Impact of a multi-level, multi-component intervention to improve elementary school physical education on student cardiorespiratory fitness: an application of the parametric g-formula.

Background: School physical education is an important population-level health intervention for improving youth fitness. The purpose of this study is to determine the causal impact of New York City's PE Works program on student cardiorespiratory fitness. Methods: This longitudinal study (2014-2019) includes 581 elementary schools (n=315,999 4th/5th-grade students; 84% non-white; 74% who qualify for free or reduced-price meals). We apply the parametric g-formula to address schools' time-varying exposure to intervention components and time-varying confounding. Results: After four years of staggered PE Works implementation, 49.7% of students per school (95% CI: 42.6%, 54.2%) met age/sex-specific cardiorespiratory fitness standards. Had PE Works not been implemented, we estimate 45.7% (95% CI: 36.9%, 52.1%) would have met fitness standards. Had PE Works been fully implemented in all schools from the program's inception, we estimate 57.4% (95% CI: 49.1%, 63.3%) would have met fitness standards. Adding a PE teacher, alone, had the largest impact (6.4% (95% CI: 1.0, 12.0) increase). Conclusion: PE Works, which included providing PE teachers, training for classroom teachers, and administrative/teacher support for PE, positively impacted student cardiorespiratory health. Mandating and funding multilevel, multicomponent PE programs is an important public health intervention to increase children's cardiorespiratory fitness.

Pregnancy exposure to PM2.5 from wildland fire smoke and preterm birth in California.

BACKGROUND: Wildfires in the Western United States are a growing and significant source of air pollution that is eroding decades of progress in air pollution reduction. The effects on preterm birth during critical periods of pregnancy are unknown. METHODS: We assessed associations between prenatal exposure to wildland fire smoke and risk of preterm birth (gestational age < 37 weeks). We assigned smoke exposure to geocoded residence at birth for all live singleton births in California conceived 2007-2018, using weekly average concentrations of particulate matter ≤ 2.5 µm (PM2.5) attributable to wildland fires from United States Environmental Protection Agency's Community Multiscale Air Quality Model. Logistic regression yielded odds ratio (OR) for preterm birth in relation to increases in average exposure across the whole pregnancy, each trimester, and each week of pregnancy. Models adjusted for season, age, education, race/ethnicity, medical insurance, and smoking of the birthing parent. RESULTS: For the 5,155,026 births, higher wildland fire PM2.5 exposure averaged across pregnancy, or any trimester, was associated with higher odds of preterm birth. The OR for an increase of 1 µg/m3 of average wildland fire PM2.5 during pregnancy was 1.013 (95 % CI:1.008,1.017). Wildland fire PM2.5 during most weeks of pregnancy was associated with higher odds. Strongest estimates were observed in weeks in the second and third trimesters. A 10 µg/m3 increase in average wildland fire PM2·5 in gestational week 23 was associated with OR = 1.034; 95 % CI: 1.019, 1.049 for preterm birth. CONCLUSIONS: Preterm birth is sensitive to wildland fire PM2.5; therefore, we must reduce exposure during pregnancy.

Diesel exhaust and respiratory dust exposure in miners and chronic obstructive pulmonary disease (COPD) mortality in DEMS II.

