Worse pulmonary function in association with cumulative exposure to nanomaterials. Hints of a mediation effect via pulmonary inflammation.

BACKGROUND: Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project. RESULTS: Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV1 and FEF25 - 75%, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1ß and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV1/FVC ratio. This pattern was not observed for other pulmonary function parameters. CONCLUSIONS: Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.

Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers.

OBJECTIVE: In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. METHODS: We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. RESULTS: The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDAEBC generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. CONCLUSION: Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter.

Recognition of COVID-19 with occupational origin: a comparison between European countries.

OBJECTIVES: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. METHODS: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. RESULTS: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. CONCLUSIONS: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.

Organizational interventions and occupational burnout: a meta-analysis with focus on exhaustion.

PURPOSE: To assess whether organizational interventions are effective to prevent or reduce exhaustion, the core dimension of occupational burnout. METHODS: We searched in PubMed, EMBASE, PsycINFO, and Cochrane Library databases randomized and non-randomized controlled trials conducted among active workers and reporting the outcome as exhaustion score. We calculated the effect sizes using the pre-test-post-test control group design's estimate. We used the random effects model in meta-analysis and Cochrane collaboration's tool for interventions to assess the risk of bias. Overall quality of evidence was appraised using the GRADE. RESULTS: From the 2425 identified records, we assessed 228 full texts for eligibility and included 11 original articles describing 13 studies, 11 on organizational interventions, and 2 on combined inventions. The interventions were participatory (n = 9), focused on workload (n = 2), or on work schedule (n = 2). The overall effect size was - 0.30 ((95% CI = - 0.42; - 0.18), I2 = 62.28%), corresponding to a small reduction in exhaustion with a very low quality of evidence. Combined interventions had a larger effect (- 0.54 (95% CI = - 0.76; - 0.32)) than organizational interventions. When split by type of intervention, both participatory interventions and interventions focused on workload had a benefic effect of exhaustion reduction, with an estimated effect size of - 0.34 (95% CI = - 0.47; - 0.20) and - 0.44 (95% CI = - 0.68, - 0.20), respectively. CONCLUSION: Interventions at combined level in workplaces could be helpful in preventing exhaustion. However, the evidence is still limited, due to a high heterogeneity between studies, bias potential, and small number of eligible studies. This calls for further research, using workload interventions at organizational level, especially in sectors with high risk of job stress and exhaustion.

Lung cancer mortality in the European cohort of titanium dioxide workers: a reanalysis of the exposure-response relationship.

OBJECTIVES: Animal bioassays have demonstrated convincing evidence of the potential carcinogenicity to humans of titanium dioxide (TiO2), but limitations in cohort studies have been identified, among which is the healthy worker survivor effect (HWSE). We aimed to address this bias in a pooled study of four cohorts of TiO2 workers. METHODS: We reanalysed data on respirable TiO2 dust exposure and lung cancer mortality among 7341 male workers employed in TiO2 production in Finland, France, UK and Italy using the parametric g-formula, considering three hypothetical interventions: setting annual exposures at 2.4 (U.S. occupational exposure limit), 0.3 (German limit) and 0 mg/m3 for 25 and 35 years. RESULTS: The HWSE was evidenced. Taking this into account, we observed a positive association between lagged cumulative exposure to TiO2 and lung cancer mortality. The estimated number of lung cancer deaths at each age group decreased across increasingly stringent intervention levels. At age 70 years, the estimated number of lung cancer deaths expected in the cohort after 35-year exposure was 293 for exposure set at 2.4 mg/m3, 235 for exposure set at 0.3 mg/m3, and 211 for exposure set at 0 mg/m3. CONCLUSION: This analysis shows that HWSE can hide an exposure-response relationship. It also shows that TiO2 epidemiological data could demonstrate an exposure-effects relationship if analysed appropriately. More epidemiological studies and similar reanalyses of existing cohort studies are warranted to corroborate the human carcinogenicity of TiO2. This human evidence, when combined with the animal evidence, strengthens the overall evidence of carcinogenicity of TiO2.

Malondialdehyde and anion patterns in exhaled breath condensate among subway workers.

