Showing papers on "Randomized controlled trial published in 1998"

Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group.

Abstract: BACKGROUND Sildenafil is a potent inhibitor of cyclic guanosine monophosphate hydrolysis [corrected] in the corpus cavernosum and therefore increases the penile response to sexual stimulation. We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, and mixed causes. METHODS In a 24-week dose-response study, 532 men were treated with oral sildenafil (25, 50, or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329 different men were treated with sildenafil or placebo, with dose escalation to 100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of the 329 men entered a 32-week, open-label extension study. We assessed efficacy according to the International Index of Erectile Function, a patient log, and a global-efficacy question. RESULTS In the dose-response study, increasing doses of sildenafil were associated with improved erectile function (P values for increases in scores for questions about achieving and maintaining erections were <0.001). For the men receiving 100 mg of sildenafil, the mean score for the question about achieving erections was 100 percent higher after treatment than at base line (4.0 vs. 2.0 of a possible score of 5). In the last four weeks of treatment in the dose-escalation study, 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil, as compared with 22 percent for those receiving placebo (P<0.001). The mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo (P<0.001). Headache, flushing, and dyspepsia were the most common adverse effects in the dose-escalation study, occurring in 6 percent to 18 percent of the men. Ninety-two percent of the men completed the 32-week extension study. CONCLUSIONS Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction.

Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial.

Abstract: Context.—Postherpetic neuralgia (PHN) is a syndrome of often intractable neuropathic pain following herpes zoster (shingles) that eludes effective treatment in many patients.Objective.—To determine the efficacy and safety of the anticonvulsant drug gabapentin in reducing PHN pain.Design.—Multicenter, randomized, double-blind, placebo-controlled, parallel design, 8-week trial conducted from August 1996 through July 1997.Setting.—Sixteen US outpatient clinical centers.Participants.—A total of 229 subjects were randomized.Intervention.—A 4-week titration period to a maximum dosage of 3600 mg/d of gabapentin or matching placebo. Treatment was maintained for another 4 weeks at the maximum tolerated dose. Concomitant tricyclic antidepressants and/or narcotics were continued if therapy was stabilized prior to study entry and remained constant throughout the study.Main Outcome Measures.—The primary efficacy measure was change in the average daily pain score based on an 11-point Likert scale (0, no pain; 10, worst possible pain) from baseline week to the final week of therapy. Secondary measures included average daily sleep scores, Short-Form McGill Pain Questionnaire (SF-MPQ), Subject Global Impression of Change and investigator-rated Clinical Global Impression of Change, Short Form-36 (SF-36) Quality of Life Questionnaire, and Profile of Mood States (POMS). Safety measures included the frequency and severity of adverse events.Results.—One hundred thirteen patients received gabapentin, and 89 (78.8%) completed the study; 116 received placebo, and 95 (81.9%) completed the study. By intent-to-treat analysis, subjects receiving gabapentin had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 points in subjects randomized to receive placebo (P<.001). Secondary measures of pain as well as changes in pain and sleep interference showed improvement with gabapentin (P<.001). Many measures within the SF-36 and POMS also significantly favored gabapentin (P≤.01). Somnolence, dizziness, ataxia, peripheral edema, and infection were all more frequent in the gabapentin group, but withdrawals were comparable in the 2 groups (15 [13.3%] in the gabapentin group vs 11 [9.5%] in the placebo group).Conclusions.—Gabapentin is effective in the treatment of pain and sleep interference associated with PHN. Mood and quality of life also improve with gabapentin therapy.

PROACT: A Phase II Randomized Trial of Recombinant Pro-Urokinase by Direct Arterial Delivery in Acute Middle Cerebral Artery Stroke

Abstract: Background and Purpose—To test the safety and recanalization efficacy of intra-arterial local delivery of plasminogen activators in acute ischemic stroke, a randomized trial of recombinant pro-urok...

Sodium Reduction and Weight Loss in the Treatment of Hypertension in Older Persons: A Randomized Controlled Trial of Nonpharmacologic Interventions in the Elderly (TONE)

Abstract: Context.—Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation.Objective.—To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension.Design.—Randomized controlled trial.Participants.—A total of 875 men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication.Setting.—Four academic health centers.Intervention.—The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention.Main Outcome Measure.—Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months).Results.—The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups.Conclusion.—Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.

