Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-30 (of 80 Records) |
Query Trace: Bertke S[original query] |
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Updated findings on temporal variation in radiation-effects on cancer mortality in an international cohort of nuclear workers (INWORKS)
Daniels RD , Bertke SJ , Kelly-Reif K , Richardson DB , Haylock R , Laurier D , Leuraud K , Moissonnier M , Thierry-Chef I , Kesminiene A , Schubauer-Berigan MK . Eur J Epidemiol 2024 The International Nuclear Workers Study (INWORKS) contributes knowledge on the dose-response association between predominantly low dose, low dose rate occupational exposures to penetrating forms of ionizing radiation and cause-specific mortality. By extending follow-up of 309,932 radiation workers from France (1968-2014), the United Kingdom (1955-2012), and the United States (1944-2016) we increased support for analyses of temporal variation in radiation-cancer mortality associations. Here, we examine whether age at exposure, time since exposure, or attained age separately modify associations between radiation and mortality from all solid cancers, solid cancers excluding lung cancer, lung cancer, and lymphohematopoietic cancers. Multivariable Poisson regression was used to fit general relative rate models that describe modification of the linear excess relative rate per unit organ absorbed dose. Given indication of greater risk per unit dose for solid cancer mortality among workers hired in more recent calendar years, sensitivity analyses considering the impact of year of hire on results were performed. Findings were reasonably compatible with those from previous pooled and country-specific analyses within INWORKS showing temporal patterns of effect measure modification that varied among cancers, with evidence of persistent radiation-associated excess cancer risk decades after exposure, although statistically significant temporal modification of the radiation effect was not observed. Analyses stratified by hire period (< 1958, 1958+) showed temporal patterns that varied; however, these analyses did not suggest that this was due to differences in distribution of these effect measure modifiers by hire year. |
Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study
Leuraud K , Laurier D , Gillies M , Haylock R , Kelly-Reif K , Bertke S , Daniels RD , Thierry-Chef I , Moissonnier M , Kesminiene A , Schubauer-Berigan MK , Richardson DB . Lancet Haematol 2024 BACKGROUND: A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. METHODS: We assembled a cohort of 309 932 radiation-monitored workers (269 487 [87%] males and 40 445 [13%] females) employed for at least 1 year by a nuclear facility in France (60 697 workers), the UK (147 872 workers), and the USA (101 363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 10·72 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes of leukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. FINDINGS: The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 2·68, 90% CI 1·13 to 4·55, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (9·57, 4·00 to 17·91, n=122) and myelodysplastic syndromes alone (3·19, 0·35 to 7·33, n=163) or combined with acute myeloid leukaemia (1·55, 0·05 to 3·42, n=598). No significant association was observed for acute lymphoblastic leukaemia (4·25, -4·19 to 19·32, n=49) or CLL (0·20, -1·81 to 2·21, n=242). A positive association was observed between radiation dose and multiple myeloma (1·62, 0·06 to 3·64, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (0·27, -0·61 to 1·39, n=1146) or Hodgkin lymphoma (0·60, -3·64 to 4·83, n=122) mortality. INTERPRETATION: This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10 000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. FUNDING: National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de Sûreté Nucléaire, Orano, Electricité de France, UK Health Security Agency. TRANSLATION: For the French translation of the abstract see Supplementary Materials section. |
Inverse probability weighting to estimate impacts of hypothetical occupational limits on radon exposure to reduce lung cancer
Keil AP , Li Y , Lan Q , Bertke S , Daniels RD , Edwards JK , Kelly-Reif K . Am J Epidemiol 2024 Radon is a known cause of lung cancer. Protective standards for radon exposure are derived largely from studies of working populations that are prone to healthy worker survivor bias. This bias can lead to under-protection of workers and is a key barrier to understanding health effects of many exposures. We apply inverse probability weighting to study a set of hypothetical exposure limits among 4,137 male, White and American Indian radon-exposed uranium miners in the Colorado Plateau followed from 1950 to 2005. We estimate cumulative risk of lung cancer through age 90 under hypothetical occupational limits. We estimate that earlier implementation of the current US Mining Safety and Health Administration annual standard of 4 working level months (implemented here as a monthly exposure limit) could have reduced lung cancer mortality from 16/100 workers to 6/100 workers (95% confidence intervals: 3/100, 8/100), in contrast with previous estimates of 10/100 workers. Our estimate is similar to that among contemporaneous occupational cohorts. Inverse probability weighting is a simple and computationally efficient way address healthy worker survivor bias in order to contrast health effects of exposure limits and estimate the number of excess health outcomes under exposure limits at work. |
Quantile regression for longitudinal data with values below the limit of detection and time-dependent covariates-application to modeling carbon nanotube and nanofiber exposures