BACKGROUND: Underground transportation systems can contribute to the daily particulates and metal exposures for both commuter and subway workers. The redox and metabolic changes in workers exposed to such metal-rich particles have yet to be characterized. We hypothesize that the distribution of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) are modified depending on exposures. RESULTS: Particulate number and size as well as mass concentration and airborne metal content were measured in three groups of nine subway workers (station agents, locomotive operators and security guards). In parallel, pre- and post-shift EBC was collected daily during two consecutive working weeks. In this biological matrix, malondialdehyde, lactate, acetate, propionate, butyrate, formate, pyruvate, the sum of nitrite and nitrate (ΣNOx) and the ratio nitrite/nitrate as well as metals and nanoparticle concentrations was determined. Weekly evolution of the log-transformed selected biomarkers as well as their association with exposure variables was investigated using linear mixed effects models with the participant ID as random effect. The professional activity had a strong influence on the pattern of anions and malondialdehyde in EBC. The daily number concentration and the lung deposited surface area of ultrafine particles was consistently and mainly associated with nitrogen oxides variations during the work-shift, with an inhibitory effect on the ΣNOx. We observed that the particulate matter (PM) mass was associated with a decreasing level of acetate, lactate and ΣNOx during the work-shift, suggestive of a build-up of these anions during the previous night in response to exposures from the previous day. Lactate was moderately and positively associated with some metals and with the sub-micrometer particle concentration in EBC. CONCLUSIONS: These results are exploratory but suggest that exposure to subway PM could affect concentrations of nitrogen oxides as well as acetate and lactate in EBC of subway workers. The effect is modulated by the particle size and can correspond to the body's cellular responses under oxidative stress to maintain the redox and/or metabolic homeostasis.

Inflammatory Biomarkers in Exhaled Breath Condensate: A Systematic Review.

Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria, and inorganic particles. A key role is played by cytokines, protein-based chemical mediators produced by a broad range of cells, including the immune cells recruited in the inflammation site. The aim of this systematic review is to compare baseline values of pro/anti-inflammatory biomarkers measured in Exhaled Breath Condensate (EBC) in healthy, non-smoking adults to provide a summary of the concentrations reported in the literature. We focused on: interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), and C reactive protein (CRP). Eligible articles were identified in PubMed, Embase, and Cochrane CENTRAL. Due to the wide differences in methodologies employed in the included articles concerning EBC sampling, storage, and analyses, research protocols were assessed specifically to test their adherence to the ATS/ERS Task Force guidelines on EBC. The development of reference intervals for these biomarkers can result in their introduction and use in both research and clinical settings, not only for monitoring purposes but also, in the perspective of future longitudinal studies, as predictive parameters for the onset and development of chronic diseases with inflammatory aetiology.

Associating Air Pollution with Cytokinesis-Block Micronucleus Assay Parameters in Lymphocytes of the General Population in Zagreb (Croatia).

Air pollution is recognized as one of the most serious public health issues worldwide and was declared to be a leading environmental cause of cancer deaths. At the same time, the cytokinesis-block micronucleus (CBMN) assay serves as a cancer predictive method that is extensively used in human biomonitoring for populations exposed to environmental contamination. The objective of this cross-sectional study is two-fold: to evaluate genomic instability in a sample (N = 130) of healthy, general population residents from Zagreb (Croatia), chronically exposed to different levels of air pollution, and to relate them to air pollution levels in the period from 2011 to 2015. Measured frequencies of CBMN assay parameters were in agreement with the baseline data for the general population of Croatia. Air pollution exposure was based on four factors obtained from a factor analysis of all exposure data obtained for the examined period. Based on the statistical results, we did not observe a significant positive association between any of the CBMN assay parameters tested and measured air pollution parameters for designated time windows, except for benzo(a)pyrene (B[a]P) that showed significant negative association. Our results show that measured air pollution parameters are largely below the regulatory limits, except for B[a]P, and as such, they do not affect CBMN assay parameters' frequency. Nevertheless, as air pollution is identified as a major health threat, it is necessary to conduct prospective studies investigating the effect of air pollution on genome integrity and human health.

Part-time work and other occupational risk factors for suicide among working women in the Swiss National Cohort.

