Showing papers by "Timothy J Wilt published in 2002"

Sildenafil for male erectile dysfunction: a systematic review and meta-analysis.

Abstract: Objective To determine the efficacy and safety of sildenafil citrate in the treatment of male erectile dysfunction. Data Sources The MEDLINE, HealthSTAR, Current Contents, and Cochrane Library databases (January 1, 1995, through December 31, 2000); bibliographies of retrieved articles and review articles; conference proceedings abstracts; the Food and Drug Administration Web site; and the manufacturer. Study Selection Trials were eligible if they included men with erectile dysfunction, compared sildenafil with control, were randomized, were of at least 7 days' duration, and assessed clinically relevant outcomes. Data Extraction Two reviewers independently evaluated study quality and extracted data in a standardized fashion. Data Synthesis Twenty-seven trials (6659 men) met the inclusion criteria. In results pooled from 14 parallel-group, flexible as-needed dosing trials, sildenafil was more likely than placebo to lead to successful sexual intercourse, with a higher percentage of successful intercourse attempts (57% vs 21%; weighted mean difference, 33.7; 95% confidence interval [CI], 29.2-38.2; 2283 men) and a greater percentage of men experiencing at least 1 intercourse success during treatment (83% vs 45%; relative benefit increase, 1.8; 95% CI, 1.7-1.9; 2205 men). In data pooled from 6 parallel-group, fixed-dose trials, efficacy appeared slightly greater at higher doses. Treatment response appeared to vary between patient subgroups, although relative to placebo, sildenafil significantly improved erectile function in all evaluated subgroups. In trials with parallel-group design and flexible dosing, men randomized to receive sildenafil were less likely than those receiving placebo to drop out for any reason and no more likely to drop out due to an adverse event or laboratory abnormality. Specific adverse events with sildenafil included flushing (12%), headache (11%), dyspepsia (5%), and visual disturbances (3%); all adverse events were significantly less likely to occur with placebo. Sildenafil was not significantly associated with serious cardiovascular events or death. Conclusions Sildenafil improves erectile function and is generally well tolerated. Treatment response seems to vary between patient subgroups, although sildenafil has greater efficacy than placebo in all evaluated subgroups.

Cost-effectiveness of gemfibrozil for coronary heart disease patients with low levels of high-density lipoprotein cholesterol: the Department of Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial.

Abstract: Background: Although numerous clinical trials and economic analyses have established the efficacy and costeffectiveness of lowering cholesterol for the prevention of coronary heart disease, there are few data on the role of raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglyceride levels. The US Department of Veterans Affairs (VA) Cooperative Studies Program HDL-C Intervention Trial (VA-HIT) was a multicenter, randomized trial of gemfibrozil, an agent that raised HDL-C levels and lowered triglyceride levels, yet had no effect on low-density lipoprotein cholesterol (LDL-C) levels. The study showed that gemfibrozil therapy significantly reduced major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in patients with coronary heart disease, low HDL-C levels, and low LDL-C levels. Objective: To report the results of a cost-effectiveness study based on the results of the VA-HIT. Methods: The cost per year of life gained with gemfibrozil therapy was calculated. Hazard functions were estimated, and the resulting probabilities were used in a Markov model simulation to estimate the effect of gemfibrozil on life expectancy and costs over a simulated lifetime. Sensitivity analyses were used to account for uncertainty. Results: Using the prices of gemfibrozil that were negotiated by the VA, gemfibrozil was cost saving. Using drug prices found outside the VA, a quality-adjusted lifeyear saved by gemfibrozil therapy cost between $6300 and $17100.

Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects

Abstract: Objective To systematically review and evaluate the effectiveness and adverse effects of the α-antagonist, terazosin, for treating urinary symptoms associated with benign prostatic obstruction (BPO). Methods Studies were sought and included in the review if they were randomized trials of at least 1 month duration, involved men with symptomatic BPO and compared terazosin with placebo or active controls. The study, patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol. Results Seventeen studies involving 5151 men met the inclusion criteria, i.e. placebo-controlled (10), α-blockers (seven), finasteride alone or combined with terazosin and placebo (one), and microwave therapy (one). The study duration was 4–52 weeks; the mean age of the men was 65 years and 82% were white. Baseline urological symptom scale scores and flow rates showed that men had moderate BPO. Efficacy outcomes were rarely reported in a way that allowed for data pooling, but indicated that terazosin improved symptom scores and flow rates more than did placebo or finasteride, and similarly to other α-antagonists. The pooled mean percentage improvement for the Boyarsky symptom score was 37% for terazosin and 15% for placebo (four studies). The mean percentage improvement for the American Urological Association symptom score was 38%, compared with 17% and 20% for placebo and finasteride, respectively (two studies). The pooled mean improvement in the International Prostate Symptom Score of 40% was similar to that with tamsulosin (43%). Peak urinary flow rates improved more with terazosin (22%) than with placebo (11%) and finasteride (15%), but did not differ significantly from the other α-antagonists. The percentage of men discontinuing terazosin was comparable with those receiving placebo and finasteride, but greater than with other α-antagonists. Adverse effects were greater than with placebo and included dizziness, asthenia, headache and postural hypotension. Conclusions The available evidence indicates that terazosin improves the symptoms and flow rates associated with BPO; it was more effective than placebo or finasteride and similar to other α-antagonists. Adverse effects were generally mild but more frequent than with other α-antagonists and associated with a two- to four-fold increase in treatment discontinuation.

Clarifying uncertainty regarding detection and treatment of early-stage prostate cancer.

Abstract: Detection and treatment of prostate cancer can theoretically identify and cure a potentially disabling and deadly disease. However, controversy exists primarily because of the absence of randomized controlled trials (RCTs) documenting that these strategies improve survival and quality of life. In the absence of definitive information from RCTs, patients seek information and recommendations from many sources. Physicians have an opportunity to help patients and their families sort through the vast array of conflicting and confusing information. Rather then recommending for or against routine prostate-specific antigen (PSA) testing, physicians should provide men who are interested in prostate cancer testing, 50 years of age and older, and have a life expectancy of at least 10 to 15 years, with balanced information about the potential benefits and established harms of screening, diagnosis, and treatment. Validated informational materials can effectively and efficiently promote shared decision making. For early prostate cancer detection, the minimum information should include: the likelihood that prostate cancer will be diagnosed, possibilities of false-positive and false-negative results, anxiety associated with a positive test, and uncertainty regarding whether screening reduces the risk for death from prostate cancer. For men with localized prostate cancer, acceptable treatment options include radical prostatectomy, radiation therapy, cryotherapy, early androgen-suppression therapy, and watchful waiting. These are all considered acceptable options because data do not provide clear-cut evidence for the superiority of any 1 treatment. The only RCT comparing surgery to watchful waiting, though of relatively small size and conducted before PSA testing, showed no difference in survival after 23 years of follow-up. Watchful waiting does not remove prostate cancer, may miss an opportunity to cure or delay disease progression, and may lead to increased patient anxiety. However, watchful waiting avoids the harmful side effects of early intervention and does provide palliative therapy if and when symptomatic disease progression occurs. Furthermore, intervention is not necessary in the vast majority of men because most prostate cancers do not cause mortality or serious morbidity. Therefore, quality of life in many men treated with watchful waiting is superior to those treated with early intervention. For the minority of men with prostate cancer likely to cause disability or death, early intervention options may not be effective. Although commonly used in other countries, watchful waiting is rarely recommended in the United States. The opportunity exists to resolve the confusion, close the gaps in knowledge, and enhance prostate cancer care by conducting RCTs. Until these RCTs are completed, physicians can assist patients by providing a balanced presentation of the known risks and potential but unproven benefits of detection and treatment options and incorporating patient preferences into health care decisions.

