Reduced mortality among children in southern India receiving a small weekly dose of vitamin A . BACKGROUND Clinical vitamin A deficiency affects millions of children worldwide , and subclinical deficiency is even more common . Supplemental vitamin A has been reported to reduce mortality among these children , but the results have been questioned . METHODS We conducted a randomized , controlled , masked clinical trial for one year in southern India involving 15,419 preschool-age children who received either 8.7 mumol ( 8333 IU ) of vitamin A and 46 mumol ( 20 mg ) of vitamin E ( the treated group ) or vitamin E alone ( the control group ) . Vitamin supplements were delivered weekly by community health volunteers who also recorded mortality and morbidity . Weekly contact was made with at least 88 percent of the children in both study groups . The base-line characteristics of the children were similar and documented a high prevalence of vitamin A deficiency and undernutrition . RESULTS One hundred twenty-five deaths occurred , of which 117 were not accidental . The risk of death in the group treated with vitamin A was less than half that in the control group ( relative risk , 0.46 ; 95 percent confidence interval , 0.30 to 0.71 ) . The risk was most reduced among children under 3 years of age ( 6 to 11 months -- relative risk , 0.28 ; 95 percent confidence interval , 0.09 to 0.85 ; 12 to 35 months -- relative risk , 0.46 ; 95 percent confidence interval , 0.26 to 0.81 ) and among those who were chronically undernourished , as manifested by stunting ( relative risk , 0.11 ; 95 percent confidence interval , 0.03 to 0.36 ) . The symptom-specific risk of mortality was significantly associated with diarrhea , convulsions , and other infection-related symptoms . CONCLUSIONS The regular provision of a supplement of vitamin A to children , at a level potentially obtainable from foods , in an area where vitamin A deficiency and under-nutrition are documented public health problems contributed substantially to children 's survival ; mortality was reduced on average by 54 percent .

vitamin A

8.7 mumol

vitamin A

46 mumol ( 20 mg ) of vitamin E

vitamin E

Vitamin supplements

vitamin A

mortality

morbidity

risk of death

symptom-specific risk of mortality

diarrhea

convulsions

infection-related symptoms


Feasibility of an obesity intervention for paediatric primary care targeting parenting and children : Helping HAND . BACKGROUND The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours , and improve weight status among children . OBJECTIVE Test the feasibility of Helping HAND ( Healthy Activity and Nutrition Directions ) , an obesity intervention for 5- to 8-year-old children in primary care clinics . METHODS A randomized controlled pilot study of Helping HAND , a 6-month intervention , targeted children with body mass index 85-99 % tile and their parents . Intervention group attended monthly sessions and self-selected child behaviours and parenting practices to change . Control group received regular paediatric care and was wait-listed for Helping HAND . Session completion , participant satisfaction , child anthropometrics , dietary intake , physical activity , TV viewing and behaviour-specific parenting practices were measured pre and post intervention . RESULTS Forty parent-child dyads enrolled : 82.5 % were Hispanic , 80 % had a girl and 65 % reported income ≤ $ 30 , 000/year . There was 20 % attrition from Helping HAND ( attended < 4/6 sessions ) . Families self-selected 4.35 ( SD 1.75 ) behaviours to target during the 6-month programme and each of the seven behaviours was selected by 45-80 % of the families . There were no between group differences in the child 's body mass index z-score , dietary intake or physical activity post intervention . Intervention group viewed 14.9 ( SE 2.3 ) h/week of TV post intervention versus control group 23.3 ( SE 2.4 ) h/week ( P < 0.05 ) . CONCLUSION Helping HAND is feasible , due to low attrition , good programme attendance , and clinically relevant improvements in some child and parenting behaviours .

obesity intervention

Helping HAND

parenting and children

children

parents

5- to 8-year-old children

children

body mass index

parents

Forty parent-child

girl


Comparison of epidural tramadol-ropivacaine and fentanyl-ropivacaine for labor analgesia : a prospective randomized study . BACKGROUND To test the hypothesis that 5 mg/mL tramadol is superior to 3 ? g/mL fentanyl when combined with 0.125 % ropivacaine in parturients undergoing labor during epidural analgesia . METHODS Sixty-one parturients undergoing labor selected for delivery with epidural analgesia were randomized into two groups : Group tramadol ( 0.125 % ropivacaine plus tramadol 5 mg/mL ) and Group fentanyl ( 0.125 % ropivacaine plus fentanyl 3 ug/mL ) . Hemodynamics , rate of cesarean delivery , sensory block level , Bromage motor scale scores , instrument-assisted delivery , oxytocin use , visual analog scale ( VAS ) scores , Apgar scores , umbilical cord artery gas analysis , and maternal side-effects including nausea , vomiting , pruritus , urinary retention , shivering , hypotension , and respiratory depression were recorded . RESULTS The two groups had no significant differences with respect to maternal hemodynamics , neonatal heart rate , VAS scores , rate of cesarean delivery , sensory block level , Bromage motor scale scores , instrument-assisted delivery , oxytocin use , hypotension , nausea , vomiting , and respiratory depression ( p > 0.05 ) . The incidence of pruritus , shivering , and urinary retention were more commonly observed in Group fentanyl despite there was no significant difference between the two groups . Umbilical artery pH was significantly lower while PCO ( 2 ) was higher in Group fentanyl than Group tramadol ( p = 0.003 and p = 0.026 , respectively ) . Birth-weight , umbilical artery PO ( 2 ) and base deficit , and Apgar scores at 1 and 5 min were comparable between the two groups ( p > 0.05 ) . CONCLUSIONS Our observations suggest that tramadol seems to be a safe alternative to fentanyl for labor analgesia due to its similar analgesic efficacy .

epidural tramadol-ropivacaine

fentanyl-ropivacaine

tramadol

fentanyl

ropivacaine

fentanyl

tramadol

tramadol

fentanyl

Hemodynamics

rate of cesarean delivery

sensory block level ,

Bromage motor scale scores

instrument-assisted delivery

oxytocin use

visual analog scale ( VAS ) scores

Apgar scores

umbilical cord artery

analysis

maternal hemodynamics

neonatal heart rate

VAS scores

rate of cesarean delivery

sensory block level

Bromage motor scale scores

instrument-assisted delivery

oxytocin use

hypotension

nausea

vomiting

respiratory depression

Umbilical artery pH

Birth-weight

umbilical artery PO ( 2 )

base deficit

Apgar scores


Effect of motivational music on lactate levels during recovery from intense exercise . The effects of music played during an exercise task on athletic performance have been previously studied . Yet , these results are not applicable for competitive athletes , who can use music only during warm-up or recovery from exercise . Therefore , the aim of this study was to determine the effect of motivational music ( music that stimulates or inspires physical activity ) during recovery from intense exercise , on activity pattern , rate of perceived exertion ( RPE ) , and blood lactate concentration . Twenty young , active men ( mean age 26.2 ± 2.1 years ) performed a 6-minute run at peak oxygen consumption speed ( predetermined from the VO ( 2 ) max test ) . The mean heart rate ( HR ) , RPE , number of steps ( determined by step counter ) , and blood lactate concentrations were determined at 3 , 6 , 9 , 12 , and 15 minutes during the recovery from the exercise , with and without motivational music ( 2 separate sessions , at random order ) . There was no difference in the mean HR during the recovery with and without music . Listening to motivational music during the recovery was associated with increased voluntary activity of the participants , determined by increased number of steps ( 499.4 ± 220.1 vs. 413.2 ± 150.6 steps , with and without music , respectively ; p ≤ 0.05 ) . The increased number of steps during the recovery was accompanied by a significantly greater decrease in blood lactate concentration percentage ( 28.1 ± 12.2 vs. 22.8 ± 10.9 % , with and without music , respectively , p ≤ 0.05 ) . This was associated with a greater decrease in RPE ( 77.7 ± 14.4 vs. 73.1 ± 14.7 % with and without music , respectively ; p ≤ 0.05 ) . Our results suggest that listening to motivational music during nonstructured recovery from intense exercise leads to increased activity , faster lactate clearance , and reduced RPE and therefore may be used by athletes in their effort to enhance recovery .

motivational music

Effect

lactate levels

recovery from intense exercise

activity pattern

rate of perceived exertion ( RPE )

blood lactate concentration

athletes

Twenty

men

mean age 26.2 ± 2.1 years


Effect of cervical spine manipulative therapy on judo athletes ' grip strength . OBJECTIVE The objective of this study was to perform an investigation evaluating if cervical spinal manipulative therapy ( SMT ) can increase grip strength on judo athletes in a top 10 national-ranked team . METHODS A single-blinded , prospective , comparative , pilot , randomized , clinical trial was performed with 18 athletes of both sexes from a judo team currently competing on a national level . The athletes were randomly assigned to 2 groups : chiropractic SMT and sham . Three interventions were performed on each of the athletes at different time points . Force measurements were obtained by a hydraulic dynamometer immediately before and after each intervention at the same period before training up to 3 weeks with at least 36 hours between interventions . RESULTS Analysis of grip strength data revealed a statistically significant increase in strength within the treatment group after the first intervention ( 6.95 % right , 12.61 % left ) as compared with the second ( 11.53 % right , 17.02 % left ) and the third interventions ( 10.53 % right , 16.81 % left ) . No statistically significant differences were found in grip strength comparison within the sham group . Overall differences in strength were consistently significant between the study groups ( P = .0025 ) . CONCLUSION The present study suggests that the grip strength of national level judo athletes receiving chiropractic SMT improved compared to those receiving sham .

cervical spine manipulative therapy

chiropractic SMT

sham

chiropractic SMT

grip strength

data

strength

grip strength

differences in

strength

judo athletes

18 athletes

both sexes

national level


Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension . OBJECTIVE To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension ( PAH ) . BACKGROUND Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury . METHODS Before sitaxsentan withdrawal , this 18-week double-blind , placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily . The primary efficacy endpoint was change from baseline in 6-min walk distance ( 6MWD ) at week 18 . Changes in World Health Organization ( WHO ) functional class and time to clinical worsening ( TTCW ) were secondary endpoints . The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo . RESULTS Of 98 randomized patients , 61 % were WHO functional class II at baseline . Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg ; a strong placebo effect was observed . At week 18 , WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo ( P = 0.038 ) ; 0 % versus 12 % of patients deteriorated , respectively . TTCW was not significantly different for 100-mg sitaxsentan patients than placebo ( P = 0.090 ) . Adverse events ( AEs ) occurring more frequently with sitaxsentan ( 50 or 100 mg ) included headache , peripheral edema , dizziness , nausea , extremity pain , and fatigue ; most AEs were of mild or moderate severity . CONCLUSION Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline . No patient receiving sitaxsentan 100 mg experienced clinical worsening ; sitaxsentan was well tolerated .

