Intermittent claudication in 8343 men and 21-year specific mortality follow-up.

PURPOSE: As Western populations live longer, peripheral vascular disease will become a greater individual and public health problem. Therefore, the long-term natural history of intermittent claudication (IC) needs further delineation. The study objective was to describe the 21-year mortality and relative risk for cause-specific mortality for subjects with incident IC. METHODS: The subjects were 8343 Israeli male governmental employees aged 40-65 years who were free of coronary heart disease and symptomatic peripheral vascular disease in 1963. These men were followed for 21 years to measure differences in mortality between those who did and did not develop incident IC. Incident IC was diagnosed in 1965 and 1968 by the London School of Hygiene IC Questionnaire. All other cardiovascular disease risk factors were measured by standardized and validated procedures. Cause-specific mortality through 1986 was determined through death certificates from the Israeli Mortality Register. RESULTS: A total of 360 men with IC and 7983 symptom-free men were followed for survival from 1965 to 1986; 159 men with IC (44%) and 2330 symptom-free men (29%) died. For total mortality, the Kaplan-Meier 21-year survival probabilities were 56% for IC and 71% for symptom-free men (P < 0.0001 for the entire 21-year survival difference between the two groups). For coronary heart disease (CHD), stroke, and other causes of death, the survival probabilities for men with IC and symptom-free men were, respectively: 85% vs. 90%, 89% vs. 97%, and 79% vs. 83% (P = 0.0004; P < 0.0001; and P = 0.007, respectively, for the entire 21-year survival difference between the two groups). Cox's proportional hazards model was used to control confounding from incident myocardial infarction and angina through 1968, as well as for demographic, physiologic, psychosocial, and other cardiovascular disease risk factors. The 21-year adjusted all-cause mortality relative risk for IC was 1.50 (95% confidence interval (CI), 1.28-1.77). For stroke deaths the relative risk was 2.76 (95% CI, 1.89-4.02). For stroke mortality, IC was the third strongest predictor of death after elevated systolic blood pressure and increasing age. Incident IC had a relative risk of CHD deaths of 1.31, but it was not statistically significant (P = 0.08; 95% CI, 0.97-1.77). IC was not statistically significantly related to other causes of death (P = 0.10) after adjustment for covariates. CONCLUSIONS: IC is strongly predictive of long-term cerebrovascular disease mortality among men. Incident IC is a stronger indicator of cerebrovascular than of CHD death.

Reliability and changes in validity of self-reported cardiovascular disease risk factors using dual response: the behavioral risk factor survey.

The authors previously studied the validity of self-reported cardiovascular disease (CVD) risk factors assessed by telephone surveys, and found the validity low, especially for self-reported hypertension and hypercholesterolemia. One way to improve validity is to combine repeated measurements (dual response) into a single measure. The authors explored this and the reliability of self-reported CVD data collected by the Behavioral Risk Factor Survey in three New York counties from January 1989 to May 1990. Nine hundred and eleven subjects were interviewed by telephone to collect CVD risk factor and health behavior information. Interviewees were offered physical examination and laboratory testing to verify self-reported CVD risk factors; 628 participated. Subjects were also reinterviewed to assess the test-retest reliability of the survey, and to study how validity of self-reported CVD data changes by dual response. Reliability coefficients for CVD risk factors, preventive health practices, and knowledge of risk factor levels ranged from 0.42 to 0.99. Minimal improvement in sensitivity of self-reported risk factors was found using dual response, and it did not improve specificity. Also, for prevalence of risk factors, dual response minimally improved self-reported rates compared to objective estimates. Combining self-reported measurements causes minimal changes in the validity of these variables. Physiological assessment for hypertension and hypercholesterolemia, or correction for misclassification, is needed for valid individual measurement and for community prevalence estimates from telephone surveys. Self-reported cigarette smoking, obesity, and diabetes mellitus have better validity, but physiological assessment or correction for misclassification may supplement these self-reported risk factors.

Validity of cardiovascular disease risk factors assessed by telephone survey: the Behavioral Risk Factor Survey.

