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OBJECTIVES: The association between asbestos exposure and asbestosis in high-exposed industrial cohorts is well-known, but there is a lack of knowledge about the exposure–response relationship for asbestosis in a general working population setting. We examined the exposure–response relationship between occupational asbestos exposure and asbestosis in asbestos-exposed workers of the Danish general working population. METHODS: We followed all asbestos-exposed workers from 1979 to 2015 and identified incident cases of asbestosis using the Danish National Patient Register. Individual asbestos exposure was estimated with a quantitative job exposure matrix (SYN-JEM) from 1976 onwards and back-extrapolated to age 16 for those exposed in 1976. Exposure–response relations for cumulative exposure and other exposure metrics were analyzed using a discrete time hazard model and adjusted for potential confounders. RESULTS: The range of cumulative exposure in the population was 0.001 to 18 fibers per milliliter-year (f/ml-year). We found increasing incidence rate ratios (IRR) of asbestosis with increasing cumulative asbestos exposure with a fully adjusted IRR per 1 f/ml-years of 1.18 [95% confidence interval (CI) 1.15– -1.22]. The IRR was 1.94 (95% CI 1.53–2.47) in the highest compared to the lowest exposure tertile. We similarly observed increasing risk with increasing cumulative exposure in the inception population. CONCLUSIONS: This study found exposure–response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population with mainly low-level exposed occupations, but there is some uncertainty regarding the exposure levels.

OBJECTIVES: This study aimed to estimate the validity of self-reported information on ever-night shift work among women with and without breast cancer and illustrate the consequences for breast cancer risk estimates. METHODS: During 2015–2016, 225 women diagnosed with breast cancer and 1800 matched controls without breast cancer employed within the Danish hospital regions during 2007–2016 participated in a questionnaire-based survey. Their reported night shift work status was linked with objective payroll register day-by-day working hour data from the Danish Working Hour Database and the Danish Cancer Registry. For the breast cancer patients and their matched controls, we estimated sensitivity and specificity for ever-working night shifts using the payroll data as the gold standard. We also used quantitative bias analysis to estimate the impact on relative risk estimates for a hypothetical population. RESULTS: For breast cancer patients, we observed a sensitivity of ever-night shifts of 86.2% and a specificity of never-night shifts of 82.6%. For controls, the sensitivity was 80.6% and the specificity 83.7%. Odds ratio for breast cancer in a hypothetical population decreased from 1.12 [95% confidence interval (CI) 1.03–1.21] to 1.05 (95% CI 0.95–1.16) when corrected by the sensitivity and specificity estimates. CONCLUSION: This study shows that female breast cancer patients had slightly better recall of previous night shift work than controls. Additionally, both breast cancer patients and controls recalled previous never-night shift work with low specificity. The net effect of this misclassification is a small over-estimation of the relative breast cancer risk due to night shift work.

OBJECTIVES: This study investigates the associations between the Danish version of a job exposure matrix for COVID-19 (COVID-19-JEM) and Danish register-based SARS-CoV-2 infection information across three waves of the pandemic. The COVID-19-JEM consists of four dimensions on transmission: two on mitigation measures, and two on precarious work characteristics. METHODS: The study comprised 2 021 309 persons from the Danish working population between 26 February 2020 and 15 December 2021. Logistic regression models were applied to assess the associations between the JEM dimensions and overall score and SARS-CoV-2 infection across three infection waves, with peaks in March–April 2020, December–January 2021, and February–March 2022. Sex, age, household income, country of birth, wave, residential region and during wave 3 vaccination status were accounted for. RESULTS: Higher risk scores within the transmission and mitigation dimensions and the overall JEM score resulted in higher odds ratios (OR) of a SARS-CoV-2 infection. OR attenuated across the three waves with ranges of 1.08–5.09 in wave 1, 1.06–1.60 in wave 2, and 1.05–1.45 in those not (fully) vaccinated in wave 3. In wave 3, no associations were found for those fully vaccinated. In all waves, the two precarious work dimensions showed weaker or inversed associations. CONCLUSIONS: The COVID-19-JEM is a promising tool for assessing occupational exposure to SARS-CoV-2 and other airborne infectious agents that mainly spread between people who are in close contact with each other. However, its usefulness depends on applied restrictions and the vaccination status in the population of interest.

OBJECTIVE: This study aimed to quantify the risk of COVID-19-related hospital admission in spouses living with partners in at-risk occupations in Denmark during 2020–21.METHODS: Within a registry-based cohort of all Danish employees (N=2 451 542), we identified cohabiting couples, in which at least one member (spouse) held a job that according to a job exposure matrix entailed low risk of occupational exposure to SARS-CoV-2 (N=192 807 employees, 316 COVID-19 hospital admissions). Risk of COVID-19-related hospital admission in such spouses was assessed according to whether their partners were in jobs with low, intermediate or high risk for infection. Overall and sex-specific incidence rate ratios (IRR) of COVID-19-related hospital admission were computed by Poisson regression with adjustment for relevant covariates.RESULTS: The risk of COVID-19-related hospital admission was increased among spouses with partners in high-risk occupations [adjusted IRR (IRRadjadjadjCONCLUSIONS: SARS-CoV-2 transmission at the workplace may pose an increased risk of severe COVID-19 among spouses in low-risk jobs living with partners in high-risk jobs, which emphasizes the need for preventive measures at the workplace in future outbreaks of epidemic contagious disease. When available, effective vaccines seem essential.

