Enhancing the experience of carers in the chemotherapy outpatient setting : an exploratory randomised controlled trial to test impact , acceptability and feasibility of a complex intervention co-designed by carers and staff . PURPOSE Supporting someone through chemotherapy can be emotionally and physically demanding . However , research has yet to establish the type of support carers require or the best way to provide this . This study tested the feasibility and acceptability of a complex intervention for carers that was co-designed by staff and carers of patients starting chemotherapy . METHODS Forty-seven carers were recruited , randomised between the intervention ( n = 24 ) and control ( n = 23 ) groups . A questionnaire was completed pre- and post-intervention measuring knowledge of chemotherapy and its side effects , experience of care , satisfaction with outpatient services , coping and emotional wellbeing . The intervention process was evaluated by carers and healthcare professionals ( HCPs ) in focus groups . RESULTS Recruitment to the study was unproblematic and attrition from it was low , suggesting the intervention and study processes were acceptable to patients and carers . Carers in receipt of the 'Take Care ' intervention reported statistically significantly better understanding of symptoms and side effects and their information needs being more frequently met than carers in the control . Confidence in coping improved between baseline and follow-up for the intervention group and declined for the control although differences were insufficient to achieve statistical significance . There was no significant difference between the two groups ' emotional wellbeing . HCP and carer focus groups confirmed the feasibility and acceptability of the intervention . CONCLUSIONS The 'Take Care ' intervention proved acceptable to carers and HCPs and demonstrates considerable promise and utility in practice . Study findings support the conduct of a fully powered RCT to determine the intervention 's effectiveness and cost-effectiveness .

complex intervention

chemotherapy

intervention

control

questionnaire

chemotherapy

chemotherapy

feasibility and acceptability

Forty-seven carers were recruited

( n = 24 )

control ( n = 23 ) groups


A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood : a randomized trial . BACKGROUND Recent experimental evidence suggests that gut microbiota may alter function within the nervous system providing new insight on the mechanism of neuropsychiatric disorders . METHODS Seventy-five infants who were randomized to receive Lactobacillus rhamnosus GG ( ATCC 53103 ) or placebo during the first 6 mo of life were followed-up for 13 y . Gut microbiota was assessed at the age of 3 wk , 3 , 6 , 12 , 18 , 24 mo , and 13 y using fluorescein in situ hybridization ( FISH ) and qPCR , and indirectly by determining the blood group secretor type at the age of 13 y . The diagnoses of attention deficit hyperactivity disorder ( ADHD ) and Asperger syndrome ( AS ) by a child neurologist or psychiatrist were based on ICD-10 diagnostic criteria . RESULTS At the age of 13 y , ADHD or AS was diagnosed in 6/35 ( 17.1 % ) children in the placebo and none in the probiotic group ( P = 0.008 ) . The mean ( SD ) numbers of Bifidobacterium species bacteria in feces during the first 6 mo of life was lower in affected children 8.26 ( 1.24 ) log cells/g than in healthy children 9.12 ( 0.64 ) log cells/g ; P = 0.03 . CONCLUSION Probiotic supplementation early in life may reduce the risk of neuropsychiatric disorder development later in childhood possible by mechanisms not limited to gut microbiota composition .

probiotic intervention

placebo

risk of

neuropsychiatric disorders

Gut microbiota

the blood group secretor type

y , ADHD

AS

neuropsychiatric disorders

childhood

Seventy-five

infants

or placebo during the first

childhood


Effect of two monophasic oral contraceptives containing gestodene or desogestrel on serum lipoprotein lipid levels . Forty-nine healthy women aged 20-35 years who had not been pregnant or using an oral contraceptive ( OC ) for the previous 3 months were randomized into two groups , one group taking an OC containing 75 micrograms gestodene ( GTD ) and 30 micrograms ethinyl estradiol ( EE ) , and the other group using an OC with 150 micrograms desogestrel ( DSG ) and 30 micrograms EE . Fasting blood samples were taken before treatment , and after cycles 3 and 6 , between the 18th and the 22nd day of the cycle . Blood lipoprotein lipid levels were measured . Serum total cholesterol did not change significantly in both groups . However , in the first three cycles , serum triglyceride increased by 46 % and 40 % and HDL-cholesterol by 14 % and 8 % in the GTD and DSG groups , respectively . The serum LDL level decreased by 6.2 % and 11.8 % , respectively . Between the third and sixth cycle , no further significant changes were observed , nor did these changes differ significantly between the two groups . In conclusion , both OC preparations exerted small and probably favorable effects on serum lipoprotein lipid levels .

monophasic oral contraceptives

gestodene

desogestrel

oral contraceptive ( OC )

OC

gestodene ( GTD )

ethinyl estradiol ( EE )

OC

desogestrel ( DSG )

GTD

DSG

OC

Fasting blood samples

Blood lipoprotein lipid levels

Serum total cholesterol

serum triglyceride increased

HDL-cholesterol

GTD and DSG

serum LDL level

serum lipoprotein lipid levels

Forty-nine

women

aged 20-35 years

oral contraceptive


Lateral MI Explains the Presence of Prominent R Wave ( R ≥ S ) in V1 . AIMS It is necessary to clarify if the presence of a prominent R wave in V1 , in post-myocardial infarction ( MI ) patients , is due to the involvement of the posterior wall ( currently inferobasal segment ) or the lateral wall ( as has been demonstrated recently by electrocardiographic contrast-enhanced cardiac magnetic resonance [ ECG-CE-CMR ] correlations studies ) . METHODS In 155 patients with inferolateral zone MI , as detected by CE-CMR , the following ECG parameters were evaluated and correlated with MI location according to CE-CMR : R/S ratio in V1 ≥ 1 ( classic criteria for posterior MI ) , R/S ratio in V1 ≥ 0.5 , and R in V1 ≥ 3 mm . RESULTS R/S ≥ 1 criterion : Present in 20 cases : 3 of lateral MI , 17 of inferolateral MI , 0 of inferior MI . Absent in 135 cases , 81 of lateral/inferolateral MI ( 28/53 ) , 54 of inferior MI ( SE 19.8 % , SP 100 % ) . R/S ≥ 0.5 criterion : Present in 47 cases : 6 of lateral MI , 39 of inferolateral MI , 2 of inferior MI . Absent in 108 cases , 56 of lateral/inferolateral MI ( 25/31 ) , 52 of inferior MI ( SE 44.6 % , SP 96.4 % ) . R ≥ 3 mm criterion : Present in 30 cases : 5 of IM lateral , 23 of inferolateral MI , 2 of inferior MI . Absent in 125 cases , 73 lateral/inferolateral MI ( 26/47 ) , 52 inferior MI ( SE 27.7 % , SP 96.4 % ) . CONCLUSIONS The presence of prominent the R wave in V1 is due to the lateral MI and not to the involvement of inferobasal segment of inferior wall ( old posterior wall ) .

Lateral MI

Prominent R Wave

following ECG parameters

to CE-CMR :

inferobasal segment

155 patients

inferolateral zone MI


[ European topic : liver surgery II -- regional chemotherapy ] . The most important methods of regional chemotherapy are exemplified by 657 cases of primary and secondary liver only malignancies . I . Adjuvant portal therapy of the liver with resection of the colorectal primary malignancy seems to be advantageous for advanced tumors . II . It is still unresolved whether survival is prolonged by adjuvant treatment of the liver following curative resection of colorectal liver metastases . III . The median survival time ( FUDR , pump ) is 17 months for palliative local chemotherapy of unresectable colorectal liver metastases . IV . Primary non-resectable liver malignancies show the best results after chemoembolisation ( Frankfurt method ) .

regional chemotherapy

palliative local chemotherapy

survival

median survival time ( FUDR , pump )


Qingre quyu granule stabilizes plaques through inhibiting the expression of tenascin-C in patients with severe carotid stenosis . OBJECTIVE To investigate the therapeutic effects of Qingre Quyu Granule ( QQG ) on the patients with severe carotid stenosis , and to explore the mechanism of it . METHODS Ninety-six patients with severe carotid stenosis were enrolled in the study and were classified into a QQG group ( n=48 ) and a control group ( n=48 ) randomly using consecutively numbered envelopes . The patients in the QQG group were given QQG and Western medicine , those in the control group were given Western medicine merely , the course of treatment was 16 weeks . All patients went through endarterectomy after treatment . Plaques were subjected to the analysis of CD3 , CD68 , soluble intercellular adhesion molecule 1 ( ICAM-1 ) , matrix metalloprotease-9 ( MMP-9 ) , CD40L , tenascin-C , and collagen content lipid content by immunohistochemistry or polarized light analysis . RESULTS By the end of experiment , the expressions of CD3 , CD68 , ICAM-1 , MMP9 , CD40L and tenascin-C on the plaques were statistically significant lower in the QQG group compared with the control group ( P < 0.01 ) . The lipid content of the plaque was also significantly lower in the QQG group compared with the control group ( P < 0.01 ) . The interstitial collagen in the tissue sections of the plaques was also significantly higher in the QQG group in comparison with the control group ( P < 0.01 ) . CONCLUSION QQG could stabilize carotid artery plaques through inhibiting pro-inflammation factors and restraining the tenascin-C and MMP9 pathway .

Qingre Quyu Granule ( QQG )

QQG

control group

QQG

QQG

Western medicine

Western medicine

QQG

QQG

QQG

therapeutic effects

lipid content of the plaque

patients with severe carotid stenosis

patients with severe carotid stenosis

Ninety-six

with severe carotid stenosis


Assessment of radiotherapy combined with adjuvant chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma : a prospective study . PURPOSE To explore the clinical efficacy of radiotherapy combined with concurrent combination chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma ( NPC ) . METHODS Two hundred patients with stage III/IV NPC were randomly allocated into the treatment group ( N=100 ) and the control group ( N=100 ) . Patients in the control group received conventional fractionated radiotherapy , while patients in the treatment group received conventional fractionated radiotherapy combined with concurrent combination chemotherapy with cisplatin and 5-fluorouracil ( 5-FU ) . Short-term efficacy , radiotherapy toxicity , shortand long-term survival were compared . RESULTS The short-term response rate of the treatment group was 96 % , which was significantly higher than that of the control group ( 87 % , p < 0.05 ) . The local radiation toxicity of the treatment group was similar to that of the control group p > 0.05 ) , but the hematological and gastrointestinal toxicities were significantly higher in the treatment group p < 0.05 ) . The 1- , 3- and 5-year overall survival rates were 87 , 80 , and 76 % , respectively , in the treatment group and 74 , 64 , and 51 % , respectively , in the control group , significantly favoring the treatment group p < 0.05 ) . CONCLUSION Radiotherapy with concurrent combination chemotherapy can improve the prognosis of patients with advanced NPC but at the cost of significant toxicity .

radiotherapy

combined with adjuvant chemotherapy

radiotherapy

conventional fractionated radiotherapy

conventional fractionated radiotherapy

efficacy

Short-term efficacy

radiotherapy toxicity

shortand long-term survival

short-term response

local radiation toxicity

overall survival rates

prognosis

toxicity .

