Explainable prediction model for the human papillomavirus status in patients with oropharyngeal squamous cell carcinoma using CNN on CT images.

Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV-) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV-), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.

Incidence of knee and hip joint replacement associated with cumulative exposure to physical factors at work.

BACKGROUND: Knee osteoarthritis (OA) has been quite consistently associated with high physical workload and specific physical factors at work, while for hip OA, fewer studies are available, which still indicate possible associations with heavy lifting and physical workload. The objective of the study was to assess the association between exposure to workplace physical factors and incidence of knee and hip arthroplasty, as markers of severe OA in these joints. METHODS: The study population was composed of employees 25-60 years who participated in the Turin 2011 census. For each job held since 1995, exposure to physical factors was assigned to individuals in the cohort through a Job-Exposure Matrix constructed from the Italian O*NET database. Using Poisson regression models, the incidence of knee and hip arthroplasty for OA, identified through hospitalizations from 2012 to 2018, was examined in relation to cumulative exposure to 7 different physical hazards and a composite indicator of physical workload constructed from 17 physical factors (Ergo-Index). RESULTS: The risk of knee OA was significantly increased in the highest cumulative exposure quartile of physical workload (incidence rate ratio = 1.98, 95% confidence interval: 1.24-3.16) and of all single hazards examined, compared to the lowest quartile, with significant trends in risk with increasing exposure. In contrast, no association was found with hip OA, whose relative risks were close to or below one in all higher-exposure quartiles of physical workload and of each single hazard. CONCLUSIONS: Our results indicate that exposure to physical hazards at work increases the likelihood of developing knee OA, but not hip OA.

Child rearing or childbearing? Risk of cardiovascular diseases associated to parity and number of children.

BACKGROUND: An increased risk of cardiovascular diseases (CVD) has been associated with women's parity, but whether or not this association reflects a direct pregnancy effect, or exposure to factors related to childrearing, still appears unclear. We assessed the CVD risk associated with number of children separately by gender and tested effect modification by socioeconomic position (SEP) and employment status, in order to elucidate the possible mechanisms underlying this association. METHODS: The study population was composed of 20,904 men and 25,246 women who were interviewed in one of two National Health Surveys conducted in 2000 and 2005 in Italy. These subjects were followed for CVD incidence up to 2014 through record-linkage with national archives of mortality and hospitalisations. CVD risk was estimated by Cox regression models that were adjusted for socio-demographics, perceived health, lifestyles, biological CVD risk factors and for other potential confounders. RESULTS: CVD incidence was significantly increased among men with 3 or more children (HR = 1.26, 95% CI: 1.02-1.56) and among women with 2 and with 3 or more children (HR = 1.42, 95% CI: 1.10-1.83; and HR = 1.39, 95% CI: 1.03-1.87, respectively) compared to subjects without children and no significant gender differences were observed. Subjects with lower SEP displayed stronger associations with parity and a higher number of children for both genders; by contrast, no modifying effect of employment status was observed. CONCLUSIONS: Taken together, the significant association between higher parity and CVD risk in both genders, and the higher risk of CVD associated with higher parity among lower SEP parents, suggests that childrearing has a potential effect on the development of CVD that is more pronounced among disadvantaged families, although a concurrent effect of childbearing cannot be completely excluded.

Occupational physical activity, all-cause mortality and incidence of cardiovascular diseases: results from three Italian cohorts.

PURPOSE: To examine the association of exposure to Occupational Physical Activity (OPA) with all-cause mortality and incidence of cardiovascular diseases (CVD). METHODS: The study population was composed of three Italian cohorts: a national cohort of employees participating in the National Health Survey 2005, followed-up until 2014 (ILS 2005), and two urban cohorts of employees resident in Turin at 2001 and 2011 censuses (TLS 2001 and TLS 2011, respectively), both followed-up until 2018. Follow-up was conducted through individual record-linkage with death registries and hospital admissions archives. Exposure to OPA was assigned through an Italian job-exposure matrix (JEM). Relative Risks of both CVD incidence and overall mortality associated with OPA quartiles (IRR) were estimated using Poisson regression models adjusted for socio-demographics and health, and in the national cohort, also for leisure time physical activity, BMI, smoking, diabetes, and hypertension. RESULTS: Compared to the lowest quartile, the highest OPA quartile was associated in both genders with significantly increased mortality in TLS 2001 (IRR = 1.11 among men, IRR = 1.20 among women) and in TLS 2011 (IRR = 1.27 among men and IRR = 1.73 among women), whereas in the ILS 2005 cohort no association was found. Among women, high OPA was also associated with CVD risk in TLS 2001 and 2011 (IRR = 1.39 and IRR = 1.16 for the highest quartile, respectively), while in the ILS cohort in both genders only the third quartile showed a significantly higher risk. CONCLUSION: Our results indicate that OPA does not have a beneficial effect on CVD and mortality, but rather suggest that it may produce deleterious health effects.

