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.

[Endometriosis, a participatory study in the Serchio Valley (Tuscany Region, Central Italy): state of the art and perspectives]. / Endometriosi, uno studio partecipato nella Valle del Serchio: stato dell'arte e prospettive.

BACKGROUND: endometriosis is a chronic condition with a significant impact on women's health, featured by endometrial tissue outside the uterine cavity. A limited number of studies have been conducted in the general population, and the true prevalence of endometriosis is unknown for many areas of the country. OBJECTIVES: to better estimate the prevalence of endometriosis in three Italian regions (Friuli Venezia Giulia, Tuscany, Apulia) and to assess the relationship between endometriosis and environmental factors in three participating areas (Trieste, Barga, and Taranto), with a focus on Tuscany Region. DESIGN: implementing a specific epidemiological registry for endometriosis, aimed at estimating the incidence and prevalence data. The registry collected information from hospital discharge records and anatomopathological reports of women residing in the three considered regions, aged 15 years or older. Additionally, the analysis includes the assessment of the spatial distribution of endometriosis at both regional and municipal levels in the three study areas. Further research investigations in these areas involve a multilevel screening of a sample of women of childbearing age. Women who test positive in the initial screening (through a self-administered questionnaire) will have the opportunity to undergo a second level of screening, consisting of a gynecological examination, transvaginal ultrasound, a swab for vaginal microbiome analysis, and the collection of blood and urine samples to assess the presence of polychlorinated biphenyls (PCBs) or heavy metals. The adopted scientific approach is based on post-normal science (PNS) concerning the extended peer community. SETTING AND PARTICIPANTS: women aged 15 years or older residing in the three regions. MAIN OUTCOMES MEASURES: estimating the incidence and prevalence of endometriosis based on data collected from the epidemiological registry. The analysis extends to assessing the spatial distribution of endometriosis at municipal levels in the three areas of interest. RESULTS: the preliminary results of the study allowed for the estimation of the spatial distribution of endometriosis incidence in Tuscany. In particular, it was found that there is variability within the region, with some coastal and North-Western areas showing values 20% higher than the regional average. Cities such as Pisa, Lucca, Livorno, Grosseto, Orbetello, and the Serchio Valley with Barga had a probability of excess risk of more than 90% compared to the regional average. CONCLUSIONS: the study is ongoing and requires the active participation of women living in the region to ensure the completeness and accuracy of the collected data. This research effort represents an important contribution to understanding endometriosis in Tuscany and its possible environmental causes.

Hospitalization-based epidemiology of systemic and cardiac amyloidosis in the Veneto Region, Italy.

AIM: Defining the epidemiology of systemic and cardiac amyloidosis (CA) is a contemporary challenge. The present study aimed to estimate incidence and time trends in amyloidosis-related hospitalizations (AH) in Veneto Region (5 million inhabitants, Northeastern Italy). METHODS: International Classification of Diseases (ICD-9) codes were used to identify AH in Veneto from 2010 to 2020. AH were defined as any hospitalization with a discharge summary reporting an ICD-9 code for systemic amyloidosis. Hospitalization for CA was defined as records with ICD-9 code for systemic amyloidosis and ICD-9 code for heart failure,cardiomyopathy or arrhythmia. Hospital/outpatient encounters for carpal tunnel syndrome (CTS) surgeries also were extracted. AH incidence was estimated using a buffer of 5 years. RESULTS: In the time range 2015-2020, the incidence rate of AH was 23.5 cases per 106 (95% confidence interval, CI, 21.8; 25.3), mainly affecting patients>65 years (76.2%) and males (63.5%), with a progressively increasing trend (percent annual increase 17%, 95% CI 12; 22%). The 10 year prevalence of AH in 2020 was 124.5 per 106 (95% CI 114.9; 134.8). In 2020, annual hospitalized prevalent cases of CA were about 70% of all cases (159/228), mainly patients >65 years and males. Among patients with multiple CTS surgeries, a subsequent code for cardiac disease was found in 913 after a median of 3.9 years, more frequently in men than in women (463/6.526 7.1% versus 450/11.406 3.9%). CONCLUSIONS: In Veneto, we recorded a significantly increasing trend in the incidence of AH, with concordant increasing prevalence estimates.

