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Background: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers., Methods: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period., Results: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter., Conclusions: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time., (© 2023 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Objectives: the health status of people living near industrial plants is often exposed to several environmental risk factors, including air pollution. The aim of this study is to assess the relationship between daily PM10 levels and cause-specific mortality in a selection of municipalities near two industrial plants from 2006 to 2015., Design: a time-series design with Poisson regression adjusted for a predefined set of confounders was used to quantify the association between exposure, calculated as daily PM10 levels extrapolated from machine-learning models using satellite data, and cause-specific mortality., Setting and Participants: twenty municipalities near the thermal power plants in Civitavecchia and Brindisi were selected. The municipalities were then divided into three scenarios of chronic exposure derived from SPRAY simulation models of pollutant deposition., Main Outcome Measures: daily cause-specific non-accidental, cardiovascular, and respiratory deaths defined according to the International Classification of Diseases code at the municipality level., Results: a total of 41,942 deaths were observed in the entire area (10,503 in the Civitavecchia area and 31,439 in the Brindisi area), of which approximately 41% were due to cardiovascular causes and 8% due to respiratory causes. The association showed an increase in shortterm effects in municipalities with higher chronic levels of pollution exposure. For example, risk estimates reported as percentage increases per 10-unit increase in PM10 were 6.7% (95% CI 0.9, 12.7%) in scenario 3 (highest exposure) compared to 4.2% (-1.2, 9.9%) and 2.7% (-4.2, 10.2%) in scenarios 2 and 1, respectively, in the area near the Civitavecchia plant. Similar effects were observed for the Brindisi area., Conclusions: despite the well-documented relationship between short-term pollution and mortality, it appears that greater chronic exposure to industrial pollutants leads to increased short-term effects of PM10. The limited number of events suggests that this study could serve as a starting point for a larger investigation.

Objectives: to assess the association between the occupational sector and respiratory mortality in the metropolitan longitudinal studies of Rome and Turin., Design: retrospective cohort study., Setting and Participants: the 2011 census cohorts of residents of Rome and Turin aged 30 years and older who had worked for at least one year in the private sector between 1970s and 2011 was analysed. The individuals included in the study were followed from 9 October 2011 to 31 December 2018. Occupational history was obtained from archives of private sector contributions at the National Social Insurance Agency (INPS) and then was linked to data from the longitudinal studies., Main Outcome Measures: the study outcome was non-malignant respiratory mortality. The exposure of interest was whether or not individuals had worked in one of the 25 occupational sectors considered (agriculture and fishing, steel industry, paper and printing, pharmaceuticals, manufacturing, textile, energy and water, food and tobacco industry, non-metal mining, glass & cement industry, metal processing, electrical construction, footwear and wood industry, construction, trade, hotel and restaurants, transportation, insurance, healthcare, services, laundries, waste management, hairdressing, cleaning services, and gas stations). The association between the occupational sector and respiratory mortality, adjusted for potential confounders (age, marital status, place of birth, educational level), was estimated using Cox models. All analyses were stratified by sex and city., Results: a total of 910,559 people were analysed in Rome and 391,541 in Turin. During the eight years of follow-up, 4,133 people in Rome and 2,772 people in Turin died from respiratory causes. The sectors associated with high respiratory mortality in both cities among men were footwear and wood industry (adjusted HR for age: 1.37 (95%CI 1.07-1.76) and 1.48 (95%CI 1.08-2.03) in Rome and Turin, respectively), construction (HR: 1.31 (95%CI 1.20-1.44) in Rome and 1.51 (95%CI 1.31-1.74) in Turin), hotel and restaurant sector (HR: 1.25 (95%CI 1.07-1.46) in Rome and 1.68 (95%CI 1.20-2.33) in Turin), and cleaning services (HR: 1.57 (95%CI 1.19-2.06) in Rome and 1.97 (95%CI 1.51-2.58) in Turin). Some sectors had high respiratory mortality only in one of the two cities: in Rome, the food& tobacco industry, and gas stations, while in Turin, the metal processing industry. Among female workers, the cleaning services sector was associated with higher respiratory mortality in both Rome and Turin (HR: 1.52, 95%CI 1.27-1.82, e 1.58, 95%CI 1.17-2.12, respectively)., Conclusions: the data confirm the previously known associations between occupational sectors and respiratory mortality for exposures characteristic of specific sectors, such as construction, hotel and restaurant sector, and cleaning services. The differences reported between the two cities reflect the different composition of the workforce and the size of the two study populations. Administrative social insurance data can provide helpful information for epidemiological studies of occupational exposure.

To reflect on the present and the future of the "millennial" epidemiologists in Italy, the starting question is who are we? The online survey "I giovani ricercatori non più giovani: chi siamo? #GIOVANIDENTRO" was launched in 2022 and advertised at conferences of the Italian association of epidemiology to gather voices from all over Italy. Information on training, job position, attitudes and difficulties encountered in our profession and in scientific production activity has been collected and contextualized to answer the starting question and provide food for thought for the perspectives of our profession.

The General data protection regulation (Gdpr) of 2016, implemented since 2018, has become a crucial issue in the field of epidemiology. The Gdpr concerns the protection of personal data, which includes all information that identifies or can identify a natural person, providing information about their habits, health status, and lifestyle, and regulates their processing. Epidemiological studies rely on the use of personal data and their interconnection. The introduction of this regulation is marking an important transition for the work of epidemiologists. There is a need to understand how this can coexist with the research activities that have always been carried out in epidemiology and public health. This section aims to lay the foundations for a discussion on the topic and provide a framework for researchers and epidemiologists that answers some of the doubts that accompany daily work.

The "millennial" epidemiologists, born between the beginning of the 80s and the end of the 90s, are the generation that most of all, today, lives between the present and the future of this discipline. This issue of Recenti Progressi in Medicina aims to talk about what young (and no longer young) epidemiologists and public health researchers are dealing with and to reflect on the most relevant topics in our field, with an eye to the future. Starting from the profile of the "millennial" epidemiologists in Italy and the topics on which they work, the issue develops through three parts dealing with relevant topics for the present and the future of Public health. The first part deals with the important issue of finding a balance between the protection of personal data and the protection of health through a dialogue between researchers, jurists and citizens. The second part aims to clarify the issue of big data and its implications for producing health. The third part touches on four relevant topics for the perspectives of epidemiology through reflections and application examples of machine learning, integration between pharmacoepidemiology and environmental epidemiology, health prevention and promotion involving citizens and other stakeholders, and epidemiology of mental health. In a constantly changing world, challenges for those who work to produce health are not lacking, as is the determination to face them. With this issue, we hope to contribute to the awareness of who we are and our potential, to help millennials (but not only) find their place in epidemiology, today and tomorrow.

