Mathematical modeling and public policy: responding to health crises.
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Biomedical subjects
Publications and source records attributed to Bruce Levin.
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The Long Island Breast Cancer Study Project is a federally mandated, population-based case-control study to determine whether breast cancer risk among women in the counties of Nassau and Suffolk, NY, is associated with selected environmental exposures, assessed by blood samples, self-reports, and environmental home samples. This report describes the collaborative project's background, rationale, methods, participation rates, and distributions of known risk factors for breast cancer by case-control status, by blood donation, and by availability of environmental home samples. Interview response rates among eligible cases and controls were 82.1% (n = 1,508) and 62.8% (n = 1,556), respectively. Among case and control respondents who completed the interviewer-administered questionnaire, 98.2 and 97.6% self-completed the food frequency questionnaire; 73.0 and 73.3% donated a blood sample; and 93.0 and 83.3% donated a urine sample. Among a random sample of case and control respondents who are long-term residents, samples of dust (83.6 and 83.0%); soil (93.5 and 89.7%); and water (94.3 and 93.9%) were collected. Established risk factors for breast cancer that were found to increase risk among Long Island women include lower parity, late age at first birth, little or no breast feeding, and family history of breast cancer. Factors that were found to be associated with a decreased likelihood that a respondent would donate blood include increasing age and past smoking; factors associated with an increased probability include white or other race, alcohol use, ever breastfed, ever use of hormone replacement therapy, ever use of oral contraceptives, and ever had a mammogram. Long-term residents (defined as 15+ years in the interview home) with environmental home samples did not differ from other long-term residents, although there were a number of differences in risk factor distributions between long-term residents and other participants, as anticipated.
BACKGROUND: Studies of IV magnesium sulfate as a treatment for acute asthma have had mixed results, with some data suggesting a benefit for acute severe asthma, but not for mild-to-moderate asthma. In a multicenter cohort, this study tests the hypothesis that administration of magnesium sulfate improves pulmonary function in patients with acute severe asthma. DESIGN: Placebo-controlled, double-blind, randomized clinical trial. SETTING: Emergency departments (EDs) of eight hospitals. PATIENTS: Patients aged 18 to 60 years presenting with acute asthma and FEV1 < or = 30% predicted on arrival to the ED. INTERVENTION: All patients received nebulized albuterol at regular intervals and IV methylprednisolone. Two grams of IV magnesium sulfate or placebo were administered 30 min after ED arrival. The primary efficacy end point was FEV1 at 240 min, and the data analysis was intent to treat. RESULTS: Two hundred forty-eight patients were included, and the mean FEV1 on ED arrival was 22.9% predicted. At 240 min, patients receiving magnesium had a mean FEV1 of 48.2% predicted, compared to 43.5% predicted in the placebo-treated group (mean difference, 4.7%; 95% confidence interval [CI], 0.29 to 9.3%; p = 0.045). A regression model confirmed the effect of magnesium compared to placebo was greater in patients with a lower initial FEV1 (p < 0.05). If the initial FEV1 was < 25% predicted, the final FEV1 was 45.3% predicted in the magnesium-treated group and 35.6% predicted in the placebo-treated group (mean difference, 9.7%; 95% CI, 4.0 to 15.3%; p = 0.001). If the initial FEV was > or = 25% predicted, magnesium administration was not beneficial; the final FEV1 was 51.1% predicted in the magnesium-treated group and 53.9% predicted in the placebo-treated group (mean difference, - 2.9%, 95% CI, - 9.4 to 3.7; p = not significant). Overall, the use of magnesium sulfate did not improve hospital admission rates. CONCLUSION: Administration of 2 g of IV magnesium sulfate improves pulmonary function when used as an adjunct to standard therapy in patients with very severe, acute asthma.
Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effect on breast cancer development in women is not clear. To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. Cases were women newly diagnosed with in situ and invasive breast cancer; controls were randomly selected women frequency matched to the age distribution of cases. Blood samples were donated by 1102 (73.0%) and 1141 (73.3%) of case and control respondents, respectively. Samples from 576 cases and 427 controls were assayed for PAH-DNA adducts using an ELISA. The geometric mean (and geometric SD) of the log-transformed levels of PAH-DNA adducts on a natural scale was slightly, but nonsignificantly, higher among cases [7.36 (7.29)] than among controls [6.21 (4.17); P = 0.51]. The age-adjusted odds ratio (OR) for breast cancer in relation to the highest quintile of adduct levels compared with the lowest was 1.51 [95% confidence interval (CI), 1.04-2.20], with little or no evidence of substantial confounding (corresponding multivariate-adjusted OR, 1.49; 95% CI, 1.00-2.21). There was no consistent elevation in risk with increasing adduct levels, nor was there a consistent association between adduct levels and two of the main sources of PAH, active or passive cigarette smoking or consumption of grilled and smoked foods. These data indicate that PAH-DNA adduct formation may influence breast cancer development, although the association does not appear to be dose dependent and may have a threshold effect.
Whether environmental contaminants increase breast cancer risk among women on Long Island, NY, is unknown. The study objective is to determine whether breast cancer risk is increased in relation to organochlorines, compounds with known estrogenic characteristics that were extensively used on Long Island and other areas of the United States. Recent reports do not support a strong association, although there are concerns with high risks observed in subgroups of women. Blood samples from 646 case and 429 control women from a population-based case-control study conducted on Long Island were analyzed. No substantial elevation in breast cancer risk was observed in relation to the highest quintile of lipid-adjusted serum levels of p,p'-bis(4-chlorophenyl)-1,1-dichloroethene (DDE) [odds ratio (OR), 1.20 versus lowest quintile; 95% confidence interval (CI), 0.76-1.90], chlordane (OR, 0.98; 95% CI, 0.62-1.55), dieldrin (OR, 1.37; 95% CI, 0.69-2.72), the sum of the four most frequently occurring PCB congeners (nos. 118, 153, 138, and 180; OR, 0.83; 95% CI, 0.54-1.29), and other PCB congener groupings. No dose-response relations were apparent. Nor was risk increased in relation to organochlorines among women who had not breastfed or were overweight, postmenopausal, or long-term residents of Long Island; or with whether the case was diagnosed with invasive rather than in situ disease, or with a hormone receptor-positive tumor. These findings, based on the largest number of samples analyzed to date among primarily white women, do not support the hypothesis that organochlorines increase breast cancer risk among Long Island women.