Exposure to low levels of hydrogen sulphide and its impact on chronic obstructive pulmonary disease and lung function in the geothermal area of Mt. Amiata in Italy: The cross-sectional InVETTA study.

BACKGROUND: The geothermal power plants for electricity production currently active in Italy are all located in Mt. Amiata area in the Tuscany region. A cross-sectional survey was conducted in the framework of the regional project "InVETTA-Biomonitoring Survey and Epidemiological Evaluations for the Protection of Health in the Amiata Territories", using objective measures of lung function to investigate the role of hydrogen sulphide (H2S) in affecting the respiratory health of the population living in this area. METHODS: 2018 adults aged 18-70 were enrolled during 2017-2019. Home and workplace addresses of participants were geocoded. Dispersion modelling was used to evaluate the spatial variability of exposure to H2S from the geothermal power plants' emissions. We estimated average long-term historical exposure to H2S and more recent exposure indicators. Chronic Obstructive Pulmonary Disease (COPD) was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Multivariable logistic regressions were performed to investigate associations between outcome and exposure. RESULTS: Our findings did not showed any evidence of an association between increasing H2S exposure and lung function impairments. Some risk reductions were observed: a -32.8% (p = 0.003) for FEV1<80% and a -51.7% (p = 0.001) risk decrease for FVC<80% were associated with interquartile increase (13.8 µg/m3) of H2S levels. CONCLUSION: Our study provides no evidence that chronic exposure to low levels of H2S is associated with decrements in pulmonary function, suggesting that ambient H2S exposure may benefit lung function.

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.

[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.

Formaldehyde and Acetaldehyde Exposure in "Non-Traditional" Occupational Sectors: Bakeries and Pastry Producers.

INTRODUCTION: Formaldehyde, a colorless and highly irritating substance, causes cancer of the nasopharynx and leukemia. Furthermore, it is one of the environmental mutagens to which humans are most abundantly exposed. Acetaldehyde was recently classified as carcinogen class 1B and mutagen class 2 in Annex VI EC regulation. Occupational exposure to the two aldehydes occurs in a wide variety of occupations and industries. The aim of this study is to deepen exposure to the two aldehydes in the non-traditional productive sectors of bakeries and pastry producers. METHODS: The evaluation of exposure to formaldehyde and acetaldehyde was conducted in Italy in 2019, in specific tasks and positions of 11 bakeries and pastry producers (115 measures, of which 57.4% were in fixed positions and the rest were personal air sampling). The measurements were performed using Radiello© radial diffusion samplers. A logarithmic transformation of the data was performed, and the correlation between the two substances was calculated. Moreover, linear models considering the log-formaldehyde as the outcome and adjusting for log-acetaldehyde values were used. RESULTS: The study identified high levels of acetaldehyde and formaldehyde exposure in the monitored workplaces. Higher mean values were observed in the leavening phase (8.39 µg/m3 and 3.39 µg/m3 for log-transformed data acetaldehyde and formaldehyde, respectively). The adjusted univariate analyses show statistically significant factors for formaldehyde as the presence of yeast, the presence of type 1 flour, the use of barley, the use of fats, the type of production, the use of spelt, and the presence of type 0 flour. CONCLUSIONS: The measurements confirmed the release of formaldehyde and acetaldehyde in bakeries and pastry industries, especially in some phases of the work process, such as leavening.

Long-term exposure to low-level arsenic in drinking water is associated with cause-specific mortality and hospitalization in the Mt. Amiata area (Tuscany, Italy).

