Occupational Epidemiology Research Articles

CONSTANCES: a general prospective population-based cohort for occupational and environmental epidemiology: cohort profile

Why the cohort was set up?CONSTANCES is a general-purpose cohort with a focus on occupational and environmental factors.Cohort participantsCONSTANCES was designed as a randomly selected sample of French adults aged...

Novel Analytic Methods Needed for Real-Time Continuous Core Body Temperature Data.

Affordable measurement of core body temperature (Tc) in a continuous, real-time fashion is now possible. With this advance comes a new data analysis paradigm for occupational epidemiology. We characterize issues arising after obtaining Tc data over 188 workdays for 83 participating farmworkers, a population vulnerable to effects of rising temperatures due to climate change. We describe a novel approach to these data using smoothing and functional data analysis. This approach highlights different data aspects compared with describing Tc at a single time point or summaries of the time course into an indicator function (e.g., did Tc ever exceed 38 °C, the threshold limit value for occupational heat exposure). Participants working in ferneries had significantly higher Tc at some point during the workday compared with those working in nurseries, despite a shorter workday for fernery participants. Our results typify the challenges and opportunities in analyzing Big Data streams from real-time physiologic monitoring.

Short-term markers of DNA damage among roofers who work with hot asphalt.

BackgroundRoofers are at increased risk for various malignancies and their occupational exposures to polycyclic aromatic hydrocarbons (PAHs) have been considered as important risk factors. The overall goal of this project was to investigate the usefulness of phosphorylated histone H2AX (γH2AX) as a short-term biomarker of DNA damage among roofers.MethodsBlood, urine, and dermal wipe samples were collected from 20 roofers who work with hot asphalt before and after 6 h of work on Monday and Thursday of the same week (4 sampling periods). Particle-bound and gas-phase PAHs were collected using personal monitors during work hours. γH2AX was quantified in peripheral lymphocytes using flow cytometry and 8-hydroxy-2-deoxyguanosine (8-OHdG) was assessed in urine using ELISA. General linear mixed models were used to evaluate associations between DNA damage and possible predictors (such as sampling period, exposure levels, work- and life-style factors). Differences in mean biomarker and DNA damage levels were tested via ANOVA contrasts.ResultsExposure measurements did not show an association with any of the urinary biomarkers or the measures of DNA damage. Naphthalene was the most abundant PAH in gas-phase, while benzo(e)pyrene was the most abundant particle-bound PAH. Post-shift levels of γH2AX and 8-OHdG were higher on both study days, when compared to pre-shift levels. Cigarette smoking was a predictor of γH2AX and urinary creatinine was a predictor of urinary 8-OHdG. Between-subject variance to total variance ratio was 35.3 % for γH2ax and 4.8 % for 8-OHdG.ConclusionγH2AX is a promising biomarker of DNA damage in occupational epidemiology studies. It has a lower within-subject variation than urinary 8-OHdG and can easily be detected in large scale groups. Future studies that explore the kinetics of H2AX phosphorylation in relation to chemical exposures may reveal the transient and persistent nature of this sensitive biomarker of early DNA damage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0182-4) contains supplementary material, which is available to authorized users.

A review of mortality associated with elongate mineral particle (EMP) exposure in occupational epidemiology studies of gold, talc, and taconite mining.

Mining of gold, taconite, and talc may involve exposure to elongate mineral particles (EMP). The involved EMPs are typically non-asbestiform, include dimensions that regulatory definitions exclude, and have been less studied. A review of the literature was undertaken for this exposure and occupational epidemiological studies that occur in gold, talc, and taconite mining. Quantitative EMP exposure information in these industries is incomplete. However, there are consistent findings of pneumoconiosis in each of these types of mining. A recent case-control study suggests a possible association between this exposure and mesothelioma. Lung cancer is inconsistently reported in these industries and is an unlikely outcome of non-asbestiform EMP exposure. There is evidence of cardiovascular mortality excess across all of these types of mining. Non-malignant respiratory disease and cardiovascular mortality have been consistently increased in these industries. Further investigation, including additional insights for the role of non-asbestiform EMP, is warranted. Am. J. Ind. Med. 59:1047-1060, 2016. © 2016 Wiley Periodicals, Inc.