sitaxsentan

Adverse events

with pulmonary arterial hypertension

61 %

baseline


Evaluation of oral beclomethasone dipropionate for prevention of acute graft-versus-host disease . Results from two randomized trials have shown that oral beclomethasone dipropionate ( BDP ) is effective for treatment of acute gastrointestinal graft-versus-host disease . Here , we report results of a double-blind , randomized placebo-controlled phase II study designed to test the hypothesis that acute graft-versus-host disease could be prevented by administration of oral BDP , beginning before hematopoietic cell transplantation and continuing until day 75 after hematopoietic cell transplantation after myeloablative conditioning . Study drug ( BDP or placebo ) was administered as 1-mg immediate-release formulation plus 1-mg delayed-release formulation orally four times daily . According to the primary endpoint , systemic glucocorticoid treatment for graft-versus-host disease was given to 60 of the 92 participants ( 65 % ) in the BDP arm , versus 31 of 46 participants ( 67 % ) in the placebo arm . The secondary efficacy endpoints showed no statistically significant differences between the two arms . The proportion of participants who took at least 90 % of the prescribed study drug during the first 4 weeks after hematopoietic cell transplantation was 54 % overall . Lower severity of mucositis strongly correlated with higher adherence to the schedule of study drug administration . Inconsistent adherence related to mucositis during recovery after myeloablative conditioning may have obscured a beneficial therapeutic effect in the current study .

beclomethasone dipropionate

oral BDP

BDP

placebo

glucocorticoid

BDP

placebo

hematopoietic cell transplantation

systemic glucocorticoid treatment

secondary efficacy endpoints

severity of mucositis

adherence

adherence


Cognitive and physical rehabilitation of intensive care unit survivors : results of the RETURN randomized controlled pilot investigation . BACKGROUND Millions of patients who survive medical and surgical general intensive care unit care every year experience newly acquired long-term cognitive impairment and profound physical and functional disabilities . To overcome the current reality in which patients receive inadequate rehabilitation , we devised a multifaceted , in-home , telerehabilitation program implemented using social workers and psychology technicians with the goal of improving cognitive and functional outcomes . METHODS This was a single-site , feasibility , pilot , randomized trial of 21 general medical/surgical intensive care unit survivors ( 8 controls and 13 intervention patients ) with either cognitive or functional impairment at hospital discharge . After discharge , study controls received usual care ( sporadic rehabilitation ) , whereas intervention patients received a combination of in-home cognitive , physical , and functional rehabilitation over a 3-month period via a social worker or master 's level psychology technician utilizing telemedicine to allow specialized multidisciplinary treatment . Interventions over 12 wks included six in-person visits for cognitive rehabilitation and six televisits for physical/functional rehabilitation . Outcomes were measured at the completion of the rehabilitation program ( i.e. , at 3 months ) , with cognitive functioning as the primary outcome . Analyses were conducted using linear regression to examine differences in 3-month outcomes between treatment groups while adjusting for baseline scores . RESULTS Patients tolerated the program with only one adverse event reported . At baseline both groups were well-matched . At 3-month follow-up , intervention group patients demonstrated significantly improved cognitive executive functioning on the widely used and well-normed Tower test ( for planning and strategic thinking ) vs. controls ( median [ interquartile range ] , 13.0 [ 11.5-14.0 ] vs. 7.5 [ 4.0-8.5 ] ; adjusted p < .01 ) . Intervention group patients also reported better performance ( i.e. , lower score ) on one of the most frequently used measures of functional status ( Functional Activities Questionnaire at 3 months vs. controls , 1.0 [ 0.0 -3.0 ] vs. 8.0 [ 6.0-11.8 ] , adjusted p = .04 ) . CONCLUSIONS A multicomponent rehabilitation program for intensive care unit survivors combining cognitive , physical , and functional training appears feasible and possibly effective in improving cognitive performance and functional outcomes in just 3 months . Future investigations with a larger sample size should be conducted to build on this pilot feasibility program and to confirm these results , as well as to elucidate the elements of rehabilitation contributing most to improved outcomes .

Cognitive

physical rehabilitation

usual care ( sporadic rehabilitation )

cognitive rehabilitation

physical/functional rehabilitation

rehabilitation

cognitive functioning

tolerated

improved

cognitive executive functioning

planning and strategic thinking

performance

Functional Activities Questionnaire

cognitive performance

and

functional outcomes

intensive care unit survivors

21 general

intensive care unit survivors


Instant Recess® : a practical tool for increasing physical activity during the school day . BACKGROUND An increased prevalence of overweight/obesity among children has led to school district level policies to increase physical activity ( PA ) among elementary school students . Interventions are needed that increase activity levels without sacrificing time spent in academics . OBJECTIVES We evaluated a policy implementation intervention for to increase in-school PA in elementary schools in Forsyth County , North Carolina , in a randomized study with a delayed intervention control group . METHODS The study included third- through fifth-grade classrooms in eight elementary schools . Instant Recess® was used to introduce 10-minute PA breaks in classrooms on schedules determined by teachers . Direct observation was used to measure activity levels , other student behaviors , and teacher behaviors related to PA in the classrooms . RESULTS Twenty-eight visits to schools were made during the spring and fall semesters of 2009 . At baseline 11 % to 44 % of intervention and control schools were engaged in classroom-based PA. PA increased from baseline to spring follow-up in intervention schools and was maintained the following fall . Control schools decreased PA from baseline to spring and increased PA once they began the intervention . Students in classrooms engaged in Instant Recess exhibited statistically significant increases in light ( 51 % ) and moderate-intensity ( 16 % ) PA and increases in time spent in on-task behavior ( 11 % ) . Control schools experienced similar benefits after they began implementing Instant Recess . CONCLUSIONS Instant Recess is useful for increasing PA and improving behavior among elementary school children . Additional research may be needed to understand how to create policies supporting classroom activity breaks and how to assess policy adherence .

physical activity


Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis . INTRODUCTION It has been reported in an open-label study that the combination of alkalinized lidocaine and heparin can immediately relieve the symptoms of urinary urgency , frequency , and pain associated with interstitial cystitis ( IC ) . This combination has also been reported to relieve pain associated with sex in patients with IC . AIM The aim of this study was to corroborate these findings in a multicenter setting . METHODS The study design was a multicenter prospective , double-blind , crossover , placebo-controlled trial . Each participant met all of the clinical National Institute of Diabetes and Digestive and Kidney Diseases criteria ( excluding cystoscopy ) for IC . Each patient received drug and control , in random order , within 48 hours of enrolling in the study . MAIN OUTCOME MEASURES The primary outcome measure was percent change in pain score ( 11-point analog pain scale ) 12 hours after receiving the drug or control . Secondary measures were the global assessment response ( GAR ) of symptoms and 12-hour average urgency reduction determined from 11-point urgency scales . RESULTS Eighteen ( 18 ) patients completed the trial . The average reduction of pain over 12 hours was 21 % for control and 42 % for active drug ( P = 0.0363 ) . GAR was 13 % for control and 50 % for drug ( P = 0.0137 ) . Average urgency reduction was 13 % for control and 35 % for drug ( P = 0.0328 ) . CONCLUSIONS The combination of alkalinized lidocaine and heparin provides up to 12 hours of relief from urgency and pain associated with IC . This combination provides significant immediate relief of symptoms for patients with IC .

Alkalinized lidocaine and heparin

alkalinized lidocaine and heparin

placebo-controlled

pain

urinary urgency , frequency

symptoms

12-hour average urgency reduction

urgency and pain

interstitial cystitis

IC

Diabetes

Kidney Diseases


Atrial fibrillation catheter ablation versus surgical ablation treatment ( FAST ) : a 2-center randomized clinical trial . BACKGROUND Catheter ablation ( CA ) and minimally invasive surgical ablation ( SA ) have become accepted therapy for antiarrhythmic drug-refractory atrial fibrillation . This study describes the first randomized clinical trial comparing their efficacy and safety during a 12-month follow-up . METHODS AND RESULTS One hundred twenty-four patients with antiarrhythmic drug-refractory atrial fibrillation with left atrial dilatation and hypertension ( 42 patients , 33 % ) or failed prior CA ( 82 patients , 67 % ) were randomized to CA ( 63 patients ) or SA ( 61 patients ) . CA consisted of linear antral pulmonary vein isolation and optional additional lines . SA consisted of bipolar radiofrequency isolation of the bilateral pulmonary vein , ganglionated plexi ablation , and left atrial appendage excision with optional additional lines . Follow-up at 6 and 12 months was performed by ECG and 7-day Holter recording . The primary end point , freedom from left atrial arrhythmia > 30 seconds without antiarrhythmic drugs after 12 months , was 36.5 % for CA and 65.6 % for SA ( P=0.0022 ) . There was no difference in effect for subgroups , which was consistent at both sites . The primary safety end point of significant adverse events during the 12-month follow-up was significantly higher for SA than for CA ( n=21 [ 34.4 % ] versus n=10 [ 15.9 % ] ; P=0.027 ) , driven mainly by procedural complications such as pneumothorax , major bleeding , and the need for pacemaker . In the CA group , 1 patient died at 1 month of subarachnoid hemorrhage . CONCLUSION In atrial fibrillation patients with dilated left atrium and hypertension or failed prior atrial fibrillation CA , SA is superior to CA in achieving freedom from left atrial arrhythmias after 12 months of follow-up , although the procedural adverse event rate is significantly higher for SA than for CA . CLINICAL TRIAL REGISTRATION URL : http : //clinicaltrials.gov . Unique identifier : NCT00662701 .