BACKGROUND: Arsenic in drinking water is a global public health concern. This study aims to investigate the association between chronic low-level exposure to arsenic in drinking water and health outcomes in the volcanic area of Mt. Amiata in Italy, using a residential cohort study design. METHODS: Chronic exposure to arsenic in drinking water was evaluated using monitoring data collected by the water supplier. A time-weighted average arsenic exposure was estimated for the period 2005-2010. The population-based cohort included people living in five municipalities in the Mt. Amiata area between 01/01/1998 and 31/12/2019. Residence addresses were georeferenced and each subject was matched with arsenic exposure and socio-economic status. Mortality and hospital discharge data were selected from administrative health databases. Cox proportional hazard models were used to test the associations between arsenic exposure and outcomes, with age as the temporal axis and adjusting for gender, socio-economic status and calendar period. RESULTS: The residential cohort was composed of 30,910 subjects for a total of 407,213 person-years. Analyses reported risk increases associated with exposure to arsenic concentrations in drinking water > 10 µg/l for non-accidental mortality (HR = 1.07 95%CI:1.01-1.13) and malignant neoplasms in women (HR = 1.14 95%CI:0.97-1.35). Long-term exposure to arsenic concentrations > 10 µg/l resulted positively associated with several hospitalization outcomes: non-accidental causes (HR = 1.06 95%CI:1.03-1.09), malignant neoplasms (HR = 1.10 95%CI:1.02-1.19), lung cancer (HR = 1.85 95%CI:1.14-3.02) and breast cancer (HR = 1.23 95%CI:0.99-1.51), endocrine disorders (HR = 1.13 95%CI:1.02-1.26), cardiovascular (HR = 1.12 95%CI:1.06-1.18) and respiratory diseases (HR = 1.10 95%CI:1.03-1.18). Some risk excesses were also observed for an exposure to arsenic levels below the regulatory standard, with evidence of exposure-related trends. CONCLUSIONS: Our population-based cohort study in the volcanic area of Mt. Amiata showed that chronic exposure to arsenic concentrations in drinking water above the current regulatory limit was associated with a plurality of outcomes, in terms of both mortality and hospitalization. Moreover, some signs of associations emerge even at very low levels of exposure, ​​below the current regulatory limit, highlighting the need to monitor arsenic concentrations continuously and implement policies to reduce concentrations in the environment as far as possible.

Levels and determinants of urinary and blood metals in the geothermal area of Mt. Amiata in Tuscany (Italy).

Natural sources and anthropogenic activities are responsible for the widespread presence of heavy metals in the environment in the volcanic and geothermal area of Mt. Amiata (Tuscany, Italy). This study evaluates the extent of the population exposure to metals and describes the major individual and environmental determinants. A human biomonitoring survey was carried out to determine the concentrations of arsenic (As), mercury (Hg), thallium (Tl), antimony (Sb), cadmium (Cd), nickel (Ni), chromium (Cr), cobalt (Co), vanadium (V), and manganese (Mn). The associations between socio-demographics, lifestyle, diet, environmental exposure, and metal concentrations were evaluated using multiple log-linear regression models, adjusted for urinary creatinine. A total of 2034 urine and blood samples were collected. Adjusted geometric averages were higher in women (except for blood Hg) and younger subjects (except for Tl and Cd). Smoking was associated with Cd, As, and V. Some dietary habits (rice, fish, and wine consumption) were associated with As, Hg, Co, and Ni. Amalgam dental fillings and contact lenses were associated with Hg levels, piercing with As, Co, and Ni. Among environmental determinants, urinary As levels were higher in subjects using the aqueduct water for drinking/cooking. The consumption of locally grown fruits and vegetables was associated with Hg, Tl, and Co. Exposure to geothermal plant emissions was associated only with Tl.

Community Concern about the Health Effects of Pollutants: Risk Perception in an Italian Geothermal Area.

