Is prophylactic intravenous administration of a proton pump inhibitor necessary for perioperative management of cardiac surgery ? BACKGROUND Mortality from gastrointestinal ( GI ) hemorrhage caused by antiplatelet or anticoagulant therapy ( or both ) is quite high after cardiac surgery . We previously reported that proton pump inhibitor ( PPI ) therapy is indispensable in preventing postoperative GI complications . PPIs are usually administered intravenously immediately after surgery and subsequently by oral formulations . We conducted a prospective study to evaluate whether intravenous PPI followed by oral administration is more efficient as prophylaxis than oral-only administration . METHODS AND RESULTS We enrolled 40 patients scheduled to undergo coronary artery bypass grafting with cardiopulmonary bypass and randomly assigned them to receive oral PPIs alone ( group 1 ) or intravenous PPI followed by oral administration ( group 2 ) . Postoperative upper GI endoscopy evaluations showed no evidence of GI bleeding . Only gastritis , esophagitis , and hiatal hernia were observed at similar incidences in the groups . Mean hospital stays were also similar , but the cost of PPI treatment was significantly lower in group 1 . CONCLUSION No additional benefits of intravenous PPIs over oral formulations were demonstrated . Oral PPIs alone were effective and economical as prophylaxis against GI complications . Intravenous PPIs might be unnecessary in selected patients after cardiac surgery .

proton pump inhibitor

antiplatelet

anticoagulant therapy

proton pump inhibitor ( PPI ) therapy

PPIs

PPI

PPIs

PPIs

GI bleeding .

Mean hospital stays

cost of PPI treatment


Efficacy of different gonadotropin combinations to support ovulation induction in WHO type I anovulation infertility : clinical evidences of human recombinant FSH/human recombinant LH in a 2:1 ratio and highly purified human menopausal gonadotropin stimulation protocols . BACKGROUND The World Helath Organization ( WHO ) Group I anovulation , or hypogonadotropic hypogonadism ( HH ) , is characterized by reduced hypothalamic/pituitary activity which results in abnormally low serum FSH and LH levels and negligible estrogen activity . AIM To compare the efficacy of human recombinant FSH ( r-hFSH ) plus human recombinant LH ( r-hLH ) in a 2:1 ratio with highly purified human menopausal gonadotropin ( hMG-HP ) urinary extract , containing LH-like activity , in women with HH . SUBJECTS AND METHODS This two-arm randomized open-label study included 35 HH women ( aged 25-36 yr ) attending our Center . Eighteen patients received 150 IU hMG-HP ( 150 IU FSH + 150 IU LH-like activity ) and seventeen received 150IU r-hFSH/75IU rhLH daily for a maximum of 16 days . Ovulation was induced by a single administration of hCG on the day after the last hMG-HP or r-hFSH/r-hLH . RESULTS The primary efficacy endpoint was ovulation induction as measured by follicle ≥17 mm , pre-ovulatory estradiol ( E 2 ) ≥400 pmol/l and mid-luteal phase progesterone ( P 4 ) ≥25 nmol/l . Secondary efficacy endpoints included E 2 levels/follicle at mid-cycle , number of follicles at mid-cycle and pregnancy rate ( PR ) . Following a total of 70 cycles , 70 % of r-hFSH/r-hLH treated patients met the primary endpoint vs 88 % in hMG-HP group ( p=0.11 ) . However , PR in r-hFSH/r-hLH group was 55.6 % compared to 23.3 % in hMG-HP group ( p=0.01 ) . CONCLUSIONS The primary endpoint achievement did not correlate with PR . This study has shown the superiority of LH compared to hCG in supporting FSH-induced follicular development in HH women .

gonadotropin combinations

150 IU hMG-HP ( 150

150IU r-hFSH/75IU rhLH

hMG-HP

r-hFSH/r-hLH

ovulation induction

ovulation induction

follicle

WHO type I anovulation infertility

women

women

Eighteen

seventeen


Pulmonary vein re-isolation for atrial fibrillation using duty-cycled phased radiofrequency ablation : safety and efficacy of a primary 2:1 bipolar/unipolar ablation mode . PURPOSE Pulmonary vein isolation ( PVI ) using phased radiofrequency ( RF ) energy has been shown to be effective in the treatment of paroxysmal atrial fibrillation ( AF ) . We characterize pulmonary vein ( PV ) conduction at repeat ablation in patients with AF after an initial successful PVI using phased RF technology and analyze the effects of a primary 2:1 ablation mode . METHODS AND RESULTS A primary 4:1 bipolar/unipolar mode in group A patients ( n = 22 ) was compared with a primary 2:1 mode in group B ( n = 22 ) acutely and during follow-up . Of all PVs , 81 % showed reconnection ( s ) ; 52 % of them had reconnected in all PVs . PVI was achieved in all patients without complications . Procedure and fluoroscopy times were shorter in group B ( 108 ± 15 vs. 126 ± 24 min and 17 ± 5 vs. 23 ± 7 min , respectively ) . This was attributed to a significant decrease of early PV reconnections within the first 30 min in 17 % of group B patients vs. 45 % of group A patients ( p < 0.001 ) . After 9.5 ± 4 months , recurrence of AF was detected in 5 of 22 patients ( 22.7 % ) in group A vs. 3 of 22 patients ( 13.6 % ) in group B ( p = 0.722 ) . CONCLUSIONS Phased RF energy applied by a 2:1 bipolar/unipolar mode seems safe and effective in redo-PVI procedures , resulting in a mid-term freedom from AF in 86.4 % . Significant shorter procedure and fluoroscopy times compared with a primary 4:1 ablation mode during repeat PVI are mainly attributed to a lower incidence of acutely reconnected PVs within the first 30 min .

Pulmonary vein isolation ( PVI )

phased radiofrequency ( RF ) energy

Procedure and fluoroscopy times


Early behavioral intervention is associated with normalized brain activity in young children with autism . OBJECTIVE A previously published randomized clinical trial indicated that a developmental behavioral intervention , the Early Start Denver Model ( ESDM ) , resulted in gains in IQ , language , and adaptive behavior of children with autism spectrum disorder . This report describes a secondary outcome measurement from this trial , EEG activity . METHOD Forty-eight 18- to 30-month-old children with autism spectrum disorder were randomized to receive the ESDM or referral to community intervention for 2 years . After the intervention ( age 48 to 77 months ) , EEG activity ( event-related potentials and spectral power ) was measured during the presentation of faces versus objects . Age-matched typical children were also assessed . RESULTS The ESDM group exhibited greater improvements in autism symptoms , IQ , language , and adaptive and social behaviors than the community intervention group . The ESDM group and typical children showed a shorter Nc latency and increased cortical activation ( decreased α power and increased θ power ) when viewing faces , whereas the community intervention group showed the opposite pattern ( shorter latency event-related potential [ ERP ] and greater cortical activation when viewing objects ) . Greater cortical activation while viewing faces was associated with improved social behavior . CONCLUSIONS This was the first trial to demonstrate that early behavioral intervention is associated with normalized patterns of brain activity , which is associated with improvements in social behavior , in young children with autism spectrum disorder .

behavioral intervention

receive the ESDM

referral to community intervention

for 2 years

EEG activity

ESDM

brain activity

EEG activity

young children

autism

children

autism spectrum disorder


Research Units of Pediatric Psychopharmacology ( RUPP ) autism network randomized clinical trial of parent training and medication : one-year follow-up . OBJECTIVE To follow up on a three-site , 24-week randomized clinical trial ( N = 124 ) comparing antipsychotic medication alone ( MED ) with antipsychotic medication plus parent training in the behavior management ( COMB ) of children with autism spectrum disorders and severe behavior problems . The COMB treatment had shown a significant advantage for child behavioral noncompliance ( p = .006 , d = 0.34 ) , irritability ( p = .01 , d = 0.48 ) , and hyperactivity/noncompliance ( p = .04 , d = 0.55 ) with a lower medication dose . METHOD One year after each participant 's termination , the authors mailed an assessment packet with a return-addressed envelope ; a telephone call alerted the family . Failure to return packets within 1 month elicited another contact and offers to resend . RESULTS Eighty-seven of 124 families ( 70.2 % ) participated in the follow-up . The improvement difference between treatments attenuated from after treatment to follow-up for noncompliance ( d = 0.32 to 0.12 ) and irritability ( d = 0.46 to 0.03 ) . The follow-up differences were nonsignificant ( the noncompliance difference also was nonsignificant after treatment for these 87 families ) . Sixty-seven percent of the COMB group and 53 % of the MED group were still taking risperidone , the original study medication . Most needed dose adjustments or additional medication , and the COMB group no longer had a significantly lower dose . All COMB families but only 39 % of MED families reported seeking parent training after treatment . Improvements in daily living skills during treatment predicted noncompliance improvement at follow-up for the COMB children , but noncompliance deterioration and especially hyperactivity/noncompliance deterioration for the MED children . CONCLUSIONS The study treatment experience/familiarity greatly influenced the follow-up treatment : those who had received parent training reported seeking it , whereas those who had not received it tended not to seek it . The superiority of COMB over MED after treatment attenuated by more than half at follow-up .

antipsychotic medication alone

risperidone

behavior management

child behavioral noncompliance

hyperactivity/noncompliance

seeking parent training

Improvements in daily living skills

( N = 124 )

children

child


End-expiratory lung volume recovers more slowly after closed endotracheal suctioning than after open suctioning : a randomized crossover study . PURPOSE Endotracheal suctioning causes significant lung derecruitment . Closed suction ( CS ) minimizes lung volume loss during suction , and therefore , volumes are presumed to recover more quickly postsuctioning . Conflicting evidence exists regarding this . We examined the effects of open suction ( OS ) and CS on lung volume loss during suctioning , and recovery of end-expiratory lung volume ( EELV ) up to 30 minutes postsuction . MATERIAL AND METHODS Randomized crossover study examining 20 patients postcardiac surgery . CS and OS were performed in random order , 30 minutes apart . Lung impedance was measured during suction , and end-expiratory lung impedance was measured at baseline and postsuctioning using electrical impedance tomography . Oximetry , partial pressure of oxygen in the alveoli/fraction of inspired oxygen ratio and compliance were collected . RESULTS Reductions in lung impedance during suctioning were less for CS than for OS ( mean difference , -905 impedance units ; 95 % confidence interval [ CI ] , -1234 to -587 ; P < .001 ) . However , at all points postsuctioning , EELV recovered more slowly after CS than after OS . There were no statistically significant differences in the other respiratory parameters . CONCLUSIONS Closed suctioning minimized lung volume loss during suctioning but , counterintuitively , resulted in slower recovery of EELV postsuction compared with OS . Therefore , the use of CS can not be assumed to be protective of lung volumes postsuctioning . Consideration should be given to restoring EELV after either suction method via a recruitment maneuver .

closed endotracheal suctioning

open suctioning :

Closed suction ( CS )

open suction ( OS )