Catheter ablation ( CA )

CA

CA

SA

CA

SA

antiarrhythmic drugs

CA

SA

SA

CA

CA

CA

SA

CA

SA

CA

One hundred twenty-four patients

( 42 patients

failed prior CA

82 patients

atrial fibrillation

dilated left atrium and hypertension

failed prior atrial fibrillation CA


[ Clinical observations on the treatment of hookworm , Ascaris and Trichuris infection with oxibendazole ] . 340 cases of hookworm infection , 196 cases of ascariasis and 178 cases of trichuriasis were treated with an anthelmintic , oxibendazole , 15mg/kg.d x 3d ; 102 , 70 and 66 cases of respective infections were treated with pyrantel 10mg/kg.d x 3d and 108 , 74 and 63 cases took placebo for comparison and as control under double-blind observations . Re-examinations of the stool were performed after the treatment . Among the cases treated with oxibendazole , the egg negative conversion rates of hookworm , Ascaris and Trichuris were 70.3-80.6 % , 92.5-97.8 and 67.0-71.0 % respectively . The egg reduction rates of hookworm were 98.1-98.6 % . The larval negative conversion rates of Ancylostoma duodenale and Necator americanus were 77.7 and 83.2 % respectively . Among the cases treated with pyrantel , the egg negative conversion rates of the three above mentioned parasites were 73.5 , 90.0 and 28.8 % respectively . The egg reduction rate of hookworm was 98.8 % . Among the cases treated with placebo , the egg negative conversion rates of the three above mentioned parasites were 6.5 , 29.7 and 7.9 % . No marked adverse reactions were observed by clinical and laboratory examinations .

oxibendazole

anthelmintic , oxibendazole

pyrantel

placebo

Ascaris

Trichuris

egg reduction rates of hookworm

egg negative conversion rates

egg reduction rate of hookworm

egg negative conversion rates

hookworm

Ascaris

Trichuris infection

hookworm infection

ascariasis

trichuriasis

respective infections


Activator protein-1 ( AP-1 ) signalling in human atherosclerosis : results of a systematic evaluation and intervention study . Animal studies implicate the AP-1 ( activator protein-1 ) pro-inflammatory pathway as a promising target in the treatment of atherosclerotic disease . It is , however , unclear whether these observations apply to human atherosclerosis . Therefore we evaluated the profile of AP-1 activation through histological analysis and tested the potential benefit of AP-1 inhibition in a clinical trial . AP-1 activation was quantified by phospho-c-Jun nuclear translocation ( immunohistochemistry ) on a biobank of aortic wall samples from organ donors . The effect of AP-1 inhibition on vascular parameters was tested through a double blind placebo-controlled cross-over study of 28 days doxycycline or placebo in patients with symptomatic peripheral artery disease . Vascular function was assessed by brachial dilation as well as by plasma samples analysed for hs-CRP ( high-sensitivity C-reactive protein ) , IL-6 ( interleukin-6 ) , IL-8 , ICAM-1 ( intercellular adhesion molecule-1 ) , vWF ( von Willebrand factor ) , MCP-1 ( monocyte chemoattractant protein-1 ) , PAI-1 ( plasminogen activator inhibitor-1 ) and fibrinogen . Histological evaluation of human atherosclerosis showed minimal AP-1 activation in non-diseased arterial wall ( i.e . vessel wall without any signs of atherosclerotic disease ) . A gradual increase of AP-1 activation was found in non-progressive and progressive phases of atherosclerosis respectively ( P < 0.044 ) . No significant difference was found between progressive and vulnerable lesions . The expression of phospho-c-Jun diminished as the lesion stabilized ( P < 0.016 ) and does not significantly differ from the normal aortic wall ( P < 0.33 ) . Evaluation of the doxycycline intervention only revealed a borderline-significant reduction of circulating hs-CRP levels ( -0.51 μg/ml , P=0.05 ) and did not affect any of the other markers of systemic inflammation and vascular function . Our studies do not characterize AP-1 as a therapeutic target for progressive human atherosclerotic disease .

Activator protein-1 ( AP-1 )

AP-1 ( activator protein-1 )

AP-1 activation

AP-1 inhibition

AP-1 activation

AP-1 inhibition

AP-1 inhibition

atherosclerosis

atherosclerotic disease

atherosclerosis

aortic wall


Paracetamol and opioid pathways : a pilot randomized clinical trial . Previous studies suggest that the antinociceptive action of paracetamol ( acetaminophen , APAP ) might involve descending inhibitory pain pathways and the opioidergic system : this study explores this issue in humans with naloxone , the opioid antagonist . After ethical approval , 12 healthy male volunteers were included in this randomized , controlled , double-blind , crossover , four-arm study . They were administered intravenous paracetamol ( APAP 1 g ) or saline ( placebo , pl ) followed at 100 min with IV naloxone ( Nal 8 mg ) or saline , every week for 4 weeks . The amplitude of cerebral potentials evoked by thermal/painful stimuli applied on the arm was recorded nine times over 150 min , witnessing of pain integration at central level . Amplitude changes as well as areas under the curve ( AUCs ) over 150 min were compared for the four treatments by repeated measures ANOVA ( significance 0.05 ) . Amplitude changes were significant for APAP/pl vs. pl/pl at t150 : -44 % ( 95 % CI -58 to -30 ) vs. -27 % ( 95 % CI -37 to -17 ; P < 0.05 ) but not vs. APAP/Nal . AUC ( 0-150 ) of APAP/pl is significantly different from pl/pl ( -3452 % .min ( 95 % CI -4705 to -2199 ) vs. -933 % min ( 95 % CI -2273 to 407 ; P = 0.015 ) but not from APAP/Nal ( -1731 % min ( 95 % CI -3676 to 214 ; P = 0.08 ) and other treatments . AUC ( 90-150 ) is not significantly different . This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception , suggesting no significant implication of the opioid system in paracetamol mechanism of action : this needs be confirmed on a larger number of subjects .

Paracetamol

paracetamol ( acetaminophen , APAP )

naloxone

opioid antagonist

intravenous paracetamol

saline

placebo

IV naloxone

saline

APAP/pl

APAP/Nal

APAP/Nal

naloxone

paracetamol

paracetamol

amplitude of cerebral potentials evoked

Amplitude changes

AUC

AUC

inhibit paracetamol antinociception

male


Maintaining tissue orientation during mohs micrographic surgery : scalpel versus marker . BACKGROUND Critical to the accuracy of Mohs surgery is the ability to maintain proper orientation of excised tissue with respect to the surrounding skin . Several techniques have been described for maintaining this orientation , although no prior investigations directly compare these techniques . OBJECTIVE To compare the incidence of tissue orientation loss resulting from inability to identify skin score marks with that occurring from failure to identify marks made using a gentian violet marker during Mohs micrographic surgery ( MMS ) . We also sought to determine the incidence of scars resulting from skin scoring . MATERIALS AND METHODS Patients undergoing MMS were prospectively randomized to have their tissue margins oriented using light scoring using a scalpel versus marking them using a gentian violet marker . Incidence of scoring scars and tissue orientation loss were the primary outcome measures . RESULTS Data were analyzed for 101 tumors . There were no instances of tissue orientation loss in the scalpel or marker arms , nor were there any visible score mark scars at follow-up . CONCLUSION Incidence of excessive scars resulting from lightly scored tissue or loss of tissue orientation caused by lost gentian violet markings appears to be low . Both methods worked well within the confines of this study .

Mohs surgery

gentian violet marker

Mohs micrographic surgery ( MMS ) .

MMS

tissue orientation loss

visible score mark scars

excessive scars

mohs micrographic surgery

Mohs micrographic surgery ( MMS )

Patients undergoing MMS


Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer . OBJECTIVE The goal of this report is to describe the on going strategies , successes , challenges and solutions for recruitment in this multi-center , phase II chemoprevention trial targeting men at high risk for prostate cancer . METHODS We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure , lead by a recruitment team of experienced and committed physicians and clinical trial staff , implementing multi-media and community outreach strategies to meet recruitment goals . Screening logs were reviewed to identify trends as well as patient , protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented . RESULTS Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94 % ( n=3092 ) determined to be ineligible based on diagnosis of cancer or benign biopsy results . Of these , 216 were considered eligible for further screening with 52 % ( n=113 ) declining to participate due to patient related factors and 14 % ( n=29 ) eliminated due to protocol-related criteria for exclusion . Ninety-four ( 94 ) subjects consented to participate with 34 % of these subjects ( n=74 ) meeting all eligibility criteria to be randomized to receive study agent or placebo . Across all sites , 99 % of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1 % responding to other recruitment strategies . CONCLUSION A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature . A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials .

multi-media and community outreach

Screening logs

prostate cancer .

men

prostate cancer

( 94


Factors associated with inadequate colorectal cancer screening with flexible sigmoidoscopy . BACKGROUND AND STUDY AIM Inadequate colorectal cancer screening wastes limited endoscopic resources . We examined patients factors associated with inadequate flexible sigmoidoscopy ( FSG ) screening at baseline screening and repeat screening 3-5 years later in 10 geographically-dispersed screening centers participating in the ongoing Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . METHODS A total of 64,554 participants ( aged 55-74 ) completed baseline questionnaires and underwent FSG at baseline . Of these , 39,385 participants returned for repeat screening . We used logistic regression models to assess factors that are associated with inadequate FSG ( defined as a study in which the depth of insertion of FSG was < 50 cm or visual inspection was limited to < 90 % of the mucosal surface but without detection of a polyp or mass ) . RESULTS Of 7084 ( 11 % ) participants with inadequate FSG at baseline , 6496 ( 91.7 % ) had < 50 cm depth of insertion ( 75.3 % due to patient discomfort ) and 500 ( 7.1 % ) participants had adequate depth of insertion but suboptimal bowel preparation . Compared to 55-59 year age group , advancing age in 5-year increments ( odds ratios ( OR ) from 1.08 to 1.51 ) and female sex ( OR = 2.40 ; 95 % confidence interval ( CI ) : 2.27-2.54 ) were associated with inadequate FSG . Obesity ( BMI > 30 kg/m ( 2 ) ) was associated with reduced odds ( OR = 0.67 ; 95 % CI : 0.62-0.72 ) . Inadequate FSG screening at baseline was associated with inadequate FSG at repeat screening ( OR = 6.24 ; 95 % CI : 5.78-6.75 ) . CONCLUSIONS Sedation should be considered for patients with inadequate FSG or an alternative colorectal cancer screening method should be recommended .

flexible sigmoidoscopy

repeat screening

FSG

repeat screening

inadequate

FSG

Obesity

64,554 participants

aged 55-74 )