Geothermal fluids for electricity and heat production have long been exploited in the Mt. Amiata area (Tuscany, Italy). Public concern about the health impact of geothermal plants has been present from the outset. Several factors influence the way people perceive risk; therefore, the objective of the present research is to develop indicators of risk perception and assess indices differences in relation to some questionnaire variables. A cross-sectional survey was conducted in the Amiata area on 2029 subjects aged 18-77. From the questionnaire section about risk perception from environmental hazards, four indicators were developed and analysed. A total of 64% of the subjects considered the environmental situation to be acceptable or excellent, 32% serious but reversible, and 4% serious and irreversible; as the values of the various perception indicators increased, an upward trend was observed in the averages. Risk perception was higher among women and young people, and was associated with higher education. Those who smelled bad odours in their surroundings reported higher risk perception. Furthermore, risk perception was higher in four municipalities. The results represent the basis for further investigations to analyse the link among risk perception indicators, exposure parameters, and health status.

[A suspect cluster of childhood cancer in Valle di Ledro (Province of Trento, Northern Italy). Epidemiological evaluation, risk management, and communication activities, 2018-2020]. / Un sospetto cluster di tumori infantili in Valle di Ledro (provincia di Trento). Valutazione epidemiologica e attività di comunicazione e gestione del rischio. Anni 2018-2020.

BACKGROUND: leukaemia is the most prevalent form of childhood cancer, an overall rare condition in childhood. Even few cases occurring in a small community can cause considerable apprehension among the population. From 2014 to 2017, 4 cases of childhood cancer occurred in Valle di Ledro, a municipality of 5,300 inhabitants in Province of Trento (Northern Italy), and a group of concerned citizens asked provincial health authorities for an investigation. OBJECTIVES: to address the community's health needs by verifying the hypothesis of a cluster of childhood cancer and through effective risk communication activities. DESIGN: retrospective cohort analysis based on data from the Cancer registry of the Autonomous Province of Trento and data collected from hospital discharge records. The communication activities were carried out according to the recommendations published by Epidemiologia&Prevenzione in 2016 in a Supplement "Childhood cancers, risk factors and investigation models for the evaluation of spatio-temporal clusters". SETTING AND PARTICIPANTS: Valle di Ledro, a municipality of 5,300 inhabitants in the Province of Trento. The participants in risk communication process were: city council; grassroot committee of concerned parents; health workforce of different services (epidemiology, cancer registry, public health; environmental health; primary health care; personnel of the Environmental Protection Agency; journalists; general population. The participants in the statistical analyses were: children of 0-14 years of age who were diagnosed a cancer from 1998 to 2014 in the Province of Trento (N. 212); leukaemia (N. 84) and acute lymphoblastic leukaemia (N. 66) incident cases in the period 1998-2017 in Trento province. MAIN OUTCOME MEASURES: verification of the presence of a cluster of childhood cancers; degree of consensus and collaboration of the different community stakeholders to the survey procedures and acceptance of the final results; atmosphere in public assemblies and feedback in the local press. RESULTS: a total of 212 incident cancer cases in children 0-14 years have been registred in Province of Trento from 1998 to 2014, leukaemia in 35% (N. 74) cases. From 2015 to 2017, another 10 cases of leukaemia occurred, for a total of 84 cases of leukaemia from 1998 to 2017. In the years from 1998 to 2017, in Valle di Ledro, taking the Italian population as reference group, the standardized incidence ratios (SIRs) were the following: cancer, all types 1,47 (IC95% 0,40-3,76); leukaemia 3,39 (IC95% 0,70-9,90), LLA 2,81 (IC95% 0,34-10,16). No cluster emerged from the geographical analyses. From the very beginning of the risk management approach, a decision-making working group was set up applying a participatory approach. Group members included the city council and the local committee of concerned parents and experts from different services of the local health unit. Data analyses was delegated to a technical working group that reported back to the decision-making group. Members of the technical working group were supervised by external experts. Following this approach, it was possible to establish a climate of trust and credibility. The involvement of all stakeholders right from the start in a totally transparent process was a key element of success. CONCLUSIONS: the cluster hypothesis was rejected for both childhood cancer (all types) and leukaemia (all types and ALL). The implementation of the risk communication process recommended by the AIE guidelines was successful in establishing a climate of reciprocal trust that allowed to overcome inevitable moments of conflict in a productive manner. Thanks to this positive atmosphere, the communication of the results of the statistical analyses was effective in reassuring the population.

