Comparison of geographical and individual deprivation index to assess the risk of Sars-CoV-2 infection and disease severity: a retrospective cohort study.

BACKGROUND: It has been shown that COVID-19 affects people at socioeconomic disadvantage more strongly. Previous studies investigating the association between geographical deprivation and COVID-19 outcomes in Italy reported no differences in case-hospitalisation and case-fatality. The objective of this research was to compare the usefulness of the geographic and individual deprivation index (DI) in assessing the associations between individuals' deprivation and risk of Sars-CoV-2 infection and disease severity in the Apulia region from February to December 2020. METHODS: This was a retrospective cohort study. Participants included individuals tested for SARS-CoV-2 infection during the study period. The individual DI was calculated employing polychoric principal component analysis on four census variables. Multilevel logistic models were used to test associations between COVID-19 outcomes and individual DI, geographical DI, and their interaction. RESULTS: In the study period, 139,807 individuals were tested for COVID-19 and 56,475 (43.5%) tested positive. Among those positive, 7902 (14.0%) have been hospitalised and 2215 (4.2%) died. During the first epidemic wave, according the analysis done with the individual DI, there was a significant inversely proportional trend between the DI and the risk of testing positive. No associations were found between COVID-19 outcomes and geographic DI. During the second wave, associations were found between COVID-19 outcomes and individual DI. No associations were found between the geographic DI and the risk of hospitalisation and death. During both waves, there were no association between COVID-19 outcomes and the interaction between individual and geographical DI. CONCLUSIONS: Evidence from this study shows that COVID-19 pandemic has been experienced unequally with a greater burden among the most disadvantaged communities. The results of this study remind us to be cautious about using geographical DI as a proxy of individual social disadvantage because may lead to inaccurate assessments. The geographical DI is often used due to a lack of individual data. However, on the determinants of health and health inequalities, monitoring has to have a central focus. Health inequalities monitoring provides evidence on who is being left behind and informs equity-oriented policies, programmes and practices. Future research and data collection should focus on improving surveillance systems by integrating individual measures of inequalities into national health information systems.

[Cancer figures in Italy: an overview]. / Panoramica sui numeri del cancro in Italia.

BACKGROUND: the description of the geographical distribution and temporal trends of cancer is relevant for prevention and improving the quality of care. This is primarily achieved through the incidence measures derived from population cancer registries (CRs). In recent years, in Italy there has been a prevalence of 'real-time' estimates and projections, although based on rather dated data. Given the significant increase in registration activity and still in absence of a national cancer registry network, the recent publication of Volume 12 of Cancer Incidence in Five Continents (CI5) provides a valuable opportunity to update cancer incidence estimates in Italy and to provide national and macroarea reference estimates. OBJECTIVES: to explore the pattern of cancer in Italy by reviewing and reorganizing the most recent data from cancer registries. MATERIALS AND METHODS: data from Italian cancer registries included in CI5 for the years 2013-2017 were obtained. Populations were verified, corrected for errors, and normalized to Italian National census reconstruction. The completeness of CR data was assessed using the mortality/incidence ratio applied to potential outlier data. Age-specific rates, Age standardized rates (ASRs), and truncated rates for adults (35-64 years) were calculated for 79 different neoplasms. Analyses were performed for individual CRs and macroareas. Temporal comparisons were made for 23 CRs with data from 2008-2012. RESULTS: the observed incidence rates show extreme heterogeneity. Among males, the overall ASR ranges from 584 per 100,000 in the province of Reggio Calabria to 809.9 per 100,000 in the province of Sondrio. Among women, ASR is highest in Emilia-Romagna (540.5) and lowest in the province of Avellino (409.9). The gradient with decreasing rates from North to South is clearly visible only for female breast cancer. Higher rates of lung cancer are observed for the city of Naples in both genders. In adult males (35-64 years), ASRs of lung cancer are maximum in the provinces of Caserta and Naples, where they are more than double the ASRs observed in the Veneto Region. In general, a significant decline in male ASRs is observed in Northern Italy compared to the previous five-year period. A significant part of this trend is influenced by lung cancer that is significantly decreasing throughout the Centre-North among men and substantially increasing among women. The database and tables with details of all calculated indicators are provided as supplementary material. CONCLUSIONS: the analysis has shown the importance of a review of real CR data and, in general, working with real data to not only develop specific estimates of cancers in Italy, but also to share reference rates and basic data for further analysis. The present review has also revealed critical issues with data submitted to the IARC. The comparison and verification of data quality through control and audit processes must represent a concrete operational perspective of the national cancer registry network. From the perspective of cancer epidemiology, important indications emerge regarding the distribution of cancers that can fuel aetiological research, as well as the planning of prevention and care activities. The data also show that it is advisable to separate the provinces of Caserta and Naples from the South in estimation and projection models. The comparison and verification of data quality through control and audit processes must represent a concrete operational perspective of the national cancer registry network.