Two hundred patients

stage III/IV NPC

advanced NPC


Examining the Relationship Between Parental Anxiety and Treatment Response in Children and Adolescents with Autism Spectrum Disorder and Anxiety . In response to the high co-occurrence of anxiety symptoms in youth with autism spectrum disorder ( ASD ) , several interventions have been developed for this population . In spite of promising findings , some youth with ASD respond only minimally to such interventions . To understand potential factors that may impact treatment response , the current study explores the role of parental anxiety in youth treatment outcome . Thirty-one youth with ASD , ages 7-18 , and their parents participated in the study . Parents completed the State/Trait Anxiety Inventory pre- and post-treatment . Contrary to previous research , there was no correlation between parental anxiety and youth anxiety at baseline or post-treatment . However , parental trait anxiety significantly decreased from pre- to post-treatment for parents of treatment responders . The findings are consistent with previous research and suggest a youth-to-parent influence .

State/Trait Anxiety Inventory

parental anxiety and youth anxiety

parental trait anxiety

Children and Adolescents

Autism Spectrum Disorder

youth with ASD

Thirty-one

youth

ages 7-18


Magnetic resonance imaging in the evaluation of clinical treatment of otospongiosis : a pilot study . OBJECTIVES To evaluate the applicability of magnetic resonance imaging ( MRI ) as a method for monitoring the activity of otospongiotic lesions before and after clinical treatment . STUDY DESIGN Prospective , randomized , controlled , double-blind study . SETTING One single tertiary care institution in a large , cosmopolitan city . METHODS Twenty-six patients ( n = 42 ears ) with clinical , audiometric , and tomographic diagnosis of otosclerosis were enrolled . If computed tomography ( CT ) demonstrated active lesions , these patients underwent MRI to detect otospongiotic foci , seen as areas of gadolinium enhancement . Patients were divided into 3 groups and received treatment with placebo , sodium alendronate , or sodium fluoride for 6 months . After this period , clinical and audiometric evaluations and a second MRI were performed . Each MRI was evaluated by both a neuroradiologist and an otolaryngologist in a subjective ( visual ) and objective ( using specific eFilm Workstation software ) manner . RESULTS Otospongiosis was most predominantly identified in the region anterior to the oval window , and this site was reliable for comparing pre- and posttreatment scans . The patients in the alendronate and sodium fluoride groups had MRI findings that suggested a decrease in activity of otospongiotic lesions , more relevant in the alendronate group . These findings were statistically significant for both subjective and objective MRI evaluations . CONCLUSIONS MRI shows higher sensitivity than clinical or audiometric assessment for detecting reduction in activity of otospongiosis . The objective MRI evaluation based on software analysis was the most accurate method of monitoring clinical treatment response in otospongiosis .

Magnetic resonance imaging

magnetic resonance imaging ( MRI )

computed tomography

MRI

placebo

sodium alendronate

sodium fluoride

MRI

MRI

MRI

MRI

MRI

otospongiosis :

Twenty-six

n = 42 ears

otosclerosis


Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults . OBJECTIVE Impaired brain insulin action has been linked to obesity , type 2 diabetes , and neurodegenerative diseases . To date , the central nervous effects of insulin in obese humans still remain ill defined , and no study thus far has evaluated the specific brain areas affected by insulin resistance . RESEARCH DESIGN AND METHODS In 25 healthy lean and 23 overweight/obese participants , we performed magnetic resonance imaging to measure cerebral blood flow ( CBF ) before and 15 and 30 min after application of intranasal insulin or placebo . Additionally , participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking . RESULTS In response to insulin compared with placebo , we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants . The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments . Furthermore , we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex , resulting in an insulin-induced CBF reduction in lean participants only . This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving . Behaviorally , we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only . CONCLUSIONS Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue , potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior .

magnetic resonance imaging

intranasal insulin

placebo

insulin

placebo

cerebral blood flow ( CBF )

CBF

insulin-induced CBF reduction

peripheral insulin sensitivity

eating behavior

wanting of sweet foods

overweight and obese

adults


Offering personalized health behavior feedback did not increase response rate : a randomized controlled trial .

personalized health behavior feedback

response rate


The neural correlates of semantic richness : evidence from an fMRI study of word learning . We investigated the neural correlates of concrete nouns with either many or few semantic features . A group of 21 participants underwent two days of training and were then asked to categorize 40 newly learned words and a set of matched familiar words as living or nonliving in an MRI scanner . Our results showed that the most reliable effects of semantic richness were located in the left angular gyrus ( AG ) and middle temporal gyrus ( MTG ) , where activation was higher for semantically rich than poor words . Other areas showing the same pattern included bilateral precuneus and posterior cingulate gyrus . Our findings support the view that AG and anterior MTG , as part of the multimodal network , play a significant role in representing and integrating semantic features from different input modalities . We propose that activation in bilateral precuneus and posterior cingulate gyrus reflects interplay between AG and episodic memory systems during semantic retrieval .

training

middle temporal gyrus ( MTG )

integrating semantic features


Safety and benefit of discontinuing statin therapy in the setting of advanced , life-limiting illness : a randomized clinical trial . IMPORTANCE For patients with limited prognosis , some medication risks may outweigh the benefits , particularly when benefits take years to accrue ; statins are one example . Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy . OBJECTIVE To evaluate the safety , clinical , and cost impact of discontinuing statin medications for patients in the palliative care setting . DESIGN , SETTING , AND PARTICIPANTS This was a multicenter , parallel-group , unblinded , pragmatic clinical trial . Eligibility included adults with an estimated life expectancy of between 1 month and 1 year , statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease , recent deterioration in functional status , and no recent active cardiovascular disease . Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year . The study was conducted from June 3 , 2011 , to May 2 , 2013 . All analyses were performed using an intent-to-treat approach . INTERVENTIONS Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group . Patients in the continuation group continued to receive statins . MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days ( primary outcome ) , survival , cardiovascular events , performance status , quality of life ( QOL ) , symptoms , number of nonstatin medications , and cost savings . RESULTS A total of 381 patients were enrolled ; 189 of these were randomized to discontinue statins , and 192 were randomized to continue therapy . Mean ( SD ) age was 74.1 ( 11.6 ) years , 22.0 % of the participants were cognitively impaired , and 48.8 % had cancer . The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different ( 23.8 % vs 20.3 % ; 90 % CI , -3.5 % to 10.5 % ; P=.36 ) and did not meet the noninferiority end point . Total QOL was better for the group discontinuing statin therapy ( mean McGill QOL score , 7.11 vs 6.85 ; P=.04 ) . Few participants experienced cardiovascular events ( 13 in the discontinuation group vs 11 in the continuation group ) . Mean cost savings were $ 3.37 per day and $ 716 per patient . CONCLUSIONS AND RELEVANCE This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL , use of fewer nonstatin medications , and a corresponding reduction in medication costs . Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted . TRIAL REGISTRATION clinicaltrials.gov Identifier : NCT01415934 .

statin therapy

statin

discontinue or continue

statin therapy

Statin therapy

receive

statins

statins

survival ,

cardiovascular events

quality of life ( QOL )

symptoms

number of nonstatin medications

cost savings

Total QOL

cardiovascular events

Mean cost savings

QOL

fewer nonstatin medications

advanced , life-limiting illness :

patients with limited prognosis

patients with limited life expectancy

patients in the palliative care setting

adults

cardiovascular disease

recent active cardiovascular disease

Mean ( SD ) age was 74.1 ( 11.6 ) years


Initial abstinence status and contingency management treatment outcomes : does race matter ? OBJECTIVE Limited research has evaluated African American substance users ' response to evidence-based treatments . This study examined the efficacy of contingency management ( CM ) in African American and White cocaine users . METHOD A secondary analysis evaluated effects of race , treatment condition , and baseline cocaine urine sample results on treatment outcomes of African American ( n = 444 ) and White ( n = 403 ) cocaine abusers participating in one of six randomized clinical trials comparing CM to standard care . RESULTS African American and White patients who initiated treatment with a cocaine-negative urine sample remained in treatment for similar durations and submitted a comparable proportion of negative samples during treatment regardless of treatment type ; CM was efficacious in both races in terms of engendering longer durations of abstinence in patients who began treatment abstinent . Whites who began treatment with a cocaine positive sample remained in treatment longer and submitted a higher proportion of negative samples when assigned to CM than standard care . African Americans who initiated treatment with a cocaine positive sample , however , did not remain in treatment longer with CM compared with standard care , and gains in terms of drug use outcomes were muted in nature relative to Whites . This interaction effect persisted through the 9-month follow-up period . CONCLUSIONS CM is not equally effective in reducing drug use among all subgroups , specifically African American patients who are using cocaine upon treatment entry . Future research on improving treatment outcomes in this population is needed .

contingency management

contingency management ( CM )

CM

standard care

CM

CM

standard care

CM

standard care

CM

contingency management ( CM )

cocaine users

cocaine abusers


Effects of four traditional Chinese medicines on the pharmacokinetics of simvastatin . 1 . Concomitant traditional Chinese medicines ( TCMs ) could be the reason for relative poor efficacy of statins in dyslipidemia patients in China . 2 . An open-label , randomized , 5-period crossover study in healthy Chinese was designed to evaluate the pharmacokinetic interaction and tolerability of multiple doses of certain TCMs on a single dose of simvastatin . In each period , subjects received one of five treatments . In Treatment A , subjects received a single dose of 20 mg simvastatin . In Treatment B , C , D or E , subjects received Tong Xin Luo , Nao Xin Tong , Guan Mai Ning or Yin Xing Ye for 7 days and a single dose of 20 mg simvastatin on Day 7 . The washout period was 7 days . 3 . The 97.5 % confidence interval of the AUC0-48 h geometric mean ratio of simvastatin acid and simvastatin for simvastatin given after multiple oral doses of one of the TCMs versus simvastatin given alone were fully contained within the prespecified bounds of ( 0.50 , 2.00 ) . 4 . Exposures to simvastatin acid and simvastatin following a single dose of simvastatin alone were similar to those following coadministration of a single dose of simvastatin with multiple doses of each of the TCM preparations tested . Simvastatin and these TCMs were well tolerated .

traditional Chinese medicines

simvastatin

interval of the AUC0-48 h geometric

0.50 , 2.00 )

Exposures to simvastatin acid and

these TCMs were well

dyslipidemia

healthy


The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample : a Double-Blind , Placebo-Controlled Laboratory Study . Methamphetamine ( MA ) use disorder is a serious psychiatric condition for which there are no FDA-approved medications . Naltrexone ( NTX ) is an opioid receptor antagonist with demonstrated efficacy , albeit moderate , for the treatment of alcoholism and opioid dependence . Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder . To inform treatment development , we conducted a double-blind , randomized , crossover , placebo-controlled human laboratory study of NTX . Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence ( n=30 ) completed two separate 5-day inpatient stays . During each admission , participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration ( 30 mg ) after receiving oral NTX ( 50 mg ) or placebo for 4 days . This study tested the hypotheses that NTX would ( a ) attenuate cue-induced MA craving , and ( b ) reduce subjective responses to MA administration . Results largely supported the study hypotheses such that ( a ) NTX significantly blunted cue-induced craving for MA and ( b ) attenuated several of the hedonic subjective effects of MA , including craving , during controlled MA administration and as compared with placebo . NTX decreased overall subjective ratings of 'crave drug , ' 'stimulated , ' and 'would like drug access , ' decreased the the post-MA administration timecourse of 'anxious ' and increased ratings of 'bad drug effects , ' as compared with placebo . These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA . This is consistent with positive treatment studies of NTX for amphetamine dependence , as well as ongoing clinical trials for MA .

