Estimating impacts of reducing acrylonitrile exposure on lung cancer mortality in an occupational cohort with the parametric g-formula.

OBJECTIVES: To inform the potential human carcinogenicity of acrylonitrile, we estimate associations between acrylonitrile exposures and lung cancer mortality in US workers with the objectives of (1) assessing potential for healthy worker survivor bias and (2) adjusting for this bias while assessing the expected lung cancer mortality under different hypothetical occupational exposure limits on acrylonitrile exposure using the parametric g-formula. METHODS: We used data from a cohort of 25 460 workers at facilities making or using acrylonitrile in the USA. We estimated HRs to quantify associations between employment and lung cancer mortality, and exposure and leaving employment. Using the parametric g-formula, we estimated cumulative lung cancer mortality at hypothetical limits on acrylonitrile exposure. RESULTS: Recent and current employment was associated with lung cancer, and exposure was associated with leaving employment, indicating potential for healthy worker survivor bias. Relative to no intervention, reducing the historical exposure under limits of 2.0, 1.0 and 0.45 parts per million would have been expected to reduce lung cancer mortality by age 90 by 4.46 (95% CI 0.78 to 8.15), 5.03 (95% CI 0.96 to 9.11) and 6.45 (95% CI 2.35 to 10.58) deaths per 1000 workers, respectively. A larger lung cancer mortality reduction would be expected under elimination of exposure: 7.21 (95% CI 2.72 to 11.70) deaths per 1000 workers. CONCLUSIONS: Healthy worker survivor bias likely led to underestimation of excess risk. Our results corroborate previous study findings of an excess hazard of lung cancer among the highest exposed workers.

Tip of the iceberg: unveiling the impact on back disorders from cumulative physical job exposure and evaluating bias from the healthy worker effect using a nationwide longitudinal cohort study.

PURPOSE: Longitudinal studies across various sectors with physically demanding jobs are notably absent in back disorder risk research. This study aimed to investigate the relationship between cumulative physical job exposure (PJE) and hospital-diagnosed back disorders among individuals in Denmark. To assess the healthy worker effect, we compared the cumulative risk estimate with results from a naive cross-sectional model ignoring PJE history. METHODS: A nationwide longitudinal cohort study was conducted using Danish registers, encompassing individuals born between 1975 and 1978 and working in 1996. Cumulative PJE was measured with a 10-year look-back period for each year 2006-2017. PJE consisted of lower-body occupational exposures, including the total weight lifted, stand/sit ratio, and the frequency of lifting more than 20 kg per day from a job exposure matrix. Odds ratio for back disorders was estimated for each year and all years combined. RESULTS: The results unveiled a significant 31% increase in the risk of hospital-diagnosed back disorders after 4 years of cumulative PJE. The lowest risk (7%) was observed for incident back disorders with 1 year of exposure, suggesting a healthy worker effect. Nevertheless, this risk is still significantly elevated. This cumulative estimate is fourfold the estimate from the 2006 naive cross section model. CONCLUSION: Our study clearly demonstrates an 31% increase in the risk of hospital-diagnosed back disorders with just 4 years of PJE over a 10-year period. Further, we find that cross-sectional studies strongly underestimate the risk of back disorders due to the healthy worker effect.

Preventing kidney injury among sugarcane workers: promising evidence from enhanced workplace interventions.

OBJECTIVES: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. METHODS: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect. RESULTS: In burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation. CONCLUSION: Kidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised.

Associations between exposure to ethylene oxide, job termination, and cause-specific mortality risk.

BACKGROUND: Previous analyses of mortality were conducted in a large cohort of ethylene oxide (EtO) exposed workers employed at 13 sterilization facilities throughout the U.S. and followed from the start of operation through 1998. Statistically significant elevated mortality was reported from hematopoietic cancer in men and breast cancer in women compared to the general population. Possible healthy worker survivor bias was not addressed. METHODS: To examine survivor bias in this cohort, employment termination was analyzed with statistical models stratified on sex and race that included age, employment duration, and cumulative EtO exposure. To reduce survivor bias employment duration was included in Poisson regression model specifications for estimating standardized mortality ratios for several cancer outcomes. RESULTS: Strong statistically significant effects of unlagged cumulative EtO exposure were observed on rate of employment termination, indicating potential healthy worker survivor effect bias. Adjustment for employment duration in analyses of mortality resulted in statistically significant and stronger associations between cumulative EtO exposure and lung cancer, female breast cancer and hematopoietic cancer. There was a striking reduction in nonmalignant respiratory disease mortality risk with increasing employment duration with a further (nonsignificant) reduction with cumulative EtO, suggesting that EtO itself is driving termination of workers with respiratory morbidity even though the average EtO exposures in this population were generally far below odor and acute irritancy thresholds. CONCLUSIONS: Important survivor bias was present in this EtO cohort and may be present in many occupational settings involving irritant exposures.

