Comparison of the effect of intra-arterial versus intravenous heparin on radial artery occlusion after transradial catheterization . Radial artery occlusion ( RAO ) is an infrequent , asymptomatic , complication of transradial catheterization and probably 1 of the few . Intravenous heparin and patent hemostasis lower its incidence . A possible local effect of intra-arterially administered heparin during transradial procedures has not been evaluated . We studied 500 consecutive patients randomized to an intravenous group ( n = 250 ) , receiving 50 U/kg of unfractionated heparin ( maximal dose 5,000 U ) intravenously , and an intra-arterial group ( n = 250 ) receiving the same dose intra-arterially . All patients received a vasodilator " cocktail " intra-arterially and underwent cardiac catheterization using a 5F introducer sheath and catheters . The activated clotting time was measured at the end of the procedure . All patients received hemostasis with a radial compression device ( TR Band ) , applied after sheath removal , for 2 hours . A plethysmographic evaluation for RAO was performed at 24 hours and 30 days after the procedure . Early RAO occurred in 5.6 % ( n = 14 ) of the intravenous group and 6 % ( n = 15 ) of the intra-arterial group . The difference was not statistically significant ( chi-square = 0.037 , p > 0.8 ) . Chronic RAO occurred in 3.2 % , ( n = 8 ) of the intravenous group compared to 4 % ( n = 10 ) of the intra-arterial group . The difference was not statistically significant ( chi-square = 0.231 , p > 0.6 ) . The activated clotting time was 211 +/- 16 seconds in the intravenous group and 213 +/- 17 seconds in the intra-arterial group , a statistically insignificant difference ( t = -1.095 , p > 0.2 ) . In conclusion , intra-arterial and intravenous heparin administration provide comparable efficacy in preventing RAO , favoring a probable systemically mediated mechanism of action , rather than a local effect .

intra-arterial

intravenous heparin

heparin

intravenous

heparin

intra-arterial group

intra-arterially

cardiac catheterization

activated clotting time

plethysmographic evaluation for RAO

Early RAO

Chronic RAO

activated clotting time

500 consecutive patients


[ Observation on therapeutic effect of electroacupuncture plus blood-letting puncture and cupping combined with diet intervention for treatment of acute gouty arthritis ] . OBJECTIVE To explore a more effective therapy for acute gouty arthritis . METHODS Sixty cases were randomly divided into an observation group and a control group , 30 cases in eachgroup . On the basis of diet intervention , the observation group was treated with electroacupuncture at local points combined with blood-letting puncture and cupping , and the control group with oral administration of Probenecid . Their therapeutic effects were ob served . RESULTS The effective rate was 96.7 % in the observation group which was better than 86.7 % in the control group ( P < 0.01 ) . After treatment , blood uric acid decreased significantly in the two groups ( both P < 0.01 ) , the observed group being lower than the control group ( P < 0.01 ) . CONCLUSION On the basis of diet intervention , electroacupuncture plus blood-letting puncture and cupping is a better therapy for acute gouty arthritis .

diet intervention

diet intervention

Probenecid

diet intervention

blood uric acid

acute gouty arthritis ]

acute gouty arthritis .

Sixty cases


Randomized clinical trial of behavioral intervention and nutrition education to improve caloric intake and weight in children with cystic fibrosis . OBJECTIVE To evaluate the efficacy of a behavioral plus nutrition education intervention , Be In CHARGE ! , compared with that of a nutrition education intervention alone on caloric intake and weight gain in children with cystic fibrosis and pancreatic insufficiency . DESIGN Randomized controlled trial . SETTING Cystic fibrosis centers in the eastern , midwestern , and southern United States . PARTICIPANTS Seventy-nine children aged 4 to 12 years below the 40th percentile for weight for age were recruited . Sixty-seven completed the intervention and 59 completed a 24-month follow-up assessment . INTERVENTION Comparison of a behavioral plus nutrition education intervention with a nutrition education intervention alone . MAIN OUTCOME MEASURES Primary outcomes were changes from pretreatment to posttreatment in caloric intake and weight gain . Secondary outcomes were changes from pretreatment to posttreatment in percentage of the estimated energy requirement and body mass index z score . These outcomes were also examined 24 months posttreatment . RESULTS After treatment , the behavioral plus nutrition education intervention as compared with the nutrition education intervention alone had a statistically greater average increase on the primary and secondary outcomes of caloric intake ( mean , 872 vs 489 cal/d , respectively ) , percentage of the estimated energy requirement ( mean , 148 % vs 127 % , respectively ) , weight gain ( mean , 1.47 vs 0.92 kg , respectively ) , and body mass index z score ( 0.38 vs 0.18 , respectively ) . At the 24-month follow-up , children in both conditions maintained an estimated energy requirement of around 120 % and did not significantly differ on any outcomes . CONCLUSIONS A behavioral plus nutrition education intervention was more effective than a nutrition education intervention alone at increasing dietary intake and weight over a 9-week period . However , across the 24-month follow-up , both treatments achieved similar outcomes . Trial Registration clinicaltrials.gov Identifier : NCT00006169 .

nutrition education intervention alone

caloric intake

weight gain

caloric intake

weight gain

body mass index z score

caloric intake

weight gain

body mass index z score

energy requirement

cystic fibrosis

cystic fibrosis

pancreatic insufficiency

Seventy-nine

aged 4 to 12 years


Mediterranean diet and high dietary acid load associated with mixed nuts : effect on bone metabolism in elderly subjects . OBJECTIVES To analyze the effect of differing diet on the acid load content on bone metabolism . DESIGN Multicentric , randomized , single-blind , parallel-group clinical trial . SETTING Outpatient clinics . PARTICIPANTS Two hundred thirty-eight elderly men and women aged 60 to 80 at high risk for cardiovascular disease were randomly assigned to three interventional groups : a recommended low-fat diet ( control diet group ) , a Mediterranean diet supplemented with virgin olive oil , or a Mediterranean diet supplemented with mixed nuts . MEASUREMENTS Main outcomes were 12-month changes from baseline in bone formation and resorption markers and bone mass measured according to quantitative ultrasound scanning . RESULTS The baseline data on the anthropometric , bone densitometry , and biochemical variables did not differ between the three groups . Dietary potential renal acid load ( PRAL ) and daily net endogenous acid production ( NEAP ) at baseline did not differ between groups . After intervention , subjects allocated to the Mediterranean diet with mixed nuts had a significant increase of PRAL and NEAP . In comparison , subjects in the Mediterranean diet with nuts group had higher parathyroid hormone ( PTH ) levels ( 2.63 , 95 % confidence interval ( CI ) =-1.01-6.35 , P=.02 ) and a nonsignificantly higher ( 0.31 , 95 % CI=-0.13-0.74 , P=.14 ) urine free deoxypyridoxine : creatinine ratio , a marker of bone resorption , than the control group and the Mediterranean diet with virgin olive oil group . CONCLUSION A Mediterranean dietary pattern associated with a high dietary acid load derived from consumption of mixed nuts does not seem to have a much greater effect on bone metabolism biomarkers , with the exception of PTH levels , than a Mediterranean diet without mixed nuts or a control diet in elderly subjects .

Mediterranean diet

high dietary acid load

mixed nuts

Mediterranean diet with mixed nuts

Mediterranean diet with nuts

Mediterranean dietary pattern

Mediterranean diet without mixed nuts

control diet

effect

bone metabolism

bone metabolism

PRAL

NEAP

parathyroid hormone ( PTH ) levels

bone metabolism biomarkers

PTH levels

elderly

Two hundred thirty-eight

elderly

men

women

60 to 80

cardiovascular disease

elderly


Long-term prospective , randomized , controlled study using repetitive education at six-month intervals and monitoring for adherence in heart failure outpatients : the REMADHE trial . BACKGROUND The effectiveness of heart failure disease management programs in patients under cardiologists ' care over long-term follow-up is not established . METHODS AND RESULTS We investigated the effects of a disease management program with repetitive education and telephone monitoring on primary ( combined death or unplanned first hospitalization and quality-of-life changes ) and secondary end points ( hospitalization , death , and adherence ) . The REMADHE [ Repetitive Education and Monitoring for ADherence for Heart Failure ] trial is a long-term randomized , prospective , parallel trial designed to compare intervention with control . One hundred seventeen patients were randomized to usual care , and 233 to additional intervention . The mean follow-up was 2.47+/-1.75 years , with 54 % adherence to the program . In the intervention group , the primary end point composite of death or unplanned hospitalization was reduced ( hazard ratio , 0.64 ; confidence interval , 0.43 to 0.88 ; P=0.008 ) , driven by reduction in hospitalization . The quality-of-life questionnaire score improved only in the intervention group ( P < 0.003 ) . Mortality was similar in both groups . Number of hospitalizations ( 1.3+/-1.7 versus 0.8+/-1.3 , P < 0.0001 ) , total hospital days during the follow-up ( 19.9+/-51 versus 11.1+/-24 days , P < 0.0001 ) , and the need for emergency visits ( 4.5+/-10.6 versus 1.6+/-2.4 , P < 0.0001 ) were lower in the intervention group . Beneficial effects were homogeneous for sex , race , diabetes and no diabetes , age , functional class , and etiology . CONCLUSIONS For a longer follow-up period than in previous studies , this heart failure disease management program model of patients under the supervision of a cardiologist is associated with a reduction in unplanned hospitalization , a reduction of total hospital days , and a reduced need for emergency care , as well as improved quality of life , despite modest program adherence over time .