Naltrexone

Methamphetamine

Methamphetamine

Naltrexone

MA

timecourse of 'anxious '

increased ratings of 'bad drug effects

Methamphetamine ( MA ) use disorder

MA abuse or dependence


The Impact of Partial Vascular Occlusion on Oxidative Stress Markers during Resistance Exercise . This study sought to examine the effects of partial vascular occlusion ( PVO ) on oxidative stress markers in response to resistance exercise and at rest in young resistance-trained males . 12 resistance-trained males performed 6 conditions in random counterbalanced order : rest ( R ) , low-intensity ( LIRE : 30 % 1RM ) and moderate-intensity ( MIRE : 70 % 1RM ) resistance exercise with or without PVO . Blood samples were obtained before and immediately after each condition and plasma protein carbonyls ( PC ) , glutathione ratio , oxygen radical absorbance capacity ( ORAC ) , and xanthine oxidase ( XO ) were evaluated . The addition of PVO resulted in significantly greater plasma PC and glutathione ratio in the rest condition . During LIRE the addition of PVO significantly attenuated plasma PC . The MIRE condition , independent of PVO , resulted in significantly higher PC concentration and glutathione ratio compared to the rest and LIRE conditions . The addition of PVO during MIRE resulted in a significant increase in PC . Thus , this study revealed that PVO increased oxidative stress at rest and enhanced the oxidative stress response to MIRE , but when combined with LIRE oxidative stress was attenuated . These findings suggest that the utilization of PVO during LIRE may alter ROS-induced accumulation in the blood which may influence cellular signaling .

Partial Vascular Occlusion

Resistance Exercise

partial vascular occlusion ( PVO )

resistance exercise

rest ( R ) , low-intensity ( LIRE

resistance exercise with or without PVO

PVO

LIRE

PVO

PVO

addition

PVO during MIRE

PVO

MIRE

LIRE

PVO

LIRE

Blood samples

plasma PC and glutathione ratio

higher PC concentration

glutathione ratio

PC .

oxidative stress

Resistance Exercise .

young

males

males


Role of warm saline mouth rinse in prevention of alveolar osteitis : a randomized controlled trial . BACKGROUND The present study was aimed at determining the role warm saline rinse in the prevention of alveolar osteitis following dental extractions . MATERIALS AND METHODS Apparently patients aged 16 and above who were referred to the Oral Surgery Clinic of our institution , with an indication for non-surgical extraction of pathologic teeth were prospectively and uniformly randomized into warm saline group and control . The experimental group ( n = 80 ) were instructed to gargle 6 times daily with warm saline and no such instructions were given to the second group ( n = 80 ) to serve as controls . Information on demographic , indications for extraction , and development of alveolar osteitis were obtained and analyzed . Comparative statistics were done using Pearson 's chi square or Fisher 's exact test as appropriate . A p value of less than 0.05 was considered significant . RESULTS The demographic and other baseline parameters such as indications for extractions were comparable among the study groups ( p > 0.05 ) . The overall prevalence of alveolar osteitis was 13.7 % . There was a statistical significant difference between the study groups with respect to development of alveolar osteitis ( X2 = 15.00 , df = 1 , p = 0.001 ) .The risk of development of alveolar osteitis was 4 times higher in the control group ( OR = 4.33 , P = 0.001 ) . CONCLUSION Warm saline mouth rinse instruction is beneficial in the prevention of development of alveolar osteitis after dental extractions .

warm saline mouth rinse

warm saline rinse

warm saline

control

gargle 6 times daily with warm saline

no such instructions

controls

Warm saline mouth rinse

alveolar osteitis :

prevention of alveolar osteitis

development of alveolar osteitis

overall prevalence of alveolar osteitis

alveolar osteitis

patients aged 16 and above

Oral Surgery Clinic

experimental group ( n = 80 )

second group ( n = 80 )


A randomised controlled comparison between stimulating and standard catheters for lumbar plexus block . The aim of this randomised , prospective , blinded study was to evaluate if stimulating catheters can decrease the minimum effective anaesthetic volume in 50 % of patients during lumbar plexus block using mepivacaine 1.5 % compared with standard catheters . Fifty-eight patients of ASA physical status 1-3 were randomly allocated to receive a lumbar plexus block via a stimulating or standard catheter , with 29 in each group . The first dose was 30 ml and subsequent doses were determined using the up-and-down staircase method . The minimum effective anaesthetic volume50 was 12.2 ml ( 95 % CI 7.3-17.1 ml ) using the stimulating catheter and 24.8 ml ( 95 % CI 23.2-27.5 ml ) with the standard catheter ( p < 0.0001 ) . Complete lumbar plexus block was achieved with the initial dose of mepivacaine in 29 ( 100 % ) patients in the stimulating catheter group and 20 ( 69 % ) patients in the standard catheter group ( p = 0.002 ) . This study showed that use of a stimulating catheter halves the minimum effective anaesthetic volume50 of mepivacaine 1.5 % while increasing the success rate in patients receiving continuous lumbar plexus block .

stimulating and

standard catheters

stimulating catheters

mepivacaine

standard catheters

standard catheter

lumbar plexus block .

minimum effective anaesthetic volume

effective anaesthetic volume50

Complete lumbar plexus block

success rate

patients during lumbar plexus block

Fifty-eight patients

lumbar plexus block

standard catheter


MDMA-assisted therapy : A new treatment model for social anxiety in autistic adults . The first study of 3,4-methylenedioxymethamphetamine ( MDMA ) -assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014 . The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population . Serious Adverse Events ( SAEs ) involving the administration of MDMA in clinical trials have been rare and non-life threatening . To date , MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations . Now that safety parameters for limited use of MDMA in clinical settings have been established , a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population . As in the case with classic hallucinogens and other psychedelic drugs , MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits . This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA , which may provide a significant advantage over medications that require daily dosing . Consequently , clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol .

MDMA-assisted therapy

MDMA

MDMA

MDMA

MDMA-assisted therapeutic interventions

MDMA

MDMA

MDMA

Serious Adverse Events ( SAEs )

unexpected drug-related SAEs

social adaptability

openness and introspection

adverse event frequency

the risk/benefit ratio of MDMA

social anxiety

social anxiety in autistic

MDMA has been administered

1133 individuals


Serotonergic psychedelics temporarily modify information transfer in humans . BACKGROUND Psychedelics induce intense modifications in the sensorium , the sense of " self , " and the experience of reality . Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs , knowledge of their actions on global brain dynamics is still incomplete . Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures , suggesting a modification in information flow between brain regions during acute effects . METHODS Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans . We measured modifications in connectivity of brain oscillations using transfer entropy , a nonlinear measure of directed functional connectivity based on information theory . Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions . They received a placebo or a dose of ayahuasca , a psychedelic preparation containing the serotonergic 5-HT2A agonist N , N-dimethyltryptamine . RESULTS The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites . Transfer entropy analysis showed that frontal sources decreased their influence over central , parietal , and occipital sites . Conversely , sources in posterior locations increased their influence over signals measured at anterior locations . Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects , while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced . CONCLUSIONS These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain .

Serotonergic psychedelics

Psychedelics

psychedelics

placebo

dose of ayahuasca

psychedelic

psychedelics

global brain dynamics

brain oscillations

anterior-to-posterior transfer entropy

anterior-to-posterior

posterior-to-anterior transfer entropy

temporary disruption

neural hierarchies

Ten

male

prior experience with psychedelics


Randomized comparative efficacy study of parent-mediated interventions for toddlers with autism . OBJECTIVE This study compared effects of two parent-mediated interventions on joint engagement outcomes as augmentations of an early intervention program for toddlers with autism spectrum disorder ( ASD ) . METHOD Participants included 86 toddlers ( range 22-36 months ) with ASD and their primary caregiver . Caregiver-child dyads were randomized to receive 10 weeks of hands-on parent training in a naturalistic , developmental behavioral intervention ( joint attention , symbolic play , engagement and regulation-JASPER ) or a parent-only psychoeducational intervention ( PEI ) . Dose was controlled in terms of researcher-parent contact and early intervention services received by the child . RESULTS Results yielded significant effects of the JASPER intervention on the primary outcome of joint engagement . The treatment effect was large ( Cohen 's f² = .69 ) and maintained over the 6-month follow-up . JASPER effects were also found on secondary outcomes of play diversity , highest play level achieved , and generalization to the child 's classroom for child-initiated joint engagement . The PEI intervention was found to be effective in reducing parenting stress associated with child characteristics . All secondary effects were generally small to moderate . CONCLUSIONS These data highlight the benefit of a brief , targeted , parent-mediated intervention on child outcomes . Future studies may consider the combination of JASPER and PEI treatments for optimal parent and child outcomes . Trial registry no . NCT00999778 .

parent-mediated interventions

parent-mediated interventions

or a

JASPER intervention

joint engagement

toddlers

autism

toddlers

autism spectrum disorder ( ASD )

toddlers ( range 22-36 months )

