A Randomized Clinical Trial Comparison Between Pivotal Response Treatment ( PRT ) and Adult-Driven Applied Behavior Analysis ( ABA ) Intervention on Disruptive Behaviors in Public School Children with Autism . Children with autism often demonstrate disruptive behaviors during demanding teaching tasks . Language intervention can be particularly difficult as it involves social and communicative areas , which are challenging for this population . The purpose of this study was to compare two intervention conditions , a naturalistic approach , Pivotal Response Treatment ( PRT ) with an adult-directed ABA approach on disruptive behavior during language intervention in the public schools . A randomized clinical trial design was used with two groups of children , matched according to age , sex and mean length of utterance . The data showed that the children demonstrated significantly lower levels of disruptive behavior during the PRT condition . The results are discussed with respect to antecedent manipulations that may be helpful in reducing disruptive behavior .

Pivotal Response Treatment ( PRT )

Pivotal Response Treatment ( PRT

adult-directed ABA approach


Effect of Chinese herbal medicine on vascular functions during 60-day head-down bed rest . PURPOSE Chinese herbal medicine is a promising countermeasure against cardiovascular dysfunction associated with a sedentary lifestyle . We examined the impact of the Chinese herb , Taikong Yangxin , on the micro- and macrovascular dysfunction associated with a 60-day bed rest . METHODS Fourteen healthy men were randomly divided into two groups : those given herbal supplement , and the control group ; the two groups underwent a 60-day bed rest . The macrovasculature was assessed by sonography . Skin microvascular functions were assessed with laser Doppler . The plasma level of endothelial microparticles ( EMPs ) , markers of endothelial injury , was determined . RESULTS Bed rest induced a 33 % decrease in the femoral artery diameter and compliance whereas carotid wall thickness , diameter , and compliance remained unchanged . The early phase of endothelium-dependent vasodilation to ACh was unmodified by bed rest , while the late phase was reduced by 30 % along with a twofold increase in EMPs . In those given Taikong Yangxin , the early phase was amplified by 2.5-fold , and the effects of bed rest on the late phase were prevented . CONCLUSION These findings indicate that Taikong Yangxin ameliorates endothelium-dependent vasodilation , likely by improving the NO pathway . The study suggests Taikong Yangxin as a new countermeasure to prevent the changes in microvascular function induced by physical inactivity .

Chinese herbal medicine

Chinese herbal medicine

Chinese herb , Taikong Yangxin

herbal supplement

60-day bed rest

Taikong Yangxin

vascular functions

cardiovascular dysfunction

micro- and macrovascular dysfunction

macrovasculature

Skin microvascular functions

endothelial injury

femoral artery diameter

compliance

carotid wall thickness , diameter

compliance

late phase

early phase

effects of bed rest

endothelium-dependent vasodilation

microvascular function

cardiovascular dysfunction

Fourteen

men


The SOFT trial : a Phase III study of the dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine S-1 and oxaliplatin ( SOX ) plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer . A combination of oxaliplatin , leucovorin and 5-fluorouracil ( FOLFOX ) plus bevacizumab has been widely used for the first-line chemotherapy of metastatic colorectal cancer ( mCRC ) . S-1 is an oral fluoropyrimidine preparation that combines tegafur , a prodrug of 5-fluorouracil , with two modulators . Several studies of combination chemotherapy with oxaliplatin plus S-1 ( SOX ) conducted in Asia have reported promising efficacy and safety in patients with mCRC , suggesting the potential to replace mFOLFOX6 . The SOFT trial ( JapicCTI-090699 ) was a randomized Phase III trial designed to evaluate the noninferiority of SOX plus bevacizumab to mFOLFOX6 plus bevacizumab in patients with mCRC . This review summarizes the drug concept of S-1 and the results of clinical trials of S-1 and SOX in CRC and presents an overview of the SOFT trial .

chemotherapy

oxaliplatin plus S-1 ( SOX )

S-1 and SOX

evaluate the noninferiority of SOX

mCRC

metastatic colorectal cancer .

metastatic colorectal cancer ( mCRC ) .

patients with mCRC

patients with mCRC


Comparison of 4 supraglotttic devices used by paramedics during simulated CPR : a randomized controlled crossover trial . BACKGROUND Ensuring an open airway during cardiopulmonary resuscitation is fundamental . The aim of this study was to determine the success rate of blind intubation during simulated cardiopulmonary resuscitation by untrained personnel . METHODS Four devices were compared in a simulated resuscitation scenario : ILMA ( Intavent Direct Ltd , Buckinghamshire , United Kingdom ) , Cobra PLA ( Engineered Medical Systems Inc , Indianapolis , IN ) , Supraglottic Airway Laryngopharyngeal Tube ( SALT ) ( ECOLAB , St. Paul , MN ) , and Air-Q ( Mercury Medical , Clearwater , FL ) . A group of 210 paramedics intubated a manikin with continuous chest compressions . RESULTS The mean times to intubation were 40.46 ± 4.64 , 33.96 ± 6.23 , 17.2 ± 4.63 , and 49.23 ± 13.19 seconds ( SALT vs ILMA , Cobra PLA , and Air-Q ; P < .05 ) . The success ratios of blind intubation for the devices were 86.7 % , 85.7 % , 100 % , and 71.4 % ( SALT vs ILMA , Cobra PLA , and Air-Q ; P < .05 ) . CONCLUSION The study showed that the most efficient device with the shortest blind intubation time was the SALT device .

supraglotttic devices

ILMA

Cobra PLA

Air-Q

The success ratios of blind intubation


Comparison of the neuroprotective effects and recovery profiles of isoflurane , sevoflurane and desflurane as neurosurgical pre-conditioning on ischemia/reperfusion cerebral injury . BACKGROUND There are a few reports regarding the comparison of these anesthetic agents , but previous studies mainly focus on the veterinary anesthesiology . Less attention has been focused comparing the effectiveness of these inhalational anesthetic agents in neurosurgery . This lack of interest is regretful particularly considering the fact that anesthetics during neurosurgery are an issue of extreme sensitivity and subtlety , where the cerebral oxygenation process plays a significant role in the neuroprotective mechanisms . OBJECTIVE The purpose of this retrospective study is to contribute to the existing knowledge of the comparative studies of the volatile anesthetic agents such as isoflurane , sevoflurane and desflurane by evaluating the maintenance and emergence characteristics after volatile anesthetics-induced preconditioning with isoflurane , sevoflurane or desflurane for inpatient ischemia/reperfusion cerebral injury during cerebral or neural surgeries . METHODS The aim was to investigate their neuroprotective mechanisms and effects by analyzing and comparing the superiority of each agent in a Chinese patient population , in terms of faster emergence , and early and intermediate recovery . The intraoperative haemodynamic profiles and postoperative adverse effects of these three agents were also systematically analyzed . RESULTS We found that sevoflurane , when compared with isoflurane and desflurane , provided anesthesia with similar hemodynamic stability but allowed for a smoother , more rapid emergence and better quality of induction and recovery to surgical patients under clinical conditions , particularly to those who were experiencing substantial cerebral vasodilation . CONCLUSION Sevoflurane offers several advantages , including a relative lack of airway irritation , a more rapid onset and recovery , and greater hemodynamic stability than other potent inhaled agents . These properties would appear to afford sevoflurane significant clinical potential .

isoflurane

sevoflurane

desflurane

isoflurane

sevoflurane

desflurane

isoflurane

sevoflurane

desflurane

sevoflurane

isoflurane

desflurane

Sevoflurane

neuroprotective effects

recovery profiles

effects

intraoperative haemodynamic profiles

postoperative adverse effects

emergence

quality of induction and recovery

airway irritation

onset and recovery

hemodynamic stability

ischemia/reperfusion cerebral injury

neurosurgery

ischemia/reperfusion cerebral injury

substantial cerebral vasodilation


Multicomponent interdisciplinary group intervention for self-management of fibromyalgia : a mixed-methods randomized controlled trial . BACKGROUND This study evaluated the efficacy of the PASSAGE Program , a structured multicomponent interdisciplinary group intervention for the self-management of FMS . METHODS A mixed-methods randomized controlled trial ( intervention ( INT ) vs. waitlist ( WL ) ) was conducted with patients suffering from FMS . Data were collected at baseline ( T0 ) , at the end of the intervention ( T1 ) , and 3 months later ( T2 ) . The primary outcome was change in pain intensity ( 0-10 ) . Secondary outcomes were fibromyalgia severity , pain interference , sleep quality , pain coping strategies , depression , health-related quality of life , patient global impression of change ( PGIC ) , and perceived pain relief . Qualitative group interviews with a subset of patients were also conducted . Complete data from T0 to T2 were available for 43 patients . RESULTS The intervention had a statistically significant impact on the three PGIC measures . At the end of the PASSAGE Program , the percentages of patients who perceived overall improvement in their pain levels , functioning and quality of life were significantly higher in the INT Group ( 73 % , 55 % , 77 % respectively ) than in the WL Group ( 8 % , 12 % , 20 % ) . The same differences were observed 3 months post-intervention ( Intervention group : 62 % , 43 % , 38 % vs Waitlist Group : 13 % , 13 % , 9 % ) . The proportion of patients who reported ≥ 50 % pain relief was also significantly higher in the INT Group at the end of the intervention ( 36 % vs 12 % ) and 3 months post-intervention ( 33 % vs 4 % ) . Results of the qualitative analysis were in line with the quantitative findings regarding the efficacy of the intervention . The improvement , however , was not reflected in the primary outcome and other secondary outcome measures . CONCLUSION The PASSAGE Program was effective in helping FMS patients gain a sense of control over their symptoms . We suggest including PGIC in future clinical trials on FMS as they appear to capture important aspects of the patients ' experience . TRIAL REGISTRATION International Standard Randomized Controlled Trial Number Register ISRCTN14526380 .

