Dataset Information

Biological and statistical approaches for modeling exposure to specific trihalomethanes and bladder cancer risk.

ABSTRACT: Lifetime exposure to trihalomethanes (THM) has been associated with increased risk of bladder cancer. We explored methods of analyzing bladder cancer risk associated with 4 THM (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) as surrogates for disinfection by-product (DBP) mixtures in a case-control study in Spain (1998-2001). Lifetime average concentrations of THM in the households of 686 incident bladder cancer cases and 750 matched hospital-based controls were calculated. Several exposure metrics were modeled through conditional logistic regression, including the following analyses: total THM (?g/L), cytotoxicity-weighted sum of total THM (pmol/L), 4 THM in separate models, 4 THM in 1 model, chloroform and the sum of brominated THM in 1 model, and a principal-components analysis. THM composition, concentrations, and correlations varied between areas. The model for total THM was stable and showed increasing dose-response trends. Models for separate THM provided unstable estimates and inconsistent dose-response relationships. Risk estimation for specific THM is hampered by the varying composition of the mixture, correlation between species, and imprecision of historical estimates. Total THM (?g/L) provided a proxy measure of DBPs that yielded the strongest dose-response relationship with bladder cancer risk. A variety of metrics and statistical approaches should be used to evaluate this association in other settings.

SUBMITTER: Salas LA

PROVIDER: S-EPMC3736753 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Biological and statistical approaches for modeling exposure to specific trihalomethanes and bladder cancer risk.

Salas Lucas A LA Cantor Kenneth P KP Tardon Adonina A Serra Consol C Carrato Alfredo A Garcia-Closas Reina R Rothman Nathaniel N Malats Núria N Silverman Debra D Kogevinas Manolis M Villanueva Cristina M CM

American journal of epidemiology 20130505 4

Lifetime exposure to trihalomethanes (THM) has been associated with increased risk of bladder cancer. We explored methods of analyzing bladder cancer risk associated with 4 THM (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) as surrogates for disinfection by-product (DBP) mixtures in a case-control study in Spain (1998-2001). Lifetime average concentrations of THM in the households of 686 incident bladder cancer cases and 750 matched hospital-based controls were calculate ...[more]

PMID: 23648803

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Project description:BACKGROUND:Trihalomethanes (THMs) are widespread disinfection by-products (DBPs) in drinking water, and long-term exposure has been consistently associated with increased bladder cancer risk. OBJECTIVE:We assessed THM levels in drinking water in the European Union as a marker of DBP exposure and estimated the attributable burden of bladder cancer. METHODS:We collected recent annual mean THM levels in municipal drinking water in 28 European countries (EU28) from routine monitoring records. We estimated a linear exposure-response function for average residential THM levels and bladder cancer by pooling data from studies included in the largest international pooled analysis published to date in order to estimate odds ratios (ORs) for bladder cancer associated with the mean THM level in each country (relative to no exposure), population-attributable fraction (PAF), and number of attributable bladder cancer cases in different scenarios using incidence rates and population from the Global Burden of Disease study of 2016. RESULTS:We obtained 2005-2018 THM data from EU26, covering 75% of the population. Data coverage and accuracy were heterogeneous among countries. The estimated population-weighted mean THM level was 11.7?g/L [standard deviation (SD) of 11.2]. The estimated bladder cancer PAF was 4.9% [95% confidence interval (CI): 2.5, 7.1] overall (range: 0-23%), accounting for 6,561 (95% CI: 3,389, 9,537) bladder cancer cases per year. Denmark and the Netherlands had the lowest PAF (0.0% each), while Cyprus (23.2%), Malta (17.9%), and Ireland (17.2%) had the highest among EU26. In the scenario where no country would exceed the current EU mean, 2,868 (95% CI: 1,522, 4,060; 43%) annual attributable bladder cancer cases could potentially be avoided. DISCUSSION:Efforts have been made to reduce THM levels in the European Union. However, assuming a causal association, current levels in certain countries still could lead to a considerable burden of bladder cancer that could potentially be avoided by optimizing water treatment, disinfection, and distribution practices, among other possible measures. https://doi.org/10.1289/EHP4495.

Project description:Autonomous Vehicles (AV) technology is emerging. Field tests on public roads have been on going in several states in the US as well as in Europe and Asia. During the US public road tests, crashes with AV involved happened, which becomes a concern to the public. Most previous studies on AV safety relied heavily on assessing drivers' performance and behaviors in a simulation environment and developing automated driving system performance in a closed field environment. However, contributing factors and the mechanism of AV-related crashes have not been comprehensively and quantitatively investigated due to the lack of field AV crash data. By harnessing California's Report of Traffic Collision Involving an Autonomous Vehicle Database, which includes the AV crash data from 2014 to 2018, this paper investigates by far the most current and complete AV crash database in the US using statistical modeling approaches that involve both ordinal logistic regression and CART classification tree. The quantitative analysis based on ordinal logistic regression and CART models has successfully explored the mechanism of AV-related crash, via both perspectives of crash severity and collision types. Particularly, the CART model reveals and visualize the hierarchical structure of the AV crash mechanism with knowledge of how these traffic, roadway, and environmental contributing factors can lead to crashes of various serveries and collision types. Statistical analysis results indicate that crash severity significantly increases if the AV is responsible for the crash. The highway is identified as the location where severe injuries are likely to happen. AV collision types are affected by whether the vehicle is on automated driving mode, whether the crashes involve pedestrians/cyclists, as well as the roadway environment. The method used in this research provides a proven approach to statistically analyze and understand AV safety issues. And this benefit is potential be even enhanced with an increasing sample size of AV-related crashes records in the future. The comprehensive knowledge obtained ultimately facilitates assessing and improving safety performance of automated vehicles.

Project description:BackgroundWhen a biologic mechanism of interest is anticipated to operate differentially according to sex, as is often the case in endocrine disruptors research, investigators routinely estimate sex-specific associations. Less attention has been given to potential sexual heterogeneity of confounder associations with outcomes. When relationships of covariates with outcomes differ according to sex, commonly applied statistical approaches for estimating sex-specific endocrine disruptor effects may produce divergent estimates.ObjectivesWe discuss underlying assumptions and evaluate the performance of two traditional approaches for estimating sex-specific effects, stratification and product terms, and introduce a simple modeling alternative: an augmented product term approach.MethodsWe describe the impact of assumptions regarding sexual heterogeneity of confounder relationships on estimates of sex-specific effects of the exposure of interest for three approaches: stratification, traditional product terms, and augmented product terms. Using simulated and applied examples, we demonstrate properties of each approach under a range of scenarios.ResultsIn simulations, sex-specific exposure effects estimated using the traditional product term approach were biased when confounders had sex-dependent associations with the outcome. Sex-specific estimates from stratification and the augmented product term approach were unbiased but less precise. In the applied example, the three approaches yielded similar estimates, but resulted in some meaningful differences in conclusions based on statistical significance.ConclusionsInvestigators should consider sexual heterogeneity of confounder associations when choosing an analytic approach to estimate sex-specific effects of endocrine disruptors on health. In the presence of sex-dependent confounding, our augmented product term approach may be advantageous over stratification when there is prior knowledge available to fit reduced models or when investigators seek an automated test for effect measure modification. https://doi.org/10.1289/EHP334.

Dataset Information

Biological and statistical approaches for modeling exposure to specific trihalomethanes and bladder cancer risk.

Publications

Biological and statistical approaches for modeling exposure to specific trihalomethanes and bladder cancer risk.

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