Equity in the recovery of elective and oncological surgery volumes after the COVID-19 lockdown: a multicentre cohort study in Italy.

BACKGROUND: The COVID-19 pandemic has had, and still has, a profound impact on national health systems, altering trajectories of care and exacerbating existing inequalities in health. Postponement of surgeries and cancellation of elective surgical procedures have been reported worldwide. In Italy, the lock-down measures following the COVID-19 pandemic caused cancellations of surgical procedures and important backlogs; little is known about potential social inequalities in the recovery process that occurred during the post-lockdown period. This study aims at evaluating whether all population social strata benefited equally from the surgical volumes' recovery in four large Italian regions. METHODS: This multicentre cohort study covers a population of approximately 11 million people. To assess if social inequalities exist in the recovery of eight indicators of elective and oncological surgery, we estimated Risk Ratios (RR) through Poisson models, comparing the incidence proportions of events recorded during COVID-19 (2020-21) with those in pre-pandemic years (2018-19) for each pandemic period and educational level. RESULTS: Compared to 2018-19, volumes of elective surgery showed a U-shape with the most significant drops during the second wave or the vaccination phase. The recovery was socially unequal. At the end of 2021, incidence proportions among highly educated people generally exceeded the expected ones; RRs were 1.31 (95%CI 1.21-1.42), 1.24 (95%CI 1.17-1.23), 1.17 (95%CI 1.08-1.26) for knee and hip replacement and prostatic surgery, respectively. Among low educated patients, RR remained always < 1. Oncological surgery indicators showed a similar social gradient. Whereas volumes were preserved among the highly educated, the low educated were still lagging behind at the end of 2021. CONCLUSIONS: Surgical procedures generally returned to pre-pandemic levels but the low educated experienced the slowest recovery. An equity-oriented appraisal of trends in healthcare provision should be included in pandemic preparedness plans, to ensure that social inequalities are promptly recognised and tackled.

Examining potential Long COVID effects through utilization of healthcare resources: a retrospective, population-based, matched cohort study comparing individuals with and without prior SARS-CoV-2 infection.

BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID. METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions. RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38). CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.

[The mortality cost of carbon dioxide emissions from a steel plant in Southern Italy: a climate change health impact assessment]. / Il "mortality cost" delle emissioni di CO2 di uno stabilimento siderurgico nel Sud Italia: una valutazione degli impatti sanitari derivanti dal cambiamento climatico.

