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Context: Although a quarter of US women undergo elective hysterectomy before menopause, controlled trials that evaluate the benefits and harms are lacking., Objective: To compare the effect of hysterectomy vs expanded medical treatment on health-related quality of life., Design, Setting, and Participants: A multicenter, randomized controlled trial (August 1997-December 2000) of 63 premenopausal women, aged 30 to 50 years, with abnormal uterine bleeding for a median of 4 years who were dissatisfied with medical treatments, including medroxyprogesterone acetate. The participants, who were patients at gynecology clinics and affiliated practices of 4 US academic medical centers, were followed up for 2 years., Interventions: Participants were randomly assigned to undergo hysterectomy or expanded medical treatment with estrogen and/or progesterone and/or a prostaglandin synthetase inhibitor. The hysterectomy route and medical regimen were determined by the participating gynecologist., Main Outcome Measures: The primary outcome was mental health measured by the Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36). Secondary outcomes included physical health measured by the Physical Component Summary (PCS), symptom resolution and satisfaction, body image, and sexual functioning, as well as other aspects of mental health and general health perceptions., Results: At 6 months, women in the hysterectomy group had greater improvement in MCS scores than women in the medicine group (8 vs 2, P =.04). They also had greater improvement in symptom resolution (75 vs 29, P<.001), symptom satisfaction (44 vs 7, P<.001), interference with sex (41 vs 22, P =.003), sexual desire (21 vs 3, P =.01), health distress (33 vs 13, P =.009), sleep problems (13 vs 1, P =.03), overall health (12 vs 2, P =.006), and satisfaction with health (31 vs 14, P =.01). By the end of the study, 17 (53%) of the women in the medicine group had requested and received hysterectomy, and these women reported improvements in quality-of-life outcomes during the 2 years that were similar to those reported by women randomized to the hysterectomy group. Women who continued medical treatment also reported some improvements (P<.001 for within-group change in many outcomes), with the result that most differences between randomized groups at the end of the study were no longer statistically significant in the intention-to-treat analysis., Conclusions: Among women with abnormal uterine bleeding and dissatisfaction with medroxyprogesterone, hysterectomy was superior to expanded medical treatment for improving health-related quality-of-life after 6 months. With longer follow-up, half the women randomized to medicine elected to undergo hysterectomy, with similar and lasting quality-of-life improvements; those who continued medical treatment also reported some improvements.

Context: In recent years, new commercial aircraft have been designed to recirculate approximately 50% of the cabin air to increase fuel efficiency. Some older aircraft use only fresh air. Whether air recirculation increases the transmission of infectious disease is unknown; some studies have demonstrated higher rates of the common cold among persons working in buildings that recirculate air., Objective: To evaluate the role of air recirculation as a predictor of postflight upper respiratory tract infections (URIs)., Design, Setting, and Participants: A natural experiment conducted among 1100 passengers departing the San Francisco Bay area in California and traveling to Denver, Colo, during January through early April 1999, and who completed a questionnaire in the boarding area and a follow-up telephone interview 5 to 7 days later. Forty-seven percent traveled aboard airplanes using 100% fresh air for ventilation, and 53% traveled aboard aircraft that recirculated cabin air., Main Outcome Measure: Incidence of reporting new URI symptoms within 1 week of the flight., Results: Passengers on airplanes that did and did not recirculate air had similar rates of postflight respiratory symptoms. The rates of reporting a cold were 19% vs 21% (P =.34); a runny nose and a cold, 10% vs 11%, (P =.70); and an aggregation of 8 URI symptoms, 3% in both groups (P>.99). Results were similar after statistical adjustment for potential confounders., Conclusion: We found no evidence that aircraft cabin air recirculation increases the risk for URI symptoms in passengers traveling aboard commercial jets.