ASD


Subcutaneous versus intravenous bortezomib in two different induction therapies for newly diagnosed multiple myeloma : an interim analysis from the prospective GMMG-MM5 trial . We investigated the impact of subcutaneous versus intravenous bortezomib in the MM5 trial of the German-Speaking Myeloma Multicenter Group which compared bortezomib , doxorubicin , and dexamethasone with bortezomib , cyclophosphamide , and dexamethasone induction therapy in newly diagnosed multiple myeloma . Based on data from relapsed myeloma , the route of administration for bortezomib was changed from intravenous to subcutaneous after 314 of 604 patients had been enrolled . We analyzed 598 patients who received at least one dose of trial medication . Adverse events were reported more frequently in patients treated with intravenous bortezomib ( intravenous=65 % ; subcutaneous=56 % , P=0.02 ) . Rates of grade 2 or more peripheral neuropathy were higher in patients treated with intravenous bortezomib during the third cycle ( intravenous=8 % ; subcutaneous=2 % , P=0.001 ) . Overall response rates were similar in patients treated intravenously or subcutaneously . The presence of International Staging System stage III disease , renal impairment or adverse cytogenetic abnormalities did not have a negative impact on overall response rates in either group . To our knowledge this is the largest study to present data comparing subcutaneous with intravenous bortezomib in newly diagnosed myeloma . We show better tolerance and similar overall response rates for subcutaneous compared to intravenous bortezomib . The clinical trial is registered at eudract.ema.europa.eu as n. 2010-019173-16 .

bortezomib

doxorubicin

dexamethasone

bortezomib

cyclophosphamide

dexamethasone

Subcutaneous

intravenous bortezomib

subcutaneous

intravenous bortezomib

Adverse events

Rates of

grade 2 or more peripheral neuropathy

Overall response rates

myeloma

tolerance

response

newly diagnosed multiple myeloma

314 of 604 patients

598 patients

treated with intravenous bortezomib


Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease . Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance . Based on demonstrated pro-tolerogenic activity , sirolimus ( rapamycin ) is an agent with promise to achieve these goals . In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant , we examined the impact of prolonged sirolimus administration ( ≥ 1 year post-transplant ) . Median follow-up time for surviving patients at time of this analysis was 41 months ( range 27-60 ) for sirolimus/tacrolimus and 49 months ( range 29-63 ) for methotrexate/tacrolimus . Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease ( 34 % vs. 65 % ; P=0.004 ) and late acute graft-versus-host disease ( 20 % vs. 43 % ; P=0.04 ) . While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus ( median time to tacrolimus discontinuation 368 days vs. 821 days ; P=0.002 ) , there was no significant difference in complete immune suppression discontinuation ( 60-month estimate : 43 % vs. 31 % ; P=0.78 ) . Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versus-host disease . Further study of determinants of successful immune suppression discontinuation is needed .

sirolimus

sirolimus ( rapamycin )

sirolimus/tacrolimus

methotrexate/tacrolimus

sirolimus

chronic graft-versus-host disease .

post-transplant ) .

lower prednisone exposure

earlier discontinuation of tacrolimus


Coronary artery bypass graft surgery provides clinically important quality-of-life improvements over medical therapy in patients with ischaemic left ventricular dysfunction .

Coronary artery bypass graft surgery

quality-of-life improvements


1H nuclear magnetic resonance-based metabolomic study on efficacy of Qingrehuatan decoction against abundant phlegm-heat syndrome in young adults with essential hypertension . OBJECTIVE To observe the influence of Qingrehuatan decoction ( QRHT ) on serum metabolic profile in young essential hypertension ( YEH ) patients with abundant phlegm-heat syndrome and provide a basis for treatment with the decoction . METHODS Twelve male YEH patients were randomly selected and serum samples were collected for examination before and after 4 weeks of the treatment with QRHT . Twelve healthy males were randomly selected and their serum samples were collected as a control . All serum samples were detected using metabolomic technology with 1H nuclear magnetic resonance . Differences in metabolites were studied by principal component analysis and partial least squares-discriminate analysis , which produced scores and loadings plots . RESULTS After 4 weeks of treatment , serum substances could be distinguished between the YEH patients with abundant phlegm-heat syndrome and the control patients . The specific serum endog- enous metabolites tended to improve after the treatment . QRHT can appropriately increase the levels of glucose , lactic acid , citric acid , high-density lipoprotein , phosphatidylcholine , glycerophosphate choline , hydroxybutyrate , alanine , and glutamate . QRHT could also decrease the levels of low-density lipoprotein/very low-density lipoprotein , lipids , N-acetyl glycoprotein , and O-acetyl glycoprotein . CONCLUSION QRHT can effectively ameliorate metabolic disorders in YEH Patients with abundant phlegm-heat syndrome . 1H NMR-based metabolomic technology can provide an objective basis for the treatment of YEH patients with abundant phlegm-heat syndrome using QRHT .

Qingrehuatan decoction

Qingrehuatan decoction ( QRHT )

QRHT .

QRHT

QRHT

QRHT

efficacy

serum metabolic profile

serum endog- enous metabolites

metabolic disorders

young adults

hypertension

young

hypertension

abundant phlegm-heat syndrome

Twelve

male

Twelve

males

phlegm-heat syndrome


A Randomized Double Blind Clinical Trial on a Sabgh Formulation for Patients With Vitiligo . BACKGROUND The cosmetic problem that vitiligo produces affects patients psychologically . Many patients with vitiligo are suggested to cover their white skin patches with cosmetic products . There are formulations in traditional Iranian pharmacy to color these white skin patches . In this study , one of these formulations was compared with a cosmetic formulation . METHODS Two groups of patients were selected . One group used a marketed formulation and other group used a traditional Iranian Pharmacy formulation . The quality of life of the patients was compared based on the Dermatology Life Quality Index Questionnaire . RESULTS Both interventions were associated with statistically improved Dermatology Life Quality Index scores over the 8-week intervention ( P < .05 ) , although the difference between the 2 was not statistically significant ( P = .436 ) . CONCLUSION Traditional Iranian Pharmacy formulation is effective in increasing the quality of life in vitiligo patients .

Sabgh Formulation

formulations

cosmetic formulation

marketed formulation

Traditional Iranian Pharmacy

quality of life

Dermatology Life Quality Index scores

quality of life


Visual Assessment of Relative Apical Sparing Pattern Is More Useful Than Quantitative Assessment for Diagnosing Cardiac Amyloidosis in Borderline or Mildly Increased Left Ventricular Wall Thickness . BACKGROUND Relative apical sparing pattern of longitudinal strain ( RapSP-LS ) was suggested in advanced cardiac amyloidosis ( CA ) . It is unclear whether it is present in less advanced CA . METHODS AND RESULTS Patients with presumptive diagnosis of CA and mean left ventricular wall thickness ( LVWT ) ≤14 mm were recruited . Apart from RapSP-LS visually identified , relative apical longitudinal strain index ( RapLSI ) was defined as [ average apical LS/ ( average basal LS+average mid-ventricle LS ) ] . Among 119 patients included , 47 were finally diagnosed with CA . RapLSI was higher in the CA group compared to other causes of increased mean LVWT ( P < 0.001 ) , but with a significant range of overlap noted . In contrast , RapSP-LS visually assessed was noted in most CA patients ( 31/47 , 66.0 % ) except in those with preserved LV ejection fraction , normal LVWT , and mildly decreased global LS , suggesting least advanced CA . On multivariate analysis of the added diagnostic role of RapSP-LS or RapLSI on top of clinical , electrocardiographic , and conventional echocardiographic parameters , addition of RapLSI produced only borderline increase in area under the curve of the multivariate model ( P=0.05 ) , whereas addition of RapSP-LS significantly increased it ( P < 0.001 ) . CONCLUSIONS Visual identification of RapSP-LS is useful in terms of added diagnostic value compared with quantitative calculation of RapLSI . Its clinical application , however , should be used with caution in patients with less advanced CA .

( RapSP-LS )

CA . RapLSI

increased mean LVWT

added diagnostic value

CA

in patients with less advanced CA


The short-term effects of transcranial direct current stimulation on electroencephalography in children with autism : a randomized crossover controlled trial . Abnormal synaptic maturation and connectivity are possible etiologies of autism . Previous studies showed significantly less alpha activity in autism than normal children . Therefore , we studied the effects of anodal tDCS on peak alpha frequency ( PAF ) related to autism treatment evaluation checklist ( ATEC ) . Twenty male children with autism were randomly assigned in a crossover design to receive a single session of both active and sham tDCS stimulation ( 11 mA ) over F3 ( left dorsolateral prefrontal cortex ) . Pre- to postsession changes in a measure of cortical activity impacted by tDCS ( PAF ) and ATEC were compared between groups . We also examined the associations between pre- and postsession changes in the PAF and ATEC . The results show significant pre- to postsession improvements in two domains of ATEC ( social and health/behavior domains ) following active tDCS , relative to sham treatment . PAF also significantly increased at the stimulation site , and an increase in PAF was significantly associated with improvements in the two domains of ATEC impacted by tDCS . The findings suggest that a single session of anodal tDCS over the F3 may have clinical benefits in children with autism and that those benefits may be related to an increase in PAF .

transcranial direct current stimulation

anodal tDCS

active and sham tDCS stimulation

anodal tDCS

tDCS ( PAF )

ATEC

PAF

ATEC .

tDCS

PAF

increased

increase in PAF

ATEC

clinical benefits

PAF .

children

autism

autism

Twenty

male

children

autism


Oxytocin reduces caloric intake in men . OBJECTIVE Preclinical studies indicate that oxytocin is anorexigenic and has beneficial metabolic effects . Oxytocin effects on nutrition and metabolism in humans are not well defined . It was hypothesized that oxytocin would reduce caloric intake and appetite and alter levels of appetite-regulating hormones . Metabolic effects of oxytocin were also explored . METHODS A randomized , placebo-controlled crossover study of single-dose intranasal oxytocin ( 24 IU ) in 25 fasting healthy men was performed . After oxytocin/placebo , subjects selected breakfast from a menu and were given double portions . Caloric content of food consumed was measured . Visual analog scales were used to assess appetite , and blood was drawn for appetite-regulating hormones , insulin , and glucose before and after oxytocin/placebo . Indirect calorimetry assessed resting energy expenditure ( REE ) and substrate utilization . RESULTS Oxytocin reduced caloric intake with a preferential effect on fat intake and increased levels of the anorexigenic hormone cholecystokinin without affecting appetite or other appetite-regulating hormones . There was no effect of oxytocin on REE . Oxytocin resulted in a shift from carbohydrate to fat utilization and improved insulin sensitivity . CONCLUSIONS Intranasal oxytocin reduces caloric intake and has beneficial metabolic effects in men without concerning side effects . The efficacy and safety of sustained oxytocin administration in the treatment of obesity warrants investigation .