PASSAGE Program

( intervention ( INT ) vs.

waitlist ( WL )

pain intensity

fibromyalgia severity

pain interference

sleep quality

pain coping strategies

depression

health-related quality of life

perceived pain relief

pain levels

functioning and quality of life

≥ 50 % pain relief

fibromyalgia

FMS

patients suffering from FMS

43 patients

helping FMS patients

on FMS


The effects of bromazepam over the central and frontal areas during a motor task : an EEG study . The present study investigates the influence of bromazepam while executing a motor task . Specifically , we intend to analyze the changes in alpha absolute power under two experimental conditions , bromazepam and placebo . We also included analyses of theta and beta frequencies . We collected electroencephalographic data before , during , and after motor task execution . We used a Two Way ANOVA to investigate the condition ( PL × Br6 mg ) and moment ( pre and post ) variables for the following electrodes : Fp1 , Fp2 , F7 , F3 , Fz , F4 , F8 , C3 , CZ and C4 . We found a main effect for condition on the electrodes FP1 , F7 , F3 , Fz , F4 , C3 and CZ , for alpha and beta bands . For beta band we also found a main effect for condition on the electrodes Fp2 , F8 and C4 ; for theta band we identified a main effect for condition on C3 , Cz and C4 electrodes . This finding suggests that the motor task did not have any influence on the electrocortical activity in alpha , and that the existing modifications were a consequence due merely to the drug use . Despite its anxiolytic and sedative action , bromazepam did not show any significant changes when the individuals executed a finger extension motor task .

bromazepam

bromazepam

bromazepam

placebo

alpha absolute power

the electrocortical activity


A Comparison of Teaching Modalities and Fidelity of Simulation Levels in Teaching Resuscitation Scenarios . INTRODUCTION The purpose of our study was to examine the ability of novices to learn selected aspects of Advanced Cardiac Life Support ( ACLS ) in training conditions that did not incorporate simulation compared to those that contained low- and high-fidelity simulation activities . We sought to determine at what level additional educational opportunities and simulation fidelity become superfluous with respect to learning outcomes . METHODS Totally 39 medical students and physician assistant students were randomly assigned to 4 training conditions : control ( lecture only ) , video-based didactic instruction , low- , and high-fidelity simulation activities . Participants were assessed using a baseline written pretest of ACLS knowledge . Following this , all participants received a lecture outlining ACLS science and algorithm interpretation . Participants were then trained in specific aspects of ACLS according to their assigned instructional condition . After training , each participant was assessed via a Megacode performance examination and a written posttest . RESULTS All groups performed significantly better on the written posttest compared with the pretest ( p < 0.001 ) ; however , no groups outperformed any other groups . On the Megacode performance test , the video-based , low- , and high-fidelity groups performed significantly better than the control group ( p = 0.028 , p < 0.001 , p = 0.019 ) . Equivalence testing revealed that the high-fidelity simulation condition was statistically equivalent to the video-based and low-fidelity simulation conditions . CONCLUSION Video-based and simulation-based training is associated with better learning outcomes when compared with traditional didactic lectures only . Video-based , low-fidelity , and high-fidelity simulation training yield equivalent outcomes , which may indicate that high-fidelity simulation is superfluous for the novice trainee .

simulation

low- and high-fidelity simulation

control

video-based didactic instruction

low- , and high-fidelity simulation

activities

lecture outlining ACLS science

video-based

low- , and high-fidelity

groups

control group

high-fidelity simulation

video-based

low-fidelity simulation

Video-based

simulation-based

Video-based

low-fidelity

high-fidelity simulation training

pretest of ACLS knowledge

Megacode performance examination

written posttest .

Megacode performance test

novices

novice trainee


Supplementation with a blend of krill and salmon oil is associated with increased metabolic risk in overweight men . BACKGROUND Krill is an increasingly popular source of marine n-3 ( ω-3 ) PUFA that is seen as a premium product . However , to our knowledge , the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported . OBJECTIVE We assessed whether supplementation with a blend of krill and salmon ( KS ) oil [ which is rich in eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ] affects insulin sensitivity in overweight men . DESIGN The design was a randomized , double-blind , controlled crossover trial . A total of 47 men with a mean ± SD age of 46.5 ± 5.1 y , who were overweight [ body mass index ( in kg/m ( 2 ) ) from 25 to 30 ] but otherwise healthy , received 5 1-g capsules of KS oil or a control ( canola oil ) for 8 wk and crossed over to another treatment after an 8-wk washout period . The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test . Secondary outcomes included lipid profiles , inflammatory markers , 24-h ambulatory blood pressure , and carotid artery intimamedia thickness . RESULTS Unexpectedly , insulin sensitivity ( per the Matsuda index ) was 14 % lower with the KS oil than with the control oil ( P = 0.049 ) . A mediation analysis showed that , after controlling for the likely positive effects of blood EPA and DHA ( i.e. , the omega-3 index ) , the reduction in insulin sensitivity after KS-oil supplementation was more marked [ 27 % lower than with the control oil ( P = 0.009 ) ] . CONCLUSIONS Supplementation with a blend of KS oil is associated with decreased insulin sensitivity . Thus , krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease . This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000602921 .

blend of krill and salmon oil

Krill

KS oil

control

insulin sensitivity

insulin sensitivity

insulin sensitivity

insulin sensitivity

overweight

men

in

overweight

men

47 men

age of 46.5 ± 5.1 y ,

overweight

overweight

adults


A randomized , double-blind , placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder . BACKGROUND This 8-week , randomized , double-blind , placebo-controlled study , conducted August 2010-May 2012 in the United States , evaluated the safety and efficacy of vortioxetine 10 mg and 15 mg in patients with major depressive disorder ( MDD ) . The mechanism of action of vortioxetine is thought to be related to direct modulation of serotonin ( 5-HT ) receptor activity and inhibition of the serotonin transporter . METHOD Adults aged 18-75 years with MDD ( DSM-IV-TR ) and Montgomery-Asberg Depression Rating Scale ( MADRS ) total score ≥ 26 were randomized ( 1:1:1 ) to receive vortioxetine 10 mg or 15 mg or placebo once daily , with the primary efficacy end point being change from baseline at week 8 in MADRS analyzed by mixed model for repeated measures . Adverse events were recorded during the study , suicidal ideation and behavior were assessed using the Columbia-Suicide Severity Rating Scale ( C-SSRS ) , and sexual dysfunction was assessed using the Arizona Sexual Experience ( ASEX ) scale . RESULTS Of the 1,111 subjects screened , 469 subjects were randomized : 160 to placebo , 157 to vortioxetine 10 mg , and 152 to vortioxetine 15 mg . Differences from placebo in the primary efficacy end point were not statistically significant for vortioxetine 10 mg or vortioxetine 15 mg. Nausea , headache , dry mouth , constipation , diarrhea , vomiting , dizziness , and flatulence were reported in ≥ 5 % of subjects receiving vortioxetine . Discontinuation due to adverse events occurred in 7 subjects ( 4.4 % ) in the placebo group , 8 ( 5.2 % ) in the vortioxetine 10 mg group , and 12 ( 7.9 % ) in the vortioxetine 15 mg group . ASEX total scores were similar across groups . There were no clinically significant trends within or between treatment groups on the C-SSRS , laboratory values , electrocardiogram , or vital sign parameters . CONCLUSIONS In this study , vortioxetine did not differ significantly from placebo on MADRS total score after 8 weeks of treatment in MDD subjects . TRIAL REGISTRATION ClinicalTrials.gov identifier : NCT01179516 .

placebo-controlled

vortioxetine

placebo-controlled

vortioxetine

vortioxetine

efficacy and safety

safety and efficacy

serotonin ( 5-HT ) receptor activity

serotonin transporter .


Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia : a randomized controlled trial . Melatonin is known for its regulation of circadian rhythm . Recently , studies have shown that melatonin may have a positive effect on the skeleton . By increasing age , the melatonin levels decrease , which may lead to a further imbalanced bone remodeling . We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans . In a double-blind RCT , we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg ( N = 20 ) , 3 mg ( N = 20 ) , or placebo ( N = 41 ) . At baseline and after 1-yr treatment , we measured bone mineral density ( BMD ) by dual X-ray absorptiometry , quantitative computed tomography ( QCT ) , and high-resolution peripheral QCT ( HR-pQCT ) and determined calciotropic hormones and bone markers . Mean age of the study subjects was 63 ( range 56-73 ) yr . Compared to placebo , femoral neck BMD increased by 1.4 % in response to melatonin ( P < 0.05 ) in a dose-dependent manner ( P < 0.01 ) , as BMD increased by 0.5 % in the 1 mg/day group ( P = 0.55 ) and by 2.3 % ( P < 0.01 ) in the 3 mg/day group . In the melatonin group , trabecular thickness in tibia increased by 2.2 % ( P = 0.04 ) , and volumetric bone mineral density ( vBMD ) in the spine , by 3.6 % ( P = 0.04 ) in the 3 mg/day . Treatment did not significantly affect BMD at other sites or levels of bone turnover markers ; however , 24-hr urinary calcium was decreased in response to melatonin by 12.2 % ( P = 0.02 ) . In conclusion , 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner , while high-dose melatonin increased vBMD in the spine . Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures .

Melatonin

Melatonin

melatonin

melatonin

melatonin

placebo

dual X-ray absorptiometry

quantitative computed tomography

high-resolution peripheral QCT

placebo

melatonin

melatonin

melatonin

femoral neck BMD

BMD

trabecular thickness in tibia

spine

BMD

levels of bone turnover markers ;

24-hr urinary calcium

BMD at femoral neck

vBMD

spine

postmenopausal

women

osteopenia

postmenopausal osteopenic

women


Managing repetitive behaviours in young children with autism spectrum disorder ( ASD ) : pilot randomised controlled trial of a new parent group intervention . Early intervention for autism spectrum disorder ( ASD ) tends to focus on enhancing social-communication skills . We report the acceptability , feasibility and impact on child functioning of a new 8 weeks parent-group intervention to manage restricted and repetitive behaviours ( RRB ) in young children with ASD aged 3-7 years . Forty-five families took part in the pilot RCT . A range of primary and secondary outcome measures were collected on four occasions ( baseline , 10 , 18 and 24 weeks ) to capture both independent ratings and parent-reported changes in RRB . This pilot established that parents were willing to be recruited and randomised , and the format and content of the intervention was feasible . Fidelity of delivery was high , and attendance was 90 % . A fully powered trial is now planned .

changes in RRB


Intradermal insulin infusion achieves faster insulin action than subcutaneous infusion for 3-day wear . Rapid uptake previously demonstrated by intradermal ( ID ) drug administration indicates compound delivery within the dermis may have clinical and pharmacological advantages for certain drug therapies . This study is the first clinical trial to evaluate continuous microneedle-based drug infusion , device wearability , and intradermal microneedle insulin kinetics over a multi-day ( 72 h ) wear period . This was a single center , open-label , two-period crossover study in T1DM patients on continuous subcutaneous insulin infusion ( CSII ) . Patients received treatment during interventional visits : one SC and one ID basal/bolus infusion of insulin aspart ( NovoRapid® U-100 ) administered over 3 days in a randomized order . Twenty-eight patients were randomized and exposed to trial product , and 23 completed the study . Bolus insulin infusions were given prior to standardized breakfast and lunch test meals on each of the three treatment days . Blood samples were drawn at predefined time points for measurements of insulin aspart and blood glucose in serum . The primary endpoint insulin Tmax demonstrated that ID bolus infusion was associated with a significantly shorter Tmax with statistically significantly smaller intra-subject variability , compared to SC infusion , and this difference was maintained over three treatment days . Analyses of secondary PK endpoints corresponded with the primary endpoint findings . Postprandial glycemic response was significantly less pronounced after ID bolus : For most endpoints ID vs. SC , differences were statistically significant within the 0-1.5 or 0-2 h time period . Intradermal delivery of insulin is a viable delivery route alternative providing reduced time for insulin absorption with less intra-subject variability and lower glycemic response .

