsia , and gestational diabetes .


Analyses used intention to treat principles .


2152 women and 2142 liveborn infants were included in the analyses .


The risk of the infant being large for gestational age was not significantly different in the two groups ( lifestyle advice 203/1075 ( 19 % ) v standard care 224/1067 ( 21 % ) ; adjusted relative risk 0.90 , 95 % confidence interval 0.77 to 1.07 ; P = 0.24 ) .


Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g ( lifestyle advice 164/1075 ( 15 % ) v standard care 201/1067 ( 19 % ) ; 0.82 , 0.68 to 0.99 ; number needed to treat ( NNT ) 28 , 15 to 263 ; P = 0.04 ) .


There were no differences in maternal pregnancy and birth outcomes between the two treatment groups .


For women who were overweight or obese , the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes .


Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ) .


Observationally lower testosterone is associated with an unhealthier cardiovascular ( CVD ) risk profile , but this association is open to confounding and reverse causality .


The authors examined the association of testosterone with well-established cardiovascular disease ( CVD ) risk factors ( blood pressure , low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol and fasting glucose ) and the Framingham score using a Mendelian randomization analysis with a separate-sample instrumental variable estimator .


To minimize reverse causality , a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong , based on three selected testosterone-related single nucleotide polymorphisms ( rs10046 , rs1008805 and rs1256031 ) .


Multivariable censored and linear regressions were used to examine the association of genetically predicted testosterone levels with CVD risk factors and Framingham score among 4212 older Chinese men from the Guangzhou Biobank Cohort Study .


Predicted testosterone was unrelated to systolic blood pressure [ -0.11 mmHg , 95 % confidence interval ( CI ) -0.70 to 0.48 ] , diastolic blood pressure ( 0.04 mmHg , 95 % CI -0.27 to 0.36 ) , fasting glucose ( 0.02 mmol/l , 95 % CI -0.02 to 0.06 ) or Framingham score ( 0.02 , 95 % CI -0.0001 to 0.03 ) but associated with higher LDL-cholesterol ( 0.02 mmol/l , 95 % CI 0.01 to 0.04 ) and lower HDL-cholesterol ( -0.01 mmol/l , 95 % CI -0.02 to -0.001 ) , after adjustment for potential confounders ( age , education , smoking status , use of alcohol and body mass index ) .


Our findings did not corroborate observed protective effects of testosterone on cardiovascular risk factors or risk of ischaemic heart disease among men , but raises the possibility that higher testosterone may be associated with an unhealthier lipid profile .


Rehabilitation of impaired cognitive functions begins to be considered a standard component of medical care after acquired brain injury .


Indeed , many evidences support the effectiveness of the two major categories of techniques , i.e. the traditional and computer-assisted ones , which are widely used in cognitive rehabilitative treatment .


Aim of this study is to evaluate the effects of pc - cognitive training in brain injury patients .


We studied 35 subjects ( randomly divided into two groups ) , affected by traumatic or vascular brain injury , having attended from January 2010 to December 2012 the Laboratory of Robotic and Cognitive Rehabilitation of IRCCS Neurolesi of Messina .


Cognitive impairment was investigated through psychometric battery , administered before ( T0 ) and two months ( T1 ) after the cognitive pc-training , which was performed only by the experimental group , in addition to conventional treatment .


Statistical analysis was performed using Wilcoxon test with a p < 0.01 .


At time T0 , all patients showed language deficits and cognitive alterations in visual attention and memory abilities .


After the rehabilitation program we noted a global improvement in both the groups .


However , at T1 , the experimental group showed a greater cognitive improvement than the control group , with significant differences in nearly all the neuropsychological tests performed .


Our data suggest that cognitive pc-training may be a promising methodology to optimize the rehabilitation outcomes following brain injury .


Study C210 was a Phase IIa , exploratory trial to assess the activity of telaprevir on hepatitis C virus ( HCV ) early viral kinetics in treatment-nave patients infected with genotype 4 ( G4 ) HCV .


Patients were randomized to receive peginterferon and ribavirin alone , telaprevir monotherapy ( T arm ) , or telaprevir in combination with peginterferon/ribavirin ( TPR arm ) for 15days , followed by a 46 - or 48-week standard treatment phase .


