Comparison of the antiemetic effect of ramosetron and combined ramosetron and midazolam in children : a double-blind , randomised clinical trial . CONTEXT Postoperative nausea and vomiting remains a clinically important problem after strabismus surgery in children . OBJECTIVE To study the benefit of adding midazolam to ramosetron on the incidence of postoperative nausea , retching or vomiting and on the incidence of postoperative agitation . DESIGN A randomised , double-blind comparison . SETTING The operating theatre suite and day care unit of Seoul National University Hospital . The study period was January to December 2010 . PATIENTS In total , 405 paediatric patients ( aged 4-12 years ) undergoing strabismus surgery were enrolled and randomly assigned to one of two groups , ramosetron or ramosetron with midazolam . INTERVENTION Patients received either ramosetron 6 μg kg or ramosetron 6 μg kg and midazolam 0.1 mg kg prior to induction of anaesthesia . MAIN OUTCOME MEASURES The incidences of nausea , retching or vomiting in the first 48 h after surgery , and the incidence of emergence agitation in the post-anaesthetic care unit . RESULT The incidences of nausea , retching or vomiting during the first and second 24-h periods after surgery were similar in the two groups . There was a small , clinically insignificant reduction in delirium scores in the ramosetron with midazolam group . CONCLUSION Adding midazolam to ramosetron had no advantages over ramosetron alone in reducing the incidence of postoperative nausea and vomiting in children undergoing strabismus surgery .

ramosetron

combined ramosetron and midazolam

midazolam to ramosetron

strabismus surgery

ramosetron or ramosetron with midazolam

children :

strabismus surgery in children .


The effect of rectal distension on bladder function in patients with overactive bladder . AIMS To investigate the effect of rectal distension on bladder sensation volumes and the number of detrusor contractions in patients with overactive bladder ( OAB ) symptoms . METHODS A prospective randomized study included patients with OAB symptoms . Multichannel urodynamic studies were completed with and without rectal balloon distension . Bladder sensation volumes and detrusor contractions were compared . RESULTS Twenty-six patients were included in the study . The mean age was 67 years and mean BMI was 28.3 kg/m ( 2 ) . Bladder sensation volumes were lower with rectal distention as follows : normal desire to void ( 139 ml SD , ±114 vs. 197 ml SD ±150 , P = 0.01 ) , strong desire to void ( 260 ml SD ±171 vs. 330 ml SD ±172 , P = 0.01 ) , and maximum cystometric capacity ( 326 ml SD ±183 vs. 403 ml SD ±180 , P = 0.0001 ) . There was no difference in the number of detrusor contractions or the bladder volume at which the first detrusor contraction had occurred with and without rectal distension . CONCLUSION Rectal distention in patients with OAB symptoms significantly lowered bladder sensation volumes ( normal desire , strong desire , and maximal capacity ) .

rectal distension

rectal distension

patients with overactive bladder .


Randomized comparison of the efficacy and safety of zotarolimus-eluting stents vs. sirolimus-eluting stents for percutaneous coronary intervention in chronic total occlusion -- CAtholic Total Occlusion Study ( CATOS ) trial . BACKGROUND Limited data are available regarding the direct comparison of angiographic and clinical outcomes after percutaneous coronary intervention ( PCI ) with drug-eluting stents ( DESs ) for chronic total occlusion ( CTO ) . METHODS AND RESULTS A prospective , randomized , multicenter trial was conducted to evaluate the non-inferiority of a zotarolimus-eluting stent ( ZES ; Endeavor Sprint® , n=80 ) to a sirolimus-eluting stent ( SES ; Cypher® , n=80 ) in patients with CTO lesion with a reference vessel diameter ≥ 2.5mm . The primary endpoint was in-segment binary restenosis rate at 9-month angiographic follow-up . Key secondary endpoints included target vessel failure ( TVF ; including cardiac death , myocardial infarction , and target vessel revascularization ) and Academic Research Consortium-defined definite/probable stent thrombosis ( ST ) within 12 months . The ZES was non-inferior to the SES with respect to the primary endpoint , which occurred in 14.1 % ( 95 % confidence interval [ CI ] : 6.0-22.2 ) and in 13.7 % ( 95 % CI : 5.8-21.6 ) of patients , respectively ( non-inferiority margin , 15.0 % ; P for non-inferiority < 0.001 ) . There were no significant between-group differences in the rate of TVF ( 10.0 % vs. 17.5 % ; P=0.168 ) nor in the rate of ST ( 0.0 % vs. 1.3 % ; P=0.316 ) during the 12-month clinical follow-up . CONCLUSIONS The effectiveness and safety of ZES are similar to those of SES and therefore it is a good treatment option in patients undergoing PCI for CTO with DESs .

zotarolimus-eluting stents

sirolimus-eluting stents

drug-eluting stents

zotarolimus-eluting stent

sirolimus-eluting stent

efficacy and safety

in-segment binary restenosis rate


[ Branch atheromatous disease : prognosis and management . The SPS3 experience ] .


Effects of a common variant in the CD38 gene on social processing in an oxytocin challenge study : possible links to autism . The intranasal application of oxytocin ( OT ) has been shown to influence behavioral and neural correlates of social processing . These effects are probably mediated by genetic variations within the OT system . One potential candidate could be the CD38 gene , which codes for a transmembrane protein engaged in OT secretion processes . A common variation in this gene ( rs3796863 ) was recently found to be associated with autism spectrum disorders ( ASD ) . Using an imaging genetics approach , we studied differential effects of an intranasal OT application on neural processing of social stimuli in 55 healthy young men depending on their CD38 gene variant in a double-blind placebo-controlled crossover design . Genotype had a significant influence on both behavioral and neuronal measures of social processing . Homozygotic risk allele carriers showed slower reaction times ( RT ) and higher activation of left fusiform gyrus during visual processing of social stimuli . Under OT activation differences between genotypes were more evident ( though not statistically significantly increased ) and RT were accelerated in homozygotic risk allele carriers . According to our data , rs3796863 mainly influences fusiform gyrus activation , an area which has been widely discussed in ASD research . OT seems to modulate this effect by enhancing activation differences between allele groups , which suggests an interaction between genetic makeup and OT availability on fusiform gyrus activation . These results support recent approaches to apply OT as a pharmacological treatment of ASD symptoms .

oxytocin

oxytocin ( OT )

OT application

placebo-controlled

OT

pharmacological treatment

social processing

neural processing of social stimuli

slower reaction times ( RT )

social stimuli

activation differences

activation differences

genetic makeup

OT availability

fusiform gyrus activation


Enhancing the self-esteem of inpatient alcoholics . This study examined the effect of pairing inpatient alcoholics with nursing home residents ( NHRs ) on the alcoholics ' self-esteem . In this PALS program , the alcoholic inpatients assumed a helping-companion relationship with the NHRs for 2 hr per day during their last 2 weeks of treatment . Fifty alcoholic inpatients were randomly assigned to the PALS program ( n = 25 ) or to the library for free reading time ( n = 25 ) . The Tennessee Self-Concept Scale ( TSCS ) was administered to all subjects in both groups before and after the interventions . Of the nine TSCS scales , the improvement on the Moral-Ethical scale was significantly greater in the PALS group . Because the alcoholic inpatients in the PALS group engaged in altruistic ( moral ) behavior , this study provides a logical link between the intervention and the outcome , which has been a prevalent weakness in previous studies of self-esteem in alcoholics .

nursing home residents ( NHRs )

PALS program

library for free reading time

self-esteem

alcoholics ' self-esteem

Tennessee Self-Concept Scale ( TSCS )

TSCS scales

Moral-Ethical scale

altruistic ( moral ) behavior

inpatient alcoholics .

Fifty alcoholic


Predictors of response to ziprasidone : results from a 6-week randomized double-blind , placebo-controlled trial for acute depressive mixed state . INTRODUCTION The present study is aimed at investigating possible predictors of response to ziprasidone in a sample of patients with mixed depressive state . METHODS 72 patients were randomized to either ziprasidone or placebo and treated prospectively for 6 weeks . The clinical response and remission were defined with various clinical variables including Montgomery Asberg Depression Rating Scale . Further outcome measures included predictors of remission and other clinical variables over time . RESULTS None of the variables under investigation were significantly associated with response or remission at 6 weeks ( all p-values > 0.003 , respectively ) . CONCLUSIONS Further investigations are warranted due to clear limitations , mostly small sample size and use of concomitant medications .

ziprasidone

placebo-controlled

ziprasidone

placebo

remission

response or remission

acute depressive mixed state

mixed depressive state


Effect of acute exercise on executive function in children with attention deficit hyperactivity disorder . This study was conducted to determine the effect of acute aerobic exercise on executive function in children with attention deficit hyperactivity disorder ( ADHD ) . Forty children with ADHD were randomly assigned into exercise or control groups . Participants in the exercise group performed a moderate intensity aerobic exercise for 30 min , whereas the control group watched a running/exercise-related video . Neuropsychological tasks , the Stroop Test and the Wisconsin Card Sorting Test ( WCST ) , were assessed before and after each treatment . The results indicated that acute exercise facilitated performance in the Stroop Test , particularly in the Stroop Color-Word condition . Additionally , children in the exercise group demonstrated improvement in specific WCST performances in Non-perseverative Errors and Categories Completed , whereas no influences were found in those performances in the control group . Tentative explanations for the exercise effect postulate that exercise allocates attention resources , influences the dorsolateral prefrontal cortex , and is implicated in exercise-induced dopamine release . These findings are promising and additional investigations to explore the efficacy of exercise on executive function in children with ADHD are encouraged .

acute exercise

acute aerobic exercise

running/exercise-related video

efficacy of exercise

executive function

executive function

Stroop Color-Word condition .

WCST performances

attention

dorsolateral prefrontal cortex

exercise-induced dopamine release .

efficacy

children

children

ADHD

children

ADHD


Prefrontal neuromodulation using rTMS improves error monitoring and correction function in autism . One important executive function known to be compromised in autism spectrum disorder ( ASD ) is related to response error monitoring and post-error response correction . Several reports indicate that children with ASD show reduced error processing and deficient behavioral correction after an error is committed . Error sensitivity can be readily examined by measuring event-related potentials ( ERP ) associated with responses to errors , the fronto-central error-related negativity ( ERN ) , and the error-related positivity ( Pe ) . The goal of our study was to investigate whether reaction time ( RT ) , error rate , post-error RT change , ERN , and Pe will show positive changes following 12-week long slow frequency repetitive TMS ( rTMS ) over dorsolateral prefrontal cortex ( DLPFC ) in high functioning children with ASD . We hypothesized that 12 sessions of 1 Hz rTMS bilaterally applied over the DLPFC will result in improvements reflected in both behavioral and ERP measures . Participants were randomly assigned to either active rTMS treatment or wait-list ( WTL ) groups . Baseline and post-TMS/or WTL EEG was collected using 128 channel EEG system . The task involved the recognition of a specific illusory shape , in this case a square or triangle , created by three or four inducer disks . ERN in TMS treatment group became significantly more negative . The number of omission errors decreased post-TMS . The RT did not change , but post-error RT became slower . There were no changes in RT , error rate , post-error RT slowing , nor in ERN/Pe measures in the wait-list group . Our results show significant post-TMS differences in the response-locked ERP such as ERN , as well as behavioral response monitoring measures indicative of improved error monitoring and correction function . The ERN and Pe , along with behavioral performance measures , can be used as functional outcome measures to assess the effectiveness of neuromodulation ( e.g. , rTMS ) in children with autism and thus may have important practical implications .

rTMS

rTMS

rTMS

active rTMS treatment

wait-list ( WTL ) groups

error processing

behavioral correction

event-related potentials ( ERP )

error-related positivity

behavioral and ERP measures .

