Compare the marginal effects for environmental exposure and biomonitoring data with repeated measurements and values below the limit of detection.

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.

Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners.

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.

Lung Cancer and Radon: Pooled Analysis of Uranium Miners Hired in 1960 or Later.

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.

The Impact of a State-Based Workers' Compensation Insurer's Risk Control Services on Employer Claim Frequency and Cost Rates.

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 to 2017 claims data from 4606 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.

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.

Quantile regression for exposure data with repeated measures in the presence of non-detects.

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.

PURPOSE: Pooling of individual-level data for workers involved in uranium refining and processing (excluding enrichment) may provide valuable insights into risks from occupational uranium and external ionizing radiation exposures. METHODS: Data were pooled for workers from four uranium processing facilities (Fernald, Mallinckrodt and Middlesex from the U.S.; and Port Hope, Canada). Employment began as early as the 1930s and follow-up was as late as 2017. Workers were exposed to high concentrations of uranium, radium, and their decay products, as well as gamma radiation and ambient radon decay products. Exposure and outcome data were harmonized using similar definitions and dose reconstruction methods. Standardized mortality ratios (SMR) were estimated. RESULTS: In total, 560 deaths from lung cancer, 503 non-malignant respiratory diseases, 67 renal diseases, 1,596 ischemic heart diseases, and 101 dementia and Alzheimer's disease (AD) were detected in the pooled cohort of over 12,400 workers (∼1,300 females). Mean cumulative doses were 45 millisievert for whole-body external ionizing radiation exposure and 172 milligray for lung dose from radon decay products. Only SMR for dementia and AD among males was statistically significant (SMR=1.29; 95% confidence interval: 1.04, 1.54). CONCLUSIONS: This is the largest study to date to examine long-term health risks of uranium processing workers.

Lung Cancer Mortality and Styrene Exposure in the Reinforced-Plastics Boatbuilding Industry: Evaluation of Healthy Worker Survivor Bias.

The evidence for styrene's being a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced-plastics industry are an ideal population in which to study this association because of their 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. Through December 31, 2016, we studied a cohort of 5,163 boatbuilders exposed to styrene in Washington State who were employed between 1959 and 1978; prior regression analyses had demonstrated little evidence for an exposure-response relationship 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 1 year of styrene exposure at more than 30 parts per million accelerated time to lung cancer death by 2.29 years (95% confidence interval: 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 from similar biases, warranting a reassessment of the evidence of long-term health effects of styrene exposure.

Ischaemic heart and cerebrovascular disease mortality in uranium enrichment workers.

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.

The effectiveness of ergonomic interventions in material handling operations.

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.

Exposure-response assessment of cancer mortality in styrene-exposed boatbuilders.

OBJECTIVES: To improve exposure estimates and reexamine exposure-response relationships between cumulative styrene exposure and cancer mortality in a previously studied cohort of US boatbuilders exposed between 1959 and 1978 and followed through 2016. METHODS: Cumulative styrene exposure was estimated from work assignments and air-sampling data. Exposure-response relationships between styrene and select cancers were examined in Cox proportional hazards models matched on attained age, sex, race, birth cohort and employment duration. Models adjusted for socioeconomic status (SES). Exposures were lagged 10 years or by a period maximising the likelihood. HRs included 95% profile-likelihood CIs. Actuarial methods were used to estimate the styrene exposure corresponding to 10-4 extra lifetime risk. RESULTS: The cohort (n= 5163) contributed 201 951 person-years. Exposures were right-skewed, with mean and median of 31 and 5.7 ppm-years, respectively. Positive, monotonic exposure-response associations were evident for leukaemia (HR at 50 ppm-years styrene = 1.46; 95% CI 1.04 to 1.97) and bladder cancer (HR at 50 ppm-years styrene =1.64; 95% CI 1.14 to 2.33). There was no evidence of confounding by SES. A working lifetime exposure to 0.05 ppm styrene corresponded to one extra leukaemia death per 10 000 workers. CONCLUSIONS: The study contributes evidence of exposure-response associations between cumulative styrene exposure and cancer. Simple risk projections at current exposure levels indicate a need for formal risk assessment. Future recommendations on worker protection would benefit from additional research clarifying cancer risks from styrene exposure.

Mortality in a cohort of US firefighters from San Francisco, Chicago and Philadelphia: an update.