CS

suctioning

CS

OS

CS

OS

CS

OS

Closed suctioning

OS

CS

endotracheal

lung volume

end-expiratory lung volume ( EELV )

postcardiac

Lung impedance

Oximetry

compliance

impedance

EELV

End-expiratory lung volume

20 patients postcardiac surgery


Dysfunctional attitudes as a moderator of pharmacotherapy and psychotherapy for chronic depression . OBJECTIVE Individuals with chronic depression exhibit heterogeneous responses to treatment . Important individual differences may therefore exist within this particularly difficult to treat population that act as moderators of treatment response . METHOD The present study examined whether pretreatment levels of dysfunctional attitudes ( DA ) moderated treatment response in a large sample of chronically depressed individuals . Data were taken from the Research Evaluating the Value of Augmenting Medication with Psychotherapy ( REVAMP ) treatment study -- a multi-site treatment and augmentation study of 808 chronically depressed individuals . REVAMP comprised two phases : 1 ) a 12-week open-label antidepressant trial and 2 ) , a subsequent phase , in which phase 1 non-remitters ( N = 491 ) were randomized to either receive an ongoing medication algorithm alone , medication plus cognitive behavioral analysis system of psychotherapy , or medication plus brief supportive psychotherapy . RESULT In phase 1 , compared to the pharmacotherapy response of patients with lower DA scores , the response for patients with higher DA scores was steeper , but leveled off toward the end of the phase . In phase 2 , DA predicted a differential response in the medication only arm , but not in the two psychotherapy + medication conditions . Specifically , in the phase 2 medication only condition , patients with higher DA improved while those with lower DA scores did not . CONCLUSION These results indicate that the relation between DA and treatment response in chronic depression is complex , but suggest that greater DA may be associated with a steeper reduction and/or better response to pharmacotherapy .

pharmacotherapy

psychotherapy

12-week open-label antidepressant trial

psychotherapy

medication

medication

pharmacotherapy .

pharmacotherapy response

improved

chronic depression

chronic depression

chronically depressed

chronically depressed

depression


Brief Report : social disability in autism spectrum disorder : results from Research Units on Pediatric Psychopharmacology ( RUPP ) Autism Network trials . There is growing interest in measuring social disability as a core element of autism spectrum disorders in medication trials . We conducted a secondary analysis on the Aberrant Behavior Checklist Social Withdrawal subscale using data from two federally-funded , multi-site , randomized trials with risperidone . Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions . Study 2 included 49 subjects assigned to risperidone only and 75 subjects assigned to risperidone plus parent training . After 8 weeks of treatment , all active treatments were superior to placebo ( effect sizes ranging from 0.42 to 0.65 ) . The findings suggest that the Social Withdrawal subscale may be a useful measure of social disability in acute treatment trials .

risperidone

placebo

risperidone

risperidone only

risperidone

parent training

social disability

social disability

social disability


ARIX : a randomised trial of acupuncture v oral care sessions in patients with chronic xerostomia following treatment of head and neck cancer . BACKGROUND Radiation treatment of head and neck cancer can cause chronic xerostomia which impairs patients ' quality of life . The study reported here examined the efficacy of acupuncture in alleviating xerostomia symptoms especially dry mouth . PATIENTS AND METHODS A total of 145 patients with chronic radiation-induced xerostomia > 18 months after treatments were recruited from seven UK cancer centres . The study employed a randomised crossover design with participants receiving two group sessions of oral care education and eight of acupuncture using standardised methods . Patient-reported outcome ( PROs ) measures were completed at baseline and weeks 5 , 9 , 13 , 17 , and 21 . The primary outcome was improvement in dry mouth . OBJECTIVE saliva measurements were also carried out . RESULTS Acupuncture compared with oral care , produced significant reductions in patient reports of severe dry mouth ( OR = 2.01 , P = 0.031 ) sticky saliva ( OR = 1.67 , P = 0.048 ) , needing to sip fluids to swallow food ( OR = 2.08 , P = 0.011 ) and in waking up at night to drink ( OR = 1.71 , P = 0.013 ) . There were no significant changes in either stimulated or unstimulated saliva measurements over time . CONCLUSION Eight sessions of weekly group acupuncture compared with group oral care education provide significantly better relief of symptoms in patients suffering from chronic radiation-induced xerostomia .

acupuncture

oral care sessions

acupuncture

oral care education

acupuncture using standardised methods

Acupuncture

acupuncture

efficacy

dry mouth

saliva measurements

severe dry mouth

sticky saliva

needing to sip fluids to swallow food

waking up at night to drink

chronic xerostomia

head and neck cancer

head and neck cancer

chronic xerostomia

chronic radiation-induced xerostomia

chronic radiation-induced xerostomia .


Effect of unfractionated and low-molecular-weight heparin on OPG , sRANKL , and von Willebrand factor concentrations during hemodialysis . BACKGROUND Endothelial dysfunction marker , von Willebrand factor ( vWF ) , is physically connected with osteoprotegerin ( OPG ) in the Weibel-Palade bodies . We aimed to compare the effect of unfractionated ( UFH ) and low-molecular-weight ( LMWH enoxaparin ) heparin used as anticoagulants during hemodialysis ( HD ) on plasma levels and relationships of OPG , soluble receptor activator of nuclear factor κB Ligand ( sRANKL ) , and vWF . METHODS Totally 21 clinically stable chronic HD patients were randomly assigned to either enoxaparin ( n = 10 ) or UFH ( n = 11 ) anticoagulation and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks . The OPG , RANKL , and vWF levels were measured at T0 , T10 , and T180 of HD session after each period of evaluation . RESULTS The baseline sRANKL level was higher under UFH treatment . Its over-HD level does not behave significantly different under enoxaparin and UFH treatment . Plasma OPG levels expressly changed during both enoxaparin ( χ ( 2 ) analysis of variance [ ANOVA ] = 31.13 , P < .016 ) and UFH ( χ ( 2 ) ANOVA = 8.26 , P = .016 ) anticoagulation , and its increment at T10 and T180 was significantly different between both the heparins . The main negative predictor of OPG concentration was the total cholesterol level ( β = -.51 , P = .025 ) . von Willebrand factor concentration remained stable during UFH anticoagulation , whereas constant , no significant increments were noticed , under enoxaparin treatment . After 10 minutes of HD , especially under enoxaparin use , a positive correlation between OPG and vWF increase was noticed ( P = .03 , R = .45 ) . CONCLUSIONS Impact of heparin on endothelial cells and simultaneously on OPG/RANK/RANKL axis reinforces the presumption of the pathophysiological linkage between bone mineralization and endothelial dysfunction in end-stage renal disease .

unfractionated

low-molecular-weight heparin

unfractionated ( UFH )

hemodialysis

hemodialysis ( HD )

dysfunction in end-stage renal disease


Acceleration of insulin pharmacodynamic profile by a novel insulin infusion site warming device . BACKGROUND AND OBJECTIVE Subcutaneously injected rapid-acting insulin analogs do not replicate physiologic insulin action due to delays in their onset and peak action resulting in postprandial glucose excursions . The InsuPatch ( IP ) is a novel insulin infusion site warming device developed to accelerate insulin action by increasing blood flow to the area of insulin absorption . Thirteen adolescents with type 1 diabetes ( T1D , mean age 14 ± 4 yr ) were enrolled in this study to investigate the effect of the IP on the pharmacodynamics and pharmacokinetics of a 0.2 unit/kg bolus dose of aspart insulin using the euglycemic clamp technique . RESEARCH DESIGN AND METHODS Each subject underwent two euglycemic clamp procedures on separate occasions : one with IP and one without IP activation in random order . RESULTS When the insulin bolus was given with IP activation as compared to without IP activation , time to reach maximum insulin action ( T ( GIRmax ) ) and to reach 50 % maximum action ( T ( 50 % GIRmax ) ) were 35 and 18 min earlier ( 125 ± 8 min vs. 90 ± 6 min , p = 0.002 and 58 ± 5 min . vs. 40 ± 3 min , p = 0.01 , respectively ) , and the area under curve , AUC ( GIR 0-90 min ) , reflecting early glucodynamic action , was significantly greater ( p = 0.001 ) . IP activation also accelerated the rise in plasma insulin levels after the bolus ( p = 0.03 ) and resulted in a higher peak ( p = 0.04 ) and greater overall increase ( p = 0.02 ) in plasma insulin levels . CONCLUSIONS Our results show that insulin infusion site warming with IP activation accelerates the time action profile of aspart insulin which may be of benefit to current open-loop and future closed-loop insulin delivery in patients with T1D .

insulin infusion site warming device

The InsuPatch ( IP )

IP

Thirteen

adolescents

type 1 diabetes

mean age 14 ± 4 yr )


Effects of strontium on the quality of bone apatite crystals : a paired biopsy study in postmenopausal osteoporotic women . UNLABELLED In paired biopsies of osteoporotic women treated with either strontium ranelate or a placebo for 36 months , characteristics of bone apatite crystals were not influenced by the presence of strontium . The mean rate of substitutions of calcium by strontium ions was 4.5 % . INTRODUCTION The potential effect of strontium ( Sr ) on bone apatite crystals was investigated in paired biopsies of osteoporotic women treated with either strontium ranelate ( SrRan ) or a placebo for 36 months . METHODS In ten paired biopsies , crystallinity , apparent length and width/thickness of crystals , interplanar distances , and lattice parameters of unit cells were assessed by X-ray diffraction and selected area electron diffraction . RESULTS All these parameters , reflecting crystal and unit cell characteristics , were not influenced by the presence of Sr and were similar in SrRan and placebo groups after 36 months of treatment . The mean rate of substitutions of calcium by Sr ions was 4.5 % . CONCLUSION Overall , the quality of bone apatite crystals was maintained after 36 months of treatment with SrRan .

strontium

strontium ranelate

placebo

strontium

strontium

strontium ranelate ( SrRan )

placebo

SrRan

placebo

SrRan

quality of bone apatite crystals :

mean rate of substitutions

quality of bone apatite crystals

postmenopausal osteoporotic

women

biopsies

osteoporotic

women

osteoporotic

women

ten


Social robots as embedded reinforcers of social behavior in children with autism . In this study we examined the social behaviors of 4- to 12-year-old children with autism spectrum disorders ( ASD ; N = 24 ) during three tradic interactions with an adult confederate and an interaction partner , where the interaction partner varied randomly among ( 1 ) another adult human , ( 2 ) a touchscreen computer game , and ( 3 ) a social dinosaur robot . Children spoke more in general , and directed more speech to the adult confederate , when the interaction partner was a robot , as compared to a human or computer game interaction partner . Children spoke as much to the robot as to the adult interaction partner . This study provides the largest demonstration of social human-robot interaction in children with autism to date . Our findings suggest that social robots may be developed into useful tools for social skills and communication therapies , specifically by embedding social interaction into intrinsic reinforcers and motivators .

children

autism


Assessing the effect of CT slice interval on unidimensional , bidimensional and volumetric measurements of solid tumours . OBJECTIVES To study the magnitude of differences in tumour unidimensional ( 1D ) , bidimensional ( 2D ) and volumetric ( VOL ) measurements determined from computed tomography ( CT ) images reconstructed at 5 , 2.5 and 1.25 mm slice intervals . MATERIALS AND METHODS A total of 118 lesions in lung , liver and lymph nodes were selected from 30 patients enrolled in early phase clinical trials . Each CT scan was reconstructed at 5 , 2.5 and 1.25 mm slice intervals during the image acquisition . Lesions were semi-automatically segmented on each interval image series and supervised by a radiologist . 1D , 2D and VOL were computed based on the final segmentation results . Average measurement differences across different slice intervals were obtained using linear mixed-effects analysis of variance models . RESULTS Lesion diameters ranged from 6.1 to 80.1 mm ( median 18.4 mm ) . The largest difference was seen between 1.25 and 5 mm ( mean difference of 7.6 % for 1D [ P < 0.0001 ] , 13.1 % for 2D [ P < 0.0001 ] , -5.7 % for VOL [ P = 0.0001 ] ) . Mean differences between 1.25 and 2.5 mm were all within ±3.5 % ( within ±6 % confidence interval ) . For VOL , there was a larger average difference between measurements on different slice intervals for the smaller lesions ( < 10 mm ) compared with the larger lesions . CONCLUSIONS Different slice intervals may give different 1D , 2D and VOL measurements . In clinical practice , it would be prudent to use the same slice interval for consecutive measurements .