Oxytocin

oxytocin

Oxytocin

oxytocin

placebo-controlled

oxytocin/placebo

insulin

Oxytocin

Oxytocin

oxytocin

oxytocin

men .

fasting healthy

men

men


Peritoneovenous shunting as compared with medical treatment in patients with alcoholic cirrhosis and massive ascites . Veterans Administration Cooperative Study on Treatment of Alcoholic Cirrhosis with Ascites . The optimal management of severe ascites in patients with alcoholic cirrhosis has not been defined . in a 5 1/2-year study , we randomly assigned 299 men with alcoholic cirrhosis , who had persistent or recurrent severe ascites despite a standard medical regimen , to receive either intensive medical treatment or peritoneovenous ( LeVeen ) shunting . We identified three risk groups : Group 1 had normal or mildly abnormal results on liver-function tests , Group 2 had more severe liver dysfunction or previous complications , and Group 3 had severe prerenal azotemia without kidney disease . For the patients who received the medical treatment and those who received the surgical treatment combined , the median survival times were 1093 days in Group 1 , 222 days in Group 2 , and 37 days in Group 3 ( P less than or equal to 0.01 ) for all comparisons ) . For all the groups combined , the median time to the resolution of ascites was 5.4 weeks for medical patients and 3.0 weeks for surgical patients ( P less than 0.01 ) . Within each risk group , mortality during the initial hospitalization and median long-term survival were similar among patients receiving either treatment . However , the median time to the recurrence of ascites in Group 1 was 4 months in medical patients , as compared with 18 months in surgical patients ( P = 0.01 ) ; in Group 2 it was 3 months in medical patients as compared with 12 months in surgical patients ( P = 0.04 ) . The median duration of hospitalization was longer in medical patients than in surgical patients ( 6.1 vs. 2.4 weeks in Group 1 [ P less than 0.001 ] and 5.0 vs. 3.1 weeks in Group 2 [ P less than 0.01 ] ) . Group 3 was too small to permit a meaningful comparison . During the initial hospitalization , the incidence of infections , gastrointestinal bleeding , and encephalopathy was similar among the medical and surgical patients . We conclude that peritoneovenous shunting alleviated disabling ascites more rapidly than medical management . However , survival was closely related to the severity of the illness at the time of randomization and was not altered by shunting .

Peritoneovenous shunting

medical treatment

intensive medical treatment

peritoneovenous ( LeVeen ) shunting

mortality

median long-term survival

recurrence of ascites

median duration of hospitalization

disabling ascites

survival

patients with alcoholic cirrhosis


A Regulated Trial of Bicuspid Aortic Valve Repair Supported by Geometric Ring Annuloplasty . BACKGROUND Annular stabilization is important during bicuspid aortic valve ( BAV ) repair to obtain the best long-term results . This report describes the early outcomes of a novel bicuspid annuloplasty ring for this purpose . METHODS Under regulatory supervision ( NCT02071849 ) , a geometric bicuspid annuloplasty ring was used during valve repair in 16 patients . Three patients had Sievers type 0 valves , 11 had Sievers type 1 , and 2 had Sievers type 2 . Thirteen patients had left-/right-coronary cusp fusion , 1 had right-/noncoronary cusp fusion , and 2 had both . Moderate to severe aortic insufficiency ( AI ) was present in 13 of 16 patients , and 3 had mild AI with aortic aneurysms . Ascending aortic aneurysms , root aneurysms , or both were replaced in 7 of 16 patients . The Dacron-covered titanium ring had circular base geometry and two outwardly flaring subcommissural posts positioned opposite on the circumference . The ring was implanted into the annulus beneath the valve , and then leaflet repair was performed . RESULTS Immediate postrepair echocardiograms showed grade 0 residual AI in all patients , with good cusp mobility and effective height , and satisfactory gradients . There were no in-hospital or late mortalities . Two patients experienced leaflet tears from long annular suture tails , requiring late valve replacement . After implementation of a lateral suture fixation technique , no more failures occurred . At a mean follow-up time of 9 months , the remaining 14 patients were in New York Heart Association class I , with predominant grade 0 AI . CONCLUSIONS As a technique for BAV repair , internal ring annuloplasty produces major annular remodeling and stabilization . Annular reduction and reshaping to a 50/50 % symmetric circular geometry facilitates leaflet repair and enhances cusp coaptation . Geometric ring annuloplasty could have useful applications in BAV repair .

Geometric Ring Annuloplasty

geometric bicuspid annuloplasty ring

Dacron-covered titanium ring

no in-hospital or late mortalities

experienced leaflet tears

requiring late valve replacement

more failures

in New York Heart Association class

predominant grade 0 AI

valve repair

Three patients

Thirteen patients


Fall rates in hospital rehabilitation units after individualised patient and staff education programmes : a pragmatic , stepped-wedge , cluster-randomised controlled trial . BACKGROUND Falls are the most frequent adverse events that are reported in hospitals . We examined the effectiveness of individualised falls-prevention education for patients , supported by training and feedback for staff , delivered as a ward-level programme . METHODS Eight rehabilitation units in general hospitals in Australia participated in this stepped-wedge , cluster-randomised study , undertaken during a 50 week period . Units were randomly assigned to intervention or control groups by use of computer-generated , random allocation sequences . We included patients admitted to the unit during the study with a Mini-Mental State Examination ( MMSE ) score of more than 23/30 to receive individualised education that was based on principles of changes in health behaviour from a trained health professional , in addition to usual care . We provided information about patients ' goals , feedback about the ward environment , and perceived barriers to engagement in falls-prevention strategies to staff who were trained to support the uptake of strategies by patients . The coprimary outcome measures were patient rate of falls per 1000 patient-days and the proportion of patients who were fallers . All analyses were by intention to treat . This trial is registered with the Australian New Zealand Clinical Trials registry , number ACTRN12612000877886 ) . FINDINGS Between Jan 13 , and Dec 27 , 2013 , 3606 patients were admitted to the eight units ( n=1983 control period ; n=1623 intervention period ) . There were fewer falls ( n=196 , 7·80/1000 patient-days vs n=380 , 13·78/1000 patient-days , adjusted rate ratio 0·60 [ robust 95 % CI 0·42-0·94 ] , p=0·003 ) , injurious falls ( n=66 , 2·63/1000 patient-days vs 131 , 4·75/1000 patient-days , 0·65 [ robust 95 % CI 0·42-0·88 ] , p=0·006 ) , and fallers ( n=136 [ 8·38 % ] vs n=248 [ 12·51 % ] adjusted odds ratio 0·55 [ robust 95 % CI 0·38 to 0·81 ] , p=0·003 ) in the intervention compared with the control group . There was no significant difference in length of stay ( intervention median 11 days [ IQR 7-19 ] , control 10 days [ 6-18 ] ) . INTERPRETATION Individualised patient education programmes combined with training and feedback to staff added to usual care reduces the rates of falls and injurious falls in older patients in rehabilitation hospital-units . FUNDING State Health Research Advisory Council , Department of Health , Government of Western Australia .

training and feedback for staff

control

individualised education

Fall rates

health behaviour

falls

significant difference

hospital rehabilitation units

Eight

Mini-Mental State Examination ( MMSE


Feasibility of a sensory-adapted dental environment for children with autism . OBJECTIVE To provide an example of an occupational therapy feasibility study and evaluate the implementation of a randomized controlled pilot and feasibility trial examining the impact of a sensory-adapted dental environment ( SADE ) to enhance oral care for children with autism spectrum disorder ( ASD ) . METHOD Twenty-two children with ASD and 22 typically developing children , ages 6-12 yr , attended a dental clinic in an urban hospital . Participants completed two dental cleanings , 3-4 mo apart , one in a regular environment and one in a SADE . Feasibility outcome measures were recruitment , retention , accrual , dropout , and protocol adherence . Intervention outcome measures were physiological stress , behavioral distress , pain , and cost . RESULTS We successfully recruited and retained participants . Parents expressed satisfaction with research study participation . Dentists stated that the intervention could be incorporated in normal practice . Intervention outcome measures favored the SADE condition . CONCLUSION Preliminary positive benefit of SADE in children with ASD warrants moving forward with a large-scale clinical trial .

two dental cleanings

3-4 mo apart

children

autism

children

autism spectrum disorder ( ASD ) .

Twenty-two

ASD

children

ages 6-12 yr

children

ASD


Effect of cool vs. warm dialysate on toxin removal : rationale and study design . BACKGROUND Cool dialysate is often recommended for prevention of intra-dialytic hypotensive episodes in maintenance hemodialysis ( HD ) patients . However , its effect on toxin removal is not studied . It is known that inter-compartmental resistance is the main barrier for toxin removal . Cool dialysate can potentially increase this resistance by vasoconstriction and thus impair the toxin removal . The aim of this trial is to compare the toxin removal outcome associated with cool vs. warm dialysate . METHOD/DESIGN This study is based on the hypothesis that dialysate temperature , a potential maneuver to maintain hemodynamic stability during HD , may influence inter-compartmental resistance and hence , toxin removal . Only stable HD patients will be recruited for this study . The quantum of removed toxins will be assessed by the total spent dialysate , which is a gold standard to quantify the efficacy of a single dialysis session . Collected samples will be analyzed for urea , creatinine , phosphate , β2-microglobulin , and uric acid . The study is a single center , self-controlled , randomized prospective clinical research where 20 study subjects will undergo 2 dialysis sessions : ( a ) cool dialysis with dialysate at 35.5°C , and ( b ) warm dialysis with dialysate at 37°C . Pre- and post-dialysis blood samples will be collected to quantify the dialysis adequacy and toxin reduction ratio . DISCUSSION This is the first clinical research to investigate the effect of dialysate temperature on removal of both small and large-sized toxins . Successful completion of this research will provide important knowledge pertaining to dialysate temperature prescription . Results can also lead to the hypothesis that cool dialysate may help in by preventing intra-dialytic hypotensive episodes , but prolonged prescription of cool dialysate may lead to comorbidities associated with excess toxin accumulation . The new knowledge will encourage for personalized dialysate temperature profiling . TRIAL REGISTRATION Clinicaltrials.gov Identifier -- NCT02064153 .

cool

warm dialysate

Cool dialysate

Cool dialysate

cool

warm dialysate

toxin removal

Only stable HD patients


Femoral neck osteotomy guide for total hip arthroplasty . BACKGROUND Total hip arthroplasty ( THA ) is a common last-resort treatment for hip disease , but postoperative patients often complain of discrepancies in leg length . This study introduces a device designed to increase the precision of the femoral neck osteotomy and reduce the incidence of leg length discrepancy . METHODS Forty-eight patients undergoing THA were divided into two groups , with and without the use of the femoral osteotomy guide . All operations were performed through a posterolateral approach . Differences in leg length were recorded before and after the operation . Measurements were also made to compare the preoperative plan with the actual amount of bone removed . RESULTS The mean average difference in femoral neck resection height was 0.84 mm when using the osteotomy guide and 1.69 mm without the guide . Discrepancies in postoperative leg length were 5.45 mm and 13.37 mm in the groups with and without the guide , respectively . CONCLUSION The femoral neck osteotomy guide is an effectively auxiliary tool for increasing the accuracy of bone resection in arthroplasty using the posterolateral approach . TRIAL REGISTRATION ChiCTR-OOC-15005904 ; date : 2015-01-30 .