OBJECTIVES: To update the mortality experience of a previously studied cohort of 29 992 US urban career firefighters compared with the US general population and examine exposure-response relationships within the cohort. METHODS: Vital status was updated through 2016 adding 7 years of follow-up. Cohort mortality compared with the US population was evaluated via life table analyses. Full risk-sets, matched on attained age, race, birthdate and fire department were created and analysed using the Cox proportional hazards regression to examine exposure-response associations between select mortality outcomes and exposure surrogates (exposed-days, fire-runs and fire-hours). Models were adjusted for a potential bias from healthy worker survivor effects by including a categorical variable for employment duration. RESULTS: Compared with the US population, mortality from all cancers, mesothelioma, non-Hodgkin's lymphoma (NHL) and cancers of the oesophagus, intestine, rectum, lung and kidney were modestly elevated. Positive exposure-response relationships were observed for deaths from lung cancer, leukaemia and chronic obstructive pulmonary disease (COPD). CONCLUSIONS: This update confirms previous findings of excess mortality from all cancers and several site-specific cancers as well as positive exposure-response relations for lung cancer and leukaemia. New findings include excess NHL mortality compared with the general population and a positive exposure-response relationship for COPD. However, there was no evidence of an association between any quantitative exposure measure and NHL.

Increased overall and cause-specific mortality associated with disability among workers' compensation claimants with low back injuries.

BACKGROUND: Mortality tends to be higher among people who do not work than among workers, but the impact of work-related disability on mortality has not been well studied. METHODS: The vital status through 2015 was ascertained for 14 219 workers with an accepted workers' compensation claim in West Virginia for a low back injury in 1998 or 1999. Mortality among the cohort compared with the West Virginia general population was assessed using standard life table techniques. Associations of mortality and disability-related factors within the cohort were evaluated using Cox proportional hazards regression. RESULTS: Compared to the general population, mortality from accidental poisoning was significantly elevated among the overall cohort and lost-time claimants. Most deaths from accidental poisoning in the cohort were due to drug overdoses involving opioids. Mortality from intentional self-harm was also significantly elevated among lost-time claimants. In internal analyses, overall mortality and mortality from cancer, heart disease, intentional self-harm, and drug overdoses involving opioids was significantly associated with lost time. Overall mortality and mortality from drug overdoses involving opioids were also significantly associated with amount of lost time, permanent partial disability, and percent permanent disability. Heart disease mortality was also significantly associated with the amount of lost time. CONCLUSIONS: The results suggest that disability itself may impact mortality risks. If confirmed, these results reinforce the importance of return to work and other efforts to reduce disability.

Comparative analyses of workers' compensation claims of injury among temporary and permanent employed workers in Ohio.

BACKGROUND: A small but increasing number of studies have examined the risk of injury among temporary workers compared to that among workers in permanent employer arrangements. The purpose of this study was to conduct a comparative analysis of injury risk among temporary and permanent employer workers using a large dataset of workers' compensation (WC) claims of injury. METHODS: Over 1.3 million accepted WC claims in Ohio during the years 2001 to 2013 were analyzed, including 45 046 claims from workers employed by temporary services agencies. General descriptive statistics, injury rates and rate ratios (temporary to permanent workers) were calculated by injury type and event, industry group, and industry manual classes. RESULTS: Injured temporary workers were younger and had less tenure compared to injured permanent workers. Temporary workers had higher injury rates, and lower lost-time and medical costs. Differences in injury rates between temporary and permanent workers varied by injury event, industry, and manual class. CONCLUSION: Temporary workers had higher overall injury rates than permanent workers, controlling for industry manual class. These differences were pronounced for certain industries and injury events. We were not able to control for age and tenure of the worker, so it is not clear how these factors affected observed results. These findings were mostly similar to those from other studies using WC data from the states of Washington and Illinois. Together, these studies provide insights to improve injury prevention among temporary workers, however, additional research is still needed to improve safety and health programming for this group of workers.

Workers' compensation injury claims among workers in the private ambulance services industry-Ohio, 2001-2011.

BACKGROUND: Ambulance service workers frequently transfer and transport patients. These tasks involve occupational injury risks such as heavy lifting, awkward postures, and frequent motor vehicle travel. METHODS: We examined Ohio workers' compensation injury claims among state-insured ambulance service workers working for private employers from 2001 to 2011. Injury claim counts and rates are presented by claim types, diagnoses, and injury events; only counts are available by worker characteristics. RESULTS: We analyzed a total of 5882 claims. The majority were medical-only (<8 days away from work). The overall injury claim rate for medical-only and lost-time cases was 12.1 per 100 full-time equivalents. Sprains and strains accounted for 60% of all injury claims. Overexertion from patient handling was the leading injury event, followed by motor vehicle roadway incidents. CONCLUSIONS: Study results can guide the development or improvement of injury prevention strategies. Focused efforts related to patient handling and vehicle incidents are needed.