Baseline and post-TMS/or WTL EEG

ERN

omission errors

RT

post-error RT

response-locked ERP

ERN

ERN

Pe


Azathioprine and the treatment of chronic inflammatory bowel disease .

Azathioprine

chronic inflammatory bowel disease .


Comparison of sedative drugs under peribulbar or topical anesthesia during phacoemulsification . BACKGROUND AND OBJECTIVE To compare dexmedetomidine and midazolam+fentanyl sedation primarily based on patient satisfaction during phacoemulsification under topical and peribulbar anesthesia . PATIENTS AND METHODS Prospective , randomized , and double-blind study of 80 American Society of Anesthesiology grade I-II patients who underwent phacoemulsification with local anesthesia under sedation . Patients were divided into four groups ( 20 patients for each ) : dexmedetomidine and topical anesthesia , dexmedetomidine and peribulbar anesthesia , midazolam+fentanyl and topical anesthesia , and midazolam+fentanyl and peribulbar anesthesia . Patient and surgeon satisfaction were determined on a 5-point scale . The pain was determined by verbal pain scale intraoperatively and postoperatively . Drugs were given to a Ramsay sedation scale of 3 . Topical and peribulbar anesthesia were performed by an ophthalmologist . Hemodynamic , respiratory , and intraocular pressure monitoring was done . Operative and recovery times were recorded . RESULTS In the midazolam+fentanyl groups , better patient and surgeon satisfaction scores were obtained ( P < .005 ) , verbal pain scale scores were significantly lower ( P < .001 ) , and patients needed less postoperative analgesia . Ramsay sedation scale scores were between 3 and 4 in all patients and there were no significant differences . Intraocular pressure alterations were similar between groups . Recovery time was longer in the dexmedetomidine groups ( P < .05 ) . CONCLUSION The study demonstrated that the midazolam+fentanyl combination provided high-level patient satisfaction scores , low-level pain scores , and shorter recovery time . Also , both of the peribulbar and topical anesthesia procedures showed similar efficiency .

sedative drugs

dexmedetomidine

midazolam+fentanyl sedation

dexmedetomidine

topical anesthesia

dexmedetomidine

peribulbar anesthesia

midazolam+fentanyl

topical anesthesia

midazolam+fentanyl

peribulbar anesthesia

midazolam+fentanyl

midazolam+fentanyl combination

patient and surgeon satisfaction scores

verbal pain scale scores

postoperative analgesia

Ramsay sedation scale scores

Intraocular pressure alterations

Recovery time

patient satisfaction scores

pain scores

recovery time

phacoemulsification


Randomised clinical trial : efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus arabinogalactan and xilooligosaccharides in children with acute diarrhoea . BACKGROUND Acute diarrhoea is a frequent problem in children with heavy economic burden for families and society . AIM To test the efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 , arabinogalactan and xilooligosaccharides in children with acute diarrhoea . METHODS Double-blind , randomised , placebo-controlled trial , including children ( age 3-36 m ) with acute diarrhoea who were allocated to placebo or synbiotic group . Major outcome was resolution rate of diarrhoea at 72 h. Total duration of diarrhoea , daily stool outputs , stool consistency , working days lost by parents , adjunctive medications , and hospitalisation were also assessed . RESULTS We enrolled 55 children in placebo group and 52 in synbiotic group . The two groups were similar for demographic and clinical characteristics . Resolution rate of diarrhoea at 72 h was significantly higher in synbiotic group ( 67 % ) compared to placebo group ( 40 % , P = 0.005 ) . Children in synbiotic group showed a significant reduction in the duration of diarrhoea ( 90.5 h , 78.1-102.9 vs. 109.8 h , 96.0-123.5 , P = 0.040 ) , daily stool outputs ( 3.3 , 2.8-3.8 vs. 2.4 , 1.9-2.8 , P = 0.005 ) and stool consistency ( 1.3 , 0.9-1.6 vs. 0.6 , 0.4-0.9 , P = 0.002 ) compared to placebo group ( data expressed as mean , 95 % CI ) . Rate of parents that missed at least one working day ( 41.8 % vs. 15.4 % , P = 0.003 ) , rate of children that needed adjunctive medications ( 25.5 % vs. 5.8 % , P = 0.005 ) or hospitalisation ( 10.9 % vs. 0 % , P = 0.014 ) after the first 72 h of treatment , were reduced in synbiotic group . CONCLUSION The synbiotic formulation studied is effective in children with acute diarrhoea . Australian New Zealand Clinical Trials Registry ( ACTRN12611000641998 ) .

placebo

synbiotic group

placebo

synbiotic

placebo

placebo

synbiotic formulation

efficacy

resolution rate of diarrhoea at 72 h.

duration of diarrhoea ,

daily stool outputs

stool consistency

working days lost by parents

adjunctive medications

hospitalisation

Resolution rate of diarrhoea

duration of diarrhoea

daily stool outputs

stool consistency

hospitalisation

acute diarrhoea

acute diarrhoea

age 3-36 m

55 children in placebo group

52 in synbiotic group


Effect of HIV infection on tolerability and bacteriologic outcomes of tuberculosis treatment . SETTING Two international , multicenter Phase 2 clinical trials examining fluoroquinolone-containing regimens in adults with smear-positive pulmonary tuberculosis ( TB ) , conducted from July 2003 to March 2007 . Both trials enrolled human immunodeficiency virus ( HIV ) infected participants who were not receiving antiretroviral therapy ( ART ) at TB treatment initiation . OBJECTIVE To assess the impact of HIV infection on TB treatment outcomes in Phase 2 clinical trials . DESIGN Cross-protocol analysis comparing the safety , tolerability and outcomes of anti-tuberculosis treatment by HIV status . RESULTS Of 750 participants who received at least one dose of study treatment , 123 ( 16 % ) were HIV-infected . Treatment completion rates were similar by HIV status ( 81 % infected vs. 85 % non-infected ) , as were rates of week 8 culture conversion ( 66 % infected vs. 63 % non-infected ) , and treatment failure ( 5 % infected vs. 3 % non-infected ) . Among HIV-infected participants , treatment failure detected using liquid media was more frequent in those treated thrice weekly ( 14 % thrice weekly vs. 2 % daily , P = 0.03 ) . HIV-infected participants more frequently experienced an adverse event during the intensive phase treatment than non-HIV-infected participants ( 30 % vs. 15 % , P < 0.01 ) . CONCLUSION HIV-infected persons not receiving ART had more adverse events during the intensive phase of anti-tuberculosis treatment , but tolerated treatment well . Failure rates were higher among HIV-infected persons treated with thrice-weekly intensive phase therapy .

fluoroquinolone-containing regimens

anti-tuberculosis treatment

tolerability and bacteriologic outcomes

safety , tolerability and outcomes

Treatment completion rates

treatment failure

adverse event

tolerated treatment well .

750 participants

HIV-infected

HIV-infected persons


The influence of penbutolol and placebo on blood sugar levels and insulin consumption in the glucose-controlled insulin infusion system ( " artificial endocrine pancreas " ) . The aim of the study was to investigate the influence of 40 mg of the beta-blocker penbutolol ( Betapressin TM ; Hoechst Ltd. , Frankfurt/Main ) in comparison to placebo on the insulin consumption on the blood sugar profile in twelve insulin-dependent diabetes ( IDDM ) patients . The patients were treated with penbutolol and placebo for a period of three days , and then were examined with the help of the glucose-controlled insulin infusion system . The blood sugar profile and insulin consumption over a 24 hour period was not affected by either penbutolol or placebo , nor could any changes be measured in these parameters when measured after food intake . After a submaximal exercise load on the bicycle ergometer ( 1 watt per kg body weight ) following an evening meal , no difference could be observed between penbutolol and placebo in the above-mentioned parameters . The same was also true for hormonal parameters as STH , ACTH , cortisol , and catecholamines . These findings demonstrated that medication of penbutolol over a three-day period has no influence on the baseline blood sugar profile and insulin consumption or on insulin consumption after food intake during rest and physical exercise .

penbutolol

placebo

penbutolol

placebo

penbutolol

placebo

blood sugar profile

insulin consumption


Bilateral transversus abdominis plane block does not decrease postoperative pain after laparoscopic cholecystectomy when compared with local anesthetic infiltration of trocar insertion sites . BACKGROUND AND OBJECTIVES Transversus abdominis plane ( TAP ) block has been shown to reduce pain and analgesic requirements after abdominal surgery . Our hypothesis was that bilateral TAP blocks decrease pain after laparoscopic cholecystectomy when compared with local anesthetic infiltration of trocar insertion sites . METHODS Eighty patients undergoing laparoscopic cholecystectomy were randomized to receive either bilateral TAP blocks or local anesthetic infiltration of trocar insertion sites with ropivacaine 0.5 % . Postoperative pain scores and analgesic use for the first 24 hrs were recorded . RESULTS Eighty patients were enrolled in the study . After exclusions , data were analyzed on 39 patients in group T ( bilateral TAP block ) and 35 patients in group I ( infiltration ) . There was no statistically significant difference in pain scores on the numeric analog scale ( 0-10 ) between the groups at 4 hrs after surgery ( P = 0.18 ) or during the 24 hrs after surgery ( P = 0.23 ) . The time interval from anesthesia start to surgery start was greater in group T than group I ( 48 vs 35 mins , P < 0.001 ) . There was no significant difference found in analgesic use during the first 24 hrs after surgery . CONCLUSIONS Bilateral ultrasound-guided TAP block is equivalent to local anesthetic infiltration of trocar insertion sites for overall postoperative pain in a heterogeneous group of patients undergoing laparoscopic cholecystectomy .