OBJECTIVE: Mounting evidence indicates increased risk of COVID-19 among healthcare personnel, but the evidence on risks in other occupations is limited. In this study, we quantify the occupational risk of COVID-19-related hospital admission in Denmark during 2020–2021. METHODS: The source population included 2.4 million employees age 20–69 years. All information was retrieved from public registers. The risk of COVID-19 related hospital admission was examined in 155 occupations with at least 2000 employees (at-risk, N=1 620 231) referenced to a group of mainly office workers defined by a COVID-19 job exposure matrix (N=369 341). Incidence rate ratios (IRR) were computed by Poisson regression. RESULTS: During 186 million person-weeks of follow-up, we observed 2944 COVID-19 related hospital admissions in at-risk occupations and 559 in referents. Adjusted risk of such admission was elevated in several occupations within healthcare (including health care assistants, nurses, medical practitioners and laboratory technicians but not physiotherapists or midwives), social care (daycare assistants for children aged 4–7, and nursing aides in institutions and private homes, but not family daycare workers) and transportation (bus drivers, but not lorry drivers). Most IRR in these at-risk occupations were in the range of 1.5–3. Employees in education, retail sales and various service occupations seemed not to be at risk. CONCLUSION: Employees in several occupations within and outside healthcare are at substantially increased risk of COVID-19. There is a need to revisit safety measures and precautions to mitigate viral transmission in the workplace during the current and forthcoming pandemics.

OBJECTIVE: Assuming that preventive measures to mitigate viral transmission of SARS-CoV-2 at the workplace may have been improved in the course of the COVID-19 pandemic, we examined the occupational risk of COVID-19 related hospital admission across the four pandemic waves in Denmark between week 8, 2020, and week 50, 2021. METHODS: The study included 4416 cases of COVID-19 related hospital admissions among 2.4 million Danish employees aged 20–69 with follow-up in 2020 through 2021. At-risk industrial sectors and a reference population were defined a priory by a job-exposure matrix on occupational risk for COVID-19. Incidence rate ratios (IRR) and potential effect modification by pandemic wave were computed with Poisson regression adjusted for demographic, social and health factors including completed COVID-19 vaccination. RESULTS: We observed an overall elevated relative risk in four of six at-risk industrial sectors, but the pandemic wave only modified the risk among healthcare employees, where the excess risk from a high initial level declined to background levels during the latest waves in models not adjusting for COVID-19 vaccination. In social care, education and transport, the elevated risk was not modified by pandemic wave. CONCLUSION: Danish healthcare employees were to some extent protected against occupational transmission of SARS-CoV-2 during the two last pandemic waves even though the absolute risk conferred by occupation may not have been eliminated. Early vaccination of this group seems not to be the only explanation. The risk in other sectors remained elevated indicating a need to revisit preventive measures.

OBJECTIVES: This discussion paper aims to provide scientifically based recommendations on night shift schedules, including consecutive shifts, shift intervals and duration of shifts, which may reduce health and safety risks. Short-term physiological effects in terms of circadian disruption, inadequate sleep duration and quality, and fatigue were considered as possible links between night shift work and selected health and safety risks, namely, cancer, cardio-metabolic disease, injuries, and pregnancy-related outcomes. METHOD: In early 2020, 15 experienced shift work researchers participated in a workshop where they identified relevant scientific literature within their main research area. RESULTS: Knowledge gaps and possible recommendations were discussed based on the current evidence. The consensus was that schedules which reduce circadian disruption may reduce cancer risk, particularly for breast cancer, and schedules that optimize sleep and reduce fatigue may reduce the occurrence of injuries. This is generally achieved with fewer consecutive night shifts, sufficient shift intervals, and shorter night shift duration. CONCLUSIONS: Based on the limited, existing literature, we recommend that in order to reduce the risk of injuries and possibly breast cancer, night shift schedules have: (i) ≤3 consecutive night shifts; (ii) shift intervals of ≥11 hours; and (iii) ≤9 hours shift duration. In special cases – eg, oil rigs and other isolated workplaces with better possibilities to adapt to daytime sleep – additional or other recommendations may apply. Finally, to reduce risk of miscarriage, pregnant women should not work more than one night shift in a week.

OBJECTIVES: This study aimed to examine the association between job strain and incident coronary heart disease (CHD) in Denmark, while accounting for changes of job strain. METHODS: We included all employees residing in Denmark in 2000, aged 30–59 years with no prevalent CHD (N=1 660 150). We determined exposure to job strain from 1996–2009 using a job exposure matrix (JEM) with annual updates. Follow-up for incident CHD was from 2001–2010 via linkage to health records. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between job strain and incident CHD. RESULTS: During 16.1 million person-years, we identified 24 159 incident CHD cases (15.0 per 10 000 person-years). After adjustment for covariates, job strain in 2000 predicted onset of CHD during a mean follow-up of 9.71 years (HR 1.10, 95% CI 1.07–1.13). When analyzing changes in job strain from one year to the next and CHD in the subsequent year, persistent job strain (HR 1.07, 95% CI 1.03–1.10), onset of job strain (HR 1.20, 95% CI 1.12–1.29) and removal of strain (HR 1.20, 95% CI 1.12–1.28) were associated with higher CHD incidence compared to persistent no job strain. Associations were similar among men and women. CONCLUSIONS: Job strain is associated with a higher risk of incident CHD in Denmark. As we used a JEM, we can rule out reporting bias. However, under- or overestimation of associations is possible due to non-differential misclassification of job strain and residual confounding by socioeconomic position.

