Cigarette smoking is associated with increased circulating proinflammatory and procoagulant markers in patients with chronic coronary artery disease : effects of aspirin treatment . BACKGROUND Smoking is associated with endothelial dysfunction . Cytokines released by injured endothelium promote vascular interactions with leukocytes and platelets . We investigated whether ( a ) cigarette smoking is linked to increased cytokine production , which may mediate platelet activation and thrombin generation in chronic coronary artery disease ( CAD ) , and ( b ) aspirin treatment inhibits smoking-related changes on cytokines , platelets , and thrombin . METHODS AND RESULTS Plasma macrophage-colony-stimulating factor ( M-CSF ) and C-reactive protein ( CRP ) were measured in 100 patients with chronic CAD , 60 of whom were chronic smokers . Prothrombin fragments 1+2 and urinary 11-dehydro-thromboxane B2 ( TXB2 ) were additionally measured in 60 of 100 patients ( 30 of whom were smokers ) and in 24 healthy controls . Smokers ( n = 20 ) matched for age , myocardial ischemia , and other risk factors with 20 nonsmokers entered a double-blind crossover trial of aspirin ( 300 mg/d for 3 weeks ) versus placebo . Blood and urine measurements were repeated after each treatment . Compared with nonsmokers , smokers had 3-fold median M-CSF ( 1499 vs 476 pg/mL ) , 2-fold CRP ( 1.5 vs 0.8 mg/L ) , and higher 11-dehydro-TXB 2 ( 3.6 vs 2.1 ng/mg creatinine , P < .01 for all comparisons ) . After aspirin treatment , M-CSF , CRP , 11-dehydro-TXB 2 , and prothrombin fragments 1+2 remained higher in smokers compared with nonsmokers despite a significant reduction of these markers by aspirin ( P < .05 ) . M-CSF remained related to 11-dehydro-TXB 2 excretion during both treatment phases ( P < .01 ) suggesting that cytokine-mediated thromboxane A 2 production was not altered by aspirin . CONCLUSIONS Smoking is associated with increased M-CSF , CRP , and platelet activity . Although aspirin treatment reduces the proinflammatory and procoagulant markers in smokers , it does not abolish the proinflammatory effects of smoking in patients with chronic CAD .

aspirin

aspirin

placebo .

aspirin

3-fold median M-CSF

2-fold CRP

M-CSF

CRP

11-dehydro-TXB 2

chronic coronary artery disease

chronic CAD

chronic smokers

smokers

Smokers

nonsmokers

chronic CAD


Effects of home strength training and stretching versus stretching alone after lumbar disk surgery : a randomized study with a 1-year follow-up . OBJECTIVE To assess the adherence to and effects of a 12-month combined strength and stretching home exercise regimen versus stretching alone , on patient outcome after lumbar disk surgery . DESIGN Randomized controlled trial . SETTING Departments of physical medicine and rehabilitation and orthopedics at a Finnish hospital . PARTICIPANTS Patients ( N=126 ) were randomized into either a combined strength training and stretching group ( STG , n=65 ) or a control group ( CG , n=61 ) . INTERVENTION The STG was instructed to perform strength training and both the STG and CG were instructed in the same stretching and stabilization exercises for 12 months . MAIN OUTCOME MEASURES Pain on the visual analog scale ( VAS ) , the Oswestry and the Million disability indexes , isometric and dynamic trunk muscle strength , mobility in the lumbar spine , and straight-leg raising were measured . RESULTS The trial was completed by 71 % and 77 % of the patients from the STG and the CG , respectively . The mean strength training frequency decreased from 1.5 to 0.6 times a week in the STG during the intervention . The mean stretching frequency decreased from 3.7 to 1.6 times a week in both groups . Median back and leg pain varied between 17 and 23 mm ( VAS ) , and the Million and Oswestry indices varied between 14 and 23 points 2 months postoperatively . No statistically significant changes took place in these outcome measures during the 12-month follow-up in both groups . The changes in isometric trunk extension favored the STG ( P =.016 ) during the first 2 months . However , during the whole 12-month training period , both dynamic and isometric back extension and flexion strength , as well as mobility of the spine and repetitive squat-test results , improved significantly in both groups , and no differences were found in any of the physical function parameters between the STG and CG . CONCLUSIONS At the 12-month follow-up , no statistically significant changes were found in the physical function , pain , or disability measures between the groups . In the STG , training adherence with regard to training frequency and intensity remained too low to lead to specific training-induced adaptations in the neuromuscular system . Progressive loading , supervision of training , and psychosocial support is needed in long-term rehabilitation programs to maintain patient motivation .

home strength training and stretching

stretching alone

stretching alone

control group

strength training

stretching and stabilization exercises

stretching

mean strength training frequency

mean stretching frequency

Median back and leg pain

Million and Oswestry indices

isometric trunk extension

physical function parameters

physical function

, pain

, or disability measures

lumbar disk surgery

after lumbar disk surgery


Efficacy of physiotherapy management of knee joint osteoarthritis : a randomised , double blind , placebo controlled trial . OBJECTIVE To determine whether a multimodal physiotherapy programme including taping , exercises , and massage is effective for knee osteoarthritis , and if benefits can be maintained with self management . METHODS Randomised , double blind , placebo controlled trial ; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial . Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks . Physiotherapy included exercise , massage , taping , and mobilisation , followed by 12 weeks of self management . Placebo was sham ultrasound and light application of a non-therapeutic gel , followed by no treatment . Primary outcomes were pain measured by visual analogue scale and patient global change . Secondary measures included WOMAC , knee pain scale , SF-36 , assessment of quality of life index , quadriceps strength , and balance test . RESULTS Using an intention to treat analysis , physiotherapy and placebo groups showed similar pain reductions at 12 weeks : -2.2 cm ( 95 % CI , -2.6 to -1.7 ) and -2.0 cm ( -2.5 to -1.5 ) , respectively . At 24 weeks , pain remained reduced from baseline in both groups : -2.1 ( -2.6 to -1.6 ) and -1.6 ( -2.2 to -1.0 ) , respectively . Global improvement was reported by 70 % of physiotherapy participants ( 51/73 ) at 12 weeks and by 59 % ( 43/73 ) at 24 weeks . Similarly , global improvement was reported by 72 % of placebo participants ( 48/67 ) at 12 weeks and by 49 % ( 33/67 ) at 24 weeks ( all p > 0.05 ) . CONCLUSIONS The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability .

physiotherapy management

placebo

multimodal physiotherapy programme

taping

exercises

massage

placebo

Physiotherapy

placebo

Physiotherapy included exercise

massage

taping

mobilisation

Placebo

physiotherapy programme

pain measured

WOMAC

knee pain scale

assessment of quality of life index

quadriceps strength

balance test

pain reductions

pain remained reduced

Global improvement

global improvement

knee joint osteoarthritis

knee osteoarthritis

knee osteoarthritis


Cost-effectiveness of combined manipulation , stabilizing exercises , and physician consultation compared to physician consultation alone for chronic low back pain : a prospective randomized trial with 2-year follow-up . STUDY DESIGN A prospective , randomized controlled trial . OBJECTIVE To examine long-term effects and costs of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain ( cLBP ) . SUMMARY OF BACKGROUND DATA An obvious gap exists in knowledge concerning long-term efficacy and cost-effectiveness of manipulative treatment methods . METHODS Of 204 patients with cLBP whose Oswestry Disability Index ( ODI ) was at least 16 % , 102 were randomized into a combined manipulative treatment , exercise , and physician consultation group ( i.e. , a combination group ) , and 102 to a consultation alone group . All patients were clinically examined , informed about their back pain , and encouraged to stay active and exercise according to specific instructions based on clinical evaluation . Treatment included 4 sessions of manual therapy and stabilizing exercises aimed at correcting the lumbopelvic rhythm . Questionnaires inquired about pain ( visual analog scale ( VAS ) ) , disability ( ODI ) , health-related quality of life ( 15D Quality of Life Instrument ) , satisfaction with care , and costs . RESULTS Significant improvement occurred in both groups on every self-rated outcome measurement . Within 2 years , the combination group showed only a slightly more significant reduction in VAS ( P = 0.01 , analysis of variance ) but clearly higher patient satisfaction ( P = 0.001 , Pearson chi2 ) as compared to the consultation group . Incremental analysis showed that for combined group compared to consultation group , a one-point change in VAS scale cost $ 512 . CONCLUSIONS Physician consultation alone was more cost-effective for both health care use and work absenteeism , and led to equal improvement in disability and health-related quality of life . It seems obvious that encouraging information and advice are major elements for the treatment of patients with cLBP .

combined manipulation

stabilizing exercises

physician consultation

physician consultation alone

physician consultation alone

consultation

alone

Physician consultation alone

pain ( visual analog scale ( VAS ) ) ,

disability ( ODI )

health-related quality of life

15D Quality of Life Instrument

satisfaction with care

costs

self-rated outcome

VAS

patient satisfaction

cost-effective

chronic low back pain :

chronic low back pain ( cLBP

cLBP


Uterine incision closure at caesarean section : a randomised comparative study of intraperitoneal closure and closure after temporary exteriorisation . BACKGROUND The safety of the technique of uterine exteriorization at caesarean section though popular among obstetricians , remains controversial . OBJECTIVE To evaluate the influence of exteriorization of uterus during uterine repair on caesarean morbidity . METHODS A randomized comparative study of 136 women undergoing primary caesarean delivery at Havana Specialist Hospital Lagos Nigeria . Data on operation time , estimated blood loss , postoperative morbidities were collected and analysed with comparison between the two groups using chi square , Fischer 's exact test and t-test as appropriate . RESULTS The mean operative time , estimated blood loss , transfusion rate and postoperative anemia rate were significantly less in the exteriorized group than the intraperitoneal group ( p = 0.000 , 0.009,0.048 0.038 and 0.028 respectively ) , but not in other outcome measures . CONCLUSION With shorter operative time , less blood loss and similar morbidity profile exteriorization of uterus during caesarean section seems to be preferred except where it is not possible because of adhesions and surgeons inexperience .

mean operative time

estimated blood loss

transfusion rate

postoperative anemia rate

women

primary caesarean delivery


Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids , hemostatic parameters and carbohydrate metabolism . OBJECTIVE To compare the effect of ethinyl estradiol 20 microg/drospirenone 3 mg ( EE 20 microg/DRSP 3 mg ) administered according to a 24/4 regimen with ethinyl estradiol 20 microg/desogestrel 150 microg ( EE 20 microg/DSG 150 microg ) administered according to the conventional 21/7 regimen on lipid , carbohydrate and hemostatic parameters . STUDY DESIGN In this open-label study , healthy women were randomized to EE 20 microg/DRSP 3 mg or EE 20 microg/DSG 150 microg for seven cycles . Mean differences in high-density lipoprotein ( HDL ) - and low-density lipoprotein ( LDL ) -cholesterol levels at cycle 7 compared to baseline were assessed . Secondary variables included changes in other lipid , hemostatic and carbohydrate parameters . RESULTS Both treatments increased HDL-cholesterol , but decreased LDL-cholesterol by a comparable extent . Although slightly elevated in both groups , blood glucose and C-peptide levels measured during oral glucose tolerance tests were within normal reference ranges at cycle 7 . Overall , the differences in lipid , hemostatic or carbohydrate parameters were not significant between the two treatments . CONCLUSION EE 20 microg/DRSP 3 mg has a good safety profile comparable with EE 20 microg/DSG 150 microg .

