Dietary docosahexaenoic acid supplementation in children with autism . OBJECTIVE The aim of the study was to determine whether docosahexaenoic acid ( DHA ) supplementation improves the behavior of children with autism . METHODS A group of 3- to 10-year-old children with autism were randomized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months . The parents and the investigator completed the Clinical Global Impressions-Improvement scale to rate changes in core symptoms of autism after 3 and 6 months . The parents completed the Child Development Inventory and the Aberrant Behavior Checklist , and both parents and teachers completed the Behavior Assessment Scale for Children ( BASC ) at enrollment and after 6 months . RESULTS A total of 48 children ( 40 [ 83 % ] boys , mean age [ standard deviation ] 6.1 [ 2.0 ] years ) were enrolled ; 24 received DHA and 24 placebo . Despite a median 431 % increase in total plasma DHA levels after 6 months , the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I . Based on the analysis of covariance models adjusted for the baseline rating scores , parents ( but not teachers ) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group ( P = 0.04 ) , and teachers ( but not parents ) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group ( P = 0.02 ) . CONCLUSIONS Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism . Our results may have been limited by inadequate sample size .

DHA

placebo

DHA

placebo

DHA

DHA

DHA

DHA

behavior

total plasma DHA levels

rating of social skills on the BASC

autism

children with autism

3- to 10-year-old children with

48 children


Does an in-season detraining period affect the shoulder rotator cuff strength and balance of young swimmers ? Imbalance in shoulder rotator muscles is a well-documented problem in swimmers , and it is important to implement land-based strength training programs . Meanwhile , the effects of a detraining period on swimmers ' shoulder rotator muscles are unknown . The purpose of this study was to analyze the effects of a strength training program and detraining on the strength and balance of shoulder rotator cuff muscles in young swimmers , despite the continuity of usual water training . An experimental group ( n = 20 ) and a control group ( n = 20 ) of young male swimmers with the same characteristics ( age , body mass , height , training volume , and maturational state ) were evaluated . In both groups , the peak torques of shoulder internal ( IR ) and external ( ER ) rotators were assessed during preseason , midseason ( 16 weeks ) , and postseason ( 32 weeks ) . The experimental group underwent a strength training regimen from baseline to 16 weeks and a detraining period from 16 to 32 weeks . Concentric action at 60°·s-1 and 180°·s-1 was measured using an isokinetic dynamometer . The ER/IR strength ratios were obtained . At 60°·s-1 , there were significant increments in IR strength and the ER/IR ratio in both shoulders . This trend was the same throughout the competitive season . The tendency was the same at 180°·s-1 because training effects were noted primarily in IR and ER/IR ratios . Moreover , the absence of land-based strength training , from 16 to 32 weeks , revealed a reduction in the ER/IR ratio values in both shoulders . Our findings suggest that young swimmers ' coaches should use dry-land strength training protocols , and that it is recommended that these should be conducted on a regular basis ( during the whole season ) .

in-season detraining

strength training regimen

detraining

ER/IR strength ratios

IR strength

ER/IR

ER/IR ratio

young

young

( n = 20

young

male


A randomized controlled trial of nonlinear frequency compression versus conventional processing in hearing aids : speech and language of children at three years of age . OBJECTIVE To determine the effect of nonlinear frequency compression ( NLFC ) on children 's development of speech and language at three years of age . DESIGN A randomized controlled trial was conducted as part of the population-based longitudinal study on outcomes of children with hearing impairment ( LOCHI ) . Participants were randomly assigned to fitting with NLFC ( Phonak Naida V SP or UP ) or with conventional processing in hearing aids , prescribed by using either the NAL or the DSL formula . Standardized tests of speech production , receptive and expressive language were administered , and parent ratings were collected . All assessments were double-blinded . STUDY SAMPLE Participants were 44 of the 450 children in the LOCHI cohort . RESULTS Compared to children using conventional processing , receptive and expressive language was higher but receptive vocabulary and consonant articulation scores were lower for children who use NLFC . There was increased substitution of affricates by fricatives for children using NLFC , compared to children using conventional amplification . After allowing for the effect of multiple demographic variables , the difference in global language scores between groups was not significant ( effect : 0.8 [ 95 % confidence interval : - 6.7 , 8.3 ] ) . CONCLUSIONS There is insufficient evidence to indicate a difference in language ability between children using NLFC and those using conventional amplification .

nonlinear frequency compression

conventional processing in hearing aids

NLFC ( Phonak Naida V SP or UP )

conventional processing in hearing aids

NAL

DSL

conventional processing

NLFC

NLFC

conventional amplification

NLFC

conventional amplification

receptive and expressive language

global language scores

language ability

children at three years of age .


Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity : a randomized trial . IMPORTANCE Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders ( ASD ) to understand communication content with conflicting verbal and nonverbal information . Despite growing prospects for oxytocin as a therapeutic agent for ASD , no direct neurobiological evidence exists for oxytocin 's beneficial effects on this core symptom of ASD . This is slowing clinical application of the neuropeptide . OBJECTIVE To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures . DESIGN , SETTING , AND PARTICIPANTS At the University of Tokyo Hospital , we conducted a randomized , double-blind , placebo-controlled , within-subject-crossover , single-site experimental trial in which intranasal oxytocin and placebo were administered . A total of 40 highly functioning men with ASD participated and were randomized in the trial . INTERVENTIONS Single-dose intranasal administration of oxytocin ( 24 IU ) and placebo . MAIN OUTCOMES AND MEASURES Using functional magnetic resonance imaging , we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task . In our previous case-control study using the same psychological task , when making decisions about social information with conflicting verbal and nonverbal contents , participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex . Therefore , our main outcomes and measures were the frequency of the nonverbal information-based judgments ( NVJs ) , the response time for NVJs , and brain activity of the medial prefrontal cortex during NVJs . RESULTS Intranasal oxytocin enabled the participants to make NVJs more frequently ( P = .03 ) with shorter response time ( P = .02 ) . During the mitigated behavior , oxytocin increased the originally diminished brain activity in the medial prefrontal cortex ( P < .001 ) . Moreover , oxytocin enhanced functional coordination in the area ( P < .001 ) , and the magnitude of these neural effects was predictive of the behavioral effects ( P ≤ .01 ) . CONCLUSIONS AND RELEVANCE These findings provide the first neurobiological evidence for oxytocin 's beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide . TRIAL REGISTRATION umin.ac.jp/ctr Identifier : UMIN000002241 and UMIN000004393 .

oxytocin-induced

oxytocin

oxytocin 's

oxytocin

placebo-controlled

oxytocin

placebo

oxytocin ( 24 IU )

placebo

oxytocin

oxytocin

effects of oxytocin

behavioral neural responses

) , the

response time for NVJs

, and

NVJs

autism

total of 40

men


12-week , placebo-controlled trial of add-on riluzole in the treatment of childhood-onset obsessive-compulsive disorder . Many children with childhood-onset obsessive-compulsive disorder ( OCD ) fail to respond adequately to standard therapies . Evidence from preclinical and clinical studies suggests that the glutamatergic neurotransmitter system might be an alternative treatment target . This study examined the efficacy of riluzole , a glutamatergic modulator , as an adjunctive therapy for children with treatment-resistant OCD . In a 12-week , double-blind , placebo-controlled study , 60 treatment-resistant children and adolescents ( mean age=14.5 ± 2.4 years ) , with moderate to severe OCD ( mean Children 's Yale-Brown Obsessive-Compulsive Scale ( CY-BOCS ) =28.2 ± 3.7 ) , 17 of whom also had concomitant autism spectrum disorder , were randomized to receive riluzole ( final dose of 100 mg/day ) or placebo in addition to the existing treatment regimen . Fifty-nine subjects completed the randomized trial . Primary outcome measures were changes on the CY-BOCS , the Clinical Global Impressions Scale , and the Children 's Global Assessment Scale . Riluzole was fairly well tolerated , although it was associated with one case of pancreatitis and five instances of slight increases in transaminases . All subjects showed significant reductions in CY-BOCS scores during treatment ; however , there was no significant difference between placebo and riluzole on any of the primary or secondary outcome measures . The study failed to demonstrate superiority of riluzole over placebo as an adjunctive treatment for children with childhood-onset OCD . However , future studies may show benefits for less treatment-refractory children with fewer concomitant medications .

placebo-controlled

riluzole

riluzole

placebo-controlled

riluzole

placebo

children

children

with treatment-resistant OCD .

60 treatment-resistant

children

adolescents

mean age=14.5 ± 2.4 years

concomitant autism spectrum disorder

Fifty-nine

children

childhood-onset OCD

concomitant medications


Similar MPA exposure on modified release and regular tacrolimus . Concomitant immunosuppression may affect the mycophenolate mofetil exposure . Astellas developed a once-daily modified release formulation of tacrolimus ( TacMR ) with the potential to reduce the likelihood of nonadherence . It is unknown whether mycophenolic acid ( MPA ) area under the concentration-time curve ( AUC ) differs between the 2 tacrolimus ( Tac ) formulations . In a 2-by-2 crossover design , 20 stable renal transplant recipients on twice-daily Tac either continued their usual Tac therapy ( n = 10 , group 1 ) or switched to TacMR for a 12-week period ( n = 10 , group 2 ) , after which the patients crossed over to the other formulation for another 12-week period . Pharmacokinetic profiles using limited sampling strategies were obtained before randomization ( visit 1 ) , and at 12 ( visit 2 ) and 24 weeks ( visit 3 ) at steady state . MPA AUC was calculated using the Pawinski formula . When analyzing visits on Tac , TacMR , and back on Tac combined , the MPA AUC for all 20 patients at baseline was 42.24 ( 16.98 ) , 37.18 ( 13.75 ) , and 40.09 ( 16.69 ) mg·h·L ( -1 ) , respectively , which was not statistically significant using repeated measures ( P = 0.1327 , R ( 2 ) = 0.1109 ) . We conclude that MPA pharmacokinetic profiles are not altered when converting patients from Tac to TacMR .

tacrolimus

mycophenolic acid ( MPA )

Tac therapy

or switched to TacMR for

Tac

TacMR

Tac

MPA AUC

regular tacrolimus .