The current analysis aimed to characterize the genotype and phenotype of HCV G4 variants emerging during telaprevir treatment .


Five of the 8 ( 62.5 % ) patients in the telaprevir ( T ) arm had viral breakthrough ( vBT ) during the investigational treatment phase ( between baseline and Day 15 ) , compared to no patients in the TPR arm .


HCV G4 viral variants with a T54A/T mutation were detected in two of these patients , as well as two other patients with detectable HCV RNA at the end of telaprevir treatment .


Emergence of the T54A/T mutation was associated with a 2 - to 4-fold decreased susceptibility to telaprevir .


All patients with vBT during the investigational treatment phase or with a T54A/T mutation achieved undetectable HCV RNA 12 or 24weeks after end of treatment with subsequent peginterferon/ribavirin treatment .


In this analysis in G4 HCV-infected patients , more patients in the telaprevir monotherapy arm experienced vBT with resistant variants compared to none with telaprevir combination therapy .


The most commonly selected mutation T54A in telaprevir-treated G4 HCV patients was previously described in the context of G1 infection .


The trial was registered with ClinicalTrials.gov ( NCT00580801 ) .


The objective was to assess associations between tenofovir disoproxil fumarate-emtricitabine ( TDF-FTC ) exposure and levonorgestrel ( LNG ) concentrations among Kenyan HIV prevention trial participants using Sino-implant ( II ) LNG implants for contraception .


Women were offered implants among other contraceptive methods , were randomized to daily TDF-FTC or placebo , and followed monthly up to 56weeks .


Associations between TDF-FTC exposure and mean LNG values were analyzed with linear mixed models .


Of 739 women , 29 ( 3.9 % ) received implants with no incident pregnancies and one discontinuation .


Mean LNG concentrations over 56weeks among 28 women contributing data ranged between 214.0 and 659.8 pg/mL with no significant difference between TDF-FTC and placebo arms or between variable levels of TDF-FTC adherence .


Concomitant TDF-FTC use was not associated with a significant change in plasma LNG concentrations among women using Sino-implant ( II ) in the first year of use .


In low-tumor burden follicular lymphoma ( FL ) , maintenance rituximab ( MR ) has been shown to improve progression-free survival when compared with observation .


It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab ( RR ) administered on an as-needed basis .


E4402 ( RESORT ) was a randomized clinical trial designed to compare MR against RR .


Eligible patients with previously untreated low-tumor burden FL received four doses of rituximab , and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure .


Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure .


The primary end point was time to treatment failure .


Secondary end points included time to first cytotoxic therapy , toxicity , and health-related quality of life ( HRQOL ) .


A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years , the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR ( P = .54 ) .


Three-year freedom from cytotoxic therapy was 84 % for those receiving RR and 95 % for those receiving MR ( P = .03 ) .


The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL .


Grade 3 to 4 toxicities were infrequent in both arms .


In low-tumor burden FL , a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy .


The impact of perioperative synbiotics on bacterial translocation and subsequent bacteraemia after oesophagectomy is unclear .


This study investigated the effect of perioperative synbiotic administration on the incidence of bacterial translocation to mesenteric lymph nodes ( MLNs ) and the occurrence of postoperative bacteraemia .


Patients with oesophageal cancer were randomized to receive perioperative synbiotics or no synbiotics ( control group ) .


MLNs were harvested from the jejunal mesentery before dissection ( MLN-1 ) and after the restoration of digestive tract continuity ( MLN-2 ) .


Blood and faeces samples were taken before and after operation .


Microorganisms in each sample were detected using a bacterium-specific ribosomal RNA-targeted reverse transcriptase-quantitative polymerase chain reaction ( RT-qPCR ) method .


Some 42 patients were included .


There was a significant difference between the two groups in detection levels of microorganisms in the MLN-1 samples .


Microorganisms were more frequently detected in MLN-2 samples in the control group than in the synbiotics group ( 10 of 18 versus 3 of 18 ; P = 0035 ) .


In addition , bacteraemia detected using RT-qPCR 1day after surgery was more prevalent in the control group than in the synbiotics group ( 12 of 21 versus 4 of 21 ; P = 0025 ) .