Challenges in the estimation of Net SURvival: The CENSUR working survival group

BackgroundNet survival, the survival probability that would be observed, in a hypothetical world, where the cancer of interest would be the only possible cause of death, is a key indicator in population-based cancer studies. Accounting for mortality due to other causes, it allows cross-country comparisons or trends analysis and provides a useful indicator for public health decision-making. The objective of this study was to show how the creation and formalization of a network comprising established research teams, which already had substantial and complementary experience in both cancer survival analysis and methodological development, make it possible to meet challenges and thus provide more adequate tools, to improve the quality and the comparability of cancer survival data, and to promote methodological transfers in areas of emerging interest. MethodThe Challenges in the Estimation of Net SURvival (CENSUR) working survival group is composed of international researchers highly skilled in biostatistics, methodology, and epidemiology, from different research organizations in France, the United Kingdom, Italy, Slovenia, and Canada, and involved in French (FRANCIM) and European (EUROCARE) cancer registry networks. ResultsThe expected advantages are an interdisciplinary, international, synergistic network capable of addressing problems in public health, for decision-makers at different levels; tools for those in charge of net survival analyses; a common methodology that makes unbiased cross-national comparisons of cancer survival feasible; transfer of methods for net survival estimations to other specific applications (clinical research, occupational epidemiology); and dissemination of results during an international training course. ConclusionThe formalization of the international CENSUR working survival group was motivated by a need felt by scientists conducting population-based cancer research to discuss, develop, and monitor implementation of a common methodology to analyze net survival in order to provide useful information for cancer control and cancer policy. A “team science” approach is necessary to address new challenges concerning the estimation of net survival.

Survival analysis with measurement error in a cumulative exposure variable: radon progeny in relation to lung cancer mortality

Exposure variables in occupational and environmental epidemiology are usually measured with error. This error tends to flatten the estimated exposure-response relationship. Here, we extended the risk set regression calibration (RRC) method to obtain unbiased point and interval estimates of relative risks corrected for exposure measurement error in Cox models to be able to analyze cumulative exposure variables. We show that the RRC methodology originally developed for use with an external validation study can also be applied to internal validation study designs. We then analyzed the 3,469 New Mexico uranium miners cohort with follow-up extended from 1957 to 2012. The exposure data were collected using several different methods of measurement, some of which had a substantial amount of error. We compare results from the standard analysis of the effect of cumulative radon exposure on lung cancer mortality to measurement error corrected results in a subset of 2337 miners observed during the time period when exposure was measured by work area samples and/or personal exposure estimates provided by the mining companies (the gold standard). The correlation these two methods of measurements was 0.33. After adjusting for bias due to exposure measurement error, the multivariate- adjusted hazard ratio for lung cancer mortality in relation to cumulative radon exposure was estimated to be 4.69 ( 95%CI 2.21-9.95), substantially higher than the estimate obtained from the standard analysis ignoring measurement error (HR=1.35, 95%CI 1.21-1.50). Publicly available user-friendly software is available that supports the new methodology.