A randomized , dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema . OBJECTIVE To evaluate the safety and tolerability of a single subconjunctival ( SCJ ) or intravitreal ( IVT ) injection of an ophthalmic sirolimus formulation in eyes with diabetic macular edema ( DME ) . DESIGN Randomized , open-label , dose-escalating phase I study . PARTICIPANTS Fifty eyes among 50 patients with DME , retinal thickness ≥ 300 microns and best-corrected visual acuity ( BCVA ) 20/40 to 20/200 . METHODS A single dose of sirolimus administered SCJ ( 220 , 440 , 880 , 1320 , or 1760 μg ) or IVT ( 44 , 110 , 176 , 264 , or 352 μg ) on day 0 ; observation through day 90 . MAIN OUTCOME MEASURES Primary end points were the frequency and severity of ocular and systemic adverse events . Secondary end points were changes in BCVA and retinal thickness . RESULTS No dose-limiting toxicities were observed and ocular adverse events were mostly mild and transient . Conjunctival hyperemia , hemorrhage , and edema were common after the SCJ injection procedure and conjunctival hemorrhage was common after the IVT injection procedure . Three patients experienced ocular adverse events considered possibly related to study drug : Conjunctival edema and reduced visual acuity were reported in 1 SCJ patient each and iritis was reported in 1 IVT patient . No serious ocular adverse events were reported . No nonocular adverse events were considered related to study drug . Systemic exposure to sirolimus was low , with blood concentrations below levels necessary for systemic immunosuppression . For the SCJ group ( n = 25 ) , a median increase in BCVA started at day 7 ( 5.0 letters ) and was 3.0 , 4.0 , and 4.0 letters at days 14 , 45 and 90 , respectively . At day 45 , median decrease in retinal thickness was -23.7 μm . For the IVT group ( n = 25 ) , the median increase in BCVA was 2.0 letters at day 7 ; at days 14 , 45 , and 90 , the median increase was maintained ( 4.0 letters ) ; the median decrease in retinal thickness was -52.0 μm at day 45 . CONCLUSIONS Locally administered sirolimus was well-tolerated with minimal systemic exposure at all doses tested in this small phase I population . These findings support advancing the present sirolimus formulation into phase II studies . FINANCIAL DISCLOSURE ( S ) Proprietary or commercial disclosure may be found after the references .

sirolimus

single subconjunctival ( SCJ )

intravitreal ( IVT ) injection

sirolimus

safety and tolerability

conjunctival hemorrhage

ocular adverse events

Conjunctival edema

reduced visual acuity

serious ocular adverse events

nonocular adverse events

diabetic macular edema


Making the connection : randomized controlled trial of social skills at school for children with autism spectrum disorders . BACKGROUND This study compared two interventions for improving the social skills of high functioning children with autism spectrum disorders in general education classrooms . One intervention involved a peer-mediated approach ( PEER ) and the other involved a child-assisted approach ( CHILD ) . METHOD The two interventions were crossed in a 2 × 2 factorial design yielding control , PEER , CHILD , and both PEER and CHILD conditions . Sixty children participated from 56 classrooms in 30 schools . Interventions involved 12 sessions over 6 weeks , with a 3-month follow-up . Outcome measures included self , peer and teacher reports of social skills and independent weekly observations of children on their school playground over the course of the intervention . RESULTS Significant improvements were found in social network salience , number of friendship nominations , teacher report of social skills in the classroom , and decreased isolation on the playground for children who received PEER interventions . Changes obtained at the end of the treatment persisted to the 3-month follow-up . CONCLUSIONS These data suggest that significant improvements can be made in peer social connections for children with autism spectrum disorders in general education classrooms with a brief intervention , and that these gains persist over time .

peer-mediated approach ( PEER )

child-assisted approach ( CHILD ) .

PEER

CHILD

both PEER and CHILD

social skills

children

autism spectrum disorders

high functioning children

autism spectrum disorders


Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency . UNLABELLED Growth hormone ( GH ) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass . The present study shows that cortical bone dimensions also benefit from GH treatment , with endosteal expansion and increased cortical thickness leading to improved bone strength . INTRODUCTION In young adults with childhood-onset growth hormone deficiency ( CO GHD ) , GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density . The objective of the study was to evaluate the influence of GH on cortical bone dimensions . METHODS Patients ( n = 160 ; mean age , 21.2 years ; 63 % males ) with CO GHD were randomised 2:1 to GH or no treatment for 24 months . Cortical bone dimensions were evaluated by digital x-ray radiogrammetry of the metacarpal bones every 6 months . RESULTS After 24 months , cortical thickness was increased compared with the controls ( 6.43 % , CI 3.34 to 9.61 % ; p = 0.0001 ) and metacarpal index ( MCI ) ( 6.14 % , CI 3.95 to 8.38 % ; p < 0.0001 ) , while the endosteal diameter decreased ( -4.64 % , CI -7.15 to -2.05 ; p < 0.001 ) . Total bone width did not change significantly ( 0.68 % , CI -1.17 to 2.57 % ; not significant ( NS ) ) . A gender effect was seen on bone width ( p < 0.0001 ) , endosteal diameter ( p < 0.01 ) and cortical thickness ( p < 0.01 ) , but not with MCI ( NS ) . CONCLUSIONS Cortical bone reacts promptly to reinstitution of GH beyond the attainment of final height by increasing the cortical thickness through endosteal bone growth . This leads to a higher peak bone mass and may reduce the risk of cortical bone fragility later in life .

Growth hormone ( GH ) treatment

cortical bone dimensions

bone mass

improved bone strength

GH

cortical bone dimensions


A clinical trial of glutathione supplementation in autism spectrum disorders . BACKGROUND Recent evidence shows that subjects diagnosed with an autism spectrum disorder ( ASD ) have significantly lower levels of glutathione than typically developing children . The purpose of this study was to examine the use of two commonly used glutathione supplements in subjects diagnosed with an ASD to determine their efficacy in increasing blood glutathione levels in subjects diagnosed with an ASD . MATERIAL/METHODS The study was an eight-week , open-label trial using oral lipoceutical glutathione ( n=13 ) or transdermal glutathione ( n=13 ) in children , 3-13 years of age , with a diagnosis of an ASD . Subjects underwent pre- and post-treatment lab testing to evaluate plasma reduced glutathione , oxidized glutathione , cysteine , taurine , free and total sulfate , and whole-blood glutathione levels . RESULTS The oral treatment group showed significant increases in plasma reduced glutathione , but not whole-blood glutathione levels following supplementation . Both the oral and transdermal treatment groups showed significant increases in plasma sulfate , cysteine , and taurine following supplementation . CONCLUSIONS The results suggest that oral and transdermal glutathione supplementation may have some benefit in improving some of the transsulfuration metabolites . Future studies among subjects diagnosed with an ASD should further explore the pharmacokinetics of glutathione supplementation and evaluate the potential effects of glutathione supplementation upon clinical symptoms .

oral lipoceutical glutathione

transdermal glutathione

glutathione

glutathione

blood glutathione levels

plasma reduced glutathione

whole-blood glutathione

plasma sulfate

cysteine

taurine

autism spectrum disorders

autism spectrum disorder ( ASD )

ASD

ASD

children

ASD

ASD


MSLT in primary insomnia : stability and relation to nocturnal sleep . STUDY OBJECTIVES To assess the stability of the multiple sleep latency test ( MSLT ) in primary insomnia and its relation to total sleep time . DESIGN Randomized , double-blind , placebo controlled , clinical trial . SETTING Outpatient with sleep laboratory assessments in months 1 and 8 of treatment . PARTICIPANTS Ninety-five primary insomniacs , 32-64 years old and 55 age- and sex-matched general population-based , representative controls . INTERVENTIONS After a screening nocturnal polysomnograms ( NPSG ) and MSLT the following day , participants with primary insomnia were randomized to take zolpidem 10 mg ( n = 50 ) or placebo ( n = 45 ) nightly for 12 months . During months 1 and 8 , while taking their prescribed treatments , NPSGs and MSLTs the following day were conducted . A population-based sample served as controls and received a single NPSG followed by MSLT . RESULTS Mean daily sleep latency on the screening MSLT of insomniacs was normally distributed across the full range of MSLT scores and significantly higher than those of a population-based representative control sample ( P < 0.006 ) . The insomniacs with the highest screening MSLTs had the shortest screening total sleep times ( P < 0.05 ) . The MSLTs of insomniacs during treatment in study month 1 were correlated ( r = 0.44 , P < 0.001 ) with their month 8 MSLT . The mean MSLT score of the zolpidem group did not differ from that of the placebo group , and the stability within treatment groups also did not differ . CONCLUSIONS These data support the hypothesis that some insomniacs show a reliable disorder of hyperarousal with increased wake drive both at night and during the day .

MSLT

multiple sleep latency test ( MSLT )

nocturnal polysomnograms ( NPSG )

MSLT

zolpidem

placebo

MSLTs

MSLT

MSLT

MSLT

MSLTs

MSLTs

MSLT

insomnia :

nocturnal sleep

primary insomnia

total sleep time

screening total sleep times

mean MSLT score

hyperarousal

wake drive

Ninety-five

insomniacs

32-64 years old and 55 age-

primary insomnia


Response prediction in metastasised colorectal cancer using intratumoural thymidylate synthase : results of a randomised multicentre trial . BACKGROUND Molecular markers to predict response to 5-fluorouracil ( FU ) -based treatment of recurrent or metastasised colorectal cancer ( mCRC ) are not established . The aim of this trial was to determine the value of thymidylate synthase ( TS ) , a key enzyme of DNA synthesis and target of 5-FU , to predict response to chemotherapy of mCRC . METHODS Tumour tissue was obtained from 168 patients with mCRC for relative thymidylate synthase ( TS ) mRNA quantitation . Patients were randomised to receive either 5-FU/folinic acid ( FA , FUFA ) alone or in combination with irinotecan 5-fluorouracil/folinic acid and irinotecan ( FOLFIRI ) stratified by TS ( low versus high ) . Primary end-point was overall response to first-line treatment among TS high patients . All parties , except for the randomisation centre , were blinded for TS status . RESULTS Biopsies ( n=168 ) were taken without complications . TS levels were available for 147 patients ( 87.5 % ) . Analysing response to FUFA and FOLFIRI in the per protocol set ( n=119 ) after un-blinding TS in the data base revealed a trend to better overall response to FOLFIRI ( 9/19 , 47 % ) in TS high compared to FUFA ( 5/23 , 22 % , p=0.077 ) . In patients with biopsies taken from liver lesions ( n=91 ) overall response to FOLFIRI and FUFA in TS high was 53 % ( 9/17 ) and 18 % ( 3/17 ) , respectively ( p=0.035 ) . In patients with low TS , no remarkable difference in overall response to FOLFIRI and FUFA was observed . CONCLUSIONS Taking a pre-treatment biopsy is a safe and feasible procedure in mCRC . After validation of our data in a larger group TS determination may have the potential to better help direct systemic treatment in patients with primarily non-resectable mCRC .

