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Spontaneous reporting systems like MEDWATCH can be effective in revealing unusual or rare adverse events that occur with the use of medications, and such reports may often be sufficient to assign causality. However, spontaneous reports do not reliably detect adverse drug reactions (ADRs) that occur widely separated in time from the original use of the drug or that represent an increased risk of an adverse event that occurs commonly in populations not exposed to the drug. In these situations, spontaneous reports alone do not provide sufficient evidence to conclude that the adverse event was an ADR. Identification of ADRs associated with long-term administration of drugs for chronic diseases also remains problematic. Methods to evaluate ADRs using data from clinical trials, medical records, and computerized databases of medication users and nonusers must be developed to complement spontaneous reporting systems. Without these methods, potentially important ADRs will remain undetected, and spurious associations between adverse outcomes and medications or devices will remain unchallenged. [ABSTRACT FROM AUTHOR]

Context: Although many studies suggest that physical activity may reduce risk of type 2 diabetes, the role of moderate-intensity activity such as walking is not well understood.Objectives: To examine the relationship of total physical activity and incidence of type 2 diabetes in women and to compare the benefits of walking vs vigorous activity as predictors of subsequent risk of type 2 diabetes.Design and Setting: The Nurses' Health Study, a prospective cohort study that included detailed data for physical activity from women surveyed in 11 US states in 1986, with updates in 1988 and 1992.Participants: A total of 70,102 female nurses aged 40 to 65 years who did not have diabetes, cardiovascular disease, or cancer at baseline (1986).Main Outcome Measure: Risk of type 2 diabetes by quintile of metabolic equivalent task (MET) score, based on time spent per week on each of 8 common physical activities, including walking.Results: During 8 years of follow-up (534, 928 person-years), we documented 1419 incident cases of type 2 diabetes. After adjusting for age, smoking, alcohol use, history of hypertension, history of high cholesterol level, and other covariates, the relative risks (RRs) of developing type 2 diabetes across quintiles of physical activity (least to most) were 1.0, 0.77, 0.75, 0.62, and 0.54 (P for trend <.001); after adjusting for body mass index (BMI), RRs were 1.0, 0.84, 0.87, 0.77, and 0.74 (P for trend = .002). Among women who did not perform vigorous activity, multivariate RRs of type 2 diabetes across quintiles of MET score for walking were 1.0, 0.91,0.73, 0.69, and 0.58 (P for trend <.001). After adjusting for BMI, the trend remained statistically significant (RRs were 1.0, 0.95, 0.80, 0.81, 0.74; P for trend = .01). Faster usual walking pace was independently associated with decreased risk. Equivalent energy expenditures from walking and vigorous activity resulted in comparable magnitudes of risk reduction.Conclusions: Our data suggest that greater physical activity level is associated with substantial reduction in risk of type 2 diabetes, including physical activity of moderate intensity and duration. [ABSTRACT FROM AUTHOR]

Context: Coffee has several metabolic effects that could reduce the risk of gallstone formation.Objective: To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men.Design and Setting: The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996.Participants: A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease.Main Outcome Measures: Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy.Results: During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk.Conclusions: In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease. [ABSTRACT FROM AUTHOR]

Context: Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse.Objective: To examine the association between egg consumption and risk of CHD and stroke in men and women.Design and Setting: Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994).Participants: A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer.Main Outcome Measures: Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire.Results: We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and > or =1 per day (1.08) (P for trend = .75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and > or =1 per day (0.82) (P for trend = .95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend = .04], and among diabetic women, 1.49 [0.88-2.52; P for trend = .008]).Conclusions: These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research. [ABSTRACT FROM AUTHOR]