BACKGROUND: Diesel exhaust and respirable dust exposures in the mining industry have not been studied in depth with respect to non-malignant respiratory disease including chronic obstructive pulmonary disease (COPD), with most available evidence coming from other settings. OBJECTIVES: To assess the relationship between occupational diesel exhaust and respirable dust exposures and COPD mortality, while addressing issues of survivor bias in exposed miners. METHODS: The study population consisted of 11,817 male workers from the Diesel Exhaust in Miners Study II, followed from 1947 to 2015, with 279 observed COPD deaths. We fit Cox proportional hazards models for the relationship between respirable elemental carbon (REC) and respirable dust (RD) exposure and COPD mortality. To address healthy worker survivor bias, we leveraged the parametric g-formula to assess effects of hypothetical interventions on both exposures. RESULTS: Cox models yielded elevated estimates for the associations between average intensity of REC and RD and COPD mortality, with hazard ratios (HR) corresponding to an interquartile range width increase in exposure of 1.46 (95 % confidence interval (CI): 1.12, 1.91) and 1.20 (95 % CI: 0.96, 1.49), respectively for each exposure. HRs for cumulative exposures were negative for both REC and RD. Based on results from the parametric g-formula, the risk ratio (RR) for COPD mortality comparing risk under an intervention eliminating REC to the observed risk was 0.85 (95 % CI: 0.55, 1.06), equivalent to an attributable risk of 15 %. The corresponding RR comparing risk under an intervention eliminating RD to the observed risk was 0.93 (95 % CI: 0.56, 1.31). CONCLUSIONS: Our findings, based on data from a cohort of nonmetal miners, are suggestive of an increased risk of COPD mortality associated with REC and RD, as well as evidence of survivor bias in this population leading to negative associations between cumulative exposures and COPD mortality in traditional regression analysis.

Exposure to Metalworking Fluids and Cancer Incidence in the United Auto Workers-General Motors Cohort.

In previous studies, investigators have reported increased risks of specific cancers associated with exposure to metalworking fluids (MWFs). In this report we broadly examine the incidence of 14 types of cancer, with a focus on digestive, respiratory, and hormonal cancers, in the United Auto Workers-General Motors (UAW-GM) cohort, a cohort of workers exposed to MWFs (1973-2015). The cohort included 39,132 workers followed for cancer incidence. Cox models yielded estimates of adjusted hazard ratios, with categorical variables for lagged cumulative exposure to 3 types of MWF (straight, soluble, and synthetic). We fitted penalized splines to examine the shape of the exposure-response relationships. There were 7,809 incident cancer cases of interest. Oil-based straight and soluble MWFs were each modestly associated with all cancers combined. Exposure-response patterns were consistent with prior reports from this cohort, and results for splined exposures generally reflected their categorically modeled counterparts. We found significantly increased incidence of stomach and kidney cancer with higher levels of straight MWF exposure and increased rectal and prostate cancer with increasing water-based synthetic MWF exposure. Only non-Hodgkin lymphoma and prostate cancer were associated with soluble MWF. All results for colon and lung cancers were null. Our results provide updated evidence for associations between MWF exposure and incidence of several types of cancer.

The Impact of Job Loss on Self-injury Mortality in a Cohort of Autoworkers: Application of a Novel Causal Approach.

BACKGROUND: Recent increases in national rates of suicide and fatal overdose have been linked to a deterioration of economic and social stability. The American auto industry experienced comparable pressures beginning in the 1980s with the emergence of a competitive global market. METHODS: Using the United Autoworkers-General Motors (GM) cohort as a case study, we examine the impact of employment loss on these self-injury mortality events. For 29,538 autoworkers employed on or after 1 January 1970, we apply incremental propensity score interventions, a novel causal inference approach, to examine how proportional shifts in the odds of leaving active GM employment affect the cumulative incidence of self-injury mortality. RESULTS: Cumulative incidence of self-injury mortality was 0.87% (255 cases) at the observed odds of leaving active GM employment (δ = 1) over a 45-year period. A 10% decrease in the odds of leaving active GM employment (δ = 0.9) results in an estimated 8% drop in self-injury mortality (234 cases) while a 10% increase (δ = 1.1) results in a 19% increase in self-injury mortality (303 cases). CONCLUSIONS: These results are consistent with the hypothesis that leaving active employment at GM increases the risk of death due to suicide or drug overdose.

Metalworking Fluid Exposure and Stroke Mortality Among US Autoworkers.