bilateral TAP blocks

local anesthetic infiltration

bilateral TAP blocks

TAP block

Bilateral ultrasound-guided TAP block

local anesthetic infiltration

Postoperative pain

statistically significant difference

pain scores on the numeric analog scale

significant difference

analgesic use

postoperative pain

Eighty patients

laparoscopic cholecystectomy

Eighty patients


Evaluation of masking study participants to intravitreal injections in a randomized clinical trial . OBJECTIVE To evaluate the success of masking study participants to treatment allocation using sham intravitreal injections . METHODS Eyes were randomized to receive sham injections plus prompt laser , intravitreal ranibizumab injections plus prompt laser , intravitreal ranibizumab injections plus deferred laser , or intravitreal triamcinolone acetonide injections plus prompt laser up to every 16 weeks with sham injections intermittently . All eyes could receive treatment or sham as often as every 4 weeks . Participants with 2 study eyes had 1 eye randomized to sham plus prompt laser and 1 eye randomized to a real injection group . Sham injections were performed by pressing the syringe hub against the conjunctiva to mimic a real injection . Laser treatment was not masked . At the 1-year visit , participants were asked if they believed that the injections received during the study were real , sham , or sometimes real and sometimes sham . RESULTS Among 423 participants with 1 study eye , the correct assignment was stated by 9.9 % of the sham plus prompt laser group , 88.0 % of the ranibizumab plus prompt laser group , 89.6 % of the unmasked ranibizumab plus deferred laser group , and 44.0 % of the triamcinolone plus prompt laser group . Among 112 participants with 2 study eyes , the correct assignment was stated for 24.1 % of the sham plus prompt laser eyes . CONCLUSIONS Successful masking of an intravitreal injection can be accomplished when a sham injection procedure carefully mimics a real injection procedure . Masking seems less successful when one eye is receiving a real injection and the other eye is receiving a sham injection or when an individual eye receives both real and sham injections .

sham intravitreal injections

sham injections plus

prompt laser

prompt laser

deferred laser

prompt laser

sham plus prompt laser

real injection

Laser treatment

sometimes real and sometimes sham

ranibizumab plus deferred laser

triamcinolone plus prompt laser

sham injection

real injection

success

correct assignment

correct assignment

Successful masking

Masking

successful

1 study eye

2 study eyes


A randomized controlled pilot trial of oral N-acetylcysteine in children with autism . BACKGROUND An imbalance in the excitatory/inhibitory systems with abnormalities in the glutamatergic pathways has been implicated in the pathophysiology of autism . Furthermore , chronic redox imbalance was also recently linked to this disorder . The goal of this pilot study was to assess the feasibility of using oral N-acetylcysteine ( NAC ) , a glutamatergic modulator and an antioxidant , in the treatment of behavioral disturbance in children with autism . METHODS This was a 12-week , double-blind , randomized , placebo-controlled study of NAC in children with autistic disorder . Subjects randomized to NAC were initiated at 900 mg daily for 4 weeks , then 900 mg twice daily for 4 weeks and 900 mg three times daily for 4 weeks . The primary behavioral measure ( Aberrant Behavior Checklist [ ABC ] irritability subscale ) and safety measures were performed at baseline and 4 , 8 , and 12 weeks . Secondary measures included the ABC stereotypy subscale , Repetitive Behavior Scale-Revised , and Social Responsiveness Scale . RESULTS Thirty-three subjects ( 31 male subjects , 2 female subjects ; aged 3.2-10.7 years ) were randomized in the study . Follow-up data was available on 14 subjects in the NAC group and 15 in the placebo group . Oral NAC was well tolerated with limited side effects . Compared with placebo , NAC resulted in significant improvements on ABC irritability subscale ( F = 6.80 ; p < .001 ; d = .96 ) . CONCLUSIONS Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder . Large randomized controlled investigations are warranted .

N-acetylcysteine

oral N-acetylcysteine ( NAC )

placebo-controlled

NAC

NAC

placebo

NAC

placebo

NAC

NAC

tolerated

ABC irritability subscale

children

autism

children

autism

children

autistic disorder

Thirty-three

male

female

3.2-10.7 years

children

autistic disorder


Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty . CONTEXT GnRH agonist ( GnRHa ) monthly injections are frequently used in the treatment of central precocious puberty ( CPP ) . The 3-month leuprolide depot 11.25- and 30-mg formulations are newly approved treatment options . OBJECTIVE The aim of the study was to investigate the safety and efficacy of leuprolide acetate 3-month depot formulations for the treatment of CPP in children . DESIGN This was a phase III , randomized , open-label , dose-ranging 6-month study . SETTING Twenty-two U.S. medical centers ( including Puerto Rico ) participated . PATIENTS Children diagnosed with CPP ( n = 84 ) , who were either treatment naive or previously treated with GnRHa , were recruited . Chronological age at onset of pubertal signs was less than 8 yr in girls and less than 9 yr in boys , and bone age was advanced over chronological age at least 1 yr . INTERVENTION Leuprolide acetate depot ( 11.25 or 30 mg ) was administered im every 3 months . MAIN OUTCOME MEASURES Biochemical [ peak-stimulated LH , estradiol ( girls ) , and testosterone ( boys ) ] and anthropometric ( growth rate , bone age acceleration , pubertal progression ) parameters and safety were assessed . RESULTS Peak-stimulated LH was suppressed in the 11.25- and 30-mg dose groups in 78.4 and 95.2 % , respectively , of children from months 2 through 6 . There were nine treatment failures ( peak-stimulated LH > 4 IU/liter ) in the 11.25-mg group and two in the 30-mg group . Basal sex steroid suppression , growth rates , pubertal progression , bone age advancement , and adverse events were similar with either dose . CONCLUSIONS Treatment with leuprolide acetate 3-month depot formulations ( 11.25 and 30 mg ) effectively suppressed the GnRH axis , was well tolerated , and may positively impact patient convenience and compliance .

leuprolide acetate 3-month

3-month leuprolide depot 11.25-

leuprolide acetate 3-month

Leuprolide acetate depot

leuprolide acetate

Efficacy and safety

Basal sex steroid suppression

growth rates

pubertal progression

bone age advancement

adverse events


Virtual reality for acute pain reduction in adolescents undergoing burn wound care : a prospective randomized controlled trial . BACKGROUND Effective pain management remains a challenge for adolescents during conscious burn wound care procedures . Virtual reality ( VR ) shows promise as a non-pharmacological adjunct in reducing pain . AIMS This study assessed off-the-shelf VR for ( 1 ) its effect on reducing acute pain intensity during adolescent burn wound care , and ( 2 ) its clinical utility in a busy hospital setting . METHODS Forty-one adolescents ( 11-17 years ) participated in this prospective randomized controlled trial . Acute pain outcomes including adolescent self-report , nursing staff behavioral observation , caregiver observation and physiological measures were collected . Length of procedure times and adolescent reactions were also recorded to inform clinical utility . RESULTS Nursing staff reported a statistically significant reduction in pain scores during dressing removal , and significantly less rescue doses of Entonox given to those receiving VR , compared to those receiving standard distraction . For all other pain outcomes and length of treatment , there was a trend for lower pain scores and treatment times for those receiving VR , but these differences were not statistically significant . CONCLUSION Despite only minimal pain reduction achieved using off-the-shelf VR , other results from this trial and previous research on younger children with burns suggest a customized , adolescent and hospital friendly device may be more effective in pain reduction .

Virtual reality

pain management

Virtual reality ( VR )

off-the-shelf VR

Entonox

VR

VR

VR

pain scores

rescue doses of Entonox

pain scores and treatment times

adolescents

burn wound care

adolescents

Forty-one

adolescents

11-17 years


ApoA-I induction as a potential cardioprotective strategy : rationale for the SUSTAIN and ASSURE studies . BACKGROUND Considerable interest has focused on the development of therapies that target the functionality of high-density lipoproteins ( HDL ) . Upregulation of endogenous synthesis of the major protein on HDL particles , apolipoprotein A-I ( apoA-I ) , represents a novel approach to generation of new HDL particles . The Study of Quantitative Serial Trends in Lipids with Apolipoprotein A-I Stimulation ( SUSTAIN , NCT01423188 ) study aims to evaluate the lipid efficacy , safety and tolerability of an apoA-I inducer ( RVX-208 ) . The ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation ( ASSURE , NCT01067820 ) study aims to evaluate the effect of RVX-208 on plaque burden . METHODS In SUSTAIN , 172 patients with low levels of HDL-C will be randomized to receive RVX-208 100 mg bid or placebo for 24 weeks . The primary efficacy parameter will be the percentage change in HDL-C levels . In ASSURE , 310 patients with angiographic coronary artery disease and low HDL-C levels will be randomized to receive RVX-208 100 mg bid or placebo for 26 weeks . The primary efficacy parameter will be the nominal change in percent atheroma volume ( PAV ) , determined by analysis of intravascular ultrasound ( IVUS ) images of matched coronary artery segments acquired at baseline and at 26-week follow-up . The effect of RVX-208 on other lipid and inflammatory markers , safety and tolerability will also be assessed in both studies . CONCLUSION ApoA-I induction represents a potential novel strategy to reduce cardiovascular risk , by generating nascent HDL particles . These studies will provide early evaluation of the effects of RVX-208 on lipids and atherosclerotic plaque .

ApoA-I

apolipoprotein A-I

Apolipoprotein A-I Stimulation

apoA-I inducer ( RVX-208 )

placebo

placebo

lipid efficacy

safety

tolerability

percentage change in HDL-C levels

percent atheroma volume ( PAV )

lipid and inflammatory markers

safety

tolerability

cardiovascular risk

In SUSTAIN ,

angiographic coronary artery disease


Use of a clay modeling task to reduce chocolate craving . Elaborated Intrusion theory ( EI theory ; Kavanagh , Andrade , & May , 2005 ) posits two main cognitive components in craving : associative processes that lead to intrusive thoughts about the craved substance or activity , and elaborative processes supporting mental imagery of the substance or activity . We used a novel visuospatial task to test the hypothesis that visual imagery plays a key role in craving . Experiment 1 showed that spending 10 min constructing shapes from modeling clay ( plasticine ) reduced participants ' craving for chocolate compared with spending 10 min 'letting your mind wander ' . Increasing the load on verbal working memory using a mental arithmetic task ( counting backwards by threes ) did not reduce craving further . Experiment 2 compared effects on craving of a simpler verbal task ( counting by ones ) and clay modeling . Clay modeling reduced overall craving strength and strength of craving imagery , and reduced the frequency of thoughts about chocolate . The results are consistent with EI theory , showing that craving is reduced by loading the visuospatial sketchpad of working memory but not by loading the phonological loop . Clay modeling might be a useful self-help tool to help manage craving for chocolate , snacks and other foods .