Synthesis of research findings has a long-standing tradition in science. While synthesis is currently required in the US food and drug regulatory process, formal meta-analysis may substitute for a pivotal study or broaden the generalizability of drug efficacy through a preplanned meta-analysis. Preplanned meta-analysis of individual trials with deliberately introduced heterogeneity may maximize the generalizability of results from randomized trials. Combining observational data may help to support an alternative claim or to quantify adverse events. In this setting, methods to address potentially greater sources of bias are required. Overall, meta-analysis adds evidence through the synthesis study findings and permits examination of how treatment effects vary across of subgroups, such as age and sex, and across study settings. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the association of physical activity, television program viewing and other forms of video viewing with the prevalence of obesity among school children. DESIGN: Cross-sectional study. SUBJECTS: 712 children, 9-16y old, from a Iow- and a middle-income town in the Mexico City area. MEASUREMENTS: Children completed a self administered questionnaire to assess time spent in physical activity and television viewing, and diet. Height weight and triceps skinfolds were measured. The outcome variable was obesity, and the covariates were hours of television programs and other video viewing, physical activity, energy intake, percentage of energy from fat, town of location of school, age, gender and perception of mother's weight status. RESULTS: Among 461 children with complete information, 24% were classified as obese. Children reported an average of 4.1 ± 2.2 h/d watching television (2.4 ± 1.5 h/d for TV programs and 1.7 ± 1.5 h/d for video cassette recorder (VCR) or videogames), and 1.8 ± 1.3 h/d in moderate and vigorous physical activities. Odds ratios (OR) of obesity were 12% higher for each hour of television program viewing per day (OR = 1.12, 95% confidence interval (CI) 1.02, -1.22), and 10% lower for each hour of moderate/vigorous physical activity per day (OR = 0.90, 95% CI 0.83-0:98), controlling for age, gender, town and perception of mother's weight status. Children in the middle-income town had higher adjusted odds of obesity (OR = 2.58, 95% CI 1.47-4.54). CONCLUSION: Physical activity and television viewing, but not VCR/videogames use, were related to obesity prevalence in Mexican children 9-16yold. [ABSTRACT FROM AUTHOR]

Physical function is a significant component of health-related quality of life among older adults. Potential correlates of healthy aging, including health behaviors and social network characteristics, were examined among 56,436 US women aged 55-72 in 1992. Healthy aging was assessed by maintenance of physical function measured by four subscales of the Medical Outcomes Study Short Form (SF)-36 Health Survey: physical functioning; role limitations; freedom from bodily pain; and vitality. Individual health behaviors, defined as current smoking, alcohol consumption, sedentary behavior, and being overweight each contributed to significant decrements in functioning across all age-groups. After controlling for these health behaviors and other confounders (age, race, education, and co-morbid conditions), elements of a woman's social network were significantly correlated with functional status. Strong predictors of high functioning among older women were having close friends and relatives and presence of a confidant. For example, the absence of a confidant was associated with a 4.44 point reduction in physical functioning (95% CI: -7.0, -1.9), and a 5.68 point reduction in vitality (95% CI: -7.9, -3.4). These effects were comparable in magnitude to those observed among heavy smokers, or women in the highest category of body mass index. [ABSTRACT FROM AUTHOR]

We examined relative weight and height in relation to subsequent breast cancer risk among 115,534 women 30 to 55 years of age and free from cancer in 1976. By 1984, six hundred fifty-eight premenopausal and 420 postmenopausal breast cancers were documented during 734,716 person-years. Among premenopausal women, risk of breast cancer decreased significantly with increasing relative weight (relative risk for the highest category was 0.6). A similar inverse association was seen for recalled relative weight at 18 years of age. Postmenopausal breast cancer was not associated with relative weight, either recent or at age 18. Height was not associated with breast cancer risk among premenopausal women and only weakly related among postmenopausal women. These data suggest that obesity among premenopausal and early postmenopausal women does not increase breast cancer risk substantially. [ABSTRACT FROM AUTHOR]