Administrative data can be precious in connecting information from different sectors. For the first time, we used data from the National Social Insurance Agency (INPS) to investigate the association between the occupational sectors and both non-accidental and accidental mortality. We retrieved information on occupational sectors from 1974 to 2011 for private sector workers included in the 2011 census cohort of Rome. We classified the occupational sectors into 25 categories and analyzed occupational exposure as ever/never have been employed in a sector or as the lifetime prevalent sector. We followed the subjects from the census reference day (9 October 2011) to 31 December 2019. We calculated age-standardized mortality rates for each occupational sector, separately in men and women. We used Cox regression to investigate the association between the occupational sectors and mortality, producing hazard ratios (HRs) and 95% confidence intervals (95%CI). We analyzed 910,559 30+-year-olds (53% males) followed for 7 million person-years. During the follow-up, 59,200 and 2560 died for non-accidental and accidental causes, respectively. Several occupational sectors showed high mortality risks in men in age-adjusted models: food and tobacco production with HR = 1.16 (95%CI: 1.09-8.22), metal processing (HR = 1.66, 95%CI: 1.21-11.8), footwear and wood (HR = 1.19, 95%CI: 1.11-1.28), construction (HR = 1.15, 95%CI: 1.12-1.18), hotels, camping, bars, and restaurants (HR = 1.16, 95%CI: 1.11-1.21) and cleaning (HR = 1.42, 95%CI: 1.33-1.52). In women, the sectors that showed higher mortality than the others were hotels, camping, bars, and restaurants (HR = 1.17, 95%CI: 1.10-1.25) and cleaning services (HR = 1.23, 95%CI: 1.17-1.30). Metal processing and construction sectors showed elevated accidental mortality risks in men. Social Insurance Agency data have the potential to characterize high-risk sectors and identify susceptible groups in the population.

Background: The role of chronic exposure to ambient air pollutants in increasing COVID-19 fatality is still unclear., Objectives: The study aimed to investigate the association between long-term exposure to air pollutants and mortality among 4 million COVID-19 cases in Italy., Methods: We obtained individual records of all COVID-19 cases identified in Italy from February 2020 to June 2021. We assigned 2016-2019 mean concentrations of particulate matter (PM) with aerodynamic diameter ≤ 10 μ m ( PM 10 ), PM with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ), and nitrogen dioxide ( NO 2 ) to each municipality ( n = 7,800 ) as estimates of chronic exposures. We applied a principal component analysis (PCA) and a generalized propensity score (GPS) approach to an extensive list of area-level covariates to account for major determinants of the spatial distribution of COVID-19 case-fatality rates. Then, we applied generalized negative binomial models matched on GPS, age, sex, province, and month. As additional analyses, we fit separate models by pandemic periods, age, and sex; we quantified the numbers of COVID-19 deaths attributable to exceedances in annual air pollutant concentrations above predefined thresholds; and we explored associations between air pollution and alternative outcomes of COVID-19 severity, namely hospitalizations or accesses to intensive care units., Results: We analyzed 3,995,202 COVID-19 cases, which generated 124,346 deaths. Overall, case-fatality rates increased by 0.7% [95% confidence interval (CI): 0.5%, 0.9%], 0.3% (95% CI: 0.2%, 0.5%), and 0.6% (95% CI: 0.5%, 0.8%) per 1   μ g / m 3 increment in PM 2.5 , PM 10 , and NO 2 , respectively. Associations were higher among elderly subjects and during the first (February 2020-June 2020) and the third (December 2020-June 2021) pandemic waves. We estimated ∼ 8 % COVID-19 deaths were attributable to pollutant levels above the World Health Organization 2021 air quality guidelines., Discussion: We found suggestive evidence of an association between long-term exposure to ambient air pollutants with mortality among 4 million COVID-19 cases in Italy. https://doi.org/10.1289/EHP11882.

Objectives: to estimate the impact of PM2.5 and PM10 in the Italian industrial areas included in the SENTIERI project characterized by industrial plants with combustion processes deriving from point emissions., Design: using satellite data, the Population Weighted Exposure (PWE) to PM2.5 and PM10 for 2011 and 2015 was estimated. The concentration-response functions available were used to estimate the number of premature deaths attributable to exposure to industrial emissions. The counterfactual levels recommended by the new WHO Air Quality Guidelines were used., Setting and Participants: for the selection of industrial plants, the European database on emissions of the European Pollutant Release and Transfer Register was used. Residents in areas of 1 km x 1 km and 4 km x 4 km around the selected industrial plants were considered., Main Outcome Measures: the number of premature deaths from non-accidental causes, cardiovascular and respiratory diseases, and lung cancer was estimated., Results: residents were exposed to PM2.5 values of 17.3 µg/m3 (Northern Italy: 23.3) and to 24.3 µg/m3 (Northern Italy: 30.3) of PM10. PWE for both pollutants tends to increase as the size of the area under study is reduced and it is generally higher everywhere in 2011 than in 2015, with values that are always higher than the average (overall) in the Norther Italy. In 2011, 1,709 (IC95% 1,309-1,903) and 1,611 (IC95% 1,225-2,353) non accidental premature deaths were estimated attributable to PM2.5 and PM10, respectively, in residents close to the industrial plants (1 km x 1 km). Deaths attributable to exposure to PM2.5 and PM10 tend to follow a North-Central-South&Islands gradient for all observed causes and for both years of analysis., Conclusions: although exposure assessment of the population by using random-forest model does not allow to disentangle the contribution of the industrial component, the results of the study are suggestive of an impact on health from PM exposure in the industrial areas considered, with a greater impact in the vicinity of the plants, recommending the implementation of urgent impact reduction actions.

Objectives: to geocode all residence addresses from Lazio Health Information System in order to obtain a geographical regional database., Design: a semiautomatic and multistep geocoding procedure using several tools and software., Setting and Participants: all residence addresses of resident population of Lazio Region (Central Italy) in 2020., Main Outcome Measures: geographic coordinates at residence addresses and accuracy level of geocoding procedure for more than 1 million of addresses., Results: the 99% of residence addresses in the Lazio Region have been geocoded thanks to the purposed procedure; almost 94% of the addresses have been geocoded with a good level of accuracy (more than 56% at civic number level). In the province of Rome, the percentage of addresses geocoded with a good level of accuracy is higher (97.1%), while in the province of Rieti and Frosinone is lower (82.7% and 84.2%, respectively)., Conclusions: this method is useful to obtain accurate geographic coordinates of residences of the entire regional population. This database will be useful for several epidemiological studies in the Region.

