Biomedical subjects

D Spiegelman

Publications and source records attributed to D Spiegelman.

At least 91 records · Page 5Linked to original sources

PubMed1999

A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.

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.

Adult↗

PubMed1999

Fluid intake and the risk of bladder cancer in men.

BACKGROUND: Studies in animals have shown that the frequency of urination is inversely associated with the level of potential carcinogens in the urothelium. In humans, an increase in total fluid intake may reduce contact time between carcinogens and urothelium by diluting urinary metabolites and increasing the frequency of voiding. The data on fluid intake in relation to the risk of bladder cancer are inconclusive. METHODS: We examined the relation between total fluid intake and the risk of bladder cancer over a period of 10 years among 47,909 participants in the prospective Health Professionals Follow-up Study. There were 252 newly diagnosed cases of bladder cancer during the follow-up period. Information on total fluid intake was derived from the reported frequency of consumption of the 22 types of beverages on the food-frequency questionnaire, which was completed by each of the 47,909 participants who were free of cancer in 1986. Logistic-regression analyses were performed to adjust for known and suspected risk factors for bladder cancer. RESULTS: Total daily fluid intake was inversely associated with the risk of bladder cancer; the multivariate relative risk was 0.51 (95 percent confidence interval, 0.32 to 0.80) for the highest quintile of total daily fluid intake (>2531 ml per day) as compared with the lowest quintile (<1290 ml per day). The consumption of water contributed to a lower risk (relative risk, 0.49 [95 percent confidence interval, 0.28 to 0.86] for > or =1440 ml [6 cups] per day vs. <240 ml [1 cup] per day), as did the consumption of other fluids (relative risk, 0.63 [95 percent confidence interval, 0.39 to 0.99] for >1831 ml per day vs. <735 ml per day). CONCLUSIONS: A high fluid intake is associated with a decreased risk of bladder cancer in men.

Adult↗

PubMed1999

A prospective study of egg consumption and risk of cardiovascular disease in men and women.

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.

Adult↗

PubMed1999

Distribution of and factors associated with serum homocysteine levels in children: Child and Adolescent Trial for Cardiovascular Health.

CONTEXT: Although evidence suggests that homocysteine is a risk factor for cardiovascular disease in adults, little information exists on homocysteine levels in children. OBJECTIVES: To describe the distribution of serum homocysteine concentrations among children and to examine the association between homocysteine levels and several characteristics, including serum levels of folic acid and vitamins B12 and B6. DESIGN: Cross-sectional analysis. SETTING: School-based cohort from California, Louisiana, Minnesota, and Texas. PARTICIPANTS: A total of 3524 US schoolchildren, aged 13 and 14 years, from the Child and Adolescent Trial for Cardiovascular Health (completed in 1994). Measurement was conducted in 1997. MAIN OUTCOME MEASURE: Nonfasting serum total homocysteine concentration. RESULTS: The distribution of homocysteine values ranged from 0.1 to 25.7 micromol/L (median, 4.9 micromol/L). Geometric mean homocysteine concentration was significantly higher in boys (5.22 micromol/L) than girls (4.84 micromol/L); blacks (5.51 micromol/L) than whites (4.96 micromol/L) or Hispanics (4.93 micromol/L); nonusers of multivitamins (5.09 micromol/L) than users (4.82 micromol/L); and smokers (5.19 micromol/L) than nonsmokers (5.00 micromol/ L). Serum homocysteine was significantly inversely correlated with serum levels of folic acid (r= -0.36; P = .001), vitamin B12 (r = -0.21; P = .001), and vitamin B6 (r = -0.18; P = .001). Serum homocysteine was not significantly associated with serum lipid levels or family history of cardiovascular disease and was only weakly related to body mass index and systolic blood pressure. After multivariate adjustment, homocysteine remained independently associated with sex, race, serum folic acid and vitamin B12 levels, and systolic blood pressure. CONCLUSIONS: The distribution of homocysteine levels in children is substantially lower than that observed for adults; however, a small percentage of children are still potentially at elevated risk for future cardiovascular disease. Serum folic acid may be an important determinant of homocysteine levels in children.

Adolescent↗

PubMed1999

Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort.