Objective: To determine whether published cost-effectiveness and cost-benefit analyses have adhered to basic analytic principles.Design: Structured methodologic review of published articles.Study Sample: Seventy-seven articles published either from 1978 to 1980 or from 1985 to 1987 in general medical, general surgical, and medical subspecialty journals.Main Outcome Measurements: Articles were reviewed to assess the use and reporting of six fundamental principles of analysis. These principles were derived by reviewing widely cited textbooks and articles describing the methods for performing economic analyses and by selecting the methods universally recommended.Main Results: Overall performance was only fair. Three articles adhered to all six principles, and the median number of principles to which articles adhered was three. Among the problems noted were failure to make underlying assumptions explicit and, therefore, verifiable, and failure to test assumptions with sensitivity analyses. No improvement in performance was observed between 1978 and 1987. Articles in general medical journals, however, were more likely to use analytic methods appropriately than articles in the general surgical or medical subspecialty literature.Conclusions: Greater attention should be devoted to ensuring the appropriate use of analytic methods for economic analyses, and readers should make note of the methods used when interpreting the results of economic analyses. [ABSTRACT FROM AUTHOR]

Objective: To prospectively examine the relationship of time since stopping smoking with risk of stroke in middle-aged women.Design: An ongoing prospective cohort of women with 12 years' follow-up data (1976 to 1988), in which information on smoking habits was updated every 2 years by postal questionnaire.Population Studied: A total of 117,006 female registered nurses aged 30 to 55 years in 1976 and free of coronary heart disease, stroke, and cancer at baseline.Main Outcome Measures: Incident strokes (fatal and nonfatal), further subdivided into ischemic stroke, subarachnoid hemorrhage, and cerebral hemorrhage.Results: The age-adjusted relative risk of total stroke among current smokers compared with never smokers was 2.58 (95% confidence interval, 2.08 to 3.19). The corresponding relative risk among former smokers was 1.34 (95% confidence interval, 1.04 to 1.73). For total and ischemic stroke, the excess risks among former smokers largely disappeared from 2 to 4 years after cessation. The same patterns of decline were observed regardless of number of cigarettes smoked, the age at starting, or the presence of other risk factors for stroke.Conclusions: The risk of suffering among cigarette smokers declines soon after cessation and the benefits are independent of the age at starting and the number of cigarettes smoked per day. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to examine prospectively the association between regular aspirin use and the risk of a first myocardial infarction and other cardiovascular events in women.Design: Prospective cohort study including 6 years of follow-up.Setting: Registered nurses residing in 11 US states.Participants: US registered nurses (n = 87,678) aged 34 to 65 years and free of diagnosed coronary heart disease, stroke, and cancer at baseline. Followup was 96.7% of total potential person-years of follow-up.Main Outcome Measures: Incidence of myocardial infarction, stroke, cardiovascular death, and all important vascular events.Results: During 475,265 person-years of follow-up, we documented 240 nonfatal myocardial infarctions, 146 nonfatal strokes, and 130 deaths due to cardiovascular disease (total, 516 important vascular events). Among women who reported taking one through six aspirin per week, the age-adjusted relative risk (RR) of a first myocardial infarction was 0.68 (95% confidence interval [CI], 0.52 to 0.89; P = .005), as compared with those women who took no aspirin. After simultaneous adjustment for risk factors for coronary disease, the RR was 0.75 (95% CI, 0.58 to 0.99; P = .04). For women aged 50 years and older, the age-adjusted RR was 0.61 (95% CI, 0.45 to 0.84; P = .002) and the multivariate RR was 0.68 (95% CI, 0.50 to 0.93; P = .02). We observed no alteration in the risk of stroke (multivariate RR = 0.99; P = .94). The multivariate RR of cardiovascular death was 0.89 (P = .56) and of important vascular events was 0.85 (P = .12). When examined separately, the results were nearly identical for the subgroups who took one through three and four through six aspirin per week. Among women who took seven or more aspirin per week, there were no apparent reductions in risk.Conclusions: The use of one through six aspirin per week appears to be associated with a reduced risk of a first myocardial infarction among women. A randomized trial in women is necessary, however, to provide conclusive data on the role of aspirin in the primary prevention of cardiovascular disease in women. [ABSTRACT FROM AUTHOR]