Prescriptive appropriateness in early breast cancer staging exams: preliminary investigation about adherence to the guidelines in the clinical practice.

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Health and labor market effects of an unanticipated rise in retirement age. Evidence from the 2012 Italian pension reform.

As retirement ages increase around the world, not all workers may be equally able to extend their working lives. In this article, we examine the health and labor market effects of an Italian pension reform that suddenly increased the normal retirement age up to 7 years for women and up to 2 years for men. To do this, we use linked labor and healthcare administrative data, jointly with survey data and difference-in-difference methods. Our results show that the reform was effective in postponing retirement among both genders, as pension claiming dropped substantially for older workers. However, there were also side effects as the reform significantly pushed previously employed men and women into unemployment and disability pension. Among women only, the reform also increased sick leave and hospitalizations related to mental health and injuries. These effects were driven by women with previously low health status, suggesting that undifferentiated and abrupt increases in pension age might harm more vulnerable workers. Coherently with the milder tightening of retirement age experienced by men, labor market responses were smaller in size, and they did not suffer any significant health effects.

Job demands and job control and their associations with disability pension-a register-based cohort study of middle-aged and older Swedish workers.

OBJECTIVES: Job demands and control at work and their combination, job strain, have been studied in relation to risk of disability pension (DP) previously. In the present study, based on registry data, we aimed to deepen the knowledge by analyzing major disease groups among the DPs, dose-response shape of the associations, and potential confounding effects of physical workload. METHODS: Approximately 1.8 million workers aged 44 or older and living in Sweden in 2005 were followed up for 16 years, up to a maximum of 65 years of age. We linked mean values of job demands and job control, estimated in a job-exposure matrice (JEM) by gender, to individuals through their occupational titles in 2005. These values were categorized by rank order, and, for the construction of job-strain quadrants, we used a median cut-off. Associations with DP were estimated in Cox proportional-hazards models. RESULTS: In models accounting for covariates including physical workload, low levels of job control were associated with higher risk of DP among both men and women. This association was most clear for DP with a psychiatric diagnosis, although a dose-response shape was found only among the men. High levels of job demands were associated with decreased risk of DP across diagnoses among men, but the same association varied from weak to non-existing among women. The high- and passive job-strain quadrants both showed increased risk of DP with a psychiatric diagnosis. CONCLUSION: The results suggest that, at the occupational level, low job control, but not high job demands, contributes to an increased incidence of DP, particularly regarding DP with a psychiatric diagnosis.

Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation.

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.

Long-term associations of psychosocial working conditions with depressive symptoms and work-related emotional exhaustion: comparing effects in a 5-year prospective study of 1949 workers in Germany.

OBJECTIVE: To test the hypothesis that psychosocial working conditions are more strongly associated with subsequent work-related emotional exhaustion (core component of burnout) than with depressive symptoms at follow-up. METHODS: A 5-year cohort study (2011/2012-2017), based on a random sample of persons in employment subject to payment of social contributions aged 31-60 years (Study on Mental Health at Work; S-MGA; N = 1949), included self-reported measures of organisational demands (organisational layoffs and restructuring), task-level demands (work pace and amount of work) and job resources (influence at work, possibilities for development, control over working time, role clarity), all taken from the COPSOQ, except the organisational demands that were single-item measures. Work-related emotional exhaustion and depressive symptoms were measured with the Oldenburg Burnout Inventory and the Patient Health Questionnaire-9, respectively. RESULTS: Cochrane Q tests revealed stronger associations between psychosocial working conditions and work-related emotional exhaustion only for the amount of work (p = 0.013) and control over working time (p = 0.027). No differences were observed for the Demands and Resources Indexes, capturing overall exposure to psychosocial working conditions. The same differences were observed in a subsample including only participants who remained at the same employer from baseline to follow-up, although more psychosocial working conditions were associated with work-related emotional exhaustion than with depressive symptoms. Supplementary analyses employing dichotomous measures of work-related emotional exhaustion and depressive symptoms confirmed these results. CONCLUSIONS: Overall, the findings provide limited evidence supporting the hypothesis that psychosocial working conditions are more strongly associated with work-related emotional exhaustion than with depressive symptoms.