insulin infusion

intradermal ( ID )

endpoint insulin Tmax

significantly shorter Tmax

smaller intra-subject variability

secondary PK endpoints

findings

Postprandial glycemic response

reduced time for insulin absorption

less intra-subject variability

lower glycemic response

Twenty-eight


The Beyond Ageing Project Phase 2 -- a double-blind , selective prevention , randomised , placebo-controlled trial of omega-3 fatty acids and sertraline in an older age cohort at risk for depression : study protocol for a randomized controlled trial . BACKGROUND Late-life depression is associated with high rates of morbidity , premature mortality , disability , functional decline , caregiver burden and increased health care costs . While clinical and public health approaches are focused on prevention or early intervention strategies , the ideal method of intervention remains unclear . No study has set out to evaluate the role of neurobiological agents in preventing depressive symptoms in older populations at risk of depression . METHODS/DESIGN Subjects with previously reported sub-threshold depressive symptoms , aged 60 to 74 years , will be screened to participate in a single-centre , double-blind , randomised controlled trial with three parallel groups involving omega-3 fatty acid supplementation or sertraline hydrochloride , compared with matching placebo . Subjects will be excluded if they have current depression or suicide ideation ; are taking antidepressants or any supplement containing omega-3 fatty acid ; or have a prior history of stroke or other serious cerebrovascular or cardiovascular disease , neurological disease , significant psychiatric disease ( other than depression ) or neurodegenerative disease . The trial will consist of a 12 month treatment phase with follow-up at three months and 12 months to assess outcome events . At three months , subjects will undergo structural neuroimaging to assess whether treatment effects on depressive symptoms correlate with brain changes . Additionally , proton spectroscopy techniques will be used to capture brain-imaging markers of the biological effects of the interventions . The trial will be conducted in urban New South Wales , Australia , and will recruit a community-based sample of 450 adults . Using intention-to-treat methods , the primary endpoint is an absence of clinically relevant depression scores at 12 months between the omega-3 fatty acid and sertraline interventions and the placebo condition . DISCUSSION The current health , social and economic costs of late-life depression make prevention imperative from a public health perspective . This innovative trial aims to address the long-neglected area of prevention of depression in older adults . The interventions are targeted to the pathophysiology of disease , and regardless of the effect size of treatment , the outcomes will offer major scientific advances regarding the neurobiological action of these agents . The main results are expected to be available in 2017 . TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry ACTRN12610000032055 ( 12 January 2010 ) .

omega-3 fatty acids

sertraline

omega-3 fatty acid supplementation

sertraline hydrochloride

placebo

morbidity

premature mortality

disability , functional decline

caregiver burden

health care costs

structural neuroimaging

proton spectroscopy

brain-imaging markers

health

social and economic costs


Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin : a 78-week randomized , double-blind , placebo-controlled trial . AIMS To investigate the efficacy and tolerability of empagliflozin added to basal insulin-treated type 2 diabetes . METHODS Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were randomized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m ( 2 ) ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . RESULTS At week 18 , the adjusted mean ± standard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( -0.1 ± 0.8 mmol/mol ) for placebo , compared with -0.6 ± 0.1 % ( -6.2 ± 0.8 mmol/mol ) and -0.7 ± 0.1 % ( -7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p < 0.001 ) . At week 78 , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all p < 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35-36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively . CONCLUSIONS Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo .

empagliflozin

placebo-controlled

empagliflozin

empagliflozin

empagliflozin

efficacy

tolerability

type 2 diabetes


Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations : a randomized , open-label , prospective trial . OBJECTIVE To analyze the efficacy of gemcitabine with or without erlotinib for pancreatic cancer , and to determine the predictive role of epidermal growth factor receptor ( EGFR ) and KRAS mutations in these patients . METHODS This was a single-center , randomized , open-label , prospective trial . Eighty-eight chemotherapy-naïve metastatic pancreatic cancer patients were randomized for treatment with gemcitabine or gemcitabine plus erlotinib . EGFR and KRAS mutations were analyzed , respectively . The primary endpoint was the disease control rate . RESULTS Disease control rate ( 64 % vs. 25 % ; P < 0.001 ) , progression-free survival ( median 3.8 vs. 2.4 months ; P < 0.001 ) , and overall survival ( median 7.2 vs. 4.4 months ; P < 0.001 ) were better in the gemcitabine plus erlotinib group than in the gemcitabine alone group . In the gemcitabine plus erlotinib group , disease control ( 85 % vs. 33 % ; P = 0.001 ) , progression-free survival ( median 5.9 vs. 2.4 months ; P = 0.004 ) , and overall survival ( median 8.7 vs. 6.0 months ; P = 0.044 ) were better in patients with EGFR mutations than in those without EGFR mutations . KRAS mutation was not associated with treatment response or survival . CONCLUSIONS Gemcitabine plus erlotinib is more effective than gemcitabine alone for treating metastatic pancreatic cancer patients , especially those with EGFR mutations . ClinicalTrials.gov number , NCT01608841 .

Erlotinib

gemcitabine

erlotinib

the disease control rate

RESULTS Disease control rate

progression-free survival

and overall survival

disease control

progression-free survival

and overall survival

pancreatic cancer with epidermal

Eighty-eight


Environmental enrichment as a therapy for autism : A clinical trial replication and extension . Based on work done in animal models showing that autism-like symptoms are ameliorated following exposure to an enriched sensorimotor environment , we attempted to develop a comparable therapy for children with autism . In an initial randomized controlled trial , children with autism who received sensorimotor enrichment at home for 6 months had significant improvements in both their cognitive ability and the severity of their autism symptoms ( Woo & Leon , 2013 ) . We now report the outcomes of a similar randomized controlled trial in which children with autism , 3 to 6 years old , were randomly assigned to groups that received either daily sensorimotor enrichment , administered by their parents , along with standard care , or they received standard care alone . After 6 months , enriched children showed statistically significant gains in their IQ scores , a decline in their atypical sensory responses , and an improvement in their receptive language performance , compared to controls . Furthermore , after 6 months of enrichment therapy , 21 % of the children who initially had been given an autism classification , using the Autism Diagnostic Observation Schedule , improved to the point that , although they remained on the autism spectrum , they no longer met the criteria for classic autism . None of the standard care controls reached an equivalent level of improvement . Finally , the outcome measures for children who received only a subset of sensory stimuli were similar to those receiving the full complement of enrichment exercises . Sensorimotor enrichment therapy therefore appears to be a cost-effective means of treating a range of symptoms for children with autism .

Environmental enrichment

enriched sensorimotor environment

sensorimotor enrichment at home

daily sensorimotor enrichment

received standard care alone

IQ scores

atypical sensory responses

receptive language performance

outcome measures

cost-effective

autism :

autism

children

autism

autism

children

autism

3 to 6 years old ,


Assessment from Functional Perspectives : Using Sensorimotor Control in the Hand as an Outcome Indicator in the Surgical Treatment of Carpal Tunnel Syndrome . To investigate whether sensorimotor control of the hand could be an outcome indicator after carpal tunnel release ( CTR ) , this work examined changes in the results of patients ' manual tactile test ( MTT ) , pinch-holding-up activity ( PHUA ) , two-point discrimination ( 2PD ) and Semmes-Weinstein monofilament ( SWM ) tests . Participants included 30 predominantly sensory neuropathy CTS patients , as confirmed by a nerve conduction study . The MTT , precision pinch performance in PHUA and traditional sensibility ( 2PD and SWM ) tests were used to examine different aspects of sensory status at the time-points of two weeks before operation and one month post-operation , with a single-blind design . The results showed significant improvements in the sensory function as detected by the 2PD and SWM tests ( p < 0.001 ) and sensorimotor function as detected by the MTT ( p < 0.001 ) and PHUA test ( p < 0.05 ) for patients receiving CTR . The responsiveness of the SWM , MTT and PHUA tests ( effect size > 0.5 , p < 0.01 ) are better than that of two-point discrimination test ( effect size < 0.5 , p < 0.001 ) . However , pinch strength saw a decline compared to baseline with a moderate effect sizes ( effect size = 0.7 , p < 0.001 ) . This cohort study found that the MTT and PHUA test can both meet all the statistical criteria with regard to assessing treatment outcomes for patients with CTS . In addition , the results of this work provide clinicians with the information that the sensorimotor functions of the hands , as assessed by MTT and PHUA , are responsive to clinical changes due to CTR .

Sensorimotor Control in the Hand

sensorimotor control

manual tactile test

pinch-holding-up activity

two-point discrimination

Semmes-Weinstein monofilament

SWM

MTT

PHUA

SWM

MTT

PHUA

MTT

PHUA

MTT

PHUA

sensorimotor control of the hand

sensory function

sensorimotor function

pinch strength

Carpal Tunnel Syndrome

CTS

nerve conduction study

patients with CTS .


Placebo-controlled clinical trial evaluating 9.5 % hydrogen peroxide high-adhesion whitening strips . OBJECTIVE To evaluate the effectiveness and tolerability of an experimental 9.5 % hydrogen peroxide whitening strip relative to a placebo control over a three-week period . METHODS In this parallel-design , double-blind clinical trial , 54 adult volunteers were randomized to an experimental 9.5 % hydrogen peroxide whitening strip or placebo strip balancing for age and baseline tooth color , and received treatment . Strips were worn on the maxillary arch 30 minutes daily for 20 days . Efficacy was measured objectively as L*a*b* color change from digital images at Days 4 , 7 , 15 , and 21 . RESULTS As early as Day 4 and at all subsequent visits , the 9.5 % strip group experienced significant ( p < 0.004 ) color improvement relative to placebo for b* and L* color parameters . The amount of color improvement increased with continuing peroxide strip use . Mean ± SE between-group differences in Ab* were -0.6 ± 0.16 , -0.8 ± 0.15 , -1.6 ± 0.19 , and -1.9 ± 0.20 at Days 4 , 7 , 15 , and 21 , respectively . Similar results were noted for AL* . Minor tooth sensitivity was the most common adverse event , as reported by 12 % of subjects in the 9.5 % strip group and 11 % of subjects in the placebo group . No subjects discontinued treatment due to an adverse event . CONCLUSION This placebo-controlled clinical trial demonstrated that an experimental 9.5 % hydrogen peroxide strip yielded significant tooth whitening relative to a placebo strip as early as after three days of product use .