Persons with diabetes experience elevated risks of a variety of other illnesses-- including circulatory, visual, neurological, renal, and skin disorders--relative to their nondiabetic peers. Previous estimates of the economic burden of diabetes, however, have not taken full account of this related morbidity and mortality and have therefore understated the cost to the nation due to this disease. Accordingly, we estimated the economic costs of type II, or non-insulin-dependent, diabetes mellitus, reflecting its contribution to the total burden of disease in the United States. In 1986, non-insulin-dependent diabetes mellitus was responsible for $11.6 billion in health care expenditures, including $6.8 billion for diabetic care and $4.8 billion attributable to an excess prevalence of related (principally cardiovascular) conditions. The human toll of non-insulin-dependent diabetes mellitus included 144,000 deaths -- about 6.8% of total US mortality -- and the total disability of 951,000 persons. The total economic burden of non-insulin-dependent diabetes mellitus in 1986, including health care expenditures and productivity forgone due to disability and premature mortality, was $19.8 billion. [ABSTRACT FROM AUTHOR]

Background: A positive relationship has generally been observed between plasma estrogen levels and breast cancer risk in postmenopausal women, but most of these studies have been small and few have evaluated specific estrogen fractions (such as percent bioavailable estradiol). In addition, few studies have evaluated plasma androgen levels in relation to breast cancer risk, and their results have been inconsistent. We prospectively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses' Health Study.Methods: Blood samples were collected during the period from 1989 through 1990. Among postmenopausal women not using hormone replacement therapy at blood collection (n = 11,169 women), 156 women were diagnosed with breast cancer after blood collection but before June 1, 1994. Two control subjects were selected per case subject and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at the time of blood collection.Results: From comparisons of highest and lowest (reference) quartiles, we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol (multivariate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06-3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05-3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23-4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11-4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy.Conclusion: Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Family history of breast cancer is an established risk factor for this disease and is used to identify women at higher risk, although the impact of risk factors for breast cancer among women with a family history is not well defined.Purpose: Using a modified extended log-incidence Pike model, we prospectively examined the impact of risk factors for breast cancer among women with and without a family history of the disease.Methods: Data analyzed were obtained prospectively from the Nurses' Health Study. Two thousand two hundred forty-nine incident cases of invasive breast cancer were identified in a cohort of 89,132 women aged 30-55 years in 1976 followed biennially through 1990 (1.1 million person years of follow-up). With the use of proportional hazards models, we evaluated the association between risk factors for breast cancer and risk among women with and those without a family history of the disease. We then fit a modified extended log-incidence Pike model to these data.Results: Among women with a family history of breast cancer, reproductive risk factors has associations that were different from those observed among women without a family history of the disease. In particular, we observed little protection from later age at menarche, no protection from multiple births when compared with nulliparity, nor from early, as compared with later, age at first birth. Fitting these data to a model of breast cancer incidence on the basis of reproductive risk factors, we observed an adverse effect of first pregnancy on risk of breast cancer among women with a family history of breast cancer that was approximately 50% greater in magnitude than among women without a family history. Additional births after the first birth conveyed little protection for women with a family history. History of benign breast disease, past use of oral contraceptives, and use of postmenopausal hormones showed relative risks that did not differ between women with a family history and those without a family history of the disease.Conclusions: We observed a consistent increase in risk of breast cancer among women with a mother or sister history of the disease that was exacerbated by first pregnancy. Among women with a family history of breast cancer, the adverse effect of pregnancy persisted so that to age 70 years, parous women were at higher risk of breast cancer than nulliparous women. Among women without a family history of the disease, first pregnancy was associated with a smaller increase in risk, and early pregnancy and higher number of births were each associated with reduced breast cancer incidence. [ABSTRACT FROM AUTHOR]