5-fluorouracil ( FU ) -based

thymidylate synthase

predict response

thymidylate synthase ( TS )

TS levels

response to FUFA and FOLFIRI


Object interest in autism spectrum disorder : a treatment comparison . A randomized control trial comparing two social communication treatments for children with autism spectrum disorder examined the effect of treatment on object interest . Thirty-two children , 18-60 months , were randomly assigned to the Picture Exchange Communication System ( PECS ) or Responsive Education and Prelinguistic Milieu Teaching ( RPMT ) condition . Assessment of object interest was conducted in an unstructured play session with different toys , activities , adult , and location than experienced in treatment . Results indicated children in the RPMT condition showed greater increases in object interest as compared to children in the PECS condition . Because child characteristics such as interest in objects may influence response to interventions using object play as contexts for treatment , it is important to improve our understanding of whether intervention can affect object interest .

social communication treatments

RPMT

PECS

Object interest

object interest

object interest

autism spectrum disorder :

children

autism spectrum disorder

Thirty-two

children , 18-60 months


In high risk hypertensive subjects with incidental and unilateral renal artery stenosis percutaneous revascularization with stent improves blood pressure control but not glomerular filtration rate . AIM In high-risk hypertensive subjects ( HTs ) with incidental unilateral renal artery stenosis ( RAS ) , the effectiveness of percutaneous revascularization with stent ( PR-STENT ) on blood pressure ( BP ) and glomerular filtration rate ( GFR ) is not established . METHODS Eighteen HTs aged 65.7 ± 9.2 years with angiographically diagnosed unilateral RAS ( ≥ 60 % ) were randomized to receive PR-STENT ( N=9 ) or to NO-STENT ( N=9 ) . BP ( mercury sphygmomanometer ) and GFR ( 99mTc-DTPA clearances during renal scintigraphy ) were evaluated yearly for three years . Echo-Doppler of renal arteries was performed to verify the anatomic patency and flow velocities of the reperfused artery . Analysis of variance compared BP and GFR values changes from baseline to the follow-up ; differences for continuous variables were evaluated between groups with the Tukey 's post hoc test after adjustment for age , change of BP between baseline and at the follow-up , GFR and body mass index ( BMI ) . RESULTS Baseline systolic BP and GFR values were not different between groups . The significantly greater GFR increase observed in PR-STENT than in NO-STENT at univariate analysis at the end of follow-up ( 62.5 ± 19.2 vs. 42.24 ± 17.6 , P < 0.02 ) disappeared after adjustment for confounding factors . However , systolic BP remained significantly lower in PR-STENT than in NO-STENT ( 140.1 ± 4.6 vs. 170.0 ± 8.3 , P < 0.0001 ) also after adjustment for age , GFR and BMI . CONCLUSION PR-STENT reduces systolic BP without improving GFR . Due to the strong association between high BP and renal damage , this study raises the question on whether PR-STENT should be performed in all HTs with unilateral and incidental RAS .

blood pressure control

glomerular filtration rate

blood pressure

glomerular filtration rate ( GFR )

high risk hypertensive

high-risk hypertensive


Outcomes of Japanese breast cancer patients treated with pre-operative and post-operative anastrozole or tamoxifen . The present study examined long-term efficacy outcomes in a subgroup of postmenopausal , estrogen receptor-positive Japanese breast cancer patients from the Pre-Operative " Arimidex " Compared with Tamoxifen trial , following pre-operative ( 3 months ) and post-operative ( 5 years ) adjuvant treatment with either anastrozole or tamoxifen . Patients with large , potentially operable , locally-advanced breast cancer were randomized to receive anastrozole ( 1 mg/day ) plus tamoxifen placebo or tamoxifen ( 20 mg/day ) plus anastrozole placebo pre-operatively . After surgery at 3 months , patients continued on the same study medication as adjuvant therapy for up to 5 years or until recurrence , intolerable toxicity or withdrawal of patient consent . Recurrence-free survival and overall survival were measured from the date of randomization to the date of recurrence or death , whichever occurred first . Patients were monitored for adverse events throughout the study period and up to 30 days following administration of the last study medication . During post-operative adjuvant therapy , 4/48 ( 8 % ) anastrozole and 25/49 ( 51 % ) tamoxifen patients experienced recurrence . There was a significant difference in recurrence-free survival between the two groups ( hazard ratio 0.14 ; 95 % confidence interval 0.05-0.41 ; P = 0.0003 ) . There was a significant increase in overall survival with anastrozole ( 0.21 ; 0.05-0.96 ; P = 0.0436 ) and there were 2/48 ( 4 % ) and 10/49 ( 20 % ) deaths with anastrozole and tamoxifen , respectively . Most patients responding to pre-operative therapy remained recurrence-free . Sequential pre-operative/post-operative treatment with anastrozole resulted in lower recurrence and death rates , compared with tamoxifen .

Arimidex

Tamoxifen

anastrozole

tamoxifen

tamoxifen placebo

tamoxifen

anastrozole placebo

adjuvant therapy

anastrozole

tamoxifen

anastrozole

anastrozole

tamoxifen

anastrozole

tamoxifen

efficacy outcomes

Recurrence-free survival

overall survival

adverse events

recurrence-free survival

overall survival

recurrence-free

recurrence

death

breast cancer patients

breast cancer patients

locally-advanced breast cancer


Brief report : effect of a focused imitation intervention on social functioning in children with autism . Imitation is an early skill thought to play a role in social development , leading some to suggest that teaching imitation to children with autism should lead to improvements in social functioning . This study used a randomized controlled trial to evaluate the effect of a focused imitation intervention on initiation of joint attention and social-emotional functioning in 27 young children with autism . Results indicated the treatment group made significantly more gains in joint attention initiations at post-treatment and follow-up and social-emotional functioning at follow-up than the control group . Although gains in social functioning were associated with treatment , a mediation analysis did not support imitation as the mechanism of action . These findings suggest the intervention improves social functioning in children with ASD .

focused imitation intervention

focused imitation intervention

social functioning

social functioning

joint attention

social-emotional functioning

joint attention initiations

social-emotional functioning

gains in social functioning

social functioning

children

autism

children

autism

young children

autism

children

ASD


Predictive and prognostic roles of BRAF mutation in stage III colon cancer : results from intergroup trial CALGB 89803 . PURPOSE Alterations in the RAS-RAF-MAP2K ( MEK ) -MAPK signaling pathway are major drivers in colorectal carcinogenesis . In colorectal cancer , BRAF mutation is associated with microsatellite instability ( MSI ) , and typically predicts inferior prognosis . We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer . METHODS We assessed status of BRAF c.1799T > A ( p.V600E ) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [ 5-fluorouracil and leucovorin ( FU/LV ) vs. irinotecan ( CPT11 ) , FU and LV ( IFL ) ; CALGB 89803 ] . Cox proportional hazards model was used to assess the prognostic role of BRAF mutation , adjusting for clinical features , adjuvant chemotherapy arm , and MSI status . RESULTS Compared with 431 BRAF wild-type patients , 75 BRAF-mutated patients experienced significantly worse overall survival [ OS ; log-rank P = 0.015 ; multivariate HR = 1.66 ; 95 % CI : 1.05-2.63 ] . By assessing combined status of BRAF and MSI , it seemed that BRAF-mutated MSS ( microsatellite stable ) tumor was an unfavorable subtype , whereas BRAF wild-type MSI-high tumor was a favorable subtype , and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes . Among patients with BRAF-mutated tumors , a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm ( multivariate HR = 0.52 ; 95 % CI : 0.25-1.10 ) . Among patients with BRAF wild-type cancer , IFL conferred no suggestion of benefit beyond FU/LV alone ( multivariate HR = 1.02 ; 95 % CI : 0.72-1.46 ) . CONCLUSIONS BRAF mutation is associated with inferior survival in stage III colon cancer . Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy .

chemotherapy

IFL

FU/LV

IFL

FU/LV

irinotecan-based therapy

overall survival [ OS

OS

survival

stage III colon cancer

colorectal carcinogenesis

patients with stage III colon cancer

stage III colon cancer

stage III colon cancer


Motion style acupuncture treatment ( MSAT ) for acute low back pain with severe disability : a multicenter , randomized , controlled trial protocol . BACKGROUND Acupuncture is widely-used to treat patients with low back pain , despite insufficient evidence of the technique 's efficacy for acute back pain . Motion style acupuncture treatment ( MSAT ) is a non-traditional acupuncture treatment requiring a patient to exercise while receiving acupuncture . In Korea , MSAT is used to reduce musculoskeletal pain and improve functional status . The study aims to evaluate the effect of MSAT on acute low back pain with severe disability . METHODS/DESIGN This study is a multicenter , randomized , active-controlled trial with two parallel arms . Participants with acute low back pain and severe functional disability , defined as an Oswestry Disability Index ( ODI ) value > 60 % , will be randomly allocated to the acupuncture group and the nonsteroidal anti-inflammatory drug ( NSAID ) injection group . The acupuncture group will receive MSAT and the NSAID injection group will receive an intramuscular injection of diclofenac . All procedures will be limited to one session and the symptoms before and after treatment will be measured by assessors blinded to treatment allocation . The primary outcome will be measured at 30 minutes after treatment using the numerical rating scale ( NRS ) of low back pain while the patient is moving . Secondary outcomes will be measured at 30 minutes after treatment using the NRS of leg pain , ODI , patient global impression of change , range of motion ( ROM ) of the lumbar spine , and degrees of straight leg raising ( SLR ) . Post-treatment follow-up will be performed to measure primary and secondary outcomes with the exception of ROM and SLR at 2 , 4 , and 24 weeks after treatment . DISCUSSION The results of this trial will be discussed . TRIAL REGISTRATION ClinicalTrial.gov NCT01315561 .

acupuncture

injection

MSAT

NSAID

diclofenac

NRS of leg pain

ODI

patient global impression of change

degrees of straight leg raising ( SLR )

ROM

SLR

acute low back pain

patients with low back pain

Korea


Effect of a vitamin/mineral supplement on children and adults with autism . BACKGROUND Vitamin/mineral supplements are among the most commonly used treatments for autism , but the research on their use for treating autism has been limited . METHOD This study is a randomized , double-blind , placebo-controlled three month vitamin/mineral treatment study . The study involved 141 children and adults with autism , and pre and post symptoms of autism were assessed . None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study . For a subset of the participants ( 53 children ages 5-16 ) pre and post measurements of nutritional and metabolic status were also conducted . RESULTS The vitamin/mineral supplement was generally well-tolerated , and individually titrated to optimum benefit . Levels of many vitamins , minerals , and biomarkers improved/increased showing good compliance and absorption . Statistically significant improvements in metabolic status were many including : total sulfate ( +17 % , p = 0.001 ) , S-adenosylmethionine ( SAM ; +6 % , p = 0.003 ) , reduced glutathione ( +17 % , p = 0.0008 ) , ratio of oxidized glutathione to reduced glutathione ( GSSG : GSH ; -27 % , p = 0.002 ) , nitrotyrosine ( -29 % , p = 0.004 ) , ATP ( +25 % , p = 0.000001 ) , NADH ( +28 % , p = 0.0002 ) , and NADPH ( +30 % , p = 0.001 ) . Most of these metabolic biomarkers improved to normal or near-normal levels.The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised ( PGI-R , Average Change , p = 0.008 ) , and on the subscores for Hyperactivity ( p = 0.003 ) , Tantrumming ( p = 0.009 ) , Overall ( p = 0.02 ) , and Receptive Language ( p = 0.03 ) . For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers ( adj . R2 = 0.61 , p < 0.0005 ) with the initial levels of biotin and vitamin K being the most significant ( p < 0.05 ) ; both biotin and vitamin K are made by beneficial intestinal flora . CONCLUSIONS Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism , including improvements in methylation , glutathione , oxidative stress , sulfation , ATP , NADH , and NADPH . The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change . This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism . TRIAL REGISTRATION CLINICAL TRIAL REGISTRATION NUMBER NCT01225198 .