Education and Monitoring

control

death

unplanned first hospitalization

quality-of-life changes

hospitalization

death

adherence

composite of death

unplanned hospitalization

hospitalization .

quality-of-life questionnaire score

Mortality

Number of hospitalizations

need for emergency visits

unplanned hospitalization

total hospital days

need for emergency care

improved quality of life

program adherence

heart failure outpatients

One hundred seventeen


Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain . BACKGROUND AND OBJECTIVES Breakthrough cancer pain ( BTcP ) represents an important clinical challenge in the care of patients with cancer . This trial evaluated the efficacy and long-term tolerability of a sublingual formulation of the fast-acting opioid fentanyl , for the treatment of BTcP in opioid-tolerant patients with cancer . RESEARCH DESIGN AND METHODS This was a randomized , placebo-controlled , multi-center , phase III trial , conducted in opioid-tolerant male and female patients ( aged > or =17 years ) with BTcP . The study was conducted at 36 centers across the USA . The study comprised a 2-week open-label titration phase , followed by a double-blind efficacy phase , during which patients received sublingual fentanyl citrate orally disintegrating tablet ( sublingual fentanyl ODT ) or placebo , in a random order . The primary efficacy endpoint was the sum of pain intensity difference ( SPID ) over 30 min post-administration . Secondary efficacy endpoints included pain intensity difference ( PID ) and pain relief ( PR ) throughout the 60-min post-dose assessment period . Following efficacy evaluation , patients entered a long-term safety phase of up to 12 months . Adverse events were recorded throughout the study . [ CLINICAL TRIAL REGISTRATION NCT00262678 ] RESULTS A total of 131 patients entered the titration phase , of whom 61 were included in the primary efficacy analysis . Sublingual fentanyl ODT provided significant improvements in SPID relative to placebo at 30 min ( 49.5 vs. 36.6 , p = 0.0004 ) and 60 min post-administration ( 143.0 vs. 104.5 , p = 0.0002 ) . Furthermore , sublingual fentanyl ODT provided significant improvements in PID and PR compared to placebo , from 10 min post-dose ( p = 0.0055 and p = 0.049 for PID and PR , respectively ) . Patient recruitment was stopped early , due to positive interim analysis results ( significant at prespecified level , p < or = 0.0414 ) . Overall , sublingual fentanyl ODT was well-tolerated both systemically and sublingually , with 41 patients experiencing > or =1 study drug-related adverse event ( AE ) . The most common AEs included nausea ( 12.2 % ) , vomiting ( 5.3 % ) and somnolence ( 4.6 % ) . One serious AE ( mild affect lability ) was considered possibly related to study medication . The observed pattern of AEs was consistent with that previously observed with fentanyl . CONCLUSIONS Sublingual fentanyl ODT was efficacious and well-tolerated for the treatment of BTcP in opioid-tolerant patients with cancer . Sublingual fentanyl ODT provided significant improvements in pain intensity compared to placebo , from 10 min post-administration and throughout the 60-min post-dose assessment period . Sublingual fentanyl ODT was well tolerated over 12 months of treatment .

fast-acting opioid fentanyl

placebo

fentanyl ODT

over 30 min post-administration

pain intensity difference ( PID )

pain relief ( PR )

Adverse events

SPID

PID

PR

drug-related adverse event

nausea

vomiting

somnolence

serious AE ( mild affect lability )

cancer

opioid-tolerant

male and female

aged > or =17 years


The effect of oral steroids with and without vitamin D3 on early efficacy of immunotherapy in asthmatic children . BACKGROUND The possibility of additional strategies to enhance the effectiveness of specific immunotherapy ( SIT ) is highly attractive . AIM The aim of our study was to assess the influence of oral corticosteroids and oral corticosteroids combined with vitamin D ( 3 ) on the early clinical and immunological effects of SIT . METHODS It was a randomized , double-blind , placebo-controlled trial conducted in 54 asthmatic children allergic to house dust mites . Intervention was based on receiving a single dose of oral steroid , with or without vitamin D ( 3 ) , or placebo only on the day of the build-up phase of SIT . RESULTS After 12 months of SIT , the median daily inhaled corticosteroid ( ICS ) dose , which controls the symptoms of asthma , was reduced by 25 % in the steroid group . However , a 50 % reduction of the median daily ICS dose was observed in the control group . The clinical effects of SIT were not affected in the steroid+D ( 3 ) group . Concomitantly , we found that intervention with prednisone significantly impaired the induction of T regulatory lymphocytes . Importantly , the clinical and immunological effects of SIT were not affected by intervention with steroids administered with vitamin D ( 3 ) . CONCLUSIONS Our study failed to show a beneficial effect of oral corticosteroids on allergen-specific immunotherapy . We observed that the combined administration of a corticosteroid drug and allergen extract suppressed the early clinical and immunological effects of SIT and that vitamin D ( 3 ) prevented this 'adverse ' influence of steroids .

steroids with and without vitamin D3

corticosteroids

placebo

steroid

median daily ICS dose

induction of T regulatory lymphocytes

asthmatic

children .

asthmatic

children

allergic to house dust mites


Comparison of fluid types for resuscitation after acute blood loss in mallard ducks ( Anas platyrhynchos ) . OBJECTIVE The purpose of this study was to determine the LD ( 50 ) for acute blood loss in mallard ducks ( Anas platyrhynchos ) , compare the mortality rate among 3 fluid resuscitation groups , and determine the time required for a regenerative RBC response . DESIGN Prospective study . SETTING Medical College of Wisconsin Research facility . ANIMALS Eighteen mallard ducks were included for the LD ( 50 ) study and 28 for the fluid resuscitation study . INTERVENTIONS Phlebotomy was performed during both the LD ( 50 ) and fluid resuscitation studies . Ducks in the fluid resuscitation study received a 5 mL/kg intravenous bolus of crystalloids , hetastarch ( HES ) , or a hemoglobin-based oxygen-carrying solution ( HBOCS ) . MEASUREMENTS AND MAIN RESULTS The LD ( 50 ) for acute blood loss was 60 % of total blood volume . This blood volume was removed in the fluid resuscitation study to create a model of acute blood loss . Following fluid administration , 6 birds in the crystalloid group ( 66 % ) , 4 birds in the HES group ( 40 % ) , and 2 birds in the HBOCS group ( 20 % ) died . No statistical difference in mortality rate was seen among the 3 fluid resuscitation groups . Relative polychromasia evaluated post-phlebotomy demonstrated regeneration starting at 24 hours and continuing through 48 hours . CONCLUSIONS The LD ( 50 ) for acute blood loss in mallard ducks was 60 % of their total blood volume . Although no statistical difference in mortality rate was appreciated among the 3 fluid resuscitation groups , a trend of decreased mortality rate was observed in the HBOCS group . An early regenerative response was apparent following acute blood loss .

fluid resuscitation

Phlebotomy

fluid resuscitation

hetastarch ( HES )

acute blood loss

acute blood loss

total blood volume

mortality rate

acute blood loss

mortality rate

mortality rate

acute blood loss

acute blood loss

acute blood loss

Eighteen


Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction : the ASTAMI randomised , controlled study . OBJECTIVE To investigate long-term safety and efficacy after intracoronary injection of autologous mononuclear bone marrow cells ( mBMCs ) in acute myocardial infarction ( AMI ) . DESIGN Randomised , controlled trial . SETTING Two university hospitals in Oslo , Norway . PATIENTS Patients from the Autologous Stem cell Transplantation in Acute Myocardial Infarction ( ASTAMI ) study were re-assessed 3 years after inclusion . INTERVENTIONS 100 patients with anterior wall ST-elevation myocardial infarction treated with acute percutaneous coronary intervention ( PCI ) were randomised to receive intracoronary injection of mBMCs ( n = 50 ) or not ( n = 50 ) . MAIN OUTCOME MEASURES Change in left ventricular ( LV ) ejection fraction ( primary ) . Change in exercise capacity ( peak VO ( 2 ) ) and quality of life ( secondary ) . Infarct size ( additional aim ) , and safety . RESULTS The rates of adverse clinical events in the groups were low and equal . There were no significant differences between groups in change of global LV systolic function by echocardiography or magnetic resonance imaging ( MRI ) during the follow-up . On exercise testing , the mBMC-treated patients had larger improvement in exercise time from 2-3 weeks to 3 years ( 1.5 minutes vs 0.6 minutes , p = 0.05 ) , but the change in peak oxygen consumption did not differ ( 3.0 ml/kg/min vs 3.1 ml/kg/min , p = 0.75 ) . CONCLUSION The results indicate that intracoronary mBMC treatment in AMI is safe in the long term . A small improvement in exercise time in the mBMC group was found , but no other effects of treatment could be identified 3 years after cell therapy .

intracoronary injection of mBMCs

mBMC-treated

mBMC

quality of life

Infarct size ( additional aim )

safety

rates of adverse clinical events

change of global LV systolic function

exercise time

peak oxygen consumption

acute myocardial infarction :

ASTAMI

acute myocardial infarction ( AMI )

Acute Myocardial Infarction ( ASTAMI )

ST-elevation myocardial infarction


Direct evidence for spinal cord involvement in placebo analgesia . Placebo analgesia is a prime example of the impact that psychological factors have on pain perception . We used functional magnetic resonance imaging of the human spinal cord to test the hypothesis that placebo analgesia results in a reduction of nociceptive processing in the spinal cord . In line with behavioral data that show decreased pain responses under placebo , pain-related activity in the spinal cord is strongly reduced under placebo . These results provide direct evidence for spinal inhibition as one mechanism of placebo analgesia and highlight that psychological factors can act on the earliest stages of pain processing in the central nervous system .

functional magnetic resonance imaging

pain responses

pain-related activity


Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders : Part A -- medical results . BACKGROUND This study investigated the effect of oral dimercapto succinic acid ( DMSA ) therapy for children with autism spectrum disorders ages 3-8 years . METHODS Phase 1 involved 65 children who received one round of DMSA ( 3 days ) . Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2 . In phase 2 , 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo . RESULTS DMSA greatly increased the excretion of lead , substantially increased excretion of tin and bismuth , and somewhat increased the excretion of thallium , mercury , antimony , and tungsten . There was some increase in urinary excretion of essential minerals , especially potassium and chromium . The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases , and greatly improved abnormal platelet counts , suggesting a significant decrease in inflammation . CONCLUSION Overall , DMSA therapy seems to be reasonably safe , effective in removing several toxic metals ( especially lead ) , dramatically effective in normalizing RBC glutathione , and effective in normalizing platelet counts . Only 1 round ( 3 days ) was sufficient to improve glutathione and platelets . Additional rounds increased excretion of toxic metals .

DMSA

therapy

oral dimercapto succinic acid ( DMSA )

DMSA

DMSA

placebo

DMSA

DMSA

Safety and efficacy

excretion of lead

excretion of tin and bismuth

urinary excretion of essential minerals

normalization of RBC glutathione

abnormal platelet counts

inflammation

safe , effective

toxic metals

normalizing RBC glutathione

normalizing platelet counts

glutathione and platelets

excretion of toxic metals

children

autism spectrum disorders

children

autism spectrum

3-8 years

children

high urinary excretion of toxic metals

2 , 49


Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders : part B - behavioral results . BACKGROUND This study investigated the effects of oral dimercapto succinic acid ( DMSA ) therapy on the behavioural symptoms of children with autism spectrum disorders ( ASD ) ages 3-8 years . METHODS Phase 1 involved 65 children with ASD who received one round of DMSA ( 3 days ) . Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2 . In phase 2 , 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo . RESULTS The groups receiving one round and seven rounds of DMSA had significant improvements on all the assessment measures . For the seven round group , the degree of improvement on the assessment measures could be partially explained by a regression analysis based on excretion of toxic metals and changes in glutathione ( adjusted R2 of 0.28-0.75 , p < 0.02 in all cases ) . One round of DMSA had nearly the same benefit as seven rounds . The assessment measures correlated reasonably with one another at the beginning of the study ( r = 0.60-0.87 ) and even better at the end of the study ( r = 0.63-0.94 ) . CONCLUSION Overall , both one and seven rounds of DMSA therapy seems to be reasonably safe in children with ASD who have high urinary excretion of toxic metals , and possibly helpful in reducing some of the symptoms of autism in those children .