Context: Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for coronary heart disease (CHD) events. However, few data exist on the clinical importance of Lp(a) lowering for CHD prevention. Hormone therapy with estrogen has been found to lower Lp(a) levels in women., Objective: To determine the relationships among treatment with estrogen and progestin, serum Lp(a) levels, and subsequent CHD events in postmenopausal women., Design and Setting: The Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled secondary prevention trial conducted from January 1993 through July 1998 with a mean follow-up of 4.1 years at 20 centers., Participants: A total of 2763 postmenopausal women younger than 80 years with coronary artery disease and an intact uterus. Mean age was 66.7 years., Intervention: Participants were randomly assigned to receive either conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in 1 tablet daily (n = 1380), or identical placebo (n = 1383)., Main Outcome Measures: Lipoprotein(a) levels and CHD events (nonfatal myocardial infarction and CHD death)., Results: Increased baseline Lp(a) levels were associated with subsequent CHD events among women in the placebo arm. After multivariate adjustment, women in the second, third, and fourth quartiles of baseline Lp(a) level had relative hazards (RHs) (compared with the first quartile) of 1.01 (95% confidence interval [CI], 0.64-1.59), 1.31 (95% CI, 0.85-2.04), and 1.54 (95% CI, 0.99-2.39), respectively, compared with women in the lowest quartile (P for trend = .03). Treatment with estrogen and progestin reduced mean (SD) Lp(a) levels significantly (-5.8 [15] mg/dL) (-0.20 [0.53] micromol/L) compared with placebo (0.3 [17] mg/dL) (0.01 [0.60] micromol/L) (P<.001). In a randomized subgroup comparison, women with low baseline Lp(a) levels had less benefit from estrogen and progestin than women with high Lp(a) levels; the RH for women assigned to estrogen and progestin compared with placebo were 1.49 (95% CI, 0.97-2.26) in the lowest quartile and 1.05 (95% CI, 0.67-1.65), 0.78 (0.52-1.18), and 0.85 (0.58-1.25) in the second, third, and fourth quartiles, respectively (P for interaction trend = .03)., Conclusions: Our data suggest that Lp(a) is an independent risk factor for recurrent CHD in postmenopausal women and that treatment with estrogen and progestin lowers Lp(a) levels. Estrogen and progestin therapy appears to have a more favorable effect (relative to placebo) in women with high initial Lp(a) levels than in women with low levels. This apparent interaction needs confirmation in other trials.

Objective: To review the findings and implications of studies of rodent carcinogenicity of lipid-lowering drugs., Data Sources: Summaries of carcinogenicity studies published in the 1992 and 1994 Physicians' Desk Reference (PDR), additional information obtained from the US Food and Drug Administration, and published articles identified by computer searching, bibliographies, and consultation with experts., Study Sample: We tabulated rodent carcinogenicity data from the 1994 PDR for all drugs listed as "hypolipidemics." For comparison, we selected a stratified random sample of antihypertensive drugs. We also reviewed methods and interpretation of carcinogenicity studies in rodents and results of clinical trials in humans., Data Synthesis: All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans. In contrast, few of the antihypertensive drugs have been found to be carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up., Conclusions: Extrapolation of this evidence of carcinogenesis from rodents to humans is an uncertain process. Longer-term clinical trials and careful postmarketing surveillance during the next several decades are needed to determine whether cholesterol-lowering drugs cause cancer in humans. In the meantime, the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.

Objective: To measure the prevalence of human immunodeficiency virus (HIV) infection and high-risk behaviors among heterosexuals in alcohol treatment., Design: Cross-sectional survey., Setting: Five public alcohol treatment centers., Subjects: Consecutive sample of 888 heterosexual clients entering treatment between October 1990 and December 1991. Respondents were 51% black, 10% Hispanic, 33% white, and 76% male. The overall response rate was 68%., Measurements: Structured interview and serotesting for HIV antibodies., Results: The overall seroprevalence of HIV infection was 5% (95% confidence interval, 3% to 6%). There were no significant differences in rates of infection by age, gender, or race. The prevalence of infection in heterosexual respondents without a history of injection drug use was 3% in men and 4% in women, several times higher than published estimates from a similar community-based heterosexual sample. Unsafe sexual practices were common: 54% of respondents reported multiple sexual partners in the previous year, 97% of nonmonogamous respondents did not use condoms during all sexual encounters, and few respondents consistently asked new sexual partners about previous high-risk behaviors., Conclusions: There is a substantial prevalence of HIV infection among heterosexual clients in San Francisco (Calif) alcohol treatment programs, much of which is not associated with injection drug use. Because of this and the high prevalence of unsafe sexual behaviors, there is a relatively high likelihood of heterosexual spread of HIV among the large population of clients seeking treatment for alcohol dependency. Interventions to prevent HIV spread should become a standard part of alcohol treatment programs.

Objective: To evaluate the relationship of the ankle/arm blood pressure index to short-term mortality in women 65 years of age or older., Design: Prospective cohort study with average follow-up of 4.3 years., Setting: Rural community near Pittsburgh, Pa., Participants: A total of 1492 white women 65 years of age or older, living in the community and ambulatory without the help of another person., Outcome Measures: All-cause and cause-specific mortality., Results: The ankle/arm index (the systolic pressure in the posterior tibial artery divided by that in the brachial artery) was measured in 1986 through 1988 and found to be 0.9 or less in 82 (5.5%) of the women, 67 of whom reported no symptoms of claudication. Comparing women with an index of 0.9 or less with those with an index greater than 0.9, the relative risk for all-cause mortality 4 years later (after adjustment for age, smoking, and other risk factors) was 3.1 (95% confidence interval [Cl], 1.7 to 5.5); for heart disease, 3.7 (95% Cl, 1.2 to 11.6); for cardiovascular diseases, 4.0 (95% Cl, 1.3 to 8.5); for cancer, 3.3 (95% Cl, 1.3 to 8.5); and for all other causes, 1.1 (95% Cl, 0.1 to 9.2). Similar levels of risk were found after excluding women with symptoms of claudication and/or a history of cardiovascular disease at baseline., Conclusions: Healthy, older women with an ankle/arm index of 0.9 or less are at high risk of death and therefore may be considered for aggressive therapy to modify cardiovascular risk factors.