Unusual clusters and outbreaks of reproductive disorders during past decades remind us of the devastating health consequences and human suffering to which exposure to industrial chemicals and pharmaceuticals may give rise. Birth defects caused by gestational exposure to thalidomide, vaginal cancer by diethylstilbestrol, azoospermia by dibromochloropropane, cerebral palsy by methyl mercury, and fetal wasting syndrome by chlorinated biphenyls are all inscribed in medical history as tragic mementos of ignorance and neglect in the past (1). In parallel with the fast-increasing entrance of women into the workforce, interest in occupational reproductive hazards accelerated in the Nordic countries in the 1970s and 80s. Women working in healthcare, industry, and agriculture are potentially exposed to high levels of chemicals, resulting in possibly substantial risk of toxicity to their unborn child. Systematic epidemiologic research addressing reproductive hazards at the workplace has fostered thousands of papers from the 1980s to present day. Reports of associations between a large range of exposures and reproductive outcomes spanning infertility, adverse pregnancy outcomes, and childhood cancer and cognitive impairment are abundant. Many studies suggest that in particular organic solvents, pesticides and heavy metals are occupational reproductive hazards, but – with noteworthy exceptions – few specific exposures survive critical systematic review to become established reproductive toxicants in the workplace (2). The introduction of the endocrine disruption hypothesis more than 20 years ago has dramatically renewed interest in reproductive toxicity and provided a new framework for research with its focus on a genuine mechanism for toxic effects related to disruption of endogenous hormone homeostasis. Initially it was thought that toxicants interfere with fetal development by mimicking or enhancing effects of natural estradiol (3), but, as evidence accumulated, the hypothesis became much broader. A capacious amount of experimental studies have demonstrated that adverse reproductive outcomes may be related to endocrine disruption of fetal development through xenobiotic interaction with several types of hormone receptors or through interference with synthesis, secretion, transport, metabolism, or degradation of natural hormones (4). If this results in pathologic outcomes, it is not always obvious, and the relevance for human exposure scenarios remain hypothetical (5). Concern increased as it became evident that virtually all people across the globe host in their bodies not only biopersistent organic pollutants such as DDT and PCBs but also substances with shorter biological half-lives that do not accumulate, such as phthalates (4). The European Chemicals Agency defines endocrine disruptors as chemicals where at least one study has shown not necessarily pathologic or adverse endocrine effects in an intact organism (typically small rodents). The list of such chemicals has become steadily more voluminous and heterogenous and now embraces many of the compounds that have been extensively studied earlier without reference to endocrine disruption – such as organic solvents, cytotoxic drugs, many pesticides, metals, and polyaromatic hydrocarbons (6). Already in 1999, an editorial advocated for the need to address reproductive toxicity of endocrine disrupting chemicals at the workplace (7), but – in contrast to many studies on exposures in the general environment – to date only few epidemiological studies explicitly addressing endocrine disruption at the workplace have been published (8–14). Therefore, the study by Shirangi and colleagues in this issue of The Scandinavian Journal of Work, Environment and Health is highly welcomed (15). They report associations between occupational exposure to endocrine disrupting chemicals during pregnancy and risk of impaired fetal growth in an English prospective birth cohort, including some 4000 pregnant women. A job exposure matrix (JEM) was used to assess exposure. Substantially elevated relative risks of 3–5 are reported for two of seven classes of endocrine disrupting chemicals – pesticides and phthalates – while no increased risk was found for organic solvents, metals and other exposures. Besides the prospective design, important strengths of this study include a high response and an impressive amount of detailed data on numerous potentially confounding factors, which are accounted for in analyses. The study is also innovative in its use of optimal birth weight in terms of the ratio of observed-to-predicted birth weight as an alternative measure of fetal growth (16). The predicted birth weight was derived from the birthweight distribution among singleton Caucasians without known pathological determinants, such as smoking and birth defects, and was standardized according to gestational age, fetal gender, maternal height, and parity (17). The optimal birth weight measure is less dependent on an appropriate reference population than the traditional small-for-gestational-age measure but neither accounts for ethnicity (almost 30% was of South Asian origin) nor solves the problem of potential collider bias, which is introduced by standardization on gestational age (18). Although Shirangi et al`s study is supported by findings in few earlier studies (9,10), it is reasonable to ask whether we have reached a point where sufficient evidence has accumulated that allows us to provide specific recommendations to work and health authorities. One crucial issue is exposure assessment. Shirangi et al used a qualitative expert-rated JEM tabulating groups of jobs into unlikely, possible, or probable exposure to one or more of ten classes of endocrine disrupting chemicals. JEM may be powerful tools to obtain complete data on exposure without risk of recall bias and at low cost (19, 20) – in particular when a crude exposure assignment based on groups of job titles can be refined by access to individual data on industries and job tasks as in the Shirangi et al study. However, occupational exposure to some endocrine disrupting chemicals, such as phthalates and bisphenol A, has only been quantified by workplace and biological measurement to a very limited extent (21, 22). For example, hairdressers and cosmetologists are the most prevalent occupations exposed to phthalates according to the endocrine disruption JEM, but this finding has not been documented by ambient air, skin or biological samples showing that these occupations do confer an exposure exceeding the background exposure (23, 24). Since phthalate metabolites are detectable in urine in almost everybody, sources of exposure other than occupational are important. Measurements of occupational exposure and validation of the endocrine disruption JEM by quantitative data is therefore highly warranted. Other occupational exposures, such as pesticides, solvents and metals, are much better documented by workplace measurements, thus their respective JEM may be more valid – in particular when a JEM either provides estimates of exposure to specific compounds or classes of compounds that share mechanism of action, toxic potency and kinetics. The above definition of an endocrine disruptor is far too broad to fulfil this criterion. We need exposure–response data to evaluate causality and provide a basis for regulation and prevention. To obtain exposure–response data, we probably have to get information on specific compounds or group of compounds known to operate by similar mechanism. At present we do not know if current occupational threshold limits for organic solvents, metals and pesticides need to be updated with data on endocrine activity and whether some exposure time windows are more sensitive than others. Numerous large birth cohorts have been established in Europe over the past 20 years (25), and many of these are designed to examine effects of environmental and occupational exposures (26, 27). It has become feasible to include a whole range of new outcomes that perhaps are more sensitive to endocrine disruption by chemicals during fetal life compared to outcomes observed at birth – for instance premature or delayed puberty (28, 29), infertility in young people (30), and airways disorders (31) The health consequences of reproductive hazards at the workplace may be grave for the individual and society. Ensuring a working environment that protects reproductive health must be a high priority. With reference to the precautionary principle, it may be tempting to exclude pregnant women from work that may carry the slightest theoretical risk. But this approach may have strong social and economic consequences for the women who thus do not necessarily benefit from the doubt. We need to know more. While experimental studies are important for risk assessment, we rely on epidemiology to address real world occupational exposure scenarios. Epidemiological methods and populations are available, but to ensure progress we need provision of resources to refine assessment of occupational exposure to endocrine disrupting chemicals by ambient air and biological measurements. The author thanks Karin Sørig Hougaard, Sandra Tøttenborg, Vivi Schlünssen and Alex Burdorf for their thoughtful comments to the initial draft. References 1. Kalter H. Teratology in the 20th century: environmental causes of congenital malformations in humans and how they were established. Neurotoxicol Teratol. 