DMSA

therapy

oral dimercapto succinic acid ( DMSA )

DMSA

placebo

DMSA

DMSA

Safety and efficacy

improvement

assessment measures

safe

children

autism spectrum disorders

autism spectrum disorders ( ASD

ages 3-8 years

children

ASD

high urinary excretion of toxic metals

children

ASD

high urinary excretion of toxic metals


Patterns of management of atrial fibrillation complicating coronary artery bypass grafting : Results from the PRoject of Ex-vivo Vein graft ENgineering via Transfection IV ( PREVENT-IV ) Trial . BACKGROUND Current practice related to the management of atrial fibrillation ( AF ) complicating coronary artery bypass grafting ( CABG ) is uncertain . METHODS We examined management of post-CABG AF in the PREVENT-IV trial , and we explored patterns of use of postoperative rhythm versus rate control and anticoagulation for AF by geographic region and type of site . We also compared outcomes of patients who developed post-CABG AF ( 663 ) with those who did not ( 2,131 ) . RESULTS The incidence of AF was 24 % . Post-CABG AF was treated with a rhythm control strategy in 81 % of patients and with warfarin in 23 % of patients . Although there were significant variations across sites in the management of post-CABG AF , patterns of use of postoperative rhythm versus rate control and anticoagulation did not differ by geographic region or by whether or not the enrolling site was an academic institution . Mortality was higher in patients with post-CABG AF than patients without AF at 30 days ( 1.5 % vs 0.7 % , P = .01 ) but not at 3 years ( 6.9 % vs 4.9 % , P = .41 ) . There was a trend toward a higher risk of mortality or stroke at 30 days in patients with AF ( 2.4 % vs 1.9 % , P = .08 ) . CONCLUSION Although a rhythm control strategy was used in most of the patients in this trial and the overall rate of use of warfarin was low , the significance of these findings is uncertain because of the lack of data from randomized clinical trials . The substantial variations in the management of post-CABG AF across sites are likely because of definitive data on the most effective therapies , highlighting the need for clinical trials on rate versus rhythm control and on anticoagulation for AF in this setting .

warfarin

atrial fibrillation ( AF )

AF

AF

Post-CABG AF

post-CABG AF

Mortality

mortality

stroke

atrial fibrillation

AF

post-CABG AF


Medication and parent training in children with pervasive developmental disorders and serious behavior problems : results from a randomized clinical trial . OBJECTIVE Many children with pervasive developmental disorders ( PDDs ) have serious , functionally impairing behavioral problems . We tested whether combined treatment ( COMB ) with risperidone and parent training ( PT ) in behavior management is superior to medication alone ( MED ) in improving severe behavioral problems in children with PDDs . METHOD This 24-week , three-site , randomized , parallel-groups clinical trial enrolled 124 children , aged 4 through 13 years , with PDDs , accompanied by frequent tantrums , self-injury , and aggression . The children were randomized 3:2 to COMB ( n = 75 ) or MED ( n = 49 ) . The participants received risperidone monotherapy from 0.5 to 3.5 mg/day ( with switch to aripiprazole if risperidone was ineffective ) . Parents in the COMB group ( n = 75 ; 60.5 % ) received a mean of 10.9 PT sessions . The primary measure of compliance was the Home Situations Questionnaire ( HSQ ) score . RESULTS Primary : intent-to-treat random effects regression showed that COMB was superior to MED on HSQ ( p = .006 ) [ effect size at week 24 ( d ) = 0.34 ] . The HSQ score declined from 4.31 ( ± 1.67 ) to 1.23 ( ± 1.36 ) for COMB compared with 4.16 ( ± 1.47 ) to 1.68 ( ± 1.36 ) for MED . Secondary : groups did not differ on Clinical Global Impressions-Improvement scores at endpoint ; compared with MED , COMB showed significant reductions on Aberrant Behavior Checklist Irritability ( d = 0.48 ; p = .01 ) , Stereotypic Behavior ( d = 0.23 ; p = .04 ) , and Hyperactivity/Noncompliance subscales ( d = 0.55 ; p = .04 ) . Final risperidone mean dose for MED was 2.26 mg/day ( 0.071 mg/kg ) , compared with 1.98 mg/day for COMB ( 0.066 mg/kg ) ( p = .04 ) . CONCLUSIONS Medication plus PT resulted in greater reduction of serious maladaptive behavior than MED in children with PDDs , with a lower risperidone dose .

combined treatment ( COMB )

risperidone and parent training ( PT )

risperidone monotherapy

aripiprazole

risperidone

COMB

severe behavioral problems

HSQ

HSQ score


Immunologic profiles of persons recruited for a randomized , placebo-controlled clinical trial of hookworm infection . Data from epidemiologic studies suggest that hookworm infections , in establishing an immunologic phenotype conducive to parasite survival , may protect against the development of allergic disease . We describe immunologic findings from a clinical study designed to investigate the safety of iatrogenic hookworm infection in participants with allergic rhinitis . The low , relatively safe level of hookworm infection used in this study was immunogenic , inducing eosinophilia and a significant specific IgG response . Importantly , no potentiation of IgE responses to the environmental allergens to which the participants were sensitized was seen . However , no evidence of systemic immune regulation was seen in infected participants . This finding may indicate that the level of infection or the frequency of infection may have to be altered in future trials to induce a therapeutically conducive immunologic phenotype .

placebo-controlled

iatrogenic hookworm infection

hookworm infection

eosinophilia

specific IgG response .

systemic immune regulation

level of infection

frequency of infection


Enhancing antiepileptic drug adherence : a randomized controlled trial . Suboptimal adherence to antiepileptic drug ( AED ) treatment is commonplace , and increases the risk of status epilepticus and sudden unexplained death in epilepsy . This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time , place , and other activity can improve AED treatment schedule adherence . Of the 81 patients with epilepsy who were randomized , 69 completed a 1-month monitoring period with an objective measure of tablet taking ( electronic registration of pill bottle openings , Medication Event Monitoring System [ MEMS ] ) . Intervention participants showed improved adherence relative to controls on all three outcomes : doses taken in total ( 93.4 % vs. 79.1 % ) , days on which correct dose was taken ( 88.7 % vs. 65.3 % ) , and doses taken on schedule ( 78.8 % vs. 55.3 % ) ( P < 0.01 ) . The implementation intention intervention may be an easy-to-administer and effective means of promoting AED adherence .

antiepileptic drug

antiepileptic drug ( AED ) treatment

self-administered questionnaire

AED

intention intervention

AED

improved adherence relative to controls

doses taken in total

correct dose was taken

doses taken on schedule


Effects of walnut consumption on endothelial function in type 2 diabetic subjects : a randomized controlled crossover trial . OBJECTIVE To determine the effects of daily walnut consumption on endothelial function , cardiovascular biomarkers , and anthropometric measures in type 2 diabetic individuals . RESEARCH DESIGN AND METHODS This study was a randomized , controlled , single-blind , crossover trial . Twenty-four participants with type 2 diabetes ( mean age 58 years ; 14 women and 10 men ) were randomly assigned to one of the two possible sequence permutations to receive an ad libitum diet enriched with 56 g ( 366 kcal ) walnuts/day and an ad libitum diet without walnuts for 8 weeks . Subjects underwent endothelial function testing ( measured as flow-mediated dilatation [ FMD ] ) and assessment of cardiovascular biomarkers before and after each 8-week treatment phase . The primary outcome measure was the change in FMD after 8 weeks . Secondary outcome measures included changes in plasma lipids , A1C , fasting glucose , insulin sensitivity , and anthropometric measures . RESULTS Endothelial function significantly improved after consumption of a walnut-enriched ad libitum diet compared with that after consumption of an ad libitum diet without walnuts ( 2.2 +/- 1.7 vs. 1.2 +/- 1.6 % ; P = 0.04 ) . The walnut-enriched diet increased fasting serum glucose and lowered serum total cholesterol and LDL cholesterol from baseline ( 10.0 +/- 20.5 mg/dl , P = 0.04 ; -9.7 +/- 14.5 mg/dl , P < 0.01 ; and -7.7 +/- 10 mg/dl , P < 0.01 , respectively ) , although these changes were not significant compared with those for an ad libitum diet without walnuts . There were no significant changes in anthropometric measures , plasma A1C , and insulin sensitivity . CONCLUSIONS A walnut-enriched ad libitum diet improves endothelium-dependent vasodilatation in type 2 diabetic individuals , suggesting a potential reduction in overall cardiac risk .

walnut consumption

walnut consumption

endothelial function testing

endothelial function

endothelial function

cardiovascular biomarkers

anthropometric measures

change in FMD

changes in plasma lipids , A1C

fasting glucose

insulin sensitivity

anthropometric measures

Endothelial function

fasting serum glucose

anthropometric measures

plasma A1C

insulin sensitivity

cardiac risk

type 2 diabetic

Twenty-four

type 2 diabetes

mean age 58 years

14 women and 10 men


Comparison of neurocognitive functioning in children previously randomly assigned to intrathecal methotrexate compared with triple intrathecal therapy for the treatment of childhood acute lymphoblastic leukemia . PURPOSE For the majority of children with acute lymphoblastic leukemia ( ALL ) , CNS prophylaxis consists of either intrathecal ( IT ) methotrexate or triple IT therapy ( ie , methotrexate with both cytarabine and hydrocortisone ) . The long-term neurotoxicities of these two IT strategies have not yet been directly compared . PATIENTS AND METHODS In this multisite study , 171 children with standard-risk ALL , age 1 to 9.99 years at diagnosis , previously randomly assigned to IT methotrexate ( n = 82 ) or to triple IT therapy ( n = 89 ) on CCG 1952 , underwent neurocognitive evaluation by a licensed psychologist at a mean of 5.9 years after random assignment . RESULTS Patients who received IT methotrexate had a mean Processing Speed Index that was 3.6 points lower , about one fourth of a standard deviation , than those who received triple IT therapy ( P = .04 ) after analysis was adjusted for age , sex , and time since diagnosis . Likewise , 19.5 % of children in the IT methotrexate group had a Processing Speed Index score in the below-average range compared with 6.9 % in the triple IT therapy group ( P = .02 ) . Otherwise , the groups performed similarly on tests of full-scale intelligence quotient , academic achievement , attention/concentration , memory , and visual motor integration . The association of treatment with measures of cognitive functioning was not modified by sex or age at diagnosis . In the post-therapy period , there were no group differences in special education services , neurologic events , or use of psychotropic medications . CONCLUSION This study did not show any clinically meaningful differences in neurocognitive functioning between patients previously randomly assigned to IT methotrexate or triple IT therapy except for a small difference in processing speed in the IT methotrexate group .

