Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort.

OBJECTIVES: Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers. METHODS: Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965-1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999-2022). A case-cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure. RESULTS: An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95% CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95% CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma. CONCLUSIONS: Associations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.

Exploring differences in the utilization of the emergency department between migrant and non-migrant populations: a systematic review.

BACKGROUND: Migrants face several barriers when accessing care and tend to rely on emergency services to a greater extent than primary care. Comparing emergency department (ED) utilization by migrants and non-migrants can unveil inequalities affecting the migrant population and pave the way for public health strategies aimed at improving health outcomes. This systematic review aims to investigate differences in ED utilization between migrant and non-migrant populations to ultimately advance research on migrants' access to care and inform health policies addressing health inequalities. METHODS: A systematic literature search was conducted in March 2023 on the Pubmed, Scopus, and Web of Science databases. The included studies were limited to those relying on data collected from 2012 and written in English or Italian. Data extracted included information on the migrant population and the ED visit, the differences in ED utilization between migrants and non-migrants, and the challenges faced by migrants prior to, during, and after the ED visit. The findings of this systematic review are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. RESULTS: After full-text review, 23 articles met the inclusion criteria. All but one adopted a quantitative methodology. Some studies reported a higher frequency of ED visits among migrants, while others a higher frequency among non-migrants. Migrants tend to leave the hospital against medical advice more frequently than the native population and present at the ED without consulting a general practitioner (GP). They are also less likely to access the ED via ambulance. Admissions for ambulatory care-sensitive conditions, namely health conditions for which adequate, timely, and effective outpatient care can prevent hospitalization, were higher for migrants, while still being significant for the non-migrant population. CONCLUSIONS: The comparison between migrants' and non-migrants' utilization of the ED did not suggest a clear pattern. There is no consensus on whether migrants access EDs more or less than non-migrants and on whether migrants are hospitalized at a higher or lower extent. However, migrants tend to access EDs for less urgent conditions, lack a referral from a GP and access the ED as walk-ins more frequently. Migrants are also discharged against medical advice more often compared to non-migrants. Findings of this systematic review suggest that migrants' access to care is hindered by language barriers, poor insurance coverage, lack of entitlement to a GP, and lack of knowledge of the local healthcare system.

Asbestos exposure and asbestosis mortality in Italian cement-asbestos cohorts: Dose-response relationship and the role of competing death causes.

OBJECTIVES: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks. METHODS: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death. RESULTS: The cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death. CONCLUSIONS: Asbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.

Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy. METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE). RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE. CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

Survival analysis for patients with cancer in Gaza applying for Israeli permits to exit the Gaza Strip for health care: a retrospective cohort study of patients from 2008 to 2017.

BACKGROUND: Gaza has been under land, sea, and aerial blockade for more than 13 years, during which time Israel has continued its permit regime to control access for Palestinian patients from Gaza to health facilities in the West Bank (including East Jerusalem), Israel, and Jordan. Specific groups, such as patients with cancer, have a high need for permits owing to a lack of services in Gaza. The approval rate for patient permits to exit Gaza dropped from 94% in 2012 to 54% in 2017. We aimed to assess the effect of access restrictions due to permit denials or delays on all-cause mortality for patients with cancer from Gaza who were referred for chemotherapy, radiotherapy, or both. METHODS: This study matched 17 072 permit applications for 3816 patients referred for chemotherapy, radiotherapy, or both, from Jan 1, 2008, to Dec 31, 2017, with referral data for the same period and mortality data from Jan 1, 2008, to Jun 30, 2018. We stratified survival analysis by period of first application (2008-14, 2015-17), in light of varying access to Egypt during these times. Primary analysis compared survival of patients according to their first referral decision (approved versus denied or delayed) using Kaplan-Meier methods and Cox regression. Consent for the study was granted by the Palestinian Ministry of Health, and ethical approval was granted by the Helsinki Committee of the Palestinian Ministry of Health. FINDINGS: Mortality was significantly higher among patients who were initially unsuccessful in permit applications from 2015 to 2017 (141 events over 493 person-years, corresponding to a rate of 286 per 100 person-years) than among patients who were initially successful in the same period (375 events over 1923 person-years, corresponding to a rate of 195 per 100 person-years) with a hazard ratio of 1·45 (95% CI 1·19-1·78, p=0.0009) after adjusting for age, sex, type of procedure, and type of cancer. There was no significant difference in mortality risk between the two groups in the 2008-14 period, with a hazard ratio of 0·84 (95% CI 0·69-1·01, p=0·071). INTERPRETATION: Barriers to patient access to health care through denied or delayed permit applications had a significant impact on mortality for patients with cancer who applied for chemotherapy, radiotherapy, or both, in the period 2015-17. Relative ease of access through Rafah from 2008 to 2014 may have mitigated the health effects of access restrictions. FUNDING: WHO received funding from the Swiss Agency for Development and Cooperation.