The large availability of both air pollution and COVID-19 data, and the simplicity to make geographical correlations between them, led to a proliferation of ecological studies relating the levels of pollution in administrative areas to COVID-19 incidence, mortality or lethality rates. However, the major drawback of these studies is the ecological fallacy that can lead to spurious associations. In this frame, an increasing concern has been addressed to clarify the possible role of contextual variables such as municipalities' characteristics (including urban, rural, semi-rural settings), those of the resident communities, the network of social relations, the mobility of people, and the responsiveness of the National Health Service (NHS), to better clarify the dynamics of the phenomenon. The objective of this paper is to identify and collect the municipalities' and community contextual factors and to synthesize their information content to produce suitable indicators in national environmental epidemiological studies, with specific emphasis on assessing the possible role of air pollution on the incidence and severity of the COVID-19 disease. A first step was to synthesize the content of spatial information, available at the municipal level, in a smaller set of "summary indexes" that can be more easily viewed and analyzed. For the 7903 Italian municipalities (1 January 2020-ISTAT), 44 variables were identified, collected, and grouped into five information dimensions a priori defined: (i) geographic characteristics of the municipality, (ii) demographic and anthropogenic characteristics, (iii) mobility, (iv) socio-economic-health area, and (v) healthcare offer (source: ISTAT, EUROSTAT or Ministry of Health, and further ad hoc elaborations (e.g., OpenStreetMaps)). Principal component analysis (PCA) was carried out for the five identified dimensions, with the aim of reducing the large number of initial variables into a smaller number of components, limiting as much as possible the loss of information content (variability). We also included in the analysis PM 2.5 , PM 10 and NO 2 population weighted exposure (PWE) values obtained using a four-stage approach based on the machine learning method, "random forest", which uses space-time predictors, satellite data, and air quality monitoring data estimated at the national level. Overall, the PCA made it possible to extract twelve components: three for the territorial characteristics dimension of the municipality (variance explained 72%), two for the demographic and anthropogenic characteristics dimension (variance explained 62%), three for the mobility dimension (variance explained 83%), two for the socio-economic-health sector (variance explained 58%) and two for the health offer dimension (variance explained 72%). All the components of the different dimensions are only marginally correlated with each other, demonstrating their potential ability to grasp different aspects of the spatial distribution of the COVID-19 pathology. This work provides a national repository of contextual variables at the municipality level collapsed into twelve informative factors suitable to be used in studies on the association between chronic exposure to air pollution and COVID-19 pathology, as well as for investigations on the role of air pollution on the health of the Italian population.

Objectives: to estimate the impact of the COVID-19 epidemic on total and cause-specific mortality in people residing and dead in the Municipality of Rome (Italy) in 2020, and to describe the causes of death of subjects with SARS-CoV-2 infection confirmed by molecular test., Design: descriptive analysis of total and cause-specific mortality in 2020 in Rome and comparison with a reference period (2015-2018 for total mortality and 2018 for cause-specific mortality); descriptive analysis of cause-specific mortality in the cohort of SARS-CoV-2 infected subjects., Setting and Participants: 27,471 deaths registered in the Lazio mortality-cause Registry, relating to people residing and died in the municipality of Rome in 2020, 2,374 of which died from COVID-19.MAIN OUCOME MEASURES: all-cause mortality by month, gender, age group and place of death, cause-specific mortality (ICD-10 codes)., Results: in the municipality of Rome in 2020, an excess of mortality from all causes equal to +10% was observed, with a greater increase in the months of October-December (+27%, +56%, and +26%, respectively) in people aged 50+, with the greatest contribution from the oldest age groups (80+) who died in the nursing homes or at home. Lower mortality was observed in the age groups 0-29 years (-30%) and 40-49 years (-13%). In 2020, COVID-19 represents the fourth cause of death in Rome after malignant tumours, diseases of the circulatory system, and respiratory diseases. Excess mortality was observed from stroke and pneumonia (both in men and women), from respiratory diseases (in men), from diabetes, mental disorders, dementia and Parkinson's disease (in women). On the contrary, mortality is lower for all cancers, for diseases of the blood and haematopoietic organs and for the causes of the circulatory system. The follow-up analysis of SARS-CoV-2 positive subjects residing in Rome shows that a share of deaths (about 20%) reports other causes of death such as cardiovascular diseases, malignant tumours, and diseases of the respiratory system on the certificate collected by the Italian National Statistics Institute., Conclusions: the 2020 mortality study highlighted excesses for acute and chronic pathologies, indicative of possible delays in the diagnosis or treatment of conditions indirectly caused by the pandemic, but also a share of misclassification of the cause of death that is recognized as COVID-19 death.

Asbestos is one of the major worldwide occupational carcinogens. The global burden of asbestos-related diseases (ARDs) was estimated around 231,000 cases/year. Italy was one of the main European asbestos producers until the 1992 ban. The WHO recommended national programs, including epidemiological surveillance, to eliminate ARDs. The present paper shows the estimate of the burden of mortality from ARDs in Italy, established for the first time. National standardized rates of mortality from mesothelioma and asbestosis and their temporal trends, based on the National Institute of Statistics database, were computed. Deaths from lung cancer attributable to asbestos exposure were estimated using population-based case-control studies. Asbestos-related lung and ovarian cancer deaths attributable to occupational exposure were estimated, considering the Italian occupational cohort studies. In the 2010-2016 period, 4400 deaths/year attributable to asbestos were estimated: 1515 from mesothelioma, 58 from asbestosis, 2830 from lung and 16 from ovarian cancers. The estimates based on occupational cohorts showed that each year 271 deaths from mesothelioma, 302 from lung cancer and 16 from ovarian cancer were attributable to occupational asbestos exposure in industrial sectors with high asbestos levels. The important health impact of asbestos in Italy, 10-25 years after the ban, was highlighted. These results suggest the need for appropriate interventions in terms of prevention, health care and social security at the local level and could contribute to the global estimate of ARDs.

Objective: To conduct a systematic review to evaluate the association between residential or occupational short- and long-term exposure to odour pollution from industrial sources and the health status of the exposed population., Methods: The searches were conducted in Medline, EMBASE and Scopus in April 2021. Exposure to an environmental odour from industrial sources in population resident near the source or in workers was considered. We considered outcomes for which there was a biological plausibility, such as wheezing and asthma, cough, headache, nausea and vomiting (primary outcomes). We also included stress-related symptoms and novel outcomes (e.g. mood states). Risk of bias was evaluated using the OHAT tool. For primary outcomes, when at least 3 studies provided effect estimates by comparing exposed subjects versus not exposed, we pooled the study-specific estimates of odour-related effect using random effects models. Heterogeneity was evaluated with Higgins I 2 ., Results: Thirty studies were eligible for this review, mainly cross-sectional (n = 23). Only one study involved school-age children and two studies involved workers. Only five studies reported odour effects on objective laboratory or clinical outcomes. Animal Feeding Operations and waste were the most common industrial sources. The overall odds ratios in exposed versus not exposed population were 1.15 (95% CI 1.01 to 1.29) for headache (7 studies), 1.09 (95% CI 0.88 to 1.30) for nausea/vomiting (7 studies), and 1.27 (95% CI 1.10 to 1.44) for cough/phlegm (5 studies). Heterogeneity was a moderate concern. Overall, the body of evidence was affected by a definitely high risk of bias in exposure and outcome assessment since most studies used self-reported information., Conclusions: Findings underline the public health importance of odour pollution for population living nearby industrial odour sources. The limited evidence for most outcomes supports the need for high quality epidemiological studies on the association between odour pollution and its effects on human health., (© 2021. The Author(s).)