intrathecal methotrexate

triple intrathecal therapy

intrathecal ( IT ) methotrexate

IT methotrexate

triple IT therapy

IT methotrexate

triple IT therapy

IT methotrexate

triple IT therapy group

IT methotrexate

triple IT therapy

IT methotrexate group .

neurocognitive functioning

mean Processing Speed Index

Processing Speed Index score

academic achievement

attention/concentration

memory

visual motor integration

measures of cognitive functioning

special education services

neurologic events

use of psychotropic medications

neurocognitive functioning

processing speed

lymphoblastic leukemia

children

acute lymphoblastic leukemia ( ALL )

children

age 1 to 9.99 years


Sustained effect of SQ-standardized grass allergy immunotherapy tablet on rhinoconjunctivitis quality of life . BACKGROUND The prevalence of allergic rhinoconjunctivitis has increased significantly over the past decades with grass pollen being a common trigger . The impact of allergy on patient 's quality of life is substantial . AIM To investigate the sustained effect on quality of life during the grass pollen season 1 year after 3 years of treatment with the SQ-standardized grass allergy immunotherapy tablet ( AIT ) , Graza ( Phleum pratense 75,000 SQ-T/2800 BAU ; ALK , Denmark ) . METHODS The trial was a randomized , parallel-group , double-blind , placebo-controlled trial in adult subjects with a history of moderate-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications . Subjects received 3 years of grass AIT ( n = 157 ) or placebo ( n = 126 ) , followed by 1 year of follow-up . Quality of life assessments were based on the standardized rhinoconjunctivitis quality of life questionnaire ( RQLQ ( S ) ) ; completed weekly during the entire grass pollen season . RESULTS During follow-up , the overall RQLQ ( S ) score for the entire grass pollen season was significantly improved in the active group ( relative difference to placebo : 23 % , P = 0.004 ) . The improvement was higher during the peak pollen season ( 28 % , P = 0.001 ) . The treatment effect of grass AIT during the follow-up year and the previous three treatment years was similar . Improvements were found in all seven RQLQ ( S ) domains . The RQLQ ( S ) as a function of the weekly average pollen counts showed a clear separation between the treatment groups ( P < 0.001 ) . CONCLUSION In subjects inadequately controlled by symptomatic medications , grass AIT provided sustained and clinically relevant improvements in rhinoconjunctivitis quality of life compared to placebo . The effect increased with increasing grass pollen exposure .

immunotherapy tablet

grass AIT

placebo

AIT

Quality of life

RQLQ ( S ) score

RQLQ ( S ) domains

RQLQ ( S )

rhinoconjunctivitis quality of life

adult


Screening , brief intervention , and referral to treatment ( SBIRT ) in a Polish emergency department : three-month outcomes of a randomized , controlled clinical trial . OBJECTIVE A randomized , controlled trial of screening , brief intervention , and referral to treatment ( SBIRT ) for drinking and related problems among at-risk and dependent drinkers was conducted in an emergency department ( ED ) in Sosnowiec , Poland , among patients ages 18 years and older . METHOD Data were collected over a 23-week period , from 4:00 PM to midnight , and resulted in 446 patients being recruited into the study ( 90 % of those who screened positive ) and randomized to three conditions following a two-stage process : screened only ( n = 147 ) , assessed ( n = 152 ) , and received intervention ( n = 147 ) . Patients in the assessment ( 85 % ) and intervention ( 83 % ) conditions were blindly reassessed at 3 months via a telephone interview . RESULTS At 3-month follow-up , both groups showed significant decreases in the proportion who were positive for at-risk drinking , the primary outcome variable . Both groups also showed significant decreases in drinking days per week , drinks per drinking day , maximum drinks per occasion , and negative consequences of drinking . Using analysis of covariance to control for baseline measures and demographic characteristics , no difference in outcome measures was found between intervention and assessment conditions . Subgroup analysis found some significant interactions between intervention and secondary outcomes . CONCLUSIONS Although the main findings were similar to those from other brief-intervention studies in Western cultures , findings here also suggest that intervention may have differential benefits for specific subgroups of patients in the ED , an area of research that may warrant additional study of brief intervention in the ED setting .

screened only

assessed

received intervention

intervention

intervention

assessment

intervention

drinking days per week

drinks per drinking day

maximum drinks per occasion

negative consequences of drinking


The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women . There is evidence to suggest accelerated bone loss following estrogen cessation . The effect of cessation of raloxifene therapy on bone turnover is unknown . Our aim was to determine the effect of cessation of raloxifene treatment on bone turnover and bone mineral density ( BMD ) in postmenopausal , osteopenic women . Women aged 50 to 80 years received raloxifene for 96 weeks and were then randomized to continue raloxifene ( group 1 , n=20 ) or placebo ( group 2 , n=20 ) for a further 96 weeks . A third group ( group 3 , n=14 ) received no treatment . Bone turnover markers and bone density ( BMD ) were measured throughout the study . Raloxifene treatment for 96 weeks resulted in a decrease in bone turnover ( PINP by 31 % ) and an increase in spine BMD ( by 2 % ) but no change in hip BMD for groups 1 and 2 . Continuation of raloxifene ( group 1 ) maintained these changes . Following cessation of raloxifene ( group 2 ) , bone markers returned to baseline levels ( by 120 weeks ) . Hip BMD was decreased by 2 % at 192 weeks compared to baseline . Bone markers in the controls ( group 3 ) remained at the upper limit of the reference range throughout , with decreases in BMD of 2.3 % ( spine ) and 2.8 % ( hip ) . Bone loss following cessation of raloxifene therapy at 96 weeks was greater than in the control group , suggesting accelerated bone loss . The beneficial effect on bone turnover of 96 weeks of raloxifene was lost 6 months after cessation of treatment .

raloxifene

raloxifene

raloxifene

raloxifene

raloxifene

or placebo

no treatment .

Raloxifene

raloxifene

raloxifene

raloxifene

bone loss

bone turnover

bone mineral density ( BMD )

decrease in bone turnover

increase in spine BMD

hip BMD

bone markers

Hip BMD

Bone markers

BMD

Bone loss

bone turnover

bone turnover in postmenopausal women .

postmenopausal

women

Women

aged 50 to 80 years

accelerated bone loss .


Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders . BACKGROUND A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction . Deficits in the ability to recognize the emotions of others are believed to contribute to this . There is currently no effective treatment for these problems . METHODS In a double-blind , randomized , placebo-controlled , crossover design , we administered oxytocin nasal spray ( 18 or 24 IU ) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger 's Disorder . Participants then completed the Reading the Mind in the Eyes Task , a widely used and reliable test of emotion recognition . RESULTS In comparison with placebo , oxytocin administration improved performance on the Reading the Mind in the Eyes Task . This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose . CONCLUSIONS This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders . Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders .

oxytocin

oxytocin nasal spray

placebo

placebo

oxytocin

oxytocin

emotion recognition

Reading the Mind in the Eyes Task

emotion recognition

emotion recognition

youth

autism spectrum disorders

male

youth aged 12 to 19

Autistic or Asperger 's Disorder

younger


Treatment of beta-hemolytic streptococcal pharyngitis with cefaclor or penicillin . Efficacy and interaction with beta-lactamase-producing organisms in the pharynx . The recommended treatment for group A beta-hemolytic streptococcal pharyngitis has continued to be penicillin given in parenteral or oral form . Treatment failures , as determined by the continued presence of the streptococcal organism in the pharynx , however , do occur in 6 % to 25 % of patients treated with penicillin . Furthermore , beta-lactamase produced by other bacteria in the pharynx could potentially inactivate the penicillin , resulting in increased treatment failures or infection relapses . A study was undertaken to compare the efficacy of cefaclor , which is relatively resistant to inactivation by beta-lactamase , with penicillin for eradicating the group A beta-hemolytic streptococcal organism from the throats of 93 patients with pharyngitis . Additionally , extensive cultures for potential beta-lactamase-producing organisms were conducted on 37 patients ; 27 % of these had one or more pharyngeal organisms that were producing beta-lactamase . No statistically significant difference was found between the clinical responses or the bacteriological cure rates of those treated with cefaclor and those treated with penicillin when stratified by the presence or absence of beta-lactamase-producing organisms . The prevalence of beta-lactamase-producing organisms in the pharynx , however , was increased after treatment with penicillin , whereas no change was noted following treatment with cefaclor .

cefaclor

penicillin

penicillin

cefaclor

Treatment failures


Conjugated equine estrogen influence on mammographic density in postmenopausal women in a substudy of the women 's health initiative randomized trial . PURPOSE Increased mammographic density is associated with increased breast cancer risk and reduced sensitivity of screening mammography and is related to hormone exposure . However , the effects of conjugated equine estrogens ( CEEs ) alone on mammographic density in diverse racial/ethnic populations are not established . We examined the effect of CEE alone on mammographic density in a subsample of the Women 's Health Initiative ( WHI ) clinical trial participants . PATIENTS AND METHODS In the WHI trial , women were randomly assigned to daily CEE 0.625 mg or placebo . The effect of CEE on mammographic percent density was determined over 1 and 2 years in a stratified random sample of 435 racially and ethnically diverse participants from 15 of 40 WHI clinics . RESULTS Use of CEE resulted in mean increase in mammographic percent density of 1.6 percentage points ( 95 % CI , 0.8 to 2.4 ) at year 1 compared with a mean decrease of 1.0 percentage point ( 95 % CI , -1.7 to -0.4 ) in the placebo group ( P < .001 ) . The effect persisted for 2 years , with a mean increase of 1.7 percentage points ( 95 % CI , 0.7 to 2.7 ) versus a mean decrease of 1.2 percentage points ( 95 % CI , -1.8 to -0.5 ; P < .001 ) in the hormone and placebo groups , respectively . These effects were greater in women age 60 to 79 years ( P = .03 for interaction across age ) . CONCLUSION Use of CEE results in a modest but statistically significant increase in mammographic density that is sustained over at least a 2-year period . The clinical significance of the CEE effect on mammographic density remains to be determined .