Although air pollution is an important risk factor for stroke, few studies have considered the impact of workplace exposure to particulate matter (PM). We examined implications of exposure to PM composed of metalworking fluids (MWFs) for stroke mortality in the United Autoworkers-General Motors cohort. Cox proportional hazards models with age as the timescale were used to estimate the association of cumulative straight, soluble, and synthetic MWF exposure with stroke mortality, controlling for sex, race, plant, calendar year, and hire year. Among 38,553 autoworkers followed during 1941-1995, we identified 114 ischemic stroke deaths and 113 hemorrhagic stroke deaths. Overall stroke mortality risk was increased among workers in the middle exposure category for straight MWF (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 0.87, 1.98) and workers in the highest exposure category for synthetic MWF (HR = 1.94, 95% CI: 1.13, 3.16) compared with workers who had no direct exposure. Ischemic stroke mortality risk was increased among workers in the highest exposure categories for straight MWF (HR = 1.45, 95% CI: 0.83, 2.52) and synthetic MWF (HR = 2.39, 95% CI: 1.39, 4.50). We observed no clear relationship between MWF exposure and hemorrhagic stroke mortality. Our results support a potentially important role for occupational PM exposures in stroke mortality and indicate the need for further studies of PM exposure and stroke in varied occupational settings.

End-stage renal disease and metalworking fluid exposure.

OBJECTIVE: Despite increasing prevalence of end-stage renal disease (ESRD), little attention has been directed to how occupational exposures may contribute to risk. Our objective was to investigate the relationship between metalworking fluids (MWF) and ESRD in a cohort of 36 703 male autoworkers. METHODS: We accounted for competing risk of death, using the subdistribution hazard approach to estimate subhazard ratios (sHRs) and 95% CIs in models with cubic splines for cumulative exposure to MWF (straight, soluble or synthetic). RESULTS: Based on 501 ESRD cases and 13 434 deaths, we did not observe an association between MWF and ESRD overall. We observed modest associations between MWF and ESRD classification of glomerulonephritis and diabetic nephropathy. For glomerulonephritis, the 60th percentile of straight MWF was associated with an 18% increased subhazard (sHR=1.18, 95% CI: 0.99 to 1.41). For diabetic nephropathy, the subhazard increased 28% at the 60th percentile of soluble MWF (sHR=1.28, 95% CI: 1.00 to 1.64). Differences by race suggest that black males may have higher disease rates following MWF exposure. CONCLUSIONS: Exposure to straight and soluble MWF may be related to ESRD classification, though this relationship should be further examined.

Working: The Role of Occupational Epidemiology.

The coronavirus disease 2019 (COVID-19) pandemic has redemonstrated the importance of work as a determinant of health. During the pandemic, extant disparities were accentuated as the workforce was divided into the roughly 50% who could safely work from home and those who could not. With the spotlight on work, one might wonder where all the occupational epidemiologists have gone. To answer, we point to diminished research support and more limited workplace access that have led many epidemiologists to shift away from a focus on workers toward other vulnerable populations. Here we build on the renewed interest in work as a driver of health and inequality during the pandemic to highlight contributions of occupational epidemiology to public health. We consider: 1) etiological studies of chronic disease based on employment records to define cohorts and reconstruct long-term exposure; 2) studies of hypothetical interventions that are particularly appropriate for evaluating potential regulations to reduce workplace exposures; and 3) studies of disparities that take advantage of work as a potential source of social stratification and economic opportunity. As we have learned during the COVID-19 pandemic, workplaces can become venues for public health messaging and delivering interventions to enumerated populations of adults. By starting with COVID-19 prevention policies for the workplace, we have a chance to better protect public health.

Racial disparities in alcohol-related liver disease mortality in a 75 year follow-up study of Michigan autoworkers.

BACKGROUND: Suicide, drug overdose, and alcohol-related liver disease (ALD) mortality have been rising in the United States. While suicide and overdose have received a great deal of attention, far less public health concern has focused on chronic ALD. To address this gap, we examine ALD mortality rates, by race, in a cohort of autoworkers to describe trends over the past 75 years, from the peak in automobile manufacturing employment through its decline. METHODS: Based on the United Autoworkers-General Motors (UAW-GM) cohort we estimated temporal trends in age-adjusted ALD mortality rates from 1941 through 2015 at three automobile manufacturing plants in Michigan. We compared these rates to county, state, and U.S. rates, directly standardized to the 2000 U.S. census, to assess the roles of race and employment on ALD mortality. RESULTS: The overall age-adjusted ALD mortality rate among 41,097 male autoworkers peaked at 46.1 per 100,000 in the 1970s, followed by a gradual decline and a recent rise. Rates were slightly higher for black than white men until early 2000s, when rates increased only for white men. ALD mortality rates in the study cohort tracked national, state, and county rates for white men until the most recent time period, but were lower throughout the study period for black men, especially in the 1970s and 1980s. CONCLUSIONS: Employment in automobile manufacturing may have offered some protection against death from ALD for black men, and loss of those manufacturing jobs may have impacted white men without a college degree more in recent decades.