Respiratory health, occupation and the healthy worker effect.

BACKGROUND: Workers are exposed to physical, chemical and other hazards in the workplace, which may impact their respiratory health. AIMS: To examine the healthy worker effect in the Canadian working population and to identify the association between occupation and respiratory health. METHODS: Data from four cycles of the Canadian Health Measures Survey were utilized. The current occupation of employed participants was classified into 10 broad categories based on National Occupation Category 2011 codes. Data relating to 15 400 subjects were analysed. RESULTS: A significantly lower proportion of those in current employment than those not in current employment reported respiratory symptoms or diseases or had airway obstruction. Similarly, those currently employed reported better general health and had greater mean values for percent-predicted forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of FVC (FEF25-75%) and FEV1/FVC ratio. Among males, females and older age groups, significant differences were observed for almost all the respiratory outcomes for those in current employment. Those in 'Occupations unique to primary industry' had a significantly greater likelihood of regular cough with sputum and ever asthma and had lower mean values of percent-predicted FEV1/FVC and FEF25-75% than those in 'Management occupations'. Those in 'Health occupations' had the highest proportion of current asthma. CONCLUSIONS: Participants in current employment were healthier than those not in current employment providing further support for the healthy worker effect. Those in 'Occupations unique to primary industry' had an increased risk of adverse respiratory outcomes and reducing workplace exposures in these occupations has the potential to improve their respiratory health.

Structure and Control of Healthy Worker Effects in Studies of Pregnancy Outcomes.

Much of the literature on the healthy worker effect focuses on studies of chronic disease and mortality; however, when studying pregnancy outcomes, these effects might differ because of the short, defined risk periods of most pregnancy outcomes. Three pregnancy-specific healthy worker effects have also been described, but the structure of these effects has not yet been investigated when occupational exposure, and not employment status, is the exposure of interest. We used directed acyclic graphs to examine healthy worker effects in studies of occupational exposures and pregnancy outcomes: the healthy hire effect, the healthy worker survivor effect, the desperation/privilege effect (differential workforce reentry after pregnancy), the reproductively unhealthy worker effect (women with live births leave the workforce, while women with nonlive births do not), and the insecure pregnancy effect (women with adverse pregnancy outcomes reduce their exposures in subsequent pregnancies). Given our assumptions, we conclude that the healthy hire effect, the desperation/privilege effect, the reproductively unhealthy worker effect, and the insecure pregnancy effect result from confounding that can be addressed if data on measured confounders, such as employment status, are available. The presence of the healthy worker survivor effect, however, varies by study design. Different types of healthy worker effects can be present in studies of occupational exposure and pregnancy outcomes, and many of them are easily addressed analytically.

Mortality and cancer incidence among female Australian firefighters.

OBJECTIVES: To investigate the mortality and cancer incidence of female firefighters, a group where there are limited published findings. METHODS: Participating fire agencies supplied records of individual firefighters including the number and type of incidents attended. The cohort was linked to the Australian National Death Index and Australian Cancer Database. Standardised mortality ratios and standardised cancer incidence ratios were calculated separately for paid and volunteer firefighters. Volunteer firefighters were grouped into tertiles by the duration of service and by a number of incidents attended and relative mortality ratios and relative incidence ratios calculated. RESULTS: For volunteer firefighters (n=37 962), the overall risk of mortality and risk from all major causes of death were reduced when compared with the general population whether or not they had ever attended incidents. Volunteer firefighters had a similar cancer incidence when compared with the general population for most major cancer categories. Female volunteer firefighters have usually attended few fires. Of those who had turned out to incidents, only one-third had attended more than 12 fires about half the number for male volunteers. Mortality and cancer incidence for paid female firefighters (n=1682) were similar to the general population but the numbers were small and so power was limited. CONCLUSIONS: Female volunteer firefighters have a cancer incidence similar to the general population but a reduced risk of mortality which is likely to be a result of a 'healthy volunteer' effect.Most of the paid female firefighters were relatively recent recruits and it will be important to monitor the health of this group as more women are recruited to front-line firefighting roles.