Context: Breast cancer is a major cause of mortality among women. It is important to identify modifiable risk factors for this disease.Objective: To examine body mass index (BMI) at the age of 18 years and at midlife and adult weight change in relation to breast cancer incidence and mortality.Design: Cohort study.Setting: A cohort of 95256 US female nurses aged 30 to 55 years who were followed up for 16 years.Main Outcome Measure: Incident and fatal breast cancer.Results: During 1203498 person-years, 2517 incident breast cancers (60% postmenopausal) were documented. Higher current BMI was associated with lower breast cancer incidence before menopause and was minimally associated with incidence after menopause. However, a stronger positive relationship was seen among postmenopausal women who never used hormone replacement (relative risk=1.59 for BMI >31 kg/m2 vs < or = 20 kg/m2; 95% confidence interval, 1.09-2.32; P for trend <.001). Higher BMI at the age of 18 years was associated with lower breast cancer incidence both before and after menopause. Weight gain after the age of 18 years was unrelated to breast cancer incidence before menopause, but was positively associated with incidence after menopause. This increased risk with weight gain was limited to women who never used postmenopausal hormones; among these women, the relative risk was 1.99 (95% confidence interval, 1.43-2.76) for weight gain of more than 20 kg vs unchanged weight (P for trend <.001). Current BMI and weight gain were even more strongly associated with fatal postmenopausal breast cancer. In this population, the percentage of postmenopausal breast cancer accounted for by weight gain alone was approximately 16% and by hormone replacement therapy alone was 5%, but when the interaction between these variables was considered, together they accounted for about one third of postmenopausal breast cancers.Conclusions: Avoiding adult weight gain may contribute importantly to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones. [ABSTRACT FROM AUTHOR]

Objective: To examine prospectively the relationship between glycemic diets, low fiber intake, and risk of non-insulin-dependent diabetes mellitus.Design: Cohort study.Setting: In 1986, a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed dietary questionnaire from which we calculated usual intake of total and specific sources of dietary fiber, dietary glycemic index, and glycemic load.Main Outcome Measure: Non-insulin-dependent diabetes mellitus.Results: During 6 years of follow-up, 915 incident cases of diabetes were documented. The dietary glycemic index was positively associated with risk of diabetes after adjustment for age, body mass index, smoking, physical activity, family history of diabetes, alcohol and cereal fiber intake, and total energy intake. Comparing the highest with the lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a global dietary insulin demand) was also positively associated with diabetes (RR= 1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles (RR=0.72, 95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI, 1.14-5.51) when compared with a low glycemic load and high cereal fiber intake.Conclusions: Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To assess the relationship between coffee consumption and risk of coronary heart disease (CHD) among women. DESIGN--Prospective cohort study with coffee consumption measured in 1980, 1984, and 1986, and follow-up through 1990. SETTING--Female registered nurses in the United States. PARTICIPANTS--A total of 85,747 US women 34 to 59 years of age in 1980 and without history of CHD, stroke, or cancer. MAIN OUTCOME MEASURE--Ten-year incidence of CHD (defined as nonfatal myocardial infarction or fatal CHD). RESULTS--During 10 years of follow-up we documented 712 cases of CHD. After adjustment for age, smoking, and other CHD risk factors, we found no evidence for any positive association between coffee consumption and risk of subsequent CHD. For women drinking six or more cups of caffeine-containing coffee per day in 1980, the relative risk was 0.95 (95% confidence interval, 0.73 to 1.26) compared with women who did not consume this beverage. Similarly, there was no association when the first 4 years of follow-up were excluded, when nonfatal and fatal CHD end points were examined separately, or when we updated coffee consumption in 1984 or 1986 and examined only CHD during the next 2-year interval. Further, there was no association with caffeine intake from all sources combined or with decaffeinated coffee consumption. CONCLUSIONS--These data indicate that coffee as consumed by US women is not an important cause of CHD. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To assess the validity of the 1990 US weight guidelines for women that support a substantial gain in weight at approximately 35 years of age and recommend a range of body mass index (BMI) (defined as weight in kilograms divided by the square of height in meters) from 21 to 27 kg/m2, in terms of coronary heart disease (CHD) risk in women. DESIGN--Prospective cohort study. SETTING--Female registered nurses in the United States. PARTICIPANTS--A total of 115,818 women aged 30 to 55 years in 1976 and without a history of previous CHD. MAIN OUTCOME MEASURE--Incidence of CHD defined as nonfatal myocardial infarction or fatal CHD. RESULTS--During 14 years of follow-up, 1292 cases of CHD were ascertained. After controlling for age, smoking, menopausal status, postmenopausal hormone use, and parental history of CHD and using as a reference women with a BMI of less than 21 kg/m2, relative risks (RRs) and 95% confidence intervals (CIs) for CHD were 1.19 (0.97 to 1.44) for a BMI of 21 to 22.9 kg/m2, 1.46 (1.20 to 1.77) for a BMI of 23 to 24.9 kg/m2, 2.06 (1.72 to 2.48) for a BMI of 25 to 28.9 kg/m2, and 3.56 (2.96 to 4.29) for a BMI of 29 kg/m2 or more. Women who gained weight from 18 years of age were compared with those with stable weight (+/- 5 kg) in analyses that controlled for the same variables as well as BMI at 18 years of age. The RRs and CIs were 1.25 (1.01 to 1.55) for a 5- to 7.9-kg gain, 1.64 (1.33 to 2.04) for an 8- to 10.9-kg gain, 1.92 (1.61 to 2.29) for an 11- to 19-kg gain, and 2.65 (2.17 to 3.22) for a gain of 20 kg or more. Among women with the BMI range of 18 to 25 kg/m2, weight gain after 18 years of age remained a strong predictor of CHD risk. CONCLUSIONS--Higher levels of body weight within the "normal" range, as well as modest weight gains after 18 years of age, appear to increase risks of CHD in middle-aged women. These data provide evidence that current US weight guidelines may be falsely reassuring to the large proportion of women older than 35 years who are within the current guidelines but have potentially avoidable risks of CHD. [ABSTRACT FROM AUTHOR]

