Showing papers by "Timothy J Wilt published in 1999"

Gemfibrozil for the Secondary Prevention of Coronary Heart Disease in Men with Low Levels of High-Density Lipoprotein Cholesterol

Abstract: Background Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary heart disease is beneficial, there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol. Methods We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less. The primary study outcome was nonfatal myocardial infarction or death from coronary causes. Results The median follow-up was 5.1 years. At one year, the mean HDL cholesterol level was 6 percent higher, the mean triglyceride level was 31 percent lower, and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group. LDL cholesterol levels...

Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer.

Abstract: Objectives With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis. Search strategy The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references. Selection criteria We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included. Data collection and analysis The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine. Main results Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)

Beta-sitosterols for benign prostatic hyperplasia.

Abstract: Background Benign prostatic hyperplasia (BPH), nonmalignant enlargement of the prostate, can lead to obstructive and irritative lower urinary tract symptoms (LUTS). The pharmacologic use of plants and herbs (phytotherapy) for the treatment of LUTS associated with BPH has been growing steadily. Phytotherapeutic preparations containing beta-sitosterols, derived from the South African star grass, Hypoxis rooperi, or from species of Pinus and Picea, are available for the treatment of BPH. Objectives This systematic review aimed to assess the effects of beta-sitosterols (B-sitosterol) on urinary symptoms and flow measures in men with of benign prostatic hyperplasia (BPH). Search methods Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. Selection criteria Trials were eligible for inclusion provided they (1) randomized men with BPH to receive B-sitosterol preparations in comparison to placebo or other BPH medications, and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Data collection and analysis Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. Main outcome measure for comparing the effectiveness of B-sitosterols with placebo and standard BPH medications was the change in urologic symptom scale scores. Secondary outcomes included changes in nocturia as well as urodynamic measures (peak and mean urine flow, residual volume, prostate size). Main outcome measure for side effects was the number of men reporting side effects. Main results Five hundred nineteen men from four randomized, placebo-controlled, double-blind trials, (lasting 4 to 26 weeks) were assessed. Three trials used non-glucosidic B-sitosterols and one utilized a preparation that contained 100% B-sitosteryl-B-D-glucoside. B-Sitosterols improved urinary symptom scores and flow measures. The weighted mean difference (WMD) for the IPSS was -4.9 IPSS points (95% CI = -6.3 to -3.5, n = 2 studies). The WMD for peak urine flow was 3.91 mL/s (95% CI = 0.91 to 6.90, n = 4 studies) and the WMD for residual volume was -28.62 mL (95% CI = -41.42 to -15.83, n = 4 studies). The trial using 100% B-sitosteryl-B-D-glucoside (WA184) show improvement in urinary flow measures. B-sitosterols did not significantly reduce prostate size compared to placebo. Withdrawal rates for men assigned to B-sitosterol and placebo were 7.8% and 8.0%, respectively. Authors' conclusions The evidence suggests non-glucosidic B-sitosterols improve urinary symptoms and flow measures. Their long term effectiveness, safety and ability to prevent BPH complications are not known.

Maximal androgen blockade for advanced prostate cancer

Abstract: Objectives This systematic review assessed the effect of maximal androgen blockade (MAB) on survival when compared to castration (medical or surgical) alone for patients with advanced prostate cancer. Search strategy Randomized controlled trials were searched in general and specialized databases (MEDLINE, EMBASE, Cancerlit, Cochrane Library, VA Cochrane Prostate Disease register) and by reviewing bibliographies. Selection criteria All published randomized trials were eligible for inclusion provided they (1) randomized men with advanced prostate cancer to receive a non-steroidal anti-androgen (NSAA) medication in addition to castration (medical or surgical) or to castration alone, and (2) reported overall survival, progression-free survival, cancer-specific survival, and/or adverse events. Eligibility was assessed by two independent reviewers. Data collection and analysis Information on patients, interventions, and outcomes were extracted by two independent reviewers using a standardized form. The main outcome measure for comparing effectiveness was overall survival at 1, 2, and 5 years. Secondary outcome measures included progression-free survival and cancer-specific survival. The relationship of specific NSAA on outcome was evaluated. Additionally, the incidence of adverse effects was measured. Main results Twenty trials enrolling 6,320 patients were included. The pooled OR for overall survival was 1.03 (95% CI:0.85 to 1.25), 1.16 (95% CI:1.00 to 1.33), and 1.29 (95% CI:1.11 to 1.50) at 1, 2, and 5 years respectively. Overall survival was only significant at 5 years. The risk difference at 5 years was 0.048 (95% CI:0.02 to 0.077) and NNT at 5 years 20.8. Progression-free survival was improved only at 1 year follow-up (OR=1.38) and cancer-free survival was improved only at 5 years (OR=1.22). Adverse events occurred more frequently in those assigned to MAB and resulted in withdrawal in 10%. Quality of life was measured in only one study favored orchiectomy alone (less diarrhea and better emotional functioning in the first 6 months). Reviewer's conclusions MAB produces a modest overall and cancer-specific survival at 5 years but is associated with increased adverse events and reduced quality of life.