OBJECTIVE: The aim of this study was to describe the factors associated with mortality by suicide among working women focusing on work-related factors. METHODS: The study population consisted in all Swiss residents recorded in the 1990 and/or the 2000 compulsory national censuses and were linked to emigration and mortality registers. We selected all women aged 18-65 and at work at the official census dates. Following work-related variables were available: socio-economic status, weekly hours of work, the sector of activity and the job title coded according to the International Standard Classification of Occupations (ISCO). The risk of suicide was modelled using negative binomial regression. RESULTS: The cohort comprised 1,771,940 women and 2526 deaths by suicide corresponding to 24.9 million person-years. The most significant non-occupational predictors of suicide were age, period, civil status, religion, nationality and geographical regions. Adjusted on these factors, part-time work was associated with increased suicide rates. According to job codes, health and social activities, in particular care-worker had the highest suicide risks. CONCLUSION: Suicide among working women depended on work-related factors even taking into account other socio-demographic factors.

How to identify the most suitable questionnaires and rating scales for your clinical practice or research?

BACKGROUND: Selection of the most suitable instrument for a health outcome or exposure assessment is challenging, as there are many different instruments and their versions, most with unknown validity. AIMS: To develop guidelines facilitating the search for the most suitable instrument. MATERIALS AND METHODS: Based on our experience, we formalised a five-step process. The first step is the search for systematic reviews of available instruments validity in COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN), International prospective register of systematic reviews (PROSPERO), or conventional (eg, Medline and Web of Science) databases. If there is no systematic review, the clinician should look for original validation studies and assess them critically. We presented two alternatives of this assessment: qualitative using COSMIN and quantitative using our methodological framework. The latter helps to decide upon the instrument validity completeness and interpret the statistical results from original studies objectively. This process was then transformed into guidelines, which were tested by three external clinicians to select the most appropriate instrument to measure depression, occupational stress and daily fatigue. RESULTS: The guidelines were proved to facilitate the instrument search and selection, practical and time-saving. DISCUSSION: The guidelines assessment highlighted that clinicians should check whether the instrument that they are looking for was developed for screening or diagnosing purposes, whether it can be self-administered or not, and for which setting it was validated (academic vs clinical). CONCLUSION: These guidelines facilitate the objective choice of the most suitable instrument in clinical practice by making the search simple, systematic and time-effective.

[Detection and treatment of burnout by physicians of Unisanté]. / Repérage et prise en charge des patients en burnout par les médecins d'Unisanté.

Lacking diagnostic standards, the prevalence of Occupational Burnout (OB) remains uncertain. Unisanté aimed to evaluate its magnitude in its patients and to evaluate the medical practices related to OB in two of its departments, the Department of the Policlinics (DDP) and the Department of Occupational and Environmental Health (DSTE). An online survey has shown that 43/55 of the physicians participating in the survey have already diagnosed patients with OB in their practice. Two focus groups allowed to evaluate the interest and usefulness of a standardized diagnostic tool for physicians of the DDP and the DSTE. The tool turned out not to be appropriate in its present form, but this work allowed to sensitize physicians to OB and to clarify the recommendations for the screening and treatment of OB patients at Unisanté.

Faute de standard diagnostique, la prévalence de burnout professionnel (BP) reste incertaine. Unisanté a souhaité évaluer son ampleur dans sa patientèle et décrire les pratiques médicales en rapport au BP dans 2 de ses départements, le Département des policliniques (DDP) et le Département santé, travail et environnement (DSTE). Une enquête en ligne a montré que 43/55 médecins participant à l'étude ont déjà diagnostiqué des patients en BP dans leur pratique. Deux focus groups ont permis d'évaluer l'intérêt et l'utilité d'un outil diagnostique standardisé pour les médecins du DDP et du DSTE. L'outil s'est avéré peu adapté sous sa forme actuelle, mais ce travail a permis de sensibiliser les médecins au BP et de clarifier les recommandations de dépistage et de prise en charge des patients en BP à Unisanté.

Lung cancer mortality in the French cohort of titanium dioxide workers: some aetiological insights.