Risk of symptomatic osteoarthritis associated with exposure to ergonomic factors at work in a nationwide Italian survey.

OBJECTIVE: The risk of developing osteoarthritis (OA) has been reported to increase with exposure to various ergonomic factors at work, although this finding is still debated in the literature. Aim of this study was to assess the association between prevalence of symptomatic OA and exposure to workplace ergonomic factors assigned through a job-exposures matrix (JEM). METHODS: The study population was composed of 24,604 persons of 40-69 years who participated in the National Health Survey 2013 and were employed at that occasion. Exposure to ergonomic factors was assigned to the study population through a JEM constructed from the Italian O*NET database, consisting of 17 physical factors, which were summed and averaged by job title (796 jobs) to obtain a combined exposure index. The outcome was self-reported OA characterized by moderate or severe limitations in daily activities. The relationship between OA prevalence and the combined exposure index in quartiles was examined using robust Poisson regression models adjusted for socio-demographics and potential confounders. RESULTS: In the analysis adjusted for age and gender, the risk of OA was increased by approximately 20-30% in the second and third quartiles, and by 80% in the highest exposure quartile, compared to the least exposed, with a risk attenuation by approximately 15-20% controlling for other significant covariates. CONCLUSION: Our results support a causal role of exposure to physical factors at work in the development of OA. As OA is associated with a great burden of disability, any effort should be made to reduce workers' exposure to ergonomic factors.

Corrigendum: Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer.

[This corrects the article DOI: 10.3389/fmed.2022.993395.].

Association between work characteristics and epigenetic age acceleration: cross-sectional results from UK - Understanding Society study.

Occupation-related stress and work characteristics are possible determinants of social inequalities in epigenetic aging but have been little investigated. Here, we investigate the association of several work characteristics with epigenetic age acceleration (AA) biomarkers. The study population included employed and unemployed men and women (n = 631) from the UK Understanding Society study. We evaluated the association of employment and work characteristics related to job type, job stability; job schedule; autonomy and influence at work; occupational physical activity; and feelings regarding the job with four epigenetic age acceleration biomarkers (Hannum, Horvath, PhenoAge, GrimAge) and pace of aging (DunedinPoAm, DunedinPACE). We fitted linear regression models, unadjusted and adjusted for established risk factors, and found the following associations for unemployment (years of acceleration): HorvathAA (1.51, 95% CI 0.08, 2.95), GrimAgeAA (1.53, 95% CI 0.16, 2.90) and 3.21 years for PhenoAA (95% CI 0.89, 5.33). Job insecurity increased PhenoAA (1.83, 95% CI 0.003, 3.67), while working at night was associated with an increase of 2.12 years in GrimAgeAA (95% CI 0.69, 3.55). We found effects of unemployment to be stronger in men and effects of night shift work to be stronger in women. These results provide evidence of associations between unemployment with accelerated ageing and suggest that insecure employment and night work may also increase age acceleration. Our findings have implications for policies relating to current changes in working conditions and highlight the utility of biological age biomarkers in studies in younger populations without long-term health information.

Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer.

Background and purpose: Although the latest breakthroughs in radiotherapy (RT) techniques have led to a decrease in adverse event rates, these techniques are still associated with substantial toxicity, including xerostomia. Imaging biomarkers could be useful to predict the toxicity risk related to each individual patient. Our preliminary work aims to develop a radiomic-based support tool exploiting pre-treatment CT images to predict late xerostomia risk in 3 months after RT in patients with oropharyngeal cancer (OPC). Materials and methods: We performed a multicenter data collection. We enrolled 61 patients referred to three care centers in Apulia, Italy, out of which 22 patients experienced at least mild xerostomia 3 months after the end of the RT cycle. Pre-treatment CT images, clinical and dose features, and alcohol-smoking habits were collected. We proposed a transfer learning approach to extract quantitative imaging features from CT images by means of a pre-trained convolutional neural network (CNN) architecture. An optimal feature subset was then identified to train an SVM classifier. To evaluate the robustness of the proposed model with respect to different manual contouring practices on CTs, we repeated the same image analysis pipeline on "fake" parotid contours. Results: The best performances were achieved by the model exploiting the radiomic features alone. On the independent test, the model reached median AUC, accuracy, sensitivity, and specificity values of 81.17, 83.33, 71.43, and 90.91%, respectively. The model was robust with respect to diverse manual parotid contouring procedures. Conclusion: Radiomic analysis could help to develop a valid support tool for clinicians in planning radiotherapy treatment, by providing a risk score of the toxicity development for each individual patient, thus improving the quality of life of the same patient, without compromising patient care.