2003;25(2):131-282. https://doi.org/10.1016/S0892-0362(03)00010-2 2. Burdorf A, Figa-Talamanca I, Jensen TK, Thulstrup AM. Effects of occupational exposure on the reproductive system: core evidence and practical implications. Occup Med (Lond). 2006;56(8):516-20. https://doi.org/10.1093/occmed/kql113 3. Sharpe RM, Skakkebæk NE. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? The Lancet. 1993;341:1392-5. https://doi.org/10.1016/0140-6736(93)90953-E 4. Bergman A, Heindel JJ, Kasten T, Kidd KA, Jobling S, Neira M, et al. The impact of endocrine disruption: a consensus statement on the state of the science. Environ Health Perspect. 2013;121(4):A104-6. https://doi.org/10.1289/ehp.1205448 5. Lamb JC, Boffetta P, Foster WG, Goodman JE, Hentz KL, Rhomberg LR, Staveley J, Swaen G, Van Der Kraak G, Williams AL. Critical comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals – 2012. Regul Toxicol Pharmacol 2014;69:22-40. https://doi.org/10.1016/j.yrtph.2014.02.002 6. Caserta D, Mantovani A, Marci R, Fazi A, Ciardo F, La Rocca C, et al. Environment and women’s reproductive health. Hum Reprod Update. 2011;17(3):418-33. https://doi.org/10.1093/humupd/dmq061 7. Burdorf A, Nieuwenhuijsen MJ. Endocrine disrupting chemicals and human reproduction: fact or fiction? Ann Occup Hyg. 1999;43(7):435-7. https://doi.org/10.1016/S0003-4878(99)00083-6 8. Snijder CA, Heederik D, Pierik FH, Hofman A, Jaddoe VW, Koch HM, et al. Fetal growth and prenatal exposure to bisphenol A: the generation R study. Environ Health Perspect. 2013;121(3):393-8. https://doi.org/10.1289/ehp.1205296 9. Snijder CA, Roeleveld N, te Velde E, Steegers EA, Raat H, Hofman A, et al. Occupational exposure to chemicals and fetal growth: the Generation R Study. Hum Reprod. 2012;27(3):910-20. https://doi.org/10.1093/humrep/der437 10. Birks L, Casas M, Garcia AM, Alexander J, Barros H, Bergström A, et al. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: A European meta-analysis. Environ Health Perspect. 2016;124(11):1785-93. https://doi.org/10.1289/EHP208 11. 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The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis. Hum Reprod Update. 2016; 23(1):104-125. https://doi.org/10.1093/humupd/dmw036 15. Shirangi A, Wright J, Blair EM, McEachan RR, Nieuwenhuijsen MJ. Occupational chemical exposures in pregnancy and fetal growth: evidence from the Born in Bradford Study. Scand J Work Environ Health. 2020;46(4):417–428. https://doi.org/10.5271/sjweh.3878 16. Wilcox MA, Johnson IR, Maynard PV, Smith SJ, Chilvers CE. The individualised birthweight ratio: a more logical outcome measure of pregnancy than birthweight alone. Brit J Obst Gyn. 1993;100(4):342-7. https://doi.org/10.1111/j.1471-0528.1993.tb12977.x 17. Blair EM, Liu Y, de Klerk NH, Lawrence DM. Optimal fetal growth for the Caucasian singleton and assessment of appropriateness of fetal growth: an analysis of a total population perinatal database. BMC Ped. 2005;5(1):13. https://doi.org/10.1186/1471-2431-5-13 18. Basso O, Wilcox AJ. Might rare factors account for most of the mortality of preterm babies? Epidemiol. 2011;22(3):320-7. https://doi.org/10.1097/EDE.0b013e31821266c5 19. Spinder N, Prins JR, Bergman JEH, Smidt N, Kromhout H, Boezen HM, et al. Congenital anomalies in the offspring of occupationally exposed mothers: a systematic review and meta-analysis of studies using expert assessment for occupational exposures. Hum Reprod. 2019;34(5):903-19. https://doi.org/10.1093/humrep/dez033 20. Tielemans E, Heederik D, Burdorf A, Vermeulen R, Veulemans H, Kromhout H, et al. Assessment of occupational exposures in a general population: comparison of different methods. Occup Environ Med. 1999;56(3):145-51. https://doi.org/10.1136/oem.56.3.145 21. Hines CJ, Jackson MV, Deddens JA, Clark JC, Ye X, Christianson AL, et al. Urinary Bisphenol A (BPA) Concentrations among Workers in Industries that Manufacture and Use BPA in the USA. Ann Work Expo Health. 2017;61(2):164-82. https://doi.org/10.1093/annweh/wxw021 22. Hines CJ, Nilsen Hopf NB, Deddens JA, Calafat AM, Silva MJ, Grote AA, et al. Urinary phthalate metabolite concentrations among workers in selected industries: a pilot biomonitoring study. Ann Occup Hyg. 2009;53(1):1-17. 23. Labrèche F, Forest J, Trottier M, Lalonde M, Simard R. Characterization of chemical exposures in hairdressing salons. App Occup Environ Hyg. 2003;18(12):1014-21. https://doi.org/10.1080/10473220390244667 24. Kopelovich L, Perez AL, Jacobs N, Mendelsohn E, Keenan JJ. Screening-level human health risk assessment of toluene and dibutyl phthalate in nail lacquers. Food Chem Toxicol. 2015;81:46-53. https://doi.org/10.1016/j.fct.2015.04.011 25. Bousquet J, Anto J, Sunyer J, Nieuwenhuijsen M, Vrijheid M, Keil T. Pooling birth cohorts in allergy and asthma: European Union-funded initiatives - a MeDALL, CHICOS, ENRIECO, and GA(2)LEN joint paper. Int Arch Allergy Immunol. 2013;161(1):1-10. https://doi.org/10.1159/000343018 26. Govarts E, Nieuwenhuijsen M, Schoeters G, Ballester F, Bloemen K, de BM, et al. Prenatal Exposure to Polychlorinated Biphenyls (PCB) and Dichlorodiphenyldichloroethylene (DDE) and Birth Weight: A Meta-analysis within 12 European Birth Cohorts. Environ Health Perspect. 2012;120(2):162-70. https://doi.org/10.1289/ehp.1103767 27. Vrijheid M, Casas M, Bergstrom A, Carmichael A, Cordier S, Eggesbo M, et al. European birth cohorts for environmental health research. Environ Health Perspect. 2012;120(1):29-37. https://doi.org/10.1289/ehp.1103823 28. Ernst A, Brix N, Lauridsen LLB, Olsen J, Parner ET, Liew Z, et al. Exposure to Perfluoroalkyl Substances during Fetal Life and Pubertal Development in Boys and Girls from the Danish National Birth Cohort. Environ Health Perspect. 2019;127(1):17004. https://doi.org/10.1289/EHP3567 29. Ernst A, Brix N, Lauridsen LLB, Strandberg-Larsen K, Bech BH, Nohr EA, et al. 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OBJECTIVE: This review aimed to examine systematically the epidemiological evidence linking work-related exposure to violence and threats thereof with risk of mental disorders and mental ill-health symptoms. METHODS: We searched PubMed, EMBASE, PsycINFO and Web of Science to identify original studies that provide quantitative risk estimates. The evidence was weighted according to completeness of reporting, potential common method bias, and bias due to differential selection and drop out, selective reporting, and misclassification of exposure and outcome. RESULTS: We identified 14 cross-sectional and 10 cohort studies with eligible risk estimates, of which 4 examined depressive disorder and reported an elevated risk among the exposed [pooled relative risk (RR) 1.42, 95% confidence interval (CI) 1.31–1.54, I^2=0%]. The occurrence of depressive and anxiety symptoms, burnout and psychological distress was examined in 17 studies (pooled RR 2.33, 95% CI 3.17, I^2=42%), and 3 studies examined risk of sleep disturbance (pooled RR 1.22, 95% CI 1.09–1.37, I2=0%). In most studies, common method bias and confounding could not be ruled out with confidence and strong heterogeneity in most outcome definitions invalidate the strict interpretation of most pooled risk estimates. CONCLUSION: The reviewed studies consistently indicate associations between workplace violence and mental health problems. However, due to methodological limitations the causal associations (if any) may be stronger or weaker than the ones reported in this study. Prospective studies with independent and validated reporting of exposure and outcome and repeated follow-up with relevant intervals are highly warranted.