Association between antidepressant use in pregnancy and gestational diabetes mellitus: Results from the Norwegian Mother, Father and Child Cohort Study.

PURPOSE: This study sought to determine the association between gestational diabetes mellitus (GDM) and antidepressant exposure during early-mid pregnancy, overall and according to antidepressant affinity to the histamine-1 (H1 ) receptor. METHODS: Data originate from the nation-wide, Norwegian Mother, Father and Child Cohort Study conducted in 1999-2008, linked to the national Medical Birth Registry. The study included 6647 pregnancies within women with depressive/anxiety disorders during and/or 6 months prior to pregnancy. Pregnancies exposed in early-mid gestation to antidepressants having low (group 1, n = 814) or high (group 2, n = 77) affinity to the H1 receptor were compared to non-medicated (n = 5756). We fit crude and weighted modified Poisson regression models using inverse probability of treatment weighting (IPTW). RESULTS: Overall, 84 (1.3%) of the pregnancies developed GDM. Relative to non-medicated pregnancies, the risk of GDM was slightly lower in antidepressant group 1 exposed (1.3% vs 1.1%), but more elevated in those exposed to group 2 antidepressants (3.9%). In the weighted analysis, there was no evidence for an association between antidepressant group 1 exposure in early-mid pregnancy and risk of GDM [relative risk (RR): 0.69, 95% confidence interval: 0.31-1.51]. CONCLUSIONS: Gestational use of antidepressants with low H1 receptor affinity, mainly SSRIs and SNRIs, does not pose a substantial risk of GDM in women with depressive/anxiety disorders in pregnancy, compared to no use.

Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials.

BACKGROUND: Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning. METHODS: In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation. RESULTS: We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, - 3.43; 95% CI - 5.17 to - 1.69 days, p < 0.001), a shorter duration of total days spent on mechanical ventilation (mean difference, - 2.04; 95% CI - 3.82 to - 0.27 days, p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality. CONCLUSIONS: Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation. TRIAL REGISTRATION: The protocol was registered to PROSPERO database on 12/06/2019 and available at PROSPERO website inserting the study code i.e., CRD42019133837.

A randomized clinical study on the impact of Comprehensive Geriatric Assessment (CGA) based interventions on the quality of life of elderly, frail, onco-hematologic patients candidate to anticancer therapy: protocol of the ONCO-Aging study.

BACKGROUND: Age is considered as one of the most important risk-factor for many types of solid and hematological cancers, as their incidence increases with age in parallel to the ever-growing elderly population. Moreover, cancer incidence is constantly increasing as a consequence of the increase in life expectancy that favors the process of cellular senescence. Geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In particular, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. Due to their frailty, elderly patients may be often under-treated and a therapeutic choice based also on a comprehensive geriatric assessment (CGA) is recommended. With these premises, we aim to test the impact of the CGA based interventions on the quality of life (QoL) of frail elderly onco-hematological patients, identified by the G8 screening, candidate for innovative target directed drugs or treatments including the combination of radiotherapy and chemotherapy (RT + CT). METHODS: Patients aged > 65 years, candidate to target directed agents or to RT + CT treatments are screened for frailty by the G8 test; those patients classified as frail (G8 ≤ 14) are randomized to receive a CGA at baseline or to conventional care. The primary endpoint is QoL, assessed by EORTC QLQ-C30C. As collateral biological study, the potential prognostic/predictive role of T-cell senescence and myeloid derived suppressor cells (MDSC) are evaluated on plasma samples. DISCUSSION: This trial will contribute to define the impact of CGA on the management of frail elderly onco-hematologic patients candidate to innovative biological drugs or to integrated schedules with the association of RT + CT. Furthermore, the use of plasma samples to assess the potential prognostic value of imbalance of immune-competent cells is expected to contribute to the individualized care of elderly patients, resulting into a fine tuning of the therapeutic strategies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04478916 . registered July 21, 2020 - retrospectively registered.