Assessment of the healthy worker survivor effect in the relationship between psychosocial work-related factors and hypertension.

OBJECTIVES: The healthy worker survivor effect (HWSE) usually leads to underestimation of the effects of harmful occupational exposures. HWSE is characterised by the concomitance of three associations: (1) job status-subsequent exposure, (2) job status-disease and (3) previous exposure-job status. No study has reported the coexistence of these associations in the relationship between psychosocial work-related factors and health. We assessed if HWSE is present when measuring the effects of cumulative exposure to psychosocial work-related factors on the prevalence of hypertension in white-collar workers. METHODS: Data were obtained from two timepoints (1991-1993 at baseline and 1999-2001 at follow-up) of a prospective cohort study. At baseline, the population was composed of 9188 white-collar employees (women: 49.9%) in Quebec City. Job strain as psychosocial work-related factor and blood pressure were measured using validated methods. Job status (retirees vs employees) at follow-up was self-reported. Multiple multilevel robust Poisson regressions were used to estimate prevalence ratios of hypertension and risk ratios of retirement separately by gender. We performed multiple imputations to control selection bias due to missing values. RESULTS: Retirement eliminated the subsequent exposure to job strain de facto and was associated with the reduction in the prevalence of hypertension in younger (-33%) and older (-11%) men and in older women (-39%). Job strain was associated with job status in younger men and in women of any age. CONCLUSION: Data showed the presence of HWSE in younger men and older women given the coexistence of the three structural associations.

Workload and cross-harvest kidney injury in a Nicaraguan sugarcane worker cohort.

OBJECTIVES: To examine the association between workload and kidney injury in a fieldworker cohort with different levels of physically demanding work over a sugarcane harvest, and to assess whether the existing heat prevention efforts at a leading occupational safety and health programme are sufficient to mitigate kidney injury. METHODS: Biological and questionnaire data were collected before (n=545) and at the end (n=427) of harvest among field support staff (low workload), drip irrigation workers (moderate), seed cutters (high) and burned sugarcane cutters (very high). Dropouts were contacted (87%) and reported the reason for leaving work. Cross-harvest incident kidney injury (IKI) was defined as serum creatinine increase ≥0.30 mg/dL or ≥1.5 times the baseline value, or among dropouts reporting kidney injury leading to leaving work. RESULTS: Mean cross-harvest estimated glomerular filtration rate change was significantly associated with workload, increasing from 0 mL/min/1.73 m2 in the low-moderate category to -5 mL/min/1.73 m2 in the high and -9 mL/min/1.73 m2 in the very high workload group. A similar pattern occurred with IKI, where low-moderate workload had 2% compared with 27% in the very high workload category. A healthy worker selection effect was detected, with 32% of dropouts reporting kidney injury. Fever and C reactive protein elevation were associated with kidney injury. CONCLUSIONS: Workers considered to have the highest workload had more cross-harvest kidney damage than workers with less workload. Work practices preventing heat stress should be strengthened and their role in preventing kidney damage examined further. Future occupational studies on chronic kidney disease of unknown aetiology should account for a healthy worker effect by pursuing those lost to follow-up.

Analysis of the association between ionizing radiation and mortality in uranium workers from five plants involved in the nuclear fuel production cycle in France.

PURPOSE: The aim is to investigate associations between mortality and exposure to ionizing radiation in a cohort of uranium workers with potential for internal and external radiation exposures. METHODS: Workers employed for at least 6 months between 1958 and 2006 in five plants involved in the French nuclear fuel cycle were included and followed up between 1968 and 2013. Cause-specific standardized mortality ratios were calculated. Analyses of associations between individual cumulative radiation dose (both internal and external, lagged by 5-15 years) and mortality were conducted using Poisson regression. RESULTS: The cohort includes 4541 workers. The mean cumulative external dose was 11.12 mGy. Mean cumulative internal doses ranged, depending on modelling hypotheses, from 0.05 to 0.09 mGy (liver) and from 4.22 to 10.90 mGy (lung). At the end of the follow-up, 838 workers were deceased and 28 lost to follow-up. A healthy worker effect was observed. The risk of prostate and lung cancers mortality was significantly higher for workers exposed to cumulative external dose above 50 mGy compared to non-exposed, but these associations were based only on three cases and became non-significant, although of similar magnitude, after adjustment for smoking. Associations with internal dose showed no consistent pattern. CONCLUSIONS: For the first time, a study was conducted in a French cohort of uranium workers with a complete reconstruction of internal dose. Results are preliminary and must be interpreted with caution because of the limited cohort size and significant sources of uncertainty. Future steps of this study will overcome these limitations.