Objective: To assess whether tubal ligation and hysterectomy affect subsequent risk of ovarian cancer.Design: Prospective cohort study with 12 years of follow-up.Setting: United States, multistate.Participants: A total of 121,700 female registered nurses who were 30 to 55 years of age in 1976; the follow-up rate was 90% as of 1988.Main Outcome Measure: Ovarian cancer of epithelial origin confirmed by medical record review.Results: We observed a strong inverse association between tubal ligation and ovarian cancer, which persisted after adjustment for age, oral contraceptive use, parity, and other ovarian cancer risk factors (multivariate relative risk [RR], 0.33; 95% confidence interval [CI], 0.16 to 0.64). The association was similar when we assessed tubal ligation status at the baseline questionnaire and excluded cases in the first 4 years to eliminate any possible short-term decrease in risk due to screening of the ovaries during ligation surgery. We noted a weaker inverse association between simple hysterectomy and ovarian cancer (RR, 0.67; 95% CI, 0.45 to 1.00). Neither vasectomy nor condom use by a partner was associated with risk of ovarian cancer.Conclusions: These data indicate that tubal ligation, and perhaps hysterectomy, may substantially reduce risk of epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Study Objective: To compare two strategies for the evaluation and management of patients who have had acute dyspepsia for four days or more: empiric high-dose antacid therapy combined with patient reassurance (empiric care) versus therapy based on prompt upper gastrointestinal radiography (traditional care).Design: Prospective, randomized trial. The patients in the empiric care group were reassured that upper gastrointestinal radiography was not necessary and were subsequently treated with high-dose empiric antacid therapy (15-30 ml of high-potency antacid one and three hours after meals and at bedtime). The traditional care group after meals and at bedtime). The traditional care group received upper gastrointestinal radiography as part of the initial evaluation. Subsequent treatment was determined by individual physicians based on test results.Settings: Fee-for-service, hospital-based primary care practice and Veteran's Administration medical center outpatient clinic.Patients: All patients were less than 70 years of age and without gastrointestinal bleeding, anemia, significant weight loss, or other specified symptoms of severe acid peptic disease. Fifty patients were randomized to traditional care, and 51 to empiric care. Pre-randomization clinical features were identical with the exception of sex distribution and baseline disability.Measurements and Main Results: After six months of follow-up, there were no significant differences in symptom scores, disability, satisfaction, and quality of life measures (as measured by the Sickness Impact Profile scores) between the two groups. Findings were unchanged when adjusted for sex, study site, alcohol consumption, and cigarette smoking. Of the radiographs obtained in the traditional care group, 13 (27%) showed duodenal ulcer disease, gastritis, or duodenitis. There were no serious complications of ulcer disease or therapy noted in either group. The average costs per patient associated with traditional care at one study site were greater, $286 versus $116 (p less than 0.0001).Conclusions: Select patients with dyspepsia receiving a combination of reassurance and empiric antacid therapy do as well as patients whose initial management strategy includes upper gastrointestinal radiography, at a substantially lower cost. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare levels of physical function, across levels of body mass index (BMI), among middle- to older-aged women. DESIGN: Cross-sectional study. Physical function, body weight and other covariates were measured in 1992. SUBJECTS: 56 510 women aged 45–71 y, free of cardiovascular disease and cancer, participating in the Nurses’ Health Study. MAIN OUTCOME MEASURES: The four physical function scores on the Medical Outcomes Study (MOS) Short Form-36 (SF36) Health Survey: physical functioning, vitality, bodily pain and role limitations. RESULTS: After adjusting for age, race, smoking status, menopausal status, physical activity and alcohol consumption, there was a significant dose-response gradient between increasing levels of BMI in 1992 and reduced function. For example, women with a BMI between 30–34.9 kg/m2 averaged: 9.0 point lower physical functioning score (95% Confidence interval (CI) -9.5, -8.5), 5.6 point lower vitality score (95% CI: -6.1, -5.1), and 7.0 point lower freedom from pain score (95% CI: -7.6, -6.4). These declines represent an approximate 10% loss of function compared to the reference category of women with BMIs ranging from 22.0–23.9 kg/m2. For the same BMI comparison, heavier women were at 66% increased risk of limitations in ability to work or perform other roles (RR=1.66; 95% odds ratio (OR) CI: 1.56, 1.76). These findings were replicated when the sample was restricted to women who had maintained their BMI over a ten year period. CONCLUSIONS: In addition to increasing risk of chronic health conditions, greater adiposity is associated with lower every day physical functioning, such as climbing stairs or other moderate activities, as well as lower feelings of well-being and greater burden of pain. [ABSTRACT FROM AUTHOR]