The Behavioral Risk Factor Surveillance System (BRFSS) collects telephone interview data on behaviors for the leading causes of premature death and disability. Its validity has never been adequately studied. The authors replicated BRFSS methodology to validate self-reported cardiovascular disease (CVD) risk factors. Nine-hundred and eleven subjects from three upstate New York counties were interviewed between 1/89 and 5/90. Interviewees were offered physical examinations and laboratory testing for CVD risk factors; 282 men and 344 women participated. The authors studied validity by comparing objectively measured to self-reported CVD risk factors. Sensitivities for self-reported hypertension, hypercholesterolemia, obesity, smoking, and diabetes were: 43, 44, 74, 82 and 75%, respectively. Only smoking sensitivity differed by gender: men, 77%; women, 86%. Specificity was > 85% for all risk factors, except hypercholesterolemia in men (75%). Prevalence was underreported for hypertension, hypercholesterolemia, obesity, and smoking by 43, 50, 25 and 17%, respectively. Results suggest telephone survey research includes physiologic measurements for blood pressure, cholesterol, height, weight, and smoking to validate self-reported CVD risk factors. When this is impossible, results such as these can be used, in similar samples, to correct risk factor prevalence rates from telephone surveys for misclassifications.

The effect of human immunodeficiency virus-1 infection and stunting on measles immunoglobulin-G levels in children vaccinated against measles in Uganda.

BACKGROUND: Measles is an important public health problem in developing nations and there is concern that immune response to measles vaccination may be compromised by paediatric human immunodeficiency virus (HIV) infection. Therefore, this study investigated the relationship of immunoglobulin-G (Ig-G) antibody levels in children vaccinated against measles and HIV-1 infection. Further analysis was done to assess the influence of nutritional status on this relationship. METHODS: The authors measured HIV and measles antibodies in 243 vaccinated children aged 17-41 months from Kampala, Uganda. Children were from paediatric and HIV clinics. Potential confounders of this relationship included nutritional anthropometric measures, age at and time since vaccination, measles exposure, family crowding, vaccination clinic and gender. Univariable and multivariable analyses were used to study these associations. RESULTS: Fifty children (21%) were HIV infected. In univariable analysis, low measles antibody (<15 ELISA units/ml) was associated with HIV (P = 0.05; odds ratio (OR) = 1.86) and stunting (P = 0.06; OR = 1.68). Stunting, measured as height-for-age and defined as <-2 standard deviations of the reference population median, was a surrogate for chronic malnutrition. HIV was strongly associated with stunting (P = 0.0001; OR = 6.62). In multiple logistic regression, HIV was not associated with low measles antibodies; however, stunting (P = 0.04; OR = 1.81), and <3 children in the home (P = 0.01; OR = 1.96) were. Conversely, being male (P = 0.05; OR = 0.58), and measles in the home in the previous month (P = 0.04; OR = 0.33) were associated with high antibody levels. CONCLUSIONS: These findings suggest that HIV in Ugandan children immunized for measles may indirectly interfere with measles antibody levels by causing malnutrition, the latter being the direct cause. Programmes to improve childhood nutrition, especially for HIV-infected children, should accompany measles control programmes in developing nations for maximum benefit from measles vaccination. HIV infection per se should not change measles vaccination programmes.

PIP: The effect of HIV infection upon measles immunity was explored in children vaccinated against measles. HIV and measles antibody levels were measured in 243 vaccinated children aged 17-41 months from pediatric and HIV clinics in Kampala, Uganda. Potential confounders of the relationship included nutritional anthropometric measures, age at and time since vaccination, measles exposure, family crowding, vaccination clinic, and gender. 50 children (21%) were infected with HIV. Multiple logistic regression analysis found HIV to not be associated with a low level of measles antibodies, but with stunting and having less than 3 children in the home. Being male and having measles in the home during the previous month were associated with high antibody levels. These findings suggest that HIV in Ugandan children immunized for measles may indirectly interfere with measles antibody levels by causing malnutrition. Programs to improve childhood nutrition, especially for HIV-infected children, should therefore accompany measles control programs in developing countries in order to reap the maximum benefit from measles vaccination.

Breast cancer risk and alcohol consumption: results from a large case-control study.

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.

Comparison of corneal endothelial image analysis by Konan SP8000 noncontact and Bio-Optics Bambi systems.