Objectives: to perform a meta-analysis of cohort studies on lung cancer mortality in occupational sectors exposed to asbestos, particularly in the construction sector, and to use data from Italian cohorts exposed to asbestos to estimate the number of lung cancer cases attributable to asbestos in Italy., Methods: systematic literature review and estimation of lung cancer deaths and cases attributable to asbestos in Italian cohorts and from the Italian National Register of Malignant Mesothelioma (ReNaM)., Setting and Participants: the literature search was conducted in Medline and Embase (Ovid), including papers published from 1999 to May 2019. The following sectors were considered most exposed to asbestos: asbestos-cement, rolling-stock, shipyards, dockyards, glass workers, insulators, asphalt roll production workers, industrial ovens, miners. Moreover, the construction sector was included., Main Outcome Measures: the standardized mortality ratio (SMR) was estimated from the meta-analysis of the literature review. The ratio lung cancer to mesothelioma attributable cases was estimated by occupational sector from the Italian cohorts. For the construction sector, the ratio lung cancer to mesothelioma cases was estimated within the exposed workers estimated by CAREX (1990-1993). The ratios were applied to the mesothelioma cases registered at the ReNaM for the 2010-2015 period, to obtain a national estimate of lung cancer cases attributable to occupational exposure to asbestos., Results: the meta-analytical SMR for lung cancer in men varied between 1.05 (asphalt roll) and 2.36 (insulation). The mean risk for all sectors was 1.37 in men and 1.60 in women. It increased in cohorts with latency higher than 20 years. Significant risks were observed in asbestos-cement (both genders), construction, and mining sectors. There was a mean of 1.1, 2.7, and 2.8 lung cancer deaths per mesothelioma death in the cement-asbestos, harbour, and construction sectors, respectively. The impact in terms of lung cancer cases estimated at the national level was equal to 3,814 cases between 2010 and 2015., Conclusions: to provide an overall assessment of the impact of the occupational asbestos exposure, it is important to consider lung cancer cases, in addition to malignant mesotheliomas. This study was able to estimate the impact of asbestos on lung cancer in Italy 25 years after the ban of this occupational carcinogen, with the largest contribution in terms of attributable cases coming from the construction sector. It is urgent to implement adequate information and prevention strategies, health surveillance of workers, and the appropriate legal framework for insurance purposes.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R 2 ) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups ( p < 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R 2 was recorded for EFT (R 2 = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.

Objective: Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers., Methods: Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period., Results: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer., Discussion: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.

The area of Civitavecchia (Lazio region, Central Italy) has been a reason of concern in the past because of environmental air contamination. The aim of this study was to evaluate the association between air pollution from different sources and respiratory symptoms and lung function in the population. A sample of 1177 residents underwent medical examination and lung function tests. Information on individual characteristics, histories of exposure and medical history were collected through a validated questionnaire. Long-term exposure to industrial, harbour, biomass combustion emissions (PM 10 ) and urban traffic (NO x ) at residential address was assessed using a Lagrangian dispersion model. The associations between exposure and wheezing and dyspnea were assessed using logistic regression models, while modified Poisson regression models were used to evaluate cough with phlegm. Relationships between exposure and lung function were analysed using linear mixed-effects models and cross-correlation. PM10 emissions from the harbour were associated with lower lung function parameters (FEV1: β = -0.12, 95% CI -0.21 -0.03; p = 0.02; FEV1/FVC: β = -1.67, (-3.10 -0.23); p = 0.02. This association was observed also in healthy subjects, but not in females. We found, even if at low exposure level, an effect of environmental PM 10 exposure from harbour on lung function., Competing Interests: The authors declare no conflict of interest.

Objectives: to estimate the environmental and health impact attributable to PM2.5 emissions from the ex-ILVA steel plant in Taranto and the ENEL power plant in Brindisi (Apulia Region, Southern Italy)., Design: a SPRAY Lagrangian dispersion model was used to estimate PM2.5 concentrations and population weighted exposures following the requirements of the Integrated Environmental Authorization (IEA) of the two plants under study. Available concentration-response functions (OMS/HRAPIE and updates) were used to estimate the number of attributable premature deaths., Setting and Participants: residents in the 40 municipalities of the domains of the VDS (assessment of health damage, according to the Regional Law n. 21/2012) of Brindisi (source: Italian National Institute of Statistics 2011 Census) and residents in Taranto, Statte, and Massafra (source: cohort study)., Main Outcome Measures: mortality from natural causes, cardiovascular and respiratory diseases, and lung cancer attributable to PM2.5. Incremental lifetime cumulative risks (ILCRs) for lung cancer associated to PM2.5 exposure., Results: there was a reduction of the estimated impacts from the pre to the post IEA-scenarios in both Taranto and Brindisi. In Taranto, ILCRs greater than 1x10 -4 ; were estimated in 2010 and 2012; the ILCR was greater than 1x10 -4 ; in the district of Tamburi (near the plant) also for the 2015 scenario. ILCRs estimated for Brindisi were between 1x10 -6 ; and 4x10 -5 ;., Conclusions: the Integrated Environmental Health Impact Assessment confirmed the results of the VDS conducted according to the toxicological risk assessment approach. An unacceptable risk was estimated for Tamburi also for the 2015 scenario, characterized by a production of 4.7 million tons of steel, about half compared to one foreseen by the IEA (8 mt.).

(1) Background : The products of guanine oxidation in DNA and RNA excreted in urine are 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Despite intra and inter-individual variability, it is possible to identify situations that significantly increase the levels of these compounds when comparing urinary concentrations of some workers to those of the general population. (2) Methods : urines from gasoline pump attendants (58 from Saudi Arabia and 102 from Italy), 24 workers of a fiberglass reinforced plastics plant, 17 painters and 6 divers were analyzed by HPLC/MS-MS. To test the individual variability, two subjects provided daily samples for one month, and 132 urine samples from the general population were analyzed. (3) Results : We summarized the results for each biomarker, and found the following were statistically higher than in the general population: 8-oxoGua in fiberglass and Italian gasoline workers; 8-oxodGuo in fiberglass and both Saudi Arabian and Italian gasoline workers; 8-oxoGuo in fiberglass workers, both Saudi Arabian and Italian gasoline workers, and painters after the working shift. (4) Conclusions : these results confirm that both 8-oxodGuo and 8-oxoGuo are valuable biomarkers for occupational exposures to dangerous chemicals and seem to suggest that 8-oxoGuo, related to RNA oxidation, is a suitable biomarker to evaluate short term, reversible effects of occupational exposures even within the health-based limit values.