OBJECTIVE: Albeit a pivotal risk for the development of hand eczema (HE), the exposure–response relationship between wet work and HE remains to be further investigated. Knowledge on exposure–response is important regarding preventive measures, medico-legal regulations and job-counseling. Recently, a job-exposure matrix (JEM) for wet work was developed, providing information on the likelihood of wet work. By combining the JEM with data on HE we aimed to investigate the relationship between extent of wet work and HE. METHODS: This study is a case–referent study including patients registered in the National Database of Contact Allergy, Denmark, and comprises data on sex, age, atopic dermatitis, HE, face eczema and patch testing results. Patients with HE served as cases and patients with facial eczema served as referents. Information on profession was retrieved from the DOC*X database in accordance with the DISCO-88 classification system. A wet-work-specific JEM provides – for each profession – an estimate for (i) the likelihood of wet work lasting ≥2 hours/day and (ii) the average number of hours of wet work per day. RESULTS: After two hours of wet hands and glove wear, the odds ratio (OR) was 3.49 and 3.19, respectively, for females and 2.41 and 1.82, respectively, for males. Females had a higher risk of HE than males with probability of wet hands

Objective This study aimed to evaluate sex-specific risks of acute myocardial infarction (AMI) according to lifting and standing/walking at work. METHODS: The study population included 1.15 million Danish wage earners. Annual job codes from 1976 onwards were linked to specific exposures using job-exposure matrices (JEM). Cases of AMI during follow-up 1996–2016 were retrieved from national registers. Incidence rate ratios (IRR) were computed by Poisson regression adjusting for demographic and JEM-assessed lifestyle factors. Models addressed physical activities at work the previous 0–2 years (short-term risk) and cumulative physical activities (long-term risk). RESULTS: During 21.4 million person-years of follow-up, 22 037 AMI occurred in men and 6942 in women. Exposure–response relationships between recent physical activities at work and AMI were not evident. In men, the fully adjusted long-term IRR for the highest of five exposure categories compared to the lowest were 1.09 [95% confidence interval (CI) 1.03–1.15] for lifting and 1.01 (95% CI 0.96–1.07) for standing/walking. In women, the corresponding figures were 1.27 (95% CI 1.15–1.40) and 1.18 (95% CI 1.07–1.30). The latter risk estimate was strongly attenuated, and the trend became insignificant when adjusted for lifting. Findings were only partially supported by sensitivity analyses. CONCLUSION: The study provides limited support to the hypothesis that long-term lifting and standing/walking at work is related to increased risk of AMI. Possible effects of acute physical exertion are not addressed and bias towards the null because of crude exposure assignment cannot be ruled out.