PURPOSE: Compare corneal endothelial image analysis by Konan SP8000 and Bio-Optics Bambi image-analysis systems. METHODS: Corneal endothelial images from 98 individuals (191 eyes), ranging in age from 4 to 87 years, with a normal slit-lamp examination and no history of ocular trauma, intraocular surgery, or intraocular inflammation were obtained by the Konan SP8000 noncontact specular microscope. One observer analyzed these images by using the Konan system and a second observer by using the Bio-Optics Bambi system. Three methods of analyses were used: a fixed-frame method to obtain cell density (for both Konan and Bio-Optics Bambi) and a "dot" (Konan) or "corners" (Bio-Optics Bambi) method to determine morphometric parameters. RESULTS: The cell density determined by the Konan fixed-frame method was significantly higher (157 cells/mm2) than the Bio-Optics Bambi fixed-frame method determination (p<0.0001). However, the difference in cell density, although still statistically significant, was smaller and reversed comparing the Konan fixed-frame method with both Konan dot and Bio-Optics Bambi comers method (-74 cells/mm2, p<0.0001; -55 cells/mm2, p<0.0001, respectively). Small but statistically significant morphometric analyses differences between Konan and Bio-Optics Bambi were seen: cell density, +19 cells/mm2 (p = 0.03); cell area, -3.0 microm2 (p = 0.008); and coefficient of variation, +1.0 (p = 0.003). There was no statistically significant difference between these two methods in the percentage of six-sided cells detected (p = 0.55). CONCLUSION: Cell densities measured by the Konan fixed-frame method were comparable with Konan and Bio-Optics Bambi's morphometric analysis, but not with the Bio-Optics Bambi fixed-frame method. The two morphometric analyses were comparable with minimal or no differences for the parameters that were studied. The Konan SP8000 endothelial image-analysis system may be useful for large-scale clinical trials determining cell loss; its noncontact system has many clinical benefits (including patient comfort, safety, ease of use, and short procedure time) and provides reliable cell-density calculations.

Radiology of pulmonary turberculosis and human immunodeficiency virus infection in Gulu, Uganda.

Pulmonary tuberculosis is a major complication of human immunodeficiency virus (HIV) infection. The radiographic manifestations of pulmonary tuberculosis in HIV-infected patients are not typical of those seen in immunologically normal individuals. We sought to determine whether these manifestations provide clues to the pathogenesis of tuberculosis in HIV-infected persons. The radiographic manifestations of pulmonary tuberculosis were reviewed and classified in 82 HIV-positive and 53 HIV-negative tuberculous patients in Gulu, Uganda. Pulmonary presentations of tuberculosis were more acute in HIV-positive patients, and often included hilar or mediastinal adenopathy and pleural effusions, findings typical of primary tuberculosis in immunologically normal individuals. Many patients also had chronic forms of tuberculosis, either alone or in combination with acute disease. The findings of this study support the hypothesis that reactivation of latent infections and progression of pre-existent chronic disease produce a substantial portion of the tuberculosis burden of HIV-positive persons in Uganda. Tuberculosis control efforts should extend beyond efforts at decreasing transmission of new infections.

Epidemiology of intermittent claudication in middle-aged men.

Intermittent claudication, myocardial infarction, and angina pectoris share many epidemiologic and biologic features. Yet few large cohort studies describing the prevalence, incidence, and risk factors for intermittent claudication have been done. The authors evaluated intermittent claudication in 10,059 Israeli men aged 40-65 years, of whom 8,343 were free of coronary heart disease and symptoms of peripheral vascular disease; this latter group was followed for 5 years from 1963 to 1968. Prevalent and incident cases of intermittent claudication were defined by the London School of Hygiene Cardiovascular Disease Questionnaire, and all cardiovascular disease risk factor evaluations were standardized. Baseline prevalence was 27.0/1,000 (211/10,029). A total of 360 previously healthy men developed intermittent claudication for a crude 5-year incidence rate of 43.1/1,000 (360/8,343) or a crude annual incidence of 8.6/1,000. Following univariate analysis with demographic, physiologic, psychosocial, and other cardiovascular disease variables, logistic regression was used to identify risk factors for intermittent claudication. These were the following: > 20 cigarettes per day, odds ratio (OR) = 2.02, 95% confidence interval (CI) 1.54-2.66; serum cholesterol (50-mg/dl difference), OR = 1.35, 95% CI 1.18-1.54; 11-20 cigarettes per day, OR = 1.69, 95% CI 1.24-2.30; anxiety (high vs. low), OR = 1.85, 95% CI 1.29-2.65; socioeconomic status, OR = 1.82, 95% CI 1.26-2.64; and diabetes, OR = 1.85, 95% CI 1.25-2.75. Other significant predictors of smaller magnitude included in the regression were age, psychosocial coping factors, Quetelet's index, and exsmoking. The risk factors for intermittent claudication were a blend of those related to myocardial infarction (smoking, cholesterol, diabetes, but not hypertension) and others related to angina pectoris but not to myocardial infarction (stress and coping variables). There is reason to believe that preventing or modifying these factors will prove effective in altering the natural history and clinical outcomes of peripheral vascular disease as shown in other forms of atherosclerosis.