Placebo-controlled

hydrogen peroxide whitening strip

placebo

color improvement

color improvement

Mean ± SE

AL*

Minor tooth sensitivity


Pulsed electromagnetic fields for postmenopausal osteoporosis and concomitant lumbar osteoarthritis in southwest China using proximal femur bone mineral density as the primary endpoint : study protocol for a randomized controlled trial . BACKGROUND Osteoporosis ( OP ) and osteoarthritis ( OA ) are prevalent skeletal disorders among postmenopausal women . Coexistence is common especially that of postmenopausal osteoporosis ( PMO ) and lumbar OA . An hypothesis has been raised that OP and OA might share the same pathogenic mechanism , and pulsed electromagnetic fields ( PEMFs ) were reported to have anti-osteoporosis and anti-osteoarthritis properties , but this suggestion was based primarily on biomarker data . Therefore , whether these two effects could take place simultaneously has not yet been investigated . This randomized controlled trial ( RCT ) is designed to explore the effect of PEMFs for PMO and concomitant lumbar OA . METHODS/DESIGN The study will include PMO patients ( postmenopausal women ; aged between 50 and 70 years ; have been postmenopausal for at least 5 years and diagnosed with OP using proximal femur T-score ) with concomitant lumbar OA ( patients with confounding disorders like diabetes , hypertension , hyperlipidemia , and previous fracture history , etcetera , will be excluded ) will be randomly assigned to two arms : PEMFs group and sham PEMFs group . There will be 25 participants in each arm ( 50 in total ) and the outcome assessment , including the primary endpoint ( proximal femur bone mineral density ) , will be performed at 5 weeks , 3 months and 6 months after enrollment . DISCUSSION PMO and lumbar OA are prominent public health problem , especially for postmenopausal women . We hope this RCT will provide scientific evidence to primary care of the postmenopausal women regarding the use of these nonpharmaceutical , noninvasive modalities , PEMFs , in managing PMO and lumbar OA . TRIAL REGISTRATION Chinese Clinical Trial Registry : ChiCTR-TRC-14005156 ( 28 August 2014 ) .

Pulsed electromagnetic fields

pulsed electromagnetic fields ( PEMFs )

PEMFs

PEMFs

sham PEMFs group

PEMFs

proximal femur bone mineral density

( proximal femur bone mineral density )

postmenopausal

women

aged between 50 and 70 years

postmenopausal

25 participants in each arm

50 in total

postmenopausal

women


Improvement in Patient-Reported Visual Function After Ocriplasmin for Vitreomacular Adhesion : Results of the Microplasmin for Intravitreous Injection-Traction Release Without Surgical Treatment ( MIVI-TRUST ) Trials . IMPORTANCE The impact of vitreomacular adhesion ( VMA ) resolution on patient-reported visual function in symptomatic VMA/vitreomacular traction ( VMT ) has not yet been documented , to our knowledge . OBJECTIVE To determine the impact of intravitreal ocriplasmin on patient-reported visual function using the 25-item National Eye Institute Visual Function Questionnaire ( NEI VFQ-25 ) during a 6-month follow-up in patients with symptomatic VMA . DESIGN , SETTING , AND PARTICIPANTS Two multicenter , randomized , masked , phase 3 clinical trials ( studies TG-MV-006 [ between December 2008 and April 2010 ] and TG-MV-007 [ between December 2008 and July 2010 ] ) at clinic-based centers in the United States and Europe . A total of 652 patients with symptomatic VMA/VMT , including when associated with a macular hole 400 μm or smaller , were studied . Analysis was by intent-to-treat population and performed in May 2013 . INTERVENTIONS Patients with symptomatic VMA/VMT were randomly assigned ( 2:1 or 3:1 in study TG-MV-006 and study TG-MV-007 , respectively ) to receive a single intravitreal injection of ocriplasmin , 125 μg , or placebo-injected vehicle ( placebo ) . The NEI VFQ-25 was administered at baseline and 6 months following ocriplasmin injection . MAIN OUTCOMES AND MEASURES Mean changes between baseline and 6-month follow-up NEI VFQ-25 composite and subscale scores and the proportion of patients with a clinically meaningful change ( ≥5 points ) in scores . RESULTS Across the 2 studies , 464 patients received ocriplasmin and 188 received placebo . At 6 months , the ocriplasmin group reported greater mean improvements from baseline in the NEI VFQ-25 composite score than the placebo group ( mean change , 3.4 vs 0.7 , respectively ; P = .005 ) . Improvements were also noted in subscale scores , with the following respective mean changes for the ocriplasmin vs placebo groups : vision-related dependency , 1.7 vs -2.1 ( P = .009 ) ; driving difficulty , 2.7 vs -1.5 ( P = .03 ) ; distance vision activities , 4.1 vs 0.8 ( P = .03 ) ; and general vision , 6.1 vs 2.1 ( P = .003 ) . A higher proportion of the ocriplasmin group had a clinically meaningful ( ≥5-point ) improvement in NEI VFQ-25 composite score from baseline than the placebo group ( 36.0 % vs 27.2 % , respectively ; P = .03 ) . Fewer ocriplasmin-treated patients had a clinically meaningful worsening in their visual function than the placebo group ( 15.0 % vs 24.3 % , respectively ; P = .005 ) . Changes in NEI VFQ-25 composite score and various subscale scores were observed in ocriplasmin-treated patients who achieved VMA resolution at day 28 . CONCLUSIONS AND RELEVANCE Ocriplasmin produces clinically meaningful improvement in patient-reported visual function in symptomatic VMA/VMT . TRIAL REGISTRATION clinicaltrials.gov Identifiers : NCT00781859 and NCT00798317 .

Ocriplasmin

vitreomacular adhesion ( VMA )

intravitreal ocriplasmin

( NEI VFQ-25 )

visual function

NEI VFQ-25

composite and subscale scores

greater mean improvements from baseline

the

NEI VFQ-25 composite score

subscale

NEI

meaningful worsening

Changes in NEI VFQ-25 composite

patients with symptomatic VMA

652 patients

symptomatic VMA/VMT

464 patients

188 received


Self-management education for adults with poorly controlled epilepsy ( SMILE ( UK ) ) : statistical , economic and qualitative analysis plan for a randomised controlled trial . BACKGROUND There is a need to test the effectiveness of new educational interventions for people with poorly controlled epilepsy . The SMILE ( self-management education for adults with poorly controlled epilepsy ) trial evaluates a complex service intervention that involves a 2-day self-management course with the aim of improving quality of life and clinical outcomes . This article describes the statistical , economic , and qualitative analysis plan for the trial . METHODS AND DESIGN SMILE is a pragmatic , parallel design , two-arm , multi-centre randomised controlled superiority trial of a group-based interactive course compared with treatment as usual for people who have experienced two or more seizures in the past 12 months . RESULTS A summary of the objectives and design of the trial are reported as well as the manner in which the data will be summarised and inferentially analysed . This includes the type of modelling that will be employed for each of the primary and secondary outcomes and the methods by which the assumptions of these models will be checked . Strategies are described for handling clustering of outcome data , missing observations , and treatment non-compliance . CONCLUSION This update to the previously published trial protocol provides a description of the trial analysis which is transparent and specified before any outcome data are available . It also provides guidance to those planning the analysis of similar trials . TRIAL REGISTRATION Current Controlled Trials ISRCTN57937389 ; date assigned : 27 March 2013 .

educational

group-based interactive course

treatment as usual

adults

SMILE ( self-management education

adults

poorly controlled epilepsy )


A Randomized , Placebo-Controlled Trial Evaluating Safety and Immunogenicity of the Killed , Bivalent , Whole-Cell Oral Cholera Vaccine in Ethiopia . Killed whole-cell oral cholera vaccine ( OCV ) has been a key component of a comprehensive package including water and sanitation measures for recent cholera epidemics . The vaccine , given in a two-dose regimen , has been evaluated in a large number of human volunteers in India , Vietnam , and Bangladesh , where it has demonstrated safety , immunogenicity , and clinical efficacy . We conducted a double-blind randomized placebo-controlled trial in Ethiopia , where we evaluated the safety and immunogenicity of the vaccine in 216 healthy adults and children . OCV was found to be safe and elicited a robust immunological response against Vibrio cholerae O1 , with 81 % adults and 77 % children demonstrating seroconversion 14 days after the second dose of vaccine . This is the first study to evaluate safety and immunogenicity of the vaccine in a population outside Asia using a placebo-controlled , double-blind , randomized study design .

Placebo-Controlled

Whole-Cell Oral Cholera Vaccine

vaccine

placebo-controlled

vaccine

OCV

vaccine

placebo-controlled

safety and immunogenicity

seroconversion

in Ethiopia

adults

children .


Effects of hydraulic circuit training on cardiovascular function . The effect of hydraulic circuit training ( HCT ) on cardiovascular ( CV ) function was assessed in 32 healthy middle-aged males ( X age = 42.2 +/- 2.1 yr ) . Maximal aerobic power ( VO2max ) , with simultaneous measurement of stroke volume ( SV ) and cardiac output ( CO ) , by impedance cardiography , was assessed pre- and post-training . Subjects were randomly assigned to a nonexercising control group , a cycle training group ( cycle ) , or one of the two HCT groups . Training groups participated in a 9 wk program , 3 d.wk-1 . Subjects assigned to HCT exercised on a 9 station circuit , completing 3 circuits.d-1 . Each circuit consisted of three 20 s work intervals at each station with a 1:1 work : rest ratio . One HCT group ( HCTmax ) completed the maximal repetitions possible ( RM ) during each work interval . The other HCT group ( HCTsub ) exercised at 70-85 % of RM . Following training VO2max ( ml.kg-1 min-1 ) was significantly increased in all training groups ( 18.0 , 12.5 , and 11.3 % for cycle , HCTsub , and HCTmax groups , respectively ; P less than 0.05 ) . The increase in VO2max observed in the cycle group was significantly greater than that recorded by the two HCT groups ( P less than 0.05 ) . For all three training groups , the increase in VO2max was associated with increases in SVmax and COmax ( P less than 0.05 for both ) . These findings suggest that both maximal and submaximal HCT programs can elicit improvements in cardiovascular fitness .