vitamin/mineral supplement

Vitamin/mineral supplements

placebo-controlled

vitamin/mineral treatment

vitamin/mineral supplement

vitamin/mineral supplement

supplement

placebo

vitamin/mineral supplementation

supplement

placebo

vitamin/mineral supplement

well-tolerated

compliance and absorption .

total sulfate

S-adenosylmethionine

glutathione

nitrotyrosine

ATP

NADH

NADPH

Parental Global Impressions-Revised

Hyperactivity

Tantrumming

Overall

Receptive Language

Average Change of the PGI-R

children

adults

autism

children and adults

autism

children ages 5-16 )

children

autism

children and adults

autism


Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia . BACKGROUND Omega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia . However , a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published . METHODS This was a randomized , single-blind , placebo-controlled , parallel study . Age , sex , and body mass index were matched among groups . All patients were recommended to maintain a low fat diet . Fifty patients in each group were given placebo , omega-3 fatty acids 2 g ( most commonly used dosage in Korean patients ) , or fenofibrate 160 mg , respectively daily for 2 months . RESULTS Omega-3 fatty acids therapy decreased triglycerides by 21 % and triglycerides/HDL cholesterol and improved flow-mediated dilation ( P < 0.01 ) , however , did not significantly change insulin , plasma adiponectin levels , and insulin sensitivity ( determined by QUICKI ) relative to baseline measurements . Fenofibrate therapy decreased total cholesterol , triglycerides by 29 % , and triglycerides/HDL-cholesterol ( all P < 0.01 ) and improved flow-mediated dilation when compared with baseline . When compared with placebo and omega-3 fatty acids , fenofibrate therapy decreased non-HDL cholesterol ( P < 0.001 ) and triglycerides/HDL cholesterol ( P=0.016 ) while increasing HDL cholesterol ( P < 0.001 ) and apolipoprotein AI ( P=0.001 ) . Of note , when compared with omega-3 fatty acids , fenofibrate therapy decreased fasting insulin ( P=0.023 ) and increased plasma adiponectin ( P=0.002 ) and insulin sensitivity ( P=0.015 ) . CONCLUSIONS Omega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation . However , fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia .

omega-3 fatty acids

fenofibrate

Omega-3 fatty acids

fenofibrate

placebo

omega-3 fatty acids

fenofibrate 160 mg

Omega-3 fatty acids therapy

Fenofibrate therapy

placebo

omega-3 fatty acids

fenofibrate therapy

hypertriglyceridemia

triglycerides

triglycerides/HDL cholesterol

flow-mediated dilation

insulin

plasma adiponectin levels

insulin sensitivity

total cholesterol

triglycerides

triglycerides/HDL-cholesterol

improved flow-mediated dilation

non-HDL cholesterol

triglycerides/HDL cholesterol

HDL cholesterol

apolipoprotein AI

fasting insulin

plasma adiponectin

insulin sensitivity

triglycerides

endothelium-dependent dilation

lipoprotein

metabolic profiles

hypertriglyceridemia

hypertriglyceridemia

Fifty

hypertriglyceridemia


Genetic associations with lipoprotein subfractions provide information on their biological nature . Adverse levels of lipoproteins are highly heritable and constitute risk factors for cardiovascular outcomes . Hitherto , genome-wide association studies revealed 95 lipid-associated loci . However , due to the small effect sizes of these associations large sample numbers ( > 100 000 samples ) were needed . Here we show that analyzing more refined lipid phenotypes , namely lipoprotein subfractions , can increase the number of significantly associated loci compared with bulk high-density lipoprotein and low-density lipoprotein analysis in a study with identical sample numbers . Moreover , lipoprotein subfractions provide novel insight into the human lipid metabolism . We measured 15 lipoprotein subfractions ( L1-L15 ) in 1791 samples using ( 1 ) H-NMR ( nuclear magnetic resonance ) spectroscopy . Using cluster analyses , we quantified inter-relationships among lipoprotein subfractions . Additionally , we analyzed associations with subfractions at known lipid loci . We identified five distinct groups of subfractions : one ( L1 ) was only marginally captured by serum lipids and therefore extends our knowledge of lipoprotein biochemistry . During a lipid-tolerance test , L1 lost its special position . In the association analysis , we found that eight loci ( LIPC , CETP , PLTP , FADS1-2-3 , SORT1 , GCKR , APOB , APOA1 ) were associated with the subfractions , whereas only four loci ( CETP , SORT1 , GCKR , APOA1 ) were associated with serum lipids . For LIPC , we observed a 10-fold increase in the variance explained by our regression models . In conclusion , NMR-based fine mapping of lipoprotein subfractions provides novel information on their biological nature and strengthens the associations with genetic loci . Future clinical studies are now needed to investigate their biomedical relevance .

lipoprotein subfractions

lipoproteins

lipoprotein subfractions

high-density lipoprotein

low-density lipoprotein

lipoprotein subfractions

15 lipoprotein subfractions ( L1-L15 )

lipoprotein subfractions

subfractions

lipoprotein subfractions

lipoprotein subfractions


A randomized trial of a behavioral intervention for black MSM : the DiSH study . OBJECTIVE To test a new behavioral intervention for black MSM in reducing sexual risk and increasing social support and intentions to use condoms . DESIGN A single-site , unblinded randomized trial in New York City with 3-month follow-up . METHODS Participants ( n = 283 ) reporting at least two sexual partners and unprotected anal intercourse with a man in the past 3 months were enrolled and randomized to a social-cognitive theory-based intervention or control comparison . Men in the intervention group participated in five 2-h group sessions focused on creating a group environment with sexual risk-reduction information and exercises woven into joint meal preparation and sharing activities , while exploring self-efficacy perceptions and outcome expectancies . Intervention ( n = 142 ) and control ( n = 141 ) groups received standard HIV counseling and testing at baseline . RESULTS No significant differences were found between study arms at 3 months in number of male partners , number of unprotected anal intercourse partners , proportion reporting unprotected sex , number of acts protected by condoms , self-efficacy , condom attitudes , condom intentions , social isolation and psychological distress . In both arms combined , declines from baseline to 3 months were observed in sexual risk behaviors , social isolation and psychological distress , whereas self-efficacy , condom attitudes and condom intentions improved . CONCLUSION As the HIV epidemic continues to have a dramatic impact on black MSM in the USA , the urgency to design innovative interventions continues .

behavioral intervention

or

control comparison


The home TEACCHing program for toddlers with autism . The study evaluated the efficacy a parent training intervention for children with autism based on the TEACCH model . Twenty families were randomly assigned to the treatment or waitlist group . All families were compared at pre- and post-treatment on formal dependent measures . Direct measures of behavior were compared across six matched pairs using a multiple baseline probe design . The results of the multiple baseline design showed robust support for improvement in child and parent behavior . Due to the sample size and short time frame , results of a repeated measures analysis of variance did not reach significance .

home TEACCHing program

parent training intervention

TEACCH model .

waitlist

measures of behavior

toddlers

autism

children

autism

Twenty families

child


Dopamine transporter gene moderates response to behavioral parent training in children with ADHD : a pilot study . There is great variability in the degree to which children with attention deficit/hyperactivity disorder ( ADHD ) improve through behavioral treatments . This study investigates the influence of the dopamine transporter gene ( SCL6A3/DAT1 ) on outcome of behavioral parent training ( BPT ) . Study subjects were a subsample ( n = 50 , for whom DAT1 genotypes were available ) of a randomized controlled BPT effectiveness study ( N = 94 ) comparing BPT plus ongoing routine clinical care ( RCC ) versus RCC alone in referred children ( 4-12 years old ) with ADHD . Treatment outcome was based on parent-reported ADHD symptoms and behavioral problems . Presence of 2 versus no or 1 DAT1 10-repeat allele served as moderator variable . Time × Treatment × Genotype effect was analyzed with repeated-measures analysis of variance , controlling for baseline medication status . Results indicate that DAT1 moderated treatment response ( p = .009 ) . In children with no or 1 DAT1 10-repeat allele , superior treatment effects of BPT + RCC compared with RCC alone were present ( p = .005 ) , which was not the case in children with 2 DAT1 10-repeat alleles ( p = .57 ) . Our findings suggest that genetic differences in DAT1 in children with ADHD influence their susceptibility to a behavioral intervention directed at shaping their environment through their parents . The role of the dopamine system in motivation and learning and in the aberrant sensitivity to reinforcement in children with ADHD may explain this moderating effect , given that the management of contingencies is typically addressed in BPT .

Dopamine transporter gene

behavioral parent training ( BPT ) .