Objectives: To introduce guidelines for the conduct, reporting, and critical appraisal of meta-analyses evaluating diagnostic tests and to apply these guidelines to recently published meta-analyses of diagnostic tests.Data Sources: Based on current concepts of how to assess diagnostic tests and conduct meta-analyses. They are applied to all meta-analyses evaluating diagnostic tests published in English-language journals from January 1990 through December 1991, identified through MEDLINE searching and by experts in the field.Study Selection: Meta-analyses were included if at least two of three independent readers regarded their main purpose as the evaluation of diagnostic tests against a concurrent reference standard.Data Extraction: By three independent readers on the extent to which meta-analyses fulfilled each guideline, with consensus defined as agreement by at least two readers.Data Synthesis: The guidelines are concerned with determining the objective of the meta-analysis, identifying the relevant literature and extracting the data, estimating diagnostic accuracy, and identifying the extent to which variability is explained by study design characteristics and characteristics of the patients and diagnostic test. In general, the guidelines were only partially fulfilled.Conclusion: Meta-analysis is potentially important in the assessment of diagnostic tests. Those reading meta-analyses evaluating diagnostic tests should critically appraise them; those doing meta-analyses should apply recently developed methods. The conduct and reporting of primary studies on which meta-analyses are based require improvement. [ABSTRACT FROM AUTHOR]