cardiovascular ( CV ) function

Maximal aerobic power ( VO2max )

cardiac output ( CO )

impedance cardiography

HCTmax groups

SVmax

COmax

cardiovascular fitness

cardiovascular function

males

42.2 +/- 2.1 yr


Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy . BACKGROUND The study reported here compared the blood pressure ( BP ) -lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide ( HCTZ ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg. METHODS Patients with sitting diastolic blood pressure ( siDBP ) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks . After 4 weeks , the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg . RESULTS Of the 263 randomized patients , 256 patients who had available efficacy data were analyzed . The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 ( 6.88±8.10 mmHg vs 3.38±7.33 , P=0.0008 ) , and the effect persisted at Week 8 ( 8.67±9.39 mmHg vs 5.02±8.27 mmHg , P=0.0023 ) . Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group ( at Week 4 , 10.50±13.76 mmHg vs 5.75±12.18 mmHg , P=0.0069 and , at Week 8 , 13.45±15.15 mmHg vs 6.84±13.57 mmHg , P=0.0007 ) . The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP < 90 mmHg after 4 weeks of treatment was higher in the fimasartan/HCTZ treatment group than in the fimasartan treatment group ( 53.6 % vs 39.8 % , P=0.0359 ) . The overall incidence of adverse drug reaction was 11.79 % with no significant difference between the treatment groups . CONCLUSION The combination treatment of fimasartan and HCTZ achieved better BP control than fimasartan monotherapy , and had comparable safety and tolerance to fimasartan monotherapy .

fimasartan monotherapy

fimasartan alone

fimasartan

Efficacy

blood pressure

hypertensive patients

diastolic blood pressure ( siDBP )


The effects of parental components in a trauma-focused cognitive behavioral based therapy for children exposed to interparental violence : study protocol for a randomized controlled trial . BACKGROUND Interparental violence is both common and harmful and impacts children 's lives directly and indirectly . Direct effects refer to affective , behavioral , and cognitive responses to interparental violence and psychosocial adjustment . Indirect effects refer to deteriorated parental availability and parent-child interaction . Standard Trauma Focused Cognitive Behavioral Therapy may be insufficient for children traumatized by exposure to interparental violence , given the pervasive impact of interparental violence on the family system . HORIZON is a trauma focused cognitive behavioral therapy based group program with the added component of a preparatory parenting program aimed at improving parental availability ; and the added component of parent-child sessions to improve parent-child interaction . METHODS/DESIGN This is a multicenter , multi-informant and multi-method randomized clinical trial study with a 2 by 2 factorial experimental design . Participants ( N = 100 ) are children ( 4-12 years ) , and their parents , who have been exposed to interparental violence . The main aim of the study is to test the effects of two parental components as an addition to a trauma focused cognitive behavioral based group therapy for reducing children 's symptoms . Primary outcome measures are posttraumatic stress symptoms , and internalizing and externalizing problems in children . The secondary aim of the study is to test the effect of the two added components on adjustment problems in children and to test whether enhanced effects can be explained by changes in children 's responses towards experienced violence , in parental availability , and in quality of parent-child interaction . To address this secondary aim , the main parameters are observational and questionnaire measures of parental availability , parent-child relationship variables , children 's adjustment problems and children 's responses to interparental violence . Data are collected three times : before and after the program and six months later . Both intention-to-treat and completer analyses will be done . DISCUSSION The current study will enhance our understanding of the efficacy interparental violence-related parental components added to trauma focused cognitive behavioral group program for children who have been exposed to IPV . It will illuminate mechanisms underlying change by considering multiple dimensions of child responses , parenting variables and identify selection criteria for participation in treatment . TRIAL REGISTRATION Netherlands Trial Register NTR4015 . Registered 4th of June , 2013 .

parental components

preparatory parenting program


A Randomized Controlled Trial to Improve Social Skills in Young Adults with Autism Spectrum Disorder : The UCLA PEERS ( ® ) Program . Research suggests that impaired social skills are often the most significant challenge for those with autism spectrum disorder ( ASD ) , yet few evidence-based social skills interventions exist for adults on the spectrum . This replication trial tested the effectiveness of PEERS , a caregiver-assisted social skills program for high-functioning young adults with ASD . Using a randomized controlled design , 22 young adults 18-24 years of age were randomly assigned to a treatment ( n = 12 ) or delayed treatment control ( n = 10 ) group . Results revealed that the treatment group improved significantly in overall social skills , frequency of social engagement , and social skills knowledge , and significantly reduced ASD symptoms related to social responsiveness following PEERS . Most treatment gains were maintained at a 16-week follow-up assessment with new improvements observed .

UCLA PEERS ( ® ) Program

evidence-based social skills

the effectiveness

in overall social skills

frequency of social engagement

social skills knowledge

Young Adults

Autism Spectrum Disorder

adults

on the spectrum

high-functioning

young adults

young adults 18-24 years of age


[ Effect of Preoperative Oral Rehydration on Onset Time and Recovery Time of Rocuronium ] . BACKGROUND Preoperative oral rehydration solution ( ORS ) prevents hypovolemia . The aim of this study was to compare the effect of intubating dose of rocuronium in patients taking and those not taking preoperative ORS . METHODS Twenty patients , ASA I aged 20-50 years scheduled for elective surgery , were investigated and randomly assigned to two groups : drinking 1,500 ml ORS 6 to 2 hours before anesthesia ( ORS group ) and nothing by mouth from 6 hours before anesthesia ( control group ) . Anesthesia was maintained with propofol and remifentanil , and rocuronium 0.6 mg x kg ( -1 ) was administrated . To evaluate the effect of rocuronium , acceleromyography at the adductor pollicis was performed using 0.1 Hz stimulation . Cardiac index ( CI ) and stroke volume variation ( SVV ) from FloTra/Vigileo , times to 95 % twitch depression as onset time ( OT ) , and times to first twitch re-detection ( TR ) were recorded . RESULTS SVV was significantly lower in ORS group ( P = 0.03 ) , and CI showed no difference . In ORS group , TR was significantly shorter than that of control group ( P=0.002 ) , and OT tended to be prolonged ( 99.0 ± 36.3 s vs. 84.0 ± 37.5 s ) , but not significantly . CONCLUSIONS Preoperative oral rehydration possibly increases circulating blood volume , and shortens the duration of rocuronium effect .

Preoperative Oral Rehydration

oral rehydration solution ( ORS )

rocuronium

ORS .

ORS

( ORS group )

nothing by mouth

( control group )

propofol

remifentanil

rocuronium

ORS

ORS

Rehydration

rehydration

hypovolemia .

preoperative ORS

depression

onset time ( OT )

twitch re-detection ( TR )


Risk of anterior cruciate ligament fatigue failure is increased by limited internal femoral rotation during in vitro repeated pivot landings . BACKGROUND A reduced range of hip internal rotation is associated with increased peak anterior cruciate ligament ( ACL ) strain and risk for injury . It is unknown , however , whether limiting the available range of internal femoral rotation increases the susceptibility of the ACL to fatigue failure . HYPOTHESIS Risk of ACL failure is significantly greater in female knee specimens with a limited range of internal femoral rotation , smaller femoral-ACL attachment angle , and smaller tibial eminence volume during repeated in vitro simulated single-leg pivot landings . STUDY DESIGN Controlled laboratory study . METHODS A custom-built testing apparatus was used to simulate repeated single-leg pivot landings with a 4×-body weight impulsive load that induces knee compression , knee flexion , and internal tibial torque in 32 paired human knee specimens from 8 male and 8 female donors . These test loads were applied to each pair of specimens , in one knee with limited internal femoral rotation and in the contralateral knee with femoral rotation resisted by 2 springs to simulate the active hip rotator muscles ' resistance to stretch . The landings were repeated until ACL failure occurred or until a minimum of 100 trials were executed . The angle at which the ACL originates from the femur and the tibial eminence volume were measured on magnetic resonance images . RESULTS The final Cox regression model ( P = .024 ) revealed that range of internal femoral rotation and sex of donor were significant factors in determining risk of ACL fatigue failure . The specimens with limited range of internal femoral rotation had a failure risk 17.1 times higher than did the specimens with free rotation ( P = .016 ) . The female knee specimens had a risk of ACL failure 26.9 times higher than the male specimens ( P = .055 ) . CONCLUSION Limiting the range of internal femoral rotation during repetitive pivot landings increases the risk of an ACL fatigue failure in comparison with free rotation in a cadaveric model . CLINICAL RELEVANCE Screening for restricted internal rotation at the hip in ACL injury prevention programs as well as in individuals with ACL injuries and/or reconstructions is warranted .

A custom-built testing apparatus


Expanding care for perinatal women with depression ( EXPONATE ) : study protocol for a randomized controlled trial of an intervention package for perinatal depression in primary care . BACKGROUND Depression is common among women during perinatal period and is associated with long-term adverse consequences for the mother and infant . In Nigeria , as in many other low- and-middle-income countries ( LMIC ) , perinatal depression usually goes unrecognized and untreated . The aim of EXPONATE is to test the effectiveness and cost-effectiveness of an intervention package for perinatal depression delivered by community midwives in primary maternal care in which physician support and enhanced patient compliance are implemented using mobile phones . METHODS/STUDY DESIGN A pragmatic two-arm parallel cluster randomized controlled trial was designed . The units of allocation are the primary maternal care clinics . Thirty eligible and consenting clinics were randomized but , due to problems with logistics , 29 eventually participated . Consenting pregnant women with a gestational age between 16 and 28 weeks who screened positive on the Edinburgh Postnatal Depression Scale ( EPDS score ≥12 ) , absent psychosis or bipolar disorder , and not actively suicidal were recruited into the trial ( N = 686 ) . Midwives in the intervention arm were trained to deliver psychoeducation , problem solving treatment , and parenting skills . Eight weekly sessions were delivered following entry into the study . Further sessions during pregnancy and 6 weeks following childbirth were determined by level of depressive symptoms . Clinical support and supervision , delivered mainly by mobile phone , were provided by general physicians and psychiatrists . Automated text and voice messages , also delivered by mobile phones , were used to facilitate patient compliance with clinic appointments and 'homework ' tasks . Patients in the control arm received care as usual enhanced by further training of the providers in that arm in the recognition and standard treatment of depression . Assessments are undertaken at baseline , 2 months following recruitment into the study and 3 , 6 , 9 and 12 months after childbirth . The primary outcome is recovery from depression ( EPDS < 6 ) at 6 months . Secondary outcomes include measures of disability , parenting skills , maternal attitudes , health care utilization as well as infant physical and cognitive development comprehensively assessed using the Bayley 's Scales . DISCUSSION To the best of our knowledge , this is the largest randomized controlled trial of an intervention package delivered by community midwives in sub-Saharan Africa . TRIAL REGISTRATION Trial is registered with the ISRTCN registry at isrtcn.com ; Trial number ISRCTN60041127 . Date of registration is 15/05/2013 .