BACKGROUND: Previous epidemiologic studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with regard to the types of fruits and vegetables consumed. We examined total fruit and vegetable intake, as well as intakes of subtypes of fruits and vegetables, in relation to bladder cancer risk in a large male prospective cohort study. METHODS: Two hundred fifty-two cases of incident bladder cancer were diagnosed from 1986 through January 31, 1996, among 47,909 men enrolled in the Health Professionals Follow-up Study. Each participant in this cohort completed a 131-item food-frequency questionnaire in 1986 and subsequently in 1990 and 1994. We used logistic regression analyses to examine fruit and vegetable intake in relation to bladder cancer risk, after adjusting for age, history of cigarette smoking, current smoking status, geographic region, total fluid intake, and caloric intake. RESULTS: We observed a weak, inverse association that was not statistically significant between total fruit and vegetable intake and bladder cancer risk. Intake of cruciferous vegetables was inversely associated with risk (relative risk = 0.49; 95% confidence interval = 0.32-0.75, for the highest category of cruciferous vegetable intake compared with the lowest), but intakes of yellow or green leafy vegetables or carotenoid-rich vegetables were not associated with risk. Individual cruciferous vegetables, except for coleslaw, were all inversely related to bladder cancer risk, but only the associations for broccoli and cabbage were statistically significant. CONCLUSIONS: Data from this study indicate that high cruciferous vegetable consumption may reduce bladder cancer risk, but other vegetables and fruits may not confer appreciable benefits against this cancer.

Adult↗

PubMed1999

Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements.

Previous cohort studies of fat intake and risk of coronary heart disease (CHD) have been inconsistent, probably due in part to methodological differences and various limitations, including inadequate dietary assessment and incomplete adjustment for total energy intake. The authors analyzed repeated assessment of diet from the Nurses' Health Study to examine the associations between intakes of four major types of fat (saturated, monounsaturated, polyunsaturated, and trans fats) and risk of CHD during 14 years of follow-up (1980-1994) by using alternative methods for energy adjustment. In particular, the authors compared four risk models for energy adjustment: the standard multivariate model, the energy-partition model, the nutrient residual model, and the multivariate nutrient density model. Within each model, the authors compared four different approaches for analyzing repeated dietary measurements: baseline diet only, the most recent diet, and two different algorithms for calculating cumulative average diets. The substantive results were consistent across all models; that is, higher intakes of saturated and trans fats were associated with increased risk of CHD, while higher intakes of monounsaturated and polyunsaturated fats were associated with reduced risk. When nutrients were considered as continuous variables, the four energy-adjustment methods yielded similar associationS. However, the interpretation of the relative risks differed across models. In addition, within each model, the methods using the cumulative averages in general yielded stronger associations than did those using either only baseline diet or the most recent diet. When the nutrients were categorized according to quintiles, the residual and the nutrient density models, which gave similar results, yielded statistically more significant tests for linear trend than did the standard and the partition models.

Adult↗

PubMed1999

The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer.

The A2 allele of CYP17 has been associated with polycystic ovarian syndrome, elevated levels of certain steroid hormones in premenopausal women, and increased breast cancer risk. We prospectively assessed the association between the A2 allele of CYP17 and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort. We also evaluated associations between this CYP17 genotype and plasma steroid hormone levels among postmenopausal controls not using hormone replacement to assess the biological significance of this genetic variant. Women with the A2 allele were not at an increased risk of incident breast cancer [OR (odds ratio), 0.85; 95% CI (confidence interval), 0.65-1.12] or advanced breast cancer (OR, 0.84; 95% CI, 0.54-1.32). We did observe evidence that the inverse association of late age at menarche with breast cancer may be modified by the CYP17 A2 allele. The protective effect of later age at menarche was only observed among women without the A2 allele (A1/A1 genotype: for age at menarche > or =13 versus <13; OR, 0.57; 95% CI, 0.36-0.90; A1/A2 and A2/A2 genotypes: OR, 1.05; 95% CI, 0.76-1.45; P for interaction = 0.07). Among controls, we found women with the A2/A2 genotype to have elevated levels of estrone (+14.3%, P = 0.01), estradiol (+13.8%, P = 0.08), testosterone (+8.6%, P = 0.34), androstenedione (+17.1%, P = 0.06), dehydroepiandrosterone (+14.4%, P = 0.02), and dehydroepiandrosterone sulfate (+7.2%, P = 0.26) compared with women with the A1/A1 genotype. These data suggest that the A2 allele of CYP17 modifies endogenous hormone levels, but is not a strong independent risk factor for breast cancer.

