Combination therapy with methotrexate and hydroxychloroquine for rheumatoid arthritis increases exposure to methotrexate . OBJECTIVE To examine the bioavailability of methotrexate ( MTX ) in the presence of hydroxychloroquine ( HCQ ) , and vice versa , to determine a possible pharmacokinetic explanation for the observation that combination treatment of rheumatoid arthritis with MTX and HCQ has been shown , clinically , to be more potent than MTX used alone . METHODS In a randomized crossover study , 10 healthy subjects received , on each of 5 dosing occasions , MTX alone as tablets or intravenous solution , HCQ alone as a tablet or oral solution , or a coadministered dose of MTX tablets with an HCQ tablet . The area under the concentration-time curve ( AUC ) was determined for each subject , on each dosing occasion , for each compound . RESULTS The mean AUC for MTX was increased ( p = 0.005 ) and the maximum MTX concentration ( Cmax ) decreased ( p = 0.025 ) when MTX was coadministered with HCQ , compared to MTX administered alone . The time to reach Cmax for MTX administration , tmax , was also increased during the coadministration with HCQ ( p = 0.072 ) . The AUC of HCQ showed no significant difference ( p = 0.957 ) between any of the dosing occasions . CONCLUSION These results may explain the increased potency of the MTX-HCQ combination over MTX as a single agent and also the sustained effects of MTX when administered with HCQ . In addition , the reduced Cmax of MTX observed during the coadministration may explain diminution of acute liver adverse effects . Extra vigilance for MTX adverse effects during combination therapy with HCQ is recommended , especially if renal function is known to be decreased .

methotrexate and hydroxychloroquine

methotrexate ( MTX )

hydroxychloroquine ( HCQ )

MTX

HCQ

MTX

MTX

HCQ

MTX

HCQ

MTX

MTX

MTX

HCQ

MTX

HCQ

HCQ

MTX-HCQ

MTX

MTX

HCQ

MTX

MTX

HCQ

concentration-time curve ( AUC )

mean AUC for MTX

maximum MTX concentration ( Cmax )

rheumatoid arthritis

healthy


Home sleep studies in the assessment of sleep apnea/hypopnea syndrome . OBJECTIVE To determine the clinical utility of a limited sleep-recording device used unsupervised in the patient 's home , compared with in-laboratory , fully supervised polysomnography for the diagnosis of sleep apnea/hypopnea syndrome ( SAHS ) , and to assess its impact on costs . DESIGN Prospective case study . SETTING The sleep-disorders unit of a tertiary referral university hospital . PATIENTS Fifty-five patients suspected of having SAHS and living within 30 km of our laboratory . METHODS Patients were studied first in their homes with the limited sleep-recording device . Polysomnography was performed within 30 days of the first study . Both studies were read by independent investigators blinded to the results of the other study . Diagnoses and therapeutic decisions regarding the use of continuous positive airway pressure obtained from the home and laboratory studies were compared . Agreement between the home and laboratory study recordings was also assessed using receiver operating characteristic ( ROC ) curves and Bland-Altman analysis . One half of the home studies were randomly assigned to be performed with a sleep technician 's set up of the equipment in the patient 's home ( group 1 ) , and the other half with the patient 's own setup of the sleep-recording device ( group 2 ) , after an instruction period in the hospital . An economic analysis was performed , considering the cost of repeating studies in cases with faulty or inconclusive home studies ( these patients should undergo polysomnography as a second step ) . RESULTS Seven percent of the home studies in group 1 , and 33 % in group 2 produced no interpretable data because of artifacts ( p < 0.05 ) . Sixteen percent of the home study findings were inconclusive . The diagnosis obtained from the limited sleep-recording device and polysomnography agreed in 75 % of the interpretable home studies ( 89 % , if inconclusive home studies were excluded ) . The area under the ROC curve for the home study-derived parameters was between 0.84 and 0.89 , compared with polysomnography . There was no bias between home and polysomnography studies in the Bland-Altman plot . The cost per study of home study recordings was less expensive than that of polysomnography ( 143.86 euros ) , either with ( 93.08 euros ) or without ( 129.97 euros ) intervention of the technician in the patient 's home . CONCLUSION Home sleep studies are a viable form of diagnosing SAHS , and are less expensive than polysomnography . Intervention of a sleep technician in the patient 's home was the least expensive strategy , because of the high percentages of faulty studies with the patient 's own setup of the equipment , when using the limited sleep-recording device .

Home sleep studies

limited sleep-recording device .

Polysomnography

polysomnography

Home sleep

sleep apnea/hypopnea syndrome

sleep apnea/hypopnea syndrome ( SAHS )

costs

area under the ROC curve

cost per study of home study recordings

expensive

expensive

sleep apnea/hypopnea syndrome .

sleep apnea/hypopnea syndrome ( SAHS )

Fifty-five patients


The lunar stent characteristics and clinical results . One of the frequent long-term complications after stent implantation is restenosis due to the building up of a neointima within the artery , as well as endovascular hyperplasia ( tissue growth ) . The interesting feature of the Lunar stent from Inflow Dynamics is that it is coated with a layer of iridium oxide . The iridium oxide coating is believed to reduce restenosis by decreasing the inflammatory response to the stent via its antioxidant action . The MOONLIGHT ( Multicenter Objective ObservatioNal Lunar Iridiumoxide intimal GrowtH Trial ) study was carried out to evaluate the immediate outcome and long-term angiographic success after implantation of Lunar stents . Between March 2001 and November 2001 , 87 patients with 99 lesions were enrolled in this study and were treated with 12 and 16 mm long iridium-oxide coated Lunar stents . Delivery of the Lunar stent was successful in most lesions and the optimal radiopacity facilitated optimal stent positioning with optimal immediate clinical and angiographic results is an unselected patient and lesion population . Preliminary clinical and angiographic follow-up show a low rate of cardiac events at 6 months ( 16.1 % MACE ) and a moderate hyperplastic response .

lunar stent

stent implantation

Lunar stent from Inflow Dynamics

iridium oxide

Lunar Iridiumoxide

implantation of Lunar stents

iridium-oxide

coated Lunar stents

Lunar stent

restenosis

inflammatory response

stent positioning

rate of cardiac events

hyperplastic response

lunar stent

lesions


Randomized trial of adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma . The aim of this study was to demonstrate the interest of using tumor-infiltrating lymphocytes ( TIL ) as adjuvant therapy for stage III ( regional lymph nodes ) melanoma . After lymph node excision , patients without any detectable metastases were randomly assigned to receive either TIL plus interleukin-2 ( IL-2 ) for 2 months , or IL-2 only . The primary endpoint was determination of the duration of the relapse-free interval . Eighty-eight patients determined as eligible for treatment were enrolled in the study . After a median follow-up of 46.9 months , for the study population the analysis did not show a significant extension of the relapse-free interval or overall survival . However , a significant interaction ( P < 0.001 ) was found between the treatment and the number of invaded lymph nodes . In the group with only one invaded lymph node , the estimated relapse rate was significantly lower ( P ( adjusted ) =0.0285 ) and the overall survival was increased ( P ( adjusted ) =0.039 ) in the TIL+IL-2 arm compared with the IL-2 only arm . No differences between the two arms , either as regards the duration of disease-free survival or overall survival , were noted in the group with more than one invaded lymph node whatever the number of invaded lymph nodes . Treatment was compatible with normal daily activity . This study demonstrates for the first time that the efficiency of TIL in stage III melanoma ( AJCC ) is directly related to the number of invaded lymph nodes , indicating that tumor burden might be a crucial factor in the efficacy and/or in vitro expansion of T cells specific for autologous tumor antigen , a finding which could be of value in future vaccine development for the treatment of melanoma .

tumor-infiltrating lymphocytes

tumor-infiltrating lymphocytes ( TIL )

TIL plus interleukin-2 ( IL-2 )

TIL

duration of the

relapse-free interval

relapse-free interval

overall survival

number of invaded lymph nodes

estimated

relapse rate

overall survival

duration of disease-free survival

overall survival

stage III melanoma

metastases

Eighty-eight


Transurethral prostate resection and bleeding : a randomized , placebo controlled trial of role of finasteride for decreasing operative blood loss . PURPOSE Bleeding associated with transurethral prostate resection can often be significant and lead to increased morbidity and occasionally mortality . It has been shown that finasteride decreases bleeding in patients with hematuria of prostatic origin . We hypothesized that bleeding in patients undergoing transurethral prostate resection could be decreased by giving finasteride for 2 weeks before surgery . MATERIALS AND METHODS A total 70 patients scheduled to undergo elective transurethral prostate resection were randomized to receive 5 mg. finasteride daily or placebo for 2 weeks before surgery . Serum hemoglobin was measured before and after surgery , and the following day . The volume of irrigation fluid used and its hemoglobin concentration as well as resected prostate weight were recorded . RESULTS Of the 68 patients who underwent transurethral prostate resection 2 were withdrawn before surgery , and so 32 received finasteride and 36 received placebo . There was significantly less mean blood loss in irrigation fluid in the finasteride group than in the control group ( 43.6 versus 69.3 gm . hemoglobin , p = 0.011 ) . The mean difference was more significant when blood loss per gm . resected prostate was calculated ( 2.65 versus 4.65 gm . hemoglobin per gm . prostate , p < 0.01 ) . CONCLUSIONS This study shows that finasteride given for 2 weeks preoperatively decreases bleeding in patients undergoing transurethral prostate resection . Further study is required to determine the optimal timing and dose duration to minimize blood loss and identify how relevant such a decrease in bleeding is in clinical practice .

Transurethral prostate resection

placebo

finasteride

finasteride

finasteride

5 mg. finasteride daily

or

placebo

finasteride

placebo

finasteride

finasteride

Serum hemoglobin

volume of irrigation fluid

withdrawn

mean blood loss in irrigation fluid

blood loss

bleeding

blood loss

Transurethral prostate resection

hematuria of prostatic origin .