Mortality by cause of death and risk behaviors in farmers versus non-farmers: the importance of avoiding the healthy worker effect.

OBJECTIVES: To compare mortality by cancer sites and by other specific causes of death, and the prevalence of risk behaviors in farmers and non-farmers in Spain. METHODS: Mortality by cause of death was calculated based on a longitudinal study with 10-years follow-up of 9.5 million men and 6 million women aged 20-64 years who were employed in 2001. The prevalence of risk behaviors was calculated from the 2001 National Health Survey in the 6464 employed men and 5573 employed women aged 20-64. The study subjects were grouped as farmers and non-farmers. For each cause of death, we estimated the ratio of age-standardized mortality rates, and for each risk behavior we estimated the age-standardized prevalence ratio in farmers versus non-farmers. RESULTS: In men, the mortality rate for most cancer sites did not differ significantly between farmers and non-farmers, except for cancers of the lip, oral cavity, stomach, larynx and skin epidermoid carcinoma-which was higher in farmers-and cancers of the liver, pancreas and mesothelioma-which was lower in farmers. In contrast, farmers had a higher rate of mortality from most other diseases and from external causes of death. In women, farmers showed lower mortality from lung cancer, breast cancer and chronic lower respiratory disease, and higher mortality from external causes. The prevalence of smoking, excessive alcohol consumption, physical inactivity and obesity was higher in farmers than in non-farmers, except smoking and excessive alcohol consumption in women where prevalence was lower in farmers. CONCLUSIONS: Findings are different from those found in other studies. In men, greater exposure to the sun and the higher prevalence of risk behaviors in farmers could explain their excess mortality from some cancer sites and the other causes of death. However, other factors may be behind this excess risk of mortality from these causes, given that farmers did not show higher mortality from some cancers related to smoking. In women, no differences were observed in mortality rate for majority of causes of death between farmers and non-farmers.

Healthy workers or less healthy leavers? Mortality in military veterans.

BACKGROUND: The 'healthy worker effect' predicts that longer employment is positively associated with reduced mortality, but few studies have examined mortality in military veterans irrespective of exposure to conflict. AIMS: To examine mortality in a large national cohort of Scottish veterans by length of service. METHODS: Retrospective cohort study comparing survival in up to 30-year follow-up among 57 000 veterans and 173 000 people with no record of service, matched for age, sex and area of residence, who were born between 1945 and 1985. We compared antecedent diagnoses in the two groups to provide information on probable risk factors. RESULTS: By the end of follow-up, 3520 (6%) veterans had died, compared with 10 947 (6%) non-veterans. Cox proportional hazard analysis confirmed no significant difference overall unadjusted or after adjusting for deprivation. On subgroup analysis, those who left prematurely (early service leavers) were at significantly increased risk of death (hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.09-1.24, P < 0.001), although the increase became non-significant after adjusting for socioeconomic status (HR 1.05, 95% CI 0.99-1.12). Longer-serving veterans were at significantly lower risk of death than non-veterans; the risk decreased both with length of service and in more recent birth cohorts. Smoking-related disease was the greatest contributor to increased mortality in early leavers. CONCLUSIONS: Among longer-serving veterans, there was evidence of a HWE partly attributable to selective attrition of early service leavers, but birth cohort analysis suggests improvements over time which may also reflect a causal effect of improved in-service health promotion.

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.

Mortality in a cohort of Danish firefighters; 1970-2014.

PURPOSE: Occupational exposure of firefighters involves a complex range of potential health threats from toxic chemicals, shift work, extreme heat, physical and emotional strain. The aim of this study is to examine overall and disease-specific mortality among Danish firefighters. METHODS: Through systematic collection of personnel and membership records from employers and trade unions, past and present male Danish firefighters were identified (n = 11,775). Using the unique Danish personal identification number, information on additional employment, vital status and cause of death was linked to each member of the cohort from the Supplementary Pension Fund Register, the Danish Civil Registration System and the Danish Register of Causes of Death. Standardized mortality ratios (SMRs) were calculated for specific causes of death using rates for two reference groups, a random sample of the male working population (n = 262,168) and the military (n = 396,739), respectively. RESULTS: Overall mortality was significantly reduced among the firefighters compared to both the sample of the working population and the military (SMR 0.74, 95% CI 0.69-0.78 and SMR 0.88, 95% CI 0.83-0.93). Further, the SMRs for endocrine diseases, mental disorders, non-traffic related accidents and other external causes were significantly lower against both reference groups. Death from stomach cancer was significantly increased among the full time firefighters, while part time/volunteer workers shared a significant increase in prostate cancer death compared to both references. CONCLUSIONS: Despite potential exposure to several occupational hazards, male Danish firefighters have a lower mortality than both the Danish working population in general and Danish military employees.