OBJECTIVES: to quantify the temperature-related global health impacts of the Taranto steel plant CO2e emissions. DESIGN: using the risk functions available in the literature, a prospective global health impact assessment of the marginal CO2e emissions declared by the steel plant for 2020 was conducted. SETTING AND PARTICIPANTS: world population in the period 2020-2100. MAIN OUTCOMES MEASURES: deaths in the period 2020-2100 attributable to the marginal CO2e emitted by the Taranto steel plant in 2020. RESULTS: considering the central estimates in the baseline emission scenario (4.1°C warming by 2100), the Taranto steel plant 2020 CO2e emissions will cause 1,876 deaths worldwide between 2020 and 2100. The largest part will be attributable to steelmaking processes, accounting for 1,093 deaths. The same emissions will cause 5.56 × 10-4 deaths worldwide between 2020 and 2100 per tonne of steel produced in 2020, i.e. one death for every 1,799 tonnes of steel. If the 2020 CO2e emissions of the steel plant had been reduced by 25%, 50% or 75%, the deaths avoided in the world in the period 2020-2100 would have been 469, 938 and 1,407 respectively. CONCLUSIONS: estimates predict a probably significant mortality impact worldwide by the end of the century associated with the greenhouse gases emissions of the Taranto steel plant. Just reducing emissions by 50% in a single year could maybe avoid over 900 deaths worldwide by the end of the century. This confirms the importance of implementing incisive policies to reduce greenhouse gases emissions in all sectors.

Impact of the educational program "Igiene Insieme"in 1,991 Italian primary schools: student behavior and incidence of SARS-CoV-2.

OBJECTIVE: To evaluate the impact of the health educational program "Igiene Insieme 2021/2022" on Italian primary school children's knowledge, attitudes and practice of hygiene and sanitation and to compare incidence of SARS-CoV-2 in schools participating the project with regional data of Lombardy and Apulia. METHODS: Participating schools were provided with a hygiene kit containing educational material for teachers and sanitizing products for students. We conducted a pre-post evaluation administering a questionnaire before and after the intervention. In addition, we compared SARS-CoV-2 incidence of the participating primary schools (225 in Lombardy and 120 in Apulia) to regional-level data. We tested the differences between groups by using the Chi-squared test. RESULTS: Of 1,991 schools, 472 responded to both questionnaires for a total of 16,988 students. 17.3% of the students learned the importance of handwashing in preventing infections, 22.6% when to wash hands, 18.5% the existence of alternative solutions in absence of soap and water, 23.2% how to correctly wash hands. A lower incidence of SARS-CoV-2 infections was recorded in primary schools participating in the project as compared to the average regional incidence in Lombardy (9.6% vs.14.8%) and Apulia (10.7% vs.12.0%) for the same age group. CONCLUSIONS: We report an overall positive effect of health education interventions in primary schools. Although the limitations in the study design, our findings are important to inform planning, implementation and monitoring of health promotion campaigns in young generations so as to contribute to limit the risk of infection spread at the community level.

Hospital admission and mortality rates for non-Covid diseases among residents of the long-term care facilities before and during the pandemic: a cohort study in two Italian regions.

Aim: Long-term-care facility residents are a vulnerable population who experienced reduced healthcare access during the pandemic. This study aimed to assess the indirect impact of the COVID-19 pandemic, in terms of hospitalisation and mortality rates, among this population in two Italian Regions, Tuscany and Apulia, during 2020 in comparison with the pre-pandemic period. Subject and methods: We conducted a retrospective cohort study on people residing in long-term-care facilities from 1 January 2018 to 31 December 2020 (baseline period: 1 January 2018-8 March 2020; pandemic period: and 9 March-31 December 2020). Hospitalisation rates were stratified by sex and major disease groups. Standardised weekly rates were estimated with a Poisson regression model. Only for Tuscany, mortality risk at 30 days after hospitalisation was calculated with the Kaplan-Meier estimator. Mortality risk ratios were calculated using Cox proportional regression models. Results: Nineteen thousand two hundred and fifty individuals spent at least 7 days in a long-term-care facility during the study period. The overall mean non-Covid hospital admission rate per 100 000 residents/week was 144.1 and 116.2 during the baseline and pandemic periods, with a decrease to 99.7 and 77.3 during the first (March-May) and second lockdown (November-December). Hospitalisation rates decreased for all major disease groups. Thirty-day mortality risk ratios for non-Covid conditions increased during the pandemic period (1.2, 1.1 to 1.4) compared with baseline. Conclusion: The pandemic resulted in worse non-COVID-related health outcomes for long-term-care facilities' residents. There is a need to prioritise these facilities in national pandemic preparedness plans and to ensure their full integration in national surveillance systems. Supplementary information: The online version contains supplementary material available at 10.1007/s10389-023-01925-1.