conjugated equine estrogens ( CEEs )

daily CEE 0.625 mg

placebo

mammographic density

mammographic percent density

mammographic density

mammographic density

postmenopausal

women

women

women

age 60 to 79 years


Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer -- a multi-centre randomised phase II study . BACKGROUND No standard treatment for locally advanced pancreatic cancer ( LAPC ) is defined . PATIENTS AND METHODS Within a multi-centre , randomised phase II trial , 95 patients with LAPC were assigned to three different chemoradiotherapy ( CRT ) regimens : patients received conventionally fractionated radiotherapy of 50 Gy and were randomised to concurrent 5-fluorouracil ( 350 mg m ( -2 ) per day on each day of radiotherapy , RT-5-FU arm ) , concurrent gemcitabine ( 300 mg m ( -2 ) ) , and cisplatin ( 30 mg m ( -2 ) ) on days 1 , 8 , 22 , and 29 ( RT-GC arm ) , or the same concurrent treatment followed by sequential full-dose gemcitabine ( 1000 mg m ( -2 ) ) and cisplatin ( 50 mg m ( -2 ) ) every 2 weeks ( RT-GC+GC arm ) . Primary end point was the overall survival ( OS ) rate after 9 months . RESULTS The 9-month OS rate was 58 % in the RT-5-FU arm , 52 % in the RT-GC arm , and 45 % in the RT-GC+GC arm . Corresponding median survival times were 9.6 , 9.3 , and 7.3 months ( P=0.61 ) respectively . The intent-to-treat response rate was 19 , 22 , and 13 % respectively . Median progression-free survival was estimated with 4.0 , 5.6 , and 6.0 months ( P=0.21 ) . Grade 3/4 haematological toxicities were more frequent in the two GC-containing arms , no grade 3/4 febrile neutropaenia was observed . CONCLUSION None of the three CRT regimens tested met the investigators ' definition for efficacy ; the median OS was similar to those previously reported with gemcitabine alone in LAPC .

radiotherapy

radiotherapy

concurrent gemcitabine

cisplatin

cisplatin

9-month OS rate

median survival times

intent-to-treat response rate

Median progression-free survival

Grade 3/4 haematological toxicities

grade 3/4 febrile neutropaenia

locally advanced pancreatic cancer --

LAPC


Brief Report : Randomized test of the efficacy of picture exchange communication system on highly generalized picture exchanges in children with ASD . A randomized control trial comparing two social-communication interventions in young children with autism examined far-transfer of the use of picture exchange to communicate . Thirty-six children were randomly assigned to one of two treatment conditions , one of which was the Picture Exchange Communication System ( PECS ) . All children had access to picture symbols during assessments . Post-treatment measurement of the number of picture exchanges in a far-transfer , assessment context favored the PECS intervention . These findings were interpreted as support for the hypothesis that the PECS curriculum can successfully teach a generalized means of showing coordinated attention to object and person without requiring eye contact to children with ASD .

picture exchange communication system

social-communication interventions

picture exchange

picture symbols during assessments

PECS

PECS

generalized picture exchanges


First-line cisplatin with docetaxel or vinorelbine in patients with advanced non-small-cell lung cancer : a quality of life directed phase II randomized trial of Gruppo Oncologico Italia Meridionale . BACKGROUND Quality of life ( QoL ) has gained greater importance in the management of metastatic non-small-cell lung cancer due to the palliative nature of treatment . Docetaxel ( DCT ) and cisplatin ( CDDP ) doublet has been reported to be associated to a better QoL than the weekly vinorelbine ( VNR ) and CDDP regimen . Recently a newer more tolerated schedule of the VNR/CDDP regimen has been published and is widely employed in medical practice . The impact of these regimens on patients ' QoL as well as symptoms control and type and grading chemo-related side-effects has been compared prospectically . METHODS Patients received CDDP 75 mg/m ( 2 ) plus DCT 75 mg/m ( 2 ) on day 1 every weeks ( arm A ) or CDDP 80 mg/m ( 2 ) on day 1 plus VNR 30 mg/m ( 2 ) day 1 and 8 every 3 weeks ( arm B ) . G-CSF and/or EPO were employed as needed . Health-related QoL was assessed at entry and after every cycle by the EORTC-QLQ-C30 and LC13 questionnaires , toxicity by the NCI-NCCN CTC vs 2 , and intent-to-treat objective response by the Recist criteria . RESULTS The QoL questionnaires were completed by 37 pts ( 88 % ) in the DCT/CDDP arm and 39 pts ( 87 % ) in the VNR/CDDP one . Baseline mean scores and rates at which pts failed to complete QoL assessment were similar in the two arms . Global health status of the EORTC QLQ-C30 scale and specific symptoms control ( LC13 module ) improved during treatment without any statistically significant difference between the two arms . Emotional functioning remained stable in both groups during treatment , whereas physical and role improved slightly . In the DCT/CDDP arm 14 pts ( 33 % ; 95 % CL 24-40 % ) had PR , and 10 ( 24 % ) SD for a 57 % TGCR . In the VNR/CDDP arm 12 pts ( 27 % ) achieved PR , 18 ( 41 % ) SD a 68 % TGCR . Differences were not statistically significant . Median time-to-progression was 4.2 months in the DCT/CDDP arm and 4.5 months in the VNR/CDDP one , and median overall survival was 12.1 ( range 1-26+ months ) and 12.5 months ( range 1-28+ months ) for DCT/CDDP and VNR/CDDP arms , respectively . Febrile neutropenia rate was higher in the VNR/CDDP arm ( p=0.02 ) as well as G3-4 anemia ( p=0.005 ) and G-CSF/EPO use ( p=0.019 ) . CONCLUSIONS Global and specific health-related QoL data similar in both treatment groups with no statistically significant difference . Efficacy measures , overall response rate , time-to-progression and overall survival were equivalent in both arms . However , severe anemia and febrile neutropenia are statistically more frequent in the VNR/CDDP arm than in the DCT/CDDP one . These data should be considered in treatment decision-making for pts with advanced non-small-cell lung cancer and for the design of future trials with chemotherapy plus biologics .

First-line cisplatin with docetaxel

vinorelbine

Docetaxel ( DCT )

cisplatin ( CDDP ) doublet

vinorelbine ( VNR )

CDDP

VNR/CDDP

G-CSF

EPO

DCT/CDDP

VNR/CDDP

DCT/CDDP

VNR/CDDP

DCT/CDDP

VNR/CDDP

DCT/CDDP

VNR/CDDP

VNR/CDDP

DCT/CDDP

Quality of life ( QoL )

symptoms control

Health-related QoL

LC13 questionnaires

toxicity

objective response

QoL questionnaires

Global health status

EORTC QLQ-C30 scale

Emotional functioning

physical

role

PR

Median time-to-progression

overall survival

Febrile neutropenia rate

anemia

Global and specific health-related QoL

Efficacy measures

response rate

time-to-progression

overall survival

severe anemia

febrile neutropenia


Conservative surgery with and without radiotherapy in elderly patients with early-stage breast cancer : a prospective randomised multicentre trial . Breast conserving therapy ( BCT ) including postoperative irradiation of the remaining breast tissue is generally accepted as the best treatment for the majority of patients with early-stage breast cancer . The question is whether there is a necessity for irradiating all patients . Between 2001 and 2005 , 749 women aged 55-75 years with infiltrating breast carcinoma were randomly assigned to breast conservative surgery , with or without radiotherapy ( RT ) , to evaluate the incidence of in-breast recurrence ( IBR ) . After 5 years of median follow-up , the cumulative incidence of IBR was 2.5 % in the surgery-only arm and 0.7 % in the surgery plus RT arm . There are no differences in terms of overall survival and distant disease-free survival . The preliminary evaluation suggests that breast irradiation after conservative surgery can be avoided without exposing these patients to an increased risk of distant-disease recurrence . Prolonged follow-up will further clarify the possible risks and late sequelae potentially induced by breast RT .

Breast conserving therapy ( BCT )

radiotherapy

cumulative incidence of IBR

no differences

overall survival

distant disease-free survival

risk of distant-disease recurrence

elderly patients

breast cancer

breast cancer

women

55-75 years

breast carcinoma


In-season effect of short-term sprint and power training programs on elite junior soccer players . The aim of this study was to examine the effects of 2 in-season short-term sprint and power training protocols on vertical countermovement jump height ( with or without arms ) , sprint ( Sprint-15m ) speed , and agility ( Agility-15m ) speed in male elite junior soccer players . Twenty highly trained soccer players ( age 18.3 +/- 0.6 years , height 177 +/- 4 cm , body mass 71.4 +/- 6.9 kg , sum skinfolds 48.1 +/- 11.4 mm ) , members of a professional soccer academy , were randomly allocated to either a CONTRAST ( n = 10 ) or SPRINT ( n = 10 ) group . The training intervention consisted of 6 supervised training sessions over 7 weeks , targeting the improvement of the players ' speed and power . CONTRAST protocol consisted of alternating heavy-light resistance ( 15-50 % body mass ) with soccer-specific drills ( small-sided games or technical skills ) . SPRINT training protocol used line 30-m sprints ( 2-4 sets of 4 x 30 m with 180 and 90 seconds of recovery , respectively ) . At baseline no difference between physical test performance was evident between the 2 groups ( p > 0.05 ) . No time x training group effect was found for any of the vertical jump and Agility-15m variables ( p > 0.05 ) . A time x training group effect was found for Sprint-15m performance with the CONTRAST group showing significantly better scores than the SPRINT group ( 7.23 +/- 0.18 vs. 7.09 +/- 0.20 m.s , p < 0.01 ) . In light of these findings CONTRAST training should be preferred to line sprint training in the short term in young elite soccer players when the aim is to improve soccer-specific sprint performance ( 15 m ) during the competitive season .

short-term sprint

and

power training programs

short-term sprint

and

power training protocols

The training intervention

6 supervised training sessions

SPRINT training protocol

CONTRAST training

speed and power

physical test performance

vertical jump and Agility-15m variables

( p

soccer-specific sprint performance

( 15 m )

elite junior soccer players .

male

18.3 +/- 0.6 years


Dose-dependent effects of the CRF ( 1 ) receptor antagonist R317573 on regional brain activity in healthy male subjects . BACKGROUND Corticotropin-releasing factor receptor type 1 ( CRF ( 1 ) ) antagonists have been proposed as therapeutic agents in the treatment of mood and anxiety disorders although clinical evidence supporting their development and understanding of a dose-response relationship has been lacking . METHODS We tested two doses of the CRF ( 1 ) antagonist R317573 for effects on regional cerebral glucose metabolism ( rCMglu ) using [ ( 18 ) F ] fluoro-2-deoxy-D : -glucose ( FDG ) positron emission tomography ( PET ) following single-dose challenges in a double-blind , placebo-controlled , cross-over design , in 12 healthy male volunteers . RESULTS Single 30- and 200-mg doses of R317573 resulted in dose-related changes in rCMglu . Relative increases in rCMglu were observed in frontal cortical regions while relative decreases occurred in the putamen and right amygdala after both doses . Relative decreases occurred in cerebellum and right parahippocampal gyrus following the higher dose . CONCLUSIONS R317573 appears to produce acute dose-dependent changes in rCMglu . Effects occurred in regions that may be behaviorally relevant to mood and anxiety disorders . In some regions , these effects may be related to the receptor ( target ) density . Measuring acute effects on rCMglu with FDG-PET may offer a method for defining pharmacologically active doses for central nervous system targets for which selective radiotracers are lacking .