Suicide, overdose and worker exit in a cohort of Michigan autoworkers.

BACKGROUND: In recent decades, suicide and fatal overdose rates have increased in the US, particularly for working-age adults with no college education. The coincident decline in manufacturing has limited stable employment options for this population. Erosion of the Michigan automobile industry provides a striking case study. METHODS: We used individual-level data from a retrospective cohort study of 26 804 autoworkers in the United Autoworkers-General Motors cohort, using employment records from 1970 to 1994 and mortality follow-up from 1970 to 2015. We estimated HRs for suicide or fatal overdose in relation to leaving work, measured as active or inactive employment status and age at worker exit. RESULTS: There were 257 deaths due to either suicide (n=202) or overdose (n=55); all but 21 events occurred after leaving work. The hazard rate for suicide was 16.1 times higher for inactive versus active workers (95% CI 9.8 to 26.5). HRs for suicide were elevated for all younger age groups relative to those leaving work after age 55. Those 30-39 years old at exit had the highest HR for suicide, 1.9 (95% CI 1.2 to 3.0). When overdose was included, the rate increased by twofold for both 19- to 29-year-olds and 30- to 39-year-olds at exit. Risks remained elevated when follow-up was restricted to 5 years after exit. CONCLUSIONS: Autoworkers who left work had a higher risk of suicide or overdose than active employees. Those who left before retirement age had higher rates than those who left after, suggesting that leaving work early may increase the risk.

Metalworking fluids and cancer mortality in a US autoworker cohort (1941-2015).

Objectives This report describes the extended follow-up (1941-2015) of a cohort of 38 549 automobile manufacturing workers with potential exposure to metalworking fluids (MWF). The outcomes of interest were mortality from cancers of the esophagus, stomach, intestine, rectum, bladder, liver, pancreas, larynx, lung, skin, prostate, brain, and female breast, as well as leukemia. This report includes 5472 deaths from cancer, more than ten times the numbers of deaths in our last summary report published 20 years ago. Methods Standardized mortality ratios were computed for the entire study period. Adjusted hazard ratios (HR) were estimated in Cox proportional hazard models with categorical variables for cumulative exposure to each type of MWF. Results Exposure-response patterns are consistent with prior mortality reports from this cohort. We found increased risk of skin and female breast cancer with straight fluids. For the first time, we found elevated risk of stomach cancer mortality. Overall, many of the exposure-response results did not suggest an association with MWF. Conclusions Mortality is a poor proxy for cancer diagnosis for treatable cancers and not the optimal outcome measure in etiological studies. Although the HR presented here handle bias from the healthy worker hire effect and left truncation, they do not handle bias from healthy worker survivor effect, which likely results in underestimates of the health impacts of MWF. Although this updated summary provides some information on the risk of cancer from MWF, targeted future analyses will help clarify associations.

Chronic obstructive pulmonary disease mortality: The Diesel Exhaust in Miners Study (DEMS).