[Privacy and epidemiology: let's find a shared solution.] / La privacy e l'epidemiologia: troviamo una soluzione condivisa.

During the pandemic period, Italian epidemiologists managed to monitor the situation despite fragmented and often low-quality data flows, comparing themselves to other countries (such as England and Israel) that were able to provide valuable indications in very short times thanks to the availability of a large amount of interconnected data at the national level. In the same months, the Italian Data Protection Authority launched several investigations that triggered an immediate stiffening of the mechanisms for accessing data by epidemiological structures at both regional and company levels, leading to a significant limitation in the conduct of epidemiological investigations, and in some cases the complete suspension of important projects. The interpretation of the General data protection regulation (Gdpr) was found to be subjective and heterogeneous among different institutions. The path to legitimizing data processing appears obscure and subject to the sensitivity of the different actors involved in the process within companies and regions. Apparently, only economic reporting is unanimously considered the primary and legitimate use of data. The work of Italian epidemiologists has been called into question to the point of making it practically impossible to carry out their institutional duties, even though they are an integral part of the National health service's (Nhs) function to promote and ensure health and well-being for the population. Today, it is necessary to immediately initiate a path to identify shared solutions among the various actors at both the central and local levels, which allow epidemiological structures and professionals to carry out their tasks with serenity, while ensuring data protection. The obstacles to conducting epidemiological studies are not a problem of individual operators or individual epidemiology structures, but a block to the production of knowledge and, ultimately, to the processes of improving the Nhs.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males:pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

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.

[BIGEPI project: environmental and health data]. / Progetto BIGEPI: dati ambientali e dati sanitari.

OBJECTIVES: the BIGEPI project, co-funded by INAIL, has used big data to identify the health risks associated with short and long-term exposure to air pollution, extreme temperatures and occupational exposures. DESIGN: the project consists of 5 specific work packages (WP) aimed at assessing: 1. the acute effects of environmental exposures over the national territory; 2. the acute effects of environmental exposures in contaminated areas, such as Sites of National Interest (SIN) and industrial sites; 3. the chronic effects of environmental exposures in 6 Italian longitudinal metropolitan studies; 4. the acute and chronic effects of environmental exposures in 7 epidemiological surveys on population samples; 5. the chronic effects of occupational exposures in the longitudinal metropolitan studies of Rome and Turin. SETTING AND PARTICIPANTS: BIGEPI analyzed environmental and health data at different levels of detail: the whole Italian population (WP1); populations living in areas contaminated by pollutants of industrial origin (WP2); the entire longitudinal cohorts of the metropolitan areas of Bologna, Brindisi, Rome, Syracuse, Taranto and Turin (WP3 and WP5); population samples participating in the epidemiological surveys of Ancona, Palermo, Pavia, Pisa, Sassari, Turin and Verona (WP4). MAIN OUTCOME MEASURES: environmental exposure: PM10, PM2,5, NO2 and O3 concentrations and air temperature at 1 Km2 resolution at national level. Occupational exposures: employment history of subjects working in at least one of 25 sectors with similar occupational exposures to chemicals/carcinogens; self-reported exposure to dust/fumes/gas in the workplace. Health data: cause-specific mortality/hospitalisation; symptoms/diagnosis of respiratory/allergic diseases; respiratory function and bronchial inflammation. RESULTS: BIGEPI analyzed data at the level of the entire Italian population, data on 2.8 million adults (>=30 yrs) in longitudinal metropolitan studies and on about 14,500 individuals (>=18 yrs) in epidemiological surveys on population samples. The population investigated in the longitudinal metropolitan studies had an average age of approximately 55 years and that of the epidemiological surveys was about 48 years; in both cases, 53% of the population was female. As regards environmental exposure, in the period 2013-2015, at national level average values for PM10, PM2.5, NO2 and summer O3 were: 21.1±13.6, 15.1±10.9, 14.7±9.1 and 80.3±17.3 µg/m3, for the temperature the average value was 13.9±7.2 °C. Data were analyzed for a total of 1,769,660 deaths from non-accidental causes as well as 74,392 incident cases of acute coronary event and 45,513 of stroke. Epidemiological investigations showed a high prevalence of symptoms/diagnoses of rhinitis (range: 14.2-40.5%), COPD (range: 4.7-19.3%) and asthma (range: 3.2-13.2%). The availability of these large datasets has made it possible to implement advanced statistical models for estimating the health effects of short- and long-term exposures to pollutants. The details are reported in the BIGEPI papers already published in other international journals and in those published in this volume of E&P. CONCLUSIONS: BIGEPI has confirmed the great potential of using big data in studies of the health effects of environmental and occupational factors, stimulating new directions of scientific research and confirming the need for preventive action on air quality and climate change for the health of the general population and the workers.