The Effect of Employment Status in Postdisaster Recovery: A Longitudinal Comparative Study Among Employed and Unemployed Affected Residents.

Population studies have shown that employed adults are healthier than unemployed adults. In this study, we examined whether this "healthy worker effect" is relevant in postdisaster mental health by examining whether trauma-exposed employed individuals have lower postdisaster initial mental health problems and/or whether they recover faster than trauma-exposed unemployed individuals. We compared the course of postevent intrusion and avoidance reactions, anxiety, depression, and sleeping difficulties of employed residents (n = 291) and unemployed residents (n = 269) affected by a fireworks disaster in a residential area of Enschede, The Netherlands. Measurements took place at 2-3 weeks (T1), 18 months (T2), and 4 years (T3) postdisaster. We used linear mixed-effect models to examine the course of mental health problems. Employment status was relevant, to a degree, in posttrauma recovery; although affected employed residents had significantly lower levels of mental health problems (initially and over time) than the unemployed, ds = 0.41-0.72, the recovery rate was the same for both groups. At T1 (neglecting the DSM 1-month criterion), T2, and T3, the prevalence of probable posttraumatic stress disorder was 45.4%, 18.9%, and 11%, respectively, among employed individuals, and 70.1%, 32.5%, and 30% among unemployed individuals. We concluded that research into the mental health of disaster victims should take employment status into account. Regarding postdisaster care, unemployed individuals may need special attention; although they may recover at the same rate as employed individuals, they suffer from more severe mental health problems, even years after the disaster.

External-cause mortality among 21 609 Norwegian male military peacekeepers deployed to Lebanon between 1978 and 1998.

OBJECTIVE: To investigate external-cause mortality among 21 609 Norwegian male military peacekeepers deployed to Lebanon during 1978-1998. METHODS: The cohort was followed from the 1st day of deployment through 2013, and mortality during deployment and post discharge was assessed using SMRs calculated from national rates in Norway. Poisson regression was used to see the effect of high-conflict versus low-conflict exposure. RESULTS: For the total cohort, external-cause mortality was within expected values during deployment (SMR=0.80) and post discharge (SMR=1.05). In the low-conflict exposure group, a lower mortality from all external causes (SMR=0.77), transport accidents (SMR=0.55) and accidental poisoning (SMR=0.53) was seen. The high-conflict exposure group showed an elevated mortality from all external causes (SMR=1.20), transport accidents (SMR=1.51) and suicide (SMR=1.30), but these risks were elevated only during the first 5 years after discharge. This group also showed elevated mortality from all external causes (rate ratio, RR=1.49), and for transport accidents (RR=3.30) when compared with the low-conflict exposure group. CONCLUSIONS: Overall external-cause mortality among our peacekeepers was equal to national rates during deployment and post discharge. High-conflict exposure was associated with elevated mortality from all external causes, transport accidents and suicide during the first 5 years after discharge from service.

Assessment of the healthy worker survivor effect in cancer studies of the United Autoworkers-General Motors cohort.

OBJECTIVE: The healthy worker survivor effect (HWSE) can affect the validity of occupational studies when data are analysed incorrectly. HWSE depends on three underlying conditions: (1) leaving work predicts future exposure, (2) leaving work is associated with disease outcome and (3) prior exposure increases probability of leaving work. If all these conditions are satisfied, then employment status is a time-varying confounder affected by prior exposure, and standard regression will produce bias. We assessed these conditions for cancer outcomes in a cohort of autoworkers exposed to metalworking fluids (MWF). METHODS: The cohort includes 31 485 workers followed for cancer incidence from 1985 to 1994. As occupational exposures to straight, soluble and synthetic MWFs are necessarily zero after leaving work, condition (1) is satisfied. Cox models for cancer incidence and for employment termination were used to assess conditions (2) and (3), respectively. Employment termination by select ages was examined to better gauge the presence of condition (2). RESULTS: The HR for leaving work as a predictor of all cancers combined and prostate cancer was null, but elevated for lung and colorectal cancers among men. Condition (2) was more clearly satisfied for all cancer outcomes when leaving work occurred by age 50. Higher exposures to all three MWF types were associated with increased rates of leaving work (condition (3)), with the exception of straight MWF among women. CONCLUSIONS: We found evidence for the structural conditions underlying HWSE in a cohort of autoworkers. G-methods should be applied to reduce HWSE bias in studies of all cancers presently examined.