clay modeling task

novel visuospatial task

'letting your mind wander '

clay modeling

Clay modeling

Clay modeling

chocolate craving

craving

craving

craving for chocolate

craving

craving

overall craving strength

strength of craving imagery

frequency of thoughts about chocolate

craving

craving

chocolate craving

craving for chocolate


Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders : a double-blind , placebo-controlled , randomized trial . Autism spectrum disorders are a neurodevelopmental disorders with reduced cortical functional connectivity relating to social cognition . Polyunsaturated fatty acids arachidonic acid ( ARA ) and docosahexaenoic acid ( DHA ) may have key role in brain network maturation . In particularly , ARA is important in signal transduction related to neuronal maturation . Supplementation with larger ARA doses added to DHA may therefore mitigate social impairment . In a 16-week , double-blind , randomized , placebo-controlled trial , we evaluated the efficacy of supplementation with large doses of ARA added to DHA ( n = 7 ) or placebo ( n = 6 ) in 13 participants ( mean age , 14.6 [ SD , 5.9 ] years ) . To examine underlying mechanisms underlying the effect of our supplementation regimen , we examined plasma levels of antioxidants transferrin and superoxide dismutase , which are useful markers of signal transduction . The outcome measures were the Social Responsiveness Scale and the Aberrant Behavior Checklist-Community . Repeated-measures analysis of variance revealed that our supplementation regimen significantly improved Aberrant Behavior Checklist-Community-measured social withdrawal and Social Responsiveness Scale-measured communication . Treatment effect sizes were more favorable for the treatment group compared with the placebo group ( communication : treatment groups , 0.87 vs , placebo , 0.44 ; social withdrawal : treatment groups , 0.88 , vs placebo , 0.54 ) . There was a significant difference in the change in plasma transferrin levels and a trend toward a significant difference in the change in plasma superoxide dismutase levels between the 2 groups . This preliminary study suggests that supplementation with larger ARA doses added to DHA improves impaired social interaction in individuals with autism spectrum disorder by up-regulating signal transduction .

placebo-controlled

docosahexaenoic acid ( DHA )

ARA

ARA doses added to DHA

placebo-controlled

ARA added to DHA

placebo

placebo

placebo

placebo

ARA doses added to DHA

change in plasma transferrin levels

plasma superoxide dismutase levels

social interaction


The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated , but not in NPM1 unmutated , AML with a normal karyotype . The impact of a FLT3-internal tandem duplication ( FLT3ITD ) on prognosis of patients with acute myeloid leukemia ( AML ) is dependent on the ratio of mutated to wild-type allele . In 648 normal karyotype ( NK ) AML patients , we found a significant independent effect of the quantitative FLT3ITD mRNA level -- measured as ( FLT3ITD/wtFLT3 ) / ( FLT3ITD/wtFLT3+1 ) -- on outcome . Moreover , this effect was clearly seen in 329 patients with a mutated NPM1 gene ( NPM1+ ) , but not in 319 patients without a NPM1 mutation ( wtNPM1 ) . In a multivariate Cox regression model , the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival ( OS ) and relapse-free survival ( RFS ) only in the NPM1+ subgroup ( OS : hazard ratio , 5.9 ; [ 95 % confidence interval [ CI ] : 3.1-11.2 ] ; RFS : hazard ratio , 7.5 [ 95 % CI : 3.4-16.5 ] ) . The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML .

FLT3ITD mRNA

level

overall survival

relapse-free survival

NPM1 mutated

but not in NPM1 unmutated

AML with a normal karyotype

NPM1-mutated AML


A randomized , placebo- and active-controlled study of paliperidone extended-release as maintenance treatment in patients with bipolar I disorder after an acute manic or mixed episode . BACKGROUND Paliperidone ER monotherapy was efficacious in treating acute mania in two 3-week studies in patients with bipolar I disorder . We assessed its efficacy in a study investigating maintenance treatment of clinically stable patients with this disorder . METHODS Patients ( n=766 ) , aged 18 to 65 years inclusive , with current manic or mixed episodes were initially randomized ( 4:1 ) to flexibly-dosed paliperidone ER ( 3-12 mg/day ) or olanzapine ( 5-20 mg/day ; 3-week acute treatment phase ) ; responders continued the same treatment ( 12-week continuation phase ) . Patients on paliperidone ER who achieved remission during this phase were randomized ( 1:1 ) to fixed-dose paliperidone ER ( n=152 ) or placebo ( n=148 ) ; those on olanzapine continued to receive that at fixed dose ( n=83 ) ( maintenance phase ) . RESULTS Median time to recurrence of any mood symptoms ( primary endpoint ) was : 558 days ( paliperidone ER ) , 283 days ( placebo ) and not observed with olanzapine ( < 50 % of patients experienced recurrence ) . Time to recurrence of any mood symptoms was significantly longer with paliperidone ER than placebo ( p=0.017 ; based on weighted Z-test at 0.0198 significance level ; hazard ratio [ placebo : paliperidone ER ; unweighted 95 % confidence interval ] : 1.43 [ 1.03 ; 1.98 ] ) ; the difference was significant for preventing recurrence of manic , but not depressive , symptoms . Treatment-emergent adverse events ( maintenance phase ) occurred more often in olanzapine group ( 64 % ) than placebo ( 59 % ) or paliperidone ER groups ( 55 % ) . LIMITATIONS Responder-enriched design prevents extrapolation of data to patients not previously stabilized on paliperidone ER . CONCLUSIONS Paliperidone ER significantly delayed the time to recurrence of any mood symptoms , versus placebo , in patients with bipolar I disorder . No new safety concerns emerged .

placebo-

paliperidone

Paliperidone ER monotherapy

paliperidone ER

olanzapine

paliperidone ER

paliperidone ER

placebo

olanzapine

paliperidone ER

placebo

olanzapine

paliperidone ER

olanzapine

placebo

paliperidone ER

paliperidone ER

Paliperidone ER

placebo

Time to recurrence of any mood symptoms

recurrence of manic

bipolar I disorder

acute manic or mixed episode

bipolar I disorder

clinically stable

18 to 65 years

current manic or mixed episodes

bipolar I disorder


Infrared LED irradiation applied during high-intensity treadmill training improves maximal exercise tolerance in postmenopausal women : a 6-month longitudinal study . Reduced aerobic fitness is associated with an increased risk of cardiovascular diseases among the older population . The aim of this study was to investigate the effects of LED irradiation ( 850 nm ) applied during treadmill training on the maximal exercise tolerance in postmenopausal women . At the beginning of the study , 45 postmenopausal women were assigned randomly to three groups , and 30 women completed the entire 6 months of the study . The groups were : ( 1 ) the LED group ( treadmill training associated with phototherapy , n = 10 ) , ( 2 ) the exercise group ( treadmill training , n = 10 ) , and ( 3 ) the sedentary group ( neither physical training nor phototherapy , n = 10 ) . The training was performed for 45 min twice a week for 6 months at intensities between 85 % and 90 % maximal heart rate ( HRmax ) . The irradiation parameters were 39 mW/cm ( 2 ) , 45 min and 108 J/cm ( 2 ) . The cardiovascular parameters were measured at baseline and after 6 months . As expected , no significant differences were found in the sedentary group ( p ≥ 0.05 ) . The maximal time of tolerance ( Tlim ) , metabolic equivalents ( METs ) and Bruce stage reached significantly higher values in the LED group and the exercise group ( p < 0.01 ) . Furthermore , the HR , double product and Borg score at isotime were significantly lower in the LED group and in the exercise group ( p < 0.05 ) . However , the time of recovery showed a significant decrease only in the LED group ( p = 0.003 ) . Moreover , the differences between before and after training ( delta values ) for the Tlim , METs and HR at isotime were greater in the LED group than in the exercise group with a significant intergroup difference ( p < 0.05 ) . Therefore , the infrared LED irradiation during treadmill training can improve maximal performance and post-exercise recovery in postmenopausal women .

Infrared LED irradiation

LED irradiation

maximal exercise tolerance

effects

maximal exercise tolerance


Combination peel with incorporated fractional prickle coral calcium for the treatment of keratosis pilaris : a pilot study . BACKGROUND Keratosis pilaris ( KP ) is a common condition of follicular plugging with variable erythema . There is a lack of reliable response to the treatment of KP . OBJECTIVE We evaluated the effect and safety of combination peel with fractional prickle coral calcium ( FCR™ ) in the treatment of KP . MATERIALS AND METHODS Sixteen Korean patients were treated with FCR™ on both upper arms for five sessions at 2-week intervals . Clinical evaluations , mexameter measurements , and assessment of patients ' satisfaction and adverse events were performed at baseline and every visit . RESULTS After treatments , statistically significant improvements in the baseline KP were observed in erythema and melanin index of mexameter on treated upper arms . Both the physicians ' and patients ' assessments correlate with the results of mexameter scores . CONCLUSION Our results suggest FCR™ should be considered as an effective and safe treatment option for the patients with KP .

baseline

effective

keratosis pilaris :

Keratosis pilaris


A double-blind placebo controlled trial of Ginkgo biloba added to risperidone in patients with autistic disorders . Ginkgo biloba has been reported to affect the neurotransmitter system and to have antioxidant properties that could impact the pathogenesis of Autism Spectrum Disorder . Based on these studies , we decided to assess the effectiveness of Ginkgo biloba extract ( Ginko T.D. , Tolidaru , Iran ) as an adjunctive agent to risperidone in the treatment of autism . Forty-seven outpatients with a DSM-IV-TR diagnosis of autism ages between 4 and 12 years were assigned to this double blinded clinical trial and were randomly divided into two groups . One group received risperidone plus Ginko T.D and the other received risperidone plus placebo . The dose of risperidone was 1-3 mg/day and the dose of Ginko T.D . was 80 mg/day for patients under 30 kg and 120 mg/day for patients above 30 kg . Patients were assessed using Aberrant Behavior Checklist-Community ( ABC-C ) rating scale and the side effect check list every 2 weeks until the endpoint . None of the 5 subscales of ABC-C rating scale showed significant differences between the two groups . Incidents of side effects were not significantly different between the two groups . Adding Ginkgo biloba to risperidone did not affect the treatment outcome of ADs . Nevertheless , further observations are needed to confirm this result .

placebo

Ginkgo biloba

risperidone

Ginkgo biloba

risperidone plus Ginko T.D and the

placebo

risperidone

Ginko T.D .

Ginkgo biloba to risperidone

and the

side effect check list

ABC-C rating scale

Incidents of side effects

patients with autistic disorders .

Autism Spectrum Disorder .

Forty-seven

DSM-IV-TR diagnosis of autism

ages between 4 and 12 years

patients under 30 kg

patients above 30 kg .