Historical occupational isocyanate exposure levels in two Canadian provinces

ABSTRACTIsocyanates such as toluene 2, 4-diisocyanate (TDI), methylene bisphenyl isocyanate (MDI), and hexamethylene diisocyanate (HDI) are known sensitizers and exposure to these chemicals can result in isocyanate-induced asthma—the leading cause of occupational asthma. A newly created exposure database was available containing occupational isocyanate measurements spanning 1981–1996 from Ontario and British Columbia (BC)—two of the largest provinces in Canada. The aim was to describe the historical measurements relative to exposure thresholds, ascertain differences in the data between provinces, and identify time trends. Descriptive statistics of the observations were summarized and stratified by isocyanate species and province. Chi-square tests and Student's t-test were performed to determine differences between provinces. To investigate time trends in the odds of a measurement exceeding the limit of detection (LOD) and time-weighted average (TWA), mixed effects logistic regression models were constructed. In total, 6,984 isocyanate measurements were analyzed, the majority of which were below the LOD (79%). Overall, 8.3% of samples were in excess of the 2014 TLV-TWA of 0.005 ppm. Comparing the two provinces, the proportion of samples exceeding the LOD and TLV-TWA was greater in BC for all isocyanate species. Differences in time trends were also observed between provinces—the odds of a sample exceeding the TLV-TWA decreased over time in the case of MDI (Ontario only), TDI (both Ontario and BC), and other isocyanates (BC only). Our finding that a majority of the exposure measurements was below the LOD is similar to that reported by others. Differences between provinces may be due the fact that isocyanates are classified as a designated substance in Ontario and must adhere to specific exposure control regulations. Limitations of the database, such as finite number of variables and measurements available until 1996 only, presents challenges for more in-depth analysis and generalization of results. An argument is made that a Canadian occupational exposure database be maintained to facilitate risk assessments as well as for occupational epidemiology research.

Linking DNA adduct formation and human cancer risk in chemical carcinogenesis.

Over two centuries ago, Sir Percival Pott, a London surgeon, published a pioneering treatise showing that soot exposure was the cause of high incidences of scrotal cancers occurring in young men who worked as chimney sweeps. Practicing at a time when cellular pathology was not yet recognized, Sir Percival nonetheless observed that the high incidence and short latency of the chimney sweep cancers, was fundamentally different from the rare scrotal cancers typically found in elderly men. Furthermore, his diagnosis that the etiology of these cancers was related to chimney soot exposure, was absolutely accurate, conceptually novel, and initiated the field of "occupational cancer epidemiology." After many intervening years of research focused on mechanisms of chemical carcinogenesis, briefly described here, it is clear that DNA damage, or DNA adduct formation, is "necessary but not sufficient" for tumor induction, and that many additional factors contribute to carcinogenesis. This review includes a synopsis of carcinogen-induced DNA adduct formation in experimental models and in the human population, with particular attention paid to molecular dosimetry and molecular cancer epidemiology. Environ. Mol. Mutagen. 57:499-507, 2016. © 2016 Wiley Periodicals, Inc.

Study sensitivity: Evaluating the ability to detect effects in systematic reviews of chemical exposures

A critical step in systematic reviews of potential health hazards is the structured evaluation of the strengths and weaknesses of the included studies; risk of bias is a term often used to represent this process, specifically with respect to the evaluation of systematic errors that can lead to inaccurate (biased) results (i.e. focusing on internal validity). Systematic review methods developed in the clinical medicine arena have been adapted for use in evaluating environmental health hazards; this expansion raises questions about the scope of risk of bias tools and the extent to which they capture the elements that can affect the interpretation of results from environmental and occupational epidemiology studies and in vivo animal toxicology studies, (the studies typically available for assessment of risk of chemicals). One such element, described here as “sensitivity”, is a measure of the ability of a study to detect a true effect or hazard. This concept is similar to the concept of the sensitivity of an assay; an insensitive study may fail to show a difference that truly exists, leading to a false conclusion of no effect. Factors relating to study sensitivity should be evaluated in a systematic manner with the same rigor as the evaluation of other elements within a risk of bias framework. We discuss the importance of this component for the interpretation of individual studies, examine approaches proposed or in use to address it, and describe how it relates to other evaluation components. The evaluation domains contained within a risk of bias tool can include, or can be modified to include, some features relating to study sensitivity; the explicit inclusion of these sensitivity criteria with the same rigor and at the same stage of study evaluation as other bias-related criteria can improve the evaluation process. In some cases, these and other features may be better addressed through a separate sensitivity domain. The combined evaluation of risk of bias and sensitivity can be used to identify the most informative studies, to evaluate the confidence of the findings from individual studies and to identify those study elements that may help to explain heterogeneity across the body of literature.