Adult↗

PubMed1999

N-acetyl transferase 2 genotypes, meat intake and breast cancer risk.

Heterocyclic amines (HAs) are carcinogens produced by high-temperature cooking of meat and animal protein; metabolism of HA is influenced by polymorphisms in the N-acetyltransferase-2 (NAT-2) gene. Data from a variety of sources suggest that HA may play a role in human carcinogenesis. We examined the associations between meat intake and cooking method, acetylator genotype and breast cancer risk in a sub-cohort of 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. Women who were diagnosed with breast cancer (n = 466) after blood draw and prior to June 1, 1994, were matched to 466 controls. Overall, rapid acetylators were not at increased risk of breast cancer compared with slow acetylators (multivariate OR = 1.1, 95% CI 0.8-1.5), and there were no associations between meat intake or cooking method of meat and breast cancer risk. Rapid acetylators with the highest red meat intake (one or more servings per day) were not at increased risk of breast cancer compared with slow acetylators with the lowest red meat intake (OR = 1.1, 95% CI 0.7-1.8). Frequent intake of charred meat among rapid acetylators (one or more times per week) was not associated with increased risk (OR = 1.2, 95% CI 0.6-2.3) compared with slow acetylators who ate charred meat less than once per month. We observed no significant associations for rapid acetylators who frequently consumed beef, pork or lamb cooked with high-temperature cooking methods, such as barbecuing (OR = 0.9, 95% CI 0.4-1.9) or roasting (OR = 0.9, 95% CI 0.5-1.6). Our data suggest that HAs may not be a major cause of breast cancer, although we cannot exclude misclassification of HA intake as the reason for the lack of association. We observed no evidence of differential susceptibility to these exposures by NAT2 genotype.

Animals↗

PubMed1999

Prevalence and predictors of depressive symptoms in older premenopausal women: the Harvard Study of Moods and Cycles.

BACKGROUND: The Harvard Study of Moods and Cycles is a community-based cohort study designed to evaluate the relationship between major depression and changes in menstrual and ovarian function. METHODS: All women aged 36 to 44 years with a verifiable address from 7 Boston, Mass, metropolitan communities were selected from the Massachusetts Town Books. A self-administered questionnaire assessed demographic characteristics and menstrual history, depression history, and current depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) in 4161 women. RESULTS: We observed a score of 16 or more on the CES-D in 22.4% of women surveyed, and 8.6% scored 25 or more. Widowed, divorced, or separated women were twice as likely as married women to have depression scores greater than 16 (95% confidence interval, 1.6-2.8), and smokers in the upper tertile of pack-years were 1.9 times more likely to have CES-D scores of 16 or more (95% confidence interval, 1.5-2.3). Relative to nulliparous women, those with 1 or 2 children had a 30% lower risk of historic mood disorder, and those with 3 or more children had an even greater reduction in risk (odds ratio, 0.4; 95% confidence interval, 0.3-0.6). Menstrual cycle irregularities were largely unassociated with current or past depression. However, 5 of 8 premenstrual symptoms were significantly associated with CES-D scores of 16 or more. CONCLUSIONS: These findings corroborate the prevalence of depression reported by other community-based studies, and also support a relationship between depressive symptoms and marital status, cigarette smoking, nulliparity, and premenstrual symptoms.

Adult↗

PubMed1999

Risk factors for cervical squamous intraepithelial lesions among HIV-1 seropositive women in Dar es Salaam, Tanzania.

