First national analysis of severe obesity hospitalizations in Italy: insights from discharge card database.

Background: Obesity is associated with numerous severe diseases necessitating intensive healthcare for diagnosis and treatment. Most patients with obesity, especially in its severe form, require at least one hospitalization. However, few studies in Italy have assessed the burden of obesity on the National Health System. This study aims to routinely estimate the 'disease burden' by analyzing hospital admissions related to severe obesity. Subjects: We analyzed the medical records of the Italian national hospital discharge database, including all patients older than 18 years discharged with the diagnosis of 'severe obesity'.' We included patients who underwent bariatric surgery, even without an explicit obesity code, such as laparoscopic restrictive gastric procedures, other stomach operations, and high gastric bypass. Special focus was given to those who underwent abdominal reshaping surgery. The cross-sectional survey PASSI in Italy served as an additional data source to estimate. The phenomenon was described using appropriate indicators, including rates and ratios between rates. Linear regression was employed to analyze trends in standardized rates over time. Results: Between 2014 and 2021, a total of 243,325 patients were discharged with a severe obesity code in Italy. Among these patients, 36.8% underwent at least one bariatric surgery procedure. We investigated the types of bariatric surgery procedures performed. The most frequent procedure was "other operations on the stomach," where sleeve gastrectomy is included which also appears to be steadily increasing during the study period together with the gastric bypass, while the gastric bondage is decreasing over time. Conclusion: These findings underscore the significant burden of severe obesity on Italy's healthcare system, a burden that is progressively increasing. The growing utilization of bariatric surgery suggests an escalating trend toward adopting drastic solutions to combat this health issue.

All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980-2018).

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. METHODS: The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20-84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater. RESULTS: During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107-109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. CONCLUSIONS: For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Relative Survival After Adult Cardiac Surgery: Analysis of the Italian Nationwide Registry Data.

OBJECTIVE: The authors aimed to investigate life expectancy after adult cardiac surgery. SETTING: Nationwide study including University and non-University hospitals. PARTICIPANTS: Consecutive adult patients who underwent heart valve and coronary artery surgery from a nationwide administrative registry. INTERVENTIONS: Surgical procedures on the heart valves and coronary arteries. METHODS: The authors estimated the 10-year relative survival of adult patients who underwent surgery for heart valve diseases and coronary artery disease taken from a nationwide administrative registry. MEASUREMENTS AND RESULTS: Overall, data on 415,472 patients were available for this study. Among them, 394,445 (94.9%) survived 90 days after surgery, and their 10-year survival was 58.0% (95% CI 57.8-58.3); the expected survival was 70.1%, and the relative survival was 0.83 (95% CI 0.82-0.83). Patients who underwent surgical repair of the mitral valve and aortic valve had relative survival of 0.96 and 0.92, respectively. Isolated coronary artery bypass grafting had a relative survival of 0.88. Surgical replacement of the heart valves had a relative survival below 0.80. Poor results with relative survival <0.70 were observed after complex cardiac surgery. Relative survival was <0.60 in patients who underwent double- or triple-valve surgery combined with coronary artery surgery. The authors observed markedly lower relative survival among women (0.77, 95% CI 0.77-0.78) compared with men (0.86, 95% CI 0.85-0.86) at 10 years. Such a difference was observed after almost all different procedures. CONCLUSIONS: The present findings provided a picture of the real expectation in terms of the late survival of patients after having undergone adult cardiac surgery. This information should be communicated to patients and their relatives before surgery, and it may be relevant in the decision-making process and in planning tertiary prevention.

Epidemiologic transition of lung cancer mortality in Italy by sex, province of residence and birth cohort (1920-1929 to 1960-1969).