renal transplant recipients


Households with young children and use of freely distributed bednets in rural Madagascar . BACKGROUND Malaria infections are the leading cause of death for children in Madagascar . Insecticide-treated bednets offer effective prevention , but it is unclear how well free bednet distribution programs reach young children . METHODS We conducted a secondary analysis of a free bednet distribution program in Madagascar from 2007-2008 . Interviews were performed at baseline and 6 months . Principal components analysis was used to construct a wealth and malaria knowledge index . Coverage efficiency was calculated as coverage of children per bednet owned . Univariable and multivariable regressions were used to determine predictors of bednet use . RESULTS Bednet use , among the 560 households in the study , increased from 6 to 91 % after 6 months . Coverage efficiency increased from 1.29 to 1.56 children covered per bednet owned . In multivariable analysis , having a child under 5 years of age was the only variable associated with bednet use ( OR 9.10 ; p=0.001 ) , yielding a 99 % likelihood of using a bednet ( 95 % CI 96.4 to 99.9 % ) versus 82 % ( 95 % CI 72.2 to 88.4 % ) in households without young children . CONCLUSION This free bednet distribution program achieved high levels of adherence after 6 months . Household presence of children was associated with bednet use , but not household income or education , suggesting that distribution to priority groups may help overcome traditional barriers to adoption in some settings .

bednets

Insecticide-treated bednets

free bednet distribution programs

free bednet distribution program

Interviews

coverage of children per bednet owned

bednet

free bednet distribution program

Bednet use

Coverage efficiency

young children

children

young children

under 5 years


Effects of water extracts of Graptopetalum paraguayense on blood pressure , fasting glucose , and lipid profiles of subjects with metabolic syndrome . This study was aimed to investigate the effects of water extracts of Graptopetalum paraguayense ( WGP , 4 g/d ) on blood pressure , blood glucose level , and lipid profiles in subjects with metabolic syndrome ( MS ) . Participants with MS ( n = 54 ) were randomly assigned to the placebo ( n = 28 ) and WGP groups ( n = 26 ) , and the intervention was administered for 12 weeks . Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , fasting glucose ( FG ) , lipid profiles ( total cholesterol ( TC ) , triglyceride ( TG ) , low density lipoprotein cholesterol ( LDL-C ) , and high density lipoprotein ( HDL-C ) ) , and antioxidant enzymes activities ( catalase ( CAT ) , superoxide dismutase ( SOD ) , and glutathione peroxidase ( GPx ) ) were measured . Forty-two subjects completed the study ( placebo , n = 19 ; WGP , n = 23 ) . FG , SBP , and LDL-C levels were significantly lower and HDL-C level and antioxidant enzymes activities ( CAT and SOD ) were significantly higher after WGP supplementation . Blood pressure , FG , and lipid profiles were significantly correlated with antioxidant enzymes activities after supplementation ( P < 0.05 ) . The present study demonstrated a significant reduction in blood pressure , blood glucose , and lipid profiles and an increase in antioxidant enzymes activities in subjects with MS after WGP supplementation . Taken together , the antioxidative capacity of WGP might exert a beneficial effect on MS . This trial is registered with ClinicalTrials.gov NCT01463748 .

placebo

WGP

placebo

WGP

WGP

WGP

blood pressure

fasting glucose

lipid profiles

blood pressure

blood glucose level

lipid profiles

Systolic blood pressure ( SBP )

lipid profiles

total cholesterol ( TC )

triglyceride ( TG )

high density lipoprotein ( HDL-C )

antioxidant enzymes

FG

SBP

LDL-C levels

HDL-C level

antioxidant enzymes activities

Blood pressure

FG

lipid profiles

blood pressure

blood glucose

lipid profiles

antioxidant enzymes activities

subjects with metabolic syndrome

n = 54

Forty-two subjects

n = 19

n = 23

subjects with MS


Evaluating the acceptability and efficacy of a psycho-educational intervention for coping and symptom management by children with cancer : a randomized controlled study . AIMS To evaluate the acceptability and efficacy of a psycho-educational intervention designed to improve effective coping and reduce symptom severity in children with cancer . BACKGROUND Cancer treatments increase survival rates and also cause physical and psychological effects on children with cancer . A psycho-educational intervention is used to assist children and adolescents with these effects and its efficacy has been described in several studies . DESIGN A randomized controlled trial . METHODS Participants being treated were recruited and randomly assigned to two groups from September 2011-February 2013 in Taiwan . The intervention group received a psycho-educational intervention in addition to standard care , while the control group received only standard care . Each participant was assessed using a paediatric cancer coping scale and perceived symptom severity was evaluated at three time points ( baseline , 1 month and 3 months ) . A repeated-measures analysis of variance was used to estimate the effects of intervention . Qualitative findings were analysed using content analysis . RESULTS No significant difference in coping scores was found between groups , but the experimental group reported significantly lower scores in gastrointestinal problems and pain . Most symptoms decreased significantly over time in both groups , except for gastrointestinal problems . The scores in pain , bone marrow suppression and body image showed significant interaction effects between groups on changes over time . Qualitative results reported that participants evaluated the intervention positively , especially about receipt of psychological support and learnt coping skills . CONCLUSIONS The psycho-educational intervention administered was acceptable for children with cancer and was found to reduce gastrointestinal problems and pain .

psycho-educational intervention

psycho-educational intervention

psycho-educational intervention

control group received

only standard care

psycho-educational intervention

gastrointestinal problems

pain

pain

bone marrow suppression and body image

children

cancer

children

cancer

cancer

children and adolescents

children

cancer


Effect of camel milk on thymus and activation-regulated chemokine in autistic children : double-blind study . BACKGROUND This study aimed to investigate the role of the effectiveness of camel milk ( CM ) ( raw and boiled ) on thymus and activation-regulated chemokine ( TARC ) serum levels and childhood autism rating scale ( CARS ) score in subjects with autism and compared to placebo group ( cow milk ) . METHODS Forty-five subjects diagnosed with autism were randomly assigned to receive boiled CM for group I ( n = 15 ) , raw CM for group II ( n = 15 ) , and placebo for group III ( n = 15 ) for 2 wk . Measures included changes in professionally completed CARS score and blood samples for TARC serum level were taken before and after milk consumption of 500 ml per day in children 's regular daily diet . RESULTS The serum levels of TARC decreased significantly ( P = 0.004 ) in boiled CM and in raw CM group ( P = 0.01 ) too , but no effect was observed ( P = 0.68 ) in placebo group . Furthermore , significant improvements were observed in CARS score ( P = 0.04 ) in raw CM group only . There were no significant relationships between the serum of TARC level and the CARS score , age , or gender for any group . CONCLUSION CM administered for 2 wk significantly improved clinical measurements of autism severity and decreased serum level of TARC in autistic children , but subsequent studies are recommended .

camel milk

camel milk ( CM ) ( raw and boiled )

placebo group ( cow milk )

boiled CM for group I

raw CM for group II

placebo for group III

CARS score

CARS score

CARS score

autistic

children

childhood

autism

autism

Forty-five

autism


Design and methods of a double blind randomized placebo-controlled trial of extended-release naltrexone for alcohol dependent and hazardous drinking prisoners with HIV who are transitioning to the community . BACKGROUND HIV-infected prisoners have a high prevalence of alcohol use disorders and commonly relapse to alcohol soon after release to the community which is linked to high morbidity , poor antiretroviral therapy ( ART ) adherence and increased sexual risk-taking behaviors . Extended-release naltrexone ( XR-NTX ) effectively reduces relapse to alcohol in alcohol dependent persons , yet it remains unexamined among criminal justice system ( CJS ) populations transitioning to the community . METHODS A randomized double-blind , placebo-controlled trial of XR-NTX to improve HIV treatment outcomes via reducing relapse to alcohol use after prison release for HIV-infected hazardous drinking and alcohol dependent prisoners is discussed . RESULTS Acceptability of study participation is high with 86 % of those referred who met eligibility criteria and 85 % of those who were able to receive injections prior to release accepted injections , yet important implementation issues are identified and addressed during the study and are discussed in this paper . CONCLUSION Medication-assisted therapies for prevention of relapse to alcohol use for CJS populations transitioning to the community , especially for HIV-infected patients , are urgently needed in order to reduce alcohol relapse after release and improve HIV treatment outcomes and contribute to improved individual and public health .

placebo-controlled

extended-release naltrexone

Extended-release naltrexone ( XR-NTX )

placebo-controlled

XR-NTX

relapse to alcohol

relapse to alcohol

relapse to alcohol

Acceptability

alcohol relapse

HIV treatment outcomes

individual and public health .

alcohol dependent

hazardous drinking prisoners

HIV

transitioning to the community

HIV-infected prisoners

alcohol dependent prisoners

HIV-infected


Weight and lean body mass change with antiretroviral initiation and impact on bone mineral density . OBJECTIVE To compare the effect that initiating different antiretroviral therapy ( ART ) regimens has on weight , BMI , and lean body mass ( LBM ) and explore how changes in body composition are associated with bone mineral density ( BMD ) . METHODS A5224s was a sub-study of A5202 , a prospective trial of 1857 ART-naive participants randomized to blinded abacavir-lamivudine ( ABC/3TC ) or tenofovir DF-emtricitabine ( TDF/FTC ) with open-label efavirenz ( EFV ) or atazanavir-ritonavir ( ATV/r ) . All participants underwent dual-energy absorptiometry ( DXA ) and abdominal computed tomography for body composition . Analyses used two-sample t-tests and linear regression . RESULTS A5224s included 269 participants : 85 % men , 47 % white non-Hispanic , median age 38 years , HIV-1 RNA 4.6 log10 copies/ml , and CD4 cell count 233 cells/μl . Overall , significant gains occurred in weight , BMI , and LBM at 96 weeks post-randomization ( all P < 0.001 ) . Assignment to ATV/r ( vs. EFV ) resulted in significantly greater weight ( mean difference 3.35 kg ) and BMI gain ( 0.88 kg/m ; both P=0.02 ) , but not LBM ( 0.67 kg ; P=0.15 ) , whereas ABC/3TC and TDF/FTC were not significantly different ( P≥0.10 ) . In multivariable analysis , only lower baseline CD4 cell count and higher HIV-1 RNA were associated with greater increase in weight , BMI , or LBM . In multivariable analyses , increased LBM was associated with an increased hip BMD . CONCLUSION ABC/3TC vs. TDF/FTC did not differ in change in weight , BMI , or LBM ; ATV/r vs. EFV resulted in greater weight and BMI gain but not LBM . A positive association between increased LBM and increased hip BMD should be further investigated through prospective interventional studies to verify the impact of increased LBM on hip BMD .

antiretroviral initiation

antiretroviral therapy ( ART )

abacavir-lamivudine ( ABC/3TC )

tenofovir DF-emtricitabine ( TDF/FTC )

atazanavir-ritonavir ( ATV/r )

dual-energy absorptiometry ( DXA )

ATV/r

CD4 cell count

higher HIV-1 RNA

hip BMD

weight

antiretroviral initiation


Whole-body CT screening : scan delay and contrast injection duration for optimal enhancement of abdominal organs and deep vessels . PURPOSE To assess the optimal scan delays and contrast injection durations for contrast-enhanced whole-body computed tomography ( CT ) . MATERIALS AND METHODS One hundred forty-two patients were randomized into three groups : protocol A-scan delay of 65 s after starting contrast injection over 30 s ; protocol B-105 and 70 s ; and protocol C-145 and 110 s , respectively . Contrast enhancement and diagnostic acceptability were assessed . RESULTS Qualitative assessment was subtle among the three protocols . Homogenous enhancement of deep veins was more assuredly achieved with protocol C. CONCLUSION With protocol C , qualitatively acceptable enhancement can be obtained in whole-body CT .