Chen IC , Bertke SJ , Dahm MM . Ann Work Expo Health 2024 BACKGROUND: In studies of occupational health, longitudinal environmental exposure, and biomonitoring data are often subject to right skewing and left censoring, in which measurements fall below the limit of detection (LOD). To address right-skewed data, it is common practice to log-transform the data and model the geometric mean, assuming a log-normal distribution. However, if the transformed data do not follow a known distribution, modeling the mean of exposure may result in bias and reduce efficiency. In addition, when examining longitudinal data, it is possible that certain covariates may vary over time. OBJECTIVE: To develop predictive quantile regression models to resolve the issues of left censoring and time-dependent covariates and to quantitatively evaluate if previous and current covariates can predict current and/or future exposure levels. METHODS: To address these gaps, we suggested incorporating different substitution approaches into quantile regression and utilizing a method for selecting a working type of time dependency for covariates. RESULTS: In a simulation study, we demonstrated that, under different types of time-dependent covariates, the approach of multiple random value imputation outperformed the other approaches. We also applied our methods to a carbon nanotube and nanofiber exposure study. The dependent variables are the left-censored mass of elemental carbon at both the respirable and inhalable aerosol size fractions. In this study, we identified some potential time-dependent covariates with respect to worker-level determinants and job tasks. CONCLUSION: Time dependency for covariates is rarely accounted for when analyzing longitudinal environmental exposure and biomonitoring data with values less than the LOD through predictive modeling. Mistreating the time-dependency as time-independency will lead to an efficiency loss of regression parameter estimation. Therefore, we addressed time-varying covariates in longitudinal exposure and biomonitoring data with left-censored measurements and illustrated an entire conditional distribution through different quantiles. |
Re: Adjustment for duration of employment in occupational epidemiology
Keil A , Kelly-Reif K , Costello S , Bertke S , Richardson DB . Ann Epidemiol 2024 |
Site-specific cancer mortality after low level exposure to ionizing radiation: Findings from an update of the International Nuclear Workers Study (INWORKS)
Richardson DB , Laurier D , Leuraud K , Gillies M , Haylock R , Kelly-Reif K , Bertke S , Daniels RD , Thierry-Chef I , Moissonnier M , Kesminiene A , Schubauer-Berigan MK . Am J Epidemiol 2024 A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer. |
Evaluating workplace protection factors (WPFs) of different firefighter PPE interface control measures for select volatile organic compounds (VOCs)
Kander MC , Mayer AC , Wilkinson AF , Bertke S , Kesler RM , Smith DL , Horn GP , Fent KW . J Occup Environ Hyg 2024 1-12 Structural firefighters are exposed to a complex set of contaminants and combustion byproducts, including volatile organic compounds (VOCs). Additionally, recent studies have found structural firefighters' skin may be exposed to multiple chemical compounds via permeation or penetration of chemical byproducts through or around personal protective equipment (PPE). This mannequin-based study evaluated the effectiveness of four different PPE conditions with varying contamination control measures (incorporating PPE interface design features and particulate blocking materials) to protect against ingress of several VOCs in a smoke exposure chamber. We also investigated the effectiveness of long-sleeve base layer clothing to provide additional protection against skin contamination. Outside gear air concentrations were measured from within the smoke exposure chamber at the breathing zone, abdomen, and thigh heights. Personal air concentrations were collected from mannequins under PPE at the same general heights and under the base layer at abdomen and thigh heights. Sampled contaminants included benzene, toluene, styrene, and naphthalene. Results suggest that VOCs can readily penetrate the ensembles. Workplace protection factors (WPFs) were near one for benzene and toluene and increased with increasing molecular weight of the contaminants. WPFs were generally lower under hoods and jackets compared to under pants. For all PPE conditions, the pants appeared to provide the greatest overall protection against ingress of VOCs, but this may be due in part to the lower air concentrations toward the floor (and cuffs of pants) relative to the thigh-height outside gear concentrations used in calculating the WPFs. Providing added interface control measures and adding particulate-blocking materials appeared to provide a protective benefit against less-volatile chemicals, like naphthalene and styrene. |
Compare the marginal effects for environmental exposure and biomonitoring data with repeated measurements and values below the limit of detection
Chen IC , Bertke SJ , Estill CF . J Expo Sci Environ Epidemiol 2024 BACKGROUND: Environmental exposure and biomonitoring data with repeated measurements from environmental and occupational studies are commonly right-skewed and in the presence of limits of detection (LOD). However, existing model has not been discussed for small-sample properties and highly skewed data with non-detects and repeated measurements. OBJECTIVE: Marginal modeling provides an alternative to analyzing longitudinal and cluster data, in which the parameter interpretations are with respect to marginal or population-averaged means. METHODS: We outlined the theories of three marginal models, i.e., generalized estimating equations (GEE), quadratic inference functions (QIF), and generalized method of moments (GMM). With these approaches, we proposed to incorporate the fill-in methods, including single and multiple value imputation techniques, such that any measurements less than the limit of detection are assigned values. RESULTS: We demonstrated that the GEE method works well in terms of estimating the regression parameters in small sample sizes, while the QIF and GMM outperform in large-sample settings, as parameter estimates are consistent and have relatively smaller mean squared error. No specific fill-in method can be deemed superior as each has its own merits. IMPACT: Marginal modeling is firstly employed to analyze repeated measures data with non-detects, in which only the mean structure needs to be correctly provided to obtain consistent parameter estimates. After replacing non-detects through substitution methods and utilizing small-sample bias corrections, in a simulation study we found that the estimating approaches used in the marginal models have corresponding advantages under a wide range of sample sizes. We also applied the models to longitudinal and cluster working examples. |
Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA
Kreuzer M , Sommer M , Deffner V , Bertke S , Demers PA , Kelly-Reif K , Laurier D , Rage E , Richardson DB , Samet JM , Schubauer-Berigan MK , Tomasek L , Wiggins C , Zablotska LB , Fenske N . Radiat Environ Biophys 2024 The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10(-4) or 5.57 × 10(-4) in the full PUMA cohort and 7.50 × 10(-4) or 7.66 × 10(-4) in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10(-4) to 9.2 × 10(-4). PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes. |
Occupational injuries among construction workers by age and related economic loss: findings from Ohio workers' compensation, USA: 2007-2017
Kaur H , Wurzelbacher SJ , Bushnell PT , Bertke S , Meyers AR , Grosch JW , Naber S , Lampl M . Saf Health Work 2023 14 (4) [Epub ahead of print] Background: This study examined age-group differences in the rate, severity, and cost of injuries among construction workers to support evidence-based worker safety and health interventions in the construction industry. Methods: Ohio workers' compensation claims for construction workers were used to estimate claim rates and costs by age group. We analyzed claims data auto-coded into five event/exposure categories: transportation incidents; slips, trips, and falls (STFs); exposure to harmful substances and environments (EHS); contact with objects and equipment (COB); and overexertion and bodily reaction. American Community Survey data were used to determine the proportion of workers by age group. Results: From 2007-2017, among 72,416 accepted injury claims for 166,000 construction full-time equivalent (FTE) per year, nearly half were caused by COB, followed by STFs (20%) and overexertion (20%). Claim rates related to COB and EHS were highest among those 18-24 years old, with claim rates of 313.5 and 25.9 per 10,000 FTE, respectively. STFs increased with age, with the highest claim rates for those 55-64 years old (94.2 claims per 10,000 FTE). Overexertion claim rates increased and then declined with age, with the highest claim rate for those 35-44 years old (87.3 per 10,000 FTE). While younger workers had higher injury rates, older workers had higher proportions of lost-time claims and costs per claim. The total cost per FTE was highest for those 45-54 years old ($1,122 per FTE). Conclusion: The variation in rates of injury types by age suggests age-specific prevention strategies may be useful. |
Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study
Richardson DB , Leuraud K , Laurier D , Gillies M , Haylock R , Kelly-Reif K , Bertke S , Daniels RD , Thierry-Chef I , Moissonnier M , Kesminiene A , Schubauer-Berigan MK . Bmj 2023 382 e074520 OBJECTIVE: To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer. DESIGN: Multinational cohort study. SETTING: Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). PARTICIPANTS: 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. MAIN OUTCOME MEASURES: Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer. RESULTS: The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos. CONCLUSIONS: This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings. |
Increased mortality associated with disability among workers' compensation claimants with upper extremity neuropathy
Martin CJ , Woods S , Bertke S , Pinkerton L , Jin C . J Occup Environ Med 2023 65 (9) 798-802 OBJECTIVE: To evaluate and compare mortality after disabling and non-disabling occupational injuries. METHODS: Vital status was ascertained through 2020 for 2077 individuals with a workers' compensation claim for upper extremity neuropathy in West Virginia in 1998 or 1999. Standardized mortality ratios (SMRs) compared mortality to the West Virginia general population. Hazard ratios (HRs) obtained from Cox regression models compared mortality among those with and without lost work time or permanent disability. RESULTS: Overall, the SMR for accidental poisoning deaths was elevated (1.75, 95% CI 1.08-2.68). All-cause mortality HRs and cancer HRs were elevated for lost work time (HR 1.09, 95% CI 0.93-1.28; HR 1.50, 95% CI 1.09-2.08, respectively) and permanent disability (HR 1.22, 95% CI 1.04-1.44; HR 1.78, 95% CI 1.27-2.48, respectively). CONCLUSIONS: Work-related disability was associated with broad elevations in mortality. |
Ionizing radiation and solid cancer mortality among US nuclear facility workers
Kelly-Reif K , Bertke SJ , Daniels RD , Richardson DB , Schubauer-Berigan MK . Int J Epidemiol 2023 52 (4) 1015-1024 BACKGROUND: The risk of solid cancers from low-level protracted ionizing radiation is not well characterized. Nuclear workers provide valuable information on the effects of ionizing radiation in contemporary exposure scenarios relevant to workers and the public. METHODS: We evaluated the association between penetrating ionizing radiation exposure and solid cancer mortality among a pooled cohort of nuclear workers in the USA, with extended follow-up to examine cancers with long latencies. This analysis includes 101 363 workers from five nuclear facilities, with 12 069 solid cancer deaths between 1944 and 2016. The association between cumulative equivalent dose measured in sieverts (Sv) and solid cancer subtypes were modelled as the excess relative rate per Sv (ERR Sv-1) using Cox regression. RESULTS: For the association between ionizing radiation exposure and all solid cancer mortality we observed an elevated rate (ERR Sv-1=0.19; 95% CI: -0.10, 0.52), which was higher among a contemporary sub-cohort of workers first hired in 1960 or later (ERR Sv-1= 2.23; 95% CI: 1.13, 3.49). Similarly, we observed an elevated rate for lung cancer mortality (ERR Sv-1= 0.65; 95% CI: 0.09, 1.30) that was higher among contemporary hires (ERR Sv-1= 2.90; 95% CI: 1.00, 5.26). CONCLUSIONS: Although concerns remain about confounding, measurement error and precision, this analysis strengthens the evidence base indicating there are radiogenic risks for several solid cancer types. |
Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners
Kelly-Reif K , Bertke SJ , Rage E , Demers PA , Fenske N , Deffner V , Kreuzer M , Samet J , Schubauer-Berigan MK , Tomasek L , Zablotska LB , Wiggins C , Laurier D , Richardson DB . Occup Environ Med 2023 80 (7) 385-391 OBJECTIVES: Radon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date pooled study of uranium miners. METHODS: The pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with <100 WLM cumulative exposure. RESULTS: In a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM. CONCLUSIONS: This new large, pooled study confirms and supports a linear exposure-response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors. |
End-stage renal disease incidence in a cohort of US firefighters from San Francisco, Chicago, and Philadelphia
Pinkerton LE , Bertke S , Dahm MM , Kubale TL , Siegel MR , Hales TR , Yiin JH , Purdue MP , Beaumont JJ , Daniels RD . Am J Ind Med 2022 65 (12) 975-984 BACKGROUND: Firefighters perform strenuous work in hot environments, which may increase their risk of chronic kidney disease. The purpose of this study was to evaluate the risk of end-stage renal disease (ESRD) and types of ESRD among a cohort of US firefighters compared to the US general population, and to examine exposure-response relationships. METHODS: ESRD from 1977 through 2014 was identified through linkage with Medicare data. ESRD incidence in the cohort compared to the US population was evaluated using life table analyses. Associations of all ESRD, systemic ESRD, hypertensive ESRD, and diabetic ESRD with exposure surrogates (exposed days, fire runs, and fire hours) were examined in Cox proportional hazards models adjusted for attained age (the time scale), race, birth date, fire department, and employment duration. RESULTS: The incidence of all ESRD was less than expected (standardized incidence ratio (SIR) = 0.79; 95% confidence interval = 0.69-0.89, observed = 247). SIRs for ESRD types were not significantly increased. Positive associations of all ESRD, systemic ESRD, and hypertensive ESRD with exposed days were observed: however, 95% confidence intervals included one. CONCLUSIONS: We found little evidence of increased risk of ESRD among this cohort of firefighters. Limitations included the inability to evaluate exposure-response relationships for some ESRD types due to small observed numbers, the limitations of the surrogates of exposure, and the lack of information on more sensitive outcome measures for potential kidney effects. |
Introducing LTASR, a new R package based on the NIOSH Life Table Analysis System
Bertke SJ , Kelly-Reif K . Occup Environ Med 2022 For over 50 years, the National Institute for Occupational Safety and Health (NIOSH) has aided epidemiologists in the analysis of occupational cohort studies with the Life Table Analysis System (LTAS).1 LTAS simplifies person-year analyses, which is a central feature of occupational epidemiology research. LTAS is regularly used in occupational epidemiology studies to calculate standardised mortality ratios (SMRs). SMRs continue to be used in occupational epidemiology to compare the mortality experience of a cohort to a national or regional population. While there are limitations to SMRs, such as the inability to evaluate a dose–response association and bias towards the null from the healthy worker effect, SMRs remain an important tool in characterising the overall occupational experience of workers across different industries. SMRs are also an important surveillance tool in occupational and environmental settings. Many occupational cohort studies have used the NIOSH-LTAS system to conduct seminal research, such as a study of first responders to the World Trade Center disaster2 and a study of neurodegenerative diseases among National Football League (NFL) players,3 among many others. |
The epidemiology of lung cancer following radiation exposure
Zablotska LB , Richardson DB , Golden A , Pasqual E , Smith B , Rage E , Demers PA , Do M , Fenske N , Deffner V , Kreuzer M , Samet J , Bertke S , Kelly-Reif K , Schubauer-Berigan MK , Tomasek L , Wiggins C , Laurier D , Apostoaei I , Thomas BA , Simon SL , Hoffman FO , Boice JDJr , Dauer LT , Howard SC , Cohen SS , Mumma MT , Ellis ED , Eckerman KF , Leggett RW , Pawel DJ . Int J Radiat Biol 2022 99 (3) 1-12 Epidemiological studies of occupational, medical, and environmental exposures have provided important information on lung cancer risk and how those risks might depend on the type of exposure, dose rate, and other potential modifying factors such as sex and age of the exposed. Analyses of data from underground miner cohorts and residential case-control studies provide convincing evidence that radon is a leading cause of lung cancer. For low-LET radiation, risk models derived from results from the Lifespan Study of Japanese atomic bomb survivors suggest that for acute exposures, lifetime attributable risks for lung cancer are greater than for other specific cancer sites and are substantially larger for females than males. However, for protracted and fractionated exposures other than from radon, results from epidemiological studies are seemingly often contradictory. |