Weight Loss Is a Reversible Factor in the Prognosis of Chronic Obstructive Pulmonary Disease

Abstract: The objective of the study was to further unravel the prognostic significance of body weight changes in patients with COPD. Two survival analyses were performed: (1) a retrospective study, including 400 patients with COPD none of whom had received nutritional therapy; (2) a post hoc analysis of a prospective study, including 203 patients with COPD who had participated in a randomized placebo-controlled trial. There was no overlap between the patient groups. Baseline characteristics of all patients were collected on admission to a pulmonary rehabilitation center in stable clinical condition. In the prospective randomized placebo-controlled trial, the physiologic effects of nutritional therapy alone (n = 71) or in combination with anabolic steroid treatment (n = 67) after 8 wk was studied in patients with COPD prestratified into a depleted group and a nondepleted group. Mortality was assessed as overall mortality. The Cox proportional hazards model was used to quantify the relationship between the baseline ...

Role of Rifampin for Treatment of Orthopedic Implant–Related Staphylococcal Infections : A Randomized Controlled Trial

Abstract: Context.— Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial. Objective.— To evaluate the clinical efficacy of a rifampin combination in staphylococcal infections associated with stable orthopedic devices. Design.— A randomized, placebo-controlled, double-blind trial conducted from 1992 through 1997. Setting.— Two infectious disease services in tertiary care centers in collaboration with 5 orthopedic surgeons in Switzerland. Patients.— A total of 33 patients with culture-proven staphylococcal infection associated with stable orthopedic implants and with a short duration of symptoms of infection (exclusion limit <1 year; actual experience 0-21 days). Intervention.— Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy. Main Outcome Measures.— Cure was defined as (1) lack of clinical signs and symptoms of infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of radiological signs of loosening or infection at the final follow-up visit at 24 months. Failure was defined as (1) persisting clinical and/or laboratory signs of infection or (2) persisting or new isolation of the initial microorganism. Results.— A total of 18 patients were allocated to ciprofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combination. Twenty-four patients fully completed the trial with a follow-up of 35 and 33 months. The cure rate was 12 (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of the 9 patients who dropped out were subsequently treated with rifampin combinations, and 5 of them were cured without removal of the device. Conclusion.— Among patients with stable implants, short duration of infection, and initial debridement, patients able to tolerate long-term (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.

Cardiovascular Events and Their Reduction With Pravastatin in Diabetic and Glucose-Intolerant Myocardial Infarction Survivors With Average Cholesterol Levels Subgroup Analyses in the Cholesterol And Recurrent Events (CARE) Trial

Abstract: Background—Although diabetes is a major risk factor for coronary heart disease (CHD), little information is available on the effects of lipid lowering in diabetic patients. We determined whether li...

Spurious precision? Meta-analysis of observational studies.

Abstract: In previous articles we have focused on the potentials, principles, and pitfalls of meta-analysis of randomised controlled trials.1 2 3 4 5 Meta-analysis of observational data is, however, also becoming common. In a Medline search we identified 566 articles (excluding those published as letters) published in 1995 and indexed with the medical subject heading (MeSH) term “meta-analysis.” We randomly selected 100 of these articles and examined them further. Sixty articles reported on actual meta-analyses, and 40 were methodological papers, editorials, and traditional reviews (1). Among the meta-analyses, about half were based on observational studies, mainly cohort and case-control studies of medical interventions or aetiological associations. View this table: Characteristics of 100 articles randomly selected from articles published in 1995 and indexed in Medline with keyword “meta-analysis” The randomised controlled trial is the principal research design in the evaluation of medical interventions. However, aetiological hypotheses—for example, those relating common exposures to the occurrence of disease—cannot generally be tested in randomised experiments. Does breathing other people's tobacco smoke cause lung cancer, drinking coffee cause coronary heart disease, and eating a diet rich in saturated fat cause breast cancer? Studies of such “menaces of daily life”6 use observational designs or examine the presumed biological mechanisms in the laboratory. In these situations the risks involved are generally small, but once a large proportion of the population is exposed, the potential public health implications of these associations—if they are causal—can be striking. Analyses of observational data also have a role in medical effectiveness research.7 The evidence available from clinical trials will rarely answer all the important questions. Most trials are conducted to establish efficacy and safety of a single agent in a specific clinical situation. Owing to the limited size of such trials, less common adverse effects of drugs may only be detected in case-control …