BACKGROUND: Miners are highly exposed to diesel exhaust emissions from powered equipment. Although biologically plausible, there is little evidence based on quantitative exposure assessment, that long-term diesel exposure increases risk of chronic obstructive pulmonary disease (COPD). To fill this gap, we examined COPD mortality and diesel exhaust exposure in the Diesel Exhaust in Miners Study (DEMS). METHODS: We fit Cox models to estimate hazard ratios (HRs) for COPD mortality and cumulative exposure (µg/m3-years) to respirable elemental carbon (REC), a key metric for diesel exhaust exposure. Separate models were fit for ever-underground and surface-only miners to allow for effect modification. Exposure was lagged by 0, 10 and 15 years. In a secondary analysis, we addressed the healthy worker survivor effect by applying the parametric g-formula to handle time-varying confounding affected by prior exposure among ever-underground workers. RESULTS: Based on 140 cases, the HRs for COPD mortality increased as categories of lagged REC exposure increased for all workers. Among surface-only workers, those in the middle exposure category (0 lag) had a significantly elevated hazard ratio of 2.34 (95% CI: 1.11-4.61) relative to those in the lowest category. Among the ever-underground, that ratio was 1.35, with wide confidence intervals. Using the g-formula, we estimated that the lifetime cumulative risk of COPD mortality would have been reduced from the observed 5.0%-3.1% under a hypothetical intervention where all ever-underground workers were always unexposed. CONCLUSIONS: Our results suggest long term exposure to diesel exhaust may increase risk of COPD in miners, though power was limited.

Accelerated lung function decline in an aluminium manufacturing industry cohort exposed to PM2.5: an application of the parametric g-formula.

OBJECTIVE: Occupational dust exposure has been associated with accelerated lung function decline, which in turn is associated with overall morbidity and mortality. In the current study, we assess potential benefits on lung function of hypothetical interventions that would reduce occupational exposure to fine particulate matter (PM2.5) while adjusting for the healthy worker survivor effect. METHODS: Analyses were performed in a cohort of 6485 hourly male workers in an aluminium manufacturing company in the USA, followed between 1996 and 2013. We used the parametric g-formula to assess lung function decline over time under hypothetical interventions while also addressing time-varying confounding by underlying health status, using a composite risk score based on health insurance claims. RESULTS: A counterfactual scenario envisioning a limit on exposure equivalent to the 10th percentile of the observed exposure distribution of 0.05 mg/m3 was associated with an improvement in forced expiratory volume in one second (FEV1) equivalent to 37.6 mL (95% CI 13.6 to 61.6) after 10 years of follow-up when compared with the observed. Assuming a linear decrease and (from NHANES reference values), a 20 mL decrease per year for a 1.8 m-tall man as they age, this 37.6 mL FEV1 loss over 10 years associated with observed exposure would translate to approximately a 19% increase to the already expected loss per year from age alone. CONCLUSIONS: Our results indicate that occupational PM2.5 exposure in the aluminium industry accelerates lung function decline over age. Reduction in exposure may mitigate accelerated loss of lung function over time in the industry.

Metalworking Fluids and Colon Cancer Risk: Longitudinal Targeted Minimum Loss-based Estimation.

Metalworking fluids (MWFs) are a class of complex mixtures of chemicals and oils, including several known carcinogens that may pose a cancer hazard to millions of workers. Reports on the relation between MWFs and incident colon cancer have been mixed. METHODS: We investigated the relation between exposure to straight, soluble, and synthetic MWFs and the incidence of colon cancer in a cohort of automobile manufacturing industry workers, adjusting for time-varying confounding affected by prior exposure to reduce healthy worker survivor bias. We used longitudinal targeted minimum loss-based estimation (TMLE) to estimate the difference in the cumulative incidence of colon cancer comparing counterfactual outcomes if always exposed above to always exposed below an exposure cutoff while at work. Exposure concentration cutoffs were selected a priori at the 90th percentile of total particulate matter for each fluid type: 0.034, 0.400, and 0.003 for straight, soluble, and synthetic MWFs, respectively. RESULTS: The estimated 25-year risk differences were 3.8% (95% confidence interval [CI] = 0.7, 7.0) for straight, 1.3% (95% CI = -2.3, 4.8) for soluble, and 0.2% (95% CI = -3.3, 3.7) for synthetic MWFs, respectively. The corresponding risk ratios were 2.39 (1.12, 5.08), 1.43 (0.67, 3.04), and 1.08 (0.51, 2.30) for straight, soluble, and synthetic MWFs, respectively. CONCLUSIONS: By controlling for time-varying confounding affected by prior exposure, a key feature of occupational cohorts, we were able to provide evidence for a causal effect of straight MWF exposure on colon cancer risk that was not found using standard analytical techniques in previous reports.