CRF ( 1 ) receptor antagonist R317573

CRF ( 1 ) antagonist R317573

rCMglu

FDG-PET

effects

rCMglu

rCMglu

healthy male subjects .

12 healthy male volunteers .


Bipolar transurethral resection of the prostate causes less bleeding than the monopolar technique : a single-centre randomized trial of 202 patients . OBJECTIVE To compare bipolar with the conventional monopolar transurethral resection of the prostate ( TURP ) for blood loss and speed of resection . PATIENTS AND METHODS In all , 202 consecutive patients from the hospital waiting list were randomized to undergo TURP using either a bipolar system ( Surgmaster TURis , Olympus , Tokyo , Japan ) or a monopolar system ( 24 F , Storz , Tübingen , Germany ) . The blood loss during and after surgery was measured using a photometer . Other variables compared included indices of resection speed and transfusion rate . RESULTS There were no statistically significant differences in operative duration , resection weight , resection speed or radicality of resection . However , the median blood loss was 235 mL for the bipolar and 350 mL for monopolar TURP ( P < 0.001 ) . The decrease in blood haemoglobin concentration during the day of surgery was smaller in the bipolar group ( 5.5 % vs 9.6 % P < 0.001 ) . Fewer patients were transfused with erythrocytes ( 4 % vs 11 % , P < 0.01 ) , which can be explained by the much lower 75th percentile for blood loss in the bipolar group ( at 472 vs 855 mL , respectively ) . CONCLUSIONS Bipolar TURP using the TURis system was performed with the same speed as monopolar TURP but caused 34 % less bleeding , the difference being greatest ( 81 % ) for the largest blood losses . Bipolar TURP also required fewer erythrocyte transfusions than the conventional monopolar technique .

monopolar technique :

bipolar

operative duration

resection weight

resection speed

radicality of resection

blood loss

blood haemoglobin concentration


Intravenous platelet blockade with cangrelor during PCI . BACKGROUND Intravenous cangrelor , a rapid-acting , reversible adenosine diphosphate ( ADP ) receptor antagonist , might reduce ischemic events during percutaneous coronary intervention ( PCI ) . METHODS In this double-blind , placebo-controlled study , we randomly assigned 5362 patients who had not been treated with clopidogrel to receive either cangrelor or placebo at the time of PCI , followed by 600 mg of clopidogrel . The primary end point was a composite of death , myocardial infarction , or ischemia-driven revascularization at 48 hours . Enrollment was stopped when an interim analysis concluded that the trial would be unlikely to show superiority for the primary end point . RESULTS The primary end point occurred in 185 of 2654 patients receiving cangrelor ( 7.0 % ) and in 210 of 2641 patients receiving placebo ( 8.0 % ) ( odds ratio in the cangrelor group , 0.87 ; 95 % confidence interval [ CI ] , 0.71 to 1.07 ; P=0.17 ) ( modified intention-to-treat population adjusted for missing data ) . In the cangrelor group , as compared with the placebo group , two prespecified secondary end points were significantly reduced at 48 hours : the rate of stent thrombosis , from 0.6 % to 0.2 % ( odds ratio , 0.31 ; 95 % CI , 0.11 to 0.85 ; P=0.02 ) , and the rate of death from any cause , from 0.7 % to 0.2 % ( odds ratio , 0.33 ; 95 % CI , 0.13 to 0.83 ; P=0.02 ) . There was no significant difference in the rate of blood transfusion ( 1.0 % in the cangrelor group and 0.6 % in the placebo group , P=0.13 ) , though major bleeding on one scale was increased in the cangrelor group , from 3.5 % to 5.5 % ( P < 0.001 ) , because of more groin hematomas . CONCLUSIONS The use of periprocedural cangrelor during PCI was not superior to placebo in reducing the primary end point . The prespecified secondary end points of stent thrombosis and death were lower in the cangrelor group , with no significant increase in the rate of transfusion . Further study of intravenous ADP blockade with cangrelor may be warranted . ( ClinicalTrials.gov number , NCT00385138 . )

cangrelor

cangrelor

cangrelor

placebo

clopidogrel

cangrelor

placebo

cangrelor

cangrelor

placebo

cangrelor

cangrelor

ADP blockade with cangrelor

composite of death

primary end point

rate of stent thrombosis

rate of death from any cause

rate of blood transfusion

major bleeding

groin hematomas .


Effects of topical boswellic acid on photo and age-damaged skin : clinical , biophysical , and echographic evaluations in a double-blind , randomized , split-face study . Boswellic acids ( BAs ) are pentacyclic triterpenes with strong anti-inflammatory activity ; their most important source is the extract of the gum resin of Boswellia serrata , a tropical tree that grows in India and Africa . In the present randomized , double-blind , split-face , comparative study we have assessed efficacy , tolerability , and safety of a base cream containing 0.5 % BAs as compared to the same cream without these active ingredients in the treatment of clinical manifestations of photoaging of facial skin . Fifteen female volunteers were enrolled ; they applied creams once daily for 30 days . At baseline , at the end of the treatment , and after a 2-month follow-up , clinical findings were assessed according to the Dover classification scale for photoaging and by biophysical and ecographic measurements . We registered a significant improvement of tactile roughness and fine lines in the half side of the face treated with BAs ; noninvasive instrumental diagnostic investigations showed an improvement of elasticity , a decrease of sebum excretion , and a change of echographic parameters suggesting a reshaping of dermal tissue . The treatment was always well tolerated without adverse effects . The present findings seem to indicate that the topical application of BAs may represent a suitable treatment option for selected features of skin photoaging .

topical boswellic acid

Boswellic acids ( BAs )

base cream containing 0.5 % BAs

BAs

BAs

clinical

biophysical

echographic evaluations

efficacy , tolerability , and safety

biophysical and ecographic measurements

tactile roughness and fine lines

elasticity

sebum excretion

reshaping of dermal tissue

tolerated

adverse effects


Effects of fluoride and chlorhexidine on the microflora of dental root surfaces and progression of root-surface caries . The effects of fluoride and chlorhexidine varnishes on the microflora of dental root surfaces and on the progression of root-surface caries were studied . Forty-four patients , surgically treated for advanced periodontal disease , were distributed at random among three groups . All patients received a standardized preventive treatment . Furthermore , the dentition of the patients in the two experimental groups was treated , at three-month intervals , with chlorhexidine and fluoride varnish , respectively . Patients in the control group received no additional treatment . In the experimental groups , plaque samples were collected from selected sound and carious root surfaces at baseline and at three , six , and nine months after the onset of the study . The presence of root-surface caries was scored at baseline and after one year . In addition , the texture , depth , and color of the root-surface lesions were monitored . Mutans streptococci on root surfaces were suppressed significantly ( p less than 0.05 ) during the whole experimental period in the chlorhexidine varnish group , but not in the fluoride varnish group . A non-significant increase in the number of Actinomyces viscosus/naeslundii was noted after treatment with chlorhexidine and fluoride varnish . The increase in the number of decayed and filled root surfaces after one year was significantly lower in the experimental groups than in the control group . After treatment with chlorhexidine varnish , significantly more initial root-surface lesions had hardened than in the other groups .

fluoride

chlorhexidine

fluoride

chlorhexidine

chlorhexidine

fluoride

control group

chlorhexidine

fluoride

chlorhexidine

fluoride

chlorhexidine

microflora of dental root surfaces


Effect of device-guided breathing exercises on blood pressure in patients with hypertension : a randomized controlled trial . OBJECTIVE Hypertension is a chronic disorder with a high prevalence worldwide . Despite considerable efforts , it is sometimes hard to reach treatment goals for blood pressure ( BP ) with classical treatment options . Reducing breathing frequency has been advocated as a method to reduce BP . METHODS A randomized , single-blind , controlled trial was conducted in 30 non-diabetic patients with hypertension over a period of 9 weeks to evaluate the effect of a device that helps to slow breathing ( Resperate ) on BP and quality of life ( QoL ) . The control group listened to music and used no other therapeutic device . RESULTS There was no significant difference in change in BP between intervention and control ; BP -4.2 mmHg ( 95 % CI -12.4 to 3.9 ) /-2.6 mmHg ( 95 % CI -8.4 to 3.3 ) . This result did not alter in post hoc analyses , when patients not achieving target breathing frequency ( < 10 breaths/min ) or non-compliant patients were excluded . QoL did not change over time . CONCLUSIONS We found no effect of the Resperate on BP or QoL compared with the control group . We conclude that , at this moment , this device has no added value in the treatment of hypertension .

device-guided breathing exercises

blood pressure

blood pressure ( BP )

BP

slow breathing

BP

quality of life ( QoL )

BP

BP

target breathing frequency

QoL

BP

QoL

hypertension

non-diabetic patients with hypertension


A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome . California Collaborative Treatment Group . BACKGROUND AND METHODS In patients with the acquired immunodeficiency syndrome ( AIDS ) , the rate of relapse after primary treatment for cryptococcal meningitis remains high . We conducted a controlled , double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole . At entry into the study , all participants had sterile cultures of cerebrospinal fluid , blood , and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis . The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy . The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase . RESULTS Of 84 patients initially enrolled , 16 ( 19 percent ) were found to have silent , persistent infection on the basis of cultures that became positive after entry into the study ; 7 other patients were lost to follow-up shortly after entry . Of the remaining 61 patients , 10 of 27 assigned to placebo ( 37 percent ) and 1 of 34 assigned to fluconazole ( 3 percent ) had a recurrence of cryptococcal infection at any site ( difference in risk , 34 percent ; 95 percent confidence interval , 15 to 53 ) . Of the 11 recurrent infections , 7 were detected in urine obtained after prostatic massage . There were four recurrent meningeal infections in the patients taking placebo , but none in those taking fluconazole ( mean duration of follow-up , 164 days ) ( P = 0.03 ) . In multivariate analyses , the best predictors of recurrence-free survival were fluconazole treatment ( P = 0.02 ; relative hazard , 13.2 ) , a lower serum cryptococcal-antigen titer ( P = 0.05 ; relative hazard , 1.2 ) , and more prolonged primary therapy with flucytosine ( P = 0.09 ; relative hazard , 1.1 ) . Survival and toxicity were similar in the two maintenance-treatment groups . CONCLUSIONS In patients with AIDS , silent persistent infection is common after clinically successful treatment for cryptococcal meningitis . Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection .

placebo-controlled

fluconazole

fluconazole

placebo

fluconazole

placebo

fluconazole

placebo

fluconazole

fluconazole

fluconazole

recurrent meningeal infections

recurrence-free survival

Survival

toxicity

cryptococcal meningitis

infection

AIDS


Routine antibiotic use in preterm neonates : a randomised controlled trial . The immature immune system of preterm neonates puts them at higher risk of neonatal sepsis . We conducted a part-blinded randomised controlled trial to compare the effect of routine antibiotic treatment on the incidence of clinical sepsis in preterm neonates . Preterm neonates without other risk factors for infection admitted in the first 12h of life were randomised to receive routine antibiotics or to a control group ( no antibiotics unless clinically indicated ) . The primary outcome variable was the incidence of clinical sepsis . Secondary outcomes were the incidence of positive blood cultures , necrotising enterocolitis ( NEC ) stage II or III , or death , and the duration of hospital stay . The incidence of clinical sepsis was comparable in both groups ( intervention 31.9 % , control 25.4 % ; P=0.392 ) . Mortality was equivalent in both groups . The control group had significantly more positive blood cultures ( P=0.002 ) . The incidence of NEC and the duration of hospital stay were comparable in both groups . In low risk preterm neonates we found no evidence that routine antibiotic use has a protective effect .