The effects of chloroquine , amodiaquine and chloroquine plus chlorpheniramine on the disposition kinetics of the hepatomegaly associated with acute , uncomplicated , Plasmodium falciparum malaria in children . The effects of chloroquine ( CQ ) , amodiaquine ( AQ ) and CQ plus chlorpheniramine ( a histamine H ( 1 ) antagonist that reverses CQ resistance in vitro and in vivo ) on the disposition of the enlarged liver associated with acute , symptomatic , uncomplicated , Plasmodium falciparum malaria were evaluated . The subjects , 131 children aged 0.6-12 years who lived in an endemic area of Nigeria , were randomly allotted to the three treatment groups . The cumulative proportions of the children with complete resolution of their enlarged livers at 48 , 96 , 168 or 336 and 504 h after commencement of treatment were significantly higher in those treated with CQ plus chlorpheniramine ( CQCP ) than in the other two treatment groups ( with P-values of 0.02 , 0.001 , 0.00000 and 0.00002 , respectively ) . Among those with complete resolution , however , the times to resolution of 50 % ( HR50 ) or 90 % ( HR90 ) of the liver enlargement were similar in all the treatment groups . Complete resolution of the enlarged liver within 168 h was associated with a sensitive response to each treatment . Overall , in children with complete or partial resolution of their enlarged livers , the area produced by plotting liver size against time ( i.e . the area under the curve of hepatomegaly v. time , or AUC ( hp ) ) and the half-life of the hepatomegaly ( t ( 1/2hp ) ) were significantly lower in the CQCP group than in the other two groups . The volume of blood completely cleared of the 'hepatic pathological processes ' which led to the hepatomegaly ( CL ( Bhp ) ) and the fractional reduction of AUC ( hp ) at 48 and 96 h ( i.e . AUC ( hpFr148 ) and AUC ( hpFr96 ) ) were significantly higher in the CQCP group than in the other treatment groups . When the children with complete resolution of their liver enlargement were considered separately , t ( 1/2hp ) ( P=0.0008 ) but not AUC ( hp ) was found to be significantly lower , and AUC ( hpFr196 ) ( P=0.01 ) and CL ( Bhl ) ( P=0.002 ) were found to be significantly higher in the CQCP group than in the other groups . Among the children with only partial resolution of their enlarged livers , the indices of resolution and the kinetic parameters of disposition were similar in all three groups . The data indicate that the addition of chlorpheniramine to chloroquine had a beneficial effect on both the early and late stages of the resolution of the liver enlargement associated with acute , symptomatic , uncomplicated , P. falciparum malaria .

chloroquine , amodiaquine

chloroquine plus chlorpheniramine

chloroquine ( CQ ) , amodiaquine ( AQ )

CQ plus chlorpheniramine

CQ plus chlorpheniramine ( CQCP )

CQCP

CQCP

CQCP

chlorpheniramine

chloroquine

complete or partial resolution

half-life of the hepatomegaly

fractional reduction of AUC ( hp

AUC ( hp

AUC ( hpFr196 )

CL ( Bhl )

resolution of the liver enlargement

Plasmodium falciparum malaria

children

enlarged liver associated

0.6-12 years

liver enlargement


A randomized trial of continuous subcutaneous insulin infusion and intensive injection therapy in type 1 diabetes for patients with long-standing poor glycemic control . OBJECTIVE To assess in a randomized crossover trial the efficacy of continuous subcutaneous insulin infusion in improving glycemic control and health-related quality of life in type 1 diabetic patients with long-standing poor glycemic control . RESEARCH DESIGN AND METHODS A total of 79 patients in 11 Dutch centers were randomized to 16 weeks of continuous subcutaneous insulin infusion followed by 16 weeks intensive injection therapy or the reverse order . Glycemic control was assessed by HbA ( 1c ) , self-reported hypoglycemic events , and blood glucose memory meter read outs . Changes in quality of life were assessed by self-report questionnaires administered at baseline and 16 weeks . RESULTS As the drop-out rate after crossover was high ( 17 of 79 patients [ 22 % ] ) , we analyzed the trial as a parallel clinical trial , using data of the first half of the crossover phase only . At 16 weeks , mean HbA ( 1c ) was 0.84 % ( 95 % CI -1.31 to -0.36 ) lower in the continuous subcutaneous insulin infusion group compared with the insulin injection group ( P = 0.002 ) . Stability of blood glucose self-measurement values , expressed as SD of the nine-point blood glucose profiles , improved in the insulin pump group by 29.3 +/- 41.1 vs. 8.2 +/- 36.5 % in the injection group ( P = 0.039 ) . The number of mild hypoglycemic episodes per patient-week was 0.99 ( 95 % CI 0.11-1.87 ) higher in the insulin pump group ( P = 0.028 ) . Weight gain was similar in both groups . Scores on the Short-Form 36-Item subscales 'general health ' and 'mental health ' improved in the continuous subcutaneous insulin infusion group , compared with stable values in the injection group ( P = 0.048 and 0.050 , respectively ) . CONCLUSIONS Continuous subcutaneous insulin infusion improves glycemic control and some aspects of health-related quality of life in patients with a history of long-term poor glycemic control .

insulin

intensive injection therapy

insulin

insulin

glycemic control

health-related quality of life

quality of life

mean HbA ( 1c )

number of mild hypoglycemic episodes

Weight gain

' and

'mental health

type 1 diabetic

poor glycemic control

poor glycemic control


Preliminary findings from a prospective , randomized trial of two palatal operations for sleep-disordered breathing . OBJECTIVES We compared the efficacy of 2 palatal surgical procedures in the treatment of patients with mild sleep-disordered breathing ( SDB ) . STUDY DESIGN AND SETTING We conducted a prospective , randomized , crossover surgical trial at a university hospital . METHODS Twenty patients with mild SDB for whom conservative treatment failed were identified and consecutively enrolled into an institutional review board-approved surgical protocol . They were randomly assigned to undergo either radiofrequency ablation of the palate ( RFAP ) for a planned 3-stage treatment or laser-assisted uvulopalatoplasty ( LAUP ) , also for 3 stages of treatment , using a CO ( 2 ) laser . Parameters assessed included severity of SDB ( polysomnography ) , subjective and objective loudness of snoring ( visual analog scale and SNAP recording ) , sleepiness ( Epworth Sleepiness Scale ) , and anatomic changes ( upper airway endoscopy ) , as well as demographic factors . Patients not achieving satisfactory improvement in their condition were crossed over to the alternative surgical therapy for attempted salvage . RESULTS Seventeen of the enrolled patients have completed the protocol . Ten of these were randomized to the RFAP group , and 7 to the LAUP group . Six of the RFAP patients ( 60 % ) achieved a satisfactory resolution of their snoring , and 4 failed and were salvaged with LAUP . Six of the LAUP patients ( 86 % ) achieved a satisfactory resolution of their snoring , and 1 patient failed and was salvaged with nasal surgery . One patient who was initially cured had a relapse after 9 months and was successfully salvaged with RFA . CONCLUSION Prospective , randomized trials of surgery for SDB are possible . Preliminary findings from the current protocol reveal a slight advantage of LAUP over RFAP but with a greater degree of discomfort postoperatively .

palatal operations

2 palatal surgical procedures

RFAP

LAUP

RFAP

LAUP

LAUP

nasal surgery

RFA

LAUP

RFAP

efficacy

severity of SDB

sleepiness

anatomic changes

snoring

snoring

Twenty


Adherence to moderate-intensity exercise during breast cancer therapy . PURPOSE The aims of this pilot study were the following : 1 ) to examine patterns of adherence to a brisk walking program in women receiving adjuvant chemotherapy or radiation therapy for newly diagnosed breast cancer using a prospective , randomized , controlled experimental design ; 2 ) to examine the influence of disease symptoms and treatment side effects on exercise levels ; and 3 ) to suggest methods that may improve future clinical trials of moderate-intensity exercise in similar populations . DESCRIPTION OF STUDY Fifty-two patients with newly diagnosed breast cancer were randomly assigned to one of two treatment arms : usual care or usual care plus exercise . Those assigned to the exercise group received a standardized , self-administered , home-based brisk walking intervention in addition to usual care . Each day subjects completed self-report diary forms that elicited information about activity levels , and the occurrence of symptoms and side effects during cancer treatment . RESULTS Analyses of self-reported daily activity levels revealed a diffusion of treatment effect . Fifty percent of the usual-care group reported maintaining or increasing their physical activity to a moderate-intensity level , while 33 % of the exercise group did not exercise at the prescribed levels . Analyses of self-reported disease symptoms and treatment side effects did not reveal clinically meaningful differences between the two groups . CLINICAL IMPLICATIONS The results of this study suggest that women who exercised regularly before receiving a breast cancer diagnosis attempted to maintain their exercise programs . Women who lead sedentary lifestyles may benefit from a structured exercise program that includes information and support related to exercise adherence strategies .

moderate-intensity exercise

brisk walking program

adjuvant chemotherapy

radiation therapy

exercise

usual care

exercise

exercise programs

structured exercise program

maintaining or increasing their

physical activity

to a moderate-intensity level

self-reported disease symptoms

treatment side effects

breast cancer

Fifty-two


Lamivudine 300 mg QD versus continued lamivudine 150 mg BID with stavudine and a protease inhibitor in suppressed patients . PURPOSE To compare the efficacy ( sustained virologic suppression ) and safety/tolerability of a switch to lamivudine 300 mg once daily ( QD ) versus continued lamivudine 150 mg twice daily ( BID ) in virologically suppressed patients ( HIV-1 RNA < 400 copies/mL for > or =3 months ) on stable ( > or =6 months ) therapy with lamivudine 150 mg BID plus stavudine and either indinavir or nelfinavir . METHOD Eighty-nine suppressed patients > or =18 years old with CD4 counts > 50 cells/mm ( 3 ) were enrolled in this phase II , open-label , multicenter , randomized , stratified ( by pretrial protease inhibitor [ PI ] ) , parallel-group clinical trial . Eighty-one patients received either lamivudine 300 mg QD ( n = 39 ) or 150 mg BID ( n = 42 ) with their pretrial stavudine/PI regimens for 24 weeks . RESULTS A high rate of virologic suppression was sustained with both regimens throughout the trial . At week 24 , intent-to-treat : exposed ( missing = failure ) analyses showed no statistically significant differences in the percentage of patients with HIV-1 RNA < 400 copies/mL ( 95 % [ QD ] vs. 90 % [ BID ] ) or < 50 copies/mL ( 82 % [ QD ] vs. 81 % [ BID ] ) or in the median change from baseline in CD4 counts ( +42 cells/mm ( 3 ) [ QD ] vs. +22 cells/mm ( 3 ) [ BID ] ) . Both regimens were well tolerated . No patient experienced virologic failure , clinical disease progression , or a drug-related serious adverse event during the trial . Self-reported medication adherence was high in both groups . CONCLUSION Patients who experience virologic suppression with a regimen of lamivudine 150 mg BID in combination with stavudine/PI can maintain that suppression by continuing their regimen or switching to lamivudine 300 mg QD and continuing the other components . Adverse event profiles were comparable among treatment regimens , and no new safety concerns were raised .