Total hip arthroplasty ( THA )

THA

femoral osteotomy guide

precision of the femoral neck osteotomy

leg length discrepancy

Differences in leg length

actual amount of bone removed .

guide .

accuracy of bone resection

total hip arthroplasty

postoperative

Forty-eight


Effect of enzalutamide on health-related quality of life , pain , and skeletal-related events in asymptomatic and minimally symptomatic , chemotherapy-naive patients with metastatic castration-resistant prostate cancer ( PREVAIL ) : results from a randomised , phase 3 trial . BACKGROUND Enzalutamide significantly increased overall survival and radiographic progression-free survival compared with placebo in the PREVAIL trial of asymptomatic and minimally symptomatic , chemotherapy-naive patients with metastatic castration-resistant prostate cancer . We report the effect of enzalutamide on health-related quality of life ( HRQoL ) , pain , and skeletal-related events observed during this trial . METHODS In this phase 3 , double-blind trial , patients were randomly assigned ( 1:1 ) to receive enzalutamide 160 mg/day ( n=872 ) or placebo ( n=845 ) orally . HRQoL was assessed at baseline and during treatment using the Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) and EQ-5D questionnaires . Pain status was assessed at screening , baseline , week 13 , and week 25 with the Brief Pain Inventory Short Form ( BPI-SF ) . The primary analysis of HRQoL data used a mixed-effects model to test the difference between least square means change from baseline at week 61 . We assessed change from baseline , percentage improvement , and time to deterioration in HRQoL and pain , the proportion of patients with a skeletal-related event , and time to first skeletal-related event . Analysis was done on the intention-to-treat population . This study is registered with ClinicalTrials.gov , number NCT01212991 . FINDINGS Median treatment duration was 16·6 months ( IQR 10·1-21·1 ) in the enzalutamide group and 4·6 months ( 2·8-9·7 ) in the placebo group . The mixed-effects model analyses showed significant treatment differences in change from baseline to week 61 with enzalutamide compared with placebo for most FACT-P endpoints and EQ-5D visual analogue scale . Median time to deterioration in FACT-P total score was 11·3 months ( 95 % CI 11·1-13·9 ) in the enzalutamide group and 5·6 months ( 5·5-5·6 ) in the placebo groups ( hazard ratio [ HR ] 0·62 [ 95 % CI 0·54-0·72 ] ; p < 0·0001 ) . A significantly greater proportion of patients in the enzalutamide group than in the placebo group reported clinically meaningful improvements in FACT-P total score ( 327 [ 40 % ] of 826 vs 181 [ 23 % ] of 790 ) , in EQ-5D utility index ( 224 [ 28 % ] of 812 vs 99 [ 16 % ] of 623 ) , and visual analogue scale ( 218 [ 27 % ] of 803 vs 106 of [ 18 % ] 603 ; all p < 0·0001 ) . Median time to progression in BPI-SF pain at its worst was 5·7 months ( 95 % CI 5·6-5·7 ) in the enzalutamide group and 5·6 months ( 5·4-5·6 ) in the placebo group ( HR 0·62 [ 95 % CI 0·53-0·74 ] ; p < 0·0001 ) . Progression of pain at its worst was less common in the enzalutamide group than in the placebo group at week 13 ( 220 [ 29 % ] of 769 vs 257 [ 42 % ] of 610 ; p < 0·0001 ) , but not at week 25 ( 225 [ 32 % ] of 705 vs 135 [ 38 % ] of 360 ; p=0·068 ) . 278 ( 32 % ) of 872 patients in the enzalutamide group and 309 ( 37 % ) of 845 patients in the placebo group had experienced a skeletal-related event by data cutoff . Median time to first skeletal-related events in the enzalutamide group was 31·1 months ( 95 % CI 29·5-not reached ) and 31·3 months ( 95 % CI 23·9-not reached ) in the placebo group ( HR 0·72 [ 95 % CI 0·61-0·84 ] ; p < 0·0001 ) . INTERPRETATION In addition to improving overall survival relative to placebo , enzalutamide significantly improves patient-related outcomes and delays occurrence of first skeletal-related event in chemotherapy-naive men with metastatic castration-resistant prostate cancer . FUNDING Astellas Pharma and Medivation .

enzalutamide

Enzalutamide

placebo

enzalutamide

enzalutamide 160 mg/day

or placebo

overall survival

radiographic progression-free survival

pain

skeletal-related events

HRQoL

Pain status

primary analysis of HRQoL data

change from baseline

percentage improvement

time to deterioration in HRQoL and pain

time to first skeletal-related event

Median treatment duration

significant treatment differences

improvements in FACT-P

[ 23 % ] of 790 ) , in EQ-5D

[ 16 % ] of 623 ) , and visual

603 ; all p < 0·0001 )

CI 0·53-0·74 ] ; p < 0·0001 )

placebo group had experienced

skeletal-related event by data cutoff

Median time to first

INTERPRETATION In addition

asymptomatic and minimally symptomatic

or

men

with metastatic


Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy ( LUX-Head & Neck 1 ) : an open-label , randomised phase 3 trial . BACKGROUND Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck ( HNSCC ) progressing after first-line platinum regimens have a poor prognosis and few treatment options . Afatinib , an irreversible ERBB family blocker , has shown efficacy in a phase 2 study in this setting . We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy . METHODS In this open-label , phase 3 , randomised controlled trial conducted in 101 centres in 19 countries , we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent , metastatic , or both who had progressed on or after first-line platinum-based therapy , were not amenable for salvage surgery or radiotherapy , and who had an Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 or 1 . Previous treatment with more than one systemic regimen in this setting was not allowed ; previous treatment with EGFR-targeted antibody therapy ( but not EGFR-targeted tyrosine-kinase inhibitors ) was allowed . We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib ( 40 mg/day ) or intravenous methotrexate ( 40 mg/m ( 2 ) per week ) , stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease . Randomisation was done centrally with an interactive voice or web-based response system . Clinicians and patients were not masked to treatment allocation ; independent review of tumour response was done in a blinded manner . The primary endpoint was progression-free survival as assessed by an independent , central imaging review committee . Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug . This ongoing study is registered with ClinicalTrials.gov , number NCT01345682 . FINDINGS Between Jan 10 , 2012 , and Dec 12 , 2013 , we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate . After a median follow-up of 6·7 months ( IQR 3·1-9·0 ) , progression-free survival was longer in the afatinib group than in the methotrexate group ( median 2·6 months [ 95 % CI 2·0-2·7 ] for the afatinib group vs 1·7 months [ 1·5-2·4 ] for the methotrexate group ; hazard ratio [ HR ] 0·80 [ 95 % CI 0·65-0·98 ] , p=0·030 ) . The most frequent grade 3 or 4 drug-related adverse events were rash or acne ( 31 [ 10 % ] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group ) , diarrhoea ( 30 [ 9 % ] vs three [ 2 % ] ) , stomatitis ( 20 [ 6 % ] vs 13 [ 8 % ] ) , fatigue ( 18 [ 6 % ] vs five [ 3 % ] ) , and neutropenia ( 1 [ < 1 % ] vs 11 [ 7 % ] ) ; serious adverse events occurred in 44 ( 14 % ) of afatinib-treated patients and 18 ( 11 % ) of methotrexate-treated patients . INTERPRETATION Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile . These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC . FUNDING Boehringer Ingelheim .

Afatinib

methotrexate

Afatinib

afatinib

methotrexate

oral afatinib ( 40 mg/day )

intravenous methotrexate

afatinib

methotrexate .

progression-free survival

Efficacy analyses

safety analyses


Icosapent Ethyl ( Eicosapentaenoic Acid Ethyl Ester ) : Effects Upon High-Sensitivity C-Reactive Protein and Lipid Parameters in Patients With Metabolic Syndrome . BACKGROUND The aim of this analysis was to examine the effects of icosapent ethyl ( eicosapentaenoic acid ethyl ester , IPE ) on high-sensitivity C-reactive protein ( hsCRP ) and lipid parameters in patients with metabolic syndrome , with and without stable statin therapy . METHODS This post hoc exploratory analysis evaluated patients with metabolic syndrome treated with IPE 4 grams/day , IPE 2 grams/day , or placebo in phase 3 , randomized , placebo-controlled studies entitled : MARINE [ triglyceride ( TG ) levels ≥500 and ≤2000 mg/dL ] and ANCHOR [ TG levels ≥200 and < 500 mg/dL , despite low-density lipoprotein cholesterol ( LDL-C ) control with stable statin therapy ] . RESULTS Compared with placebo in patients with metabolic syndrome in MARINE ( n=204 ) and ANCHOR ( n=645 ) , at the approved dose of 4 grams/day , IPE significantly lowered hsCRP levels 40.0 % ( P=0.0007 ) in MARINE and 23.0 % ( P=0.0003 ) in ANCHOR . Compared with placebo in MARINE , which included patients with and without statin therapy , IPE 4 grams/day significantly reduced hsCRP levels 78.0 % in statin-treated patients ( P=0.0035 , n=16 ) . Compared with placebo in MARINE , IPE 4 grams/day significantly reduced TG levels ( 35.0 % ; P < 0.0001 ) , non-high-density lipoprotein cholesterol ( non-HDL-C ; 19.9 % ; P < 0.0001 ) , and apolipoprotein B levels ( ApoB ) ( 9.1 % ; P=0.0015 ) without raising LDL-C levels . Compared with placebo in ANCHOR , IPE 4 grams/day significantly reduced TG ( 21.7 % ; P < 0.0001 ) , non-HDL-C ( 13.5 % ; P < 0.0001 ) , ApoB ( 8.8 % ; P < 0.0001 ) , LDL-C ( 5.2 % ; P=0.0236 ) , and HDL-C levels ( 4.0 % ; P=0.0053 ) . CONCLUSIONS Compared with placebo , IPE 4 grams/day significantly lowered hsCRP levels and improved lipids without raising LDL-C levels in patients with metabolic syndrome and high ( ≥200 and < 500 mg/dL ) or very high ( ≥500 and ≤2000 mg/dL ) TG levels , with or without stable statin therapy .