Background: the assessment of individual exposure to toxicants in industrially contaminated areas is difficult when multiple productions are actively close to residential areas. Two thermoelectric power plants (one recently converted to coal) and a large harbour have been operating since the Sixties in the area of Civitavecchia (North of Rome, Lazio Region, Central Italy). Detailed exposure assessment of pollutants from industrial sources, heating (biomass combustion), and urban traffic were not available., Objectives: to assess the individual exposure of residents by using both dispersion models and human biomonitoring., Design: cross-sectional study., Setting and Participants: residents in the area of Civitavecchia since 2001 aged 35-69 years were enrolled and their addresses were geocoded. Exposure assessment to power plants emissions (PM10), traffic (NOx), harbour (PM10), and biomass burning (PM10) was performed at individual residential address using Lagrangian dispersion models. The "Ambiente e Biomarcatori a Civitavecchia" study (Environment and biomarkers in Civitavecchia - ABC study) made available urinary concentrations of metals (i.e., Cd, Pt, W, Pd, Hg, Tl, Cr, Pd, Ni, As) in a sample of residents, while information on personal characteristics, lifestyles, work history, clinical history, and use of drugs was collected by interview., Main Outcome Measures: for each metal, a linear regression analysis was implemented to study the association between its log-transformed values (adjusted for urinary creatinine) and the linear terms of the estimated pollutants concentrations, adjusted for age, gender, period, and other risk factors (i.e., educational level, smoking habit, alcohol, BMI). Geometric Mean Ratios (GMR) and the corresponding confidence intervals (95%CI) were computed., Results: in the ABC sample of 1,141 residents (42% male, mean age 53.5 years, SD 9.7), there was a positive association between PM10 from power plants and urinary cadmium (Cd) (GMR: 1.12; 95%CI 1.00-1.25), traffic pollution (NOx) and platinum (Pt) (GMR: 1.17; 95%CI 1.00-1.38), PM10 from biomass burning and Cd (GMR: 1.14; 95%CI 1.05-1.24), and tungsten (W) (GMR: 1.19; 95%CI 1.03-1.37) and palladium (Pd) (GMR: 1.11; 95%CI 1.00-1.23). Other associations observed did not reach statistical significance., Conclusions: although it may not be said that dispersion models can replace biomonitoring studies, they certainly represent an excellent tool for exposure assessment and, therefore, they may be used for the estimation of the individual exposure of populations living in industrially contaminated areas.

Background: industrially contaminated sites (ICSs) have been recognised as a major public health concern since they involve exposure to multiple environmental stressors, normally distributed unevenly within population. The COST Action on Industrially Contaminated Sites and Health Network (ICSHNet) comprises a European network of experts and institutions to clarify needs and priorities for better characterising the impact on environment and health of ICS., Objectives: evaluate the availability of information and studies concerning selected ICSs in participating Countries within the ICSHNet, with particular consideration on the accessibility to environmental, health and demographic data, and research and assessment tools., Methods: to evaluate the availability of data, an Action Questionnaire (AQ) was developed based on previous questionnaires used in different European projects and on expert consultation. The AQ, with 84 items organised in eight sections, was adapted to an on-line version using the software LimeSurvey. The survey was sent to 47 participants within the ICSHNet, to report over a list of 99 ICSs previously identified., Results: information was gathered from 81 sites out of the initially selected 99, reported by 45 participants from 27 Countries (82% of Countries in the ICSHNet). The predominant polluting activities were waste disposal (46%) and chemical industries (37%), affecting all environmental media, but more extensively surface and groundwater (70%) and soil (68%). Main categories of contaminants affecting different media were heavy metals and chlorinated hydrocarbons, but also BTEX (benzene, toluene, ethylbenzene, and xylene) and ambient air pollutants (e.g., particulate matter, SOx). Human health risk assessment was the most prevalent methodological approach for characterising impacts on health (32%), followed by epidemiological studies (26%), and health impact assessment (12%). The low reporting, both referring to data availability or methodologies, could be due to absence of data, or to the fact that the reporting person (many of them from the public health sector) did not know how to reach the environmental information., Conclusions: survey findings suggest that improving the collection and access to specific environmental, health and demographic data related to ICSs is crucial to meet the methodological requirement to better analyse the health impact of ICSs.

Background and Aims: Residents near industrial areas are exposed to several toxins from various sources and the assessment of the health effects is difficult. The area of Civitavecchia (Italy) has several sources of environmental contamination with potential health effects. We evaluated the association between exposure to pollutants from multiple sources and mortality in a cohort of people living in the area., Methods: All residents of the area in 1996 were enrolled (from municipal registers) and followed until 2013. Long-term exposures to emissions from industrial sources (PM10) and traffic (NO x ) at the residential addresses were assessed using a dispersion model. Residence close to the harbour was also considered. Cox survival analysis was conducted including a linear term for industrial PM10 and NO x exposure and a dichotomous variable to indicate residence within 500 m of the harbour. Age, sex, calendar period, occupation and area-based socioeconomic position (SEP) were considered (HRs, 95% CI)., Results: 71 362 people were enrolled (52% female, 43% low SEP) and 14 844 died during the follow-up. We found an association between industrial PM10 and mortality from non-accidental causes (HR=1.06, 95% CI 1.01 to 1.12), all cancers (HR=1.11, 95% CI 1.01 to 1.21) and cardiac diseases (HR=1.12, 95% CI 1.01 to 1.23). We also found an association between NO x exposure from traffic and mortality from all cancers (HR=1.13, 95% CI 1.01 to 1.26) and neurological diseases (HR=1.50, 95% CI 1.01 to 2.20). Living near the harbour was associated with higher mortality from lung cancer (HR=1.31, 95% CI 1.04 to 1.66) and neurological diseases (HR=1.51, 95% CI 1.05 to 2.18)., Conclusions: Estimated exposures to different pollution sources in this area were independently associated with several mortality outcomes while adjusting for occupation and socioeconomic status., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Polycyclic aromatic hydrocarbons (PAH) are products of the incomplete combustion of organic materials, and exposure of the general population to PAH is ubiquitous. They are also present in tobacco smoke. Some PAH are classified as carcinogens. Urine samples from 747 non-smoking and 269 smoking subjects living in the same area of Central Italy were analyzed in order to determine reference values for PAHs exposure of a general population. The concentration of cotinine, urinary metabolite of nicotine was also measured in these samples in order to classify the subjects as smokers or not. The median concentration and 50th percentile in females was higher than in males for all metabolites; 1- and 2-hydroxynaphtalene (1-OHNAP and 2-OHNAP) and 1-hydroxypyrene (1-OHPy), are significantly higher in smokers; on the other side 3-hydroxybenzo[a]pyrene (3-OHBaPy) and 6-hydroxynitropyrene (6-OHNPy) do not correlate with the cotinine concentration.

Objectives: to test the validity of algorithms to identify diabetes, chronic obstructive pulmonary disease (COPD), hypertension, and hypothyroidism from routinely collected health data using information from self-reported diagnosis and laboratory or functional test., Setting and Participants: clinical or self-reported diagnosis from three surveys conducted in Lazio Region (Central Italy) between year 2010 and 2014 were assumed as gold standard and compared to the results of the algorithms application to administrative data., Main Outcome Measures: prevalence resulted from administrative data and from information available in the surveys were compared. Sensitivity, specificity, positive predictive value, and positive likelihood ratio of algorithms with respect to self-reported diagnosis, laboratory or functional test, assumed as gold standards, were calculated., Results: we analyzed data of 7,318 subjects (1,545 for diabetes, 1,783 for COPD, 2,448 for hypertension, and 1,542 for hypothyroidism). For hypertension and hypothyroidism, we observed a higher prevalence from laboratory or functional test compared to self-reported diagnosis (54.5% vs. 44.9% and 7.5% vs. 1.5%). Sensitivity of administrative data with respect to self-reported diagnosis resulted 90.9%, 38.5%, 88.3%, and 47.8%, respectively, for diabetes, COPD, hypertension, and hypothyroidism. Respectively, specificity was 97.4%, 91.7%, 84.8% and 91.8%; positive predictive value was 70,9%, 38.1%, 82.6% and 8.1%. All values of positive likelihood ratio resulted moderate (about 5), with exception of the diabetes algorithm and the disease-specific payment exemptions register for hypertension (respectively 35.5 and 17.4)., Conclusion: hypertension and hypothyroidism resulted markedly underdiagnosed from self-reported data. Case identification algorithms are highly specific, allowing their utilization for selection of cohort of subject affected by chronic diseases. The sub-optimal sensitivity observed for COPD and hypothyroidism could limit the utilization of the algorithms for prevalence estimation.