Lamivudine

lamivudine

stavudine

protease inhibitor

lamivudine

lamivudine

pretrial protease inhibitor

lamivudine

pretrial stavudine/PI regimens

lamivudine

combination with stavudine/PI

lamivudine

rate of virologic suppression

percentage of patients with HIV-1 RNA

CD4 counts

drug-related serious adverse event

Self-reported medication adherence

virologic suppression

suppression

suppressed

virologically suppressed

suppressed

CD4 counts > 50 cells/mm ( 3 )

virologic suppression


A randomized , double-blind , placebo-controlled trial of porcine versus synthetic secretin for reducing symptoms of autism . OBJECTIVE To compare the effects of a single dose of biologic and synthetic porcine secretin to placebo on a variety of autism symptoms . METHOD Eighty-five children with autism without other medical conditions and not taking other psychotropic medications participated ( ages between 3 and 12 years , mean IQ = 55 ) . Children were grouped into trios matched by age and communication level and then randomly assigned to one of three treatment groups : biologic secretin ( 2 CU/kg ) , synthetic secretin ( 0.4 microg/kg ) , and placebo . Measures collected 1 week before and 4 weeks after infusion included autism symptoms , language skills , and problem behaviors , gathered from parents , teachers , and investigators , who were all blind to treatment . Two-factor , repeated-measures analyses of variance ( 3 treatment levels by 2 repeated measures , pre- and postinfusion ) were used to examine efficacy . RESULTS Direct observation measures did not show change over time related to secretin . Parent reports showed an overall reduction of symptom severity for all treatment groups , including the placebo group . One teacher-report measure showed decreases in autism symptoms in the placebo and synthetic secretin groups . CONCLUSIONS No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed . This held true when children with and without gastrointestinal problems were examined separately .

placebo-controlled

porcine

synthetic secretin

biologic

synthetic porcine secretin

placebo

biologic secretin

synthetic secretin

placebo

secretin

placebo

placebo

synthetic secretin

biologic

synthetic secretin

placebo

symptoms of autism

symptom severity

autism .

autism

Eighty-five children

ages between 3 and 12 years

children

gastrointestinal problems


Evaluation of different inhaled combination therapies ( EDICT ) : a randomised , double-blind comparison of Seretide ( 50/250 microg bd Diskus vs. formoterol ( 12 microg bd ) and budesonide ( 800 microg bd ) given concurrently ( both via Turbuhaler ) in patients with moderate-to-severe asthma . The aim of this study was to compare the efficacy safety and cost of Seretide ( salmeterol/fluticasone propionate ( Salm/FP ) , 50/250 microg bd ) via Diskus with formoterol ( Form ; 12 microg bd ) and budesonide ( Bud ; 800 microg bd ) given concurrently ( Form+Bud ) via Turbuhaler in patients with moderate-to-severe asthma who were uncontrolled on existing corticosteroid therapy . The study used a randomised , double-blind , double-dummy , parallel-group design , consisting of a 2-week run-in period on current corticosteroid therapy ( 1000-1600 microg/day of BDP or equivalent ) and a 12-week treatment period . Symptomatic patients ( n = 428 ) with FEV1 of 50-85 % predicted and increased symptom scores or reliever use during run-in were randomly allocated to receive either Salm/FP ( 50/250 microg bd ) via a single Diskus inhaleror Form+Bud ( 12+800 microg bd ) via separate Turbuhalers . Clinic , diary card and asthma-related health-care resource utilisation data were collected . Improvement in mean morning peak expiratory flow ( PEFam was similar in the Salm/FP and Form+Bud groups . Both PEFam and mean evening PEF ( PEFpm ) increased by a clinically significant amount ( > 20 L/min ) from baseline in both treatment groups . The mean rate of exacerbations ( mild , moderate or severe ) was significantly lower in the Salm/FP group ( 0.472 ) compared with the Form+Bud group ( 0.735 ) ( ratio = 0.64 ; P < 0.001 ) , despite the three-fold lower microgram inhaled corticosteroid dose in the Salm/FP group . Patients in the Salm/FP group also experienced significantly fewer nocturnal symptoms , with a higher median percentage of symptom-free nights ( P = 0.04 ) , nights with a symptom score < 2 ( P = 0.03 ) , and nights with no awakenings ( P = 0.02 ) . Total asthma-related health-care costs were significantly lower in the Salm/FP group than the Form+Bud group ( P < 0.05 ) . Both treatments were well tolerated , with a similar low incidence of adverse events . This study showed that in symptomatic patients with moderate-to-severe asthma , Salm/FP ( 50/250 microg bd ) , administered in a single convenient device ( Diskus ) , was at least as effective as an approximately three-fold higher microgram corticosteroid dose of Bud ( 800 microg bd ) given concurrently with Form ( 12 microg bd ) in terms of improvement in PEFam , and superior at reducing exacerbations and nights with symptoms or night-time awakenings . Salm/FP was also the less costly treatment due primarily to lower hospitalisation and drug costs .

inhaled combination therapies ( EDICT )

Seretide

Diskus

formoterol

budesonide

Diskus with formoterol

budesonide

current corticosteroid therapy

Salm/FP

corticosteroid dose of Bud ( 800

Salm/FP

efficacy safety and cost

symptom scores

PEFam

mean evening PEF ( PEFpm )

mean rate of exacerbations

fewer nocturnal symptoms

symptom-free nights

nights with a symptom score

nights with no awakenings

Total asthma-related health-care costs

well tolerated

similar low incidence

adverse events .

less costly

lower hospitalisation and drug costs .

moderate-to-severe asthma

n = 428


An exploratory study : the use of paroxetine for methamphetamine craving . Methamphetamine abuse and dependence are growing problems nationally and worldwide . There are currently no effective pharmocologic treatments . Animal studies with SSRI 's suggest that serotonergic modulation alters methamphetamine 's behavioral effects . This exploratory study is a trial of the effects of the SSRI paroxetine versus placebo ( in a double blind design ) on craving and use in a population of methamphetamine users . Many subjects dropped out of the study , but those in active treatment who completed the eight week trial had a decrease in methamphetamine craving compared to the placebo treatment as measured by the OCDS modified for use in this population . Statistical analyses were not performed due to the low number of subjects . The preliminary data suggest that serotonergic agents may play a role in the effective treatment of methamphetamine abuse and dependence within the context of other effective behavioral interventions .

paroxetine

Methamphetamine

methamphetamine 's

SSRI paroxetine

placebo

methamphetamine

methamphetamine

methamphetamine

methamphetamine craving

behavioral effects

methamphetamine craving

methamphetamine abuse and dependence

methamphetamine craving


Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis : a randomised controlled trial . BACKGROUND Cryptosporidiosis in children in developing countries causes persistent diarrhoea and malnutrition and is associated with increased mortality , but there is no effective treatment . We aimed to assess the effect of nitazoxanide-a new broad-spectrum antiparasitic drug-on morbidity and mortality in Zambian children with diarrhoea due to Cryptosporidium parvum . METHODS Children with cryptosporidial diarrhoea who were admitted to the University Teaching Hospital , Lusaka , Zambia , between November , 2000 , and July , 2001 , and whose parents consented to their having an HIV test were randomly assigned nitazoxanide ( 100 mg twice daily orally for 3 days ) or placebo . The primary endpoint was clinical response on day 7 after the start of treatment . Secondary endpoints included parasitological response by day 10 and mortality at day 8 . Analysis was by intention to treat , with exclusion of patients subsequently found to be negative for C parvum or co-infected at baseline . The trial was stratified by HIV serology . FINDINGS 50 HIV-seropositive and 50 HIV-seronegative children were recruited for the study , four of whom were subsequently excluded . In HIV-seronegative children , diarrhoea resolved in 14 ( 56 % ) of 25 receiving nitazoxanide and 5 ( 23 % ) of 22 receiving placebo ( difference 33 % , 95 % CI 7-59 ; p=0.037 ) . C parvum was eradicated from stool in 13 ( 52 % ) of 25 receiving nitazoxanide and three ( 14 % ) of 22 receiving placebo ( 38 % , 95 % CI 14-63 ; p=0.007 ) . Four children ( 18 % ) of 22 in the placebo group had died by day 8 , compared with none of 25 in the nitazoxanide group ( -18 % , -34 to 2 ; p=0.041 ) . HIV-seropositive children did not benefit from nitazoxanide . Nitazoxanide was not significantly associated with adverse events in either stratum . INTERPRETATION A 3-day course of nitazoxanide significantly improved the resolution of diarrhoea , parasitological eradication , and mortality in HIV-seronegative , but not HIV-seropositive , children .

nitazoxanide

nitazoxanide-a

nitazoxanide

placebo

morbidity and mortality

morbidity and mortality

clinical response on day 7

parasitological response by day 10

mortality at day 8

diarrhoea

C parvum

died

adverse events

resolution of diarrhoea

Zambian

children

cryptosporidiosis

Cryptosporidiosis

children

developing countries

Zambian

children

diarrhoea due to Cryptosporidium parvum

Children

cryptosporidial diarrhoea

C parvum

children


Global contour saliency and local colinear interactions . Our visual system can link components of contours and segregate contours from complex backgrounds based on geometric grouping rules . This is an important intermediate step in object recognition . The substrate for contour integration may be based on contextual interactions and intrinsic horizontal connections seen in primary visual cortex ( V1 ) . We examined the perceptual rules governing contour saliency to determine whether the spatial extents of contextual interactions and horizontal connections match those mediating saliency . To quantify these rules , we used stimuli composed of randomly oriented nonoverlapping line segments . Salient contours within this complex background were formed by colinear alignment of nearby segments . Contour detectability was measured using a 2-interval-forced-choice design . Contour detectability deteriorated with increasing spacing between contour elements and improved as the number of colinear line elements was increased . At short contour spacing , the detectability reached a plateau with alignment of a few line segments that together formed a contour subtending several visual degrees . At intermediate spacing , saliency built up progressively with a greater number of colinear lines , extending up to 30 degrees . When contour spacing was beyond a critical range ( about 2 degrees ) , however , the detectability dropped to chance levels , regardless of the number of colinear lines . Contour detectability was found to be a function not only of the relative spacing of contour elements with respect to the noise elements but also of the average density of the overall pattern . Furthermore , training significantly improved contour detection , increasing the critical spacing of line elements beyond which contours were no longer detectable . Our data suggest that global contour integration is based on mechanisms of limited spatial extent , comparable to the interactions observed in V1 . These interactions can cascade over larger distances provided the spacing of stimulus elements is kept within a limited range .