Vaginal birth after caesarean section: a multicentre study on prognostic factors and feasibility.

PURPOSE: Vaginal birth after caesarean (VBAC) is an option to avoid major abdominal surgery and many consequences related to repeated caesarean delivery. In the last years, many efforts have been made to increase the number of patients attempting trial of labour after caesarean (TOLAC). The aim of our study was to identify the most important factors associated with the success of VBAC. METHODS: A retrospective study was conducted in two Italian referral centres. Subjects included were singleton and morphologically normal pregnancy with previous C-section. Subjects with an inter-pregnancy interval shorter than 18 months, a large for gestational age baby, a pregnancy complicated with gestational diabetes and a previous unclassified uterine scar were excluded. The characteristics of the subjects were compared and a logistic regression was performed to evaluate variables associated with successful VBAC. RESULTS: Of the 300 patients included, 224 (74.7%) achieved VBAC while 76 (25.3%) underwent C-section after failed TOLAC. The number of previous C-sections was not significantly associated with the success of TOLAC. Factors positively associated with achievement of VBAC were previous vaginal delivery (OR of 6.88 for one and 9.68 for more than one) and oxytocin implementation (OR 3.32). No maternal and neonatal adverse events occurred. CONCLUSION: Our results show that attempting VBAC is a feasible option in referral centres after adequate evaluation of the potential factors affecting the probability of success. A careful record of obstetrical history and management of labour can provide clinicians useful information to counsel women before and during labour.

Effect of national and local lockdowns on the control of COVID-19 pandemic: a rapid review.

OBJECTIVES: to describe and compare the effectiveness of national and local lockdowns in controlling the spread of COVID-19. METHODS: a rapid review of published and grey literature on COVID-19 pandemic was conducted following predefined eligibility criteria by searching electronic databases, repositories of pre-print articles, websites and databases of international health, and research related institutions and organisations. RESULTS: of 584 initially identified records up to 5 July 2020, 19 articles met the inclusion criteria and were included in the review. Most of the studies (No. 11) used the reproduction  number (Rt) as a measure of effect and in all of them areduction of the estimated value at post-intervention period was found. The implementation of lockdown in 11 European countries was associated with an average 82% reduction of Rt, ranging from a  posterior Rt of 0.44 (95%CI 0.26-0.61) for Norway to a posterior Rt of 0.82 (95%CI 0.73- 0.93) for  Belgium. Changes in infection rates and transmission rates were estimated in 8 studies. Daily changes in infection rates ranged from -0.6% (Sweden) to -11.3% (Hubei and Guangdong provinces). Additionally, other studies reported a change in the trend of hospitalizations (Italy, Spain) and positive effects on the  doubling time of cases (Hubei, China) after lockdown. CONCLUSIONS: results of this rapid review suggest a positive effect of the containment measures on the spread of COVID-19 pandemic, with a major effect in  countries where lockdown started early and was more restrictive. Rigorous research is warranted to evaluate which approach is the most effective in each stage of the epidemic and in specific social contexts, in particular addressing if these approaches should be implemented on the whole population or target specific risk groups.

Initial plans for a large-scale investigation into the chronic health effects of earthquakes in Italy: building on Barbara Pacelli's legacy.

Barbara Pacelli, a young Italian epidemiologist, passed away unexpectedly in September 2019. During her prolific professional life, she gave several scientific contributions to natural disaster epidemiology, particularly in relation to the medium and long-term health effects of earthquakes. In this opinion paper, we reflect on Barbara's legacy and outline potential actions that could arise from her work. Particularly, availability of electronic health records would enable a systematic and large-scale investigation into the long-term health effects of earthquakes in Italy, a country with high seismic risk. This effort would have high societal value as it would likely enable mitigation of substantial morbidity and mortality in areas affected by earthquakes. In this paper, we define scope, objectives, potential data sources, and analysis methods that could be used to systematically assess the chronic health effects of recent earthquakes in Italy. Keywords: earthquakes; chronic diseases; electronic health records; retrospective cohort; case crossover study.

[Effects of Asbestos on Human Health. Document of the Italian Epidemiological Association (AIE)]. / Effetti dell'amianto sulla salute. Documento dell'Associazione Italiana di Epiemiologia (AIE).