CT slice interval

1D , 2D and VOL

Lesion diameters


Linguistic alignment in adults with and without Asperger 's syndrome . Individuals with Asperger 's syndrome ( AS ) often have difficulties with social interactions and conversations . We investigated if these difficulties could be attributable to a deficit in the ability to linguistically converge with an interlocutor , which is posited to be important for successful communication . To that end , participants completed two cooperative tasks with a confederate , which allowed us to measure linguistic alignment with the confederate in terms of lexical choice , syntactic structure and spatial frame of reference . There was no difference in the performance of individuals with AS and matched controls and both groups showed significant alignment with the confederate at all three levels . We conclude that linguistic alignment is intact in adults with AS engaged in structured , goal-directed social interactions .

Linguistic alignment

linguistic alignment

Asperger 's syndrome ( AS )

AS

AS


Effects of a standardized pamphlet on insomnia in children with autism spectrum disorders . OBJECTIVE Sleep difficulties are common reasons why parents seek medical intervention in children with autism spectrum disorders ( ASDs ) . We determined whether a pamphlet alone could be used by parents to help their child 's insomnia . METHODS Thirty-six children with ASD , ages 2 to 10 years , were enrolled . All had prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of 30 minutes or more . Parents were randomly assigned to receive the sleep education pamphlet or no intervention . Children wore an actigraphy device to record baseline sleep parameters , with the primary outcome variable being change in sleep latency . Actigraphy data were collected a second time 2 weeks after the parent received the randomization assignment and analyzed by using Student 's t test . Parents were also asked a series of questions to gather information about the pamphlet and its usefulness . RESULTS Although participants randomized to the 2 arms did not differ statistically in age , gender , socioeconomic status , total Children 's Sleep Habits Questionnaire score , or actigraphy parameters , some differences may be large enough to affect results . Mean change in sleep-onset latency did not differ between the randomized groups ( pamphlet versus no pamphlet ) . Parents commented that the pamphlet contained good information , but indicated that it would have been more useful to be given specific examples of how to take the information and put it into practice . CONCLUSIONS A sleep education pamphlet did not appear to improve sleep latency in children with ASDs .

standardized pamphlet

pamphlet

sleep education pamphlet or

no intervention

actigraphy device

pamphlet

pamphlet versus

no pamphlet

pamphlet

sleep education pamphlet

Sleep difficulties

insomnia .

sleep latency

sleep latency

sleep parameters

change in sleep latency .

Mean change in sleep-onset latency

information

sleep latency

insomnia

children

autism spectrum disorders

ASDs

Thirty-six

children

ASD

ages 2 to 10 years


Clinical trial : marine lipid suppositories as laxatives . UNLABELLED Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory , anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases . We developed suppositories and ointment with 30 % free fatty acid ( FFA ) extract from omega-3 fish oil . Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories . Thirty healthy volunteers were randomized either to a study group administrating 30 % FFA suppositories and applying 30 % FFA ointment to the perianal region twice per day for two weeks , or to a control group using placebo suppositories and ointment in a double blinded manner . RESULTS No serious toxic effects or irritation were observed . In the study group 93 % felt the urge to defecate after administration of the suppositories as compared to 37 % in the control group ( P = 0.001 ) . Subsequently 90 % in the study group defecated , compared to 33 % in the control group ( P = 0.001 ) . CONCLUSION The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period . The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials .

marine lipid suppositories

FFA suppositories

FFA ointment

placebo suppositories

safety

laxative effect

serious toxic effects or irritation

urge to defecate

defecated

toxic side effects

laxative effect

healthy volunteers


Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer : results from IBCSG Trials VIII and IX . INTRODUCTION The prognostic significance of p53 protein expression in early breast cancer remains uncertain , with some but not all studies finding an association with poorer outcomes . Estrogen receptor ( ER ) expression is both a positive prognostic marker and predictive of response to endocrine therapies . The relationship between these biomarkers is unknown . METHODS We constructed tissue microarrays ( TMAs ) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer . Expression of p53 defined as > 10 % positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections . RESULTS ER was present ( i.e . > 1 % positive tumor cell nuclei ) in 80.1 % ( 880/1092 ) . p53 expression was significantly more frequent when ER was absent , 125/212 ( 59 % ) than when ER was present , 171/880 ( 19 % ) , p < 0.0001 . A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival ( DFS ) and overall survival ( OS ) among patients whose tumors did not express ER , but worse DFS and OS among patients whose tumors expressed ER . The interaction remained significant after allowance for pathologic variables , and treatment . Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared . CONCLUSIONS Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER . The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression . TRIAL REGISTRATION Current Controlled Trials ACTRN12607000037404 ( Trial VIII ) and ACTRN12607000029493 ( Trial IX ) .

endocrine therapy alone

chemo-endocrine therapy

expression of p53

poorer outcomes .

Estrogen receptor ( ER ) expression

Expression of p53

ER

p53 expression

disease-free survival ( DFS )

overall survival ( OS )

DFS

OS

p53 expression

expression of ER .

p53 mutations

p53 expression

node-negative breast cancer

node-negative breast cancer


Monitoring of CA19-9 and SPan-1 can facilitate the earlier confirmation of progressing pancreatic cancer during chemotherapy . BACKGROUND Measurement of objective response to chemotherapy using imaging modalities is sometimes difficult in pancreatic cancer ( PC ) . We aimed to verify whether monitoring of serum tumor markers ( TMs ) , namely carcinoembryonic antigen , CA19-9 , DUPAN-2 , SPan-1 , can facilitate earlier confirmation of treatment failure . METHODS Monitoring of serum TMs and computed tomography were performed every 4 weeks until progression of disease in 90 patients with PC undergoing gemcitabine therapy . In Group A ( January 2006-October 2007 ) , we analyzed the fluctuation rates of TMs with high pretreatment positive rates , and defined the criteria of progressive disease under TM monitoring ( TM-PD ) . In Group B ( November 2007-October 2008 ) , we calculated the time to progression ( TTP ) under this TM-PD criteria , which was compared with the TTP under the RECIST criteria . RESULTS CA19-9 and SPan-1 had the highest pretreatment positive rates : 83 % and 90 % , respectively . In Group A ( CA19-9 , n = 38 ; SPan-1 , n = 36 ) , TM-PD criteria were defined as follows : fluctuation rates were ≥25 % for a month or ≥10 % for 2 consecutive months in CA19-9 , and ≥10 % for a month in SPan-1 . In Group B ( CA19-9 , n = 18 ; SPan-1 , n = 17 ) , under these criteria , one-month earlier confirmation of treatment failure was feasible in 61 % by CA19-9 and 59 % by SPan-1 . Furthermore , the combination could facilitate this determination in 72 % ( 35/49 ) , significantly better than CA19-9 alone ( P = 0.004 ) . CONCLUSION Monitoring of serum CA19-9 and SPan-1 is helpful for earlier confirmation of treatment failure during gemcitabine therapy in PC .

objective response to chemotherapy

using imaging modalities

serum tumor markers ( TMs )

serum TMs

computed tomography

fluctuation rates of TMs

time to progression ( TTP )

pancreatic cancer ( PC )

PC

gemcitabine therapy


The effect of values affirmation on race-discordant patient-provider communication . BACKGROUND Communication between African American patients and white health care providers has been shown to be of poorer quality when compared with race-concordant patient-provider communication . Fear on the part of patients that providers stereotype them negatively might be one cause of this poorer communication . This stereotype threat may be lessened by a values-affirmation intervention . METHODS In a blinded experiment , we randomized 99 African American patients with hypertension to perform a values-affirmation exercise or a control exercise before a visit with their primary care provider . We compared patient-provider communication for the 2 groups using audio recordings of the visit analyzed with the Roter Interaction Analysis System . We also evaluated visit satisfaction , trust , stress , and mood after the visit by means of a questionnaire . RESULTS Patients in the intervention group requested and provided more information about their medical condition ( mean [ SE ] number of utterances , 66.3 [ 6.8 ] in the values-affirmation group vs 48.1 [ 5.9 ] in the control group [ P = .03 ] ) . Patient-provider communication in the intervention group was characterized as being more interested , friendly , responsive , interactive , and respectful ( P = .02 ) and less depressed and distressed ( P = .03 ) . Patient questionnaires did not detect differences in visit satisfaction , trust , stress , or mood . Mean visit duration did not differ significantly between the groups ( 19.2 minutes in the control group vs 20.5 minutes in the intervention group [ P = .29 ] ) . CONCLUSIONS A values-affirmation exercise improves aspects of patient-provider communication in race-discordant primary care visits . The clinical impact of the intervention must be defined before widespread implementation can be recommended .

values-affirmation exercise

or a

control exercise

values-affirmation exercise

information

medical condition

depressed and distressed

visit satisfaction

trust , stress , or mood

Mean visit duration

hypertension


Emotional reactivity to social rejection and negative evaluation among persons with borderline personality features . The present study examined the emotional reactivity of persons with heightened borderline personality ( BP ) features to social rejection and negative evaluation in the laboratory . Individuals with high levels of BP features ( n = 30 ) and controls with low levels of BP features ( n = 44 ) were randomly assigned to a condition involving negative evaluation based on writing ( negative evaluation/academic ) , or a condition involving negative evaluation based on personal characteristics as well as social rejection ( negative evaluation/social rejection ) . Hypothesis 1 was that high-BP individuals , but not low-BP controls , would show greater emotional reactivity to the negative evaluation/social rejection stressor , compared with the negative evaluation/academic ( writing ) stressor . Hypothesis 2 was that high-BP individuals would specifically show greater reactivity of shame- and anger-related emotions to the negative evaluation/social rejection stressor compared with the negative evaluation/academic stressor . Findings indicated that high-BP individuals showed heightened emotional reactivity to the social rejection stressor but not to the negative evaluation stressor , but the opposite pattern occurred for controls . In addition , there was evidence for heightened reactivity of irritability , distress , and shame for the high-BP group , specifically in the social rejection condition .