OBJECTIVES: Titanium dioxide (TiO2) is widely used in construction, food, cosmetic and medical industry. The current evidence on TiO2 carcinogenicity in humans is considered inadequate. As French participants of the European cohort of TiO2 workers exhibited an increase in mortality from lung cancer, we aimed at investigating whether TiO2 exposure, co-exposures or smoking can explain this increase. METHODS: We reanalysed the data of 833 French male workers (follow-up period 1968-1997) and used multiple imputation to complete their smoking status. We considered respirable TiO2 dust as primary exposure of interest, estimated as continuous cumulative (mg/m3-year) and annual average (mg/m3) concentrations and binary and 4-class categorical variables, with cut-off values of 0.3 and 2.4 mg/m3 (the German and American occupational exposure limits, respectively). For each exposure metric, we estimated HRs and associated 95% CIs, using Cox regression models adjusted for calendar period, exposure duration and smoking. RESULTS: The fully adjusted model yielded a HR=3.7 (95% CI=0.79 to 17.95) for TiO2-exposed workers vs unexposed and a HR=27.33 (95% CI=4.35 to 171.84) for those exposed to >2.4 mg/m3 as annual average concentration. Employment duration was negatively related with lung cancer mortality, therefore cumulative exposure had a small effect on mortality (HR=1.03 (95% CI=0.99 to 1.08) per mg/m3-year). CONCLUSION: This study suggests a positive relationship between TiO2 exposure and lung cancer mortality in TiO2 workers, whatever the exposure variable used, despite a limited statistical power in some models. The results question the current evidence on TiO2 carcinogenicity in humans but need to be confirmed in other cohorts, using different statistical approaches.

Sex-specific risks and trends in lung cancer mortality across occupations and economic activities in Switzerland (1990-2014).

OBJECTIVES: To assess lung cancer mortality across occupations and economic activities/industries in Switzerland using three statistical estimates. METHODS: All Swiss residents aged 18-65 during the 1990 or 2000 censuses were followed through 2014 to ascertain information on date and cause of death. For every occupation and economic activity/industry, causal mortality ratios (CMR) and standardised mortality ratios (SMR) were computed using national cause-specific mortality rates. We also calculated relative SMR (rSMR) and conducted analyses stratified by socioeconomic variables, job skill level and calendar periods. RESULTS: The study sample comprised 5 834 618 participants (111 162 348 person-years). SMR and CMR led to similar results, while rSMR were generally higher. We found 18 occupations in men, 10 occupations in women and 3 industries in each sex with an excess of lung cancer mortality. Among men, rubber and plastic products machine operators, and workers in mining and quarrying, and construction industries were at high risk. Among women, motor vehicle drivers and workers in trade, repair of motor vehicles and of domestic articles and manufacture of goods industries showed the highest risks. In both sexes, hotel and restaurant workers presented an excess of lung cancer mortality. CONCLUSION: Most of the activities and occupations in which we observed excess lung cancer mortality have previously been observed to involve occupational exposure to lung carcinogens. These findings suggest that the number of occupational lung cancer is likely underestimated by the official Swiss statistics. Further research should address this question and the exposure-effect relationships in the most at-risk occupational groups.

Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis.

Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed.

Reference Ranges of 8-Isoprostane Concentrations in Exhaled Breath Condensate (EBC): A Systematic Review and Meta-Analysis.

Isoprostanes are physiopathologic mediators of oxidative stress, resulting in lipid peroxidation. 8-isoprostane seems particularly useful for measuring oxidative stress damage. However, no reference range values are available for 8-isoprosante in exhaled breath condensate (EBC) of healthy adults, enabling its meaningful interpretation as a biomarker. We conducted this systematic review and meta-analysis according to the protocol following PROSPERO (CRD42020146623). After searching and analyzing the literature, we included 86 studies. After their qualitative synthesis and risk of bias assessment, 52 studies were included in meta-analysis. The latter focused on studies using immunological analytical methods and investigated how the concentrations of 8-isoprostane differ based on gender. We found that gender had no significant effect in 8-isoprostane concentration. Among other studied factors, such as individual characteristics and factors related to EBC collection, only the device used for EBC collection significantly affected measured 8-isoprostane concentrations. However, adjustment for the factors related to EBC collection, yielded uncertainty whether this effect is due to the device itself or to the other factors. Given this uncertainty, we estimated the reference range values of 8-isoprostane stratified by gender and EBC collection device. A better standardization of EBC collection seems necessary; as well more studies using chemical analytical methods to extend this investigation.

FranceCoag: a 22-year prospective follow-up of the national French cohort of patients with inherited bleeding disorders.