Objective: To examine the temporal relationship between stopping smoking and total mortality rates among middle-aged women.Design: Prospective cohort study with 12 years of follow-up.Setting: Registered nurses residing in the United States.Participants: 117,001 female registered nurses, ages 30 to 55 years, who were free of manifest coronary heart disease, stroke, and cancer (except nonmelanoma skin cancer) in 1976.Main Outcome Measures: Total mortality, further categorized into deaths from cardiovascular diseases, cancers, and violent deaths.Results: A total of 2847 deaths (933 among "never smokers," 799 among former smokers, and 1115 among current smokers) occurred during 1.37 million person-years of follow-up. The multivariate relative risks for total mortality compared with never smokers were 1.87 (95% CI, 1.65 to 2.13) for current smokers and 1.29 (CI, 1.14 to 1.46) for former smokers. Participants who started smoking before the age of 15 years had the highest risks for total mortality (multivariate relative risk, 3.15; CI, 2.16 to 4.59), cardiovascular disease mortality (relative risk, 9.94; CI, 5.15 to 19.19), and deaths from external causes of injury (relative risk, 5.39; CI, 1.84 to 15.78). Compared with continuing smokers, former smokers had a 24% reduction in risk for cardiovascular disease mortality within 2 years of quitting. The excess risks for total mortality and both cardiovascular disease and total cancer mortality among former smokers approached the level of that for never smokers after 10 to 14 years of abstinence. The health benefits of cessation were clearly present regardless of the age at starting and daily number of cigarettes smoked.Conclusions: The risk of cigarette smoking on total mortality among former smokers decreases nearly to that of never smokers 10 to 14 years after cessation. [ABSTRACT FROM AUTHOR]

Previous studies have established a relationship between low levels of social networks and total mortality, but few have examined cause specific mortality or disease incidence. This study aimed to examine prospectively the relationships between social networks and total and cause specific mortality, as well as cardiovascular disease incidence. This was a four year follow up study in an ongoing cohort of men, for whom information on social networks was collected at baseline. The main outcome measures were total mortality, further categorised into deaths from cardiovascular disease (stroke and coronary heart disease), total cancer, accidents/suicides, and all other causes; as well as stroke and coronary heart disease incidence. Altogether 32,624 US male health professionals aged 42 to 77 years in 1988, who were free of coronary heart disease, stroke, and cancer at baseline. A total of 511 deaths occurred during 122,911 person years of follow up. Compared with men with the highest level of social networks, socially isolated men (not married, fewer than six friends or relatives, no membership in church or community groups) were at increased risk for cardiovascular disease mortality (age adjusted relative risk, 1.90; 95% CI 1.07, 3.37) and deaths from accidents and suicides (age adjusted relative risk 2.22; 95% CI 0.76, 6.47). No excess risks were found for other causes of death. Socially isolated men were also at increased risk of stroke incidence (relative risk, 2.21; 95% CI, 1.12, 4.35), but not incidence of non-fatal myocardial infarction. Social networks were associated with lower total mortality by reducing deaths from cardiovascular disease and accidents/suicides. Strong social networks were associated with reduced incidence of stroke, though not of coronary heart disease. However, social networks may assist in prolonging the survival of men with established coronary heart disease. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to describe the effect of screening endoscopy (sigmoidoscopy or colonoscopy) on colorectal cancer incidence and mortality.Methods: We used data from a prospective cohort study of 24,744 men aged 40 to 75 years in 1986, free from cancer and colon polyps, followed until 1994. The outcomes are diagnosis of colorectal cancer and death from colorectal cancer.Results: Screening endoscopy in 1986-87 was associated with a lower risk of all colorectal cancer (multivariate relative risk [RR] = 0.58, 95 percent confidence interval [CI] = 0.36-0.96); cancer in the distal colon or rectum (multivariate RR = 0.40, CI = 0.19-0.84); Dukes stage A&B (multivariate RR = 0.66, CI = 0.35-1.25); and Dukes stage C&D (multivariate RR = 0.50, CI = 0.20-1.26) colorectal cancer; and death from colorectal cancer (multivariate RR = 0.56, CI = 0.20-1.60), after adjusting for age and a wide range of colon cancer risk factors. Screening endoscopy in 1988-87 appeared to provide strong protection against distal stage C&D cancers (age-adjusted RR = 0.16, CI = 0.02-1.23) but no protection against proximal stage C&D cancers (age-adjusted RR = 0.96, CI = 0.32-2.91).Conclusions: This study provides strong evidence for a protective effect of screening sigmoidoscopy on colorectal cancer incidence and mortality and supports recommendations for screening sigmoidoscopy as an approach to colon cancer prevention. [ABSTRACT FROM AUTHOR]