Space-time analysis of mortality risk is useful to evaluate the epidemiologic transitions at the subnational level. In our study, we analysed the death certificate records for lung cancer in Italy in 1995-2016, obtained from the Italian National Institute of Statistics. Our objective was to investigate the spatial-temporal evolution of lung cancer mortality by sex and province of residence (n = 107) using the birth cohort as relevant time axis. We built Bayesian space-time models with space-time interactions. Among males (n = 554 829), mortality peaked in the 1920-1929 cohort, followed by a generalised decline. Among females (n = 158 619), we found novel original evidence for a peak in the 1955-1964 cohort, equivalent to a 35-year delay, with a downward trend being observed thereafter. Over time, the documented north-south decreasing mortality gradient has been replaced by a west-east decreasing gradient. Naples has become the province at highest risk in Italy, both among males and females. This pattern is consistent with an epidemiologic transition of risk factors for lung cancer to the south-west of the country and raises concern, because 5-year age-standardised net survival from the disease in this geographic area is lower than in northern and central Italy. The variability of mortality rates among provinces has changed over time, with an increasing homogeneity for males and an opposite trend for females in the more recent birth cohorts. These unprecedented observations provide evidence for a profound spatio-temporal transition of lung cancer mortality in Italy.

The health impact of hazardous waste landfills and illegal dumps contaminated sites: An epidemiological study at ecological level in Italian Region.

Background and aim: The implementation of idoneous management of hazardous waste, in contrast to illegal practices, is one of the environment and health priorities of the WHO. The aim of the present study, based on a collaborative agreement between the Italian National Health Institute and a Prosecution Office located in Naples North, was to evaluate the health effects of illegal landfills and burning of urban and hazardous waste in the territory of the Prosecution Office. Methods: The municipalities included in the study territory were investigated with respect to the regional population. Regression analyses were performed in the study area between four classes of an environmental municipal indicator of waste risk (MRI) previously defined, computing the relative risks (RRs) in 2-4 MRI classes, with respect to the first MRI class (the least impacted). The prevalence of reproductive outcomes and cause-specific mortality and hospitalization were analyzed in the general population and in the 0-19-year-old population using SAS software. Results: An increase of mortality and hospitalization risk in both the genders of the whole area, with respect to regional population, were found for overall all cancer cases, cancer of the stomach, the liver, the lung and the kidney, and ischemic heart diseases. An increase of mortality for leukemias in the 0-19-year-old population and in hospitalization risk for certain conditions originating in the perinatal period were observed. Correlation between MRI and the risk of mortality from breast tumors in women (MRI class 2: RR = 1.06; MRI class 3: RR = 1.15; MRI class 4: RR = 1.11) and between MRI and the risk of hospitalization from testis tumors (MRI class 2: RR = 1.25; MRI class 3: RR = 1.31; MRI class 4: RR = 1.32) were found. The hospitalization risk from breast tumors and asthma exceeded significantly in both genders of three and four MRI classes. Among the 0-19-year-old population, correlation between MRI and hospitalization from leukemias (MRI class 2: RR = 1.48; MRI class 3: RR = 1.60; MRI class 4: RR = 1.41) and between MRI and the prevalence of preterm birth (MRI class 2: RR = 1.17; MRI class 3: RR = 1.08; MRI class 4: RR = 1.25) were found. Conclusion: A correlation between health outcomes and the environmental pressure by uncontrolled waste sites was found. Notwithstanding the limitation of the study, the results promote implementing the actions of environmental remediation and the prosecution of illegal practices.

[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.

[Methodological approaches to evaluate the over-time mortality in SENTIERI epidemiological surveillance system: a focus on cohort analyses]. / Approcci metodologici per valutare l'andamento della mortalità nel lungo periodo nel sistema di sorveglianza SENTIERI: focus sull'analisi di coorte.

The SENTIERI Project analyses the health profile of the populations residing in Italian national priority contaminated sites in specific calendar periods using a cross-sectional approach. An aspect that has not been evaluated so far is the analysis over a long period, for understanding the changes in health profiles over time and studying them also in function of the changes occurred in the territories. This article studies temporal trends by birth cohort and calendar period for overall mortality and lung cancer mortality from 1980 to 2018, separately for men and women, for three sites: Priolo (Sicily Region, Southern Italy), Pitelli (Liguria Region, Northern Italy), and Terni-Papigno (Umbria Region, Central Italy). A method for selecting the temporal model that best fits the data is then proposed. General mortality presents complex temporal profiles when considering cumulative risks, and usually the most important temporal axis is the birth cohort for cumulative SMRs (i.e., after adjusting for trends in the reference population). For lung cancer, the most important time axis is the birth cohort and the age-cohort model is the most appropriate, in particular for men of Priolo and Terni.