FranceCoag is an ongoing open prospective multicentre cohort project aimed at improving epidemiological knowledge about inherited bleeding disorders in France. The main objective of this article was to evaluate the project's progress as of the 30th December 2016. Between 1994 and this date, of the 10,047 patients included in the study, 384 (3.8%) were reported by clinicians to have died and 159 (1.6%) to be lost to follow-up. Among the remaining 9504 patients still being followed up, 5748 (60.5%) had haemophilia A, 1300 (13.7%) haemophilia B, 1980 (20.8%) von Willebrand Disease while 476 (5.0%) had another clotting factor deficiency (Factor I, II, V, combined V and VIII, VII, X, XI and XIII). The median age of the population was 32 years (Inter-quartile range (IQR) 18-50 years) at data extraction on December 30th, 2016. The subgroup of children (i.e., < 18 years old) with severe haemophilia and comprehensive information available since the first exposure to treatment was identified as the PUPs (Previously Untreated Patients) cohort. Data for the 643 children included in the PUPs' cohort had been collected since their birth. Follow-up data were collected by the clinicians in haemophilia treatment centres (HTC) every 12.9 months on median (IQR 11.4-21.3). In the PUPS cohort, data were updated every 6.2 months on median (IQR 3.7-11.7). A unique patient number assigned at study inclusion was kept at individual HTC by participating clinicians. The data collected included demographic, clinical, therapeutic and biological items on standard electronic forms. As of December 30th 2016, a plasma and serum samples was available for 2581 patients (27.1%).

Suicide mortality follow-up of the Swiss National Cohort (1990-2014): sex-specific risk estimates by occupational socio-economic group in working-age population.

PURPOSE: To identify occupations and socio-economic groups with detrimental or protective effect on suicide mortality. METHODS: For every occupation and economic activity/industry, we computed directly age-standardized mortality rates (DSRs) using the age structure of the European population (2010) and standardized mortality ratios (SMRs) for suicide using national cause-specific mortality rates. We further stratified analyses by socio-economic variables, job-skill level, and by three calendar periods (1990-1998/1999-2006/2007-2014). RESULTS: The study sample comprised 5,834,618 participants (94,918,456 person-years). The highest DSRs were observed among unemployed/job-seeking group, in agricultural, fishery and related male workers, and in health and social activities female workers. The lowest DSRs were observed in real estate and renting, research and development, IT and other business activities in men and in agriculture, hunting and forestry industry in women. A consistent reduction in DSRs across three calendar periods was observed in men. In female corporate managers, DSRs increased over the 2007-2014 period compared with 1999-2006. Compared to general working-age population, unemployed/job-seeking people, manufacturing labourers, personal care and related workers, and motor vehicle drivers of both sexes were identified at risk of suicide. Moreover, an excess of suicide was observed among male material recording and transport clerks; nursing and midwife-associated professionals; and agricultural workers as well as among female writers and performing artists. CONCLUSIONS: The findings suggest the detrimental effect of low socioeconomic positions, including unemployment, with respect to suicide mortality and a relationship between suicide and poor psychosocial working conditions in elementary occupations. Sex-specific results need further investigation.

Circulatory disease in French nuclear fuel cycle workers chronically exposed to uranium: a nested case-control study.

OBJECTIVES: There is growing evidence of an association between low-dose external γ-radiation and circulatory system diseases (CSDs), yet sparse data exist about an association with chronic internal uranium exposure and the role of non-radiation risk factors. We conducted a nested case-control study of French AREVA NC Pierrelatte nuclear workers employed between 1960 and 2005 to estimate CSD risks adjusting for major CSD risk factors (smoking, blood pressure, body mass index, total cholesterol and glycaemia) and external γ-radiation dose. METHODS: The study included 102 cases of death from CSD and 416 controls individually matched on age, gender, birth cohort and socio-professional status. Information on CSD risk factors was collected from occupational medical records. Organ-specific absorbed doses were estimated using biomonitoring data, taking into account exposure regime and uranium physicochemical properties. External γ-radiation was measured by individual dosimeter badges. Analysis was conducted with conditional logistic regression. RESULTS: Workers were exposed to very low radiation doses (mean γ-radiation dose 2 and lung uranium dose 1 mGy). A positive but imprecise association was observed (excess OR per mGy 0.2, 95% CI 0.004 to 0.5). Results obtained after adjustment suggest that uranium exposure might be an independent CSD risk factor. CONCLUSIONS: Our results suggest that a positive association might exist between internal uranium exposure and CSD mortality, not confounded by CSD risk factors. Future work should focus on numerous uncertainties associated with internal uranium dose estimation and on understanding biological pathway of CSD after protracted low-dose internal radiation exposure.