2-interval-forced-choice design

object recognition .

Contour detectability

Contour detectability

spacing

saliency

detectability

Contour detectability

contour detection

critical spacing

global contour integration


Effects of two types of social support and education on adaptation to early-stage breast cancer . A Roy adaptation model-based support and education intervention for women with early-stage breast cancer was tested in a three-group , three-phase randomized clinical trial of a sample of 125 women . The experimental group received 13 months of combined individual telephone and in-person group support and education , Control Group 1 received 13 months of telephone-only individual support and education , and Control Group 2 received one-time mailed educational information . The experimental group and Control Group 1 reported less mood disturbance at the end of all three phases , less loneliness at the end of Phases II and III , and a higher-quality relationship with a significant other at the end of Phase II than did Control Group 2 . No group differences were found for cancer-related worry or well-being . The findings suggest that individual telephone support may provide an effective alternative to in-person support groups . Further study of telephone interventions is recommended using ethnically and economically heterogeneous samples .

social support and education

mood disturbance

less loneliness

cancer-related worry or well-being

early-stage breast cancer

women

early-stage breast cancer

women


Immunologic and hemodynamic effects of " low-dose " hydrocortisone in septic shock : a double-blind , randomized , placebo-controlled , crossover study . Within the last few years , increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy . To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation , 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 ( n = 20 ) or placebo ( n = 20 ) , followed by the opposite medication until Day 6 . Hydrocortisone infusion induced an increase of mean arterial pressure , systemic vascular resistance , and a decline of heart rate , cardiac index , and norepinephrine requirement . A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support . The inflammatory response ( interleukin-6 and interleukin-8 ) , endothelial ( soluble E-selectin ) and neutrophil activation ( expression of CD11b , CD64 ) , and antiinflammatory response ( soluble tumor necrosis factor receptors I and II and interleukin-10 ) were attenuated . In peripheral blood monocytes , human leukocyte antigen-DR expression was only slightly depressed , whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased . Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects . In conclusion , hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression .

" low-dose " hydrocortisone

placebo-controlled

hydrocortisone

hydrocortisone

hydrocortisone

placebo

Hydrocortisone

Hydrocortisone

hydrocortisone

heart rate

cardiac index

norepinephrine requirement

plasma nitrite/nitrate

nitric oxide formation

reduction of vasopressor support

endothelial ( soluble E-selectin )

neutrophil activation

antiinflammatory response

human leukocyte antigen-DR expression

in vitro phagocytosis

hemodynamic stability

immunologic response to stress

septic shock :

adrenal insufficiency

septic shock

septic shock


A randomized , double-blind , vehicle-controlled study to assess 5 % imiquimod cream for the treatment of multiple actinic keratoses . BACKGROUND Actinic keratoses ( AKs ) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun . Several case studies published recently have indicated that 5 % imiquimod cream , currently licensed for the treatment of genital warts , may be an effective treatment for AK . OBJECTIVE To assess the efficacy and safety of imiquimod for the treatment of AK . DESIGN Patients in this randomized , double-blind , vehicle-controlled study applied 5 % imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved . In the event of an adverse reaction , application of imiquimod was reduced to 1 or 2 times per week . Rest periods were also allowed if necessary . SETTING A specialized outpatient dermatology clinic within a state-funded hospital in Germany . PATIENTS The study population was aged 45 to 85 years . Of 52 patients screened , 36 men and women with AK confirmed by histological diagnosis were enrolled . Patients were excluded from the study if they did not have a histological diagnosis for AK , if they were older than 85 years , or if they did not comply with the protocol . All patients had responded to a notice asking for volunteers . MAIN OUTCOME MEASURES The number and appearance of lesions were evaluated before , during , and after treatment . All adverse effects were recorded . RESULTS Lesions treated with 5 % imiquimod cream were clinically cleared in 21 ( 84 % ) of 25 patients and partially cleared in 2 ( 8 % ) . Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free . Only 10 % of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment . No reduction in the size or number of AK lesions was observed in vehicle-treated patients . Adverse effects reported by patients treated with imiquimod included erythema , edema , induration , vesicles , erosion , ulceration , excoriation , and scabbing . However , imiquimod was well tolerated since all patients completed the 12-week treatment . Only a few , mild adverse reactions to the vehicle cream were reported . CONCLUSION Application of 5 % imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK .

imiquimod cream

imiquimod cream

imiquimod

imiquimod cream

imiquimod

imiquimod

imiquimod

imiquimod cream

multiple actinic keratoses

Actinic keratoses ( AKs )

AK

AK lesions

number and appearance of lesions

adverse effects

clinically cleared

partially cleared

Clearance

tolerated

AK

multiple actinic keratoses

45 to 85

men and women


Determinants of serum creatinine trajectory in acute contrast nephropathy . The aim of this study was to describe the trajectory of creatinine ( Cr ) rise and its determinants after exposure to radiocontrast media . Included were 98 subjects who underwent cardiac catheterization and were randomized to forced diuresis with i.v . crystalloid , furosemide , mannitol ( if pulmonary capillary wedge pressure was < 20 mmHg ) , and low dose dopamine versus intravenous crystalloid and matching placebos . Baseline and postcatheterization serum Cr levels were analyzed in a longitudinal fashion , allowing for differences in the time between blood draws , to determine the different critical trajectories of serum Cr . The mean age , baseline serum Cr , and Cr clearance ( CrCl ) were 69.3 +/- 10.8 years , 2.5 +/- 0.9 mg/dL , and 31.4 +/- 12.1 mL/min , respectively . The clinically driven postprocedural observation time was 5.5 +/- 5.1 days ( range 19 hours and one Cr value to 25.7 days and 18 values ) . The mean maximum Cr was 3.3 +/- 1.4 , range 1.7-8.7 mg/dL ) . Longitudinal models support baseline Cr clearance predictions for the change in Cr at 24 hours , time as the determinant of Cr trajectory , and requisite monitoring . For any given individual , a rise in Cr of < or = 0.5 mg/dL in the first 24 hours after contrast exposure predicted a favorable outcome . Baseline renal function is the major determinant of the rate of rise , height , and duration of Cr trajectory after contrast exposure . Length of observation and frequency of laboratory measures can be anticipated from these models .

low dose dopamine

crystalloid

matching placebos

creatinine ( Cr )

serum Cr levels

mean age

baseline serum Cr

Cr clearance ( CrCl )

mean maximum Cr

Cr clearance

Cr

Baseline renal function

nephropathy

radiocontrast

cardiac catheterization

baseline serum Cr

Cr clearance

69.3 +/- 10.8 years ,


Reactive balance adjustments to unexpected perturbations during human walking . The purpose of this investigation was to determine the effect of unexpected forward perturbations ( FP ) during gait on lower extremity joint mechanics and muscle Electromyographic ( EMG ) patterns in healthy adults . The muscles surrounding the hip were found to be most important in maintaining control of the trunk and preventing collapse in response to the FP . Distinct lower extremity joint moment and power patterns were observed in response to the FP but an overall positive moment of support ( M ( s ) ) was maintained . Therefore , reactive balance control was a synchronized effort of the lower extremity joints to prevent collapse during the FP .

unexpected perturbations

unexpected forward perturbations ( FP )

FP

FP

lower extremity joint mechanics

moment of support ( M ( s ) )

reactive balance control

healthy

adults


Lofexidine in hyperactive and impulsive children with autistic disorder .

Lofexidine

hyperactive and impulsive

children

autistic disorder


Hypnosis treatment for severe irritable bowel syndrome : investigation of mechanism and effects on symptoms . Hypnosis improves irritable bowel syndrome ( IBS ) , but the mechanism is unknown . Possible physiological and psychological mechanisms were investigated in two studies . Patients with severe irritable bowel syndrome received seven biweekly hypnosis sessions and used hypnosis audiotapes at home . Rectal pain thresholds and smooth muscle tone were measured with a barostat before and after treatment in 18 patients ( study I ) , and treatment changes in heart rate , blood pressure , skin conductance , finger temperature , and forehead electromyographic activity were assessed in 24 patients ( study II ) . Somatization , anxiety , and depression were also measured . All central IBS symptoms improved substantially from treatment in both studies . Rectal pain thresholds , rectal smooth muscle tone , and autonomic functioning ( except sweat gland reactivity ) were unaffected by hypnosis treatment . However , somatization and psychological distress showed large decreases . In conclusion , hypnosis improves IBS symptoms through reductions in psychological distress and somatization . Improvements were unrelated to changes in the physiological parameters measured .

Hypnosis treatment

Hypnosis

All central IBS symptoms

Rectal pain thresholds

somatization and psychological distress

psychological distress and somatization


Investigation of the effect of FK506 ( tacrolimus ) and cyclosporin on gingival overgrowth following paediatric liver transplantation . INTRODUCTION Gingival overgrowth associated with immunosuppression following liver transplantation is a commonly recognized clinical problem . The aims of this study were to determine the incidence of gingival overgrowth in a group of children post liver transplantation and to compare gingival overgrowth in children receiving FK506 with those receiving cyclosporin . METHODS Seventy-nine children ( aged 15-196 months ) undergoing liver transplantation at Birmingham Children 's Hospital between October 1998 and October 2000 were studied . Gingival overgrowth was assessed in a blinded fashion and scored in a previously validated manner . Gingival overgrowth scores of the patients on each immunosuppressant drug were then compared . RESULTS Fifty-two patients were treated with cyclosporin and 27 treated with tacrolimus . Eighteen children were also receiving nifedipine ( also known to cause gingival overgrowth ) and were considered separately . Of the 41 children receiving cyclosporin alone , 26 exhibited gingival overgrowth compared to zero of 20 patients receiving tacrolimus alone . Those children treated with immunosuppression plus nifedipine developed gingival overgrowth , however , this was much less marked in the tacrolimus group . CONCLUSION Tacrolimus , unlike cyclosporin , is not associated with gingival overgrowth when used for immunosuppression following liver transplantation in children , and may be the drug of choice for children .