Mortality in a combined cohort of uranium enrichment workers.

OBJECTIVE: To examine the patterns of cause-specific mortality and relationship between internal exposure to uranium and specific causes in a pooled cohort of 29,303 workers employed at three former uranium enrichment facilities in the United States with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Internal comparison of the dose-response relation between selected outcomes and estimated organ doses was evaluated using regression models. RESULTS: External comparison with the U.S. population showed significantly lower SMRs in most diseases in the pooled cohort. Internal comparison showed positive associations of absorbed organ doses with multiple myeloma, and to a lesser degree with kidney cancer. CONCLUSION: In general, these gaseous diffusion plant workers had significantly lower SMRs than the U.S. POPULATION: The internal comparison however, showed associations between internal organ doses and diseases associated with uranium exposure in previous studies. Am. J. Ind. Med. 60:96-108, 2017. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Occupational Diesel Exposure, Duration of Employment, and Lung Cancer: An Application of the Parametric G-Formula.

BACKGROUND: If less healthy workers terminate employment earlier, thus accumulating less exposure, yet remain at greater risk of the health outcome, estimated health effects of cumulative exposure will be biased downward. If exposure also affects termination of employment, then the bias cannot be addressed using conventional methods. We examined these conditions as a prelude to a reanalysis of lung cancer mortality in the Diesel Exhaust in Miners Study. METHODS: We applied an accelerated failure time model to assess the effect of exposures to respirable elemental carbon (a surrogate for diesel) on time to termination of employment among nonmetal miners who ever worked underground (n = 8,307). We then applied the parametric g-formula to assess how possible interventions setting respirable elemental carbon exposure limits would have changed lifetime risk of lung cancer, adjusting for time-varying employment status. RESULTS: Median time to termination was 36% shorter (95% confidence interval = 33%, 39%), per interquartile range width increase in respirable elemental carbon exposure. Lung cancer risk decreased with more stringent interventions, with a risk ratio of 0.8 (95% confidence interval = 0.5, 1.1) comparing a limit of ≤25 µg/m respirable elemental carbon to no intervention. The fraction of cases attributable to diesel exposure was 27% in this population. CONCLUSIONS: The g-formula controlled for time-varying confounding by employment status, the signature of healthy worker survivor bias, which was also affected by diesel exposure. It also offers an alternative approach to risk assessment for estimating excess cumulative risk, and the impact of interventions based entirely on an observed population.

Mortality (1968-2008) in a French cohort of uranium enrichment workers potentially exposed to rapidly soluble uranium compounds.

OBJECTIVES: Until recently, enrichment of uranium for civil and military purposes in France was carried out by gaseous diffusion using rapidly soluble uranium compounds. We analysed the relationship between exposure to soluble uranium compounds and exposure to external γ-radiation and mortality in a cohort of 4688 French uranium enrichment workers who were employed between 1964 and 2006. METHODS: Data on individual annual exposure to radiological and non-radiological hazards were collected for workers of the AREVA NC, CEA and Eurodif uranium enrichment plants from job-exposure matrixes and external dosimetry records, differentiating between natural, enriched and depleted uranium. Cause-specific mortality was compared with the French general population via standardised mortality ratios (SMR), and was analysed via Poisson regression using log-linear and linear excess relative risk models. RESULTS: Over the period of follow-up, 131 161 person-years at risk were accrued and 21% of the subjects had died. A strong healthy worker effect was observed: all causes SMR=0.69, 95% CI 0.65 to 0.74. SMR for pleural cancer was significantly increased (2.3, 95% CI 1.06 to 4.4), but was only based on nine cases. Internal uranium and external γ-radiation exposures were not significantly associated with any cause of mortality. CONCLUSIONS: This is the first study of French uranium enrichment workers. Although limited in statistical power, further follow-up of this cohort, estimation of internal uranium doses and pooling with similar cohorts should elucidate potential risks associated with exposure to soluble uranium compounds.