Background: this paper is based upon work from COST Action ICSHNet. Industrial contaminated sites (ICSs) are of high concern since industrial plants have produced widespread contamination potentially affecting the health of local population OBJECTIVES: to assess the types of epidemiological designs applied in studies of health effects related to ICSs according to time periods, type of ICS, and geography., Methods: a literature search was conducted in Medline (OVID) through June 30th, 2018, using MeSH and customized terms, and no restrictions on publication year or language. We included all studies throughout the world where a potential contamination of industrial origin occurred, an epidemiological approach (including biomonitoring, HBM) was applied, and health outcomes or exposure biomarkers among residents were investigated. Data on publication year, geographical localization and ICS characterization, study design (systematic reviews, cohort, case-control, temporal changes, cross-sectional, ecological, descriptive - area-level, case-series, narrative reviews, and HBM), and health outcomes were extracted from the abstracts. To check the sensitivity of the main search strategy, a case-study on Italy was conducted applying an ad-hoc search., Results: from a literature search capturing 5,485 studies, 655 studies on resident populations were identified. The review includes more than 376 different ICSs, 86% from Europe, North America, and Asia combined, mostly dealing with nuclear sites and mining industries, waste and petrochemical activities. Most of the studies were descriptive (32.5%), cross-sectional (16.3%), or narrative review (14.8%), while analytical studies - case-control and cohort studies (9.6% and 8.4%, respectively) - were rarer; HBM were only 6.9%. A total of 235 studies, conducted mostly in Asia (34.5%), Europe (25.5%), and North America (22.3%), included children. The most frequently studied outcome was cancer (33.7%), followed by respiratory diseases (11.4%), and reproductive health (11.4%). The ad-hoc strategy greatly increased the number of detected papers (+122%)., Conclusions: future research should adopt the most valid and suitable study design, according to the area-specific social and environmental context, also in areas of the world which are less studied, but with very high environmental worries of the resident population suffering the industrial contamination. Involvement of local experts on ICSs and local inventories are recommended to improve the coverage of the present inventory.

Background: Benzene is an important component of cigarette smoke and car exhaust. Products containing benzene in concentrations greater than 0.1% are prohibited in Europe, but 1% of benzene is still allowed in gasoline. The purpose of the study was to assess the levels of urine benzene biomarkers in a sample of the general population not occupationally exposed to benzene, resident in the period 2013⁻2014 in Central Italy, compared to other groups., Methods: The urinary levels of the benzene metabolites S-phenyl-mercapturic acid (SPMA) and cotinine (nicotine metabolite) were determined by means of HPLC with mass spectrometric detection in 1076 subjects., Results: The median SPMA value in smokers was 1.132 &micro;g/g of creatinine while in non-smokers it was 0.097 &micro;g/g of creatinine, and the 95th percentile results were seven times higher., Conclusion: The main source of benzene exposure in the studied population was active smoking, however, non-smokers were also exposed to airborne benzene concentrations. The concentration ranges found in this study can be used as a background reference for occupational exposure assessment to benzene by means of SPMA biomonitoring.

Background: Urinary cotinine, a metabolite of nicotine, is a marker of tobacco smoke exposure. A cutoff value for cotinine concentration can be set to distinguish smokers from non-smokers, independently from self-declared status. Method: Cotinine was determined by isotopic dilution High Performance Liquid Chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) between 2013 and 2014 on urine samples of a population of 1075 subjects. Results : 296 subjects have a cotinine level higher than 100 &mu;g/g of creatinine (cutoff), with a median cotinine concentration of 1504.70 &mu;g/g of creatinine. The mean is 27.5% of smokers and 60.5% in this group are females. The median value for non-smokers is 5.6 &mu;g/g of creatinine. Two hundred and seventy-five subjects declared to be smokers in the questionnaire, but 6 (2.2%) present urinary cotinine levels lower than cutoff; 800 subjects declared to be non-smokers, but 26 of them presented urinary cotinine levels that were higher than the cutoff (3.3%). Conclusion: Using the cutoff of 100 &mu;g/g, the misclassification of smokers resulted to be 2.2%, indicating that the selected value is suitable for studying the human exposures to environmental and occupational pollutants, including those produced by smoking.

Context: Several urinary PAHs metabolites can be detected by HPLC-MS/MS for individual exposure assessment., Objective: Quantitation of urinary metabolites of four PAHs, selected on the basis of their significance, with reduced costs and high sensitivity., Materials and Methods: HPLC-MS/MS was used and pure standards and isotope-labeled internal analogs of the analytes. Two hundred samples were tested after enzymatic hydrolysis., Results: Accuracy was higher than 90% and variability lower than 19%; LODs permit to measure 1-hydroxypyrene, 1 and 2-hydroxynaphthalene in all subjects, 6-hydroxynitropyrene in the 65% and 3-hydroxybenzo[a]pyrene in the 70%., Discussion and Conclusion: The method is suitable both for occupational and for environmental studies. This is the first paper reporting urinary levels of 6-hydroxynitropyrene in European subjects, nonoccupationally exposed to nitro-PAHs.

Inhaled corticosteroid (ICS) use in chronic obstructive pulmonary disease (COPD) patients is associated with a reduction of exacerbations and a potential risk of pneumonia. The objective was to determine if ICS use, with or without long-acting β 2 -agonist, increases pneumonia risk in COPD patients. A cohort study was performed using linked hospital and drug prescription databases in the Lazio region. Patients (45+) discharged with COPD in 2006-2009 were enrolled and followed from cohort entry until first admission for pneumonia, death or study end, 31 December, 2012. A nested case-control approach was used to estimate the rate ratio (RR) associated with current or past use of ICS adjusted for age, gender, number of exacerbations in the previous year and co-morbidities. Current users were defined as patients with their last ICS prescribed in the 60 days prior to the event. Past users were those with the last prescription between 61 and 365 days before the event. Current use was classified into three levels (high, medium, low) according to the medication possession ratio. Among the cohort of 19288 patients, 3141 had an event of pneumonia (incidence rate for current use 87/1000py, past use 32/1000py). After adjustment, patients with current use were 2.29 (95% confidence interval [CI]: 1.99-2.63) times more likely to be hospitalised for pneumonia with respect to no use; for past use RR was 1.23 (95% CI: 1.07-1.42). For older patients (80+), the rate was higher than that for younger patients. ICS use was associated with an excess risk of pneumonia. The effect was greatest for higher doses and in the very elderly.