negative evaluation/academic stressor

social rejection stressor

negative evaluation stressor

Emotional reactivity

emotional reactivity

writing

personal characteristics

emotional reactivity

reactivity of shame-

anger-related emotions

heightened emotional reactivity

borderline personality

high levels

BP

low levels

BP

high-BP

low-BP

high-BP

high-BP


[ Effects of transcutaneous electrical stimulation of auricular Shenmen point on postoperative nausea and vomiting and patient-controlled epidural analgesia in cesarean section ] . OBJECTIVE To investigate the effects of transcutaneous electrical stimulation of auricular Shenmen point on postoperative nausea and vomiting and patient-controlled epidural analgesia in cesarean section . METHODS After IRB approval and informed consent , one hundred and eighty singleton primiparas undergoing elective cesarean section , in Qingdao Municipal Hospital , and Qingdao Hiser Medical Center , from November 2011 to March 2012 , were randomly assigned to three groups : transcutaneous electrical stimulation of auricular Shenmen point group ( group A , n = 60 ) , transcutaneous electrical stimulation of auricular Eye point group ( group B , n = 60 ) and control group ( group C , n = 60 ) . Women of group A received transcutaneous electrical stimulation of auricular Shenmen point ( frequency 1.5 HZ ) at the time of preoperation , 4 , 10 and 22 hours of postoperation for 30 minutes . The strength was controlled by themselves . Women of group B received stimulation of auricular Eye point as group A . Women of group C received pressurization and connected line were the same with group A , but without electrical stimulation . The following indexes was observed : the incidence of postoperative nausea and vomiting ( PONV ) for 48 hours ; the rate of metoclopramide ; the visual analogue scale ( VAS ) score of rest pain , uterine contration pain and dynamic pain at the time of postoperation for 6 , 12 , 24 and 48 hours ( T ( 1 ) -T ( 4 ) ) ; the total number and effective compressions number of patient-controlled epidural analgesia ( PCEA ) ; the dose of analgesia mixture ; the anal exhaust time ; the volume of postoperative bleeding for 6 hours of postoperation and the other side effects . RESULTS Compared with group B and group C , the incidence of PONV , the rate of metoclopramide , the VAS score at the time T ( 1 ) -T ( 4 ) , the total number and effective compressions number of PCEA , the ratio of the total number with effective compressions number and the dose of analgesia mixture were decreased in group A ( P < 0.05 ) , but no difference compared group B with group C ( P > 0.05 ) . The anal exhaust time and the volume of postoperative bleeding for 6 hours of postoperation were no difference in the three groups ( P > 0.05 ) . No other side effects were observed . CONCLUSION Transcutaneous electrical stimulation of auricular Shenmen point can reduce the incidence of PONV and improves analgesia effect of PCEA in postoperation of cesarean section .

electrical stimulation

electrical stimulation

electrical stimulation

control

transcutaneous electrical stimulation

pressurization

electrical stimulation

side effects


The paroxetine 352 bipolar trial : A study in medical ghostwriting . BACKGROUND The problem of ghostwriting in corporate-sponsored clinical trials is of concern to medicine , bioethics , and government agencies . We present a study of the ghostwritten archival report of an industry-sponsored trial comparing antidepressant treatments for bipolar depression : GlaxoSmithKline ( GSK ) paroxetine study 352 . This analysis is based upon publicly available evidence presented in a complaint of research misconduct filed with the Office of Research Integrity of the Department of Health and Human Services . OBJECTIVES We performed a deconstruction of the published study to show how primary and secondary outcome analyses were conflated , turning a 'negative ' clinical trial into a 'positive ' study - with conclusions and recommendations that could adversely affect patient health . METHODS The paroxetine 352 study was a randomized , double-blind , placebo-controlled , 19-site trial comparing paroxetine and imipramine in 117 patients with bipolar type I major depressive episode which was unresponsive to prior lithium carbonate therapy . RESULTS Analysis of the primary outcome measures found no statistically significant difference between paroxetine or imipramine versus placebo . However , the published article concluded that both drugs were efficacious versus placebo for a post hoc subgroup of patients . CONCLUSIONS Few industry-sponsored studies gain public scrutiny . It is important to make these articles transparent to the scientific and medical community .

paroxetine

paroxetine

paroxetine

paroxetine

imipramine

paroxetine

imipramine

placebo

bipolar depression

bipolar type I major depressive episode

efficacious

bipolar

bipolar depression

bipolar type I major depressive episode


Individual differences in the efficacy of a short theory of mind intervention for children with autism spectrum disorder : a randomized controlled trial . BACKGROUND Having a 'theory of mind ' , or having the ability to attribute mental states to oneself or others , is considered one of the most central domains of impairment among children with an autism spectrum disorder ( ASD ) . Many interventions focus on improving theory of mind skills in children with ASD . Nonetheless , the empirical evidence for the effect of these interventions is limited . The main goal of this study is to examine the effectiveness of a short theory of mind intervention for children with ASD . A second objective is to determine which subgroups within the autism spectrum profit most from the intervention . METHODS This study is a randomized controlled trial . One hundred children with ASD , aged 7 to 12 years will be randomly assigned to an intervention or a waiting list control group . Outcome measures include the completion of theory of mind and emotion understanding tasks , and parent and teacher questionnaires on children 's social skills . Follow-up data for the intervention group will be collected 6 months after the interventions . DISCUSSION This study evaluates the efficacy of a theory of mind intervention for children with ASD . Hypotheses , strengths , and limitations of the study are discussed . TRIAL REGISTRATION Netherlands Trial Register NTR2327 .

short theory of mind intervention

theory of mind skills

short theory of mind intervention

control

mind intervention

efficacy

Hypotheses

strengths

limitations


Effect of whole-body mild-cold exposure on arterial stiffness and central haemodynamics : a randomised , cross-over trial in healthy men and women . Aortic pulse wave velocity ( PWV ) and augmentation index ( AIx ) are independent predictors of cardiovascular risk and mortality , but little is known about the effect of air temperature changes on these variables . Our study investigated the effect of exposure to whole-body mild-cold on measures of arterial stiffness ( aortic and brachial PWV ) , and on central haemodynamics [ including augmented pressure ( AP ) , AIx ] , and aortic reservoir components [ including reservoir and excess pressures ( P ex ) ] . Sixteen healthy volunteers ( 10 men , age 43 ± 19 years ; mean ± SD ) were randomised to be studied under conditions of 12 °C ( mild-cold ) and 21 °C ( control ) on separate days . Supine resting measures were taken at baseline ( ambient temperature ) and after 10 , 30 , and 60 min exposure to each experimental condition in a climate chamber . There was no significant change in brachial blood pressure between mild-cold and control conditions . However , compared to control , AP [ +2 mmHg , 95 % confidence interval ( CI ) 0.36-4.36 ; p = 0.01 ] and AIx ( +6 % , 95 % CI 1.24-10.1 ; p = 0.02 ) increased , and time to maximum P ex ( a component of reservoir function related to timing of peak aortic in-flow ) decreased ( -7 ms , 95 % CI -15.4 to 2.03 ; p = 0.01 ) compared to control . Yet there was no significant change in aortic PWV ( +0.04 m/s , 95 % CI -0.47 to 0.55 ; p = 0.87 ) or brachial PWV ( +0.36 m/s ; -0.41 to 1.12 ; p = 0.35 ) between conditions . We conclude that mild-cold exposure increases central haemodynamic stress and alters timing of peak aortic in-flow without differentially affecting arterial stiffness .

whole-body mild-cold exposure

whole-body mild-cold

arterial stiffness

central haemodynamics

Aortic pulse wave velocity ( PWV )

augmentation index ( AIx )

cardiovascular risk

mortality

aortic reservoir components

reservoir

excess pressures ( P ex )

men

women


Randomized trial of early developmental intervention on outcomes in children after birth asphyxia in developing countries . OBJECTIVE To determine if early developmental intervention ( EDI ) improves developmental abilities in resuscitated children . STUDY DESIGN This was a parallel group , randomized controlled trial of infants unresponsive to stimulation who received bag and mask ventilation as part of their resuscitation at birth and infants who did not require any resuscitation born in rural communities in India , Pakistan , and Zambia . Intervention infants received a parent-implemented EDI delivered with home visits by parent trainers every other week for 3 years starting the first month after birth . Parents in both intervention and control groups received health and safety counseling during home visits on the same schedule . The main outcome measure was the Mental Development Index ( MDI ) of the Bayley Scales of Infant Development , 2nd edition , assessed at 36 months by evaluators unaware of treatment group and resuscitation history . RESULTS MDI was higher in the EDI ( 102.6 ± 9.8 ) compared with the control resuscitated children ( 98.0 ± 14.6 , 1-sided P = .0202 ) , but there was no difference between groups in the nonresuscitated children ( 100.1 ± 10.7 vs 97.7 ± 10.4 , P = .1392 ) . The Psychomotor Development Index was higher in the EDI group for both the resuscitated ( P = .0430 ) and nonresuscitated children ( P = .0164 ) . CONCLUSIONS This trial of home-based , parent provided EDI in children resuscitated at birth provides evidence of treatment benefits on cognitive and psychomotor outcomes . MDI and Psychomotor Development Index scores of both nonresuscitated and resuscitated infants were within normal range , independent of early intervention .

early developmental intervention

early developmental intervention

bag and mask ventilation

parent-implemented EDI

health and safety counseling

birth asphyxia

Mental Development Index ( MDI )

MDI

children

birth asphyxia

resuscitated

children

infants

infants

infants


[ Clinical study of treating knee osteoarthritis ( Bi syndrome of knee ) by massage combined Chinese materia medica footbath fumigation and washing ] . OBJECTIVE To evaluate the clinical efficacy of treating knee osteoarthritis ( KOA , Bi syndrome of knee ) by massage combined Chinese materia medica ( CMM ) footbath fumigation and washing , and to observe the changes of the Lysholm knee score ( LKSS ) . METHODS Totally 61 patients with grade I to III KOA were randomly assigned to two groups , the treatment group and the control group . Patients in the treatment group were treated with massage combined CMM footbath fumigation and washing , while those in the control group were treated with oral administration of meloxicam . They were treated for 20 days ( times ) . The LKSS was assessed before treatment , 10 days of treatment , by the end of the treatment , and 1 month after treatment . RESULTS ( 1 ) The therapeutic efficacy in the treatment group was superior to that in the control group ( P < 0.05 ) . Thirteen cases were clinically controlled , with 11 markedly effective , 6 effective , and 1 ineffective in the treatment group , while 5 cases were clinically controlled , with 11 markedly effective , 10 effective , and 4 ineffective in the control group . ( 2 ) The LKSS : The post-treatment LKSS was higher than that before treatment in the two groups . The LKSS at 10 days ( times ) of treatment was lower in the treatment group than in the control group , but with no statistical difference ( P > 0.05 ) . The LKSS by the end of the treatment was higher in the treatment group than in the control group ( P < 0.05 ) . ( 3 ) The case number of patients in need of receiving the treatment again within 1-month follow-up and the difference between the LKSS at follow-ups and that by the end of the treatment were lower in the treatment group than in the control group ( P < 0.01 ) . CONCLUSION Massage combined CMM footbath fumigation and washing had better clinical efficacy on patients suffering from KOA .

oral administration of

meloxicam

knee osteoarthritis

Lysholm knee score ( LKSS ) .