OBJECTIVES: To determine the prevalence and risk factors for cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Dar es Salaam, Tanzania. METHODS: Between July 1996 and December 1997 we interviewed 691 HIV-infected women to obtain information about risk factors for SIL. Cervical smears and samples for lymphocyte subsets and sexually transmitted diseases (STD) diagnosis were collected. RESULTS: The prevalence of SIL was 2.9% (20/686) (95% CI = 1.7-4.2%). Eleven women had low-grade SIL while nine women had high-grade SIL. The number of lifetime sexual partners and live births was associated with a marginally non-significant increased risk of SIL. The risk of SIL was significantly increased among women with CD4+ cell count < 200/mm3 (multivariate odds ratio (OR) = 6.15, 95% CI = 1.19-41.37) and decreased by 68% for each 5-cm increase in mid-upper arm circumference (multivariate OR = 0.32, 95% CI = 0.10-0.93). CONCLUSIONS: HIV-related immunosuppression and wasting and long-term sexual behavior were the major determinants of SIL in this population. Federation of Gynecology and Obstetrics.

Adolescent↗

PubMed1999

Rationale and design of the Tanzania Vitamin and HIV Infection Trial.

We present the rationale and design of a randomized, double-blind, placebo-controlled trial of vitamin supplements among HIV-positive pregnant women in Dar es Salaam, Tanzania. Higher levels of intake of vitamins A, B, C, and E may decrease the risk of vertical transmission and progression of HIV infection by enhancing maternal and infant immune function; by reducing viral load in the blood, breast milk, or lower genital tract secretions; and/or by strengthening the placental barrier to infection. Eligible pregnant women were randomized to receive vitamin A, multivitamins excluding A, vitamin A and multivitamins, or placebo. The main endpoints include vertical transmission of HIV infection, as assessed by examination of infection in infants using polymerase chain reaction (PCR), and progression of HIV disease as measured by the WHO clinical staging system. Over a period of 2 years, 13,876 women were tested for HIV infection, with appropriate pre- and posttest counseling, to enroll 1085 consenting HIV-positive women. The trial assesses women and their children once a month for a minimum of 18 months after delivery or up to the end of this 5-year study. We examine recruitment strategies and means of enhancing cohort retention in long-term follow-up. We assess compliance with the use of supplements by direct questioning, by counting pills, and biochemically by using serum beta-carotene and urine riboflavin levels. Briefly, we discuss ethical issues related to the conduct of AIDS prevention trials in this setting. In sub-Saharan Africa, most HIV-infected persons lack access to the relevant antiretroviral and prophylactic drugs, and the region urgently needs low-cost treatments and preventive strategies. The Tanzania trial should provide valuable data to address the effect of vitamin supplements in the transmission and progression of HIV infection.

Child, Preschool↗

PubMed1999

Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece.

Although several dietary compounds are hypothesized to have anticarcinogenic properties, the role of specific micronutrients in the development of breast cancer remains unclear. To address this issue, we assessed intake of retinol, beta-carotene, vitamin C and vitamin E in relation to breast cancer risk in a case-control study in Greece. Eight hundred and twenty women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collected through a 115-item semiquantitative food frequency questionnaire. Data were modelled by logistic regression, with adjustment for total energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients. Among post-menopausal women, there was no association between any of the micronutrients evaluated and risk of breast cancer. Among premenopausal women, beta-carotene, vitamin C and vitamin E were each inversely associated with breast cancer risk, but after mutual adjustment among the three nutrients only beta-carotene remained significant; the odds ratio (OR) for a one-quintile increase in beta-carotene intake was 0.84 (95% confidence interval 0.73-0.97). The inverse association observed with beta-carotene intake, however, is slightly weaker than the association previously observed with vegetable intake in these data, raising the possibility that the observed beta-carotene effect is accounted for by another component of vegetables.

Ascorbic Acid↗

PubMed1999

Oral contraceptive use and risk of melanoma in premenopausal women.