Nonmalignant respiratory disease mortality in male Colorado Plateau uranium miners, 1960-2016
Kelly-Reif K , Bertke S , Daniels RD , Richardson DB , Schubauer-Berigan MK . Am J Ind Med 2022 65 (10) 773-782 BACKGROUND: To evaluate trends of nonmalignant respiratory disease (NMRD) mortality among US underground uranium miners on the Colorado Plateau, and to estimate the exposure-response association between cumulative radon progeny exposure and NMRD subtype mortality. METHODS: Standardized mortality ratios (SMRs) and excess relative rates per 100 working level months (excess relative rate [ERR]/100 WLM) were estimated in a cohort of 4021 male underground uranium miners who were followed from 1960 through 2016. RESULTS: We observed elevated SMRs for all NMRD subtypes. Silicosis had the largest SMR (n = 52, SMR = 41.4; 95% confidence interval [CI]: 30.9, 54.3), followed by other pneumoconiosis (n = 49, SMR = 39.6; 95% CI: 29.6, 52.3) and idiopathic pulmonary fibrosis (IPF) (n = 64, SMR = 4.77; 95% CI 3.67, 6.09). SMRs for silicosis increased with duration of employment; SMRs for IPF increased with duration of employment and calendar period. There was a positive association between cumulative radon exposure and silicosis with evidence of modification by smoking (ERR/100 WLM(≥10 pack-years) = 0.78; 95% CI: 0.05, 24.6 and ERR/100 WLM(<10 pack-years) = 0.01; 95% CI: -0.03, 0.52), as well as a small positive association between radon and IPF (ERR/100 WLM = 0.06, 95% CI: 0.00, 0.24); these associations were driven by workers with prior employment in hard rock mining. CONCLUSIONS: Uranium mining workers had excess NMRD mortality compared with the general population; this excess persisted throughout follow-up. Exposure-response analyses indicated a positive association between radon exposure and IPF and silicosis, but these analyses have limitations due to outcome misclassification and missing information on occupational co-exposures such as silica dust. |
Lung cancer and radon: Pooled analysis of uranium miners hired in 1960 or later
Richardson DB , Rage E , Demers PA , Do MT , Fenske N , Deffner V , Kreuzer M , Samet J , Bertke SJ , Kelly-Reif K , Schubauer-Berigan MK , Tomasek L , Zablotska LB , Wiggins C , Laurier D . Environ Health Perspect 2022 130 (5) 57010 BACKGROUND: Despite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated. OBJECTIVES: To strengthen the basis for radiation protection, we report on the follow-up of workers employed in the later periods of mine operations for whom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings. METHODS: We conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer. RESULTS: The analysis included 1.9 million person-years of observation and 1,217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 WLM = 1.33; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure, and annual exposure rate; for attained ages < 55 y, the ERR/100 WLM was 8.38 (95% CI: 3.30, 18.99) among miners who were exposed at ≥ 35 years of age and at annual exposure rates of < 0.5 working levels. This association decreased with older attained ages, younger ages at exposure, and higher exposure rates. DISCUSSION: Estimates of association between radon progeny exposure and lung cancer mortality among relatively contemporary miners are coherent with estimates used to inform current protection guidelines. https://doi.org/10.1289/EHP10669. |
Health burdens of uranium miners will extend beyond the radiation exposure compensation act deadline
Kelly-Reif K , Bertke SJ , Samet J , Sood A , Schubauer-Berigan MK . Occup Environ Med 2022 79 (7) 503-4 The US Radiation Exposure Compensation Act (RECA) is a government compensation programme, which provides partial restitution to individuals whose health was affected by nuclear weapons testing or uranium industry employment. RECA covers US uranium miners employed between 1942 and 1971 who developed or died from lung cancer, pulmonary fibrosis, silicosis, pneumoconiosis or cor pulmonale related to lung fibrosis. RECA is set to terminate this year. The filing deadline for living claimants or spouses of deceased claimants is 10 July 2022.1 To assess evidence of whether uranium miners will continue to develop compensable diseases after the termination of RECA, we examined mortality rate trends within the US Colorado Plateau uranium miner cohort. |
The impact of a state-based workers' compensation insurer's risk control services on employer claim frequency and cost rates
Wurzelbacher SJ , Bertke SJ , Lampl MP , Bushnell PT , Robins DC , Naber SJ , Moore LL . J Occup Environ Med 2022 64 (7) 562-572 OBJECTIVE: This study evaluated the impact of a state workers' compensation (WC) insurer's onsite risk control (RC) services on insured employers' WC claim frequency and cost. METHODS: We used two methods to model 2004-2017 claims data from 4,606 employers that received RC visits over time and compare this claims experience to matching employers that did not receive RC services. RESULTS: Relative total WC claim rates increased slightly after RC services, while relative lost-time claims rates either remained similar or decreased and WC cost rates decreased. The impact of RC services on reducing WC costs was cumulative up to the fourth visit but diminished thereafter. CONCLUSIONS: The insurer RC consultation program was effective in reducing WC cost rates for serviced employers. This is consistent with other research conducted on insurer RC services and related regulatory visits. |
Workers compensation claim counts and rates by injury event/exposure among state-insured private employers in Ohio, 2007-2017