Vagus nerve stimulation therapy for partial-onset seizures A randomized active-control trial

Abstract: Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Screening and brief intervention for high-risk college student drinkers: results from a 2-year follow-up assessment.

Abstract: This randomized controlled trial evaluated the efficacy of a brief intervention designed to reduce the harmful consequences of heavy drinking among high-risk college students. Students screened for risk while in their senior year of high school (188 women and 160 men) were randomly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition. A normative group selected from the entire screening pool provided a natural history comparison. Follow-up assessments over a 2-year period showed significant reductions in both drinking rates and harmful consequences, favoring students receiving the intervention. Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period, most showed a decline in problems over time, suggesting a developmental maturational effect.

Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association

Abstract: Since the 1950s carotid endarterectomy has been performed in patients with symptomatic carotid artery stenosis, based on suggestive but inconclusive evidence for its effectiveness. Only during the last 5 years have randomized studies clarified the indications for surgery. In preparing this report, panel members used the same rules of evidence used in the previous report1 2 (Table⇓). View this table: Table 1. Levels of Evidence and Grading of Recommendations Few studies have analyzed control of risk factors in a randomized, prospective manner following carotid endarterectomy. However, a wealth of data are available regarding the general relationship between risk factor control and stroke risk. These data provide some guidance for the care of endarterectomy patients. ### Hypertension Hypertension is the most powerful, prevalent, and treatable risk factor for stroke.3 Both systolic and diastolic blood pressure are independently related to stroke incidence. Isolated systolic hypertension, which is common in the elderly, also considerably increases risk of stroke. Reduction of elevated blood pressure significantly lowers risk of stroke. Meta-analyses of randomized trials found that an average reduction in diastolic blood pressure of 6 mm Hg produces a 42% reduction in stroke incidence.3 4 Treatment of isolated systolic hypertension in people older than 60 years also reduces stroke incidence by 36% without an excessive number of side effects such as depression or dementia.5 Long-term care of patients after endarterectomy should include careful control of hypertension (Grade A recommendation for treatment of hypertension in general; Grade C recommendation for postendarterectomy care). Perioperative treatment of hypertension after carotid endarterectomy represents a special situation. Poor control of blood pressure after endarterectomy increases risk of cerebral hyperperfusion syndrome.6 7 8 9 This complication is characterized by unilateral headache, seizures, and occasionally altered mental status or focal neurological signs. Neuroimaging may show intracerebral hemorrhages10 11 12 or white …

Preventing conduct problems in Head Start children: strengthening parenting competencies.

Abstract: The effectiveness of a parenting program with 394 Head Start mothers was examined. Nine Head Start centers were randomly assigned to either an experimental condition in which parents, teachers, and family service workers participated in the intervention or a control condition in which the regular Head Start program was offered. Mothers in the intervention group were observed at home to have significantly fewer critical remarks and commands, to use less harsh discipline, and to be more positive and competent in their parenting when compared with control mothers. Teachers reported that intervention mothers were more involved in their children's education and that their children were more socially competent. Intervention children were observed to exhibit significantly fewer conduct problems, less noncompliance, less negative affect, and more positive affect than control children. One year later most of the improvements were maintained.