Routine antibiotic use

routine antibiotic treatment

routine antibiotics

control group

no antibiotics

antibiotic

incidence of clinical sepsis

incidence of positive blood cultures

death

the duration of hospital stay

incidence of clinical sepsis

Mortality

blood cultures

incidence of NEC

the duration of hospital stay

preterm neonates

preterm

neonates

Preterm

neonates

risk factors for infection

first 12h of life


The effect of posture on Cheyne-Stokes respirations and hemodynamics in patients with heart failure . STUDY OBJECTIVES Cheyne-Stokes respirations occur in 40 % of patients with heart failure . Orthopnea is a cardinal symptom of heart failure and may affect the patient 's sleeping angle . The objective of this study was to assess the respiratory and hemodynamic response to sleeping angle in a group of subjects with stable heart failure . DESIGN Twenty-five patients underwent overnight polysomnography with simultaneous and continuous impedance cardiographic monitoring . Sleeping polysomnographic and impedance cardiographic data were recorded . SETTING The study was conducted in a sleep center . PATIENTS All 25 patients had clinically stable heart failure and left ventricular ejection fractions < 40 % . INTERVENTIONS The patients slept at 0 degrees , 15 degrees , 30 degrees , and 45 degrees in random order . MEASUREMENTS AND RESULTS Seventeen patients had Cheyne-Stokes apneas ( index > 5/h ) and 23 patients had hypopneas ( index > 5/h ) . The hypopnea index showed no response to sleeping angle . The Cheyne-Stokes apnea index decreased with increasing sleeping angle ( P < 0.001 ) . This effect was seen only during supine sleep and non-rapid eye movement sleep and was absent in non-supine sleep , rapid eye movement sleep , and during periods of wakefulness . Thoracic fluid content index and left ventricular hemodynamics measured by impedance cardiography showed no response to sleeping angle . CONCLUSIONS Changing the heart failure patient 's sleeping angle from 0 degrees to 45 degrees results in a significant decrease in Cheyne-Stokes apneas . This decrease occurs on a constant base of hypopneas . The changes in Cheyne-Stokes apneas are not related to changes in lung congestion and left ventricular hemodynamics .

posture

sleeping angle

effect

Cheyne-Stokes apneas

hypopneas

hypopnea index

Cheyne-Stokes apnea index

heart failure

heart failure

Twenty-five

clinically stable heart failure

ventricular ejection fractions < 40 %


Tetracaine ( ametop ) compared to placebo for reducing pain associated with intramuscular injection of palivizumab ( synagis ) . Infants receive many painful immunizations before they are 2 years old . The purpose of this study was to evaluate if topical tetracaine reduces the pain of intramuscular palivizumab compared to placebo . There were two study injections , one with tetracaine and one with placebo . Pain was scored by their parents and a pediatric nurse . Topical tetracaine was not associated with a significant reduction in pain score , although it did lead to faster recovery times . Additional pain-reduction strategies are required .

Tetracaine ( ametop )

topical tetracaine

palivizumab

placebo .

tetracaine

placebo

tetracaine

Pain

pain score

recovery

Infants

pain of intramuscular palivizumab


Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) affects event-related potential measures of novelty processing in autism . In our previous study on individuals with autism spectrum disorder ( ASD ) ( Sokhadze et al. , Appl Psychophysiol Biofeedback 34:37-51 , 2009a ) we reported abnormalities in the attention-orienting frontal event-related potentials ( ERP ) and the sustained-attention centro-parietal ERPs in a visual oddball experiment . These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli . In the present study we examine the effects of low-frequency , repetitive Transcranial Magnetic Stimulation ( rTMS ) on novelty processing as well as behavior and social functioning in 13 individuals with ASD . Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex ( DLFPC ) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons . We expected to find post-TMS differences in amplitude and latency of early and late ERP components . The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism . After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets ; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli . Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli . Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings . These results indicate a significant change in early , middle-latency and late ERP components at the frontal , centro-parietal , and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment . Overall , our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders .

low-frequency rTMS

increased responses to relevant stimuli

autism

ASD


Randomized , controlled trial of an intervention for toddlers with autism : the Early Start Denver Model . OBJECTIVE To conduct a randomized , controlled trial to evaluate the efficacy of the Early Start Denver Model ( ESDM ) , a comprehensive developmental behavioral intervention , for improving outcomes of toddlers diagnosed with autism spectrum disorder ( ASD ) . METHODS Forty-eight children diagnosed with ASD between 18 and 30 months of age were randomly assigned to 1 of 2 groups : ( 1 ) ESDM intervention , which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents for 2 years ; or ( 2 ) referral to community providers for intervention commonly available in the community . RESULTS Compared with children who received community-intervention , children who received ESDM showed significant improvements in IQ , adaptive behavior , and autism diagnosis . Two years after entering intervention , the ESDM group on average improved 17.6 standard score points ( 1 SD : 15 points ) compared with 7.0 points in the comparison group relative to baseline scores . The ESDM group maintained its rate of growth in adaptive behavior compared with a normative sample of typically developing children . In contrast , over the 2-year span , the comparison group showed greater delays in adaptive behavior . Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder , not otherwise specified , than the comparison group . CONCLUSIONS This is the first randomized , controlled trial to demonstrate the efficacy of a comprehensive developmental behavioral intervention for toddlers with ASD for improving cognitive and adaptive behavior and reducing severity of ASD diagnosis . Results of this study underscore the importance of early detection of and intervention in autism .

intervention

Early Start Denver Model ( ESDM )

ESDM intervention

ESDM

efficacy

rate of growth in adaptive behavior

change in diagnosis

toddlers

autism

toddlers

autism spectrum disorder ( ASD )

Forty-eight

children

ASD

18 and 30 months of age

toddlers

ASD


Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder . OBJECTIVE The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these . METHODS This 8-week , double-blind , randomized , placebo-controlled , parallel-group study was conducted of children and adolescents ( aged 6-17 years ) with autistic disorder . Patients were randomly assigned ( 1:1 ) to flexibly dosed aripiprazole ( target dosage : 5 , 10 , or 15 mg/day ) or placebo . Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression-Improvement score ( CGI-I ) . Safety and tolerability were also assessed . RESULTS Ninety-eight patients were randomly assigned to receive placebo ( n = 51 ) or aripiprazole ( n = 47 ) . Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8 . Aripiprazole demonstrated significantly greater global improvements than placebo , as assessed by the mean CGI-I score from week 1 through week 8 ; however , clinically significant residual symptoms may still persist for some patients . Discontinuation rates as a result of adverse events ( AEs ) were 10.6 % for aripiprazole and 5.9 % for placebo . Extrapyramidal symptom-related AE rates were 14.9 % for aripiprazole and 8.0 % for placebo . No serious AEs were reported . Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8 . CONCLUSIONS Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated .

Aripiprazole

aripiprazole

flexibly dosed aripiprazole

placebo

placebo

aripiprazole

placebo

aripiprazole

placebo

aripiprazole

placebo

Aripiprazole

irritability

short-term efficacy and safety

irritability

Safety and tolerability

CGI-I score

residual symptoms

Extrapyramidal symptom-related AE rates

weight gain

children and adolescents

autistic disorder

children and adolescents

autistic disorder

children

adolescents ( aged 6-17 years )

Ninety-eight patients

children

adolescents


The role of ethnic matching between patient and provider on the effectiveness of brief alcohol interventions with Hispanics . BACKGROUND Evaluating the effectiveness of treatments such as brief alcohol interventions among Hispanics is essential to effectively addressing their treatment needs . Clinicians of the same ethnicity as the client may be more likely to understand the culture-specific values , norms , and attitudes and , therefore , the intervention may be more effective . Thus , in cases in which Hispanic patients were provided intervention by a Hispanic clinician improved drinking outcomes were expected . METHODS Patients were recruited from an urban Level I Trauma following screening for an alcohol-related injury or alcohol problems . Five hundred thirty-seven Hispanics were randomly assigned to brief intervention or treatment as usual . Hierarchical linear modeling was used to determine the effects of ethnic match on drinking outcomes including volume per week , maximum amount , and frequency of 5 or more drinks per occasion . Analyses controlled for level of acculturation and immigration status . RESULTS For Hispanics who received brief motivational intervention , an ethnic match between patient and provider resulted in a significant reduction in drinking outcomes at 12-month follow-up . In addition , there was a tendency for ethnic match to be most beneficial to foreign-born Hispanics and less acculturated Hispanics . CONCLUSION As hypothesized , an ethnic match between patient and provider significantly enhanced the effectiveness of brief intervention among Hispanics . Ethnic concordance between patient and provider may have impacted the effectiveness of the intervention through several mechanisms including cultural scripts , ethnic-specific perceptions pertaining to substance abuse , and ethnic-specific preferred channels of communication .

brief alcohol interventions

brief intervention

treatment as usual

effectiveness

beneficial

effectiveness

effectiveness

Hispanics

Hispanics

Hispanic patients

Five hundred thirty-seven

Hispanics

Hispanics


Comparison between obtained mydriasis in type 2 diabetics and non-diabetic patients . BACKGROUND/AIMS To evaluate and compare obtained mydriasis with phenylephrine 10 % associated with tropicamide 1 % in type 2 diabetics and non-diabetic patients . METHODS A total of 50 patients ( 100 eyes ) scheduled for fundoscopy were dilated with phenylephrine 10 % and yropicamide 1 % ( group 0 : n = 20 type 2 diabetic patients , 40 eyes , and group 1 : n = 30 non-diabetic patients , 60 eyes ) . Only one drop per eye of each drug was administered . In both groups , pupil diameter was measured after 40 minutes of eye drops instillation . RESULTS Both groups were similar regarding age ( p = 0.06 , Mann-Whitney test ) . Mean pupil diameter in group 0 was 8.57 and 8.73 in group 1 . There was no statistic difference between both groups ( p = 0.44 ) . Pupil diameter was greater than 7 mm in all patients ( 100 % ) . CONCLUSION When an appropriate drug combination is used , diabetic patients can achieve mydriasis as satisfactory as non-diabetic patients , allowing adequate fundus examination and/or retinopathy treatment .