FK506 ( tacrolimus )

cyclosporin

cyclosporin

cyclosporin

tacrolimus

nifedipine

cyclosporin

tacrolimus

tacrolimus

Tacrolimus

cyclosporin

Gingival overgrowth

Gingival overgrowth

gingival overgrowth

gingival overgrowth

gingival overgrowth

gingival overgrowth

paediatric

liver transplantation .

children

gingival overgrowth

children

Seventy-nine

children ( aged 15-196 months )

Fifty-two patients

children

children

gingival overgrowth

zero of 20 patients

children

children


Gastroesophageal reflux and tracheal aspiration in the thoracotomy position : should ranitidine premedication be routine ? UNLABELLED Aspiration of gastric contents may contribute to pulmonary complications after thoracotomy . The incidence of gastroesophageal reflux ( GER ) and tracheal acid aspiration in patients undergoing thoracotomy in the lateral position is unknown . Ranitidine premedication reduces gastric volume , increases gastric pH , and may reduce GER . We used continuous intraluminal esophageal and tracheal pH monitoring probes to investigate the effect of ranitidine on the incidence of GER and tracheal aspiration in 80 adult patients undergoing thoracotomy . The study was placebo-controlled , randomized , and double-blinded . Patients at high risk of GER were excluded from the study . The incidence of acid GER in the placebo and ranitidine groups was 28.2 % and 2.5 % , respectively ( P = 0.006 ) . Multiple episodes of GER occurred in some patients in the placebo group only . The total number of episodes of GER in the placebo and ranitidine groups was 16 and 1 , respectively ( P = 0.002 ) . The incidence of tracheal acid aspiration in the placebo and ranitidine groups was 7.7 % and 2.5 % , respectively ( not significant ) . Patients undergoing thoracotomy are therefore at high risk of acid GER , which may lead to tracheal acid aspiration in an appreciable proportion . Premedication with ranitidine significantly reduces , but does not eliminate , the incidence of this potentially life-threatening complication . IMPLICATIONS Gastroesophageal reflux ( GER ) and tracheal aspiration of acid may increase morbidity and mortality in patients undergoing thoracotomy . This randomized , double-blinded , placebo-controlled study demonstrates frequent incidences of both acid GER and tracheal acid aspiration during surgery that are significantly reduced by premedication with ranitidine .

ranitidine

Ranitidine

ranitidine

placebo-controlled

placebo

ranitidine

placebo

ranitidine

placebo

ranitidine

thoracotomy

ranitidine

thoracotomy

placebo-controlled

ranitidine

gastroesophageal reflux ( GER )

tracheal acid aspiration

GER

GER

tracheal aspiration

incidence of acid GER

episodes of GER

total number of episodes of GER

incidence of tracheal acid aspiration

risk of acid GER

tracheal acid aspiration

Gastroesophageal reflux ( GER )

tracheal aspiration of acid

acid GER

tracheal acid aspiration


Pharmacokinetics of azithromycin in lung tissue , bronchial washing , and plasma in patients given multiple oral doses of 500 and 1000 mg daily . The present study compares the pharmacokinetics of azithromycin in plasma , lung tissue , and bronchial washing after oral administration of 500 mg ( standard dose ) versus 1000 mg daily for 3 days . Samples were taken during surgery for lung resection at various time points up to 204 h after the last drug dose , and azithromycin levels were analyzed by HPLC method . Azithromycin was widely distributed within the lower respiratory tract ; sustained concentrations of the drug were detectable at the last sampling time ( 204 h ) in lung tissue and bronchial washing , with long terminal half-lives of 132.86 and 74.32 h at 500 mg daily and 133.32 and 70.5 h at 1000 mg daily , respectively . Doubling the drug dose resulted in a remarkable increase in lung area under the curve ( AUC , 1318 hx microg g ( -1 ) vs 2502 hx microg g ( -1 ) ) and peak tissue concentration ( 9.13+/-0.53 microg g ( -1 ) vs 17.85+/-2.4 microg g ( -1 ) ) . In addition to this , enhanced azithromycin penetration from plasma into bronchial secretion and lung tissue was evidenced by the increase in the ratio of AUC ( bronchial washing ) versus AUC ( plasma ) ( 2.96 vs 5.27 at 500 and 1000 mg , respectively ) and AUC ( lung ) versus AUC ( plasma ) ( 64.35 vs 97.73 at 500 and 1000 mg , respectively ) . In conclusion , the exposure of lung and bronchial washing to azithromycin is increased by doubling the dose , which results in favorable pharmacokinetic profile of the drug in the lower respiratory tract .

azithromycin

azithromycin

azithromycin

Azithromycin

azithromycin

azithromycin

sustained concentrations of the drug

lung area under the curve

AUC ( lung ) versus AUC ( plasma )

pharmacokinetic profile


Prospective randomized trial of an anterior surface modified prolate intraocular lens . PURPOSE We compare the contrast sensitivity obtained with an anterior surface modified prolate intraocular lens with the contrast sensitivity obtained with a standard spherical intraocular lens . METHODS Patients presenting for cataract surgery in one eye were randomized to receive either the Tecnis Z9000 intraocular lens ( Pharmacia ) or the AMO AR40e Opti-Edge intraocular lens ( AMO ) . Sine wave grating contrast sensitivity testing under mesopic and photopic conditions served as the principal outcome measure . RESULTS The Tecnis Z9000 intraocular lens provided statistically significantly better contrast sensitivity at 1.5 and 3 cycles per degree under mesopic conditions and at 6 , 12 and 18 cycles per degree under photopic conditions . CONCLUSION The use of a modified prolate intraocular lens during cataract surgery has the potential to improve contrast sensitivity under both mesopic and photopic conditions .

contrast sensitivity

contrast sensitivity

contrast sensitivity


Comparison of acustimulation and ondansetron for the treatment of established postoperative nausea and vomiting . BACKGROUND This study was designed to evaluate transcutaneous electrical acupoint stimulation ( acustimulation ) using the ReliefBand compared with ondansetron for the treatment of established postoperative nausea and vomiting ( PONV ) after outpatient laparoscopic surgery . METHODS After the authors obtained institutional review board approval and written informed consent , 268 outpatients were enrolled in this randomized , double-blind , placebo- and sham-controlled study . All patients received antiemetic prophylaxis with metoclopramide , 10 mg intravenously , or droperidol , 0.625 mg intravenously , after induction of anesthesia . A total of 90 patients developed PONV in the recovery units and were randomized to one of three treatment groups : ( 1 ) the ondansetron group received 4 mg intravenous ondansetron and a sham ReliefBand ; ( 2 ) the acustimulation group received 2 ml intravenous saline and a ReliefBand ; and ( 3 ) the combination group received 4 mg intravenous ondansetron and a ReliefBand . A rescue antiemetic ( 10 mg intravenous metoclopramide ) was administered only if the PONV symptoms persisted for 15 min or longer after initiating the treatment . A blinded observer recorded the recovery times , emetic symptoms , rescue antiemetics , maximum nausea scores , complete response to study treatment , and time to achieve discharge criteria . Postdischarge side effects , as well as patient satisfaction and quality of recovery scores , were assessed at 24 and 72 h after surgery . RESULTS The combination group had a significantly higher complete response rate than the acustimulation group ( 73 % vs.40 % , P < 0.01 ) . In addition , fewer patients ( 8 vs. 18 ) in the combination ( vs. acustimulation ) group experienced subsequent emetic events ( P < 0.03 ) . However , there were no significant differences between the three groups with respect to patient satisfaction and quality of recovery scores . CONCLUSIONS Acustimulation with the ReliefBand can be used as an alternative to ondansetron for the treatment of established PONV . However , the use of ondansetron ( 4 mg intravenously ) in combination with the ReliefBand device improved the complete response rate to the acustimulation therapy .

recovery times ,

emetic symptoms

rescue antiemetics

maximum nausea scores

complete response

subsequent

emetic events

PONV

established PONV .


Secretin and sleep in children with autism . The objectives of this pilot study were 1 ) to examine possible effects of secretin infusions on sleep-wake state organization in children with autism , and 2 ) to assess the feasibility of home recordings using time-lapse videosomnography in children with autism . Participants were a subset of subjects from two double blind , placebo-control , multi-center clinical trials . One trial , the UC Irvine study , assessed the effects of porcine secretin vs. saline infusions on children 's behavior , language and IQ . The UC Davis trial assessed the effects of synthetic human secretin vs. saline infusions on behavior , language and gastrointestinal function . The sleep study enrolled some of the children from each of the two trials to observe possible secretin effects on sleep . To examine sleep , the UC Irvine trial used the Children 's Sleep Habits Questionnaire and daily sleep diaries , whereas the UC Davis study used home-recorded time-lapse videosomnography . Because of the small sample size , the results from both trials are preliminary . They suggest that secretin , porcine or synthetic , does not improve sleep-wake state organization dramatically .

Secretin

secretin

porcine secretin

saline infusions

synthetic human secretin

saline infusions

secretin , porcine or synthetic

behavior , language

IQ

behavior , language

gastrointestinal function .

sleep-wake state organization


Pharmacokinetic and safety assessments of galantamine and risperidone after the two drugs are administered alone and together . To explore the steady-state pharmacokinetic profile after coadministration of galantamine and risperidone , an open-label , randomized , single-center , two-way crossover drug-drug interaction study was conducted in 16 healthy elderly subjects , ages 60 years and older . The results showed that risperidone , when administered with galantamine , did not change the bioavailability of galantamine at steady state . In addition , systemic exposure of risperidone active moiety ( risperidone plus 9-hydroxyrisperidone ) , the most clinically relevant component of risperidone treatment , was not affected by galantamine coadministration , while systemic exposure was increased by approximately 10 % for risperidone and decreased by about 10 % for 9-hydroxyrisperidone ( active metabolite of risperidone ) . Galantamine and risperidone were both safe and well tolerated administered either alone or together . Thus , no dose adjustment for either risperidone orgalantamine is necessary when these two drugs are administered together in the dose range evaluated .