[P-value and the probability of direction of effect]. / P-value e probabilità di direzione dell'effetto.

The p-value has been widely criticized in the scientific literature for its naive use in classifying results as 'significant' and 'non significant'. Much has been written about it; for example, see the American Statistical Association position statement of march 2016. To date, few alternative measures have been suggested and few changes were observed in the scientific practice regarding the use of p-value despite general agreement on the critics raised on it. In this paper, we use an alternative measure to p-value. It consists in the probability of the direction of the effect, that is the strength of empirical evidence in favour of the alternative directional hypothesis. In the context of scientific research, reporting the probability of the direction of the effect is easier to understand. Moreover, it focuses on the effect in the study rather than on the value under the null hypothesis, which sometimes has little meaning or has been used opportunistically. The proposal is not intended as an alternative to using the confidence interval, but as a probabilistic metric to be used instead of the p-value when we refer to particular hypotheses to be tested.

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.

[Mortality study of residents of the municipality of Piazzola sul Brenta (Veneto Region, Northern Italy), 2003-2018]. / Profilo di mortalità per causa nel Comune di Piazzola sul Brenta (Padova), anni 2003-2018.

Currently, there are more and more requests for a characterization of the health profile by populations living in areas affected by several types of environmental contaminations, notably for the presence of previously unknown and accidentally discovered landfills. The aim of the present paper is to describe the mortality profile of the residents of Piazzola sul Brenta (Veneto Region, Northern Italy). In this area, it was discovered an environmental contamination of the soil in the nearby of a large school building, where was formerly located a phosphate fertiliser plant. Using cause of death data provided by the Italian National Institute of Health, 10th International Classification 2013-2018, standardised mortality ratios (SMRs) and 90% confidence intervals (CIs) were calculated by gender and specific causes of death. Compared to the provincial reference population, no excess was found, for both genders, for all-causes mortality and for circulatory diseases. However, an excess for malignant tumours was found, 523 observed deaths over 498 expected deaths, an SMR of 105 (IC90% 98-113), and 85% probability of excess cancer mortality; lung cancer (SMR 117; IC90% 100-135) and lympho-hematopoietic tumours (in men only, SMR 134; IC90% 101-178).In light of these results and of the potential human exposure to carcinogenic substances, present results support further epidemiological investigations and environmental remediation.

[Perfluoroalchilic food contamination in the PFAS high-risk area of the Veneto Region (Northern Italy)]. / Sostanze perfluoroalchiliche (PFAS) negli alimenti dell'area rossa del Veneto.

In a wide area among the provinces of Vicenza, Verona, and Padua (Veneto Region, Northern Italy), one of the larger known massive contamination of the environment by per- and polyfluoroalkyl substances (PFASs) occurred since the year 1965. The most important source of human exposure was through aquiferous and contaminated water supplies (the regional authorities distinguished red zone A - aquiferous - and red zone B - water supply) for a total of slightly less than two hundred thousand exposed people. Food contamination and food contribution to total human exposure were assessed by a food monitoring campaign on the years 2016-2017 by the National Health Institute sponsored by Veneto Region.Thanks to the availability of the individual records of the monitoring campaign, we evaluated the spatial distribution of PFAS contamination by food matrix. Generally speaking, PFAS contamination was widespread over the entire red zone (either A or B). Some zones appeared to be higher contaminated consistently with the water plume. Other higher contaminated zones were less consistent and such result raises questions about routes of environmental pollution.