[Global evaluation of the mortality and hospitalization in the Italian contaminated sites included in the SENTIERI project]. / Stime globali della mortalità e ospedalizzazione nei siti contaminati italiani inclusi nel progetto SENTIERI.

Since 2006, epidemiological surveillance of populations living in Italian contaminated sites has been ongoing (SENTIERI Project). Updated global estimates of mortality (2013-2017) and hospitalization (2014-2018) are reported. The excess deaths (observed-expected) for the main groups of diseases were calculated for all the 46 sites together. Through a random-effect meta-analysis of the standardized mortality and hospitalization rates (SMR/SHR), the pooled SMR/SHR for all the sites and their groupings were estimated. In the 46 sites, 8,342 exceeding deaths (1,668/year) were estimated, 4,353 in males and 3,989 in females, resulting in an excess risk of 2% in both genders. The risk of hospitalization for all causes was in excess of 3%. These excesses are mainly attributable to malignant tumours. In subgroups of sites, exceeding SMRs were observed for all mesotheliomas and pleural mesotheliomas, lung and colorectal cancers in both genders. SHR for all causes were observed in excess in the first year of life (+8%), in the group 0-19 and 20-29 years (+3-5%); no excesses of mortality were observed in the group 0-29 years.

Unveiling the incidences and trends of the neglected zoonosis cystic echinococcosis in Europe: a systematic review from the MEmE project.

The neglected zoonosis cystic echinococcosis affects mainly pastoral and rural communities in both low-income and upper-middle-income countries. In Europe, it should be regarded as an orphan and rare disease. Although human cystic echinococcosis is a notifiable parasitic infectious disease in most European countries, in practice it is largely under-reported by national health systems. To fill this gap, we extracted data on the number, incidence, and trend of human cases in Europe through a systematic review approach, using both the scientific and grey literature and accounting for the period of publication from 1997 to 2021. The highest number of possible human cases at the national level was calculated from various data sources to generate a descriptive model of human cystic echinococcosis in Europe. We identified 64 745 human cystic echinococcosis cases from 40 European countries. The mean annual incidence from 1997 to 2020 throughout Europe was 0·64 cases per 100 000 people and in EU member states was 0·50 cases per 100 000 people. Based on incidence rates and trends detected in this study, the current epicentre of cystic echinococcosis in Europe is in the southeastern European countries, whereas historical endemic European Mediterranean countries have recorded a decrease in the number of cases over the time.

Spatial Analysis of Shared Risk Factors between Pleural and Ovarian Cancer Mortality in Lombardy (Italy).

BACKGROUND: Asbestos exposure is a recognized risk factor for ovarian cancer and malignant mesothelioma. There are reports in the literature of geographical ecological associations between the occurrence of these two diseases. Our aim was to further explore this association by applying advanced Bayesian techniques to a large population (10 million people). METHODS: We specified a series of Bayesian hierarchical shared models to the bivariate spatial distribution of ovarian and pleural cancer mortality by municipality in the Lombardy Region (Italy) in 2000-2018. RESULTS: Pleural cancer showed a strongly clustered spatial distribution, while ovarian cancer showed a less structured spatial pattern. The most supported Bayesian models by predictive accuracy (widely applicable or Watanabe-Akaike information criterion, WAIC) provided evidence of a shared component between the two diseases. Among five municipalities with significant high standardized mortality ratios of ovarian cancer, three also had high pleural cancer rates. Wide uncertainty was present when addressing the risk of ovarian cancer associated with pleural cancer in areas at low background risk of ovarian cancer. CONCLUSIONS: We found evidence of a shared risk factor between ovarian and pleural cancer at the small geographical level. The impact of the shared risk factor can be relevant and can go unnoticed when the prevalence of other risk factors for ovarian cancer is low. Bayesian modelling provides useful information to tailor epidemiological surveillance.