Allopurinol for chronic prostatitis

Abstract: Background Chronic prostatitis is a condition that causes men substantial morbidity through the associated constellation of urinary symptoms, sexual dysfunction, and pelvic pain. The etiology of chronic prostatitis is unknown, and the many and varied treatments for chronic prostatitis reflect in part this knowledge gap. One novel etiologic theory is that the reflux of urine into prostatic ducts causes prostatic inflammation via high concentrations of purine and pyrimidine base-containing metabolites in prostatic secretions. This theory has led to the use of allopurinol for treatment of chronic prostatitis in hopes of lowering prostatic levels of uric acid and improving symptoms. Objectives To determine the effects of allopurinol in the treatment of chronic prostatitis Search methods Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library, Cochrane Prostate Group database), bibliographies of obtained articles, and direct contact with authors. Selection criteria All randomized trials of allopurinol versus placebo used to treat patients with chronic prostatitis. Acute prostatitis, bacterial prostatitis, and asymptomatic prostatitis were excluded. The main outcome measure was the change in patient-reported discomfort. Data collection and analysis The reviewers extracted the data independently for the outcomes of change in patient-reported discomfort, investigator graded prostate pain, leukocyte counts, and biochemical indices. Main results In this update, no new trials were identified (08/2002). Only one trial with 54 men lasting 240 days (with 330 days of follow up) met study inclusion criteria. There was a statistically significant change favoring allopurinol in patient-reported discomfort between the study and control groups at follow up. Between days 45 to 225, the mean score was -0.95 (SD 0.19) for the allopurinol group (seven men), compared with -0.47 (SD 0.21) for the placebo group (seven men). The weighted mean difference (WMD) was -0.48 (95% CI -0.690 to -0.270). The mean score between days 45-135 was -1.08 (SD 1.29) for the 25 men in the allopurinol group, compared with -0.21 (SD 0.97) for the 14 men in the control group. The WMD was -0.87 (95%CI -1.587 to -0.153). The allopurinol group had significantly less investigator graded prostate pain and had lower levels of serum urate, urine urate, and expressed prostatic secretion urate and xanthine. No significant differences between the two groups regarding leukocyte counts were found. No patient receiving allopurinol had any significant side effects. Three patients in the placebo group dropped out because of side effects. Authors' conclusions One small trial of allopurinol for treating chronic prostatitis showed improvements in patient-reported symptom improvement, investigator-graded prostate pain, and biochemical parameters. However, the data provided, the measures used, and the statistics presented do not make these findings convincing that changes in urine and prostatic secretion composition regarding purine and pyrimidine bases resulted in the relief of symptoms. Further studies of allopurinol treatment using standardized and validated outcomes measures and analyses are necessary to determine whether allopurinol is effective.

Treatment options for benign prostatic hyperplasia: Choice depends on patient's weighting of severity and bother, with risks and benefits of various options

Abstract: Papers p 1059 Lower urinary tract symptoms consistent with benign prostatic hyperplasia become increasingly prevalent with age. While rarely life threatening, bothersome irritative urinary symptoms like urgency, frequency, and nocturia, and obstructive ones like a weak stream, hesitancy, intermittency, and incomplete emptying occur in up to 70% of men aged 70 years and older. Community and practice based studies suggest that men can expect slow progression of the symptoms. However, these symptoms can wax and wane without treatment, and rates of acute urinary retention range from 1-2% per year.1 By the age of 80 years, an estimated one in four men will have undergone treatment to relieve symptoms due to benign prostatic hyperplasia that reduce quality of life.2 Treatment options depend, in part, on the severity of symptoms and how bothersome they are. Options include watchful waiting (conservative or lifestyle management), phytotherapies, prescription medications, surgical procedures, and minimally invasive techniques. To help choose between treatments patients and providers rely on evidence from randomised controlled trials and systematic reviews to provide reliable information about efficacy and safety of various treatments. For many years, transurethral resection of the prostate has been the gold standard treatment for benign prostatic hyperplasia. In 1994, almost 400 000 procedures were performed in the United States at a total cost of $5 billion.3 In the United Kingdom approximately 40 000 resections are carried out annually.4 …