An evaluation of radical prostatectomy at Veterans Affairs Medical Centers: time trends and geographic variation in utilization and outcomes.

Abstract: OBJECTIVE To examine temporal trends and geographic variation in utilization of radical prostatectomy (RP) as well as 30-day mortality and complication rates. DESIGN Administrative data-base study of radical prostatectomy (RP) using the Department of Veterans Affairs Patient Treatment File and Outpatient Clinic File between 1986 to 1996. Logistic regression was used to estimate temporal and geographic effects on the use of RP. SETTING All Departments of Veterans Affairs Medical Centers (VAMC) in the contiguous United States. PATIENTS Men aged 45 to 84 years who underwent RP at a VAMC (n = 13,398). MAIN OUTCOME MEASURES Number and utilization of RP, rate of 30-day mortality, major cardiopulmonary or vascular complications, and colorectal injuries requiring surgical repair within 30 days of RP. RESULTS From 1986 to 1996, the annual number of RP at VAMCs (range, 695-1,545 RP) more than doubled, and the rate of RP at VAMCs per male VA user increased by 40% (range, 48/100,000-66/100,000). After controlling for age and year, the utilization of RP in West North Central, Mountain, West South Central, and Pacific census divisions was 70%, 14%, 10%, and 8% higher, respectively, whereas the utilization of RP in New England, East North Central, and Mid-Atlantic divisions was 38%, 31%, and 25% lower, respectively, than the rest of the nation (P<0.001). Geographic variation in utilization decreased during the period between 1986 and 1996, but a twofold difference in RP utilization in 1996 remained between high- and low-utilization divisions. Major cardiopulmonary complications, vascular complications, and colorectal injuries occurred in 1.7%, 0.2%, and 1.8% of men, respectively. Thirty-day mortality was 0.73%, declined from 1986 to 1996, and was associated with a history of diabetes and congestive heart failure. CONCLUSION Utilization of RP at VAMCs increased over time and varied across geographic areas. Thirty-day mortality was less than 1% and decreased with time. Differences in utilization may be caused by uncertainty regarding the effectiveness of early detection and treatment of prostate cancer.

Interventions for chronic abacterial prostatitis.