A Method for Semi-quantitative Assessment of Exposure to Pesticides of Applicators and Re-entry Workers: An Application in Three Farming Systems in Ethiopia.

To develop an inexpensive and easily adaptable semi-quantitative exposure assessment method to characterize exposure to pesticide in applicators and re-entry farmers and farm workers in Ethiopia. Two specific semi-quantitative exposure algorithms for pesticides applicators and re-entry workers were developed and applied to 601 farm workers employed in 3 distinctly different farming systems [small-scale irrigated, large-scale greenhouses (LSGH), and large-scale open (LSO)] in Ethiopia. The algorithm for applicators was based on exposure-modifying factors including application methods, farm layout (open or closed), pesticide mixing conditions, cleaning of spraying equipment, intensity of pesticide application per day, utilization of personal protective equipment (PPE), personal hygienic behavior, annual frequency of application, and duration of employment at the farm. The algorithm for re-entry work was based on an expert-based re-entry exposure intensity score, utilization of PPE, personal hygienic behavior, annual frequency of re-entry work, and duration of employment at the farm. The algorithms allowed estimation of daily, annual and cumulative lifetime exposure for applicators, and re-entry workers by farming system, by gender, and by age group. For all metrics, highest exposures occurred in LSGH for both applicators and female re-entry workers. For male re-entry workers, highest cumulative exposure occurred in LSO farms. Female re-entry workers appeared to be higher exposed on a daily or annual basis than male re-entry workers, but their cumulative exposures were similar due to the fact that on average males had longer tenure. Factors related to intensity of exposure (like application method and farm layout) were indicated as the main driving factors for estimated potential exposure. Use of personal protection, hygienic behavior, and duration of employment in surveyed farm workers contributed less to the contrast in exposure estimates. This study indicated that farmers' and farm workers' exposure to pesticides can be inexpensively characterized, ranked, and classified. Our method could be extended to assess exposure to specific active ingredients provided that detailed information on pesticides used is available. The resulting exposure estimates will consequently be used in occupational epidemiology studies in Ethiopia and other similar countries with few resources.

The application of causal diagrams to conceptualize mechanisms in occupational epidemiology

Although a goal of epidemiological research is to identify causal relationships between a risk factor and a health problem, the methodology employed often sacrifices internal validity to gain capacity to detect associations. There are new graphical and statistical methods that can help unravel the possible causal mechanisms and better understand this "black box". This paper presents causal diagrams, one of the most useful tools for mapping out, prior to analysis, whether a possible association is causal or just due to bias. To demonstrate its usefulness, we use occupational health examples, showing how associations may arise through non-causal pathways as a result of bias. In conclusion, we recommend the routine practice of using causal diagrams in epidemiological research.

Peritoneal Mesothelioma and Asbestos: Clarifying the Relationship by Epidemiology

Peritoneal mesothelioma has been recognized for over a half century, but causality with asbestos of different fiber types and the incidence of this fatal tumor in relation to asbestos exposure dose still needs clarification. In order to help bring clarity, the most important studies on peritoneal mesothelioma, including a brief history, relationship to asbestos exposures, diagnostic issues and experimental studies are reviewed including case series, case-control, occupational, and registry epidemiology studies. This review concludes that all types of asbestos, including amphiboles and chrysotile, are causative for peritoneal mesothelioma. Many cases have been found in both males and females from asbestos exposures in occupational and neighborhood settings, shown in differing epidemiology study designs. It is clear that there is a causal relationship between all types of asbestos at all dose levels for peritoneal mesothelioma and no threshold of exposure to asbestos appears safe.

Human exposure to carbon-based fibrous nanomaterials: A review.