Wurzelbacher SJ , Meyers AR , Lampl MP , Bushnell PT , Bertke SJ , Robins DC , Tseng C-Y , Naber SJ . J Safety Res 2021 79 148-167 Introduction: This study analyzed workers compensation (WC) claims among private employers insured by the Ohio state-based WC carrier to identify high-risk industries by detailed cause of injury. Methods: A machine learning algorithm was used to code each claim by U.S. Bureau of Labor Statistics (BLS) event/exposure. The codes assigned to lost-time (LT) claims with lower algorithm probabilities of accurate classification or those LT claims with high costs were manually reviewed. WC data were linked with the state's unemployment insurance (UI) data to identify the employer's industry and number of employees. BLS data on hours worked per employee were used to estimate full-time equivalents (FTE) and calculate rates of WC claims per 100 FTE. Results: 140,780 LT claims and 633,373 medical-only claims were analyzed. Although counts and rates of LT WC claims declined from 2007 to 2017, the shares of leading LT injury event/exposures remained largely unchanged. LT claims due to Overexertion and Bodily Reaction (33.0%) were most common, followed by Falls, Slips, and Trips (31.4%), Contact with Objects and Equipment (22.5%), Transportation Incidents (7.0%), Exposure to Harmful Substances or Environments (2.8%), Violence and Other Injuries by Persons or Animals (2.5%), and Fires and Explosions (0.4%). These findings are consistent with other reported data. The proportions of injury event/exposures varied by industry, and high-risk industries were identified. Conclusions: Injuries have been reduced, but prevention challenges remain in certain industries. Available evidence on intervention effectiveness was summarized and mapped to the analysis results to demonstrate how the results can guide prevention efforts. Practical Applications: Employers, safety/health practitioners, researchers, WC insurers, and bureaus can use these data and machine learning methods to understand industry differences in the level and mix of risks, as well as industry trends, and to tailor safety, health, and disability prevention services and research. 2021 |
Quantile regression for exposure data with repeated measures in the presence of non-detects
Chen IC , Bertke SJ , Curwin BD . J Expo Sci Environ Epidemiol 2021 31 (6) 1057-1066 BACKGROUND: Exposure data with repeated measures from occupational studies are frequently right-skewed and left-censored. To address right-skewed data, data are generally log-transformed and analyses modeling the geometric mean operate under the assumption the data are log-normally distributed. However, modeling the mean of exposure may lead to bias and loss of efficiency if the transformed data do not follow a known distribution. In addition, left censoring occurs when measurements are below the limit of detection (LOD). OBJECTIVE: To present a complete illustration of the entire conditional distribution of an exposure outcome by examining different quantiles, rather than modeling the mean. METHODS: We propose an approach combining the quantile regression model, which does not require any specified error distributions, with the substitution method for skewed data with repeated measurements and non-detects. RESULTS: In a simulation study and application example, we demonstrate that this method performs well, particularly for highly right-skewed data, as parameter estimates are consistent and have smaller mean squared error relative to existing approaches. SIGNIFICANCE: The proposed approach provides an alternative insight into the conditional distribution of an exposure outcome for repeated measures models. |
Cohort profile: Four early uranium processing facilities in the US and Canada
Golden AP , Milder CM , Ellis ED , Anderson JL , Boice JDJr , Bertke SJ , Zablotska LB . Int J Radiat Biol 2021 97 (6) 1-33 PURPOSE: Risks of occupational radiation exposures of workers involved in uranium refining and processing ("uranium processing workers") may be different from risks of other workers from the nuclear fuel cycle. Pooling of individual-level data from published studies and analysis using similar dosimetry and statistical methods might provide valuable insights into risks from occupational uranium and external ionizing radiation exposures. METHODS: We pooled the data for workers from four uranium processing facilities (Fernald Feed Materials Production Center, Ohio; Mallinckrodt Chemical Works Uranium Division, Missouri; Middlesex Sampling Plant, New Jersey; and the Port Hope Radium and Uranium Refining and Processing Plant, Canada). Employment began as early as the 1930s in Canada and follow-up for vital status was as late as 2017. These facilities used similar methods to process Belgian Congo pitchblende ore which contained high concentrations of uranium, radium, and their decay products. In addition, workers were exposed to elevated levels of gamma radiation, fission product contaminants in recycled uranium and ambient radon decay products. Non-radiation exposures of industrial hygiene concern were silica dust inhalation, heavy metal toxicity from uranium, solvents, acid mists and chemicals associated with uranium processing. Exposure and outcome data were harmonized using similar definitions and dose reconstruction methods. Standardized mortality ratios (SMR) were estimated by comparing mortality in the pooled cohort with age-, sex- and calendar time-specific general population mortality rates for the U.S. and Canada. RESULTS: Over 12,400 workers will be evaluated for cancer and non-cancer mortality in relation to exposures to uranium byproducts and gamma radiation (including ∼1,300 females). In total, death from 560 lung cancers, 503 nonmalignant respiratory diseases, 67 renal diseases, 1,596 ischemic heart diseases, and 101 dementia and Alzheimer's diseases (AD) were detected among male workers during follow-up. Mean cumulative doses were 45 millisievert for whole-body external exposures and 172 milligray for lung dose from radon decay products. Of the 16 pooled SMRs, seven were above 1.00, none were significantly low, and only one was significantly high, i.e., dementia and AD among males (SMR =1.29; 95% confidence interval: 1.04,1.54). CONCLUSIONS: This is the largest study to date to examine health risks in uranium processing workers (excluding uranium enrichment workers). The pooling of uranium processing worker data will address issues of importance today, specifically the concerns for cleanup workers and environmental contamination from the operation of past and present nuclear reactor and radiation facilities, reactor accidents, and possible terrorist events. |