Randomised trial of early diet in preterm babies and later intelligence quotient

Abstract: Objectives: To determine whether perinatal nutrition influences cognitive function at 7 1/2 - 8 years in children born preterm. Design: Randomised, blinded nutritional intervention trial. Blinded follow up at 7 1/2 - 8 years. Setting: Intervention phase in two neonatal units; follow up in a clinic or school setting. Subjects: 424 preterm infants who weighed under 1850 g at birth; 360 of those who survived were tested at 7 1/2 - 8 years. Interventions: Standard infant formula versus nutrient enriched preterm formula randomly assigned as sole diet (trial A) or supplements to maternal milk (trial B) fed for a mean of 1 month. Main outcome measures: Intelligence quotient (IQ) at 7 1/2 - 8 years with abbreviated Weschler intelligence scale for children (revised). Results: There was a major sex difference in the impact of diet. At 7 1/2 - 8 years boys previously fed standard versus preterm formula as sole diet had a 12.2 point disadvantage (95% confidence interval 3.7 to 20.6; P Conclusions: Preterm infants are vulnerable to suboptimal early nutrition in terms of their cognitive performance—notably, language based skills—at 7 1/2 - 8 years, when cognitive scores are highly predictive of adult ones. Our data on cerebral palsy generate a new hypothesis that suboptimal nutritional management during a critical or plastic early period of rapid brain growth could impair functional compensation in those sustaining an earlier brain insult. Cognitive function, notably in males, may be permanently impaired by suboptimal neonatal nutrition.

Cholesterol Lowering With Statin Drugs, Risk of Stroke, and Total Mortality: An Overview of Randomized Trials

Abstract: OBJECTIVE To examine whether cholesterol lowering with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin drugs) reduces the risks of stroke and total mortality. DATA SOURCES We conducted a computerized literature search from 1985 through 1995 to identify all published trials testing statin drugs. The Cholesterol and Recurrent Events (CARE) data were added after the report was published in October 1996. Our search was limited to English-language articles and included published overviews containing relevant individual trials. TRIAL SELECTION Criteria for inclusion of randomized trials in the overview were (1) statin drugs alone used to reduce lipid levels rather than multifactorial interventions including another type of cholesterol-lowering drug and (2) inclusion of data on deaths and/or strokes. DATA EXTRACTION Data were extracted by 2 researchers, and only minor discrepancies, which were easily resolved by discussion, occurred. Principal investigators of the trials and their funding agencies were also contacted to secure any relevant data not included in the published reports. DATA SYNTHESIS A total of 16 individual trials including approximately 29 000 subjects treated and followed up an average of 3.3 years were included in the overview. The average reductions in total and low-density lipoprotein cholesterol achieved were large-22% and 30%, respectively. A total of 454 strokes (fatal plus nonfatal) and 1175 deaths occurred. Those assigned to statin drugs experienced significant reductions in risks of stroke of 29% (95% confidence interval [CI], 14%-41%) as well as total mortality of 22% (95% CI, 12%-31%), which was attributable to a significant reduction in cardiovascular disease (CVD) deaths of 28% (95% CI, 16%-37%). There was no evidence of any increased risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI, 0.75-1.14). There was also no significant increase in risk of cancer (RR, 1.03; 95% CI, 0.90-1.17). CONCLUSION This overview of all published randomized trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence.

ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation)

Abstract: The publication of major studies dealing with the natural history of bradyarrhythmias and tachyarrhythmias and major advances in the technology of pacemakers and implantable cardioverter-defibrillators (ICDs) has mandated this revision of the 1991 ACC/AHA Guidelines for Implantation of Pacemakers and Antiarrhythmia Devices. This executive summary appears in the April 7, 1998 issue of Circulation. The full text of the guidelines, including the ACC/AHA Class I, II, and III recommendations, is published in the April 1998 issue of the Journal of the American College of Cardiology. Reprints of both the executive summary and the full text are available from both organizations. Following extensive review of the medical literature and related documents previously published by the American College of Cardiology, the American Heart Association, and the North American Society for Pacing and Electrophysiology, the writing committee developed recommendations that are evidence based whenever possible. Evidence supporting current recommendations is ranked as level A if the data were derived from multiple randomized clinical trials involving a large number of individuals. Evidence was ranked as level B when data were derived from a limited number of trials involving comparatively small numbers of patients or from well-designed data analysis of nonrandomized studies or observational data registries. Evidence was ranked as level C when consensus of expert opinion was the primary source of recommendation. The committee emphasizes that for certain conditions for which no other therapies are available, the indications for device therapies are based on years of clinical experience as well as expert consensus and are thus well supported, even though the evidence was ranked as level C. These guidelines include expanded sections on selection of pacemakers and ICDs, optimization of technology, cost, and follow-up of implanted devices. The follow-up sections are relatively brief because in many instances the type and frequency of follow-up examinations …

Econometrics in outcomes research: the use of instrumental variables.