galantamine

risperidone

galantamine

risperidone

risperidone

galantamine

galantamine

risperidone

risperidone plus 9-hydroxyrisperidone

risperidone

galantamine

risperidone

risperidone

Galantamine

risperidone orgalantamine

Pharmacokinetic

and

safety

assessments

bioavailability

systemic exposure

safe and well tolerated


A randomized prospective controlled trial of oral ganciclovir versus oral valacyclovir for prophylaxis of cytomegalovirus disease after renal transplantation . Oral ganciclovir and valacyclovir reduce the incidence of cytomegalovirus ( CMV ) disease after renal transplantation ( RTx ) . Our study was designed to compare the efficacy , costs , and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease over the first 6 months after RTx . A total of 38 patients was randomized to 3-month treatment with either oral ganciclovir ( 1 g t.i.d. , n=14 , GAN group ) or oral valacyclovir ( 2 g q.i.d. , n=12 , VAL group ) . A third group ( C , n=12 ) received no prophylaxis . The patients were monitored by CMV-nested PCR in whole blood . No differences were found between the groups in their demographic characteristics , immunosuppressive protocols , or donor and recipient CMV serology . Thirty-six out of 38 ( 94.7 % ) recipients were CMV-seropositive . Over the 6-month post-RTx period , there were 13 episodes of CMV disease in eight ( 66.7 % ) patients of the C group compared with none in the GAN and VAL groups ( P=0.0005 , GAN vs C ; P=0.001 , VAL vs C ) . The incidence of CMV viremia was 30.8 % , 50.0 % , and 91.7 % in the GAN , VAL , and C groups , respectively ( P=0.004 , GAN vs C ; P=0.07 , VAL vs C ; P=NS , GAN vs VAL ) . Treatment failure ( death , graft loss , CMV disease , or withdrawal from study ) occurred in 14.3 % , 0 % and 66.7 % in the GAN , VAL , and C groups , respectively ( P=0.014 , GAN vs C ; P=0.001 , VAL vs C ; P=NS , GAN vs VAL ) . The average CMV-associated costs per patient ( in 2001 euros ) were 2,449+/-1,178 , 2,485+/-581 , and 4,259+/-4,616 in the GAN , VAL , and C groups , respectively . Ganciclovir and valacyclovir were well tolerated , with ganciclovir having had to be withdrawn shortly in one patient only because of thrombocytopenia . In conclusion , oral ganciclovir and valacyclovir are equally safe and effective in the prophylaxis of CMV disease after RTx . Both are cost-effective and help reduce CMV-associated costs by some 40 % compared with patients without prophylaxis .

ganciclovir

valacyclovir

ganciclovir

valacyclovir

ganciclovir

valacyclovir

oral ganciclovir

oral valacyclovir

no prophylaxis

cytomegalovirus disease

cytomegalovirus ( CMV ) disease

efficacy

costs

safety

CMV-seropositive .

CMV

incidence of CMV viremia

death

graft loss

CMV disease

withdrawal from study

well tolerated

equally safe and effective

cost-effective

CMV-associated costs

renal transplantation .


Galantamine may be effective in treating autistic disorder .

Galantamine

autistic disorder


Increased concentration of corticosteroid-binding globulin due to antidepressant treatment with amitritpyline , but not paroxetine .

amitritpyline

paroxetine .

antidepressant treatment

amitritpyline


Risperidone improves behavior in children with autism .

Risperidone

behavior

children

autism


Comparison of percutaneous transmitral commissurotomy with Inoue balloon technique and metallic commissurotomy : immediate and short-term follow-up results of a randomized study . BACKGROUND The Inoue balloon technique for mitral commissurotomy is well established and carried out worldwide . Metallic commissurotomy is reported to be a cheaper and effective alternative to balloon mitral commissurotomy . METHODS One hundred patients were randomized into 2 groups to undergo percutaneous transmitral commissurotomy ( PTMC ) by means of the Inoue balloon technique ( IBMC , n = 49 ) or metallic commissurotomy ( PMMC , n = 51 ) . Patients were crossed over to the other technique when the initial technique was a failure . Success of valvotomy , procedure-related complications , and follow-up events of the 2 techniques were compared . RESULTS Basal echocardiographic and hemodynamic data were similar in both groups . Procedural success was similar in both groups : 45 of 49 procedures ( 91.8 % ) in the IBMC group , compared with 46 of 51 procedures ( 90.18 % ) in the PMMC group ( P = 1.0 ) . Crossover was also comparable , with 1 occurring in the IBMC group , compared with 3 in the PMMC group . Complications such as cardiac tamponade and mitral regurgitation ( requiring or not requiring mitral valve replacement ) were similar in both groups , with 3 complications in the IBMC group , compared with 4 complications in the PMMC group ( P =.29 ) . After a follow-up period of approximately 4 months , both groups had similar event rates and comparable hemodynamic parameters ( P = not significant ) . CONCLUSIONS Both IBMC and PMMC are successful means of providing relief from severe mitral stenosis with a gain in valve area and reduction in transmitral gradient . Both techniques have similar procedural success , complication rates , and follow-up events .

metallic commissurotomy ( PMMC

, n = 51 )

technique

Success of valvotomy

procedure-related complications

follow-up events

Basal echocardiographic

hemodynamic data

One hundred

severe mitral stenosis


Ankle cryotherapy facilitates soleus function . STUDY DESIGN A 2-factor ( group and time ) experimental design with repeated measures on time . OBJECTIVES To determine the effects of ankle cryotherapy on voluntary and resting motor function of the soleus over a 60-minute period . To determine if a relationship exists between changes in torque production and Hoffmann reflex ( H-reflex ) following ankle joint cryotherapy treatment . BACKGROUND Controversy surrounds the use of cryotherapy prior to activity and rehabilitation . While cooling muscle may have a deleterious effect on motor function , cooling the joint may enhance motor function around the joint . The H-reflex is a good resting measure of motoneuronal activity . However , its relationship to voluntary activity is unknown . METHODS AND MEASURES Thirty subjects were pretested ( baseline ) for normalized H-reflex ( defined as the ratio of maximum H-reflex [ Hmax ] to maximum direct motor response [ Mmax ] ) and peak plantar flexion torque . A crushed ice bag was placed over the ankle of 15 subjects for 30 minutes . H-reflex and torque measurements were collected immediately following the cryotherapy treatment at 30 , 60 , and 90 minutes . Surface temperatures were recorded from the ankle and electrode site with each measurement interval . RESULTS Both peak H-reflex and plantar flexion torque at 30 , 60 , and 90 minutes increased relative to baseline measurements . Each measurement was also greater than the corresponding control at 30 , 60 , and 90 minutes . A weak correlation ( r = 0.38 ; P = 0.036 ) existed between changes in H-reflex and plantar flexion torque at 30 minutes . CONCLUSIONS The soleus motoneuron pool is facilitated following a 30-minute crushed ice application to the ankle and over a 60-minute postcooling period . These data support the use of joint cooling prior to activity and rehabilitation .

Ankle cryotherapy

ankle cryotherapy

ankle joint cryotherapy

crushed ice application

soleus function .

torque production

Hoffmann reflex ( H-reflex )

motor function

motor function

H-reflex

H-reflex

peak plantar flexion torque .

H-reflex

torque measurements

Surface temperatures

peak H-reflex

plantar flexion torque

H-reflex

plantar flexion torque

soleus

Thirty subjects


Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger 's disorders . Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains : repetitive behaviors , social deficits , and language abnormalities . There is evidence that abnormalities exist in peptide systems , particularly the oxytocin system , in autism spectrum patients . Furthermore , oxytocin and the closely related peptide vasopressin are known to play a role in social and repetitive behaviors . This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Asperger 's disorder via randomized double-blind oxytocin and placebo challenges . The primary outcome measure was an instrument rating six repetitive behaviors : need to know , repeating , ordering , need to tell/ask , self-injury , and touching . Patients with autism spectrum disorders showed a significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion . Repetitive behavior in autism spectrum disorders may be related to abnormalities in the oxytocin system , and may be partially ameliorated by synthetic oxytocin infusion .

Oxytocin infusion

oxytocin

oxytocin

placebo

repetitive behaviors

repetitive behaviors

repetitive behaviors

repetitive behaviors

Repetitive behavior

adults

autistic and Asperger 's disorders

autism spectrum


Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria : a longitudinal randomised trial . BACKGROUND New antimalarial treatments are urgently needed in sub-Saharan Africa . Improved therapies should decrease failure rates in the short term , but their effect on incidence of subsequent episodes of malaria is little studied . We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala , Uganda . METHODS We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo , 25 mg/kg amodiaquine , or 12 mg/kg artesunate . Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up . Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 ( MSP2 ) . Our primary endpoint was the total number of treatments for malaria per time at risk . Analyses were done per protocol . FINDINGS 183 ( 61 % ) of 316 participants were diagnosed with at least one episode of uncomplicated malaria . A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs ; all regimens were safe and well tolerated . Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group ( 38 of 215 , 18 % ) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group ( two of 164 , 1 % ; p < 0.0001 ) or sulfadoxine/pyrimethamine plus artesunate group ( one of 198 , 1 % ; p < 0.0001 ) . After 28 and 42 days , patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups . Overall , sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54 % ( 95 % CI 36-66 , p < 0.0001 ) compared with sulfadoxine/ pyrimethamine alone and by 37 % ( 12-54 , p=0.007 ) compared with sulfadoxine/pyrimethamine plus artesunate . INTERPRETATION Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria .

placebo

uncomplicated malaria

failure rates

total number of treatments for malaria

safe

tolerated

Clinical treatment failure

malaria

uncomplicated malaria

children

6 months to 5 years


Treatment effects of eptifibatide in planned coronary stent implantation in patients with chronic kidney disease ( ESPRIT Trial ) . The role of platelet glycoprotein IIb/IIIa inhibitor therapy in patients with mild renal impairment is not well characterized . Our objective was to explore the associations of creatinine clearance ( CrCl ) with outcomes in a trial of eptifibatide therapy in patients who underwent percutaneous coronary intervention ( PCI ) . We analyzed 48-hour and 30-day outcomes of patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy ( ESPRIT ) trial . Patients were randomly assigned to placebo or eptifibatide as an adjunct to stent implantation ( 1,755 with CrCl > or =60 ml/min and 289 with CrCl < 60 ml/min ) . CrCl was calculated using the Cockcroft and Gault formula , and the associations of CrCl with outcomes were evaluated using logistic regression models . Patients with CrCl < 60 ml/min were more likely to be older , women , hypertensive , and have a history of coronary artery bypass surgery , stroke , or peripheral vascular disease . The interaction of eptifibatide with CrCl had borderline significance for the 30-day outcome ( p = 0.109 ) . Treatment effect trended toward a greater magnitude in patients with lower CrCl ( 60 ml/min ) ( odds ratio 0.53 , confidence interval 0.34 to 0.83 ) compared with those with higher CrCl ( 90 ml/min ) ( odds ratio 0.68 , confidence interval 0.49 to 0.94 ) . An accompanying increase in bleeding risk also was not apparent with lower CrCl . The treatment effect of eptifibatide is realized regardless of renal function and trends toward being greater in patients with mild renal impairment .

eptifibatide

eptifibatide therapy

Integrilin Therapy ( ESPRIT ) trial

placebo

eptifibatide

eptifibatide

CrCl

the Cockcroft and Gault formula

CrCl

logistic regression models

bleeding risk

renal impairment


Is the orientation of the apical defibrillation paddle of importance during manual external defibrillation ? OBJECTIVE Transthoracic impedance ( TTI ) is a factor determining the magnitude of the transmyocardial current during external defibrillation . Minimising TTI increases the chances of successful defibrillation . Most external defibrillation paddles are rectangular in shape and can , therefore , be placed in a transverse or longitudinal orientation . The apical paddle is often placed in a transverse orientation . This may theoretically result in a higher TTI than a longitudinal orientation because of poorer contact at the lateral paddle edges . We compared TTI with the apical paddle in both a transverse and longitudinal orientation . MATERIALS AND METHODS Twenty sequential anaesthetised patients were studied . A pair of defibrillator paddles were instrumented to measure paddle force . TTI was recorded pre-operatively at end-expiration with the apical paddle in both longitudinal and transverse orientations . The sternal paddle was placed in a longitudinal orientation for all measurements . RESULTS TTI decreased in both transverse and longitudinal orientations as paddle force increased . Transverse paddle orientation resulted in a significantly ( P < 0.01 ) higher TTI than longitudinal orientation at all paddle forces below 12 kg force . CONCLUSION The longitudinal orientation of a rectangular defibrillation paddle provides a lower TTI than orientation horizontally .

manual external defibrillation

external defibrillation

defibrillator paddles

Transverse paddle orientation

Transthoracic impedance ( TTI )

paddle force .