Chromosome Translocations and Cosmic Radiation Dose in Male U.S. Commercial Airline Pilots.

BACKGROUND: Chromosome translocations are a biomarker of cumulative exposure to ionizing radiation. We examined the relation between the frequency of translocations and cosmic radiation dose in 83 male airline pilots. METHODS: Translocations were scored using fluorescence in situ hybridization chromosome painting. Cumulative radiation doses were estimated from individual flight records. Excess rate and log-linear Poisson regression models were evaluated. RESULTS: Pilots' estimated median cumulative absorbed dose was 15 mGy (range 4.5-38). No association was observed between translocation frequency and absorbed dose from all types of flying [rate ratio (RR) = 1.01 at 1 mGy, 95% confidence interval (CI) 0.97-1.04]. However, additional analyses of pilots' dose from only commercial flying suggested an association (RR = 1.04 at 1 mGy, 95% CI 0.97-1.13). DISCUSSION: Although this is the largest cytogenetic study of male commercial airline pilots to date of which the authors are aware, future studies will need additional highly exposed pilots to better assess the translocation-cosmic radiation relation.Grajewski B, Yong LC, Bertke SJ, Bhatti P, Little MP, Ramsey MJ, Tucker JD, Ward EM, Whelan EA, Sigurdson AJ, Waters MA. Chromosome translocations and cosmic radiation dose in male U.S. commercial airline pilots. Aerosp Med Hum Perform. 2018; 89(7):616-625.

Association of pulmonary, cardiovascular, and hematologic metrics with carbon nanotube and nanofiber exposure among U.S. workers: a cross-sectional study.

BACKGROUND: Commercial use of carbon nanotubes and nanofibers (CNT/F) in composites and electronics is increasing; however, little is known about health effects among workers. We conducted a cross-sectional study among 108 workers at 12 U.S. CNT/F facilities. We evaluated chest symptoms or respiratory allergies since starting work with CNT/F, lung function, resting blood pressure (BP), resting heart rate (RHR), and complete blood count (CBC) components. METHODS: We conducted multi-day, full-shift sampling to measure background-corrected elemental carbon (EC) and CNT/F structure count concentrations, and collected induced sputum to measure CNT/F in the respiratory tract. We measured (nonspecific) fine and ultrafine particulate matter mass and count concentrations. Concurrently, we conducted physical examinations, BP measurement, and spirometry, and collected whole blood. We evaluated associations between exposures and health measures, adjusting for confounders related to lifestyle and other occupational exposures. RESULTS: CNT/F air concentrations were generally low, while 18% of participants had evidence of CNT/F in sputum. Respiratory allergy development was positively associated with inhalable EC (p=0.040) and number of years worked with CNT/F (p=0.008). No exposures were associated with spirometry-based metrics or pulmonary symptoms, nor were CNT/F-specific metrics related to BP or most CBC components. Systolic BP was positively associated with fine particulate matter (p-values: 0.015-0.054). RHR was positively associated with EC, at both the respirable (p=0.0074) and inhalable (p=0.0026) size fractions. Hematocrit was positively associated with the log of CNT/F structure counts (p=0.043). CONCLUSIONS: Most health measures were not associated with CNT/F. The positive associations between CNT/F exposure and respiratory allergies, RHR, and hematocrit counts may not be causal and require examination in other studies.

Dose-response relationships between internally-deposited uranium and select health outcomes in gaseous diffusion plant workers, 1948-2011.

OBJECTIVE: To examine dose-response relationships between internal uranium exposures and select outcomes among a cohort of uranium enrichment workers. METHODS: Cox regression was conducted to examine associations between selected health outcomes and cumulative internal uranium with consideration for external ionizing radiation, work-related medical X-rays and contaminant radionuclides technetium (99 Tc) and plutonium (239 Pu) as potential confounders. RESULTS: Elevated and monotonically increasing mortality risks were observed for kidney cancer, chronic renal diseases, and multiple myeloma, and the association with internal uranium absorbed organ dose was statistically significant for multiple myeloma. Adjustment for potential confounders had minimal impact on the risk estimates. CONCLUSION: Kidney cancer, chronic renal disease, and multiple myeloma mortality risks were elevated with increasing internal uranium absorbed organ dose. The findings add to evidence of an association between internal exposure to uranium and cancer. Future investigation includes a study of cancer incidence in this cohort.