phenylephrine

tropicamide

phenylephrine 10 % and yropicamide 1 %

pupil diameter

Mean pupil diameter

statistic difference

mydriasis

phenylephrine


Different therapeutic modalities for treatment of melasma . BACKGROUND Chemical peels and topical depigmenting agents have become a popular modality in the treatment of melasma . AIMS To compare the clinical efficacy of trichloroacetic acid peel 20 % vs . Jessner 's solution peel vs. the topical mixture of hydroquinone 2 % and kojic acid . PATIENTS AND METHODS Forty five patients with melasma were randomly assigned into three groups of fifteen patients each . Group A received Jessner 's solution peel , group B received trichloroacetic acid peel 20 % , and group C received topical hydroquinone 2 % and kojic acid . All patients were seen in follow-up period after 16 weeks ; clinical evaluation using Melasma Area and Severity Index ( MASI ) score and photography were recorded before and after treatment and after 16 weeks . RESULTS There was a decrease in MASI score in all three groups after treatment and after follow-up period but after treatment MASI score was statistically significantly lower in group A than group C ( P = 0.01 ) , and it was also statistically significantly lower in group B than group C ( P < 0.001 ) but there was no statistically significant difference between groups A and B . After the follow-up period , MASI score was statistically significantly lower in group A than group C ( P < 0.001 ) , statistically significantly lower in group B than group C ( P < 0.001 ) , and statistically significantly lower in group B than group A ( P = 0.035 ) . The statistical analysis was done through one-way anova followed by least significant difference ( LSD ) . CONCLUSION Trichloroacetic acid 20 % showed better results than Jessner 's solution as peeling agent and hydroquinone 2 % with kojic acid as a topical agent in the treatment of melasma .

Chemical peels

topical depigmenting agents

trichloroacetic acid peel 20 % vs

Jessner 's solution peel

trichloroacetic acid peel 20 %

topical hydroquinone 2 % and kojic acid

Trichloroacetic acid 20 %

Jessner 's solution

hydroquinone 2 % with kojic acid

clinical efficacy

MASI score

MASI score

MASI score

Forty five

melasma


A prospective , randomized trial of nerve monitoring of the external branch of the superior laryngeal nerve during thyroidectomy under local/regional anesthesia and IV sedation . BACKGROUND The aim of this study was to assess the impact of the neuromonitoring of the external branch of the superior laryngeal nerve ( EBSLN ) on the voice quality after mini-incision thyroidectomy under local/regional anesthesia and intravenous sedation . METHODS Patients undergoing mini-incision thyroidectomy under local anesthesia were prospectively randomized for either nerve monitoring of the EBSLN ( group 1 ) or no nerve monitoring ( group 2 ) . Voice and swallowing assessment were obtained by using the Voice Handicap Index-10 ( VHI-10 ) and the Reflux Symptom Index questionnaires ( RSI ) before surgery and at 3 weeks and 3 months after surgery . RESULTS Recruitment led to 22 patients in group 1 and 25 patients in group 2 . The rate of visualized EBSLN was higher in group 1 ( 66 % vs 21 % ; P = .003 ) . Contrary to group 1 , in group 2 , the median total VHI-10 score was significantly higher 3 months after surgery ( P = .034 ) compared with preoperatively , indicating a subjective voice handicap . In both groups , there was no difference in median total RSI score before surgery or at 3 weeks and 3 months after surgery . CONCLUSION Nerve monitoring aids in the visualization of the EBSLN during mini-incision thyroidectomy under local/regional anesthesia and leads to an improvement in patient-assessed voice quality after surgery but does not impact swallowing .

thyroidectomy

mini-incision thyroidectomy

nerve monitoring of the EBSLN

or no nerve monitoring

mini-incision thyroidectomy

local/regional anesthesia

voice quality

Voice

swallowing

Voice Handicap Index-10 ( VHI-10 )

rate of visualized EBSLN

median total VHI-10 score

median total RSI score

EBSLN

voice quality

swallowing

mini-incision thyroidectomy

local anesthesia


The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia : overall results and results in genotypic subgroups defined by mutations in NPM1 , FLT3 , and CEBPA . We investigated the benefit of adding all-trans retinoic acid ( ATRA ) to chemotherapy for younger patients with nonacute promyelocytic acute myeloid leukemia and high-risk myelodysplastic syndrome , and considered interactions between treatment and molecular markers . Overall , 1075 patients less than 60 years of age were randomized to receive or not receive ATRA in addition to daunorubicin/Ara-C/thioguanine chemotherapy with Ara-C at standard or double standard dose . There were data on FLT3 internal tandem duplications and NPM1 mutations ( n = 592 ) , CEBPA mutations ( n = 423 ) , and MN1 expression ( n = 195 ) . The complete remission rate was 68 % with complete remission with incomplete count recovery in an additional 16 % ; 8-year overall survival was 32 % . There was no significant treatment effect for any outcome , with no significant interactions between treatment and demographics , or cytarabine randomization . Importantly , there were no interactions by FLT3/internal tandem duplications , NPM1 , or CEBPA mutation . There was a suggestion that ATRA reduced relapse in patients with lower MN1 levels , but no significant effect on overall survival . Results were consistent when restricted to patients with normal karyotype . ATRA has no overall effect on treatment outcomes in this group of patients . The study did not identify any subgroup of patients likely to derive a significant survival benefit from the addition of ATRA to chemotherapy .

all-trans retinoic acid ( ATRA )

chemotherapy

ATRA

ATRA

ATRA to chemotherapy

complete remission rate

8-year overall survival

FLT3/internal tandem duplications

CEBPA mutation

relapse

overall survival .

younger

mutations in NPM1 , FLT3 , and CEBPA

younger

high-risk myelodysplastic syndrome

less than 60 years of age


The efficacy of melatonin for sleep problems in children with autism , fragile X syndrome , or autism and fragile X syndrome . STUDY OBJECTIVE To determine the efficacy of melatonin on sleep problems in children with autistic spectrum disorder ( ASD ) and fragile X syndrome ( FXS ) . METHODS A 4-week , randomized , double blind , placebo-controlled , crossover design was conducted following a 1-week baseline period . Either melatonin , 3 mg , or placebo was given to participants for 2 weeks and then alternated for another 2 weeks . Sleep variables , including sleep duration , sleep-onset time , sleep-onset latency time , and the number of night awakenings , were recorded using an Actiwatch and from sleep diaries completed by parents . All participants had been thoroughly assessed for ASD and also had DNA testing for the diagnosis of FXS . RESULTS Data were successfully obtained from the 12 of 18 subjects who completed the study ( 11 males , age range 2 to 15.25 years , mean 5.47 , SD 3.6 ) . Five participants met diagnostic criteria for ASD , 3 for FXS alone , 3 for FXS and ASD , and 1 for fragile X premutation . Eight out of 12 had melatonin first . The conclusions from a nonparametric repeated-measures technique indicate that mean night sleep duration was longer on melatonin than placebo by 21 minutes ( p = .02 ) , mean sleep-onset latency was shorter by 28 minutes ( p = .0001 ) , and mean sleep-onset time was earlier by 42 minutes ( p = .02 ) . CONCLUSION The results of this study support the efficacy and tolerability of melatonin treatment for sleep problems in children with ASD and FXS .

melatonin

melatonin

melatonin

placebo

melatonin

melatonin

placebo

melatonin

Sleep variables

mean night sleep duration

mean sleep-onset latency

mean sleep-onset time

sleep problems

children

2 to 15.25 years

Five

Eight


Evaluation of reducing postoperative hip precautions in total hip replacement : a randomized prospective study . Currently , many rehabilitation protocols for total hip replacements ( THRs ) include activity restrictions to prevent postoperative dislocation . There is increasing demand for more efficient and safe rehabilitation protocols . This randomized prospective study evaluates the need for hip restrictions following a modified anterolateral procedure . From 2004 to 2008 , 81 patients seeking elective THRs were randomly assigned into a standard rehabilitation group or an early rehabilitation group . The standard group included restrictions to avoid hip flexion > 90 degrees and avoidance of riding in a car for the first postoperative month . The early group had no flexion or car riding restrictions . Forty-three patients were in the standard group and 38 patients were in the early group . There were no significant demographic differences between the 2 groups . All patients completed the Short Form 12-question Health Survey and Harris Hip Score preoperatively and at 4 weeks , 1 month , 3 months , and 1 year postoperatively . The time-points at which the patient first drove and ambulated with a cane , without a cane , and without a limp were also collected . No incidents of dislocation occurred . Patients in the early group were faster to ambulate with only a cane ( P=.03 ) , without a cane ( P < .001 ) , and without a limp ( P=.003 ) . They also drove earlier ( P=.02 ) . Pace of recovery was the only significant difference between the 2 groups . The early rehabilitation protocol increases the pace of recovery compared to a pathway with hip precautions without increasing complications .

no flexion or car riding restrictions

early rehabilitation protocol

dislocation

ambulate with only a cane

without a cane

without a limp

drove

Pace of recovery

complications

total hip replacement

THRs

Forty-three


Repeatability and protocol comparability of presyncopal symptom limited lower body negative pressure exposures . Data on repeatability and comparability of different presyncopal symptom-limited lower body negative pressure ( PSL-LBNP ) exposure protocols , while scarce , are critical to the interpretation of studies using PSL-LBNP methods . To investigate if PSL-LBNP tolerance , heart rate , and blood pressure were repeatable , 11 subjects were exposed to 4 PSL-LBNP tests ; each test occurring at the same time of day , separated by at least 72 h , and using the same protocol . No significant differences were found in either the heart rate or blood pressure responses to the PSL-LBNP or the tolerance indices ( cumulative stress index ; maximum negative pressure tolerated ; and duration of negative pressure exposure ) . To study the comparability of different PSL-LBNP protocols , nine subjects were exposed randomly to five PSL-LBNP tests using protocols that varied in stage duration but not pressure profile . The protocols had 1- , 3- , 5- , 7- , or 9-min stage durations . These PSL-LBNP exposures were conducted at the same time of day and separated by at least 72 h. While no differences were noted in either the response pattern or magnitude of heart rate or blood pressure to the differing protocols , the cumulative stress index and the duration of negative pressure exposure varied proportionally with the length of the stage durations . With the exception of the 1-min protocol , the maximum negative pressure tolerated did not vary regardless of the protocol used . ( ABSTRACT TRUNCATED AT 250 WORDS )

presyncopal

limited lower body negative pressure

PSL-LBNP

PSL-LBNP tests

PSL-LBNP

PSL-LBNP

PSL-LBNP

PSL-LBNP

heart rate or blood pressure responses

tolerance indices

heart rate or blood pressure

cumulative stress index

nine