Background: The assessment of individual exposure to toxicants in industrially contaminated areas is difficult when multiple productions are active close to residential areas. Two thermoelectric power plants and a large harbor have been operating since the '60s in the area of Civitavecchia (North of Rome)., Methods: The ABC (Ambiente e Biomonitoraggio nell'area di Civitavecchia, Environment and Biomonitoring in Civitavecchia) program involved, in the period 2013-2014, residents in Civitavecchia and in the nearby municipalities (Santa Marinella, Allumiere, Tolfa and Tarquinia). They were randomly selected from the Municipal Register's data and their residence addresses were geocoded using GIS techniques. Biomonitoring of the following urinary metals, Sb, Be, Mo, Cd, Sn, W, Ir, Pt, Hg, Tl, V, Cr, Mn, Co, Ni, Cu, Zn, Rh, Pd, As were performed. Glucose and lipid metabolism, liver, renal, and endocrine function were evaluated through blood laboratory tests. Tests of lung functionwere also carried out as well as saturometry (oxygen rate in the blood with an illuminated sensor placed on the fingertip), anthropometric and blood pressure measurements. Information on individual characteristics, histories of exposure, such as the consumption of local food, occupational history, lifestyle and medical history were collected through a validated questionnaire. Samples of nails and hair were also collected. The biological material (blood, urine, nails and hair) was stored in a biobank for future analysis related to the possible mechanisms of biological damage. The study protocol received the approval of the local ethics committee., Results: A total of 1177 residents were enrolled (58% female, 60% with a secondary or graduate school degree). No particular differences in metal concentrations based on the municipality of residence were observed. For arsenic, mercury, lead, and tungsten some differences between the two geographical areas were observed, probably due to different diet, lifestyle (e.g., alcohol consumption, smoking, use of jewelry and piercings, tattoos, physical activity, hormonal and mineral supplements, and drugs), and occupational exposure., Conclusions: The undergoing study on the association between biomarkers concentration and pollutants concentrations - estimated using a dispersion modeling approach, and adjusting for personal characteristics and concomitant other environmental exposure - could clarify the individual exposure of the residents in this industrial area.

Purpose: Chronic therapy with long-acting bronchodilators (LB) is recommended to treat moderate-to-severe COPD. Although the benefits of adding inhaled corticosteroid (ICS) to LB are still unclear, patients who experience repeated exacerbations are suggested to add ICS to their LB treatment. The objective of this study is to analyze whether adding ICS to LB therapy reduces mortality., Methods: We identified a cohort of patients discharged from hospital with COPD diagnosis between 2006 and 2009. The first prescription for LB or ICS following discharge was defined as the index prescription. Only new users were included (no use of any study drug in the 6 months before treatment). A 4-day time window was used to classify patients into "LB alone" or "LB plus ICS" initiators. We used propensity score to balance the study groups. Sensitivity analyses were performed in patients with recent out-of-hospital exacerbations., Results: Among the 18615 adults enrolled, 12207 initiated "LB plus ICS" therapy and 6408 "LB alone." Crude mortality rates were 110 and 143 cases per 1000 person-years in the "LB plus ICS" and "LB alone" groups, respectively. The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.72-0.97; p-value: 0.024). When analyzing patients with recent out-of-hospital exacerbations, the benefit of the combination therapy was more pronounced, HR = 0.63 (95% CI: 0.44-0.90; p-value: 0.012)., Discussion: Our findings showed a beneficial effect on mortality of adding inhaled corticosteroids to long-acting bronchodilators. The advantage was much more pronounced in patients with frequent exacerbations.

Purpose: Long-acting bronchodilators, i.e. beta-2-agonists (LABA) and tiotropium are commonly used in COPD treatment. Choice of a specific agent is based on effectiveness and safety. Evidence yields controversial results with respect to mortality. The present study compared one-year mortality associated to treatment with tiotropium versus LABA., Methods: A population-based cohort study using data from Italian health information systems was performed. Patients aged 45+ years, discharged with COPD diagnosis in 2006-2009 were identified. Through record linkage with drug claims, patients who received a first prescription of LABA or tiotropium within 6 months after discharge were enrolled. The main analysis was restricted to naïve users (no prior use of either LABA or tiotropium). We used 'intention to treat' (ITT) and 'as treated' (AT) approaches. We followed patients for a maximum of 12 months. Hazard ratios (HRs) were calculated by Cox regression including quintiles of propensity score. In sensitivity analysis patients receiving tiotropium + LABA combination were included in the tiotropium group., Results: Among the 33 891 enrolees, 28% were exposed to Tio, 56% to LABA, 16% to both. Overall mean age was 74 years and the mortality rate was 122/1000 person-years (py) at the ITT analysis and 108/1000 py at the AT analysis. The adjusted HR for tiotropium only compared with LABA only was 1.06 (95%CI: 0.94-1.20) at the ITT analysis and 1.00 (95%CI: 0.93-1.08) at the AT analysis. Results were robust in sensitivity analysis., Conclusions: In this real-world study use of tiotropium was not associated with an increased risk of one-year mortality compared with LABA. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd., (© 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.)

Objectives: Time-window bias was described in case-control studies and led to a biased estimate of drug effect. No studies have measured the impact of this bias on the assessment of the effect of medication adherence on health outcomes. Our goals were to estimate the association between adherence to drug therapies after myocardial infarction (MI) and the incidence of a new MI, and to quantify the error that would have been produced by a time-window bias., Setting: This is a population-based study. Data were obtained from the Regional Health Information Systems of the Lazio Region in Central Italy (around 5 million inhabitants)., Participants: Patients discharged after MI in 2006-2007 were enrolled in the cohort and followed through 2009., Outcome Measure: The study outcome was reinfarction: either mortality, or hospital admission for MI, whichever occurred first., Design: A nested case-control study was performed. Controls were selected using both time-dependent and time-independent sampling. Adherence to antiplatelets, β-blockers, ACE inhibitors/angiotensin receptor blockers (ACEI/ARBs) and statins was calculated using the proportion of days covered (PDC)., Results: A total of 6880 patients were enrolled in the cohort. Using time-dependent sampling, a protective effect was detected for all study drugs. Conversely, using time-independent sampling, the beneficial effect was attenuated, as in the case of antiplatelet agents and statins, or completely masked, as in the case of ACEI/ARBs and β-blockers. For ACEI/ARBs, the time-dependent approach produced ORs of 0.83 (95% CI 0.57 to 1.21) and 0.72 (0.55 to 0.95), respectively, for '0.5 < PDC ≤ 0.75' and 'PDC>0.75' versus '0 ≤ PDC ≤ 0.5'. Using the time-independent approach, the ORs were 0.96 (0.65 to 1.43) and 1.00 (0.76 to 1.33), respectively., Conclusions: A time-independent definition of a time-dependent exposure introduces a bias when the length of follow-up varies with the outcome. The persistence of time-related biases in peer-reviewed papers strongly suggests the need for increased awareness of this methodological pitfall., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aims: We evaluated adherence to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for patients in the Lazio region of Italy and the impact of discharge ward type on therapy discontinuation., Methods: From the Hospital Information System, we selected patients who underwent PCI from 2006 to 2007 and obtained Regional Drug Dispense Registry data for antiplatelet drugs prescribed for 12 months after discharge. Appropriate therapy was defined as DAPT with prescribed daily doses for each drug covering at least 75% of each individual follow-up period. The association between discharge ward type and antiplatelet therapy adherence at 12 months post discharge was estimated using multilevel logistic regression analysis., Results: A total of 11 186 patients with PCI were included, and fewer than half (4984; 44.56%) were on adequate DAPT. Only 2930 of 5390 patients (54.36%) with DAPT in the first 6 months post discharge continued DAPT in the second 6 months. Patients discharged from cardiology units or intensive coronary care units were more likely (odds ratio = 1.26; P = 0.003) to receive appropriate antiplatelet therapy, and elderly patients were less likely (odds ratio = 0.65; P < 0.001) to do so., Conclusion: The proportion of PCI patients receiving appropriate DAPT after discharge is suboptimal in this region, and elderly patients are less likely to receive appropriate therapy. These findings could be important for improving patient management and ensuring adherence to clinical guidelines and indicate the need for a systematic evaluation of the appropriateness of postdischarge therapy.