Diesel Exhaust, Respirable Dust, and Ischemic Heart Disease: An Application of the Parametric g-formula.

BACKGROUND: Although general population studies of air pollution suggest that particulate matter-diesel exhaust emissions in particular-is a potential risk factor for cardiovascular disease, direct evidence from occupational cohorts using quantitative metrics of exposure is limited. In this study, we assess counterfactual risk of ischemic heart disease (IHD) mortality under hypothetical scenarios limiting exposure levels of diesel exhaust and of respirable mine/ore dust in the Diesel Exhaust in Miners Study cohort. METHODS: We analyzed data on 10,779 male miners from 8 nonmetal, noncoal mines-hired after diesel equipment was introduced in the respective facilities-and followed from 1948 to 1997, with 297 observed IHD deaths in this sample. We applied the parametric g-formula to assess risk under hypothetical scenarios with various limits for respirable elemental carbon (a surrogate for diesel exhaust), and respirable dust, separately and jointly. RESULTS: The risk ratio comparing the observed risk to cumulative IHD mortality risk at age 80 under a hypothetical scenario where exposures to elemental carbon and respirable dust are eliminated was 0.79 (95% confidence interval [CI]: 0.64, 0.97). The corresponding risk difference was -3.0% (95% CI: -5.7, -0.3). CONCLUSION: Our findings, based on data from a cohort of nonmetal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk.

Lung cancer mortality and exposure to synthetic metalworking fluid and biocides: controlling for the healthy worker survivor effect.

OBJECTIVES: Synthetic metalworking fluids (MWFs), widely used to cool and lubricate industrial machining and grinding operations, have been linked with increased risk of several cancers. Estimates of their relation with lung cancer, however, are inconsistent. Controlling for the healthy worker survivor effect, we examined the relations between lung cancer mortality and exposure to synthetic MWF, as well as to biocides added to water-based fluids to control microbial growth, in a cohort of autoworkers. Biocides served as a marker for endotoxin, which has reported antitumour effects, and were hypothesised to be the reason prior studies found reduced lung cancer risk associated with exposure to synthetic fluids. METHODS: Using the parametric g-formula, we estimated risk ratios (RRs) comparing cumulative lung cancer mortality under no intervention with what would have occurred under hypothetical interventions reducing exposure to zero (ie, a ban) separately for two exposures: synthetic fluids and biocides. We also specified an intervention on synthetic MWF and biocides simultaneously to estimate joint effects. RESULTS: Under a synthetic MWF ban, we observed decreased lung cancer mortality risk at age 86, RR=0.96 (0.91-1.01), but when we also intervened to ban biocides, the RR increased to 1.03 (0.95-1.11). A biocide-only ban increased lung cancer mortality (RR=1.07 (1.00-1.16)), with slightly larger RR in younger ages. CONCLUSIONS: Findings suggest a modest positive association for synthetic MWF with lung cancer mortality, contrary to the negative associations reported in earlier studies. Biocide exposure, however, was inversely associated with risk of lung cancer mortality.

Estimating Counterfactual Risk Under Hypothetical Interventions in the Presence of Competing Events: Crystalline Silica Exposure and Mortality From 2 Causes of Death.

Exposure to silica has been linked to excess risk of lung cancer and nonmalignant respiratory disease mortality. In this study we estimated risk for both these outcomes in relation to occupational silica exposure as well as the reduction in risk that would result from hypothetical interventions on exposure in a cohort of exposed workers. Analyses were carried out using data from an all-male study population consisting of 2,342 California diatomaceous earth workers regularly exposed to crystalline silica and followed between 1942 and 2011. We estimated subdistribution risk for each event under the natural course and interventions of interest using the parametric g-formula to adjust for healthy-worker survivor bias. The risk ratio for lung cancer mortality, comparing an intervention in which a theoretical maximum exposure limit was set at 0.05 mg/m3 (the current US regulatory limit) with the observed exposure concentrations, was 0.86 (95% confidence interval: 0.63, 1.22). The corresponding risk ratio for nonmalignant respiratory disease mortality was 0.69 (95% confidence interval: 0.52, 0.93). Our findings suggest that risks from both outcomes would have been considerably lower if historical silica exposures in this cohort had not exceeded current regulatory limits.