depression

perinatal depression

Depression

perinatal depression

perinatal depression

absent psychosis or bipolar disorder

depressive symptoms

recovery from depression

measures of

disability

parenting skills

maternal attitudes

health care utilization

the Bayley 's Scales


The effect of the video game Mindlight on anxiety symptoms in children with an Autism Spectrum Disorder . BACKGROUND In the clinical setting , a large proportion of children with an autism spectrum disorder ( ASD ) experience anxiety symptoms . Because anxiety is an important cause of impairment for children with an ASD , it is necessary that effective anxiety interventions are implemented for these children . Recently , a serious game called Mindlight has been developed that is focused on decreasing anxiety in children . This approach is based on recent research suggesting that video games might be suitable as an intervention vehicle to enhance mental health in children . In the present study it will be investigated whether Mindlight is effective in decreasing ( sub ) clinical anxiety symptoms in children who are diagnosed with an ASD . METHODS/DESIGN The present study involves a randomized controlled trial ( RCT ) with two conditions ( experimental versus control ) , in which it is investigated whether Mindlight is effective in decreasing ( sub ) clinical anxiety symptoms in children with an ASD . For this study , children of 8-16 years old with a diagnosis of an ASD and ( sub ) clinical anxiety symptoms will be randomly assigned to the experimental ( N = 60 ) or the control ( N = 60 ) condition . Children in the experimental condition will play Mindlight for one hour per week , for six consecutive weeks . Children in the control condition will play the puzzle game Triple Town , also for one hour per week and for six consecutive weeks . All children will complete assessments at baseline , post-intervention and 3-months follow-up . Furthermore , parents and teachers will also complete assessments at the same time points . The primary outcome will be child report of anxiety symptoms . Secondary outcomes will be parent report of child anxiety , child/parent report of depressive symptoms , and parent/teacher report of social functioning and behavior problems . DISCUSSION This paper aims to describe a study that will examine the effect of the serious game Mindlight on ( sub ) clinical anxiety symptoms of children with an ASD in the age of 8-16 years old . It is expected that children in the experimental condition will show lower levels of anxiety symptoms at 3-months follow-up , compared to children in the control condition . If Mindlight turns out to be effective , it could be an important contribution to the already existing interventions for anxiety in children with an ASD . Mindlight could then be implemented as an evidence-based treatment for anxiety symptoms in children with an ASD in mental health institutes and special education schools . TRIAL REGISTRATION Dutch Trial Register NTR5069 . Registered 20 April 2015 .

video game Mindlight

game called Mindlight

video games

Mindlight

Mindlight

play Mindlight

puzzle game Triple Town

Mindlight

Mindlight

anxiety symptoms

anxiety symptoms

clinical anxiety symptoms

anxiety symptoms

anxiety symptoms

child report of anxiety symptoms

parent report of child anxiety

ASD in the age of 8-16 years old .

anxiety symptoms

anxiety symptoms

children

an Autism Spectrum Disorder

children

an ASD

children

who are diagnosed with an ASD

children of 8-16 years old

with an ASD


Effects of Combined Resistive Underwater Exercises and Interferential Current Therapy in Patients with Juvenile Idiopathic Arthritis : A Randomized Controlled Trial . OBJECTIVE The objective of this study was to verify the effects of combined resistive underwater exercises and interferential current on the peak torque of the quadriceps and hamstrings and pain levels in patients with juvenile idiopathic arthritis . DESIGN This is a randomized controlled study ; 30 children with polyarticular juvenile idiopathic arthritis were randomly distributed into two groups : the control group ( n = 15 ) received the traditional physical therapy program and the study group ( n = 15 ) received resistive underwater exercises and interferential current therapy . Peak torque of the quadriceps and hamstrings and pain levels were evaluated before treatment , 1 mo later , and after 3 mos using the HUMAC NORM , CSMI Testing and Rehabilitation Isokinetic System and visual analog scale , respectively . RESULTS In the control group , all measures showed significant differences ( P < 0.05 ) after 1 mo except peak torque of left quadriceps and pain levels , and significant differences were found after 3 mos ( P < 0.05 ) in all . In the study group , all measures showed significant differences after 1 and 3 mos ( P < 0.05 ) and there were significant differences between groups after 1 and 3 mos in favor of the study group ( P < 0.05 ) . CONCLUSION The combination of resistive underwater exercises and interferential current therapy is a potentially valuable treatment for patients with juvenile idiopathic arthritis .

traditional physical therapy program

Effects

effects

measures

Juvenile

Idiopathic Arthritis

juvenile

idiopathic arthritis

children

juvenile

idiopathic arthritis


Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer : Development and External Validation of the Amsterdam Prognostic Model . PURPOSE A prognostic model for 5-year overall survival ( OS ) , consisting of recursive partitioning analysis ( RPA ) and a nomogram , was developed for patients with early-stage non-small cell lung cancer ( ES-NSCLC ) treated with stereotactic ablative radiation therapy ( SABR ) . METHODS AND MATERIALS A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training ( 67 % ) and an internal validation ( 33 % ) dataset . In the former group , 21 unique parameters consisting of patient , treatment , and tumor factors were entered into an RPA model to predict OS . Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS . A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots . Both the RPA and the nomogram were externally validated in independent surgical ( n = 193 ) and SABR ( n = 543 ) datasets . RESULTS RPA identified 2 distinct risk classes based on tumor diameter , age , World Health Organization performance status ( PS ) and Charlson comorbidity index . This RPA had moderate discrimination in SABR datasets ( c-index range : 0.52-0.60 ) but was of limited value in the surgical validation cohort . The nomogram predicting OS included smoking history in addition to RPA-identified factors . In contrast to RPA , validation of the nomogram performed well in internal validation ( r ( 2 ) = 0.97 ) and external SABR ( r ( 2 ) = 0.79 ) and surgical cohorts ( r ( 2 ) = 0.91 ) . CONCLUSIONS The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making . The nomogram retained strong performance across surgical and SABR external validation datasets . RPA performance was poor in surgical patients , suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities .

Stereotactic Ablative Radiation Therapy

SABR

patient , treatment , and tumor factors

RPA performance

ES-NSCLC SABR


Disclosure of HSV-2 serological test results in the context of an adolescent HIV prevention trial in Kenya . OBJECTIVES Herpes simplex virus type 2 ( HSV-2 ) biomarkers are often used in adolescent sub-Saharan HIV prevention studies , but evaluations of test performance and disclosure outcomes are rare in the published literature . Therefore , we investigated the proportion of ELISA-positive and indeterminate samples confirmed by western blot ( WB ) , the psychosocial response to disclosure and whether reports of sexual behaviour and HSV-2 symptoms are consistent with WB confirmatory results among adolescent orphans in Kenya . METHODS In 2011 , 837 Kenyan orphan youth in grades 7 and 8 enrolled in an HIV prevention clinical trial with HSV-2 biomarker outcomes . We used a modified algorithm for the Kalon HSV-2 ELISA to improve specificity ; positive and indeterminate results were WB tested . We developed culturally sensitive protocols for disclosing positive results , and documented psychosocial responses , reports of sexual contact and HSV-2 symptoms . RESULTS 28 adolescents ( 3.3 % ) were identified as HSV-2 seropositive , six as indeterminate . Of these , 22 positive and all indeterminates were WB tested ; 20 and 5 , respectively , were confirmed positive . Most youth reported moderate brief stress after disclosure ; 22 % reported longer and more severe distress . Boys were more likely to be in the latter category . Self-reported virginity was highly inconsistent with WB-confirmed positives . CONCLUSIONS The higher than manufacturer 's cut-off for Kalon ELISA modestly reduced the rate of false-positive test results , but also increased false negatives . Investigators should consider the risk : benefit ratio in deciding whether or not to disclose HSV-2 results to adolescent participants under specific field conditions . TRIAL REGISTRATION NUMBER NCT01501864 .

western blot

moderate brief stress after disclosure

longer and more severe distress

Self-reported virginity

WB-confirmed positives

false-positive test results

false negatives

adolescent

HIV

adolescent

adolescent

youth

adolescent participants


Gluten and casein supplementation does not increase symptoms in children with autism spectrum disorder . AIM A gluten- and casein-free diet is often given to children with autism spectrum disorder ( ASD ) . We aimed to determine the effect of gluten and casein supplementation on maladaptive behaviour , gastrointestinal symptom severity and intestinal fatty acids binding protein ( I-FABP ) excretion in children with ASD . METHODS A randomised , controlled , double-blind trial was performed on 74 children with ASD with severe maladaptive behaviour and increased urinary I-FABP . Subjects were randomised to receive gluten-casein or a placebo for seven days . We evaluated maladaptive behaviour before and after supplementation , using I-FABP excretion , the approach withdrawal problem composite subtest of the Pervasive Developmental Disorder Behavior Inventory and the Gastrointestinal Symptom Severity Index . RESULTS The mean approach withdrawal problem composite score was significantly higher before supplementation than after , both in the placebo and in the gluten-casein group . However , the mean difference was not significant and may have been caused by additional therapy . There was no significant difference in gastrointestinal symptoms and urinary I-FABP excretion . CONCLUSION Administrating gluten-casein to children with ASD for one week did not increase maladaptive behaviour , gastrointestinal symptom severity or urinary I-FABP excretion . The effect of prolonged administration or other mechanisms of enterocyte damage in ASD should be explored .

Gluten and casein supplementation

gluten- and casein-free diet

gluten-casein

placebo

gluten-casein

gluten-casein

children

autism spectrum disorder

children

maladaptive behaviour

urinary I-FABP


A controlled trial of the SibworkS group program for siblings of children with special needs . Siblings of children with a disability are an at risk group for emotional and behavioral problems . This study evaluated an intervention to promote the emotional and behavioral functioning of siblings of children with disabilities and chronic health conditions . SibworkS is a six-week manual-based , cognitive-behavioral group support program focussed on strengthening siblings ' perceived social support , self-esteem , problem-solving skills , adaptive coping behaviors and positive sibling relationships . Fifty-six children aged 7-12 were allocated to either the SibworkS program ( n=30 ) or waitlist control ( n=26 ) in alternating sequence . The primary outcome was siblings ' emotional and behavioral functioning . Additional outcomes were self-esteem , perceived social support , the sibling relationship and coping behaviors . Siblings were followed-up immediately after the intervention and at 3-months . Siblings participating in the SibworkS intervention were reported to have fewer emotional and behavioral difficulties than siblings in the control group immediately following the intervention and at the 3-month follow-up . Participation in SibworkS was associated with fewer emotional and behavioral difficulties for siblings . Implications for practice and future research include recommendations for improving program participation .