Reliability of O*NET physical exposures between Italian and US databases.

BACKGROUND: Comparison between cross-national job-exposure matrices (JEMs) may provide indications of their reliability, particularly if created using the same items. This study evaluated concordance between two JEMs created from United States (US) and Italian O*NET data, using job codes linked through international job codes. METHODS: Twenty-one physical exposures were obtained from the US and Italian O*NET databases. Italian O*NET items were direct translations of US O*NET items. Six hundred and eighty-four US and 586 Italian job codes were linked via crosswalks to 281 ISCO-08 job codes. A sensitivity study also assessed concordance on 258 jobs matched one-to-one across the two national job classifications. Concordance of US and Italian O*NET exposures was estimated by intraclass correlation coefficients (ICC) in multilevel models adjusted and not adjusted for country. RESULTS: ICCs showed moderate to poor agreement for all physical exposures in jobs linked through ISCO-08 codes. There was good to moderate agreement for 14 out of 21 exposures in models with one-to-one matched jobs between countries; greater agreement was found in all models adjusted for country. Exposure to whole-body vibration, time standing, and working outdoor exposed to weather showed the highest agreement. CONCLUSIONS: These results showed moderate to good agreement for most physical exposures across the two JEMs when US and Italian jobs were matched one-to-one and the analysis was adjusted for country. Job code assignments through crosswalks and differences in exposure levels between countries might greatly influence the observed cross-country agreement. Future multinational epidemiological studies should consider the quality of the cross-national job matching, and potential cross-national differences in exposure levels.

Long-term sick leave for back pain, exposure to physical workload and psychosocial factors at work, and risk of disability and early-age retirement among aged Swedish workers.

PURPOSE: To assess the risk of disability and early-age retirement associated with previous long-term sickness absence for back pain (back-pain SA), exposure to high physical workload, low job control, high demands and high strain, and to evaluate effect modification by work factors on the relationship between back-pain SA and premature retirement. METHODS: All employed Swedish residents born 1946-1955 (n = 835,956) were followed up from 2010 to 2016 for disability (DP) and early-age pension (EAP). Associations of premature retirement with exposure to work factors and back-pain SA in the 3 years before follow-up were estimated through proportional hazards models. Retirement, back-pain SA and covariates were assessed through administrative sources, and exposure to work factors through a job-exposure matrix. RESULTS: In both genders, back-pain SA was associated with DP (> 1 episode: HR 3.23 among men; HR 3.12 among women) and EAP (> 1 episode: HR 1.24 among men; HR 1.18 among women). Higher physical workload and lower job control were also associated with an increased DP risk in both genders, whereas higher job demands showed a decreased risk. For EAP, associations with work factors were weak and inconsistent across genders. No effect modification by work factors was found, except for a negative effect modification by job strain on DP risk among women, i.e. a reduced effect of back-pain SA with increasing exposure. CONCLUSION: Back-pain SA was a significant predictor of both DP and EAP, while work factors were consistently associated only with DP. Our results indicate that the joint effect of back-pain SA and work factors on DP is additive and does not support effect modification by work factors.

Work-related stress and well-being in association with epigenetic age acceleration: A Northern Finland Birth Cohort 1966 Study.

Recent evidence indicates consistent association of low socioeconomic status with epigenetic age acceleration, measured from DNA methylation. As work characteristics and job stressors are crucial components of socioeconomic status, we investigated their association with various measures of epigenetic age acceleration. The study population included employed and unemployed men and women (n=604) from the Northern Finland Birth Cohort 1966. We investigated the association of job strain, effort-reward imbalance and work characteristics with five biomarkers of epigenetic aging (Hannum, Horvath, PhenoAge, GrimAge, and DunedinPoAm). Our results indicate few significant associations between work stress indicators and epigenetic age acceleration, limited to a range of ±2 years, and smoking recording the highest effect on GrimAge age acceleration biomarker between current and no smokers (median difference 4.73 years (IQR 1.18, 8.41). PhenoAgeAA was associated with job strain active work (ß=-1.301 95%CI -2.391, -0.212), slowing aging of less than 1.5 years, and working as white-collar slowed aging six months (GrimAgeAA ß=-0.683, 95%CI -1.264, -0.102) when compared to blue collars. Association was found for working for more than 40 hours per week that increased the aging over 1.5 years, (HorvathAA ß =2.058 95%CI 0.517,3.599, HannumAA ß=1.567, 95%CI 0.415,2.719). The pattern of associations was different between women and men and some of the estimated effects are inconsistent with current literature. Our results provide the first evidence of association of work conditions with epigenetic aging biomarkers. However, further epidemiological research is needed to fully understand how work-related stress affects epigenetic age acceleration in men and women in different societies.