IPE

placebo

significantly lowered hsCRP

significantly reduced hsCRP

apolipoprotein

raising LDL-C

Patients With Metabolic Syndrome

metabolic syndrome

metabolic syndrome


Effect of parent training vs parent education on behavioral problems in children with autism spectrum disorder : a randomized clinical trial . IMPORTANCE Disruptive behavior is common in children with autism spectrum disorder . Behavioral interventions are used to treat disruptive behavior but have not been evaluated in large-scale randomized trials . OBJECTIVE To evaluate the efficacy of parent training for children with autism spectrum disorder and disruptive behavior . DESIGN , SETTING , AND PARTICIPANTS This 24-week randomized trial compared parent training ( n = 89 ) to parent education ( n = 91 ) at 6 centers ( Emory University , Indiana University , Ohio State University , University of Pittsburgh , University of Rochester , Yale University ) . We screened 267 children ; 180 children ( aged 3-7 years ) with autism spectrum disorder and disruptive behaviors were randomly assigned ( 86 % white , 88 % male ) between September 2010 and February 2014 . INTERVENTIONS Parent training ( 11 core , 2 optional sessions ; 2 telephone boosters ; 2 home visits ) provided specific strategies to manage disruptive behavior . Parent education ( 12 core sessions , 1 home visit ) provided information about autism but no behavior management strategies . MAIN OUTCOMES AND MEASURES Parents rated disruptive behavior and noncompliance on co-primary outcomes : the Aberrant Behavior Checklist-Irritability subscale ( range , 0-45 ) and the Home Situations Questionnaire-Autism Spectrum Disorder ( range , 0-9 ) . On both measures , higher scores indicate greater severity and a 25 % reduction indicates clinical improvement . A clinician blind to treatment assignment rated the Improvement scale of the Clinical Global Impression ( range , 1-7 ) , a secondary outcome , with a positive response less than 3 . RESULTS At week 24 , the Aberrant Behavior Checklist-Irritability subscale declined 47.7 % in parent training ( from 23.7 to 12.4 ) compared with 31.8 % for parent education ( 23.9 to 16.3 ) ( treatment effect , -3.9 ; 95 % CI , -6.2 to -1.7 ; P < .001 , standardized effect size = 0.62 ) . The Home Situations Questionnaire-Autism Spectrum Disorder declined 55 % ( from 4.0 to 1.8 ) compared with 34.2 % in parent education ( 3.8 to 2.5 ) ( treatment effect , -0.7 ; 95 % CI , -1.1 to -0.3 ; P < .001 , standardized effect size = 0.45 ) . Neither measure met the prespecified minimal clinically important difference . The proportions with a positive response on the Clinical Global Impression-Improvement scale were 68.5 % for parent training vs 39.6 % for parent education ( P < .001 ) . CONCLUSIONS AND RELEVANCE For children with autism spectrum disorder , a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes , although the clinical significance of the improvement is unclear . The rate of positive response judged by a blinded clinician was greater for parent training vs parent education . TRIAL REGISTRATION clinicaltrials.gov Identifier : NCT01233414 .

parent training

parent education

parent training

behavioral problems

children

autism spectrum disorder

children

autism spectrum disorder

autism spectrum disorder

disruptive behavior

parent

n = 89 )

parent

education ( n = 91

267 children

180 children

aged 3-7 years

autism spectrum disorder

children


Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man . 1 . Effects of a single intravenous dose of aspirin ( 600 mg ) on bradykinin-stimulated prostaglandin ( PG ) and on thromboxane ( TX ) biosynthesis were determined in nine healthy male volunteers . Plasma concentrations of 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha were measured in samples obtained during repeated 10 min intravenous infusions of bradykinin before and up to 6 h after the dose of aspirin . TXB2 was measured in serum from blood allowed to clot at 37 degrees C. 2 . Aspirin inhibited bradykinin stimulated PG and platelet TX biosynthesis 0.5 h after the dose . Serum TXB2 remained low , whereas PG synthesis recovered within 6 h. 3 . Effects of intravenous sodium salicylate ( 600 mg ) were studied identically in eight subjects . Prostanoid biosynthesis was not inhibited . 4 . Biosynthesis of prostacyclin and TXA2 under basal conditions was studied in eight subjects by measuring 2,3-dinor-6-oxo-PGF1 alpha and 2,3-dinor-TXB2 in hourly urine samples obtained during and after intravenous infusion of aspirin and , on a separate occasion , of vehicle . 5 . Aspirin infusion reduced urinary excretion of both metabolites greater than 90 % , but excretion of 2,3-dinor-6-oxo-PGF1 alpha recovered more rapidly than did that of 2,3-dinor-TXB2 . 6 . We conclude that cyclo-oxygenase is rapidly synthesised in bradykinin-responsive tissues in vivo and that this reflects similarly rapid enzyme biosynthesis in tissues that produce PGI2 under basal conditions .

aspirin

aspirin

aspirin

Aspirin

intravenous sodium salicylate

infusion of aspirin

Aspirin infusion

TXB2 was measured in serum

Serum TXB2 remained low

PG synthesis recovered

Prostanoid biosynthesis

Biosynthesis of prostacyclin and TXA2

2,3-dinor-6-oxo-PGF1 alpha

urinary excretion

man

nine

healthy

male


Effect of cooling proparacaine 0.5 % eye drops on patient 's comfort during instillation .

proparacaine 0.5 % eye drops

Effect of cooling

patient 's comfort


Investigating a Multimodal Intervention for Children With Limited Expressive Vocabularies Associated With Autism . PURPOSE This study investigated a new intervention package aimed at increasing expressive word learning by school-age children with autism who have limited expressive vocabularies . This pilot investigation was intended to show proof of concept . METHOD Ten children between the ages of 6 and 10 years participated , with educational diagnoses of autism and limited expressive vocabularies at the outset of the study . A multimodal intervention composed of speech sound practice and augmentative and alternative communication was used to teach individualized vocabulary words that were selected on the basis of initial speech sound repertoires and principles of phonotactic probability and neighborhood density . A multiple-probe design was used to evaluate learning outcomes . RESULTS Five children showed gains in spoken-word learning across successive word sets ( high responders ) . Five children did not meet learning criteria ( low responders ) . Comparisons of behaviors measured prior to intervention indicated that high responders had relatively higher skills in receptive language , prelinguistic communication , vocal/verbal imitation , adaptive behavior , and consonant productions . CONCLUSIONS The intervention package holds promise for improving spoken word productions for some children with autism who have limited expressive vocabularies . Further research is needed to better describe who may most benefit from this approach as well as investigate generalized benefits to untaught contexts and targets .

Multimodal Intervention

multimodal intervention

speech sound practice

intervention package

Children

Limited Expressive Vocabularies

Autism

school-age children

Ten

autism

children

children

children

autism


Effects of the Quest to Lava Mountain Computer Game on Dietary and Physical Activity Behaviors of Elementary School Children : A Pilot Group-Randomized Controlled Trial . BACKGROUND Computer-based educational games present an opportunity for health education in school ; however , their feasibility in school settings and effectiveness in changing behavior are poorly understood . OBJECTIVE To evaluate the feasibility , acceptability , and effects of the Quest to Lava Mountain ( QTLM ) computer game on dietary behaviors , physical activity behaviors , and psychosocial factors among ethnically diverse children in Texas . DESIGN Quasi-experimental group-randomized controlled trial conducted during the 2012-2013 school year . PARTICIPANTS/SETTING A total of 107 children in fourth and fifth grade consented . There was an attrition rate of 8.8 % with a final sample size of 44 children in three intervention schools , and a sample of 50 children in three comparison schools . Dietary intake was measured using two random 24-hour recalls , whereas child self-report surveys measured diet , physical activity , and psychosocial factors before and after the intervention . Process data on QTLM usability and back-end server data on QTLM exposure and progress achieved were collected . INTERVENTION QTLM was implemented as part of the in-school or afterschool program . Recommended game exposure duration was 90 min/wk for 6 weeks . STATISTICAL ANALYSIS Analysis of covariance or logistic regression models evaluated effects of QTLM on diet , physical activity , and psychosocial factors . Post hoc exploratory analysis examined the changes before and after the intervention in outcome variables among children in the intervention group . Significance was set at P < 0.05 . RESULTS Children played an average of 274±110 minutes ( approximately 4.6 hours ) of QTLM during the 6 weeks ( 51 % of recommended dosage ) . Compared with the comparison group , children in the intervention group reported decreased sugar consumption ( P=0.021 ) and higher nutrition/physical activity attitudes ( P=0.041 ) pre- to postintervention . There were no significant effects of QTLM on physical activity . However , post hoc analysis showed that higher QTLM exposure and gaming progress was associated with increased frequency of physical activity ( P < 0.05 ) . CONCLUSIONS QTLM has some promising acceptability and initial effects on diet and physical activity behaviors among children in elementary school .

Quest to Lava Mountain Computer Game

Computer-based educational games

QTLM

QTLM

QTLM

QTLM

QTLM

QTLM

Dietary and Physical Activity Behaviors

dietary behaviors

physical activity behaviors

psychosocial factors

diet

physical activity

psychosocial factors

diet

physical activity

psychosocial factors

sugar consumption

nutrition/physical activity attitudes

physical activity

diet

physical activity behaviors

Children

children

children

children

children


Peritonsillar infiltration with levobupivacaine for posttonsillectomy pain relief : does concentration have any effect ? A double-blind randomized controlled clinical study . OBJECTIVE Post-tonsillectomy pain is believed to be mediated by noxious stimulation of C-fiber afferents located in the peritonsillary space , and local anesthetic infiltration to this area may decrease pain by blocking the sensory pathways and thus preventing the nociceptive impulses . We aimed to compare the effects of different concentrations of preincisional peritonsillar levobupivacaine ( 0.25 % and 0.5 % ) infiltration on postoperative pain and bleeding in a placebo-controlled design . PATIENTS AND METHODS After obtaining Institutional Ethics Committee approval , 72 ASA I-II patients between 3 and 12 years of age , scheduled to undergo tonsillectomy were enrolled and randomly assigned to one of the three groups using the sealed envelope technique , as Group I ( Control group ) , Group II , and Group III receiving preincisional bilateral peritonsillar infiltration with saline , 0.25 % levobupivacaine and 0.5 % levobupivacaine , respectively ( 3 mL to each tonsil ) . Pain , fever , dysphagia ; nausea-vomiting and hemorrhage were evaluated at postoperative 0 , 30 , and 60 minutes and 2 , 6 , 12 , and 24 hours . Oral paracetamol was administered at a dose of 15 mg/kg when FLACC score was > 4 . The number of paracetamol administrations within the first 24 hours were recorded . RESULTS The patients in Groups I , II and III defined pain ( FLACC > 4 ) at a rate of 87 % , 60.9 % , and 54.2 % within the postoperative first 24 hours , respectively . The total number of additional analgesic requirements was significantly low in Group II and III when compared with Group I . There was no difference between groups in terms of fever , dysphagia , nausea-vomiting , hemorrhage . CONCLUSIONS Both concentrations ( 0.50 % and 0.25 % ) of levobupivacaine were found to be equally safe and effective during preincisional peritonsillar infiltration in children . NCT number : 02322346 .