SibworkS group program

SibworkS

SibworkS program

waitlist control

SibworkS

SibworkS

emotional and behavioral functioning .

emotional and behavioral difficulties

special needs

children

disability

Fifty-six

aged 7-12


Replacing Non-Active Video Gaming by Active Video Gaming to Prevent Excessive Weight Gain in Adolescents . OBJECTIVE The aim of the current study was to evaluate the effects of and adherence to an active video game promotion intervention on anthropometrics , sedentary screen time and consumption of sugar-sweetened beverages and snacks among non-active video gaming adolescents who primarily were of healthy weight . METHODS We assigned 270 gaming ( i.e . ≥ 2 hours/week non-active video game time ) adolescents randomly to an intervention group ( n = 140 ) ( receiving active video games and encouragement to play ) or a waiting-list control group ( n = 130 ) . BMI-SDS ( SDS = adjusted for mean standard deviation score ) , waist circumference-SDS , hip circumference and sum of skinfolds were measured at baseline , at four and ten months follow-up ( primary outcomes ) . Sedentary screen time , physical activity , consumption of sugar-sweetened beverages and snacks , and process measures ( not at baseline ) were assessed with self-reports at baseline , one , four and ten months follow-up . Multi-level-intention to treat-regression analyses were conducted . RESULTS The control group decreased significantly more than the intervention group on BMI-SDS ( β = 0.074 , 95 % CI : 0.008 ; 0.14 ) , and sum of skinfolds ( β = 3.22 , 95 % CI : 0.27 ; 6.17 ) ( overall effects ) . The intervention group had a significantly higher decrease in self-reported non-active video game time ( β = -1.76 , 95 % CI : -3.20 ; -0.32 ) and total sedentary screen time ( Exp ( β = 0.81 , 95 % CI : 0.74 ; 0.88 ) than the control group ( overall effects ) . The process evaluation showed that 14 % of the adolescents played the Move video games every week ≥ 1 hour/week during the whole intervention period . CONCLUSIONS The active video game intervention did not result in lower values on anthropometrics in a group of 'excessive ' non-active video gamers ( mean ~ 14 hours/week ) who primarily were of healthy weight compared to a control group throughout a ten-month-period . Even some effects in the unexpected direction were found , with the control group showing lower BMI-SDS and skin folds than the intervention group . The intervention did result in less self-reported sedentary screen time , although these results are likely biased by social desirability . TRIAL REGISTRATION Dutch Trial Register NTR3228 .

non-active video gaming

BMI-SDS

BMI-SDS

and sum of skinfolds

Excessive Weight Gain

Adolescents .

adolescents

adolescents

n = 140

showed that 14 % of the adolescents


Physical exercise at the workplace reduces perceived physical exertion during healthcare work : cluster randomized controlled trial . BACKGROUND High physical exertion during work is a risk factor for musculoskeletal pain and long-term sickness absence . Physical exertion ( RPE ) reflects the balance between physical work demands and physical capacity of the individual . Thus , increasing the physical capacity through physical exercise may decrease physical exertion during work . This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work ( WRPE ) among healthcare workers . METHODS 200 female healthcare workers ( age : 42.0 , body mass index : 24.1 , average pain intensity : 3.1 on a scale of 0 to 10 , average WRPE : 3.6 on a scale of 0 to 10 ) from 18 departments at three participating hospitals . Participants were randomly allocated at the cluster level to 10 weeks of : ( 1 ) workplace physical exercise ( WORK ) performed in groups during working hours for 5×10 minutes per week and up to five group-based coaching sessions on motivation for regular physical exercise , or ( 2 ) home-based physical exercise ( HOME ) performed during leisure time for 5×10 minutes per week . Physical exertion was assessed at baseline and at 10-week follow-up . RESULTS 2.2 ( SD : 1.1 ) and 1.0 ( SD : 1.2 ) training sessions were performed per week in WORK and HOME , respectively . Physical exertion was reduced more in WORK than HOME ( p < 0.01 ) . Between-group differences in physical exertion at follow-up ( WORK vs. HOME ) was -0.5 points ( 95 % CI -0.8 to -0.2 ) . Within-group effect size ( Cohen 's d ) in WORK and HOME was 0.43 and 0.13 , respectively . CONCLUSIONS Physical exercise performed at the workplace appears more effective than home-based exercise in reducing physical exertion during daily work tasks in healthcare workers .

Physical exercise at the workplace

High physical exertion

female

age : 42.0


Optimal vaccination program for healthy adults in China . There is still no suitable routine hepatitis B immunization strategy for adults in China . To establish an optimal vaccination schedule for healthy adults , we investigated various schedules in healthy adults . In this randomized 5143 healthy adults received 10 μg hepatitis B vaccine at 0 , 1 and 3 months ( group A ) , 0 , 1 and 6 months ( group B ) , or 0 , 1 and 12 months ( group C ) . Blood samples were collected after 1 month and 12 months after the third dose . The geometric mean titer ( GMT ) , seroconversion rate ( levels of anti-HBs ≥ 10 mIU/mL ) and high response rate ( levels of anti-HBs ≥ 100 mIU/mL ) were assayed . In our study , 2438 healthy adults finished the full vaccination program and follow-up . The seroconversion/sero-protective rate of groups A-C at one and 12 month after administration of the third vaccine dose was 100 % , 99.9 % and 97.9 % verse 64.9 % , 75.7 % and 79.0 % , respectively . GMT for anti-HBs tested in group A to C within 1 or 12 month after the third vaccination was 213.16 , 432.58 and 451.47 mIU/ml verse 22.07 , 46.70 and 56.18 mIU/ml , respectively . There were significant differences of seroconversion/sero-protective rate and GMT among the 3 groups ( p < 0.01 ) . Given the high anti-HBs seroconversion rate and GMT in all 3 groups , a flexible schedule for Hepatitis B vaccine should be recommended to adults , but 0-1-12 schedule is a better choice .

Optimal vaccination

hepatitis B immunization

optimal vaccination schedule

Optimal vaccination

optimal vaccination schedule

Blood samples

The seroconversion/sero-protective

respectively

GMT for anti-HBs

high anti-HBs seroconversion rate and

healthy

adults

adults

healthy

adults

healthy

adults

adults


Transcranial Magnetic Stimulation to Address Mild Cognitive Impairment in the Elderly : A Randomized Controlled Study . Transcranial magnetic stimulation ( TMS ) is a noninvasive brain stimulation technique with potential to improve memory . Mild cognitive impairment ( MCI ) , which still lacks a specific therapy , is a clinical syndrome associated with increased risk of dementia . This study aims to assess the effects of high-frequency repetitive TMS ( HF rTMS ) on everyday memory of the elderly with MCI . We conducted a double-blinded randomized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) . Thirty-four elderly outpatients meeting Petersen 's MCI criteria were randomly assigned to receive 10 sessions of either active TMS or sham , 10 Hz rTMS at 110 % of motor threshold , 2,000 pulses per session . Neuropsychological assessment at baseline , after the last session ( 10th ) and at one-month follow-up , was applied . ANOVA on the primary efficacy measure , the Rivermead Behavioural Memory Test , revealed a significant group-by-time interaction ( p = 0.05 ) , favoring the active group . The improvement was kept after one month . Other neuropsychological tests were heterogeneous . rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions . These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration .

Transcranial Magnetic Stimulation

rTMS

the Rivermead Behavioural Memory Test

rTMS at 10 Hz enhanced everyday memory

Mild Cognitive Impairment

Mild cognitive impairment ( MCI )

MCI

Thirty-four

elderly

MCI

elderly


1H Magnetic Resonance Spectroscopy Predicts Hepatocellular Carcinoma in a Subset of Patients With Liver Cirrhosis : A Randomized Trial . The goal of this study was to investigate the utility of H magnetic resonance spectroscopy ( H-MRS ) to quantify the differences in liver metabolites . Magnetic resonance spectroscopy was used as a means of predicting the probability of developing hepatocellular carcinoma ( HCC ) in patients with liver cirrhosis secondary to chronic hepatitis B.This study included 20 healthy volunteers , 20 patients with liver cirrhosis secondary to chronic hepatitis B ( cirrhosis group ) , and 20 patients with small HCC secondary to cirrhosis liver parenchyma ( HCC group ) . All patients underwent routine MRI and H-MRS scanning . LCModel software was used to quantify Cho ( Choline ) , Lip ( lipid ) , and Cho/Lip in the 3 groups , and a one-way ANOVA was used to compare the differences in these metabolites between groups.Choline levels were significantly different between the control and HCC group and between the cirrhosis group and the HCC group ( all P < 0.001 ) . There was also a significant difference in Lip levels between the control and cirrhosis group and the control and HCC groups ( all P < 0.001 ) . There were also differences in Cho/Lip between the control and cirrhosis groups , the control and HCC groups , and the cirrhosis and HCC groups ( all P < 0.001 ) .H-MRS followed by the analysis with LCModel can be used to measure changes in hepatic metabolite levels in patients with liver cirrhosis secondary to chronic hepatitis B and HCC . Thus , H-MRS may be helpful in monitoring HCC and liver cirrhosis development .

routine MRI and H-MRS scanning

quantify Cho ( Choline )

Lip ( lipid )

Cho/Lip

ANOVA

significant difference in Lip levels

differences in

measure changes in hepatic metabolite


Eltrombopag dose predictors in thrombocytopenic subjects with hepatitis C virus infection . This study aims to identify patient characteristics that predict effective eltrombopag dosage for the treatment of Hepatitis C virus ( HCV ) -related thrombocytopenia . Demographic , clinical and genetic data collected from thrombocytopenic patients ( n = 1463 , age ≥ 18 years ) with chronic HCV infection who were able to achieve a target platelet count of > 90 × 10 ( 9 ) /L following eltrombopag treatment . Patients were categorized into four groups ( 25 , 50 , 75 , and 100 mg ) based on the eltrombopag dose needed to achieve the target platelet count . Eltrombopag dose predictors were identified using a two stage approach . First , bivariate analysis , using anova for continuous variables and Chi-square test for categorical variables , was performed to identify possible predictors of eltrombopag dose ( P < 0.05 ) . Second , ordinal logistic regression with stepwise addition followed by backward deletion was then performed using predictors identified in bivariate analysis step to produce final model containing independent predictors at P < 0.05 . Ordinal logistic model identified several predictors of eltrombopag dose . Predictors of higher eltrombopag dose include : having a HCV genotype 2 or 3 , being Central/South Asian , being White ( Caucasian or European heritage ) , increased weight , and increased spleen length . Predictors of lower eltrombopag dose include : female gender , increased age , having a higher ALP plasma concentration , increased creatinine clearance , increased baseline lymphocytes count , and increased baseline platelet count . In conclusion , this study identified patient characteristics that predict effective eltrombopag dose for the treatment of HCV-related thrombocytopenia . Early selection of the optimal eltrombopag dose expedites the initiation of antiviral therapy . This is expected to improve the antiviral therapy outcome before the patient progress into liver decompensation .

thrombocytopenic

n = 1463

age ≥ 18 years

HCV infection


Brief Report : Cobicistat Compared With Ritonavir as a Pharmacoenhancer for Atazanavir in Combination With Emtricitabine/Tenofovir Disoproxil Fumarate : Week 144 Results . BACKGROUND Cobicistat ( COBI ) is a pharmacoenhancer with no antiretroviral activity . METHODS International , randomized double-blind active-controlled trial to evaluate the efficacy and safety of COBI vs ritonavir ( RTV ) as a pharmacoenhancer of atazanavir in combination with emtricitabine/tenofovir disoproxil fumarate in HIV treatment-naive patients followed through week 144 . RESULTS At Week 144 , virologic suppression was achieved in 72 % ( COBI ) and 74 % ( RTV ) of patients . Adverse events leading to study drug discontinuation occurred in 11 % of patients in each group . Median changes in serum creatinine ( mg/dL ) were +0.13 ( COBI ) and +0.07 ( RTV ) and were unchanged from week 48 . CONCLUSIONS Once-daily COBI is a safe and effective pharmacoenhancer of the protease inhibitor atazanavir .