OBJECTIVE: Job-exposure matrices (JEM) may be efficient for exposure assessment in occupational epidemiological studies, but they rely on valid job information. We evaluated the agreement between JEM-based exposure estimates according to self-reported job titles converted to DISCO-88 codes and according to register-based DISCO-88 codes in the Danish Occupational Cohort with eXposure data (DOC*X). Furthermore, we evaluated the agreement between these two sets of DISCO-88 codes. METHODS: We used JEM regarding wood dust, lifting, standing/walking, arm elevation >90°, and noise from DOC*X. Participants from previous questionnaire studies were assigned JEM-based exposure estimates using (i) self-reported job titles converted to DISCO-88 codes and (ii) DISCO-88 codes registered in DOC*X, in four time periods (1976–78: N=7707; 1981–83: N=2193; 1991–94: N=2664; 2004: N=11 782). Agreement between the exposure estimates and between the DISCO-88 codes (four-digit levels, 1–4) was evaluated by kappa (κ) statistics. Sensitivities were calculated using the self-reported observation as the gold standard. RESULTS: We found substantial agreement (κ>0.60) between exposure estimates for all types of job-exposures and all time periods except for one κ. Low sensitivity (30–65%) was found for the period 1981–83, but for the other time periods the sensitivities varied between 60–91%. For individual 4-digit DISCO-88 codes, the sensitivities varied substantially and overall the sensitivities increased by lower digit level of DISCO-88. CONCLUSION: The validity of the DISCO-88 codes in DOC*X was generally high. Substantial agreement was found for the JEM-based exposure estimates and the DISCO-88 codes per se, although the DISCO-88 code-specific agreement varied across digit levels and time periods.

OBJECTIVES: Many women experience absence periods from work during pregnancy. Several single risk factors for absence are identified, whereas the impact of multiple concurrent exposures has been sparsely studied. We hypothesized that the presence of multiple occupational exposures would be associated with an increased risk of absence from work during pregnancy. METHODS: We included women from the Danish National Birth Cohort (1996–2002), pregnant with one child and working ≥30 hours/week at interview (mean gestational week 17 (standard deviation 4.0); N=50 142). Information about five occupational exposures (job demands, job control, work posture, work shift, lifting) were retrieved from the interview, each assigned values of 0/1, and summed into an index (0–5). The woman’s first absence from work (both regular and related to pregnancy) after the interview was available from a nationwide administrative register. We analyzed data with Cox regression using gestational age as the underlying time-variable. RESULTS: Few women experienced none of the occupational exposures (3.6%) and most experienced two exposures (34.7%). Only 24.3% of the women were absent from work before gestational week 31. The number of occupational exposures was associated with an increasing risk of absence. The adjusted hazard ratio for absence increased from 1.3 [95% confidence interval (CI) 1.1–1.5] for one exposure to 2.9 (95% CI 2.5–3.3) for four to five exposures compared to no occupational exposure. CONCLUSION: The higher the number of potentially adverse occupational exposures pregnant women experienced, the higher the risk for absence from work during pregnancy.

OBJECTIVE: Prolonged seated immobility during long-distance flights is related to an increased risk of venous thromboembolism (VTE), but little, if anything, is known about the risk related to sedentary work. The objective of this paper was to examine the risk of VTE according to sitting posture at work. METHODS: This prospective study includes a total of 78 936 participants from the Copenhagen City Heart Study and the Copenhagen General Population Study, all without previous thromboembolic events and aged

OBJECTIVE: We aimed to investigate the association of night work during pregnancy with the risk of severe postpartum depression (PPD). METHODS: We performed a nationwide register-based cohort study of workers in all Danish public hospitals. Daily information on working hours was retrieved from the Danish Working Hour Database from January 2007 to December 2015. Pregnancies, covariates and outcome were identified from national registries for births and hospital contacts. We performed logistic regression of the risk of severe PPD in relation to the number and duration of night shifts, spells of consecutive night shifts, and short shift intervals during the first 32 pregnancy weeks. Analyses were adjusted for age, body mass index, socioeconomic status, parity, sickness absence three months prior to pregnancy, and prior diagnosis of severe depression. RESULTS: The study cohort comprised 25 009 singleton pregnancies from 19 382 workers. The majority were nurses or physicians. Overall, we did not observe an increased risk of PPD for any of the dimensions of night work analyzed. We found, however, an increased risk of PPD (adjusted odds ratio 2.08, 95% confidence interval 1.09–4.00) among women who stopped working night shifts after the first pregnancy trimester (N=3094). CONCLUSION: Overall, our results do not support night work during pregnancy as a risk factor for severe PPD among hospital employees. However, we observed a 2-fold increased risk of PPD among women who stopped working night shifts after the first pregnancy trimester. This may reflect the influence of the healthy worker survivor effect and warrants further attention.