Whole-body CT screening

scan delay

contrast injection

A-scan delay of 65 s

B-105 and 70 s

C-145 and 110 s

protocol C

whole-body CT

Qualitative assessment

Homogenous enhancement of deep veins

One hundred forty-two patients


Addressing dental fear in children with autism spectrum disorders : a randomized controlled pilot study using electronic screen media . BACKGROUND Dental care is a significant unmet health care need for children with autism spectrum disorders ( ASD ) . Many children with ASD do not receive dental care because of fear associated with dental procedures ; oftentimes they require general anesthesia for regular dental procedures , placing them at risk of associated complications . Many children with ASD have a strong preference for visual stimuli , particularly electronic screen media . The use of visual teaching materials is a fundamental principle in designing educational programs for children with ASD . PURPOSE To determine if an innovative strategy using 2 types of electronic screen media was feasible and beneficial in reducing fear and uncooperative behaviors in children with ASD undergoing dental visits . METHODS We conducted a randomized controlled trial at Boston Children 's Hospital dental clinic . Eighty ( 80 ) children aged 7 to 17 years with a known diagnosis of ASD and history of dental fear were enrolled in the study . Each child completed 2 preventive dental visits that were scheduled 6 months apart ( visit 1 and visit 2 ) . After visit 1 , subjects were randomly assigned to 1 of 4 groups : ( 1 ) group A , control ( usual care ) ; ( 2 ) group B , treatment ( video peer modeling that involved watching a DVD recording of a typically developing child undergoing a dental visit ) ; ( 3 ) group C , treatment ( video goggles that involved watching a favorite movie during the dental visit using sunglass-style video eyewear ) ; and ( 4 ) group D , treatment ( video peer modeling plus video goggles ) . Subjects who refused or were unable to wear the goggles watched the movie using a handheld portable DVD player . During both visits , the subject 's level of anxiety and behavior were measured using the Venham Anxiety and Behavior Scales . Analyses of variance and Fisher 's exact tests compared baseline characteristics across groups . Using intention to treat approach , repeated measures analyses were employed to test whether the outcomes differed significantly : ( 1 ) between visits 1 and 2 within each group and ( 2 ) between each intervention group and the control group over time ( an interaction ) . RESULTS Between visits 1 and 2 , mean anxiety and behavior scores decreased significantly by 0.8 points ( P = .03 ) for subjects within groups C and D. Significant changes were not observed within groups A and B . Mean anxiety and behavior scores did not differ significantly between groups over time , although group A versus C pairwise comparisons showed a trend toward significance ( P = .06 ) . CONCLUSION These findings suggest that certain electronic screen media technologies may be useful tools for reducing fear and uncooperative behaviors among children with ASD undergoing dental visits . Further studies are needed to assess the efficacy of these strategies using larger sample sizes . Findings from future studies could be relevant for nondental providers who care for children with ASD in other medical settings .

electronic screen media

electronic screen media

control ( usual care )

treatment (

video peer modeling plus video goggles

mean anxiety and behavior scores

Mean anxiety and behavior scores

autism spectrum disorders ( ASD )

children

ASD

ASD

ASD

Eighty ( 80 )

aged 7 to 17 years

ASD

ASD


Population pharmacokinetic/pharmacodynamic analysis of the DPP-4 inhibitor linagliptin in Japanese patients with type 2 diabetes mellitus . OBJECTIVES Linagliptin is a novel , highly selective and long acting DPP-4 inhibitor for the treatment of type 2 diabetes mellitus ( T2DM ) . Linagliptin exhibits non-linear pharmacokinetics ( PK ) due to saturable binding to plasma and tissue DPP-4 . The aim of this study was to characterize the PK and PK/DPP-4 inhibition relationship of linagliptin in Japanese patients with T2DM using a population PK/DPP-4 model and to support the rationale for the therapeutic dose in Japanese patients by simulation . METHODS Linagliptin plasma concentration and DPP-4 inhibition measurements from a placebo-controlled , parallel group multiple ( 28 days ) dose trial that included 36 T2DM patients ( 18 patients each in 2.5 mg and 10 mg dose group ) were used for analysis . Modeling was performed using FOCE INTERACTION estimation method implemented in NONMEM V. The linagliptin plasma concentration- and DPP-4 inhibition- time profiles were simulated for Japanese patients receiving 5 mg linagliptin once daily by the model established . RESULTS Nonlinear PK of linagliptin in T2DM patients were well described by a 2-compartment model assuming concentration-dependent binding to DPP-4 in the central and peripheral compartment . Plasma DPP-4 inhibition was integrated in the model by relating the model-predicted DPP-4 occupancy with linagliptin linearly to DPP-4 inhibition . The simulation predicted that for the 5 mg dose group the trough DPP-4 inhibition at steady-state was 84.2 % , which is higher than the target inhibition ( ≥80 % ) for an effective dose of DPP-4 inhibitor . In 2.5 mg dose group , steady-state DPP-4 inhibition of > 80 % was not maintained over 24 hours ( observed and simulated ) . CONCLUSIONS The nonlinear PK of linagliptin and its plasma DPP-4 inhibition in patients were well characterized by a target-mediated drug disposition model relating DPP-4 occupancy with linagliptin to DPP-4 inhibition . Simulations of plasma DPP-4 inhibition suggest that 5 mg linagliptin once daily is an appropriate therapeutic dose for Japanese patients with T2DM .

Linagliptin

Linagliptin

linagliptin

Linagliptin

placebo-controlled

linagliptin

linagliptin

Plasma DPP-4 inhibition

DPP-4 inhibition

with type 2 diabetes mellitus


Utilization patterns of conventional and complementary/alternative treatments in children with autism spectrum disorders and developmental disabilities in a population-based study . OBJECTIVE To compare the utilization of conventional treatments and utilization of complementary and alternative medicine in preschoolers with autism spectrum disorders ( ASD ) and other developmental disabilities ( DD ) . METHODS Participants were 578 children who were part of an ongoing population-based , case-control study of 2- to 5-year olds with ASD , DD , and the general population . Parents completed an interview on past and current services . RESULTS Four hundred fifty-three children with ASD and 125 DD children were included . ASD families received more hours of conventional services compared with DD families ( 17.8 vs 11 ; p < .001 ) . The use of psychotropic medications was low in both groups ( approximately 3 % ) . Overall , complementary and alternative medicine ( CAM ) use was not significantly different in ASD ( 39 % ) versus DD ( 30 % ) . Hispanic families in both groups used CAM less often than non-Hispanic families . Variables such as level of function , immunization status , and the presence of an identified neurogenetic disorder were not predictive of CAM use . A higher level of parental education was associated with an increased CAM use in ASD and DD . Families who used > 20 hours per week of conventional services were more likely to use CAM , including potentially unsafe or disproven CAM . Underimmunized children were marginally more likely to use CAM but not more likely to have received potentially unsafe or disproven CAM . CONCLUSION Use of CAM is common in families of young children with neurodevelopmental disorders , and it is predicted by higher parental education and non-Hispanic ethnicity but not developmental characteristics . Further research should address how health care providers can support families in making decisions about CAM use .

conventional

complementary/alternative treatments

conventional treatments

complementary and alternative medicine

conventional services

CAM

CAM

CAM

conventional services

CAM

CAM

CAM

CAM

CAM

CAM

conventional services

CAM

level of parental education

CAM

children

autism

preschoolers

children

2- to 5-year olds

Four hundred fifty-three

children

children

young children


A phase II , randomized , multicenter study evaluating the combination of lapatinib and vinorelbine in women with ErbB2 overexpressing metastatic breast cancer . Lapatinib is approved in combination with capecitabine for treatment of patients with human epidermal growth factor receptor 2 ( HER2 ) -positive metastatic breast cancer ( MBC ) who have progressed on prior trastuzumab in the metastatic setting . Vinorelbine is an important chemotherapy option for MBC . We evaluated efficacy and safety of lapatinib plus vinorelbine , compared with lapatinib plus capecitabine , in women with HER2-positive MBC . In this open-label , multicenter , phase II study , eligible patients ( N = 112 ) were randomized 2:1 to lapatinib plus vinorelbine [ ( N = 75 ) 1,250 mg orally once daily ( QD ) continuously plus 20 mg/m ( 2 ) /day intravenously ] or lapatinib plus capecitabine [ ( N = 37 ) 1,250 mg orally QD continuously plus 2,000 mg/m ( 2 ) /day orally , 2 doses ] . The primary endpoint was progression-free survival ( PFS ) . Other endpoints included overall survival ( OS ) and safety . Patients progressing within the study were given the option of crossover to the other treatment arm ; time to second progression was an exploratory endpoint . Patient demographics , stratification , and prognostic factors were well balanced between treatments . Median PFS in both arms was 6.2 months [ 95 % confidence interval ( CI ) 4.2 , 8.8 ( lapatinib plus vinorelbine ) ; 4.4 , 8.3 ( lapatinib plus capecitabine ) ] . Median OS on lapatinib plus vinorelbine was 24.3 months ( 95 % CI 16.4 , NE ) and 19.4 months ( 95 % CI 16.4 , 27.2 ) on lapatinib plus capecitabine . In total , 42 patients opted to cross over ; median PFS was 3.2 months ( 95 % CI 1.7 , 5.1 ) on lapatinib plus vinorelbine and 4.0 months ( 95 % CI 2.1 , 5.8 ) on lapatinib plus capecitabine . Lapatinib plus vinorelbine offers an effective treatment option for patients with HER2-overexpressing MBC , having displayed comparable efficacy and tolerability rates to lapatinib plus capecitabine .