Cobicistat

Ritonavir

Atazanavir

Cobicistat

COBI

ritonavir ( RTV )

COBI

RTV

COBI

efficacy and safety

virologic suppression

Adverse events

changes in serum creatinine

HIV treatment-naive patients


A Double-Blind Placebo-Controlled Study of the Effects of Olprinone , a Specific Phosphodiesterase III Inhibitor , for Preventing Postoperative Atrial Fibrillation in Patients Undergoing Pulmonary Resection for Lung Cancer . BACKGROUND We previously reported that patients with elevated preoperative B-type natriuretic peptide ( BNP ) levels have an increased risk for postoperative atrial fibrillation following lung cancer surgery . The present study evaluated whether the specific phosphodiesterase III inhibitor olprinone can reduce the incidence of postoperative atrial fibrillation in patients with elevated BNP levels undergoing pulmonary resection for lung cancer . METHODS A prospective randomized study was conducted with 40 patients who had elevated preoperative BNP levels ( ≥ 30 pg/mL ) and underwent scheduled lung cancer surgery . All patients were in sinus rhythm at surgery . Low-dose olprinone or placebo was continuously infused for 24 h and started just before anesthesia induction . The primary end point was the incidence of postoperative atrial fibrillation . The secondary end points were perioperative hemodynamics and levels of BNP , WBC counts , and C-reactive protein . RESULTS The incidence of postoperative atrial fibrillation was significantly lower in the olprinone group than in the placebo group ( 10 % vs 60 % , P < .001 ) . Patients in the olprinone group showed significantly lower BNP , WBC counts , and C-reactive protein levels after surgery . CONCLUSIONS Continuous infusion of olprinone during lung cancer surgery was safe and reduced the incidence of postoperative atrial fibrillation following pulmonary resection in patients with elevated preoperative BNP levels . TRIAL REGISTRY Japan Primary Registries Network ; No . : JPRN-UMIN2404 ; URL : http : //www.umin.ac.jp/ctr/ .

Placebo-Controlled

Olprinone

olprinone


Multiorgan protection of remote ischemic perconditioning in valve replacement surgery . BACKGROUND Remote ischemic perconditioning ( RIPerc ) is a new alternative of remote ischemic conditioning and has not been well studied . RIPerc attenuates myocardial injury when applied during cardiac surgery . However , its protective effects on other organs remain unknown . MATERIALS AND METHODS Patients with rheumatic heart disease undergoing valve replacement surgery were randomized into the RIPerc group ( n = 101 ) or the control group ( n = 100 ) . RIPerc was achieved by three cycles of 5-min ischemia-5-min reperfusion in the right thigh during surgery . Clinical data and the levels of injury biomarkers for the heart , lungs , liver , and kidneys within 48 h after surgery were compared using one-way or repeated measurement analysis of variance . RESULTS In the RIPerc group , the release of serum cardiac troponin I ( 128.68 ± 102.56 versus 172.33 ± 184.38 , P = 0.04 ) and the inotropic score ( 96.4 ± 73.8 versus 121.5 ± 89.6 , P = 0.032 ) decreased compared with that of the control ; postoperative drainage ( 458.2 ± 264.2 versus 545.1 ± 349.0 ml , P = 0.048 ) and the incidence of acute lung injury was reduced ( 36.6 % versus 51 % , P = 0.04 ) , and the extent of hyperbilirubinemia was also attenuated . No significant difference was observed in the levels of biomarkers for renal injury and systemic inflammation response . CONCLUSIONS RIPerc applied during the valve replacement surgery induced multiple beneficial effects postoperatively including reduced drainage and myocardial damage , lower incidence of acute lung injury , and attenuated hyperbilirubinemia .

remote ischemic perconditioning

RIPerc

control

surgery . Clinical data

the release of serum cardiac troponin

P = 0.04 )

the inotropic

that of the control ; postoperative

545.1 ± 349.0 ml , P = 0.048 )

the incidence

P = 0.04 )

valve replacement surgery .


A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone : Effects on aberrant behavior in children with autism . To assess the safety and efficacy of pioglitazone added to risperidone in the treatment of irritability in autistic disorder ( AD ) , we conducted this study . In a 10-week , randomized , double-blind , parallel-group , placebo-controlled clinical trial , 44 outpatients of both genders aged 4-12 years with a diagnosis of AD and a score of ≥12 on the Aberrant Behavior Checklist-Community ( ABC-C ) irritability subscale were included . Mean change of ABC-C irritability subscale score as primary outcome , change in other ABC-C subscale scores and partial and complete responses were compared between two groups . Twenty patients completed the trial in each group . Level of reduction and effect of time×treatment interaction in the treatment group were significant for irritability ( P=0.03 ) , lethargy/social withdrawal ( P=0.04 ) and hyperactivity/non-compliance ( P=0.03 ) but not for stereotypic behavior and inappropriate speech subscales compared with the placebo group . Vomiting and headache were the most frequent reported side-effects . Results of this preliminary study indicate positive effects of pioglitazone compared with placebo in improving the behavioral symptoms of AD .

placebo-controlled

pioglitazone

pioglitazone added to risperidone

placebo-controlled

safety and efficacy

and hyperactivity/non-compliance

Vomiting and headache

the behavioral symptoms of

children

autism

autistic disorder ( AD )

both genders

4-12 years

AD

Twenty patients


Fixed-dose combination of AR-13324 and latanoprost : a double-masked , 28-day , randomised , controlled study in patients with open-angle glaucoma or ocular hypertension . BACKGROUND/AIMS To evaluate the ocular hypotensive efficacy of fixed-dose combinations of the Rho kinase inhibitor and norepinephrine transport inhibitor AR-13324 ( 0.01 % and 0.02 % ) and latanoprost ( PG324 Ophthalmic Solution ) relative to the active components AR-13324 0.02 % and latanoprost 0.005 % , used bilaterally at night . METHODS This was a double-masked , randomised , parallel comparison study in patients with open-angle glaucoma or ocular hypertension . After washout , patients were randomised to one of four treatment arms and treated for 28 days . The primary efficacy variable was mean diurnal intraocular pressure ( IOP ) at day 29 . RESULTS We randomised 298 patients , of whom 292 ( 98 % ) completed the study . Mean unmedicated diurnal IOPs ( study eye ) was 25.1 , 25.1 , 26.0 and 25.4 in the PG324 0.01 % , PG324 0.02 % , latanoprost and AR-13324 0.02 % groups , respectively . On day 29 , mean diurnal IOP decreased to 17.3 , 16.5 , 18.4 and 19.1 mm Hg , respectively . For the primary efficacy variable of mean diurnal IOP at day 29 , PG324 0.02 % met the criterion for statistical superiority relative to both latanoprost and AR-13324 0.02 % ( p < 0.0001 ) , providing additional IOP lowering of 1.9 and 2.6 mm Hg , respectively . PG324 0.01 % also met the criterion for superiority . The most frequently reported adverse event was conjunctival hyperaemia with an incidence of 41 % ( 30/73 ) , 40 % ( 29/73 ) , 14 % ( 10/73 ) and 40 % ( 31/78 ) in the PG324 0.01 % , PG324 0.02 % , latanoprost and AR-13324 0.02 % groups , respectively . CONCLUSIONS In this short-term study , the fixed-dose combination of AR-13324 0.02 % and latanoprost 0.005 % in PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations . The only safety finding of note was transient asymptomatic conjunctival hyperaemia which was typically of mild severity . TRIAL REGISTRATION NUMBER NCT02207491 .

AR-13324 and latanoprost

latanoprost

efficacy

Mean unmedicated diurnal IOPs

mean diurnal IOP

mean diurnal

conjunctival hyperaemia

298 patients


Radiofrequency thermocoagulation combined with pulsed radiofrequency helps relieve postoperative complications of trigeminal neuralgia . Trigeminal neuralgia is a sudden , severe condition characterized by stabbing and recurrent pain . Radiofrequency thermocoagulation ( RFT ) and pulsed radiofrequency ( PRF ) are common surgical interventions used to treat trigeminal neuralgia . This study aimed to investigate the therapeutic effects and associated complications of a combination of RFT and PRF in the treatment of trigeminal neuralgia . Computed tomography-guided percutaneous RFT of the Gasserian ganglion was performed on 80 patients with trigeminal neuralgia . Patients were randomly assigned to either group A ( RFT at 70°C ) or group B ( RFT at 75°C ) . Patients in each group were divided into 2 subgroups , receiving percutaneous RFT ( 240 s ) with or without PRF ( 42°C , 2 Hz , 240 s ) . Six months later , pain relief and complication status were evaluated . There was no significant difference in visual analogue scores among groups with RFT at 70° or 75°C , with or without PRF . Data showed that facial numbness and postoperative masticatory muscle weakness recovered more rapidly in patients receiving combined RFT and PRF treatment . Decreased corneal reflex was relieved to a significantly greater extent in groups receiving PRF than those without . Thus , compared to the use of RFT at 75°C alone , the combination of PRF and RFT helped eliminate postoperative complications , such as facial numbness , masticatory muscle weakness , and decreased corneal reflex , indicating that it could be useful for surgically treating trigeminal neuralgia .

pain relief

visual analogue scores

Decreased corneal reflex

trigeminal neuralgia