oral contraceptives

ethinyl estradiol

drospirenone

desogestrel

ethinyl estradiol 20 microg/desogestrel

high-density lipoprotein ( HDL )

HDL-cholesterol

LDL-cholesterol

blood glucose and C-peptide levels

lipid

hemostatic or carbohydrate parameters

healthy

women


Are brand-name and generic warfarin interchangeable ? Multiple n-of-1 randomized , crossover trials . BACKGROUND Warfarin is a commonly used anticoagulant in North America . Several generic formulations have been approved , raising concern over the safety and efficacy of these products compared with brand-name Coumadin . OBJECTIVE To ensure that generic warfarin products can be safely interchanged with Coumadin . METHODS Multiple n-of-1 randomized , double-blind , crossover trials switched outpatients ( N = 7 ) between a generic warfarin formulation ( Apo-warfarin ) and Coumadin over 30 weeks . Study patients took each drug for five 3-week periods , with international normalized ratio ( INR ) measurements taken twice per period . Inter- and intrapatient differences between generic warfarin and Coumadin were compared , and overall study patient results were compared with those of a Coumadin control group . RESULTS There were no differences between warfarin products in terms of mean INR results or number of dosage adjustments required . There also was no difference in INR variation based on warfarin formulation ( p > 0.69 ) , nor was a patient and warfarin interaction found ( p > 0.81 ) . The INR results were not influenced by whether patients were maintained on Coumadin only ( control group ) or interchanged between Coumadin and generic warfarin ( p = 0.98 ) . CONCLUSIONS It appears that patients can safely and effectively switch between generic warfarin and Coumadin .

generic warfarin

Warfarin

Coumadin

Coumadin over 30 weeks

warfarin

Coumadin

Coumadin

generic warfarin

warfarin

Coumadin

safety

efficacy

international normalized ratio ( INR )

INR results

safely and effectively switch

( N = 7 )


Enhancement of blood glucose lowering effect of a sulfonylurea when coadministered with an ACE inhibitor : results of a glucose-clamp study . BACKGROUND To investigate if coadministration of enalapril alters the metabolic effect of glibenclamide by employing an euglycemic glucose-clamp technique in healthy volunteers . METHODS A double-blind crossover study with nine healthy normotensive volunteers ( age 27 +/- 3 y , BMI 23.3 +/- 2.0 kg m ( -2 ) ; mean +/- SD ) -randomly assigned to a 3-day treatment of either 5 mg enalapril or placebo . In the morning of the fourth day , volunteers orally received 3.5 mg glibenclamide together with either 10 mg enalapril or placebo . Blood glucose levels of volunteers were allowed to fall by 10 % from fasting levels and were kept constant thereafter by employing a Biostator-based euglycemic glucose clamp . RESULTS Coadministration of enalapril-compared with placebo-resulted in a temporarily higher metabolic effect of glibenclamide ( AUC GIR ( 0-120 ) 229 +/- 173 vs 137 +/- 44 mg kg ( -1 ) , p < 0.01 ; mean +/- SD ) , which lasted from 120 min to 240 min after enalapril administration . In parallel , the maximal metabolic effect of glibenclamide tended to be higher with enalapril ( GIR ( max ) 5.2 +/- 1.9 vs 4.1 +/- 1.3 mg kg ( -1 ) min ( -1 ) ; p = 0.19 ) . However , the total metabolic effect of glibenclamide was almost identical between volunteers taking enalapril or placebo ( AUC GIR ( 0-600 ) 1267 +/- 334 vs 1286 +/- 249 mg kg ( -1 ) , ns ) . In contrast , serum insulin levels , C-peptide levels , and serum glibenclamide profiles were not significantly different between enalapril and placebo . CONCLUSIONS The results of this study may explain the higher incidence of hypoglycemic episodes observed in patients with type 2 diabetes when taking ACE inhibitors together with sulfonylureas or insulin . ACE inhibitors may cause a temporary increase of the insulin sensitivity , which leads to an increased risk of hypoglycemia under these conditions .

sulfonylurea

ACE inhibitor :

enalapril

glibenclamide

5 mg enalapril

placebo

glibenclamide

enalapril

placebo

enalapril-compared

placebo-resulted

glibenclamide

enalapril

glibenclamide

enalapril

glibenclamide

enalapril

placebo

glibenclamide

enalapril

placebo

ACE inhibitors

sulfonylureas

insulin

ACE inhibitors

Blood glucose levels

metabolic effect of glibenclamide

total metabolic effect of glibenclamide

serum insulin levels

C-peptide levels

serum glibenclamide profiles

hypoglycemic episodes

insulin sensitivity

increased risk of hypoglycemia

age 27 +/- 3 y


Association between platelet activation and fibrinolysis in acute stroke patients . We aimed to evaluate platelet activation and fibrinolyis in acute atherosclerotic ischemic stroke patients to clarify the relationship between them . Plasma P-selectin antigen , tissue plasminogen activator ( tPA ) antigen and activity , and plasminogen activator inhibitor-1 ( PAI-1 ) activity were determined in 60 acute atherosclerotic stroke patients and matched control subjects . All patients were examined within 72 h after stroke onset . The levels of P-selectin , tPA antigen , and PAI-1 activity were all significantly higher in stroke patients compared with controls ( all p < 0.0001 ) ; the level of tPA activity was significantly lower in patients than that in controls ( p < 0.0001 ) . These markers did not change much at different time points within 72 h. In stroke group , P-selectin concentration was highly correlated to PAI-1 activity ( r = 0.8433 , p < 0.001 ) , but not to tPA antigen ( r = -0.1752 , p > 0.05 ) , and tPA activity ( r = 0.2465 , p > 0.05 ) , which was further confirmed in the multiple linear regression analysis ( F = 47.052 , p < 0.0001 ) . Our results indicate increased platelet activation and decreased fibrinolysis in patients with acute atherosclerotic ischemic stroke . Increased platelet activation may be correlated with decreased fibrinolysis .

Plasma P-selectin antigen

P-selectin , tPA antigen

P-selectin

tPA

tPA

Plasma P-selectin antigen

levels of P-selectin , tPA antigen

PAI-1 activity

significantly higher

level of tPA activity

P-selectin concentration

PAI-1 activity

tPA antigen

tPA activity

increased platelet activation

decreased fibrinolysis

platelet activation

acute stroke

acute atherosclerotic ischemic stroke

stroke

stroke

stroke


Results of a multicenter , 8-week , parallel-group , randomized , double-blind , double-dummy , Phase III clinical trial to evaluate the efficacy and tolerability of amlodipine maleate versus amlodipine besylate in Korean patients with mild to moderate hypertension . BACKGROUND Recently , amlodipine maleate was developed and tested in preclinical and Phase I clinical trials in Korea . The studies found pharmacokinetics and pharmacodynamics similar to those of amlodipine besylate . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of amlodipine maleate with those of amlodipine besylate in Korean patients with mild to moderate hypertension . METHODS This was a multicenter , 8-week , parallel-group , randomized , double-blind , double-dummy , Phase III clinical trial . Eligible patients were Korean , aged 18 to 75 years , had hypertension , and were either taking antihypertensive medications or had a documented sitting diastolic blood pressure of 90 to 109 mm Hg . After a washout period of 2 weeks , patients were randomized to amlodipine maleate or amlodipine besylate for 8 weeks . In both groups , the medications were initiated at 5 mg QD . At day 29 , the medication dose was increased to 10 mg QD if sitting diastolic blood pressure ( SiDBP ) was > or = 90 mm Hg . RESULTS One hundred eighteen patients were enrolled . Fifty-seven patients received amlodipine maleate ( 29 men , 28 women ; mean [ SD ] age , 49.0 [ 11.4 ] years ) and 61 received amlodipine besylate ( 35 men , 26 women ; mean [ SD ] age , 51.6 [ 9.4 ] years ) . Baseline mean ( SD ) values for sitting systolic blood pressure and SiDBP were 152.0 ( 12.2 ) mm Hg and 98.1 ( 5.6 ) mm Hg , respectively , for the amlodipine maleate group and 153.4 ( 14.0 ) mm Hg and 98.1 ( 5.5 ) mm Hg , respectively , for the amlodipine besylate group . In this population , amlodipine maleate was not inferior to amlodipine besylate : the lower limit of the 2-sided 95 % CI for the treatment difference in SiDBP was greater than -4 mm Hg . The between-group difference in SiDBP response rate ( the proportion of patients who experienced adequate SiDBP reductions ) did not reach statistical significance : 85.7 % ( 42/49 ) for the amlodipine maleate group and 91.8 % ( 45/49 ) for the amlodipine besylate group . Compliance rates were similar between groups , with mean ( SD ) compliance rates of 97.4 % ( 2.8 % ) and 97.1 % ( 3.6 % ) in the amlodipine maleate and amlodipine besylate groups , respectively . Also , there were no significant differences in the incidences of drug-related clinical and laboratory adverse events ; the most common were headache , flushing , facial edema , and paresthesia . CONCLUSION In this population , the efficacy and tolerability observed with amlodipine maleate were similar to those seen with amlodipine besylate .

amlodipine maleate

amlodipine besylate

amlodipine maleate

amlodipine besylate

amlodipine maleate

amlodipine besylate

amlodipine maleate

amlodipine besylate

amlodipine maleate

amlodipine besylate :

amlodipine maleate

amlodipine maleate

amlodipine besylate

Baseline mean ( SD ) values

SiDBP

SiDBP response rate

mean ( SD ) compliance rates

mild to moderate hypertension

Korean patients

mild to moderate hypertension

aged 18 to 75 years

hypertension

One hundred eighteen


[ Final evaluation of the randomized multicenter study SAKK 40/81 : adjuvant portal chemotherapy of curatively resected colorectal cancer ] . Between 1981 and 1987 , 533 patients from 9 institutions have been entered in a randomized trial to assess the value of adjuvant portal infusion ( 5-Fluorouracil , Mitomycin C ) compared to radical surgery alone . Analysis of 469 evaluable patients at a median follow-up of 5.8 years revealed 110 recurrences in the control and 94 recurrences in the infusion group . Estimated 5-year disease-free survival was 52 % and 61 % respectively ( hazard ratio 1:0.75 ; 95 % confidence interval 0.57-0.99 ; p = 0.046 ) . Overall survival was 59 % in the control and 69 in the infusion group ( p = 0.048 ) . Adjuvant portal infusion did not influence the occurrence of liver metastases but reduced the overall recurrence rate .