LKSS

therapeutic efficacy

LKSS

LKSS

LKSS

LKSS

LKSS

clinical efficacy

grade I to III KOA


[ Therapeutic efficacy of youdujing preparation in treating cervical high-risk human papilloma virus infection patients ] . OBJECTIVE To study the clinical efficacy and mechanisms of Youdujing ( YDJ ) preparation in treating the cervical high-risk human papilloma virus ( HR-HPV ) infection . METHODS Totally HR-HPV infection 70 patients were assigned to the treatment group and the control group using random single blind method , 35 cases in each group . YDJ external lotion and YDJ cream were applied to patients in the treatment group , while normal saline was applied for those in the control group . HR-HPV DNA detection was performed by the end of the 1st menstruation after 3 menstrual cycles . The cervical biopsy and cervical smear were performed using vaginoscope before and after treatment . The mRNA expression of human telomerase reverse transcriptase ( hTERT ) was detected from fresh tissues of the cervical lesion . RESULTS The total effective rate was 96.6 % in the treatment group , higher than that of the control group ( 70.00 % , P < 0.01 ) . Before treatment there was no statistical difference in the pathological results of the cervix and the mRNA expression of hTERT between the two groups ( P > 0.05 ) . The mRNA expression of hTERT decreased in the two groups after treatment , showing statistical difference ( P < 0.01 ) . Better effects on the pathological results of the cervix and the mRNA expression of hTERT were obtained in the treatment group after treatment ( P < 0.05 ) . CONCLUSION YDJ played a role in clearing HR-HPV infection and reversing the cervical precancerous changes possibly through down-regulating the mRNA expression of hTERT and lowering the telomerase activation .

youdujing preparation

Youdujing ( YDJ ) preparation

treatment

control

YDJ external lotion and YDJ cream

control

YDJ

Therapeutic efficacy

HR-HPV DNA detection

total effective rate

pathological results of the cervix

mRNA expression of hTERT

mRNA expression of hTERT

mRNA expression of hTERT

cervical precancerous changes


Methylphenidate and baseball playing in ADHD children : who 's on first ? The effects of 0.3 and 0.6 mg/kg methylphenidate were analyzed in a double-blind , placebo-controlled , cross-over study in which 17 boys ( ages 7.8-9.9 years ) with attention deficit hyperactivity disorder ( ADHD ) played in baseball games . Drug effects were evaluated on children 's attention during the game , as indicated by their on-task behavior on the field and their ability to answer questions about the status of the game at all times . Judgment during batting , batting skill during the game , and performance on skill drills prior to the game were also assessed as a function of medication . Results revealed that methylphenidate had a beneficial effect on attending during the game .

Methylphenidate

0.3 and 0.6 mg/kg methylphenidate

placebo-controlled

methylphenidate

attention during the game

ability to answer questions

ADHD children :

17 boys

ages 7.8-9.9 years )


B-type natriuretic peptide and risk of contrast-induced acute kidney injury in acute ST-segment-elevation myocardial infarction : a substudy from the HORIZONS-AMI trial . BACKGROUND Contrast-induced acute kidney injury ( CI-AKI ) after percutaneous coronary intervention is associated with adverse short- and long-term outcomes . However , identification of patients at risk for CI-AKI is challenging . Using a large contemporary randomized trial database of patients with ST-segment-elevation myocardial infarction , we therefore sought to examine whether admission B-type natriuretic peptide ( BNP ) levels predict the development of CI-AKI . METHODS AND RESULTS A total of 979 ST-segment-elevation myocardial infarction patients enrolled in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction ( HORIZONS-AMI ) trial had BNP levels measured in the emergency room prior to primary percutaneous coronary intervention as part of the study protocol . CI-AKI was defined as a relative increase in serum creatinine of ≥25 % , or an absolute increase of ≥0.5 mg/dL , occurring within 48 hours after contrast administration . Logistic regression analysis was used to estimate the association of admission BNP with development of CI-AKI . CI-AKI occurred in 131 patients ( 13.3 % ) . Baseline BNP was a significant univariable correlate of CI-AKI ( odds ratio 1.31 , 95 % confidence interval , 1.14-1.51 ; P=0.0001 ) . After multivariable adjustment for clinical , laboratory , and angiographic variables , BNP remained a significant independent predictor of CI-AKI ( 1.29 [ 1.10 , 1.51 ] ; P < 0.001 ) . Significant net reclassification improvement was achieved by addition of BNP to the current clinical risk prediction model ( net reclassification improvement=0.177 ; P < 0.001 ) and to the Mehran Risk Score ( net reclassification improvement=0.100 ; P=0.015 ) . CONCLUSIONS Measurement of serum BNP at hospital admission may help identify patients who are at risk for developing CI-AKI after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction . CLINICAL TRIAL REGISTRATION URL : http : //www.clinicaltrials.gov . Unique identifier : NCT00433966 .

percutaneous coronary intervention

BNP levels

percutaneous coronary intervention

development

BNP levels

CI-AKI


Thrombin-activatable fibrinolysis inhibitor in hypothyroidism and hyperthyroxinaemia . Endocrine disorders affect both the coagulation and fibrinolytic systems , and have been associated with the development of cardiovascular diseases . Thrombin-activatable fibrinolysis inhibitor ( TAFI ) is a link between coagulation and the fibrinolytic system . The aim of this study was to determine the effect of thyroid hormone excess and deficiency on TAFI levels and function . The effect of hyperthyroxinemia on TAFI was studied in healthy volunteers who were randomised to receive levothyroxine or no medication for 14 days in a crossover design . The effect of hypothyroidism on TAFI was studied in a multicentre observational cohort study . Blood was drawn before treatment of patients with newly diagnosed hypothyroidism and when euthyroidism was achieved . Plasma clot-lysis times , activated TAFI ( TAFIa ) -dependent prolongation of clot-lysis and TAFI levels were measured . Thyroid hormone excess resulted in a hypofibrinolytic condition and in an enhanced TAFIa-dependent prolongation of clot lysis . A trend towards decreased plasma TAFI levels was observed in healthy volunteers who used levothyroxine . Hypothyroidism resulted in hyperfibrinolysis and a reduced TAFIa-dependent prolongation of clot lysis . In conclusion , alterations of TAFIa-dependent prolongation of clot lysis in patients with thyroid disorders may cause an impaired haemostatic balance . The disturbed haemostatic balance in patients with hyperthyroidism might make them prone to thrombosis , while the risk for bleeding may increase in patients with hypothyroidism .

TAFI

TAFI

levothyroxine

no medication

TAFI

TAFI ( TAFIa ) -dependent

TAFI

levothyroxine

TAFIa-dependent

Plasma clot-lysis times

TAFI levels

Thyroid hormone excess

hypofibrinolytic condition

decreased plasma TAFI levels

hyperfibrinolysis

haemostatic balance

disturbed haemostatic balance

bleeding

hypothyroidism and hyperthyroxinaemia .

healthy

newly diagnosed hypothyroidism

healthy

patients with hyperthyroidism

patients with hypothyroidism .


Exposure to the self-face facilitates identification of dynamic facial expressions : influences on individual differences . A growing literature suggests that the self-face is involved in processing the facial expressions of others . The authors experimentally activated self-face representations to assess its effects on the recognition of dynamically emerging facial expressions of others . They exposed participants to videos of either their own faces ( self-face prime ) or faces of others ( nonself-face prime ) prior to a facial expression judgment task . Their results show that experimentally activating self-face representations results in earlier recognition of dynamically emerging facial expression . As a group , participants in the self-face prime condition recognized expressions earlier ( when less affective perceptual information was available ) compared to participants in the nonself-face prime condition . There were individual differences in performance , such that poorer expression identification was associated with higher autism traits ( in this neurocognitively healthy sample ) . However , when randomized into the self-face prime condition , participants with high autism traits performed as well as those with low autism traits . Taken together , these data suggest that the ability to recognize facial expressions in others is linked with the internal representations of our own faces .

self-face facilitates

self-face

self-face representations

self-face prime

) or faces of others

( nonself-face prime

processing the facial expressions

recognized expressions

expression identification

ability to recognize facial expressions

autism

neurocognitively healthy sample

high autism traits

low autism traits


An internet-based cognitive-behavioural training for acute tinnitus : secondary analysis of acceptance in terms of satisfaction , trial attrition and non-usage attrition . OBJECTIVES Recent studies on tinnitus have focused on the efficacy of Internet-based interventions . Other core features of the quality of service , e.g . acceptance and attrition , have often been overlooked . This study analyses Internet-based training regarding acceptance and attrition in a trial on minimal-contact interventions for acute tinnitus . Whenever possible , we give information on other forms of training for comparison . METHODS In a randomised controlled trial with 337 participants , 87 persons took part in the Internet training . RESULTS The participants were as satisfied with the Internet-based training as with a face-to-face group training . There was a 34.48 % dropout from the Internet-based training ( dropout attrition ) . The training attrition from the Internet-based training was even higher at 64.4 % . CONCLUSIONS Two out of three indicators for acceptance-satisfaction and dropout attrition-provide comparable results between the Internet-based training and a face-to-face group training . The third indicator , training attrition , shows a better result for the group training . Future research should focus on attrition in order to enhance the overall effectiveness of training .