Exposure-Lag-Response in Longitudinal Studies: Application of Distributed-Lag Nonlinear Models in an Occupational Cohort.

Prolonged exposures can have complex relationships with health outcomes, as timing, duration, and intensity of exposure are all potentially relevant. Summary measures such as cumulative exposure or average intensity of exposure may not fully capture these relationships. We applied penalized and unpenalized distributed-lag nonlinear models (DLNMs) with flexible exposure-response and lag-response functions in order to examine the association between crystalline silica exposure and mortality from lung cancer and nonmalignant respiratory disease in a cohort study of 2,342 California diatomaceous earth workers followed during 1942-2011. We also assessed associations using simple measures of cumulative exposure assuming linear exposure-response and constant lag-response. Measures of association from DLNMs were generally higher than those from simpler models. Rate ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3 during lag years 31-50 prior to the age of observed cases were 1.47 (95% confidence interval (CI): 0.92, 2.35) for lung cancer mortality and 1.80 (95% CI: 1.14, 2.85) for nonmalignant respiratory disease mortality. Rate ratios from the simpler models for the same exposure scenario were 1.15 (95% CI: 0.89, 1.48) and 1.23 (95% CI: 1.03, 1.46), respectively. Longitudinal cohort studies of prolonged exposures and chronic health outcomes should explore methods allowing for flexibility and nonlinearities in the exposure-lag-response.

Occupational silica exposure and mortality from lung cancer and nonmalignant respiratory disease: G-estimation of structural nested accelerated failure time models.

BACKGROUND: Occupational exposure to crystalline silica is known to increase risks of both lung cancer and noninfectious nonmalignant respiratory diseases (NMRD). However, associations between silica exposure and survival times have not been described. METHODS: In a longitudinal cohort of diatomaceous earth workers exposed to crystalline silica (primarily cristobalite) and followed from 1942 to 2011, we applied g-estimation of structural nested accelerated failure time models to adjust for time-varying confounding that could result in healthy worker survivor bias. A continuous measure of exposure was used in analyses estimating the hypothetical effect of banning exposure to silica on survival time. Since a ban is infeasible, sensitivity analyses examined the hypothetical effects of enforcing various Occupational Exposure Limits. RESULTS: The estimated median number of years of life lost per worker (for all natural causes) due to silica exposure was 0.48 (95% confidence interval = 0.02, 1.01). For NMRD deaths, the corresponding estimate was 3.22 (0.82, 7.75) and for lung cancer deaths, 2.21 (0.97, 3.56). Cause-specific estimates were sensitive to the use of weights to adjust for competing events. Lung cancer mortality, which tended to occur at younger ages, was an important competing event for NMRD mortality. Sensitivity analyses supported the main results, but with larger estimates, and suggested that a strict limit would be nearly as effective as a complete ban on silica exposure. CONCLUSIONS: Workplace exposure to crystalline silica in this industry appears to shorten survival times significantly, particularly for those who die of lung cancer or NMRD. More stringent exposure limits are probably warranted.

The Healthy Worker Survivor Effect: Target Parameters and Target Populations.

PURPOSE OF REVIEW: We offer an in-depth discussion of the time-varying confounding and selection bias mechanisms that give rise to the healthy worker survivor effect (HWSE). RECENT FINDINGS: In this update of an earlier review, we distinguish between the mechanisms collectively known as the HWSE and the statistical bias that can result. This discussion highlights the importance of identifying both the target parameter and the target population for any research question in occupational epidemiology. Target parameters can correspond to hypothetical workplace interventions; we explore whether these target parameters' true values reflect the etiologic effect of an exposure on an outcome or the potential impact of enforcing an exposure limit in a more realistic setting. If a cohort includes workers hired before the start of follow-up, HWSE mechanisms can limit the transportability of the estimates to other target populations. We summarize recent publications that applied g-methods to control for the HWSE, focusing on their target parameters, target populations, and hypothetical interventions.