Testing and Validating Semi-automated Approaches to the Occupational Exposure Assessment of Polycyclic Aromatic Hydrocarbons
Santiago-Colón A , Rocheleau CM , Bertke S , Christianson A , Collins DT , Trester-Wilson E , Sanderson W , Waters MA , Reefhuis J . Ann Work Expo Health 2021 65 (6) 682-693 INTRODUCTION: When it is not possible to capture direct measures of occupational exposure or conduct biomonitoring, retrospective exposure assessment methods are often used. Among the common retrospective assessment methods, assigning exposure estimates by multiple expert rater review of detailed job descriptions is typically the most valid, but also the most time-consuming and expensive. Development of screening protocols to prioritize a subset of jobs for expert rater review can reduce the exposure assessment cost and time requirement, but there is often little data with which to evaluate different screening approaches. We used existing job-by-job exposure assessment data (assigned by consensus between multiple expert raters) from a large, population-based study of women to create and test screening algorithms for polycyclic aromatic hydrocarbons (PAHs) that would be suitable for use in other population-based studies. METHODS: We evaluated three approaches to creating a screening algorithm: a machine-learning algorithm, a set of a priori decision rules created by experts based on features (such as keywords) found in the job description, and a hybrid algorithm incorporating both sets of criteria. All coded jobs held by mothers of infants participating in National Birth Defects Prevention Study (NBDPS) (n = 35,424) were used in developing or testing the screening algorithms. The job narrative fields considered for all approaches included job title, type of product made by the company, main activities or duties, and chemicals or substances handled. Each screening approach was evaluated against the consensus rating of two or more expert raters. RESULTS: The machine-learning algorithm considered over 30,000 keywords and industry/occupation codes (separate and in combination). Overall, the hybrid method had a similar sensitivity (87.1%) as the expert decision rules (85.5%) but was higher than the machine-learning algorithm (67.7%). Specificity was best in the machine-learning algorithm (98.1%), compared to the expert decision rules (89.2%) and hybrid approach (89.1%). Using different probability cutoffs in the hybrid approach resulted in improvements in sensitivity (24-30%), without the loss of much specificity (7-18%). CONCLUSION: Both expert decision rules and the machine-learning algorithm performed reasonably well in identifying the majority of jobs with potential exposure to PAHs. The hybrid screening approach demonstrated that by reviewing approximately 20% of the total jobs, it could identify 87% of all jobs exposed to PAHs; sensitivity could be further increased, albeit with a decrease in specificity, by adjusting the algorithm. The resulting screening algorithm could be applied to other population-based studies of women. The process of developing the algorithm also provides a useful illustration of the strengths and potential pitfalls of these approaches to developing exposure assessment algorithms. |
Lung Cancer Mortality and Styrene Exposure in the Reinforced Plastics Boatbuilding Industry: Evaluation of Healthy Worker Survivor Bias
Bertke SJ , Keil A , Daniels RD . Am J Epidemiol 2021 190 (9) 1784-1792 The evidence of styrene as a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced plastics industry are an ideal population to study this association due to relatively high levels of exposure to styrene and lack of concomitant exposures to other known carcinogens. However, healthy worker survivor bias (HWSB), where healthier workers stay employed longer and thus have higher exposure potential, is a likely source of confounding bias for exposure-response associations, in part due to styrene's acute effects. We studied a cohort of 5163 boatbuilders exposed to styrene in Washington state employed between 1959 and 1978; prior regression analyses demonstrated little evidence for an exposure-response between styrene exposure and lung cancer mortality. Based on estimates of necessary components of HWSB, we found evidence for a potentially large HWSB. Using g-estimation of a structural nested model to account for HWSB we estimated that one year of exposure >30 ppm accelerates time to lung cancer death by 2.3 years (95% Confidence intervals=1.53, 2.94). Our results suggest possibly strong HWSB in our small cohort and indicate that large, influential studies of styrene exposed workers may suffer similar biases, warranting a re-assessment of the evidence of long-term health effects of styrene exposure. |
Impact of select PPE design elements and repeated laundering in firefighter protection from smoke exposure