Melanoma has been increasing in white populations. Incidence rates rise steeply in women until about age 50, suggesting oestrogen as a possible risk factor. Oestrogens can increase melanocyte count and melanin content and cause hyperpigmentation of the skin. We examined prospectively the association between oral contraceptive (OC) use and diagnoses of superficial spreading and nodular melanoma among 183,693 premenopausal white women in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) cohorts. One hundred and forty six cases were confirmed in NHS during follow-up from 1976 to 1994, and 106 cases were confirmed in NHS II from 1989 to 1995. Skin reaction to sun exposure, sunburn history, mole counts, hair colour, family history of melanoma, parity, height and body mass index were also assessed and included in logistic regression models. A significant twofold increase in risk of melanoma (relative risk (RR) = 2.0, 95% confidence interval (CI) 1.2-3.4) was observed among current OC users compared to never users. Risk was further increased among current users with 10 or more years of use (RR = 3.4, 95% CI 1.7-7.0). Risk did not appear elevated among past OC users, even among those with longer durations of use, and risk did not decline linearly with time since last use. In conclusion, risk of premenopausal melanoma may be increased among women who are current OC users, particularly among those with longer durations of use. Further research is needed to determine whether low-dose oestrogen pills in particular are associated with an increase in risk and to describe possible interactions between OC use and sun exposure or other risk factors for melanoma.

Adult↗

PubMed1999

A prospective study of carotenoid intake and risk of cataract extraction in US men.

BACKGROUND: Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. DESIGN: US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. RESULTS: We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative to men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. CONCLUSIONS: Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily.

Adult↗

PubMed1999

A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania.

OBJECTIVES: To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children. DESIGN: Randomized, double blind, placebo-controlled trial. METHODS: Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1). RESULTS: Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01). CONCLUSION: Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children.

Child, Preschool↗

PubMed1999

Matrix methods for estimating odds ratios with misclassified exposure data: extensions and comparisons.

Misclassification of exposure variables is a common problem in epidemiologic studies. This paper compares the matrix method (Barron, 1977, Biometrics 33, 414-418; Greenland, 1988a, Statistics in Medicine 7, 745-757) and the inverse matrix method (Marshall, 1990, Journal of Clinical Epidemiology 43, 941-947) to the maximum likelihood estimator (MLE) that corrects the odds ratio for bias due to a misclassified binary covariate. Under the assumption of differential misclassification, the inverse matrix method is always more efficient than the matrix method; however, the efficiency depends strongly on the values of the sensitivity, specificity, baseline probability of exposure, the odds ratio, case-control ratio, and validation sampling fraction. In a study on sudden infant death syndrome (SIDS), an estimate of the asymptotic relative efficiency (ARE) of the inverse matrix estimate was 0.99, while the matrix method's ARE was 0.19. Under nondifferential misclassification, neither the matrix nor the inverse matrix estimator is uniformly more efficient than the other; the efficiencies again depend on the underlying parameters. In the SIDS data, the MLE was more efficient than the matrix method (ARE = 0.39). In a study investigating the effect of vitamin A intake on the incidence of breast cancer, the MLE was more efficient than the matrix method (ARE = 0.75).

Anti-Bacterial Agents↗

PubMed1999

Design of validation studies for estimating the odds ratio of exposure-disease relationships when exposure is misclassified.

We compared several validation study designs for estimating the odds ratio of disease with misclassified exposure. We assumed that the outcome and misclassified binary covariate are available and that the error-free binary covariate is measured in a subsample, the validation sample. We considered designs in which the total size of the validation sample is fixed and the probability of selection into the validation sample may depend on outcome and misclassified covariate values. Design comparisons were conducted for rare and common disease scenarios, where the optimal design is the one that minimizes the variance of the maximum likelihood estimator of the true log odds ratio relating the outcome to the exposure of interest. Misclassification rates were assumed to be independent of the outcome. We used a sensitivity analysis to assess the effect of misspecifying the misclassification rates. Under the scenarios considered, our results suggested that a balanced design, which allocates equal numbers of validation subjects into each of the four outcome/mismeasured covariate categories, is preferable for its simplicity and good performance. A user-friendly Fortran program is available from the second author, which calculates the optimal sampling fractions for all designs considered and the efficiencies of these designs relative to the optimal hybrid design for any scenario of interest.

Biometry↗

PubMed1999

Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.

OBJECTIVE: Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. SETTING: The New Jersey Medicare population. DESIGN: A retrospective cohort study using linked Medicare and drug claims data. PARTICIPANTS: Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. MEASUREMENTS: The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. RESULTS: Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). CONCLUSION: Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.

Aged↗