Should we measure blood cholesterol levels in all adults, or only in those at high risk of coronary heart disease (CHD)? Most men under the age of 35 years and women under the age of 45 years--roughly half the adult population--are at very low short-term risk of CHD. One consequence is that drug treatment to lower high blood cholesterol levels in the average young adult is an extremely expensive means of prolonging life; the estimated $1 million to $10 million per year of life is 100 to 1000 times the cost of other approaches. Individualized dietary treatment is somewhat cheaper but relatively ineffective. Another consequence of the low CHD risk in young adults is the greater likelihood that intervention may have harmful effects that outweight the benefits. Meta-analysis of primary prevention trials in middle-aged men reveal an increase in non-CHD deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths. This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death. We conclude that the policy of screening and treating high blood cholesterol levels in young adults is neither cost-effective, nor does it satisfy ethical standards requiring strong evidence that preventive interventions do more good than harm. Fortunately, cholesterol screening in young adults is also not necessary: most CHD events associated with high blood cholesterol levels in this population will not occur for decades and can be prevented by treatment that is begun in middle age. Cholesterol screening and treatment in young adults should be limited to individuals with known coronary disease or other unusual factors that place them at high short-term risk of CHD death.

Objective: To examine the extent and correlates of infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in an inner-city community, we studied the prevalence of antibodies to these viruses and their association with risk behaviors in a representative sample of unmarried white, black, and Hispanic adults living in San Francisco, Calif., Design: Cross-sectional, community-based, random household survey., Participants: In 1988 and 1989, we surveyed 1770 unmarried men and women aged 20 to 44 years from three San Francisco neighborhoods of varying geographic and cultural characteristics., Main Outcome Measures: HSV-1 and HSV-2 antibodies based on an immunodot assay using type-specific glycoproteins gG-1 and gG-2., Results: Of blood samples from 1212 participants available for testing, 750 (62%) had HSV-1 antibodies and 400 (33%) had HSV-2 antibodies. After controlling for other variables, HSV-1 antibody was significantly correlated (P less than .05) with older age (in heterosexual men, women, and homosexually active men), less education (in heterosexual men and women), and Hispanic (especially those not born in the United States) or black race. HSV-2 antibody was significantly correlated (P less than .05) with female gender, number of lifetime sexual partners and older age (in heterosexual men and women), and low levels of education and black or Hispanic race (in women). Among those with antibody to HSV-2, only 28 (19%) of 149 men and 32 (13%) of 251 women reported a history of genital herpes. However, most men (62%) and women (84%) who reported a history of genital herpes had HSV-2 antibodies. We observed a similar pattern (low sensitivity and moderate specificity) for a history of facial herpes and the presence of HSV-1 antibodies. After controlling for other variables, HSV-2 antibodies were associated with a lower frequency of HSV-1 antibodies among homosexual men infected with the human immunodeficiency virus., Conclusions: HSV-1 antibodies were found in nearly two thirds of single urban adults and were most common among Hispanics not born in the United States. HSV-2 antibodies were found in one third of this population and were associated with risk behaviors for sexually transmitted diseases. For both facial and genital herpes infections, self-reporting of infection was very insensitive and moderately specific.

Objective: To investigate the patterns of electrolyte abnormalities resulting from thiazide administration and whether they cause ventricular arrhythmias, and to help resolve the controversy over whether clinicians should routinely prescribe potassium-conserving therapy to all patients treated with thiazides., Design: Double-blind, randomized controlled trial., Participants: A total of 233 hypertensive men aged 35 to 70 years., Interventions: Participants were withdrawn from prior diuretic treatment and were replenished with oral potassium chloride and magnesium oxide. They were then randomized to 2 months of treatment with (1) hydrochlorothiazide; (2) hydrochlorothiazide with oral potassium; (3) hydrochlorothiazide with oral potassium and magnesium; (4) hydrochlorothiazide and triamterene; (5) chlorthalidone; or (6) placebo., Main Outcome Measures: Ventricular arrhythmias on 24-hour Holter monitoring and serum and intracellular potassium and magnesium levels., Results: Of the 233 participants, 212 (91%) completed the study. Serum potassium levels were 0.4 mmol/L lower in the hydrochlorothiazide group than in the placebo group (P less than 0.01), and this mean difference was not affected by supplementation with potassium, with potassium and magnesium, or with triamterene. However, the supplements did prevent the occasional occurrence of marked hypokalemia; all 12 of the men who developed serum potassium levels of 3.0 mmol/L or less were among the 90 who received diuretics without supplementation (P less than 0.01). Similarly, the overall proportion of men with ventricular arrhythmias was not affected by randomized treatment, but there was a twofold increase in the proportion with arrhythmias among the 12 men with serum potassium levels of 3.0 mmol/L or less (P = .02). Serum magnesium and intracellular potassium and magnesium levels were not reduced by hydrochlorothiazide, nor were they related to ventricular arrhythmias., Conclusions: In the majority of hypertensive patients, treatment with 50 mg/d of hydrochlorothiazide does not cause marked hypokalemia or ventricular arrhythmias. However, because some individuals will develop hypokalemia after starting diuretic therapy, serum potassium levels should be monitored and potassium-sparing strategies should be used when indicated.