A population-based cohort approach to assess excess mortality due to the spread of COVID-19 in Italy, January-May 2020.

AIMS: To assess the impact of the COVID-19 pandemic on all-cause mortality in Italy during the first wave of the epidemic, taking into consideration the geographical heterogeneity of the spread of COVID-19. METHODS: This study is a retrospective, population-based cohort study using national statistics throughout Italy. Survival analysis was applied to data aggregated by day of death, age groups, sex, and Italian administrative units (107 provinces). We applied Cox models to estimate the relative hazards (RH) of excess mortality, comparing all-cause deaths in 2020 with the expected deaths from all causes in the same time period. The RH of excess deaths was estimated in areas with a high, moderate, and low spread of COVID-19. We reported the estimate also restricting the analysis to the period of March-April 2020 (first peak of the epidemic). RESULTS: The study population consisted of 57,204,501 individuals living in Italy as of January 1, 2020. The number of excess deaths was 36,445, which accounts for 13.4% of excess mortalities from all causes during January-May 2020 (i.e., RH = 1.134; 95% confidence interval (CI): 1.129-1.140). In the macro-area with a relatively higher spread of COVID-19 (i.e., incidence rate, IR): 450-1,610 cases per 100,000 residents), the RH of excess deaths was 1.375 (95% CI: 1.364-1.386). In the area with a relatively moderate spread of COVID-19 (i.e., IR: 150-449 cases) it was 1.049 (95% CI: 1.038-1.060). In the area with a relatively lower spread of COVID-19 (i.e., IR: 30-149 cases), it was 0.967 (95% CI: 0.959-0.976). Between March and April (peak months of the first wave of the epidemic in Italy), we estimated an excess mortality from all causes of 43.5%. The RH of all-cause mortality for increments of 500 cases per 100,000 residents was 1.352 (95% CI: 1.346-1.359), corresponding to an increase of about 35%. CONCLUSIONS: Our analysis, making use of a population-based cohort model, estimated all-cause excess mortality in Italy taking account of both time period and of COVID-19 geographical spread. The study highlights the importance of a temporal/geographic framework in analyzing the risk of COVID-19-epidemy related mortality.

Excess Mortality in Italy During the COVID-19 Pandemic: Assessing the Differences Between the First and the Second Wave, Year 2020.

COVID-19 dramatically influenced mortality worldwide, in Italy as well, the first European country to experience the Sars-Cov2 epidemic. Many countries reported a two-wave pattern of COVID-19 deaths; however, studies comparing the two waves are limited. The objective of the study was to compare all-cause excess mortality between the two waves that occurred during the year 2020 using nationwide data. All-cause excess mortalities were estimated using negative binomial models with time modeled by quadratic splines. The models were also applied to estimate all-cause excess deaths "not directly attributable to COVD-19", i.e., without a previous COVID-19 diagnosis. During the first wave (25th February-31st May), we estimated 52,437 excess deaths (95% CI: 49,213-55,863) and 50,979 (95% CI: 50,333-51,425) during the second phase (10th October-31st December), corresponding to percentage 34.8% (95% CI: 33.8%-35.8%) in the second wave and 31.0% (95%CI: 27.2%-35.4%) in the first. During both waves, all-cause excess deaths percentages were higher in northern regions (59.1% during the first and 42.2% in the second wave), with a significant increase in the rest of Italy (from 6.7% to 27.1%) during the second wave. Males and those aged 80 or over were the most hit groups with an increase in both during the second wave. Excess deaths not directly attributable to COVID-19 decreased during the second phase with respect to the first phase, from 10.8% (95% CI: 9.5%-12.4%) to 7.7% (95% CI: 7.5%-7.9%), respectively. The percentage increase in excess deaths from all causes suggests in Italy a different impact of the SARS-CoV-2 virus during the second wave in 2020. The decrease in excess deaths not directly attributable to COVID-19 may indicate an improvement in the preparedness of the Italian health care services during this second wave, in the detection of COVID-19 diagnoses and/or clinical practice toward the other severe diseases.