Background: Studies of Idiopathic Pulmonary Fibrosis (IPF) epidemiology show regional variations of incidence and prevalence; no epidemiological studies have been carried out in Italy., Objective: To determine incidence and prevalence rates of IPF in the population of a large Italian region., Methods: in this cross-sectional study study data were collected on all patients of 18 years of age and older admitted as primary or secondary idiopathic fibrosing alveolitis (ICD9-CM 516.3) to Lazio hospitals, from 1/1/2005 to 31/12/2009, using regional hospital discharge, population and cause of death databases. Reporting accuracy was assessed on a random sample of hospital charts carrying the ICD9-CM 516.3, 516.8, 516.9 and 515 codes, by reviewing radiology and pathology findings to define cases as IPF "confident", "possible" or "inconsistent"., Results: Annual prevalence and incidence of IPF were estimated at 25.6 per 100,000 and 7.5 per 100,000 using the ICD9-CM code 516.3 without chart audit while they were estimated at 31.6 per 100,000 and at 9,3 per 100,000 for the IPF "confident" definition after hospital chart audit., Conclusion: The data provide a first estimate of IPF incidence in Italy and indicate that incidence and prevalence in southern European regions may be similar to those observed in northern Europe and North America.

Background: COPD is the fourth leading cause of death in the world. In the case of exacerbations or persistent symptoms, regular treatment with long-acting bronchodilators is recommended to control the symptoms, reduce exacerbations and improve health status. Objectives. To describe patterns of drug utilization among patients diagnosed with COPD, to measure continuity with long-acting bronchodilators, to identify determinants of not receiving long-acting therapy continuously., Methods: We identified a cohort of patients discharged from hospital with diagnosis of COPD between 2006 and 2008. Patients were observed for a two-year follow-up period, starting from the day of discharge. Follow-up was segmented in six-month periods, in order to dynamically evaluate prescription patterns of Long-Acting Beta-Agonists (LABA), tiotropium, and inhaled corticosteroids. Patients with prescriptions for LABA and/or tiotropium in each of the six-month periods were defined as "continuously treated with long-acting bronchodilators." The degree of drug treatment coverage was measured through the Medication Possession Ratio (MPR). Logistic regression was performed to identify determinants of not receiving long-acting bronchodilators continuously., Results: A total of 11,452 patients diagnosed with COPD were enrolled. Only 34.8% received long-acting bronchodilators continuously. The MPR was greater than 75% in 19.6% of cases. Among the determinants of not receiving long-acting bronchodilators continuously, older age and co-morbidities played an important role., Conclusions: In clinical practice, the COPD pharmacotherapy is not consistent with clinical guidelines. Medical education is needed to disseminate evidence-based prescribing patterns for COPD, and to raise awareness among physicians and patients on the health benefits of an appropriate pharmacological treatment.

Purpose: There are some methodological concerns regarding results from observational studies about the effectiveness of evidence-based (EB) drug therapy in secondary prevention after myocardial infarction. The present study used a nested case–control approach to address these major methodological limitations., Methods: A cohort of 6880 patients discharged from hospital after acute myocardial infarction (AMI) in 2006–2007 was enrolled and followed-up throughout 2009. Exposure was defined as adherence to each drug in terms of the proportion of days covered (cutoff ≥ 75%). Composite treatment groups, that is, groups with no EB therapy or therapy with one, two, three, or four EB drugs), were analyzed. Outcomes were overall mortality and reinfarction. Nested case–control studies were performed for both outcomes, matching four controls to every case (841 deaths, 778 reinfarctions) by gender, age, and individual follow-up. The association between exposure to EB drug therapy and outcomes was analyzed using conditional logistic regression, adjusting for revascularization procedures, comorbidities, duration of index admission, and use of the study drugs prior to admission., Results: Mortality and reinfarction risk decreased with the use of an increasing number of EB drugs. Combinations of two or more EB drugs were associated with a significant protective effect (p < 0.001) versus no EB drugs (mortality: 4 EB drugs: ORadj = 0.35; 95%CI: 0.21–0.59; reinfarction: 4 EB drugs: ORadj = 0.23; 95%CI: 0.15–0.37)., Conclusions: These findings of the beneficial effects of EB polytherapy on mortality and morbidity in a population-based setting using a nested case–control approach strengthen existing evidence from observational studies.

Objective: To develop and validate a predictive model for the identification of patients with Chronic Obstructive Pulmonary Disease (COPD) among the resident population of the Lazio region, using information available in the regional administrative systems (SIS) as well as clinical data of a panel of COPD patients., Setting and Participants: All residents in the Lazio region over 40 years of age in 2007 (2,625,102 inhabitants), Main Outcome Measures: The predictive model was developed through record linkage of health care related consumption patterns among 428 panel patients with confirmed COPD diagnosis in 2006 and a control group of patients without COPD (selection from outpatients specialized health care registry, 1:4). Hospital admission for COPD was defined a priori to be sufficient to identify a COPD patient. For all other panel patients and controls, specific drug use (minimum 2 prescriptions during 12 months) and hospitalization for respiratory causes during the past 9 years were retrieved and compared between panel and control patients. COPD associated factors were selected through a Bootstrap- Stepwise (BS) procedure. The predictive model was validated through internal (cross-validation-bootstrap) and external validation (comparison with external COPD patients with confirmed diagnosis), and through comparison with other COPD identification approaches., Results: The BS procedure identified the following predictors of COPD: consumption of beta 2 agonists, anticholinergics, corticosteroids, oxygen, and previous hospitalization for respiratory failure. For each patient, the expected probability of being affected by COPD was estimated. Depending on the cut-point of expected probability, sensibility ranged from 74.5% to 99.6% and specificity from 37.8% to 86.2%. Using the 0.30 cut-point, the model succeeded in identifying 67% of patients with diagnosis of COPD confirmed with spirometry. The predictive performance increased with increasing COPD severity. Prevalence of COPD turned out to be 7.8 %. The age-specific estimation was similar to results from other approaches., Conclusion: The predictive model shows good performance to identify COPD patients, even if it does not allow to identify those patients who have not been registered in the regional health care service or do not request any public health care service.