Utility of the bladder flap at cesarean delivery : a randomized controlled trial . OBJECTIVE To test the hypothesis that omission of the bladder flap in primary and repeat cesarean deliveries shortens operating time without increasing intraoperative and postoperative complications . METHODS We randomized 258 women undergoing primary and repeat cesarean deliveries at 32 weeks of gestation or more to creation ( n=131 ) or omission ( n=127 ) of the bladder flap . Emergency cesarean deliveries , planned vertical uterine incisions , and previous abdominal surgeries besides cesarean deliveries were excluded . The primary outcome measure was total operating time . Secondary outcomes were bladder injury , incision-to-delivery time , incision-to-fascial closure time , estimated blood loss , postoperative microhematuria , postoperative pain , hospital days , endometritis , and urinary tract infection . Analysis followed the intention-to-treat principle . RESULTS The median skin incision to delivery interval was shorter with omission of the bladder flap ( 9 [ range 1-43 ] compared with 10 [ range 2-70 ] minutes ; P=.04 ) , but there was no difference in total operating time ( 51 [ range 18-124 ] minutes compared with 51 [ range 16-178 ] ; P=.10 ) . No bladder injuries occurred in either group and there were no significant differences in estimated blood loss , change in hemoglobin level , postoperative microhematuria , postoperative pain , hospital days , endometritis , or urinary tract infection . CONCLUSION Omission of the bladder flap at primary and repeat cesarean deliveries does not increase intraoperative or postoperative complications . Incision-to-delivery time is shortened but total operating time appears unchanged . CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , www.ClinicalTrials.gov , NCT00918996 . LEVEL OF EVIDENCE I .

bladder flap

cesarean delivery

bladder flap

cesarean deliveries

primary and repeat cesarean deliveries

creation

omission

abdominal surgeries

cesarean deliveries

omission of the bladder flap

total operating time .

bladder injury

incision-to-delivery time

incision-to-fascial closure time

estimated blood loss

postoperative microhematuria

postoperative pain

hospital days

endometritis

urinary tract infection

total operating time

bladder injuries

estimated blood loss

change in hemoglobin level

postoperative microhematuria

postoperative pain

hospital days

endometritis

urinary tract infection

women

primary and repeat cesarean deliveries


Efficiency of slush nitrogen vitrification of human oocytes vitrified with or without cumulus cells in relation to survival rate and meiotic spindle competence . OBJECTIVE To evaluate the efficiency of slush nitrogen vitrification of human oocytes with or without cumulus cells in terms of survival rate and maintenance of meiotic spindle . DESIGN Randomized , comparative study . SETTING Medical center . PATIENT ( S ) A total of 274 oocytes obtained from 46 couples undergoing infertility treatment . INTERVENTION ( S ) Metaphase II oocytes were divided into groups A and B , vitrified with and without cumulus cells , respectively . MAIN OUTCOMES MEASURE ( S ) Survival rates and maintenance of meiotic spindle observed immediately after warming and 3 hours after incubation . RESULT ( S ) No statistically significant difference was detected between the two groups in terms of survival rate , but a significantly higher percentage of detectable spindle was observed in group B ( completely denuded oocytes ) , either immediately after warming or 3 hours after incubation . CONCLUSION ( S ) Complete denudation of oocytes before slush nitrogen vitrification does not influence survival rates but positively affects oocyte meiotic spindle competence . These data support the hypothesis that cumulus cells during vitrification represent an obstacle to cryoprotectant penetration more than having a protective role for the oocyte .

slush nitrogen vitrification

vitrified with or without cumulus cells

slush nitrogen vitrification

with or without cumulus cells

Efficiency

survival rate

meiotic spindle competence

efficiency

maintenance of meiotic spindle

Survival rates

survival rate

detectable spindle

survival rates

meiotic spindle competence

infertility


Development of an adaptive low-pass filtered speech test for the identification of auditory processing disorders . OBJECTIVE One type of test commonly used to examine auditory processing disorders ( APD ) is the low-pass filtered speech test ( LPFST ) , of which there are various versions . In LPFSTs , a monaural , low-redundancy speech sample is distorted by using filtering to modify its frequency content . Due to the richness of the neural pathways in the auditory system and the redundancy of acoustic information in spoken language , a normal listener is able to recognize speech even when parts of the signal are missing , whereas this ability is often impaired in listeners with APD . One limitation of the various versions of the LPFST is that they are carried out using a constant level of low-pass filtering ( e.g . a fixed 1kHz corner frequency ) which makes them prone to ceiling and floor effects . The purpose of this study was to counter these effects by modifying the LPFST using a computer-based adaptive procedure , and to evaluate the performance of normal-hearing participants of varying ages on the test . METHODS In this preliminary study , 33 adults and 30 children ( aged 8-11 years ) with no known history of listening difficulties were tested . The University of Canterbury Adaptive Speech Test ( UCAST ) platform was used to administer a four-alternative forced-choice adaptive test that altered a low-pass filter ( LPF ) to track the corner frequency at which participants correctly identified a certain percentage of the word stimuli . RESULTS Findings on the University of Canterbury Adaptive Speech Test-Filtered Words ( UCAST-FW ) indicated a significant maturational effect . Adult participants performed significantly better on the UCAST-FW in comparison to the child participants . The UCAST-FW test was reliable over repeated administrations . CONCLUSIONS An adaptive low-pass filtered speech test such as the UCAST-FW is sensitive to maturational changes in auditory processing ability .

low-pass filtered speech test

LPFST

auditory processing disorders

significant maturational effect

UCAST-FW

UCAST-FW


Successful difficult intubation . Tracheal tube placement over a gum-elastic bougie . A randomised study was carried out to assess the effect of tracheal tube rotation on the passage of a tube over a gum-elastic bougie into the trachea in 100 patients . The effect of the presence or absence of a laryngoscope on successful tube placement was also assessed . A grade 3 difficult intubation was simulated in patients with a laryngoscope . There was a significant difference in the rates for successful first-time intubation in those patients with tube orientation of -90 degrees ( with the bevel facing posteriorly ) as compared with a tube orientation of 0 degrees ( the normal orientation with the bevel facing left ) . The unsuccessful first-time intubations with a 0 degree orientation were frequently converted to successful intubations with the -90 degrees position at a second attempt . The presence of a laryngoscope in the mouth while rail-roading a tube over the bougie also made a significant difference to the rate of successful first-time intubations . The most successful method was to leave the laryngoscope in the mouth and rotate the tube to -90 degrees .

intubation

Tracheal tube placement

gum-elastic bougie

tracheal tube rotation

simulated

laryngoscope

first-time intubation

intubations

laryngoscope

laryngoscope

successful first-time intubation

unsuccessful first-time intubations

successful intubations

presence of a laryngoscope

successful

patients with a laryngoscope .


Theta burst stimulation in the rehabilitation of the upper limb : a semirandomized , placebo-controlled trial in chronic stroke patients . BACKGROUND Noninvasive cortical stimulation could represent an add-on treatment to enhance motor recovery after stroke . However , its clinical value , including anticipated size and duration of the treatment effects , remains largely unknown . OBJECTIVE The authors designed a small semi-randomized clinical trial to explore whether long-lasting clinically important gains can be achieved by adding theta burst stimulation ( TBS ) , a form of repetitive transcranial magnetic stimulation ( TMS ) , to a rehabilitation program for the hand . METHODS A total of 41 chronic stroke patients received excitatory TBS to the ipsilesional hemisphere or inhibitory TBS to the contralesional hemisphere in 2 centers ; each active group was compared with a group receiving sham TBS . TBS was followed by physical therapy for 10 working days . Patients and therapists were blinded to the type of TBS . Primary outcome measures ( 9-hole Peg Test [ 9HPT ] , Jebsen Taylor Test [ JTT ] , and grip and pinch-grip dynamometry ) were assessed 4 , 30 , and 90 days post treatment . The clinically important difference was defined as 10 % of the maximum score . RESULTS There were no differences between the active treatment and sham groups in any of the outcome measures . All patients achieved small sustainable improvements -- 9HPT , 5 % of maximum ( confidence interval [ CI ] = 3 % -7 % ) ; JTT , 5.7 % ( CI = 3 % -8 % ) ; and grip strength , 6 % ( CI = 2 % -10 % ) -- all below the defined clinically important level . CONCLUSIONS Cortical stimulation did not augment the gains from a late rehabilitation program . The effect size anticipated by the authors was overestimated . These results can improve the design of future work on therapeutic uses of TMS .

Theta burst stimulation

cortical stimulation

theta burst stimulation ( TBS )

TBS

inhibitory TBS

sham TBS

TBS

TBS

motor recovery

improvements -- 9HPT , 5 % of maximum

JTT

grip strength

chronic stroke patients

A total of

41 chronic stroke patients


Ambulatory activity of children with cerebral palsy : which characteristics are important ? AIM To assess ambulatory activity of children with cerebral palsy ( CP ) , aged 7 to 13 years , and identify associated characteristics . METHOD Sixty-two children with spastic CP ( 39 males , 23 females ; mean age 10y 1mo , SD 1y 8mo ; age range 7-13y ) , classified as Gross Motor Function Classification System ( GMFCS ) levels I to III , participated . Ambulatory activity was measured during 1 week with a StepWatch activity monitor as steps per day , and time spent at medium and high step rates . Multiple linear regression analyses were performed following a backward selection procedure until only independent variables with p < 0.05 remained in the model . Ambulatory activity outcome parameters served as dependent variables , and disease , personal , and environmental characteristics as independent variables . Ambulatory activity was corrected for body height . RESULTS Children took more steps during school days ( 5169 steps , SD 1641 ) than during weekend days ( 4158 steps , SD 2048 ; p < 0.001 ) . Higher GMFCS level , bilateral CP , and higher age were associated with lower ambulatory activity on school days ( R ( 2 ) ranged from 43-53 % ) , whereas bilateral CP , higher age , and no sport club participation were associated with lower ambulatory activity in the weekend ( R ( 2 ) ranged from 21-42 % ) . Correcting for body height decreased the association with age . INTERPRETATION Interventions should focus at increasing physical activity at the weekend for children with bilateral spastic CP .

Ambulatory activity

ambulatory activity

Ambulatory activity

ambulatory activity


Noradrenergic moderation of working memory impairments in adults with autism spectrum disorder . In addition to having difficulties with social communications , individuals with an autism spectrum disorder ( ASD ) often also experience impairment in higher-order , executive skills . The present study examined the effects of pharmacological modulation of the norepinephrine system on the severity of such impairments . A sample of 14 high-functioning adults with ASD and a demographically-matched comparison group of 13 typically developing individuals participated . An AX continuous performance test ( AX-CPT ) was used to evaluate working memory and inhibitory control . AX-CPT performance was assessed following administration of a single dose of propranolol ( a beta adrenergic antagonist ) and following placebo ( sugar pill ) administration . Individuals with ASD performed more poorly than non-ASD individuals in the working memory condition ( BX trials ) . Importantly , administration of propranolol attenuated this impairment , with the ASD group performing significantly better in the propranolol condition than the placebo condition . Working memory performance of the non-ASD group was unaffected by propranolol/placebo administration . No group or medication effects were observed for the inhibition condition ( AY trials ) . The present findings suggest that norepinephrine may play a role in some , but not necessarily all , cognitive impairments associated with ASD . Additional research is needed to fully understand whether this role is primarily causal or compensatory in nature .