[Long-term exposure to air pollution and incidence of coronary heart diseases and stroke in the longitudinal metropolitan studies (LMS) network: the BIGEPI project]. / Esposizione di lungo periodo all'inquinamento atmosferico e incidenza di malattia coronarica acuta e ictus nella rete degli studi longitudinali metropolitani: il progetto BIGEPI.

OBJECTIVES: to assess the potential of using longitudinal metropolitan studies (LMS) to study the association between long-term exposure to air pollution and the incidence of acute coronary events and stroke. DESIGN: closed cohort. SETTING AND PARTICIPANTS: subjects aged >=30 years, who took part in the 2011 census, residents in 5 cities (Turin, Bologna, Rome, Brindisi and Taranto). Annual concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2) and warm-season ozone (O3) (annual O3 in Taranto and Brindisi), estimated through satellite (Turin, Bologna, Rome) or photochemical models (Taranto and Brindisi) with a spatial resolution of 1 km2, were assigned to the census address. MAIN OUTCOME MEASURES: incidence of coronary heart disease (CHD) and stroke until 31.12.2018 (2019 in Bologna). Cohort-specific Hazard Ratios (HRs), estimated using Cox regression models progressively adjusting for individual and contextual covariates, were pooled with random-effect meta-analysis. RESULTS: there were 71,872 incident CHD cases and 43,884 incident cases of stroke in almost 18 million person-years. No association was observed between the exposures studied and incidence of CHD and stroke, except for an increase in the incidence of CHD associated with warm-season O3 exposure (HR 1.034 per 5 µg/m3 increase). Some positive associations were found in specific cities (both outcomes in Brindisi with PM10 exposure and in Taranto with NO2 exposure, stroke in Rome with both PM10 and PM2.5), although estimates were not significant in some instances. CONCLUSIONS: LMS are a high potential tool for the study of comparative medium- and long-term effects of air pollution. Their further development (different definitions of exposure, outcomes, characteristics of the urban areas and extension to other LMS) may make them even more valuable tools for monitoring and planning public health interventions.

[Long-term exposure to air pollution and natural mortality: variations related to the use of different exposure indicators in the cohorts of BIGEPI project]. / Esposizione di lungo periodo all'inquinamento atmosferico e mortalità naturale: variazioni legate all'utilizzo di diversi indicatori di esposizione nelle coorti del progetto BIGEPI.