TTI


Trials and tribulations : current challenges in conducting clinical trials . Randomized controlled trials are the gold standard for the evaluation of new therapies and surgical procedures and as such require strict attention to study design and statistical analysis . There are , however , multiple challenges in conducting a well-designed clinical trial . This article describes the difficulties encountered at a single institution participating in a multicenter drug study and reviews the challenges involved in developing a high-quality randomized controlled study .


The efficacy of intramammary tilmicosin at drying-off , and other risk factors for the prevention of new intramammary infections during the dry period . The objective of this study was to compare the efficacy of an intramammary infusion , containing tilmicosin phosphate , to an infusion of a negative control intramammary placebo for preventing new intramammary infections ( IMI ) during the dry period . Cows were enrolled from 24 dairy herds from three geographical regions of Canada . Data from 248 cows and 938 bacteriologically negative quarters at drying-off are summarized . Overall , the rate of new IMI during the dry period was 16.7 % of quarters . The new infection rates for quarters that received intramammary tilmicosin compared with the intramammary placebo were 14.4 and 19.4 % , respectively . The majority of new IMI was caused by coagulase-negative staphylococci ( 49 % ) and environmental streptococcal organisms ( 26.8 % ) . The probability for quarters to develop new IMI in the dry period was significantly increased when cows had higher milk production before drying-off ( P = 0.04 ) , when cows had longer dry periods ( P = 0.02 ) , and when dry cows were housed in tie-stall barns ( P = 0.002 ) . Higher parity cows and those that had a linear score somatic cell count ( SCC ) above 4 on the last DHI test were also at increased risk for new IMI ( P < 0.10 ) . Administration of intramammary tilmicosin appears to be an efficacious therapy for prevention of new IMI ; however , there is currently no approved intramammary formulation of this product available . Use of blanket dry cow antibiotic therapy compared to selective dry cow therapy , as well as the importance of identifying risk factors and managing the environment of dry cows are discussed .

intramammary tilmicosin

intramammary tilmicosin

intramammary placebo

intramammary tilmicosin

efficacy

intramammary infections ( IMI )

rate of new IMI

new infection rates

new IMI

new IMI

linear score somatic cell count ( SCC )

risk for new IMI

prevention of new IMI ;

Cows


Anabolic steroids in athelics : crossover double-blind trial on weightlifters . Thirteen experienced male weightlifters taking high-protein diets and regular exercise took part in a double-blind crossover trial of methandienone 10 or 25 mg/day to seeif the drug improved athletic performance . Their improvemments were significantly greater on methandienone than on placebo ; their body weights rose ( though this seemed to be associated with water retention ) ; and systolic blood pressure rose significantly . Methandienone caused many side effects , and three men had to withdraw because of them . All side effects disappeared after the drug was stopped . Anabolic steroids are effective only when given combination with exercise and high-protein diet . We deprecate their use in athletics but can suggest no way of stopping it .

Anabolic steroids

methandienone

methandienone

placebo

Methandienone

Anabolic steroids

athletic performance

greater

body weights rose

systolic blood pressure rose

side effects

side effects

Thirteen

male


Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia : a report from the Children 's Cancer Group . Conventional therapy for childhood acute lymphoblastic leukemia ( ALL ) includes prednisone and oral 6-mercaptopurine . Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous ( IV ) over oral 6-mercaptopurine , which remain to be validated . We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine . Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 x 2 factorial design to receive dexamethasone ( 6 mg/m ( 2 ) /d ) for 28 days in induction , plus taper , compared with prednisone ( 40 mg/m ( 2 ) /d ) . The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation . During maintenance , 5 days of the randomized steroid was given monthly , at the same dose , and all patients received daily oral 6-mercaptopurine . During delayed intensification , all patients received a dexamethasone dosage of 10 mg/m ( 2 ) /d for 21 days , with taper . Intrathecal ( IT ) methotrexate was the sole central nervous system-directed therapy . Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous system-relapse rate of 3.7 % +/- 0.8 % , compared with 7.1 % +/- 1.1 % for prednisone ( P =.01 ) . There was also a trend toward fewer isolated bone marrow relapses with dexamethasone . The 6-year event-free survival ( EFS ) was 85 % +/- 2 % for dexamethasone and 77 % +/- 2 % for prednisone ( P =.002 ) . EFS was similar with oral or IV 6-mercaptopurine ; however , patients assigned to IV 6-mercaptopurine had decreased survival after relapse .

Dexamethasone

prednisone

intravenous mercaptopurine

Conventional therapy

prednisone

dexamethasone

prednisone

intravenous ( IV )

oral 6-mercaptopurine

dexamethasone

IV 6-mercaptopurine

prednisone

IV 6-mercaptopurine

oral 6-mercaptopurine

dexamethasone

Intrathecal ( IT ) methotrexate

dexamethasone

prednisone

dexamethasone

dexamethasone

prednisone

oral or IV 6-mercaptopurine

IV 6-mercaptopurine

efficacy

isolated bone marrow relapses

6-year event-free survival ( EFS )

survival after relapse .


Direct aortic cannulation in minimally invasive mitral-valve operations . The minimally invasive Port-Access ( Heartport , Redwood City , CA ) approach in mitral-valve operations originally required femoral arterial cannulation , which is considered a disadvantage , especially in patients with peripheral vessel disease . In this study 20 patients were prospectively randomized into 2 groups , to undergo either standard femoral ( group A ) or direct aortic cannulation ( group B ) . Pre- and postoperative data as well as markers for myocardial damage were assessed . Postoperatively , patients of group B showed lower levels of damage , indicating that direct aortic cannulation might provide better myocardial protection . Furthermore , the direct aortic cannulation technique may eliminate complications associated with the standard femoral artery cannulation .

Direct aortic cannulation

minimally invasive Port-Access

femoral arterial cannulation

standard femoral

direct aortic cannulation

direct aortic cannulation

direct aortic cannulation

standard femoral artery cannulation

levels of damage

complications

mitral-valve operations


A comparison of the upper lip bite test ( a simple new technique ) with modified Mallampati classification in predicting difficulty in endotracheal intubation : a prospective blinded study . We explored the possibility that a simple and single test could replace the modified Mallampati score for either a difficult or an unaccomplished tracheal intubation in an impending hypoxic patient . Three hundred adult patients were enrolled in this study . They were subjected to the following assessments : 1 ) oropharyngeal class according to the modified Mallampati criteria ; 2 ) the new , upper lip bite criteria-class I = lower incisors can bite the upper lip above the vermilion line , class II = lower incisors can bite the upper lip below the vermilion line , and class III = lower incisors can not bite the upper lip ; and 3 ) laryngeal view grading according to Cormack 's criteria . The incidence of difficult intubation was 5.7 % . The upper lip bite test showed significantly higher specificity and accuracy than the modified Mallampati test ( P < 0.001 ) . Comparisons of sensitivity , positive and negative predictive values , between the two tests , however , did not reveal any significant differences ( P > 0.05 ) . In conclusion , the upper lip bite test is an acceptable option for predicting difficult intubation as a simple , single test .

The upper lip bite test

modified Mallampati test

endotracheal intubation

Mallampati score

tracheal intubation

impending hypoxic

Cormack 's criteria

incidence of difficult intubation

specificity

accuracy

Mallampati test

endotracheal intubation

hypoxic

Three hundred

adult

difficult intubation


A pilot randomised control trial of a parent training intervention for pre-school children with autism . Preliminary findings and methodological challenges . Few attempts have been made to conduct randomised control trials ( RCTs ) of interventions for pre-school children with autism . We report findings of a pilot RCT for a parent training intervention with a focus on the development of joint attention skills and joint action routines . Twenty-four children meeting ICD-10 criteria for childhood autism ( mean age = 23 months ) were identified using the CHAT screen and randomised to the parent training group or to local services only . A follow-up was conducted 12 months later ( mean age = 35 months ) . There was some evidence that the parent training group made more progress in language development than the local services group . However , the present pilot study was compromised by several factors : a reliance on parental report to measure language , non-matching of the groups on initial IQ , and a lack of systematic checking regarding the implementation of the parent training intervention . Furthermore , three parents in the local services group commenced intensive , home-based behavioural intervention during the course of the study . The difficulties encountered in the conduct of RCTs for pre-school children with autism are discussed . Methodological challenges and strategies for future well-designed RCTs for autism interventions are highlighted .

parent training intervention

parent training intervention

parent training

local services

home-based behavioural intervention

language development

pre-school children with autism

pre-school children with autism

Twenty-four children

( mean age = 23 months )


[ The problems of prophylactic chemotherapy , the second-look operation and the maintenance of the remission in the treatment of ovarian cancer ( author 's transl ) ] . The results of the treatment of 1022 ovarian cancers were reviewed and the problems of prophylactic chemotherapy , a second look operation and the maintenance of the remission were studied . In ovarian cancers of stage 1 and stage 2 , a post-operative prophylactic chemotherapy is useful only in cases with tumor cells in the secretions of the pouch of Douglas or in the ascites and in cases where a sensitivity to the chemotherapy can be assumed . In about 50 % of primarily inoperable stage 3 ovarian cancers , the random treatment with cyclophosphamide ( Endoxan ) results in a clinical remission . A significant five year cure rate can only be obtained if the uterus and the adnexa are removed . Radical operation during the remission appears to be very important for survival of the patient . For the maintenance of the remission continuous chemotherapy for at least 2 years following treatment by operation and radiotherapy is necessary .