adjuvant portal chemotherapy

5-year disease-free survival

Overall survival

occurrence of liver metastases

overall recurrence rate .

curatively resected colorectal cancer


[ A multicenter , randomized clinical trial of intravenous diltiazem in treatment of unstable angina ] . OBJECTIVE To investigate the clinical efficacy and safety of intravenous diltiazem compared with nitroglycerin in the patients with unstable angina pectoris . METHODS A multicenter , randomized , open-label , parallel group trial was conducted . A total of 213 eligible patients were enrolled . They were randomized either to diltiazem or nitroglycerin treatment . The diltiazem was administered from 100 microg/min at the initiation of treatment , the largest dosage was 200 - 300 microg/min ; the nitroglycerin was administered from 20 microg/min at the initiation of treatment . The largest dosage was 80 - 100 microg/min . Intravenous infusion was kept over 48 hours . The endpoints included refractory angina pectoris , acute myocardial infarction , death , emergency PTCA and CABG . RESULTS ( 1 ) Intravenous diltiazem was effective on the improvement of symptom and electrocardiogram , and its effects were similar to intravenous nitroglycerin . ( 2 ) Compared with nitroglycerin , intravenous diltiazem lowered heart rate and myocardial oxygen consumption index ( systolic pressure x heart rate ) to more extent significantly . ( 3 ) After treatment , the onsets of refractory angina pectoris were reduced more significantly in the diltiazem group than in nitroglycerin group [ 4 ( 3.8 % ) vs 13 ( 11.9 % ) , RR 0.32 ( 95 % CI 0.11 - 0.96 ) , P < 0.05 ] . ( 4 ) The patients whose heart rate were reduced significantly ( < or= 50 beats per minute ) in the diltiazem group were more than in the nitroglycerin group [ 8 ( 7.7 % ) vs 0 ( 0 % ) , P < 0.01 ] . But these patients could tolerate the lower heart rate very well in the diltiazem group . ( 5 ) The needs of beta receptor blocker or calcium antagonists were reduced more significantly in the diltiazem group compared with those in the nitroglycerin group [ 2 ( 1.9 % ) vs 13 ( 11.9 % ) , P < 0.01 ] . CONCLUSION Intravenous diltiazem therapy is effective and safe for patients with unstable angina pectoris . It may significantly lower the risk of refractory angina pectoris compared with intravenous nitroglycerin .

diltiazem

diltiazem

nitroglycerin

diltiazem

nitroglycerin

diltiazem

nitroglycerin

nitroglycerin

diltiazem

diltiazem

diltiazem

diltiazem

refractory angina pectoris

acute myocardial infarction

death

emergency PTCA

CABG

symptom and electrocardiogram

lowered heart rate

myocardial oxygen consumption index

onsets of refractory angina pectoris

reduced more significantly

heart rate

reduced significantly

heart rate

angina

unstable angina pectoris


Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants . OBJECTIVE Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years , the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated . The objective of this study was to determine if restrictive guidelines for red blood cell ( RBC ) transfusions for preterm infants can reduce the number of transfusions without adverse consequences . DESIGN , SETTING , AND PATIENTS We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion . INTERVENTION The infants were assigned randomly to either the liberal- or the restrictive-transfusion group . For each group , transfusions were given only when the hematocrit level fell below the assigned value . In each group , the transfusion threshold levels decreased with improving clinical status . MAIN OUTCOME MEASURES We recorded the number of transfusions , the number of donor exposures , and various clinical and physiologic outcomes . RESULTS Infants in the liberal-transfusion group received more RBC transfusions ( 5.2 +/- 4.5 [ mean +/- SD ] vs 3.3 +/- 2.9 in the restrictive-transfusion group ) . However , the number of donors to whom the infants were exposed was not significantly different ( 2.8 +/- 2.5 vs 2.2 +/- 2.0 ) . There was no difference between the groups in the percentage of infants who avoided transfusions altogether ( 12 % in the liberal-transfusion group versus 10 % in the restrictive-transfusion group ) . Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia , and they had more frequent episodes of apnea , including both mild and severe episodes . CONCLUSIONS Although both transfusion programs were well tolerated , our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants .

liberal- or the restrictive-transfusion

RBC transfusions

restrictive-transfusion

transfusion

restrictive transfusions

number of transfusions

number of transfusions

number of donor exposures

RBC transfusions

number of donors

more frequent episodes of apnea

mild and severe episodes

major adverse neurologic events

preterm infants .


Clinical evaluation of the contact sensitization potential of a transdermal nicotine system ( Nicoderm ) BACKGROUND Transdermal nicotine therapy has shown promise as a smoking cessation aid , but questions about its contact sensitization potential and long-term topical safety have been raised . The purpose of this study was to determine the contact sensitization potential of one nicotine transdermal system ( Nicoderm , Marion Merrell Dow Inc , Kansas City , Mo , and ALZA Corporation , Palo Alto , Calif ) in a population who were allowed to continue smoking . METHODS This study comprised two phases separated by a 2-week rest interval . During phase 1 , a 42-day open-label induction period , subjects wore only active transdermal nicotine systems . During phase 2 , a 4-day double-blind challenge period , subjects wore active and placebo systems concurrently . Upon removal of each patch , skin sites were evaluated for signs of irritation , and subjective complaints such as itching or burning were recorded . RESULTS Of the 186 subjects completing the study , 3 ( 1.6 % ) exhibited evidence of delayed contact sensitization manifested as erythema with or without infiltration and confined solely to sites of active transdermal nicotine system application . Nonallergic skin irritation was observed in less than 3 % of all applications . All reactions resolved without incident . No subjects developed systemic reactions . CONCLUSIONS The transdermal nicotine system used in this trial had a low contact sensitization incidence and was well tolerated topically with minimal irritation .

Transdermal nicotine therapy

one nicotine transdermal system

active transdermal nicotine systems .

active

placebo systems concurrently

transdermal nicotine system

transdermal nicotine system

signs of irritation

subjective complaints

itching

or

burning

erythema with or without infiltration

Nonallergic skin irritation

systemic reactions

tolerated


A comparison of urinary and sexual outcomes in women experiencing vaginal and Caesarean births . OBJECTIVE To evaluate the urinary and sexual consequences of vaginal delivery compared with Caesarean section . METHODS We performed a cohort analysis of data from a randomized controlled trial of episiotomy conducted in 3 Montreal hospitals in 1990-1991 . Of the 999 trial participants for whom follow-up data were available , 135 delivered by Caesarean section ( CS ) , and 864 had a vaginal birth ( VB ) . After stratifying for parity , we compared rates of urinary incontinence ( UI ) and sexual functioning at 3 months postpartum in women who had a VB with the rates in women who had a CS . RESULTS Primiparous women reported unspecified UI at 3 months postpartum more often ( 17.9 % ) in the VB group than in the CS group ( 6.4 % ) . This difference remained significant whether or not there was a prior history of UI . Multiparous women showed no difference in rates of UI ( VB 17.1 % vs. CS 16.0 % ) , whether there was a prior history of UI or not . Stress incontinence was greater among primiparous women in the VB group ( VB 34.5 % vs. CS 12.8 % ) regardless of prior UI history , but the proportion of women whose UI was severe enough to wear a pad was similar in primiparous women ( VB 16.0 % , CS 15.4 % ) and multiparous women ( VB 23.8 % , CS 25.0 % ) . Women 's sexual dissatisfaction was greater among primiparous women who had a vaginal birth ( VB 70.1 % , CS 54.5 % ) , but in multiparous women , the rates of sexual dissatisfaction were similar ( VB 64.2 % , CS 71.4 % ) . The frequency of dyspareunia for each mode of delivery was similar in primiparous women ( VB 30.7 % , CS 31.6 % ) . Overall , both primiparous and multiparous women who had intact perineums after VB had less dyspareunia than those undergoing CS ( VB 26.2 , CS 40.7 % ) . However , the proportion of women experiencing dyspareunia was greatest among those who had an episiotomy with or without forceps .

vaginal delivery

Caesarean section

Caesarean section ( CS )

vaginal birth ( VB )

urinary and sexual consequences

urinary incontinence ( UI )

sexual functioning

UI

rates of

Stress incontinence

UI

Women 's sexual dissatisfaction

sexual dissatisfaction

frequency of dyspareunia

dyspareunia

dyspareunia

women

vaginal and Caesarean

vaginal delivery

women

women


Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma : a prospectively planned combined survival analysis of two multicenter trials . BACKGROUND Fulvestrant is an estrogen receptor antagonist with no agonist effects . In the second-line treatment of advanced breast carcinoma , fulvestrant was shown previously to be as effective as the third-generation aromatase inhibitor , anastrozole , in terms of time to disease progression and objective response rates . The authors reported the overall survival results from these studies . METHODS A prospectively planned , combined , overall survival analysis was performed , including data from two Phase III trials that compared the efficacy and tolerability of fulvestrant ( 250 mg monthly ; n = 428 ) with anastrozole ( 1 mg daily ; n = 423 ) in the treatment of postmenopausal women with advanced breast carcinoma who had disease progression after receipt of previous endocrine treatment . RESULTS At an extended median follow-up of 27.0 months ( range , 0-66.9 months ) , 319 ( 74.5 % ) patients in the fulvestrant group and 322 ( 76.1 % ) patients in the anastrozole group had died . Prolonged survival was observed with both drugs , with 10-20 % of patients still alive > 5 years after randomization . The median overall survival was similar between treatments , being 27.4 months and 27.7 months in fulvestrant and anastrozole-treated patients , respectively ( hazards ratio , 0.98 ; 95 % confidence interval , 0.84-1.15 ; P = 0.809 ) . Fulvestrant continued to be well tolerated , and was associated with a significantly lower incidence of joint disorders compared with anastrozole ( P = 0.0234 ) . CONCLUSIONS The current analysis showed that fulvestrant was similar to anastrozole with respect to overall survival in the second-line treatment of postmenopausal women with advanced breast carcinoma .