OBJECTIVES: the Italian Epidemiological Association (AIE) intends to formulate assessments and recommendations on the most relevant and critical aspects in the preparation, conduct, and interpretation of epidemiological investigations on the health effects of exposure to asbestos and asbestos-like fibres. DESIGN, SETTING, AND PARTICIPANTS: the document was prepared by a working group of AIE associates, with a broad curriculum of epidemiological investigations, starting from the evaluation of scientific evidence, and was subsequently evaluated by the AIE governing body. RESULTS: the topics covered included: • consumption and presence of asbestos; • association between asbestos exposure and disease; • epidemiological surveillance of asbestos related diseases in Italy; • risk function for asbestos related diseases; • increased risk and anticipation of the disease; • interaction between asbestos and other carcinogens; • diagnosis in epidemiological studies; • assessment of exposure to asbestos; • epidemiological evidence on asbestos related diseases. CONCLUSIONS: the document ends with a summary of the conclusions of scientific research shared by AIE, with reflection on the methodology to be followed for the application at individual level of the results of epidemiological studies, and the proposal of themes on which to direct research.

Patterns and trends of utilization of incretin-based medicines between 2008 and 2014 in three Italian geographic areas.

BACKGROUND: The incretin-based medicines GLP1 analogues (GLP1a) and dipeptidyl peptidase-4 inhibitors (DPP4i) are hypoglycaemic agents licensed for the treatment of type 2 diabetes mellitus (T2DM). Although these drugs possess comparable efficacy and low risk of hypoglycaemia, differences in terms of route of administration (subcutaneous versus oral), effect on body weight and gastrointestinal tolerabily can impact their actual use in clinical practice. This study aimed to describe the real-world utilization of incretin-based medicines in the Italian clinical practice. METHODS: A multi-database, population-based, descriptive, cohort study was performed using administrative data collected between 2008 and 2014 from three Italian geographic areas. Subjects aged ≥18 were selected. New users were defined as those with ≥1 dispensing of GLP1a or DPP4i during the year of interest and none in the past. Trends of cumulative annual incidence of use in the general adult population were observed. New users of GLP1a or DPP4i were respectively described in terms of demographic characteristics and use of antidiabetic drugs during 1 year before and after the first incretin dispensing. RESULTS: The overall study population included 4,943,952 subjects. A total of 7357 new users of GLP1a and 41,907 of DPP4i were identified during the study period. Incidence of use increased between 2008 (0.2‰ for both GLP1a and DPP4i) and 2011 (GLP1a = 0.6‰; DPP4i = 2.5‰) and slightly decreased thereafter. In 2014, 61% of new GLP1a users received once-daily liraglutide while 52% of new DPP4i users received metformin/DPP4i in fixed-dose. The percentage of new DPP4i users older than 65 years of age increased from 30.9 to 62.6% during the study period. Around 12% of new users had not received any antidiabetic before starting an incretin. CONCLUSIONS: During the study period, DPP4i rapidly became the most prescribed incretin-based medicine, particularly among older new user. The choice of the specific incretin-based medicine at first prescription appeared to be directed towards those with higher convenience of use (e.g. oral DPP4i rather than subcutaneous GLP1a, once-daily liraglutide rather than twice-daily exenatide). The non-negligibile use of incretin-based medicines as first-line pharmacotherapy for T2DM warrants further effectiveness and safety evaluations to better define their place in therapy.

Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis. METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time. RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer. CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

Gender differences in pleural mesothelioma occurrence in Lombardy and Piedmont, Italy.

BACKGROUND: Higher mesothelioma rates in men (vs women) reflect more frequent and more intense asbestos exposure. We assessed the impact of exposure difference between genders on age-specific rates of pleural mesothelioma (PM) occurrence using data from two Italian regions. METHODS: We used data from the Lombardy and Piedmont mesothelioma registries (period 2000-2016, age 45-74 years) to compare rates of PM in men and women and to estimate the rate advancement period (RAP). RESULTS: Based on 3384 cases (2405 men, 979 women) in Lombardy and 2042 (1389 men, 653 women) in Piedmont, the rate ratio was 2.81 (90% confidence interval: 2.61-3.03) in Lombardy and 2.39 (2.17-2.62) in Piedmont. In both regions RAP ranged from 7 to 10 years (at age 45 and 63 in men, respectively). CONCLUSION: Men showed more than twofold increased PM rates and reached the same incidence as women 7-10 years earlier. RAP can be a useful measure of exposure impact on premature disease occurrence.

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.

BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.