Asbestos fibre dimensions and lung cancer mortality among workers exposed to chrysotile

ObjectivesTo estimate exposures to asbestos fibres of specific sizes among asbestos textile manufacturing workers exposed to chrysotile using data from transmission electron microscopy (TEM) and to evaluate the extent to which the risk of lung cancer varies with fibre length and diameter.Methods3803 workers employed for at least 1 day between 1 January 1950 and 31 December 1973 in any of three plants in North Carolina, USA that produced asbestos textile products and followed for vital status through 31 December 2003 were included. Historical exposures to asbestos fibres were estimated from work histories and 3578 industrial hygiene measurements taken in 1935–1986. Exposure–response relationships for lung cancer were examined within the cohort using Poisson regression.ResultsIndicators of fibre length and diameter obtained by TEM were positively and significantly associated with increasing risk of lung cancer. Exposures to longer and thinner fibres tended to be most strongly associated with lung cancer, and models for these fibres fit the data best. Simultaneously modelling indicators of cumulative mean fibre length and diameter yielded a positive coefficient for fibre length and a negative coefficient for fibre diameter.ConclusionsThe results support the hypothesis that the risk of lung cancer among workers exposed to chrysotile asbestos increases with exposure to longer fibres. More research is needed to improve the characterisation of exposures by fibre size and number and to analyse the associated risks in a variety of industries and populations

Lung Cancer Risk Associated with Regulated and Unregulated Chrysotile Asbestos Fibers

BACKGROUND: Regulation of asbestos fibers in the workplace is partly determined by which fibers can be visually counted. However, a majority of fibers are too short and thin to count this way and are, consequently, not subject to regulation. METHODS: We estimate lung cancer risk associated with asbestos fibers of varying length and width. We apply an order-constrained prior both to leverage external information from toxicological studies of asbestos health effects. This prior assumes that risk from asbestos fibers increases with increasing length and decreases with increasing width. RESULTS: When we apply a shared mean for the effect of all asbestos fiber exposure groups, the rate ratios for each fiber group per unit exposure appear mostly equal. Rate ratio estimates for fibers of diameter 40 μm in the thinnest fiber group are similar in magnitude to estimates of risk associated with long fibers in the regulated fraction of airborne asbestos fibers. Rate ratio estimates for longer fibers are larger than those for shorter fibers, but thicker and thinner fibers do not differ as the toxicologically derived prior had expected. CONCLUSION: Credible intervals for fiber size-specific risk estimates overlap; thus, we cannot conclude that there are substantial differences in effect by fiber size. Nonetheless, our results suggest that some unregulated asbestos fibers may be associated with increased incidence of lung cancer

Assessing Strength of Evidence of Appropriate Use Criteria for Diagnostic Imaging Examinations

Objective For health information technology tools to fully inform evidence-based decisions, recommendations must be reliably assessed for quality and strength of evidence. We aimed to create an annotation framework for grading recommendations regarding appropriate use of diagnostic imaging examinations. Methods The annotation framework was created by an expert panel (clinicians in three medical specialties, medical librarians, and biomedical scientists) who developed a process for achieving consensus in assessing recommendations, and evaluated by measuring agreement in grading the strength of evidence for 120 empirically selected recommendations using the Oxford Levels of Evidence. Results Eighty-two percent of recommendations were assigned to Level 5 (expert opinion). Inter-annotator agreement was 0.70 on initial grading (κ = 0.35, 95% CI, 0.23-0.48). After systematic discussion utilizing the annotation framework, agreement increased significantly to 0.97 (κ = 0.88, 95% CI, 0.77-0.99). Conclusions A novel annotation framework was effective for grading the strength of evidence supporting appropriate use criteria for diagnostic imaging exams

IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health

IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans

Precision of circadian wake and activity onset timing in the mouse

In each circadian cycle, a mouse begins its major activity period with discrete wake onset and activity onset events. The precision with which these events are timed in constant darkness was analyzed using the approach outlined by Pittendrigh and Daan (1976). 1. Negative serial correlations of observed circadian period values (mean r1=−0.471 for wake data, −0.409 for activity data) imply that deviations in period tend to be compensated by opposite deviations in the following cycle. 2. As a result, precision of the circadian pacemaker must be better than that of observed rhythms. Standard deviation of the pacemaker periodσ(Τ) was estimated at 5.1 min. Some individual data series had estimates s(Τ)=0, implying a nearly perfect pacemaker. 3. Previous speculation was that wake onset would be under more direct pacemaker control than activity onset, and would therefore be timed more precisely (Pittendrigh and Daan 1976; Richardson et al. 1985). Contrary to this prediction, intervals between successive wake onsets exhibited significantly greater variance than intervals between successive activity onsets. Two possible interpretations of this finding were proposed

Assessing the component associations of the healthy worker survivor bias: occupational asbestos exposure and lung cancer mortality

BACKGROUND: The healthy worker survivor bias is well-recognized in occupational epidemiology. Three component associations are necessary for this bias to occur: i) prior exposure and employment status; ii) employment status and subsequent exposure; and iii) employment status and mortality. Together, these associations result in time-varying confounding affected by prior exposure. We illustrate how these associations can be assessed using standard regression methods. METHOD: We use data from 2975 asbestos textile factory workers hired between January 1940 and December 1965 and followed for lung cancer mortality through December 2001. RESULTS: At entry, median age was 24 years, with 42% female and 19% non-Caucasian. Over follow-up, 21% and 17% of person-years were classified as at work and exposed to any asbestos, respectively. For a 100 fiber-year/mL increase in cumulative asbestos, the covariate-adjusted hazard of leaving work decreased by 52% (95% confidence interval [CI], 46–58). The association between employment status and subsequent asbestos exposure was strong due to nonpositivity: 88.3% of person-years at work (95% CI, 87.0–89.5) were classified as exposed to any asbestos; no person-years were classified as exposed to asbestos after leaving work. Finally, leaving active employment was associated with a 48% (95% CI, 9–71) decrease in the covariate-adjusted hazard of lung cancer mortality. CONCLUSIONS: We found strong associations for the components of the healthy worker survivor bias in these data. Standard methods, which fail to properly account for time-varying confounding affected by prior exposure, may provide biased estimates of the effect of asbestos on lung cancer mortality under these conditions