placebo

propranolol

moderation

AX-CPT performance

attenuated this impairment

Working memory performance

effects

inhibition condition

cognitive impairments

adults

autism spectrum disorder

autism spectrum disorder ( ASD )

adults

ASD

ASD


Most effective regimen of tranexamic acid in knee arthroplasty : a prospective randomized controlled study in 240 patients . BACKGROUND The antifibrinolytic tranexamic acid reduces surgical blood loss , but studies have not identified an optimal regimen . QUESTIONS/PURPOSES We studied different dosages , timings , and modes of administration to identify the most effective regimen of tranexamic acid in achieving maximum reduction of blood loss in TKA . METHODS We prospectively studied five regimens ( four intravenous , one local ; 40 patients each ) with a control group ( no tranexamic acid ) . The four intravenous ( 10-mg/kg dose ) regimens included ( 1 ) intraoperative dose ( IO ) given before tourniquet deflation , ( 2 ) additional preoperative dose ( POIO ) , ( 3 ) additional postoperative dose ( IOPO ) , and ( 4 ) all three doses ( POIOPO ) . The fifth regimen was a single local application ( LA ) . Two independent parameters of drain loss and total blood loss , calculated by the hemoglobin balance method , were evaluated statistically . RESULTS Both parameters were reduced in all five regimens as against the control . A significant reduction in drain loss was seen in the POIO , IOPO , and POIOPO groups whereas total blood loss was significantly reduced in the POIO , POIOPO , and LA groups . The POIOPO group had the least drain loss ( 303 mL ) and least total blood loss ( 688 mL ) . The IO group had the greatest drain loss and the IOPO group the greatest total blood loss . CONCLUSIONS Single-dose tranexamic acid did not give effective results . The two-dose regimen of POIO was the least amount necessary for effective results . When compared against the control , this regimen produced reduction of drain loss and total blood loss , whereas the IOPO regimen did not . The three-dose regimen of POIOPO produced maximum effective reduction of drain loss and total blood loss .

tranexamic acid

antifibrinolytic tranexamic acid

tranexamic acid

intravenous

local

intravenous

intraoperative dose ( IO )

additional preoperative dose ( POIO )

additional postoperative dose ( IOPO )

local application

tranexamic acid

drain loss

total blood loss

drain loss

blood loss

drain loss

blood loss

drain loss

total blood loss

drain loss

total blood loss

drain loss

total blood loss

knee arthroplasty

240 patients

40 patients


Randomized crossover study comparing efficacy of transnasal endoscopy with that of standard endoscopy to detect Barrett 's esophagus . BACKGROUND Unsedated transnasal endoscopy ( TNE ) may be safer and less expensive than standard endoscopy ( SE ) for detecting Barrett 's esophagus ( BE ) . Emerging technologies require robust evaluation before routine use . OBJECTIVE To evaluate the sensitivity , specificity , and acceptability of TNE in diagnosing BE compared with those of SE . DESIGN Prospective , randomized , crossover study . SETTING Single , tertiary-care referral center . PATIENTS This study enrolled consecutive patients with BE or those referred for diagnostic assessment . INTERVENTION All patients underwent TNE followed by SE or the reverse . Spielberger State-Trait Anxiety Inventory short-form questionnaires , a visual analogue scale , and a single question addressing preference for endoscopy type were administered . MAIN OUTCOME MEASUREMENTS Diagnostic accuracy and tolerability of TNE were compared with those of SE . RESULTS Of 95 patients randomized , 82 completed the study . We correctly diagnosed 48 of 49 BE cases by TNE for endoscopic findings of columnar lined esophagus compared with the criterion standard , SE , giving a sensitivity and specificity of 0.98 and 1.00 , respectively . The BE median length was 3 cm ( interquartile range [ IQR ] 1-5 cm ) with SE and 3 cm ( IQR 2-4 cm ) with TNE , giving high correlations between the two modalities ( R ( 2 ) = 0.97 ; P < .001 ) . The sensitivity and specificity for detecting intestinal metaplasia by TNE compared with those by SE was 0.91 and 1.00 , respectively . The mean ( ± standard deviation ) post-endoscopy Spielberger State-Trait Anxiety Inventory short-form score for TNE ( 30.0 ± 1.10 standard error of the mean [ SEM ] ) was lower than that for SE ( 30.7 ± 1.29 SEM ) , ( P = .054 ) . The visual analogue scale scores were no different ( P = .07 ) . The majority of patients ( 59 % ) expressed a preference for TNE . LIMITATIONS This is a small study , with limited generalizability , a high prevalence of patients with BE , differential drop-out between the two procedures , and use of sedation . CONCLUSION TNE is an accurate and well-tolerated method for diagnosing BE compared with SE . TNE warrants further evaluation as a screening tool for BE .

Unsedated transnasal endoscopy ( TNE )

standard endoscopy ( SE )

TNE

SE .

TNE

SE

TNE

SE .

TNE

SE

TNE

TNE

SE

TNE

SE

efficacy

sensitivity , specificity ,

and

acceptability

a visual analogue scale

Diagnostic accuracy and tolerability

BE median length

sensitivity and specificity

Barrett 's esophagus ( BE ) .

BE

95 patients


Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer : final results of a randomized , double-blind , placebo-controlled , phase 3 study . BACKGROUND Recurrent or metastatic squamous cell carcinoma of the head and neck ( SCCHN ) is associated with poor survival . Platinum-based chemotherapy is often a first-line treatment . Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors . This trial examined the efficacy of pemetrexed-cisplatin for SCCHN . METHODS In a double-blind phase 3 trial , patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed ( 500 mg/m ( 2 ) ) plus cisplatin ( 75 mg/m ( 2 ) ; n = 398 ) or placebo plus cisplatin ( 75 mg/m ( 2 ) ; n = 397 ) to assess overall survival ( OS ) and secondary endpoints . RESULTS Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm ( hazard ratio [ HR ] , 0.87 ; 95 % confidence interval [ CI ] , 0.75-1.02 ; P = .082 ) . Median progression-free survival ( PFS , months ) was similar in both treatment arms ( pemetrexed-cisplatin , 3.6 ; placebo-cisplatin , 2.8 ; HR , 0.88 ; 95 % CI , 0.76-1.03 ; P = .166 ) . Among patients with performance status 0 or 1 , pemetrexed-cisplatin ( n = 347 ) led to longer OS and PFS than placebo-cisplatin ( n = 343 ; 8.4 vs 6.7 months ; HR , 0.83 ; P = .026 ; 4.0 vs 3.0 months ; HR , 0.84 ; P = .044 , respectively ) . Among patients with oropharyngeal cancers , pemetrexed-cisplatin ( n = 86 ) resulted in longer OS and PFS than placebo-cisplatin ( n = 106 ; 9.9 vs 6.1 months ; HR , 0.59 ; P = .002 ; 4.0 vs 3.4 months ; HR , 0.73 ; P = .047 , respectively ) . Pemetrexed-cisplatin toxicity was consistent with studies in other tumors . CONCLUSIONS Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-to-treat population . However , in a prespecified subgroup analysis , pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers .

placebo-controlled

Platinum-based chemotherapy

Pemetrexed

pemetrexed-cisplatin

pemetrexed

plus cisplatin

placebo plus cisplatin

pemetrexed-cisplatin

placebo-cisplatin

( pemetrexed-cisplatin

pemetrexed-cisplatin

pemetrexed-cisplatin

Pemetrexed-cisplatin

Pemetrexed-cisplatin

pemetrexed-cisplatin

overall survival ( OS )

Median OS

longer OS

and

PFS

OS

PFS

Pemetrexed-cisplatin toxicity

survival

OS

PFS

head and neck cancer

squamous cell carcinoma

SCCHN

oropharyngeal cancers


Comparison of active-learning strategies for motivational interviewing skills , knowledge , and confidence in first-year pharmacy students . OBJECTIVE To compare 3 strategies for pharmacy student learning of motivational interviewing skills , knowledge of motivational interviewing principles , and confidence in and attitudes toward their application . DESIGN Following a motivational interviewing lecture , first-year students were randomized to perform practice activities ( written dialogue , peer role-play , or mock-patient counseling activities ) . Motivational interviewing skills , knowledge , confidence , and attitudes were measured . ASSESSMENT All students demonstrated improvement in skills , knowledge , and confidence . Students in the mock-patient counseling group demonstrated significantly better motivational interviewing skills during practice and trended toward higher scores on the summative evaluation . They also demonstrated a significant improvement in knowledge compared with that of the written dialogue group during practice . Feedback at the end was generally positive , with students expressing recognition for the value of motivational interviewing . CONCLUSIONS Students demonstrated their best performance of motivational interviewing during assessments using interactions with mock or standardized patients .

active-learning strategies

motivational interviewing lecture

mock-patient counseling

skills , knowledge

confidence

attitudes

skills , knowledge , and confidence .

skills

knowledge

motivational interviewing


Elevated concentration of placental growth factor ( PlGF ) and long term risk in patients with acute coronary syndrome in the PROVE IT-TIMI 22 trial . Placental growth factor ( PlGF ) , a member of the vascular endothelial growth factor ( VEGF ) family , acts via the flt-1 receptor and promotes endothelial activation and macrophage recruitment into atherosclerotic lesions . We investigated the relationship of PlGF with cardiovascular outcomes in a large cohort of patients presenting across the spectrum of ACS . PlGF was measured at baseline ( n = 3,761 ) and at four-months ( n = 3,369 ) in patients randomized to atorvastatin 80 mg or pravastatin 40 mg after ACS in the PROVE IT-TIMI 22 trial . The primary endpoint was death , myocardial infarction ( MI ) , unstable angina , revascularization or stroke ( mean follow-up 24 months ) . Elevated baseline PlGF was associated with a higher incidence of the primary endpoint through 2 years ( Q1 vs. Q5 : 18.7 vs. 29.3 % , p < 0.0001 ) . The risk of death or MI was also higher in patients with elevated baseline PlGF ( Q1 vs. Q5 : 7.0 vs. 11.6 % , p = 0.029 ) . Adjusting for baseline characteristics and risk factors , elevated baseline PlGF was independently associated with the risk of the primary endpoint ( adjusted-HR for Q5 vs. Q1 1.45 ; 95 % CI 1.16-1.83 ; p = 0.001 ) . Elevated PlGF at four months was associated with higher risk of death or MI ( Adjusted HR Q5 vs. Q1 2.79 , 95 % CI : 1.37-5.68 ; p = 0.005 ) , and higher risk of the primary endpoint ( Adjusted HR Q5 vs. Q1 1.78 , 95 % CI : 1.26-2.51 ; p = 0.001 ) . Higher concentration of PlGF after ACS is associated with long-term risk of recurrent cardiovascular events independent of traditional risk factors . This association is present early after ACS and appears to be stronger at four months .