Longitudinal changes in dehydroepiandrosterone concentrations in men and women.

Dehydroepiandrosterone, an adrenal steroid, has many purported roles in the body and has been used as an oral supplement in the treatment of various illnesses. Because little is known about normal changes over time in dehydroepiandrosterone concentrations, we studied the 5-year change in plasma dehydroepiandrosterone concentrations in 614 free-living adults. Two hundred seventy-three males and 341 females had dehydroepiandrosterone and dehydroepiandrosterone sulfate concentrations measured in 1989 and 1994. Demographic data were also obtained. Dehydroepiandrosterone concentrations differed significantly by sex and 5-year age group. The average decline in dehydroepiandrosterone was 5.6%/year, and the rate of decline was directly related to age but not to sex, measures of adiposity, or serum glucose. Dehydroepiandrosterone sulfate concentrations differed significantly by sex and age group. The average decline in the sulfated hormone was 2.0%/year and was not related to age, sex, measures of adiposity, or serum glucose. Knowledge of the natural course of age-related changes in dehydroepiandrosterone and dehydroepiandrosterone sulfate concentrations is essential to our understanding of the relationship of dehydroepiandrosterone to chronic diseases.

Use of antibiotics in preventing recurrent acute otitis media and in treating otitis media with effusion. A meta-analytic attempt to resolve the brouhaha.

OBJECTIVE: To determine the efficacy of antibiotics for prophylaxis of recurrent otitis media and treatment of otitis media with effusion (OME) in children. DATA SOURCES: MEDLINE from 1966 through April 1993, textbooks, Current Contents, and bibliographies of selected articles. STUDY SELECTION: Thirty-three studies initially identified were reviewed by three blinded reviewers assessing study quality and suitability for inclusion. Twenty-seven met inclusion criteria for the meta-analyses. DATA EXTRACTION: We abstracted quantitative data and calculated rate differences (RDs) using tympanometry as the preferred outcome measure. DATA SYNTHESIS: Nine studies of antibiotic prophylaxis of recurrent otitis media with 958 subjects had an RD of 0.11 (95% confidence interval [Cl], 0.03 to 0.19) favoring antibiotic treatment. Twelve studies of short-term patient outcomes of OME with 1697 subjects had an RD favoring antibiotics of 0.16 (95% Cl, 0.03 to 0.29), while eight studies using the ear as the outcome measure with 2052 ears studied had an RD of 0.25 (95% Cl, 0.10 to 0.40). No significant difference was shown between placebo and antibiotics (RD, 0.06; 95% Cl, -0.03 to 0.14) in the eight studies of longer-term outcome of OME. Subgroup analyses by antibiotic grouping, duration of treatment, and duration of disease did not show significant differences. CONCLUSIONS: Antibiotics appear to have beneficial but limited effect on recurrent otitis media and short-term resolution of OME. Longer-term benefit for OME has not been shown. The findings are limited by the failure of most studies to consider potential confounders and by inability to identify groups of patients most likely to benefit.

An ecological study of the effectiveness of mammography in reducing breast cancer mortality.

OBJECTIVES: The purpose of this study was to determine the relation of screening mammography to breast cancer incidence and case fatality. METHODS: In a sample of White female Medicare beneficiaries hospitalized in 1990-1991, age-adjusted breast cancer incidence and 2-year case fatality rates were estimated and compared with the frequency of mammographic screening from a population-based survey. RESULTS: The average rates for incidence, case fatality, and mammography within 5 years in 29 states were 414/100,000, 18.8%, and 59.2%, respectively. There was a positive state-level correlation between mammography rates and incidence and an inverse correlation between mammography and case fatality. CONCLUSIONS: High screening mammography rates in some states are associated with reduced breast cancer case fatality rates, presumably as a result of diagnosis of earlier stage cancers.

Coronary bypass in vascular patients: a relatively high-risk procedure.

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.