Because some authorities have proposed blood cholesterol screening for children to prevent coronary heart disease, we reviewed published studies to estimate the potential risks and benefits of such screening. Childhood cholesterol levels are a poor predictor of high cholesterol levels in young adulthood and will be an even poorer predictor of coronary heart disease later in life. There is no evidence that blood cholesterol levels can be lowered more easily in children than in adults, and it seems unlikely that cholesterol reduction in childhood will be much more effective at preventing coronary heart disease than cholesterol reduction begun in middle age. Screening and interventions to lower blood cholesterol levels for millions of children would be expensive, could lead to labeling and family conflicts, and may cause malnutrition and increased noncardiovascular mortality. Because the benefits of cholesterol screening are unlikely to exceed these risks, we conclude that children should not be screened for high blood cholesterol levels.

Determinants of circulating high density lipoproteins (HDL) were sought in 301 men studied during a year of participation in a coronary prevention program. Mean plasma HDL-cholesterol concentration rose by 2.8 mg/dl (6%) in the group receiving multifactor intervention, but the change did not differ significantly from that in the comparison group. Larger changes in both directions were seen in many individuals. Multiple regression analysis of these changes indicates that increased plasma HDL levels occur when plasma triglyceride level is decreased, cigarette smoking is reduced, and habitual alcohol intake is increased. Increases in the concentration of HDL-cholesterol also tended to accompany adherence to the fat-controlled diet, reduction in LDL-cholesterol level, and loss of body weight. Conventional coronary prevention programs are unlikely to have an adverse influence on this new, risk-lowering factor.

The hospital records for all patients (N = 131) admitted during 1984 to San Francisco General Hospital because of firearm injuries were studied to determine the hospital costs and sources of payment for these injuries. Because San Francisco General Hospital is the regional trauma center, the sample is population based, representing all firearm victims hospitalized in San Francisco during 1984. Only hospital costs (excluding professional fees) for the first hospitalization were studied. The total costs for the year were $905,809, an average cost per patient of $6915. Public sources paid 85.6% of this cost, while private sources paid only 14.4%. These findings have important implications for legislators considering bills to restrict the availability of firearms. These legislators must be aware that the issue is not simply one of individual rights, since taxpayers pay most of the costs (estimated to be more than $1 billion per year for the United States) associated with firearm injuries.

Are patients concerned about going to a physician who is infected with human immunodeficiency virus (HIV) or one who is treating HIV-infected patients? To answer these questions, we surveyed a nationwide sample of 2000 interviews (response rate, 75%). Forty-five percent of all respondents believed that physicians who were HIV infected should not be allowed to continue to practice. More than half of those who had seen a physician in the past 5 years said they would change physicians if they knew their physician were HIV infected, while one fourth said they would seek care elsewhere if their physician were treating people with HIV disease. These data suggest that patients are concerned about HIV in their physicians' offices. The American Medical Association recommends that HIV-infected physicians continue to practice as long as there is no risk to their patients. Physicians and the public need to be educated about this policy and its appropriateness.

Several prospective studies have demonstrated an association between low serum cholesterol level and subsequent mortality from cancer. This finding was explored in the large cohort (361,662) of men aged 35 to 57 years who were screened for possible randomization to the Multiple Risk Factor Intervention Trial. Mortality follow-up revealed a significant excess of cancer in the lowest decile of serum cholesterol level during the early years of follow-up, which attenuated over time. In contrast, the association between high serum cholesterol and coronary heart disease did not diminish during the average of seven years of follow-up. These findings are consistent with the inference that the association between low serum cholesterol level and cancer is at least in part due to an effect of preclinical cancer on serum cholesterol level. A subset of the cohort (12,866 men) participated in the randomized Multiple Risk Factor Intervention Trial protocol, which called for annual measurements of serum cholesterol level. Among the 150 of these men who died of cancer during the trial, cholesterol level fell 22.7 mg/dL (0.59 mmol/L) more than in the survivors over an equivalent period. These data are consistent with the foregoing inference.