prophylactic chemotherapy

prophylactic chemotherapy

cyclophosphamide ( Endoxan )

chemotherapy

radiotherapy

clinical remission

cure

rate

survival

1022 ovarian cancers

ovarian cancers

stage 1

stage 2

inoperable stage 3 ovarian cancers


Effects of prelinguistic milieu teaching and parent responsivity education on dyads involving children with intellectual disabilities . This study tested the effect of a method of facilitating prelinguistic communication on parents ' responsivity and children 's communication and productive language development . The method involved Responsivity education for the parents and Prelinguistic Milieu Teaching for the children ( RPMT ) . Thirty-nine prelinguistic toddlers with intellectual disabilities and their primary caregivers participated in this study . Parent-child pairs were randomly assigned to either the RPMT group or a control group . Communication and language were assessed at study entry and 6 , 9 , and 12 months later . RPMT facilitated parental responsivity in the posttreatment period . The effect of RPMT on growth rate of child-initiated comments ( i.e. , the most common type of initiating joint attention ) varied by pretreatment measures of that variable . The effect of RPMT on growth rate of child-initiated requests ( i.e. , the most common type of initiating behavior regulation ) varied by presence or absence of Down syndrome . Finally , the effect of RPMT on growth of productive language varied by pretreatment frequency of canonical vocal communication . Recommended alterations in PMT and implications for defining which nonspeaking children are appropriate for prelinguistic goals and treatment were discussed .

Responsivity education for the parents

RPMT

control group .

RPMT

RPMT

RPMT

RPMT

PMT

Communication and language

parental responsivity

growth rate of child-initiated comments

growth rate of child-initiated requests

growth of productive language


Acute intravenous L-arginine infusion decreases endothelin-1 levels and improves endothelial function in patients with angina pectoris and normal coronary arteriograms : correlation with asymmetric dimethylarginine levels . BACKGROUND We tested the hypothesis that asymmetric dimethylarginine ( ADMA ) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X ( CSX ) . In addition , we evaluated whether an intravenous infusion of L-arginine would improve endothelial function in these subjects . METHODS AND RESULTS Nine patients with CSX and 14 control subjects underwent a continuous infusion of L-arginine ( 0.125 g/min ) or saline for 120 minutes . Sixty minutes after L-arginine or saline infusions , an intravenous insulin bolus ( 0.1 U/kg ) combined with a euglycemic clamp was performed . Basal ADMA and endothelin-1 levels were higher in patients with CSX than in controls . At the end of the first hour of infusion , compared with saline , L-arginine infusion increased basal forearm blood flow , nitrite and nitrate ( NOx ) , and forearm cGMP release and decreased endothelin-1 . After insulin bolus , during saline , insulin-induced NOx , endothelin-1 , and forearm cGMP release was almost abolished . Conversely , L-arginine restored a physiological profile of all endothelial variables compared with control subjects . In control subjects , compared with saline infusion , L-arginine infusion did not modify any parameter . ADMA levels were positively correlated with basal endothelin-1 levels and negatively correlated with insulin-induced incremental levels of NOx and forearm cGMP release . CONCLUSIONS Plasma ADMA levels are increased in patients with CSX , and they are correlated with increases in endothelin-1 and reductions in insulin-induced increments in plasma NOx and cGMP , effects that are reversed by intravenous L-arginine . These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX .

Acute intravenous L-arginine infusion

asymmetric dimethylarginine

nitric oxide

L-arginine

L-arginine ( 0.125 g/min ) or saline

L-arginine

saline infusions

insulin

euglycemic clamp

saline

L-arginine

saline infusion

L-arginine infusion

endothelin-1 levels

endothelial function

dimethylarginine levels .

nitric oxide release and action

endothelial function

Basal ADMA

endothelin-1 levels

basal forearm blood flow

nitrite and nitrate ( NOx )

forearm cGMP

insulin-induced NOx

forearm cGMP

endothelial variables

ADMA levels

endothelin-1 levels

levels of NOx

forearm cGMP

Plasma ADMA levels

NOx

cGMP

ADMA levels

angina pectoris

arteriograms

cardiac syndrome X

Nine


Variance in albumin loading in exchange transfusions . To assess the rationale of albumin priming prior to exchange transfusions , 42 hyperbilirubinemic infants who required exchange transfusions were randomly assigned to one of two groups . Group I consisted of 15 infants who were given intravenously 1 gm/kg of salt-poor human serum albumin one hour before the exchanges . Group II , which consisted of 27 infants , received simple exchanges . No statistical differences were found in variations in reserve albumin-binding capacity , bilirubin , albumin , or red cell bilirubin at pre and one-hour post albumin infusion in the primed infants . The amount of bilirubin removed per kilogram is directly correlated to plasma bilirubin concentration ( r=0.87 ) . No significant difference in efficiency on bilirubin removal was seen between the two groups . Beneficial effects of albumin therapy was apparent only in those infants with low RABC as determined by the sephadex gel filtration technique .

albumin

plasma bilirubin concentration

efficiency on bilirubin removal

15 infants


Lack of benefit of intravenous synthetic human secretin in the treatment of autism . The objective of this study was to determine if an intravenous infusion of synthetic human secretin improves language and behavioral symptoms in children with autism . Forty-two children with the diagnosis of autism were randomized to one of two groups in this double-blind cross-over trial . One group received 2 IU/kg of intravenous synthetic human secretin at the first visit , followed by an equal volume of intravenous saline placebo at week 6 . The other group received treatments in the reverse order . All children were evaluated at weeks 1 , 3 , 6 , 9 , and 12 with standardized assessments of language , behavior , and autism symptomatology . There were no significant differences in the mean scores on any measure of language , behavior , or autism symptom severity after treatment with secretin compared to treatment with placebo . The results of this study do not support secretin as a treatment for autism .

intravenous synthetic human secretin

intravenous saline placebo

language

behavioral symptoms

autism

children

autism

Forty-two

children

autism


Intravenous levosimendan treatment is cost-effective compared with dobutamine in severe low-output heart failure : an analysis based on the international LIDO trial . BACKGROUND Levosimendan , a novel calcium sensitiser , improves cardiac performance and symptoms without increasing oxygen consumption , and decreases the mortality of patients with low-output heart failure . AIMS To estimate the cost-effectiveness of intravenous treatment with levosimendan compared with dobutamine in patients with severe low-output heart failure . METHODS This economic evaluation was based on a European clinical trial ( LIDO ) , in which 203 patients with severe heart failure randomly received a 24 h infusion with either levosimendan or dobutamine . Survival and resource utilisation data were collected for 6 months ; survival was extrapolated assuming a mean additional lifetime of 3 years based on data from the Cooperative North Scandinavian Enalapril Survival Study trial . Costs were based on study drug usage and hospitalisation in the 6-month follow-up . A sensitivity analysis on dosage of drug and duration of survival was performed . RESULTS The mean survival over 6 months was 157+/-52 days in the levosimendan group and 139+/-64 days in the dobutamine group ( P < 0.01 ) . When extrapolated up to 3 years , the gain in life expectancy was estimated at 0.35 years ( discounted at 3 % ) . Levosimendan increased the mean cost per patient by 1108 , which was entirely due to the cost of the study drug . The incremental cost per life-year saved ( LYS ) was 3205 at the European level ; in the individual countries the cost per LYS ranged between 3091 and 3331 . The result was robust in the sensitivity analysis . CONCLUSIONS Although the patients in the levosimendan group were alive for more days and thus at risk of hospitalisation for longer , there was no increase in hospitalisation or hospitalisation costs with levosimendan treatment . The cost per LYS using levosimendan compares favourably with other cost-effectiveness analyses in cardiology .

levosimendan

dobutamine

Levosimendan

levosimendan

dobutamine

levosimendan

dobutamine

levosimendan

dobutamine

Levosimendan

levosimendan

levosimendan

dosage of drug

duration of survival

mean survival over 6 months

gain in life expectancy

mean cost per patient

incremental cost per life-year

risk of hospitalisation

cost-effectiveness analyses

severe low-output heart failure


Long-term use of Viozan ( sibenadet HCl ) in patients with chronic obstructive pulmonary disease : results of a 1-year study . Viozan ( sibenadet HCl , AR-C68397AA ) is a novel dual D2 dopamine receptor , beta2-adrenoceptor agonist that has been investigated for efficacy in alleviating the symptoms of chronic obstructive pulmonary disease ( COPD ) . The slowly progressive nature of this disease means that patients will require ongoing therapeutic management for many years , or even decades . With such long-term treatment , the safety profile of new agents will be of paramount importance . As part of the large-scale assessment of sibenadet , a 12-month safety study has been conducted . Following completion of a 2-week baseline period , 435 adults with stable , symptomatic , smoking-related COPD were randomized to receive either 500 microg sibenadet or placebo delivered via pressurized metered dose inhaler ( pMDI ) , three times daily for 52 weeks . Sibenadet therapy was generally well tolerated , with the only notable differences seen in the incidence of tremor and taste of treatment ( 16.9 % vs. 4.1 % and 14.5 % vs. 4.1 % in the sibenadet and placebo groups respectively ) . There were a total of 79 patients with serious adverse events ( SAEs ) , 43 ( 14.8 % ) in the sibenadet pMDI group and 36 ( 24.8 % ) in the placebo group . No clinically significant abnormal laboratory values or overall differences between treatment groups were noted . Similarly , there were no clinically significant differences between the two treatment groups for cardiac variables , or in vital signs . The secondary variables showed no notable differences with respect to lung function , exacerbations or health-related quality of life . Due to the effective beta2-agonist properties , patients in the sibenadet group did , however , report reduced rescue medication usage at all timepoints . While the results of this study show that , overall , sibenadet therapy was well tolerated , the lack of sustained benefit reported in large-scale clinical efficacy studies means that sibenadet development will not be continued .

Viozan ( sibenadet HCl )

Viozan

sibenadet HCl

sibenadet

500 microg sibenadet

placebo

Sibenadet

placebo

placebo

well tolerated

notable differences

serious adverse events

overall differences

no clinically significant differences

cardiac variables , or in vital signs

no notable differences

lung function

well tolerated

lack of sustained benefit

large-scale clinical efficacy studies

chronic obstructive pulmonary disease

adults

serious adverse events

SAEs

sibenadet pMDI

placebo