levobupivacaine

peritonsillar levobupivacaine

placebo-controlled

Control group

0.25 % levobupivacaine

0.5 % levobupivacaine

Oral paracetamol

paracetamol

analgesic

levobupivacaine

pain relief :

postoperative pain and bleeding

Pain

fever

dysphagia

nausea-vomiting

number of paracetamol administrations

pain

additional analgesic requirements

fever

dysphagia

nausea-vomiting

hemorrhage

safe and effective

posttonsillectomy pain

Post-tonsillectomy pain

between 3 and 12 years of age

children


Indicators for Cervical Length in Twin Pregnancies . OBJECTIVE Cervical length ( CL ) is associated with the risk of preterm birth ( PTB ) in multiple pregnancies . However , the position of CL within the pathophysiological pathway of PTB is unclear , and it is unknown which factors are predictive for CL . This study aims to investigate whether in twin pregnancies baseline maternal and obstetrical characteristics are potential indicators for CL , to improve insight in the pathophysiological pathway of PTB . STUDY DESIGN Secondary analysis of data on twin pregnancies and CL measurement between 16 and 22 weeks . A set of 10 potential indicators , known to be associated with an increased risk of PTB and/or which have a plausible mechanism resulting in a change of CL were selected . We used multivariable linear regression with backward selection to identify independent indicators for CL . RESULTS A total of 1,447 women with twin pregnancies were included . Mean CL was 43.7 ( ±8.9 ) mm . In multivariable analysis , age ( 0.27 mm/y ; 95 % confidence interval [ CI ] 0.16 to 0.39 ) , use of assisted reproductive technologies ( ART ) ( -1.42 mm , 95 % CI -2.6 to -0.25 ) , and having delivered at term in a previous pregnancy ( 1.32 mm , 95 % CI 0.25 to 2.39 ) were significantly associated with CL . CONCLUSION This study shows that in twin pregnancies , age , use of ART and having delivered term in a previous pregnancy has an association with CL .

CL measurement

Cervical length ( CL )

CL .

CL

analysis of data on twin pregnancies

CL measurement

a change of CL

indicators for CL .

Mean CL

twin pregnancies

women

twin pregnancies

that in twin pregnancies


The impact of amalgam dental fillings on the frequency of Helicobacter pylori infection and H. pylori eradication rates in patients treated with concomitant , quadruple , and levofloxacin-based therapies . BACKGROUND AND AIM Mercury exposure is encountered most commonly in individuals with amalgam fillings . The toxic , bactericidal , and immunosuppressive effects of mercury are well known . Furthermore , multiple antibiotic resistance can be transferred , together with mercury resistance . The aim of this study was to investigate the frequency of Helicobacter pylori infection in dyspeptic patients with amalgam fillings and the effect of the amalgam fillings on H. pylori eradication rates in these patients . PATIENTS AND METHODS Four hundred and seventy-five patients who presented with dyspeptic complaints and underwent upper gastrointestinal endoscopy and gastric biopsy were included in this study . One hundred and sixty-nine ( 35.6 % ) patients were negative and 306 ( 64.4 % ) patients were positive for H. pylori . All of the participants underwent dental examinations in a blinded manner . The participants were divided into two groups on the basis of the presence of amalgam fillings . The H. pylori-positive patients were divided randomly into three subgroups : patients who received concomitant therapy ( CT ) ( rabeprazole-amoxicillin-clarithromycin-metronidazole for 14 days ; n=122 ) ; patients who received quadruple therapy ( QT ) ( rabeprazole-tetracycline-metronidazole-colloidal bismuth subcitrate for 10 days ; n=97 ) ; and patients who received levofloxacin-based therapy ( LT ) ( rabeprazole-amoxicillin-levofloxacin for 10 days ; n=87 ) . Eradication success was detected by a urea breath test 6 weeks after the end of treatment . RESULTS The frequency of H. pylori infection was significantly lower in the filling group compared with the nonfilling group ( 53.7 and 78.8 % , respectively ; P < 0.001 ) . The eradication rates in the CT , QT , and LT groups were 65.5 , 67.0 , and 58.6 % , respectively , in the intention-to-treat ( ITT ) analysis and 69.6 , 70.7 , and 62.2 % , respectively , in the per-protocol ( PP ) analysis . In all of the H. pylori-positive patients and separately in the CT and LT groups , the eradication rates were significantly lower in the filling group compared with the nonfilling group . However , in the QT group , there was no significant difference between the patients with and without fillings ( P=0.001 , 0.003 , 0.012 , 0.14 , respectively ) . Logistic regression analysis showed that the absence of amalgam filling exerts independent effects on the increased frequency of H. pylori infection and increased rate of H. pylori eradication . CONCLUSION This is the first study to show a lower frequency of H. pylori colonization in patients with amalgam fillings than without and that H. pylori eradication rates are lower in patients with amalgam fillings compared to those without .

amalgam dental fillings

concomitant

quadruple

levofloxacin-based therapies

amalgam fillings

concomitant therapy ( CT )

filling

CT

QT

LT

CT

LT

filling

nonfilling

QT

amalgam fillings

amalgam fillings

pylori eradication rates

H.

pylori eradication rates

Eradication success

frequency

pylori infection

eradication rates

eradication rates

frequency of H. pylori infection

increased rate of H. pylori eradication

frequency of H. pylori colonization

H. pylori eradication rates

patients treated with concomitant

individuals with amalgam fillings .

Four hundred and seventy-five patients

dyspeptic complaints

gastric biopsy

pylori-positive patients

patients with amalgam fillings

patients with amalgam fillings


Effect of motor training involving the less-affected side ( MTLA ) in post-stroke subjects : a pilot randomized controlled trial . INTRODUCTION Poststroke , less-severe motor impairment occurs on the ipsilesional side of body . The objective of the present study was to evaluate the effectiveness of the motor training involving the less-affected side ( MTLA ) in stroke . METHODS This was a randomized , controlled , double-blinded pilot study conducted in the occupational therapy unit of a rehabilitation Institute . A convenience sample of 35 stroke subjects ( mean poststroke duration , 28.76 weeks ) was randomized into two groups ( the experimental group : 17 and control group : 18 ) . Thirty-two participants completed the entire study protocol . The experimental group and control group were provided MTLA and neurophysiological-based conventional therapy respectively . Both the groups received 24 treatment sessions ( 60 minutes each ) over the period of two months . The Affected side was assessed using Brunnstrom recovery stage ( BRS ) and Fugl-Meyer assessment ( FMA ) whereas the less-affected side was evaluated by Minnesota manual dexterity test ( MMDT ) , Purdue peg board test ( PPBT ) and Manual Muscle Testing ( MMT ) . RESULTS Postintervention , the less-affected side of experimental group demonstrated significant improvement for MMDT ( P = 0.003 ) , PPBT ( P = 0.01 ) and MMT ( P < 0.001 to 0.043 ) in comparison to the control group . Further , as compared to the control group , the experimental group exhibited positive significant change for the measure of affected side [ BRS ( P < 0.001 ) and FMA ( P < 0.001 to 0.03 ) ] at post assessment . CONCLUSION MTLA enhanced the muscle strength , dexterity and coordination of the less-affected side as well as the motor recovery of the affected side in poststroke hemiparetic subjects .

motor training

motor training

Brunnstrom recovery stage ( BRS )

Fugl-Meyer assessment ( FMA )

Purdue peg board test ( PPBT )

Manual Muscle Testing ( MMT )

MMDT

PPBT

MMT

0.001 ) and

CONCLUSION

post-stroke subjects

Thirty-two

side in poststroke hemiparetic subjects


A trial of d-cycloserine to treat the social deficit in older adolescents and young adults with autism spectrum disorders . Autism spectrum disorders are difficult for older adolescents and young adults as impaired social communication affects the transition to adult life . d-Cycloserine , a partial glycine agonist at the N-methyl-d-aspartic acid receptor , was tested in a double-blind randomized trial in 20 older adolescents and young adults with autism spectrum disorders using two dosing strategies ( 50 mg daily versus 50 mg weekly ) for 8 weeks with a 2-week follow-up after discontinuation . d-Cycloserine caused statistically and clinically significant improvement with no differentiation between dosing strategies on the Social Responsiveness Scale and the Aberrant Behavior Checklist before and after d-cycloserine administration .

d-cycloserine

d-Cycloserine

d-Cycloserine

d-cycloserine

older adolescents

young adults

autism spectrum disorders

Autism spectrum disorders

older adolescents

young adults

older adolescents

young adults

autism spectrum disorders


Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system . OBJECTIVE To assess 3-year data on the efficacy and safety of a new 52-mg levonorgestrel intrauterine contraceptive ( LNG20 ) designed for up to 7 years use . STUDY DESIGN Nulliparous and parous women aged 16-45 years at enrollment with regular menstrual cycles and requesting contraception were enrolled in an open-label , partially randomized trial to evaluate LNG20 . The primary outcome was pregnancy rate for women aged 16-35 years calculated as the Pearl Index . Women aged 36-45 years received LNG20 for safety evaluation only . All participants had in-person or phone follow-up approximately every 3 months during the study . RESULTS A total of 1600 women aged 16-35 years and 151 women aged 36-45 years agreed to LNG20 placement , including 1011 ( 57.7 % ) nulliparous and 438 ( 25.1 % ) obese women . Successful placement occurred in 1714 ( 97.9 % ) women . Six pregnancies occurred , four of which were ectopic . The Pearl Index for LNG20 was 0.15 ( 95 % CI 0.02-0.55 ) through Year 1 , 0.26 ( 95 % CI 0.10-0.57 ) through Year 2 , and 0.22 ( 95 % CI 0.08-0.49 ) through Year 3 . The cumulative life-table pregnancy rate was 0.55 ( 95 % CI 0.24-1.23 ) through 3 years . Expulsion was reported in 62 ( 3.5 % ) participants , most ( 50 [ 80.6 % ] ) during the first year of use . Of women who discontinued LNG20 and desired pregnancy , 86.8 % conceived spontaneously within 12 months . Pelvic infection was diagnosed in 10 ( 0.6 % ) women . Only 26 ( 1.5 % ) LNG20 users discontinued due to bleeding complaints . CONCLUSION The LNG20 intrauterine system is highly effective and safe over 3 years of use in nulliparous and parous women . IMPLICATIONS STATEMENT A new 52-mg levonorgestrel-releasing intrauterine system is effective and safe for nulliparous and parous women for at least 3 years .

levonorgestrel-releasing

women

16-45 years

Women

women

aged 16-35 years

women

aged 36-45 years

women

women

women

women

women