lapatinib plus vinorelbine

lapatinib plus capecitabine

progression-free survival ( PFS )

overall survival ( OS ) and safety

Patient demographics

stratification

prognostic factors

Median PFS

Median OS

women


Changes in body weight and blood pressure : paradoxical outcome events in overweight and obese subjects with cardiovascular disease . BACKGROUND/OBJECTIVES The Sibutramine Cardiovascular OUTcomes ( SCOUT ) trial showed a significantly increased relative risk of nonfatal cardiovascular events , but not mortality , in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise . We examined the relationship between early changes ( both increases and decreases ) in body weight and blood pressure , and the impact of these changes on subsequent cardiovascular outcome events . SUBJECTS/METHODS A total of 9804 male and female subjects , aged 55 years or older , with a body mass index of 27-45 kg m ( -2 ) were included in this current subanalysis of the SCOUT trial . Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor ( hypertension , dyslipidemia , current smoking or diabetic nephropathy ) to assess cardiovascular outcomes . Post hoc subgroup analyses of weight change ( categories ) and blood pressure were performed overall and by treatment group ( 6-week sibutramine followed by randomized placebo or continued sibutramine ) . The primary outcome event ( POE ) was a composite of nonfatal myocardial infarction , nonfatal stroke , resuscitated cardiac arrest or cardiovascular death . Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment , subgroups and interactions . RESULTS During the initial 6-week sibutramine treatment period , systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects ( -8.1±10.5 mm Hg with < 5 kg weight loss to -10.8±11.0 mm Hg with ⩾5 kg weight loss ) . The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure . However , with long-term sibutramine treatment , a markedly lower blood pressure tended to increase POEs . CONCLUSION Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events , as expected . However , the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population .

body weight

blood pressure

nonfatal cardiovascular events

mortality

body weight

blood pressure

cardiovascular outcome events .

analyses of weight change

and blood pressure

systolic blood pressure

weight loss

weight loss ) .

weight

pressure

loss

weight loss

blood

male

female

aged 55 years or older

cardiovascular disease

type 2 diabetes mellitus

hypertension

dyslipidemia


A randomized controlled trial of the Korean version of the PEERS ( ® ) parent-assisted social skills training program for teens with ASD . Impaired social functioning is a hallmark feature of autism spectrum disorder ( ASD ) , often requiring treatment throughout the life span . PEERS ( ® ) ( Program for the Education and Enrichment of Relational Skills ) is a parent-assisted social skills training for teens with ASD . Although PEERS ( ® ) has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America , the efficacy of this treatment has yet to be established in cross-cultural validation trials . The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS ( ® ) for enhancing social skills through a randomized controlled trial ( RCT ) .The English version of the PEERS ( ® ) Treatment Manual ( Laugeson & Frankel , 2010 ) was translated into Korean and reviewed by 21 child mental health professionals . Items identified as culturally sensitive were surveyed by 447 middle school students , and material was modified accordingly . Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient ( IQ ) ≥ 65 . Eligible teens were randomly assigned to a treatment group ( TG ) or delayed treatment control group ( CG ) . Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD . Secondary outcome measures included scales for depressive symptoms , anxiety , and other behavioral problems . Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS ( ® ) treatment . Independent samples t-tests revealed no significant differences at baseline across the TG and CG conditions with regard to age ( 14.04 ± 1.64 and 13.54 ± 1.50 years ) , IQ ( 99.39 ± 18.09 & 100.67 ± 16.97 ) , parental education , socioeconomic status , or ASD symptoms ( p < 0.05 ) , respectively . Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule , interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale ( p 's < 0.01 ) , social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge-Revised ( p < 0.01 ) , and decreased depressive symptoms on the Child Depression Inventory following treatment ( p < 0.05 ) . Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables ( p < 0.05 ) . Despite cultural and linguistic differences , the PEERS ( ® ) social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment . In an RCT , participants receiving the PEERS ( ® ) treatment showed significant improvement in social skills knowledge , interpersonal skills , and play/leisure skills , as well as a decrease in depressive symptoms and ASD symptoms . This study represents one of only a few cross-cultural validation trials of an established evidence-based treatment for adolescents with ASD .

Korean version of the PEERS ( ® )

of a Korean version of PEERS ( ® )

the PEERS ( ® )

( TG )

or

delayed treatment control


Evaluating intervention using time aids in children with disabilities . OBJECTIVE The aim of this study was to evaluate complex intervention using time aids for children with intellectual and developmental disabilities who exhibit limitations in daily time management . METHODS Participating children ( n = 47 ) ( F17/M30 ) were aged 6-11 with ADHD , autism spectrum disorders , mild or moderate intellectual disability , spina bifida , and cerebral palsy . This study used a Randomized Block and Waiting List control group design , with 25 children allocated to control and 22 to intervention group . In total 10 children ( 21.3 % ) , five from each group , dropped out , leaving 37 children in the data analysis . RESULTS Children in both groups gained significantly in time-processing ability between the first and second data collection , but the children in the intervention group improved time-processing ability significantly more than controls . The control group also displayed significant changes after receiving intervention between the second and third data collection . The intervention had a large effect ( ES Cohen 's d = 0.81 ) on time-processing ability and a medium effect ( ES Cohen 's d = 0.68 ) on managing one 's time . CONCLUSIONS This study provides preliminary evidence that time-processing ability and managing one 's time can be improved by intervention using time aids in children with intellectual and developmental disabilities , supporting the need to consider time aids in intervention in these children .

time aids

complex intervention using time aids

control

intervention

time-processing ability

time-processing ability

time-processing ability

managing one 's time .

time-processing ability

managing one 's time

children

disabilities

children

children

aged 6-11

10 children

five


The effect of recent bereavement on outcomes in a primary care depression intervention study . OBJECTIVES Although bereavement and depression are both common in older primary care patients , the effect of bereavement on depression intervention outcomes is unknown . We examined whether standard interventions for depression in primary care were as effective for bereaved as for non-bereaved depressed patients . DESIGN Randomized controlled trial . SETTING Twenty community-based primary care practices in New York City , greater Philadelphia , and Pittsburgh . Randomization to either intervention or usual care occurred by practice . PARTICIPANTS Patients aged 60 years or older who met criteria for major depression or clinically significant minor depression ( N = 599 ) . Patients who did not complete the bereavement measure or who were missing 4-month data were excluded ( final N = 417 ) . INTERVENTION Study-trained depression care managers offered guideline-concordant recommendations to primary care physicians at intervention sites and assisted patients with treatment adherence . Patients who did not wish to take antidepressants could receive interpersonal psychotherapy . MEASUREMENTS Bereavement was captured using the Louisville Older Persons Events Schedule . Depression severity was assessed using the 24-item Hamilton Depression Rating Scale ( HDRS ) . Outcomes at 4 months were remission ( HDRS ≤7 ) and response ( HDRS reduction ≥50 % from baseline ) . RESULTS Logistic regressions indicated that , for non-bereaved participants , response and remission were higher in intervention than usual care . However , recently bereaved older adults were less likely to achieve response or remission at 4 months if treated in the intervention condition . CONCLUSIONS Standard depression care management appears to be ineffective among recently bereaved older primary care patients . Greater attention should be paid in primary care to emotional distress in the context of bereavement .

standard interventions

intervention

usual care occurred by practice

primary care depression

depression

Depression severity

aged 60 years or older

major depression

clinically significant minor depression

N = 599


A comparison of the effectiveness of treating those with and without the complications of superficial venous insufficiency . OBJECTIVE To test the hypothesis that patients with soft tissue changes related to superficial venous insufficiency ( SVI ) have greater benefits from treatment than those with only symptomatic varicose veins . BACKGROUND A commonly held view is that SVI is only a minor ailment , yet randomized clinical trials ( RCTs ) show that treatment improves quality of life ( QoL ) and is cost-effective . In an effort to curb the treatment costs of this common disorder , rationing is applied in many health care systems , often limiting the reimbursement of treatment to those with soft tissue changes . METHODS This cohort study draws its data from an interventional RCT . After informed consent , consecutive patients with symptomatic unilateral SVI were randomized to receive surgical ligation and stripping or endovenous laser ablation . This analysis differentially studies the outcomes of patients with simple varicose veins ( C2 : n = 191 ) and soft tissue complications ( C3-4 : n = 76 ) . Effectiveness outcomes measured up to 1 year included the following : Qol [ short form 36 ( SF36 ) , EuroQol , and the Aberdeen Varicose Veins Questionnaire ] , clinical recurrence , and the need for secondary procedures . Multivariable regression analysis was used to control for potential confounding factors . RESULTS Both groups saw significant improvements in QoL . All improvements were equal between groups apart from the SF36 domain of Bodily Pain , where C2 saw an improvement of 12.8 [ 95 % confidence interval ( CI ) : 4.8-20.8 ] points over C3-4 participants ( P = 0.002 ) , who also suffered more recurrence [ odds ratio ( OR ) = 2.7 , 95 % CI : 1.2-6.1 , P = 0.022 ] and required more secondary procedures ( OR = 4.4 , 95 % CI : 1.2-16.3 , P = 0.028 ) . CONCLUSIONS This study suggests that rationing by clinical severity contradicts the evidence . Delaying treatment until the development of skin damage leads to a degree of irreversible morbidity and greater recurrence . TRIAL REGISTRATION NCT00759434 Clinicaltrials.gov .

interventional RCT .

receive surgical ligation

stripping or endovenous laser ablation

superficial venous insufficiency

quality of life ( QoL )

QoL .