RCC alone

children

ADHD

children

ADHD


Non-verbal communication of compassion : measuring psychophysiologic effects . BACKGROUND Calm , compassionate clinicians comfort others . To evaluate the direct psychophysiologic benefits of non-verbal communication of compassion ( NVCC ) , it is important to minimize the effect of subjects ' expectation . This preliminary study was designed to a ) test the feasibility of two strategies for maintaining subject blinding to non-verbal communication of compassion ( NVCC ) , and b ) determine whether blinded subjects would experience psychophysiologic effects from NVCC . METHODS Subjects were healthy volunteers who were told the study was evaluating the effect of time and touch on the autonomic nervous system . The practitioner had more than 10 years ' experience with loving-kindness meditation ( LKM ) , a form of NVCC . Subjects completed 10-point visual analog scales ( VAS ) for stress , relaxation , and peacefulness before and after LKM . To assess physiologic effects , practitioners and subjects wore cardiorespiratory monitors to assess respiratory rate ( RR ) , heart rate ( HR ) and heart rate variability ( HRV ) throughout the 4 10-minute study periods : Baseline ( both practitioner and subjects read neutral material ) ; non-tactile-LKM ( subjects read while the practitioner practiced LKM while pretending to read ) ; tactile-LKM ( subjects rested while the practitioner practiced LKM while lightly touching the subject on arms , shoulders , hands , feet , and legs ) ; Post-Intervention Rest ( subjects rested ; the practitioner read ) . To assess blinding , subjects were asked after the interventions what the practitioner was doing during each period ( reading , touch , or something else ) . RESULTS Subjects ' mean age was 43.6 years ; all were women . Blinding was maintained and the practitioner was able to maintain meditation for both tactile and non-tactile LKM interventions as reflected in significantly reduced RR . Despite blinding , subjects ' VAS scores improved from baseline to post-intervention for stress ( 5.5 vs. 2.2 ) , relaxation ( 3.8 vs. 8.8 ) and peacefulness ( 3.8 vs. 9.0 , P < 0.05 for all comparisons ) . Subjects also had significant reductions in RR ( P < 0.0001 ) and improved HRV ( P < 0.05 ) with both tactile and non-tactile LKM . CONCLUSION It is possible to test the effects of LKM with tactile and non-tactile blinding strategies ; even with blinding in this small preliminary study , subjects reported significant improvements in well-being which were reflected in objective physiologic measures of autonomic activity . Extending compassion is not only good care ; it may also be good medicine . TRIAL REGISTRATION NUMBER US National ClinicalTrials.gov registration number , NCT01428674 .

Non-verbal communication of compassion

loving-kindness meditation

NVCC

subjects rested ; the practitioner read

VAS

stress

relaxation

peacefulness

physiologic effects

respiratory rate ( RR )

heart rate ( HR )

heart rate variability ( HRV )

meditation

RR

VAS scores

stress

relaxation

peacefulness

RR

improved HRV


Comparison of cefuroxime axetil , cefaclor , and amoxicillin-clavulanate potassium suspensions in acute otitis media in infants and children . In this randomized , blinded , multicenter comparison study , 377 infants and children with acute otitis media ( AOM ) received a 10-day course of an oral suspension of one of the following : cefuroxime axetil ( CAE ) , 30 mg/kg/day ; cefaclor ( CEC ) , 40 mg/kg/day ; or amoxicillin-clavulanate potassium ( AMX-CL ) , 40 mg/kg/day . Clinical efficacy was determined by pneumatic otoscopy and tympanometric testing 3 to 5 , 11 to 14 , and 22 to 26 days after the initiation of therapy . There was a statistically significant difference among the three treatment groups with respect to clinical outcome ; more patients in the CAE group ( 62 % ) than in the CEC group ( 46 % ) or the AMX-CL group ( 52 % ) had complete resolution of signs and symptoms of AOM ( including effusion ) . Paired comparisons revealed a significant difference in efficacy between CAE and CEC and a nearly significant difference between AMX-CL and CEC . Taste acceptability was highest for CEC and lowest for this formulation of CAE . Significantly more patients in the AMX-CL group than in the CAE or CEC group had a side effect , primarily diarrhea , vomiting , or diaper rash . We conclude that CAE suspension has greater clinical efficacy than CEC and fewer side effects than AMX-CL .

cefuroxime axetil

amoxicillin-clavulanate potassium

cefuroxime axetil ( CAE )

cefaclor ( CEC )

CAE

AMX-CL

CAE

CEC

AMX-CL

CEC

CEC

CAE

AMX-CL

CAE

CEC

AMX-CL

Clinical efficacy

efficacy

Taste acceptability

primarily diarrhea

clinical efficacy

side effects

acute otitis media

infants and children

infants and children

acute otitis media ( AOM )


Granulocyte-colony stimulating factor for mobilizing bone marrow stem cells in subacute stroke : the stem cell trial of recovery enhancement after stroke 2 randomized controlled trial . BACKGROUND AND PURPOSE Granulocyte-colony stimulating factor ( G-CSF ) is neuroprotective in experimental stroke and mobilizes CD34 ( + ) peripheral blood stem cells into the circulation . We assessed the safety of G-CSF in recent stroke in a phase IIb single-center randomized , controlled trial . METHODS G-CSF ( 10 μg/kg ) or placebo ( ratio 2:1 ) was given SC for 5 days to 60 patients 3 to 30 days after ischemic or hemorrhagic stroke . The primary outcome was the frequency of serious adverse events . Peripheral blood counts , CD34 ( + ) count , and functional outcome were measured . MRI assessed lesion volume , atrophy , and the presence of iron-labeled CD34 ( + ) cells reinjected on day 6 . RESULTS Sixty patients were recruited at mean of 8 days ( SD ± 5 ) post ictus , with mean age 71 years ( ± 12 years ) and 53 % men . The groups were well matched for baseline minimization/prognostic factors . There were no significant differences between groups in the number of participants with serious adverse events : G-CSF 15 ( 37.5 % ) of 40 versus placebo 7 ( 35 % ) of 20 , death or dependency ( modified Rankin Score : G-CSF 3.3 ± 1.3 , placebo 3.0 ± 1.3 ) at 90 days , or the number of injections received . G-CSF increased CD34 ( + ) and total white cell counts of 9.5- and 4.2-fold , respectively . There was a trend toward reduction in MRI ischemic lesion volume with respect to change from baseline in G-CSF-treated patients ( P=0.06 ) . In 1 participant , there was suggestion that labeled CD34 ( + ) cells had migrated to the ischemic lesion . CONCLUSIONS This randomized , double-blind , placebo-controlled trial suggests that G-CSF is safe when administered subacutely . It is feasible to label and readminister iron-labeled CD34 ( + ) cells in patients with ischemic stroke . CLINICAL TRIAL REGISTRATION URL : www.controlled-trials.com . Unique identifier : ISRCTN63336619 .

Granulocyte-colony stimulating factor

stem cell

G-CSF

ischemic or hemorrhagic stroke

Sixty

mean age 71 years ( ± 12 years

men


Pilot study of the effectiveness of weighted vests . OBJECTIVE In this pilot study , we determined the effectiveness of a weighted vest on attention to task for second-grade general education students with difficulty attending . METHOD We used an intervention and a control group and an ABA design to compare participants ' percentage of time on task with and without a vest . Ten participants from nine elementary schools in a suburban Texas school district were randomly assigned to an intervention or a control group . Control group participants wore a nonweighted vest . Participants , classroom teachers , and research assistants who coded the data were blind as to the group to which the participants were assigned . RESULTS A repeated measures analysis of variance indicated no significant differences between groups or between baseline , intervention , and withdrawal conditions . CONCLUSION Our results indicated that the weighted vests were not effective in increasing time on task . These results should be generalized cautiously owing to the small sample size and participant selection process .

weighted vests

weighted vest

intervention

control

with and without a vest

intervention

nonweighted vest

weighted vests

time on task

second-grade

with difficulty attending

Ten


Exploring the social impact of being a typical peer model for included children with autism spectrum disorder . This study examined the social impact of being a typical peer model as part of a social skills intervention for children with autism spectrum disorder ( ASD ) . Participants were drawn from a randomized-controlled-treatment trial that examined the effects of targeted interventions on the social networks of 60 elementary-aged children with ASD . Results demonstrated that typical peer models had higher social network centrality , received friendships , friendship quality , and less loneliness than non-peer models . Peer models were also more likely to be connected with children with ASD than non-peer models at baseline and exit . These results suggest that typical peers can be socially connected to children with ASD , as well as other classmates , and maintain a strong and positive role within the classroom .

typical peer model

social skills intervention

interventions

Peer models

social impact

social impact

social networks

strong and positive role

autism spectrum disorder

autism spectrum disorder ( ASD )

elementary-aged children

ASD


Pre-bent instruments used in single-port laparoscopic surgery versus conventional laparoscopic surgery : comparative study of performance in a dry lab . BACKGROUND Different types of single-incision laparoscopic surgery ( SILS ) have become increasingly popular . Although SILS is technically even more challenging than conventional laparoscopy , published data of first clinical series seem to demonstrate the feasibility of these approaches . Various attempts have been made to overcome restrictions due to loss of triangulation in SILS by specially designed SILS-specific instruments . This study involving novices in a dry lab compared task performances between conventional laparoscopic surgery ( CLS ) and single-port laparoscopic surgery ( SPLS ) using newly designed pre-bent instruments . METHODS In this study , 90 medical students without previous experience in laparoscopic techniques were randomly assigned to undergo one of three procedures : CLS , SPLS using two pre-bent instruments ( SPLS-pp ) , or SPLS using one pre-bent and one straight laparoscopic instrument ( SPLS-ps ) . In the dry lab , the participants performed four typical laparoscopic tasks of increasing difficulty . Evaluation included performance times or number of completed tasks within a given time frame . All performances were videotaped and evaluated for unsuccessful attempts and unwanted interactions of instruments . Using subjective questionnaires , the participants rated difficulties with two-dimensional vision and coordination of instruments . RESULTS Task performances were significantly better in the CLS group than in either SPLS group . The SPLS-ps group showed a tendency toward better performances than the SPLS-pp group , but the difference was not significant . Video sequences and participants` questionnaires showed instrument interaction as the major problem in the single-incision surgery groups . CONCLUSIONS Although SILS is feasible , as shown in clinical series published by laparoscopically experienced experts , SILS techniques are demanding due to restrictions that come with the loss of triangulation . These can be compensated only partially by currently available SILS-designed instruments . The future of SILS depends on further improvements in the available equipment or the development of new approaches such as needlescopically assisted or robotically assisted procedures .

Pre-bent instruments

single-port laparoscopic surgery

SPLS

task performances

performance times

performances

subjective questionnaires

Task performances

performances

instrument interaction

major problem


Randomised controlled trial of improvisational music therapy 's effectiveness for children with autism spectrum disorders ( TIME-A ) : study protocol . BACKGROUND Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication . However , generalisability of previous findings has been restricted , as studies were limited in either methodological accuracy or the clinical relevance of their approach . The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders . An additional aim of the study is to examine if variation in dose of treatment ( i.e. , number of music therapy sessions per week ) affects outcome of therapy , and to determine cost-effectiveness . METHODS/DESIGN Children aged between 4 ; 0 and 6 ; 11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions . Parents of all participants will receive three sessions of parent counselling ( at 0 , 2 , and 5 months ) . In addition , children randomised to the two intervention groups will be offered individual , improvisational music therapy over a period of five months , either one session ( low-intensity ) or three sessions ( high-intensity ) per week . Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors ( Autism Diagnostic Observation Schedule , ADOS ) and parents ( Social Responsiveness Scale , SRS ) before and 2 , 5 , and 12 months after randomisation . Cost effectiveness will be calculated as man years . A group sequential design with first interim look at N = 235 will ensure both power and efficiency . DISCUSSION Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders , this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice . Addressing the issue of dose variation , this study 's results will also provide information on the relevance of session frequency for therapy outcome . TRIAL REGISTRATION Current Controlled Trials ISRCTN78923965 .

improvisational music therapy 's

music therapy

three sessions of parent counselling

effectiveness

skills

social interaction and communication

social communication skills

outcome of therapy

cost-effectiveness

standardised scales

Cost effectiveness

session frequency

children

autism spectrum disorders

autism spectrum disorders

children

autism spectrum disorders

autism spectrum disorder

autism spectrum disorders


Impact of antisecretory treatment on respiratory symptoms of gastroesophageal reflux disease in children . The effect of antisecretory treatment on extraesophageal symptoms of gastroesophageal reflux disease was evaluated . Seventy-eight children presenting with typical and extraesophageal symptoms of gastroesophageal reflux disease underwent a multichannel intraluminal impedance and pH monitoring ( MII/pH ) . Children with a positive MII/pH were randomly treated with proton pump inhibitors ( PPIs ) or histamine H ( 2 ) -receptor antagonists ( H ( 2 ) RAs ) during 3 months . At the end of the treatment period , all patients were recalled . A second treatment period of 3 months was given to those patients who were not symptom-free after 3 months . Thirty-five of the forty-one ( 85.4 % ) children with a pathologic MII/pH presented with extraesophageal symptoms and were treated with PPIs ( omeprazole ; n:19 ) or H ( 2 ) RAs ( ranitidine ; n:16 ) for 12 weeks . After 3 months , 11/19 ( 57.9 % ) PPI-treated patients had a complete resolution of symptoms ; 6/8 nonresponders were treated with PPI for another 3 months and became all symptom-free . The other two underwent a Nissen fundoplication . Only 5/16 ( 31.2 % ) patients treated with H ( 2 ) RAs had a complete resolution of symptoms after 3 months ; 1/11 was treated again with H ( 2 ) RAs during 3 months , and 10/11 were changed to PPIs . In 3/10 , a partial resolution of symptoms was achieved , while in 7/10 , a complete remission was obtained ( P < 0.05 ) . Antisecretory reflux treatment improves extraesophageal reflux symptoms . The efficacy of PPIs is superior to that of H ( 2 ) RAs in these children .

antisecretory treatment

antisecretory treatment

proton pump inhibitors ( PPIs )

PPIs ( omeprazole

H ( 2 ) RAs ( ranitidine

PPI-treated

PPI

H ( 2 ) RAs

H ( 2 ) RAs

PPIs

Antisecretory reflux treatment

PPIs

H ( 2 ) RAs

effect

extraesophageal symptoms

resolution of symptoms

symptom-free

complete resolution of symptoms

partial resolution of symptoms

complete remission

extraesophageal reflux symptoms

efficacy


[ Pharmacological correction of free radical disturbances and endotoxicosis in patients with diffuse peritonitis at the postoperative period ] . The examination and treatment of 64 patients have shown that inclusion of complex antioxidant cytoflavin in intensive therapy at the postoperative period of diffuse peritonitis allows the hypoxia degree to be decreased that in its turn results in quicker recovery of the antioxidant system and decreased activity of peroxidation and endotoxicosis level . The clinical course of the postoperative period of diffuse peritonitis with cytoflavin included in intensive therapy is characterized by shorter terms of artificial lung ventilation , shorter time of staying in critical condition , more favorable course of complications .

complex antioxidant cytoflavin

cytoflavin

artificial lung ventilation

staying in critical condition

course of complications


Efficacy of a total occlusive ionic silver-containing dressing combination in decreasing risk of surgical site infection : an RCT . OBJECTIVE To perform a comparative assessment of the efficacy of total occlusive ionic silver-containing dressing ( TOISD ) combination vs no dressing after colorectal surgery . METHOD The surgical sites from both groups were swabbed and sent for culture and sensitivity upon wound closure ( superficial incisional skin surface ) in the operating theatre , as a baseline for bacterial colonisation . The patients ' surgical wounds in the study group were dressed with TOISD combination and the patient 's surgical wounds in the control group received the conventional method of no dressing . A second swab was taken from the superficial incisional skin surface for culture and sensitivity investigation between the fifth to seventh postoperative day for comparison of the bacterial colonisation in the two groups . RESULTS One-hundred and sixty-six patients were recruited . Six patients dropped out before the fifth postoperative day , leaving 79 patients in the control group and 81 patients in the study group . Microbial swab cultures revealed significant differences between the two groups ( p < 0.001 , mean=1.43±0.63 ) in bacterial colonisation . The odds ratio ( OR ) of patients with wounds in the control group was 4.1 ( 95 % CI is 1.884 , 8.964 ) more likely to be contaminated with bacteria compared with wounds covered with occlusive ionic silver-containing dressing . CONCLUSION TOISD was found to be effective in reducing bacterial colonisation on the surgical site compared with no dressing . However , it properties were unable to be put into use if there were the surgical sites were not infested with bacterial . Although TOISD might not be necessarily on surgical incisional site not infested with bacteria for the initial post-operation days , it is helpful in preventing further transcription and division for opportunistic bacteria , thus might reduce the risk of superficial incisional SSI . The use of TOSID though statistically insignificant compared to no dressing , could also be possible in reducing the risk and exaceration of deep incisional SSI .

no dressing

TOISD

risk of surgical site infection :


The relationship of alexithymia to emotional dysregulation within an alcohol dependent treatment sample . Difficulties regulating emotions have implications for the development , maintenance , and recovery from alcohol problems . One construct thought to impede the regulation of emotion is alexithymia . Alexithymia is characterized by difficulties identifying , differentiating and expressing feelings , a limited imagination and fantasy life , and an externally-oriented thinking style ( e.g. , prefer talking about daily activities rather than feelings ) . Given that poor emotion regulation skills have been found to predict posttreatment levels of alcohol use , and that several defining characteristics of alexithymia bear similarity to deficits in emotion regulation skills , it is possible that alexithymia may predict poorer alcohol treatment outcomes . Thus , the present study first examined the relationship of alexithymia to several other emotion regulation measures and then investigated the impact of alexithymia on attrition and alcohol treatment outcomes in men and women ( N=77 ) enrolled in a 12-week cognitive-behavioral intervention for alcohol dependence . At baseline , higher scores on alexithymia were associated poorer emotion regulation skills , fewer percent days abstinent , greater alcohol dependence severity , and several high-risk drinking situations . Alexithymia was unrelated to attrition and to level of alcohol consumption at posttreatment . Overall , the construct of alexithymia is shown to be related to several theoretically-related constructs ( e.g. , emotion regulation , mindfulness ) but demonstrated a limited relationship to drinking outcomes in those seeking treatment for alcohol dependence .

alexithymia

emotion regulation measures

alexithymia

emotion regulation measures

poorer emotion regulation skills

fewer percent days abstinent

greater alcohol dependence severity

several high-risk drinking situations


Recombinant human erythropoietin .

Recombinant human erythropoietin

Recombinant human erythropoietin .


Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers . Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers . A single oral dose of 1500 mg mefloquine hydrochloride was administered to 11 patients and 5 volunteers and 750 mg was given to 16 patients and 5 volunteers . Efficacy was 82 % for 1500 mg and 63 % for 750 mg . In cured patients taking 750 mg mefloquine , peak plasma drug concentration ( Cmax ) and area under the plasma concentration-time curve ( AUC ) were significantly greater than in the patients for whom treatment failed ( p less than 0.0005 and p less than 0.01 , respectively ) , and plasma mefloquine levels were significantly higher from 8 hours to 18 days after treatment . Mefloquine AUC was reduced and variable in the presence of diarrhea . Compared with noninfected volunteers , clinically ill patients displayed a delayed time to reach peak concentration ( p less than 0.01 ) and significantly higher mefloquine plasma levels in the first 2 days after administration of either the 750 mg or the 1500 mg dose . Mefloquine AUC was similar in patients with malaria and healthy volunteers . Because plasma levels increased in temporal relationship with clinical illness , mefloquine volume of distribution or clearance ( or both ) was reduced during the acute phase of illness .

Mefloquine kinetics

Mefloquine

mefloquine hydrochloride

mefloquine

Efficacy

peak plasma drug concentration

( Cmax )

plasma mefloquine levels

Mefloquine AUC

time to reach peak concentration

mefloquine plasma levels

Mefloquine AUC


Effects of risperidone and parent training on adaptive functioning in children with pervasive developmental disorders and serious behavioral problems . OBJECTIVE Children with Pervasive Developmental Disorders ( PDDs ) have social interaction deficits , delayed communication , and repetitive behaviors as well as impairments in adaptive functioning . Many children actually show a decline in adaptive skills compared with age mates over time . METHOD This 24-week , three-site , controlled clinical trial randomized 124 children ( 4 through 13 years of age ) with PDDs and serious behavioral problems to medication alone ( MED ; n = 49 ; risperidone 0.5 to 3.5 mg/day ; if ineffective , switch to aripiprazole was permitted ) or a combination of medication plus parent training ( PT ) ( COMB ; n = 75 ) . Parents of children in COMB received an average of 11.4 PT sessions . Standard scores and Age-Equivalent scores on Vineland Adaptive Behavior Scales were the outcome measures of primary interest . RESULTS Seventeen subjects did not have a post-randomization Vineland assessment . Thus , we used a mixed model with outcome conditioned on the baseline Vineland scores . Both groups showed improvement over the 24-week trial on all Vineland domains . Compared with MED , Vineland Socialization and Adaptive Composite Standard scores showed greater improvement in the COMB group ( p = .01 and .05 , and effect sizes = 0.35 and 0.22 , respectively ) . On Age Equivalent scores , Socialization and Communication domains showed greater improvement in COMB versus MED ( p = .03 and 0.05 , and effect sizes = 0.33 and 0.14 , respectively ) . Using logistic regression , children in the COMB group were twice as likely to make at least 6 months ' gain ( equal to the passage of time ) in the Vineland Communication Age Equivalent score compared with MED ( p = .02 ) . After controlling for IQ , this difference was no longer significant . CONCLUSION Reduction of serious maladaptive behavior promotes improvement in adaptive behavior . Medication plus PT shows modest additional benefit over medication alone . Clinical trial registration information-RUPP PI PDD : Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders ; http : //www.clinicaltrials.gov ; NCT00080145 .

risperidone

and parent training

medication alone

risperidone

aripiprazole

combination of medication

parent training

( PT )

PT sessions

Medication

PT

medication alone

Socialization and Communication domains