Exploring methods for the assessment of temporal trends in mortality and hospitalization in Italian industrially contaminated sites.

INTRODUCTION: The Italian contaminated sites of interest for remediation are monitored by SENTIERI, an epidemiological surveillance system describing the health status of populations living nearby these sites. There is an increasing concern on how to assess temporal changes in the health status of these populations. METHODS: A sequence of three statistical techniques was adopted to analyse temporal trends of mortality and hospitalization, by using different indicators and reference populations, in a sample of 36 sites with industrial sources of contamination monitored by SENTIERI. RESULTS: Positive temporal trends in health risks are detected reflecting mainly long term effects of industrial activities. The adopted methodology identifies multiple factors influencing the temporal patterns: type of health outcomes, type of disease, and its link with gender and type of emission sources. CONCLUSIONS: Reliable methods to assess health profile changes in local populations attributable to contaminations are key elements to measure the impact of remediation activities.

Ecological meta-analytic study of kidney disease in Italian contaminated sites.

INTRODUCTION: Environmental heavy metals exposure has been associated with kidney disease. There is also some evidence that exposure to solvents may be a risk factor for kidney disease. We estimated the risk of hospitalization for kidney diseases (ICD-9 580-586) and chronic kidney disease (CDK, ICD-9 585) in residents in thirty-four Italian National Priority Contaminated Sites (NPCSs) polluted by heavy metals. METHODS: Random-effects model meta-analyses of SHR (Standard Hospitalization Ratio) computed for each NPCS was performed for all the NPCSs together, and separately, according to the presence/absence of selected industrial activities (petrochemical/refinery and steel plants), and the presence/absence of solvents contamination. RESULTS: Pooled SHRs of overall NPCSs were in excess in both genders. Statistically significant excesses were found for CKD in both genders, and for kidney diseases in females, residing in NPCSs with the combined presence of heavy metals and solvents contamination. The pooled SHRs for CKD and kidney diseases were not statistically significant in excess in NPCSs with petrochemical/refinery and steel plants, and only petrochemical/refinery plants. CONCLUSIONS: The results are suggestive of a possible kidney disease risk in population living in the above-mentioned NPCSs. Epidemiological surveillance and remediation actions in these areas are recommended.

Trends in hip and distal femoral fracture rates in Italy from 2007 to 2017.

Osteoporosis-related fractures are a growing public health concern worldwide due to high societal and economic burden. The study aims to assess trends in incidence rates of hip and distal femoral fractures and in the use of anti-osteoporosis drugs in Italy between 2007 and 2017. Patients with hip and distal femoral fractures (ICD-9-CM codes 820.x and 821.x) were identified in the Italian National Hospital Discharge Database while anti-osteoporosis medication data were retrieved from the National Observatory on the Use of Medicines Database. A joinpoint regression analysis was performed to identify the years where the trends in incidence rates of hip and distal femoral fractures changed significantly; the average annual percentage change for the period of observation was estimated. Hospitalizations for femoral fractures were 991,059, of which 91.4% were hip fractures and 76.5% occurred in women. Age-standardized hip fractures rate per 100,000 person-years decreased both in women (-8.7%; from 789.9 in 2007 to 721.5 in 2017) and in men (-4.3%; from 423.9 to 405.6), while the rate of distal femoral fractures increased by 23.9% in women (from 67.78 to 83.95) and 22.7% in men (from 27.76 to 34.06). These changes were associated with an increment in the use of anti-osteoporosis drugs from 2007 to 2011 (from 9.1 to 12.4 DDD/1000 inhabitants/day), followed by a plateau in the period 2012-2017. The use of bisphosphonates increased progressively from 2007 to 2010 (from 8.2 to 10.5 DDD/1000 inhabitants/day), followed by a plateau and then decreased from 2015 onwards. The decreasing trend of hip fractures could be related to a major intake of anti-osteoporosis medications while the increment of distal femoral fractures might be due to population aging and to the use of bisphosphonates and denosumab. Further research is needed to identify and implement interventions to prevent hip and distal femoral fractures.

The Role of COVID-19 in the Death of SARS-CoV-2-Positive Patients: A Study Based on Death Certificates.