In an emerging field of nanotechnologies, assessment of exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF) is an integral component of occupational and environmental epidemiology, risk assessment and management, as well as regulatory actions. The current state of knowledge on exposure to carbon-based fibrous nanomaterials among workers, consumers and general population was studied in frame of the International Agency for Research on Cancer (IARC) Monographs-Volume 111 "Some Nanomaterials and Some Fibres". Completeness and reliability of available exposure data for use in epidemiology and risk assessment were assessed. Occupational exposure to CNT/CNF may be of concern at all stages of the material life-cycle from research through manufacture to use and disposal. Consumer and environmental exposures are only estimated by modeled data. The available information of the final steps of the life-cycle of these materials remains incomplete so far regarding amounts of handled materials and levels of exposure. The quality and amount of information available on the uses and applications of CNT/CNF should be improved to enable quantitative assessment of human exposure to these materials. For that, coordinated effort in producing surveys and exposure inventories based on harmonized strategy of material test, exposure measurement and reporting results is strongly encouraged.

Environmental & Occupational Health and Epidemiology

Environmental & Occupational Health and Epidemiology

An approach to adjust standardized mortality ratios for competing cause of death in cohort studies.

PurposeThe calculation of standardized mortality ratios (SMRs) is a standard tool for the estimation of health risks in occupational epidemiology. An increasing number of studies deal with the analysis of the mortality in employees suffering from an occupational disease like silicosis or coal-worker pneumoconiosis (CWP). Their focus lies not on the mortality risk due to the occupational disease itself, but on other diseases such as lung cancer or heart diseases. Using population-based reference rates in these studies can cause misleading results because mortality rates of the general population do not reflect the elevated mortality due to the occupational disease investigated. Hence, the purpose of the present paper is to develop an approach to adjust the risk estimates for other causes of death with respect to the effect of an occupational disease as a competing cause of death in occupational mortality cohort studies.MethodsTo overcome the problems associated with SMRs, the paper makes use of proportional mortality ratios (PMR), which are a further approach for the estimation of health risks in occupational epidemiology. The cause-specific SMR can be rewritten as a product of PMR times the overall SMR. The PMR can be adjusted by ignoring the competing cause of death. Hence, an adjusted cause-specific SMR can be derived by multiplying this adjusted PMR with the overall SMR. This approach is applied to studies concerning lung cancer risk in coal miners suffering from CWP.Results and conclusionsThe usual approach for calculating SMRs leads to an underestimation of the real lung cancer risk in subgroups of miners suffering from CWP. The same effect can be observed in workers exposed to respirable silica already suffering from silicosis. The presented approach results in more realistic risk estimation in mortality cohort studies of employees suffering from an occupational disease. It is easily calculable on the basis of usually published values of observed cases and the corresponding cause-specific SMR.

Two hundred years of occupational epidemiology in Norway

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The Relationship Between Caregiving and Mortality After Accounting for Time-Varying Caregiver Status and Addressing the Healthy Caregiver Hypothesis

Previous studies have shown inconsistent associations between caregiving and mortality. This may be due to analyzing caregiver status at baseline only, and that better health is probably related to taking on caregiving responsibilities and continuing in that role. The latter is termed The Healthy Caregiver Hypothesis, similar to the Healthy Worker Effect in occupational epidemiology. We applied common approaches from occupational epidemiology to evaluate the association between caregiving and mortality, including treating caregiving as time-varying and lagging exposure up to 5 years. Caregiving status among 1,068 women (baseline mean age = 81.0 years; 35% caregivers) participating in the Caregiver-Study of Osteoporotic Fractures study was assessed at five interviews conducted between 1999 and 2009. Mortality was determined through January 2012. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals adjusted for sociodemographics, perceived stress, and functional limitations. A total of 483 participants died during follow-up (38.8% and 48.7% of baseline caregivers and noncaregivers, respectively). Using baseline caregiving status, the association with mortality was 0.77, 0.62-0.95. Models of time-varying caregiving status showed a more pronounced reduction in mortality in current caregivers (hazard ratios = 0.54, 0.38-0.75), which diminished with longer lag periods (3-year lag hazard ratio = 0.68, 0.52-0.88, 5-year lag hazard ratios = 0.76, 0.60-0.95). Overall, caregivers had lower mortality rates than noncaregivers in all analyses. These associations were sensitive to the lagged period, indicating that the timing of leaving caregiving does influence this relationship and should be considered in future investigations.

Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment?

Biomonitoring has become a standard approach for exposure assessment in occupational and environmental epidemiology. The use of biological effect markers to identify early adverse changes in target organs has also become widely adopted. However, the potential for kidney function to affect biomarker levels in the body and the optimal approach to adjustment of biomarker concentrations in spot urine samples for hydration status are two important but underappreciated challenges associated with biomarker use. Several unexpected findings, such as positive associations between urine nephrotoxicant levels and estimated glomerular filtration rate (eGFR), have been reported recently in research using biomarkers. These and other findings, discussed herein, suggest an impact of kidney glomerular filtration or tubule processing on biomarker levels. This is more commonly raised in the context of decreased kidney filtration, traditionally referred to as reverse causality; however, recent data suggest that populations with normal kidney filtration may be affected as well. Misclassification bias would result if biomarkers reflect kidney function as well as either exposures or early biological effect outcomes. Furthermore, urine biomarker associations with eGFR that differ markedly by approach used to adjust for urine concentration have been reported. Associations between urine measures commonly used for this adjustment, such as urine creatinine, and specific research outcomes could alter observed biomarker associations with outcomes. Research recommendations to address the potential impact of kidney function and hydration status adjustment on biomarkers are provided, including a range of approaches to study design, exposure and outcome assessment, and adjustment for urine concentration.

Commentary

Commentary

Work-related skin diseases in Norway may be underreported: data from 2000 to 2013.

Contact DermatitisVolume 72, Issue 6 p. 409-412 Contact Points Work-related skin diseases in Norway may be underreported: data from 2000 to 2013 Jose H. Alfonso, Corresponding Author Jose H. Alfonso Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health (STAMI), N-0033 Oslo, NorwayCorrespondence: Jose H. Alfonso, Pb 8149 Dep, N-0033 Oslo, Norway. Tel: +47 23195185. E-mail: jose.alfonso@stami.noSearch for more papers by this authorEva K. Løvseth, Eva K. Løvseth Department of National Work Environment Surveillance, National Institute of Occupational Health, N-0033 Oslo, NorwaySearch for more papers by this authorYogindra Samant, Yogindra Samant Norwegian Labour Inspectorate, 7468 Trondheim, NorwaySearch for more papers by this authorJan-Ø. Holm, Jan-Ø. Holm Department of Dermatology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, 03180 Oslo, NorwaySearch for more papers by this author Jose H. Alfonso, Corresponding Author Jose H. Alfonso Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health (STAMI), N-0033 Oslo, NorwayCorrespondence: Jose H. Alfonso, Pb 8149 Dep, N-0033 Oslo, Norway. Tel: +47 23195185. E-mail: jose.alfonso@stami.noSearch for more papers by this authorEva K. Løvseth, Eva K. Løvseth Department of National Work Environment Surveillance, National Institute of Occupational Health, N-0033 Oslo, NorwaySearch for more papers by this authorYogindra Samant, Yogindra Samant Norwegian Labour Inspectorate, 7468 Trondheim, NorwaySearch for more papers by this authorJan-Ø. Holm, Jan-Ø. Holm Department of Dermatology, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, 03180 Oslo, NorwaySearch for more papers by this author First published: 18 February 2015 https://doi.org/10.1111/cod.12355Citations: 16 Funding: This research received no specific grant from any funding agency in the public, commercial or non-profit sectors. Conflicts of interest: The authors declare no conflict of interests. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume72, Issue6June 2015Pages 409-412 RelatedInformation