[Mortality and cancer risk in agricultural nursery workers: a cohort study in Tuscany Region (Central Italy)]. / Mortalità e rischio cancerogeno nei florovivaisti: uno studio di coorte in Toscana.

OBJECTIVES: to follow-up mortality of agricultural nursery workers of the province of Pistoia (Tuscany Region, Central Italy). DESIGN: the cohort of nursery workers of the Pistoia province was assembled from two sources: subjects who obtained a pesticide license (PAT) and subjects who had been working in agricultural nursery, based on the 2003 regional census (LIF). Vital status and causes of deaths were ascertained through the official records of the municipalities and the Tuscany Mortality Register. The follow-up period for PAT cohort was from 01.01.1984 to 31.12.2015 and for LIF cohort was from 01.01.2003 al 31.12.2015. SETTING AND PARTICIPANTS: the total cohort included 2,732 males and 326 females: the PAT cohort included 1,602 males and 106 females, and the LIF cohort included 1,130 males and 220 females MAIN OUTCOME MEASURES: general and cause-specific Standardized Mortality Ratios (SMRs) and 95% confidence intervals were calculated for the entire cohort and for the PAT and LIF sub-cohorts. Expected deaths by age and gender for each cause of death were obtained from applying the respective rates in the Tuscan population. RESULTS: overall mortality was lower than expected, with notable deficits for all cancers and some specific causes in both genders. Among males, increased SMRs were observed for pancreas (17 observed cases: SMR 129; CI95% 75-207), prostate (22 cases: SMR 121; CI95% 76-183), bladder (18 cases: SMR 139; CI95% 83-220) cancer, and also for multiple myeloma (5 cases: SMR 120; CI95% 39-281). Among females, increased SMR for cancer of digestive system and peritoneum was observed (3 cases: SMR 152; IC95% 31-445). The analyses by calendar period also shown excess for cancers of the genital and urinary system and the lymphohematopoietic system. CONCLUSIONS: although overall deficits for all causes and all cancer were observed, there were notable exceptions for some specific cancer causes, that might be related to pesticides exposure.

Predicting Hemodynamic Failure Development in PICU Using Machine Learning Techniques.

The present work aims to identify the predictors of hemodynamic failure (HF) developed during pediatric intensive care unit (PICU) stay testing a set of machine learning techniques (MLTs), comparing their ability to predict the outcome of interest. The study involved patients admitted to PICUs between 2010 and 2020. Data were extracted from the Italian Network of Pediatric Intensive Care Units (TIPNet) registry. The algorithms considered were generalized linear model (GLM), recursive partition tree (RPART), random forest (RF), neural networks models, and extreme gradient boosting (XGB). Since the outcome is rare, upsampling and downsampling algorithms have been applied for imbalance control. For each approach, the main performance measures were reported. Among an overall sample of 29,494 subjects, only 399 developed HF during the PICU stay. The median age was about two years, and the male gender was the most prevalent. The XGB algorithm outperformed other MLTs in predicting HF development, with a median ROC measure of 0.780 (IQR 0.770-0.793). PIM 3, age, and base excess were found to be the strongest predictors of outcome. The present work provides insights for the prediction of HF development during PICU stay using machine-learning algorithms.

Mortality trend for multiple sclerosis in Italy during the period 1980-2015.