OBJECTIVES: The aim of this review was to assess the evidence that occupational safety and health (OSH) legislative and regulatory policy could improve the working environment in terms of reduced levels of industrial injuries and fatalities, musculoskeletal disorders, worker complaints, sick leave and adverse occupational exposures. METHODS: A systematic literature review covering the years 1966‒2017 (February) was undertaken to capture both published and gray literature studies of OSH work environment interventions with quantitative measures of intervention effects. Studies that met specified in- and exclusion criteria went through an assessment of methodological quality. Included studies were grouped into five thematic domains: (i) introduction of OHS legislation, (ii) inspection/enforcement activity, (iii) training, such as improving knowledge, (iv), campaigns, and (v) introduction of technical device, such as mechanical lifting aids. The evidence synthesis was based on meta-analysis and a modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The search for peer-reviewed literature identified 14 743 journal articles of which 45 fulfilled the inclusion criteria and were eligible for meta-analysis. We identified 5181 articles and reports in the gray literature, of which 16 were evaluated qualitatively. There was moderately strong evidence for improvement by OHS legislation and inspections with respect to injuries and compliance. CONCLUSIONS: This review indicates that legislative and regulatory policy may reduce injuries and fatalities and improve compliance with OHS regulation. A major research gap was identified with respect to the effects of OSH regulation targeting psychological and musculoskeletal disorders.

OBJECTIVES: This study aimed to examine the association between negative life events, job stressors (low job control or high psychosocial job demands) and offspring asthma phenotypes (early-onset transient, early-onset persistent and late-onset asthma). METHODS: In a population-based cohort study comprising 547 533 liveborn singletons, we determined negative life events and offspring asthma at age six years using data from Danish nationwide registers. We assessed job demands and job control from gender-specific job exposure matrices. Prevalence ratios (PR) of each asthma phenotype were estimated using log-binomial regression. RESULTS: Maternal exposure to negative life events prenatally was not significantly associated with offspring asthma. Among mothers with low job demands, low job control was associated with increased risk for early-onset transient asthma [PR=1.14, 95% confidence interval (CI) 1.09–1.19], early-onset persistent asthma (PR=1.17, 95% CI 1.11–1.23), and late-onset asthma (PR=1.06, 95% CI 1.00–1.14). Among mothers with high job demands, low job control was not associated with offspring asthma apart from a reduced risk of early-onset persistent asthma (PR=0.94, 95% CI 0.90–0.97). These associations were independent of child sex and parental atopic history. CONCLUSIONS: Maternal stressors in private life do not seem to influence offspring asthma significantly. Low job control is associated with offspring asthma, which is modified by maternal psychosocial job demands. Our findings warrant further exploration.

OBJECTIVES: Organizational changes are associated with higher rates of subsequent employee exit from the workplace, but the mediating role of social capital is unknown. We examined the associations between organizational changes and subsequent employee exit from the work unit and mediation through social capital. METHODS: Throughout 2013, 14 059 healthcare employees worked in the Capital Region of Denmark. Data on work-unit changes (yes/no) from July‒December 2013 were collected via a survey distributed to all managers (merger, split-up, relocation, change of management, employee layoff, budget cuts). Eight employee-reported items assessing social capital were aggregated into work-unit measures (quartiles: low-high). Data on employee exit from the work unit in 2014 were obtained from company registries. RESULTS: We found a somewhat higher rate of employee exit from the work unit after changes versus no changes [hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.01–1.19] and an inverse dose‒response relationship between social capital and employee-exit rates (low versus high: HR 1.65, 95% CI 1.46–1.86). We also showed a higher risk of low social capital in work units exposed to changes [low versus high: odds ratio (OR) 2.04, 95% CI 1.86–2.23]. Accounting for potential mediation through social capital seemed slightly to reduce the association between changes and employee-exit rates (HR 1.07, 95% CI 0.98–1.16 versus HR 1.10). CONCLUSIONS: Work-unit organizational changes prospectively predict lower work-unit social capital, and lower social capital is associated with higher employee-exit rates. Detection of weak indications of mediation through social capital, if any, were limited by inconsistent associations between changes and employee exit from the work unit.

OBJECTIVE: The aim of this study was to investigate whether night work expressed by number and duration of night shifts, number of consecutive night shifts, and number of quick returns during the first 20 weeks of pregnancy is a risk factor for hypertensive disorders of pregnancy (HDP). METHODS: The study population comprised Danish workers in public administration and hospitals who gave birth between 2007 and 2013. Exposure was assessed objectively through payroll data. Information on the outcome was retrieved from the National Patient Register. We performed logistic regression on the risk for HDP according to night work adjusted for age, body mass index (BMI), parity, socioeconomic status, and sickness absence prior to pregnancy. RESULTS: Among 18 724 workers, 60% had at least one night shift during the first 20 weeks of pregnancy. The prevalence of HDP was 3.7%. Among night workers, the risk of HDP grew with increasing number of consecutive night shifts [odds ratio (OR) 1.41, 95% confidence interval (CI) 1.01–1.98) and of quick returns after night shifts (OR 1.28, 95% CI 0.87–1.95). Among obese women (body mass index ≥30 kg/m^2), those who worked long night shifts and longer spells of consecutive night shifts, and had the highest number of quick returns after night shifts, had a 4–5 fold increased risk of HDP compared to day workers. CONCLUSION: Working consecutive night shifts and quick returns after night shifts during the first 20 pregnancy weeks was associated with an increased risk of HDP, particularly among obese women.