Mayer AC , Horn GP , Fent KW , Bertke SJ , Kerber S , Kesler RM , Newman H , Smith DL . J Occup Environ Hyg 2020 17 1-10 As the Fire Service becomes more aware of the potential health effects from occupational exposure to hazardous contaminants, personal protective equipment (PPE) manufacturers, and fire departments have responded by developing and implementing improved means of firefighter protection, including more frequent laundering of PPE after exposures. While laboratory testing of new PPE designs and the effect of laundering on PPE fabric provides a useful way to evaluate these approaches, laboratory scale testing does not necessarily translate to full garment protection. Utilizing a fireground smoke exposure simulator, along with air and/or filter-substrate sampling for polycyclic aromatic hydrocarbons (PAHs) and benzene, this pilot study tested the chemical-protective capabilities of firefighting PPE of different designs (knit hood vs. particulate-blocking hood, turnout jacket with zipper closure vs. hook & dee closure), including the impact of repeatedly exposing and cleaning (through laundering or decontamination on-scene) PPE 40 times. Overall, PAH contamination on filters under hoods in the neck region were higher (median PAHs = 14.7 µg) than samples taken under jackets in the chest region (median PAHs = 7.05 µg). PAH levels measured under particulate-blocking hoods were lower than levels found under knit hoods. Similarly, zippered closures were found to provide a greater reduction in PAHs compared to hook & dee closures. However, neither design element completely eliminated contaminant ingress. Measurements for benzene under turnout jackets were similar to ambient chamber air concentrations, indicating little to no attenuation from the PPE. The effect of laundering or on-scene decontamination on contaminant breakthrough appeared to depend on the type of contaminant. Benzene breakthrough was negatively associated with laundering, while PAH breakthrough was positively associated. More research is needed to identify PPE features that reduce breakthrough, how targeted changes impact exposures, and how fireground exposures relate to biological absorption of contaminants. |
Ischaemic heart and cerebrovascular disease mortality in uranium enrichment workers
Anderson JL , Bertke SJ , Yiin J , Kelly-Reif K , Daniels RD . Occup Environ Med 2020 78 (2) 105-111 OBJECTIVE: Linear and non-linear dose-response relationships between radiation absorbed dose to the lung from internally deposited uranium and external sources and circulatory system disease (CSD) mortality were examined in a cohort of 23 731 male and 5552 female US uranium enrichment workers. METHODS: Rate ratios (RRs) for categories of lung dose and linear excess relative rates (ERRs) per unit lung dose were estimated to evaluate the associations between lung absorbed dose and death from ischaemic heart disease (IHD) and cerebrovascular disease. RESULTS: There was a suggestion of modestly increased IHD risk in workers with internal uranium lung dose above 1 milligray (mGy) (RR=1.4, 95% CI 0.76 to 2.3) and a statistically significantly increased IHD risk with external dose exceeding 150 mGy (RR=1.3, 95% CI 1.1 to 1.6) compared with the lowest exposed groups. ERRs per milligray were positive for IHD and uranium internal dose and for both outcomes per gray external dose, although the CIs generally included the null. CONCLUSIONS: Non-linear dose-response models using restricted cubic splines revealed sublinear responses at lower internal doses, suggesting that linear models that are common in radioepidemiological cancer studies may poorly describe the association between uranium internal dose and CSD mortality. |
Manganese fractionation using a sequential extraction method to evaluate welders flux core arc welding exposures in a shipyard, structural steel and custom parts manufacturers
Hanley KW , Andrews RN , Bertke S , Carter T , Navarro K , Ashley K . Gefahrst Reinhalt Luft 2020 80 (5) 185-193 The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in flux core arc welding fume at three facilities. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Sixty-seven worker-days were monitored for either total or respirable Mn. The samples were analyzed using an experimental method to separate four Mn fractions based on chemical solubility: soluble Mn in a mild ammonium acetate solution; Mn0,2+ in 25% acetic acid; Mn3+,4+ in hydroxylamine hydrochloride in 25% acetic acid; and insoluble Mn fractions in hydrochloric/nitric acid. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.51 to 43; 2.9 to 850; 1.7 to 620; and 0.56 to 331 gm-3, for the different Mn fractions, respectively. The summation of all the total particulate Mn fractions yielded results that ranged from 16 to 1,530 g m-3. The ranges of respirable size Mn TWA concentrations were 0.27 to 75 for soluble Mn; 1.6 to 690 for Mn0,2+; 1.3 to 740 for Mn3+,4+; 0.52 to 570 for insoluble Mn; and 3.8 to 1,800 gm-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn(sum) were 56 (GSD = 4.0), 380 (GSD = 2.7), and 176 (GSD = 3.3) gm-3 for the shipyard, structural steel and custom parts facilities. Although most of the workers exposures measured were below the NIOSH Recommended Exposure Limit for Mn (1,000 gm-3), 44 welders exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 gm-3) and 46 exceeded the new respirable Mn TLV (20 gm-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding in enclosed or confined spaces. |
The effectiveness of ergonomic interventions in material handling operations
Wurzelbacher SJ , Lampl MP , Bertke SJ , Tseng CY . Appl Ergon 2020 87 103139 This study evaluated the effectiveness of ergonomic interventions in material handling operations involving 33 employers and 535 employees from 2012 to 2017. Outcomes included employee-reported low back/upper extremity pain and safety incidents at baseline, every three months, and annually for up to two years. A total of 32.5% of employees completed at least one survey, while 13.6% completed all nine surveys over two years. Among highly exposed employees (who reported handling >= 50 lbs. > 33% of the time), upper extremity pain frequency and severity were lower among those who reported using the intervention routinely versus those that reported using their body strength alone to handle objects >= 50 lbs. After excluding from analyses one employer that used anti-fatigue mats, low back pain frequency was also significantly lower among highly exposed intervention users. In conclusion, there was some evidence that the interventions were effective in reducing employee-reported pain for highly exposed employees. |
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