Abstract: We describe an econometric technique, instrumental variables, that can be useful in estimating the effectiveness of clinical treatments in situations when a controlled trial has not or cannot be done. This technique relies upon the existence of one or more variables that induce substantial variation in the treatment variable but have no direct effect on the outcome variable of interest. We illustrate the use of the technique with an application to aggressive treatment of acute myocardial infarction in the elderly.

Indications for ACE inhibitors in the early treatment of acute myocardial infarction - Systematic overview of individual data from 100,000 patients in randomized trials

Abstract: BACKGROUND Several large-scale trials have demonstrated improved survival with ACE-inhibitor therapy started during acute myocardial infarction. A systematic overview was conducted to resolve uncertainties regarding time of initiation, time course of effect, and identification of patients in whom the benefits or the risks may be greater. METHODS AND RESULTS This overview aimed to include individual data from all randomized trials involving more than 1000 patients in which ACE-inhibitor treatment was started in the acute phase (0 to 36 hours) of myocardial infarction and continued for a short time (4 to 6 weeks). Data were available for 98,496 patients from 4 eligible trials, and the results were consistent among the trials. Thirty-day mortality was 7.1% among patients allocated to ACE inhibitors and 7.6% among control subjects, corresponding to a 7% (SD, 2%) proportional reduction (95% CI, 2% to 11%; 2P<0.004). This represented avoidance of approximately 5 (SD, 2) deaths per 1000 patients, with most of the benefit observed within the first week. The proportional benefit was similar in patients at different underlying risk. The absolute benefit was particularly large in some high-risk groups (ie, Killip class 2 to 3, heart rate > or = 100 bpm at entry) and in anterior MI. ACE-inhibitor therapy also reduced the incidence of nonfatal cardiac failure (14.6% versus 15.2%, 2P=0.01) but was associated with an excess of persistent hypotension (17.6% versus 9.3%, 2P<0.01) and renal dysfunction (1.3% versus 0.6%, 2P<0.01). CONCLUSIONS These results support the use of ACE inhibitors early in the treatment of acute MI, either to a wide range of patients or selectively in patients with anterior MI and in those at increased risk of death.

Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study.

Abstract: Background—Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated. Methods—Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization. Results—In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio50.6 [95% CI 0.36 to 0.98], P50.03). Major cardiac-related events in electively stented patients were less common (odds ratio50.23 [95% CI 0.05 to 0.91], P50.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3 63.6 versus 6.463.7 days, P50.0001). Conclusions—Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation. (Circulation. 1998;98:1597-1603.)

Clinical Effects of β-Adrenergic Blockade in Chronic Heart Failure A Meta-Analysis of Double-Blind, Placebo-Controlled, Randomized Trials

Abstract: Background—β-Blockers have improved symptoms and reduced the risk of cardiovascular events in studies of patients with heart failure, but it is unclear which end points are most sensitive to the therapeutic effects of these drugs. Methods and Results—We combined the results of all 18 published double-blind, placebo-controlled, parallel-group trials of β-blockers in heart failure. From this combined database of 3023 patients, we evaluated the strength of evidence supporting an effect of treatment on left ventricular ejection fraction, NYHA functional class, hospitalizations for heart failure, and death. β-Blockers exerted their most persuasive effects on ejection fraction and on the combined risk of death and hospitalization for heart failure. β-Blockade increased the ejection fraction by 29% (P 90% of the trials were eliminated from the analysis or if a large numbe...