Placental growth factor

Placental growth factor ( PlGF )

PlGF

death

risk of

death

or

MI

risk of death

or

MI

PlGF


[ Simvastatin versus gemfibrozil in the treatment of primary hypercholesterolemia in hypertensive patients treated with hydrochlorothiazide ] . Recent pharmacological studies confirmed the role of hypercholesterolemia in the pathogenesis of coronary atherosclerosis . A 10 % reduction in cholesterol levels can reduce the risk of coronary heart disease by 15 % . However many hypercholesterolemic patients often suffer from arterial hypertension and drugs such as thiazide diuretics cause an imbalance in lipid metabolism . The efficacy and the tolerability of simvastatin ( a inhibitor of HGM-CoA reductase ) with that of gemfibrozil ( a fibric acid derivative , which can reduce the VLDL level ) were compared in a placebo-controlled study in 2 groups of patients with primary hypercholesterolemia and mild-to-moderate essential hypertension treated with hydrochlorothiazide . After 10 weeks standard hypolipidemic diet and hydrochlorothiazide ( 25 mg od ) therapy , 30 patients whose cholesterol levels were still greater than or equal to 250 mg/100 ml and whose diastolic blood pressure was less than 95 mmHg were randomized to one of the following treatments : simvastatin , 20 mg od , gemfibrozil , 600 mg bid or placebo , while continuing dietetic and diuretic treatment . After 24 weeks treatment , simvastatin induced a 37 % reduction in cholesterol plasma levels , a 9 % increase of HDL and a 16 % reduction of LDL . APO-A1 showed a 4 % increase , while APO-B showed a 3 % reduction . Gemfibrozil induced a 20 % reduction in plasma triglycerides and a 13 % decrease in plasma cholesterol , with a significant 19 % increase in HDL and a 11 % reduction in LDL . No significant variations in any of the lipid parameters monitored were observed in the placebo group . Treatment with simvastatin or gemfibrozil in hypertensive patients in hydrochlorothiazide monotherapy can reduce total cholesterol and LDL-cholesterol plasma levels , while significantly increasing HDL plasma levels compared to placebo . Simvastatin , however , resulted more efficient than gemfibrozil on total cholesterol or cholesterol fractions .

[ Simvastatin versus gemfibrozil

hydrochlorothiazide ]

thiazide diuretics

simvastatin

gemfibrozil

placebo-controlled

standard hypolipidemic diet

hydrochlorothiazide

simvastatin

gemfibrozil

or placebo

simvastatin

Gemfibrozil

placebo

simvastatin

gemfibrozil

hydrochlorothiazide

Simvastatin

gemfibrozil

efficacy and the tolerability

cholesterol levels

diastolic blood

cholesterol plasma levels

HDL

LDL . APO-A1

plasma triglycerides

plasma cholesterol

HDL

LDL .

HDL plasma levels

mild-to-moderate essential hypertension


Are prenatal ultrasound scans associated with the autism phenotype ? Follow-up of a randomised controlled trial . An existing randomised controlled trial was used to investigate whether multiple ultrasound scans may be associated with the autism phenotype . From 2,834 single pregnancies , 1,415 were selected at random to receive ultrasound imaging and continuous wave Doppler flow studies at five points throughout pregnancy ( Intensive ) and 1,419 to receive a single imaging scan at 18 weeks ( Regular ) , with further scans only as indicated on clinical grounds . There was no significant difference in the rate of Autism Spectrum Disorder between the Regular ( 9/1,125 , 0.8 % ) and Intensive ( 7/1,167 , 0.6 % ) groups , nor a difference between groups in the level of autistic-like traits in early adulthood . There is no clear link between the frequency and timing of prenatal ultrasound scans and the autism phenotype .

prenatal ultrasound scans

controlled

controlled

multiple ultrasound scans

ultrasound imaging

single imaging scan

prenatal ultrasound scans

autism phenotype

autism phenotype

rate of

Autism Spectrum Disorder

level of autistic-like traits

frequency

timing

autism phenotype


Relation of improvement in estimated glomerular filtration rate with atorvastatin to reductions in hospitalizations for heart failure ( from the Treating to New Targets [ TNT ] study ) . Impaired kidney function often accompanies heart failure ( HF ) and is associated with a worse prognosis . This post hoc analysis of the Treating to New Targets ( TNT ) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function . Of 10,001 TNT participants , 9,376 had estimated glomerular filtration rate ( eGFR ) measurements at baseline and 1 year and were included in this analysis . The association of change in year-1 eGFR and subsequent HF hospitalization was examined using Cox regression models . In total 218 participants developed subsequent HF hospitalization . Little change in eGFR occurred over 1 year in the atorvastatin 10-mg group , whereas eGFR improved in the 80-mg group by 1.48 ml/min/1.73 m ( 2 ) ( 95 % confidence interval 1.29 to 1.67 , p < 0.0001 ) . Subsequent HF was preceded by a decrease in eGFR over 1 year compared to modest improvement in those without subsequent HF ( -0.09 ± 7.89 vs 0.81 ± 6.90 ml/min/1.73 m ( 2 ) , p = 0.0015 ) . After adjusting for baseline eGFR , each 5-ml/min/1.73 m ( 2 ) increase in eGFR at 1 year was associated with a lower risk of subsequent HF hospitalization ( hazard ratio 0.85 , 95 % confidence interval 0.77 to 0.94 , p = 0.002 ) . This relation was independent of treatment effect or change in low-density lipoprotein cholesterol level at 1 year . In conclusion , treatment with high- compared to low-dose atorvastatin was associated with improvement in eGFR at 1 year , which was related to a decrease in subsequent HF hospitalization . This suggests that improvement in kidney function may be related to the beneficial effect of high-dose atorvastatin on HF hospitalization .

atorvastatin

atorvastatin

eGFR

Treating to New Targets [ TNT ] study )


Comparison of dual-axis rotational coronary angiography ( XPERSWING ) versus conventional technique in routine practice . INTRODUCTION AND OBJECTIVES Coronary angiography is the gold standard for the study of coronary artery disease . This technique requires several orthogonal projections . Rotational angiography is a new technique which involves pre-set rotation of the X-ray tube around the patient and allows visualization of each coronary artery in different views , using a single contrast injection . The purpose of this study was to compare conventional coronary angiography ( A ) vs rotational angiography ( B ) , focusing on radiation dose , amount of contrast administered , and total procedure time for both diagnostic and therapeutic percutaneous coronary interventions . METHODS Prospective study of 104 consecutive patients undergoing coronary angiography who were randomized to one of these techniques . RESULTS We found a significant reduction in the amount of contrast administered ( A vs B , 93.1 [ 41.7 ] vs 50.9 [ 14.7 ] mL ; P < .0001 ) and radiation exposure ( 27.6 [ 11.5 ] vs 18 [ 6.4 ] mGycm ( 2 ) ; P < .0001 ) . A significant increase in total procedure time was noted in the rotational angiography arm . However , when only the last 50 patients were analyzed , we found no difference in procedure time between the groups , probably related to the learning curve of the operators . Angioplasty was performed in 29 patients in group A and 28 patients in group B . Contrast reduction was maintained in the rotational angiography group compared to the conventional technique ( A vs B , 335.1 [ 192.1 ] vs 238.5 [ 114.4 ] mL ; P=.02 ) . CONCLUSIONS The rotational angiography technique leads to a significant decrease in radiation exposure and contrast dose administered for diagnostic procedures when compared to conventional coronary angiography . In patients who undergo percutaneous coronary intervention , contrast reduction remains significant .

conventional

angiography

Rotational angiography

coronary angiography

rotational angiography

conventional coronary angiography

amount of contrast administered

radiation exposure

total procedure time

procedure time

Angioplasty

Contrast reduction

radiation exposure

contrast dose


Evaluation of oral zinc sulfate effect on obsessive-compulsive disorder : a randomized placebo-controlled clinical trial . OBJECTIVE Obsessive-compulsive disorder is a common neuropsychiatric condition . Although various pharmaceutical agents are available for the treatment of obsessive-compulsive disorder , psychiatrists often find that many patients can not tolerate the side effects of these medications , the patients do not respond properly to the treatment , or the medications lose their effectiveness after a period of treatment . The augmentation with safe supplementation of medication , such as with trace elements , may be a solution to some of these problems . METHODS This study was a prospective , double-blinded , 8-wk trial . Twelve patients were given fluoxetine ( 20 mg/d ) plus zinc ( 440 mg/d ) and 11 patients were given fluoxetine plus placebo for 8 wk . RESULTS Both groups showed a decrease in the mean Yale-Brown Obsessive-Compulsive Scale score . Based on t tests , in weeks 2 and 8 , patients treated with fluoxetine plus zinc had significantly lower scores than those treated with fluoxetine plus placebo . CONCLUSION The results show that zinc , as adjuvant agent for obsessive-compulsive disorder , produces improved outcomes .

oral zinc sulfate

placebo-controlled

fluoxetine

plus zinc

fluoxetine

placebo

obsessive-compulsive disorder

side effects


Temporal discounting : the differential effect of proximal and distal consequences on confession decisions . Drawing on the psychological principle that proximal consequences influence behavior more strongly than distal consequences , the authors tested the hypothesis that criminal suspects exhibit a short-sightedness during police interrogation that increases their risk for confession . Consistent with this hypothesis , Experiment 1 showed that participants ( N = 81 ) altered how frequently they admitted to criminal and unethical behaviors during an interview to avoid a proximal consequence even though doing so increased their risk of incurring a distal consequence . Experiment 2 ( N = 143 ) yielded the same pattern , but with a procedure that reversed the order of the proximal and distal consequences , thereby ruling out the possibility that it was the unique characteristics of the consequences rather than their proximity that influenced the admission rate . The authors discuss the supported psychological process as a potential explanation for several well-established findings reported in the literature on confessions .

confession decisions .

risk for confession .

distal consequence .

proximal and distal consequences

admission rate

criminal suspects


Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine . BACKGROUND Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains . METHODS An open-label , randomized , phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted , inactivated whole-virus H1N1 A/California/07/2009 vaccine . 408 subjects were stratified by age ( 18-59 and > 60 years ) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart . Safety , immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed . RESULTS A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition ( HI ) and neutralizing ( MN ) antibody titers in both adult and elderly subjects . A single 7.5 μg dose induced seroprotection rates of 86.9 % in adults and 75.2 % in elderly subjects . Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9 % and 89.1 % , respectively . The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers . Both HI and MN antibodies persisted for ≥ 6 months post-vaccination . Between 34 % and 49 % of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline . Higher baseline HI titers were associated with receipt of the 2008-09 or 2009-10 seasonal influenza vaccine . High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99 , a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000-01 to 2006-07 . Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55 % of tested sera . The vaccine was well tolerated with low rates of fever . CONCLUSIONS A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines , probably due to immunological priming by previous seasonal influenza vaccines or infections .