Bodily


Multisensory temporal integration in autism spectrum disorders . The new DSM-5 diagnostic criteria for autism spectrum disorders ( ASDs ) include sensory disturbances in addition to the well-established language , communication , and social deficits . One sensory disturbance seen in ASD is an impaired ability to integrate multisensory information into a unified percept . This may arise from an underlying impairment in which individuals with ASD have difficulty perceiving the temporal relationship between cross-modal inputs , an important cue for multisensory integration . Such impairments in multisensory processing may cascade into higher-level deficits , impairing day-to-day functioning on tasks , such as speech perception . To investigate multisensory temporal processing deficits in ASD and their links to speech processing , the current study mapped performance on a number of multisensory temporal tasks ( with both simple and complex stimuli ) onto the ability of individuals with ASD to perceptually bind audiovisual speech signals . High-functioning children with ASD were compared with a group of typically developing children . Performance on the multisensory temporal tasks varied with stimulus complexity for both groups ; less precise temporal processing was observed with increasing stimulus complexity . Notably , individuals with ASD showed a speech-specific deficit in multisensory temporal processing . Most importantly , the strength of perceptual binding of audiovisual speech observed in individuals with ASD was strongly related to their low-level multisensory temporal processing abilities . Collectively , the results represent the first to illustrate links between multisensory temporal function and speech processing in ASD , strongly suggesting that deficits in low-level sensory processing may cascade into higher-order domains , such as language and communication .

Multisensory temporal integration

multisensory temporal tasks

temporal processing

language and communication

autism spectrum disorders

ASD

ASD

High-functioning

children

ASD

ASD


Goodstart : a cluster randomised effectiveness trial of an integrated , community-based package for maternal and newborn care , with prevention of mother-to-child transmission of HIV in a South African township . BACKGROUND Progress towards MDG4 for child survival in South Africa requires effective prevention of mother-to-child transmission ( PMTCT ) of HIV including increasing exclusive breastfeeding , as well as a new focus on reducing neonatal deaths . This necessitates increased focus on the pregnancy and early post-natal periods , developing and scaling up appropriate models of community-based care , especially to reach the peri-urban poor . METHODS We used a randomised controlled trial with 30 clusters ( 15 in each arm ) to evaluate an integrated , scalable package providing two pregnancy visits and five post-natal home visits delivered by community health workers in Umlazi , Durban , South Africa . Primary outcomes were exclusive and appropriate infant feeding at 12 weeks post-natally and HIV-free infant survival . RESULTS At 12 weeks of infant age , the intervention was effective in almost doubling the rate of exclusive breastfeeding ( risk ratio 1.92 ; 95 % CI : 1.59-2.33 ) and increasing infant weight and length-for-age z-scores ( weight difference 0.09 ; 95 % CI : 0.00-0.18 , length difference 0.11 ; 95 % CI : 0.03-0.19 ) . No difference was seen between study arms in HIV-free survival . Women in the intervention arm were also more likely to take their infant to the clinic within the first week of life ( risk ratio 1.10 ; 95 % CI : 1.04-1.18 ) . CONCLUSIONS The trial coincided with national scale up of ARVs for PMTCT , and this could have diluted the effect of the intervention on HIV-free survival . We have demonstrated that implementation of a pro-poor integrated PMTCT and maternal , neonatal and child health home visiting model is feasible and effective . This trial could inform national primary healthcare reengineering strategies in favour of home visits . The dose effect on exclusive breastfeeding is notable as improving exclusive breastfeeding has been resistant to change in other studies targeting urban poor families .

effectiveness

HIV-free infant survival

rate of exclusive breastfeeding

HIV-free survival

HIV-free survival

peri-urban poor

12 weeks of infant age


Early psychosocial intervention in Alzheimer 's disease : cost utility evaluation alongside the Danish Alzheimer 's Intervention Study ( DAISY ) . OBJECTIVE To assess the cost utility of early psychosocial intervention for patients with Alzheimer 's disease and their primary caregivers . DESIGN Cost utility evaluation alongside a multicentre , randomised controlled trial with 3 years of follow-up . SETTING Primary care and memory clinics in five Danish districts . PARTICIPANTS 330 community-dwelling patients and their primary caregivers . INTERVENTION Psychosocial counselling and support lasting 8-12 months after diagnosis and follow-up at 3 , 6 , 12 and 36 months in the intervention group or follow-up only in the control group . MAIN OUTCOME MEASURES The primary outcome measure was the cost of additional quality-adjusted life years ( QALYs ) . Costs were measured from a societal perspective , including the costs of healthcare , social care , informal care and production loss . QALYs were estimated separately for the patient and the caregiver before aggregation for the main analysis . RESULTS None of the observed cost and QALY measures were significantly different between the intervention and control groups , although a tendency was noted for psychosocial care leading to cost increases with informal care that was not outweighed by the tendency for cost savings with formal care . The probability of psychosocial intervention being cost-effective did not exceed 36 % for any threshold value . The alternative scenario analysis showed that the probability of cost-effectiveness increased over the range of threshold values used if the cost perspective was restricted to formal healthcare . CONCLUSIONS A multifaceted , psychosocial intervention programme was found unlikely to be cost-effective from a societal perspective . The recommendation for practice in settings that are similar to the Danish setting is to provide follow-up with referral to available local support programmes when needed , and to restrict large multifaceted intervention programmes to patients and caregivers with special needs until further evidence for cost-effectiveness emerges . TRIAL REGISTRATION The study was registered in the Clinical Trial Database as ISRCTN74848736 .

cost utility evaluation

cost utility

Cost utility

Psychosocial counselling and support

follow-up

control group

control groups

costs of healthcare

social care

informal care

production loss

QALYs

cost

QALY measures

cost-effective

cost-effective

Alzheimer 's disease :


No gains in efficacy observed by adding gemcitabine to adjuvant therapy for lymph node-positive breast cancer .

gemcitabine to adjuvant therapy

efficacy

lymph node-positive breast cancer


[ Rehabilitation of the patients presenting with combined pathology : dyscirculatory encephalopathy and climacteric syndrome ] . The present paper reports the data on rehabilitation of women presenting with combined pathology : dyscirculatory encephalopathy and climacteric syndrome . It is shown that the introduction of ozonotherapy and klimadynon , a herbal medicine possessed of the estrogen-like action , into combined rehabilitative treatment ensures the significant improvement of the parameters of interest , such as climacteric symptoms , short-term memory , lipid profile , endothelial function , cerebral circulation , and quality of life .

ozonotherapy

klimadynon


Phosphorylated p-70S6K predicts tamoxifen resistance in postmenopausal breast cancer patients randomized between adjuvant tamoxifen versus no systemic treatment . INTRODUCTION Activation of the phosphatidylinositol-3-kinase ( PI3K ) and/or mitogen-activated protein kinase ( MAPK ) pathways results in anti-estrogen resistance in vitro , but a biomarker with clinical validity to predict intrinsic resistance has not been identified . In metastatic breast cancer patients with previous exposure to endocrine therapy , the addition of a mammalian target of rapamycine ( mTOR ) inhibitor has been shown to be beneficial . Whether or not patients on adjuvant endocrine treatment might benefit from these drugs is currently unclear . A biomarker that predicts intrinsic resistance could potentially be used as companion diagnostic in this setting . We tested the clinical validity of different downstream-activated proteins in the PI3K and/or MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary breast cancer patients . METHODS We recollected primary tumor tissue from patients who participated in a randomized trial of adjuvant tamoxifen ( 1-3 years ) versus observation . After constructing a tissue micro-array , cores from 563 estrogen receptor α positive were immunostained for p-AKT ( Thr308 ) , p-AKT ( Ser473 ) , p-mTOR , p-p706SK and p-ERK1/2 . Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interactions between these markers and tamoxifen treatment efficacy . RESULTS Interactions were identified between tamoxifen and p-AKT ( Thr308 ) , p-mTOR , p-p70S6K and p-ERK1/2 . Applying a conservative level of significance , p-p70S6K remained significantly associated with tamoxifen resistance . Patients with p-p70S6K negative tumors derived significant benefit from tamoxifen ( HR 0.24 , P < 0.0001 ) , while patients whose tumor did express p-p70S6K did not ( HR = 1.02 , P =0.95 ) , P for interaction 0.004 . In systemically untreated breast cancer patients , p-p70S6K was associated with a decreased risk for recurrence . CONCLUSIONS Patients whose tumor expresses p-p70S6K , as a marker of downstream PI3K and/or MAPK pathway activation , have a favorable prognosis , but do not benefit from adjuvant tamoxifen . A potential benefit from inhibitors of the PI3K/Akt/mTOR pathway in these patients needs to be further explored .

Phosphorylated p-70S6K

tamoxifen

tamoxifen

no systemic treatment .

phosphatidylinositol-3-kinase ( PI3K )

rapamycine ( mTOR )

adjuvant endocrine treatment

tamoxifen

adjuvant tamoxifen ( 1-3 years

observation

tissue micro-array

tamoxifen resistance

anti-estrogen resistance

intrinsic tamoxifen resistance

assess hazard ratios

with tamoxifen resistance

decreased risk for recurrence

postmenopausal breast cancer patients

primary tumor tissue

tumor


Assessment of osteopontin in early breast cancer : correlative study in a randomised clinical trial . INTRODUCTION Osteopontin ( OPN ) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness . In metastatic breast cancer , we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis . METHODS We measured OPN in plasma by ELISA , and in tumors by immunohistochemistry , in 624 ( 94 % ) and 462 ( 69 % ) , respectively , of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/- octreotide in a randomized trial ( NCIC CTG MA.14 ; National Cancer Institute of Canada Clinical Trials Group Mammary.14 ) . RESULTS Plasma OPN was measured in 2,540 samples ; 688 at baseline and 1,852 collected during follow-up . Mean baseline plasma OPN was 46 ng/ml ( range 22.6 to 290 ) which did not differ from normal levels . Mean percentage OPN tumor cell positivity was 33.9 ( 95 % CI : 30.2 to 37.9 ) . There was no correlation between plasma and tumor OPN values . In multivariate analysis , neither was associated with event-free survival ( EFS ) , relapse-free survival ( RFS ) , overall survival ( OS ) , bone RFS or non-bone RFS . An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml ( 23.9 to 543 ) in the recurrence period compared with baseline levels . CONCLUSIONS The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population . Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients . However , our finding of elevated mean OPN plasma level around the time of recurrence warrants further study . TRIAL REGISTRATION NCT00002864 , http : //clinicaltrials.gov/show/NCT00002864 .