Nurse Case Management To Improve Glycemic Control in Diabetic Patients in a Health Maintenance Organization: A Randomized, Controlled Trial

Abstract: Background: Control of hyperglycemia delays or prevents complications of diabetes, but many persons with diabetes do not achieve optimal control. Objective: To compare diabetes control in patients receiving nurse case management and patients receiving usual care. Design: Randomized, controlled trial. Setting: Primary care clinics in a group-model health maintenance organization (HMO). Patients: 17 patients with type 1 diabetes mellitus and 121 patients with type 2 diabetes mellitus. Intervention: The nurse case manager followed written management algorithms under the direction of a family physician and an endocrinologist. Changes in therapy were communicated to primary care physicians. All patients received ongoing care through their primary care physicians. Measurements: The primary outcome, hemoglobin A 1c (HbA 1c ) value, was measured at baseline and at 12 months. Fasting blood glucose levels, medication type and dose, body weight, blood pressure, lipid levels, patient-perceived health status, episodes of severe hypoglycemia, and emergency department and hospital admissions were also assessed. Results: 72% of patients completed follow-up. Patients in the nurse case management group had mean decreases of 1.7 percentage points in HbA 1c values and 43 mg/dL (2.38 mmol/L) in fasting glucose levels; patients in the usual care group had decreases of 0.6 percentage points in HbA 1c values and 15 mg/dL (0.83 mmol/L) in fasting glucose levels (P < 0.01). Self-reported health status improved in the nurse case management group (P = 0.02). The nurse case management intervention was not associated with statistically significant changes in medication type or dose, body weight, blood pressure, or lipids or with adverse events. Conclusions: A nurse case manager with considerable management responsibility can, in association with primary care physicians and an endocrinologist, help improve glycemic control in diabetic patients in a group-model HMO.

Ebselen in Acute Ischemic Stroke A Placebo-Controlled, Double-blind Clinical Trial

Abstract: Background and Purpose—The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase–like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial. Methods—Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures. Results—Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149 given placebo) revealed that ebselen treatment achieved a significantly better outcom...

Randomised controlled trial of compliance therapy. 18-month follow-up.

Abstract: BACKGROUND: A randomised controlled trial was conducted in an acute treatment setting to examine the effectiveness of compliance therapy, a brief pragmatic intervention targeting treatment adherence in psychotic disorders, based on motivational interviewing and recent cognitive approaches to psychosis. METHOD: Seventy-four patients with psychotic disorders according to DSM-III-R criteria recruited from consecutive admissions to an acute in-patient unit, received 4-6 sessions of either compliance therapy or non-specific counselling, and were followed-up over 18 months. The principal outcome measures were observer-rated compliance, attitudes to treatment, insight and social functioning. RESULTS: Significant advantages were found for the compliance therapy group post-treatment on measures of insight, attitudes to treatment and observer-rated compliance which were retained over the follow-up period. Global social functioning improved relatively more over time in the compliance therapy group compared with the control group. Survival in the community prior to readmission was significantly longer in the compliance therapy group. CONCLUSIONS: The results support the effectiveness of compliance therapy in improving functioning and community tenure after an acute psychotic episode.

Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability

Abstract: When 251 relapsing-remitting patients with multiple sclerosis were randomized to receive daily subcutaneous injections of glatiramer acetate, previously called copolymer 1 (Copaxone; n = 125) or placebo (n = 126) for 24 months, there were no laboratory abnormalities associated with glatiramer acetate treatment and it was well tolerated with few side effects. Patients receiving glatiramer acetate had significantly fewer relapses and were more likely to be neurologically improved, whereas those receiving placebo were more likely to worsen. This study was extended for 1 to 11 months (mean of 5.2 months for the glatiramer acetate group and 5.9 months for the placebo group). The blinding and study conditions used during the core 24-month study were unchanged throughout the extension. The results of this extension study confirm the excellent tolerance and safety profile of glatiramer acetate for injection. The clinical benefit of glatiramer acetate for both the relapse rate and for neurologic disability was sustained at the end of the extension trial.

Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy

Abstract: Objective The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy. Background The pain of diabetic neuropathy is a major cause of morbidity among these patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain. Methods This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washoutlscreening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n = 65) or placebo (n = 66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics. Results Tramadol, at an average dosage of 210 mg/day, was significantly ( p p = 0.02) and social functioning (p = 0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence. Conclusions The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy.