Showing papers on "Randomized controlled trial published in 1998"

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.

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 …

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.

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.

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.

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.

Aspirin and risk of hemorrhagic stroke: A meta-analysis of randomized controlled trials

Abstract: Context.—Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke.Objective.—To estimate the risk of hemorrhagic stroke associated with aspirin treatment.Data Sources.—Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors' reference files.Study Selection.—All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported.Data Extraction.—Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol.Data Synthesis.—Data from 16 trials with 55,462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10,000 persons (95% confidence interval [CI], 107-167; P<.001) and in ischemic stroke, a reduction of 39 events per 10,000 persons (95% CI, 17-61; P<.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10,000 persons (95% CI, 5-20; P<.001). This risk did not differ by participant or study design characteristics.Conclusions.—These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.

The clinical course and prognostic factors of non-specific neck pain: a systematic review

Abstract: Neck pain occurs frequently in western societies. In the majority of cases, no specific cause can be identified. In order to gain insight into the clinical course and prognostic factors of non-specific neck pain, a systematic review was conducted. A computerized literature search was carried out to identify observational studies on non-specific neck pain and randomized clinical trials (RCTs) on conservative treatment of non-specific neck pain. Two reviewers scored independently, the methodological quality of all identified publications, using a standardized set of 13 criteria which were divided into five categories according to: study population, study design, follow-up, outcome measures and analysis/data presentation. To determine prognosis per study, an overall percentage of recovery for the most important outcome measures (pain, general improvement, functional status, health care utilization and lost days of work) was calculated. In total 23 eligible publications were identified (six observational studies and 17 RCTs). Only seven of 23 studies scored 50% or more of the 13 items, indicating a generally poor quality of methods. The most prevalent methodological shortcomings appeared to be selection of the study population, the sample size and analysis techniques. Most information regarding the clinical course is available for the group of patients with complaints for more than 6 months, who are treated in a secondary care or an occupational setting. In this group of patients, 46% (median) had less pain, with a range of 22-79% and a general improvement that ranged between 37 and 95% (47% median). The reduction in the use of analgesics ranged between 32 and 80% (37% median). Six studies reported on prognostic factors. Bearing in mind the limited number of studies and the low methodological quality, there are some indications that the localization (radiation to the arms/neurologic signs) and radiologic findings (degenerative changes in the discs and joints) are not associated with a worse prognosis. A higher severity of pain and a history of previous attacks however, seems to be associated with a worse prognosis.

Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial

Abstract: Context.—Urinary incontinence is a common condition caused by many factors with several treatment options.Objective.—To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women.Design.—Randomized placebo-controlled trial conducted from 1989 to 1995.Setting.—University-based outpatient geriatric medicine clinic.Patients.—A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia.Intervention.—Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition.Main Outcome Measures.—Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment.Results.—For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% "much better" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups.Conclusion.—Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.

Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication Results From a Multicenter, Randomized, Prospective, Double-blind Trial

Abstract: Background—Cilostazol is a new phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. This prospective, randomized, placebo-controlled, parallel-group clinical trial evaluated the efficacy of cilostazol for treatment of stable, moderately severe intermittent claudication. Methods and Results—Study inclusion criteria included age ≥40 years, initial claudication distance (ICD) on treadmill (12.5% incline, 3.2 km/h) between 30 and 200 m, and confirmation of diagnosis of chronic lower-extremity arterial occlusive disease. After stabilization and single-blind placebo lead-in, 81 subjects (62 male, 19 female) from 3 centers were randomized unequally (2:1) to 12 weeks of treatment with cilostazol 100 mg PO BID or placebo. Primary outcome measures included ICD and maximum distance walked (absolute claudication distance, or ACD). Secondary outcome measures included ankle pressures, subjective assessments of benefit by patients and physicians, and safety. Tr...

A Randomized, Controlled Trial of a Group Intervention to Reduce Fear of Falling and Associated Activity Restriction in Older Adults

Abstract: A randomized, single-blind controlled trial was conducted to test the efficacy of a community-based group intervention to reduce fear of falling and associated restrictions in activity levels among older adults. A sample of 434 persons age 60+ years, who reported fear of falling and associated activity restriction, was recruited from 40 senior housing sites in the Boston metropolitan area. Data were collected at baseline, and at 6-week, 6-month, and 12-month follow-ups. Compared with contact control subjects, intervention subjects reported increased levels of intended activity (p < .05) and greater mobility control (p < .05) immediately after the intervention. Effects at 12 months included improved social function (p < .05) and mobility range (p < .05). The intervention had immediate but modest beneficial effects that diminished over time in the setting with no booster intervention.

Randomised controlled trial of patient centred care of diabetes in general practice: impact on current wellbeing and future disease risk

Abstract: Objective To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes. Design Pragmatic parallel group design, with randomisation between practice teams to routine care (comparison group) or routine care plus additional training (intervention group); analysis at one year, allowing for practice effects and stratifiers; self reporting by patients on communication with practitioners, satisfaction with treatment, style of care, and lifestyle. Setting 41 practices (21 in intervention group, 20 in comparison group) in a health region in southern England. Subjects 250/360 patients (aged 30-70 years) diagnosed with type 2 diabetes and completing follow up at one year (142 in intervention group, 108 in comparison group). Intervention 1.5 days9 group training for the doctors and nurses—introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions. Main outcome measures Quality of life, wellbeing, haemoglobin A 1c and lipid concentrations, blood pressure, body mass index (kg/m 2 ). Results Compared with patients in the C group, those in the intervention group reported better communication with the doctors (odds ratio 2.8; 95% confidence interval 1.8 to 4.3) and greater treatment satisfaction (1.6;1.1 to 2.5) and wellbeing (difference in means (d) 2.8; 0.4 to 5.2). However, their body mass index was significantly higher (d=2.0; 0.3 to 3.8), as were triglyceride concentrations (d=0.4 mmol/l; 0.07 to 0.73 mmol/l), whereas knowledge scores were lower −2.74;−0.23 to −5.25. Differences in lifestyle and glycaemic control were not significant. Conclusions The findings suggest greater attention to the consultation process than to preventive care among trained practitioners; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management.

Effectiveness of High-Dose Riboflavin in Migraine Prophylaxis. A Randomized Controlled Trial

Abstract: A deficit of mitochondrial energy metabolism may play a role in migraine pathogenesis. We found in a previous open study that high-dose riboflavin was effective in migraine prophylaxis. We now compared riboflavin (400 mg) and placebo in 55 patients with migraine in a randomized trial of 3 months duration. Using an intention-to-treat analysis, riboflavin was superior to placebo in reducing attack frequency (p = 0.005) and headache days (p = 0.012). Regarding the latter, the proportion of patients who improved by at least 50%, i.e. "responders," was 15% for placebo and 59% for riboflavin (p = 0.002) and the number-needed-to-treat for effectiveness was 2.3. Three minor adverse events occurred, two in the riboflavin group (diarrhea and polyuria) and one in the placebo group (abdominal cramps). None was serious. Because of its high efficacy, excellent tolerability, and low cost, riboflavin is an interesting option for migraine prophylaxis and a candidate for a comparative trial with an established prophylactic drug.