Internet-based interventions

Internet-based training

Internet training

Internet-based training

Internet-based training

Internet-based training

satisfied

dropout

training attrition

acceptance-satisfaction

dropout attrition-provide

training attrition

acute tinnitus

acute tinnitus


Risperidone dosing in children and adolescents with autistic disorder : a double-blind , placebo-controlled study . Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism . Patients ( N = 96 ; 5-17 years ) , received risperidone ( low-dose : 0.125 mg/day [ 20 to < 45 kg ] , 0.175 mg/day [ > 45 kg ] or high-dose : 1.25 mg/day [ 20 to < 45 kg ] , 1.75 mg/day [ > 45 kg ] ) or placebo . Mean baseline ( range 27-29 ) to endpoint change in Aberrant Behavior Checklist-Irritability ( primary endpoint ) was significantly greater in the high-dose- ( -12.4 [ 6.5 ] ; p < 0.001 ) , but not low-dose ( -7.4 [ 8.1 ] ; p = 0.164 ) group , versus placebo ( -3.5 [ 10.7 ] ) . Clinical Global Impressions-Severity and Children 's Yale-Brown Obsessive Compulsive Scale scores improved significantly only in the high-dose group , consistent with ABC-I results . Somnolence , sedation and increased appetite occurred more frequently in high-versus low-dose groups . Overall , increased appetite occurred most frequently .

Risperidone

risperidone

risperidone ( low-dose

high-dose

Efficacy

safety


Parents ' state and trait anxiety : relationships with anxiety severity and treatment response in adolescents with autism spectrum disorders . Comorbid anxiety is common among children with Autism Spectrum Disorder ( ASD ) , and parents of children with ASD are more likely to have anxiety disorders . This study investigated the relationship between parents ' state and trait anxiety and parent-reported internalizing and externalizing symptoms among adolescents ( n = 30 ) with ASD , as well as the relationship of parents ' anxiety symptoms and adolescent treatment response in the context of a randomized controlled trial . Parental state anxiety correlated with severity of adolescent anxiety , and trait anxiety in parents correlated with parent-reported adolescent internalizing and externalizing symptoms . Also , parents of adolescent treatment responders experienced a decrease in their own trait anxiety . Findings highlight the importance of considering parental anxiety when targeting anxiety among youth with ASD .

parents ' state and trait anxiety

anxiety severity

state

and

trait anxiety

Parents '

adolescents

autism spectrum disorders

children

Autism Spectrum Disorder ( ASD

parents

ASD

parents

anxiety

parent-reported

adolescents

ASD

parents

adolescent


Myocardial extracellular volume by cardiac magnetic resonance imaging in patients treated with anthracycline-based chemotherapy . We aimed to determine whether the myocardial extracellular volume ( ECV ) , measured using T1 measurements obtained during cardiac magnetic resonance imaging were increased in patients treated with anthracyclines . We performed cardiac magnetic resonance imaging and echocardiography and measured the ECV in 42 patients treated with anthracyclines . The data from the cardiac magnetic resonance study were compared to those from healthy volunteers . The anthracycline-treated cohort consisted of 21 men and 21 women with a mean age of 55 ± 17 years , who presented a median of 84 months after chemotherapy with a cumulative anthracycline exposure of 282 ± 65 mg/m ( 2 ) and a mean left ventricular ejection fraction of 52 ± 12 % . The ECV was elevated in the anthracycline-treated patients compared to the age- and gender-matched controls ( 0.36 ± 0.03 vs 0.28 ± 0.02 , p < 0.001 ) . A positive association was found between the ECV and left atrial volume ( ECV vs indexed left atrial volume , r = 0.65 , p < 0.001 ) , and negative association was found between the ECV and diastolic function ( E ' lateral , r = -0.64 , p < 0.001 ) . In conclusion , the myocardial ECV is elevated in patients with previous anthracycline treatment and is associated with the diastolic function and increased atrial volumes .

anthracyclines

anthracyclines .

myocardial extracellular volume ( ECV )

T1 measurements

ECV

patients treated with anthracyclines

42 patients

treated with anthracyclines

healthy volunteers

men

women

age of 55 ± 17 years


Does single use of an autologous transfusion system in TKA reduce the need for allogenic blood ? : a prospective randomized trial . BACKGROUND Mechanical autotransfusion systems for washed shed blood ( WSB ) were introduced to reduce the need for postoperative allogenic blood transfusions ( ABTs ) . Although some authors have postulated decreased requirements for ABT by using autologous retransfusion devices , other trials , mostly evaluating retransfusion devices for unwashed shed blood ( USB ) , verified a small or no benefit in reducing the need for postoperative ABT . Because of these contradictory findings it is still unclear whether autologous retransfusion systems for WSB can reduce transfusion requirements . QUESTIONS/PURPOSES We therefore asked whether one such autologous transfusion system for WSB can reduce the requirements for postoperative ABT . METHODS In a prospective , randomized , controlled study , we enrolled 151 patients undergoing TKA . In Group A ( n=76 patients ) , the autotransfusion system was used for a total of 6 hours ( intraoperatively and postoperatively ) and the WSB was retransfused after processing . In Control Group B ( n=75 patients ) , a regular drain without suction was used . We used signs of anemia and/or a hemoglobin value less than 8 g/dL as indications for transfusion . If necessary , we administered one or two units of allogenic blood . RESULTS Twenty-three patients ( 33 % ) in Group A , who received an average of 283 mL ( range , 160-406 mL ) of salvaged blood , needed a mean of 2.1 units of allogenic blood , compared with 23 patients ( 33 % ) in Control Group B who needed a mean of 2.1 units of allogenic blood . CONCLUSIONS We found the use of an autotransfusion system did not reduce the rate of postoperative ABTs . LEVEL OF EVIDENCE Level II , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence .

Mechanical autotransfusion systems

controlled

autotransfusion system

WSB was retransfused after processing

regular drain without suction

was used

TKA

TKA


A randomised controlled trial of bumetanide in the treatment of autism in children . Gamma aminobutyric acid ( GABA ) -mediated synapses and the oscillations they orchestrate are altered in autism . GABA-acting benzodiazepines exert in some patients with autism paradoxical effects , raising the possibility that like in epilepsies , GABA excites neurons because of elevated intracellular concentrations of chloride . Following a successful pilot study , ( 1 ) we have now performed a double-blind clinical trial using the diuretic , chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition . Sixty children with autism or Asperger syndrome ( 3-11 years old ) received for 3 months placebo or bumetanide ( 1 mg daily ) , followed by 1-month wash out . Determination of the severity of autism was made with video films at day 0 ( D0 ) and D90 by blind , independent evaluators . Bumetanide reduced significantly the Childhood Autism Rating Scale ( CARS ) ( D90-D0 ; P < 0.004 treated vs placebo ) , Clinical Global Impressions ( P < 0.017 treated vs placebo ) and Autism Diagnostic Observation Schedule values when the most severe cases ( CARS values above the mean ± s.d . ; n=9 ) were removed ( Wilcoxon test : P-value=0.031 ; Student 's t-test : P-value=0.017 ) . Side effects were restricted to an occasional mild hypokalaemia ( 3.0-3.5 mM l ( -1 ) K ( + ) ) that was treated with supplemental potassium . In a companion study , chronic bumetanide treatment significantly improved accuracy in facial emotional labelling , and increased brain activation in areas involved in social and emotional perception ( Hadjikhani et al. , submitted ) . Therefore , bumetanide is a promising novel therapeutic agent to treat autism . Larger trials are warranted to better determine the population best suited for this treatment .

bumetanide

benzodiazepines

bumetanide

placebo

bumetanide

Bumetanide

placebo

placebo

effects

Childhood Autism Rating Scale ( CARS )

Clinical Global Impressions

autism in children .


Is chronic sildenafil therapy safe and clinically beneficial in patients with systolic heart failure ? Sildenafil is a selective phosphodiesterase-5 inhibitor and causes vasodilatation , particularly in pulmonary circulation . Since left heart failure may be associated with pulmonary hypertension " out of proportion to left heart disease , " sildenafil may have beneficial effect in such patients . The present investigation was designed as a 12-week , single-center , randomized , double-blind , placebo-controlled study evaluating the effects of sildenafil on mean blood pressure ( primary endpoint ) in patients with left systolic heart failure . Secondary endpoints included exercise capacity assessed by 6-minute walk test . A total of 106 patients were randomized 1:1 to sildenafil ( n=53 ) or placebo ( n=53 ) . Patients received sildenafil 25 mg twice a day or matching placebo for the first 2 weeks and 50 mg 3 times a week for the remainder of the trial . The placebo-corrected effect on mean blood pressure was 1.16 mm Hg ( 95 % confidence interval , -1.6 to 5.1 , P > .05 ) , demonstrating that sildenafil did not decrease mean blood pressure . Compared with placebo , sildenafil increased the 6-minute walk test by a nonsignificant treatment effect of 14 m ( P=.67 ) . Adverse effects occurred in a comparable proportion of patients taking sildenafil and placebo , and none of the patients needed to discontinue therapy . Sildenafil is well tolerated in left heart failure patients and does not decrease blood pressure . It can be safely added to standard heart failure therapy .

chronic sildenafil therapy

Sildenafil

sildenafil

placebo-controlled

sildenafil

sildenafil

placebo

sildenafil

placebo

sildenafil

sildenafil

mean blood pressure

exercise capacity

6-minute walk test .

mean blood pressure

mean blood pressure .

6-minute walk test

Adverse effects

tolerated

blood pressure .

systolic heart failure

left heart failure

left systolic heart failure


Differences in reach and attrition between Web-based and print-delivered tailored interventions among adults over 50 years of age : clustered randomized trial . BACKGROUND The Internet has the potential to provide large populations with individual health promotion advice at a relatively low cost . Despite the high rates of Internet access , actual reach by Web-based interventions is often disappointingly low , and differences in use between demographic subgroups are present . Furthermore , Web-based interventions often have to deal with high rates of attrition . OBJECTIVE This study aims to assess user characteristics related to participation and attrition when comparing Web-based and print-delivered tailored interventions containing similar content and thereby to provide recommendations in choosing the appropriate delivery mode for a particular target audience . METHODS We studied the distribution of a Web-based and a print-delivered version of the Active Plus intervention in a clustered randomized controlled trial ( RCT ) . Participants were recruited via direct mailing within the participating Municipal Health Council regions and randomized to the printed or Web-based intervention by their region . Based on the answers given in a prior assessment , participants received tailored advice on 3 occasions : ( 1 ) within 2 weeks after the baseline , ( 2 ) 2 months after the baseline , and ( 3 ) within 4 months after the baseline ( based on a second assessment at 3 months ) . The baseline ( printed or Web-based ) results were analyzed using ANOVA and chi-square tests to establish the differences in user characteristics between both intervention groups . We used logistic regression analyses to study the interaction between the user characteristics and the delivery mode in the prediction of dropout rate within the intervention period . RESULTS The printed intervention resulted in a higher participation rate ( 19 % ) than the Web-based intervention ( 12 % ) . Participants of the Web-based intervention were significantly younger ( P < .001 ) , more often men ( P=.01 ) , had a higher body mass index ( BMI ) ( P=.001 ) and a lower intention to be physically active ( P=.03 ) than participants of the printed intervention . The dropout rate was significantly higher in the Web-based intervention group ( 53 % ) compared to the print-delivered intervention ( 39 % , P < .001 ) . A low intention to be physically active was a strong predictor for dropout within both delivery modes ( P < .001 ) . The difference in dropout rate between the Web-based and the printed intervention was not explained by user characteristics . CONCLUSIONS The reach of the same tailored physical activity ( PA ) intervention in a printed or Web-based delivery mode differed between sociodemographic subgroups of participants over 50 years of age . Although the reach of the Web-based intervention is lower , Web-based interventions can be a good channel to reach high-risk populations ( lower PA intention and higher BMI ) . While the dropout rate was significantly higher in the Web-based intervention group , no specific user characteristics explained the difference in dropout rates between the delivery modes . More research is needed to determine what caused the high rate of dropout in the Web-based intervention . TRIAL REGISTRATION Dutch Trial Register ( NTR ) : 2297 : http : //www.trialregister.nl/trialreg/admin/rctview.asp ? TC=2297 ( Archived by WebCite at http : //www.webcitation.org/65TkwoESp ) .

printed or Web-based intervention

user characteristics

dropout rate

higher participation rate

dropout rate

intention to be physically active

dropout

dropout

tailored physical activity ( PA )

dropout rate

dropout rates

rate of dropout

adults over 50 years of age


The added value of a brief self-efficacy coaching on the effectiveness of a 12-week physical activity program . BACKGROUND Self-efficacy has been found to be an important precondition for behavioral change in sedentary people . The current study examined the effectiveness and added value of including a 15-minute self-efficacy coaching at the start of a 12-week lifestyle physical activity ( PA ) program . METHODS Participants were randomly assigned to a standard-intervention group ( without additional self-efficacy coaching , N = 116 ) or extra-intervention group ( with additional self-efficacy coaching , N = 111 ) . Body mass index ( BMI ) , cardiovascular fitness , self-reported PA , and self-efficacy beliefs were assessed at baseline and immediately after the intervention period . Perceived adherence to the PA program was assessed postintervention . RESULTS At posttest , a significant increase in cardiovascular fitness and decrease in BMI were found in both groups . Significant intervention effects emerged on PA behavior , self-efficacy , and program adherence , in favor of the extra-intervention group . Self-efficacy mediated the intervention effect on program adherence whereas no evidence was found for its role as mediator of PA change . CONCLUSIONS Adding a 15-minute self-efficacy coaching at the start of a lifestyle PA program is a promising strategy to enhance the intervention effects on PA behavior , self-efficacy beliefs , and program adherence . However , the role of self-efficacy as mediator of the intervention effect on in PA was not fully supported .

self-efficacy coaching

physical activity program

randomly assigned to a

extra-intervention group

Body mass index ( BMI )

cardiovascular fitness

self-reported PA

self-efficacy beliefs

lifestyle PA program

self-efficacy

Self-efficacy

Body mass index ( BMI )

cardiovascular fitness

self-reported PA

self-efficacy beliefs

cardiovascular fitness

BMI

PA behavior

self-efficacy

program adherence

Self-efficacy

PA

PA behavior

self-efficacy beliefs

program adherence


Simvastatin reduces sympathetic outflow and augments endothelium-independent dilation in non-hyperlipidaemic primary hypertension . OBJECTIVES Previous reports , involving hypercholesterolaemic hypertensive subjects , that statins reduce muscle sympathetic nerve activity ( MSNA ) did not investigate potential neural sites of such sympathoinhibition or determine its consequences for endothelial function or insulin resistance . This study of hypertensive subjects with lower plasma cholesterol tested the hypotheses that lipophilic simvastatin would attenuate resting sympathoexcitation and augment baroreflex modulation of MSNA and heart rate ( HR ) , flow-mediated vasodilation and insulin sensitivity . DESIGN Prospective , randomised , double-blind , placebo-controlled crossover study . SETTING Academic hospital-based study . PATIENTS Fourteen non-hyperlipidaemic primary hypertensive subjects ( 10 men ; overall mean±SD age 58±12 years ) . INTERVENTIONS Four weeks of simvastatin ( 80 mg/day ) or placebo . MAIN OUTCOME MEASURES Resting blood pressure ( BP ) , HR , MSNA , spontaneous arterial baroreflex MSNA and HR modulation , endothelium-dependent and endothelium-independent vasodilation , and the homoeostatic model assessment of insulin resistance ( HOMA-IR ) . RESULTS Simvastatin lowered MSNA burst frequency ( from 32±12 to 25±9 bursts/min ) and MSNA burst incidence ( from 55±23 % to 43±17 % ; all p < 0.01 ) without affecting BP , HR , baroreflex modulation of either MSNA or HR , or HR variability ( all p > 0.05 ) . Plasma glucose , insulin , HOMA-IR and endothelium-dependent vasodilation ( all p > 0.05 ) were unchanged , whereas endothelium-independent vasodilation increased ( 7.1±3.8 % to 9.7±3.9 % , n=13 ; p < 0.01 ) . The fall in MSNA was unrelated to the decrease in low-density lipoprotein cholesterol ( r=0.41 , p=0.14 ) . CONCLUSIONS These findings are consistent with the concept that , in non-hyperlipidaemic subjects with primary hypertension , simvastatin causes a cholesterol-independent reduction in an elevated central set-point for MSNA , without affecting arterial baroreflex modulation of either MSNA or HR . There may be less neurogenic constraint on endothelium-independent vasodilation as a consequence .

Simvastatin

simvastatin

Resting blood pressure ( BP )

low-density lipoprotein cholesterol

hypercholesterolaemic hypertensive

hypertensive

lower plasma cholesterol

10 men

mean±SD age 58±12 years


Pseudoephedrine and preexercise feeding : influence on performance . PURPOSE This study examined the influence of preexercise food intake on plasma pseudoephedrine ( PSE ) concentrations and subsequent high-intensity exercise . In addition , urinary PSE concentrations were measured under the same conditions and compared with the present threshold of the World Anti-Doping Agency ( WADA ) . METHODS Ten highly trained male cyclists and triathletes ( age = 30.6 ± 6.6 yr , body mass [ BM ] = 72.9 ± 5.1 kg , and V˙O2max = 64.8 ± 4.5 mL·kg·min ; mean ± SD ) undertook four cycling time trials ( TT ) , each requiring the completion of a set amount of work ( 7 kJ·kg BM ) in the shortest possible time . Participants were randomized into a fed or nonfed condition and orally ingested 2.8 mg·kg BM of PSE or a placebo ( PLA ) 90 min before exercise ; in the fed trials , they consumed a meal providing 1.5 g·kg BM of CHO . Venous blood was sampled at 30 , 50 , and 70 min and pre-warm-up and postexercise for the analysis of plasma PSE and catecholamine concentrations , and urine was also collected for the analysis of PSE concentration . RESULTS Independent of the preexercise meal , 2.8 mg·kg BM of PSE did not significantly improve cycling TT performance . The fed trials resulted in lower plasma PSE concentrations at all time points compared with the nonfed trials . Both plasma epinephrine and blood lactate concentrations were higher in the PSE compared with the PLA trials , and preexercise and postexercise urinary PSE concentrations were significantly higher than the threshold ( 150 μg·mL ) used by WADA to determine illicit PSE use . CONCLUSION Irrespective of the preexercise meal , cycling TT performance of approximately 30 min was not improved after PSE supplementation . Furthermore , 2.8 mg·kg BM of PSE taken 90 min before exercise , with or without food , resulted in urinary PSE concentrations exceeding the present WADA threshold .

Pseudoephedrine

preexercise feeding :

performance

subsequent

high-intensity exercise


A phase III study of laparoscopy-assisted versus open distal gastrectomy with nodal dissection for clinical stage IA/IB gastric Cancer ( JCOG0912 ) . A Phase III study was started in Japan to evaluate the non-inferiority of overall survival of laparoscopy-assisted distal gastrectomy with open distal gastrectomy in patients with clinical IA ( T1N0 ) or IB [ T1N1 or T2 ( MP ) N0 ] gastric cancer . This study followed the previous Phase II study to confirm the safety of laparoscopy-assisted distal gastrectomy ( JCOG0703 ) and began in March 2010 . A total of 920 patients will be accrued from 33 institutions within 5 years . The primary endpoint is overall survival . The secondary endpoints are relapse-free survival , proportion of laparoscopy-assisted distal gastrectomy completion , proportion of conversion to open surgery , adverse events , short-term clinical outcomes , postoperative quality of life . Only a credentialed surgeon can be responsible for both open distal gastrectomy and laparoscopy-assisted distal gastrectomy .

laparoscopy-assisted

open

distal gastrectomy

laparoscopy-assisted distal gastrectomy

open distal gastrectomy

laparoscopy-assisted distal gastrectomy

laparoscopy-assisted distal gastrectomy

surgery

open distal gastrectomy

laparoscopy-assisted distal gastrectomy

overall survival

relapse-free survival

adverse events

short-term clinical outcomes

postoperative quality of life

T2 ( MP ) N0 ] gastric cancer .

920 patients


Treatment of adults with acute lymphoblastic leukemia : do the specifics of the regimen matter ? : Results from a prospective randomized trial . BACKGROUND Induction therapy for adults with acute lymphoblastic leukemia ( ALL ) is similar across essentially all regimens , comprised of vincristine , corticosteroids , and anthracyclines intensified with cyclophosphamide , asparaginase , or both . Given the lack of randomized data , to date , no regimen has emerged as standard . The authors previously evaluated cytarabine 3 g/m ( 2 ) daily for 5 days with mitoxantrone 80 mg/m ( 2 ) ( the ALL-2 regimen ) as a novel induction regimen . Compared with historic controls , the ALL-2 regimen was superior in terms of incidence of complete remission , failure with resistant disease , and activity in patients with Philadelphia chromosome ( Ph ) -positive ALL . METHODS The authors conducted a multicenter , prospective , randomized trial of the ALL-2 regimen compared with a standard 4-drug induction ( the L-20 regimen ) . Patients also received consolidation , maintenance therapy , and central nervous system prophylaxis . The trial accrued patients from August 1996 to October 2004 . RESULTS The median follow-up for survivors was 7 years , and the median patient age was 43 years . Responses were evaluated in 164 patients . The treatment arms were balanced in terms of pretreatment characteristics . The frequency of complete remission for the ALL-2 regimen versus the L-20 regimen was 83 % versus 71 % ( P = .06 ) . More patients on the L-20 arm failed with resistant disease ( 21 % vs 8 % ; P = .02 ) . Induction deaths were comparable at 9 % ( ALL-2 ) versus 7 % ( L-20 ) . The median survival was similar ; and , at 5 years , the survival rate was 33 % alive on the ALL-2 arm versus 27 % on the L-20 . CONCLUSIONS Despite superior results of induction therapy with the ALL-2 regimen , this treatment did not improve long-term outcomes . When coupled to the reported experience of other studies in adults with ALL , the results of this randomized trial raise the possibility that ultimate outcomes in adult ALL may be independent of the specific regimen chosen . Cancer 2013 . © 2012 American Cancer Society .

cytarabine

mitoxantrone

4-drug induction ( the L-20 regimen ) .