Osteopontin

OPN

immunohistochemistry

surgery

tamoxifen +/- octreotide

Plasma OPN

Mean baseline plasma OPN

between plasma and tumor OPN values

that OPN tumor expression

population

Plasma OPN levels

elevated mean OPN plasma level

early breast cancer :

624 ( 94 % )

postmenopausal

women

breast cancer

2,540 samples

women

early breast cancer


Improved frontoparietal white matter integrity in overweight children is associated with attendance at an after-school exercise program . Aerobic fitness is associated with white matter integrity ( WMI ) in adults as measured by diffusion tensor imaging ( DTI ) . This study examined the effect of an 8-month exercise intervention on WMI in children . Participants were 18 sedentary , overweight ( BMI≥85th percentile ) 8- to 11-year-old children ( 94 % Black ) , randomly assigned to either an aerobic exercise ( n=10 ) or sedentary attention control group ( n=8 ) . Each group was offered an instructor-led after-school program every school day for approximately 8 months . Before and after the program , all subjects participated in DTI scans . Tractography was conducted to isolate the superior longitudinal fasciculus and investigate whether the exercise intervention affected WMI in this region . There was no group by time interaction for WMI in the superior longitudinal fasciculus . There was a group by time by attendance interaction , however , such that higher attendance at the exercise intervention , but not the control intervention , was associated with increased WMI . Heart rate and the total dose of exercise correlated with WMI changes in the exercise group . In the overall sample , increased WMI was associated with improved scores on a measure of attention and improved teacher ratings of executive function . This study indicates that participating in an exercise intervention improves WMI in children as compared to a sedentary after-school program .

after-school exercise program

exercise intervention

frontoparietal white matter integrity

white matter integrity ( WMI )

diffusion tensor imaging ( DTI )

WMI

overweight

children


A randomized pilot study with daily walking during adjuvant chemotherapy for patients with breast and colorectal cancer . BACKGROUND Physical activity during chemotherapy has been shown in several studies to reduce fatigue , improve symptoms and impact positively on health-related quality of life ( HRQoL ) . Challenges associated with intervention studies on physical activity during cancer treatment relate to consistent adherence . The primary objective was to study feasibility and adherence of physical activity intervention among patients with cancer during adjuvant chemotherapy treatment . The secondary objective was to investigate the effects of physical activity on health aspects , including HRQoL , symptoms and surrogate markers for cardiovascular disease . MATERIAL AND METHODS This randomized controlled trial included patients with breast cancer ( BRCA ) and colorectal cancer ( CRC ) during adjuvant chemotherapy . The intervention continued for 10 weeks and included daily walks of 10 000 steps and a weekly supervised group walk . Adherence was assessed by a pedometer and the number of participants who reported step counts every week and percentage of participants who achieved the target steps every week . RESULTS Adherence average reached 91 % during the intervention period ; in total 74 % completed the exercise intervention . The majority of the participants achieved an average of 83 % of the target of 10 000 steps per day for 10 weeks . There was a significant increase in daily physical activity ( p = 0.016 ) in the intervention group . Significant differences were also found for some breast cancer-specific symptoms [ swelling , mobility and pain ( p = 0.045 ) ] . The study showed a relatively small weight gain an average of 0.9 kg in the intervention group and 1.3 kg in the control group . CONCLUSION Physical activity in the form of walking is feasible during adjuvant chemotherapy treatment despite increasing symptoms . The physical activity increased in the intervention group during the study time and had a positive impact on breast symptoms and the weight gain was lower in comparison to previous studies .

daily walking

Physical activity

physical activity

physical activity intervention

physical activity

adjuvant chemotherapy

daily walks

exercise

daily physical activity

control group

Physical activity

physical activity

health aspects

Adherence

Adherence

daily physical activity

[ swelling

mobility

pain

small weight gain

breast symptoms

weight gain


Deslorelin implants in pre-pubertal female dogs : short- and long-term effects on the genital tract . Deslorelin acetate is a GnRH agonist used for contraception in dogs . This study aimed to evaluate the treatment of pre-pubertal female dogs with deslorelin acetate implants , to better investigate the primary stimulatory effect of the drug and the long-term effects on the genital tract , throughout repeated treatments . Sicilian hound female dogs ( 24 ) were randomly assigned to treated group , control group 1 and control group 2 . First group bitches were implanted at 4.5 , 9.0 and 13.5 months and monitored clinically , ultrasonographically and endocrinologically , throughout the study period ( 13.5 months ) . Control group 1 bitches were not implanted and clinically monitored for the same period . At 18 months , the animals underwent ovariohysterectomy , thus allowing evaluation of the internal genitalia . Control group 2 bitches were ovariohysterectomized at the age of 4.5 months . The suppression of oestrus was obtained in the treated group despite the fact that the first implant caused a modest increase in plasmatic levels of 17-beta estradiol and an evident cornification of the vaginal mucosa cells ( 50-80 % ) . Estradiol and progesterone were at baseline levels for the remaining study period , in which no other oestrous manifestations were observed . The external genitalia maintained a juvenile appearance . The ovaries , ultrasonographically , showed no follicular structures and stayed the same size . At 18 months , the genital tract was still juvenile with inactive small ovaries and a thin filiform uterus . Deslorelin suppressed ovarian activity in pre-pubertal bitches , and oestrous induction was not observed despite the presence of the primary stimulatory effect of the drug . Juvenile genitalia were an expected side effect of the treatment .

Deslorelin implants

Deslorelin acetate

deslorelin acetate implants

not implanted

ovariohysterectomy

primary stimulatory effect

evaluation of the internal genitalia .

suppression of oestrus

plasmatic levels of 17-beta estradiol

Estradiol and progesterone

suppressed ovarian activity

oestrous induction was not observed

Juvenile genitalia

pre-pubertal

female

pre-pubertal

female

deslorelin acetate implants

female


Preschool-based social communication treatment for children with autism : 12-month follow-up of a randomized trial . OBJECTIVE This study reports 12-month follow-up data from a randomized controlled trial of preschool-based social communication treatment for young children with autism . METHOD A total of 61 children ( 48 males ) with autism , 29 to 60 months of age , had earlier been randomized either to 8 weeks of preschool-based social communication treatment in addition to standard preschool program ( n = 34 ) or to standard preschool program only ( n = 27 ) . Significant short-term effects on targeted social communication skills have previously been published . Long-term gains in social communication , language and global social functioning and communication were assessed from video-taped preschool teacher-child and mother-child interactions , Early Social Communication Scales , Reynell Developmental Language Scale , and Social Communication Questionnaire . RESULTS Compared with those in the control group , the treated children achieved significantly larger improvements in joint attention and joint engagement from baseline to 12-month follow-up . However , no effects were detected on language and global ratings of social functioning and communication . The treatment effect on child initiation of joint attention increased with increasing level of sociability at baseline , whereas nonverbal IQ and expressive language had no moderating effect . CONCLUSIONS This study is the first to show that , similar to specialist-delivered treatment , preschool-based treatment may produce small but possibly clinically important long-term changes in social communication in young children with autism . The treatment did not affect language and global ratings of social functioning and communication . More studies are needed to better understand whether treatment effects may be improved by increasing the intensity and duration of the treatment . Clinical trial registration information -- Joint Attention Intervention and Young Children With Autism ; http : //clinicaltrials.gov/ ; NCT00378157 .

standard preschool program only

preschool-based treatment

children

autism

young children

autism

48 males

autism

, 29 to 60 months of age ,


Does privatisation of vocational rehabilitation improve labour market opportunities ? Evidence from a field experiment in Sweden . This paper analyses if privatisation of vocational rehabilitation can improve labour market opportunities for individuals on long-term sickness absence . We use a field experiment performed by the Public Employment Service and the Social Insurance Agency in Sweden during 2008-2010 , in which over 4000 participants were randomly offered private and public rehabilitation . We find no differences in employment rates following rehabilitation between individuals who received rehabilitation by private and public providers . Also the average cost of rehabilitation was essentially equal for the two types of providers . This suggests that there are no large efficiency gains from privatising vocational rehabilitation .

private and public rehabilitation

rehabilitation

employment rates

average cost of rehabilitation

efficiency gains

sickness absence

over 4000 participants

public rehabilitation


A parent-mediated intervention that targets responsive parental behaviors increases attachment behaviors in children with ASD : results from a randomized clinical trial . The current study is a randomized clinical trial evaluating the efficacy of Focused Playtime Intervention ( FPI ) in a sample of 70 children with Autism Spectrum Disorder . This parent-mediated intervention has previously been shown to significantly increase responsive parental communication ( Siller et al . in J Autism Dev Disord 43:540-555 , 2013a ) . The current analyses focus on children 's attachment related outcomes . Results revealed that children who were randomly assigned to FPI showed bigger increases in attachment-related behaviors , compared to children assigned to the control condition . Significant treatment effects of FPI were found for both an observational measure of attachment-related behaviors elicited during a brief separation-reunion episode and a questionnaire measure evaluating parental perceptions of child attachment . The theoretical and clinical implications of these findings are discussed .

parent-mediated intervention

Focused Playtime Intervention ( FPI )

FPI

FPI

attachment behaviors

attachment related outcomes

attachment-related behaviors

attachment-related behaviors

children

ASD

children

Autism Spectrum Disorder


Examining the effectiveness of psychological strategies on physiologic markers : evidence-based suggestions for holistic care of the athlete . CONTEXT Current holistic rehabilitation blends both physical and psychological techniques . However , validation of the usefulness of psychological strategies is limited in the literature . OBJECTIVE To quantify the effects of psychological strategies on both physiologic ( salivary cortisol ) and subjective assessments of stress . DESIGN Randomized controlled clinical trial . SETTING Laboratory . PATIENTS OR OTHER PARTICIPANTS A total of 97 college-aged students ( age = 20.65 ± 4.38 years ) , most with little to no experience with psychological strategies . INTERVENTION ( S ) A 15-minute script via an iPod led the participant through visual imagery ( cognitive relaxation ) or deep breathing exercises ( somatic relaxation ) cues . The control group listened to 15 minutes of ambient nature sounds . MAIN OUTCOME MEASURE ( S ) Two samples ( pretest , posttest ) of salivary cortisol were analyzed using an enzyme immunoassay kit ; the average was used for statistical analysis . Descriptive statistics and correlations were conducted to examine group differences in time of day , salivary cortisol , sex , Stress-O-Meter values , and Perceived Stress Scale scores . RESULTS Salivary cortisol levels were lower in the treatment group than the control group ( F2,97 = 15.62 , P < .001 ) . Females had higher scores on both the pretest Stress-O-Meter ( 5.15 ± 1.796 ) and the Perceived Stress Scale ( 18.31 ± 5.833 ) than males ( 4.25 ± 1.741 and 15.272 ± 5.390 , respectively ) . CONCLUSIONS Both cognitive and somatic relaxation strategies reduced cortisol levels . Participants who received verbal guidance achieved a larger cortisol reduction . However , the change in cortisol level was uncorrelated with the change in report of acute stress ; females reported higher levels of stress . Clinical implications include attention to sex when assessing stress and providing coping skills during the rehabilitation process .