seroprotection rates

Higher baseline HI titers

tolerated


Impact of the quantity and flavonoid content of fruits and vegetables on markers of intake in adults with an increased risk of cardiovascular disease : the FLAVURS trial . PURPOSE Limited robust randomised controlled trials investigating fruit and vegetable ( F & V ) intake in people at risk of cardiovascular disease ( CVD ) exist . We aimed to design and validate a dietary strategy of increasing flavonoid-rich versus flavonoid-poor F & V consumption on nutrient biomarker profile . METHODS A parallel , randomised , controlled , dose-response dietary intervention study . Participants with a CVD relative risk of 1.5 assessed by risk scores were randomly assigned to one of the 3 groups : habitual ( control , CT ) , high-flavonoid ( HF ) or low-flavonoid ( LF ) diets . While the CT group ( n = 57 ) consumed their habitual diet throughout , the HF ( n = 58 ) and LF ( n = 59 ) groups sequentially increased their daily F & V intake by an additional 2 , 4 and 6 portions for 6-week periods during the 18-week study . RESULTS Compliance to target numbers and types of F & V was broadly met and verified by dietary records , and plasma and urinary biomarkers . Mean ( ± SEM ) number of F & V portions/day consumed by the HF and LF groups at baseline ( 3.8 ± 0.3 and 3.4 ± 0.3 ) , 6 weeks ( 6.3 ± 0.4 and 5.8 ± 0.3 ) , 12 weeks ( 7.0 ± 0.3 and 6.8 ± 0.3 ) and 18 weeks ( 7.6 ± 0.4 and 8.1 ± 0.4 ) , respectively , was similar at baseline yet higher than the CT group ( 3.9 ± 0.3 , 4.3 ± 0.3 , 4.6 ± 0.4 , 4.5 ± 0.3 ) ( P = 0.015 ) . There was a dose-dependent increase in dietary and urinary flavonoids in the HF group , with no change in other groups ( P = 0.0001 ) . Significantly higher dietary intakes of folate ( P = 0.035 ) , non-starch polysaccharides ( P = 0.001 ) , vitamin C ( P = 0.0001 ) and carotenoids ( P = 0.0001 ) were observed in both intervention groups compared with CT , which were broadly supported by nutrient biomarker analysis . CONCLUSIONS The success of improving nutrient profile by active encouragement of F & V intake in an intervention study implies the need for a more hands-on public health approach .

fruits and vegetables

fruit and vegetable ( F & V ) intake

habitual ( control , CT )

high-flavonoid ( HF )

low-flavonoid ( LF ) diets

quantity and flavonoid content

fruit and vegetable ( F & V ) intake

F & V consumption

plasma and urinary biomarkers

adults


Moclobemide , imipramine and placebo in the treatment of major depression . Moclobemide was compared with imipramine and placebo in the treatment of major depressive episodes in 75 outpatients . The dosage of moclobemide ( 25 patients ) was 300 mg daily for the first 5 days , after which it could be increased to 600 mg. Imipramine ( 25 patients ) was given in a dosage starting with 33 mg and gradually increased to 100 mg/day in the first 5 days , after which it could be further increased ; 25 patients received placebo . Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression , the overall assessment of efficacy and the Zung Self-rating Scale , and clearly superior to placebo ; there were no significant differences between the 2 active drugs . Moclobemide was better tolerated than imipramine , and was almost comparable to placebo in this respect .

placebo .

Moclobemide

imipramine

depression

Hamilton Rating Scale for Depression

Zung Self-rating Scale

better tolerated

depression


Tinzaparin versus dalteparin for periprocedure prophylaxis of thromboembolic events in hemodialysis patients : a randomized trial . BACKGROUND Low-molecular-weight heparin ( LMWH ) is cleared predominantly by the kidneys and hence there is uncertainty about the safety of its use in hemodialysis ( HD ) patients . Our primary objective was to compare whether tinzaparin and dalteparin differentially accumulate in HD patients . STUDY DESIGN Open-label randomized controlled trial . SETTING & PARTICIPANTS HD patients undergoing periprocedure bridging anticoagulation . INTERVENTION After warfarin therapy was discontinued , participants were randomly assigned to either 3 daily doses of tinzaparin ( 175 IU/kg ) or dalteparin ( 200 IU/kg ) , with 2 intervening HD treatments between the first dose of study drug and their procedure . OUTCOMES The primary outcome was predialysis anti-Xa levels 20 to 24 hours after the third LMWH dose ( therapeutic target , < 0.2 IU/mL ) . Secondary outcomes included thromboembolic events and major bleeding . RESULTS Of 29 eligible and consenting patients , 17 patients received tinzaparin and 12 patients received dalteparin . Mean predialysis anti-Xa level 20-24 hours after the third LMWH dose was 0.37 ± 0.23 ( SD ) IU/mL for tinzaparin and 0.62 ± 0.41 IU/mL for dalteparin ( P = 0.1 ) , indicating clinically important accumulation for both drugs . No invasive procedures were canceled due to study drug accumulation . 4 patients experienced serious adverse events ( 1 major bleed after traumatic arteriovenous fistula puncture in the tinzaparin arm , 2 non-ST-elevation myocardial infarctions [ 1 in each group ] , and 1 upper-extremity deep venous thrombosis [ dalteparin group ] ) . LIMITATIONS Small sample size . CONCLUSIONS Dalteparin and tinzaparin significantly accumulate in HD patients at therapeutic doses . " Bridging therapy " with LMWHs at therapeutic doses in HD patients who require temporary interruption of warfarin therapy has the potential for complications and is of uncertain benefit . Other anticoagulation strategies , including no bridging therapy or intravenous heparin , need comparative evaluation in this unique patient population .

Tinzaparin

dalteparin

Low-molecular-weight heparin ( LMWH )

tinzaparin

dalteparin

warfarin therapy

dalteparin

tinzaparin

dalteparin

dalteparin

hemodialysis

hemodialysis ( HD )

HD patients .

HD

anticoagulation


Procalcitonin is a good tool to guide duration of antibiotic therapy in patients with severe acute pancreatitis . A randomized prospective single-center controlled trial . OBJECTIVE To investigate the clinical usefulness of procalcitonin ( PCT ) for guiding duration of antibiotic therapy in patients with severe acute pancreatitis ( SAP ) . METHODS A total of 71 patients with confirmed severe acute pancreatitis from March 2009 to September 2011 in the Department of Critical Care Medicine of Huizhou Municipal Central Hospital , Guangdong , China were enrolled in this study . Procalcitonin was measured daily by a semi-quantitative immunoassay in the study group . Patients were randomly assigned into 2 groups including a PCT-guided group ( study group ) and a prophylactic antibiotic therapy ( control group ) . Antibiotic therapy in the study group was not applied until clinical signs and symptoms of infection appeared ( PCT value was > 0.5ng/ml ) . We discontinued the antibiotic therapy if clinical signs and symptoms of infection improved and PCT was < 0.5ng/ml over 3 days . In the control group , antibiotic therapy was administrated for 2 weeks , or antibiotic therapy was continued because of confirmed infection until clinical signs and symptoms of infection disappeared over 3 days . RESULTS In the study group ( 35 patients ) , the duration of antibiotic therapy and hospitalization was significantly shorter than the control group ( 36 patients ) ( 10.89+/-2.85 versus 16.06+/-2.48 days , p < 0.001 , and 16.66+/-4.02 days versus 23.81+/-7.56 days , p < 0.001 ) without negative clinical effects and the cost of hospitalization was significantly lower . CONCLUSION Procalcitonin is a helpful and safe tool for guiding duration of antibiotic treatment in patients with severe acute pancreatitis .

Procalcitonin

antibiotic therapy

procalcitonin

antibiotic therapy

Procalcitonin

2 groups including a

PCT-guided group ( study group )

a

prophylactic antibiotic therapy

( control group )

Antibiotic therapy

antibiotic therapy

Procalcitonin

negative clinical effects

cost of hospitalization

severe acute pancreatitis

severe acute pancreatitis ( SAP )

71 patients

severe acute pancreatitis


A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease . Abnormal blood flow accounts for most of the clinical morbidity of sickle cell disease ( SCD ) [ 1,2 ] . Most notably , occlusion of flow in the microvasculature causes the acute pain crises [ 3 ] that are the commonest cause for patients with SCD to seek medical attention [ 4 ] and major determinants of their quality of life [ 5 ] . Based on evidence that endothelial P-selectin is central to the abnormal blood flow in SCD we provide results from four of our studies that are germane to microvascular blood flow in SCD . A proof-of-principle study established that doses of heparin lower than what are used for anticoagulation but sufficient to block P-selectin improved microvascular blood flow inpatients with SCD . An in vitro study showed that Pentosan Polysulfate Sodium ( PPS ) had greater P-selectin blocking activity than heparin . A Phase I clinical study demonstrated that a single oral dose of PPS increased microvascular blood flow in patients with SCD . A Phase II clinical study that was not completed documented that daily oral doses of PPS administered for 8 weeks lowered plasma levels of sVCAM-1 and tended to improve microvascular blood flow in patients with SCD . These data support the concept that P-selectin on the microvascular endothelium is critical to both acute vascular occlusion and chronically impaired microvascular blood flow in SCD . They also demonstrate that oral PPS is beneficial to microvascular sickle cell blood flow and has potential as an efficacious agent for long-term prophylactic therapy of SCD .

P-selectin blocking agent

heparin

Pentosan Polysulfate Sodium ( PPS )

PPS

PPS

marker of endothelial cell injury

Abnormal blood flow

abnormal blood flow in SCD

microvascular blood flow

microvascular blood flow

sickle cell disease

SCD

SCD


A web-based computer-tailored smoking prevention programme for primary school children : intervention design and study protocol . BACKGROUND Although the number of smokers has declined in the last decade , smoking is still a major health problem among youngsters and adolescents . For this reason , there is a need for effective smoking prevention programmes targeting primary school children . A web-based computer-tailored feedback programme may be an effective intervention to stimulate youngsters not to start smoking , and increase their knowledge about the adverse effects of smoking and their attitudes and self-efficacy regarding non-smoking . METHODS & DESIGN This paper describes the development and evaluation protocol of a web-based out-of-school smoking prevention programme for primary school children ( age 10-13 years ) entitled 'Fun without Smokes ' . It is a transformation of a postal mailed intervention to a web-based intervention . Besides this transformation the effects of prompts will be examined . This web-based intervention will be evaluated in a 2-year cluster randomised controlled trial ( c-RCT ) with three study arms . An intervention and intervention + prompt condition will be evaluated for effects on smoking behaviour , compared with a no information control condition . Information about pupils ' smoking status and other factors related to smoking will be obtained using a web-based questionnaire . After completing the questionnaire pupils in both intervention conditions will receive three computer-tailored feedback letters in their personal e-mail box . Attitudes , social influences and self-efficacy expectations will be the content of these personalised feedback letters . Pupils in the intervention + prompt condition will - in addition to the personalised feedback letters - receive e-mail and SMS messages prompting them to revisit the 'Fun without Smokes ' website . The main outcome measures will be ever smoking and the utilisation of the 'Fun without Smokes ' website . Measurements will be carried out at baseline , 12 months and 24 months of follow-up . DISCUSSION The present study protocol describes the purpose , intervention design and study protocol of 'Fun without Smokes ' . Expectations are that pupils receiving tailored advice will be less likely to smoke after 24 months in contrast to pupils in the control condition . Furthermore , tailored feedback letters and prompting is expected to be more effective than providing tailored feedback letters only . TRIAL REGISTRATION Dutch Trial Register NTR3116 .

smoking prevention programme

feedback programme

smoking behaviour

pupils ' smoking status

Attitudes

social influences

self-efficacy expectations

ever smoking

primary school children :

youngsters and adolescents .

primary school children .