OBJECTIVE: Occupational hand eczema has adverse health and socioeconomic impacts for the afflicted individuals and society. Prevention and treatment strategies are needed. This study aimed to assess the effectiveness of an educational intervention on sickness absence, quality of life and severity of hand eczema. METHODS: PREVEX (PreVention of EXema) is an individually randomized, parallel-group superiority trial investigating the pros and cons of one-time, 2-hour, group-based education in skin-protective behavior versus treatment as usual among patients with newly notified occupational hand eczema, with follow-up after one year. Co-primary outcomes were total sickness absence, health-related quality of life (HR-QoL), and self-reported severity of hand eczema. RESULTS: Patients (N=1668) with notified occupational skin diseases from July 2012 to November 2014 were invited to participate in the trial. Of these, 756 were randomized to the intervention (N= 376) versus control (N=380) group. The intervention group had 21% fewer sickness absence days compared with the control group [95% confidence interval (CI) -55–40%, P=0.43]. We found no significant difference in the change of HR-QoL for the intervention compared with the control group (4% lower in the intervention group, 95% CI -18–13%, P=0.67). The ordinal odds of scoring worse on self-reported hand eczema severity was 15% lower in the intervention compared with the control group (95% CI -39–18%, P=0.34). Post-hoc sub-group analyses indicated that the effect of the intervention on severity differed between occupations, being detrimental to healthcare workers and beneficial in all other occupations. CONCLUSION: The educational skincare program had no marked effect on the primary outcomes sickness absence, HR-QoL, and severity of hand eczema when compared with treatment as usual.

OBJECTIVES: The aims of this study were to (i) investigate the association between night work or long work weeks and the risk of accidental injuries and (ii) test if the association is affected by age, sex or socioeconomic status. METHODS: The study population was drawn from the Danish version of the European Labour Force Survey from 1999–2013. The current study was based on 150 438 participants (53% men and 47% women). Data on accidental injuries were obtained at individual level from national health registers. We included all 20–59-year-old employees working ≥32 hours a week at the time of the interview. We used Poisson regression to estimate the relative rates (RR) of accidental injuries as a function of night work or long work weeks (>40 hours per week) adjusted for year of interview, sex, age, socioeconomic status (SES), industry, and weekly working hours or night work. Age, sex and SES were included as two-way interactions. RESULTS: We observed 23 495 cases of accidental injuries based on 273 700 person years at risk. Exposure to night work was statistically significantly associated with accidental injuries (RR 1.11, 99% CI 1.06–1.17) compared to participants with no recent night work. No associations were found between long work weeks (>40 hours) and accidental injuries. CONCLUSION: We found a modest increased risk of accidental injuries when reporting night work. No associations between long work weeks and risk of accidental injuries were observed. Age, sex and SES showed no trends when included as two-way interactions.

OBJECTIVE: This study examines the impact of organizational change and psychosocial work environment on non-disability early retirement among senior public service employees. METHODS: In January and February 2011, Danish senior public service employees aged 58–64 years (N=3254) from the Capital Region of Denmark responded to a survey assessing psychosocial work environment (ie, social capital, organizational justice, and quality of management). Work-unit organizational changes (ie, change of management, merging, demerging, and relocation) were recorded from January 2009 to March 2011. Weekly data on non-disability early retirement transfer were obtained from the DREAM register database, which holds weekly information about all public benefit payments in Denmark. Hazard ratios (HR) for early retirement following employees’ 60^th birthday were estimated with Cox regression adjusted for age, gender, and socioeconomic status. RESULTS: Exposure to change of management [HR 1.37, 95% confidence interval (95% CI) 1.13–1.66], mergers (HR 1.23, 95% CI 1.02–1.48), and relocation of work unit (HR 1.24, 95% CI 1.01–1.54) increased rate of non-disability early retirement, while demerging of work unit did not (HR 1.03, 95% CI 0.79–1.33). Work units with lower levels of social capital (HR 1.22, 95% CI 1.05–1.41), organizational justice, (HR 1.18, 95% CI 1.04–1.32), and quality of management (HR 1.14, 95% CI 1.02–1.25) increased rate of early retirement. CONCLUSION: Organizational change and poor psychosocial work environment contribute to non-disability early retirement among senior public service employees, measured at work-unit level.

OBJECTIVES: The objective was to examine if night shift work is a short-term risk factor for breast cancer, including combined estrogen receptor (ER) and human epidermal growth factor 2 (HER2) breast cancer subtypes. METHODS: The cohort comprised 155 540 public sector female workers in Denmark who were followed from 2007–2012. Day-to-day work-hour information was available from payroll registers and 1245 incident cases of breast cancer were identified in national cancer registries together with receptor subtype information. RESULTS: A rate ratio (RR) of 0.90 [95% confidence interval (95% CI) 0.80–1.01] was observed for workers ever working night shifts during the follow-up period compared with workers only working day shifts after adjustment for age, age at first child, parity, family history of breast or ovarian cancer, sex hormones, medications related to alcoholism, family educational level, mammography screening, and other potential confounders. Comparable results were seen for the inception population of employees with first recorded employment after 2007. Modestly increased RR were suggested for breast cancer subtypes characterized by a positive HER2 status irrespective of ER status. CONCLUSIONS: These findings do not support an overall short-term effect of night shift work on breast cancer risk. Future studies should explore further the impact of HER2 status.