Patrick Y. Lee

CONTEXT: Elderly persons and women were underrepresented in randomized controlled trials (RCTs) prior to 1990. Since then, efforts have been made to correct these biases, but their effect is unclear. OBJECTIVE: To determine whether the percentage of elderly persons and women in published clinical trials of acute coronary syndromes has increased and how this enrollment compared with disease prevalence. DATA SOURCES: The MEDLINE and Cochrane databases were searched for English-language articles from January 1966 to March 2000 regarding myocardial infarction, unstable angina, or acute coronary syndromes. Additional data sources included meta-analyses, review articles, and cardiology textbooks. Estimates of community-based myocardial infarction rates came from the National Registry of Myocardial Infarction and the Worcester Heart Study. STUDY SELECTION: Published RCTs of acute coronary syndrome patients were included and trials enrolling 50 patients or fewer, those without clinical end points, papers published in a language other than English, and unpublished manuscripts were excluded. Of 7645 studies identified, 593 RCTs were selected for review. DATA EXTRACTION: The RCTs were abstracted by 2 of the authors for year of publication, source of support (ie, funding), pharmacotherapy, study phase, number of study sites, trial location, number of patients, mean age of the study population, and any age exclusion criteria for enrollment. DATA SYNTHESIS: The number of published RCTs with explicit age exclusions has declined from 58% during 1966-1990 to 40% during 1991-2000. Trial enrollment of patients aged 75 years or older increased from 2% for studies published during 1966-1990 to 9% during 1991-2000, but remains well below their representation among all patients with myocardial infarction (37%) in the United States. Enrollment of women has risen from 20% for studies published between 1966-1990 to 25% during 1991-2000, but remains well below their proportion of all patients with myocardial infarction (43%) in the United States. CONCLUSIONS: Attempts at making cardiovascular RCTs more inclusive appear to have had limited success; thus, women and elderly persons remain underrepresented in published trial literature relative to their disease prevalence. Because safety and efficacy can vary as a function of sex and age, these enrollment biases undermine efforts to provide evidence-based care to all cardiac patients.

BACKGROUND: Physicians have several treatment options for influenza, including vaccination and various antiviral therapies. However, the optimal influenza prevention and treatment strategy is unknown. OBJECTIVE: To compare the relative health values of contemporary treatment strategies for influenza in a healthy sample of working adults. DESIGN: Cost-benefit analysis using a decision model. DATA SOURCES: Previously published data. TARGET POPULATION: Healthy employed adults 18 to 50 years of age. TIME HORIZON: A complete influenza season. PERSPECTIVE: Societal. INTERVENTIONS: Eight treatment options (yes or no) based on the possible combinations of vaccination and antiviral therapy (rimantadine, oseltamivir, or zanamivir or no treatment) should infection develop. OUTCOME MEASURES: Cost in U.S. dollars, including the value of symptom relief and medication side effects, which was assigned a monetary value through a conjoint analysis that used a "willingness-to-pay" approach. RESULTS: In the base-case analysis, all strategies for influenza vaccination had a higher net benefit than the nonvaccination strategies. Vaccination and use of rimantadine, the most cost-beneficial strategy, was $30.97 more cost-beneficial than nonvaccination and no use of antiviral medication. The health benefits of most antiviral treatments equaled or exceeded their costs for most scenarios. The choice of the most cost-beneficial antiviral strategy was sensitive to the prevalence of influenza B and to the comparative workdays gained by each antiviral therapy. CONCLUSIONS: Vaccination is cost-beneficial in most influenza seasons in healthy working adults. Although the benefits of antiviral therapy for persons with influenza infection appear to justify its cost, head-to-head trials of the various antiviral therapies are needed to determine the optimal treatment strategy.

UNLABELLED: Vaginal fistula (VF) is a devastating complication following restorative proctocolectomy. PURPOSE: This study was designed to examine the perioperative factors influencing the outcome and management of vaginal fistula. METHOD: Between October 1983 and September 1994, 526 women underwent restorative proctocolectomy. Nineteen develop VF (3.6 percent), and six were referred from other institutions with this complication. These 25 women were followed for a minimum of nine months. RESULTS: Preoperative diagnosis of ulcerative colitis was made in 23 of the patients with VF (92 percent), and indeterminate colitis and familial adenomatous polyposis was determined in the rest of the patients. Postoperatively, 12 of the 23 women (52 percent) with a preoperative diagnosis of ulcerative colitis had clinical/pathologic findings of Crohn's disease, and 1 woman was reclassified as having indeterminate colitis. Postoperative pelvic sepsis was significantly higher in women with VF than in those without VF (26.3 vs. 6.3 percent; P = 0.003). Median time until occurrence of VF following loop ileostomy closure was later for women with delayed findings of Crohn's disease at 16.5 (range, <1-72) months, compared with women without Crohn's disease at 0.5 (range, <1-67) months (P < 0.05). Of the 163 women with handsewn anastomosis performed at our institution, 12 developed VF (7.4 percent). In contrast, 7 of the 363 patients with stapled anastomosis had VF (1.9 percent; P = 0.003). Site of VF was found at the anastomosis in 12 patients, below in 12 patients, and above in 1 patient. Presence of Crohn's disease and anastomotic technique did not influence the site of VF. Initial management of VF consisted of transanal repair in 20 patients (advancement flap, 12; direct repair, 6; and neoileoanal anastomosis, 2), seton in 1 patient, transabdominal approach in 1 patient, transvaginal in 1 patient, observation in 1 patient, and pouch excision in 1 patient. Of the 13 women without Crohn's disease, 12 had transanal repair (10 healed, 1 had recurrence, and 1 had pouch excision), and 1 had successfully repair with transabdominal technique, for an overall success rate of 84.6 percent. Of the 12 women with VF and delayed findings of Crohn's disease, transanal repair was performed on 9, 1 had pouch excision without repair, 1 had seton placement and pouch excision, and 1 underwent observation. Transanal technique of repair in women with Crohn's disease successfully healed three women (33.3 percent). Overall, of the 12 women with delayed findings of Crohn's disease, 6 had pouch excision, 3 had recurrences, and 3 healed. CONCLUSION: VF is an uncommon complication following restorative proctocolectomy and is associated with a high incidence of pelvic sepsis and handsewn anastomosis. Late presentation of VF is more common with Crohn's disease and is associated with a poor prognosis and pouch salvage rate. Transanal techniques are an effective means of VF repair.