Abstract: BACKGROUND Chronic abacterial prostatitis is a common disabling but enigmatic condition with a symptom complex of pelvic area pain and lower urinary tract symptoms. The scope of treatments recommended for chronic abacterial prostatitis is a testament to how little is known about what causes the condition and how to treat it. As a result, chronic abacterial prostatitis often causes physician frustration, patient confusion and dissatisfaction, variable thresholds for referral, and potentially inappropriate antibiotic use. OBJECTIVES Examine the evidence regarding the effectiveness of therapies for chronic abacterial prostatitis. SEARCH STRATEGY Studies were identified through a search of MEDLINE (1966-2000), the Cochrane Library, bibliographies of identified articles and reviews, and contact with an expert. SELECTION CRITERIA Studies were eligible if they: (1) are randomized controlled trials (RCTs) or controlled clinical trials (CCTs) (2) involve men with chronic abacterial prostatitis (3) control group receives placebo, sham intervention, active pharmacologic or device therapy for chronic abacterial prostatitis and (4) outcomes data are provided. Eligibility was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS Study information on patients, interventions, and outcomes was extracted independently by 2 reviewers. The main outcome was the efficacy of treatment for chronic abacterial prostatitis vs. control in improving urologic symptom scale scores or global report of urinary tract symptoms. Secondary outcomes included changes in the prostate examination, uroflowmetry, urodynamics, analysis of urine, expressed prostatic secretions and seminal fluid, and prostate ultrasonography. MAIN RESULTS The 15 treatment trials involved: medications used to treat benign prostatic hyperplasia (n=4 trials); anti-inflammatory medications (n=2 trials); antibiotics (n=1 trial); thermotherapy (n=5 trials); and miscellaneous medications (n=3 trials). The disparity between studies did not permit quantitative analysis. There were a total of 600 enrollees (age range 38-45). All but one of the trials were done outside the United States. REVIEWER'S CONCLUSIONS The treatment trials are few, weak methodologically, and involve small sample sizes. The routine use of antibiotics and alpha blockers for chronic abacterial prostatitis is not supported by the existing evidence. The small studies examining thermal therapy appear to demonstrate benefit of clinical significance and merit further evaluation. Additional treatment trials are required and they should report important patient characteristics (e.g., race), study design details and utilize clinically relevant and validated assessment measures.

Internal medical residents' ability to diagnose and characterize major depression.

Abstract: The purpose of this study was to assess medical residents' knowledge of symptom criteria and subtypes of major depressive episode and their accuracy in diagnosing major depressive disorders and classifying episode severity and subtype according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Thirty-five third-year internal medicine residents completed a self-administered, written instrument containing 2 open-ended questions and 21 hypothetical scenarios. The sensitivity for recognizing major depressive disorder was 64%, and the specificity was 69%. The sensitivity for classifying severity was 86% for mild, 66% for moderate, 71% for severe, and 66% for severe with psychosis. Misclassification of severity was most commonly to a less severe class. For scenarios with a diagnosable subtype of a major depressive disorder, the sensitivity for classification was 34% for atypical, 51% for catatonic, 74% for melancholic, 100% for postpartum, and 94% for seasonal depression. When asked to enumerate the criteria symptoms for depression, 80% or more of the residents listed sad mood, loss of interest, weight change, and sleep disturbances; 14 to 21 (40%-60%) listed thoughts of death and worthlessness; other criteria were listed by 7 to 11 (20%-31%). When asked to list the episode subtypes, none was listed by more than 3 (9%) residents, although 13 (37%) residents volunteered psychotic as a subtype. Residents frequently failed to recognize the presence or absence of major depressive disorder and often misclassified episode severity and subtype on scenarios. Few could spontaneously list the episode subtypes. Methods must be developed to improve the recognition and classification of major depressive episodes to better direct treatment.

Rationale and design of the arterial disease multiple intervention trial (ADMIT) pilot study

Abstract: The primary objectives of the pilot study were to: (1) evaluate the feasibility of recruiting patients with peripheral arterial disease (PAD); (2) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment, low-density lipoprotein (LDL)-lowering therapy, antioxidant therapy, antithrombotic therapy, and their combinations; and (3) assess adherence to a complex multiple drug regimen. Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers, maintenance of therapy masking (in particular with niacin), and measurement of the intervention's impact on functional status and on quality of life. To date, no secondary prevention trial has been conducted specifically among patients with PAD. Intermittent claudication affects about 0.5% to 1.0% of persons aged >35 years. There is a striking increase in incidence of PAD with age, particularly among those aged >50 years in both sexes, although men are twice as likely as women to develop PAD. The Arterial Disease Multiple Intervention Trial was a double-blind randomized pilot trial of 468 participants with documented PAD. A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions. The pilot incorporated several major novel design features: first, the use of a simple noninvasive method (measurement of ankle brachial index) to identify a population with either symptomatic or asymptomatic PAD; and second, a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group. Two other arms, the antioxidant arm (consisting of beta-carotene and vitamins E and C) and the antithrombotic arm (using warfarin) were also added. Adherence to therapy was measured by pill count, and success in treatment was measured by the proportion of values in target range for HDL, LDL, and the international normalized ratio.