Fulvestrant

anastrozole

Fulvestrant

fulvestrant

anastrozole

fulvestrant

anastrozole-treated

fulvestrant

overall survival

overall survival

efficacy

tolerability

died

Prolonged survival

alive

median overall survival

incidence of joint disorders

postmenopausal

women

advanced breast carcinoma

postmenopausal

women

advanced breast carcinoma


Efficacy of rofecoxib , celecoxib , and acetaminophen in patients with osteoarthritis of the knee . A combined analysis of the VACT studies . OBJECTIVE To compare efficacy among 1578 patients with osteoarthritis randomized to take acetaminophen 4000 mg ( n=269 ) , celecoxib 200 mg ( n=523 ) , rofecoxib 12.5 mg ( n=259 ) , or rofecoxib 25 mg ( n=527 ) in a double blind trial [ Vioxx , Acetaminophen , Celecoxib Trial ( VACT2 ) ] . Results were also pooled with the similarly designed VACT1 trial . METHODS Patients evaluated over Days 1 to 6 and 6 weeks with Patient Global Assessment of Response to Therapy ( PGART ) and Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index . RESULTS For VACT2 , median time to good or excellent PGART response was 6 , 5 , 4 , and 3 days for acetaminophen , celecoxib , rofecoxib 12.5 mg , and rofecoxib 25 mg ( COX-2 inhibitors vs acetaminophen , p < or=0.035 ; rofecoxib 25 mg vs celecoxib , p=0.01 ) . WOMAC response over the first 6 days was greater ( p < 0.05 ) with both rofecoxib doses than acetaminophen and celecoxib . At Week 6 , all COX-2 inhibitors provided significantly greater efficacy than acetaminophen . Good or excellent PGART was numerically , but not significantly , greater with rofecoxib 25 mg ( 55.4 % ) than celecoxib ( 50.6 % ) at Week 6 ; a significant difference was seen at Weeks 2 ( 6.9 , p=0.022 ) and 4 ( 6.7 , p=0.027 ) and over 6 weeks with analysis of all 5 PGART categories of response ( p=0.035 ) . Rofecoxib 25 mg provided greater response ( p < 0.05 ) than celecoxib on WOMAC subscales . Pooled analysis of VACT1/VACT2 demonstrated greater PGART ( p=0.023 ) with rofecoxib 25 mg ( 56.1 % ) than celecoxib ( 49.8 % ) at 6 weeks and greater response to all other PGART and WOMAC endpoints , and confirmed superiority of COX-2 inhibitors to acetaminophen . Overall , tolerability of the study medications was generally good and similar . There was no significant difference between treatment groups in the percentage of patients who experienced a clinical adverse experience ( AE ) . The incidence of discontinuations due to an AE was significantly lower with celecoxib ( 2.5 % ) compared to rofecoxib 25 mg ( 6.3 % , p=0.004 ) or acetaminophen ( 7.8 % , p < 0.001 ) , and did not differ significantly from rofecoxib 12.5 mg ( 4.6 % ) . Discontinuation rates due to edema and hypertension related AE were similar among all COX-2 inhibitors . CONCLUSION Rofecoxib and celecoxib provided superior efficacy to acetaminophen . There was a more rapid and greater response with rofecoxib 25 mg than celecoxib 200 mg. Rofecoxib 12.5 mg demonstrated greater efficacy than celecoxib 200 mg over the first 6 days , and was similar over 6 weeks . All study medications were generally well tolerated .

rofecoxib

celecoxib

acetaminophen

acetaminophen

celecoxib

rofecoxib

rofecoxib

Vioxx

Acetaminophen

Celecoxib

acetaminophen

celecoxib

rofecoxib

rofecoxib

acetaminophen

rofecoxib

celecoxib

rofecoxib

rofecoxib

celecoxib

Rofecoxib

celecoxib

rofecoxib

celecoxib

acetaminophen

celecoxib

rofecoxib

acetaminophen

Rofecoxib

celecoxib

acetaminophen

celecoxib

Rofecoxib

celecoxib

WOMAC response

greater efficacy

PGART

PGART

WOMAC subscales

greater PGART

greater response to all other PGART

WOMAC endpoints

tolerability

good and similar

clinical adverse experience ( AE )

discontinuations due to an AE

Discontinuation rates

edema and hypertension related AE

efficacy

response

efficacy

tolerated


A short-term cognitive group treatment program gives substantial weight reduction up to 18 months from the end of treatment . A randomized controlled trial . OBJECTIVE To describe and evaluate long-term efficacy ( 18 months from the end of treatment ) of a new cognitive short-term weight reducing treatment program for obese patients . SUBJECTS One hundred and five obese [ Body Mass Index ( BMI ) > or = 30 ] patients participated in the study . Of these , 62 took part in the treatment program and 43 served as controls . METHOD From an obesity unit 's waiting list , the patients were randomly assigned to either a treatment group or remained in the waiting list to serve as a control group . The treatment group participated in a 10-week ( 30 hours ) cognitive group treatment program . All participants were weighed at the outset of the study , directly after treatment and at a 6- , 12- and 18-month post-treatment follow-up without any booster treatment after the 10-week program . RESULTS Fifty-seven ( 92 % ) patients completed treatment . For the 34 ( 60 % ) patients who participated in the study 18 months after treatment was terminated , the mean weight loss at treatment 's end was 8.5 kg ( SD=16.1 ) . Eighteen months later their mean weight loss was 10.4 kg ( SD=10.8 ) . The control patients ( n=31.72 % ) that participated in the study during the same period increased in weight by 2.3 kg ( SD=7.0 ) . The weight difference between the treatment and control group at the 18-month follow-up was highly significant ( p < 0.001 ) . CONCLUSION The cognitive group treatment program was highly acceptable among the participants and was completed by nearly all the patients . The 10-week treatment program resulted in satisfactory weight loss . The weight difference between the treatment group and controls was nearly the same at 18 months after end of treatment as at six months . The study , therefore , does not provide support for the contention that a lengthy therapy for obesity is necessary if treatment results are lasting .

control

post-treatment

treatment

treatment

cognitive group treatment program

treatment

weight reduction

mean weight loss

mean weight loss

weight

weight difference

weight loss

obesity unit 's waiting list


Effect of Orlistat in obese patients with heart failure : a pilot study . Heart failure is the leading cause of hospitalization . Obesity is increasingly common and is a major public health problem . The aim of this study is to assess whether obese patients with heart failure can benefit from losing weight via an orlistat-assisted diet . This randomized clinical trial included obese patients with ejection fractions < or =40 % . Orlistat and diet counseling were compared with diet counseling alone . Twenty-one consecutive obese patients with heart failure were recruited . Significant improvement in 6-minute walk test ( 45.8 m ; 95 % confidence interval , 5.2-86.4 m ; p=0.031 ) , functional class ( -0.6+/-0.5 , p=0.014 ) , weight loss ( -8.55 kg ; 95 % confidence interval , -13.0 to -4.1 kg ; p < 0.001 ) and also significant decreases in total cholesterol ( p=0.017 ) , low-density lipoprotein cholesterol ( p=0.03 ) , and triglycerides ( p=0.036 ) were observed in the orlistat group . Orlistat can promote significant weight loss and symptoms of relief in obese patients with heart failure , as measured by 6-minute walk test and functional capacity . The lipid profile improved . Orlistat was safe and well tolerated .

Orlistat

orlistat-assisted diet

Orlistat

Orlistat

6-minute walk test

functional class

weight loss

total cholesterol

low-density lipoprotein cholesterol

triglycerides

weight loss

symptoms of relief

obese

heart failure

obese

heart failure

obese

Twenty-one

obese

heart failure


Lessons learnt in conducting a clinical drug trial in children with Asperger Syndrome . OBJECTIVE To describe the authors ' experience of conducting a clinical drug trial in children with Asperger Syndrome , including the pitfalls encountered and lessons learnt . CONCLUSIONS The main barrier encountered was in the recruitment of children : it was not possible to recruit the target of 60 patients . The recruitment of children is often the major barrier to the progress of a successful clinical trial . Conducting the clinical drug trial was greatly facilitated by the appropriate setting and experienced clinical pharmacology staff .

recruitment of children

recruitment of children

children

Asperger Syndrome .

children

Asperger Syndrome


TENS for the treatment of writer 's cramp dystonia : a randomized , placebo-controlled study . Manipulation of afferent inputs may temporarily modulate dystonic spasms . Ten patients with writer 's cramp were enrolled in a double-blind , randomized , crossover study in which the effects of transcutaneous electrical stimulation ( TENS ) and placebo treatment were compared . Patients were evaluated using four measures of dystonic impairment . The TENS group showed a significant improvement that persisted for 3 weeks in three of the four measures .

TENS

placebo-controlled

placebo

TENS

measures of dystonic impairment .

significant improvement


Acute pressor and hormonal effects of beta-endorphin at high doses in healthy and hypertensive subjects : role of opioid receptor agonism . CONTEXT The opioid system is involved in blood pressure regulation in both normal humans and patients with essential hypertension . OBJECTIVE The objective of the study was to investigate the effects of a high-dose infusion of beta-endorphin , an opioid peptide , on blood pressure and on the hormonal profile in healthy subjects and in hypertensive patients and the mediation played by opioid receptor agonism . DESIGN , SETTING , AND PARTICIPANTS According to a randomized double-blind design , 11 healthy subjects ( controls ) and 12 hypertensive inpatients ( mean age , 38.9 and 40.4 yr , respectively ) received 1-h iv infusion of beta-endorphin ( 250 mug/h ) and , on another occasion , the same infusion protocol preceded by the opioid antagonist naloxone ( 8 mg ) . MAIN OUTCOME MEASURES Hemodynamic and hormonal measurements were performed at established times during the infusion protocols . RESULTS At baseline , circulating beta-endorphin , norepinephrine , and endothelin-1 in hypertensive patients were significantly ( P < 0.05 ) higher than in controls . In controls , beta-endorphin reduced blood pressure ( P < 0.01 ) and circulating norepinephrine ( P < 0.02 ) and increased plasma atrial natriuretic factor ( P < 0.003 ) and GH ( P < 0.0001 ) . In hypertensive patients , beta-endorphin decreased systemic vascular resistance ( P < 0.0001 ) , blood pressure ( P < 0.0001 ) , and plasma norepinephrine ( P < 0.0001 ) and endothelin-1 ( P < 0.0001 ) and raised circulating atrial natriuretic factor ( P < 0.0001 ) , GH ( P < 0.0001 ) , and IGF-I ( P < 0.0001 ) . These hemodynamic and hormonal responses to beta-endorphin in hypertensive patients were significantly ( P < 0.0001 ) greater than in controls but were annulled in all individuals when naloxone preceded beta-endorphin infusion . CONCLUSIONS High doses of beta-endorphin induce hypotensive and beneficial hormonal effects in humans , which are enhanced in essential hypertension and are mediated by opioid receptors .

beta-endorphin

beta-endorphin

opioid antagonist naloxone ( 8 mg )

beta-endorphin

beta-endorphin

Hemodynamic and hormonal measurements

blood pressure

circulating norepinephrine

plasma atrial natriuretic factor

systemic vascular resistance

blood pressure

plasma norepinephrine

circulating atrial natriuretic factor

GH

IGF-I

hemodynamic and hormonal responses

healthy and hypertensive

normal

essential hypertension


Combined therapy for obese type 2 diabetes : suppertime mixed insulin with daytime sulfonylurea . Combined insulin and sulfonylurea therapy for type 2 diabetes may improve the effectiveness of a single injection of insulin , thereby postponing the need for multiple injections . This concept was tested in 21 obese subjects imperfectly controlled by 20 mg of glyburide daily in a double masked , placebo-controlled , parallel design , 16-week protocol . Premixed 70 % NPH/30 % Regular insulin was taken before supper , and the dosage was adjusted weekly by an algorithm seeking nearly normal fasting glycemia . Eleven subjects using insulin plus 10 mg glyburide before breakfast had lower mean fasting glucose at 10-16 weeks than 10 subjects using insulin with placebo ( mean +/- SEM ; 5.9 +/- 0.3 versus 7.5 +/- 0.7 mmol/L ; p less than 0.05 ) , and had a greater decrement of glycosylated hemoglobin from baseline values ( 1.3 +/- 0.1 versus 0.8 +/- 0.2 % A1 , p less than 0.05 ) . After 16 weeks the combined therapy group used half as much insulin as the insulin-only group ( 50 +/- 5 versus 101 +/- 13 units/d ; p less than 0.01 ) . Fasting serum free insulin values increased 58 % from baseline after insulin therapy in the insulin-only group ( p less than 0.05 ) but did not increase with combined therapy . Weight gain was similar in the two groups . These data support this form of combined therapy as one option for treating obese persons with type 2 diabetes no longer responsive to oral therapy alone .