psychological strategies

holistic rehabilitation

psychological strategies

salivary cortisol

salivary cortisol

Stress-O-Meter

Perceived Stress Scale scores

Salivary cortisol levels

Stress-O-Meter

Perceived Stress Scale

cortisol levels

cortisol reduction

psychological strategies


A randomized controlled trial investigating the safety and efficacy of aripiprazole in the long-term maintenance treatment of pediatric patients with irritability associated with autistic disorder . OBJECTIVE To evaluate the efficacy and safety of aripiprazole versus placebo in preventing relapse of irritability symptoms associated with autistic disorder in pediatric patients . METHOD This multicenter , double-blind , randomized , placebo-controlled , relapse-prevention trial enrolled patients ( 6-17 years ) who met the current Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision ( DMS-IV-TR ) criteria for autistic disorder and who also had serious behavioral problems ( ie , tantrums , aggression , self-injurious behavior , or a combination of these behavioral problems ) between March 2011 and June 2012 . In phase 1 , single-blind aripiprazole was flexibly dosed ( 2-15 mg/d ) for 13-26 weeks . Patients with a stable response ( ≥ 25 % decrease in Aberrant Behavior Checklist-irritability subscale score and a rating of " much improved " or " very much improved " on the Clinical Global Impressions-Improvement scale ) for 12 consecutive weeks were randomized into phase 2 to continue aripiprazole or switch to placebo . Treatment was continued until relapse or up to 16 weeks . The primary end point was time from randomization to relapse . RESULTS Eighty-five patients were randomized in phase 2 . The difference in time to relapse between aripiprazole and placebo was not statistically significant ( P = .097 ) . Kaplan-Meier relapse rates at week 16 were 35 % for aripiprazole and 52 % for placebo ( hazard ratio [ HR ] = 0.57 ; number needed to treat [ NNT ] = 6 ) . The most common adverse events during phase 1 were weight increase ( 25.2 % ) , somnolence ( 14.8 % ) , and vomiting ( 14.2 % ) ; and , during phase 2 ( aripiprazole vs placebo ) , they were upper respiratory tract infection ( 10.3 % vs 2.3 % ) , constipation ( 5.1 % vs 0 % ) , and movement disorder ( 5.1 % vs 0 % ) . CONCLUSIONS In this study , there was no statistically significant difference between aripiprazole and placebo in time to relapse during maintenance therapy . However , the HR and NNT suggest some patients will benefit from maintenance treatment . Patients receiving aripiprazole should be periodically reassessed to determine the continued need for treatment . TRIAL REGISTRATION ClinicalTrials.gov identifier : NCT01227668 .

aripiprazole

aripiprazole

placebo

placebo-controlled

aripiprazole

safety and efficacy

irritability symptoms

pediatric

irritability

autistic disorder

autistic disorder

pediatric

6-17 years

autistic disorder

serious behavioral problems


Addictive internet use among Korean adolescents : a national survey . BACKGROUND A psychological disorder called 'Internet addiction ' has newly emerged along with a dramatic increase of worldwide Internet use . However , few studies have used population-level samples nor taken into account contextual factors on Internet addiction . METHODS AND FINDINGS We identified 57,857 middle and high school students ( 13-18 year olds ) from a Korean nationally representative survey , which was surveyed in 2009 . To identify associated factors with addictive Internet use , two-level multilevel regression models were fitted with individual-level responses ( 1st level ) nested within schools ( 2nd level ) to estimate associations of individual and school characteristics simultaneously . Gender differences of addictive Internet use were estimated with the regression model stratified by gender . Significant associations were found between addictive Internet use and school grade , parental education , alcohol use , tobacco use , and substance use . Female students in girls ' schools were more likely to use Internet addictively than those in coeducational schools . Our results also revealed significant gender differences of addictive Internet use in its associated individual- and school-level factors . CONCLUSIONS Our results suggest that multilevel risk factors along with gender differences should be considered to protect adolescents from addictive Internet use .

'Internet addiction

individual-level responses

addictive Internet use

Addictive internet use

addictive Internet use

addictive Internet

Internet use

use Internet addictively

addictive Internet

addictive Internet use

adolescents

13-18 year olds

Female

adolescents


Management of large bowel obstruction with self-expanding metal stents . A multicentre retrospective study of factors determining outcome . AIM UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent ( SEMS ) . Considerable variation in practice exists due to a lack of expertise , technical difficulties and other , as yet ill-defined features . This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention . METHOD A regional programme of colonic stenting for large bowel obstruction , in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success , survival , complications and reoperation . RESULTS A SEMS was inserted in 334 patients , including 264 ( 79.0 % ) for palliation and 52 ( 15.6 % ) as a bridge to surgery . Technical success was achieved in 292 ( 87.4 % ) patients , with 46 ( 13.8 % ) experiencing a complication or technical failure . Reoperation was required in 39 ( 14.8 % ) patients stented for palliation of colorectal cancer of whom 16 ( 6.1 % ) subsequently required a colostomy . A one-stage primary anastomosis was achieved in 35 ( 67.3 % ) of the 52 patients undergoing stenting as a bridge to resection . Technical success did not vary by indication or site of obstruction ( P = 0.60 ) but was higher for operators who had performed more than 10 procedures ( OR 3.34 , P = 0.001 ) . ASA grade ≥3 predicted a worse clinical outcome ( OR 0.43 , P = 0.04 ) . The through-the-scope ( TTS ) endoscopy technique was more successful than radiological placement alone ( 90.3 % vs 74.8 % , P < 0.001 ) . CONCLUSION Experienced operators using a TTS technique achieved a better outcome for the emergency management of large bowel obstruction . Older , sicker patients and those with extracolonic and benign strictures fared less well .

self-expanding metal stents

SEMS

technical and clinical success

survival

complications

Technical success

Reoperation

one-stage primary anastomosis

Technical success

indication or site of obstruction

colonic obstruction

malignancy

334 patients

colorectal cancer


Effects of iron on the pharmacokinetics of paracetamol in saliva . Paracetamol has been reported to chelate with iron . It was found that no in vitro reaction between ferrous ion and paracetamol . Other studies found that there is an aerobic ( in the gastrointestinal tract ) oxidation of ferrous ion to ferric ion caused in iron-paracetamol in vivo reactions . The objective of this study was to determine if iron interacts with paracetamol and reduces paracetamol absorption . A randomized , double-blind , cross-over study design was used to assess the in vivo interaction of paracetamol and ferrous ion . Paracetamol ( 1.0 g ) was co-ignested alone or with ( 300 mg ) ferrous sulphate by ten healthy male volunteers , using saliva drug levels as a parameter . Concomitant administration of ferrous sulphate and paracetamol , decreased AUC8 from 42.88 +/- 3.8-34.25 +/- 2.8 microg h mL ( -1 ) ( p = 0.04 ) and Cmax from 18.75 +/- 1.9 to 15.9 +/- 1.7 microg mL ( -1 ) ( p = 0.11 ) , while no change in tmax ( p = 0.5 ) was originated . A significant difference was found in the paracetamol pharmacokinetic parameter oral clearance ( C1/F ) ( p = 0.02 ) and slightly increased in volume of distribution ( V ( d ) /F ) ( p = 0.10 ) . Co-administration of iron and paracetamol results in decreased paracetamol absorption due to an interaction between iron and paracetamol .

iron

paracetamol

Paracetamol

iron

paracetamol

ferrous ion

Paracetamol

ferrous sulphate

ferrous sulphate

paracetamol

iron

paracetamol

paracetamol absorption

Cmax

volume of distribution

paracetamol absorption

ten

healthy

male


Participant characteristics and intervention processes associated with reductions in television viewing in the High Five for Kids study . OBJECTIVE To evaluate the High Five for Kids intervention effect on television within subgroups , examine participant characteristics associated with process measures and assess perceived helpfulness of television intervention components . METHOD High Five ( randomized controlled trial of 445 overweight/obese 2-7 year-olds in Massachusetts [ 2006-2008 ] ) reduced television by 0.36 h/day . 1-year effects on television viewing , stratified by subgroup , were assessed using linear regression . Among intervention participants ( n=253 ) , associations of intervention component helpfulness with television reduction were examined using linear regression and associations of participant characteristics with processes linked to television reduction ( choosing television and completing intervention visits ) were examined using logistic regression . RESULTS High Five reduced television across subgroups . Parents of Latino ( versus white ) children had lower odds of completing ≥2 study visits ( Odds Ratio : 0.39 [ 95 % Confidence Interval : 0.18 , 0.84 ] ) . Parents of black ( versus white ) children had higher odds of choosing television ( Odds Ratio : 2.23 [ 95 % Confidence Interval : 1.08 , 4.59 ] ) , as did parents of obese ( versus overweight ) children and children watching ≥2 h/day ( versus < 2 ) at baseline . Greater perceived helpfulness was associated with greater television reduction . CONCLUSION Clinic-based motivational interviewing reduces television viewing in children . Low cost education approaches ( e.g. , printed materials ) may be well-received . Parents of children at higher obesity risk could be more motivated to reduce television .

High Five for Kids intervention

reduced television by 0.36 h/day .

intervention component

Kids

Kids

overweight/obese

2-7 year-olds

( n=253

Parents

Latino ( versus white )

children

Parents

black ( versus white )

children

parents

obese ( versus overweight )

children

children

children

Parents

children

higher obesity risk


Non-contrast-enhanced 4D MR angiography with STAR spin labeling and variable flip angle sampling : a feasibility study for the assessment of Dural Arteriovenous Fistula . INTRODUCTION This study aimed to evaluate the feasibility of non-contrast-enhanced 4D magnetic resonance angiography ( NCE 4D MRA ) with signal targeting with alternative radiofrequency ( STAR ) spin labeling and variable flip angle ( VFA ) sampling in the assessment of dural arteriovenous fistula ( DAVF ) in the transverse sinus . METHODS Nine patients underwent NCE 4D MRA for the evaluation of DAVF in the transverse sinus at 3 T. One patient was examined twice , once before and once after the interventional treatment . All patients also underwent digital subtraction angiography ( DSA ) and/or contrast-enhanced magnetic resonance angiography ( CEMRA ) . For the acquisition of NCE 4D MRA , a STAR spin tagging method was used , and a VFA sampling was applied in the data readout module instead of a constant flip angle . Two readers evaluated the NCE 4D MRA data for the diagnosis of DAVF and its type with consensus . The results were compared with those from DSA and/or CEMRA . RESULTS All patients underwent NCE 4D MRA without any difficulty . Among seven patients with patent DAVFs , all cases showed an early visualization of the transverse sinus on NCE 4D MRA . Except for one case , the type of DAVF of NCE 4D MRA was agreed with that of reference standard study . Cortical venous reflux ( CVR ) was demonstrated in two cases out of three patients with CVR . CONCLUSION NCE 4D MRA with STAR tagging and VFA sampling is technically and clinically feasible and represents a promising technique for assessment of DAVF in the transverse sinus . Further technical developments should aim at improvements of spatial and temporal coverage .