OBJECTIVES: appropriate assessment of exposure to air pollution is crucial for the estimation of adverse effects on human health, both in the short and long term. Within the BIGEPI project, different indicators of long-term exposure to air pollution, in association with mortality by cause, were tested within the Italian longitudinal metropolitan studies (LMS). This allowed an evaluation of differences in effect estimates using the different exposure indicators. DESIGN: closed cohort. SETTING AND PARTICIPANTS: subjects aged >=30, who took part in the 2011 census, residents in 5 cities (Turin, Bologna, Rome, Brindisi and Taranto). MAIN OUTCOME MEASURES: at the time of enrolment, residential exposure levels to particulate matter <=10 µm (PM10), PM <=2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone (O3) for the period April-September (O3 warm season) were obtained from models at different spatial resolutions, from 1x1km to 200x200m (from the BEEP project) to 100x100m (ELAPSE project). In addition, locally developed models were used in each area (FARM photochemical model at 1x1-km for the cities of Rome, Taranto and Brindisi, Land-Use Regression (LUR) model for the city of Turin, PESCO model for Bologna). Cox proportional hazards models were applied to assess the association between exposure to air pollution (assessed using different exposure indicators) and natural mortality, adjusting for both individual and area covariates. RESULTS: the exposure levels derived by the different models varied between pollutants, with differences between the averages ranging from 3 to 20% for PM10, from 1 to 23% for PM2.5, and from 3 to 28% for NO2; the results for O3 were more heterogeneous. A total of 267,350 deaths from natural causes were observed. There is low heterogeneity in the effect estimates calculated from different environmental models, while there is greater variability in average exposure values, with different behaviour depending on the model and the characteristics of the area investigated. Differences are more pronounced where local risk factors are relevant, e.g., in industrial cities, thus suggesting the need of considering industrial exposure separately from other sources. CONCLUSIONS: the numerous heterogeneities in the data used make it difficult to draw conclusions about the comparisons studied. Nevertheless, this study suggests that different approaches to the assessment of environmental exposure should be evaluated depending on the national or local level of interest, also according to the specifities of the investigated areas.

Environmental pressures, tumor characteristics, and death rate in a female breast cancer cohort: a seven-years Bayesian survival analysis using cancer registry data from a contaminated area in Italy.

Introduction: In Taranto, Southern Italy, adverse impacts on the environment and human health due to industrial installations have been studied. In the literature, few associations have been reported between environmental factors and breast cancer mortality in women. The aim of this study was to investigate the relationships between residence in areas with high environmental pressures, female breast cancer characteristics, and death rate. Methods: Data from the Taranto Cancer Registry were used, including all women with invasive breast cancer diagnosed between 01 January 2015 and 31 December 2020 and with follow-up to 31 December 2021. Bayesian mixed effects logistic and Cox regression models were fitted with the approach of integrated nested Laplace approximation, adjusting for patients and disease characteristics. Results: A total of 10,445 person-years were observed. Variables associated with higher death rate were residence in the contaminated site of national interest (SIN) (HR 1.22, 95% CrI 1.01-1.48), pathological/clinical stage III (HR 2.77, 95% CrI 1.93-3.97) and IV (HR 17.05, 95% CrI 11.94-24.34), histological grade 3 (HR 2.50, 95% CrI 1.20-5.23), Ki-67 proliferation index of 21-50% (HR 1.42, 95% CrI 1.10-1.83) and > 50% (HR 1.81, 95% CrI 1.29-2.55), and bilateral localization (HR 1.65, 95% CrI 1.01-2.68). Variables associated with lower death rate were estrogen and/or progesterone receptor positivity (HR 0.61, 95% CrI 0.45-0.81) and HER2/neu oncogene positivity (HR 0.59, 95% CrI 0.44-0.79). Discussion: The findings confirmed the independent prognostic values of different female breast cancer characteristics. Even after adjusting for patients and disease characteristics, residence in the SIN of Taranto appeared to be associated with an increased death rate.

Gender differences, environmental pressures, tumor characteristics, and death rate in a lung cancer cohort: a seven-years Bayesian survival analysis using cancer registry data from a contaminated area in Italy.