median follow-up for survivors

frequency of complete remission

resistant disease

Induction deaths

median survival

survival rate

long-term outcomes

adults

acute lymphoblastic leukemia

median patient age was 43 years


No pain relief with the rubber hand illusion . The sense of body ownership can be easily disrupted during illusions and the most common illusion is the rubber hand illusion . An idea that is rapidly gaining popularity in clinical pain medicine is that body ownership illusions can be used to modify pathological pain sensations and induce analgesia . However , this idea has not been empirically evaluated . Two separate research laboratories undertook independent randomized repeated measures experiments , both designed to detect an effect of the rubber hand illusion on experimentally induced hand pain . In Experiment 1 , 16 healthy volunteers rated the pain evoked by noxious heat stimuli ( 5 s duration ; interstimulus interval 25 s ) of set temperatures ( 47° , 48° and 49°C ) during the rubber hand illusion or during a control condition . There was a main effect of stimulus temperature on pain ratings , but no main effect of condition ( p = 0.32 ) , nor a condition x temperature interaction ( p = 0.31 ) . In Experiment 2 , 20 healthy volunteers underwent quantitative sensory testing to determine heat and cold pain thresholds during the rubber hand illusion or during a control condition . Secondary analyses involved heat and cold detection thresholds and paradoxical heat sensations . Again , there was no main effect of condition on heat pain threshold ( p = 0.17 ) , nor on cold pain threshold ( p = 0.65 ) , nor on any of the secondary measures ( p < 0.56 for all ) . We conclude that the rubber hand illusion does not induce analgesia .

rubber hand illusion

rubber hand illusion

body ownership illusions

rubber hand illusion

noxious heat stimuli

pain relief

hand pain .

pain


HOXB13 G84E mutation in Finland : population-based analysis of prostate , breast , and colorectal cancer risk . BACKGROUND A recently identified germline mutation G84E in HOXB13 was shown to increase the risk of prostate cancer . In a family-based analysis by The International Consortium for Prostate Cancer Genetics ( ICPCG ) , the G84E mutation was most prevalent in families from the Nordic countries of Finland ( 22.4 % ) and Sweden ( 8.2 % ) . METHODS To further investigate the importance of G84E in the Finns , we determined its frequency in more than 4,000 prostate cancer cases and 5,000 controls . In addition , 986 breast cancer and 442 colorectal cancer ( CRC ) cases were studied . Genotyping was conducted using TaqMan , MassARRAY iPLEX , and sequencing . Statistical analyses were conducted using Fisher exact test , and overall survival was analyzed using Cox modeling . RESULTS The frequency of the G84E mutation was significantly higher among patients with prostate cancer and highest among patients with a family history of the disease , hereditary prostate cancer [ 8.4 % vs. 1.0 % in controls ; OR 8.8 ; 95 % confidence interval ( CI ) , 4.9-15.7 ] . The mutation contributed significantly to younger age ( ≤55 years ) at onset and high prostate-specific antigen ( PSA ; ≥20 ng/mL ) at diagnosis . An association with increased prostate cancer risk in patients with prior benign prostate hyperplasia ( BPH ) diagnosis was also revealed . No statistically significant evidence for a contribution in CRC risk was detected , but a suggestive role for the mutation was observed in familial BRCA1/2-negative breast cancer . CONCLUSIONS These findings confirm an increased cancer risk associated with the G84E mutation in the Finnish population , particularly for early-onset prostate cancer and cases with substantially elevated PSA . IMPACT This study confirms the overall importance of the HOXB13 G84E mutation in prostate cancer susceptibility .

HOXB13 G84E mutation

G84E in HOXB13

G84E mutation

Genotyping

overall survival

frequency of the G84E mutation

mutation

increased prostate cancer risk

contribution in CRC risk

Finland


Contingency management for the treatment of antipsychotic-induced weight gain : a randomized controlled pilot study . OBJECTIVE Weight gain is common for individuals with serious mental illness ( SMI ) receiving antipsychotic drug therapy . Contingency management ( CM ) is a behavioral intervention that rewards positive performance and has demonstrated effectiveness in reducing drug use in SMI populations . This study evaluated the feasibility of using CM to promote weight loss in individuals with SMI over 8 weeks . METHOD 30 individuals ( BMI ≥ 28 kg/m ( 2 ) ) were randomized to one of three conditions : i ) The combination of a standardized lifestyle modification ( LM ) program for individuals with SMI and payment for group attendance ( CM ( attendance ) ) , ii ) The combination of LM and payment for weight loss ( CM ( weight ) ) , and iii ) waitlist control ( CON ) . After the waitlist period , those participants joined a LM group and received payment for behavioral change ( CM ( behavior ) ) . RESULTS Subjects in the CM ( attendance ) and in the CM ( weight ) group lost a mean of 1.16 kg and 1.23 kg , respectively , while subjects in the CON gained a mean of 0.68 kg . Subjects receiving CM ( behavior ) , lost a mean of 2.54 kg , which was a significant weight loss compared to the control period . CONCLUSION LM supplemented with CM may facilitate weight loss in patients taking antipsychotic medications ; financial reimbursement for behavioral change may be particularly effective in this population .

Contingency management

Contingency management ( CM )

CM

weight gain

SMI

antipsychotic medications


Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the type of infusion fluid . CONTEXT Measurement of blood haemoglobin concentration by pulse oximetry could be of value in determining when erythrocytes should be transfused during surgery , but the effect of infusion fluids on the results is unclear . OBJECTIVE To study the effect of crystalloid and colloid fluid on the accuracy ( bias ) and precision of pulse oximetry haemoglobin estimation to indicate the venous haemoglobin concentration in volunteers . DESIGN Open interventional crossover study . SETTING Single university hospital . PARTICIPANTS Ten male volunteers aged 18-28 ( mean 22 ) years . INTERVENTIONS Each volunteer underwent three infusion experiments on separate days and in random order . The infusions were Ringer 's acetate ( 20 ml kg ) , hydroxyethyl starch 130/0.4 ( 10 ml kg ) and a combination of both . RESULTS At the end of the infusions of Ringer 's acetate , pulse oximetry haemoglobin concentration had decreased more than the true haemoglobin concentration ( 15 vs. 8 % ; P < 0.005 ; n = 10 ) whereas starch solution decreased pulse oximetry haemoglobin concentration less than true haemoglobin concentration ( 7 vs. 11 % ; P < 0.02 ; n = 20 ) . The same differences were seen when the fluids were infused separately and when they were combined . The overall difference between all 956 pairs of pulse oximetry haemoglobin concentration and true haemoglobin concentrations ( the bias ) averaged only -0.7 g l whereas the 95 % prediction interval was wide , ranging from -24.9 to 23.7 g l. In addition to the choice of infusion fluid , the bias was strongly dependent on the volunteer ( each factor , P < 0.001 ) . CONCLUSION The bias of measuring haemoglobin concentration by pulse oximetry is dependent on whether a crystalloid or a colloid fluid is infused . TRIAL REGISTRATION ClinicalTrials identifier : NCT01195025 .

pulse oximetry

pulse oximetry

infusion experiments

noninvasive haemoglobin measurement

haemoglobin

haemoglobin

oximetry haemoglobin


Translating the Dietary Approaches to Stop Hypertension ( DASH ) diet for use in underresourced , urban African American communities , 2010 . INTRODUCTION Randomized trials have demonstrated the effectiveness of the Dietary Approaches to Stop Hypertension ( DASH ) program for lowering blood pressure ; however , program participation has been limited in some populations . The objective of this pilot study was to test the feasibility of using a culturally modified version of DASH among African Americans in an underresourced community . METHODS This randomized controlled pilot study recruited African Americans in 2 North Carolina neighborhoods who had high blood pressure and used fewer than 3 antihypertension medications . We offered 2 individual and 9 group DASH sessions to intervention participants and 1 individual session and printed DASH educational materials to control participants . We collected data at baseline ( March 2010 ) and 12 weeks ( June 2010 ) . RESULTS Of 152 potential participants , 25 were randomly assigned to either the intervention ( n = 14 ) or the control ( n = 11 ) group ; 22 were women , and 21 were educated beyond high school . At baseline , mean blood pressure was 130/78 mm Hg ; 19 participants used antihypertension medications , and mean body mass index was 35.9 kg/m ( 2 ) . Intervention participants attended 7 of 9 group sessions on average . After 12 weeks , we observed significant increases in fruit and vegetable consumption and increases in participants ' confidence in their ability to reduce salt and fat consumption and eat healthier snacks in intervention compared with control participants . We found no significant decreases in blood pressure . CONCLUSION Implementation of a culturally modified , community-based DASH intervention was feasible in our small sample of African Americans , which included people being treated for high blood pressure . Future studies should evaluate the long-term effect of this program in a larger sample .

DASH

individual

group DASH sessions

intervention

control

community-based DASH intervention

blood pressure ;

fruit and vegetable consumption

blood pressure .


Intravenous aflibercept administered in combination with irinotecan , 5-fluorouracil and leucovorin in patients with advanced solid tumours : results from the expansion cohort of a phase I study . BACKGROUND Following the dose-escalation stage , this double-blind expansion stage of the phase I study evaluated the safety , pharmacodynamics , pharmacokinetics , anti-vascular effects and antitumour activity of aflibercept 4 mg/kg with irinotecan , 5-fluorouracil and leucovorin ( LV5FU2 ) . PATIENTS AND METHODS Patients with advanced solid tumours were randomised at cycle-1 to placebo or aflibercept ( 4 mg/kg ) on day 1 then irinotecan-LV5FU2 on days 1 and 2 . Subsequently , all patients received aflibercept with irinotecan-LV5FU2 every 2 weeks . Anti-vascular effects were assessed using dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) . RESULTS Twenty-seven patients were treated ; 14 received placebo in cycle-1 followed by aflibercept in later cycles and 13 received aflibercept 4 mg/kg upfront . The median number of aflibercept cycles was 16 ( range 1-44 ) , 12 patients received ≥20 cycles . Most frequent grade 3/4 adverse events were neutropenia ( 37 % ) , fatigue ( 33 % ) and hypertension ( 30 % ) . No anti-aflibercept antibodies were detected . Four patients achieved partial responses and 17 had stable disease , lasting > 3 months in 14 patients . Plasma levels of free over vascular endothelial growth factor-bound aflibercept were adequate , with steady-state achieved from cycle-3 . Exploratory DCE-MRI showed no significant perfusion changes with aflibercept . CONCLUSION Aflibercept 4 mg/kg plus irinotecan-LV5FU2 every 2 weeks had acceptable toxicity and pharmacokinetics , and showed promising antitumour activity .

aflibercept

aflibercept

placebo

aflibercept

aflibercept

placebo

aflibercept

aflibercept

aflibercept

median number of aflibercept cycles

neutropenia

fatigue

hypertension

advanced solid tumours

advanced solid tumours

Twenty-seven