Education inequalities in cardiovascular and coronary heart disease in Italy and the role of behavioral and biological risk factors.

BACKGROUND AND AIMS: Behavioral and biological risk factors (BBRF) explain part of the variability in socioeconomic differences in health. The present study aimed at evaluating education differences in incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) in Italy and the role of BBRF. METHODS AND RESULTS: All subjects aged 30-74 years (n = 132,686) who participated to the National Health Interview Surveys 2000 and 2005 were included and followed-up for ten years. Exposure to smoking, physical activity, overweight/obesity, diabetes and hypertension at baseline was considered. Education level was used as an indicator of socioeconomic status. The outcomes were incident cases of CVD and CHD. Hazard ratios by education level were estimated, adjusting for sociodemographic covariates and stratifying by sex and geographic area. The contribution of BBRF to education inequalities was estimated by counterfactual mediation analysis, in addition to the assessment of the risk attenuation by comparing the models including BBRF or not. 22,214 participants had a CVD event and 6173 a CHD event. After controlling for sociodemographic factors, the least educated men showed a 21% higher risk of CVD and a 17% higher risk of CHD compared to the most educated (41% and 61% among women). The mediating effect (natural indirect effect) of BBRF between extreme education levels was 52% for CVD and 84% for CHD among men (16% among women for CVD). CONCLUSIONS: More effective strategies aiming at reducing socioeconomic disparities in CVD and CHD are needed, through programs targeting less educated people in combination with community-wide initiatives.

Use of antipsychotics and long-term risk of parkinsonism.

INTRODUCTION: Few epidemiological studies have assessed the risk of parkinsonisms after prolonged use of neuroleptics. We aimed to examine the long-term risk of degenerative parkinsonisms (DP) associated with previous use of neuroleptics. METHODS: All residents in Piedmont, Northern-west Italy, older than 39 years (2,526,319 subjects), were retrospectively followed up from 2013 to 2017. Exposure to neuroleptics was assessed through the regional archive of drug prescriptions. The development of DP was assessed using the regional archives of both drug prescriptions and hospital admissions. We excluded prevalent DP cases at baseline as well as those occurred in the first 18 months (short-term risk). The risk of DP associated with previous use of neuroleptics was examined through Cox regression, using a matched cohort design. RESULTS: The risk of DP was compared between 63,356 exposed and 316,779 unexposed subjects. A more than threefold higher risk of DP was observed among subjects exposed to antipsychotics, compared to those unexposed (HR = 3.27, 95% CI 3.00-3.57), and was higher for exposure to atypical than typical antipsychotics. The risk decreased after 2 years from therapy cessation but remained significantly elevated (HR = 2.38, 95% CI 1.76-3.21). CONCLUSIONS: These results indicate a high risk of developing DP long time from the start of use and from the cessation for both typical and atypical neuroleptics, suggesting the need of monitoring treated patients even after long-term use and cessation.

Occupational physical activity, mortality and CHD events in the Italian Longitudinal Study.

PURPOSE: Several recent studies have suggested a 'physical activity paradox' whereby leisure-time physical activity benefits health, but occupational physical activity is harmful. However, other studies imply that occupational physical activity is beneficial. Using data from a nationally representative Italian sample, we investigate if the context, or domain, of physical activity matters for mortality and coronary heart disease (CHD) events. METHODS: Among 40,220 men and women aged 40-55 at baseline, we used Cox models to compare associations of occupational, domestic and leisure-time physical activity with risk of mortality and CHD events over a follow-up period of up to 14 years. We accounted for sociodemographic factors, smoking, body mass index (BMI), physical and mental health, and educational qualifications. RESULTS: Occupational physical activity was not significantly associated with risk of mortality or CHD events for women, or with CHD events for men. In crude models, risk of mortality was higher for men in the highest occupational activity group, compared to the lowest (HR 1.26, 95% CI 1.01, 1.57). This attenuated with adjustment for health-related behaviours, health, and education (HR 1.03, 95% CI 0.77, 1.38). In crude models, leisure-time physical activity was significantly associated with decreased mortality and CHD risk only for men. Domestic physical activity was not associated with either outcome for either gender. CONCLUSION: In a large sample of middle-aged Italian workers, we found limited evidence of harmful or beneficial effects of occupational physical activity on mortality or CHD events. However, confidence intervals were wide, and results consistent with a range of effects in both directions.