Background: Death certificates are considered the most reliable source of information to compare cause-specific mortality across countries. The aim of the present study was to examine death certificates of persons who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to (a) quantify the number of deaths directly caused by coronavirus 2019 (COVID-19); (b) estimate the most common complications leading to death; and (c) identify the most common comorbidities. Methods: Death certificates of persons who tested positive for SARS-CoV-2 provided to the National Surveillance system were coded according to the 10th edition of the International Classification of Diseases. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death. Complications were defined as those conditions reported as originating from COVID-19, and comorbidities were conditions independent of COVID-19. Results: A total of 5311 death certificates of persons dying in March through May 2020 were analysed (16.7% of total deaths). COVID-19 was the underlying cause of death in 88% of cases. Pneumonia and respiratory failure were the most common complications, being identified in 78% and 54% of certificates, respectively. Other complications, including shock, respiratory distress and pulmonary oedema, and heart complications demonstrated a low prevalence, but they were more commonly observed in the 30-59 years age group. Comorbidities were reported in 72% of certificates, with little variation by age and gender. The most common comorbidities were hypertensive heart disease, diabetes, ischaemic heart disease, and neoplasms. Neoplasms and obesity were the main comorbidities among younger people. Discussion: In most persons dying after testing positive for SARS-CoV-2, COVID-19 was the cause directly leading to death. In a large proportion of death certificates, no comorbidities were reported, suggesting that this condition can be fatal in healthy persons. Respiratory complications were common, but non-respiratory complications were also observed.

Primary Sclerosing Cholangitis: Burden of Disease and Mortality Using Data from the National Rare Diseases Registry in Italy.

Introduction: Studies on the epidemiology of primary sclerosing cholangitis (PSC) are mainly based on tertiary referral centers; and are retrospective case series susceptible to selection bias. The aim of this study was to estimate incidence; survival and cause of mortality of PSC in Italy; using population-based data. Methods: Data collected from the National Rare Diseases Registry (RNMR) and the National Mortality Database (NMD) were integrated and analyzed. Results: We identified 502 PSC incident cases. The crude incidence rate between 2012 and 2014 was 0.10 per 100,000 individuals. Sixty percent were male; mean age at disease onset and at diagnosis were 33 and 37 years; respectively; highlighting a mean diagnostic delay of 4 years. The rate of interregional mobility was 12%. Ten-year survival was 92%. In 32% of cases the cause of death was biliary-related; 12% died of biliary or gallbladder cancer. Conclusions: For rare diseases such as PSC; population-based cohort's studies are of paramount importance. Incidence rates of PSC in Italy are markedly lower and survival much longer than the ones reported from tertiary; single-centre series. Moreover; the diagnostic delay and the patient interregional mobility highlights the need for increasing awareness on the disease and for resource reallocation among Italian regions within the National Health Service.

A National Hospital-Based Study of Hospitalized Patients With Primary Biliary Cholangitis.

Epidemiological studies on primary biliary cholangitis (PBC) have been based primarily on tertiary referral case series. We aimed to estimate the incidence and prevalence and describe comorbidities in hospitalized patients with PBC in Italy using a national hospital-based data source. Data were extracted from the National Hospital Discharge Database, which includes all Italian individuals discharged from any hospital in the country. All adults diagnosed with biliary cirrhosis (International Classification of Diseases, Ninth Revision, Clinical Modification, 571.6) as the primary or secondary diagnosis from 2011 to 2015 were included. To determine whether a comorbidity was either more or less frequent in PBC patients compared with the general hospitalized Italian population, the standardized hospitalization ratio (SHR) was calculated. A total of 5,533 incident cases were identified from 2011 to 2015, 3,790 of whom were females (68.5%; female to male [F:M] ratio, 2.2:1). Prevalent cases were 9,664, of whom 7,209 were females (74.6%; F:M ratio, 2.9:1). The incident rate was 1.03 × 100,000 in males and 1.92 × 100,000 in females; prevalence was 1.89 × 100,000 in males and 4.75 × 100,000 in females. Extrahepatic autoimmune diseases, malignant neoplasms of liver and intrahepatic biliary ducts, and malignant neoplasms of gallbladder and extrahepatic bile ducts were found more frequently in PBC patients than in the general hospitalized population (SHR > 100), whereas cerebrovascular diseases and ischemic heart diseases were less frequent in PBC individuals (SHR < 100). Conclusion: This national study provides a survey of comorbidities associated with PBC. Hospitalized patients with PBC are more likely to have extrahepatic autoimmune diseases, hepatocellular carcinoma, and biliary tract cancers and a low risk of cardiovascular events.