Combined insulin

sulfonylurea therapy

injection of insulin

20 mg of glyburide daily

placebo-controlled

Regular insulin

insulin plus

glyburide

placebo

obese type 2 diabetes

type 2 diabetes

effectiveness

glycosylated hemoglobin

Fasting serum free insulin values

Weight gain

type 2 diabetes

Eleven

type 2 diabetes


Lanthanum carbonate ( Fosrenol ) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease . AIMS High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment . Lanthanum carbonate ( Fosrenol ) is a new non-aluminum , non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . We report data from a recent trial , which , for the first time , assessed the efficacy and tolerability of lanthanum carbonate treatment , compared with placebo , in Chinese patients with ESRD . PATIENTS AND METHODS Following a one- to three-week washout phase and a four-week , open-label lanthanum carbonate dose-titration phase , male and female hemodialysis patients were randomized ( 1:1 ) to receive either lanthanum carbonate or placebo for four weeks . The primary efficacy parameter of the study was the control of serum phosphorus levels ( < or =1.8 mmol/l [ < or = 5.6 mg/dl ] ) . Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone , calcium , and calcium x phosphorus ( Ca x P ) product levels . The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study . RESULTS Mean serum phosphorus level at the end of washout was 2.5 +/- 0.5 mmol/l ( 7.7 +/- 1.5 mg/dl ; n=73 ) , and there was no evidence of a difference in levels between the treatment groups pre-randomization . At the end of the study , lanthanum carbonate-treated patients had significantly lower phosphorus levels ( 1.6 +/- 0.5 mmol/l [ 5.1 +/- 1.5 mg/dl ] ; n=30 ) than those receiving placebo ( 2.3 +/- 0.4 mmol/l [ 7.2 +/- 1.3 mg/dl ] ; n=31 ; p < 0.001 ) . In addition , a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels ( 60 % ) compared with the placebo group ( 10 % ; p < 0.001 ) . Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of randomized treatment ( p < 0.001 ) . Lanthanum carbonate was well tolerated ; only one serious adverse event was reported , which was unrelated to treatment . CONCLUSIONS Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD . This finding supports the results of previous US and European studies , which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels .

Lanthanum carbonate ( Fosrenol )

Lanthanum carbonate ( Fosrenol )

lanthanum carbonate treatment

placebo

lanthanum carbonate

lanthanum carbonate

placebo

lanthanum carbonate

lanthanum carbonate-treated

lanthanum carbonate

lanthanum carbonate

Lanthanum carbonate

Lanthanum carbonate

lanthanum carbonate

efficacy and tolerability

efficacy

tolerability

serum phosphorus levels

calcium

adverse events

Mean serum phosphorus level

phosphorus levels

serum phosphorus levels

Ca x P product levels

tolerated

serious adverse event

effective

well-tolerated

serum phosphorus levels


Just-in-time evidence-based e-mail " reminders " in home health care : impact on nurse practices . OBJECTIVE To test the effectiveness of two interventions designed to improve the adoption of evidence-based practices by home health nurses caring for heart failure ( HF ) patients . DATA SOURCES/STUDY SETTING Information on nurse practices was abstracted from the clinical records of patients admitted between June 2000 and November 2001 to the care of 354 study nurses at a large , urban , nonprofit home care agency . STUDY DESIGN The study employed a randomized design with nurses assigned to usual care or one of two intervention groups upon identification of an eligible patient . The basic intervention was a one-time e-mail reminder highlighting six HF-specific clinical recommendations . The augmented intervention consisted of the initial e-mail reminder supplemented by provider prompts , patient education material , and clinical nurse specialist outreach . DATA COLLECTION At each home health visit provided by a study nurse to an eligible HF patient during the 45-day follow-up period , a structured chart abstraction tool was used to collect information on whether the nurse provided the care practices highlighted in the e-mail reminder . PRINCIPAL FINDINGS Both the basic and the augmented interventions greatly increased the practice of evidence-based care , according to patient records , in the areas of patient assessment and instructions about HF disease management . While not all results were statistically significant at conventional levels , intervention effects were positive in virtually all cases and effect magnitudes frequently were large . CONCLUSIONS The results of this randomized trial strongly support the efficacy of just-in-time evidence-based reminders as a means of changing clinical practice among home health nurses who are geographically dispersed and spend much of their time in the field .

practice of evidence-based care

intervention effects

effect magnitudes frequently

efficacy

just-in-time evidence-based reminders

impact on nurse practices .

home health nurses


Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure . OBJECTIVES This study was designed to determine whether reductions in morning systolic blood pressure ( BP ) elicited by treatment of moderate to severe obstructive sleep apnea ( OSA ) in heart failure ( HF ) patients are associated with a reduction in sympathetic vasoconstrictor tone . BACKGROUND Daytime muscle sympathetic nerve activity ( MSNA ) is elevated in HF patients with coexisting OSA . In our recent randomized trial in HF , abolition of OSA by continuous positive airway pressure ( CPAP ) increased left ventricular ejection fraction ( LVEF ) and lowered morning systolic BP . METHODS Muscle sympathetic nerve activity , BP , and heart rate ( HR ) of medically treated HF patients ( EF < 45 % ) and OSA ( apnea-hypopnea index > or =20/h of sleep ) were recorded on the morning after overnight polysomnography , and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP ( control ) . RESULTS In nine control patients , there were no significant changes in the severity of OSA , MSNA , systolic BP , or HR . In contrast , in the 8 CPAP-treated patients , OSA was attenuated , and there were significant reductions in daytime MSNA ( from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min ; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats ; p < 0.001 and p = 0.003 , respectively ) , systolic BP ( from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg , p = 0.03 ) , and HR ( from 69 +/- 2 min ( -1 ) to 66 +/- 2 min ( -1 ) ; p = 0.013 ) . CONCLUSIONS Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA , systolic BP , and HR . Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA .

nocturnal CPAP treatment

no CPAP ( control )

CPAP-treated

CPAP

nocturnal CPAP

morning systolic blood pressure ( BP )

obstructive sleep apnea

sympathetic vasoconstrictor tone

morning systolic BP

Muscle sympathetic nerve activity

BP

heart rate ( HR )

apnea-hypopnea index

OSA

MSNA

systolic BP ,

HR

OSA

daytime MSNA

systolic BP

HR

daytime MSNA

systolic BP

HR .

BP

heart failure

obstructive sleep apnea

heart failure ( HF )

HF

coexisting OSA

HF

OSA

nine

coexisting OSA

HF

HF

OSA


Safety , tolerability , and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers . Amyloid beta ( Abeta ) may play a central role in the pathogenesis of Alzheimer disease . A functional gamma-secretase inhibitor , LY450139 , was developed that inhibits Abeta formation in whole cell assays , transgenic mice , and beagle dogs . The authors wished to determine the safety and tolerability of this drug , and the reduction of Abeta in plasma and cerebrospinal fluid ( CSF ) after multiple doses . Volunteer subjects ( N = 37 ) were studied using doses from 5 to 50 mg/day given for 14 days . Plasma and CSF concentrations of LY450139 , Abeta ( 1-40 ) and Abeta ( 1-X ) ( " Abeta ( total ) " ) were determined , and safety and tolerability were assessed . The plasma half-life of LY450139 was approximately 2.5 hours . Pharmacokinetic analyses showed a linear relationship between dose and plasma concentrations , with a Cmax of 828 +/- 19.2 ng/mL after a 50-mg dose . Plasma Abeta concentrations decreased in a dose-dependent manner over a 6-hour interval following drug administration , with a maximum decrease of approximately 40 % relative to baseline . After returning to baseline , Abeta concentrations were transiently increased . CSF Abeta concentrations were unchanged . Adverse events reported by subjects taking 5-mg , 20-mg , or 40-mg doses were similar to those reported by subjects taking placebo . Two of 7 subjects taking 50 mg/day experienced adverse events that may have been drug related . In this phase 1 volunteer study , reported adverse events after taking LY450139 were manageable . A dose-dependent reduction in plasma Abeta was demonstrated , and changes in plasma Abeta concentrations were temporally related to the pharmacokinetic characteristics of LY450139 .

gamma-secretase inhibitor

Safety

tolerability

changes in amyloid beta concentrations

Abeta ( 1-X ) ( " Abeta ( total ) " )

Plasma Abeta concentrations

Abeta concentrations

CSF Abeta concentrations

Adverse events

plasma Abeta

plasma Abeta

subjects taking placebo .


Montelukast treatment of moderate to severe atopic dermatitis in adults : a randomized , double-blind , placebo-controlled trial . In a randomized , double-blind , placebo-controlled 4-week trial , 59 patients with moderate to severe atopic dermatitis were treated orally with 10 mg of the leukotriene antagonist montelukast . Forty-seven patients completed the study . No difference in efficacy was seen among patients who received montelukast and the group given a placebo .