Non-contrast-enhanced 4D MR angiography

NCE 4D MRA

early visualization of the

transverse sinus

Cortical venous reflux ( CVR )

Dural Arteriovenous Fistula .

underwent NCE 4D MRA


Alleviating social avoidance : effects of single dose testosterone administration on approach-avoidance action . Testosterone is an important regulator of social-motivational behavior and is known for its dominance-enhancing and social-anxiolytic properties . However , to date no studies have systematically investigated the causal effect of testosterone on actual social approach-avoidance behavior in humans . The present study sets out to test the effects of testosterone administration in healthy female volunteers using an objective implicit measure of social motivational behavior : the social Approach-Avoidance Task , a reaction time task requiring participants to approach or avoid visually presented emotional ( happy , angry , and neutral ) faces . Participants showed significantly diminished avoidance tendencies to angry faces after testosterone administration . Testosterone did not affect approach-avoidance tendencies to social affiliation ( happy ) faces . Thus , a single dose testosterone administration reduces automatic avoidance of social threat and promotes relative increase of threat approach tendencies in healthy females . These findings further the understanding of the neuroendocrine regulation of social motivational behavior and may have direct treatment implications for social anxiety , characterized by persistent social avoidance .

single dose testosterone administration

Testosterone

testosterone administration

testosterone

Testosterone

testosterone

approach-avoidance action .

social-motivational behavior

social motivational behavior :

social Approach-Avoidance Task

avoidance tendencies

angry faces

social anxiety

social avoidance .

female

females


The effect of deep brain stimulation randomized by site on balance in Parkinson 's disease . BACKGROUND The effect of the surgical site of DBS on balance and gait in Parkinson 's Disease ( PD ) is uncertain . This is the first double-blind study of subjects randomized to either the STN ( N = 14 ) or GPi ( N = 14 ) who were assessed on a range of clinical balance measures . METHODS Balance testing occurred before and 6 months postsurgery . A control PD group was tested over the same period without surgery ( N = 9 ) . All subjects were tested on and off medication and DBS subjects were also tested on and off DBS . The Postural Instability and Gait Disability items of the UPDRS and additional functional tests , which we call the Balance and Gait scale , were assessed . Activities of Balance Confidence and Activities of Daily Living questionnaires were also recorded . RESULTS Balance was not different between the best-treated states before and after DBS surgery for both sites . Switching DBS on improved balance scores , and scores further improved with medication , compared to the off state . The GPi group showed improved performance in the postsurgery off state and better ratings of balance confidence after surgery , compared to the STN group . CONCLUSIONS Clinical measures of balance function for both the STN and GPi sites showed that balance did not improve beyond the best medically treated state before surgery . Both clinical balance testing in the off/off state and self-reported balance confidence after surgery showed better performance in the GPi than the STN group .

deep brain stimulation

STN

GPi

control

on and off medication

on and off DBS

balance scores

balance confidence


Accumulated brisk walking reduces arterial stiffness in overweight adults : evidence from a randomized control trial . Arterial stiffness is a major contributor to the development of atherosclerosis and consequently cardiovascular disease . This study aimed to examine whether 6 months of accumulated ( 3 × 10 minutes , 5 days/week ) brisk walking was sufficient to reduce arterial stiffness in sedentary , overweight individuals . Seventy-seven individuals ( 19 men , 58 women ; age , 30-55 years ) were randomly allocated to one of three groups ; two groups completed 30 minutes of accumulated walking with either monthly or weekly telephone support ; the third group ( control ) performed stretching exercises . The walking groups were combined and telephone support included as a covariate . Anthropometry , blood pressure ( BP ) , blood lipids , pulse wave velocity ( PWV ) , and NOx ( surrogate marker for nitric oxide ) were measured at baseline , post-intervention and 4 months post-intervention . No changes were observed for anthropometry , BP , or lipids . However , at the end of the intervention , there was a decrease in PWV ( P < .001 ) accompanied by an increase in NOx ( P < .001 ) , with changes maintained 4 months post-intervention . A strong negative correlation between PWV and NOx was also observed ( P < .001 ; r = -0.65 ) . A lifestyle approach to meeting current physical activity guidelines results in favorable alterations in arterial function in overweight individuals .

Accumulated brisk walking

blood pressure ( BP )

blood lipids

anthropometry

in overweight adults :


Evaluation of an interactive multi-media device for delivering information on Le Fort I osteotomy . This study was carried out on volunteers to evaluate a newly developed interactive software package aimed at informing prospective Le Fort I osteotomy patients regarding the surgical technique and possible complications . The aim of the study was to compare two methods of information delivery ; a multi-media tablet device delivering both graphic and verbal information , and an audio device delivering essentially the same information in verbal form only . The null hypothesis was that there would be no difference between the efficiencies of the two methods . The subjects ' ability to recall the information delivered by both devices was assessed using a questionnaire . The tablet device participants scored an average of 15.48 points , while the audio device participants scored an average of 268 points . The difference was statistically significant ( p < 0.001 ) , suggesting that the multi-media tablet device was more effective method .

efficiencies

ability to recall the information

volunteers

prospective Le Fort I osteotomy


Pharmacokinetics and disposition of carvedilol in humans . Pharmacokinetics of carvedilol ( C ) have been studied in healthy volunteers after a single i.v . and oral administration , and the metabolic disposition after oral administration of 14C-labeled drug . C demonstrates dose-linear behavior . The absolute bioavailability reaches 24 % probably due to a first-pass effect . After a 50 mg oral dose , maximum concentrations of 66 micrograms/l are achieved within 1.2 h. C is extensively distributed to the tissues ( Vz = 132 l ) and eliminated primarily by hepatic metabolism ( total clearance 590 ml/min , renal clearance 4 ml/min ) . Because of the longer half-life of 6.4 h after oral administration in contrast to 2.4 h after i.v . administration , C is assumed to be absorption dependent since no sustained-release formulation was used . The half-life of radioactivity in plasma is 39 h ; 16 % of C is excreted in urine in the form of metabolites and only 0.3 % unchanged . The urinary metabolites consist of carvedilol glucuronide ( 5.2 % of the dose ) , cleavage products of the beta-blocking side chain ( 2.1 % ) , and ring-hydroxylated forms ( 2.9 % ) . Sixty percent of the dose is recovered in the feces . A demethylated product of C exhibits only minor beta-blocking activity . This metabolite is detected in plasma in concentrations ten times lower than the parent compound .

carvedilol

carvedilol

14C-labeled drug

Pharmacokinetics

half-life

beta-blocking activity

metabolite


A randomised double-blind control study of early intracoronary autologous bone marrow cell infusion in acute myocardial infarction ( REGENERATE-AMI ) . INTRODUCTION Acute myocardial infarction ( AMI ) remains a major cause of mortality and morbidity worldwide despite the latest therapeutic advances designed to decrease myocardial injury . Preclinical and emerging clinical evidence show that the intracoronary injection of autologous bone marrow mononuclear cells ( BMCs ) following AMI leads to improvement in left ventricular ejection function ( LVEF ) . In this clinical trial we will for the first time assess the effect of early ( < 24 h ) infusion of autologous BMCs following AMI on cardiac function . METHODS AND ANALYSIS REGENERATE-AMI is a double-blind , randomised , multicentre , placebo-controlled trial to determine whether early ( < 24 h ) intracoronary infusion of BMCs improves LVEF after AMI . The study will enrol 100 patients presenting with an anterior AMI demonstrating anterior regional wall motion abnormality . Patients will be randomised to receive intracoronary infusion of BMCs or placebo ( 0.9 % saline ) . Primary endpoint will be change in LVEF at 1 year compared to baseline , measured by cardiac MRI . Secondary endpoints at 6 months include the change in global LVEF relative to baseline measured by quantitative left ventriculography and echocardiography , as well as major adverse cardiac events which is also measured at 1 year . ETHICS AND DISSEMINATION The study will be performed in agreement with the Declaration of Helsinki and is approved by local ethics committee ( NRES Committee London West London : 07/Q0603/76 ) . TRIAL REGISTRATION http : //clincialtrials.gov ( NCT00765453 ) . The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals .

placebo-controlled

intracoronary infusion of BMCs

placebo

saline

effect

measured by cardiac MRI

major adverse cardiac events

acute myocardial infarction

100 patients

AMI


Two to ten years : developmental trajectories of joint attention in children with ASD who received targeted social communication interventions . This study follows 40 children who were participants in a randomized controlled early intervention trial ( Kasari et al . ) from early childhood ( 2-5 years of age ) to elementary school age ( 8-10 years ) . To fully utilize the available longitudinal data , the general linear mixed model was the primary analytical approach . The growth trajectories of joint attention skills ( pointing , coordinated joint looking , and showing ) and expressive language outcomes in these children were estimated based on five time points during the measurement period . The children were grouped by diagnosis at the last follow-up ( autism , autism spectrum disorder ( ASD ) , no diagnosis ) and by their original treatment group assignment ( joint attention , symbolic play , control ) , and differences between these groups were evaluated . Results showed that joint attention skills of coordinated joint looking and showing increased over time , and pointing to share interest increased over the first year measured and decreased thereafter . These trajectories were influenced by both original treatment assignment and diagnostic status at follow-up . In addition , a cross-lagged panel analysis revealed a causal relationship between early pointing and later language development . This study highlights the longitudinal and developmental importance of measures of early core deficits in autism , and suggests that both treatment and ASD symptomatology may influence growth in these skills over time .

expressive language outcomes

joint attention skills

children

ASD

children