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

INTRODUCTION AND OBJECTIVES: This volume provides an update of the health status of the populations living in the National Priority Contaminated Sites (NPCSs) included in the SENTIERI Project. This update is part of an epidemiological surveillance programme carried out in NPCSs, promoted by the Italian Ministry of Health as a further step of a project started in 2006, when the health status of residents in contaminated sites was first addressed within the National Strategic Program "Environment and Health". The Report focuses on five health outcomes: mortality, cancer incidence, hospital discharges, congenital anomalies, and children, adolescents and young adults' health. A key element of SENTIERI project is the a priori evaluation of the epidemiological evidence of a causal association between the considered cause of disease and the exposure. When an a priori evidence is identified, it is given a greater importance in the comment of the study findings. METHODS: The present update of the SENTIERI Project concerns 45 NPCSs including in all 319 Italian Municipalities (out of over 8,000 Municipalities), with an overall population of 5,900,000 inhabitants at the 2011 Italian Census. Standardized Mortality Ratios (SMRs) and Standardized Hospitalization Ratios (SHRs), referring to a time window of 2006-2013, were computed for all the 45 NPCSs, using as a reference the corresponding mortality and hospitalization rates of the Regions where each NCPS is located. Standardized Incidence Ratios (SIRs) were computed by the Italian Association of Cancer Registries (AIRTUM) for the 22 NPCSs served by a Cancer Registry. AIRTUM covers about 56% of Italy, with partly different time-windows. SIRs have been estimated using as reference population the 4 macroareas in which Italy is divided (North-West, North-East, Centre, South). Prevalence of congenital anomalies was computed for 15 NPCSs. RESULTS: An all-cause excess of 5,267 and 6,725 deaths was observed, respectively, in men and women; the cancer death excess was of 3,375 in men and 1,910 in women. It was estimated an excess of cancer incidence of 1,220 case in men and 1,425 in women over a five-year time window. With regard to the diseases with an a priori environmental aetiological validity, an excess for malignant mesothelioma, lung, colon, and gastric cancer, and for non-malignant respiratory diseases was observed. Cancer excess mainly affected NPCSs with presence of chemical and petrochemical plants, oil refineries, and dumping hazardous wastes. An excess of non-malignant respiratory disease was also detected in NPCSs in which steel industries and thermoelectric plants were present. An excess of mesothelioma was observed in NPCSs characterized by presence of asbestos and fluoro-edenite; it was also observed where the presence of asbestos was not reported in the legislative national decrees which define the NPCS areas. It is worth noting that, even if the presence of asbestos is not reported in many NPCSs legislative decrees, petrochemical plants and steel industries, for instance, are often characterized by the presence of a large amount of this mineral that, in the past, was extensively used as an insulating material. For the first time, the present Report includes a focus on the health status of children and adolescents (1,160,000 subjects, aged 0-19 years), and young adults (660,000 subjects, aged 20-29 years). Among infants (0-1 year), an excess of 7,000 hospitalizations was observed, 2,000 of which due to conditions of perinatal origin. In the age class 0-14, an excess of 22,000 hospitalizations for all causes was observed; 4,000 of them were due to acute respiratory diseases, and 2,000 to asthma. Data on cancer incidence for subjects aged 0-24 years were derived from general population cancer registries for twenty NPCSs, and from children cancer registries (age group: 0-19 years) for six NPCSs; 666 cases where diagnosed in the age group 0-24 years, corresponding to an excess of 9%. The main contributions to this excess are from soft tissue sarcomas in children (aged 0-14 years), acute myeloid leukaemia in children (aged 0-14 years) and in the age group 0-29 years, non-Hodgkin lymphoma and testicular cancer in young adults (aged 20-29 years). In seven out of 15 NPCSs, an excess prevalence rate of overall congenital anomalies at birth was observed. Congenital anomalies excesses included the following sites: genital organs, heart, limbs, nervous system, digestive system, and urinary system. CONCLUSIONS: The main findings of SENTIERI Project have been the detection of excesses for the diseases which showed an a priori epidemiological evidence of a causal association with the environmental exposures specific for each considered NPCS. These observations are valuable within public health, because they contribute to priority health promotion activities. Looking ahead, the health benefits of an improved environmental quality might be appreciated in terms of reduction of the occurrence of adverse health effects attributable to each Site major pollutant agents. Due to the methodological approach of the present study, it was not possible to adjust for several confounding factors reported to be risk factors for the studied diseases (e.g., smoking, alcohol consumption, obesity). Even if excesses of mortality, hospitalization, cancer incidence, and prevalence of congenital anomalies were found in several NPCSs, the study design and the multifactorial aetiology of the considered diseases do not permit, for all of them, to draw conclusions in terms of causal links with environmental contamination. Moreover, it must be taken into consideration that economic factors and the availability of health services may also play a relevant role in a diseases outcome. A few observations regarding some methodological limitations of SENTIERI Project should be made. There is not a uniform environmental characterisation of the studied NPCSs in term of quality and detection of the pollutants, because this information is present in different databases which at present are not adequately connected. Moreover, the recognition of a contaminated site as a National Priority Site is based on soil and groundwater pollution, and the available information on air quality is currently sparse and not homogenous. Another limitation, in term of statistical power, is the small population size of many NPCSs and the low frequency of several health outcomes. A special caution must be paid in data interpretation when considering the correspondence between the contaminated areas and the municipality boundaries, as they do not always coincide perfectly: in some cases, a small municipality with a large industrial site, while in other settings only a part of the municipality is exposed to the sources of pollution. Furthermore, all available health information systems are currently accessible at municipality level. The real breakthrough is essentially comprised of the development and fostering of a networking system involving all local health authorities and regional environmental protection agencies operating in the areas under study. The possibility to integrate the geographic approach of SENTIERI Project with a set of ad hoc analytic epidemiological investigations, such as residential cohort studies, case control studies, children health surveys, biomonitoring surveys, and with socioepidemiological studies, might greatly contribute to the identification of health priorities for environmental remediation activities. Finally, as discussed in the last section of the report, there is a need to adopt, in each NPCS, a two-way oriented communication plan involving public health authorities, scientific community, and resident population, taking into account that the history, the cultural frame and the network of relationships specific of each local context play a major role in the risk perception perspective.