Neutrophil counts on postoperative days 1 , 2 and 7 after surgery were all significantly higher in the control group than in the synbiotics group .


Perioperative use of synbiotics reduces the incidence of bacteria in the MLNs and blood .


These beneficial effects probably contribute to a reduction in the inflammatory response after oesophagectomy .


ID 000003262 ( University Hospital Medical Information Network , http://www.umin.ac.jp ) .


Population sequencing ( PS ) has shown that telaprevir-resistant variants are not typically detectable at baseline ( prevalence , 5 % of patients ) , and most variants present at the time of treatment failure are no longer detectable at the end of the study .


To gain insight into the evolution of telaprevir-resistant variants , their baseline prevalence and persistence after treatment was investigated using a more sensitive , deep-sequencing ( DS ) technique in a large number of treatment-experienced patients from the REALIZE study who were infected with hepatitis C virus genotype 1 .


Before treatment initiation , telaprevir-resistant variants ( T54A , T54S , or R155K in 1 % -2 % of the viral population ) were detected by DS in a fraction ( 2 % ) of patients for whom PS failed to detect resistance ; these variants were not necessarily detected at the time of treatment failure .


Of 49 patients in whom telaprevir-resistant variants were detected by PS at the time of treatment failure but not at the end of the study , DS revealed the presence of variants ( V36A/L/M , T54S , or R155K in 1 % -36 % of the viral population ) in 16 patients ( 33 % ) at the end of the study .


Similar to PS findings , DS analysis revealed that the frequency of telaprevir-resistant variants before treatment was also low , and variants detected at the time of treatment failure were no longer detectable in the majority of patients during follow-up .


Abnormal forms of grief , currently referred to as complicated grief or prolonged grief disorder , have been discussed extensively in recent years .


While the diagnostic criteria are still debated , there is no doubt that prolonged grief is disabling and may require treatment .


To date , few interventions have demonstrated efficacy .


We investigated whether outpatients suffering from prolonged grief disorder ( PGD ) benefit from a newly developed integrative cognitive behavioural therapy for prolonged grief ( PG-CBT ) .


A total of 51 patients were randomized into two groups , stratified by the type of death and their relationship to the deceased ; 24 patients composed the treatment group and 27 patients composed the wait list control group ( WG ) .


Treatment consisted of 20-25 sessions .


Main outcome was change in grief severity ; secondary outcomes were reductions in general psychological distress and in comorbidity .


Patients on average had 2.5 comorbid diagnoses in addition to PGD .


Between group effect sizes were large for the improvement of grief symptoms in treatment completers ( Cohens d = 1.61 ) and in the intent-to-treat analysis ( d = 1.32 ) .


Comorbid depressive symptoms also improved in PG-CBT compared to WG .


The completion rate was 79 % in PG-CBT and 89 % in WG .


The major limitations of this study were a small sample size and that PG-CBT took longer than the waiting time .


PG-CBT was found to be effective with an acceptable dropout rate .


Given the number of bereaved people who suffer from PGD , the results are of high clinical relevance .


The first CE-approved bioresorbable vascular scaffold ( BVS ) is effective at treating simple lesions and stable coronary artery disease , but it has yet to be assessed versus the best-in-class drug-eluting stents ( DES ) .


This study sought to compare the performance of a BVS with that of everolimus-eluting stents ( EES ) and biolimus-eluting stents ( BES ) in all-comer patients .


The EVERBIO II ( Comparison of Everolimus - and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents II ) trial was a single-center , assessor-blinded study of 240 patients randomly assigned in a 1:1:1 ratio to EES , BES , or BVS .


The only exclusion criterion was a reference vessel diameter > 4.0 mm , which precluded treatment with BVS .


The primary endpoint was angiographic late lumen loss ( LLL ) at 9 months .


Secondary endpoints included patient-oriented major acute coronary events ( MACE ) ( death , myocardial infarction [ MI ] , and any revascularization ) , device-oriented MACE ( cardiac death , MI , and target lesion revascularization ) , and stent thrombosis at the 9-month clinical follow-up .