Montelukast treatment

placebo-controlled

placebo-controlled

leukotriene antagonist montelukast

montelukast

placebo

No difference in efficacy

severe atopic dermatitis in adults :


Anti-Xa effect of a low molecular weight heparin ( dalteparin ) does not accumulate in extended duration therapy for venous thromboembolism in cancer patients . Many patients with venous thromboembolism are being treated with low molecular weight heparin for extended periods of time . It is not certain if it is necessary to assess anti-Xa levels for extended treatment periods . This study is a prospective assessment of anti-Xa levels in patients on long-term therapy for acute venous thromboembolism who have active cancer . Consecutive consenting patients from one center in a multicenter trial that compared 6 months of low molecular weight heparin with oral anticoagulant therapy were treated with therapeutic doses of dalteparin ( 200 IU per kilogram ) subcutaneously daily . Anti-Xa levels were assessed at the end of weeks 1 and 4,4-6 hours after injection of dalteparin . Patients were followed for bleeding and recurrent venous thromboembolism . There were 24 patients who had anti-Xa levels measured at weeks 1 and 4 . Two other patients had week 1 measurements performed but died before the week 4 sample was collected due to their underlying cancer . The mean anti-Xa levels at weeks 1 and 4 were 1.11 and 1.03 anti-Xa units/ml respectively ( P=0.13 ) . These results suggest that for patients with active cancer receiving extended duration therapy with low molecular weight heparin ( dalteparin ) there is no accumulation of anti-Xa effect over the first month of therapy . Monitoring of anti-Xa levels in this situation is usually not required .

heparin ( dalteparin )

oral anticoagulant therapy

extended duration therapy

heparin

dalteparin

anti-Xa levels

anti-Xa levels

Anti-Xa levels

bleeding

recurrent venous thromboembolism

anti-Xa levels

died

mean anti-Xa levels

accumulation of anti-Xa effect

anti-Xa levels

venous thromboembolism

cancer

venous thromboembolism

acute venous thromboembolism

active cancer

24 patients

anti-Xa levels

active cancer


Stapled hemorrhoidopexy versus milligan-morgan hemorrhoidectomy : a prospective , randomized , multicenter trial with 2-year postoperative follow up . PURPOSE The purpose of this study was to compare the outcome of stapled hemorrhoidopexy ( SH group ) performed using a circular stapler with that of the Milligan-Morgan technique ( MM group ) . The goals of the study were to evaluate the efficacy and reproducibility of stapled hemorrhoidopexy and define its place among conventional techniques . METHODS A series of 134 patients were included at 7 hospital centers . They were randomized according to a single-masked design and stratified by center ( with balancing every 4 patients ) . Patients were clinically evaluated preoperatively and at 6 weeks , 1 year , and a minimum of 2 years after treatment . Patients completed a questionnaire before and 1 year after surgery to evaluate symptoms , function , and overall satisfaction . RESULTS The mean follow-up period was 2.21 years +/- 0.26 ( 1.89-3.07 ) . Nine patients ( 7 % ) could not be monitored at 1 or 2 years , but 4 of these 9 nevertheless filled in the 1-year questionnaire . The patients in the SH group experienced less postoperative pain/discomfort as scored by pain during bowel movement ( P < 0.001 ) , total analgesic requirement over the first 3 days ( according to the World Health Organization [ WHO ] class II analgesics [ P = 0.002 ] ; class III [ P = 0.066 ] ) , and per-patient consumption frequency of class III analgesics ( P = 0.089 ) . A clear difference in morphine requirement became evident after 24 hours ( P = 0.010 ) . Hospital stay was significantly shorter in the SH group ( SH 2.2 +/- 1.2 [ 0 ; 5.0 ] versus MM 3.1 +/- 1.7 [ 1 ; 8.0 ] P < 0.001 ) . At 1 year , no differences in the resolution of symptoms were observed between the 2 groups , and over 2 years , the overall incidence of complications was the same , specifically fecaloma ( P = 0.003 ) in the MM group and external hemorrhoidal thrombosis ( P = 0.006 ) in the SH group . Impaired sphincter function was observed at 1 year with no significant difference between the groups for urgency ( 12 % ) , continence problems ( 10 % ) , or tenesmus ( 3 % ) . No patient needed a second procedure for recurrence within 2 years , although partial residual prolapse was detected in 4 SH patients ( 7.5 % ) versus 1 MM patient ( 1.8 % ) ( P = 0.194 ) . CONCLUSION Stapled hemorrhoidopexy causes significantly less postoperative pain . The technique is reproducible and can achieve comparable outcomes as those of the MM technique as long as the well-described steps of the technique are followed . Like with conventional surgery , anorectal dysfunction can occur after stapled hemorrhoidopexy in some patients . Its effectiveness in relieving symptoms is equivalent to conventional surgery , and the number of hemorrhoidal prolapse recurrences at 2 years is not significantly different . Hemorroidopexy is applicable for treating reducible hemorrhoidal prolapse .

Stapled hemorrhoidopexy

milligan-morgan hemorrhoidectomy

stapled hemorrhoidopexy ( SH group )

Milligan-Morgan technique ( MM group )

stapled hemorrhoidopexy

questionnaire

SH

SH

MM

MM

SH

SH

MM

Stapled hemorrhoidopexy

MM

surgery

stapled hemorrhoidopexy

Hemorroidopexy

Stapled hemorrhoidopexy

milligan-morgan hemorrhoidectomy

stapled hemorrhoidopexy

efficacy and reproducibility

postoperative pain/discomfort

pain during bowel movement

morphine requirement

Hospital stay

resolution of symptoms

overall incidence of complications

fecaloma

external hemorrhoidal thrombosis

Impaired sphincter function

partial residual prolapse

postoperative pain

anorectal dysfunction

effectiveness

hemorrhoidectomy


Removal of inflammatory cytokines and endotoxin by veno-venous continuous renal replacement therapy for burned patients with sepsis . OBJECTIVE To evaluate the effect of veno-venous continuous renal replacement therapy ( CRRT ) on the plasma levels of endotoxin and cytokines in severely burned patients with sepsis . METHODS Twenty adult severely burned patients with sepsis were studied . For the diagnosis of sepsis , patients were randomly divided into CRRT ( n=10 ) and Control ( n=10 ) . Both groups received conventional therapy after admission . Veno-venous CRRT was administered to 10 patients in the CRRT group whenever patients were determined to be septic . The plasma level of endotoxin , TNF-alpha , IL-1 beta , IL-6 and IL-8 were measured at 0 , 1 , 2 , 6 , 12 , 36 and 60 h after CRRT initiation , and at 0 , 12 , 36 and 60 h after the patients were diagnosed as having sepsis in the Control group . MAIN RESULTS Plasma level of endotoxin and all the cytokines after CRRT initiation were significantly lower than those before the treatment ( P < 0.01 ) . The serial change of endotoxin , IL-1 beta , IL-6 and IL-8 was significantly lower at 12 , 36 and 60 h after treatment compared with Control groups ( P < 0.01 ) . A significant decrease in plasma TNF-alpha levels was seen at 36 and 60 h after treatment compared with Control groups ( P < 0.01 ) . CONCLUSION Plasma endotoxin and cytokines ( TNF-alpha , IL-1 beta , IL-6 and IL-8 ) can be removed effectively with CRRT in severely burned patients with sepsis .

CRRT

Control

conventional therapy

Veno-venous CRRT

Plasma level of endotoxin

all the cytokines after CRRT initiation

plasma TNF-alpha levels

burned patients

sepsis

severely burned patients

sepsis

Twenty

severely burned patients with sepsis


Endovascular aneurysm repair and outcome in patients unfit for open repair of abdominal aortic aneurysm ( EVAR trial 2 ) : randomised controlled trial . BACKGROUND Endovascular aneurysm repair ( EVAR ) to exclude abdominal aortic aneurysm ( AAA ) was introduced for patients of poor health status considered unfit for major surgery . We instigated EVAR trial 2 to identify whether EVAR improves survival compared with no intervention in patients unfit for open repair of aortic aneurysm . METHODS We did a randomised controlled trial of 338 patients aged 60 years or older who had aneurysms of at least 5.5 cm in diameter and who had been referred to one of 31 hospitals in the UK . We assigned patients to receive either EVAR ( n=166 ) or no intervention ( n=172 ) . Our primary endpoint was all-cause mortality , with secondary endpoints of aneurysm-related mortality , health-related quality of life ( HRQL ) , postoperative complications , and hospital costs . Analyses were by intention to treat . FINDINGS 197 patients underwent aneurysm repair ( 47 assigned no intervention ) and 80 % of patients adhered to protocol . The 30-day operative mortality in the EVAR group was 9 % ( 13 of 150 , 95 % CI 5-15 ) and the no intervention group had a rupture rate of 9.0 per 100 person years ( 95 % CI 6.0-13.5 ) . By end of follow up 142 patients had died , 42 of aneurysm-related factors ; overall mortality after 4 years was 64 % . There was no significant difference between the EVAR group and the no intervention group for all-cause mortality ( hazard ratio 1.21 , 95 % CI 0.87-1.69 , p=0.25 ) . There was no difference in aneurysm-related mortality . The mean hospital costs per patient over 4 years were UK pound sterling 13,632 in the EVAR group and pound sterling 4983 in the no intervention group ( mean difference pound sterling 8649 , SE 1248 ) , with no difference in HRQL scores . INTERPRETATION EVAR had a considerable 30-day operative mortality in patients already unfit for open repair of their aneurysm . EVAR did not improve survival over no intervention and was associated with a need for continued surveillance and reinterventions , at substantially increased cost . Ongoing follow-up and improved fitness of these patients is a priority .

Endovascular aneurysm repair ( EVAR )

EVAR

aneurysm repair

EVAR

survival

all-cause mortality

aneurysm-related mortality

health-related quality of life ( HRQL )

postoperative complications

hospital costs

died

overall mortality

all-cause mortality

aneurysm-related mortality

30-day operative mortality

unfit for major surgery

338 patients

aged 60 years or older


The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients : a double blind , placebo controlled study . BACKGROUND AND AIM The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks . METHODS Evaluation parameters consisted of ongoing pain intensity ( VAS ) , patient satisfaction , side effects , global efficacy and tolerance . Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia , allodynia , detection and pain thresholds to electrical and heat stimuli , temporal summation of repetitive electrical and heat stimuli . RESULTS A total of 55 patients completed the study . VAS scores decreased significantly compared to the baseline measurements in all groups . There was no significant difference between the groups regarding pain intensity and escape medication . The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo . There was no significant difference between the groups regarding the detection thresholds ( electrical and heat ) . The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups . In addition , the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo . CONCLUSION The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation , but not on the ongoing pain intensity . Furthermore , the quantitative sensory tests provided complementing information to the clinical measures .

venlafaxine

placebo

placebo

venlafaxine XR 75 and 150 mg

venlafaxine

venlafaxine

venlafaxine

VAS scores

pain intensity and escape medication .

pain threshold

and the

summation threshold to heat stimuli

neuropathic pain

neuropathic pain


Long term follow up of patients treated for Helicobacter pylori infection . BACKGROUND Helicobacter pylori infection induces progressive inflammatory changes in the gastric mucosa that may lead to gastric cancer . Understanding long term effects resulting from the cure of this infection is needed to design cancer prevention strategies . METHODS A cohort of 795 adults with preneoplastic gastric lesions was randomised to receive anti-H pylori treatment and/or antioxidants . At the end of six years of intervention , those who did not receive anti-H pylori treatment were offered it . Gastric biopsies were obtained at baseline , and at 3 , 6 , and 12 years . A histopathology score was utilised to document changes in gastric lesions . Non-linear mixed models were used to estimate the cumulative effect of H pylori clearance on histopathology scores adjusted for follow up time , interventions , and confounders . RESULTS Ninety seven per cent of subjects were H pylori positive at baseline , and 53 % were positive at 12 years . Subjects accumulated 1703 person years free of infection . A multivariate model showed a significant regression in histopathology score as a function of the square of H pylori negative time . Subjects who were H pylori negative had 14.8 % more regression and 13.7 % less progression than patients who were positive at 12 years ( p = 0.001 ) . The rate of healing of gastric lesions occurred more rapidly as years free of infection accumulated , and was more pronounced in less advanced lesions . CONCLUSIONS Preneoplastic gastric lesions regress at a rate equal to the square of time in patients rendered free of H pylori infection . Our findings suggest that patients with preneoplastic gastric lesions should be treated and cured of their H pylori infection .