BACKGROUND: The epidemiology of Multiple Sclerosis (MS) is relevant for health-services planning. Most of MS prevalence and incidence studies in Italy referred to specific geographical areas and periods, whereas mortality data are routinely collected at the national level. The aim was to assess MS mortality trend and geographical differences in Italy from 1980 to 2015. METHODS: Mortality data were provided by the Italian Institute of Statistics. Due to a low number of annual deaths, mortality data were analysed for both the entire period under study and for sub-periods. Temporal trends were first evaluated using age-adjusted mortality rates (AMRs) comparing each sub-period with the initial one. Then, the annual percent change in mortality was estimated through the joinpoint regression model. Spatial differences between 5 main geographical areas were evaluated using standardized mortality ratios (SMRs). RESULTS: During the study period, 4,959 deaths for males and 7,434 for females were observed. The higher overall AMR was observed for females (F:0.71 vs. M: 0.56 per 100,000 persons per year). Analysing mortality by gender and geographical area, SMRs 〈 100 were observed in South Italy for both sexes, and in Central Italy for males only, whereas SMRs 〉 100 for Islands for both sexes, and in North-East and North-West for females only. The analysis of the mortality trend through AMRs calculated for sub-periods revealed no difference between the first and the last period for males, whereas a significant increase in mortality was observed for females. The joinpoint regression analysis showed a significant decrease in mortality up to 1995 for males (APC -3.23%) and up to 1999 for females, (APC -1.01%), followed by a significant increase for both sexes, but more marked for females (APC +1.9% M, +2.34% F). CONCLUSION: The increasing trend of mortality for MS, especially for females, may reflect the increase in the prevalence of MS and the improvement in the quality of diagnosis or coding of the cause of death.

Estimation of Occupational Exposure to Asbestos in Italy by the Linkage of Mesothelioma Registry (ReNaM) and National Insurance Archives. Methodology and Results.

The identification and monitoring of occupational cancer is an important aspect of occupational health protection. The Italian law on the protection of workers (D. Leg. 81/2008) includes different cancer monitoring systems for high and low etiologic fraction tumors. Record linkage between cancer registries and administrative data is a convenient procedure for occupational cancer monitoring. We aim to: (i) Create a list of industries with asbestos exposure and (ii) identify cancer cases who worked in these industries. The Italian National Mesothelioma Registry (ReNaM) includes information on occupational asbestos exposure of malignant mesothelioma (MM) cases. We developed using data from seven Italian regions a methodology for listing the industries with potential exposure to asbestos linking ReNaM to Italian National Social Security Institute (INPS) data. The methodology is iterative and adjusts for imprecision and inaccuracy in reporting firm names at interview. The list of asbestos exposing firms was applied to the list of cancer cases (all types associated or possibly associated with asbestos according to International Agency for Research on Cancer (IARC) monograph 100C) in two Italian regions for the indication of possible asbestos exposure. Eighteen percent of the cancer cases showed at least one work period in firms potentially exposing to asbestos, 48% of which in regions different from where the cases lived at diagnosis. The methodology offers support for the preliminary screening of asbestos exposing firms in the occupational history of cancer cases.

INSIDE Project: Individual Air Pollution Exposure, Extracellular Vesicles Signaling and Hypertensive Disorder Development in Pregnancy.

Hypertensive disorders are common complications during pregnancy (HDP) with substantial public health impact. Acute and chronic particulate matter (PM) exposure during pregnancy increases the risk of HDP, although the underlying molecular mechanisms remain unclear. Extracellular vesicles (EVs) may be the ideal candidates for mediating the effects of PM exposure in pregnancy as they are released in response to environmental stimuli. The INSIDE project aims to investigate this mechanism in pregnancy outcomes. The study population is enrolled at the Fetal Medicine Unit of Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico at 10-14 weeks of gestation. Exposure to PM10 and PM2.5 is assessed using the flexible air quality regional model (FARM) and Bayesian geostatistical models. Each woman provides a blood sample for EV analysis and circulating biomarker assessment. Moreover, a subgroup of recruited women (n = 85) is asked to participate in a cardiovascular screening program including a standard clinical evaluation, a non-invasive assessment of right ventricular function, and pulmonary circulation at rest and during exercise. These subjects are also asked to wear a personal particulate sampler, to measure PM10, PM2.5, and PM1. The INSIDE study is expected to identify the health impacts of PM exposure on pregnancy outcomes.