Follow-up angiography was performed in 216 patients ( 90.7 % ) at 9 months .


In-stent LLL was similar between patients treated with BVS ( 0.28 0.39 mm ) and those treated with EES/BES ( 0.25 0.36 mm ; p = 0.30 ) .


Clinical outcomes were similar at 9 months : the patient-oriented MACE rate was 27 % in BVS and 26 % in the EES/BES group ( p = 0.83 ) and the device-oriented MACE rate was 12 % in BVS and 9 % in the EES/BES group ( p = 0.6 ) .


New-generation metallic DES ( EES/BES ) were not superior to BVS in terms of angiographic LLL and clinical outcomes .


( Comparison of Everolimus - and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents [ EVERBIO II ] ; NCT01711931 ) .


Common clinical practice recommends dual antiplatelet therapy ( DAPT ) for transcatheter aortic valve implantation ( TAVI ) .


The aim of the study was to evaluate , in a double blind randomized study , the safety of TAVI , with adjunctive pharmacotherapy consisting of single antiplatelet therapy .


From April 2010 to April 2011 , 120 consecutive patients , undergoing TAVI , have been enrolled in the study .


Patients were randomly assigned to DAPT group ( aspirin and clopidogrel 75 mg/qd or ticlopidine 500 mg/bid ) or ASA group ( aspirin only ) .


TAVI device was the Sapien XT-Novaflex Delivery System ( Edwards Lifesciences , Inc. ) .


All patients were followed up to 6 months .


Device success was achieved in 100 % of patients .


No difference in the VARC combined 30 day safety endpoint , all cause and cardiovascular mortality was observed .


At 30 days vascular complications were reduced in the ASA group ( p < 0.05 ) .


No differences in the clinical status were detected between the groups up to 6 months .


This study suggests that TAVI procedures can be performed without DAPT without increasing the morbidity and mortality .


These findings , if confirmed in a larger multicenter randomized trial , will no longer support the use of DAPT for TAVI .


Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG ( Radiation Therapy Oncology Group ) 9402 lived much longer after chemoradiotherapy ( CRT ) than radiation therapy ( RT ) alone .


However , some patients with noncodeleted tumors also benefited from CRT ; survival curves separated after the median had been reached , and significantly more patients lived 10 years after CRT than RT. .


Thus , 1p/19q status may not identify all responders to CRT .


Using trial data , we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT .


IDH status was evaluable in 210 of 291 patients ; 156 ( 74 % ) had mutations .


rs55705857 was evaluable in 245 patients ; 76 ( 31 % ) carried the G risk allele .


Both were associated with longer progression-free survival after CRT , and mutant IDH was associated with longer overall survival ( 9.4 v 5.7 years ; hazard ratio [ HR ] , 0.59 ; 95 % CI , 0.40 to 0.86 ; P = .006 ) .


For those with wild-type tumors , CRT did not prolong median survival ( 1.3 v 1.8 years ; HR , 1.14 ; 95 % CI , 0.63 to 2.04 ; P = .67 ) or 10-year survival rate ( CRT , 6 % v RT , 4 % ) .


Patients with codeleted mutated tumors ( 14.7 v 6.8 years ; HR , 0.49 ; 95 % CI , 0.28 to 0.85 ; P = .01 ) and noncodeleted mutated tumors ( 5.5 v 3.3 years ; HR , 0.56 ; 95 % CI , 0.32 to 0.99 ; P < .05 ) lived longer after CRT than RT. .


IDH mutational status identified patients with oligodendroglial tumors who did ( and did not ) benefit from alkylating-agent chemotherapy with RT. .


Although patients with codeleted tumors lived longest , patients with noncodeleted IDH-mutated tumors also lived longer after CRT .


Despite the widespread use and advancements of mobile technology that facilitate rich communication modes , there is little evidence demonstrating the value of smartphones for effective interclinician communication and knowledge processes .


The objective of this study was to determine the effects of different synchronous smartphone-based modes of communication , such as ( 1 ) speech only , ( 2 ) speech and images , and ( 3 ) speech , images , and image annotation ( guided noticing ) on the recall and transfer of visually and verbally represented medical knowledge .