Helicobacter pylori infection .

inflammatory changes

histopathology score

gastric lesions .

H pylori

free of infection .

regression in histopathology score

H pylori negative time .

H pylori

regression

progression

rate of healing of gastric lesions

years free of infection

Preneoplastic gastric lesions

Helicobacter pylori infection

adults

preneoplastic gastric lesions

preneoplastic gastric lesions


D-dimer predicts outcome after aneurysmal subarachnoid hemorrhage : no effect of thromboprophylaxis on coagulation activity . OBJECTIVE Approximately one-third of all patients with acute nontraumatic subarachnoid hemorrhage ( SAH ) experience complications owing to delayed ischemic deficit . We reported recently that enoxaparin 40 mg once daily for 10 days seems safe and demonstrates thromboprophylactic efficacy , but it failed to improve outcome in a randomized SAH trial . In the present study , we assessed hemostatic variables associated with clinical status and outcome of SAH . We also monitored the effect of enoxaparin on activation of coagulation and fibrinolysis after closure of the ruptured aneurysm . METHODS Blood samples to measure activation of coagulation and fibrinolysis were collected from 42 patients participating in the enoxaparin trial for acute aneurysmal SAH at four time points : 1 ) at hospital admission ; 2 ) 12 to 24 hours after aneurysm surgery but before initiation of enoxaparin therapy ; 3 ) 3 hours after the first dose ; and 4 ) at the conclusion of treatment . RESULTS At admission , several variables of coagulation and fibrinolysis were elevated and correlated well with clinical status . Specifically , D-dimer levels at all four time points correlated with patients ' long-term outcomes . A single dose of enoxaparin suppressed early coagulation activity , but thrombin generation was not inhibited during thromboprophylaxis . However , PAI-1 activity was suppressed . CONCLUSION D-dimer offers a useful laboratory tool for assessing early and late clinical severity of SAH . A thromboprophylactic dose of enoxaparin inhibited PAI-1 activity but failed to down-regulate coagulation activity and D-dimer . These findings are compatible with the lack of efficacy of enoxaparin in reducing ischemic deficit after SAH .

enoxaparin

enoxaparin

enoxaparin

enoxaparin

enoxaparin

enoxaparin

enoxaparin

coagulation activity

thromboprophylactic efficacy

hemostatic variables

Blood samples

activation of coagulation

fibrinolysis

D-dimer levels

early coagulation activity

thrombin generation

PAI-1 activity

severity of SAH

PAI-1 activity

coagulation activity and D-dimer

subarachnoid hemorrhage :

acute aneurysmal SAH


The assessment of erythema and thickness on burn related scars during pressure garment therapy as a preventive measure for hypertrophic scarring . The aim of this study was threefold : ( 1 ) Assess the pressure loss of two types of pressure garments that are used in the treatment of hypertrophic scars after burn injury , ( 2 ) investigate the influence of two different levels of compression on erythema and thickness of burn scars and ( 3 ) examine the association between erythema and thickness . The study was a prospective trial in which 76 burn scars in 60 patients were objectively assessed with the Minolta Chromameter CR-300 for erythema and with the Dermascan C for thickness of the scar over a period of 3 months . Each patient was randomly assigned to a " normal " or " lower " compression class treatment , with respectively mean values of 15 and 10 mmHg pressure after wearing the garment for 1 month . Measurements for both parameters were taken at 0 , 1 , 2 and 3 months of treatment . Pressure garments with " normal " compression did lose significantly more compression over 1 month ( 4.82 mmHg ) than did the garments from the low compression class ( 2.57 mmHg ) . Scars that were treated with garments from a " normal " compression class did score significantly better for thickness compared to the " low " compression class . The difference in thickness was most evident at 1 month . Thereafter no further significant improvement between the two different treatments over time could be obtained . This difference was not found for erythema . Positive correlations could be found between erythema and thickness values at all of the three test points while changes in erythema and thickness only correlated significantly after the first month . The pattern of change of both parameters correlated at a high level of significance after 3 months of treatment . These data suggest that pressure garments that deliver a pressure of at least 15 mmHg pressure tend to accelerate scar maturation and that measurements of the pattern of change of the erythema can be used to predict changes in scar thickness and vice versa .

pressure garment therapy

two types of pressure garments

two different levels of compression

Minolta Chromameter CR-300 for erythema

Dermascan C

for thickness of the scar

wearing the garment

erythema and thickness of burn scars

erythema and thickness .

Minolta Chromameter CR-300

Dermascan C for thickness of the scar

compression

Scars

thickness

thickness

erythema .

erythema and thickness values

erythema and thickness

scar maturation

hypertrophic scars after burn injury

burn scars

60 patients


Risperidone treatment of autistic disorder : longer-term benefits and blinded discontinuation after 6 months . OBJECTIVE Risperidone is effective for short-term treatment of aggression , temper outbursts , and self-injurious behavior in children with autism . Because these behaviors may be chronic , there is a need to establish the efficacy and safety of longer-term treatment with this agent . METHOD The authors conducted a multisite , two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums , aggression , and/or self-injurious behavior who showed a positive response in an earlier 8-week trial . Part I consisted of 4-month open-label treatment with risperidone , starting at the established optimal dose ; part II was an 8-week randomized , double-blind , placebo-substitution study of risperidone withdrawal . Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale . RESULTS Part I included 63 children . The mean risperidone dose was 1.96 mg/day at entry and remained stable over 16 weeks of open treatment . The change on the Aberrant Behavior Checklist irritability subscale was small and clinically insignificant . Reasons for discontinuation of part I included loss of efficacy ( N=5 ) and adverse effects ( N=1 ) . The subjects gained an average of 5.1 kg . Part II included 32 patients . The relapse rates were 62.5 % for gradual placebo substitution and 12.5 % for continued risperidone ; this difference was statistically significant . CONCLUSIONS Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums , aggression , and/or self-injurious behavior . Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects .

Risperidone

Risperidone

risperidone

risperidone

placebo-substitution

risperidone

risperidone

risperidone ;

Risperidone

loss of efficacy

adverse effects

relapse rates

efficacy

tolerability

children

autism

children

5 to 17 years

autism


Longterm safety , efficacy , and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis . OBJECTIVE To evaluate safety , efficacy , and radiographic progression in patients with early rheumatoid arthritis ( RA ) undergoing longterm treatment with etanercept . METHODS Patients with early RA ( disease duration of 3 years or less ) who had completed a 2-year efficacy study comparing etanercept and methotrexate ( MTX ) were followed in an extension where they received 25 mg etanercept twice weekly . Safety was summarized descriptively and compared with data from the efficacy study . Efficacy and radiographic progression were assessed using American College of Rheumatology response criteria , disease activity scores , and Total Sharp Score ( TSS ) . RESULTS Rates of serious adverse events and serious infections did not increase with longterm exposure to etanercept , and were similar to rates reported for the blinded portion of the efficacy study . Efficacy was sustained in patients who completed 5 years of etanercept treatment at the time of this report ( N = 201 ) , even in those who decreased or discontinued use of MTX or corticosteroids . No radiographic progression ( change in TSS < or = 0 ) was seen in 55 % of patients with 5-year radiographs ; negative change ( TSS < 0 ) was seen in 11 % . CONCLUSION Etanercept treatment in patients with early RA was generally well tolerated for up to 5 years . The results indicate sustained efficacy and decreased rate of radiographic progression . The rate of radiographic progression was low compared with other studies , emphasizing the benefit gained in patients with early aggressive RA who undergo longterm treatment with etanercept .

etanercept

etanercept

etanercept

methotrexate

etanercept

etanercept

Etanercept

etanercept

Longterm safety

efficacy

radiographic outcome

safety , efficacy

radiographic progression

Safety

Efficacy

radiographic progression

Efficacy

radiographic progression

efficacy

rate of radiographic progression

rate of radiographic progression

early rheumatoid arthritis

early rheumatoid arthritis ( RA )

early RA

etanercept and methotrexate ( MTX )

patients with early RA

patients with early aggressive RA


Prospective , randomized comparison of transperitoneal versus retroperitoneal laparoscopic adrenalectomy . PURPOSE We report a prospective , randomized comparison of transperitoneal laparoscopic adrenalectomy ( TLA ) vs retroperitoneal laparoscopic adrenalectomy ( RLA ) for adrenal lesions with long-term followup . MATERIALS AND METHODS Between December 1997 and November 1999 , 57 consecutive eligible patients with surgical adrenal disease were prospectively randomized to undergo TLA ( 25 ) or RLA ( 32 ) . Study exclusion criteria were patient age greater than 80 years , body mass index greater than 40 , bilateral adrenalectomy and significant prior abdominal surgery in the quadrant of interest . Mean followup was 5.96 years in the 2 groups . RESULTS The groups were matched in regard to patient age ( p = 0.84 ) , body mass index ( p = 0.43 ) , American Society of Anesthesiologists class ( p = 0.81 ) and laterality ( p = 0.12 ) . Median adrenal mass size was 2.7 cm ( range 1 to 9 ) in the TLA group and 2.6 cm ( range 0.5 to 6 ) in the RLA group ( p = 0.83 ) . TLA was comparable to RLA in terms of operative time ( 130 vs 126.5 minutes , p = 0.64 ) , estimated blood loss ( p = 0.92 ) , specimen weight ( p = 0.81 ) , analgesic requirements ( p = 0.25 ) , hospital stay ( p = 0.56 ) and the complication rate ( p = 0.58 ) . One case per group was electively converted to open surgery . Pathology data on the intact extracted specimens were similar between the groups . Averaged convalescence was 4.7 weeks in the TLA group and 2.3 weeks in the RLA group ( p = 0.02 ) . During a mean followup of 6 years 2 patients in the TLA group had a late complication ( port site hernia ) . Mortality occurred in 5 patients , including 1 with TLA and 4 with RLA , during the 6-year followup . CONCLUSIONS For most benign adrenal lesions requiring surgery laparoscopic adrenalectomy can be performed safely and effectively by the transperitoneal or the retroperitoneal approach .

transperitoneal

TLA

RLA

laparoscopic adrenalectomy

adrenal mass size

operative time

estimated blood loss

specimen weight

analgesic requirements

hospital stay

complication rate

convalescence

late complication ( port site hernia )

Mortality

safely

effectively


Effect of cigarette smoking on gastric emptying of solids in Japanese smokers : a crossover study using the 13C-octanoic acid breath test . BACKGROUND Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease . Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases . Thus , studies examining a link between smoking and gastric emptying disorders have clinical relevance . This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers . METHODS The ( 13 ) C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions ( either sham smoking or actively smoking ) . The time vs ( 13 ) CO ( 2 ) excretion rate curve was mathematically fitted to a conventional formula of y ( t ) = m*k*beta*e ( -k*t ) * ( 1 - e ( -k*t ) ) ( beta-1 ) , and the parameters of k and beta were determined : under the crossover protocol , a larger ( smaller ) beta indicates slower ( faster ) emptying in the early phase , and a larger ( smaller ) k indicates faster ( slower ) emptying in the later phase . The half ( 13 ) CO ( 2 ) excretion time ( t ( 1/2b ) = - [ ln ( 1 - 2 ( -1/beta ) ) ] /k ) and the time of maximal ( 13 ) CO ( 2 ) excretion rate ( t ( max ) = [ lnbeta ] /k ) were also calculated . Between the two occasions , k , beta , t ( 1/2b ) , and t ( max ) were compared by the Wilcoxon signed-rank test . RESULTS After smoking , k was significantly increased . No significant differences were found in beta , t ( 1/2 ) , and t ( max ) between the two occasions . CONCLUSIONS The increase in k suggests the acceleration of gastric emptying in the later phase . For the first time , this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers .

( 13 ) C-octanoic acid breath test

effect of smoking

acid breath test

excretion rate

parameters of k and beta

slower ( faster ) emptying

faster ( slower ) emptying

half ( 13 ) CO ( 2 ) excretion time

k was significantly increased

significant differences

Japanese habitual smokers .


Tolerance and efficacy of combined diethylcarbamazine and albendazole for treatment of Wuchereria bancrofti and intestinal helminth infections in Haitian children . This randomized , placebo-controlled trial investigated the tolerance , efficacy , and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis . Children were infected with Ascaris ( 30.7 % ) , Trichuris ( 53.4 % ) , and hookworm ( 9.7 % ) with 69.9 % having more than one of these parasites . A total of 15.8 % of the children had Wuchereria bancrofti microfilariae . Children were randomly assigned treatment with placebo , albendazole ( ALB ) , diethylcarbamazine ( DEC ) , or combined therapy . The combination of DEC/ALB reduced microfilarial density compared with placebo , ALB , or DEC ( P < or = 0.03 ) . Albendazole and DEC/ALB reduced the prevalence of Ascaris , Trichuris , and hookworm more than placebo or DEC ( P < or = 0.03 ) . Among Trichuris-infected children , those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo ( P < or = 0.05 ) . Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia , DEC/ALB was more effective than DEC , with no increase in severity of adverse reactions .

placebo-controlled

placebo

albendazole ( ALB )

diethylcarbamazine ( DEC ) ,

combined therapy

Albendazole

DEC/ALB

ALB

DEC/ALB

placebo

Albendazole

DEC/ALB

DEC/ALB

DEC

Tolerance and efficacy

children

Children

children

Wuchereria bancrofti microfilariae

Children

Trichuris-infected

children

children

bancrofti microfilaremia


Simvastatin and preparation of polyunsaturated phospholipids produce similar changes in the phospholipid composition of high-density lipoproteins during hypercholesterolemia . We studied the phospholipid composition of high-density lipoproteins in patients with coronary heart disease and hypercholesterolemia treated with simvastatin ( Zocor , inhibitor of the key enzyme of cholesterol synthesis ) and preparation of polyunsaturated phospholipids ( lipostabil forte ) . Simvastatin produced a hypolipidemic effect and modulates the phospholipid composition of high-density lipoproteins ( similarly to lipostabil forte ) . These changes contribute to functional activity of high-density lipoproteins in the reverse cholesterol transport .

Simvastatin

polyunsaturated phospholipids

simvastatin ( Zocor

phospholipids ( lipostabil forte )

Simvastatin

lipostabil forte

functional activity

high-density lipoproteins

hypercholesterolemia

coronary heart disease

hypercholesterolemia


Administrative Data Feedback for Effective Cardiac Treatment : AFFECT , a cluster randomized trial . CONTEXT Hospital report cards are increasingly being implemented for quality improvement despite lack of strong evidence to support their use . OBJECTIVE To determine whether hospital report cards constructed using linked hospital and prescription administrative databases are effective for improving quality of care for acute myocardial infarction ( AMI ) . DESIGN The Administrative Data Feedback for Effective Cardiac Treatment ( AFFECT ) study , a cluster randomized trial . SETTING AND PATIENTS Patients with AMI who were admitted to 76 acute care hospitals in Quebec that treated at least 30 AMI patients per year between April 1 , 1999 , and March 31 , 2003 . INTERVENTION Hospitals were randomly assigned to receive rapid ( immediate ; n = 38 hospitals and 2533 patients ) or delayed ( 14 months ; n = 38 hospitals and 3142 patients ) confidential feedback on quality indicators constructed using administrative data . MAIN OUTCOME MEASURES Quality indicators pertaining to processes of care and outcomes of patients admitted between 4 and 10 months after randomization . The primary indicator was the proportion of elderly survivors of AMI at each study hospital who filled a prescription for a beta-blocker within 30 days after discharge . RESULTS At follow-up , adjusted prescription rates within 30 days after discharge were similar in the early vs late groups ( for beta-blockers , odds ratio [ OR ] , 1.06 ; 95 % confidence interval [ CI ] , 0.82-1.37 ; for angiotensin-converting enzyme inhibitors , OR , 1.17 ; 95 % CI , 0.90-1.52 ; for lipid-lowering drugs , OR , 1.14 ; 95 % CI , 0.86-1.50 ; and for aspirin , OR , 1.05 ; 95 % CI , 0.84-1.33 ) . In addition , adjusted mortality was similar in both groups , as were length of in-hospital stay , physician visits after discharge , waiting times for invasive cardiac procedures , and readmissions for cardiac complications . CONCLUSIONS Feedback based on one-time , confidential report cards constructed using administrative data is not an effective strategy for quality improvement regarding care of patients with AMI . A need exists for further studies to rigorously evaluate the effectiveness of more intensive report card interventions .

Effective Cardiac Treatment

rapid

delayed

report card interventions

Effective Cardiac Treatment

quality of care

adjusted mortality

length of in-hospital stay

physician visits after discharge

readmissions for cardiac complications

effectiveness

acute myocardial infarction

AMI


Trichuris infections in pigs : a treatment trial in the field .

treatment trial


Determinants of the effect of estrogen on the progression of subclinical atherosclerosis : Estrogen in the Prevention of Atherosclerosis Trial . OBJECTIVE To determine the extent to which the estrogen-induced changes in lipids and markers of carbohydrate metabolism explain the beneficial effect of estrogen therapy on the progression of carotid artery intima-media thickness ( IMT ) in postmenopausal women . DESIGN A randomized , double-blind , placebo-controlled , single-center trial enrolling 222 postmenopausal women 45 years and older without cardiovascular disease and with low-density lipoprotein ( LDL ) cholesterol levels of 3.37 mmol/L or greater ( > or = 130 mg/dL ) . Intervention was unopposed micronized 17beta-estradiol versus placebo . Measurements were made using high-resolution B-mode ultrasonography to measure carotid artery IMT at baseline and every 6 months on-trial . RESULTS Progression of carotid IMT was inversely related to on-trial high-density lipoprotein ( HDL ) cholesterol ( P = 0.04 ) and was directly related to on-trial LDL-cholesterol ( P = 0.005 ) . Compared with placebo , women randomized to estradiol showed a higher mean on-trial HDL-cholesterol level and a lower mean on-trial LDL-cholesterol level . In contrast , fasting glucose , insulin , and hemoglobin A1C were lowered and insulin sensitivity increased with estradiol therapy , but the changes were not related to carotid IMT progression . On-trial HDL-cholesterol and LDL-cholesterol were significant independent determinants of carotid IMT progression , jointly explaining 30 % of the treatment effect of unopposed estrogen on the progression of carotid IMT . CONCLUSION Unopposed 17beta-estradiol reduced carotid IMT progression in postmenopausal women in part by increasing HDL-cholesterol and decreasing LDL-cholesterol . Although women randomized to estradiol showed improvement in all the markers of carbohydrate metabolism , these factors did not play a significant role in carotid IMT progression .

estrogen

Estrogen

estrogen therapy

placebo-controlled

unopposed micronized 17beta-estradiol

placebo

B-mode ultrasonography

placebo

estradiol

estradiol

unopposed estrogen

Unopposed 17beta-estradiol

estradiol

subclinical atherosclerosis

carotid artery IMT

carotid IMT

HDL-cholesterol level

LDL-cholesterol level .

fasting glucose

insulin

hemoglobin A1C

HDL-cholesterol

LDL-cholesterol

carotid IMT

carotid IMT

carotid IMT

HDL-cholesterol

LDL-cholesterol

carotid IMT

postmenopausal

women

women

45 years and older

cardiovascular disease

postmenopausal

women

women


Superior efficacy of clopidogrel plus acetylsalicylic acid compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in healthy volunteers . INTRODUCTION Recent ex vivo platelet aggregometry data indicate that clopidogrel 75 mg/day plus acetylsalicylic acid ( ASA ) 75 mg/day is a more potent antiplatelet regimen than the marketed combination of dipyridamole+ASA . The present study was designed to assess the antithrombotic effect of both dual antiplatelet regimens using a human ex vivo model of arterial thrombosis . MATERIALS AND METHODS This was a randomized , double-blind , placebo-controlled , crossover study . During two 10-day treatment periods separated by a 14-day washout period , 23 healthy male volunteers received once-daily clopidogrel 75 mg plus acetylsalicylic acid 75 mg , or twice-daily extended-release dipyridamole 200 mg plus acetylsalicylic acid 25 mg . Assessments were made at baseline and on Day 10 of each period . Arterial thrombus formation was induced ex vivo by exposing a collagen-coated surface in a parallel-plate perfusion chamber to native blood for 3 min ( arterial wall shear rate 2600 s ( -1 ) ) . Total platelet and fibrin deposition was determined by immunoenzymatic methods . RESULTS Compared with baseline values , the mean inhibition of total platelet deposition was 63.9+/-5.9 % with clopidogrel plus acetylsalicylic acid , compared with 18.4+/-5.6 % for extended-release dipyridamole plus acetylsalicylic acid ( 67 % reduction ; 95 % CI , 49-79 % ; p < 0.0001 ) . Corresponding figures for fibrin deposition were 64.9+/-4.8 % and 18.3+/-9.7 % , respectively ( 58 % reduction ; 95 % CI , 45-67 % ; p < 0.0001 ) . Both treatments were well tolerated . CONCLUSIONS Clopidogrel plus acetylsalicylic acid showed significantly superior antithrombotic efficacy compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in humans .

clopidogrel plus acetylsalicylic acid

clopidogrel

plus acetylsalicylic acid ( ASA )

dipyridamole+ASA

dual antiplatelet regimens

clopidogrel

acetylsalicylic acid

extended-release dipyridamole

acetylsalicylic acid

Clopidogrel

acetylsalicylic acid

extended-release dipyridamole

acetylsalicylic acid

Total platelet

fibrin deposition

fibrin deposition

tolerated

healthy

healthy

male