The Italian National Rare Diseases Registry: a model of comparison and integration with Hospital Discharge Data.

BACKGROUND: Italy has been the first country at European level to implement a population-based public health registry dedicated to rare diseases. This study describes the current situation of the Italian National Rare Diseases Registry (NRDR) and compares its data with those from the National Hospital Discharge Database (HDD). METHODS: Three rare diseases were analysed: Huntington disease (HD), Hereditary Haemorragic Telangiectasia (HHT) and Prader-Willi Syndrome (PWS), selected for their different characteristics. The two sources (NRDR and HDD) were linked: incidence rate ratio (IRR), sensitivity and predictive positive value (PPV) were calculated. RESULTS: Incidence rates from NRDR and from HDD were compared by age groups, and IRR calculated: 1.08 for HD, 1.41 for HHT, 1.21 for PSW. For HD, sensitivity was 0.52 and PPV 0.48; for HHT sensitivity was 0.71 and PPV 0.52; for PWS the sensitivity was 0.71 and PPV 0.58. We found a strong regional variability in the results. CONCLUSIONS: The integrated use of the two sources helps tracking those cases that are not captured by the Registry; further, it is a precious tool to accurately describe clinical histories of rare disease affected individuals, in terms of concomitant pathologies and medical procedures performed during hospitalization.