Introduction: In Taranto, Southern Italy, adverse impacts on the environment and human health due to industrial installations have been studied. In the literature, associations have been reported between gender, environmental factors, and lung cancer mortality in women and men. The aim of this study was to investigate the relationships between gender, residence in areas with high environmental pressures, bronchus/lung cancer characteristics, and death rate. Methods: Data from the Taranto Cancer Registry were used, including all women and men with invasive bronchus/lung cancer diagnosed between 1 January 2016 and 31 December 2020 and with follow-up to 31 December 2022. Bayesian mixed effects logistic and Cox regression models were fitted with the approach of integrated nested Laplace approximation, adjusting for patients and disease characteristics. Results: A total of 2,535 person-years were observed. Male gender was associated with a higher prevalence of histological grade 3 (OR 2.45, 95% CrI 1.35-4.43) and lung squamous-cell carcinoma (OR 3.04, 95% CrI 1.97-4.69). Variables associated with higher death rate were male gender (HR 1.24, 95% CrI 1.07-1.43), pathological/clinical stage II (HR 2.49, 95% CrI 1.63-3.79), III (HR 3.40, 95% CrI 2.33-4.97), and IV (HR 8.21, 95% CrI 5.95-11.34), histological grade 3 (HR 1.80, 95% CrI 1.25-2.59), lung squamous-cell carcinoma (HR 1.18, 95% CrI 1.00-1.39), and small-cell lung cancer (HR 1.62, 95% CrI 1.31-1.99). Variables associated with lower death rate were other-type lung cancer (HR 0.65, 95% CrI 0.44-0.95), high immune checkpoint ligand expression (HR 0.75, 95% CrI 0.59-0.95), lung localization (HR 0.73, 95% CrI 0.62-0.86), and left localization (HR 0.85, 95% CrI 0.75-0.95). Discussion: The results among patients with lung cancer did not show an association between residence in the contaminated site of national interest (SIN) and the prevalence of the above mentioned prognostic factors, nor between residence in SIN and death rate. The findings confirmed the independent prognostic values of different lung cancer characteristics. Even after adjusting for patients and disease characteristics, male gender appeared to be associated with a higher prevalence of poorly differentiated cancer and squamous-cell carcinoma, and with an increased death rate.

Trends in Liver Cancer Incidence and Survival in Italy by Histologic Type, 2003-2017.

(1) Background: Liver cancer in Italy is characterised by one of the highest incidence rates worldwide outside of Asia coupled with comparatively favourable survival figures. The objective of this study was to evaluate the most recent epidemiologic trends of the disease. (2) Methods: Thirteen cancer registries covering a population of about 12,740,000 (21% of the national population) made available the records of 35,574 cases registered between 2003 and 2017. Trends in age-standardised (Europe 2013) incidence rates were analysed using the results of age-drift models. Trends in survival were analysed using 1-year, 2-year, 5-year and 10-year net survival (NS) and 5|1-year and 5|2-year conditional NS. (3) Results: Over the study period, the average annual incidence rates per 100,000 persons were 29.4 (men) and 9.4 (women) for total liver cancer; 14.6 and 3.5 for hepatocellular carcinoma (HCC); 1.8 and 1.1 for intrahepatic cholangiocarcinoma (ICC); and 13.0 and 4.8 for the 'other liver cancer types' group. The incidence of total liver cancer and HCC decreased significantly for both sexes. For total liver cancer, the estimated average annual percent change was -1.6% among men and -2.1% among women. For HCC, the change was -1.3% among men and -2.7% among women. ICC followed an opposite trend. For men, the risk of HCC had two peaks, one in the birth cohorts of 1928 and 1933 and another, more moderate peak in the cohort of 1958. Men and women exhibited comparable improvements in both early and mid-term conditional NS from HCC. In 2013-2017, 5-year NS was 28.9% (95% CI: 27.3%; 30.6%) for men and 30.1% (95% CI: 26.9%; 33.5%) for women. The uptrend in survival from ICC was less pronounced and was weakly significant, with a 5-year NS in 2013-2017 of 13.9% (95% CI: 10.8%; 17.3%) for men and 17.4% (95% CI: 13.5%; 21.7%) for women. (4) Conclusions: The opposite incidence trends of HCC and ICC confirm a pattern observed in other populations. The generalised, albeit slow, improvement in survival from HCC indicates a trend towards earlier detection coupled with improvements in treatments.

Covid-19 vaccination programme effectiveness against SARS-CoV-2 related infections, hospital admissions and deaths in the Apulia region of Italy: a one-year retrospective cohort study.

