759 research outputs found
An estimating equations approach to fitting latent exposure models with longitudinal health outcomes
The analysis of data arising from environmental health studies which collect
a large number of measures of exposure can benefit from using latent variable
models to summarize exposure information. However, difficulties with estimation
of model parameters may arise since existing fitting procedures for linear
latent variable models require correctly specified residual variance structures
for unbiased estimation of regression parameters quantifying the association
between (latent) exposure and health outcomes. We propose an estimating
equations approach for latent exposure models with longitudinal health outcomes
which is robust to misspecification of the outcome variance. We show that
compared to maximum likelihood, the loss of efficiency of the proposed method
is relatively small when the model is correctly specified. The proposed
equations formalize the ad-hoc regression on factor scores procedure, and
generalize regression calibration. We propose two weighting schemes for the
equations, and compare their efficiency. We apply this method to a study of the
effects of in-utero lead exposure on child development.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS226 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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Immunotoxicity of Perfluorinated Alkylates: Calculation of Benchmark Doses Based on Serum Concentrations in Children
Background: Immune suppression may be a critical effect associated with exposure to perfluorinated compounds (PFCs), as indicated by recent data on vaccine antibody responses in children. Therefore, this information may be crucial when deciding on exposure limits.
Methods: Results obtained from follow-up of a Faroese birth cohort were used. Serum-PFC concentrations were measured at age 5 years, and serum antibody concentrations against tetanus and diphtheria toxoids were obtained at age 7 years. Benchmark dose results were calculated in terms of serum concentrations for 431 children with complete data using linear and logarithmic curves, and sensitivity analyses were included to explore the impact of the low-dose curve shape.
Results: Under different linear assumptions regarding dose-dependence of the effects, benchmark dose levels were about 1.3 ng/mL serum for perfluorooctane sulfonic acid and 0.3 ng/mL serum for perfluorooctanoic acid at a benchmark response of 5%. These results are below average serum concentrations reported in recent population studies. Even lower results were obtained using logarithmic dose–response curves. Assumption of no effect below the lowest observed dose resulted in higher benchmark dose results, as did a benchmark response of 10%.
Conclusions:The benchmark dose results obtained are in accordance with recent data on toxicity in experimental models. When the results are converted to approximate exposure limits for drinking water, current limits appear to be several hundred fold too high. Current drinking water limits therefore need to be reconsidered
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Separation of Risks and Benefits of Seafood Intake
Background: Fish and seafood provide important nutrients but may also contain toxic contaminants, such as methylmercury. Advisories against pollutants may therefore conflict with dietary recommendations. In resolving this conundrum, most epidemiologic studies provide little guidance because they address either nutrient benefits or mercury toxicity, not both. Objectives: Impact on the same health outcomes by two exposures originating from the same food source provides a classical example of confounding. To explore the extent of this bias, we applied structural equation modeling to data from a prospective study of developmental methylmercury neurotoxicity in the Faroe Islands. Results: Adjustment for the benefits conferred by maternal fish intake during pregnancy resulted in an increased effect of the prenatal methylmercury exposure, as compared with the unadjusted results. The dietary questionnaire response is likely to be an imprecise proxy for the transfer of seafood nutrients to the fetus, and this imprecision may bias the confounder-adjusted mercury effect estimate. We explored the magnitude of this bias in sensitivity analysis assuming a range of error variances. At realistic imprecision levels, mercury-associated deficits increased by up to 2-fold when compared with the unadjusted effects. Conclusions: These results suggest that uncontrolled confounding from a beneficial parameter, and imprecision of this confounder, may cause substantial underestimation of the effects of a toxic exposure. The adverse effects of methylmercury exposure from fish and seafood are therefore likely to be underestimated by unadjusted results from observational studies, and the extent of this bias will be study dependent
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