Studies reporting vaccine effectiveness against COVID-19 outcomes concentrate mainly on estimates of one single type of vaccine and variant, seldom considering waning effects. We aimed to estimate the effectiveness of the overall COVID-19 vaccination programme implemented in the Apulia region of Italy at preventing SARS-CoV-2 infections, COVID-19-related hospital admissions and deaths during alpha and delta variant dominant periods. We conducted a retrospective cohort study using electronic health records of persons 16 years and older resident in the Apulia region, assessing the effectiveness of the combined use of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines against confirmed COVID-19 infections, hospitalisations and deaths, for fully and partially vaccinated persons as well as by time since vaccination and variants. Cox regression models yielding hazard ratios were used to calculate the overall vaccination programme effectiveness. From 1 January to 1 December 2021, we included 3,530,967 eligible persons in the cohort, of whom 2,770,299 were fully vaccinated and 158,313 were COVID-19 positive at the end of the study period. The effectiveness of the programme over the entire study period for fully vaccinated persons against COVID-19 infection, hospitalisation and death were 87.69% (CI95% 87.73-88.18), 94.08% (93.58-94.54) and 95.95% (CI95% 95.26-96.54), respectively. The effectiveness against COVID-19 infection of fully vaccinated subjects during the alpha and delta period was respectively 88.20% (CI95% 87.60-99.78) and 59.31% (CI95% 57.91-60.67), against hospitalisation 93.89% (CI95% 92.67-94.90) and 88.32% (CI95% 86.50-89.90) and against death 93.83% (CI95% 91.65-95.45) and 85.91 (CI95% 79.98-90.09). The waning effects of the programme regarding COVID-19 infection during the delta period were stronger than for alpha, with 75.85% (CI95% 74.38-77.24) effectiveness after 1-2 months and 8.35% (CI95% 3.45-13.01) after 5-6 months after full vaccination. The effectiveness against hospitalisation and death during the delta period waned rapidly and at 7-8-months after the full vaccination respectively decreased to 27.67% (CI95% 7.48-43.45) and 48.47 (CI95% 53.97-34.82). Our study suggests that the COVID-19 vaccination program in Apulia was strongly protective against COVID-19 infection, hospitalisation, and death due to alpha as well as delta variants, although its effectiveness is reduced over time.

Cancer Incidence and Mortality According to Pre-Existing Heart Failure in a Community-Based Cohort.

Background: Studies assessing whether heart failure (HF) is associated with cancer and cancer-related mortality have yielded conflicting results. Objectives: This study assessed cancer incidence and mortality according to pre-existing HF in a community-based cohort. Methods: Among individuals ≥50 years of age from the Puglia region in Italy with administrative health data from 2002 to 2018, no cancer within 3 years before the baseline evaluation, and ≥5-year follow-up, the study matched 104,020 subjects with HF at baseline with 104,020 control subjects according to age, sex, drug-derived complexity index, Charlson comorbidity index, and follow-up duration. Cancer incidence and mortality were defined based on International Classification of Diseases-Ninth Revision codes in hospitalization records or death certificates. Results: The incidence rate of cancer in HF patients and control subjects was 21.36 (95% CI: 20.98-21.74) and 12.42 (95% CI: 12.14-12.72) per 1000 person-years, respectively, with the HR being 1.76 (95% CI: 1.71-1.81). Cancer mortality was also higher in HF patients than control subjects (HR: 4.11; 95% CI: 3.86-4.38), especially in those <70 years of age (HR: 7.54; 95% CI: 6.33-8.98 vs HR: 3.80; 95% CI: 3.44-4.19 for 70-79 years of age; and HR: 3.10; 95% CI: 2.81-3.43 for ≥80 years of age). The association between HF and cancer mortality was confirmed in a competing risk analysis (subdistribution HR: 3.48; 95% CI: 3.27-3.72). The HF-related excess risk applied to the majority of cancer types. Among HF patients, prescription of high-dose loop diuretic was associated with higher cancer incidence (HR: 1.11; 95% CI: 1.03-1.21) and mortality (HR: 1.35; 95% CI: 1.19-1.53). Conclusions: HF is associated with an increased risk of cancer and cancer-related mortality, which may be heightened in decompensated states.